Life sciences最新文献

{"title":"Autophagy regulation in ovarian cancer chemoresistance: Molecular mechanisms and emerging frontiers","authors":"Yi-Fan Yang,&nbsp;Lumeng Rui,&nbsp;Bo-Wen Zhang,&nbsp;Ting Huang,&nbsp;Gen-Bao Shao","doi":"10.1016/j.lfs.2025.123966","DOIUrl":"10.1016/j.lfs.2025.123966","url":null,"abstract":"<div><div>Chemotherapy resistance is currently the primary cause of death in patients with ovarian cancer. An increasing amount of data indicates a close relationship between autophagy and chemotherapy resistance in this malignancy. Autophagy, an intracellular degradation process essential for maintaining cellular homeostasis, can promote chemotherapy resistance when dysregulated. This review synthesizes current knowledge on how autophagy-related drugs, proteins, RNAs, and pathway interventions influence chemoresistance in ovarian cancer, along with their underlying molecular mechanisms. It also outlines the broader relationship between autophagy and tumor, with a specific focus on ovarian cancer. Additionally, we evaluate the potential of combination therapies involving autophagy-modulating agents and conventional chemotherapeutic drugs, based on their synergistic effects. Although the majority of studies indicate that autophagy activation promotes cisplatin resistance in ovarian cancer, a minority of reports suggest opposing roles. This review aims to provide new perspectives for overcoming chemotherapy resistance in ovarian cancer. Resistance is currently the primary cause of death in patients with ovarian cancer. An increasing amount of data indicates a close relationship between autophagy and chemotherapy resistance in ovarian cancer. Autophagy is an intracellular degradation process that maintains cellular homeostasis. Imbalances in autophagy can lead to chemotherapy resistance in ovarian cancer.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123966"},"PeriodicalIF":5.1,"publicationDate":"2025-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145045612","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":"Biliverdin alleviates cerebral ischemia-reperfusion injury by inhibiting autophagy via the lncRNA TUG1 /miR-204-5p/P4HB axis","authors":"Guilin Zhou ,&nbsp;Wenya Bai ,&nbsp;Huan Jiang ,&nbsp;Junjie Li ,&nbsp;Junjie Huangfu ,&nbsp;Xuelian Li ,&nbsp;Shi Shu ,&nbsp;Jia Liu ,&nbsp;Jianlin Shao","doi":"10.1016/j.lfs.2025.123967","DOIUrl":"10.1016/j.lfs.2025.123967","url":null,"abstract":"<div><h3>Background</h3><div>Biliverdin (BV), a heme metabolite, alleviates cerebral ischemia-reperfusion injury (CIRI) by regulating non-coding RNAs. Long non-coding RNA taurine-upregulated gene 1 (lncRNA TUG1) has been implicated in CIRI pathogenesis. This study investigates the mechanism of lncRNA TUG1 in BV-mediated CIRI mitigation in vivo and in vitro.</div></div><div><h3>Methods</h3><div>In vivo CIRI was induced in rats via middle cerebral artery occlusion-reperfusion (MCAO/R), while in vitro CIRI was modeled in PC12 cells using oxygen-glucose deprivation/reoxygenation (OGD/R). BV was administered prior to reperfusion (in vivo) or reoxygenation (in vitro). Western blot and transmission electron microscopy (TEM) were used to evaluate BV's neuroprotective effects and its impact on autophagy. Quantitative real-time PCR (qPCR) and dual-luciferase reporter assays were performed to assess the expression levels of lncRNA TUG1, miR-204-5p, and P4HB mRNA, and their interactions. Functional rescue experiments were conducted by plasmid/siRNA transfection to overexpress lncRNA TUG1 or knockdown miR-204-5p. Autophagy and apoptosis were evaluated using MDC staining, Western blot, and flow cytometry.</div></div><div><h3>Results</h3><div>BV significantly reduced neurological deficit scores and neuronal apoptosis in CIRI rats, decreased the LC3 II/I ratio, Beclin1, and P4HB protein levels, and reversed rapamycin-induced autophagy activation. BV downregulated lncRNA TUG1 and P4HB mRNA while upregulating miR-204-5p. Overexpression of lncRNA TUG1 or inhibition of miR-204-5p exacerbated OGD/R-induced cell damage through enhanced autophagy, thereby abolishing BV's protective effects.