Life sciences最新文献_第6页

SGK1 inhibits oxidative injury and extracellular matrix degradation by activating the GSK-3β (Ser9)/Fyn/NRF2 pathway in pelvic organ prolapse SGK1通过激活盆腔器官脱出中的GSK-3β (Ser9)/Fyn/NRF2通路抑制氧化损伤和细胞外基质降解

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-30 DOI: 10.1016/j.lfs.2025.123939

Yunfang Yan , Jing Peng , Wei He , Yan Chen , Wei Ye , Zongzhi Yin , Yunxia Cao

{"title":"SGK1 inhibits oxidative injury and extracellular matrix degradation by activating the GSK-3β (Ser9)/Fyn/NRF2 pathway in pelvic organ prolapse","authors":"Yunfang Yan , Jing Peng , Wei He , Yan Chen , Wei Ye , Zongzhi Yin , Yunxia Cao","doi":"10.1016/j.lfs.2025.123939","DOIUrl":"10.1016/j.lfs.2025.123939","url":null,"abstract":"<div><h3>Aims</h3><div>Sustained oxidative stress (OS) promotes the development of pelvic organ prolapse (POP); however, the pathogenesis of POP under OS conditions remains unclear. This study aimed to investigate the role of serum and glucocorticoid-induced protein kinase 1 (SGK1) in the progression of POP in OS and elucidate its potential molecular mechanisms.</div></div><div><h3>Materials and methods</h3><div>The protein levels of SGK1 in fibroblasts and other cells within the uterosacral ligament tissues (ULTs) from patients with POP in OS were measured by immunofluorescence (IF). Human uterosacral ligament fibroblasts (hUSLFs) were treated with hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>) to establish an <em>in vitro</em> model of oxidative damage. SGK1 was overexpressed and knocked down using a lentivirus to investigate oxidative damage and extracellular matrix (ECM) degradation under H<sub>2</sub>O<sub>2</sub> stimulation. The interaction between SGK1 and GSK-3β was explored using co-immunoprecipitation assays, molecular docking models, and IF.</div></div><div><h3>Key findings</h3><div>SGK1 was upregulated in fibroblasts within the ULTs from patients with POP under OS conditions and in H<sub>2</sub>O<sub>2</sub>-induced hUSLFs. SGK1 overexpression in H<sub>2</sub>O<sub>2</sub>-treated hUSLFs inhibited H<sub>2</sub>O<sub>2</sub>-triggered apoptosis, reactive oxygen species generation, and collagen loss, whereas SGK1 depletion promoted these processes. Mechanistically, SGK1 suppressed OS-induced oxidative damage, and ECM degradation in hUSLFs by binding with GSK-3β to activate the GSK-3β (Ser9)/Fyn/NRF2 pathway.</div></div><div><h3>Significance</h3><div>Our results revealed that SGK1 could potentially slow down the progression of POP under OS by interacting with GSK-3β to promote the GSK-3β (Ser9)/Fyn/NRF2 pathway, which provides a potential therapeutic approach for treating POP.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123939"},"PeriodicalIF":5.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933147","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}

引用次数: 0

IL-11-mediated macrophage crosstalk drives renal inflammation and fibrosis: A novel therapeutic target in chronic kidney disease il -11介导的巨噬细胞串扰驱动肾脏炎症和纤维化：慢性肾脏疾病的新治疗靶点

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-30 DOI: 10.1016/j.lfs.2025.123949

