Life sciences最新文献

{"title":"Urine-derived stem cells from patients alleviate lupus nephritis via regulating macrophage polarization in a CXCL14-dependent manner","authors":"Yunfei Xia ,&nbsp;Yanju Zhang ,&nbsp;Juan Ji ,&nbsp;Guijuan Feng ,&nbsp;Tianxing Chen ,&nbsp;Haitao Li ,&nbsp;Fengyan Zhou ,&nbsp;Yanfeng Bao ,&nbsp;Xuhui Zeng ,&nbsp;Zhifeng Gu","doi":"10.1016/j.lfs.2025.123623","DOIUrl":"10.1016/j.lfs.2025.123623","url":null,"abstract":"<div><h3>Aim</h3><div>Mesenchymal stem cells (MSC) exhibit hopeful therapeutic potential for the treatment of lupus nephritis (LN). Nevertheless, most MSC are harvested invasively and only transplantation of allogeneic MSC takes effect. Urine-derived stem cells (USC) can be obtained by noninvasive and safe access. Whether USC can be used for autologous stem cell transplantation to treat LN remains unknown.</div></div><div><h3>Materials and methods</h3><div>USC were harvested from healthy individuals, systemic lupus erythematosus (SLE) patients with no LN (NLN) and LN patients. The biological characteristics and immunomodulatory ability of three USC types were compared. Therapeutic value of USC for LN in MRL/<em>lpr</em> mice and influence of USC on macrophages were assessed. We further explored the mechanism of USC from LN patients (LN-USC) on macrophage polarization.</div></div><div><h3>Key findings</h3><div>LN-USC exhibited faster proliferation and less apoptosis, significantly upregulated regulatory T cells (Treg) and downregulated antibody secreting cells (ASC). Importantly, LN-USC showed the best effect on LN in MRL/<em>lpr</em> mice among the three USC types. Additionally, LN-USC markedly downregulated M1 polarization of macrophages when injected into MRL/<em>lpr</em> mice or co-cultured with human acute monocytic leukemia cell (THP1)-derived M0 macrophages. Moreover, the regulative effect on macrophage polarization and therapeutic efficacy on LN were reversed after knocking down C-X-C motif chemokine ligand 14 (CXCL14) of LN-USC.</div></div><div><h3>Significance</h3><div>These results suggested that transplantation of LN-USC alleviated LN in MRL/<em>lpr</em> mice <em>via</em> inhibiting M1 polarization of macrophages in a CXCL14-dependent manner, indicating that USC serve as a prospective candidate for autologous stem cell therapy of LN.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123623"},"PeriodicalIF":5.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143839383","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":"Fibroblast to macrophage-like cell transition in renal inflammatory injury through the MR/CSF1 pathway induced by aldosterone","authors":"Ruyan Lv ,&nbsp;Ziqian Liu ,&nbsp;Haixia Guo ,&nbsp;Boya Zhang ,&nbsp;Xuan Wang ,&nbsp;Yunsong Peng ,&nbsp;Yi Chang ,&nbsp;Fan Yang ,&nbsp;Yunzhao Xiong ,&nbsp;Juan Hao ,&nbsp;Xiaomeng Gao ,&nbsp;Xiangting Wang ,&nbsp;Qingyou Xu ,&nbsp;Tatsuo Shimosawa ,&nbsp;Panpan Qiang","doi":"10.1016/j.lfs.2025.123627","DOIUrl":"10.1016/j.lfs.2025.123627","url":null,"abstract":"<div><h3>Aims</h3><div>Inflammatory injury promotes the chronic kidney disease (CKD) progression，with renal macrophage accumulation and proliferation of as typical manifestations of inflammatory injury. We aimed to verify fibroblast to macrophage-like cell transition as a new source of macrophages that participate in renal inflammatory injury.</div></div><div><h3>Materials and methods</h3><div>Wistar rats were divided into Sham, ALD (aldosterone infusion for 12 weeks), and ESA (aldosterone infusion and esaxerenone by diet for 12 weeks) groups. Rat kidney interstitial fibroblast (RKF) were cultured, induced with aldosterone or CSF1, and treated with antagonists in vitro. The proportions of FSP-1⁺ F4/80⁺ cells in the rat kidney and RKF, including M1 marker iNOS/CD86 and M2 marker CD206/CD163 were assessed by flow cytometry and immunofluorescence staining. Single-cell RNA sequencing was used to assess the origin of macrophages in the rat kidneys and related gene expression. Additionally, immunofluorescence was used to detect FSP-1⁺ F4/80⁺ cells in kidney biopsy samples from CKD patients.</div></div><div><h3>Key findings</h3><div>Fibroblast to macrophage-like cell transition was observed in both the kidneys of aldosterone-infused rats and in vitro aldosterone-treated RKF, with a predominant differentiation into the M1 phenotype. This transformation was mediated through the MR/CSF1 signalling pathway, revealing a novel source of macrophages and providing significant insights into the mechanisms underlying organ fibrosis.