Biomedicines最新文献

{"title":"Molecular Classifications and Candidate Biomarkers for Personalizing BCG Therapy in Non-Muscle-Invasive Bladder Cancer.","authors":"Airat Bilyalov, Andrey Kotov, Natalia Bodunova, Maxim Zingerenko, Igor Khatkov, Ludmila Zhukova","doi":"10.3390/biomedicines14092098","DOIUrl":"10.3390/biomedicines14092098","url":null,"abstract":"<p><p>Intravesical Bacillus Calmette-Guérin (BCG) remains the standard adjuvant treatment for intermediate- and high-risk non-muscle-invasive bladder cancer. However, 30-50% of patients fail to respond or experience recurrence within two years, while clinical and pathological risk models have limited accuracy in predicting individual response. This narrative review summarizes molecular classifications and candidate biomarkers associated with BCG response and assesses their potential clinical utility, based on a focused search of PubMed, Scopus, and Web of Science through July 2026, supplemented by ClinicalTrials.gov, regulatory documents, and current guidelines. Transcriptomic classifications, including UROMOL2021, BCG Response Subtypes (BRS), MSP888, and subtypes defined in stage T1 disease, identify tumor phenotypes associated with differences in recurrence, progression, and outcomes after BCG. <i>BRS3</i> is characterized by basal-squamous and immunosuppressive features and is associated with shorter recurrence-free and progression-free survival. Genomic alterations, including <i>FGFR3</i> and <i>TERT</i> promoter mutations and <i>APOBEC</i> signatures; DNA methylation markers such as <i>GATA2</i>, <i>TBX3</i>, and <i>GPR158</i>; and tumor microenvironment features, including regulatory T cells, exhausted CD8+ T cells, and PD-L1 expression, have been associated with outcomes in individual cohorts but remain unvalidated as treatment-specific predictors. Bladder-preserving options for BCG-unresponsive disease include pembrolizumab, nadofaragene firadenovec, nogapendekin alfa inbakicept-pmln with BCG, and the gemcitabine intravesical system. Randomized trials adding checkpoint inhibition to BCG in BCG-naive disease have reported inconsistent results. No molecular biomarker is currently validated for treatment selection. Molecular profiling remains investigational and may complement, but not replace, established clinical risk assessment. Clinical implementation requires prospective biomarker-stratified trials with standardized definitions, assays, and endpoints.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604516/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting Metabolic Pathways to Direct T-Cell Trafficking: Therapeutic Perspectives.","authors":"Xiayinan Song, Shengxuan Zhao, Weiheng Zhang, Yan Wang, Fengjie Zheng","doi":"10.3390/biomedicines14092100","DOIUrl":"10.3390/biomedicines14092100","url":null,"abstract":"<p><p>Despite advances in immunomodulatory therapies, dysregulated T-cell trafficking persists as a pathological cornerstone in chronic inflammation, autoimmunity, and cancer. This spatially precise navigation-orchestrated by receptor-ligand cascades-ensures immune surveillance but drives disease when impaired. Targeting individual receptors faces limitations due to functional redundancy. Emerging research establishes metabolic reprogramming as a critical regulator of trafficking efficiency, where glucose, amino acid, lipid, and mitochondrial metabolism dynamically control all stages: from chemotaxis, selectin-mediated rolling, and integrin-dependent adhesion to transendothelial migration and interstitial migration. Critically, these pathways integrate energy supply, metabolite signaling, and epigenetic modulation to influence T-cell trafficking fates. Here, we dissect how reprogramming core metabolic networks calibrates trafficking cascades and highlight therapeutic strategies targeting key nodes to correct pathological migration in autoimmunity, cancer, and transplantation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058142","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Alleviates Endometriosis in Sexually Mature Female Mice by Targeting PKA and Inhibiting De Novo Estrogen Synthesis.","authors":"Haiyang Zhao, Xudong Chen, Sirui Zhang, Jieyi Zhang, Yueyuan Wang, Zhengrong Xia, Hui Wang, Zhaohui Xu","doi":"10.3390/biomedicines14092099","DOIUrl":"10.3390/biomedicines14092099","url":null,"abstract":"<p><p><b>Background:</b> Endometriosis