Life sciences最新文献

{"title":"Cold stress exacerbates preeclampsia pathogenesis by upregulating Map7 expression in placental macrophages.","authors":"Shasha Fan, Ying Zhang, Lijie Zhang, Guangze Wang, Siyu Wang, Jiayu Bai, Gaoyuan Wang, Manyu Gong, Haodong Li, Yanwei Zhang, Hao Wang, Jie Liu, Xuelian Li, Ying Zhang, Yuhong Sun","doi":"10.1016/j.lfs.2026.124608","DOIUrl":"https://doi.org/10.1016/j.lfs.2026.124608","url":null,"abstract":"<p><strong>Aims: </strong>Preeclampsia (PE) is a severe hypertension-related complication of pregnancy, driven by crosstalk between environmental exposures and genetic susceptibility. Cold exposure is recognized as a risk factor for PE, yet its underlying molecular mechanisms remain unclear. This study aimed to determine whether cold stress exacerbates PE-like phenotypes and clarify the pathogenic function of placental Map7.</p><p><strong>Materials and methods: </strong>Pregnant mice were subjected to an L-NAME-induced PE-like model with or without chronic cold exposure. Maternal phenotypes, placental pathology, inflammation, and angiogenic balance were evaluated. Proteomics and immunofluorescence were used to identify and localize placental candidate proteins. In vitro macrophage manipulation and conditioned medium assays evaluated Map7's effects on macrophage polarization and trophoblast function.</p><p><strong>Key findings: </strong>Cold exposure markedly worsened PE-like manifestations, including hypertension, proteinuria, fetal growth restriction, and placental injury. Proteomics identified Map7 as progressively upregulated from controls to PE-like mice, and further in cold-exposed PE-like mice, prominently localizing in placental macrophages. MAP7 overexpression promoted M1-like macrophage polarization and inflammatory cytokine production via activating the NF-κB signaling pathway, whereas MAP7 knockdown attenuated these effects. Furthermore, conditioned medium from Map7-overexpressing macrophages impaired trophoblast proliferation, migration, invasion, and angiogenesis, which was reversed by MAP7 silencing.</p><p><strong>Significance: </strong>Map7 mediates the cold stress-aggravated PE-like phenotype. Targeting the macrophage-associated Map7/NF-κB axis represents a potential therapeutic strategy for environmentally triggered placental immune dysfunction.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124608"},"PeriodicalIF":6.4,"publicationDate":"2026-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148604437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardioprotective effects of metformin and empagliflozin in STZ-induced diabetic rats: Role of BACH1-mediated ferroptosis and YAP1/PD-L1 signaling","authors":"Ola A. Yahia ,&nbsp;Dina Elzeiny ,&nbsp;Dina S. Elshenawy ,&nbsp;Ahmed E. Elsukary ,&nbsp;Nehal H.M. Abdel-Halim ,&nbsp;Sara E. Elsherbini ,&nbsp;Yomna F. Hassan","doi":"10.1016/j.lfs.2026.124470","DOIUrl":"10.1016/j.lfs.2026.124470","url":null,"abstract":"<div><h3>Aims</h3><div>Diabetic cardiomyopathy (DCM) is a serious complication driven by diabetes-associated oxidative stress and ferroptosis. This study compared the cardioprotective efficacy of metformin and empagliflozin in streptozotocin (STZ)-induced diabetic rats, focusing on ferroptosis-related mechanisms.</div></div><div><h3>Materials and methods</h3><div>Forty adult male Sprague-Dawley rats were divided into a control group (<em>n</em> = 10) and a diabetic group induced by STZ (55 mg/kg; <em>n</em> = 30). Following successful induction, the surviving diabetic rats were subdivided into untreated, metformin-treated (200 mg/kg/day), and empagliflozin-treated (10 mg/kg/day) subgroups (<em>n</em> = 8 each). After 12 weeks, biochemical, molecular, and histological analyses were conducted.</div></div><div><h3>Key findings</h3><div>Diabetic rats showed a 6.4-fold increase in fasting blood glucose (FBG) and a 3.9-fold rise in lactate dehydrogenase (LDH). These systemic changes were accompanied by marked myocardial oxidative stress imbalance and a 1.5-fold increase in cardiac iron. BTB and CNC homology 1 (BACH1) mRNA expression was upregulated 2.2-fold, coupled with suppression of heme oxygenase 1 (HO-1) and glutathione peroxidase 4 (GPX4) to 0.5 and 0.7-fold, respectively. Histological analysis revealed a 4-fold increase in the percentage area of collagen fibers, alongside a 6.2-fold and 4.5-fold increase in Yes-associated protein 1 (YAP1) and programmed death ligand 1 (PD-L1), respectively, and a 0.3-fold reduction in nuclear factor erythroid 2-related factor 2 (NRF2) expressions, accompanied by ultrastructural damage characteristic of ferroptosis. Empagliflozin significantly improved antioxidant status, molecular and immunohistochemical marker expression, and myocardial integrity more effectively than metformin.