Life sciences最新文献

{"title":"Molecular pathological characteristics and mechanisms of the liver in metabolic disease-susceptible transgenic pigs","authors":"Juan Du,&nbsp;Kaiyi Zhang,&nbsp;Jiakun Miao,&nbsp;Yu Yang,&nbsp;Yuying Tian,&nbsp;Tianwen Wu,&nbsp;Cong Tao,&nbsp;Yanfang Wang,&nbsp;Shulin Yang","doi":"10.1016/j.lfs.2024.123337","DOIUrl":"10.1016/j.lfs.2024.123337","url":null,"abstract":"<div><h3>Aims</h3><div>This study aimed to explore the molecular pathological mechanisms of the liver in metabolic disease-susceptible transgenic pigs via multiomics analysis.</div></div><div><h3>Materials and methods</h3><div>The triple-transgenic (<em>PNPLA3</em>^{<em>I148M</em>}<em>-GIPR</em>^<em>dn</em><em>-hIAPP</em>) pig model (TG pig) was successfully constructed in our laboratory via the CRISPR/Cas9 technique previously described. Wild-type (WT) pigs and TG pigs after 2 or 12 months of high-fat and high-sucrose diet (HFHSD) induction (WT2, TG2, WT12, and TG12 groups, respectively) were used as materials. The transcriptome, metabolome, and lipidome were used to investigate the molecular mechanisms of the liver in pigs.</div></div><div><h3>Key findings</h3><div>The TG2 pigs presented mild metaflammation and insulin resistance (IR) which was similar to WT12 pigs. Compared with the other three groups, the TG12 pigs presented severe hepatocyte ballooning, fat deposition, and portal area fibrosis. The transcriptome data suggested that the TG2 pigs presented upregulated gene expression in the extracellular matrix (ECM). The TG12 pigs presented more severe metaflammation and exhibited imbalanced glycolipid metabolism. Interestingly, genes such as <em>ETNPPL</em>, <em>GABBR2</em>, and <em>BMP8B</em> might be key regulatory targets for liver injury. The metabolome and lipidome suggested that long-chain polyunsaturated fatty acids (LCPUFAs) and phospholipids with corresponding LCPUFAs were remodelled. Importantly, bis(monoacylglycerol) phosphates (BMPs) and sulfatides (SLs) could be the key regulatory metabolites in liver injury.</div></div><div><h3>Significance</h3><div><em>ETNPPL</em>, <em>GABBR2</em>, and <em>BMP8B</em> might be potential therapeutic targets for liver injury. BMPs and SLs might be biomarkers for the diagnosis and treatment of liver diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123337"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903343","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":"AAV2-mediated ABD-FGF21 gene delivery produces a sustained anti-hyperglycemic effect in type 2 diabetic mouse","authors":"Sen-lin Lu ,&nbsp;Zhi-hao Pan ,&nbsp;Zhi Cui ,&nbsp;Ji-li Wang ,&nbsp;Jian-lin Yang ,&nbsp;Ya-feng Lv ,&nbsp;Chun-yu Cao ,&nbsp;Xiao-fei Huang","doi":"10.1016/j.lfs.2024.123344","DOIUrl":"10.1016/j.lfs.2024.123344","url":null,"abstract":"<div><h3>Background</h3><div>Fibroblast Growth Factor 21 (FGF21) is a naturally occurring peptide hormone involved in the regulation of glycolipid metabolism, and it shows promise as a potential treatment for type 2 diabetes mellitus (T2DM). However, the short half-life and poor pharmacokinetics of native FGF21 limit its efficacy in reducing hyperglycemia in vivo. Therefore, maintaining stable and sustained blood concentrations of FGF21 is crucial for its role as an effective regulator of glycolipid metabolism in vivo. In this study, we developed an AAV2-mediated gene delivery system incorporating an Albumin-binding domain (ABD) fused to FGF21, and we evaluated its effects in a type 2 diabetic mouse model.</div></div><div><h3>Methods</h3><div>The plasmids pAAV-FGF21-Luciferase, pHelper, and the capsid plasmid were transfected into HEK293T cells to generate recombinant AAV (rAAV) virus. A type 2 diabetes mellitus (T2DM) mouse model was established for evaluation. The rAAV was administered via tail vein injection into the mice. The effects of rAAV injection on various parameters were assessed using commercial kits. Histological changes in the liver and adipose tissue of T2DM mice were examined using hematoxylin and eosin (H&amp;E) staining.