Life sciences最新文献

{"title":"MPNN-CWExplainer: An enhanced deep learning framework for HIV drug bioactivity prediction with class-weighted loss and explainability","authors":"Aga Basit Iqbal ,&nbsp;Assif Assad ,&nbsp;Basharat Bhat ,&nbsp;Muzafar A. Macha ,&nbsp;Syed Zubair Ahmad Shah","doi":"10.1016/j.lfs.2025.123835","DOIUrl":"10.1016/j.lfs.2025.123835","url":null,"abstract":"<div><h3>Aims</h3><div>Human Immunodeficiency Virus (HIV) remains a critical global health concern due to its impact on the immune system and its progression to Acquired Immunodeficiency Syndrome (AIDS) if untreated. While antiretroviral therapy has advanced significantly, challenges such as drug resistance, adverse effects, and viral mutation necessitate the development of novel therapeutic strategies. This study aims to improve HIV bioactivity prediction and provide interpretable insights into molecular determinants influencing bioactivity.</div></div><div><h3>Materials and methods</h3><div>We propose MPNN-CWExplainer, a novel graph-based deep learning framework for molecular property prediction. The model integrates a Message Passing Neural Network (MPNN) with a class-weighted loss function to effectively address class imbalance in HIV datasets. Furthermore, GNNExplainer is incorporated to provide post-hoc interpretability by identifying key atom- and bond-level substructures contributing to model predictions. Model robustness is ensured through Bayesian hyperparameter optimization and multiple independent runs.</div></div><div><h3>Key findings</h3><div>MPNN-CWExplainer achieved state-of-the-art predictive performance on the HIV dataset, with an AUC-ROC of 87.631 % and AUC-PRC of 86.02 %, surpassing existing baseline models. The class-weighted approach enhanced minority class representation, and GNNExplainer successfully highlighted chemically meaningful substructures correlating with bioactivity.</div></div><div><h3>Significance</h3><div>The proposed framework not only improves prediction accuracy for HIV bioactivity but also enhances transparency and interpretability, crucial for medicinal chemists in understanding model behaviour. MPNN-CWExplainer serves as a robust and interpretable tool for computational drug discovery, supporting informed decision-making in lead optimization and molecular design.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123835"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144567621","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":"Unravelling the roles of Vav3 in cytoskeletal control and angiogenesis","authors":"Yan Wang ,&nbsp;Zhaoran Wang ,&nbsp;Wenya Diao ,&nbsp;Tong Shi ,&nbsp;Jiahe Xu ,&nbsp;Tiantian Deng ,&nbsp;Chaoying Wen ,&nbsp;Jienan Gu ,&nbsp;Tingting Deng ,&nbsp;Cheng Xiao","doi":"10.1016/j.lfs.2025.123834","DOIUrl":"10.1016/j.lfs.2025.123834","url":null,"abstract":"<div><div>The oncogene Vav guanine nucleotide exchange factor 3 (Vav3) can accelerate neovascularization in the context of cancer by increasing cell proliferation and metastasis, making it a useful reference for understanding the process of pannus development in rheumatoid arthritis (RA). The overactivation of synovial tissue leads to increased cell invasion and inflammatory infiltration, resulting in a tumour-like immune microenvironment. Pannus formation, an early complication of RA, can progress to bone injury. The regulatory effect of Vav3 on cell invasion mainly involves increased adhesion and metastasis to support neovascularization, with effects on inflammatory cells, osteoclasts, and the cytoskeleton, resulting in microvessel formation and even bone destruction. The influence of Vav3 on cell proliferation and differentiation manifests as the promotion of immune cell formation and activation, as well as the intensification of immune infiltration into the local tissue. Targeted inhibition of Vav3 expression can reduce the pathological damage described above and may be a potential therapeutic target to limit pannus formation. Notably, as Vav3 is a cytoskeleton-associated protein, the association between epigenetic modifications of Vav3 (such as methylation and acetylation) and metabolic reprogramming is an interesting direction for future research on autoimmune diseases. Therefore, we summarize the latest information related to the biological role of Vav3, emphasizing the regulatory effects of the cytoskeleton in pannus development