Biomedicines最新文献

{"title":"Special Issue \"Leishmaniasis: Pathophysiology, Diagnostics and Current and Emerging Therapeutic Approaches\".","authors":"Raimunda Nonata Ribeiro Sampaio, Valdir Sabbaga Amato, Regina Maia de Souza, Daniel Holanda Barroso, João Vitor Matachon Viana","doi":"10.3390/biomedicines14092041","DOIUrl":"10.3390/biomedicines14092041","url":null,"abstract":"<p><p>Leishmaniasis remains a major neglected tropical disease and a persistent challenge for biomedical research [...].</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604751/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058158","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":"Antioxidants in Oxidative Stress and Obesity-Associated Diseases: Molecular Mechanisms and Potential Health Implications.","authors":"Bee Ling Tan","doi":"10.3390/biomedicines14092049","DOIUrl":"10.3390/biomedicines14092049","url":null,"abstract":"<p><p>Obesity has become a major global public health concern, with prevalence rates rising dramatically over the past several decades and affecting more than one billion people worldwide. The increasing burden of obesity has been largely driven by sedentary lifestyles and the consumption of energy-dense, nutrient-poor diets, although its etiology is multifactorial, involving complex interactions among genetic, metabolic, endocrine, and environmental factors. Beyond excess adiposity, obesity is closely associated with numerous chronic diseases, including cardiovascular disease (CVD), type 2 diabetes mellitus (T2DM), hypertension, cancer, and chronic inflammatory disorders. Emerging evidence indicates that oxidative stress plays a pivotal role in the pathogenesis of obesity and its related metabolic complications. Reactive oxygen species (ROS) and reactive nitrogen species (RNS), which are generated during normal cellular metabolism, serve important physiological functions in cell signaling and redox regulation. However, excessive production of these reactive species or impairment of endogenous antioxidant defense systems disrupts redox homeostasis, leading to oxidative damage to lipids, proteins, and nucleic acids. Such alterations contribute to cellular dysfunction, chronic inflammation, and disease progression. In this context, dietary antioxidants have attracted considerable attention due to their ability to neutralize free radicals, inhibit lipid peroxidation, and restore redox balance. Natural antioxidants derived from fruits, vegetables, and other plant-based foods may act individually or synergistically to enhance cellular defense mechanisms against oxidative stress. Furthermore, growing evidence suggests that antioxidant-rich dietary patterns may offer protective effects against obesity-associated metabolic disturbances and chronic diseases. However, clinical benefits of isolated antioxidant supplementation remain inconsistent and appear to depend on dose, bioavailability, baseline redox status, disease stage, and the preservation of physiological redox signaling. Understanding the molecular mechanisms underlying antioxidant-mediated regulation of redox homeostasis may facilitate the development of nutritional strategies for obesity prevention and management, while contributing to the reduction in oxidative stress and obesity-related disease burden and the promotion of long-term health.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057877","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":"SOCS2 Downregulation Is Associated with a Ferro-Aging-Related Transcriptomic Signature in Proximal Tubular Cells in Chronic Kidney Disease.","authors":"Bin Xia, Rujie Zhou, Jianglong Chen, Guang Li","doi":"10.3390/biomedicines14092047","DOIUrl":"10.3390/biomedicines14092047","url":null,"abstract":"<p><p><b>Objectives:</b> This study aimed to identify ferro-aging-related hub genes in chronic kidney disease (CKD) and elucidate their potential roles in proximal tubular (PT) cells. <b>Methods:</b> Differential expression analysis was performed using GSE104954, and the differentially expressed genes were intersected with a set of ferro-aging-related genes. Feature selection was conducted using the least absolute shrinkage and selection operator (LASSO), support vector machine-recursive feature elimination (SVM-RFE), and random-forest algorithms. The findings were externally validated in GSE180394. Single-cell transcriptomic data from GSE183276 were then used to define the cellular localization and expression profile of the hub genes, and their regulatory networks were investigated using scTenifoldKnk-based in silico knockout and gene set enrichment analysis (GSEA). <b>Results:</b> Fourteen candidate genes were identified, of