International Journal of Molecular Sciences | An Open Access Journal from MDPI

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acceptance to publication is undertaken in 2.8 days (median values for papers published in this journal in the first half of 2024).</li> <li><strong>Recognition of Reviewers:</strong> reviewers who provide timely, thorough peer-review reports receive vouchers entitling them to a discount on the APC of their next publication in any MDPI journal, in appreciation of the work done.</li> <li><strong>Testimonials:</strong> <a href="https://www.mdpi.com/testimonials?type=all&journal_id=2&page_count=20">See what our editors and authors say about the <em>IJMS</em></a>.</li> <li><strong>Companion journals for <em>IJMS</em> include:</strong> <em><a href="https://www.mdpi.com/journal/biophysica">Biophysica</a></em>, <em><a href="https://www.mdpi.com/journal/stresses">Stresses</a>,</em> <em><a href="https://www.mdpi.com/journal/lymphatics">Lymphatics</a></em> and <a href="https://www.mdpi.com/journal/synbio"><em>SynBio</em></a>.</li> </ul> </div> <div style="margin-bottom: 15px;"> <strong>Impact Factor:</strong> 4.9 (2023); 5-Year Impact Factor: 5.6 (2023) </div> <div> <a href="/journal/ijms/imprint" class="UI_JournalImprintsInfoButton"> <i class="material-icons spaced-link">subject</i> Imprint Information </a>    <a href="/journal/ijms/ijms_flyer.pdf" class="UD_JournalFlyer"> <i class="material-icons spaced-link">get_app</i> Journal Flyer </a>     <a class="oa-link" href="https://www.mdpi.com/about/openaccess"> <i class="material icons spaced-link"></i> Open Access </a>     <strong> ISSN: 1422-0067 </strong> </div> <div style="clear: both;"></div> </div> </div> </div> <div class="content__container content__container--overflow-initial"> <div class="custom-accordion-for-small-screen-link active"> <h2 class="no-padding-left">Latest Articles</h2> </div> <div class="custom-accordion-for-small-screen-content"> <div class="expanding-div collapsed"> <div class="generic-item article-item no-border"> <div class="article-content"> <div class="label right label__btn"> <a data-dropdown="drop-supplementary-1530289" aria-controls="drop-supplementary-1530289" aria-expanded="false" title="Supplementary Material"> <i class="material-icons">attachment</i> </a> <div id="drop-supplementary-1530289" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide" data-dropdown-content aria-hidden="true" tabindex="-1"> Supplementary material: <br/> <a href="/1422-0067/25/23/12720/s1?version=1732639267"> Supplementary File 1 (ZIP, 432 KiB) </a><br/> </div> </div> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 23 pages, 1396 KiB   </span> <a href="/1422-0067/25/23/12720/pdf?version=1732639266" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="In Vitro and In Vivo Translational Insights into the Intraoperative Use of Antiseptics and Lavage Solutions Against Microorganisms Causing Orthopedic Infections" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12720">In Vitro and In Vivo Translational Insights into the Intraoperative Use of Antiseptics and Lavage Solutions Against Microorganisms Causing Orthopedic Infections</a> <div class="authors"> by <span class="inlineblock "><strong>Bartłomiej Dudek</strong>, </span><span class="inlineblock "><strong>Malwina Brożyna</strong>, </span><span class="inlineblock "><strong>Michał Karoluk</strong>, </span><span class="inlineblock "><strong>Mariusz Frankiewicz</strong>, </span><span class="inlineblock "><strong>Paweł Migdał</strong>, </span><span class="inlineblock "><strong>Konrad Szustakiewicz</strong>, </span><span class="inlineblock "><strong>Tomasz Matys</strong>, </span><span class="inlineblock "><strong>Adrian Wiater</strong> and </span><span class="inlineblock "><strong>Adam Junka</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12720; https://doi.org/10.3390/ijms252312720 (registering DOI) - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> The growing antibiotic resistance of microorganisms causing postoperative infections following orthopedic surgeries underscores the urgent need for localized antiseptic and lavage delivery systems to enhance infection control. This study evaluates the in vitro effectiveness of antiseptic and lavage solutions—including polyhexanide, povidone–iodine, low-concentrated hypochlorite, <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12720/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> The growing antibiotic resistance of microorganisms causing postoperative infections following orthopedic surgeries underscores the urgent need for localized antiseptic and lavage delivery systems to enhance infection control. This study evaluates the in vitro effectiveness of antiseptic and lavage solutions—including polyhexanide, povidone–iodine, low-concentrated hypochlorite, Ringer’s solution, and saline—against <i>Staphylococcus epidermidis</i>, <i>Staphylococcus aureus</i> MRSA, <i>Cutibacterium acnes</i>, <i>Corynebacterium amycolatum</i>, <i>Pseudomonas aeruginosa</i>, and <i>Candida albicans</i>. Using microplate models (Minimum Inhibitory Concentration, Minimum Biofilm Eradication Concentration, and Biofilm-Oriented Antiseptic Test assays), flow-based models (Bioflux system), and surfaces relevant to orthopedic implants (e.g., stainless steel disks/screws, Co-Cr-Mo, Ti-Al-Nb orthopedic alloys, and ultra-high-molecular-weight polyethylene), as well as a bio-nano-cellulose scaffold representing tissue, we assessed the solutions’ activity. The cytotoxicity of the solutions was evaluated using osteoblast and keratinocyte cell lines, with additional in vivo insights gained through the <i>Galleria mellonella</i> larval model. The results show that polyhexanide-based solutions outperformed povidone–iodine in biofilm eradication in most tests applied, particularly on complex surfaces, whereas iodine demonstrated higher cytotoxicity in applied in vitro and in vivo tests. Low-concentration hypochlorite solutions exhibited minimal antibiofilm activity but also showed no cytotoxicity in cell line and <i>G. mellonella</i> larval models. These findings highlight the importance of careful antiseptic selection and rinsing protocols to balance infection control efficacy with tissue compatibility in orthopedic applications. <a href="/1422-0067/25/23/12720">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/ZKWJ508B1Q ">New Types of Antimicrobial Biocides: 2nd Edition</a>)<br/> </div> </div> </div> </div> <div class="extending-content content-ready"> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 14 pages, 907 KiB   </span> <a href="/1422-0067/25/23/12719/pdf?version=1732638929" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Advancements in Mesenchymal Stem Cell-Based Therapy for Enhancing Arteriovenous Fistula Patency" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Review</span></div> <a class="title-link" href="/1422-0067/25/23/12719">Advancements in Mesenchymal Stem Cell-Based Therapy for Enhancing Arteriovenous Fistula Patency</a> <div class="authors"> by <span class="inlineblock "><strong>Gaurav Baranwal</strong>, </span><span class="inlineblock "><strong>Haseeb Mukhtar</strong>, </span><span class="inlineblock "><strong>Jamie Kane</strong>, </span><span class="inlineblock "><strong>Alaura Lemieux</strong> and </span><span class="inlineblock "><strong>Sanjay Misra</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12719; https://doi.org/10.3390/ijms252312719 (registering DOI) - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Chronic kidney disease (CKD) affects more than 10% of the world’s population. Hemodialysis, along with peritoneal dialysis and renal transplant, is one of the renal replacement therapies offered to patients with CKD/end-stage renal disease (ESRD). To proceed with hemodialysis, vascular access is required. <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12719/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Chronic kidney disease (CKD) affects more than 10% of the world’s population. Hemodialysis, along with peritoneal dialysis and renal transplant, is one of the renal replacement therapies offered to patients with CKD/end-stage renal disease (ESRD). To proceed with hemodialysis, vascular access is required. The two means of long-term access are arteriovenous fistula (AVF) and arteriovenous graft (AVG). Multiple therapies have been created to help the long-term patency of AVFs. These therapies are needed as 40% of AVFs fail within the first year and additional intervention is required. Much of the existing research has focused on biomarkers, immune cells, hypoxia, and cell-based therapies. Regeneration therapy using mesenchymal stem cells seeks to investigate other ways that we can treat AVF failure. Mesenchymal stem cells are harvested as two main types, fetal and adult. Fetal cells are harvested at different times in fetal gestation and from multiple sources, placental blood, Whartons jelly, and amniotic stem cell fluid. Taken together, this review summarizes the different preclinical/clinical studies conducted using different types of MSCs towards vascular regenerative medicine and further highlights its potential to be a suitable alternative approach to enhance AVF patency. <a href="/1422-0067/25/23/12719">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/1VBU2GA8I6 ">Mesenchymal Stromal and Immune Cells’ Involvement in Human Diseases and Their Treatment</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <a data-dropdown="drop-supplementary-1530263" aria-controls="drop-supplementary-1530263" aria-expanded="false" title="Supplementary Material"> <i class="material-icons">attachment</i> </a> <div id="drop-supplementary-1530263" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide" data-dropdown-content aria-hidden="true" tabindex="-1"> Supplementary material: <br/> <a href="/1422-0067/25/23/12718/s1?version=1732637617"> Supplementary File 1 (ZIP, 5566 KiB) </a><br/> </div> </div> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 14 pages, 1083 KiB   </span> <a href="/1422-0067/25/23/12718/pdf?version=1732637617" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Ascorbic Acid Ameliorates Molecular and Developmental Defects in Human-Induced Pluripotent Stem Cell and Cerebral Organoid Models of Fragile X Syndrome" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12718">Ascorbic Acid Ameliorates Molecular and Developmental Defects in Human-Induced Pluripotent Stem Cell and Cerebral Organoid Models of Fragile X Syndrome</a> <div class="authors"> by <span class="inlineblock "><strong>Keith M. Gunapala</strong>, </span><span class="inlineblock "><strong>Aseel Gadban</strong>, </span><span class="inlineblock "><strong>Faiza Noreen</strong>, </span><span class="inlineblock "><strong>Primo Schär</strong>, </span><span class="inlineblock "><strong>Nissim Benvenisty</strong> and </span><span class="inlineblock "><strong>Verdon Taylor</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12718; https://doi.org/10.3390/ijms252312718 (registering DOI) - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Fragile X Syndrome (FX) is the most common form of inherited cognitive impairment and falls under the broader category of Autism Spectrum Disorders (ASD). FX is caused by a CGG trinucleotide repeat expansion in the non-coding region of the X-linked <i>Fragile X Messenger</i> <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12718/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Fragile X Syndrome (FX) is the most common form of inherited cognitive impairment and falls under the broader category of Autism Spectrum Disorders (ASD). FX is caused by a CGG trinucleotide repeat expansion in the non-coding region of the X-linked <i>Fragile X Messenger Ribonucleoprotein 1</i> (<i>FMR1</i>) gene, leading to its hypermethylation and epigenetic silencing. Animal models of FX rely on the deletion of the <i>Fmr1</i> gene, which fails to replicate the epigenetic silencing mechanism of the <i>FMR1</i> gene observed in human patients. Human stem cells carrying FX repeat expansions have provided a better understanding of the basis of epigenetic silencing of <i>FMR1</i>. Previous studies have found that 5-Azacytidine (5Azac) can reverse this methylation; however, 5Azac can be toxic, which may limit its therapeutic potential. Here, we show that the dietary factor Ascorbic Acid (AsA) can reduce DNA methylation in the <i>FMR1 </i>locus and lead to an increase in <i>FMR1 </i>gene expression in FX iPSCs and cerebral organoids. In addition, AsA treatment rescued neuronal gene expression and morphological defects observed in FX iPSC-derived cerebral organoids. Hence, we demonstrate that the dietary co-factor AsA can partially revert the molecular and morphological defects seen in human FX models in vitro. Our findings have implications for the development of novel therapies for FX in the future. <a href="/1422-0067/25/23/12718">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/JA31UNKK6J ">Current Molecular Science of Fragile X Syndrome and Associated Disorders</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <a data-dropdown="drop-supplementary-1530247" aria-controls="drop-supplementary-1530247" aria-expanded="false" title="Supplementary Material"> <i class="material-icons">attachment</i> </a> <div id="drop-supplementary-1530247" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide" data-dropdown-content aria-hidden="true" tabindex="-1"> Supplementary material: <br/> <a href="/1422-0067/25/23/12717/s1?version=1732637087"> Supplementary File 1 (ZIP, 49 KiB) </a><br/> </div> </div> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 16 pages, 3078 KiB   </span> <a href="/1422-0067/25/23/12717/pdf?version=1732637086" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Exogenous Calcium Enhances Castor Tolerance to Saline–Alkaline Stress by Regulating Antioxidant Enzyme Activity and Activating Ca²⁺ and ROS Signaling Crosstalk" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12717">Exogenous Calcium Enhances Castor Tolerance to Saline–Alkaline Stress by Regulating Antioxidant Enzyme Activity and Activating Ca²⁺ and ROS Signaling Crosstalk</a> <div class="authors"> by <span class="inlineblock "><strong>Fei Hao</strong>, </span><span class="inlineblock "><strong>Zhigang Cui</strong>, </span><span class="inlineblock "><strong>Xuan Dong</strong>, </span><span class="inlineblock "><strong>Yan Gao</strong>, </span><span class="inlineblock "><strong>Rongjin Wang</strong>, </span><span class="inlineblock "><strong>Hui Zhang</strong> and </span><span class="inlineblock "><strong>Guolin Lin</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12717; https://doi.org/10.3390/ijms252312717 (registering DOI) - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Saline–alkaline stress is a major factor limiting agricultural development, with calcium (Ca<sup>2+</sup>) playing a role in regulating plant tolerance through multiple signaling pathways. However, the specific mechanisms by which Ca<sup>2+</sup> mediates saline–alkaline stress tolerance at the molecular level remain incompletely <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12717/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Saline–alkaline stress is a major factor limiting agricultural development, with calcium (Ca<sup>2+</sup>) playing a role in regulating plant tolerance through multiple signaling pathways. However, the specific mechanisms by which Ca<sup>2+</sup> mediates saline–alkaline stress tolerance at the molecular level remain incompletely understood. This study investigates the effects of exogenous Ca<sup>2+</sup> application on enhancing plant tolerance to saline–alkaline stress, focusing on its impact on the antioxidant system and Ca<sup>2+</sup> and reactive oxygen species (ROS) signaling pathways. Through physiological assays and transcriptomic analyses, we evaluated oxidative damage markers, antioxidant enzyme activities, and the expression of key Ca<sup>2+</sup> and ROS signaling genes. The results showed that saline–alkaline stress significantly elevated ROS levels, which led to increased membrane lipid peroxidation and induced upregulation of antioxidant response elements in castor roots. Exogenous calcium treatment reduced ROS accumulation by increasing superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities and decreasing malondialdehyde (MDA) levels, demonstrating a marked improvement in the antioxidant system. Transcriptomic analysis identified <i>CAT2</i> (LOC107261240) as the primary target gene associated with increased CAT activity in response to exogenous calcium. Additionally, the upregulation of specific Ca<sup>2+</sup> channels, Ca<sup>2+</sup> sensors, ROS receptors, and antioxidant-related genes with calcium treatment highlights the critical role of Ca<sup>2+</sup>–ROS signaling crosstalk in enhancing stress tolerance. Protein–protein interaction analysis identified <i>APX3</i> and other hub genes involved in Ca<sup>2+</sup>–ROS signaling transduction and the regulation of antioxidant activity. These findings enhance our understanding of calcium’s complex regulatory roles in plant abiotic stress responses, offering new theoretical insights for improving crop resilience in agriculture. <a href="/1422-0067/25/23/12717">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/2K36V0A1VH ">Abiotic Stress in Plant</a>)<br/> </div> <a href="#" class="abstract-figures-show" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12717/show" ><span >►</span><span style=" display: none;">▼</span> Show Figures </a><div class="abstract-image-preview "><div class="absgraph cycle-slideshow"><div class='openpopupgallery cycle-slide' data-imgindex='0' data-target='article-1530247-popup'><span class="helper"></span><img src="data:image/gif;base64,R0lGODlhAQABAAD/ACwAAAAAAQABAAACADs=" data-src="https://pub.mdpi-res.com/ijms/ijms-25-12717/article_deploy/ijms-25-12717-ag.jpg?1732637087" alt="" style="border: 0;"><p>Graphical abstract</p></div></div></div><div id="article-1530247-popup" class="popupgallery" style="display: inline; line-height: 200%"><a href="https://pub.mdpi-res.com/ijms/ijms-25-12717/article_deploy/ijms-25-12717-ag.jpg?1732637087" title=" <strong>Graphical abstract</strong><br/><strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12717'>Full article</a></strong> "></a></div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 16 pages, 2946 KiB   </span> <a href="/1422-0067/25/23/12716/pdf?version=1732636361" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Comparative Metabolic Defense Responses of Three Tree Species to the Supplemental Feeding Behavior of Anoplophora glabripennis" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12716">Comparative Metabolic Defense Responses of Three Tree Species to the Supplemental Feeding Behavior of <i>Anoplophora glabripennis</i></a> <div class="authors"> by <span class="inlineblock "><strong>Ruohan Qi</strong>, </span><span class="inlineblock "><strong>Jiahe Pei</strong>, </span><span class="inlineblock "><strong>Quan Zhou</strong>, </span><span class="inlineblock "><strong>Keyu Hao</strong>, </span><span class="inlineblock "><strong>Yi Tian</strong>, </span><span class="inlineblock "><strong>Lili Ren</strong> and </span><span class="inlineblock "><strong>Youqing Luo</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12716; https://doi.org/10.3390/ijms252312716 (registering DOI) - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> <i>Elaeagnus angustifolia</i> L. can attract adult Asian longhorned beetle (ALB), <i>Anoplophora glabripennis</i> (Motschulsky), and kill their offspring by gum secretion in oviposition scars. This plant has the potential to be used as a dead-end trap tree for ALB management. However, there is a <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12716/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> <i>Elaeagnus angustifolia</i> L. can attract adult Asian longhorned beetle (ALB), <i>Anoplophora glabripennis</i> (Motschulsky), and kill their offspring by gum secretion in oviposition scars. This plant has the potential to be used as a dead-end trap tree for ALB management. However, there is a limited understanding of the attraction ability and biochemical defense response of <i>E. angustifolia</i> to ALB. In this study, we conducted host selection experiments with ALB and then performed physiological and biochemical assays on twigs from different tree species before and after ALB feeding. We analyzed the differential metabolites using the liquid chromatograph–mass spectrometer method. The results showed that ALB’s feeding preference was <i>E. angustifolia</i> > <i>P.