Frontiers in Molecular Biosciences最新文献

{"title":"Integrated bulk and single-cell transcriptomic analyses with experimental validation identify PLOD1 as a diagnostic biomarker and TGF-β1-responsive profibrotic mediator in dupuytren's disease.","authors":"Xianjie Lin, Mingming Wang, Yutian Lin, Yinshen Zhu, Zhijiang Ye, Haoran Chen","doi":"10.3389/fmolb.2026.1924451","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1924451","url":null,"abstract":"<p><strong>Background: </strong>Dupuytren's disease (DD) is a progressive fibroproliferative disease characterized by palmar fascia fibrosis, extracellular matrix deposition, and finger contractures. Reliable diagnostic biomarkers and regulatory mechanisms have not yet been fully defined.</p><p><strong>Methods: </strong>Firstly, integrate the public transcriptome datasets GSE59746 and GSE75152. Then, limma was used to identify differentially expressed genes (DEGs) and combined with Weighted Gene Co expression Network Analysis (WGCNA) to screen candidate genes related to DD. PPI network analysis, functional enrichment, and four machine learning algorithms (LASSO, Boruta, Random Forest, and SVM-RFE) were applied to identify key biomarkers. Use CIBERSORT to assess immune infiltration. Analyze the single-cell RNA sequencing dataset GSE173252 to determine cell localization and pseudo time series analysis. Virtual knockout analysis is used to predict downstream regulatory targets. <i>In vitro</i> validation was conducted using TGF - β 1 stimulation and SB431542 inhibition.</p><p><strong>Results: </strong>A total of 598 DEGs were identified, and the WGCNA brown module showed the strongest correlation with DD. Cross analysis identified 346 candidate genes, mainly enriched in extracellular matrix tissue, collagen containing matrix, and collagen trimer formation. Procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) has been identified as the only overlapping biomarker among the four machine learning algorithms. PLOD1 is significantly upregulated in DD tissues and exhibits strong diagnostic performance, with an AUC of 0.908. Immunoassay showed a decrease in M0 macrophage infiltration, while there was a positive correlation between PLOD1 and M2 macrophages. Single cell analysis showed that PLOD1 was mainly enriched in chondrocyte related populations and increased along the late pseudotime trajectory. Virtual knockout indicates that FGF7 is a key downstream gene. TGF - β 1 significantly induces PLOD1 and pro fibrotic markers, while SB431542 inhibits these effects.</p><p><strong>Conclusion: </strong>PLOD1 is a promising biomarker and potential functional regulator for DD diagnosis, closely related to extracellular matrix remodeling, pro fibrotic signaling, and immune microenvironment changes.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1924451"},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662546/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lipid droplet organized metabolic vulnerabilities in melanoma: from the MITF low state to ferroptosis sensitization.","authors":"Mengzhen Chen, Yi Wu, Muxin Zhao","doi":"10.3389/fmolb.2026.1948743","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1948743","url":null,"abstract":"<p><p>Melanoma's ability to progress and develop resistance to therapies are the result of both genotypic changes and substantial levels of adaptability at the phenotypic and metabolic level. One of the most clinically relevant adaptive states is the microphthalmia associated transcription factor MITF low, which has been correlated with de-differentiation, invasion potential and drug tolerance, as well as altered redox status. As important regulators of this adaptation, lipid droplets have become involved in coordinating fat stores and mobilization, organelle signaling, membrane lipid composition and protection against oxidative stress. However, their role is context-dependent. For example, under certain melanoma conditions lipid droplets are able to isolate poly-unsaturated fatty acids (PUFA) from membrane phospholipids thus preventing ferroptosis. Under other conditions lipid droplet degradation through processes such as lipolysis, lipophagy or inter organelle lipid transfer results in the release of potentially oxidizable substrates increasing ferroptotic sensitivity. This review describes the impact of MITF-loss on melanoma cell lipid acquisition, desaturation, triglyceride synthesis and fatty acid oxidation, as well as phospholipid remodeling, antioxidant defense mechanisms and iron compartmentalization. An emphasis is placed on understanding the roles of several enzymes including DGAT1/2, SCD1, ACSL3, ACSL4, LPCAT3, MBOAT1/2, CPT1A, ACOX1, GPX4, FSP1 and lysosome-mitochondrial iron trafficking in defining whether melanoma cells are susceptible to or resistant to ferroptotic cell death. Additionally, this review provides an overview of clinical approaches that target protective lipid droplet programs, enhance membrane PUFA content, block compensatory fatty acid oxidation pathways and/or compromise ferroptosis-defensive systems. A major conclusion from this review is that the MITF low state is not uniformly ferroptotic; rather susceptibility depends upon a balance among lipid sequestration, membrane remodeling, oxidative metabolism, antioxidant defenses and cellular iron content. Identifying these state-specific metabolic requirements should provide a rationale for developing biomarker guided combinations of MAPK targeted therapy and immunotherapy-based treatments to selectively kill persistent populations of melanoma.