Experimental Biology and Medicine最新文献

{"title":"Mitochondrial metabolic plasticity in cancer: hybrid bioenergetic states and translational targeting in surgical oncology.","authors":"Debdeep Chattopadhyay, Ramya Lakshmi Rajendran, Nida Mubin, Durva Tendulkar, Thoudam Debraj Singh, Subhrojyoti Ghosh, Saurabh Kumar Jha, Prakash Gangadaran, Byeong-Cheol Ahn","doi":"10.3389/ebm.2026.11244","DOIUrl":"10.3389/ebm.2026.11244","url":null,"abstract":"<p><p>Mitochondrial metabolism is increasingly recognized as an active determinant of tumor growth and cancer-cell adaptation rather than solely a source of cellular energy. Mitochondrial metabolism supports tumor anabolism, while mitochondrial DNA (mtDNA) alterations can affect respiratory chain function, redox homeostasis, and adaptation to changing tumor environments. At the same time, tumor metabolism is heterogeneous and flexible and cannot be explained by a uniform Warburg model. Tumor cells may use glycolysis, oxidative phosphorylation (OXPHOS), or hybrid glycolysis/OXPHOS states, with the relative contribution of these pathways varying across tumor types, tumor regions, microenvironmental conditions, and therapeutic pressure. This metabolic flexibility may contribute to tumor progression, metastasis, and treatment resistance. In this review, we examine mitochondrial metabolic phenotypes in cancer and their relevance to therapeutic targeting and surgical oncology. We discuss OXPHOS-dependent tumor states, mitochondrial DNA mutations, mitochondrial dynamics, reactive oxygen species, mitochondrial membrane potential, and mitochondrial regulation of intrinsic apoptosis. We further evaluate therapeutic strategies targeting these vulnerabilities, including OXPHOS inhibitors, BCL-2 family inhibitors, ROS modulators, mitochondrial dynamics modulators, mitochondrial genome-editing approaches, and emerging mitochondria-directed immunotherapies. Clinical evidence indicates that broad mitochondrial-targeted interventions may be limited by toxicity, narrow therapeutic windows, limited efficacy, or lack of benefit in unselected populations, supporting the need for metabolic phenotype classification, biomarker-guided patient selection, and rational combination strategies. Particular emphasis is placed on the potential integration of mitochondrial targeting with surgical oncology. Metabolic heterogeneity within tumors and the tumor microenvironment may influence treatment response, residual disease, and recurrence. Emerging approaches such as mass spectrometry imaging, single-cell sequencing, and spatial transcriptomic analysis may allow metabolic features to be mapped within anatomically defined regions of surgical specimens and linked to specific malignant, stromal, and immune-cell populations. Such approaches may help identify OXPHOS-dependent, glycolytic, and metabolically flexible tumor populations and provide clinically relevant biomarkers for treatment selection and monitoring. Overall, mitochondrial vulnerabilities represent a context-dependent therapeutic opportunity rather than a universal metabolic target. Better characterization of mtDNA alterations, metabolic plasticity, spatial heterogeneity, and tumor-specific metabolic dependencies will be important for developing biomarker-guided mitochondrial therapies and for determining how these interventions can be safely integrated into neoadjuvant, adjuvant, and perioperative cancer care.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"11244"},"PeriodicalIF":3.8,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149164303","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Refined protocol for quantifying hippocampal neurogenesis in organotypic slice cultures.","authors":"Irem Akyel, Graham K Sheridan","doi":"10.3389/ebm.2026.11165","DOIUrl":"10.3389/ebm.2026.11165","url":null,"abstract":"<p><p>While human iPSC-derived models of the brain provide valuable genetic context, organotypic slice cultures from rodents remain essential for capturing the physiological complexity of intact neural tissue. This protocol describes a refinement of the interface method originally established by Stoppini and colleagues in 1991, providing a robust platform for the long-term cultivation of rodent hippocampal slices. Unlike dissociated monolayer systems, these 3-dimensional (3D) brain slices preserve the endogenous cytoarchitecture and the native extracellular matrix (ECM) of the central nervous system (CNS). This structural integrity is paramount for investigating hippocampal neurogenesis, as the proliferation, migration, and circuit integration of neural progenitors are governed by mechanical and biochemical cues present in the specialized local niche. By maintaining the spatial relationships between neurons, astrocytes, and microglia, this organotypic system replicates the arrangement of hippocampal neural networks more precisely than emergent stem cell models. Our protocol outlines an optimized workflow for McIlwain tissue chopper-based sectioning and maintenance of slices on porous hydrophilic membranes, ensuring efficient nutrient