</div></div><div><h3>Significance</h3><div>Empagliflozin demonstrated greater cardioprotective effects than metformin in STZ-induced DCM, though further clinical studies are needed to confirm the translational relevance.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"400 ","pages":"Article 124470"},"PeriodicalIF":5.1,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148005942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression of Concern: Anti-apoptotic and neurogenic properties in the hippocampus as possible mechanisms for learning and memory improving impacts of vitamin D in hypothyroid rats during the growth period [Life Sciences 312 (2023) 121209].","authors":"","doi":"10.1016/j.lfs.2026.124278","DOIUrl":"10.1016/j.lfs.2026.124278","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"392 ","pages":"124278"},"PeriodicalIF":5.1,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147490899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirtuin 1 inhibits NLRP3 inflammasome activation through protein-protein interaction","authors":"Li-Chun Ho ,&nbsp;Yi-Ling Tsang ,&nbsp;Hsiao-Chien Hung ,&nbsp;Yu-Hsing Chen ,&nbsp;Ching-Chun Yang ,&nbsp;Yi-Ning Cheng ,&nbsp;Yu-Ting Tu ,&nbsp;Ai-Ning Shao ,&nbsp;Pei-Jane Tsai ,&nbsp;Yi-Che Lee ,&nbsp;Hsi-Hao Wang ,&nbsp;Shih-Yuan Hung ,&nbsp;Yau-Sheng Tsai","doi":"10.1016/j.lfs.2026.124260","DOIUrl":"10.1016/j.lfs.2026.124260","url":null,"abstract":"<div><div>Sirtuin 1 (SIRT1) is known to suppress NLRP3 inflammasome activation via NF-κB inhibition, but its role in inflammasome assembly remains unclear. Here, using a HEK293T reconstitution system, we show that SIRT1 directly interacts and co-localizes with NLRP3 upon inflammasome activation. SIRT1 co-expression disrupts NLRP3-ASC interaction and NLRP3-dependent ASC oligomerization, thereby impairing inflammasome assembly. Co-immunoprecipitation analyses reveal that the N-terminus of SIRT1 is essential for binding and inhibitory function, whereas its deacetylase activity is dispensable. These findings highlight that SIRT1 suppresses NLRP3 inflammasome activation primarily through protein–protein interaction rather than deacetylation, suggesting a potential basis for targeting NLRP3–SIRT1 interaction in inflammasome-related diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"390 ","pages":"Article 124260"},"PeriodicalIF":5.1,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146135656","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of miR-338-3p and miR-378a-3p as regulators in Crohn's disease pathogenesis: Potential therapeutic implications in inflammatory bowel disease","authors":"Ki-Uk Kim ,&nbsp;Jung Min Moon ,&nbsp;Eunsu Lim ,&nbsp;Kang-Bin Dan ,&nbsp;Jeongkuk Seo ,&nbsp;Kyuwon Kim ,&nbsp;Seung Yong Shin ,&nbsp;Hyeyoung Min ,&nbsp;Chang Hwan Choi","doi":"10.1016/j.lfs.2026.124217","DOIUrl":"10.1016/j.lfs.2026.124217","url":null,"abstract":"<div><h3>Aims</h3><div>Epithelial cell-derived microRNAs (miRNAs) are increasingly recognized as contributors to inflammatory bowel disease (IBD) through altered epithelial permeability and inflammatory cytokine production. This prospective study compared epithelial miRNA expression in Crohn's disease (CD) patients and healthy controls, and investigated their immunoregulatory role in experimental IBD models</div></div><div><h3>Materials and methods</h3><div>Terminal ileum samples were collected via ileocolonoscopy from healthy controls and CD patients (remission and active state). Small-RNA sequencing identified unique miRNA profiles, including miR-338-3p and miR-378a-3p, validated by qRT-PCR. In dextran sodium sulfate-induced colitis mice, mimics were administered, and disease severity, gene expression, and immune cell infiltration were assessed by clinical, histological, and molecular assays</div></div><div><h3>Key findings</h3><div>miR-338-3p/miR-378a-3p mimics reduced disease activity scores, attenuated colon shortening, and decreased Th17 cell infiltration in colonic tissues. Histological and immunohistochemical analyses confirmed improved tissue integrity and reduced macrophage/T-cell infiltration in the colon. Mechanistically, miR-338-3p targeted <em>MACC1</em>, while miR-378a-3p suppressed <em>IL33</em>, a proinflammatory cytokine linked to CD pathogenesis.