</div></div><div><h3>Significance</h3><div>Aldosterone induces fibroblast to macrophage-like cell transition through the MR/ CSF1 pathway.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123627"},"PeriodicalIF":5.2,"publicationDate":"2025-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826343","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":"Loss of LSD1 ameliorates myocardial infarction by regulating angiogenesis via transcriptional activation of Vegfa","authors":"Jinghan Yuan ,&nbsp;Tian Deng ,&nbsp;Qingshan Yang ,&nbsp;Danyi Lv ,&nbsp;Zhenfang Zhou ,&nbsp;Lu You ,&nbsp;Qipu Feng ,&nbsp;Xiangmin Meng ,&nbsp;Qiuyu Pang ,&nbsp;Hao Li ,&nbsp;Bingmei Zhu","doi":"10.1016/j.lfs.2025.123613","DOIUrl":"10.1016/j.lfs.2025.123613","url":null,"abstract":"<div><h3>Aims</h3><div>Our study aims to explore the regulatory role and underlying mechanisms of Lysine-specific demethylase 1 (LSD1) in angiogenesis following myocardial infarction (MI).</div></div><div><h3>Materials and methods</h3><div>We generated inducible cardiomyocyte-specific <em>Lsd1</em> knockout (<em>Lsd1-</em>cKO) mice and established a MI model. The function of LSD1 in cardiac angiogenesis in MI mice was assessed through echocardiography, histopathological staining, and immunofluorescence analysis. In vitro, <em>Lsd1</em> silencing in cardiomyocytes was achieved by transfecting small interfering RNA (siRNA), followed by hypoxic treatment to simulate the in vivo MI model. The above cardiomyocyte-conditioned medium was collected and used to treat endothelial cells to observe changes in endothelial function. Additionally, we employed Cleavage Under Targets and Tagmentation sequencing (CUT&amp;Tag-seq) to investigate the potential mechanisms by which LSD1 exerts its effects.</div></div><div><h3>Key findings</h3><div>We found that the absence of LSD1 protected against cardiac dysfunction and promoted angiogenesis in mice with MI. <em>Lsd1</em>-silenced cardiomyocytes enhance the migration and tube formation function of endothelial cells by releasing vascular endothelial growth factor A (VEGF-A) under hypoxic conditions. The combined analysis of CUT&amp;Tag-seq data revealed that silencing of <em>Lsd1</em> promoted the monomethylation of H3K4 at the <em>Vegfa</em> promoter and region, leading to the transcriptional activation of <em>Vegfa</em> mRNA in cardiomyocytes.</div></div><div><h3>Significance</h3><div>Our research indicates that lowered level of LSD1 in cardiomyocytes enhances VEGF-A paracrine secretion and improves endothelial cell function through cross-talk, ultimately promoting angiogenesis. These findings suggest that targeting LSD1 might be an effective therapeutic approach to protect against MI.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123613"},"PeriodicalIF":5.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143835267","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":"Exerkine-mediated organ interactions: A new interpretation of exercise on cardiovascular function improvement","authors":"Renhan Liu,&nbsp;Yue Xi,&nbsp;Xinyan Duan,&nbsp;Yifei Zhao,&nbsp;Zhenjun Tian","doi":"10.1016/j.lfs.2025.123628","DOIUrl":"10.1016/j.lfs.2025.123628","url":null,"abstract":"<div><div>Cardiovascular diseases impair the structure and function of distal organs, including the liver, skeletal muscle, kidney, and adipose tissue. Exercise stimulates the interaction between the cardiovascular system and distal organs that is important for disease rehabilitation and organ health. However, the mechanisms by which exercise improves cardiovascular function through exerkine-mediated organ crosstalk remain incompletely elucidated. We used cardiovascular, exercise, exerkines, skeletal muscle, liver, kidney, and adipose tissue as keywords to search for the relevant articles, sorted out the differences between different exercise types, summarized the functions of 17 exerkines, focused on reviewing and categorizing the molecular mechanisms of interactions between the cardiovascular system and remote organs. We also look forward to future research perspectives on exercise prevention and control of chronic metabolic diseases. The aim of this review is to provide a new theoretical basis for establishing clinical rehabilitation and exercise prescriptions for cardiovascular system diseases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123628"},"PeriodicalIF":5.