International Journal of Molecular Sciences最新文献

{"title":"RETRACTED: Ardissino et al. Short-Term Effect of Nutraceutical Fruit Juices on Lipid Metabolism in Patients with Acquired Hypercholesterolemia. <i>Int. J. Mol. Sci</i>. 2023, <i>24</i>, 7358.","authors":"Diego Ardissino, Alessandro Colletti, Marzia Pellizzato, Gianna Pagliari, Francesco Di Pierro, Giancarlo Cravotto","doi":"10.3390/ijms27209087","DOIUrl":"10.3390/ijms27209087","url":null,"abstract":"<p><p>The journal retracts the article titled \"Short-Term Effect of Nutraceutical Fruit Juices on Lipid Metabolism in Patients with Acquired Hypercholesterolemia\" [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13663323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149181759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Wang et al. Behavior of Gingival Fibroblasts on Titanium Implant Surfaces in Combination with Either Injectable-PRF or PRP. <i>Int. J. Mol. Sci.</i> 2017, <i>18</i>, 331.","authors":"Xuzhu Wang, Yufeng Zhang, Joseph Choukroun, Shahram Ghanaati, Richard J Miron","doi":"10.3390/ijms27209019","DOIUrl":"https://doi.org/10.3390/ijms27209019","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 20","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149227943","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epitalon and Epithalamin: A Narrative Review of Mechanistic, Preclinical, and Clinical Evidence.","authors":"Ankur Jain, David M Gallacher, Mohammed A Issa, Timothy R Deer, Robert J Yong, Sudhir Diwan, Woojin Lee, Dawood Sayed, Kasra Amirdelfan, Christopher L Robinson","doi":"10.3390/ijms27198922","DOIUrl":"10.3390/ijms27198922","url":null,"abstract":"<p><p>Epitalon (Ala-Glu-Asp-Gly) is a synthetic tetrapeptide developed from the amino-acid composition of epithalamin, a chemically distinct pineal-derived polypeptide preparation. This narrative review evaluates the mechanistic, preclinical, and human evidence for synthetic epitalon in the context of regenerative and longevity medicine, while considering epithalamin studies separately as historical context. PubMed and Google Scholar were searched through 22 September 2026, with primary experimental and clinical studies prioritized and evidence appraised by study design, model, sample size, intervention, outcomes, safety reporting, and independent replication. Epitalon has been reported to modulate telomere-maintenance pathways, circadian and neuroendocrine function, oxidative stress, and cellular aging markers. Preclinical studies suggest biological activity, but direct evidence in musculoskeletal disease models is lacking. Human evidence is limited to small physiological or biomarker studies and an older controlled study in retinitis pigmentosa; no adequately powered randomized trial has established therapeutic efficacy. Pharmacokinetic, dose-ranging, and long-term safety data remain inadequate, while oncologic, immunogenicity, product-quality, and regulatory uncertainties following a 2026 FDA advisory review remain unresolved. Epitalon is therefore biologically active but clinically unproven, and further standardized pharmacologic, safety, and disease-specific studies are needed before clinical translation.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664938/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Genes to Gonads: Molecular Control Points of Reproduction in the Sea Urchin as a Framework for Aquaculture.","authors":"Alfonso Rodríguez, Jorge Olmos","doi":"10.3390/ijms27198939","DOIUrl":"10.3390/ijms27198939","url":null,"abstract":"<p><p>The economic output of sea urchin aquaculture depends almost entirely on a single organ. Gonads, marketed as <i>uni</i>, determine value through their size, color, texture and flavor, and feed formulations have been optimized empirically for decades with limited reference to the molecular machinery governing gametogenesis, sex differentiation and gonadal maturation in echinoids. This review integrates four lines of mechanistic evidence around the adult gonad, namely developmental gene regulatory networks, sex-biased gonadal transcriptomics, germ-cell and nutritive-phagocyte biology, and endocrine, neuroendocrine and retinoid signaling, and reads them in terms of the control points connecting molecular state to production outcome. Rather than advancing a unified mechanistic model, which the current evidence does not support, each component is classified by the strength of the evidence attached to it: demonstrated in an echinoid, inferred from another taxon, plausible but untested, or hypothetical. The resulting picture is one in which descriptive resources have outpaced functional tests. Candidate sex-determination transcription factors have been identified but none have yet been directly perturbed in an echinoid, the retinoid pathway is architecturally present yet biochemically incomplete, and responses to exogenous steroids remain heterogeneous across species and protocols. Priority experimental directions are ranked by commercial return and by experimental falsifiability.