</div></div><div><h3>Significance</h3><div>The results underscore the distinct features of miR-338-3p and miR-378a-3p in CD mucosa and suggest their therapeutic potential for modulating immune responses in CD</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"389 ","pages":"Article 124217"},"PeriodicalIF":5.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146041020","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhanced antiproliferative and anti-inflammatory effects of combined metformin, tadalafil, and tamsulosin in a rat model of testosterone-induced benign prostatic hyperplasia","authors":"Samar S. Khalaf ,&nbsp;Aya M. Sherif ,&nbsp;Eman T. Mehanna ,&nbsp;Ranwa A. Elrayess ,&nbsp;Noha M. Mesbah ,&nbsp;Dina M. Abo-Elmatty ,&nbsp;Mohamed M. Hafez","doi":"10.1016/j.lfs.2026.124240","DOIUrl":"10.1016/j.lfs.2026.124240","url":null,"abstract":"<div><h3>Aims</h3><div>Benign prostatic hyperplasia (BPH) is a common condition in aging men, associated with hormonal imbalances, oxidative stress, and inflammation. This study evaluated the effects of metformin, tadalafil, and tamsulosin administered individually or in combination on testosterone-induced BPH.</div></div><div><h3>Materials and methods</h3><div>Following BPH induction, 48 male Wistar rats were divided into six groups: normal control, BPH control, and four treatment groups receiving metformin (500 mg/kg/day), tadalafil (2 mg/kg/day), tamsulosin (10 μg/kg/day), or their combination for two weeks. Serum levels of urea, creatinine, uric acid, reduced glutathione (GSH), and malondialdehyde (MDA) were measured using enzymatic colorimetric assays. Prostate tissue levels of prostate-specific antigen (PSA), estradiol, dihydrotestosterone (DHT), nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and tumor necrosis factor-alpha (TNF-α) were analyzed via ELISA. mRNA expression of cyclooxygenase-2 (COX-2), transforming growth factor β-2 (TGFβ-2), insulin growth factor-2 (IGF-2), and bone morphogenetic protein 5 (BMP5) was assessed by quantitative real-time PCR.</div></div><div><h3>Key findings</h3><div>Histopathological examination confirmed BPH induction through increased prostate weight and prostate index. While monotherapies alleviated BPH-related changes, com-bination therapy showed superior antioxidant activity and significantly improved kidney function markers. It also markedly reduced PSA, estradiol, and DHT levels, along with significant downregulation of COX-2, TGFβ-2, IGF-2, BMP5, NF-κB, and TNF-α.</div></div><div><h3>Significance</h3><div>although individual treatments provided benefits, their combined use enhanced therapeutic outcomes through modulation of oxidative stress, inflammation, and androgenic activity in BPH management.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"389 ","pages":"Article 124240"},"PeriodicalIF":5.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080721","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of Galectin-3 in the epidermis exacerbates psoriasis pathogenesis via inhibiting autophagy","authors":"Shanshan Han ,&nbsp;Meiqi Cheng ,&nbsp;Shengtao Jiang ,&nbsp;Pei Liu ,&nbsp;Yue Hu ,&nbsp;Qiong Wang ,&nbsp;Yu Cai ,&nbsp;Yinhong Song ,&nbsp;Xuan Xia ,&nbsp;Yuxin Wang ,&nbsp;Yang Li ,&nbsp;Jin Chao ,&nbsp;Decheng Wang","doi":"10.1016/j.lfs.2026.124238","DOIUrl":"10.1016/j.lfs.2026.124238","url":null,"abstract":"<div><h3>Aims</h3><div>Galectin-3 (Gal3) is linked to psoriasis pathophysiology, however, the detailed mechanism of Gal3 involved in this course still needs further addressing. This study aimed to elucidate the role of Gal3 in psoriasis.</div></div><div><h3>Materials and methods</h3><div>Imiquimod (IMQ)-induced psoriasis model in wild-type (WT) as well as Gal3 knockout (<em>Gal3</em>^−/−) mice were established to investigate the impact of Gal3 expression on the development of psoriasis. Autophagy markers LC3 and P62 (SQSTM1) were detected. In vitro, HaCaT cells with Gal3 knockdown were established to detect the effect on the autophagic flux. Then the Sirt1 agonist SRT1720 was used to demonstrate whether Gal3 affects autophagy via Sirt1. The regulation of Sirt1 by Gal3 was demonstrated through half-life experiments.