Xiaoran Wang , Wei Zhou , Xinyin Liu , Zhili Huang , Wen Zhang

{"title":"IL-11-mediated macrophage crosstalk drives renal inflammation and fibrosis: A novel therapeutic target in chronic kidney disease","authors":"Xiaoran Wang , Wei Zhou , Xinyin Liu , Zhili Huang , Wen Zhang","doi":"10.1016/j.lfs.2025.123949","DOIUrl":"10.1016/j.lfs.2025.123949","url":null,"abstract":"<div><h3>Aims</h3><div>To investigate the pathogenic role of Interleukin-11 (IL-11) in chronic kidney disease (CKD) progression and evaluate the therapeutic potential of IL-11 neutralizing antibodies in attenuating renal inflammation and fibrosis.</div></div><div><h3>Materials and methods</h3><div>We conducted systematic molecular and cellular analyses to characterize IL-11-mediated signaling pathways in CKD models. The effects of IL-11 on macrophage polarization, cellular transitions, and stress responses were examined. Preclinical efficacy studies were performed using selective IL-11 neutralizing antibodies to assess their impact on renal pathology.</div></div><div><h3>Key findings</h3><div>IL-11 orchestrates renal injury through immune crosstalk between macrophages and tubular epithelial cells (TECs) via STAT3 signaling activation. IL-11 promotes M1 macrophage polarization, facilitates the macrophage-to-myofibroblast transition (MMT), and triggers epithelial-to-mesenchymal transition (EMT) in TECs. Additionally, IL-11 amplifies oxidative and endoplasmic reticulum stress responses. Treatment with IL-11 neutralizing antibodies effectively interrupted IL-11/IL-11Rα1 interaction and downstream STAT3/ERK1/2-mediated metadherin activation, resulting in reduced pro-fibrotic extracellular matrix deposition, enhanced TEC regenerative capacity, and improved renal parenchymal repair.</div></div><div><h3>Significance</h3><div>These findings establish the IL-11 signaling axis as a promising therapeutic target in CKD. The demonstrated efficacy of antibody-based interventions presents a novel precision medicine approach for CKD treatment, offering significant potential for clinical translation in nephrology.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123949"},"PeriodicalIF":5.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933150","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}

引用次数: 0

FGF21-loaded M2 macrophage-derived exosomes attenuate sepsis-induced lung injury by regulating M2 macrophage polarization and glycolysis 负载fgf21的M2巨噬细胞来源外泌体通过调节M2巨噬细胞极化和糖酵解来减轻败血症诱导的肺损伤。

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-30 DOI: 10.1016/j.lfs.2025.123932

Fangfang Wu , Yaolu Zhang , Yingdan Tang , Yihao Kang , Yan Li , Xiyi Hu , Jiaxin Liu , Xi Tian , Zhongqiu Lu

{"title":"FGF21-loaded M2 macrophage-derived exosomes attenuate sepsis-induced lung injury by regulating M2 macrophage polarization and glycolysis","authors":"Fangfang Wu , Yaolu Zhang , Yingdan Tang , Yihao Kang , Yan Li , Xiyi Hu , Jiaxin Liu , Xi Tian , Zhongqiu Lu","doi":"10.1016/j.lfs.2025.123932","DOIUrl":"10.1016/j.lfs.2025.123932","url":null,"abstract":"<div><div>Sepsis, a critical lethal critical illness, involves glucose and lipid metabolism disorders. However, the specific mechanisms underlying these alterations require further investigation. Acute lung injury (ALI), one of the most serious complications of sepsis, has a high mortality rate. Fibroblast growth factor 21 (FGF21), a key metabolic regulator, can regulate glucose metabolism. However, the short half-life (t½) of FGF21 limits its clinical application. In this study, we designed FGF21-loaded M2 macrophage-derived exosomes, named FGF21-M2-Exos, for the treatment of sepsis-induced ALI. We demonstrated that FGF21-M2-Exos were able to release FGF21 in a controlled and sustained manner. In addition, FGF21-M2-Exos were present in the lungs of mice at 24 h. Importantly, our results suggest that FGF21-M2-Exos alleviate sepsis-induced lung damage. Moreover, the RNA sequencing results revealed that FGF21-M2-Exos regulate immune function via several inflammatory signalling pathways. Furthermore, we found that FGF21-M2-Exo administration protects against sepsis-induced lung injury by downregulating inflammation-related protein expression, promoting M2 macrophage polarization, inhibiting glycolysis and reducing cellular apoptosis. Overall, the use of FGF21-M2-Exos, which regulate inflammatory and metabolic processes, may be a promising strategy for treating sepsis-induced ALI.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123932"},"PeriodicalIF":5.1,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959485","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}