exchange and sustained tissue viability for several weeks. This configuration provides simultaneous access to the hippocampal slices and culture medium, facilitating the use of multiple investigative techniques such as live-cell imaging, electrophysiology, or pharmacological treatments. Despite relying predominantly on rodent tissue due to the scarcity of live human brain samples; the ability to observe developmental processes within the preserved architectural framework of the hippocampus makes this technique a cornerstone for studying neurogenesis and circuit assembly. Importantly, this refined approach bridges the gap between disorganised monolayers of <i>in vitro</i> neural networks and complex <i>in vivo</i> studies, offering accessible and reproducible physiological models to interrogate biochemical enhancers of neurogenesis or the pathological mechanisms of neurodevelopmental disorders.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"11165"},"PeriodicalIF":3.8,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13654857/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149167861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<i>CERKL-</i>related inherited retinal dystrophy in a Brazilian cohort: genotype-phenotype correlation.","authors":"E S Yasaki, M V Salles, F L Motta, J M F Sallum","doi":"10.3389/ebm.2026.10935","DOIUrl":"10.3389/ebm.2026.10935","url":null,"abstract":"<p><p>The purpose of this study was to analyze the genotype-phenotype of <i>CERKL</i>-related inherited retinal dystrophy in an outpatient clinic. For the study, 2841 medical records of Brazilian patients with a diagnosis of an inherited retinal dystrophy (IRD) registered at Instituto de Genética Ocular, Brazil, between January 2006 and July 2025 were retrospectively reviewed and 52 patients from 50 unrelated families with a molecular diagnosis of an IRD related to the <i>CERKL</i> gene were selected. Clinical data and molecular tests results were analyzed for genotype-phenotype correlation. Most patients (50/52) presented with the cone rod dystrophy (CORD) and two patients presented with the macular dystrophy (MD) phenotype. Age of presenting symptoms ranged from early childhood (7 years old) to adulthood (40 years old). BCVA Snellen measured at the first visit ranged from 20/25 to light perception, corresponding to 0.1 to 2.7 in log MAR visual acuity. Visual acuity data according to disease duration at the first visit of 37 double null (DN) alleles patients disclosed a Pearson coefficient R² of 0.315 for the right eye and 0.405 for the left eye, respectively. A highly significant association between disease duration and visual acuity loss was found suggesting consistent and predictable visual deterioration in patients with complete CERKL loss-of-function over time. Twenty-four different variants described in the <i>CERKL</i> gene were identified. The c.847C>T (p.Arg283) nonsense variant in exon 6 was the most common variant in this cohort, identified in 24 homozygous out of 52 individuals and in 12 compound heterozygous. The phenotype of <i>CERKL</i>-related IRD is CORD with an early age of presentation and fast decrease in visual acuity. In addition to OMIM classifying this gene as an retinitis pigmentosa IRD, we believe <i>CERKL</i> has CORD phenotype, in concordance with evidence described in the literature.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"10935"},"PeriodicalIF":3.8,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13642226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149127098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary biliary cirrhosis and inflammatory bowel disease: a two-sample bidirectional Mendelian randomization study.","authors":"Mingyi Yang, Jiale Xie, Jing Hu, Pengfei Wen, Lin Liu, Zhi Yang, Ming Zhang, Changliang Zhu, Yani Su","doi":"10.3389/ebm.2026.10940","DOIUrl":"https://doi.org/10.3389/ebm.2026.10940","url":null,"abstract":"<p><p>Observational studies have frequently reported an association between primary biliary cirrhosis (PBC) and inflammatory bowel disease (IBD). In this study, we leveraged summary-level data from genome-wide association studies (GWAS) to conduct a two-sample bidirectional Mendelian randomization (MR) analysis, with the primary objective of investigating the genetic causal relationship between PBC and IBD, comprising ulcerative colitis (UC) and Crohn's disease (CD). Additionally, a validation analysis was performed by repeating the bidirectional MR framework, alternately defining PBC and IBD as the exposure and outcome variables to confirm the directionality of the observed associations. A comprehensive panel of sensitivity analyses was implemented to test the robustness of the findings. We first examined the genetic causality at the subtype level. In the forward MR, PBC exerted a significant positive causal effect on UC (P < 0.001, OR 95% CI = 1.081 [1.037-1.127]) and on CD (P = 0.002, OR 95% CI = 1.136 [1.047-1.232]). In the reverse MR, only UC showed a significant negative causal influence on PBC (P > 0.003, OR 95% CI = 0.788 [0.672-0.924]), whereas no significant effect was detected from CD on PBC (P = 0.431, OR 95% CI = 0.956 [0.856-1.068]). We then extended the analysis to the overall IBD phenotype. The forward MR demonstrated a significant positive genetic relationship between PBC on IBD (P < 0.001, OR 95% CI = 1.076 [1.042-1.110]). Conversely, the reverse MR did not support a causal effect of IBD on PBC (P = 0.357, OR 95% CI = 0.898 [0.714-1.129]). The robustness of all these findings was confirmed by comprehensive sensitivity analyses, which showed no evidence of heterogeneity, horizontal pleiotropy, or undue influence from individual instrumental variables. Our MR analysis demonstrates that PBC serves as a genetic determinant of IBD as a whole and of UC/CD separately, whereas reverse causation is limited to a protective effect of UC on PBC. This direction-dependent and subtype-specific causal architecture provides novel insights into the shared etiological pathways between PBC and IBD.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"10940"},"PeriodicalIF":3.8,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13627073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106385","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The causal relationship between antibody-mediated immune responses to infections and Graves' disease: a bi-directional Mendelian randomization analysis.","authors":"Xinwei Zhang, Wenyu Xu, Zhou Liu, Jinan Zhang, Xiaorong Yang","doi":"10.3389/ebm.2026.11238","DOIUrl":"https://doi.org/10.3389/ebm.2026.11238","url":null,"abstract":"<p><p>The pathogenesis of Graves' disease (GD) has not been fully elucidated, and antibody-mediated immune responses following microbial infection may be involved in its development. We conducted a bidirectional two-sample Mendelian randomization analysis using genetic variants associated with GD and 46 antibody-mediated immune-response phenotypes obtained from large-scale genome-wide association studies. In the forward analysis, none of the antibody-mediated immune-response phenotypes was significantly associated with GD risk after Bonferroni or false discovery rate (FDR) correction. Three Epstein-Barr virus antibody phenotypes showed nominal inverse associations with GD under the inverse-variance weighted method, but these findings did not survive multiple-testing correction and showed evidence of heterogeneity, with additional evidence of horizontal pleiotropy for the ZEBRA antibody phenotype. In the reverse analysis, several associations survived multiple-testing correction, although sensitivity analyses indicated heterogeneity or horizontal pleiotropy for the corrected associations except anti-polyomavirus 2 IgG seropositivity. After jointly considering multiple-testing correction and sensitivity analyses, genetic liability to GD was associated with higher anti-polyomavirus 2 IgG seropositivity (OR = 1.156, 95% CI: 1.050-1.273; P = 0.003), which remained significant after FDR correction but did not reach the Bonferroni-corrected threshold. Four additional associations-lower cytomegalovirus pp52 and pp150 antibody levels and higher <i>Helicobacter pylori</i> UreA antibody levels and anti-Merkel cell polyomavirus IgG seropositivity-were nominally significant and should be considered hypothesis-generating. Overall, this bidirectional MR study suggests that genetic liability to GD may influence selected humoral immune-response phenotypes. Notably, the association with anti-polyomavirus 2 IgG seropositivity remained significant after FDR correction, while additional suggestive associations were observed for antibody responses related to CMV, <i>Helicobacter pylori</i>, and Merkel cell polyomavirus. These findings provide new genetic insights into the potential relationship between GD and infection-related humoral immunity, while the potential influence of antibody-mediated immune responses on GD risk warrants further investigation.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"11238"},"PeriodicalIF":3.8,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13623762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal effects of gut microbiota on functional gastrointestinal disorders: a bidirectional Mendelian randomization study.","authors":"Yutong Cheng, Qiuai Shu, Ziwei Wang, Jian Wu, Yuxin Peng, Jiale Xie, Xiru Liang, Zhiwei Tao, Haitao Shi, Zhongcao Wei, Jinhai Wang, Ning Xie","doi":"10.3389/ebm.2026.11023","DOIUrl":"10.3389/ebm.2026.11023","url":null,"abstract":"<p><p>Emerging evidence suggests that gut microbiota is associated with functional gastrointestinal disorders (FGIDs). However, findings regarding microbial alterations in FGIDs have been inconsistent across observational studies, and the direction and causality of these associations remain unclear. We conducted a bidirectional two-sample Mendelian randomization (MR) study to investigate potential causal associations between gut microbiota and two common FGIDs, irritable bowel syndrome (IBS) and functional dyspepsia (FD). Genome-wide association study (GWAS) summary statistics of gut microbiota, IBS, and FD were