in the context of tumour-related research and discussing the clinical value of Vav3 epigenetic modification and energy metabolism in angiogenesis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123834"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575803","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":"Microcystin-LR exacerbates chronic kidney disease in rats: insights into gut microbiome and host proteome dysregulation","authors":"Suppakrit Kongsintaweesuk ,&nbsp;Keerapach Tunbenjasiri ,&nbsp;Thatsanapong Pongking ,&nbsp;Sitiruk Roytrakul ,&nbsp;Sawanya Charoenlappanit ,&nbsp;Sirirat Anutrakulchai ,&nbsp;Chawalit Pairojkul ,&nbsp;Kitti Intuyod ,&nbsp;Pakornkiat Tanasuka ,&nbsp;David Blair ,&nbsp;Somchai Pinlaor ,&nbsp;Porntip Pinlaor","doi":"10.1016/j.lfs.2025.123840","DOIUrl":"10.1016/j.lfs.2025.123840","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to investigate the effects of microcystin-leucine arginine (MC-LR), an environmental nephrotoxin, on the gut-kidney axis in chronic kidney disease (CKD), focusing on interactions between the gut microbiome and host proteome.</div></div><div><h3>Materials and methods</h3><div>Male Sprague-Dawley rats were administered adenine (200 mg/kg/day) for 10 days to induce kidney injury, followed by MC-LR (10 μg/mL/kg, i.p., every other day for 4 weeks). Renal function (Blood urea nitrogen, BUN; Serum creatinine, SCr and urine albumin to creatinine ratio, uACR) and kidney pathology (EGTI histology scores and picrosirius-red staining) were assessed. Expression of kidney injury (KIM-1), fibrosis (CTGF), inflammation (HMGB1 and CD3), oxidative stress (H2AX) markers were evaluated by immunohistochemical staining. Gut microbiota was analyzed by 16S rRNA sequencing, and fecal proteomics by LC-MS/MS.</div></div><div><h3>Key findings</h3><div>MC-LR markedly exacerbated adenine-induced kidney injury, leading to impair kidney function (elevated BUN, SCr, and uACR levels) and worsen kidney histopathology (higher EGTI histology scores and prominent fibrosis). Elevated expression levels of KIM1, HMBG1, CTGF, H2AX and CD3 were observed following MC-LR exposure. Notably, pro-inflammatory bacterial families (<em>Enterococcaceae</em>, <em>Enterobacteriaceae</em>) were elevated, while beneficial taxa (<em>Bifidobacteriaceae</em>, <em>Muribaculaceae</em>) decreased in the combination group. Proteomic analysis revealed upregulation of inflammatory markers (TXNIP, Itgb3bp), which correlated with <em>Enterococcaceae</em> abundance. <em>Bifidobacteriaceae</em> negatively correlated with kidney injury markers.</div></div><div><h3>Significance</h3><div>Our study reveals that MC-LR exacerbates chronic kidney disease progression by disrupting the gut-kidney axis. We highlight gut barrier integrity and inflammation as crucial therapeutic targets, offering novel insights and intervention strategies for CKD management, particularly in beyond early stages.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123840"},"PeriodicalIF":5.2,"publicationDate":"2025-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144575802","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 “Highland barley attenuates high fat and cholesterol diet induced hyperlipidemia in mice revealed by 16S rRNA gene sequencing and untargeted metabolomics” [Life Sci. 334 (2023) 122142]","authors":"Xiang Li ,&nbsp;Li Wang","doi":"10.1016/j.lfs.2025.123824","DOIUrl":"10.1016/j.lfs.2025.123824","url":null,"abstract":"","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"377 ","pages":"Article 123824"},"PeriodicalIF":5.2,"publicationDate":"2025-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564874","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":"METTL3-mediated TUG1 regulation of miR-9 in doxorubicin resistance in HCC","authors":"Enliang Li ,&nbsp;Rongshou Wu ,&nbsp;Yuexiao Tang ,&nbsp;Jun Yang ,&nbsp;Kehao Li ,&nbsp;Zhenduo Shao ,&nbsp;Jiayan Mao ,&nbsp;Jianghui Xiong ,&nbsp;Xiu Hu ,&nbsp;Wei Chen ,&nbsp;Linquan Wu","doi":"10.1016/j.lfs.2025.123832","DOIUrl":"10.1016/j.lfs.2025.123832","url":null,"abstract":"<div><h3>Aims</h3><div>Hepatocellular carcinoma (HCC) is one of the most prevalent malignant human tumors and a main cause of cancer death worldwide. Drug resistance limits the use of doxorubicin (DOX), a proliferation inhibitor used to treat HCC. This study aims to reveal the molecular mechanisms underlying DOX resistance and develop more effective therapies for HCC.