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666137/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Waterpipe Smoke Condensate Impairs p53 Nuclear Localization in Association with HIF-1α Stabilization.","authors":"Husam Nawafleh, Jerome Thiery, Yehya Elsayed, Abderemane Abdou, Salem Chouaib, Rania F Zaarour","doi":"10.3390/ijms27198927","DOIUrl":"10.3390/ijms27198927","url":null,"abstract":"<p><p>Waterpipe (shisha or hookah) smoking is recognized as a risk factor for lung cancer; however, its interference with hypoxia stress and tumor suppressor pathways in non-small cell lung cancer (NSCLC) is poorly defined. In this study, NSCLC cell lines (A549, H460, H226 with endogenous wild-type p53, and H1299 transiently expressing wild-type or p53 mutants) were exposed to waterpipe smoke condensate (WPSC) under normoxic and/or hypoxic conditions. WPSC induced HIF-1α stabilization under normoxic conditions, accompanied by predominantly cytoplasmic localization and without corresponding induction of the canonical HIF-1 target genes examined. In parallel, WPSC transiently reduced nuclear p53 localization without altering total p53 protein levels. In A549 cells, WPSC pretreatment attenuated irradiation-induced expression of the p53 target genes cyclin-dependent kinase inhibitor 1A (<i>CDKN1A</i>) and BTG anti-proliferation factor 2 (<i>BTG2</i>). Pharmacological inhibition of HIF-1α partially restored nuclear p53 localization, supporting the involvement of HIF-1α in this response. Co-immunoprecipitation demonstrated an association between HIF-1α and p53 following WPSC exposure. Collectively, these findings show that WPSC-induced HIF-1α stabilization under normoxic conditions is associated with transient alterations in p53 localization and transcriptional response, supporting an involvement of HIF-1α in this process.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665274/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193866","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: Yang et al. Molecular Mechanism of Metformin Regulating the Regeneration of Planarian <i>Dugesia japonica</i> Through <i>miR-27b</i>. <i>Int. J. Mol. Sci.</i> 2025, <i>26</i>, 7092.","authors":"Kexin Yang, Minmin Feng, Chunmei Zhang, Zelong Zhao, Dandan Yin, Linxia Song, Zhenbiao Xu","doi":"10.3390/ijms27198916","DOIUrl":"10.3390/ijms27198916","url":null,"abstract":"<p><p>In the original publication [...].</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13664993/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193425","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"LGH-Transformer: A Hybrid CNN-Transformer Model for Multi-Class Bladder Tissue Classification from Cystoscopic Images.","authors":"Hasan Anıl Kurt, Sabire Kılıçarslan, Meliha Merve Çiçekliyurt, Serhat Kiliçarslan","doi":"10.3390/ijms27198929","DOIUrl":"10.3390/ijms27198929","url":null,"abstract":"<p><p>Automated analysis of cystoscopic images may support consistent characterization of bladder tissue patterns, but reported performance is highly sensitive to patient composition, data partitioning, and evaluation methodology. Objective: This study provides an exploratory comparison of convolutional neural networks, Transformer-based models, and a proposed Local-Global Hybrid Transformer (LGH-Transformer) for four-class bladder tissue image classification. The dataset comprised 1754 frames and used the publicly released 1257/308/189 training-validation-held-out test split. The annotation-defined held-out test composition was HGC = 74, LGC = 53, NST = 37, and NTL = 25 (<i>n</i> = 189). Images were resized to 224 × 224 pixels, normalized, and augmented only in the training subset. Adam and RMSprop were evaluated. Accuracy and macro-averaged precision, recall, and F1-score were calculated from the integer-count evaluation matrices. The highest held-out accuracy, 187/189 (0.9894), was reached by seven model-optimizer configurations: DenseNet201-RMSprop, XCiT Medium 24 P16-Adam, ConvNeXt Base-Adam, CoAtNet-Adam, ConvNeXt Base-RMSprop, CoAtNet-RMSprop, and the proposed LGH-Transformer-RMSprop; MobileNet-Adam and Xcep-tion-RMSprop each yielded 185/189 (0.9788), and LGH-Transformer-Adam yielded 186/189 (0.9841). On a 189-frame test set, differences in one to two frames do not establish statistical superiority, so these configurations are reported as a top-accuracy tier rather than as a ranked superiority claim. Within