Biomolecules & biomedicine最新文献

{"title":"Cardiovascular risk assessment in adults with type 1 diabetes: A cross-sectional comparison of two prediction models.","authors":"Ognjen Milanovic, Mia Manojlovic, Marko Bojovic, Shady Abohashem, Milena Mitrovic, Djordje S Popovic, Andrijana Milankov","doi":"10.17305/bb.2026.14748","DOIUrl":"https://doi.org/10.17305/bb.2026.14748","url":null,"abstract":"<p><p>Accurate cardiovascular risk assessment is essential in type 1 diabetes (T1D), but agreement between disease-specific prediction models remains insufficiently characterized. This retrospective, single-center, cross-sectional study compared 10-year cardiovascular risk estimates from the Steno Type 1 Risk Engine (ST1RE) and the Scottish/Swedish risk prediction model in 100 adults aged 20-35 years with T1D and no previous atherosclerotic cardiovascular disease or major cardiovascular event. Continuous and categorical agreement were assessed using Bland-Altman analysis and linearly weighted Cohen's κ, respectively, with identical thresholds applied for risk classification. Risk estimates were strongly correlated (Spearman's ρ = 0.849, p < 0.001), with no significant paired difference on the Wilcoxon signed-rank test (p = 0.893). However, categorical agreement was fair, with a weighted κ of 0.334 and a 95% confidence interval (CI) of 0.078-0.590. The mean difference (ST1RE - Scottish/Swedish) was -1.46 percentage points (95% CI: -2.48 to -0.44), with 95% limits of agreement from -11.54 to 8.62 percentage points. Significant proportional bias indicated progressively higher Scottish/Swedish estimates as mean predicted risk increased (β = 0.91, p < 0.001). Despite strong correlation, individual-level discrepancies and proportional bias suggest limited interchangeability of these models in this cohort. Larger prospective studies assessing cardiovascular outcomes are needed to establish their comparative predictive accuracy and clinical utility.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978939","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":"Tissue MICA/B expression and serum soluble MICA in cholangiocarcinoma: Associations with survival and advanced disease.","authors":"Pornsinee Wilaikaew, Songpol Haohan, Malinee Thanee, Molin Wongwattanakul, Supakan Amontailak, Sutthiwan Janthamala, Attapol Titapun, Anchalee Techasen","doi":"10.17305/bb.2026.14764","DOIUrl":"https://doi.org/10.17305/bb.2026.14764","url":null,"abstract":"<p><p>Cholangiocarcinoma (CCA) has a poor prognosis, highlighting the need for clinically informative biomarkers. This retrospective study examined associations of major histocompatibility complex class I chain-related molecules A (MICA) and B (MICB) and serum soluble MICA (sMICA) with clinical characteristics and survival. Transcript levels, combined tissue MICA and MICB (MICA/B) protein expression, and serum sMICA were assessed using real-time reverse transcription polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay in partially overlapping cohorts of 30, 101, and 118 patients, respectively; serum from 10 controls was also analyzed. Survival associations were evaluated using Kaplan-Meier and Cox regression analyses. MICA transcript levels were elevated in tumors compared with paired adjacent normal tissues (p = 0.006), whereas MICB transcripts were detected in 7/30 tumors. High tissue MICA/B expression was associated with longer median overall survival (40.70 versus 16.36 months; p = 0.008) and lower mortality after multivariable adjustment (hazard ratio, 0.47; 95% confidence interval, 0.25-0.89; p = 0.020). Serum sMICA was elevated in advanced CCA. Exploratory analyses yielded areas under the receiver operating characteristic curve of 0.689 for advanced versus non-advanced CCA and 0.770 for advanced CCA versus controls. At an exploratory upper-quartile threshold (>1466.62 pg/mL), high sMICA was associated with shorter survival (p = 0.014), but the adjusted association was not statistically significant (hazard ratio, 1.89; 95% confidence interval, 0.93-3.84; p = 0.081). Tissue MICA/B expression may have prognostic relevance, whereas serum sMICA may reflect advanced disease; independent prospective validation is required.