</div></div><div><h3>Materials and methods</h3><div>An N⁶-methyladenosine (m⁶A) RNA immunoprecipitation sequencing-quantitative real-time polymerase chain reaction experiment was performed to assess m⁶A RNA methylation in HCC cells. A patient-derived xenograft mouse model was established to investigate the function of a chimeric peptide supramolecular nanoparticle system (SP94 dR/ miR-9 nanoparticles) <em>in vivo</em>.</div></div><div><h3>Results</h3><div>We found that the expression levels of <em>METTL3</em> and <em>TUG1</em> were upregulated in HCC, which was closely related to poor overall survival. Moreover, METTL3 and TUG1 depletion increased HCC cell sensitivity to DOX. <em>METTL3</em> silencing repressed <em>TUG1</em> expression in an m⁶A-dependent manner. Meanwhile, <em>TUG1</em> depletion sensitized HCC cells to DOX <em>via</em> EIF5A2 by upregulating miR-9. Furthermore, SP94-dR/miR-9 nanoparticles dramatically enhanced HCC cell sensitivity to DOX by regulating autophagy <em>in vitro</em> and inhibiting tumor growth <em>in vivo</em>.</div></div><div><h3>Significance</h3><div>Our data identified a novel molecular pathway comprising the METTL3-m⁶A-<em>TUG1</em>-miR-9-EIF5A2 signaling axis in HCC, providing new targets for future DOX resistance management.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123832"},"PeriodicalIF":5.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564873","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":"Proteomics reveals crosstalk between calcium disturbance and multiple stresses facilitating lethal ventricular arrhythmias-sudden cardiac death under the co-morbidity of acute myocardial ischemia and type II diabetes mellitus","authors":"Ye Zhang ,&nbsp;Xiaojun Zhang ,&nbsp;Huishan Liang ,&nbsp;Haiyan Li ,&nbsp;Wei Zhang ,&nbsp;Mengxuan Zhang ,&nbsp;Danya Zhou ,&nbsp;Mengting Zhu ,&nbsp;Xudong Xiao ,&nbsp;Junyao Lv ,&nbsp;Guanghui Zhu ,&nbsp;Xiaojun Yu ,&nbsp;Minchao Lai ,&nbsp;Dian Wang","doi":"10.1016/j.lfs.2025.123826","DOIUrl":"10.1016/j.lfs.2025.123826","url":null,"abstract":"<div><h3>Aims</h3><div>Diabetes mellitus (DM) often co-exists with myocardial ischemia (MI). Whether DM increases sudden cardiac death (SCD) susceptibility in early MI remains unclear, and the underlying mechanism needs to be further explored.</div></div><div><h3>Materials and methods</h3><div>We induced type II DM in mice to produce a co-morbidity model of DM and MI. Proteomic analysis was conducted to identify proteomic features associated with DM-SCD and MI. Additionally, a neonatal rat ventricular myocyte (NRVM) model was established under conditions of hypoxia and high glucose (HG) to elucidate the interplay between oxidative stress and endoplasmic reticulum (ER) stress in MI co-morbid with DM.</div></div><div><h3>Key findings</h3><div>Our findings revealed that DM increased the incidence of lethal ventricular arrhythmia (LVA)-SCD in early MI. Proteomic data indicate that Ca²⁺-mediated oxidative stress and ER stress may synergistically contribute to the increased SCD incidence. SCD mice exhibited increased mitochondrial ROS (mROS) and cytosolic ROS (cytoROS), decreased mitochondrial membrane potential (MMP) and reduced/oxidized glutathione ratio, upregulation of RyR2-S2814 phosphorylation, and increased expression of ER stress-related proteins in the ischemic myocardium. NRVMs subjected to hypoxia and HG showed cytosolic and mitochondrial Ca²⁺ overload, excessive ROS production, and reduced intracellular K⁺ levels. Treatment with MitoTEMPO to scavenge mROS and 4-PBA to inhibit ER stress normalized SCD-associated alterations in mice and hypoxia- and HG-associated alterations in NRVMs, preventing LVA-SCD.</div></div><div><h3>Significance</h3><div>Our study uncovers that DM increases the incidence of LVA-SCD in early MI, which is associated with the crosstalk between calcium dysregulation and multiple stresses.