</div></div><div><h3>Results</h3><div>The data showed that the inclusion of ABD significantly prolonged the half-life of FGF21 in the serum of mice. Additionally, AAV2-mediated delivery of ABD-FGF21 to the liver resulted in sustained gene expression and a significant increase in circulating FGF21 levels in mice. Treatment with AAV2-ABD-FGF21 led to several benefits, including reduced fasting glucose, improved insulin sensitivity, decreased triglyceride and total cholesterol levels, and improved body weight in T2DM mice. Furthermore, serum analysis and histological examination showed no significant liver damage at the study endpoint after seven weeks.</div></div><div><h3>Conclusion</h3><div>In conclusion, we have developed a novel strategy for producing long-acting FGF21 using the AAV vector, and AAV2-ABD-FGF21 shows promise as a therapeutic approach for type 2 diabetes mellitus and other glycolipid metabolic disorders.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123344"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142906559","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":"Research progress on pathogenesis and treatment of febrile seizures","authors":"Chang Wu ,&nbsp;Qingmei Wang ,&nbsp;Wenmi Li ,&nbsp;Mingxuan Han ,&nbsp;Huawei Zhao ,&nbsp;Zhenghao Xu","doi":"10.1016/j.lfs.2024.123360","DOIUrl":"10.1016/j.lfs.2024.123360","url":null,"abstract":"<div><div>Febrile seizures (FSs) are the most common pediatric neurological disorder, affecting approximately 5 % of children aged 6 months to 5 years. While most FSs are self-limiting and benign, about 20–30 % present as complex FSs (CFSs), which pose a risk of acute brain injury and the development of temporal lobe epilepsy. Various factors, including age, geographical distribution, and type of infection influence the occurrence of FS. Infection is the primary external trigger for FS, while the underlying intrinsic factors are linked to the immature and incomplete myelination of the brain during specific developmental stages. Although the precise pathogenesis of FS is not yet fully understood, it is likely caused by the interaction of immature brain development, fever, neuroinflammation, and genetic susceptibility. This review discussed the pathogenesis of febrile seizures, focusing on factors such as age, fever, neuroinflammation, genetics, and intestinal microbiota, and summarized existing therapeutic approaches. Our review may facilitate the identification of new targets for mechanistic studies and clinical treatment of febrile seizures.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123360"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142921622","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":"Anticancer and therapeutic efficacy of XPO1 inhibition in pancreatic ductal adenocarcinoma through DNA damage and modulation of miR-193b/KRAS/LAMC2/ERK/AKT signaling cascade","authors":"Anuradha Kirtonia ,&nbsp;Gouri Pandya ,&nbsp;Aishwarya Singh ,&nbsp;Rachana Kumari ,&nbsp;Bhavana Singh ,&nbsp;Sonia Kapoor ,&nbsp;Ekta Khattar ,&nbsp;Amit Kumar Pandey ,&nbsp;Manoj Garg","doi":"10.1016/j.lfs.2024.123364","DOIUrl":"10.1016/j.lfs.2024.123364","url":null,"abstract":"<div><div>Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and grave malignancies with confined and ineffective therapeutic options. XPO1 is a critical regulator of nuclear export and activation of tumor suppressor proteins. The present study evaluated the therapeutic potential and molecular mechanisms of XPO1 inhibition against PDAC. Firstly, we observed significant overexpression of <em>XPO1</em> transcript in 179 PDAC patients than 171 normal pancreatic tissues in TCGA transcriptomic dataset. Higher <em>XPO1</em> transcript levels displayed worse overall and disease-free survival. Further, we confirmed significant upregulation of XPO1 in a panel of PDAC cells. Eltanexor treatment resulted in significant inhibition of cell viability, clonogenic growth, migration, and epithelial-mesenchymal transition (EMT), along with the induction of cell cycle arrest. Mechanistically, eltanexor modulated the expression of key proteins including p21, p27, p53, cyclin B1, cyclin D1, c-Myc, N-cadherin, vimentin, E-cadherin associated with the cell viability, growth, cell cycle and EMT. Additionally, the eltanexor treatment resulted in marked increase in expression of γH2AX, and cleaved PARP, cleaved caspase-9 leading to induction of DNA damage and apoptosis of PDAC cells, respectively. Moreover, eltanexor treatment regulated the expression of key non-coding RNAs including miR193b, DINO, MALAT-1, H19, and SOX21-AS1 linked with tumorigenesis. Our results revealed a correlation