which IRF7 and SOCS2 were consistently selected by all three machine-learning algorithms. SOCS2 was significantly downregulated in both the discovery and validation cohorts and showed strong tissue-level discriminatory performance in the discovery cohort, with more modest performance in the external cohort. Single-cell analysis showed that SOCS2 downregulation occurred predominantly in PT cells; CKD PT cells also exhibited increased ACSL4 expression and the enrichment of the ferroptosis pathway. In silico SOCS2 knockout further identified 77 significantly perturbed genes, primarily associated with mitochondrial oxidative phosphorylation, oxidative stress, and metabolic homeostasis. <b>Conclusions:</b> Collectively, these findings identify SOCS2 as a candidate gene associated with a ferro-aging-related transcriptomic signature in CKD PT cells. The observed changes in ACSL4, ferroptosis-related pathways, mitochondrial oxidative phosphorylation, and oxidative stress networks are compatible with, but do not establish, a ferro-aging phenotype. Further functional validation is required to determine whether SOCS2 contributes causally to iron-lipid dysregulation and tubular injury in CKD.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058095","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":"Molecular Signaling Pathways, Regulatory and Coactivator Networks, and Emerging Mechanisms in Hepatocellular Carcinoma.","authors":"Rohit K Srivastava, Pratibha Singh, David M Lonard","doi":"10.3390/biomedicines14092046","DOIUrl":"10.3390/biomedicines14092046","url":null,"abstract":"<p><p>Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of cancer-related mortality worldwide. Despite advances in diagnosis and therapy, the prognosis for advanced HCC remains poor due to late-stage diagnosis, high recurrence rates, therapeutic resistance, and pronounced molecular heterogeneity. HCC development is driven by complex somatic gene alterations, epigenetic reprogramming, dysregulated signaling pathways, metabolic changes, and an immunosuppressive tumor microenvironment. Molecular profiling studies have identified key oncogenic pathways involved in HCC progression, including MAPK/ERK (mitogen-activated protein kinase/extracellular signal-regulated kinase), Wnt/β-catenin, PI3K/AKT/mTOR (Phosphoinositide 3-kinase/Protein Kinase B/mechanistic Target of Rapamycin), Hippo-YAP/TAZ, (Yes-associated protein/transcriptional co-activator with PDZ-binding motif) cell cycle regulators, and p53-mediated tumor suppression. These pathways coordinate critical cellular processes such as proliferation, survival, metabolism, invasion, and genomic stability. Emerging mechanisms, including cancer stem cell plasticity, immune evasion, epigenetic dysregulation, and steroid receptor coactivator (SRC)-dependent transcriptional regulation, further contribute to tumor progression and therapeutic resistance. Additionally, recent bioinformatic analyses suggest a potential role for progesterone-mediated oocyte maturation pathways in HCC, although their functional relevance remains unclear. A thorough understanding of these interconnected mechanisms could lead to novel therapeutic targets and the development of more effective, personalized treatment strategies for HCC. This review discusses key signaling pathways and emerging mechanisms in HCC and their roles in disease development and treatment.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604898/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057878","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":"A Multiphase Combined Treatment Including Individualized Multimodal Immunotherapy and Tumor Microenvironment Therapy for Glioblastoma: A Decade of Experience with Real-World Patients.","authors":"Linde F C Kampers, Jennifer Kosmal, Peter Van de Vliet, Stefaan W Van Gool","doi":"10.3390/biomedicines14092044","DOIUrl":"10.3390/biomedicines14092044","url":null,"abstract":"<p><p><b>Background/Objectives</b>: A potential association between individualized multimodal immunotherapy (IMI) within a multiphase combined treatment strategy and prolonged survival was explored through retrospective real-world data analysis. <b>Methods</b>: The patient selection criteria were as follows: treatment after 27 May 2015, adults between ages 18 and 70, GB diagnosis and IDH1wt status documented, known MGMT promoter methylation status (methylated versus unmethylated), known status of OS, and no second malignancy. IMI is currently only accessible to patients with a >60 KPI and sufficient financial resources. <b>Results</b>: A total of 104 patients were identified, distributed as per MGMT methylation versus unmethylation