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123826"},"PeriodicalIF":5.2,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144557624","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":"Human urine-derived stem cells from different donor sources ameliorate diabetic nephropathy in mice by activating autophagy and restoring mitochondrial function of podocyte","authors":"Jie-Zhou ,&nbsp;Ya-Yi Lin ,&nbsp;Wei-Fen Cheng ,&nbsp;Xi-Yan Wang ,&nbsp;Zi-Wei Chen ,&nbsp;Xin-Yi Jiang ,&nbsp;Shao-Bo Li ,&nbsp;Xiang-Cheng Zhang ,&nbsp;Ling-Fei Yan ,&nbsp;Lin-Xie ,&nbsp;Jing-Yuan Li ,&nbsp;Quan-Wen Liu","doi":"10.1016/j.lfs.2025.123831","DOIUrl":"10.1016/j.lfs.2025.123831","url":null,"abstract":"<div><h3>Background</h3><div>Human urine-derived stem cells (hUSCs) are a novel type of mesenchymal stem cells (MSCs) originating from the kidney, with promising potential for personalized therapies. However, it remains unclear whether hUSCs can be successfully isolated from individuals of different ages and disease states-including healthy young individuals, healthy elderly individuals, and patients with diabetic nephropathy (DN), as well as their therapeutic potential and mechanism in DN.</div></div><div><h3>Methods</h3><div>hUSCs were isolated from healthy young men (hUSC-HY), healthy elderly men (hUSC-HE), and male DN patients (hUSC-DN), and their biological characteristics were systematically evaluated. The therapeutic effects of early-passage (P3-P5) hUSC-HY, hUSC-HE, and hUSC-DN were assessed in DN mouse models. <em>In vitro</em>, the effects of conditioned medium (CM) derived from each hUSC group on apoptosis in high glucose (HG)-injured mouse podocytes (MPC5) were assessed. To explore the underlying mechanisms, autophagy activation and mitochondrial function were further analyzed in HG-injured MPC5 cells treated with or without hUSC-CM.</div></div><div><h3>Results</h3><div>Early-passage (P0-P5) hUSC-HY, hUSC-HE, and hUSC-DN exhibited comparable biological characteristics. However, after passage 5, hUSC-HE and hUSC-DN progressively developed senescent phenotypes. Early-passage hUSC-HY, hUSC-HE, and hUSC-DN effectively improved renal function and ameliorated tissue damage in DN mice, primarily by inhibiting HG-induced podocyte apoptosis. <em>In vitro</em>, CM derived from all three hUSCs types (P3–P5) significantly attenuated HG-induced apoptosis in podocytes (MPC5 cells) by the activation of autophagy through suppression of the PI3K/AKT/mTOR and ERK/mTOR signaling pathways. Additionally, hUSCs were shown to deliver functional mitochondria to injured MPC5 cells, thereby restoring mitochondrial function and further contributing to the inhibition of podocyte apoptosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123831"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536202","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":"Comprehensive overview of the complex gut microbiota–miRNA crosstalk in immunocompromised pediatric patients","authors":"Regiane Nogueira Spalanzani ,&nbsp;Thaís Muniz Vasconcelos ,&nbsp;Lorena Bavia ,&nbsp;Luiza Souza Rodrigues ,&nbsp;Dany Mesa ,&nbsp;Aline Simoneti Fonseca ,&nbsp;Luciane Regina Cavalli ,&nbsp;Libera Maria Dalla-Costa","doi":"10.1016/j.lfs.2025.123833","DOIUrl":"10.1016/j.lfs.2025.123833","url":null,"abstract":"<div><div>Immunocompromised pediatric patients, particularly those diagnosed with leukemia, often experience immune suppression due to prolonged use of immunosuppressive medication and chemotherapy. Consequently, these patients are highly vulnerable to infections caused by both pathogenic and non-pathogenic microorganisms. To prevent such infections, antibiotics and antifungals are routinely administered as prophylactic treatments. However, the use of antimicrobials significantly impacts the patient's microbiota, particularly the gut microbiota, which plays a crucial role in immunomodulating the mucosa and maintaining the integrity of the intestinal epithelium. Disruption of these functions may transform the intestinal epithelium into a potential entry point for harmful microorganisms. The regulation of gut homeostasis and the composition of the intestinal microbiota have been linked to different host-derived microRNAs (miRNAs) that regulate gene expression. Intestinal epithelial cells release miRNAs into the lumen, where they modulate the growth of gut microbes and the microbiota's composition. This review summarizes current insights into the relationship between the gut microbiota and intestinal miRNAs, emphasizing their potential as diagnostic and prognostic biomarkers for immunocompromised pediatric patients.