Biomolecules & biomedicine最新文献

{"title":"Preoperative neutrophil-to-lymphocyte ratio and overall survival after biliary tract cancer resection: A retrospective cohort study.","authors":"Xin Long, Han Wu, You Wang, Lei Yang, Hui Xu, Jin Peng, Fuxiang Zhou","doi":"10.17305/bb.2026.14636","DOIUrl":"https://doi.org/10.17305/bb.2026.14636","url":null,"abstract":"<p><p>The comparative prognostic value of preoperative inflammatory markers in resected biliary tract cancer (BTC) remains uncertain. We evaluated the associations of neutrophil-to-lymphocyte ratio (NLR), derived neutrophil-to-lymphocyte ratio (dNLR), platelet-to-lymphocyte ratio (PLR), and lymphocyte-to-monocyte ratio (LMR) with overall survival (OS), focusing on NLR versus dNLR. This single-center retrospective cohort included 109 patients undergoing curative-intent resection. Exploratory cut-offs were derived using receiver operating characteristic analysis and the Youden index. Survival associations were assessed using Kaplan-Meier analysis and separate multivariable Cox models for NLR and dNLR to address multicollinearity. During follow-up, 70 patients died, and median OS was 19.43 months. Elevated NLR and dNLR were associated with shorter OS in univariable analyses. After adjustment, NLR ≥2.11 remained associated with shorter OS (hazard ratio, 4.043; 95% confidence interval, 1.199-13.635; p = 0.024), whereas dNLR ≥1.75 did not (p = 0.321). Neither marker was statistically significant when modeled continuously in adjusted analyses. PLR and LMR showed no statistically significant univariable associations with OS. Combining NLR, dNLR, and PLR yielded only modest discrimination (area under the curve, 0.666). These findings support further investigation of preoperative NLR as a prognostic marker in resected BTC. However, cohort-derived cut-offs and combined risk stratification remain exploratory and require validation in larger independent cohorts before clinical application.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978964","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stroke-associated pneumonia risk prediction: Development and internal validation of a preliminary nomogram.","authors":"Baichen Wang","doi":"10.17305/bb.2026.14918","DOIUrl":"https://doi.org/10.17305/bb.2026.14918","url":null,"abstract":"<p><p>Stroke-associated pneumonia (SAP) is a common complication of acute stroke, highlighting the need for early risk identification. This study aimed to develop and internally validate a preliminary SAP nomogram using routinely available clinical and hematological parameters. This single-center retrospective study included 650 patients randomly divided into training (n = 454) and internal validation (n = 196) cohorts. Baseline blood samples were obtained within 24 hours of admission and before SAP onset; the outcome was SAP within 7 days of stroke onset. Least absolute shrinkage and selection operator (LASSO) regression followed by multivariable logistic regression was used to select predictors and construct the nomogram. SAP occurred in 190 patients (29.2%). Older age, atrial fibrillation, higher white blood cell count, lower lymphocyte percentage, and lower hemoglobin were independently associated with SAP. The area under the receiver operating characteristic curve (AUC) was 0.772 in the training cohort and 0.738 in the internal validation cohort, with respective 95% confidence intervals of 0.723-0.820 and 0.662-0.815. The optimism-corrected training AUC was 0.762. The validation Brier score was 0.181, and decision curve analysis suggested potential clinical net benefit. This preliminary nomogram may support early SAP risk stratification. However, the single-center retrospective design and omission of key neurological predictors, including stroke severity and dysphagia, necessitate prospective multicenter validation before clinical implementation.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TFPI-high myofibroblast states and a meta-program-related five-gene prognostic signature in breast cancer.","authors":"Yu Huang, Xianmin Wu, Xiangnan Li, Xueting Zhu, Xiaoyun Huang, An Huang, Haitao Liu, Yan Yang, Guanghui Zhou, Yining Zhang, Jingpei Long, Qingjing Feng","doi":"10.17305/bb.2026.14562","DOIUrl":"https://doi.org/10.17305/bb.2026.14562","url":null,"abstract":"<p><p>Intratumoral heterogeneity and tumor-microenvironment interactions limit prognostic stratification in breast cancer, but the prognostic relevance and cellular context of recurrent transcriptional meta-programs remain unclear. We aimed to derive a meta-program-related prognostic signature and characterize its component transcripts at single-cell resolution. Six paired institutional tumors and adjacent non-tumor