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816053","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":"Phospholipid metabolism and drug resistance in cancer","authors":"Hu Zhao ,&nbsp;Qian Xiao ,&nbsp;Yangfang An ,&nbsp;Mu Wang ,&nbsp;Jing Zhong","doi":"10.1016/j.lfs.2025.123626","DOIUrl":"10.1016/j.lfs.2025.123626","url":null,"abstract":"<div><div>Phospholipids, complex lipids prevalent in the human body, play crucial roles in various pathophysiological processes. Beyond their synthesis and degradation, phospholipids can influence chemoresistance by participating in ferroptosis. Extensive evidence highlights the significant link between tumor drug resistance and phospholipids. Therefore, drugs targeting phospholipid metabolism itself or the synthesis of corresponding composite materials will effectively overcome the difficulties of clinical tumor treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123626"},"PeriodicalIF":5.2,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829835","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":"MZT1 protects gastric cancer against glucose starvation through targeting NEDD1","authors":"Ruiyang Zhao ,&nbsp;Bo Cao ,&nbsp;Hanghang Li ,&nbsp;Jingwang Gao,&nbsp;Qixuan Xu,&nbsp;Hao Cui,&nbsp;Zhen Yuan,&nbsp;Huiguang Ren,&nbsp;Bo Wei","doi":"10.1016/j.lfs.2025.123622","DOIUrl":"10.1016/j.lfs.2025.123622","url":null,"abstract":"<div><div>A fasting mimic diet (FMD) has been proven to be a potential therapeutic regimen for gastric cancer (GC) patients. However, the intolerance of energy restriction and limited efficacies hinder wide application of FMD. To identify critical targets mediating resistance against glucose starvation and explore novel approaches to GC therapy, proteomics profiling was performed to depict the landscape of protein expression changes in cells under glucose deprivation. MZT1 was found to be greatly upregulated. We next investigated potential clinical value and regulatory functions of MZT1. Compared to adjacent normal tissues, MZT1 was upregulated in GC specimens and associated with unfavorable patient prognosis. Both <em>in vitro</em> and <em>in vivo</em> experiments indicated that downregulation of the MZT1 level inhibited GC proliferation, migration, invasion, glycolysis and sensitized cells to glucose starvation. Mechanistically, MZT1 functioned as an oncogenic factor by inhibiting NEDD1 ubiquitination and increasing its expression. In conclusion, during glucose starvation, MZT1 is upregulated in GC cells, which promotes resistance by directly suppression of NEDD1 ubiquitination. Our findings unveil the novel mechanisms by which MZT1 can promote GC malignancy. The potential clinical value of MZT1 as GC biomarkers has been first revealed. Suppression of MZT1 may become a promising approach to improve FMD efficacy, which require further validation by future investigations.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123622"},"PeriodicalIF":5.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826342","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":"Akkermansia muciniphila restrains type 1 diabetes onset by eliciting cDC2 and Treg cell differentiation in NOD and STZ-induced experimental models","authors":"Vanessa Fernandes Rodrigues ,&nbsp;Jefferson Elias-Oliveira ,&nbsp;Ítalo Sousa Pereira ,&nbsp;Jéssica Assis Pereira ,&nbsp;Sara Cândida Barbosa ,&nbsp;Melissa Santana Gonsalez Machado ,&nbsp;Jhefferson Barbosa Guimarães ,&nbsp;Thaílla Cristina Faria Pacheco ,&nbsp;Jonatã Bortolucci ,&nbsp;Lívia Soares Zaramela ,&nbsp;Vânia Luiza Deperon Bonato ,&nbsp;João Santana Silva ,&nbsp;Flaviano Santos Martins ,&nbsp;José Carlos Alves-Filho ,&nbsp;Luiz Gustavo Gardinassi ,&nbsp;Valeria Reginatto ,&nbsp;Daniela Carlos","doi":"10.1016/j.lfs.2025.123624","DOIUrl":"10.1016/j.lfs.2025.123624","url":null,"abstract":"<div><h3>Aims</h3><div><em>Akkermansia muciniphila</em> (<em>A. muciniphila</em>), a Gram-negative anaerobic mucus-layer-degrading bacterium found in the intestinal mucosa, exhibits potential as a probiotic, showing promise in mitigating autoimmune and chronic inflammatory diseases. This study aims to investigate whether <em>A. muciniphila</em> supplementation might confer protection against type 1 diabetes (T1D) and to elucidate the immunological pathways through which it exerts its beneficial effects.