× xiaohei</i> var. <i>gansuensis</i> > <i>P. alba</i> var. <i>pyramidalis</i>. After ALB feeding, the content of soluble sugars, soluble proteins, flavonoids, and tannins decreased significantly in all species. In three comparison groups, a total of 492 differential metabolites were identified (<i>E. angustifolia</i>:195, <i>P.× xiaohei</i> var. <i>gansuensis</i>:255, <i>P. alba</i> var. <i>pyramidalis</i>:244). Differential metabolites were divided into overlapping and specific metabolites for analysis. The overlapping differential metabolites 7-isojasmonic acid, zerumbone, and salicin in the twigs of three tree species showed upregulation after ALB feeding. The specific metabolites silibinin, catechin, and geniposide, in <i>E. angustifolia,</i> significantly increased after being damaged. Differential metabolites enriched in KEGG pathways indicated that ALB feeding activated tyrosine metabolism and the biosynthesis of phenylpropanoids in three tree species, with a particularly high enrichment of differential metabolites in the flavonoid biosynthesis pathway in <i>E. angustifolia</i>. This study provides the metabolic defense strategies of different tree species against ALB feeding and proposes candidate metabolites that can serve as metabolic biomarkers, potentially offering valuable insights into using <i>E. angustifolia</i> as a control measure against ALB. <a href="/1422-0067/25/23/12716">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Section <a href="/journal/ijms/sections/molecular_plant_sciences">Molecular Plant Sciences</a>)<br/> </div> <a href="#" class="abstract-figures-show" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12716/show" ><span >►</span><span style=" display: none;">▼</span> Show Figures </a><div class="abstract-image-preview "><div class="arrow left-arrow" id="prev1530222"><i class="fa fa-caret-left"></i></div><div class="arrow right-arrow" id="next1530222"><i class="fa fa-caret-right"></i></div><div class="absgraph cycle-slideshow manual" data-cycle-fx="scrollHorz" data-cycle-timeout="0" data-cycle-next="#next1530222" data-cycle-prev="#prev1530222" data-cycle-progressive="#images1530222" data-cycle-slides=">div" data-cycle-log="false"><div class='openpopupgallery cycle-slide' data-imgindex='0' data-target='article-1530222-popup'><span class="helper"></span><img src="data:image/gif;base64,R0lGODlhAQABAAD/ACwAAAAAAQABAAACADs=" data-src="https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g001-550.jpg?1732636446" alt="" style="border: 0;"><p>Figure 1</p></div><script id="images1530222" type="text/cycle" data-cycle-split="---"><div class='openpopupgallery' data-imgindex='1' data-target='article-1530222-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g002-550.jpg?1732636449'><p>Figure 2</p></div> --- <div class='openpopupgallery' data-imgindex='2' data-target='article-1530222-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g003-550.jpg?1732636450'><p>Figure 3</p></div> --- <div class='openpopupgallery' data-imgindex='3' data-target='article-1530222-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g004-550.jpg?1732636452'><p>Figure 4</p></div> --- <div class='openpopupgallery' data-imgindex='4' data-target='article-1530222-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g005-550.jpg?1732636456'><p>Figure 5</p></div> --- <div class='openpopupgallery' data-imgindex='5' data-target='article-1530222-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g006-550.jpg?1732636457'><p>Figure 6</p></div></script></div></div><div id="article-1530222-popup" class="popupgallery" style="display: inline; line-height: 200%"><a href="https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g001-550.jpg?1732636446" title=" <strong>Figure 1</strong><br/> <p>(<b>a</b>–<b>d</b>) Nutrient and secondary matter content of different trees after ALB feeding. Note: <span class="html-italic">E. angustifolia</span> (S), <span class="html-italic">P.× xiaohei</span> var. <span class="html-italic">gansuensis</span> (Y), <span class="html-italic">P. alba</span> var. <span class="html-italic">pyramidalis</span> (J) ** indicates statistically significant differences (<span class="html-italic">p</span> &lt; 0.01).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12716'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g002-550.jpg?1732636449" title=" <strong>Figure 2</strong><br/> <p>Dimensionality reduction analysis of differential metabolites. Note: (<b>a</b>,<b>b</b>): Principal Component Analysis (PCA); (<b>c</b>,<b>d</b>): Orthogonal Partial Least Squares Discriminant Analysis (OPLS-DA); positive ion mode on the left, negative ion mode on the right. <span class="html-italic">E. angustifolia</span> (S), <span class="html-italic">P.× xiaohei</span> var. <span class="html-italic">gansuensis</span> (Y), <span class="html-italic">P. alba</span> var. <span class="html-italic">pyramidalis</span> (J); J-s, S-s, and Y-s represent healthy twigs, and J-s-H, S-s-H, and Y-s-H represent twigs after ALB feeding.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12716'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g003-550.jpg?1732636450" title=" <strong>Figure 3</strong><br/> <p>Statistical analysis of differential metabolites in three tree species twigs. Note: (<b>a</b>): Venn; (<b>b</b>): Bar chart. <span class="html-italic">E. angustifolia</span> (S), <span class="html-italic">P.× xiaohei</span> var. <span class="html-italic">gansuensis</span> (Y), <span class="html-italic">P. alba</span> var. <span class="html-italic">pyramidalis</span> (J); J_s, S_s, and Y_s represent healthy twigs, and J_s_H, S_s_H, and Y_s_H represent twigs after ALB feeding.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12716'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g004-550.jpg?1732636452" title=" <strong>Figure 4</strong><br/> <p>Classification of differential metabolites across different tree species. Note: <span class="html-italic">E. angustifolia</span> (S), <span class="html-italic">P.× xiaohei</span> var. <span class="html-italic">gansuensis</span> (Y), <span class="html-italic">P. alba</span> var. <span class="html-italic">pyramidalis</span> (J).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12716'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g005-550.jpg?1732636456" title=" <strong>Figure 5</strong><br/> <p>Cluster analysis of overlapping differential metabolites among twigs of three species. Note: <span class="html-italic">E. angustifolia</span> (S), <span class="html-italic">P.× xiaohei</span> var. <span class="html-italic">gansuensis</span> (Y), <span class="html-italic">P. alba</span> var. <span class="html-italic">pyramidalis</span> (J).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12716'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12716/article_deploy/html/images/ijms-25-12716-g006-550.jpg?1732636457" title=" <strong>Figure 6</strong><br/> <p>KEGG pathway analysis of different tree species. Note: (<b>a</b>) <span class="html-italic">P. alba</span> var. <span class="html-italic">pyramidalis</span>, (<b>b</b>) <span class="html-italic">E. angustifolia</span>, (<b>c</b>) <span class="html-italic">P.× xiaohei</span> var. <span class="html-italic">gansuensis</span>.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12716'>Full article</a></strong> "></a></div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <a data-dropdown="drop-supplementary-1530172" aria-controls="drop-supplementary-1530172" aria-expanded="false" title="Supplementary Material"> <i class="material-icons">attachment</i> </a> <div id="drop-supplementary-1530172" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide" data-dropdown-content aria-hidden="true" tabindex="-1"> Supplementary material: <br/> <a href="/1422-0067/25/23/12715/s1?version=1732635041"> Supplementary File 1 (ZIP, 1416 KiB) </a><br/> </div> </div> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 21 pages, 8695 KiB   </span> <a href="/1422-0067/25/23/12715/pdf?version=1732635351" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Machine Learning Integration with Single-Cell Transcriptome Sequencing Datasets Reveals the Impact of Tumor-Associated Neutrophils on the Immune Microenvironment and Immunotherapy Outcomes in Gastric Cancer" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12715">Machine Learning Integration with Single-Cell Transcriptome Sequencing Datasets Reveals the Impact of Tumor-Associated Neutrophils on the Immune Microenvironment and Immunotherapy Outcomes in Gastric Cancer</a> <div class="authors"> by <span class="inlineblock "><strong>Jingcheng Zhang</strong>, </span><span class="inlineblock "><strong>Mingsi Zhang</strong>, </span><span class="inlineblock "><strong>Jiaheng Lou</strong>, </span><span class="inlineblock "><strong>Linyue Wu</strong>, </span><span class="inlineblock "><strong>Shuo Zhang</strong>, </span><span class="inlineblock "><strong>Xiaojuan Liu</strong>, </span><span class="inlineblock "><strong>Yani Ke</strong>, </span><span class="inlineblock "><strong>Sicheng Zhao</strong>, </span><span class="inlineblock "><strong>Zhiyuan Song</strong>, </span><span class="inlineblock "><strong>Xing Bai</strong>, </span><span class="inlineblock "><strong>Yan Cai</strong>, </span><span class="inlineblock "><strong>Tao Jiang</strong> and </span><span class="inlineblock "><strong>Guangji Zhang</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12715; https://doi.org/10.3390/ijms252312715 (registering DOI) - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> The characteristics of neutrophils play a crucial role in defining the tumor inflammatory environment. However, the function of tumor-associated neutrophils (TANs) in tumor immunity and their response to immune checkpoint inhibitors (ICIs) remains incompletely understood. By analyzing single-cell RNA sequencing data from over <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12715/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> The characteristics of neutrophils play a crucial role in defining the tumor inflammatory environment. However, the function of tumor-associated neutrophils (TANs) in tumor immunity and their response to immune checkpoint inhibitors (ICIs) remains incompletely understood. By analyzing single-cell RNA sequencing data from over 600,000 cells in gastric cancer (GSE163558 and GSE183904), colorectal cancer (GSE205506), and lung cancer (GSE207422), we identified neutrophil subsets in primary gastric cancer that are associated with the treatment response to ICIs. Specifically, we focused on neutrophils with high expression of <i>CD44</i> (CD44_NEU), which are abundant during tumor progression and exert significant influence on the gastric cancer immune microenvironment. Machine learning analysis revealed 22 core genes associated with CD44_NEU, impacting inflammation, proliferation, migration, and oxidative stress. In addition, multiple immunofluorescence staining and gastric cancer spatial transcriptome data (GSE203612) showed a correlation between CD44_NEU and T-cell infiltration in gastric cancer tissues. A risk score model derived from seven essential genes (<i>AQP9</i>, <i>BASP1</i>, <i>BCL2A1</i>, <i>PLEK</i>, <i>PDE4B</i>, <i>PROK2</i>, and <i>ACSL1</i>) showed better predictive capability for patient survival compared to clinical features alone, and integrating these scores with clinical variables resulted in a prognostic nomogram. Overall, this study highlights the heterogeneity of TANs, particularly the CD44_NEU critical influence on immunotherapy outcomes, paving the way for personalized treatment strategies. <a href="/1422-0067/25/23/12715">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Section <a href="/journal/ijms/sections/molecular_immunology">Molecular Immunology</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 21 pages, 547 KiB   </span> <a href="/1422-0067/25/23/12714/pdf?version=1732634359" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="The Role of microRNA Expression and DNA Methylation in HPV-Related Cervical Cancer: A Systematic Review" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Review</span></div> <a class="title-link" href="/1422-0067/25/23/12714">The Role of microRNA Expression and DNA Methylation in HPV-Related Cervical Cancer: A Systematic Review</a> <div class="authors"> by <span class="inlineblock "><strong>Alessandra Pulliero</strong>, </span><span class="inlineblock "><strong>Giulia Cassatella</strong>, </span><span class="inlineblock "><strong>Pietro Astuni</strong>, </span><span class="inlineblock "><strong>Zumama Khalid</strong>, </span><span class="inlineblock "><strong>Stefano Fiordoro</strong> and </span><span class="inlineblock "><strong>Alberto Izzotti</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12714; https://doi.org/10.3390/ijms252312714 (registering DOI) - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Human papillomavirus (HPV) infection is a major etiologic factor in cervical cancer, a major cause of cancer-related morbidity and mortality among women worldwide. The role of microRNA (miRNA) dysregulation in cervical carcinogenesis is still largely unknown, but epigenetic changes, including DNA methylation and <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12714/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Human papillomavirus (HPV) infection is a major etiologic factor in cervical cancer, a major cause of cancer-related morbidity and mortality among women worldwide. The role of microRNA (miRNA) dysregulation in cervical carcinogenesis is still largely unknown, but epigenetic changes, including DNA methylation and miRNA regulation, are crucial factors. The integration of HPV DNA into the host genome can lead to alterations in DNA methylation patterns and miRNA expression, contributing to the progression from normal epithelium to cervical intraepithelial neoplasia and, ultimately, to cervical cancer. This review aimed to examine the relationship between epigenetic changes in the development and progression of HPV associated with cervical cancer. A systematic literature search was conducted in major databases using predefined inclusion and exclusion criteria. Studies that investigated the expression, function, and clinical significance of miRNAs, DNA methylation, and the expression of oncoproteins in HPV-related cervical cancer were included. Data extraction, quality assessment, and synthesis were performed to provide a comprehensive overview of the current state of knowledge. We provide an overview of the studies investigating miRNA expression in relation to cervical cancer progression, highlighting their common outcomes and their weaknesses/strengths. To achieve this, we systematically searched the Pubmed database for all articles published between January 2018 and December 2023. Our systematic review revealed a substantial body of evidence supporting the pivotal role of miRNA dysregulation in the pathogenesis of HPV-related cervical cancer and related oncoproteins. From the 28 studies retrieved, miR-124, FAM194/miR-124-2, and DNA methylation are the most frequently down- or up-regulated in CC progression. Notably, FAM194/miR-124-2 and DNA methylation emerged as a promising molecular marker for distinguishing between cases requiring immediate surgical intervention and those amenable to a more conservative wait-and-see approach. This systematic review underscores the critical involvement of microRNA in the context of HPV-related cervical cancer and sheds light on the potential clinical utility of FAM194/miR-124-2 and DNA methylation as a discriminatory tool for guiding treatment decisions. The identification of patients who may benefit from early surgical intervention versus those suitable for observation has important implications for personalized and targeted management strategies in the era of precision medicine. <a href="/1422-0067/25/23/12714">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/8BA6E6X6TH ">Recent Advances in Molecular Mechanisms of Human Papillomavirus Family (HPV) Induced Oncogenesis</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <a data-dropdown="drop-supplementary-1530138" aria-controls="drop-supplementary-1530138" aria-expanded="false" title="Supplementary Material"> <i class="material-icons">attachment</i> </a> <div id="drop-supplementary-1530138" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide" data-dropdown-content aria-hidden="true" tabindex="-1"> Supplementary material: <br/> <a href="/1422-0067/25/23/12713/s1?version=1732634153"> Supplementary File 1 (ZIP, 1656 KiB) </a><br/> </div> </div> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 22 pages, 41503 KiB   </span> <a href="/1422-0067/25/23/12713/pdf?version=1732634152" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="BAMBI Is a Prognostic Biomarker Associated with Macrophage Polarization, Glycolysis, and Lipid Metabolism in Hepatocellular Carcinoma" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12713">BAMBI Is a Prognostic Biomarker Associated with Macrophage Polarization, Glycolysis, and Lipid Metabolism in Hepatocellular Carcinoma</a> <div class="authors"> by <span class="inlineblock "><strong>Huijie Gao</strong>, </span><span class="inlineblock "><strong>Cuimin Hu</strong>, </span><span class="inlineblock "><strong>Qing Wu</strong> and </span><span class="inlineblock "><strong>Zhongze Fang</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12713; https://doi.org/10.3390/ijms252312713 (registering DOI) - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide. Affected patients have poor prognoses due to high rates of post-surgical recurrence and metastasis. Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) reportedly contributes to the development and progression of <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12713/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Hepatocellular carcinoma (HCC) is one of the most common types of cancer worldwide. Affected patients have poor prognoses due to high rates of post-surgical recurrence and metastasis. Bone morphogenetic protein and activin membrane-bound inhibitor (BAMBI) reportedly contributes to the development and progression of various human cancers. Thus far, there have been no comprehensive studies regarding the expression of BAMBI in HCC; similarly, no studies have investigated the prognostic significance of BAMBI and its associated mechanisms in HCC. In this study, we analyzed the expression profiles of BAMBI, along with its contributions to pathological findings, metastasis characteristics, and prognosis, in multiple human cancers. We found that upregulation of BAMBI was associated with poor prognosis in HCC. Next, we explored the associations of BAMBI with multiple cell signaling pathways, immune cells, and immune checkpoints in HCC. The results showed that BAMBI was associated with tumor proliferation, epithelial–mesenchymal transition (EMT) markers, glycolysis, fatty acid biosynthesis and degradation pathways, and immune checkpoint regulation in HCC. In vitro and in vivo experiments showed that BAMBI promoted polarization of M1 macrophages and is linked to the expression of key genes involved in glycolipid metabolism. Furthermore, protein–protein interaction analysis suggested that BAMBI plays multiple roles in HCC by regulating genes in the transforming growth factor (TGF)-β and Wnt signaling pathways. Our findings elucidated that BAMBI is a prognostic biomarker and is associated with macrophage polarization, glycolysis, and lipid metabolism in HCC. <a href="/1422-0067/25/23/12713">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/3YK0899670 ">Cancer Diagnosis and Treatment: Exploring Molecular Research</a>)<br/> </div> <a href="#" class="abstract-figures-show" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12713/show" ><span >►</span><span style=" display: none;">▼</span> Show Figures </a><div class="abstract-image-preview "><div class="arrow left-arrow" id="prev1530138"><i class="fa fa-caret-left"></i></div><div class="arrow right-arrow" id="next1530138"><i class="fa fa-caret-right"></i></div><div class="absgraph cycle-slideshow manual" data-cycle-fx="scrollHorz" data-cycle-timeout="0" data-cycle-next="#next1530138" data-cycle-prev="#prev1530138" data-cycle-progressive="#images1530138" data-cycle-slides=">div" data-cycle-log="false"><div class='openpopupgallery cycle-slide' data-imgindex='0' data-target='article-1530138-popup'><span class="helper"></span><img src="data:image/gif;base64,R0lGODlhAQABAAD/ACwAAAAAAQABAAACADs=" data-src="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g001-550.jpg?1732634219" alt="" style="border: 0;"><p>Figure 1</p></div><script id="images1530138" type="text/cycle" data-cycle-split="---"><div class='openpopupgallery' data-imgindex='1' data-target='article-1530138-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g002-550.jpg?1732634222'><p>Figure 2</p></div> --- <div class='openpopupgallery' data-imgindex='2' data-target='article-1530138-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g003-550.jpg?1732634225'><p>Figure 3</p></div> --- <div class='openpopupgallery' data-imgindex='3' data-target='article-1530138-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g004-550.jpg?1732634227'><p>Figure 4</p></div> --- <div class='openpopupgallery' data-imgindex='4' data-target='article-1530138-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g005-550.jpg?1732634230'><p>Figure 5</p></div> --- <div class='openpopupgallery' data-imgindex='5' data-target='article-1530138-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g006-550.jpg?1732634234'><p>Figure 6</p></div> --- <div class='openpopupgallery' data-imgindex='6' data-target='article-1530138-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g007-550.jpg?1732634236'><p>Figure 7</p></div> --- <div class='openpopupgallery' data-imgindex='7' data-target='article-1530138-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g008-550.jpg?1732634238'><p>Figure 8</p></div> --- <div class='openpopupgallery' data-imgindex='8' data-target='article-1530138-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g009-550.jpg?1732634239'><p>Figure 9</p></div> --- <div class='openpopupgallery' data-imgindex='9' data-target='article-1530138-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g010-550.jpg?1732634242'><p>Figure 10</p></div></script></div></div><div id="article-1530138-popup" class="popupgallery" style="display: inline; line-height: 200%"><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g001-550.jpg?1732634219" title=" <strong>Figure 1</strong><br/> <p>Analysis of BAMBI expression in 20 types of cancers, validated using the UALCAN database. (<b>A</b>–<b>H</b>) BAMBI expression was increased in BRCA (<b>A</b>), CHOL (<b>B</b>), COAD (<b>C</b>), ESCA (<b>D</b>), KIRP (<b>E</b>), HCC (<b>F</b>), READ (<b>G</b>), and STAD (<b>H</b>) compared with normal tissues. (<b>I</b>–<b>K</b>) BAMBI expression was decreased in LUAD (<b>I</b>), KICH (<b>J</b>), and KIRC (<b>K</b>) compared with normal tissues. (<b>L</b>–<b>T</b>) There were no significant differences in BAMBI expression between cancer and normal tissues in CESC (<b>L</b>), GBM (<b>M</b>), PAAD (<b>N</b>), PRAD (<b>O</b>), PCPG (<b>P</b>), OV (<b>Q</b>), SKCM (<b>R</b>), THCA (<b>S</b>), or UCEC (<b>T</b>). ns, not significant; *** <span class="html-italic">p</span> &lt; 0.001.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g002-550.jpg?1732634222" title=" <strong>Figure 2</strong><br/> <p>Analysis of overall survival according to BAMBI expression in 11 types of cancers, as determined using the GEPIA database. (<b>A</b>–K) Plots of overall survival according to BAMBI expression in BRCA (<b>A</b>), CHOL (<b>B</b>), COAD (<b>C</b>), ESCA (<b>D</b>), KIRP (<b>E</b>), HCC (<b>F</b>), READ (<b>G</b>), STAD (<b>H</b>), CESC (<b>I</b>), KICH (<b>J</b>), and KIRC (<b>K</b>). <span class="html-italic">p</span>-values &lt; 0.05 were considered statistically significant.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g003-550.jpg?1732634225" title=" <strong>Figure 3</strong><br/> <p>Prediction and analysis of cell signaling pathways in HCC with potential BAMBI involvement. (<b>A</b>–<b>P</b>) Correlations of BAMBI expression with tumor proliferation (<b>A</b>), EMT markers (<b>B</b>), MYC targets (<b>C</b>), cellular response to hypoxia (<b>D</b>), glycolysis/gluconeogenesis (<b>E</b>), fatty acid degradation pathways (<b>F</b>), PI3K-AKT-mTOR pathway (<b>G</b>), p53 pathway (<b>H</b>), TGF-β (<b>I</b>), inflammatory response (<b>J</b>), IL-10 anti-inflammatory signaling pathway (<b>K</b>), tumor inflammation (<b>L</b>), angiogenesis (<b>M</b>), apoptosis (<b>N</b>), ECM-related genes (<b>O</b>), and fatty acid biosynthesis (<b>P</b>). All correlations were analyzed using the GSVA package in R software (version 4.0.3) with the method parameter set to ‘ssgsea’. Relationships of BAMBI expression with cell signaling pathway scores were analyzed by Spearman correlation. <span class="html-italic">p</span>-values &lt; 0.05 were considered statistically significant. The density curve on the right shows the distribution trend of the pathway score, while the density curve on the top represents the distribution trend of the expression of BAMBI. The values at the top represent the results of the Spearman correlation analysis, including the <span class="html-italic">p</span>-value, correlation coefficient, and correlation calculation method. The blue lines depicted the trends of the correlation.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g004-550.jpg?1732634227" title=" <strong>Figure 4</strong><br/> <p>The expression levels of the six key genes in the glycolysis and lipid metabolism pathways in Huh7 cells and mice. (<b>A</b>) After overexpression (BAMBI) or knockdown (shR-BAMBI) of BAMBI in Huh7 cells, the mRNA levels of BAMBI, four key genes (SLC2A1, PIGQ, PKM, and LDHA) in the glycolysis pathway and two key genes (SIRT1 and ACACA) in the lipid metabolism pathway were detected. (<b>B</b>–<b>D</b>) The mRNA levels of BAMBI, SLC2A1, PIGQ, PKM, LDHA, SIRT1, and ACACA in mouse tumors (<b>B</b>), lungs (<b>C</b>), and livers (<b>D</b>). All experiments were performed at least in triplicate. Data are presented as mean ± standard deviation. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 compared with the corresponding control group (BAMBI vs. pcDNA3 and shR-BAMBI vs. pSilencer-NC for Huh7 cells; high BAMBI expression vs. control for mouse tumors and tissues).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g005-550.jpg?1732634230" title=" <strong>Figure 5</strong><br/> <p>Relationships of BAMBI expression with immune cell infiltration in HCC. (<b>A</b>) Effects of different copies of BAMBI on different immune cell infiltration in HCC. (<b>B</b>) Correlations of BAMBI expression with the levels of infiltration by B cells, CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells in HCC. The blue lines illustrated the correlation trends between BAMBI and the levels of immune cell infiltration. <span class="html-italic">p</span>-values &lt; 0.05 were considered statistically significant.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g006-550.jpg?1732634234" title=" <strong>Figure 6</strong><br/> <p>Relationships of BAMBI expression with biomarkers for immune cells in HCC. Correlations of BAMBI expression with the expression levels of biomarkers CD19 (<b>A</b>), CD79A (<b>B</b>), CD8A (<b>C</b>), CD8B (<b>D</b>), ITGM (<b>E</b>), CCR7 (<b>F</b>), CD1C (<b>G</b>), ITGAX (<b>H</b>), HLA-DPA1 (<b>I</b>), HLA-DPB1 (<b>J</b>), CD4 (<b>K</b>), CD11c (<b>L</b>), IRF5 (<b>M</b>), IL-12 (<b>N</b>), CD206 (<b>O</b>), and ARG-1 (<b>P</b>) in HCC. <span class="html-italic">p</span>-values &lt; 0.05 were considered statistically significant.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g007-550.jpg?1732634236" title=" <strong>Figure 7</strong><br/> <p>The expression levels and correlation of BAMBI and biomarkers for M1 and M2 macrophages in mouse tumors and tissues. (<b>A</b>,<b>C</b>,<b>E</b>) The RNA expression levels of BAMBI, CD11c, IL-12A, CD206, and ARG-1 in mouse tumors (<b>A</b>), lungs (<b>C</b>), and livers (<b>E</b>). (<b>B</b>,<b>D</b>,<b>F</b>) Correlation analysis between BAMBI expression and the levels of biomarkers for M1 and M2 macrophages in mouse tumors (<b>B</b>), lungs (<b>D</b>), and livers (<b>F</b>). All experiments were performed at least in triplicate. Data are presented as mean ± standard deviation. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 compared with the control group (high BAMBI expression vs. control).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g008-550.jpg?1732634238" title=" <strong>Figure 8</strong><br/> <p>The expression and co-localization of BAMBI with CD11c in mouse tumors were determined by immunofluorescence staining. (<b>A</b>) The expression of BAMBI (red) and CD11c (green) in tumors of mice injected with high-BAMBI-expression Huh7 cells (high BAMBI expression) or the control Huh7 cells (Control). Nuclei are stained with DAPI (blue). Scale bar =20 µm. (<b>B</b>) Relative fluorescence intensity is expressed as the mean ± SD. **, <span class="html-italic">p</span> &lt; 0.01 (high BAMBI expression vs. control). (<b>C</b>) The co-localization of BAMBI with CD11c in mouse tumors. Scale bar = 5 µm.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g009-550.jpg?1732634239" title=" <strong>Figure 9</strong><br/> <p>BAMBI contributed to M1 polarization of macrophages in vitro. (<b>A</b>,<b>B</b>) The mRNA (<b>A</b>) and the protein (<b>B</b>) expression levels of BAMBI and CD11c in M1, M2, and M0 macrophages. The samples were derived from the same experiment and the blots were processed in parallel. Data are presented as mean ± standard deviation. * <span class="html-italic">p</span> &lt; 0.05, compared with M0 macrophages (M1 or M2 macrophages vs. M0 macrophages). (<b>C</b>,<b>D</b>) The differentiation of M1 and M2 macrophages was induced 48 h after overexpression or knockdown of BAMBI in THP-1 cells. The RNA expression levels of BAMBI, CD11c, and IL-12A in M1 macrophages (<b>C</b>) or BAMBI, CD206, and ARG-1 in M2 macrophages (<b>D</b>) were detected by RT-qPCR. All experiments were performed at least in triplicate. Data are presented as mean ± standard deviation. * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, and *** <span class="html-italic">p</span> &lt; 0.001 compared with the corresponding control group (BAMBI vs. pcDNA3 and shR-BAMBI vs. pSilencer-NC).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12713/article_deploy/html/images/ijms-25-12713-g010-550.jpg?1732634242" title=" <strong>Figure 10</strong><br/> <p>Relationships of BAMBI expression with immune checkpoints in HCC. (<b>A</b>) Distribution of immune checkpoint molecules expressed in HCC tissues and normal tissues. (<b>B</b>–<b>I</b>) Associations of BAMBI with CTLA–4 (<b>B</b>), HAVCR2 (<b>C</b>), PDCD1 (<b>D</b>), TIGIT (<b>E</b>), CD274 (<b>F</b>), LAG3 (<b>G</b>), SIGLEC15 (<b>H</b>), and PDCD1LG2 (<b>I</b>) in HCC. The blue lines depicted the trends of the correlation. <span class="html-italic">p</span>-values &lt; 0.05 were considered statistically significant; *** <span class="html-italic">p</span> &lt; 0.001.