tissues served as a proof-of-concept comparison. Univariable Cox screening and least absolute shrinkage and selection operator Cox regression were used to derive a five-gene score from a prespecified meta-program-related candidate set in The Cancer Genome Atlas Breast Invasive Carcinoma (TCGA-BRCA) training cohort; the score was tested internally and assessed in GSE20685 using fixed coefficients and cohort-specific median cutoffs. GSE161529 single-cell transcriptomic data were used to map signature transcripts across 136,526 quality-controlled cells, while donor-aware pseudobulk analysis compared upper- and lower-quartile TFPI expression states in annotated myofibroblasts. The score comprised TCN1, FOXJ1, PIGR, SLAIN1, and TFPI and was associated with overall survival in the training, testing, and external cohorts, with concordance indices of 0.782, 0.756, and 0.721, respectively. TFPI transcripts were detected across endothelial, fibroblast, and myofibroblast compartments. TFPI-high myofibroblasts showed transcriptional enrichment of extracellular matrix and collagen fibril organization, transforming growth factor beta signaling, epithelial-mesenchymal transition, and myogenesis, together with lower oxidative phosphorylation and fatty acid metabolism programs. In bulk TCGA-BRCA tissue, TFPI expression correlated positively with stromal (r = 0.48), immune (r = 0.25), and composite microenvironment scores (r = 0.40; all p < 0.001). These findings identify a hypothesis-generating five-gene bulk-tissue prognostic signature and an expression-associated TFPI-high myofibroblast state but do not establish a discrete lineage, the cellular source of bulk TFPI, a TFPI-dependent mechanism, or clinical utility. Independent prospective cohorts, spatial and protein-level validation, and functional perturbation studies are required.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148931900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circulating FNDC4 levels and 12-month major adverse cardiovascular events in patients with STEMI undergoing PCI: A prospective cohort study.","authors":"Xiaojun Pu, Shengchao Xiao, Shanhong Liu, Liwen Gong","doi":"10.17305/bb.2026.14625","DOIUrl":"https://doi.org/10.17305/bb.2026.14625","url":null,"abstract":"<p><p>Fibronectin type III domain-containing protein 4 (FNDC4) is a circulating hepatokine with anti-inflammatory and cardioprotective properties, but its prognostic relevance after ST-segment elevation myocardial infarction (STEMI) remains uncertain. We investigated whether admission serum FNDC4 levels were associated with 12-month major adverse cardiovascular events (MACE) in patients with STEMI undergoing primary or urgent percutaneous coronary intervention (PCI). This single-center prospective observational study included 274 patients. Serum FNDC4 was measured before PCI using an enzyme-linked immunosorbent assay, and participants were followed for 12 months. Associations and prognostic performance were assessed using Spearman correlation, receiver operating characteristic, Kaplan-Meier, and Cox proportional hazards analyses. During follow-up, 51 patients (18.6%) experienced MACE. Serum FNDC4 levels were significantly lower in patients with MACE and were inversely correlated with interleukin-6 (IL-6) and N-terminal pro-B-type natriuretic peptide (NT-proBNP). The area under the receiver operating characteristic curve (AUC) for FNDC4 was 0.771 (95% confidence interval [CI], 0.695-0.839). Adding FNDC4 to a clinical model increased the AUC from 0.874 to 0.905 (ΔAUC, 0.031; 95% CI, 0.009-0.061). After adjustment for age, NT-proBNP, left ventricular ejection fraction (LVEF), estimated glomerular filtration rate (eGFR), and Killip class III/IV, each 10 ng/mL decrease in FNDC4 was associated with a higher risk of MACE (hazard ratio, 1.821; 95% CI, 1.360-2.438; p<0.001). Lower admission FNDC4 levels were independently associated with 12-month MACE after PCI for STEMI and may provide complementary prognostic information; however, multicenter external validation and serial FNDC4 measurements are required before clinical application.