Frontiers in Molecular Biosciences最新文献

{"title":"Editorial: Adoption of artificial intelligence in human and clinical genomics: volume II.","authors":"Li Zhang, Matteo Becatti","doi":"10.3389/fmolb.2026.1949944","DOIUrl":"https://doi.org/10.3389/fmolb.2026.1949944","url":null,"abstract":"","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1949944"},"PeriodicalIF":4.4,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526459/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864166","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":"Molecular dynamics analysis of a docking-derived baicalein-PPARγ ligand-binding-domain model suggests a pocket-associated AF-2-anchor-silent ensemble.","authors":"Xingyuan Kou, Ping Wu, Zhuo Liu, Jing Yan, Le Li","doi":"10.3389/fmolb.2026.1870075","DOIUrl":"10.3389/fmolb.2026.1870075","url":null,"abstract":"<p><p>Baicalein was examined in a selected docking-derived peroxisome proliferator-activated receptor γ (PPARγ) ligand-binding-domain (LBD) model to test whether pocket association, local helix 12 (H12) organization, and canonical activation function-2 (AF-2) anchoring were coupled under the sampled simulation conditions. Because no baicalein-bound PPARγ cocrystal structure was used, the results are interpreted as a selected-pose molecular dynamics model rather than as a definitive experimental binding mode. Three independent 100-ns replicas were analyzed with bound-state filtering, H12 and AF-2 descriptors, arm-resolved energetic decomposition, interaction fingerprints, a local Tyr473-engagement potential of mean force (PMF), and exploratory state annotation. Baicalein remained spatially associated with the ligand-binding pocket by the minimum-distance and center-of-mass criteria, whereas pocket-shell contact persistence was replica-dependent, with retained fractions of 94.20%, 94.00%, and 71.64% in replicas 1-3. Within bound-state-filtered frames and under the selected neutral baicalein/HIE histidine model, direct ligand hydrogen bonds to Ser289, His323, His449, and Tyr473 were not detected, and the AF-2 anchor-panel union occupancy was 0.00%. This anchor-negative pattern occurred despite measurable local H12 order, indicating that local H12 structural persistence and canonical AF-2 anchor assembly were separable in the selected model. Arm-resolved molecular mechanics/generalized Born surface area (MM/GBSA) descriptors and ProLIF fingerprints supported mixed Arm II/Arm III participation, with recurrent van der Waals contacts involving Cys285, Ile341, Leu330, Leu333, Arg288, and Ile326. The local Tyr473 PMF favored a displaced baicalein geometry, with a minimum at 0.66 nm along the Tyr473 hydroxyl-to-ligand-acceptor coordinate. Limited ligand-protonation and His323/His449-tautomer sensitivity screens did not recover persistent canonical AF-2 anchoring under the tested short-screen conditions. Exploratory state analysis resolved in-pocket heterogeneity but did not identify a descriptor-supported state with persistent canonical AF-2 anchoring. These simulations support a constrained structural model in which baicalein samples a pocket-associated, measurably H12-organized, anchor-negative PPARγ ensemble stabilized by non-canonical pocket interactions. The interpretation is limited to simulation descriptors and does not establish receptor activation, partial agonism, phosphorylation regulation, or transcriptional output.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1870075"},"PeriodicalIF":4.4,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13526570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864251","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":"Late-onset mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes with chronic intestinal pseudo-obstruction: a case-based review.","authors":"Lin Zhang, Junjian Lin, Fengying Li, Yujie Jia, Junhua Li, Xiaopeng Wang","doi":"10.3389/fmolb.2026.1857438","DOIUrl":"10.3389/fmolb.2026.1857438","url":null,"abstract":"<p><strong>Background: </strong>Mitochondrial Encephalomyopathy Lactic Acidosis and Stroke-like episodes (MELAS) is rare in people over 40 years of age, and gastrointestinal complications of MELAS are also rare, especially Chronic Intestinal Pseudo-Obstruction (CIPO).</p><p><strong>Case presentation: </strong>This report describes a 60 years old MELAS patient with a mutation rate of only 6.29% in the m.3243A>G gene, accompanied by CIPO. After treatment, MELAS symptoms can be controlled, but intestinal obstruction recurs and worsens. At present, patients fast and rely on intravenous nutrition to sustain their lives.