among miR193b/KRAS/LAMC2, XPO1/KRAS, and LAMC2/KRAS. The findings also revealed that eltanexor treatment rescued the expression of miR193b which acts as a sponge for LAMC2 and KRAS resulting in the suppression of AKT/ERK downstream signaling cascade in PDAC. Interestingly, the combination of eltanexor with gemcitabine showed significant anticancer activity in PDAC cells. Altogether, our findings revealed the crucial role of XPO1 in modulating the expression of oncogenic proteins, ncRNAs, and DNA damage during PDAC progression as well as identified novel therapeutic miR-193b/KRAS/LAMC2/ERK/AKT axis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123364"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950976","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":"Progesterone signaling in uterine fibroids: Molecular mechanisms and therapeutic opportunities","authors":"Ioanna Ploumaki ,&nbsp;Valeria I. Macri ,&nbsp;James H. Segars ,&nbsp;Md Soriful Islam","doi":"10.1016/j.lfs.2024.123345","DOIUrl":"10.1016/j.lfs.2024.123345","url":null,"abstract":"<div><div>Progesterone (P4) is a vital female sex hormone involved in various physiological processes, including the maintenance of the endometrium, mammary gland development, and bone health. Beyond its reproductive roles, P4 is implicated in the pathogenesis of hormone-dependent conditions like uterine fibroids, the most common benign tumors in women, which can severely affect quality of life and fertility. Traditionally, estrogen was considered the primary driver of fibroid growth, but recent research highlights the significant role of P4 in fibroid growth. P4 interacts with progesterone receptors (PRs) and non-genomic membrane receptors (mPRs and PGRMCs) to activate signaling pathways that enhance tumor growth and survival. P4 promotes vascular changes that improve the blood supply to fibroids and modifies the extracellular matrix, a key component of fibroid structure. This understanding has led to the investigation of selective progesterone receptor modulators (SPRMs) as potential therapies for fibroids. Clinical trials have demonstrated the effectiveness of SPRMs like mifepristone, asoprisnil, and ulipristal acetate in reducing fibroid size and symptoms, though concerns about safety, particularly with long-term use, remain. Newer SPRMs, such as vilaprisan, show promise, but further research is necessary to assess the long-term safety and effectiveness. This review discusses the mechanisms by which progesterone contributes to fibroid growth and examines clinical effectiveness of SPRMs as potential treatments for uterine fibroids.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123345"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909777","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":"Utilizing zebrafish models to elucidate mechanisms and develop therapies for skeletal muscle atrophy","authors":"Jing Zhao ,&nbsp;Yimeng Fang ,&nbsp;Junying Qu ,&nbsp;Jiaxuan He ,&nbsp;Jia Yi ,&nbsp;Rongbing Chen ,&nbsp;Qinsi Yang ,&nbsp;Kun Zhang ,&nbsp;Wei Wu ,&nbsp;Da Sun ,&nbsp;Bin Fang","doi":"10.1016/j.lfs.2024.123357","DOIUrl":"10.1016/j.lfs.2024.123357","url":null,"abstract":"<div><div>Skeletal muscle atrophy, resulting from an imbalance in muscle protein synthesis and degradation, compromises muscle quality and function, imposing significant burdens on movement and metabolic stability. Animal models are crucial for understanding the mechanisms of skeletal muscle atrophy and developing clinical prevention and treatment strategies. Zebrafish, as small aquatic vertebrates, exhibit high genetic homology with humans and offer advantages such as rapid reproduction, development, and transparent embryos. Their physiological and anatomical similarities to mammals, including a substantial proportion of skeletal muscle and observable swimming behavior reflecting body dysfunction, make zebrafish an ideal model for studying skeletal muscle-related diseases. This review outlines the development of zebrafish skeletal muscle and highlights key pathways regulating muscle proteins, emphasizing their anatomical and genetic consistency with humans. Various zebrafish models of skeletal muscle atrophy created through physical, chemical, and gene-editing methods are systematically summarized. Current challenges and proposed improvement strategies are also