this tier, the LGH-Transformer had the smallest computational footprint (≈18.2 M parameters and ≈4.1 GFLOPs, versus 20.0-88.6 M parameters and 4.3-16.2 GFLOPs for the other top-tier models). Component-wise ablation experiments showed accuracy decreases of 0.0106, 0.0053, and 0.0053 after removing the CNN tokenizer, local attention, and global attention, respectively. The LGH-Transformer reaches the top accuracy tier of this 18-architecture benchmark at the lowest parameter and FLOP budget within that tier, supporting an internally consistent, efficiency-oriented comparison within the available cohort. The absence of task-aligned external validation and the small number of held-out patients require the findings to be interpreted as exploratory internal validation rather than evidence of clinical generalizability.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"CD180-Associated B-Cell Alterations in Type 1 Diabetes and the In Vitro Effects of Chlorogenic Acid: An Integrated Transcriptomic and Experimental Study.","authors":"Zihang Wang, Arzu Mijit, Rong Han, Mengjia Li, Yang Wu, Lufeng Cheng","doi":"10.3390/ijms27198933","DOIUrl":"10.3390/ijms27198933","url":null,"abstract":"<p><p>Type 1 diabetes mellitus (T1DM) is an autoimmune disease involving progressive loss of pancreatic β-cells. Although B cells have been implicated in T1DM progression, the molecular characteristics associated with disease-related B-cell states remain unclear. Here, we investigated B-cell-associated molecular alterations in T1DM and explored the potential immunomodulatory effects of a natural compound. Public T1DM transcriptomic datasets were analyzed using differential expression analysis, WGCNA, and machine-learning approaches. Single-cell RNA sequencing was used to characterize <i>Cd180</i> expression across B-cell states. Molecular docking and molecular dynamics simulations were used to explore potential interactions between CD180 and candidate compounds, and an exploratory DARTS assay was performed to assess CGA-associated changes in CD180 proteolytic susceptibility. CD180 expression was examined in pancreatic tissues from vehicle- and MSA-2-treated NOD mice. The effects of chlorogenic acid (CGA) were evaluated in vitro by exposing B cells to CGA during inflammatory stimulation, followed by washing and co-culture with MIN6 cells in CGA-free medium. Integrated transcriptomic analysis identified four T1DM-associated genes (<i>CD180</i>, <i>KCNJ2</i>, <i>STEAP4</i>, and <i>ZXDA</i>), among which <i>CD180</i> showed the strongest association with B-cell-related immune alterations. Single-cell analysis showed increased <i>Cd180</i> expression in inflammatory B-cell states together with enrichment of antigen-presentation-related programs. An exploratory DARTS experiment with matched loading-control data suggested altered CD180 proteolytic susceptibility following CGA exposure, although independent reproducibility remains to be established. In vitro, CGA exposure during inflammatory stimulation was associated with reduced CD180 expression in B cells and improved MIN6 cell viability and insulin-secretory responses during subsequent co-culture in CGA-free medium. CD180 is associated with inflammatory B-cell alterations in T1DM and may represent a candidate molecular feature of B-cell dysregulation. CGA treatment was associated with changes in CD180 expression in activated B cells and improved β-cell functional outcomes in vitro. These findings support further investigation of the relationship between CGA and CD180; however, whether the effects of CGA are specifically mediated through CD180 requires further experimental validation.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13666279/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-Target Regulation of Diabetic Nephropathy by Alkaloids: Molecular Targets, Signaling Pathways and Therapeutic Potential.","authors":"Jiying Wang, Qing Li, Wentao Chen, Lingli Zhou, Rongyu Li, Na Zhou, Shifang Luo, Linao Zhang, Xue Wu, Yuhuan Xie, Peixin Guo","doi":"10.3390/ijms27198938","DOIUrl":"10.3390/ijms27198938","url":null,"abstract":"<p><p>In the context of the global diabetes epidemic, diabetic nephropathy (DN)-a condition directly associated with diabetes-has become the primary cause of end-stage renal disease, significantly impacting patients' quality of life and placing substantial demands on public healthcare resources. The pathogenesis of DN is characterized by metabolic disturbances induced by high glucose levels, hemodynamic abnormalities, and the synergistic amplification of various stress signals. These factors collectively contribute to the progressive loss of nephrons and irreversible renal dysfunction. Although current standard