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12713'>Full article</a></strong> "></a></div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 20 pages, 1073 KiB   </span> <a href="/1422-0067/25/23/12712/pdf?version=1732633006" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="A New Approach for Orbital Wall Reconstruction in a Rabbit Animal Model Using a Hybrid Hydroxyapatite–Collagen-Based Implant" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12712">A New Approach for Orbital Wall Reconstruction in a Rabbit Animal Model Using a Hybrid Hydroxyapatite–Collagen-Based Implant</a> <div class="authors"> by <span class="inlineblock "><strong>Victor A. Vasile</strong>, </span><span class="inlineblock "><strong>Sinziana Istrate</strong>, </span><span class="inlineblock "><strong>Laura-Madalina Cursaru</strong>, </span><span class="inlineblock "><strong>Roxana M. Piticescu</strong>, </span><span class="inlineblock "><strong>Aurelian M. Ghita</strong>, </span><span class="inlineblock "><strong>Diana M. Popescu</strong>, </span><span class="inlineblock "><strong>Gerhard Garhöfer</strong>, </span><span class="inlineblock "><strong>Ana M. Catrina</strong>, </span><span class="inlineblock "><strong>Sonia Spandole-Dinu</strong>, </span><span class="inlineblock "><strong>Cerasela Haidoiu</strong>, </span><span class="inlineblock "><strong>Vladimir Suhaianu</strong>, </span><span class="inlineblock "><strong>Oana C. Voinea</strong>, </span><span class="inlineblock "><strong>Dumitru Valentin Dragut</strong> and </span><span class="inlineblock "><strong>Alina Popa-Cherecheanu</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12712; <a href="https://doi.org/10.3390/ijms252312712">https://doi.org/10.3390/ijms252312712</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Reconstructing the orbit following complex craniofacial fractures presents significant challenges. Throughout the years, several materials have been used for orbital reconstruction, taking into account factors such as their durability, compatibility with living tissue, cost efficiency, safety, and capacity to be adjusted during surgery. <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12712/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Reconstructing the orbit following complex craniofacial fractures presents significant challenges. Throughout the years, several materials have been used for orbital reconstruction, taking into account factors such as their durability, compatibility with living tissue, cost efficiency, safety, and capacity to be adjusted during surgery. Nevertheless, a consensus has not yet been reached on the optimal material for orbital restoration. This study investigates the potential of a hybrid hydroxyapatite–collagen (HAp-COL) material 3D-printed on Ti mesh to be used as an implant for orbital wall reconstruction. HAp-COL powder was synthesized using a high-pressure hydrothermal technique. The powder was further used to 3D-print HAp-COL structures on titanium mesh, with the latter having potential uses in orbital wall reconstruction. Biocompatibility was assessed by evaluating the effects of the HAp-COL material on the adhesion and proliferation of fibroblasts (3T3) and mesenchymal stem cells (MSCs) in culture. In vitro and in vivo results showed that HAp-COL is highly biocompatible and has a good integration of the implant in the bone. The findings reported in this study offer convincing evidence to support the use of our designed HAp-COL for the restoration of orbital wall fractures, with a high level of safety. <a href="/1422-0067/25/23/12712">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/I7H6U3TQ81 ">Biomaterials and Tissue Regeneration in Craniofacial Defect Reconstruction</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <a data-dropdown="drop-supplementary-1530068" aria-controls="drop-supplementary-1530068" aria-expanded="false" title="Supplementary Material"> <i class="material-icons">attachment</i> </a> <div id="drop-supplementary-1530068" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide" data-dropdown-content aria-hidden="true" tabindex="-1"> Supplementary material: <br/> <a href="/1422-0067/25/23/12711/s1?version=1732631915"> Supplementary File 1 (ZIP, 505 KiB) </a><br/> </div> </div> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 17 pages, 1198 KiB   </span> <a href="/1422-0067/25/23/12711/pdf?version=1732631915" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="The Role of Glutamate Metabolism and the GABA Shunt in Bypassing the Tricarboxylic Acid Cycle in the Light" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12711">The Role of Glutamate Metabolism and the GABA Shunt in Bypassing the Tricarboxylic Acid Cycle in the Light</a> <div class="authors"> by <span class="inlineblock "><strong>Alexander T. Eprintsev</strong>, </span><span class="inlineblock "><strong>Galina B. Anokhina</strong>, </span><span class="inlineblock "><strong>Zakhar N. Shakhov</strong>, </span><span class="inlineblock "><strong>Polina P. Moskvina</strong> and </span><span class="inlineblock "><strong>Abir U. Igamberdiev</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12711; <a href="https://doi.org/10.3390/ijms252312711">https://doi.org/10.3390/ijms252312711</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Glutamate is an essential amino acid in both the energy and biosynthetic processes in plant cells. The aim of this work was to study changes in glutamate metabolism upon irradiation of maize (<i>Zea mays</i> L.) leaves with light of different spectral compositions, <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12711/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Glutamate is an essential amino acid in both the energy and biosynthetic processes in plant cells. The aim of this work was to study changes in glutamate metabolism upon irradiation of maize (<i>Zea mays</i> L.) leaves with light of different spectral compositions, as well as to identify mechanisms regulating the work of enzymes involved in the studied process. A study was conducted of light-induced changes in glutamate metabolism in maize leaves, mediated by redirecting the glutamate flow to the γ-aminobutyric acid (GABA) shunt. Glutamate dehydrogenase (GDH) was more active in darkness, and the irradiation by red light inhibited the expression of both the <i>Gdh1</i> and <i>Gdh2 </i>genes. EGTA and ruthenium red abolished the effects of light, indicating the participation of Ca<sup>2+</sup> ions in phytochrome signal transduction. Contrary to GDH, glutamate decarboxylase (GAD) activity was moderately higher in the light, stimulated by red light, while far-red light reversed the effect. The effect of light on <i>Gad</i> expression was more pronounced than on GAD activity. Irradiation by red light also resulted in the increase in activity of GABA transaminase (GTA), which was abolished by far-red light. The third enzyme of the GABA shunt, succinic semialdehyde dehydrogenase (SSADH), was also activated by light. The effect of light on the expression of <i>Ssadh1</i>, but not on <i>Ssadh2</i>, was phytochrome-dependent. It is concluded that irradiation by light shifts glutamate metabolism from GDH to GAD with the activation of GABA transaminase and SSADH. This suggests that the GABA pathway plays a role in the maintenance of the tricarboxylic acid cycle in the light via bypassing its reactions when the 2-oxoglutarate dehydrogenase complex is inhibited and the cycle switches to the open mode. <a href="/1422-0067/25/23/12711">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Section <a href="/journal/ijms/sections/molecular_plant_sciences">Molecular Plant Sciences</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 16 pages, 1136 KiB   </span> <a href="/1422-0067/25/23/12710/pdf?version=1732632067" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Exploring Potential Diagnostic Biomarkers for Mechanical Asphyxia in the Heart Based on Proteomics Technology" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12710">Exploring Potential Diagnostic Biomarkers for Mechanical Asphyxia in the Heart Based on Proteomics Technology</a> <div class="authors"> by <span class="inlineblock "><strong>Yuebing Huang</strong>, </span><span class="inlineblock "><strong>Hai Qiu</strong>, </span><span class="inlineblock "><strong>Qianling Chen</strong>, </span><span class="inlineblock "><strong>Zilin Meng</strong>, </span><span class="inlineblock "><strong>Dongfang Qiao</strong> and </span><span class="inlineblock "><strong>Xia Yue</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12710; <a href="https://doi.org/10.3390/ijms252312710">https://doi.org/10.3390/ijms252312710</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Mechanical asphyxia presents a challenging diagnostic issue in forensic medicine due to its often covert nature, and the signs visible during an autopsy are usually not specific. Despite some progress in understanding hypoxia’s effects, traditional methods’ inherent limitations might overlook new biomarkers in <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12710/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Mechanical asphyxia presents a challenging diagnostic issue in forensic medicine due to its often covert nature, and the signs visible during an autopsy are usually not specific. Despite some progress in understanding hypoxia’s effects, traditional methods’ inherent limitations might overlook new biomarkers in mechanical asphyxia. This study employed 4D-DIA proteomics to explore the protein expression profiles of cardiac samples under conditions of mechanical asphyxia. Proteomic analysis identified 271 and 371 differentially expressed proteins in the strangulation and suffocation groups, respectively, compared to the control group. Seventy-eight differentially expressed proteins were identified across different mechanical asphyxia groups compared to the control group. GO and KEGG analysis showed enrichment in pathways, including complement and coagulation cascades, cAMP and cGMP-PKG signaling pathways, inflammatory mediator regulation of TRP channels, and phagosomes. Through stringent selection based on protein interactions, ALKBH5, NAA10, and CLPB were identified as potential diagnostic biomarkers. ALKBH5 showed increased expression in asphyxia models, while NAA10 and CLPB were downregulated; these biomarker changes were validated in both animal models and human cardiac samples. This study highlights the potential of proteomics in discovering reliable biomarkers, which can enhance the specificity of mechanical asphyxia diagnosis in forensic practice, provide new insights into the pathophysiological mechanisms of mechanical asphyxia, and offer new perspectives for diagnosing mechanical asphyxia. <a href="/1422-0067/25/23/12710">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Section <a href="/journal/ijms/sections/Pathology_Diagnostics_Therapeutics">Molecular Pathology, Diagnostics, and Therapeutics</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 20 pages, 2555 KiB   </span> <a href="/1422-0067/25/23/12709/pdf?version=1732630808" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Chitosan-Electrospun Fibers Encapsulating Norfloxacin: The Impact on the Biochemical, Oxidative and Immunological Profile in a Rats Burn Model" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12709">Chitosan-Electrospun Fibers Encapsulating Norfloxacin: The Impact on the Biochemical, Oxidative and Immunological Profile in a Rats Burn Model</a> <div class="authors"> by <span class="inlineblock "><strong>Corneliu-George Coman</strong>, </span><span class="inlineblock "><strong>Alexandru Anisiei</strong>, </span><span class="inlineblock "><strong>Sandu Cibotaru</strong>, </span><span class="inlineblock "><strong>Daniela Ailincai</strong>, </span><span class="inlineblock "><strong>Sorin Aurelian Pasca</strong>, </span><span class="inlineblock "><strong>Caroline Chabot</strong>, </span><span class="inlineblock "><strong>Ioannis Gardikiotis</strong> and </span><span class="inlineblock "><strong>Liliana Mititelu-Tartau</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12709; <a href="https://doi.org/10.3390/ijms252312709">https://doi.org/10.3390/ijms252312709</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> This study investigates the impact of chitosan-based nanofibers on burn wound healing in a rat model. Two formulations of chitosan nanofibers were prepared through electrospinning. The formulations were then incorporated with different amounts of norfloxacin and underwent surface modifications with 2-formylphenylboronic acid. The <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12709/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> This study investigates the impact of chitosan-based nanofibers on burn wound healing in a rat model. Two formulations of chitosan nanofibers were prepared through electrospinning. The formulations were then incorporated with different amounts of norfloxacin and underwent surface modifications with 2-formylphenylboronic acid. The burn model was applied to <i>Wistar</i> male rats by the contact method, using a heated steel rod attached to a thermocouple. The effectiveness of the nanofibers was tested against a negative control group and a standard commercial dressing (Atrauman Ag) on the described model and evaluated by wound diameter, histological analysis and biochemical profiling of systemic inflammatory markers. The results showed that chitosan-based dressings significantly accelerated burn healing compared to the control treatments. The high-concentration norfloxacin-infused chitosan coated with 2-formylphenylboronic acid’ groups exhibited significant improvements in wound closure and reduced inflammation compared to the other groups; antioxidant enzymes SOD and GPx expression was significantly higher, <i>p</i><i> </i><<i> </i>0.05, whereas pro-oxidative markers such as cortisol were lower (<i>p</i><i> </i><<i> </i>0.05). Macroscopically, the wound area itself was significantly diminished in the chitosan-treated groups (<i>p</i><i> </i><<i> </i>0.05). Furthermore, a histological evaluation indicated enhanced epithelialization and granulation tissue formation within the experiment time frame, while the biochemical panel revealed lower levels of inflammatory cytokines and lower leukocyte counts in the treated groups. These findings highlight the potential of the studied chitosan nanofibers as novel nanosystems for next-generation wound therapies, as well as the clinical utility of the novel chitosan fibers obtained by electrospinning technique. <a href="/1422-0067/25/23/12709">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/3EYU0FJ94L ">The Chitosan Biomaterials: Advances and Challenges—2nd Edition</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <a data-dropdown="drop-supplementary-1530054" aria-controls="drop-supplementary-1530054" aria-expanded="false" title="Supplementary Material"> <i class="material-icons">attachment</i> </a> <div id="drop-supplementary-1530054" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide" data-dropdown-content aria-hidden="true" tabindex="-1"> Supplementary material: <br/> <a href="/1422-0067/25/23/12708/s1?version=1732631462"> Supplementary File 1 (ZIP, 2966 KiB) </a><br/> </div> </div> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 33 pages, 3700 KiB   </span> <a href="/1422-0067/25/23/12708/pdf?version=1732631462" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Design, Synthesis and Biological Exploration of Novel N-(9-Ethyl-9H-Carbazol-3-yl)Acetamide-Linked Benzofuran-1,2,4-Triazoles as Anti-SARS-CoV-2 Agents: Combined Wet/Dry Approach Targeting Main Protease (Mpro), Spike Glycoprotein and RdRp" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12708">Design, Synthesis and Biological Exploration of Novel <i>N</i>-(9-Ethyl-9<i>H</i>-Carbazol-3-yl)Acetamide-Linked Benzofuran-1,2,4-Triazoles as Anti-SARS-CoV-2 Agents: Combined Wet/Dry Approach Targeting Main Protease (M<sup>pro</sup>), Spike Glycoprotein and RdRp</a> <div class="authors"> by <span class="inlineblock "><strong>Ameer Fawad Zahoor</strong>, </span><span class="inlineblock "><strong>Saba Munawar</strong>, </span><span class="inlineblock "><strong>Sajjad Ahmad</strong>, </span><span class="inlineblock "><strong>Fozia Iram</strong>, </span><span class="inlineblock "><strong>Muhammad Naveed Anjum</strong>, </span><span class="inlineblock "><strong>Samreen Gul Khan</strong>, </span><span class="inlineblock "><strong>Jamila Javid</strong>, </span><span class="inlineblock "><strong>Usman Nazeer</strong> and </span><span class="inlineblock "><strong>Mashooq Ahmad Bhat</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12708; <a href="https://doi.org/10.3390/ijms252312708">https://doi.org/10.3390/ijms252312708</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> A novel series of substituted benzofuran-tethered triazolylcarbazoles was synthesized in good to high yields (65–89%) via <i>S</i>-alkylation of benzofuran-based triazoles with 2-bromo-<i>N</i>-(9-ethyl-9<i>H</i>-carbazol-3-yl)acetamide. The inhibitory potency of the synthesized compounds against SARS-CoV-2 was evaluated by enacting molecular docking against <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12708/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> A novel series of substituted benzofuran-tethered triazolylcarbazoles was synthesized in good to high yields (65–89%) via <i>S</i>-alkylation of benzofuran-based triazoles with 2-bromo-<i>N</i>-(9-ethyl-9<i>H</i>-carbazol-3-yl)acetamide. The inhibitory potency of the synthesized compounds against SARS-CoV-2 was evaluated by enacting molecular docking against its three pivotal proteins, namely, M<sup>pro</sup> (main protease; PDB ID: 6LU7), the spike glycoprotein (PDB ID: 6WPT), and RdRp (RNA-dependent RNA polymerase; PDB ID: 6M71). The docking results indicated strong binding affinities between SARS-CoV-2 proteins and the synthesized compounds, which were thereby expected to obstruct the function of SARS proteins. Among the synthesized derivatives, the compounds <b>9e</b>, <b>9h</b>, <b>9i</b>, and <b>9j</b> exposited the best binding scores of −8.77, −8.76, −8.87, and −8.85 Kcal/mol against M<sup>pro</sup>, respectively, −6.69, −6.54, −6.44, and −6.56 Kcal/mol against the spike glycoprotein, respectively, and −7.61, −8.10, −8.01, and −7.54 Kcal/mol against RdRp, respectively. Furthermore, the binding scores of <b>9b </b>(−8.83 Kcal/mol) and <b>9c </b>(−8.92 Kcal/mol) against 6LU7 are worth mentioning. Regarding the spike glycoprotein, <b>9b</b>, <b>9d</b>, and <b>9f</b> expressed high binding energies of −6.43, −6.38, and −6.41 Kcal/mol, accordingly. Correspondingly, the binding affinity of <b>9g</b> (−7.62 Kcal/mol) against RdRp is also noteworthy. Furthermore, the potent compounds were also subjected to ADMET analysis to evaluate their pharmacokinetic properties, suggesting that the compounds <b>9e</b>, <b>9h</b>, <b>9i</b>, and <b>9j</b> exhibited comparable values. These potent compounds may be selected as inhibitory agents and provide a pertinent context for further investigations. <a href="/1422-0067/25/23/12708">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Section <a href="/journal/ijms/sections/biochemistry">Biochemistry</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 14 pages, 2347 KiB   </span> <a href="/1422-0067/25/23/12707/pdf?version=1732628766" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Effect of Chloroplast ATP Synthase on Reactive Oxygen Species Metabolism in Cotton" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12707">Effect of Chloroplast ATP Synthase on Reactive Oxygen Species Metabolism in Cotton</a> <div class="authors"> by <span class="inlineblock "><strong>Li Zhang</strong>, </span><span class="inlineblock "><strong>Panpan Jing</strong>, </span><span class="inlineblock "><strong>Biao Geng</strong>, </span><span class="inlineblock "><strong>Jinlong Zhang</strong>, </span><span class="inlineblock "><strong>Jinjiang Shi</strong>, </span><span class="inlineblock "><strong>Dong Liang</strong>, </span><span class="inlineblock "><strong>Yujie Yang</strong>, </span><span class="inlineblock "><strong>Yunfang Qu</strong> and </span><span class="inlineblock "><strong>Jinling Huang</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12707; <a href="https://doi.org/10.3390/ijms252312707">https://doi.org/10.3390/ijms252312707</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Abnormal programmed cell death in the tapetum is induced by reactive oxygen species (ROS), which are the main factors leading to cytoplasmic male sterility (CMS). These abnormalities are caused by genetic interactions between nuclear