status, respectively, as 18% female/25% male versus 23% f/38% m; the median age at intake was 54 y versus 50 y; the resection extent was 12 R0, 28 < R0 and three not documented versus 25, 28 and eight; and the median KPI at intake was 70 overall. Patients received a median of 37 versus 31 modulated electro-hyperthermia sessions, 37 versus 32 NDV injections, and two versus one dendritic cell vaccines. The median OS and percentage 2 y OS were 33.1 months and 69.7% <i>versus</i> 19.0 months and 35.4%. There were no major adverse reactions (ARs), but the AR burden increased with checkpoint inhibitor use. A 33-patient subset was analyzed on health-related quality of life (HRQoL) throughout IMI treatment, based on at least five EQ-5D-5L questionnaires available from intake. Mobility and self-care affected HRQoL less than usual activity, pain/discomfort and anxiety/depression. Throughout IMI, HRQoL remained stable. Before progressive disease, the median health utility index was 0.86, resulting in a median quality-adjusted life-months of 4.6 versus a median of 5.4 calendar months. <b>Conclusions</b>: Real-world observation indicates IMI may prolong GB patient OS while maintaining HRQoL.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604673/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057839","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":"Multi-Omics Analysis Identifies Fibroblast-Associated Stromal-Immune Networks Linked to Pregnancy-Associated Attenuation of Imiquimod-Induced Psoriatic Dermatitis.","authors":"Jiaqing Shen, Lisha Song, Zihan Ye, Mingjun Jiang, Yi Liu","doi":"10.3390/biomedicines14092048","DOIUrl":"10.3390/biomedicines14092048","url":null,"abstract":"<p><p><b>Background:</b> Psoriasis is a chronic, immune-mediated inflammatory skin disorder that frequently exhibits spontaneous clinical remission during pregnancy. However, the underlying cell-type-specific transcriptomic alterations-particularly the involvement of dermal fibroblasts and hormone receptor signaling-remain poorly understood. <b>Methods:</b> We established an imiquimod (IMQ)-induced psoriasis-like dermatitis model in BALB/c mice comparing pregnant and non-pregnant cohorts. Multi-omics profiling combing bulk and single-cell RNA sequencing was integrated with computational intercellular communication and trajectory analysis. In vitro hormone-stimulation assays with ELISA quantification and in situ multiplex immunofluorescence were performed for experimental evaluation. <b>Results:</b> Compared with non-pregnant IMQ-treated mice, pregnant mice exhibited reduced psoriasis area and severity index scores and diminished epidermal thickening. Bulk RNA sequencing revealed downregulated Th1/Th17 inflammatory transcripts and upregulated hormone-associated genes (e.g., <i>Pgr</i>, <i>Esr1</i>, <i>Ghr</i>). Single-cell RNA sequencing identified 11 distinct cell types, with fibroblasts displaying distinct hormone receptor profiles and functional heterogeneity. Fibroblasts displayed transcripts encoding both anti-inflammatory factors (e.g., <i>Tgfb2</i>, <i>Gas6</i>, <i>Grn</i>) and pro-inflammatory factors (e.g., <i>Fgf7</i>, <i>Mif</i>). Keratinocytes exhibited an anti-inflammatory transcriptional phenotype with attenuated proliferation signatures. Monocytes/macrophages shifted toward M2-like transcriptional signatures and displayed computationally predicted communication with fibroblasts via candidate pathways including GRN and Gas6. Experimentally, primary mouse dermal fibroblasts stimulated with estradiol, progesterone, and growth hormone in vitro significantly increased secretion of PGRN. Gas6 secretion was significantly augmented by estradiol and growth hormone, whereas progesterone induced a modest elevation with borderline significance (<i>p</i> = 0.060). In contrast, TGF-β2 protein remained undetectable in culture supernatants. Furthermore, multiplex immunofluorescence demonstrated significantly increased expression of the Gas6 receptor MerTK on dermal macrophages in the IMQ + pregnancy group. <b>Conclusions:</b> Pregnancy-induced hormonal fluctuations may be associated with the amelioration of IMQ-induced psoriatic dermatitis, which correlates with a fibroblast-involved immunoregulatory network. These findings highlight the association of stromal-immune crosstalk in disease remission and suggest the GRN and Gas6 pathways as candidate pathways for future functional validation.