</div></div><div><h3>Key findings</h3><div>Gal3 was significantly reduced in the epidermis in IMQ-induced psoriasis model. The skin inflammation in <em>Gal3</em>^−/− mice more severe than that in WT controls. A deficiency of Gal3 not only reduced the autophagy in psoriatic lesions of the mice model but also effectively inhibited autophagy in a cultured HaCaT cell model. Gal3 was demonstrated to be involved in the assembly of autophagosomes by regulating autophagic flux. In Gal3-depleted mouse skin and HaCaT cells, Sirt1 was downregulated, and SRT1720 could compensate for the impaired autophagy caused by Gal3 deficiency. Gal3 may be involved in the regulation of Sirt1 protein stability.</div></div><div><h3>Significance</h3><div>Gal3 loss exacerbates psoriasis by impairing the autophagic process. These findings position Gal3 as a key protective factor against psoriasis, providing new insights into its role in the pathogenesis of this disease.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"389 ","pages":"Article 124238"},"PeriodicalIF":5.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146080720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"ERCC6L promotes cutaneous melanoma progression via PLK1-mediated aerobic glycolysis: Mechanisms and therapeutic implications","authors":"Mengdi Zhang ,&nbsp;Shengbo Zhou ,&nbsp;Bing Han ,&nbsp;Yining Ge","doi":"10.1016/j.lfs.2026.124216","DOIUrl":"10.1016/j.lfs.2026.124216","url":null,"abstract":"<div><h3>Aims</h3><div>To elucidate the oncogenic role and mechanistic basis of ERCC6L in cutaneous melanoma, focusing on its impact on tumor metabolism and progression.</div></div><div><h3>Materials and methods</h3><div>Multi-omics bioinformatics analysis of public datasets (GEO, TCGA) defined the clinical relevance of ERCC6L. <em>In vitro</em> functional assays (CCK-8, colony formation, Transwell, flow cytometry) were performed in melanoma cell lines following genetic manipulation. Mechanistic studies employed gene set enrichment analysis, chromatin immunoprecipitation-quantitative PCR, dual-luciferase reporter assays, western blotting, and metabolic flux analysis. The functional significance of the ERCC6L-PLK1 axis was validated in an NSG mouse subcutaneous xenograft model.</div></div><div><h3>Key findings</h3><div>ERCC6L is significantly upregulated in melanoma tissues, and its high expression is an independent prognostic factor for poor survival. Genetic ablation of ERCC6L potently inhibited melanoma cell proliferation, migration, invasion, and tumor growth, while promoting apoptosis. Mechanistically, <em>ERCC6L</em> transcriptionally activates <em>PLK1</em> by directly binding to its promoter. This ERCC6L-PLK1 axis drives aerobic glycolysis (the Warburg effect), upregulating key glycolytic enzymes (GLUT1, LDHA, PKM2, HK2) and enhancing lactate production and ATP generation. Crucially, PLK1 inhibition or glycolysis blockade effectively reversed the tumor-promoting phenotypes induced by ERCC6L.</div></div><div><h3>Significance</h3><div>Our study identifies <em>ERCC6L</em> as a novel upstream transcriptional regulator of <em>PLK1</em> that fuels melanoma progression by reprogramming glucose metabolism. The ERCC6L-PLK1-glycolysis axis represents a promising prognostic biomarker and a potential therapeutic target for cutaneous melanoma.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"389 ","pages":"Article 124216"},"PeriodicalIF":5.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146018876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversible ubiquitination regulates HSF1 phase separation in response to proteotoxic stress","authors":"Yue Zhu ,&nbsp;Jianhua Wang ,&nbsp;Shuhong Tang ,&nbsp;Zhiqiang Li ,&nbsp;Ruilin Wang ,&nbsp;Peng Wang ,&nbsp;Jiayu Li ,&nbsp;Shaoxuan Cheng ,&nbsp;Han Liu ,&nbsp;Yingqiu Zhang ,&nbsp;Zhaoxia Dai ,&nbsp;Qitao Yan ,&nbsp;Shuyan Liu","doi":"10.1016/j.lfs.2026.124224","DOIUrl":"10.1016/j.lfs.2026.124224","url":null,"abstract":"<div><h3>Aims</h3><div>Heat shock factor 1 (HSF1) undergoes phase separation to form nuclear condensates in response to proteotoxic stress, which governs cell fate. Protein ubiquitination is a widely existed post-translational modification and closely participated in liquid-liquid phase separation. However, the exact roles of ubiquitination in HSF1 condensation remain obscure. Here, we aimed to investigate the regulation of HSF1 phase separation by ubiquitination in cells under proteotoxic conditions.