is an estrogen-dependent disorder with limited treatment options. The precise molecular targets of curcumin and its effects on local estrogen synthesis in this disease remain unclear. <b>Methods:</b> We investigated curcumin's efficacy and mechanism via network pharmacology, in vitro functional assays in ectopic endometrial cells, an allogeneic mouse model, and target validation through molecular docking, thermal shift, and hydrolysis stability assays. <b>Results:</b> Curcumin significantly inhibited ectopic cell malignant phenotypes, reducing migration distance by 55.60 ± 7.32%, 80.34 ± 11.19%, and 82.88 ± 13.67% at 5, 10, and 15 μM, respectively, and decreasing invasive cell numbers by 40.38 ± 7.67%, 58.33 ± 12.70%, and 60.18 ± 9.07%, respectively (all <i>p</i> < 0.05). In a mouse model, curcumin (200 mg/kg/day) reduced lesion number by 38.46% (2.167 ± 0.752 vs. 1.333 ± 0.516, <i>p</i> = 0.0493) and lesion volume by 59.73% (0.0497 ± 0.0173 vs. 0.0200 ± 0.0130 mm³, <i>p</i> = 0.00732). It also suppressed de novo estrogen synthesis and modulated the estrogen receptor α (ERα) and β (ERβ) ratio. Mechanistically, curcumin directly bound to and inhibited protein kinase A (PKA), a key kinase in the cAMP signaling pathway. <b>Conclusions:</b> We first demonstrate that curcumin alleviates endometriosis by targeting PKA to inhibit local estrogen synthesis, identifying PKA as a novel therapeutic target and curcumin as a promising treatment candidate.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced External Counterpulsation Versus Standard Medical Therapy for Chronic Refractory Angina: A Systematic Review and Meta-Analysis.","authors":"Praneeth Ulavala, Maruf Sarwar, Utkrash Mishra, Stephen Deji Adedokun, Gilbert-Roy Kamoga","doi":"10.3390/biomedicines14092093","DOIUrl":"10.3390/biomedicines14092093","url":null,"abstract":"<p><p><b>Background:</b> Chronic refractory angina is a disabling syndrome of persistent ischemic symptoms despite guideline-directed medical therapy and, in many patients, prior coronary revascularization. Enhanced external counterpulsation [EECP] is a noninvasive therapy that augments diastolic coronary perfusion, reduces systolic afterload, improves endothelial function, and may promote collateral recruitment. Although developed for obstructive coronary artery disease, its vascular and microvascular effects may also be relevant to contemporary ischemic syndromes, including ischemia with non-obstructive coronary arteries [INOCA] and myocardial infarction with non-obstructive coronary arteries [MINOCA]. A contemporary quantitative synthesis of EECP across angina burden, functional capacity, quality of life, and safety is therefore warranted. <b>Methods:</b> We performed a systematic review and meta-analysis of randomized trials and prospective studies of adults with chronic refractory angina treated with EECP versus standard medical therapy, usual care, or sham EECP. Outcomes were Canadian Cardiovascular Society [CCS] angina class, nitroglycerin use, the 6 min walk test [6MWT], treadmill exercise testing, quality-of-life measures, adverse events, and treatment withdrawal. Because the eligible evidence combined sham-controlled randomized trials with single-arm and registry cohorts, pooled estimates were derived using random-effects models and are interpreted in that context. <b>Results:</b> Twenty-six studies were included. EECP was associated with improvement across every prespecified domain: CCS angina class [standardized mean difference [SMD] -1.56; 95% confidence interval [CI], -2.54 to -0.58; <i>p</i> = 0.002], nitroglycerin use [SMD -2.41; 95% CI, -3.34 to -1.49; <i>p</i> < 0.00001], 6MWT [SMD 1.59; 95% CI, 0.64 to 2.54; <i>p</i> = 0.001], treadmill exercise testing [SMD 1.03; 95% CI, 0.15 to 1.91; <i>p</i> = 0.02], and quality of life [SMD 1.12; 95% CI, 0.71 to 1.53; <i>p</i> < 0.00001]. Heterogeneity was high for all pooled outcomes [I² ≥ 79%], and the largest effect sizes were driven substantially by uncontrolled before-after data. <b>Conclusions:</b> EECP is associated with statistically significant and clinically meaningful reductions in angina burden and nitrate use, with parallel improvements in objective exercise capacity and patient-reported quality of life among patients with chronic refractory angina. These findings support EECP as a reasonable adjunctive option for appropriately selected patients who remain symptomatic despite conventional treatment, while the magnitude of heterogeneity and the contribution of non-randomized data temper the certainty of the pooled estimates and underscore the need for standardized protocols, contemporary sham-controlled trials, and dedicated investigation in INOCA and MINOCA populations.