</div></div><div><h3>Conclusion</h3><div>BV alleviates CIRI by suppressing excessive autophagy via the lncRNA TUG1/miR-204-5p/P4HB axis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123967"},"PeriodicalIF":5.1,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145040643","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":"Retraction notice to \"Ameliorative effect of bone marrow-derived mesenchymal stem cells on burn-induced hepatic and metabolic derangements in rats\" [Life Sci. 307 (2022) 120891].","authors":"Nourhan G Shibl, Ebtehal Mohammad Fikry, Hanaa A Mansour, Amira Ebrahim Alsemeh, Rasha H Abdel-Ghany, Shaimaa S El-Sayed","doi":"10.1016/j.lfs.2025.123905","DOIUrl":"10.1016/j.lfs.2025.123905","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123905"},"PeriodicalIF":5.1,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145030288","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":"Generation and phenotypic characterization of a sigma-1 receptor knockout rat","authors":"Miguel Á. Huerta ,&nbsp;Xavier Codony ,&nbsp;M. Carmen Ruiz-Cantero ,&nbsp;Mónica Porras ,&nbsp;Miguel Á. Tejada ,&nbsp;Aitana Rickert-Llàcer ,&nbsp;Antonia Artacho-Cordón ,&nbsp;Daniel Zamanillo ,&nbsp;Enrique J. Cobos ,&nbsp;Francisco R. Nieto","doi":"10.1016/j.lfs.2025.123953","DOIUrl":"10.1016/j.lfs.2025.123953","url":null,"abstract":"<div><div>The sigma-1 receptor (σ1R) is a chaperone involved in multiple physiological and pathological processes, including pain modulation, neuroprotection, and neurodegenerative diseases. Despite its functional significance, its precise roles remain unclear due to the lack of suitable models for detailed mechanistic studies. In this work, we describe the generation and phenotypic characterization of a novel σ1R knockout (σ1R KO) rat model. Using CRISPR/Cas9 technology, we introduced a specific 218-base-pair deletion into the σ1R gene, resulting in a complete loss of receptor expression, as confirmed by Western blot, immunohistochemistry, and binding assays. Comprehensive phenotypic analyses revealed no major developmental or behavioral abnormalities in σ1R KO rats under baseline conditions, suggesting that σ1R is not essential for development or survival. Additionally, no genotype-related differences were observed in cellular or biochemical blood parameters. Motor function tests (rotarod, grip strength, and wheel running) showed no deficits; however, σ1R KO rats displayed reduced exploratory behavior in actimetry and markedly diminished burrowing behavior. By contrast, no anxiodepressive-like behaviors were observed in the open field, startle, or forced swim tests. Sensory testing of naive rats revealed no significant genotype-related differences in responses to mechanical, heat, or cold stimuli, or in the formalin test (chemical-induced pain). However, σ1R KO rats displayed attenuated neuropathic pain after traumatic nerve injury (spared nerve injury), highlighting the role of σ1R in pain sensitization pathways. This study establishes the σ1R KO rat as a valuable tool for investigating σ1R-mediated mechanisms and for developing therapeutic strategies targeting σ1R for chronic pain, neurodegeneration, and psychiatric disorders.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123953"},"PeriodicalIF":5.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019788","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":"Nuclear trafficking of PDK1 in importin7-dependent manner is required for insulin-induced AKT ubiquitination","authors":"Fangdi Wang ,&nbsp;Li Hu ,&nbsp;Xingyue Zeng ,&nbsp;Wenbin You ,&nbsp;Huijun Li ,&nbsp;Bing Liu ,&nbsp;Xiaohan Zhang","doi":"10.1016/j.lfs.2025.123934","DOIUrl":"10.1016/j.lfs.2025.123934","url":null,"abstract":"<div><div>AKT is a pivotal kinase involved in diverse cellular processes, including tumorigenesis and glycogen metabolism. Ubiquitination modification of AKT has been reported as a critical cellular event that regulates its kinase activity and membrane translocation; however, the molecular mechanisms involved