</p><p><strong>Discussion: </strong>The low proportion of m.3243A>G mutations in patients may be related to their advanced age, but the high or low proportion of gene mutations detected in blood samples is not related to the severity of symptoms. MELAS combined with CIPO is rare and different from other intestinal obstructions. CIPO has no cause of mechanical intestinal obstruction and may be related to dysfunction of smooth muscle mitochondria or involvement of the enteric nervous system.</p><p><strong>Conclusion: </strong>For complications of MELAS beyond the nervous system, early consideration should be given to the possibility of MELAS. Early genetic testing has important clinical significance for the treatment and prognosis of patients. This article will provide a literature review on the multi system performance of MELAS.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1857438"},"PeriodicalIF":4.4,"publicationDate":"2026-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522698/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148850205","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":"Regulation of TMEM2-mediated hyaluronan degradation by CD44 and LYVE-1.","authors":"Yuki Tobisawa, Fumiakira Yano, Risa Tomioka-Inagawa, Fumitoshi Irie, Takuya Koie, Yu Yamaguchi","doi":"10.3389/fmolb.2026.1852012","DOIUrl":"10.3389/fmolb.2026.1852012","url":null,"abstract":"<p><p>Hyaluronan (HA) is a major glycosaminoglycan of the extracellular matrix that regulates cell migration, signaling, and tissue homeostasis. Its turnover is controlled by coordinated synthesis by HA synthases and degradation by hyaluronidases. Among these hyaluronidases, TMEM2, the only known transmembrane hyaluronidase, plays a unique role in HA degradation at the cell surface; however, the cellular conditions that support its activity remain incompletely understood. To address this, we developed a cell-based HA turnover assay to examine TMEM2-mediated degradation of endogenously synthesized HA, rather than exogenously added, fluorescently labeled HA used in previous studies. Using this system, we show that TMEM2 readily degrades high-molecular weight HA synthesized by co-expressed HAS3. This degradation occurs only when TMEM2 and HAS3 are co-expressed in the same cells (<i>cis</i>), whereas co-culture of TMEM2-expressing cells with HAS3-expressing cells supports little or no degradation. Interestingly, HA-binding cell surface receptors CD44 and its homolog LYVE-1 promote efficient TMEM2-mediated HA degradation even under <i>trans</i> conditions, whereas other HA-binding proteins, including TSG-6, layilin, TLR2, RHAMM, and ICAM-1, do not. These findings suggest a spatially regulated mechanism of TMEM2 activity in which capture of HA at the cell surface, mediated by CD44 or LYVE-1, contributes to efficient HA degradation by TMEM2.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1852012"},"PeriodicalIF":4.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826549","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":"Serum vitamins and microelements levels and their association with children with attention deficit hyperactivity disorder (ADHD).","authors":"Tianzhu Chen, Jiaxiong Yao, Yang Su, Jingya Li, Panli Tan","doi":"10.3389/fmolb.2026.1786113","DOIUrl":"10.3389/fmolb.2026.1786113","url":null,"abstract":"<p><strong>Background: </strong>Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders in children. The impact of environmental factors on ADHD is very important. Therefore, we analyzed and measured the correlation between the serum vitamin and microelement levels of Chinese children and the incidence rate of ADHD, hoping to provide some guidance for the prevention, diagnosis and treatment of ADHD.</p><p><strong>Methods: </strong>128 children (69 boys and 59 girls, with an average age of 9.38 ± 2.5 years) were diagnosed with ADHD. In addition, 133 healthy children were recruited as the healthy control group (HC). The levels of serum vitamins and elements were determined by liquid chromatography-mass spectrometry (LC-MS) and inductively coupled plasma mass spectrometry (ICP-MS). Use statistical analysis to compare the differences in the content of two groups of indicators and analyze their correlation with ADHD.</p><p><strong>Results: </strong>Compared with the healthy control group (HC group), children with ADHD exhibited significantly lower levels of serum vitamin A, vitamin D and vitamin D₃, while the levels of lead and copper were also significantly elevated. Logistic regression analysis indicated a negative correlation between vitamin D levels and ADHD.