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604707/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057905","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exosomes in Metabolic Bone Diseases: Regulators, Biomarkers and Targeted Delivery Systems.","authors":"Linxiao Wang, Xi Gao, Shasha Jiang, Yiran Zhang, Jiangang Xie, Haifan Yang, Yinghui Li, Lin Liu","doi":"10.3390/biomedicines14092092","DOIUrl":"10.3390/biomedicines14092092","url":null,"abstract":"<p><p><b>Background:</b> Metabolic bone diseases represent prevalent global disorders characterized by disrupted bone homeostasis and chronic inflammation. This review utilizes a broad working definition encompassing osteoporosis and other classic metabolic bone disorders, including osteoarthritis, a primarily degenerative joint disease marked by significant metabolic-driven subchondral bone remodeling. Conventional diagnostic modalities prove inadequate for early-stage disease screening, while classical pharmacological interventions face limitations due to unsatisfactory targeting performance and severe long-term adverse reactions. An urgent clinical need persists for innovative diagnostic biomarkers and targeted therapeutic strategies. Exosomes, a sub-population of small extracellular vesicles (sEVs), are natural nanoscale intercellular vesicles derived from multivesicular bodies, playing critical regulatory roles in bone metabolism and offering substantial clinical translational potential. This review systematically elaborates the regulatory networks associated with exosomes, the biomarker potential of exosomal non-coding RNAs, and advanced engineering modifications for bone-targeted delivery in metabolic bone diseases. <b>Methods:</b> This narrative review involved a literature search conducted across PubMed, Web of Science, Scopus, and Embase from inception to December 2025, focusing on exosome biology, metabolic bone disorders, non-coding RNA biomarkers, and engineered bone-targeted delivery. Inclusion criteria encompassed peer-reviewed English original and review articles, while conference abstracts, case reports, editorials, and non-English literature were excluded. Eighty-two eligible studies underwent thematic analysis without a formal systematic search protocol or preregistration. <b>Results:</b> Exosomes orchestrate osteogenic and osteoclastogenic processes through established bone-metabolic signaling cascades. Exosomal microRNAs and circular RNAs demonstrate promising diagnostic performance in exploratory observational cohorts for early-stage screening and prognostic assessment of metabolic bone diseases; however, large-scale multi-center clinical validation remains insufficient. Engineered exosomes facilitate precise local bone intervention in preclinical animal models, overcoming significant drawbacks of conventional therapies in experimental settings. Nevertheless, clinical translation is obstructed by non-standardized production workflows and unresolved biosafety risks. <b>Conclusions:</b> Exosomes present promising dual diagnostic and therapeutic potential to enhance precision and individualized management of metabolic bone diseases. Further technical refinement in exosome preparation and modification will expedite orthopedic clinical translation and improve patient outcomes in metabolic bone disorders.