引用次数: 0

The role of FGF21 in the metabolic adjustments required for exercise capacity FGF21在运动能力所需的代谢调节中的作用

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-29 DOI: 10.1016/j.lfs.2025.123940

Lisa Abe , Robert Dantzer

{"title":"The role of FGF21 in the metabolic adjustments required for exercise capacity","authors":"Lisa Abe , Robert Dantzer","doi":"10.1016/j.lfs.2025.123940","DOIUrl":"10.1016/j.lfs.2025.123940","url":null,"abstract":"<div><div>Fatigue is one of the most common and persistent symptoms experienced by patients with various medical conditions. It is characterized by its enduring nature, lack of improvement after a good night's sleep, and interference with daily functioning. The mechanisms behind fatigue remain controversial. In cancer patients, inflammation and mitochondrial dysfunction appear to be the predominant contributors. Mitochondrial dysfunction results from oxidative stress and inflammation. This condition leads to the production and release of soluble mediators known as mitokines, which act in an autocrine, paracrine, and endocrine manner to help the body adapt to the changes in energy metabolism caused by mitochondrial dysfunction. The main mitokines include growth differentiation factor (GDF) 15 and fibroblast growth factor (FGF) 21. We have already gathered evidence highlighting the pivotal role of GDF15 in the behavioral fatigue that arises in response to chemotherapy. In this perspective article, we explore whether the existing knowledge about the role of FGF21 in metabolic adaptations during cellular stress positions this mitokine as a potential candidate for cancer-related fatigue. To do this, we <strong>summarize</strong> how FGF21 is produced at the level of each organ involved in energy metabolism and how its local and distant effects may influence the capacity to engage in energy-intensive activities such as physical exercise.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123940"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925010","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}

引用次数: 0

Dysregulation of the TNF-α-OTUD3-PPARγ signaling axis exacerbates retinal oxidative stress and inflammation in diabetic retinopathy TNF-α-OTUD3-PPARγ信号轴的失调加剧了糖尿病视网膜病变的视网膜氧化应激和炎症

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-29 DOI: 10.1016/j.lfs.2025.123933

Jialin Zhang , Zhen Wang , Junjun Liu , Wenchang Xu , Lu Lu , Na Zhou , Yongfeng Song

{"title":"Dysregulation of the TNF-α-OTUD3-PPARγ signaling axis exacerbates retinal oxidative stress and inflammation in diabetic retinopathy","authors":"Jialin Zhang , Zhen Wang , Junjun Liu , Wenchang Xu , Lu Lu , Na Zhou , Yongfeng Song","doi":"10.1016/j.lfs.2025.123933","DOIUrl":"10.1016/j.lfs.2025.123933","url":null,"abstract":"<div><h3>Aims</h3><div>Diabetic retinopathy (DR) is one of the major complications of diabetes. In addition to hyperglycemia, various mechanisms contribute to the development of microvascular damage to the retina, which have not been fully elucidated. The aim of this study was to investigate Ovarian tumor domain-containing protein 3 (OTUD3)'s protection against DR by targeting peroxisome proliferator-activated receptor γ (PPARγ)-mediated dysfunction and identifying therapeutic strategies.</div></div><div><h3>Materials and methods</h3><div>We conducted clinical analysis of 208 type 2 diabetes mellitus (T2DM) patients with OTUD3 genotyping, combined with diabetic homozygous mutated (<em>Otud3</em><sup><em>−/−</em></sup>) mouse models and retinal pigment epithelium (RPE) cell lines (OTUD3 knockdown/mutation).</div></div><div><h3>Key findings</h3><div>We found increased hyperreflective foci (HRF) associated with an increased immune activation in diabetic <em>Otud3</em><sup><em>−/−</em></sup> mice compared to <em>Otud3</em> wild-type (<em>Otud3</em><sup><em>+/+</em></sup>) mice. OTUD3 knockdown or mutated cells showed increased cell dysfunction and oxidative stress markers under inflammatory conditions. Further upstream transcription factors predict analysis suggest PPARγ as the potential target of OTUD3. Finally, we found PPARγ agonist could rescue the phenotype in RPE cells characterized by increased ROS levels, enhanced migration, and elevated apoptosis resulting from OTUD3 loss of function through knockdown or mutation.</div></div><div><h3>Significance</h3><div>Our study offers novel insights into how deubiquitylase OTUD3 maintains the normal function of the retina by deubiquitylating PPARγ and provides a novel therapeutic target for this vision-threatening diabetic complications.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123933"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933146","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}