obtained from public databases and applied to our MR analysis. The inverse-variance-weighted method was used as the primary analysis, with weighted median and complementary sensitivity analyses used to assess the consistency and robustness of the findings. Higher genetically predicted abundances of <i>order Bifidobacteriales</i> (OR: 0.741, 95% CI: 0.570 to 0.963, <i>P</i> = 0.025) and <i>genus Eubacterium ventriosum group</i> (OR: 0.684, 95% CI: 0.524 to 0.893, <i>P</i> = 0.005) were associated with a lower risk of IBS. <i>Genus Lachnospiraceae NK4A136 group</i> (OR: 1.368, 95% CI: 1.086 to 1.722, <i>P</i> = 0.008) correlated to a high risk of FD while <i>family Desulfovibrionaceae</i> and <i>order Desulfovibrionales</i> (OR: 0.649, 95% CI: 0.471 to 0.893, <i>P</i> = 0.008) were protective for FD. In the reverse MR analysis, genetically predicted IBS risk was associated with lower abundances of <i>Turicibacter</i> and <i>Slackia</i>, whereas no robust reverse associations were observed for FD. These findings identify several microbial taxa as candidates for further mechanistic and clinical validation rather than established risk factors or therapeutic targets. Further experimental research to investigate the underlying mechanisms is warranted.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"11023"},"PeriodicalIF":3.8,"publicationDate":"2026-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13601021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149037420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Maternal high-fat diet and risk of cardiovascular disease in offspring: a review of mechanisms, controversies, and interventions.","authors":"Heyu Meng, Jianjun Ruan, Qing Wang, Fanbo Meng","doi":"10.3389/ebm.2026.11199","DOIUrl":"10.3389/ebm.2026.11199","url":null,"abstract":"<p><p>A high-fat diet (HFD) is a well-established risk factor for coronary artery disease (CAD). Accumulating evidence indicates that maternal nutritional status before and during pregnancy critically influences long-term cardiovascular outcomes in offspring. This review systematically synthesizes current mechanistic, epidemiological, and clinical evidence regarding the impact of HFD on CAD while also examining its effects on broader cardiovascular phenotypes that are integral to CAD pathogenesis, such as endothelial dysfunction, cardiac remodeling, and metabolic derangements. A particular focus is placed on the potential effects of maternal pre-pregnancy HFD exposure on offspring CAD risk in adulthood. Existing studies suggest that HFD induces coronary injury primarily through metabolic dysregulation, endothelial dysfunction, and epigenetic reprogramming. Notably, maternal exposure to HFD during the perinatal period may predispose offspring to coronary artery disease via these mechanisms. Conversely, appropriate maternal nutritional interventions during pregnancy have shown promise in mitigating these adverse effects, although their long-term efficacy and underlying molecular mechanisms remain to be fully elucidated. Future research should prioritize large-scale prospective cohort studies with extended follow-up to determine the optimal timing, mechanisms, and efficacy of dietary interventions. Such evidence would provide a scientific foundation for developing preventive and therapeutic strategies aimed at reducing cardiovascular disease risk from the earliest developmental stages.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"11199"},"PeriodicalIF":3.8,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575961/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148976316","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular vesicles for abdominal aortic aneurysm: mechanisms, therapeutic potential, and translational challenges.","authors":"Huibo Ma, Zongyou Xie, Yihang Cai, Fangda Li, Jianqiang Wu, Yuehong Zheng","doi":"10.3389/ebm.2026.11246","DOIUrl":"10.3389/ebm.2026.11246","url":null,"abstract":"<p><p>Abdominal aortic aneurysm (AAA) is a progressive and potentially fatal vascular disease for which no effective pharmacological therapy is currently available. While surgical repair remains the only definitive treatment for advanced aneurysms, patients with small AAAs are mainly managed by surveillance, highlighting the need for disease-modifying strategies. Extracellular vesicles (EVs) have emerged as promising cell-free therapeutic tools because of their biocompatibility, ability to transfer bioactive cargo, and capacity to regulate multiple pathological processes involved in AAA progression. This review summarizes recent advances in EV-based therapies for AAA, focusing on mesenchymal stromal cell-derived EVs, immune cell-derived EVs, and engineered EV platforms. Preclinical studies suggest that therapeutic EVs can attenuate aneurysm formation by suppressing macrophage-driven inflammation, regulating macrophage polarization, inhibiting neutrophil extracellular trap-associated injury, protecting vascular smooth muscle cells from senescence, ferroptosis, apoptosis, and mitochondrial dysfunction, and limiting