and cytoplasmic genes. To explore the role of chloroplast <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12707/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Abnormal programmed cell death in the tapetum is induced by reactive oxygen species (ROS), which are the main factors leading to cytoplasmic male sterility (CMS). These abnormalities are caused by genetic interactions between nuclear and cytoplasmic genes. To explore the role of chloroplast genes in ROS metabolism, next-generation and single-molecule real-time sequencing of the chloroplast genome were performed in the cotton CMS line Jin A (Jin A-CMS). Our results showed that the chloroplast genome is 160,042 bp in length and consists of 131 genes, including 112 functional genes. An analysis of the functional annotation and sequence comparison with the <i>Gossypium hirsutum</i> chloroplast genome as a reference revealed that 29 genes in Jin A-CMS have single-nucleotide polymorphisms, including subunits of ATP synthase, NAD(P)H-quinone redox reductase, and photosystem complexes. Compared to the Jin B maintainer, the anthers of Jin A-CMS at the microspore abortion stage have significantly lower expression of <i>atpB</i>, <i>atpE</i>, and <i>atpF</i>. The relative expression of these genes is significantly higher in the three-line F1 hybrids compared to Jin A-CMS. The ROS levels in the leaves increased in response to the silencing of <i>atpE</i> and <i>atpF</i> in cotton plants. In summary, the results of our study show that the ATP synthase subunit genes <i>atpE</i> and <i>atpF</i> are closely linked with ROS metabolism. These results provide basic information for the functional analysis of ATP synthase in cotton. <a href="/1422-0067/25/23/12707">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Section <a href="/journal/ijms/sections/molecular_plant_sciences">Molecular Plant Sciences</a>)<br/> </div> <a href="#" class="abstract-figures-show" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12707/show" ><span >►</span><span style=" display: none;">▼</span> Show Figures </a><div class="abstract-image-preview "><div class="arrow left-arrow" id="prev1529981"><i class="fa fa-caret-left"></i></div><div class="arrow right-arrow" id="next1529981"><i class="fa fa-caret-right"></i></div><div class="absgraph cycle-slideshow manual" data-cycle-fx="scrollHorz" data-cycle-timeout="0" data-cycle-next="#next1529981" data-cycle-prev="#prev1529981" data-cycle-progressive="#images1529981" data-cycle-slides=">div" data-cycle-log="false"><div class='openpopupgallery cycle-slide' data-imgindex='0' data-target='article-1529981-popup'><span class="helper"></span><img src="data:image/gif;base64,R0lGODlhAQABAAD/ACwAAAAAAQABAAACADs=" data-src="https://pub.mdpi-res.com/ijms/ijms-25-12707/article_deploy/html/images/ijms-25-12707-g001-550.jpg?1732628843" alt="" style="border: 0;"><p>Figure 1</p></div><script id="images1529981" type="text/cycle" data-cycle-split="---"><div class='openpopupgallery' data-imgindex='1' data-target='article-1529981-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12707/article_deploy/html/images/ijms-25-12707-g002-550.jpg?1732628844'><p>Figure 2</p></div> --- <div class='openpopupgallery' data-imgindex='2' data-target='article-1529981-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12707/article_deploy/html/images/ijms-25-12707-g003-550.jpg?1732628845'><p>Figure 3</p></div> --- <div class='openpopupgallery' data-imgindex='3' data-target='article-1529981-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12707/article_deploy/html/images/ijms-25-12707-g004-550.jpg?1732628846'><p>Figure 4</p></div></script></div></div><div id="article-1529981-popup" class="popupgallery" style="display: inline; line-height: 200%"><a href="https://pub.mdpi-res.com/ijms/ijms-25-12707/article_deploy/html/images/ijms-25-12707-g001-550.jpg?1732628843" title=" <strong>Figure 1</strong><br/> <p>Circular map diagram of the chloroplast genome in Jin A-CMS. The details of the DNA strands transcribed clockwise (+) and counterclockwise (−) are displayed on the inside and outside of the circle, respectively. The color indicates the function of the gene, as shown in the legend at the bottom left of the figure.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12707'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12707/article_deploy/html/images/ijms-25-12707-g002-550.jpg?1732628844" title=" <strong>Figure 2</strong><br/> <p>Expression analysis of ATP synthase subunit genes during anther development in Jin A-CMS. (<b>a</b>) The relative expression of <span class="html-italic">atpB</span>; (<b>b</b>) The relative expression of <span class="html-italic">atpE</span>; (<b>c</b>) The relative expression of <span class="html-italic">atpF</span>. S (before microspore abortion stage), M1 (microspore abortion stage) and M2 (after microspore abortion stage). Values are means ± SD of three replicates (* <span class="html-italic">p <span class="html-small-caps">&lt;</span></span> 0.05; ** <span class="html-italic">p <span class="html-small-caps">&lt;</span></span> 0.01, Student’s <span class="html-italic">t</span>-tests).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12707'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12707/article_deploy/html/images/ijms-25-12707-g003-550.jpg?1732628845" title=" <strong>Figure 3</strong><br/> <p>The NBT and DAB staining of gene-silenced cotton leaves. (<b>a</b>) Determination of gene expression of gene-silenced plants. Values are means ± SD of three replicates (** <span class="html-italic">p <span class="html-small-caps">&lt;</span></span> 0.01, Student’s <span class="html-italic">t</span>-tests); (<b>b</b>) NBT staining of gene-silenced plant leaves; (<b>c</b>) DAB staining of gene-silenced plant leaves. Bar = 1 mm.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12707'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12707/article_deploy/html/images/ijms-25-12707-g004-550.jpg?1732628846" title=" <strong>Figure 4</strong><br/> <p>Determination of singlet oxygen in gene-silenced cotton leaves. SOSG detects <sup>1</sup>O<sub>2</sub> in leaves. GFP, green fluorescence; Bright, bright field; Merged, superposition field, bar = 1 mm.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12707'>Full article</a></strong> "></a></div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <a data-dropdown="drop-supplementary-1529956" aria-controls="drop-supplementary-1529956" aria-expanded="false" title="Supplementary Material"> <i class="material-icons">attachment</i> </a> <div id="drop-supplementary-1529956" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide" data-dropdown-content aria-hidden="true" tabindex="-1"> Supplementary material: <br/> <a href="/1422-0067/25/23/12706/s1?version=1732627988"> Supplementary File 1 (ZIP, 2770 KiB) </a><br/> </div> </div> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 19 pages, 1846 KiB   </span> <a href="/1422-0067/25/23/12706/pdf?version=1732627988" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Anorectal Remodeling in the Transitional Zone with Increased Expression of LGR5, SOX9, SOX2, and Keratin 13 and 5 in a Dextran Sodium Sulfate-Induced Mouse Model of Ulcerative Colitis" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12706">Anorectal Remodeling in the Transitional Zone with Increased Expression of LGR5, SOX9, SOX2, and Keratin 13 and 5 in a Dextran Sodium Sulfate-Induced Mouse Model of Ulcerative Colitis</a> <div class="authors"> by <span class="inlineblock "><strong>Mio Kobayashi</strong>, </span><span class="inlineblock "><strong>Tatsuya Usui</strong>, </span><span class="inlineblock "><strong>Mohamed Elbadawy</strong>, </span><span class="inlineblock "><strong>Tetsuhito Kigata</strong>, </span><span class="inlineblock "><strong>Masahiro Kaneda</strong>, </span><span class="inlineblock "><strong>Tomoaki Murakami</strong>, </span><span class="inlineblock "><strong>Takuma Kozono</strong>, </span><span class="inlineblock "><strong>Yoshiyuki Itoh</strong>, </span><span class="inlineblock "><strong>Makoto Shibutani</strong> and </span><span class="inlineblock "><strong>Toshinori Yoshida</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12706; <a href="https://doi.org/10.3390/ijms252312706">https://doi.org/10.3390/ijms252312706</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Although hyperplasia of the anorectal transitional zone (TZ) has been reported in mouse models of ulcerative colitis, the mechanisms underlying this phenomenon are not fully understood. We characterized keratin subtypes and examined the expression of stem cell markers in the TZ. Dextran sodium <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12706/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Although hyperplasia of the anorectal transitional zone (TZ) has been reported in mouse models of ulcerative colitis, the mechanisms underlying this phenomenon are not fully understood. We characterized keratin subtypes and examined the expression of stem cell markers in the TZ. Dextran sodium sulfate-treated mice showed abnormal repair of the anorectal region, which consisted of mixed hyperplastic TZ and regenerating crypts. Liquid chromatography-tandem mass spectrometry from the paraffin-embedded TZ in the treated mice revealed that the major keratins were type I cytokeratin (CK)13 and type II CK5, but notable expression of type I CK10 and CK42 and type II CK1, CK4, CK6a, CK8, and CK15 was also detected. Hyperplastic TZ was characterized by the expression of tumor protein 63, sex-determining region Y-box 2 (SOX2), SOX9, and leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5). Lgr5 was highly expressed in the TZ in the early stages of colitis, followed by higher expression levels of SOX2. The TZ-derived organoids expressed LGR5, SOX2, and SOX9. The present study suggests that transitional zones showing abnormal keratin assembly and stem cell activation may interfere with rectal crypt regeneration, leading to pathological anorectal remodeling in severe colitis. <a href="/1422-0067/25/23/12706">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/13GIY48DQG ">Stem Cell Regenerative Medicine: From Molecular Basis to Translational Research</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 17 pages, 4290 KiB   </span> <a href="/1422-0067/25/23/12705/pdf?version=1732627296" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Accumulation of Anthocyanin in the Aleurone of Barley Grains by Targeted Restoration of the MYC2 Gene" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12705">Accumulation of Anthocyanin in the Aleurone of Barley Grains by Targeted Restoration of the <i>MYC2</i> Gene</a> <div class="authors"> by <span class="inlineblock "><strong>Anastasiya A. Egorova</strong>, </span><span class="inlineblock "><strong>Tatyana E. Zykova</strong>, </span><span class="inlineblock "><strong>Christian W. Hertig</strong>, </span><span class="inlineblock "><strong>Iris Hoffie</strong>, </span><span class="inlineblock "><strong>Sergey V. Morozov</strong>, </span><span class="inlineblock "><strong>Elena I. Chernyak</strong>, </span><span class="inlineblock "><strong>Artem D. Rogachev</strong>, </span><span class="inlineblock "><strong>Anna M. Korotkova</strong>, </span><span class="inlineblock "><strong>Alexander V. Vikhorev</strong>, </span><span class="inlineblock "><strong>Gennady V. Vasiliev</strong>, </span><span class="inlineblock "><strong>Olesya Y. Shoeva</strong>, </span><span class="inlineblock "><strong>Jochen Kumlehn</strong>, </span><span class="inlineblock "><strong>Sophia V. Gerasimova</strong> and </span><span class="inlineblock "><strong>Elena K. Khlestkina</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12705; <a href="https://doi.org/10.3390/ijms252312705">https://doi.org/10.3390/ijms252312705</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Blue barley grain pigmentation results from anthocyanin accumulation in the aleurone layer. Anthocyanins are known for their beneficial effects on human health. The gene encoding the MYELOCYTOMATOSIS 2 (MYC2) transcription factor is potentially responsible for the blue coloration of the aleurone. In non-pigmented <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12705/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Blue barley grain pigmentation results from anthocyanin accumulation in the aleurone layer. Anthocyanins are known for their beneficial effects on human health. The gene encoding the MYELOCYTOMATOSIS 2 (MYC2) transcription factor is potentially responsible for the blue coloration of the aleurone. In non-pigmented barley, a single nucleotide insertion in this gene causes a frameshift mutation with a premature stop codon. It was hypothesized that restoring the <i>MYC2</i> reading frame could activate anthocyanin accumulation in the aleurone. Using a targeted mutagenesis approach in the present study, the reading frame of <i>MYC2</i> was restored in the non-pigmented cultivar Golden Promise. Genetic constructs harboring <i>cas9</i> and <i>gRNA</i> expression units were developed, pre-validated in protoplasts, and then functional <i>MYC2</i> alleles were generated at the plant level via <i>Agrobacterium</i>-mediated transformation. Anthocyanin accumulation in the aleurone layer of grains from these mutants was confirmed through microscopy and chemical analysis. The expression of anthocyanin biosynthesis genes was analyzed, revealing that the restoration of MYC2 led to increased transcript levels of <i>F3H</i> and <i>ANS</i> genes. These results confirm the critical role of the MYC2 transcription factor in the blue aleurone trait and provide a biotechnological solution for enriching barley grain with anthocyanins. <a href="/1422-0067/25/23/12705">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Section <a href="/journal/ijms/sections/molecular_plant_sciences">Molecular Plant Sciences</a>)<br/> </div> <a href="#" class="abstract-figures-show" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12705/show" ><span >►</span><span style=" display: none;">▼</span> Show Figures </a><div class="abstract-image-preview "><div class="absgraph cycle-slideshow"><div class='openpopupgallery cycle-slide' data-imgindex='0' data-target='article-1529946-popup'><span class="helper"></span><img src="data:image/gif;base64,R0lGODlhAQABAAD/ACwAAAAAAQABAAACADs=" data-src="https://pub.mdpi-res.com/ijms/ijms-25-12705/article_deploy/ijms-25-12705-ag.jpg?1732627297" alt="" style="border: 0;"><p>Graphical abstract</p></div></div></div><div id="article-1529946-popup" class="popupgallery" style="display: inline; line-height: 200%"><a href="https://pub.mdpi-res.com/ijms/ijms-25-12705/article_deploy/ijms-25-12705-ag.jpg?1732627297" title=" <strong>Graphical abstract</strong><br/><strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12705'>Full article</a></strong> "></a></div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 19 pages, 1451 KiB   </span> <a href="/1422-0067/25/23/12704/pdf?version=1732626806" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Steroid Profiles and Precursor-to-Product Ratios Are Altered in Pregnant Women with Preeclampsia" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12704">Steroid Profiles and Precursor-to-Product Ratios Are Altered in Pregnant Women with Preeclampsia</a> <div class="authors"> by <span class="inlineblock "><strong>Olivia Trummer</strong>, </span><span class="inlineblock "><strong>Christina Stern</strong>, </span><span class="inlineblock "><strong>Sharmaine Reintar</strong>, </span><span class="inlineblock "><strong>Karoline Mayer-Pickel</strong>, </span><span class="inlineblock "><strong>Mila Cervar-Zivkovic</strong>, </span><span class="inlineblock "><strong>Ulrich Dischinger</strong>, </span><span class="inlineblock "><strong>Max Kurlbaum</strong>, </span><span class="inlineblock "><strong>Berthold Huppertz</strong>, </span><span class="inlineblock "><strong>Herbert Fluhr</strong> and </span><span class="inlineblock "><strong>Barbara Obermayer-Pietsch</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12704; <a href="https://doi.org/10.3390/ijms252312704">https://doi.org/10.3390/ijms252312704</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Steroid hormone imbalance is associated with the pathogenesis of preeclampsia. However, affected enzymes of steroid metabolism and gene and protein expression in serum and placenta have not been elucidated yet. We aimed to investigate steroid hormone profiles and precursor-to-product ratios in preeclamptic women <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12704/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Steroid hormone imbalance is associated with the pathogenesis of preeclampsia. However, affected enzymes of steroid metabolism and gene and protein expression in serum and placenta have not been elucidated yet. We aimed to investigate steroid hormone profiles and precursor-to-product ratios in preeclamptic women compared to women with healthy pregnancy (controls) to identify potentially affected steroid hormones and their metabolizing enzymes. Also, we aimed to investigate whether the mRNA expression of these enzymes is different between the study groups and whether levels of serum mRNA expression reflect postnatal placental protein expression. Serum levels of 14 steroid hormones were measured at eight time points throughout pregnancy in nine preeclamptic women and 36 controls. Serum mRNA expression of selected steroid-metabolizing enzymes was assessed, and their protein expression was analyzed in additional nine preeclamptic women. Mean levels of sex steroid and corticosteroid hormones were significantly altered in preeclamptic women. Precursor-to-product ratios of 5α-reductase, aromatase and 11β-hydroxysteroid dehydrogenase 1 were significantly increased, those of steroid 17α-hydroxylase, 17β-hydroxysteroid-dehydrogenase, steroid 11β-hydroxylase and 11β-hydroxysteroid dehydrogenase 2 were significantly decreased. Serum mRNA expression and placenta protein expression were comparable between the groups. Results contribute to understanding the heterogeneity of preeclampsia and can thus promote future