in AKT ubiquitination remain elusive. Here, we employed loss-of-function approaches and mutants of PDK1 with altered phosphorylation and modified nucleocytoplasmic shuttling behaviors to identify the functional roles of PDK1 on the ubiquitination of AKT. Our findings reveal that the nuclear entry of PDK1 in an importin7-dependent manner is required for insulin-induced TRAF6-mediated ubiquitination of AKT, which has been previously shown to occur in the nucleus. Moreover, the phosphorylation of PDK1 at S241 and the PI3K-mediated phosphorylation of PDK1 at S396 both regulate AKT ubiquitination by controlling nuclear entry of PDK1. These results provide new insights into the control of AKT signaling and suggest potential avenues for developing targeted AKT-modulating therapeutics.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123934"},"PeriodicalIF":5.1,"publicationDate":"2025-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145019789","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":"Prim-O-glucosylcimifugin attenuates intestinal fibrosis by modulating TGF-β/MAPK signaling and ECM remodeling","authors":"Han Na Kang ,&nbsp;Seokwon Kim ,&nbsp;Sun Joo Lee ,&nbsp;Ami Lee ,&nbsp;Seo-Young Lee ,&nbsp;Younghoon Go ,&nbsp;Jun Hwan Yoo ,&nbsp;Sang-Min Park ,&nbsp;Yoon Jeong Choi ,&nbsp;Youn-Hwan Hwang","doi":"10.1016/j.lfs.2025.123951","DOIUrl":"10.1016/j.lfs.2025.123951","url":null,"abstract":"<div><h3>Background</h3><div>Intestinal fibrosis is a severe and progressive complication of inflammatory bowel disease (IBD), particularly Crohn's disease (CD), for which no effective anti-fibrotic therapies currently exist.</div></div><div><h3>Purpose</h3><div>This study aimed to investigate the anti-fibrotic efficacy and underlying mechanisms of Prim-O-glucosylcimifugin (POG), a natural chromone derivative, in TGF-β1-stimulated human intestinal fibroblasts.</div></div><div><h3>Methods</h3><div>Fibrosis was modeled in human intestinal fibroblast cell lines (CCD-18Co) and human primary intestinal myofibroblasts (HIMF) using TGF-β1. POG was administered at varying concentrations, and its effects on fibrotic marker expression, MMP1 activity, and cell migration were evaluated using qPCR, western blotting, immunofluorescence, and wound healing assays. Transcriptomic profiling and integrative pathway analysis were used to identify target signaling cascades.</div></div><div><h3>Results</h3><div>POG significantly attenuated TGF-β-induced myofibroblast activation, reducing α-SMA, fibronectin, collagen I/III, and N-cadherin levels. Mechanistically, POG suppressed both canonical TGF-β/Smad and non-canonical MAPK/ERK signaling and enhanced extracellular matrix (ECM) turnover by upregulating MMP1 while downregulating TIMP1. Transcriptomic analysis corroborated the involvement of ECM remodeling and ERK pathway inhibition. Importantly, POG exhibited no cytotoxicity in intestinal epithelial cells.</div></div><div><h3>Conclusion</h3><div>POG demonstrates anti-fibrotic potential in intestinal fibroblasts via dual inhibition of the TGF-β/Smad and MAPK/ERK pathways and selective modulation of ECM-degrading enzymes. These findings highlight POG as a promising therapeutic candidate for the treatment of intestinal fibrosis in IBD.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123951"},"PeriodicalIF":5.1,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145010665","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":"Subcutaneous administration of the sphingosine kinase 2 inhibitor ABC294640 has no metabolic benefits in high fat diet-induced obesity in male mice","authors":"Cecilia Skoug ,&nbsp;Lotte Vanherle ,&nbsp;Lisa Teresa Porschen ,&nbsp;Claes Fryklund ,&nbsp;Karin G. Stenkula ,&nbsp;Anja Meissner ,&nbsp;João M.N. Duarte","doi":"10.1016/j.lfs.2025.123952","DOIUrl":"10.1016/j.lfs.2025.123952","url":null,"abstract":"<div><h3>Aims</h3><div>Experimental evidence suggests an important role for sphingosine-1-phosphate (S1P) and its generating enzymes sphingosine kinase 1/2 (SphK1/2) in obesity. We and others have shown that plasma S1P levels are elevated in obese mice and humans. Preclinical studies suggest that genetic SphK2 ablation in mice protects from age- and diet-induced obesity and metabolic dysfunction. We aimed at investigating the therapeutic potential of pharmacological SphK2 inhibition using a high-fat diet (HFD)-induced obesity model.