引用次数: 0

Maternal obesogenic diet causes insulin resistance by modulating insulin signaling pathways in peripheral tissues of offspring: a systematic review 母体致肥性饮食通过调节后代外周组织中的胰岛素信号通路引起胰岛素抵抗：一项系统综述

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-29 DOI: 10.1016/j.lfs.2025.123947

Carolina Ramos de Mendonça , Lígia Cristina Monteiro Galindo , Bruna Karoline Alves de Melo Silva , Brenda Hilary Avelino de Vasconcelos , Vitor Carlos de Araújo Bandeira , Sandro Massao Hirabara , Beatrice Morio , Diogo Antonio Alves de Vasconcelos

{"title":"Maternal obesogenic diet causes insulin resistance by modulating insulin signaling pathways in peripheral tissues of offspring: a systematic review","authors":"Carolina Ramos de Mendonça , Lígia Cristina Monteiro Galindo , Bruna Karoline Alves de Melo Silva , Brenda Hilary Avelino de Vasconcelos , Vitor Carlos de Araújo Bandeira , Sandro Massao Hirabara , Beatrice Morio , Diogo Antonio Alves de Vasconcelos","doi":"10.1016/j.lfs.2025.123947","DOIUrl":"10.1016/j.lfs.2025.123947","url":null,"abstract":"<div><div>Overweight and obesity during critical periods, gestation and/or lactation, can harm offspring metabolic health. Maternal obesogenic diets may program offspring long-term, impairing physiology and increasing risk for insulin resistance. A key mechanism is the reduced expression/activity of insulin signaling proteins in peripheral glucose-metabolizing tissues. This systematic review examined the impact of maternal obesogenic diets on insulin resistance in the offspring of rats, through modulation of insulin signaling proteins in skeletal muscle, liver, and white adipose tissue. Searches in LILACS, PubMed, Web of Science, Scopus, and Sigle via Opera Gray yielded 2212 studies; 43 met inclusion criteria, following a PROSPERO-registered protocol. Findings showed reduced expression and activity of IRS-1, PI3K, AKT and GLUTs in peripheral tissues, alongside increased body weight, glucose intolerance, and insulin resistance. Thus, maternal obesogenic diets impair insulin signaling and related metabolic outcomes in offspring.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123947"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933136","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}

引用次数: 0

CpG-mediated TLR9 signaling pathway enhances the efficacy of the OprF/PcrV DNA vaccine with cGAS-STING-activating properties cpg介导的TLR9信号通路增强了具有cgas - sting激活特性的OprF/PcrV DNA疫苗的效力

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-29 DOI: 10.1016/j.lfs.2025.123930

