Life sciences最新文献

{"title":"Artery tertiary lymphoid organs in atherosclerosis: A review.","authors":"Yanni Li, Sihe Gong, Kaijie Yan, Zhonghong Shi, Yimin Bao, Ke Ning","doi":"10.1016/j.lfs.2025.123549","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123549","url":null,"abstract":"<p><p>Atherosclerosis (AS) is the common pathological basis for many cardiovascular diseases. Initial investigations into AS predominantly centered on endothelial immune responses associated with plaque formation. However, recent studies increasingly underscore the salutary immune modulation occurring on the aorta adventitia as the atheromatous plaque progresses. The immune responses extend from the intima of the vessel to the adventitia, and the artery tertiary lymphoid organ (ATLO) assumes a major immune role in advanced stages of AS, according to available studies conducted on ApoE^-/- mice. In this review, we collate the history of studies on the participation of ATLOs in immunity to AS, detailing its structure, classification, cellular composition, and formation mechanisms. We elucidate the distinct roles of ATLO components in immune regulation, emphasizing unique features such as territorial organization, T cell-driven autoimmunity, and the T follicular helper-germinal center B cell axis, which distinguish ATLOs from conventional lymphoid responses. Furthermore, based on the latest research, we propose that ATLOs cooperate with the nervous system to regulate the progression of AS. Moreover, we highlight that aging has a great impact on the deterioration of AS and this impact is related to ATLOs. We conclude by suggesting that a focus on ATLOs is important for the clinical management of AS, and we offer a perspective for further research on ATLO and suggest whether it will be beneficial or detrimental to ATLOs.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123549"},"PeriodicalIF":5.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586192","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":"Olmesartan attenuates doxorubicin-elicited testicular toxicity: The interaction between sirtuin-1, HMGB1/NLRP3 inflammasome/gasdermin D signaling, and AMPK/mTOR-driven autophagy.","authors":"Hemat A Elariny, Hanan Abdelmawgoud Atia, Marwa H Abdallah, Amany M Khalifa, Maaly A Abd Elmaaboud, Mennatallah A Elkady, Ahmed M Kabel","doi":"10.1016/j.lfs.2025.123545","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123545","url":null,"abstract":"<p><strong>Background: </strong>In the recent years, there has been an increased incidence of testicular toxicity associated with doxorubicin (DOX) use in cancer therapy. The mechanisms of this adverse effect may include induction of oxidative stress with augmentation of the inflammatory and the apoptotic signals in the testicular tissues. The ongoing research is directed towards the exploration of new agents that are capable of overcoming this health problem. This study was a trial to evaluate the efficacy of Olmesartan as a protective agent against DOX-induced testicular dysfunction in male rats.</p><p><strong>Materials and methods: </strong>Forty adult male Sprague-Dawley rats were divided into control group, DOX-injected group, and three DOX-injected groups treated with olmesartan at 3 dose levels (1, 5, and 10 mg/kg/day). The effect of the different treatments was assessed at the biochemical and the morphological levels.</p><p><strong>Key findings: </strong>Olmesartan administered to DOX-treated rats induced dose-dependent restoration of the testicular weight and functions, normalization of the hormonal profile, augmentation of the antioxidant defenses, and potentiation of AMPK/mTOR-driven autophagy in comparison to rats treated with DOX alone. These effects were accompanied with a dose-dependent significant mitigation of the cellular events related to pyroptosis and inflammation and a significant amelioration of the testicular morphological changes induced by DOX.</p><p><strong>Significance: </strong>Olmesartan may represent a promising therapy for DOX-elicited testicular dysfunction, possibly via dose-dependent antioxidant, anti-pyroptotic, anti-inflammatory, and autophagy enhancing effects.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123545"},"PeriodicalIF":5.