treatments can partially slow disease progression, they significantly fail to meet clinical needs. Therefore, there is an urgent necessity to identify multi-target intervention strategies that utilize novel mechanisms of action. Alkaloids, a class of natural nitrogen-containing compounds known for their significant structural diversity, have recently demonstrated multiple renoprotective effects in experimental models of DN. This review is based on a search of the PubMed, Web of Science and CNKI databases. The keywords alkaloids, diabetic nephropathy, diabetic nephropathies, diabetic kidney disease, inflammation, oxidative stress, fibrosis, autophagy and apoptosis were used to search for original research articles in both Chinese and English, published between 2010 and 2026, which investigated the mechanisms by which alkaloid compounds exert their anti-DN effects. Focusing on anti-inflammatory effects, anti-oxidative stress, anti-renal fibrosis, autophagy modulation, apoptosis regulation and ferroptosis inhibition, the review then summarized the relevant literature by systematizing the experimental models, intervention protocols, dosages and key results. This provided a new theoretical perspective and experimental basis for the clinical translation and new drug development of alkaloid compounds for the treatment of DN. The review provides a new theoretical perspective and an experimental basis for the clinical translation of, and new drug development based on, alkaloid compounds for the treatment of DN.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665509/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149193635","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrated Transcriptomic and Network Analysis Identifies Candidate Kinase-Mediated Thyroid-Associated Targets of Withaferin A.","authors":"Ejlal Mohamed Abdullah, Alaa Alnoor Alameen, Nouf Omar AlAfaleq, Mona Shujaa Alharbi","doi":"10.3390/ijms27198926","DOIUrl":"10.3390/ijms27198926","url":null,"abstract":"<p><p>Withaferin A (WA), a bioactive steroidal lactone derived from <i>Withania somnifera</i>, has been reported to exhibit diverse pharmacological activities, including anti-inflammatory and metabolic regulatory effects. Although previous studies suggest a potential link between WA and thyroid-related molecular pathways, the molecular mechanisms underlying these effects remain incompletely understood. Here, we employed a comprehensive computational approach to explore WA-responsive molecular changes potentially relevant to thyroid-associated processes. RNA-sequencing data from WA-treated MCF-10A human mammary epithelial cells (GSE158085) were analysed to identify differentially expressed genes (DEGs). Because thyroid-specific WA transcriptomic datasets are not currently available, the DEGs were intersected with curated hypothyroidism-associated genes to generate a cross-tissue, exploratory set of candidate genes. The genes that overlapped were used to construct protein-protein interaction networks, prioritize high-centrality candidate genes, and conduct enrichment analyses for transcription factors and kinases. Further analysis of selected upstream kinases was performed using molecular docking and molecular dynamics simulations with WA. A total of 1458 differentially expressed genes (DEGs) were identified, 10 of which overlapped with hypothyroidism-associated genes. Network analysis identified candidate interactions among the overlapping genes, while higher-confidence analysis retained four connected genes (PTPN22, STAT4, DUOX2, and DUOXA2). Transcription factor enrichment identified ERG, SUZ12, NANOG, TCF3, RUNX1, and TP63 as potential upstream regulators, while kinase enrichment identified candidate upstream kinases associated with the predicted regulatory network. Based on enrichment evidence, structural availability, and literature-supported biological relevance, MAPK14 (p38α), AKT1, and MAPK8 (JNK1) were selected for molecular docking and molecular dynamics simulations. Structural analyses suggested potential interactions between WA and the selected kinases, with target-specific dynamic behaviour across the simulated systems. Collectively, the findings highlight WA-responsive genes and predicted gene-TF-kinase relationships that may be relevant to thyroid-associated molecular processes. However, these associations are hypothesis-generating and provide a basis for further investigation in thyroid-derived experimental models.</p>","PeriodicalId":14156,"journal":{"name":"International Journal of Molecular Sciences","volume":"27 19","pages":""},"PeriodicalIF":4.9,"publicationDate":"2026-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13665287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}