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148979003","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":"Renal pseudocontinuous arterial spin labeling radiomics for early diagnosis and staging of chronic kidney disease.","authors":"Haiyun Xu, Wei Mao, Lingwei Zhou, Ran Guo, Chengxiu Zhang, Jing Yang, Huihui Xu, Caixia Fu, Mengxiao Liu, Bernd Kuehn, Fang Lu, Guang Yang, Shuohui Yang","doi":"10.17305/bb.2026.14800","DOIUrl":"https://doi.org/10.17305/bb.2026.14800","url":null,"abstract":"<p><p>Early chronic kidney disease (CKD) may be difficult to detect with conventional renal function measures, whereas pseudocontinuous arterial spin labeling (pCASL) can noninvasively quantify renal blood flow (RBF) and characterize perfusion heterogeneity. This prospective two-center study aimed to develop and validate pCASL-derived RBF radiomics models for early CKD diagnosis and staging. We included 364 patients with CKD and 41 healthy volunteers (HVs); Center 1 data were split 7:3 into training and internal test sets, while Center 2 data formed an independent external test set. After semi-automated deep-learning and clustering-based segmentation of the renal cortex and medulla with manual refinement, radiomics, clinical, and combined models were developed for HVs versus CKD stage 1, HVs versus CKD stages 1-2, and CKD stages 1-2 versus stages 3-4. The combined model achieved area under the receiver operating characteristic curve (AUC) values of 0.927, 0.754, and 0.929 for HVs versus CKD stage 1; 0.883, 0.901, and 0.775 for HVs versus CKD stages 1-2; and 0.970, 0.952, and 0.984 for CKD stages 1-2 versus stages 3-4 in the training, internal test, and external test sets, respectively. It significantly outperformed individual models in selected analyses but not consistently across datasets, showed satisfactory calibration in the training and internal test sets, and suggested potential net clinical benefit in exploratory training-set analyses. Combining pCASL-derived RBF radiomics with clinical variables may support noninvasive early CKD assessment and staging; however, the small external cohort, particularly for stage 1 disease, necessitates validation in larger, more diverse multicenter populations.</p>","PeriodicalId":72398,"journal":{"name":"Biomolecules & biomedicine","volume":" ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148978971","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":"Red blood cell distribution width and systemic immune-inflammation index in older adults with sepsis: Associations with in-hospital mortality.","authors":"Yadigar Yilmaz, Beste Gunduz, Mukaddes Degirmi Yurdakul, Dilek Dondu Yamac, Suheyla Abitagaoglu","doi":"10.17305/bb.2026.14660","DOIUrl":"https://doi.org/10.17305/bb.2026.14660","url":null,"abstract":"<p><p>The prognostic value of red blood cell distribution width (RDW) and the systemic immune-inflammation index (SII) in older adults with sepsis remains uncertain. We evaluated their associations with mortality and incremental value beyond clinical predictors. This single-center retrospective cohort study included patients aged ≥65 years admitted to the intensive care unit (ICU) with sepsis between January 2020 and December 2025. RDW and SII were assessed within 24 hours of admission. In-hospital mortality was the primary outcome, and ICU mortality was the secondary outcome. Receiver operating characteristic analysis and multivariable logistic regression assessed discrimination, adjusted associations, and incremental model fit. Among 261 patients (mean age, 79.8 ± 8.9 years), in-hospital and ICU mortality were 62.1% and 55.6%, respectively. RDW was higher in non-survivors and showed weak-to-modest discrimination for in-hospital mortality, with an area under the curve (AUC) of 0.600 and a 95% confidence interval (CI) of 0.538-0.660; findings were similar for ICU mortality (AUC, 0.606; 95% CI, 0.543-0.665). SII showed no significant discrimination. Neither biomarker was independently associated with either outcome after adjustment, and adding both to clinical models did not significantly improve model fit (p = 0.289 and p = 0.089, respectively). Acute Physiology and Chronic Health Evaluation II (APACHE II) score and septic shock remained independently associated with both outcomes. These findings suggest limited incremental prognostic value of admission RDW and SII beyond established clinical predictors in geriatric sepsis.</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":"148978956","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":"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}