</div></div><div><h3>Materials and methods</h3><div>Endogenous and exogenous HSF1 condensate formation was detected by immunofluorescence assays. HSF1 phase separation properties were analyzed by fluorescence recovery after photobleaching (FRAP) analysis. Western blotting, immunofluorescence, immunoprecipitation and co-transfection assays were performed to identify E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) regulating HSF1 phase separation. The influence of ubiquitination sites on HSF1 phase separation was investigated by site-directed mutagenesis.</div></div><div><h3>Key findings</h3><div>Proteasome inhibitor PS341 induced HSF1 to form nuclear phase-separated condensates in a time-dependent manner. E3 ubiquitin ligase STUB1 promoted the phase separation of HSF1 by enhancing HSF1 ubiquitination, while DUBs USP13 and ATXN3 negatively regulated HSF1 condensation. Mutations of all nine ubiquitination sites within HSF1 dramatically inhibited condensate formation, with single-site mutations also showing significantly attenuated phase separation.</div></div><div><h3>Significance</h3><div>Ubiquitination at multiple lysine residues jointly drives HSF1 phase separation in cells exposed to proteotoxic stress, which is coordinately regulated by E3 ubiquitin ligase STUB1 and DUBs including USP13 and ATXN3.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"389 ","pages":"Article 124224"},"PeriodicalIF":5.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Light exposure-induced circadian rhythm disruption impairs male reproductive health through oxidative stress and apoptosis","authors":"Guodong Liu ,&nbsp;Yuyang Zhang ,&nbsp;Hui Gao ,&nbsp;Xu Wu ,&nbsp;Feng Li ,&nbsp;Wei Zhang ,&nbsp;Hui Jiang ,&nbsp;Xiansheng Zhang","doi":"10.1016/j.lfs.2026.124222","DOIUrl":"10.1016/j.lfs.2026.124222","url":null,"abstract":"<div><h3>Aims</h3><div>Artificial light exposure at night and irregular light schedules are increasingly prevalent environmental stressors in modern society and have been implicated in male reproductive disorders. This study aimed to determine how distinct patterns of circadian rhythm disruption differentially affect male reproductive function and to elucidate the underlying mechanisms.</div></div><div><h3>Materials and methods</h3><div>Three groups of male rats were subjected to standard 12-h light/12-h dark cycles (LD), fixed inverted light-dark cycles (DL), and a dynamic alternating light-dark-dark-light cycle (LDDL) designed to induce circadian rhythm instability. Reproductive outcomes including body weight, testicular index, serum testosterone levels, and sperm parameters were assessed. Testicular oxidative status was evaluated by measuring NOX4/5, HO-1, SOD, and MDA levels, while apoptosis was examined using Bax/Bcl-2 ratio, cleaved caspase-3 expression, and TUNEL staining.</div></div><div><h3>Key findings</h3><div>Male rats exposed to the LDDL cycle exhibited significant reproductive dysfunction, manifested as markedly reduced testicular index, decreased serum testosterone concentration, and impaired sperm motility. Mechanistically, LDDL conditions enhanced testicular oxidative stress, manifested by NOX4/5 upregulation and HO-1/SOD suppression. This redox imbalance was accompanied by germ cell apoptosis activation, evidenced by elevated Bax/Bcl-2 ratios, increased cleaved caspase-3 expression, and a higher proportion of TUNEL-positive cells. Notably, reproductive damage was more pronounced under dynamic circadian rhythm disruption than under fixed light-dark reversal conditions.</div></div><div><h3>Significance</h3><div>By linking dynamically light-induced circadian disruption to testicular oxidative stress and apoptotic signaling pathways, it elucidates potential mechanisms by which modern lighting environments impair male fertility and provides strategies for circadian rhythm intervention and environmental mitigation.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"389 ","pages":"Article 124222"},"PeriodicalIF":5.1,"publicationDate":"2026-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146081266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}