</div></div><div><h3>Materials and methods</h3><div>Non-obese diabetic (NOD) mice and streptozotocin (STZ)-induced type 1 diabetes (T1D) models were used to evaluate the protective effects of <em>A. muciniphila</em> during T1D course. Body weight, blood glucose levels, and T1D incidence were monitored. Immune responses in the pancreas, pancreatic (PLN) and cecal lymph nodes (CLN) and bone marrow-derived dendritic cells (BMDC) were evaluated by flow cytometry and ELISA.</div></div><div><h3>Key findings</h3><div>Viable <em>A. muciniphila</em> supplementation conferred protection against T1D onset in STZ-induced T1D and NOD mouse models. T1D modulation by <em>A. muciniphila</em> in the STZ model was independent of the gut microbiota, and it was associated with increased tolerogenic type-2 dendritic cells (SIRP-α⁺CD11b⁺CD103⁺) and regulatory T (Treg) cells in PLN and pancreas. BMDC differentiated in the presence of <em>A. muciniphila</em> exhibited a tolerogenic profile and induced Treg cell generation in vitro. <em>A. muciniphila</em>-induced protection in T1D outcome was abrogated in FOXP3-DTR mice depleted of Treg cells, indicating that its mechanism of action is dependent on the CD4⁺Foxp3⁺ Treg cells.</div></div><div><h3>Significance</h3><div><em>A. muciniphila</em> supplementation attenuates T1D development in mice by modulating the tolerogenic immune response and is a promising new therapeutic tool for this autoimmune disease.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123624"},"PeriodicalIF":5.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143829836","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":"Pan-cancer analysis reveals BAF complexes as immune-related biomarkers and validation in triple-negative breast cancer","authors":"Shuying Dai ,&nbsp;Bei Li ,&nbsp;Qingqian Wu ,&nbsp;Shuang Han ,&nbsp;Qingwen Zhao ,&nbsp;Yule Wang ,&nbsp;Yingjuan Zhang ,&nbsp;Yue Gao","doi":"10.1016/j.lfs.2025.123607","DOIUrl":"10.1016/j.lfs.2025.123607","url":null,"abstract":"<div><h3>Aims</h3><div>BAF complexes (BAFs), ATP-dependent regulators of chromatin structure, play a significant role in cancer progression. This pan-cancer study aimed to decode the potential of specific BAFs in the pathology, immunity, and therapy of targeted cancers.</div></div><div><h3>Materials and methods</h3><div>Data were retrieved from The Cancer Genome Atlas, Gene Expression Omnibus, and IMvigor210 databases and were analyzed for expression patterns, prognostic value, mutational signatures, biological pathways, tumor immune microenvironment (TIME) remodeling, and therapeutic resistance of BAFs. Experimental validation was also conducted.</div></div><div><h3>Key findings</h3><div>BAFs exhibit abnormal expression in various human cancers. The BAFs model and nomogram (based on multiple variables) were developed as prognostic tools. BAFs regulate the TIME and influence the response to anti-PD-L1 therapy, particularly through ACTL6A, as observed in RNA sequencing and single-cell RNA sequencing datasets (high-resolution gene expression data at the single-cell level). ACTLA6 is a major adverse gene in the prognostic model. Patients with high ACTL6A expression showed significantly worse overall survival (hazard ratio = 1.32, 95 % CI: 1.26–1.39, <em>p</em> &lt; 0.001). ACTL6A expression escalates with breast cancer (BRCA) malignancy, particularly in triple-negative BRCA (TNBC), and correlates with immune checkpoint expression while playing a crucial role in promoting cancer metastasis in TNBC.</div></div><div><h3>Significance</h3><div>Our findings first emphasize the significance of a novel BAFs model for patient prognosis and corroborate the considerable role of BAFs as immune-related biomarkers in pan-cancer progression. ACTL6A has a dual role as an immune-related biomarker and potential therapeutic target in TNBC, deepening our comprehension of its function as an oncogene.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123607"},"PeriodicalIF":5.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803472","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":"Mesenchymal stem cells attenuate hyperoxaluria-induced kidney injury and crystal depositions via inhibiting the activation of NLRP3 inflammasome","authors":"Bangyu Zou ,&nbsp;Ding Wang ,&nbsp;Jinghua Zhong ,&nbsp;Zhiqing He ,&nbsp;Yuhao Zhou ,&nbsp;Houmeng Yang ,&nbsp;Yongda Liu ,&nbsp;Guohua Zeng ,&nbsp;Xiaolu Duan","doi":"10.1016/j.lfs.2025.123608","DOIUrl":"10.1016/j.lfs.2025.123608","url":null,"abstract":"<div><h3>Aims</h3><div>Calcium oxalate (CaOx) is the predominant form of kidney stones, associated with significant morbidity and recurrence rates. Mesenchymal stem cells (MSCs) have shown promise in treating renal injury, but their impact on CaOx stone formation remains unclear.