discussed to enhance the reliability and applicability of zebrafish models, providing a comprehensive reference for advancing research on skeletal muscle atrophy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123357"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931449","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 effect of conditioned medium from human amniotic membrane-derived mesenchymal stem cells on thymus involution","authors":"Catarina S. Silva ,&nbsp;Marta R. Casanova ,&nbsp;Pedro Ferreirinha ,&nbsp;Alain da Silva Morais ,&nbsp;Hugo Osório ,&nbsp;Ana C. Lima ,&nbsp;Joana F. Fangueiro ,&nbsp;Mariana T. Cerqueira ,&nbsp;Rui L. Reis ,&nbsp;Nuno L. Alves ,&nbsp;Albino Martins ,&nbsp;Nuno M. Neves","doi":"10.1016/j.lfs.2024.123366","DOIUrl":"10.1016/j.lfs.2024.123366","url":null,"abstract":"<div><h3>Aims</h3><div>The development and selection of T cells occur within the thymus. This organ involutes throughout life, compromising the generation of T cells and, consequently, the efficacy of the immune system. Mesenchymal stem cells (MSC) have beneficial effects on the immune system. Therefore, MSC have been applied in different pathologies related with thymic function. However, there is a lack of knowledge on the potential role of MSC-derived secretome on thymus involution. This work aims at studying the effect of human amniotic membrane-derived MSC conditioned media (hAMMSC CM) on aged thymus.</div></div><div><h3>Materials and methods</h3><div>The proteomic profile of hAMMSC CM was determined by liquid chromatography-tandem mass spectrometry. The CM was then intravenously injected in 12 months old mice, and the thymic stromal compartment and the different T cell populations characterized by flow cytometry.</div></div><div><h3>Key findings</h3><div>The hAMMSC CM is mostly enriched in proteins involved in extracellular matrix interaction, composition and organization, endodermal cell differentiation and angiogenesis. Its intravenous administration tends to increase the total thymic cellularity. A positive effect on the thymic epithelial cell (TEC) compartment was observed, with an increase of all TEC subsets. The hAMMSC CM also induced an increase in the thymocyte populations, accompanied by a confirmed positive selection. Mature single positive thymocytes expressed high levels of CD62L and low levels of CD24, indicating their ability to egress the thymus into the periphery.</div></div><div><h3>Significance</h3><div>Experimental findings support the potential role of hAMMSC CM as a cell-free therapeutic strategy for thymus involution.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123366"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950795","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":"Epitalon-activated telomerase enhance bovine oocyte maturation rate and post-thawed embryo development","authors":"Safeer Ullah ,&nbsp;Zaheer Haider ,&nbsp;Chalani Dilshani Perera ,&nbsp;Su Hyeon Lee ,&nbsp;Muhammad Idrees ,&nbsp;Song Park ,&nbsp;Il-Keun Kong","doi":"10.1016/j.lfs.2025.123381","DOIUrl":"10.1016/j.lfs.2025.123381","url":null,"abstract":"<div><div>Telomerase is highly expressed in oocyte cumulus cells and plays a significant role in follicular development and oocyte maturation. In this study, we hypothesized that in vitro culture conditions may affect telomerase activity during in vitro embryo production (IVP) and that its activation may improve embryo quality. We first examined telomerase protein levels and localization in bovine cumulus-oocyte complexes via immunofluorescence assays. The results showed that healthy cumulus-oocyte complexes have the nuclear localization of the telomerase while the degraded cumulus-oocyte complex had reduced telomerase levels and that telomerase was localized in the cytoplasm. We activated telomerase via Epitalon, a tetrapeptide with the amino acid sequence Ala-Glut-Asp-Gly. We observed a significant improvement in the oocyte maturation rate compared with the control group (<em>p</em> &lt; 0.05). Furthermore, telomerase activity was significantly compromised in post-thawed embryos, and Epitalon treatment significantly improved blastocyst hatching rate and implantation potential (<em>p</em> &lt; 0.05). Moreover, we performed qPCR, reactive oxygen species, and JC-1 (ΔΨm) assays to evaluate the effect of Epitalon on the health of in vitro mature oocytes, cumulus cells, and post-thawed blastocysts, and the result showed that Epitalon highly enhances the quality and health of the oocyte, cumulus cell, and post-thawed blastocyst. Our results suggest that telomerase activation via Epitalon improves bovine in vitro embryo production.