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057934","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Echinatin Ameliorates Insulin Resistance and Hepatic Lipid Accumulation in db/db Mice.","authors":"Hong Xu, Lijie Jiang, Yuanjun Zhang, Jingqing Hu","doi":"10.3390/biomedicines14092091","DOIUrl":"10.3390/biomedicines14092091","url":null,"abstract":"<p><p><b>Background:</b> Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by hyperglycemia, insulin resistance, hepatic steatosis, chronic inflammation, and oxidative damage. Echinatin (ECH), a naturally occurring chalcone compound, has shown potential metabolic regulatory activities, but its effects and underlying mechanisms in T2DM remain unclear. This study aimed to investigate the effects of ECH and its underlying mechanisms in db/db mice. <b>Methods:</b> Male db/db mice were orally administered ECH at low and high doses for 8 weeks. Glucose metabolism was evaluated by fasting blood glucose measurement and oral glucose tolerance test (OGTT). Insulin sensitivity was assessed by serum insulin levels and hepatic AKT phosphorylation. Pancreatic β-cell integrity was examined by insulin immunohistochemistry. Hepatic glucose metabolism-related genes, including <i>Pck1</i>, <i>G6pc</i>, <i>Gys1</i>, <i>Gys2</i>, <i>Gck</i>, and <i>Slc2a2</i>, were analyzed by quantitative PCR. Serum and hepatic lipid profiles, hepatic steatosis, inflammatory cytokines, and oxidative stress markers were also evaluated. <b>Results:</b> ECH treatment significantly reduced fasting blood glucose levels and improved glucose tolerance, as indicated by ECH-preserved pancreatic β-cell integrity and increased serum insulin levels. Furthermore, ECH enhanced hepatic insulin signaling, as demonstrated by an increased p-AKT/AKT ratio. At the transcriptional level, high-dose ECH significantly suppressed the expression of gluconeogenic genes <i>Pck1</i> and <i>G6pc</i>, while upregulating the glucose transporter gene <i>Slc2a2</i> without significantly altering <i>Gys1</i>, <i>Gys2</i>, or <i>Gck</i> expression. In addition, ECH reduced serum and hepatic triglyceride and total cholesterol levels, alleviated hepatic lipid accumulation by H&E and Oil Red O staining, and decreased circulating inflammatory cytokines (TNF-α and IL-1β) and oxidative markers (4-HNE and 8-OHdG). <b>Conclusions:</b> ECH treatment was associated with improvements in multiple metabolic parameters in db/db mice, including glucose homeostasis, insulin sensitivity, hepatic steatosis, and systemic inflammation and oxidative stress. These observations may provide a basis for further studies on the effects of ECH on T2DM-related glucose and lipid metabolism.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604247/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057947","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From Glycan Biology to Drug Candidates: An Integrated Sialylation Niche Index and AI-Guided Therapeutic Framework for Head and Neck Squamous Cell Carcinoma.","authors":"Wei Gu, Chuan Liu, Jinglei Li, Jian Wang","doi":"10.3390/biomedicines14092102","DOIUrl":"10.3390/biomedicines14092102","url":null,"abstract":"<p><p><b>Background:</b> Head and neck squamous cell carcinoma (HNSCC) responds poorly (<20%) to immune checkpoint blockade. Since sialylation suppresses anti-tumour immunity through Siglec signalling independently of the PD-L1/PD-1 axis, we mapped its prognostic landscape in HNSCC by integrating prognostic modelling, molecular subtyping, and AI-guided drug discovery. <b>Methods:</b> Transcriptomic data from seven GEO cohorts and TCGA-HNSC (<i>n</i> = 501) were analysed with a 1204-gene sialylation compendium. The Sialylation Niche Index (SNI) was built in TCGA-HNSC from 117 machine-learning algorithm combinations (nominally 101), with survival-based feature selection and model fitting confined to the training set; model selection used TCGA-HNSC and the external model-selection cohort GSE42743 (<i>n</i> = 74 with overall survival), and the three independent test cohorts were scored without re-fitting (E-MTAB-8588, <i>n</i> = 83; GSE65858, <i>n</i> = 270; and GSE41613, <i>n</i> = 97). Key model genes were characterised by single-cell RNA sequencing (168,742 cells), spatial transcriptomics, and AI-guided screening of 249,455 compounds. <b>Results:</b> Thirty-one prognostic sialylation-associated DEGs defined an immunosuppressive subtype (C1) and an immune-active subtype (C2) with divergent survival. The SNI achieved a C-index of 0.88 in TCGA-HNSC, 0.68 in GSE42743, and 0.58-0.62 in the three independent test cohorts and remained independently prognostic after adjustment for age and other clinicopathological variables in multivariable analysis. SHAP analysis identified HSPH1 (risk-associated) and ST6GALNAC1 (protective) as principal contributors with opposing microenvironmental associations. <b>Conclusions:</b> Sialylation constitutes a distinct immunosuppressive axis in HNSCC, complementary