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1948743"},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13662471/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149192778","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Cancer biomarkers: molecular insights into diagnosis, prognosis, and risk prediction: volume II.","authors":"Matteo Becatti, Giuseppe Bronte, Shaoquan Zheng","doi":"10.3389/fmolb.2026.1999668","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1999668","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1999668"},"PeriodicalIF":4.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13661436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Understanding the strengths and limitations of recombinant protein studies.","authors":"Daniele Dell'Orco, Karl-Wilhelm Koch","doi":"10.3389/fmolb.2026.1927411","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1927411","url":null,"abstract":"<p><p>Recombinant proteins are the workhorse of modern biochemical research, yet their use <i>in vitro</i> is routinely questioned on grounds of physiological relevance. Here we provide a structured guide to the strengths and limitations of recombinant protein studies, framed within the broader contrast between systemic (top-down) and reductionist (bottom-up) approaches to biological questions. We examine the main sources of concern. These are incorrect or incomplete folding, missing or aberrant post-translational modifications, the absence of native cofactors, the consequences of purification, and the lack of cellular crowding. Each of them is an experimentally measurable property rather than an assumption to be conceded. Against these we set the corresponding strengths: molecular-level resolution, well-defined interaction studies, and access to biophysical techniques that require purified material. The guide is organized around three practical tools, designed to be used in sequence: a comparison of expression hosts, a minimum checklist for validating a preparation before quantitative use, and a troubleshooting table for when a check fails. We argue that recombinant proteins are best understood not as a substitute for physiological studies but as a bridge between <i>in silico</i>, <i>in vitro</i>, and <i>in vivo</i> research.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1927411"},"PeriodicalIF":4.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180476","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telomeric autophagy in human health, aging, and diseases.","authors":"Xingyao Li, Xili Wu","doi":"10.3389/fmolb.2026.1922188","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1922188","url":null,"abstract":"<p><p>Telomeres are repetitive DNA sequences that cap chromosome ends and protect genomic stability. The term \"telomeric autophagy\" has been applied to the relationship between telomere dysfunction and autophagy, but it has been used to describe two processes that are not equivalent, and much of the confusion in this literature follows from conflating them. The first is the induction of autophagy by dysfunctional telomeres. This is established: during replicative crisis, telomeric damage generates cytosolic chromatin fragments that activate cGAS-STING signalling and engage the autophagy machinery, an induction specific to telomeric damage and not produced by intrachromosomal breaks, and one that has been independently reproduced in cells maintaining telomeres through alternative lengthening. The second is the selective autophagic degradation of telomeric chromatin itself. For this we were unable to identify direct evidence: no receptor bridging telomeric chromatin to ATG8-family proteins has been described, telomeric cargo has not been recovered from autolysosomes, and no compound acts selectively on the process. This review therefore separates the two throughout, grades the evidence for each claim it makes, and applies the same grading to the disease literature, where cancer emerges as the only setting in which telomeric and autophagic endpoints have been measured in the same system. Its aim is to establish what is known with confidence, what rests on inference, and what would have to be shown for telomere-selective autophagy to be regarded as a pathway. Telomeric autophagy; telomere; aging; cellular senescence; autophagy; cancer; neurodegenerative diseases.