Linxia Tian, Hongxi He, Hanbai Liu, Yating Zhang, Xian Yu

{"title":"CpG-mediated TLR9 signaling pathway enhances the efficacy of the OprF/PcrV DNA vaccine with cGAS-STING-activating properties","authors":"Linxia Tian, Hongxi He, Hanbai Liu, Yating Zhang, Xian Yu","doi":"10.1016/j.lfs.2025.123930","DOIUrl":"10.1016/j.lfs.2025.123930","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to overcome the limited protective efficacy of the bivalent DNA vaccine (DNA-OprF/PcrV) against <em>Pseudomonas aeruginosa</em> (PA) infection by developing a complexed adjuvant strategy to enhance immunogenicity and protection, providing a novel clinical candidate vaccine.</div></div><div><h3>Materials and methods</h3><div>We formulated a bivalent DNA vaccine encoding PA antigens OprF and PcrV (DNA-OprF/PcrV) complexed with the TLR9 agonist CpG adjuvant (DNA-OprF/PcrV + CpG). In vitro mechanistic studies assessed synergistic pathway activation and dendritic cell maturation, while murine models evaluated humoral immunity (antibody titers), cellular immunity (Th1/CTL responses), and protective efficacy via pulmonary infection models with bacterial burden quantification and inflammation analysis.</div></div><div><h3>Key findings</h3><div>The CpG-adjuvanted vaccine synergistically activated both cGAS-STING (vaccine-mediated) and TLR9 (CpG-mediated) pathways, significantly enhancing dendritic cell maturation and innate immunity. Consequently, it amplified adaptive immunity, including potentiated Th1 polarization and cytotoxic T lymphocyte (CTL) activity alongside elevated PA-specific antibody titers. In pulmonary infection models, this formulation conferred superior protection marked by significantly reduced bacterial burden and attenuated inflammation compared to the non-adjuvanted vaccine.</div></div><div><h3>Significance</h3><div>This work demonstrates that the CpG-adjuvanted DNA vaccine complex overcomes DNA vaccine limitations through dual-pathway synergy, providing a clinically translatable strategy against multidrug-resistant PA infection and pioneering a cGAS-STING/TLR9 co-activation paradigm for antibacterial vaccine design.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123930"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925009","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}

引用次数: 0

New role of obscure acylation modifications in cardiovascular diseases: what's beyond? 模糊的酰化修饰在心血管疾病中的新作用：还有什么？

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-29 DOI: 10.1016/j.lfs.2025.123944

Zhongyi Zhang , Wei Hu , Qian Ding , Yi Zhun Zhu

{"title":"New role of obscure acylation modifications in cardiovascular diseases: what's beyond?","authors":"Zhongyi Zhang , Wei Hu , Qian Ding , Yi Zhun Zhu","doi":"10.1016/j.lfs.2025.123944","DOIUrl":"10.1016/j.lfs.2025.123944","url":null,"abstract":"<div><div>Cardiovascular diseases remain the leading cause of global mortality, yet their molecular mechanisms are incompletely understood. Recent advances highlight the critical role of obscure acylation modifications in regulating cardiac homeostasis and disease pathogenesis, such as succinylation, crotonylation, malonylation, β-hydroxybutyrylation, and lactylation. These post-translational modifications serve as metabolic sensors, dynamically linking cellular metabolism to epigenetic and functional changes in proteins. This mini-review synthesizes emerging evidence on how dysregulated obscure acylations contribute to cardiovascular diseases, including heart failure, ischemic injury, and atherosclerosis, by altering mitochondrial function, gene expression, or cellular signaling. We further discuss the therapeutic potential of targeting acyl-modifying enzymes and innovative strategies like machine learning for modification prediction. Despite technological challenges in profiling rare modifications, this field offers promising avenues for novel biomarkers and precision therapies. By elucidating the relationship between cardiovascular pathologies and obscure acylation modifications, this mini-review aims to inspire future research for clinical intervention of cardiovascular diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123944"},"PeriodicalIF":5.1,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144925011","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}

引用次数: 0

A PBX1-IL7R axis mediates liver fibrosis in non-alcoholic fatty liver disease PBX1-IL7R轴介导非酒精性脂肪性肝病的肝纤维化。

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-28 DOI: 10.1016/j.lfs.2025.123948