to PD-1 blockade. The SNI provides a biologically anchored prognostic framework whose cross-platform transfer requires recalibration; putative candidate compounds require experimental validation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604810/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Oxeiptosis-Associated Molecular Subtyping and Immune Microenvironment Heterogeneity in Osteoarthritis.","authors":"Huiwen Huang, Xuwu Chen, Wenxia Sun, Xiyan Lan, Zhiyi Zeng, Yushang Liu, An Yin, Qiong Deng, Yanbiao Zhong, Maoyuan Wang","doi":"10.3390/biomedicines14092079","DOIUrl":"10.3390/biomedicines14092079","url":null,"abstract":"&lt;p&gt;&lt;p&gt;&lt;b&gt;Background:&lt;/b&gt; Oxeiptosis is a ROS-induced, caspase-independent form of regulated cell death, but its role in osteoarthritis (OA) remains largely unexplored. This study aimed to identify oxeiptosis-associated molecular markers in OA synovium and establish an oxeiptosis-based molecular classification system. &lt;b&gt;Methods:&lt;/b&gt; This study integrated five publicly available GEO datasets for comprehensive analysis. GSE55235 and GSE55457 were used as discovery cohorts to identify DEGs between OA and normal synovial tissues. The GSE206848 dataset was utilized to perform correlation analysis with the key oxeiptosis regulators, including &lt;i&gt;KEAP1&lt;/i&gt;, &lt;i&gt;PGAM5&lt;/i&gt;, &lt;i&gt;AIFM1&lt;/i&gt;, and &lt;i&gt;CUL3&lt;/i&gt;, thereby establishing an oxeiptosis-associated gene set. These genes were intersected with OA-related DEGs to obtain ORDEGs. Subsequently, LASSO regression, SVM-RFE, and RF algorithms were jointly applied to identify hub differential genes. Based on the identified oxeiptosis-related feature genes, molecular subtypes of OA were constructed, with the GSE46750 dataset used for machine learning-based feature selection. Consensus clustering was then performed based on the selected features to identify distinct OA molecular subtypes. The immune microenvironment characteristics and potential regulatory networks of different subtypes were further investigated using CIBERSORT, ESTIMATE, and WGCNA. Finally, an independent GSE89408 cohort was employed for external validation. &lt;b&gt;Results:&lt;/b&gt; A total of 159 common differentially expressed genes were identified from the two OA synovial cohorts, which were mainly enriched in cellular response to hydrogen peroxide, the MAPK signaling pathway, the PI3K-Akt signaling pathway, and NF-κB-related inflammatory processes. Further screening identified seven ORDEGs, including &lt;i&gt;OTUD4&lt;/i&gt;, &lt;i&gt;GATM&lt;/i&gt;, &lt;i&gt;KTN1&lt;/i&gt;, &lt;i&gt;FGGY&lt;/i&gt;, &lt;i&gt;ACACB&lt;/i&gt;, &lt;i&gt;RERE&lt;/i&gt;, and &lt;i&gt;APLP2&lt;/i&gt;. Machine learning analysis ultimately identified &lt;i&gt;ACACB&lt;/i&gt; and &lt;i&gt;FGGY&lt;/i&gt; as potential molecular features of OA. Molecular clustering based on oxeiptosis-related features demonstrated that OA samples could be stably classified into two subtypes, C1 and C2. The C2 subtype exhibited higher ORDEG scores, increased &lt;i&gt;ACACB&lt;/i&gt; expression levels, greater M1 macrophage infiltration, and higher ESTIMATE scores, indicating oxidative stress-related transcriptional characteristics and enhanced inflammatory features, whereas &lt;i&gt;FGGY&lt;/i&gt; was mainly highly expressed in the C1 subtype. WGCNA further revealed that the salmon module closely associated with the C2 subtype was mainly enriched in calcium signaling, focal adhesion, cytoskeletal remodeling, and cell adhesion-related pathways. In the independent GSE89408 validation cohort, exploratory clustering analysis again identified two potential molecular subtypes, and &lt;i&gt;FGGY&lt;/i&gt; remained significantly differentially expressed between the two subtypes. In addition, &lt;i&gt;ACACB&lt;/i&gt; and &lt;i&gt;FGGY&lt;/i&gt; showed AUC values of 0.735 and","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sarcopenia and Skeletal Muscle Dysfunction in Liver Cirrhosis: Clinical Perspectives of Myostatin Inhibition.","authors":"Olga Sukocheva, Damian Harding, Tsai-Wing Ow, Edmund Tse","doi":"10.3390/biomedicines14092082","DOIUrl":"10.3390/biomedicines14092082","url":null,"abstract":"<p><p>Liver cirrhosis is frequently complicated by sarcopenia, a progressive and systemic loss of skeletal muscle mass and