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586199","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":"Unveiling the potential of tankyrase I inhibitors for the treatment of type 2 diabetes mellitus: A hybrid approach using network pharmacology, 2D structural similarity, molecular docking, MD simulation and in-vitro studies.","authors":"Ruchi Yadav, Krishnaprasad Baby, Yogendra Nayak, Dhaval Patel, Kasinath Viswanathan, Krishnarup Ghoshdastidar, Ankit Patel, Bhumika Patel","doi":"10.1016/j.lfs.2025.123548","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123548","url":null,"abstract":"<p><strong>Aims: </strong>This study explores the association between the Wnt signaling pathway and T2DM, emphasizing the role of Tankyrase1 (TNKS1) in metabolic regulation. Using network pharmacology and computational approaches, it aims to identify potential FDA-approved drugs for repurposing as Wnt inhibitors to improve insulin sensitivity and reduce fat accumulation.</p><p><strong>Materials and methods: </strong>Network pharmacology analysis was performed to explore the association between the Wnt pathway and T2DM, identifying Catenin Beta 1 (CTNBB1) as a key hub gene involved in disease progression. A 2D structural similarity search was conducted using reference tankyrase inhibitors (E7449 and XAV939). Potential drug candidates were subjected to molecular docking and 100 ns molecular dynamics (MD) simulations with the Tankyrase I (PDB ID: 4W6E) protein. The shortlisted compounds were further evaluated for Wnt inhibitory activity using the TCF/LEF reporter assay, while their anti-diabetic potential was assessed through a glucose uptake assay in L6 myoblast cells.</p><p><strong>Key findings: </strong>Niclosamide, Capmatinib, Esomeprazole, and Fenofibrate were identified as promising candidates with strong binding affinities and stable interactions with key amino acids (Gly1185, Ser1221, Tyr1224, Asp1198, Tyr1213, and His1201). Experimental validation through in-vitro Wnt inhibition and glucose uptake assays confirmed that drugs Fenofibrate and Conivaptan exhibited significant Wnt inhibitory activity, suggesting their potential role in modulating T2DM-related pathways.</p><p><strong>Significance: </strong>This study highlights the role of the Wnt signaling pathway in T2DM pathogenesis and identifies potential drug candidates for repurposing as Tankyrase1/Wnt inhibitors. The findings provide a foundation for further in-vivo investigations into the anti-diabetic potential of the identified drugs, paving the way for novel therapeutic strategies in T2DM management.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123548"},"PeriodicalIF":5.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586201","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":"Characterization of a novel virulent mycobacteriophage Kashi-SSH1 (KSSH1) depicting genus-specific broad-spectrum anti-mycobacterial activity.","authors":"Tanmayee Nayak, Anuja Kakkar, Lav Kumar Jaiswal, Garima Kandwal, Anand Kumar Singh, Louise Temple, Ankush Gupta","doi":"10.1016/j.lfs.2025.123546","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.123546","url":null,"abstract":"<p><strong>Aim: </strong>Tuberculosis (TB) is one of the leading infectious disease causing mortality in the world and the rise of drug resistance; multi-drug resistance (MDR) and extensive-drug resistance (XDR) has added to extra complicacy of the disease. In this scenario, phage therapy has emerged as a potential treatment option against drug-sensitive/-resistant strains.</p><p><strong>Materials and methods: </strong>The mycobacteriophage Kashi-SSH1 (KSSH1) was isolated from soil sample and was genomically, phenotypically, and functionally characterized. It includes genome assembly/annotation, transmission electron microscopy, multiplicity of infection (MOI), one-step growth curve, temperature/pH stability, confocal microscopy, host range determination and host growth reduction assays.</p><p><strong>Key findings: </strong>KSSH1 is a novel polyvalent virulent mycobacteriophage from the Myoviridae family, classified under cluster C1 with a 155,659 bp genome carrying key lysis genes-Holliday junction resolvase, Holin, Lysin A, and Lysin B, has an optimal MOI of 0.01, a 60-min latent period, and a burst size of 200 phages/bacterial cell. It remains stable up to 55 °C and within pH 7-10, exhibiting broad-spectrum activity against Mycobacterium species, like M. fortuitum (opportunistic pathogen), M. tuberculosis H37Ra (attenuated pathogen), and M. smegmatis, but not non-mycobacterial hosts. KSSH1 exhibits comparable growth inhibition of M. smegmatis like the antibiotics isoniazid and rifampicin as compared to the control, in liquid cultures for over 50 h without regrowth.