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148913851","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLP-1 receptor agonists and ocular safety- Pharmacokinetic insights into ischemic optic neuropathy and diabetic retinopathy risk: A review.","authors":"Marwan Malluhi, Ahmad Al-Naemi, Saghir Akhtar","doi":"10.17305/bb.2026.14701","DOIUrl":"https://doi.org/10.17305/bb.2026.14701","url":null,"abstract":"<p><p>Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed the management of type 2 diabetes mellitus and obesity, but their expanding use has raised concerns about ocular safety. This narrative review aimed to evaluate associations between individual GLP-1 RAs and the risk of developing non-arteritic anterior ischemic optic neuropathy (NAION) or diabetic retinopathy (DR), with particular emphasis on whether pharmacokinetic exposure and formulation explain within-class heterogeneity. PubMed was searched through June 2026, without a lower date limit, for human clinical trials, observational studies, and meta-analyses reporting quantitative ocular outcomes; reference lists, regulatory prescribing information, and pharmacokinetic data were also reviewed. Reported hazard ratios ranged from 1.29 to 7.64 for NAION and from 0.42 to 1.76 for DR. The most consistent NAION signal involved high-exposure subcutaneous semaglutide, whereas findings for oral semaglutide, liraglutide, dulaglutide, exenatide, and tirzepatide were absent, inconsistent, or weaker. DR worsening was likewise most evident with high-bioavailability subcutaneous semaglutide, but appeared more closely related to rapid, large reductions in glycated hemoglobin (HbA1c), particularly reductions of at least 2%, than to a class-specific retinal effect. Observational exposure patterns supported a preliminary, hypothesis-generating NAION threshold at a steady-state concentration (Css) of approximately 30-55 nmol/L. Semaglutide 7.2 mg, with an estimated Css of approximately 230 nmol/L, and highly bioavailable oral orforglipron warrant formulation-specific postmarketing ocular surveillance, although direct evidence of NAION risk remains unavailable. Current evidence does not support class-wide prescribing restrictions. An individualized approach considering patient-specific ocular risk, agent, formulation, and dose is more appropriate, while prospective studies with standardized ophthalmic endpoints are needed to establish causality and validate pharmacokinetic and pharmacogenomic risk parameters.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149018773","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Trigonelline improves mitochondrial calcium homeostasis and reduces calpain activity after skeletal muscle ischemia-reperfusion injury in mice.","authors":"Anastasia E Stepanova, Anna S Ustinova, Anastasia D Igoshkina, Shravani Prashant Utture, Svetlana O Rakhmaeva, Ekaterina I Khoroshavina, Tatyana A Baranovskaya, Konstantin N Belosludtsev, Mikhail V Dubinin","doi":"10.17305/bb.2026.14854","DOIUrl":"https://doi.org/10.17305/bb.2026.14854","url":null,"abstract":"<p><p>Skeletal muscle ischemia-reperfusion injury (IRI) causes persistent tissue damage and functional impairment, partly through mitochondrial calcium dysregulation and calpain-mediated proteolysis. This study investigated whether trigonelline (TG), a natural alkaloid, improves skeletal muscle recovery and mitochondrial homeostasis after IRI. Male C57BL/10 mice were randomly assigned to sham control, untreated IRI, or IRI plus TG groups. After 2 h of bilateral hindlimb ischemia, mice received a single intraperitoneal dose of TG (150 mg/kg) immediately before tourniquet release and were evaluated after 7 days of reperfusion. Functional performance, serum creatine kinase (CK) activity, quadriceps mass and histology, mitochondrial respiration and calcium handling, 4-hydroxynonenal (4-HNE) levels, and calpain activity were assessed. TG did not reduce CK activity, prevent quadriceps mass loss, restore grip strength, or significantly improve mitochondrial respiration. Exploratory wheel-running data suggested faster recovery of spontaneous activity. TG increased the number of regenerating fibers and shifted the fiber-diameter distribution toward larger fibers. It also reduced alamethicin-induced mitochondrial calcium release, restored calcium retention capacity to near-control levels, and decreased calpain activity. Although 4-HNE was elevated in both ischemic groups at 2 h, it remained elevated at day 7 only after TG treatment. Thus, a single post-ischemic dose of TG selectively improved mitochondrial calcium handling and reduced calpain activity and was associated with histological features consistent with muscle repair, but did not prevent muscle loss or restore strength. These preliminary findings support further investigation of TG as a potential strategy for recovery after ischemic muscle injury.