</div></div><div><h3>Materials and methods</h3><div>Male C57BL/6J mice were fed either a HFD (60 % fat) or a nutrient-matched control diet (CD; 10 % fat) for 9 weeks. After 7 weeks of diet exposure, when HFD-fed mice exhibited increased weight gain, impaired glucose tolerance and reduced insulin sensitivity, mice were subjected to subcutaneous SphK2 inhibitor (SphK2i, ABC294640, 5 mg/kg) or vehicle treatment every second day for two weeks.</div></div><div><h3>Key findings</h3><div>SphK2 expression was upregulated in adipose and liver tissue in response to HFD. Despite this, SphK2 inhibition did not attenuate hepatic steatosis, reduce liver weight, or improve metabolic hepatic gene expression profiles. Moreover, SphK2 inhibition exacerbated certain HFD-induced impairments, including worsened insulin tolerance and increased adipocyte hypertrophy. In CD-fed mice, SphK2 inhibition altered adipocyte size distribution but had no significant impact on systemic metabolism.</div></div><div><h3>Significance</h3><div>Contrary to prior studies, our findings reveal no therapeutic benefit of SphK2 inhibition in diet-induced obesity. These results underscore the importance of tissue and context specificity in targeting the sphingosine kinase pathway and caution against broadly applying SphK2 inhibition as a strategy for treating obesity-associated metabolic dysfunction.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123952"},"PeriodicalIF":5.1,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145004435","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":"Molecular insights into the role of ferroptosis in cardiorenal cross-talk: Mechanisms and future directions","authors":"Pranjali Anil Indian,&nbsp;Mansi Trivedi,&nbsp;Anil Bhanudas Gaikwad","doi":"10.1016/j.lfs.2025.123950","DOIUrl":"10.1016/j.lfs.2025.123950","url":null,"abstract":"<div><div>Cardiorenal syndrome (CRS) is a bidirectional relationship shared between the heart and kidneys, both in physiological and pathophysiological perspectives. The metabolic, hemodynamic, and neurohormonal alterations between the heart and kidneys drive this dual-organ damage and are responsible for one of the highest medical concerns around the globe. From a pathophysiological perspective, activation of the renin-angiotensin system, persistent inflammation, oxidative stress, and reactive fibrosis are accountable for the damage to the heart and kidneys. The review focuses on ferroptosis, which is an iron-dependent lipid peroxidation of the plasma membrane that directs the cell towards cell death. The iron-catalyzed lipid peroxides (LOOH), redox imbalance, inactivation of protective machinery systems such as system X_c, glutathione peroxidase (GPX4), increased iron intake by divalent metal transporter 1 (DMT1) and transferrin receptor 1(TFR1), and ferritinophagy promote cellular lipid peroxidation, the fenton reaction, and intracellular Fe⁺² overload that disrupts homeostasis, and the cells are directed towards ferroptotic cell death. Recently, ferroptotic cell death has been described in a multitude of kidney and cardiac disorders, including acute and chronic kidney diseases, myocardial infarction, heart failure, and so on. This review summarizes recent developments in the context of ferroptosis and its involvement in CRS. The molecular pathways and mechanisms, and how modulating the same could be beneficial for dual-organ protection in the heart and kidneys, are discussed.