research in personalized medicine. <a href="/1422-0067/25/23/12704">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/504F223MZ7 ">Steroid Metabolism in Human Health and Disease 3.0</a>)<br/> </div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 9 pages, 2551 KiB   </span> <a href="/1422-0067/25/23/12703/pdf?version=1732626472" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Effect of the Protic vs. Non-Protic Molecular Environment on the cis to trans Conformation Change of Phototrexate Drug" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12703">Effect of the Protic vs. Non-Protic Molecular Environment on the <i>cis</i> to <i>trans</i> Conformation Change of Phototrexate Drug</a> <div class="authors"> by <span class="inlineblock "><strong>Flórián Bencze</strong>, </span><span class="inlineblock "><strong>László Kiss</strong>, </span><span class="inlineblock "><strong>Heng Li</strong>, </span><span class="inlineblock "><strong>Hui Yan</strong>, </span><span class="inlineblock "><strong>László Kollár</strong> and </span><span class="inlineblock "><strong>Sándor Kunsági-Máté</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12703; <a href="https://doi.org/10.3390/ijms252312703">https://doi.org/10.3390/ijms252312703</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> The therapeutical applicability of the anticancer drug phototrexate, a photoswitchable derivative of the antimetabolite dihydrofolate reductase inhibitor methotrexate, highly depends on the stability of its bioactive isomer. Considering that only the <i>cis</i> configuration of phototrexate is bioactive, in this work, the effect of <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12703/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> The therapeutical applicability of the anticancer drug phototrexate, a photoswitchable derivative of the antimetabolite dihydrofolate reductase inhibitor methotrexate, highly depends on the stability of its bioactive isomer. Considering that only the <i>cis</i> configuration of phototrexate is bioactive, in this work, the effect of the molecular environment on the stability of the <i>cis</i> isomer of this drug has been investigated. UV-vis absorption and fluorescence-based solvent relaxation methods have been used. Protic methanol and non-protic dimethylsulfoxide were used as medium-ranged permittivity solvents. The results showed a decreased rate of <i>cis → trans</i> conversion and enhanced stabilities of the <i>cis</i> isomer in methanol. Temperature-dependent measurements of the isomerization rate reflect the increased activation energy in methanol. <a href="/1422-0067/25/23/12703">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Section <a href="/journal/ijms/sections/Molecular_Biophysics">Molecular Biophysics</a>)<br/> </div> <a href="#" class="abstract-figures-show" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12703/show" ><span >►</span><span style=" display: none;">▼</span> Show Figures </a><div class="abstract-image-preview "><div class="arrow left-arrow" id="prev1529929"><i class="fa fa-caret-left"></i></div><div class="arrow right-arrow" id="next1529929"><i class="fa fa-caret-right"></i></div><div class="absgraph cycle-slideshow manual" data-cycle-fx="scrollHorz" data-cycle-timeout="0" data-cycle-next="#next1529929" data-cycle-prev="#prev1529929" data-cycle-progressive="#images1529929" data-cycle-slides=">div" data-cycle-log="false"><div class='openpopupgallery cycle-slide' data-imgindex='0' data-target='article-1529929-popup'><span class="helper"></span><img src="data:image/gif;base64,R0lGODlhAQABAAD/ACwAAAAAAQABAAACADs=" data-src="https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g001-550.jpg?1732626568" alt="" style="border: 0;"><p>Figure 1</p></div><script id="images1529929" type="text/cycle" data-cycle-split="---"><div class='openpopupgallery' data-imgindex='1' data-target='article-1529929-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g002-550.jpg?1732626569'><p>Figure 2</p></div> --- <div class='openpopupgallery' data-imgindex='2' data-target='article-1529929-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g003-550.jpg?1732626570'><p>Figure 3</p></div> --- <div class='openpopupgallery' data-imgindex='3' data-target='article-1529929-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g004-550.jpg?1732626571'><p>Figure 4</p></div> --- <div class='openpopupgallery' data-imgindex='4' data-target='article-1529929-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g005-550.jpg?1732626572'><p>Figure 5</p></div> --- <div class='openpopupgallery' data-imgindex='5' data-target='article-1529929-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g006-550.jpg?1732626572'><p>Figure 6</p></div> --- <div class='openpopupgallery' data-imgindex='6' data-target='article-1529929-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g007-550.jpg?1732626573'><p>Figure 7</p></div> --- <div class='openpopupgallery' data-imgindex='7' data-target='article-1529929-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g008-550.jpg?1732626575'><p>Figure 8</p></div></script></div></div><div id="article-1529929-popup" class="popupgallery" style="display: inline; line-height: 200%"><a href="https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g001-550.jpg?1732626568" title=" <strong>Figure 1</strong><br/> <p>Chemical structures of <span class="html-italic">trans</span>-Phototrexate (<span class="html-italic">trans</span>-PHX) and <span class="html-italic">cis</span>-Phototrexate (<span class="html-italic">cis</span>-PHX) and the reversible isomerization of PHX. Bottom: 3D structure of the two isomers of the PHX: <span class="html-italic">trans</span>-PHX (left) and <span class="html-italic">cis</span>-PHX (right).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12703'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g002-550.jpg?1732626569" title=" <strong>Figure 2</strong><br/> <p>Changes of absorption spectra of PHX with 50 μM concentrations in differently composed methanol–DMSO mixtures. (<b>Left</b>) DMSO concentration varies within the 10 vol % and 50 vol % range. The spectra remain unchanged above 50 vol % DMSO. (<b>Right</b>) DMSO concentration varies within the range of 10 vol % and 28 vol %.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12703'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g003-550.jpg?1732626570" title=" <strong>Figure 3</strong><br/> <p>Correlation of the solvent relaxation times and the composition of the solvation shell of phototrexate molecules estimated from the absorption spectra. DMSO concentration varies within the range of 6 vol % and 28 vol %.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12703'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g004-550.jpg?1732626571" title=" <strong>Figure 4</strong><br/> <p>Shows the time-dependent representative absorption spectra of PHX in two cases: (<b>a</b>) the solvent composed of pure DMSO and (<b>b</b>) the solvent composed of 90 vol % methanol and 10 vol % DMSO.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12703'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g005-550.jpg?1732626572" title=" <strong>Figure 5</strong><br/> <p>(<b>Left</b>) Representative <span class="html-italic">cis</span> → <span class="html-italic">trans</span> conversion curves of PHX in two cases: the solvent is pure DMSO or consists of 90 vol % methanol and 10 vol % DMSO. (<b>Right</b>): k<sub>2</sub> plotted against vol % DMSO.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12703'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g006-550.jpg?1732626572" title=" <strong>Figure 6</strong><br/> <p>Arrhenian plots of the rates of the second conversion step associated with the <span class="html-italic">cis</span> → <span class="html-italic">trans</span> conversion of PHX in two cases: (<b>a</b>) the solvent composed of pure DMSO and (<b>b</b>) the solvent composed of 90 vol % methanol and 10 vol % DMSO. The slopes determine 86 kJ/mol and 234 kJ/mol activation energy for the (<b>a</b>,<b>b</b>) processes, respectively.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12703'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g007-550.jpg?1732626573" title=" <strong>Figure 7</strong><br/> <p>Optimized structure of the coordination of two methanol molecules to the <span class="html-italic">cis</span>-PHX. (HF/6-31G* level of calculation) The methanol molecules are stabilized preferably by the hydrogen bonds.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12703'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12703/article_deploy/html/images/ijms-25-12703-g008-550.jpg?1732626575" title=" <strong>Figure 8</strong><br/> <p>Schematic scheme of the synthesis of PHX.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12703'>Full article</a></strong> "></a></div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 23 pages, 5592 KiB   </span> <a href="/1422-0067/25/23/12702/pdf?version=1732625239" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Genetic Manipulation of Caveolin-1 in a Transgenic Mouse Model of Aortic Root Aneurysm: Sex-Dependent Effects on Endothelial and Smooth Muscle Function" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12702">Genetic Manipulation of Caveolin-1 in a Transgenic Mouse Model of Aortic Root Aneurysm: Sex-Dependent Effects on Endothelial and Smooth Muscle Function</a> <div class="authors"> by <span class="inlineblock "><strong>Tala Curry-Koski</strong>, </span><span class="inlineblock "><strong>Brikena Gusek</strong>, </span><span class="inlineblock "><strong>Ross M. Potter</strong>, </span><span class="inlineblock "><strong>T. Bucky Jones</strong>, </span><span class="inlineblock "><strong>Raechel Dickman</strong>, </span><span class="inlineblock "><strong>Nathan Johnson</strong>, </span><span class="inlineblock "><strong>John N. Stallone</strong>, </span><span class="inlineblock "><strong>Roshanak Rahimian</strong>, </span><span class="inlineblock "><strong>Johana Vallejo-Elias</strong> and </span><span class="inlineblock "><strong>Mitra Esfandiarei</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12702; <a href="https://doi.org/10.3390/ijms252312702">https://doi.org/10.3390/ijms252312702</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> Marfan syndrome (MFS) is a systemic connective tissue disorder stemming from mutations in the gene encoding Fibrillin-1 (Fbn1), a key extracellular matrix glycoprotein. This condition manifests with various clinical features, the most critical of which is the formation of aortic root aneurysms. Reduced <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12702/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> Marfan syndrome (MFS) is a systemic connective tissue disorder stemming from mutations in the gene encoding Fibrillin-1 (Fbn1), a key extracellular matrix glycoprotein. This condition manifests with various clinical features, the most critical of which is the formation of aortic root aneurysms. Reduced nitric oxide (NO) production due to diminished endothelial nitric oxide synthase (eNOS) activity has been linked to MFS aortic aneurysm pathology. Caveolin-1 (Cav1), a structural protein of plasma membrane caveolae, is known to inhibit eNOS activity, suggesting its involvement in MFS aneurysm progression by modulating NO levels. In this study, we examined the role of Cav1 in aortic smooth muscle and endothelial function, aortic wall elasticity, and wall strength in male and female MFS mice (<i>FBN1<sup>+/Cys1041Gly</sup></i>) by generating developing Cav1-deficient MFS mice (MFS/<i>Cav1</i>KO). Our findings reveal that <i>Cav1</i> ablation leads to a pronounced reduction in aortic smooth muscle contraction in response to phenylephrine, attributable to an increase in NO production in the aortic wall. Furthermore, we observed enhanced aortic relaxation responses to acetylcholine in MFS/<i>Cav1</i>KO mice, further underscoring Cav1’s inhibitory impact on NO synthesis within the aorta. Notably, van Gieson staining and chamber myography analyses showed improved elastin fiber structure and wall strength in male MFS/<i>Cav1KO</i> mice, whereas these effects were absent in female counterparts. Cav1’s regulatory influence on aortic root aneurysm development in MFS through NO-mediated modulation of smooth muscle and endothelial function, with notable sex-dependent variations. <a href="/1422-0067/25/23/12702">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/95009PGIF5 ">Genetic and Molecular Susceptibility in Human Diseases: 2nd Edition</a>)<br/> </div> <a href="#" class="abstract-figures-show" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12702/show" ><span >►</span><span style=" display: none;">▼</span> Show Figures </a><div class="abstract-image-preview "><div class="arrow left-arrow" id="prev1529913"><i class="fa fa-caret-left"></i></div><div class="arrow right-arrow" id="next1529913"><i class="fa fa-caret-right"></i></div><div class="absgraph cycle-slideshow manual" data-cycle-fx="scrollHorz" data-cycle-timeout="0" data-cycle-next="#next1529913" data-cycle-prev="#prev1529913" data-cycle-progressive="#images1529913" data-cycle-slides=">div" data-cycle-log="false"><div class='openpopupgallery cycle-slide' data-imgindex='0' data-target='article-1529913-popup'><span class="helper"></span><img src="data:image/gif;base64,R0lGODlhAQABAAD/ACwAAAAAAQABAAACADs=" data-src="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g001-550.jpg?1732625312" alt="" style="border: 0;"><p>Figure 1</p></div><script id="images1529913" type="text/cycle" data-cycle-split="---"><div class='openpopupgallery' data-imgindex='1' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g002-550.jpg?1732625313'><p>Figure 2</p></div> --- <div class='openpopupgallery' data-imgindex='2' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g003a-550.jpg?1732625314'><p>Figure 3</p></div> --- <div class='openpopupgallery' data-imgindex='3' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g003b-550.jpg?1732625315'><p>Figure 3 Cont.</p></div> --- <div class='openpopupgallery' data-imgindex='4' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g004-550.jpg?1732625317'><p>Figure 4</p></div> --- <div class='openpopupgallery' data-imgindex='5' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g005a-550.jpg?1732625318'><p>Figure 5</p></div> --- <div class='openpopupgallery' data-imgindex='6' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g005b-550.jpg?1732625319'><p>Figure 5 Cont.</p></div> --- <div class='openpopupgallery' data-imgindex='7' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g006-550.jpg?1732625321'><p>Figure 6</p></div> --- <div class='openpopupgallery' data-imgindex='8' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g007-550.jpg?1732625322'><p>Figure 7</p></div> --- <div class='openpopupgallery' data-imgindex='9' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g008-550.jpg?1732625323'><p>Figure 8</p></div> --- <div class='openpopupgallery' data-imgindex='10' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g009-550.jpg?1732625325'><p>Figure 9</p></div> --- <div class='openpopupgallery' data-imgindex='11' data-target='article-1529913-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g010-550.jpg?1732625326'><p>Figure 10</p></div></script></div></div><div id="article-1529913-popup" class="popupgallery" style="display: inline; line-height: 200%"><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g001-550.jpg?1732625312" title=" <strong>Figure 1</strong><br/> <p>Genetic <span class="html-italic">Cav1</span> deletion disrupts the formation of caveolae invagination in the aortic wall. Representative transition electron microscopy images of 9-month-old aortic sections in CTRL (<b>A</b>), MFS (<b>B</b>), <span class="html-italic">Cav1KO</span> (<b>C</b>), and MFS/<span class="html-italic">Cav1KO</span> (<b>D</b>) mice visualize the structure of caveolae invaginations in the aortic wall and shows that deletion of <span class="html-italic">Cav1</span> gene impacts the structural integrity and membrane distribution of caveolae.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g002-550.jpg?1732625313" title=" <strong>Figure 2</strong><br/> <p><span class="html-italic">Cav1</span> deletion does not affect the progression of aortic root growth in MFS mice. Presented bar graphs showcase measurements of aortic root diameter using the myograph chambers. Aortic root diameters are increased in both male and female MFS mice compared to age- and sex-matched healthy CTRL mice. <span class="html-italic">Cav1</span> gene deletion has no impact on artic root growth in both male and female MFS mice aorta. (Means ± SE, N = 6–9 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g003a-550.jpg?1732625314" title=" <strong>Figure 3</strong><br/> <p><span class="html-italic">Cav1</span> deletion increases endothelium-dependent vasorelaxation in MFS mice. Measurements of acetylcholine (Ach)-induced relaxation in aortic rings isolated from different experimental groups using isometric small chamber myography. (<b>A</b>) Dose–response curves (50 pM–1 µM) for acetylcholine (Ach)-induced relaxation in aortic rings isolated from 9-month-old male and female CTRL, MFS, CTRL/<span class="html-italic">Cav1</span>KO, and MFS/<span class="html-italic">Cav1</span>KO mice. Aortic rings were pre-contracted with sub-max of PE prior to cumulative application of Ach. Relaxation responses were compared to values for CTRL aortic rings that were arbitrarily set as 100% of relaxation. All values were normalized to peak values for PE-induced contraction for each aortic ring (* CTRL vs. MFS, # CTRL vs. CTRL/<span class="html-italic">Cav1</span>KO, and <span>$</span> MFS vs. MFS/Cav1KO, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.001, <span>$</span> <span class="html-italic">p</span> &lt; 0.05, <span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.001, <span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.0001, <span>$</span><span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.00001, ## <span class="html-italic">p</span> &lt; 0.001, ### <span class="html-italic">p</span> &lt; 0.0001, #### <span class="html-italic">p</span> &lt; 0.00001). (<b>B</b>) The Emax values for Ach were derived from the dose–response curves. (N = 9–12 mice/group). Aortic relaxation in response to Ach is significantly decreased in aortic rings isolated from male MFS mice compared to age- and sex-matched healthy CTRL aorta. Female MFS aortic rings show a higher peak relaxation compared to age-matched male MFS mice. <span class="html-italic">Cav1</span> gene deletion leads to an increase in maximum Ach-induced aortic vasorelaxation (Emax) in male and female MFS/<span class="html-italic">Cav1</span>KO mice compared to age- and sex-matched MFS groups, indicating significant increases in aortic wall NO production in the absence of Cav1 protein. (<b>C</b>) EC50 values for Ach are markedly increased in male MFS mice compared to sex- and age-matched CTRL, but no difference is observed in age-matched female CTRL and MFS aorta. Deletion of <span class="html-italic">Cav1</span> results in a significant drop in Ach EC<sub>50</sub> values in age-matched male MFS/<span class="html-italic">Cav1</span>KO aorta compared to MFS mice, indicating an increased sensitivity of aortic endothelial layer to Ach treatment in male mice aortic rings. However, in female mice, <span class="html-italic">Cav1</span> deletion does not impact aortic endothelial cell sensitivity to Ach. (<b>D</b>) Deletion of <span class="html-italic">Cav1</span> increased Ach-induced vasorelaxation in female CTRL mice aorta, with no changes observed in male CTRL subjects. In this bar graph, the average values for Ach-induced vasorelaxation in male CTRL aorta are arbitrarily set as 100% of relaxation. (Means ± SE, N = 9–12 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g003b-550.jpg?1732625315" title=" <strong>Figure 3 Cont.