</div></div><div><h3>Materials and methods</h3><div>We established a hyperoxaluria-induced AKI model in mice through intraperitoneal injection of glyoxylate. Two types of MSCs, bone marrow-derived MSCs (BMSCs) and umbilical cord-derived mesenchymal stem cells (UMSCs), were injected through tail vein injection. Histological evaluations and blood biochemical tests were performed to assess crystal deposition and kidney function. The inflammatory response and NLRP3 inflammasome activation were assessed using immunofluorescence, immunohistochemistry, TUNEL staining, and qPCR. In vitro, macrophages were cocultured in the presence of MSCs. ELISA was used to measure IL-1β and IL-18 release. MTS assays assessed renal epithelial cell protection. Western blotting evaluated NLRP3 inflammasome activation in macrophages.</div></div><div><h3>Key findings</h3><div>Both BMSCs and UMSCs significantly inhibited CaOx crystal deposition and kidney injury by inhibiting NLRP3 inflammasome activation. In vitro, both MSC types suppressed NLRP3 inflammasome activation in macrophages through the NF-κB signaling pathway, leading to decreased release of IL-1β and IL-18 and enhanced protection of renal epithelial cells. This attenuation of renal tubular cell injury is a critical factor in preventing CaOx stone formation.</div></div><div><h3>Significance</h3><div>Our findings reveal that Both BMSCs and UMSCs effectively attenuate hyperoxaluria-induced kidney injury and crystal deposition by inhibiting NLRP3 inflammasome activation. This discovery is helpful for developing new effective therapeutic means for nephrolithiasis.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123608"},"PeriodicalIF":5.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143791098","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":"Vitamin D supplementation as a prophylactic therapy in the management of pre-eclampsia: Focus on VEGF, Ki67, oxidative stress markers in correlation to placental ultra structure","authors":"Hanan Eissa ,&nbsp;Eman Mohamed Abdelsalam ,&nbsp;Somaia A. Mokbel ,&nbsp;Nada H. Elhadedy ,&nbsp;Rania M. Khalil ,&nbsp;Amany AbdElfattah Mohamed AbdElfattah ,&nbsp;Dalia M. Abdel Ghaffar ,&nbsp;Eman Mohamad El Nashar ,&nbsp;Alshehri Hanan Hassan ,&nbsp;Norah Saeed Al-Zahrani ,&nbsp;Rashid A. Aldahhan ,&nbsp;Neimat Abd Elhakam Yassin","doi":"10.1016/j.lfs.2025.123605","DOIUrl":"10.1016/j.lfs.2025.123605","url":null,"abstract":"<div><h3>Background</h3><div>Pre-eclampsia (PE) is a progressive hypertension condition that manifests in the second or third trimester of pregnancy and causes significant proteinuria. A lack of vitamin D (Vit. D) is linked to different pregnancy problems, including impaired placental development. Vitamin D has been shown to enhance fetal growth and lower the incidence of PE.</div></div><div><h3>Aim of the work</h3><div>To better understand the pathophysiological mechanisms behind the PE disease and the therapeutic approaches used to manage it, this study examines the role of Vit. D in placental ischemia and its regulatory effects in Nitro L-arginine Methyl Ester (L-NAME) animal model of PE.</div></div><div><h3>Methods</h3><div>Fifty female rats in the estrus stage were mated with 30 male rats. Thirty female rats were pregnant and divided into three equal groups: control, Preeclampsia group (PE); using L-NAME for induction of PE, and Vit. D group from 7th day then induction by L-NAME at 10th day till end of pregnancy. Mean arterial Bp, proteinuria, oxidative stress markers, histological structure and immunohistochemical expression of Ki67 and VEGF, Morphometric study, and transmission electron microscopy(TEM) were assessed. The results of the current study suggested that, Vit. D supplementation could lower blood pressure, reduce oxidative stress, and restore angiogenic balance through vascular endothelial growth factor (VEGF) and Ki67.</div></div><div><h3>Conclusion</h3><div>For the first time, we conclude that vitamin D supplementation may not only have direct effects on blood pressure regulation and angiogenic hemostasis but also recover placental function, actually contributing to the prevention or management of PE.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"372 ","pages":"Article 123605"},"PeriodicalIF":5.2,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143803476","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}