Life sciences最新文献

{"title":"Hepatoprotective and neuroprotective effects of quinacrine against bile duct ligation-induced hepatic encephalopathy in rats: Role of bone morphogenetic proteins signaling","authors":"Manar M. Esmail ,&nbsp;Noha M. Saeed ,&nbsp;Diana M.F. Hanna ,&nbsp;Haidy E. Michel ,&nbsp;Reem N. El-Naga ,&nbsp;Samar S. Azab","doi":"10.1016/j.lfs.2024.123229","DOIUrl":"10.1016/j.lfs.2024.123229","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to assess the potential protective effect of quinacrine, an FDA approved antimalarial drug with reported anti-inflammatory effects, on hepatic encephalopathy (HE) in a bile duct ligation (BDL) experimental model and to investigate the mechanisms responsible for this effect, namely those associated with the liver-brain axis, particularly, bone morphogenetic protein 2 (BMP2) signaling.</div></div><div><h3>Materials and methods</h3><div>Five groups of rats were selected at random: sham, BDL, (BDL+ quinacrine 5), (BDL+ quinacrine 10), and (quinacrine 10 + sham). Daily Intraperitoneal (I.P.) administration of quinacrine was initiated on the surgery day and continued for 28 days.</div></div><div><h3>Key findings</h3><div>Results showed that rats that underwent BDL exhibited marked elevation of serum liver enzymes, ammonia, total bilirubin, together with oxidative stress, inflammation, dysregulated farnesoid x receptor (FXR), dysregulated BMP2 signaling and escalated fibrotic markers indicating hepatotoxicity, cholestasis and fibrosis. Besides, neurotoxicity was detected as manifested by cognitive deficits and dysregulation of hippocampal FXR, BMP2 signaling, WNT3A signaling, brain derived neurotrophic factor (BDNF), phospholipase A2 (PLA2) and glial fibrillary acidic protein (GFAP). In contrast, co-treatment with quinacrine mitigated BDL-induced hepatotoxicity, cholestasis, fibrosis, and neurotoxicity. Notably, quinacrine improved learning and memory and restored FXR, BMP2 signaling in the liver and hippocampus. In addition, quinacrine restored hippocampal WNT3A signaling, BDNF, whereas it downregulated expression of hippocampal PLA2 and GFAP.</div></div><div><h3>Significance</h3><div>These findings demonstrated implication of BMP2 signaling in the molecular process of BDL-induced HE and proposed that quinacrine has potential hepatoprotective and neuroprotective properties against HE.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123229"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The roles of pyroptosis in the pathogenesis of autoimmune diseases","authors":"Yingqiu Song ,&nbsp;Yanhui Peng ,&nbsp;Bing Wang ,&nbsp;Xinyue Zhou ,&nbsp;Yikang Cai ,&nbsp;Haiyong Chen ,&nbsp;Chenggui Miao","doi":"10.1016/j.lfs.2024.123232","DOIUrl":"10.1016/j.lfs.2024.123232","url":null,"abstract":"<div><div>The occurrence of autoimmune diseases is a result of the immune system's immune response against healthy components of the body. Pyroptosis is an innovative form of programmed cell death dependent on inflammatory caspases, leading to the release of cytokines. Excessive pyroptosis can lead to a sustained inflammatory response, which may aggravate the development of autoimmune diseases. In rheumatoid arthritis (RA), tumor necrosis factor (TNF) and NLRP3 enhance pyroptosis, exacerbating the disease. In systemic lupus erythematosus (SLE), the release of nuclear antigen promotes the development of SLE. In multiple sclerosis (MS), elevated active caspase-11 in primary astrocytes induces oligodendrocyte pyroptosis, advancing MS progression. This review outlines the mechanisms of pyroptosis in autoimmune diseases. Meanwhile, we elaborated the possible therapeutic targets from the perspective of pyroptosis. We conclude that pyroptosis is expected to be a therapeutic target for autoimmune diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123232"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623318","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":"Total minor ginsenosides exert anti-fatigue effects via antioxidant, anti-inflammatory, regulating gut microbiota and serum metabolism","authors":"Yuhang Zhang ,&nbsp;Ge Yang ,&nbsp;Yansong Gao ,&nbsp;Lei Gao ,&nbsp;You Kang ,&nbsp;Yujuan Zhao ,&nbsp;Lei Zhao ,&nbsp;Shengyu