Zhen Yang , Jinbo Zhang , Qihang Wang , Huihui Xu , Xihu Qin , Fangqiao Lv

{"title":"A PBX1-IL7R axis mediates liver fibrosis in non-alcoholic fatty liver disease","authors":"Zhen Yang , Jinbo Zhang , Qihang Wang , Huihui Xu , Xihu Qin , Fangqiao Lv","doi":"10.1016/j.lfs.2025.123948","DOIUrl":"10.1016/j.lfs.2025.123948","url":null,"abstract":"<div><h3>Aims</h3><div>Non-alcoholic fatty liver disease (NAFLD), also known as metabolic dysfunction associated steatotic liver disease (MASLD), represents a spectrum of chronic liver diseases that eventually lead to cirrhosis and hepatocellular carcinoma. Liver fibrosis is both a pathological feature and a contributing factor in NAFLD. In the present study we investigated whether targeting pre-B cell leukemia transcription factor 1 (PBX1) and interleukin 7 receptor (IL7R) might ameliorate liver fibrosis in the context of NAFLD.</div></div><div><h3>Methods and materials</h3><div>NAFLD was induced in C57/B6j mice by feeding with a choline-deficient amino acid defined high-fat diet (CDAA-HFD).</div></div><div><h3>Key findings</h3><div>Both PBX1 expression and IL7R expression were up-regulated in hepatic stellate cells (HSCs) isolated from the mice fed the CDAA-HFD compared to those isolated from the control mice. Myofibroblast-specific PBX1 depletion, by injecting the mice with AAV6 carrying short-hairpin RNA (shRNA) against PBX1, significantly attenuated liver fibrosis induced by CDAA-HFD feeding. Similarly, myofibroblast-specific IL7R depletion significantly mitigated NAFLD-associated liver fibrosis. Of note, liver injury and steatosis were not influenced by either PBX1 or IL7R depletion. Importantly, IL7R blockade with a neutralizing antibody likewise diminished NAFLD-associated liver fibrosis. Finally, a positive correlation between PBX1 expression, IL7R expression, and myofibroblast activation was identified in liver specimens from NAFLD patients.</div></div><div><h3>Significance</h3><div>Our data demonstrate the feasibility of targeting the PBX1-IL7R axis for the intervention of NAFLD-associated liver fibrosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123948"},"PeriodicalIF":5.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144959393","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}

引用次数: 0

The role of ferroptosis in doxorubicin-induced cardiotoxicity – An update 铁下垂在阿霉素诱导的心脏毒性中的作用-最新进展

IF 5.1 2区医学

Life sciences Pub Date : 2025-08-28 DOI: 10.1016/j.lfs.2025.123945

Pammi Bhadra , Prisha Yadav , Sanjot Kaur , Padmini Topinar Hanumantharayudu, Sankarganesh Arunachalam

{"title":"The role of ferroptosis in doxorubicin-induced cardiotoxicity – An update","authors":"Pammi Bhadra , Prisha Yadav , Sanjot Kaur , Padmini Topinar Hanumantharayudu, Sankarganesh Arunachalam","doi":"10.1016/j.lfs.2025.123945","DOIUrl":"10.1016/j.lfs.2025.123945","url":null,"abstract":"<div><div>Doxorubicin is a chemotherapeutic drug used in the treatment of a variety of cancers, such as cancer of the blood, bladder, breast, lymph system, stomach, neuroblasts, etc. Currently, its potential is severely limited as it leads to cardiotoxicity, a fatal side effect. Several studies have been carried out in the past few decades to elucidate the molecular mechanisms of this Doxorubicin-induced cardiotoxicity. This study aims to analyse the role of ferroptosis in the mechanism of Doxorubicin-induced cardiotoxicity, an area which remains comparatively unexplored. The article elaborates on the molecular pathogenesis of ferroptosis and the role of doxorubicin in triggering the same. Several biological pathways, especially Nrf2 (Nuclear factor erythroid 2-related factor 2)-mediated pathways, are influenced by doxorubicin, leading to ferroptosis. The study of molecular mechanisms of doxorubicin-induced cardiotoxicity is instrumental for developing therapeutic interventions that alleviate cardiotoxicity and improve the outcomes of doxorubicin usage, such as targeting ferritinophagy, which is one of the key factors in causing ferroptosis, and can reduce cardiotoxicity and can be a potential therapeutic strategy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"380 ","pages":"Article 123945"},"PeriodicalIF":5.1,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144933149","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}

引用次数: 0