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148901661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development and internal validation of prognostic nomograms for overall and breast cancer-specific survival in de novo stage IV HER2-positive breast cancer.","authors":"Xiaojie Yu, Deyuan Fu, Longdi Yao","doi":"10.17305/bb.2026.14655","DOIUrl":"https://doi.org/10.17305/bb.2026.14655","url":null,"abstract":"<p><p>The widespread adoption of contemporary human epidermal growth factor receptor 2 (HER2)-targeted therapies has altered survival in HER2-positive metastatic breast cancer, potentially limiting the applicability of older prognostic models. We aimed to develop and internally validate nomograms for overall survival (OS) and breast cancer-specific survival (BCSS) in patients with de novo stage IV HER2-positive breast cancer diagnosed during 2018-2021. Using the Surveillance, Epidemiology, and End Results (SEER) database, 1,516 patients were randomly assigned to training (n = 1,061) and internal hold-out validation (n = 455) cohorts. Random Survival Forest analysis with a 98% out-of-bag concordance index criterion selected variables for multivariable Cox regression models predicting 1-, 3-, and 5-year survival. Discrimination, calibration, clinical utility, and risk stratification were assessed. Nine variables were retained for OS and seven for BCSS. Concordance indices in the training and validation cohorts were 0.764 and 0.741 for OS and 0.747 and 0.736 for BCSS, respectively. Areas under the time-dependent receiver operating characteristic curves (AUCs) ranged from 0.73 to 0.82. Calibration was generally acceptable, and decision curve analysis suggested potential net clinical benefit. High-risk patients had markedly poorer OS (hazard ratios, 5.05 in training and 5.07 in validation) and BCSS (4.32 and 4.09, respectively; all p < 0.001). Sensitivity analyses addressing the time-varying chemotherapy effect and competing risks broadly supported the primary findings. The nomograms showed good internal discrimination and may support individualized prognostic assessment once initial treatment information is available. However, SEER does not record specific HER2-targeted regimens; therefore, this cohort represents a contemporary calendar period rather than a treatment-confirmed dual-HER2-blockade population. External validation in treatment-annotated cohorts is required, and 5-year estimates should be interpreted cautiously given the median follow-up of 27 months.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148898297","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of general versus spinal anesthesia with perioperative changes in serum neuron-specific enolase, adiponectin, and visinin-like protein-1.","authors":"Oguzhan Cucu, Ergun Gunduz, Hafize Uzun, Naile Fevziye Misirlioglu, Bagnu Dundar, Seza Apiliogullari","doi":"10.17305/bb.2026.14652","DOIUrl":"https://doi.org/10.17305/bb.2026.14652","url":null,"abstract":"<p><p>Anesthesia and surgical stress may produce distinct neuronal and metabolic responses, but comparative data on perioperative biomarker trajectories after general and spinal anesthesia remain limited. This prospective observational study aimed to compare circulating neuron-specific enolase (NSE), adiponectin, and visinin-like protein-1 (VSNL1) in adults undergoing elective surgery under general anesthesia (GA) or spinal anesthesia (SA). Ninety-seven patients (GA, n = 52; SA, n = 45) underwent serum sampling preoperatively and at 6 and 24 hours postoperatively, and biomarker concentrations were measured using enzyme-linked immunosorbent assay (ELISA). Longitudinal associations were assessed using linear mixed-effects models adjusted for age, body mass index (BMI), operation duration, and surgical procedure type, with additional baseline-adjusted analyses for adiponectin. NSE increased in both groups but rose less in the SA group than in the GA group at 6 hours (adjusted interaction estimate, -7.765 ng/mL; p < 0.001) and 24 hours (-4.005 ng/mL; p < 0.001). Adiponectin decreased postoperatively, but group-by-time interactions were not significant, and baseline-adjusted analyses showed no significant association between anesthesia modality and adiponectin at either postoperative time point. VSNL1 increased over time; the group-by-time interaction was not significant at 6 hours but was significant at 24 hours (estimate, 0.635 ng/mL; p < 0.001), indicating a differential late trajectory. Perioperative biomarker trajectories differed between GA and SA, most consistently for NSE. However, nonrandom anesthesia assignment, substantial differences in surgical case mix and operation duration, and the absence of neurocognitive outcome assessment preclude causal or clinical interpretation. These findings should be regarded as exploratory adjusted associations and validated in larger, more homogeneous surgical cohorts.