</strong><br/> <p><span class="html-italic">Cav1</span> deletion increases endothelium-dependent vasorelaxation in MFS mice. Measurements of acetylcholine (Ach)-induced relaxation in aortic rings isolated from different experimental groups using isometric small chamber myography. (<b>A</b>) Dose–response curves (50 pM–1 µM) for acetylcholine (Ach)-induced relaxation in aortic rings isolated from 9-month-old male and female CTRL, MFS, CTRL/<span class="html-italic">Cav1</span>KO, and MFS/<span class="html-italic">Cav1</span>KO mice. Aortic rings were pre-contracted with sub-max of PE prior to cumulative application of Ach. Relaxation responses were compared to values for CTRL aortic rings that were arbitrarily set as 100% of relaxation. All values were normalized to peak values for PE-induced contraction for each aortic ring (* CTRL vs. MFS, # CTRL vs. CTRL/<span class="html-italic">Cav1</span>KO, and <span>$</span> MFS vs. MFS/Cav1KO, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.001, <span>$</span> <span class="html-italic">p</span> &lt; 0.05, <span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.001, <span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.0001, <span>$</span><span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.00001, ## <span class="html-italic">p</span> &lt; 0.001, ### <span class="html-italic">p</span> &lt; 0.0001, #### <span class="html-italic">p</span> &lt; 0.00001). (<b>B</b>) The Emax values for Ach were derived from the dose–response curves. (N = 9–12 mice/group). Aortic relaxation in response to Ach is significantly decreased in aortic rings isolated from male MFS mice compared to age- and sex-matched healthy CTRL aorta. Female MFS aortic rings show a higher peak relaxation compared to age-matched male MFS mice. <span class="html-italic">Cav1</span> gene deletion leads to an increase in maximum Ach-induced aortic vasorelaxation (Emax) in male and female MFS/<span class="html-italic">Cav1</span>KO mice compared to age- and sex-matched MFS groups, indicating significant increases in aortic wall NO production in the absence of Cav1 protein. (<b>C</b>) EC50 values for Ach are markedly increased in male MFS mice compared to sex- and age-matched CTRL, but no difference is observed in age-matched female CTRL and MFS aorta. Deletion of <span class="html-italic">Cav1</span> results in a significant drop in Ach EC<sub>50</sub> values in age-matched male MFS/<span class="html-italic">Cav1</span>KO aorta compared to MFS mice, indicating an increased sensitivity of aortic endothelial layer to Ach treatment in male mice aortic rings. However, in female mice, <span class="html-italic">Cav1</span> deletion does not impact aortic endothelial cell sensitivity to Ach. (<b>D</b>) Deletion of <span class="html-italic">Cav1</span> increased Ach-induced vasorelaxation in female CTRL mice aorta, with no changes observed in male CTRL subjects. In this bar graph, the average values for Ach-induced vasorelaxation in male CTRL aorta are arbitrarily set as 100% of relaxation. (Means ± SE, N = 9–12 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g004-550.jpg?1732625317" title=" <strong>Figure 4</strong><br/> <p><span class="html-italic">Cav1</span> deletion reduces KCl-induced aortic contraction in MFS mice. Bar graphs present maximum force generation in isolated aortic rings in response to KCl (60 mM) in the myograph chambers. (<b>A</b>) KCl-induced aortic contraction is reduced in female MFS mice compared to age- and sex-matched controls. No genotype-associated differences are observed in age-matched male CTRL and MFS. The maximum force generated in response to KCl in male CTRL aortic rings was arbitrarily set as 100% of generated force in aortic rings. (<b>B</b>) <span class="html-italic">Cav1</span> deletion reduces KCl-induced smooth muscle contraction in male and female MFS/Cav1KO mice compared to age- and sex-matched MFS aorta. (Means ± SE, N = 9–12 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g005a-550.jpg?1732625318" title=" <strong>Figure 5</strong><br/> <p><span class="html-italic">Cav1</span> deletion decreases phenylephrine-induced aortic contraction in CTRL and MFS mice. Measurements of mouse aortic ring contractions in response to sub-max concentration (1 µM) of phenylephrine (PE) in the myograph chambers. (<b>A</b>) Dose–response curves (1 nM–50 µM) for PE-induced contraction in aortic rings isolated from 9-month-old male and female CTRL, MFS, CTRL/<span class="html-italic">Cav1</span>KO, and MFS/<span class="html-italic">Cav1</span>KO mice. All values were normalized to peak values for KCl-induced contraction for each aortic ring. Recorded contraction responses were compared to values for CTRL aortic rings that were arbitrarily set as 100% of generated contractile force. (* CTRL vs. MFS, # CTRL vs. CTRL/<span class="html-italic">Cav1</span>KO, and <span>$</span> MFS vs. MFS/Cav1KO, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.001, *** <span class="html-italic">p</span> &lt; 0.0001, **** <span class="html-italic">p</span> &lt; 0.00001, <span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.0001, <span>$</span><span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.00001, ### <span class="html-italic">p</span> &lt; 0.0001, #### <span class="html-italic">p</span> &lt; 0.00001).). (<b>B</b>) In both male and female MFS mice, aortic ring contractions in response to PE are significantly lower compared to healthy CTRL aorta. When we compared age-matched male and female MFS aorta, we observed a significant reduction in female MFS aortic contraction compared to male MFS mice. (<b>C</b>) <span class="html-italic">Cav1</span> deletion reduces PE-induced aortic contraction in male MFS mice, but not in females, indicating a sex-specific effect of <span class="html-italic">Cav1</span> deletion on aortic wall contraction. However, it is important to notice that <span class="html-italic">Cav1</span> deletion reduces PE-induced contraction in male MFS aorta to levels that are similar to the values observed in female MFS/Cav1KO mice. (Means ± SE, N = 7–10 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g005b-550.jpg?1732625319" title=" <strong>Figure 5 Cont.</strong><br/> <p><span class="html-italic">Cav1</span> deletion decreases phenylephrine-induced aortic contraction in CTRL and MFS mice. Measurements of mouse aortic ring contractions in response to sub-max concentration (1 µM) of phenylephrine (PE) in the myograph chambers. (<b>A</b>) Dose–response curves (1 nM–50 µM) for PE-induced contraction in aortic rings isolated from 9-month-old male and female CTRL, MFS, CTRL/<span class="html-italic">Cav1</span>KO, and MFS/<span class="html-italic">Cav1</span>KO mice. All values were normalized to peak values for KCl-induced contraction for each aortic ring. Recorded contraction responses were compared to values for CTRL aortic rings that were arbitrarily set as 100% of generated contractile force. (* CTRL vs. MFS, # CTRL vs. CTRL/<span class="html-italic">Cav1</span>KO, and <span>$</span> MFS vs. MFS/Cav1KO, * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.001, *** <span class="html-italic">p</span> &lt; 0.0001, **** <span class="html-italic">p</span> &lt; 0.00001, <span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.0001, <span>$</span><span>$</span><span>$</span><span>$</span> <span class="html-italic">p</span> &lt; 0.00001, ### <span class="html-italic">p</span> &lt; 0.0001, #### <span class="html-italic">p</span> &lt; 0.00001).). (<b>B</b>) In both male and female MFS mice, aortic ring contractions in response to PE are significantly lower compared to healthy CTRL aorta. When we compared age-matched male and female MFS aorta, we observed a significant reduction in female MFS aortic contraction compared to male MFS mice. (<b>C</b>) <span class="html-italic">Cav1</span> deletion reduces PE-induced aortic contraction in male MFS mice, but not in females, indicating a sex-specific effect of <span class="html-italic">Cav1</span> deletion on aortic wall contraction. However, it is important to notice that <span class="html-italic">Cav1</span> deletion reduces PE-induced contraction in male MFS aorta to levels that are similar to the values observed in female MFS/Cav1KO mice. (Means ± SE, N = 7–10 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g006-550.jpg?1732625321" title=" <strong>Figure 6</strong><br/> <p><span class="html-italic">Cav1</span> deletion decreases mouse aortic contraction by increasing NO production. Bar graphs present maximum (Emax) aortic contraction in response to sub-maximum concentration (1 µM) of phenylephrine (PE) in CTRL, MFS, and MFS/<span class="html-italic">Cav1</span>KO mice in the absence or presence of L-NAME (200 µM), which is a general inhibitor of NO synthesis. (<b>A</b>) Pre-treatment of aortic rings with L-NAME increases aortic root contraction in age-matched male CTRL and MFS aorta. (<b>B</b>) Pre-treatment of aortic rings with L-NAME also increases aortic root contraction in age-matched female CTRL and MFS aorta. (<b>C</b>) L-NAME increases PE-induced aortic contraction in male and female MFS/<span class="html-italic">Cav1KO</span> mice. (Means ± SE, N = 6–9 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g007-550.jpg?1732625322" title=" <strong>Figure 7</strong><br/> <p><span class="html-italic">Cav1</span> deletion-mediated increases in aortic NO production are not through iNOS. Presented bar graphs showcase the impact of 1400 W, a potent inhibitor of inducible NOS (iNOS) on maximum (Emax) PE-induced contraction in aortic rings isolated from male and female MFS/<span class="html-italic">Cav1</span>KO mice. (<b>A</b>) Pre-treatment of MFS/<span class="html-italic">Cav1</span>KO mice aortic rings with the iNOS inhibitor 1400 W (1 µM) has no effects on PE-induced aortic contraction in age-matched male and female MFS/<span class="html-italic">Cav1</span>KO mice, indicating that the excessive increase in aortic endogenous NO production in the absence of Cav1 is not mediated by iNOS activation. (<b>B</b>) Pre-treatment of CTRL and MFS mice aortic rings with the iNOS inhibitor 1400 W (1 µM) significantly increased PE-induced vasoconstriction in both male and female MFS mice aorta, indicating that iNOS-mediated NO response elevated in male and female MFS aorta. (Means ± SE, N = 6–8 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g008-550.jpg?1732625323" title=" <strong>Figure 8</strong><br/> <p><span class="html-italic">Cav1</span> deletion markedly improves aortic wall strength in male MFS/Cav1KO mice. Scatter plot graphs show the force generated (mN) at the rupture point. The rupture point of these aortic segments represents the maximum force generated by each segment at the point of maximum stretch, just before the aortic wall ruptures. (<b>A</b>) As expected, aortic wall rupture point is significantly reduced in both male and female MFS groups compared to age- and sex-matched healthy CTRL mice. Deletion of <span class="html-italic">Cav1</span> gene increases the aortic ring rupture points in male CTRL mice, with no effects observed in female CTRL subjects. (<b>B</b>) Similarly, <span class="html-italic">Cav1</span> deletion further increases aortic wall strength (rupture point) only in male MFS mice, indicating a sex-dependent effect. (Means ± SE, N = 4 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g009-550.jpg?1732625325" title=" <strong>Figure 9</strong><br/> <p><span class="html-italic">Cav1</span> deletion improves aortic wall elastin structure in male MFS/<span class="html-italic">Cav1</span>KO mice. Data presents measurements of aortic wall elastin fragment counts and length within the aortic wall sections isolated from CTRL, MFS, and MFS/<span class="html-italic">Cav1</span>KO mice. (<b>A</b>) Representative images showing Van Gieson staining of 10 µm aortic sections isolated from male CTRL, MFS, CTRL/<span class="html-italic">Cav1</span>KO, and MFS/<span class="html-italic">Cav1</span>KO mice, showing elastin in dark purple in the medial layer of mouse aortic wall (scale bar = 50 µm). (<b>B</b>) Quantification of elastin fiber counts shows a significant decrease in fragment counts in male MFS/<span class="html-italic">Cav1</span>KO aorta compared to MFS mice. (<b>C</b>) Similarly, <span class="html-italic">Cav1</span> deletion reduces elastin fiber fragment length in MFS mice, indicating a marked improvement in elastin structure within the aortic wall of MFS/<span class="html-italic">Cav1</span>KO mice. (Means ± SE, N = 4 mic/group, Two-Way ANOVA followed by Tukey’s pairwise comparison, <span class="html-italic">p</span> ≤ 0.05.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12702/article_deploy/html/images/ijms-25-12702-g010-550.jpg?1732625326" title=" <strong>Figure 10</strong><br/> <p>Potential impact of <span class="html-italic">Cav1</span> ablation on MFS aeropathy. In MFS mice, <span class="html-italic">Cav1</span> deletion results in improvement in aortic wall elastin structure and aortic wall strength. The deletion of <span class="html-italic">Cav1</span> also increases endothelium-mediated vasorelaxation in the aorta, while decreasing smooth muscle contraction in response to vasoconstricting agent phenylephrine. The overall conclusion is that <span class="html-italic">Cav1</span> deletion provides some levels of beneficial impacts on aortic structure and function in MFS mice. The image was generated by Biorender (Toronto, ON, Canada).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12702'>Full article</a></strong> "></a></div> </div> </div> </div> <div class="expanding-div collapsed"> <div class="generic-item article-item"> <div class="article-content"> <div class="label right label__btn"> <a data-dropdown="drop-supplementary-1529932" aria-controls="drop-supplementary-1529932" aria-expanded="false" title="Supplementary Material"> <i class="material-icons">attachment</i> </a> <div id="drop-supplementary-1529932" class="f-dropdown label__btn__dropdown label__btn__dropdown--wide" data-dropdown-content aria-hidden="true" tabindex="-1"> Supplementary material: <br/> <a href="/1422-0067/25/23/12701/s1?version=1732626673"> Supplementary File 1 (ZIP, 2681 KiB) </a><br/> </div> </div> <div class="label right label__btn"> <span style="font-size: 12px; color: #1a1a1a;"> 25 pages, 10207 KiB   </span> <a href="/1422-0067/25/23/12701/pdf?version=1732626672" class="UD_Listings_ArticlePDF" title="Article PDF" data-name="Neurotrophic Effects of Foeniculum vulgare Ethanol Extracts on Hippocampal Neurons: Role of Anethole in Neurite Outgrowth and Synaptic Development" data-journal="ijms"> <i class="material-icons custom-download"></i> </a> </div> <div class="article-icons"><span class="label openaccess" data-dropdown="drop-article-label-openaccess" aria-expanded="false">Open Access</span><span class="label articletype">Article</span></div> <a class="title-link" href="/1422-0067/25/23/12701">Neurotrophic Effects of <i>Foeniculum vulgare</i> Ethanol Extracts on Hippocampal Neurons: Role of Anethole in Neurite Outgrowth and Synaptic Development</a> <div class="authors"> by <span class="inlineblock "><strong>Sarmin Ummey Habiba</strong>, </span><span class="inlineblock "><strong>Ho Jin Choi</strong>, </span><span class="inlineblock "><strong>Yeasmin Akter Munni</strong>, </span><span class="inlineblock "><strong>In-Jun Yang</strong>, </span><span class="inlineblock "><strong>Md. Nazmul Haque</strong> and </span><span class="inlineblock "><strong>Il Soo Moon</strong></span> </div> <div class="color-grey-dark"> <em>Int. J. Mol. Sci.</em> <b>2024</b>, <em>25</em>(23), 12701; <a href="https://doi.org/10.3390/ijms252312701">https://doi.org/10.3390/ijms252312701</a> - 26 Nov 2024 </div> <div class="abstract-div"> <a href="#" onclick="$(this).next('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> <strong>Abstract </strong> </a> <div class="abstract-cropped inline"> <i>Foeniculum vulgare</i> Mill, commonly known as fennel, is an aromatic herb traditionally used for culinary and medicinal purposes, with potential therapeutic effects on neurological disorders. However, limited research has focused on its neurotrophic impact, particularly on neuronal maturation and synaptic development. This study <a href="#" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12701/more" onclick="$(this).parents('.abstract-cropped').toggleClass('inline').next('.abstract-full').toggleClass('inline'); return false;"> [...] Read more.