</p><p><strong>Significance: </strong>KSSH1 exhibits strong lytic activity against various Mycobacterium species, lacks lysogeny-associated genes like integrases/transcriptional repressors, antibiotic resistance and virulence genes and remains stable from 4 °C to 37 °C and pH 8-10 ensuring safety/stability making it an ideal candidate for therapeutic use.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123546"},"PeriodicalIF":5.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143586196","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":"Regulation of autophagy: Insights into O-GlcNAc modification mechanisms","authors":"Chengzhi Liu ,&nbsp;Xinyu Wang ,&nbsp;Shengnan Xu ,&nbsp;Mingyue Liu ,&nbsp;Xusheng Cao","doi":"10.1016/j.lfs.2025.123547","DOIUrl":"10.1016/j.lfs.2025.123547","url":null,"abstract":"<div><div>Autophagy is a “self-eating” biological process that degrades cytoplasmic contents to ensure cellular homeostasis. Its response to stimuli occurs in two stages: Within a few to several hours of exposure to a stress condition, autophagic flow rapidly increases, which is mediated by post-translational modification (PTM). Subsequently, the transcriptional program is activated and mediates the persistent autophagic response. O-linked β-<em>N</em>-acetylglucosamine (O-GlcNAc) modification is an inducible and dynamically cycling PTM; mounting evidence suggests that O-GlcNAc modification participates in the total autophagic process, including autophagy initiation, autophagosome formation, autophagosome-lysosome fusion, and transcriptional process. In this review, we summarize the current knowledge on the emerging role of O-GlcNAc modification in regulating autophagy-associated proteins and explain the different regulatory effects on autophagy exerted by O-GlcNAc modification.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123547"},"PeriodicalIF":5.2,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578673","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":"The path winds along isolation and analyses of fetal nucleated red blood cells in maternal peripheral blood: Past, present, and future toward non-invasive prenatal diagnosis","authors":"Chun Feng ,&nbsp;Jing Tang ,&nbsp;Ke Wu ,&nbsp;Lin Cheng ,&nbsp;Lei Zhao ,&nbsp;Wentao Zhu ,&nbsp;Yuanzhen Zhang ,&nbsp;Xingzhong Zhao ,&nbsp;Bo Cai ,&nbsp;Rongxiang He","doi":"10.1016/j.lfs.2025.123530","DOIUrl":"10.1016/j.lfs.2025.123530","url":null,"abstract":"<div><div>Traditional prenatal diagnosis detects fetal disorders through invading uterus to access fetal cells, which may cause maternal complications, fetal injury, or even miscarriage. Safe and convenient non-invasive prenatal testing (NIPT) by analyzing fetal materials (cell-free DNA/RNA, cells, and extracellular vesicles) that circulate in maternal peripheral blood attracts great attention and has been applied in risk evaluation of several fetal disorders. Among those fetal analytes, fetal nucleated red blood cells (fNRBCs) comprise entire fetal genome, possess distinct membrane antigens, and have a lifespan limited in every single gestation. They were once expected to be an ideal biomarker for NIPT and even definitive prenatal diagnosis. However, recent advances of fNRBC-based NIPT are limited and their applications toward clinical practices are still challenging. Herein, we comprehensively overview research on fNRBCs in maternal peripheral blood, trying to dissect current predicament and inspire potential solutions. The source and lineage of fNRBCs, their entrance into maternal peripheral blood, and their physiochemical characteristics are discussed, and various strategies of label-free or immuno-affinitive isolation and subsequential identification of fNRBCs from maternal blood cells are summarized. Although proof-of-concept analyses toward detecting a few fetal disorders are demonstrated, current fNRBC-based NIPT still suffers many challenges when applied to clinical practices. Nevertheless, <em>via</em> thorough investigation and new analytical technologies, it is believed fNRBC-based NIPT will provide a promising platform to supplement the insufficiency of current strategies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123530"},"PeriodicalIF":5.