</p><p><strong>Conclusion: </strong>Children with ADHD exhibit significantly lower serum VD levels and higher Pb levels (only in boys), suggesting VD deficiency and sex-specific Pb susceptibility may be key factors associated with ADHD.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1786113"},"PeriodicalIF":4.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506877/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826625","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":"EMCN is associated with vascular-immune crosstalk and represents a potential biomarker in lung adenocarcinoma.","authors":"Yan Zhuang, Qingfeng Wang, Kaimin Wei, Fangjuan Wei, Xiaowei Yao, Yongliang Wang","doi":"10.3389/fmolb.2026.1752442","DOIUrl":"10.3389/fmolb.2026.1752442","url":null,"abstract":"<p><strong>Background: </strong>While MUC family genes have been established as prognostic biomarkers in gastric cancer, and GWAS studies link EMCN mutations to chemotherapy-induced myelosuppression in NSCLC, the systematic characterization of EMCN in lung adenocarcinoma (LUAD) remains elusive.</p><p><strong>Methods: </strong>This multi-omics strategy combining bulk and single-cell transcriptomics study integrated differential expression analysis, WGCNA, and machine learning algorithms (LASSO/SVM-RFE/Random Forest) to identify EMCN as a diagnostic hub gene, followed by experimental validation using immunohistochemistry Western blot and qRT-PCR.</p><p><strong>Results: </strong>EMCN (Endomucin) is a sialomucin-like glycoprotein predominantly expressed in vascular endothelial cells. Using bulk transcriptomic datasets and single-cell RNA-seq analysis, we found that EMCN expression was reduced in lung adenocarcinoma (LUAD) compared with non-tumor controls and was primarily localized to the endothelial compartment. Survival analysis using the median expression cutoff showed that high EMCN expression was associated with improved overall survival (Cox HR_high vs. low = 0.73, p = 0.04), indicating that low EMCN expression correlates with poorer prognosis. Machine learning-based feature selection (LASSO, Random Forest, and SVM) further prioritized EMCN among consensus candidate genes, supporting its potential relevance to the vascular-associated tumor microenvironment in LUAD. EMCN expression levels also showed a significant positive correlation with the degree of immune cell infiltration. Gene set enrichment analysis (GSEA) revealed that high EMCN expression in tumor tissues activates negative regulatory pathways associated with angiogenesis. Receiver operating characteristic (ROC) curve analysis highlights EMCN's excellent diagnostic potential for LUAD, with an area under the curve (AUC) of 0.963. <i>In vitro</i> experiments confirm the downregulation of EMCN at both protein and mRNA levels, consistent with our bioinformatics predictions.</p><p><strong>Conclusion: </strong>This first comprehensive study establishes EMCN as a dual-functional regulator of vascular-immune crosstalk in LUAD, providing both a molecular diagnostic tool and therapeutic target for precision oncology.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1752442"},"PeriodicalIF":4.4,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13506425/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148826526","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":"Exploring the toxicity of extracts, fractions, and their bioactive components from raw and roasted sea buckthorn seeds on selected human cells.","authors":"Natalia Sławińska, Michał Juszczak, Katarzyna Woźniak, Beata Olas","doi":"10.3389/fmolb.2026.1898968","DOIUrl":"10.3389/fmolb.2026.1898968","url":null,"abstract":"<p><strong>Introduction: </strong>With cancer being one of the leading causes of death worldwide, research into new chemical compounds that could be used in its prevention and treatment is of utmost importance. Plants are rich in diverse active compounds and can be a source of effective anticancer agents. Sea buckthorn (<i>Hippophae rhamnoides</i> L.) is a promising plant that shows anti-proliferative potential; however, its molecular mechanisms remain unclear. Isorhamnetin glycosides (including isorhamnetin 3-<i>O</i>-β-glucoside-7-<i>O</i>-α-rhamnoside) are major components of sea buckthorn seeds; multiple studies showed that isorhamnetin possesses anticancer properties, however, the activity of its many derivatives remains unclear. On the other hand, sea buckthorn seeds also contain serotonin (5-HT), which might stimulate the growth of several types of cancer.