Li","doi":"10.1016/j.lfs.2024.123231","DOIUrl":"10.1016/j.lfs.2024.123231","url":null,"abstract":"<div><div>Minor ginsenosides have demonstrated notable anti-fatigue capabilities. The aim of this study was to investigate the anti-fatigue mechanisms of total minor ginsenosides (TMGs) derived from a process involving probiotic fermentation and high-pressure steam treatment. The fatigue model was established in BALB/c male mice using weight-bearing swimming and TMGs were administered by orally at a dosage of 200 mg/kg for four weeks. The anti-fatigue mechanisms of TMGs were explored by assessing liver oxidative stress, skeletal muscle inflammation markers, as well as their impact on gut microbiota and serum metabolism. The results indicated that TMGs could significantly increase the levels of SOD, CAT, ATP and Na⁺-K⁺-ATPase and enhance the antioxidant capacity by modulating the PGC-1α/KEAP1/NRF2/HO-1 pathway. Meanwhile, TMGs reducing the levels of inflammatory factors TNF-α, IL-1β and IL-6 and inhibited inflammation by modulating the AMPK/TORC2/CREB/PGC-1α pathway. TMGs also regulated the gut microbiota, increasing the abundance of probiotic bacteria and the content of short-chain fatty acids (SCFAs) in the cecum. Serum metabolomics analyses have shown that TMGs can significantly affect the serum metabolic profile of fatigue model mice, regulating metabolic markers through affecting anti-fatigue-related metabolic pathways. In conclusion, TMGs exerted significant anti-fatigue effects through antioxidant and anti-inflammatory effects, and alleviate fatigue by regulating gut microbiota and serum metabolism.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123231"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623319","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":"Metabolomics for enhanced clinical understanding of inflammatory bowel disease.","authors":"Theresa Louise Boye, Alexander Hammerhøj, Ole Haagen Nielsen, Yulan Wang","doi":"10.1016/j.lfs.2024.123238","DOIUrl":"10.1016/j.lfs.2024.123238","url":null,"abstract":"<p><p>Metabolomics is an emerging field involving the systematic identification and quantification of numerous metabolites in biological samples. Precision medicine applies multiomics systems biology to individual patients for reliable diagnostic classification, disease monitoring, and treatment. Multiomics systems biology encompasses genomics, transcriptomics, proteomics, epigenomics, and metabolomics. Therefore, metabolomic techniques could be highly valuable for future clinical decision-making. This review provides a technical overview of two commonly used techniques for metabolomics measurements: mass spectrometry (MS) and proton nuclear magnetic resonance (¹H NMR) spectroscopy. We also discuss recent clinical advances in these techniques. Individuals with inflammatory bowel disease (IBD) exhibit significant variability in prognosis and response to treatment. Since both genetic predisposition and environmental factors contribute to this condition, targeting the metabolome may provide key insights for distinguishing and profiling patients with different clinical needs. Additionally, the considerable overlap in the clinical presentation of various disease subtypes emphasizes the need for enhanced diagnostic methods to improve patient care.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123238"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623313","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":"Glioblastoma therapy: State of the field and future prospects","authors":"Nadia Allahyarzadeh Khiabani ,&nbsp;Mohammad Amin Doustvandi ,&nbsp;Darren Story ,&nbsp;Shima Alizadeh Nobari ,&nbsp;Masoumeh Hajizadeh ,&nbsp;Robert Petersen ,&nbsp;Gary Dunbar ,&nbsp;Julien Rossignol","doi":"10.1016/j.lfs.2024.123227","DOIUrl":"10.1016/j.lfs.2024.123227","url":null,"abstract":"<div><div>Glioblastoma (GB) is a cancerous brain tumor that originates from glial cells and leads to thousands of deaths each year and a five-year survival of only 6.8 %. Treatments for GB include surgery, chemotherapy, radiation, and immunotherapy. GB is an incurable fatal disease, necessitating the development of innovative strategies to find a developing effective therapy. Genetic