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123381"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950990","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":"Roflumilast attenuates doxorubicin and cyclophosphamide combination-induced chemobrain in rats through modulation of NLRP3/ASC/caspase-1/GSDMD axis","authors":"Georgette Eskander ,&nbsp;Sherihan G. Abdelhamid ,&nbsp;Sara A. Wahdan ,&nbsp;Sara M. Radwan","doi":"10.1016/j.lfs.2025.123378","DOIUrl":"10.1016/j.lfs.2025.123378","url":null,"abstract":"<div><h3>Aim</h3><div>The aim of this study is to investigate the neuroprotective effect of roflumilast, a phosphodiesterase-4 (PDE-4) inhibitor on cognitive impairment induced by doxorubicin (DOX)/cyclophosphamide (CP) combination therapy and to elucidate its modulatory effect on the pyroptosis pathway.</div></div><div><h3>Materials and methods</h3><div>Rats were allocated into five groups: a control group, a DOX/CP-intoxicated group, two groups receiving DOX/CP plus low-dose (0.5 mg/kg/day) or high-dose (1 mg/kg/day) roflumilast, and a roflumilast-only group. Behavioral assessments and brain tissue analyses were conducted, including histopathological staining and the measurement of inflammatory and oxidative stress markers.</div></div><div><h3>Findings</h3><div>DOX/CP treatment resulted in cognitive impairment, abnormal brain histology. It significantly elevated the levels of tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), and malondialdehyde (MDA). Concurrently, superoxide dismutase (SOD) activity was reduced. Pyroptosis-associated markers, including nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3), apoptosis-associated speck-like protein (ASC), caspase-1, gasdermin-D (GSDMD), and interleukin-18 (IL-18) were upregulated. Apoptotic marker caspase-3 also exhibited increased expression. Conversely, administration of roflumilast (1 mg/kg/day) for four weeks ameliorated these pathological changes. Roflumilast improved cognitive function, reduced oxidative stress, and modulated inflammatory signaling. Additionally, it suppressed pyroptotic and apoptotic pathways within hippocampal tissue.</div></div><div><h3>Significance</h3><div>These results suggest that roflumilast exerts neuroprotective effects against chemotherapy-induced cognitive dysfunction and neurodegeneration through inhibition of the NLRP3/ASC/caspase-1/GSDMD pyroptosis pathway.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123378"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142951018","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":"Insight into a multifunctional potassium channel Kv1.3 and its novel implication in chronic kidney disease","authors":"Zac Dragan,&nbsp;Carol A. Pollock,&nbsp;Chunling Huang","doi":"10.1016/j.lfs.2024.123338","DOIUrl":"10.1016/j.lfs.2024.123338","url":null,"abstract":"<div><div>Chronic kidney disease (CKD), a global public health problem, causes substantial morbidity and mortality worldwide. Innovative therapeutic strategies to mitigate the progression of CKD are needed due to the limitations of existing treatments. Kv1.3, a voltage-gated potassium ion channel, plays a crucial role in multiple biological processes, including cell proliferation, apoptosis, energy homeostasis, and migration. Inhibition of the Kv1.3 channels has shown beneficial effects in the therapy of a wide range of human diseases such as cancer, autoimmune and neuroinflammatory diseases. Increasing evidence reveals a close link between Kv1.3 and CKD. This review summarises the most recent insights into the physiological functions of the Kv1.3 channel and its pharmacological modulators. Furthermore, the therapeutic potential of targeting Kv1.3 for CKD is also discussed. Collectively, these studies suggested that Kv1.3 channels may serve as a novel target for CKD therapy.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"362 ","pages":"Article 123338"},"PeriodicalIF":5.2,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142895691","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}