function that contributes substantially to increased morbidity, mortality, and healthcare utilisation. The pathogenesis of sarcopenia in cirrhosis is multifactorial, involving hyperammonaemia, altered protein turnover, hormonal and cytokine dysregulation, chronic inflammation, malnutrition, and broader metabolic disturbances. Increasing evidence suggests that these convergent pathological processes are mediated, at least in part, through dysregulation of myokine signalling pathways, particularly those involving myostatin. Myostatin, in concert with downstream effectors such as mechanistic target of rapamycin (mTOR), plays a central role not only in skeletal muscle homeostasis but also in systemic metabolic regulation, highlighting its relevance beyond muscle biology alone. Therapeutic strategies targeting myostatin signalling have been developed, with several myostatin inhibitors advancing into clinical trials. Emerging data indicate that these agents may increase skeletal muscle mass, reduce adiposity, and improve glucose metabolism in patients with sarcopenia and other metabolic disorders, supporting their pleiotropic metabolic effects. However, the mechanistic role and therapeutic implications of myostatin modulation in the specific context of coexisting cirrhosis and sarcopenia remain incompletely understood. This review summarises current knowledge on myokine-mediated regulation of muscle metabolism in cirrhosis, with a focus on the myostatin-mTOR axis. We critically evaluate existing and emerging myostatin-targeting approaches, including pharmacological inhibition and gene-based therapies, as potential strategies to restore muscle mass and function. Finally, we outline future directions for translational research aimed at modulating myostatin signalling in cirrhosis-associated sarcopenia, emphasising the need to elucidate its systemic metabolic effects to identify novel therapeutic targets and improve clinical outcomes in this population.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058118","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Can the Prognostic Nutritional Index Be a Predictor of Acute Exacerbation of Idiopathic Pulmonary Fibrosis?","authors":"Mustafa Çolak, Hikmet Çoban","doi":"10.3390/biomedicines14092088","DOIUrl":"10.3390/biomedicines14092088","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Idiopathic pulmonary fibrosis (IPF) is a fibrotic lung disease that can be accompanied by acute exacerbations. To investigate the predictive value of the prognostic nutritional index (PNI) for acute exacerbation in patients with IPF. <b>Methods:</b> Ninety-seven patients diagnosed with IPF between 03/2019 and 03/2024 were retrospectively evaluated. Patients were divided into two groups according to exacerbation status (acute exacerbation group <i>n</i> = 28, non-acute exacerbation group <i>n</i> = 69). PNI values were calculated. The predictive value of the PNI for acute exacerbation was analyzed between groups. ROC analysis and multivariable logistic regression were performed. <b>Results:</b> Of the 97 patients, 78 (80.4%) were male with a mean age of 71.31 ± 6.61 years. The mean disease duration was 24.77 ± 15.69 months. During follow-up, 28 patients (28.9%) had acute exacerbations. Lymphocyte count and albumin level were significantly lower in the acute exacerbation group (<i>p</i> < 0.001, <i>p</i> < 0.001, respectively). The mean PNI value was significantly lower in the acute exacerbation group (46.62 ± 6.28) compared to the non-acute exacerbation group (52.04 ± 5.46) (<i>p</i> < 0.001). In addition, FEV₁%, FVC%, and DLCO% values were significantly lower in the acute exacerbation group (<i>p</i> < 0.001, <i>p</i> < 0.001, <i>p</i> < 0.001, respectively). In ROC analysis, the cut-off value of PNI ≤ 48.50 had a sensitivity of 64.29% and specificity of 78.26% (AUC:0.744, <i>p</i> < 0.001). In multivariable logistic regression analysis, the PNI (OR = 0.857, <i>p</i> = 0.007) and FVC% (OR = 0.949, <i>p</i> = 0.008) were independent predictors of acute exacerbation. <b>Conclusions:</b> The PNI may serve as a negative biomarker for predicting acute exacerbation risk in IPF patients. This simple, cost-effective parameter could be useful in risk assessment.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057875","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}