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123833"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560509","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":"Rab26-mediated lysosomal translocation of eEF1A alleviates myocardial hypertrophy and cardiac remodeling","authors":"Yifan Tong ,&nbsp;Yutong Li ,&nbsp;Yaguang Bi ,&nbsp;Yajiao Liu ,&nbsp;Xiaoping Peng ,&nbsp;Binfeng He ,&nbsp;Xiang Wang","doi":"10.1016/j.lfs.2025.123830","DOIUrl":"10.1016/j.lfs.2025.123830","url":null,"abstract":"<div><h3>Backgrounds</h3><div>Pathological myocardial hypertrophy and cardiac remodeling are a maladaptive response to stressors such as hypertension and genetic mutations, characterized by cardiomyocyte enlargement, fibrosis, cardiomyocyte apoptosis and impaired cardiac function. Rab26, a small GTPase, plays a crucial role in vesicle trafficking, secretion and apoptosis. However, its role in myocardial hypertrophy and cardiac remodeling remains unclear.</div></div><div><h3>Methods</h3><div>Transverse aortic constriction (TAC) model was employed to induce myocardial hypertrophy and cardiac remodeling, with functional and histological assessments. Cardiac-specific Rab26 overexpression was achieved via AAV9-cTnT-Rab26 delivery, while Rab26 knockout was used for loss-of-function analysis. Molecular mechanisms were explored using protein interaction studies, fluorescence co-localization, and protease inhibition assays.</div></div><div><h3>Results</h3><div>Our findings indicated a significant downregulation of Rab26 protein expression in the disease model, while its mRNA levels remained unaltered. Notably, cardiac-specific overexpression of Rab26 led to improved cardiac function, decreased cardiac fibrosis, suppressed myocardial hypertrophy and cardiomyocyte apoptosis. Furthermore, the knockout of Rab26 aggravated myocardial hypertrophy and cardiac remodeling. At the mechanistic level, Rab26 facilitates lysosomal translocation and degradation of eEF1A. Additionally, eEF1A silencing eliminated the protective effect of Rab26 on the heart. Comprehensive evaluation revealed the critical role of the Rab26-eEF1A axis in mediating pathological myocardial hypertrophy and cardiac remodeling.</div></div><div><h3>Conclusions</h3><div>This study suggests that Rab26 prevents cardiac remodeling and dysfunction under pressure overload by promoting the lysosome translocation and degradation of eEF1A. Targeting the Rab26-eEF1A axis thus provides a potential strategy for preventing or reversing myocardial hypertrophy and cardiac remodeling.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123830"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560510","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":"Regulatory mechanism of ferroptosis in acute kidney injury and potential therapeutic strategies","authors":"Wendi Zhong ,&nbsp;Zihuang Xie ,&nbsp;Siqi Wei ,&nbsp;Tian Zhong ,&nbsp;Tao Jiang","doi":"10.1016/j.lfs.2025.123828","DOIUrl":"10.1016/j.lfs.2025.123828","url":null,"abstract":"<div><div>Ferroptosis is a type of iron-dependent programmed cell death distinguished by increased oxidative stress and the pathological accumulation of lipid peroxides within the cell membrane. Emerging evidence suggests a strong link between ferroptosis and both the occurrence and progression of acute kidney injury (AKI). However, many outstanding issues remain to be solved in the development of drugs that target ferroptosis. Therefore, it is imperative to present a comprehensive overview of the most recent advancements in the field of ferroptosis. In this review, we systematically summarize the predisposing factors and defense mechanisms of ferroptosis in AKI. Moreover, we focused on the role of specific regulators related to ferroptosis, including STING, CX3CL1, FXR, and CD36, in AKI. These regulatory factors may be potential targets for treating AKI in the future. Additionally, potential strategies for preventing AKI by targeting ferroptosis were also highlighted in this study. Numerous studies have demonstrated that targeting ferroptosis to alleviate inflammation and renal fibrosis, modulate metabolic reprogramming, and regulate reactive oxygen species may represent an effective strategy for mitigating the progression of AKI. These findings offer novel potential targets and therapeutic strategies for managing AKI through ferroptosis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"378 ","pages":"Article 123828"},"PeriodicalIF":5.2,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144536201","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}