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1922188"},"PeriodicalIF":4.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13658900/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180442","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating arginine-nitric oxide pathway metabolites and nitrated fatty acids in relation to pathological features of colorectal cancer.","authors":"Jakub Klekowski, Paulina Fortuna, Łukasz Lewandowski, Gabriela Maciejewska, Wioleta Szewczak, Karolina Mosna, Marek Zawadzki, Mariusz Chabowski, Mariusz Fleszar","doi":"10.3389/fmolb.2026.1910147","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1910147","url":null,"abstract":"<p><strong>Introduction: </strong>Colorectal cancer (CRC) is associated with metabolic and inflammatory disturbances, including alterations in the arginine-nitric oxide (NO) pathway. This study assessed serum metabolites related to the arginine-NO-nitrated fatty acid (NO₂-FA) axis in patients with CRC and examined their associations with tumor stage and pathological features.</p><p><strong>Methods: </strong>A total of 122 patients undergoing colorectal resection for CRC were prospectively enrolled, of whom 117 had complete measurements for the candidate-metabolite panel and were included in the analyses. Preoperative serum samples were analyzed using targeted LC-MS/MS. Associations between metabolite concentrations and tumor stage were evaluated using complementary exploratory modelling approaches, including ordinal regression for TNM stage, tumor extent (T), and nodal involvement (N), as well as binary logistic regression for advanced disease (TNM III-IV), angioinvasion, and neuroinvasion.</p><p><strong>Results: </strong>Among the analyzed metabolites, SDMA showed the most recurrent inverse association with pathological disease stage in the initial models. However, these associations attenuated after adjustment for age and sex and were further weakened after additional adjustment for serum creatinine, with all fully adjusted 95% confidence intervals (CIs) including unity. Thus, the observed SDMA pattern was not independent of renal function and should be regarded as hypothesis-generating rather than as a convincing stage-associated metabolic signal. In a complementary binary analysis of TNM stages III-IV versus I-II, an inverse association with SDMA persisted after adjustment only under the stepwise selection strategy. Lower agmatine concentrations were associated with higher T category under the elastic-net strategy. Under the stepwise strategy, higher ADMA concentrations were associated with lower odds of angioinvasion and neuroinvasion, whereas higher citrulline concentrations were associated with higher odds of neuroinvasion. These invasive-feature associations were not reproduced under the elastic-net strategy and should therefore be considered procedure-dependent exploratory findings. No clear association was detected between circulating nitrooleates and the analyzed pathological outcomes.</p><p><strong>Discussion: </strong>These exploratory findings identify preliminary stage-associated metabolic patterns within patients with CRC and require validation in independent cohorts.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1910147"},"PeriodicalIF":4.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657980/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Editorial: Metabolomic analysis of plant matrices: identification of compounds of therapeutic and nutraceutical interest.","authors":"Mariacaterina Lianza, Victor Aguilar-Hernández","doi":"10.3389/fmolb.2026.1996217","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1996217","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1996217"},"PeriodicalIF":4.4,"publicationDate":"2026-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13657960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: Butyrate suppresses glucose metabolism of colorectal cancer cells via GPR109a-AKT signaling pathway and enhances chemotherapy.","authors":"","doi":"10.3389/fmolb.2026.1993113","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1993113","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1993113"},"PeriodicalIF":4.