</a> </div> <div class="abstract-full "> <i>Foeniculum vulgare</i> Mill, commonly known as fennel, is an aromatic herb traditionally used for culinary and medicinal purposes, with potential therapeutic effects on neurological disorders. However, limited research has focused on its neurotrophic impact, particularly on neuronal maturation and synaptic development. This study investigates the neurotrophic effects of <i>F. vulgare</i> ethanol extracts (FVSE) on the maturation of rat primary hippocampal neurons. Results show that FVSE and its prominent component, anethole, significantly promote neurite outgrowth in a dose-dependent manner. Optimal axonal and dendritic growth occurred at concentrations of 40 µg/mL FVSE and 20 µM anethole, respectively, without causing cytotoxicity, underscoring the safety of FVSE for neuronal health. Additionally, FVSE enhances the formation of synapses, essential for neuronal communication. Network pharmacology analysis revealed that FVSE components influence critical neurotrophic pathways, including PI3K-AKT and Alzheimer’s disease pathways. Specifically, FVSE modulates key proteins, including tropomyosin receptor kinase (Trk), glycogen synthase kinase 3 (GSK3β<sup>ser9</sup>), phosphatidylinositol 3-kinase (PI3K), and extracellular signal-regulated protein kinase (Erk1/2). Anethole was found to play a key role in regulating these pathways, which was confirmed by immunocytochemistry experiments demonstrating its effect on promoting neuronal growth and synaptic development. In conclusion, this study highlights the neurotrophic properties of FVSE, with anethole emerging as a critical bioactive compound. These findings provide valuable insights into the therapeutic potential of fennel in treating neurological disorders, offering a basis for future research into interventions promoting neuronal growth and survival. <a href="/1422-0067/25/23/12701">Full article</a> </div> </div> <div class="belongsTo" style="margin-bottom: 10px;"> (This article belongs to the Special Issue <a href=" /journal/ijms/special_issues/24PEA1Q0O0 ">Trends in Neuroscience: From Molecular Mechanisms to Innovative Therapeutics</a>)<br/> </div> <a href="#" class="abstract-figures-show" data-counterslink = "https://www.mdpi.com/1422-0067/25/23/12701/show" ><span >►</span><span style=" display: none;">▼</span> Show Figures </a><div class="abstract-image-preview "><div class="arrow left-arrow" id="prev1529932"><i class="fa fa-caret-left"></i></div><div class="arrow right-arrow" id="next1529932"><i class="fa fa-caret-right"></i></div><div class="absgraph cycle-slideshow manual" data-cycle-fx="scrollHorz" data-cycle-timeout="0" data-cycle-next="#next1529932" data-cycle-prev="#prev1529932" data-cycle-progressive="#images1529932" data-cycle-slides=">div" data-cycle-log="false"><div class='openpopupgallery cycle-slide' data-imgindex='0' data-target='article-1529932-popup'><span class="helper"></span><img src="data:image/gif;base64,R0lGODlhAQABAAD/ACwAAAAAAQABAAACADs=" data-src="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g001-550.jpg?1732626885" alt="" style="border: 0;"><p>Figure 1</p></div><script id="images1529932" type="text/cycle" data-cycle-split="---"><div class='openpopupgallery' data-imgindex='1' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g002-550.jpg?1732626887'><p>Figure 2</p></div> --- <div class='openpopupgallery' data-imgindex='2' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g003-550.jpg?1732626888'><p>Figure 3</p></div> --- <div class='openpopupgallery' data-imgindex='3' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g004-550.jpg?1732626891'><p>Figure 4</p></div> --- <div class='openpopupgallery' data-imgindex='4' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g005-550.jpg?1732626894'><p>Figure 5</p></div> --- <div class='openpopupgallery' data-imgindex='5' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g006-550.jpg?1732626895'><p>Figure 6</p></div> --- <div class='openpopupgallery' data-imgindex='6' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g007-550.jpg?1732626897'><p>Figure 7</p></div> --- <div class='openpopupgallery' data-imgindex='7' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g008-550.jpg?1732626899'><p>Figure 8</p></div> --- <div class='openpopupgallery' data-imgindex='8' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g009-550.jpg?1732626901'><p>Figure 9</p></div> --- <div class='openpopupgallery' data-imgindex='9' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g010-550.jpg?1732626903'><p>Figure 10</p></div> --- <div class='openpopupgallery' data-imgindex='10' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g011-550.jpg?1732626905'><p>Figure 11</p></div> --- <div class='openpopupgallery' data-imgindex='11' data-target='article-1529932-popup'><span class="helper"></span><img src='https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g012-550.jpg?1732626907'><p>Figure 12</p></div></script></div></div><div id="article-1529932-popup" class="popupgallery" style="display: inline; line-height: 200%"><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g001-550.jpg?1732626885" title=" <strong>Figure 1</strong><br/> <p>Diagram illustrating the evaluation of FVSE on hippocampal neurons, covering stages from chemical analysis (GC/MS and HPLC) to neuronal differentiation, growth, and synaptogenesis under FVSE (40 µg/mL) treatment.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g002-550.jpg?1732626887" title=" <strong>Figure 2</strong><br/> <p>Neurite Outgrowth Quantification in FVSE-treated Neurons: Hippocampal neurons were cultured for three days and treated with FVSE at varying concentrations. Immuno-stained images illustrate neurite outgrowth, with representative images comparing FVSE (40 μg/mL) and vehicle treatments. Morphometric analysis assessed the number of neurites, total neurite length, and the length of the longest neurite. Statistical significance was determined by one-way ANOVA, followed by Tukey’s post hoc test (* <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001). Each experiment was replicated three times (<span class="html-italic">n</span> = 3), with 10 neurons per replicate. Data are presented as Mean ± S.E.M.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g003-550.jpg?1732626888" title=" <strong>Figure 3</strong><br/> <p>Effects of FVSE on Neuronal Cell Viability. (<b>A</b>) Trypan blue-stained images showing viable neurons, with dead neurons indicated by red arrows in panel (<b>a</b>). The bar graph (<b>b</b>) illustrates the percentage of surviving cells after treatment with varying concentrations of FVSE (10–60 μg/mL). The scale bar represents 50 μm. Neuronal viability was determined by counting the number of unstained (live) cells relative to the total number of assessed cells (living and dead). Results were analyzed using one-way analysis of variance (ANOVA) and are presented as mean ± standard error of the mean (SEM) from three independent studies (<span class="html-italic">n</span> = 6, with 400–500 neurons per study). Statistical significance is indicated by *** <span class="html-italic">p</span> &lt; 0.001.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g004-550.jpg?1732626891" title=" <strong>Figure 4</strong><br/> <p>During the initial stages of neuronal differentiation, FVSE was applied at a concentration of 40 μg/mL to assess early developmental maturation. Neurons were fixed at DIV1 and DIV2 and stained with antibodies for MAP2 (green) and tau (red) under consistent culture conditions throughout the experiment. (<b>A</b>(-b)) Representative fluorescence image showing early development at 24 h (DIV1), with insets representing normal developmental stages: Stage 1 (lamellipodia formation), Stage 2 (minor process formation), and Stage 3 (neurite outgrowth). (<b>A</b>(-a)) Statistical analysis displaying the percentage of neurons reaching each developmental stage at the corresponding time points. (<b>B</b>(-b)) Representative fluorescence images taken at 48 h (DIV2), along with the corresponding statistical analysis (<b>B</b>(-a)). Scale bars represent 50 μm and 10 μm (insets). Values in the bar graphs are presented as mean ± SEM from 300 to 400 neurons. Statistical significance compared to the vehicle is indicated by *** <span class="html-italic">p</span> &lt; 0.001.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g005-550.jpg?1732626894" title=" <strong>Figure 5</strong><br/> <p>FVSE Enhances Axon Morphogenesis in Hippocampal Neurons. Hippocampal neurons were cultured for 5 days under the conditions described in <a href="#ijms-25-12701-f002" class="html-fig">Figure 2</a>. After culture, cells were fixed and subjected to double immunostaining with ankyrin G (red) and α-tubulin (green). Ankyrin G, located at the axon initial segment (AIS), was used to identify axons, while α-tubulin marked dendrites. Representative fluorescence images of DIV5 cultures were used to assess neuronal morphology, with a scale bar of 50 μm. Morphometric analysis includes (<b>A</b>) sholl analysis and (<b>B</b>) immune-fluorescent images comparing FVSE-treated and control neurons. Quantitative measurements showed significant increases in FVSE-treated neurons for (<b>C</b>(-a)) axon length, (<b>C</b>(-b)) number of axonal branches by branching order, and (<b>C</b>(-c)) axonal collateral branch length by branching order. Sholl analysis also highlighted enhanced axonal complexity in FVSE-treated neurons, as observed in (<b>D</b>(-a)) the number of axonal intersections and (<b>D</b>(-b)) the total length of axonal branches. Data are presented as mean ± SEM (from three independent biological replicates). Statistical significance compared to the control is indicated by * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001 (Student’s <span class="html-italic">t</span>-test).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g006-550.jpg?1732626895" title=" <strong>Figure 6</strong><br/> <p>FVSE Promotes Dendritic Morphogenesis in Neurons. Representative photomicrographs for dendritic morphogenesis, similar to those in <a href="#ijms-25-12701-f005" class="html-fig">Figure 5</a>B, show the differences between FVSE-treated and control neurons. Morphometric analysis includes (<b>A</b>(-a)) the number of primary dendrites, (<b>A</b>(-b)) the total length of primary dendrites, (<b>A</b>(-c)) the number of dendritic branches, and (<b>A</b>(-d)) the total length of dendritic branches. Beyond that, Sholl analysis illustrates (<b>B</b>(-a)) the number of dendritic intersections and (<b>B</b>(-b)) the branching points at various distances from the cell center. Bar graphs present mean values ± S.E.M. (<span class="html-italic">n</span> = 3, 10 neurons per group). Statistical significance relative to the vehicle control is denoted by * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g007-550.jpg?1732626897" title=" <strong>Figure 7</strong><br/> <p>Impact of FVSE on Synaptic Connections. (<b>A</b>) Fluorescence microscopy images illustrating synaptic connections with dual labeling of SV2 (green) and NMDA receptor subunits (GluN2A and GluN2B) or PSD95 (red), showing co-localization (yellow puncta) in control and FVSE-treated neurons. Panels a–c show the synaptic co-localization of SV2 with GluN2A, GluN2B, and PSD95, respectively, highlighting an increase in synapse density with FVSE treatment. The scale bar represents 2 µm. (<b>B</b>) Quantification of puncta density for SV2 and each respective marker in a 50 µm segment. Panels (<b>B</b>(-a))–(<b>B</b>(-c)) display the density of SV2 co-localized with GluN2A, GluN2B, and PSD95, respectively, showing significant increases in co-localized puncta in FVSE-treated neurons compared to controls. (<b>C</b>) Immunoblotting analysis of neuronal lysates from DIV14, verifying the expression levels of GluN2A, GluN2B, and PSD95 in FVSE-treated versus control neurons, with α-tubulin as a loading control. Panels (<b>C</b>(-a))–(<b>C</b>(-c)) present the immunoblotting results for GluN2A, GluN2B, and PSD95, respectively, with increased expression in FVSE-treated neurons. (<b>D</b>) Bar graphs quantifying the relative intensity of GluN2A, GluN2B, and PSD95 normalized to α-tubulin, as shown in panels (<b>D</b>(-a))–(<b>D</b>(-c)). These results demonstrate a significant upregulation of synaptic components in FVSE-treated neurons, supporting enhanced synaptic connectivity and plasticity. Statistical data are presented as mean ± standard error of the mean (S.E.M.) from three independent experiments (<span class="html-italic">n</span> = 3, with 10 neurons per experiment). Student’s <span class="html-italic">t</span>-tests were used to determine statistical significance (** <span class="html-italic">p</span> &lt; 0.01 and *** <span class="html-italic">p</span> &lt; 0.001).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g008-550.jpg?1732626899" title=" <strong>Figure 8</strong><br/> <p>Analysis of Synaptic Protein Expression in the Cortex of 5-Week-Old ICR Mice Treated with FVSE. (<b>A</b>) Representative Western blot images showing the levels of GluN2A, GluN2B, PSD95, and the loading control α-Tubulin in cortical tissue from control and FVSE-treated groups. (<b>B</b>) Quantitative analysis of Western blot band intensity normalized to α-Tubulin for (a) GluN2A, (b) GluN2B, and (c) PSD95. Data are expressed as mean ± S.E.M. from four mice per group. Statistically significant differences compared to the control group are indicated by *** <span class="html-italic">p</span> &lt; 0.001 (Student’s <span class="html-italic">t</span>-test).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g009-550.jpg?1732626901" title=" <strong>Figure 9</strong><br/> <p>Network and Enrichment Analysis of FVSE Bioactive Compounds and Neuronal Development Targets. (<b>A</b>) Venn diagram showing the overlap between genes associated with FVSE bioactive compounds and those involved in neuronal development, identifying 376 common genes. (<b>B</b>) Protein-protein interaction (PPI) network of the 20 common genes, with key hub genes highlighted in red, including AKT1, SRC, and TP53. (<b>C</b>) Bar chart displaying the top 20 genes related to neuronal development, with critical genes labeled. (<b>D</b>) Dot plots representing enrichment analysis of common target genes, showing significant involvement in (a) biological processes, (b) cellular components, (c) molecular functions, and (d) KEGG pathways, highlighting pathways such as Neurotrophin signaling, PI3K-AKT signaling, and Alzheimer’s disease pathways.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g010-550.jpg?1732626903" title=" <strong>Figure 10</strong><br/> <p>(<b>A</b>) Bright-field images illustrating the neuritogenetic effects of various treatments, including Scoparone (37.5 μM), Linalool (10 μM), Stigmasterol (37.5 μM), Anethole (20 μM), and FVSE (40 μg/mL), compared to the control. Neurite outgrowth is visible across the different treatments, with the scale bar representing 50 μm. (<b>B</b>) Quantitative analysis of morphometric parameters, including (a) the number of primary neurites per neuron, (b) the length of the primary neurites, and (c) the length of the longest neurite. Data are presented as the mean ± standard error of the mean (S.E.M.) from three independent experiments (<span class="html-italic">n</span> = 3, with 10 neurons per experiment). Statistical significance was determined using one-way analysis of variance (ANOVA), with * <span class="html-italic">p</span> &lt; 0.05 and *** <span class="html-italic">p</span> &lt; 0.001 indicating levels of significance.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g011-550.jpg?1732626905" title=" <strong>Figure 11</strong><br/> <p>Immunofluorescence Characterization of Neurotrophin Signaling Proteins in Primary Cultured Neurons. (<b>A</b>) Representative fluorescence images of neurons labeled with α-tubulin (green) as a structural marker, alongside neurotrophin proteins (red): NGF, BDNF, Trk-A, Trk-B, and GSK3βser9. Merged images show areas of co-localization (yellow), indicating overlap between α-tubulin and the specific neurotrophin markers. Scale bar represents 50 µm. (<b>B</b>) Quantitative analysis of mean fluorescence intensity for neurotrophin markers relative to α-tubulin expression: (a) NGF, (b) BDNF, (c) Trk-A, (d) Trk-B, and (e) GSK3βser9. Data are expressed as mean ± S.E.M. from three independent experiments with 30 neurons per group. Statistical significance is denoted by *** <span class="html-italic">p</span> &lt; 0.001 (Student’s <span class="html-italic">t</span>-test).</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a><a href="https://pub.mdpi-res.com/ijms/ijms-25-12701/article_deploy/html/images/ijms-25-12701-g012-550.jpg?1732626907" title=" <strong>Figure 12</strong><br/> <p>The diagram illustrates the neurotrophic activity of FVSE via activation of the Trk-B receptor in the Neurotrophin signaling pathway. This activation triggers the PI3K/Akt pathway, which regulates Bcl2, NF-κB, and GSK3β<sup>ser9</sup> to promote neuronal survival, differentiation, and synaptic plasticity. Solid arrows represent activation, and blunt arrows indicate inhibition.</p> <strong style='display: block; margin-top: 10px; font-size: 18px;'><a style='color: #fff' href='/1422-0067/25/23/12701'>Full article</a></strong> "></a></div> </div> </div> </div> </div> <div class="generic-item last-item"> <a class="bold" href="/search?q=&journal=ijms&sort=pubdate&page_count=50">More Articles...</a> </div> </div> </div> </div> <div id="left-column" class="content__column large-3 large-pull-6 medium-3 medium-pull-6 small-12 columns"> <div id="js-large-main-top-container"> <div id="js-main-top-container" class="content__container"> <a href="/journal/ijms"> <img src="https://pub.mdpi-res.com/img/journals/ijms-logo.png?41930e44070e4940" alt="ijms-logo" title="International Journal of Molecular Sciences" style="max-height: 60px; margin: 0 0 0 0;"> </a> <div class="generic-item no-border" style="position: relative;"> <div class=""> <a class="button button--color button--color-journal 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