</p><p><strong>Methods: </strong>Our present study assessed the <i>in vitro</i> cytotoxicity and genotoxicity of two extracts (from raw and roasted seeds), seven fractions (three fractions (a, b, and c) from raw sea buckthorn seeds and four fractions (d, e, f, and g) from roasted sea buckthorn seeds), and two chemical compounds (isorhamnetin 3-<i>O</i>-β-glucoside-7-<i>O</i>-α-rhamnoside, and serotonin) toward PBMC (peripheral blood mononuclear cells), HL-60 (human acute promyelocytic leukemia), and A549 (human lung adenocarcinoma) cells. Their pro-apoptotic potential, toxicity toward blood platelets, and effect on ROS generation were assessed as well.</p><p><strong>Results and discussion: </strong>Fraction b (containing mostly flavonol glycosides) had the most promising anticancer activity out of all the tested samples - at the concentration of 50 μg/mL, it decreased the viability of HL-60 cells through the induction of apoptosis. At the same time, it was safe for PBMC and blood platelets. On the other hand, fraction c (that contained serotonin, B-type proanthocyanidins, and other compounds) stimulated A549 cells and, therefore, should be treated with caution. Fractions from roasted seeds were overall weaker than fractions from raw seeds, suggesting that thermal processing might have reduced their activity. In conclusion, fraction b from raw sea buckthorn seeds showed anticancer potential against HL-60 cells, but it should be studied further to determine the activity of individual compounds contained within, their mechanisms of action, and efficiency <i>in vivo</i>.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1898968"},"PeriodicalIF":4.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503588/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817840","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":"Adaptive-to-maladaptive IRE1α signaling as a driver of amyloidogenic APP processing in Alzheimer's disease.","authors":"Daniel Wang, Qinan Yin","doi":"10.3389/fmolb.2026.1903849","DOIUrl":"10.3389/fmolb.2026.1903849","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is increasingly recognized as a disorder of proteostatic failure characterized by progressive disruption of neuronal protein quality control, culminating in amyloid-β (Aβ) accumulation and synaptic dysfunction. Chronic activation of the endoplasmic reticulum (ER) stress response represents one of the earliest molecular alterations detected in vulnerable brain regions and correlates with Braak progression before overt plaque deposition. Inositol-requiring enzyme 1 alpha (IRE1α), the most evolutionarily conserved sensor of the unfolded protein response (UPR), functions as a signaling rheostat within this network through its divergent downstream outputs. Under moderate proteotoxic stress, adaptive IRE1α- X-box binding protein 1 (XBP1) signaling supports ER proteostasis, preserves amyloid precursor protein (APP) quality control, and favors non-amyloidogenic α-secretase processing. Persistent ER stress, however, drives sustained IRE1α hyperactivation and engages regulated IRE1α-dependent decay (RIDD), which destabilizes microRNA (miRNA) networks that normally constrain beta-site APP-cleaving enzyme 1 (BACE1) expression, thereby favoring amyloidogenic APP processing. Accumulating evidence suggests that aging progressively compromises ER proteostatic capacity, thereby redirecting IRE1α signaling away from adaptive XBP1s-mediated responses toward a predominantly RIDD-driven state. This shift may reinforce a self-sustaining cycle in which accumulating Aβ further amplifies ER stress signaling. Here, we examine how dynamic changes in IRE1α signaling bias contribute to amyloidogenic progression in AD and consider whether selective modulation of adaptive versus maladaptive IRE1α outputs may offer stage-dependent therapeutic benefit.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1903849"},"PeriodicalIF":4.4,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13503739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148817868","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":"Combination treatment with intravesical interferon-alpha gene therapy and an oral pan-ErbB receptor family blocker improves survival in mice with bladder cancer.","authors":"Akshay Sood, Alberto Martini, Paulo Genitiano, Mikael Rauf, Ganiraju Manyam, Jan K Rudzinski, Come Tholomier, Roberto Contieri, I-Ling Lee, Nigel R Parker, Seppo Yla-Herttuala, David J McConkey, Colin P N Dinney, Sharada Mokkapati","doi":"10.3389/fmolb.2026.1804161","DOIUrl":"10.3389/fmolb.2026.1804161","url":null,"abstract":"<p><strong>Introduction: </strong>Intravesical interferon-alpha (IFNα) gene therapy is approved by the FDA for BCG-unresponsive non-muscle invasive bladder cancer (NMIBC). Identifying resistance mechanisms and deploying targeted combination treatment strategies is a rational approach to improving treatment responses. We identified the ErbB pathway as a resistance mechanism to IFNα gene therapy, and we hypothesized that combination treatment with an ErbB pathway blocker and IFN-α could improve outcomes in resistant tumors.