therapies may be crucial in treating GB by identifying the mutations and amplifications of multiple genes, which drive its proliferation and spread. Use of small interfering RNAs (siRNAs) provides a novel technology used to suppress the genes associated with disease, which forms a basis for targeted therapy in GB and its stem cell population, which are recognized for their ability to develop resistance to chemotherapy and tumorigenic capabilities. This review examines the use of siRNAs in GB, emphasizing their effectiveness in suppressing key oncogenes and signaling pathways associated with tumor development, invasion, stemness, and resistance to standard treatments. siRNA-based gene silencing is a promising approach for developing targeted therapeutics against GB and associated stem cell populations, potentially enhancing patient outcomes and survival rates in this devastating disease.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123227"},"PeriodicalIF":5.2,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623311","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":"Albumin binding domain fusion improved the therapeutic efficacy of Inhibitor of Differentiation-2 protein in colitis mice","authors":"Lingyun Xu ,&nbsp;Yuxin Wang ,&nbsp;Dong Yan ,&nbsp;Min Li ,&nbsp;Lin Qiao ,&nbsp;Zhiguo Chen ,&nbsp;Minna Wu ,&nbsp;Genshen Zhong","doi":"10.1016/j.lfs.2024.123237","DOIUrl":"10.1016/j.lfs.2024.123237","url":null,"abstract":"<div><h3>Aims</h3><div>The human Inhibitor of Differentiation-2 (hID2) protein is a promising candidate for the treatment of colitis. However, its relatively low molecular weight limits its clinical application. To extend the therapeutic half-life, an albumin-binding domain (ABD), known for its high affinity for human serum albumin (HSA), was fused to hID2, resulting in a recombinant ABD-hID2. The anti-colitis bioactivity of ABD-hID2 than that of hID2 was evaluated in this study.</div></div><div><h3>Main methods</h3><div>Western blotting, size-exclusion high-performance chromatography, HSA binding assay, and pharmacokinetic studies were used to characterise ABD-hID2, which was induced by dextran sulfate sodium salt (DSS), <em>Citrobacter rodentium</em> (<em>CR</em>), and ABD-hID2 and hID2. The Disease Activity Index, histological pathologies, inflammatory response, Alcian blue or tuft cell staining, and tight junction proteins were determined. Alterations in the intestinal microbiota after ABD-hID2 treatment were analysed <em>via</em> 16S rRNA gene sequencing.</div></div><div><h3>Key findings</h3><div>Compared with hID2, ABD-hID2 exhibited a decreased dimer complex, bound to HSA with high affinity, and demonstrated an extended blood retention time <em>in vivo</em>. Consequently, ABD-hID2 exhibited increased therapeutic efficacy in both DSS- and <em>CR</em>-induced colitis mouse models, as evidenced by the alleviation of colitis symptoms, preservation of goblet and tuft cell functions, restoration of the intestinal mucus barrier, and suppression of abnormal immune-inflammatory responses. Additionally, the modulation of the gut microbiota may play a role in the protective effects of ABD-hID2 in mice with <em>CR</em>-induced ulcerative colitis.</div></div><div><h3>Significance</h3><div>ABD-hID2 enhances the bioactivity of hID2 and has the potential for further development as a treatment for colitis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123237"},"PeriodicalIF":5.2,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623320","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":"Integrating multi-omics data reveals neuroblastoma subtypes in the tumor microenvironment","authors":"Jinhua Fan ,&nbsp;Shuxin Tang ,&nbsp;Xiangru Kong ,&nbsp;Yupeng Cun","doi":"10.1016/j.lfs.2024.123236","DOIUrl":"10.1016/j.lfs.2024.123236","url":null,"abstract":"<div><div>Neuroblastoma (NB) is a severe pediatric tumor originating from the developing sympathetic nervous system, characterized by diverse clinical outcomes, including spontaneous regression and aggressive metastasis. This variability suggests the existence of different NB subtypes, necessitating accurate classification for effective targeted treatment. In this study, we employed the similarity