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13655526/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164752","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-order chromatin structures mediated by phase separation in cell senescence.","authors":"Wenjing Sun, Boxian Li, Zhaoyong Xu, Jing Wang, Jing Cao, Yangzhong Wang, Jiale Wang, Wenbo Gu, Pengjun Xu, Liang Wang, Wenyan Xie","doi":"10.3389/fmolb.2026.1896884","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1896884","url":null,"abstract":"<p><p>Liquid-liquid phase separation (LLPS) coordinates biomolecular condensates to establish three-dimensional chromatin architecture and epigenetic regulation. The progressive loss of epigenetic information is a fundamental, reversible driver of cellular senescence. In this review, we systematically synthesize emerging evidence on the spatiotemporal dynamics of LLPS-mediated chromatin compartmentalization during the aging process. We highlight how age-dependent alterations in histone, RNA, and DNA modifications disrupt multivalent interactions, leading to constitutive heterochromatin dissolution, aberrant transcriptional condensate formation, and nucleolar expansion. Furthermore, biomolecular condensates undergo age-dependent biophysical maturation-shifting from dynamic liquid states to solid-like aggregates-which dictates structural chromatin erosion and topologically associating domain (TAD) fusion. These diverse biophysical defects can be consolidated within a unified \"condensatopathy\" framework, encompassing both loss-of-function failures and toxic gain-of-function protein aggregations across somatic aging, stem cell exhaustion, and neurodegeneration. Understanding how phase separation regulates higher-order chromatin structures provides profound insights into aging trajectories. Ultimately, selectively modulating the material properties of biomolecular condensates, rather than merely dissolving them, offers a transformative precision therapeutic paradigm to restore epigenetic fidelity and counteract age-related diseases.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1896884"},"PeriodicalIF":4.4,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149180460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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 computational investigation of <i>Glycosmis pentaphylla</i>-derived compounds against major venom proteins of <i>Daboia russelii</i>.","authors":"Sana S Hussain, Danie J Kingsley","doi":"10.3389/fmolb.2026.1906533","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1906533","url":null,"abstract":"<p><p>Snakebite envenomation remains a significant neglected tropical disease, particularly in South Asia, where <i>Daboia russelii</i> (Russell's viper) causes substantial morbidity and mortality. Current antivenom therapy is limited by poor efficacy against local tissue damage, high production costs, restricted toxin specificity, and adverse immune reactions, highlighting the need for alternative or adjunct therapeutic strategies. Using an integrated computational and experimental approach, phytocompounds identified from <i>Glycosmis pentaphylla</i> leaf extracts were evaluated as potential inhibitors of major venom proteins. A total of 32 compounds identified by GC-MS were screened against phospholipase A₂ (PLA₂), snake venom metalloproteinases (SVMPs), snake venom serine proteases (SVSPs), L-amino acid oxidase (LAAO), and snake C-type lectin-like proteins (SNACLECs) using molecular docking. Representative high-affinity protein-ligand complexes were further evaluated by 100 ns molecular dynamics simulations. Pharmacokinetic, toxicity, protein-protein interaction, and pathway enrichment analyses were also performed to assess the therapeutic potential of the identified compounds. Preliminary experimental validation was conducted using trypsin-casein protease inhibition, skim milk agar protease inhibition, and erythrocyte membrane stabilization assays. Compared with N-acetyl cysteine (NAC), β-sitosterol, 3-chloro-5-cholestene, and vitamin E exhibited stronger binding affinities and more stable interactions with multiple venom proteins. Molecular dynamics analyses (RMSD, RMSF, radius of gyration, solvent-accessible surface area, and hydrogen bonding) further supported the stability of the selected protein-ligand complexes. Pharmacokinetic and toxicity predictions indicated acceptable drug-likeness and comparatively safe toxicity profiles for most selected compounds. STRING-based protein-protein interaction and pathway enrichment analyses revealed associations with inflammatory, coagulation, oxidative stress, and extracellular matrix-related pathways involved in venom pathology. The <i>G. pentaphylla</i> extract demonstrated concentration-dependent protease inhibition (56.86% at 5 mg/mL), reduced caseinolytic activity (28.19% inhibition), and significant erythrocyte membrane stabilization (39.23%), providing preliminary experimental support for the computational predictions. Overall, these findings identify <i>G. pentaphylla</i>-derived phytocompounds as potential lead compounds for future antivenom development and provide a computational foundation for subsequent venom-specific biochemical and <i>in vivo</i> validation toward safer and more affordable adjunct therapies for snakebite management.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1906533"},"PeriodicalIF":4.4,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13649486/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149165423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}