</p><p><strong>Methods: </strong>Murine bladder cancer cells were treated <i>in vitro</i> with lentiviral IFNα (LV-IFNα) gene therapy, with/without afatinib (Afa), a pan-ErbB inhibitor, and cell viability and migration assays were performed. <i>In vivo</i> studies were conducted in a syngeneic MB49 orthotopic murine bladder cancer model, and mice were randomized into five treatment groups and treated with single treatments: Ctrl (vehicle), LV-Ctrl, LV-IFNα, and combination treatments with LV-Ctrl/Afa or LV-IFNα/Afa.</p><p><strong>Results: </strong>Combination therapy with LV-IFNα/Afa significantly reduced MB49 cell viability <i>in vitro</i> compared to all other treatment conditions. This additive effect on cell viability appeared to be driven by a combination of early-cytostatic and late-cytolytic effects. The combination treatment also markedly inhibited cell migration. Finally, the <i>in vivo</i> studies demonstrated improved overall survival (OS) with LV-IFNα/Afa (median OS was 49 days in the LV-IFNα/Afa group vs. 15, 14, 29, and 26 days in Ctrl, LV-Ctrl, LV-IFNα, and LV-Ctrl/Afa groups, respectively; log-rank <i>p</i> < 0.001).</p><p><strong>Conclusion: </strong>Our findings suggest that the ErbB pathway may serve as a clinically actionable resistance mechanism to intravesical IFNα gene therapy and, when targeted concurrently, it may improve treatment efficacy.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1804161"},"PeriodicalIF":4.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13500216/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812332","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":"Regulatory T cells in the bladder cancer tumor microenvironment: mechanisms of immune suppression and therapeutic opportunities.","authors":"Yusuke Fukiage, Nodoka Okubo, Minekatsu Taga, Yohei Sato, Naoki Terada","doi":"10.3389/fmolb.2026.1898769","DOIUrl":"10.3389/fmolb.2026.1898769","url":null,"abstract":"<p><p>Bladder cancer is characterized by a highly dynamic tumor microenvironment (TME) that critically influences tumor progression, immune evasion, and therapeutic responsiveness. Among the immune populations in the TME, regulatory T cells (Tregs) play a central role in maintaining immune tolerance but also suppress effective antitumor immunity. Increasing evidence suggests that Tregs accumulate in bladder tumors and are associated with disease progression and reduced response to immunotherapies. The bladder cancer TME provides multiple signals that promote Treg recruitment, expansion, and functional stabilization, including chemokine-mediated trafficking, metabolic adaptation, and cytokine-driven differentiation. Interactions between Tregs and other microenvironmental components, such as cancer-associated fibroblasts, tumor-associated macrophages, endothelial cells, and extracellular matrix elements, further reinforce the immunosuppressive niche that facilitates tumor survival and therapy resistance. Recent advances in single-cell transcriptomics, spatial profiling, and multiomics analyses have revealed substantial heterogeneity among tumor-infiltrating Tregs, suggesting the existence of specialized subsets with distinct functional and metabolic properties in the bladder TME. These emerging insights highlight the importance of understanding Treg-TME crosstalk in shaping the immune landscape of bladder cancer. Targeting the mechanisms regulating Treg recruitment, stability, or suppressive function may represent a promising strategy to enhance the efficacy of immunotherapies including <i>Bacillus</i> Calmette-Guérin therapy. This review summarizes recent advances in Treg biology in bladder cancer and highlights potential therapeutic strategies to modulate Treg-mediated immunosuppression in the TME.</p>","PeriodicalId":12465,"journal":{"name":"Frontiers in Molecular Biosciences","volume":"13 ","pages":"1898769"},"PeriodicalIF":4.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13501578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148812359","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}