network fusion (SNF) algorithm and identified three NB subtypes, including mesenchymal-like (MES), <em>MYCN</em>-like (MYCN), and neurogenic-like (Neurogenic). The MES subtype exhibited the highest activation of immune-related pathways. The MYCN subtype demonstrated the worst prognosis, with enrichment in cell growth and proliferation pathways. Conversely, the Neurogenic subtype showed the best prognosis, with enrichment in sympathetic nervous system development processes. Through single-cell RNA sequencing (scRNA-seq) analysis, we examined the tumor microenvironments of these distinct NB subtypes, revealing divergent differentiation trajectories for adrenergic cells within the MYCN and Neurogenic subtypes. We also identified a significant presence of naïve T cells in the MES subtype, as well as mesenchymal cell subtypes associated with the unique plasticity observed in both the MES and MYCN subtypes. Drug sensitivity prediction analysis suggested that the MES subtype may respond favorably to MEK inhibitors, while the MYCN subtype may be susceptible to Bcl-2 inhibitors. Our integrative multi-omics approach enabled precise stratification of NB into biologically distinct subtypes, potentially facilitating the development of subtype-specific therapeutic strategies for improved patient management and survival outcomes.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123236"},"PeriodicalIF":5.2,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623323","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":"Targeting AMPK with Irisin: Implications for metabolic disorders, cardiovascular health, and inflammatory conditions - A systematic review.","authors":"Lucas Fornari Laurindo, Victória Dogani Rodrigues, Lívia Fornari Laurindo, Luana Maria Amaral Cherain, Enzo Pereira de Lima, Beatriz Leme Boaro, Jéssica da Silva Camarinha Oliveira, Eduardo Federighi Baisi Chagas, Vitor Cavallari Strozze Catharin, Jesselina Francisco Dos Santos Haber, Patrícia Cincotto Dos Santos Bueno, Rosa Direito, Sandra Maria Barbalho","doi":"10.1016/j.lfs.2024.123230","DOIUrl":"10.1016/j.lfs.2024.123230","url":null,"abstract":"<p><p>Irisin-based interventions have gained attention for their potential to modulate the adenosine monophosphate (AMP)-activated protein kinase (AMPK) pathway in various diseases. Physiologically, irisin is a myokine released during physical exercise that exerts anti-inflammatory effects and is a metabolic and cardiometabolic enhancer. On the other hand, AMPK is crucial for maintaining energy balance and metabolic homeostasis. Therefore, individuals presenting low blood levels of irisin and AMPK dysregulation are more predisposed to metabolic disorders and cardiovascular health inflammatory conditions since regulating energy balance and metabolic homeostasis are crucial for preventing or treating these disorders. In light of those mentioned above and considering that no review has addressed the intricate relationships between irisin and AMPK regulation in the realm of metabolic disorders, cardiovascular health, and inflammatory conditions, we comprehensively reviewed studies involving irisin's effects on AMPK signaling in different models and interventions. Our systematic analysis involved in vitro studies, animal models, and their relevant clinical implications of irisin targeting AMPK due to the absence of relevant clinical trials. The outcomes and limitations of the included studies were extensively highlighted. Objectively, irisin improved metabolic disorders by enhancing β-cell function and insulin secretion in diabetes, mitigating myocardial injury in cardiovascular conditions, and reducing inflammation and oxidative stress in various injury models by targeting AMPK. However, the lack of clinical trials limits the generalizability of these findings to human subjects. Future research should focus on translating these findings into clinical applications and exploring the broader implications of irisin-based interventions in human health.