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578670","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":"Female mice exposed to varying ratios of stearic to palmitic acid in a high-fat diet during gestation and lactation shows differential impairments of beta-cell function","authors":"Chenchen Geng ,&nbsp;Xiaohan Li ,&nbsp;Lingfeng Dan ,&nbsp;Liyan Xie ,&nbsp;Min Zhou ,&nbsp;Kaile Guan ,&nbsp;Qi Chen ,&nbsp;Yan Xu ,&nbsp;Rong Ding ,&nbsp;Jiaqi Li ,&nbsp;Yue Zhang ,&nbsp;Mohammad Sharifzadeh ,&nbsp;Rui Liu ,&nbsp;Wenting Li ,&nbsp;Huimin Lu","doi":"10.1016/j.lfs.2025.123532","DOIUrl":"10.1016/j.lfs.2025.123532","url":null,"abstract":"<div><h3>Aims</h3><div>While emerging evidence implicates an abnormal stearic-to-palmitic acid ratio in saturated fats in beta-cell dysfunction, their gestational/lactational impacts remain underexplored. This study evaluates the differential transient and long-lasting effects of high-fat diets with contrasting stearic-to-palmitic acid ratios on maternal beta-cell function.</div></div><div><h3>Materials and methods</h3><div>Female mice were fed high-fat diets with high/low stearic-to-palmitic acid ratios during gestation/lactation, followed by a recovery period and subsequent exposure to an obesogenic diet. Beta-cell function was assessed using <em>ex-vivo</em> glucose-stimulated insulin secretion (GSIS) and immunohistochemistry. Islets mRNA profiling was performed using RNA-sequencing.</div></div><div><h3>Key findings</h3><div>Both high- and low-ratio groups showed impaired GSIS post-lactation. High-ratio-fed dams exhibited pronounced compensatory responses, including increased islet size, number, and elevated <em>Stx1a</em>, <em>Stx4</em>, <em>Pdx1</em>, <em>Mafa</em> expression. Following metabolic re-challenge, high-ratio group demonstrated more severely impaired <em>ex vivo</em> insulin release. No significant differences in islet apoptosis and senescence were observed between the two groups. Transcriptomic profiling, however, revealed distinct mechanistic pathways: the high-ratio diet was likely to disrupt beta-cell organelles ultrastructure, while the low-ratio diet predominantly dysregulated chemokine-mediated immune signaling networks.</div></div><div><h3>Significance</h3><div>Gestational/lactational exposure to high-fat diets with both high and low ratios of stearic-to-palmitic acid exerts pronounced transient impacts on beta-cell function, with the high-ratio diet inducing more severe and persistent detrimental effects. These findings highlight the critical influence and importance of dietary saturated fatty acid composition in maternal metabolic programming and beta-cell vulnerability.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123532"},"PeriodicalIF":5.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578675","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":"A critique review of fetal hemoglobin modulators through targeting epigenetic regulators for the treatment of sickle cell disease","authors":"Chandu Ala ,&nbsp;Sivaprakash Ramalingam ,&nbsp;Chandra Sekhar Kondapalli Venkata Gowri ,&nbsp;Murugesan Sankaranarayanan","doi":"10.1016/j.lfs.2025.123536","DOIUrl":"10.1016/j.lfs.2025.123536","url":null,"abstract":"<div><div>Sickle cell disease (SCD) is one of the most prevalent hereditary blood disorders characterized by aberrant hemoglobin synthesis that causes red blood cells (RBCs) to sickle and result in vaso-occlusion. The complex pathophysiological mechanisms that underlie SCD are explored in this study, including hemoglobin polymerization, the formation of fetal hemoglobin (HbF), and hemoglobin switching regulation. Notably, pharmaceutical approaches like hydroxyurea, <span>l</span>-glutamine, voxelotor, and crizanlizumab, in addition to therapeutic techniques like gene therapies like Casgevy and Lyfgenia, signify noteworthy advancements in the management of issues connected to SCD. Furthermore, the deciphering of the molecular mechanisms that dictate hemoglobin switching has revealed several potentially therapeutic targets, including key transcriptional repressors such as β-cell lymphoma/leukemia 11A (BCL11A), Zinc finger and BTB domain-containing 7A (ZBTB7A), Nuclear Factor IX (NFIX), and Nuclear Factor IA (NFIA), which play crucial roles in γ-globin silencing. Additionally, transcriptional activators such as Nuclear Factor Y (NF-Y), and Hypoxia-inducible factor 1α (HIF1α) have emerged as promising regulators that can disrupt repression and enhance HbF synthesis. Other epigenetic regulators, such as lysine-specific histone demethylase 1 (LSD1), euchromatic histone methyltransferases 1/2 (EHMT1/2), histone deacetylases (HDACs), DNA methyltransferases (DNMTs), and protein arginine methyltransferases (PRMTs). It has been demonstrated that inhibiting these targets can prevent the silencing of the gene encoding for the formation of γ-chains and, in turn, increase the synthesis of HbF, providing a possible treatment option for SCD symptoms. These approaches could pave the way for innovative, mechanism-driven therapies that address the unmet medical needs of SCD patients.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123536"},"PeriodicalIF":5.2,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578672","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":"Increased seizure susceptibility in the collagen-induced arthritis mouse model depends on neuronal IL-1R1","authors":"Shengyu Chen ,&nbsp;Rongrong Chen ,&nbsp;Mengxian Luo ,&nbsp;Yijun Luo ,&nbsp;Xiao Ma ,&nbsp;Huawei Zhao ,&nbsp;Zhenghao Xu","doi":"10.1016/j.lfs.2025.123537","DOIUrl":"10.1016/j.lfs.2025.123537","url":null,"abstract":"<div><h3>Aims</h3><div>Numerous clinical studies have revealed a positive correlation between rheumatoid arthritis (RA) and an elevated risk of epilepsy. This study aimed to investigate the seizure susceptibility in the collagen-induced arthritis (CIA) mice model.</div></div><div><h3>Main methods</h3><div>The classic CIA model was used to mimic RA pathogenesis in mice. The pentylenetetrazole (PTZ)-induced seizure model and audiogenic seizure model were used to evaluate seizure susceptibility. Neuroinflammation was assessed through ELISA, Western blot, and immunofluorescence staining. Additionally, electrophysiological techniques were applied to investigate the excitation/inhibition (E/I) balance.</div></div><div><h3>Key findings</h3><div>CIA modeling raised the level of IL-1β, induced E/I imbalance in the dentate gyrus (DG) region, and enhanced seizure susceptibility to PTZ in C57BL/6 mice. However, knockout (KO) of IL-1β attenuated peripheral inflammatory symptoms and blocked the increase in seizure susceptibility in CIA-modeled mice. Additionally, conditional IL-1R1 KO in CaMKIIα-positive neurons did not affect the peripheral inflammatory symptoms but rescued both the increased seizure susceptibility and E/I imbalance in CIA-modeled mice. Furthermore, increased susceptibility to audiogenic seizure susceptibility was also observed in CIA-modeled BDA/1 mice, accompanied by the elevated IL-1β levels and neuronal IL-1R1-related Akt phosphorylation in the hippocampus.</div></div><div><h3>Significance</h3><div>Increased seizure susceptibility in the CIA mouse model depends on IL-1β and neuronal IL-1R1. These data indicated that IL-1β and neuronal IL-1R1 may be the key targets for its intervention.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123537"},"PeriodicalIF":5.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578674","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":"Advancements in the study of DLK1 in the pathogenesis of diabetes","authors":"Min Li,&nbsp;Yanqiu Peng,&nbsp;Yuke Shi,&nbsp;Yunfei Liu,&nbsp;Jian Zhang","doi":"10.1016/j.lfs.2025.123535","DOIUrl":"10.1016/j.lfs.2025.123535","url":null,"abstract":"<div><div>DLK1, as a membrane-bound protein, has been extensively studied in the field of cancer research. As a ligand downstream of the Notch pathway, it broadly influences developmental and metabolic processes in the body. With deeper research, it has been found that DLK1 can induce the synthesis and secretion of insulin through the ERK and AKT pathways, playing a crucial role in the development of metabolic diseases. Diabetes mellitus (DM) is a chronic metabolic disorder characterized by insufficient insulin production by the pancreas or inadequate utilization of insulin by the body. This article aims to review the relationship between DLK1 and diabetes, recent research advancements, and to discuss future research directions and challenges.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"369 ","pages":"Article 123535"},"PeriodicalIF":5.2,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578671","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}