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hantavirus infections in Southeastern Europe - Epidemiology, outbreak dynamics, and One Health preparedness: A narrative review.","authors":"Edmond Puca, Rok Čivljak, Aleksandra Barac, Luka Laura, Goran Stevanovic, Magdalena Baymakova, Sotirios Tsiodras, Casandra Bulescu, Gramoz Bunjaku, Jurica Arapović","doi":"10.17305/bb.2026.14790","DOIUrl":"https://doi.org/10.17305/bb.2026.14790","url":null,"abstract":"<p><p>Human-pathogenic orthohantaviruses are significant rodent-borne zoonotic pathogens in Europe. Southeastern Europe (SEE) is a distinct endemic region where Dobrava-Belgrade virus (DOBV) and Puumala virus (PUUV) co-circulate, causing hemorrhagic fever with renal syndrome (HFRS) of varying severity. This narrative review synthesizes the epidemiology, transmission dynamics, clinical characteristics, ecological drivers, and public health challenges of hantavirus infections across SEE, identifying priorities for regional preparedness. We searched PubMed, Scopus, and Web of Science from their inception through June 2026, supplementing with reference screening. Regional epidemiological patterns were assessed descriptively using national surveillance data, European surveillance reports, published studies, and available population-based incidence estimates. Long-term surveillance reveals persistent endemic transmission with significant geographic and interannual heterogeneity. Slovenia and Croatia exhibit the highest cumulative burden and most pronounced periods of increased HFRS activity. Several years-2008, 2012, 2014, 2017, 2019, 2021, and 2023-showed partially synchronized increases across multiple neighboring countries. These patterns align with shared ecological influences, including rodent population fluctuations, mast-seeding events, and climatic variability. However, local ecology, human exposure, and differences in surveillance capacity modify their magnitude. The coexistence of generally milder PUUV-associated disease and more severe DOBV-associated HFRS further distinguishes SEE's clinical landscape. Therefore, hantavirus epidemiology in SEE is best understood as an interconnected regional ecological system. Integrated human, animal, environmental, and genomic surveillance within a coordinated One Health framework is crucial for improving outbreak prediction, cross-border preparedness, and future disease control.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148868156","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gut microbiota-associated metabolites and microbial components in acute ischemic stroke - Neuroimmune inflammation, biomarkers, and therapeutic targets: A narrative review.","authors":"Zhiyuan Hou, Yingyue Ding, Xu Wang, Meilin Pan, Jinjian Li, Dexi Zhao","doi":"10.17305/bb.2026.14621","DOIUrl":"https://doi.org/10.17305/bb.2026.14621","url":null,"abstract":"<p><p>Acute ischemic stroke (AIS) induces gut microbiota dysbiosis and intestinal barrier disruption, potentially influencing neuroimmune inflammation via altered microbial metabolites and components. This narrative review synthesizes current evidence on the mechanisms, biomarker potential, and therapeutic implications of gut microbiota-associated molecules in AIS. We searched PubMed, Web of Science, and Scopus for peer-reviewed studies published between May 1999 and May 2026. From 283 identified records, 87 animal and clinical studies met eligibility and were included. Evidence indicates that trimethylamine N-oxide (TMAO), lipopolysaccharide (LPS), and the tryptophan (TRP)-derived metabolite quinolinic acid predominantly promote neuroinflammation. They achieve this by disrupting blood-brain barrier integrity, activating pro-inflammatory signaling, inducing excitotoxicity, or enhancing thrombosis. Conversely, short-chain fatty acids (SCFAs), kynurenic acid, indole-3-propionic acid, and secondary bile acids exert anti-inflammatory and neuroprotective effects through immune modulation and microglial polarization. Clinical studies suggest TMAO may aid first-stroke risk stratification, while fecal SCFAs, TRP-related metabolites, and circulating bile acids show potential for assessing stroke severity or functional prognosis. However, findings vary based on specimen type, disease stage, and sampling time. Therapeutic approaches targeting these molecules-including metabolite supplementation, modulation of endogenous metabolite production, and nanodelivery systems-have shown encouraging effects, primarily in preclinical models. In conclusion, gut microbiota-associated metabolites and microbial components represent promising AIS biomarkers and therapeutic targets. However, substantial methodological heterogeneity and limited clinical validation currently restrict their translation into routine practice for ischemic stroke management.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148820332","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}