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604052/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057903","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":"Immunometabolic Dysregulation in Female Obesity: Mechanistic Links to Ovarian Dysfunction, Implantation Failure, and Preeclampsia.","authors":"Rodolfo Oliveira Medeiros, Feres Abrão, Laila Abrão, Cintia Gisele de Andrade Pozenato, Camila Abrão Costa Buzeto, Marines Laveso de Brito, Isis Carrero Zequini de Freitas, Vitória Auler do Santo, Gustavo Henrique de Paulo Ribeiro Ponciano, Bianca Marques, Juliana Ferreira Marcandelli, Isabele de Assis Nagahashi Campos, Maria Clara de Castro Ferreira, Gabriela Novaes Garcia, Cynthia de Paula Costa Borba, José Antonio Pizzolato Neto, Ludmila Trambaiolli de Souza, Felipe Ravazzi Guzzo, Amanda Santiago Ribeiro, Pedro Henrique Lima Domingues, Kelly Karine Pasqual, Felipe Neves Brandão","doi":"10.3390/biomedicines14092039","DOIUrl":"10.3390/biomedicines14092039","url":null,"abstract":"<p><p>Obesity is one of the most pressing public health challenges of our time, with a growing impact on metabolic and reproductive dysfunction in women. The expansion of visceral adipose tissue drives a chronic, low-grade systemic inflammatory state that has been associated with functional changes in the ovary, the endometrium, and the placenta across different stages of the reproductive process. This structured narrative review, guided by a PICo-framed research question and literature searches across PubMed/MEDLINE, Scopus, Web of Science, Embase, and ScienceDirect, examined the main immunometabolic mechanisms underlying female obesity and their reported associations with ovarian dysfunction, implantation failure, placental dysfunction, infertility, and preeclampsia. The evidence indicates that chronic low-grade inflammation, insulin resistance (IR), and functional hyperandrogenemia may impair folliculogenesis, oocyte quality, and ovarian reserve, while cytokine and adhesion-molecule dysregulation in the endometrium has been linked to impaired decidualization and a narrower implantation window. At the maternal-fetal interface, this same inflammatory substrate has been associated with deficient trophoblast invasion, inadequate spiral artery remodeling, and angiogenic imbalance, mechanisms widely implicated in the pathophysiology of preeclampsia. Rather than demonstrating a proven longitudinal chain within the same individual, the evidence reviewed here, drawn from heterogeneous populations, study designs, and experimental models, supports a conceptual, hypothesis-generating model in which obesity-related systemic inflammation may contribute to dysfunction across the ovary, endometrium, and placenta. Clinically, these findings support further investigation of reproductive biomarkers and early screening strategies for women with obesity, particularly in the context of assisted reproduction, alongside emerging preconception therapeutic approaches that remain largely investigational. Female obesity should therefore be understood not merely as a metabolic disorder, but as an immunometabolic condition potentially associated with dysfunction across the ovary-endometrium-placenta axis, an integrative framework that may help guide future preventive and therapeutic strategies for reproductive health, pending confirmation in longitudinal studies.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058021","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":"A Cross-Region Meta-Analysis and Machine Learning Identifies a 37-Gene Signature Associated with Alzheimer's Disease.","authors":"Kashvi Chirag Shah, Ethan Littlestone, Md Roungu Ahmmad, Chunmei Wang, Yong Xu, Xiaoli Zhang","doi":"10.3390/biomedicines14092032","DOIUrl":"10.3390/biomedicines14092032","url":null,"abstract":"<p><p><b>Background/Objectives</b>: Alzheimer's disease (AD) shows marked transcriptomic heterogeneity across brain regions, limiting reproducibility. We aimed to identify robust cross-region gene signatures using meta-analysis. <b>Methods</b>: Differential expression (limma-voom) was performed on five bulk RNA-seq datasets (n = 230; 154 AD donors, 76 controls) from the hippocampus to cortical regions. Consensus DEGs were identified via Stouffer's Z, random effects, and MetaVolcanoR models. Pathway enrichment and associations with Braak stage were evaluated. Validation was conducted in two independent cohorts, with predictive performance assessed using machine learning. <b>Results</b>: Thirty-seven consensus DEGs (16 up, 21 down; FDR ≤ 0.05) were identified across ≥4 datasets. The enrichment results revealed increased expression of glial and ECM-associated genes and decreased expression of synaptic and GABAergic genes. Thirty-six of 37 genes correlated with Braak stage, with all 37 remaining significantly associated after covariate adjustment. The signature predicted AD with AUCs of 0.784 and 0.861 for validation in two independent cohorts. <b>Conclusions:</b>: We identified a consistent cross-region signature linking synaptic and glial changes to neuropathological severity, highlighting new mechanisms and potential biomarkers.