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123230"},"PeriodicalIF":5.2,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623316","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":"Exercise, exerkines and exercise mimetic drugs: Molecular mechanisms and therapeutics","authors":"Vedant Samant,&nbsp;Arati Prabhu","doi":"10.1016/j.lfs.2024.123225","DOIUrl":"10.1016/j.lfs.2024.123225","url":null,"abstract":"<div><div>Chronic diseases linked with sedentary lifestyles and poor dietary habits are increasingly common in modern society. Exercise is widely acknowledged to have a plethora of health benefits, including its role in primary prevention of various chronic conditions like type 2 diabetes mellitus, obesity, cardiovascular disease, and several musculoskeletal as well as degenerative disorders. Regular physical activity induces numerous physiological adaptations that contribute to these positive effects, primarily observed in skeletal muscle but also impacting other tissues.</div><div>There is a growing interest among researchers in developing pharmaceutical interventions that mimic the beneficial effects of exercise for therapeutic applications. Exercise mimetic medications have the potential to be helpful aids in enhancing functional outcomes for patients with metabolic dysfunction, neuromuscular and musculoskeletal disorders. Some of the potential targets for exercise mimetics include pathways involved in metabolism, mitochondrial function, inflammation, and tissue regeneration. The present review aims to provide an exhaustive overview of the current understanding of exercise physiology, the role of exerkines and biomolecular pathways, and the potential applications of exercise mimetic drugs for the treatment of several diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123225"},"PeriodicalIF":5.2,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623322","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":"Electroacupuncture combined with NSCs-Exo alters the response of hippocampal neurons in a chronic unpredictable mild stress paradigm in ovx rats","authors":"Qin Lyu ,&nbsp;Liu-Qing Shi ,&nbsp;Hai-Yang Chen ,&nbsp;Mei Lu ,&nbsp;Xi-Cai Liang ,&nbsp;Xian-De Ma ,&nbsp;Xin Zhou ,&nbsp;Lu Ren","doi":"10.1016/j.lfs.2024.123235","DOIUrl":"10.1016/j.lfs.2024.123235","url":null,"abstract":"<div><div>Electroacupuncture (EA) is a form of Traditional Chinese Medicine (TCM) that combines acupuncture with microcurrents mimicking the body's bioelectricity to prevent and treat diseases. Previous studies have demonstrated its antidepressant-like effects in chronic unpredictable mild stress (CUMS)-induced ovariectomy (OVX) rats. Neural stem cell-derived exosomes (NSCs-Exo) are heterogeneous and targeted, effectively promoting nerve regeneration and repairing neuronal damage, while potentially conveying the effects of EA. However, the precise mechanism remains unclear. In this study, perimenopausal depressive disorder (PDD) rat model were established using a two-step protocol CUMS + OVX. Treatment with EA combined with NSCs-Exo (EA-Exo) significantly improved depression-like behaviors in PDD rats, as indicated by increased sucrose intake in the Sucrose Preference Test (SPT), reduced immobility in the Forced Swimming Test (FST), and prolonged activity in the Out-of-Field Test (OFT). EA-Exo treatment improved depression-like behaviors by increasing serum levels of 5-hydroxytryptamine (5-HT) and decreasing immobility in the FST. It also alleviated OVX-CUMS-induced disturbances in energy metabolism, inflammation, and oxidative stress responses by enhancing serum levels of 5-HT, dopamine (DA), ATP, superoxide dismutase (SOD), and interleukin-10 (IL-10), while reducing cyclic AMP (cAMP), interleukin-6 (IL-6), reactive oxygen species (ROS), and malondialdehyde (MDA). Furthermore, EA-Exo treatment reversed structural and functional impairments in hippocampal synapses and mitochondria. This was evidenced by reductions in hippocampal synaptic plasticity proteins PSD95, SYN, and GAP43, as well as decreased expression of energy metabolism pathway proteins AMPK, NRF1, PGC1α, and TFAM. These findings suggest that EA-Exo ameliorates depressive behavior in OVX-CUMS rats by modulating synaptic plasticity and activating the AMPK/NRF1/PGC1α/TFAM signaling pathway.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123235"},"PeriodicalIF":5.2,"publicationDate":"2024-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}