extracellular matrix degradation. Engineered EVs, including cargo-enriched, peptide-targeted, magnetically guided, chemotaxis-enabled, and biomaterial-assisted systems, may further improve lesion targeting, vascular retention, and therapeutic potency. However, EV-based AAA therapy remains at an early preclinical stage. Key barriers include unclear biodistribution and clearance, insufficient evidence of lesion-specific target engagement, heterogeneous EV isolation and characterization methods, uncertain dosing strategies, and the need for standardized potency, safety, manufacturing, and regulatory frameworks. Overall, EVs offer a biologically rational platform for non-surgical AAA therapy, but clinical translation requires rigorous standardization and robust evidence linking EV delivery to vascular repair.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"11246"},"PeriodicalIF":3.8,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13561958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148955350","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The interaction between oxidative stress and Schwann cells.","authors":"Sihan Yang, Zijun Zhang, Qing Liao, Qipeng Ouyang, Yongyou Ye, Wei Lu, Zhendong Jiang","doi":"10.3389/ebm.2026.11146","DOIUrl":"10.3389/ebm.2026.11146","url":null,"abstract":"<p><p>After peripheral nerve injury (PNI), a moderate increase in reactive oxygen species (ROS) levels can promote the proliferation and differentiation of Schwann cells (SCs) and participate in signal transduction. However, excessive ROS can trigger oxidative stress, and its harmful effects can overshadow the beneficial ones, such as inducing apoptosis, activating inflammation, disrupting environmental stability, and severely hindering neural processes. Therefore, if the damage caused by oxidative stress to SCs can be effectively alleviated, it will provide a new approach for the precise regeneration between peripheral nerves and target organs, thereby reducing the complications of PNI. With the advancements in materials science and neural tissue engineering, functional and precisely designed neural scaffolds and conduits have emerged as highly promising therapeutic strategies. This article focuses on revealing the interaction between SCs and oxidative stress during nerve injury, as well as the innovative tissue engineering technologies and new paradigms for damage repair that have emerged based on this interaction. It aims to provide effective new methods for addressing temporary or permanent functional impairments of PNI/peripheral neuropathies.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"11146"},"PeriodicalIF":3.8,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13558126/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148929328","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered serum interleukin-4 and monocyte chemoattractant protein-3 levels are associated with generalized anxiety disorder: a case-control study.","authors":"Most Humayra Binta Rashid, Mehedi Islam, Sardar Mohammad Ashraful Islam, Md Rabiul Islam","doi":"10.3389/ebm.2026.11144","DOIUrl":"10.3389/ebm.2026.11144","url":null,"abstract":"<p><p>Generalized Anxiety Disorder (GAD) is a long-term mental health condition often associated with immune system dysregulation. While pro-inflammatory and anti-inflammatory cytokines are known to influence neuroinflammation, their specific roles in GAD remain less understood. This study investigates the relationship between serum levels of IL-4 and MCP-3 and GAD in a Bangladeshi population. This case-control study included 44 patients with GAD and 44 healthy controls (HCs). Participants were examined using the GAD-7 scale. Serum IL-4 and MCP-3 levels were measured using ELISA. Data were analyzed using t-tests, Spearman's correlation, and Receiver Operating Characteristic (ROC) curve analysis to assess diagnostic performance. GAD patients had significantly lower serum IL-4 levels (11.82 ± 10.91 pg/mL) and higher MCP-3 levels (57.80 ± 19.85 pg/mL) compared to HCs (IL-4: 24.51 ± 15.36 pg/mL; MCP-3: 34.01 ± 15.75 pg/mL; p < 0.001). IL-4 levels showed a significant negative correlation with GAD-7 scores (r = -0.496, p < 0.001), while MCP-3 showed a positive correlation (r = 0.544, p < 0.001). ROC analysis indicated that MCP-3 had higher diagnostic accuracy (AUC = 0.848, sensitivity = 87.6%, specificity = 84.3%) compared to IL-4 (AUC = 0.782, sensitivity = 80.2%, specificity = 78.5%). Moreover, decreased IL-4 and elevated MCP-3 levels were found to be significantly associated with GAD severity, suggesting an immune imbalance. These cytokines may serve as promising diagnostic biomarkers and therapeutic targets for GAD. Further longitudinal studies are recommended to investigate this causal relationship and its underlying mechanisms.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"251 ","pages":"11144"},"PeriodicalIF":3.8,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13556653/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148918400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}