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057834","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":"Anti-NMDA Receptor Encephalitis Associated with Ovarian Teratoma: A Comprehensive Review.","authors":"Hanna Miski, Kamila Krupa, Bartosz Balasiewicz, Dominik Kucharski, Hubert Rzewuski, Andrzej Deptała, Anna Badowska-Kozakiewicz","doi":"10.3390/biomedicines14092040","DOIUrl":"10.3390/biomedicines14092040","url":null,"abstract":"<p><p>Anti-N-methyl-D-aspartate receptor encephalitis (anti-NMDAR-E) is a severe autoimmune encephalitis that predominantly affects young women and is frequently associated with ovarian teratomas. Increasing evidence indicates that these tumors play a central role in disease initiation by providing a peripheral immunological trigger. This comprehensive review summarizes current knowledge on the immunopathogenesis, clinical manifestations, diagnostic approach, therapeutic strategies, and long-term outcomes of ovarian teratoma-associated anti-NMDAR-E. We discuss the unique immunogenic properties of ovarian teratomas, including the presence of neuroglial tissue expressing the GluN1 receptor subunit (formerly known as NR1) of the N-methyl-D-aspartate receptor (NMDAR), dense immune cell infiltrates, and tertiary lymphoid structure-like formations that support local antibody production. These features are thought to promote molecular mimicry and loss of immune tolerance, leading to B-cell activation, intrathecal antibody synthesis, and antibody-mediated neuronal dysfunction. Furthermore, we review the characteristic multistage clinical course, key diagnostic findings in cerebrospinal fluid, imaging and electrophysiology, and the importance of early tumor removal combined with immunotherapy. Emerging therapeutic approaches and experimental models that provide insight into disease mechanisms and novel treatment targets are also highlighted. An improved understanding of tumor-driven neuroimmunological interactions is essential for earlier diagnosis, optimized treatment strategies, and better long-term outcomes in affected patients.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057893","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":"Preliminary Evaluation of SGLT2 Inhibitors in Human Bladder Cancer T24 Cells.","authors":"Martyna Szachniewicz, Michał Baran, Maciej Gagat, Marta Hałas-Wiśniewska","doi":"10.3390/biomedicines14092037","DOIUrl":"10.3390/biomedicines14092037","url":null,"abstract":"<p><p><b>Background/Objectives:</b> Sodium-glucose cotransporter 2 (SGLT2) inhibitors have recently gained attention for their potential anticancer properties. However, their effects in bladder cancer remain poorly understood. In this preliminary study, we assessed the effects of canagliflozin, dapagliflozin, and empagliflozin on metabolic activity, cell cycle distributions, migratory behavior, and SGLT2 expression in the human bladder cancer cell line T24. <b>Methods:</b> Cellular metabolic activity, cell cycle distribution, apoptosis and necrosis, migration, and SGLT2 protein expression were assessed using 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry, wound-healing and single-cell migration assays, Western blotting, and fluorescence microscopy. Bioinformatic analyses of <i>SLC5A2</i> were additionally performed. <b>Results:</b> All three compounds reduced MTT-derived metabolic activity in a concentration-dependent manner and induced G0/G1 cell-cycle accumulation without increasing apoptosis or necrosis after 24 h. Flozins also impaired collective wound closure and altered single-cell migration parameters, although replicate-level analysis showed no significant differences between individual treatment conditions and control after multiple-comparison correction. SGLT2 protein was detected in T24 cells and decreased following treatment, with compound-dependent differences in magnitude. <b>Conclusions:</b> Flozins affect metabolic activity, cell-cycle progression, wound closure, and migratory behavior in T24 cells. However, these findings do not establish SGLT2-specific mechanisms and were obtained at concentrations exceeding typical clinical plasma exposure. Further target-validation and mechanistic studies are required.</p>","PeriodicalId":8937,"journal":{"name":"Biomedicines","volume":"14 9","pages":""},"PeriodicalIF":4.5,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604264/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058133","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}