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123950"},"PeriodicalIF":5.1,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145006360","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":"Advances in therapeutic strategies for acute kidney injury","authors":"Shuangyan Song ,&nbsp;Wuyue Su ,&nbsp;Hongbo Wang ,&nbsp;Xuechuan Hong ,&nbsp;Yuling Xiao ,&nbsp;Xiaodong Zeng","doi":"10.1016/j.lfs.2025.123943","DOIUrl":"10.1016/j.lfs.2025.123943","url":null,"abstract":"<div><div>Acute Kidney Injury (AKI) is a complex clinical syndrome marked by a rapid decline in renal function, most commonly triggered by ischemia, hypoxia, or nephrotoxic insults, and is associated with significant morbidity and mortality. Despite advances in understanding its underlying mechanisms, current treatments remain predominantly supportive, with no effective therapies available to reverse or repair renal damage. Although biomarker-guided precision medicine holds promise, its clinical utility requires further validation through large-scale trials. This review summarizes recent progress in AKI therapy, with a particular focus on injury induced by nephrotoxic drugs (cisplatin, aminoglycosides, contrast media), sepsis, and ischemia-reperfusion. It discusses innovative strategies including nanomedicine-based drug delivery, plant-derived therapeutics, ferroptosis inhibition, and gene or microRNA-targeted approaches, alongside emerging clinical interventions and assessment tools. By bridging experimental findings with clinical application, this review provides insight into evolving therapeutic avenues and emphasizes the ongoing need for targeted, effective interventions to improve outcomes in AKI.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123943"},"PeriodicalIF":5.1,"publicationDate":"2025-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144988843","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":"Repurposing of rebamipide as a neuroprotective agent to alleviate letrozole-induced depressive-like behaviors in female rats: Targeting SIRT1/FoxO1/wnt/ β-catenin, and related ferroptosis pathways","authors":"Aya Hamdy ,&nbsp;Rabab H. Sayed ,&nbsp;Mohammed F. El-Yamany ,&nbsp;Gouda K. Helal ,&nbsp;Mohmed I. Fahmy","doi":"10.1016/j.lfs.2025.123941","DOIUrl":"10.1016/j.lfs.2025.123941","url":null,"abstract":"<div><h3>Aims</h3><div>Polycystic ovarian syndrome (PCOS) is a hormonal disorder affecting females worldwide. PCOS is associated with the development of depression, which is exacerbated by oxidative stress, neuro-inflammation, and ferropotosis. Rebamipide (Reba) is a potent antioxidant agent exhibiting cytoprotective effects. Reba notably activates SIRT1, which in turn plays a major role in ameliorating cellular iron deposition, thus preventing ferooptosis-related cell death. This study aimed to elucidate the neuroprotective effects of Reba against letrozole-induced depressive-like behaviour in female rats and further explore the role of SIRT1/FoxO/wnt/β-catenin and related ferroptosis pathways.</div></div><div><h3>Materials and methods</h3><div>Forty female Wistar rats were allocated into four groups: control group, a letrozole-treated group (1 mg/kg/day, p.o.), a Reba-treated group (80 mg/kg/day, p.o.) and a group receiving niacinamide (NAM), a selective SIRT1 blocker (100 mg/kg/day, i.p.) in addition to Reba.</div></div><div><h3>Key findings</h3><div>Reba restored the normal morphological structure of the hippocampi with significant improvement in the rats' behaviors. Reba up-regulated SIRT1, a key regulator of numerous antioxidant and anti-inflammatory cascades, including Nrf2, SOD, and HO-1. The anti-inflammatory activity of SIRT-1 was revealed by the downregulation of NF-κB-p65, TNF-α, and NLRP3 inflammasome, as well as the upregulation of FoxO/wnt/β-catenin signaling. Furthermore, the anti-ferroptosis effects were demonstrated by the inhibition of total iron and ferrous levels as well as the upregulation of Gpx4 and SLC7A11 genes. Pre-treatment with NAM abolished Reba's neuroprotective effects.</div></div><div><h3>Significance</h3><div>Reba has a major neuroprotective role via activating SIRT1 and inhibiting related oxidative, neuroinflammatory, and ferroptosis pathways.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123941"},"PeriodicalIF":5.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959512","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}