Life sciences最新文献_第10页

Retraction notice to “Exogenous hydrogen sulfide ameliorates high glucose-induced myocardial injury & inflammation via the CIRP-MAPK signaling pathway in H9c2 cardiac cells” [Life Sci. 208 (2018) 315–324] “外源性硫化氢通过CIRP-MAPK信号通路改善H9c2心肌细胞的高糖诱导心肌损伤和炎症”[生命科学]. 208(2018)315-324。

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-28 DOI: 10.1016/j.lfs.2025.123572

Hong-Lei Zhao , Bao-Quan Wu , Ying Luo , Wen-Ying Zhang , Yun-Ling Hao , Jin-Jie Liang , Fang Fang , Wei Liu , Xie-Hui Chen

引用次数: 0

GDF15 promotes trophoblast invasion and pregnancy success via the BMPR1A/BMPR2/p-SMAD1 pathway: Implications for recurrent miscarriage GDF15通过BMPR1A/BMPR2/p-SMAD1途径促进滋养细胞侵袭和妊娠成功：对复发性流产的影响

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-27 DOI: 10.1016/j.lfs.2025.123586

Shu-Han Yang , Long Yang , Yan Shi , Hao-Ran Xu , Jie Gan , Jia-Xin Shi , Yu Zhang , Shi-Long Shen , Jian Wang , Xuan Zhang

{"title":"GDF15 promotes trophoblast invasion and pregnancy success via the BMPR1A/BMPR2/p-SMAD1 pathway: Implications for recurrent miscarriage","authors":"Shu-Han Yang , Long Yang , Yan Shi , Hao-Ran Xu , Jie Gan , Jia-Xin Shi , Yu Zhang , Shi-Long Shen , Jian Wang , Xuan Zhang","doi":"10.1016/j.lfs.2025.123586","DOIUrl":"10.1016/j.lfs.2025.123586","url":null,"abstract":"<div><div>Insufficient invasion of extravillous trophoblasts (EVTs) is associated with adverse pregnancy outcomes, including recurrent miscarriage (RM). Dysregulated expression of growth differentiation factor 15 (GDF15) has been implicated in RM, but the underlying mechanism remains unclear. This study investigated the role of GDF15 in EVTs function and pregnancy outcomes. Spearman correlation analysis revealed a positive correlation between GDF15 and both BMPR1A and BMPR2 in EVTs. Furthermore, GDF15, BMPR1A, BMPR2, and phosphorylated SMAD1 (p-SMAD1) expression were significantly reduced in placental tissue from RM patients compared to Normal controls. Mechanistically, GDF15 activated the p-SMAD1 signaling pathway, inducing expression of its downstream targets, ID1 and Snail, and enhancing migratory and invasive activity in HTR-8/SVneo cells through interaction with the BMPR1A-BMPR2 receptor complex. Eriodictyol, a small molecule activator of BMPR2, was identified and shown to improve pregnancy outcomes in a mouse model of lipopolysaccharide (LPS)-induced early pregnancy loss (EPL). Eriodictyol can also enhance EVTs migration and invasion as well as activated the p-SMAD1 pathway by activating BMPR2. In conclusion, this study identifies BMPR1A as a receptor for GDF15 in EVTs and demonstrates that GDF15 promotes EVTs invasion and improves pregnancy outcomes via the BMPR1A/BMPR2/p-SMAD1 signaling axis. Eriodictyol, acting as a BMPR2 agonist, may offer a novel therapeutic strategy for preventing early pregnancy loss.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123586"},"PeriodicalIF":5.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143738774","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

CELF2 inhibits bladder cancer progression by decreasing the stability of CXCL5 CELF2通过降低CXCL5的稳定性抑制膀胱癌的进展

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-26 DOI: 10.1016/j.lfs.2025.123585

Shiqiang Dong , Lili Wang , Xinyu Liu , Dingkun Hou , Qing Liu , Ji Zheng , Haitao Wang

{"title":"CELF2 inhibits bladder cancer progression by decreasing the stability of CXCL5","authors":"Shiqiang Dong , Lili Wang , Xinyu Liu , Dingkun Hou , Qing Liu , Ji Zheng , Haitao Wang","doi":"10.1016/j.lfs.2025.123585","DOIUrl":"10.1016/j.lfs.2025.123585","url":null,"abstract":"<div><h3>Aims</h3><div>CUGBP Elav-like family (CELF), an RNA-binding protein group, has been implicated in numerous diseases, including cancer. The role of CELF2 in bladder cancer is still not well understood. This study aims to investigate the role of CELF2 in bladder cancer <em>in vitro</em> and <em>in vivo</em> using bioinformatics, biochemical, and functional methods.</div></div><div><h3>Materials and methods</h3><div>We explored <em>CELF2</em> and <em>CELF</em>s expression patterns and their association with bladder cancer by analyzing The Cancer Genome Atlas, University of California, Santa Cruz XENA, and Cancer Cell Line Encyclopedia databases using various computational and statistical analyses, including unsupervised clustering, Kaplan–Meier analysis, and correlation assessments. We utilized the bladder cancer cell lines T24 and J82 for functional analyses. We performed <em>in vitro</em> and <em>in vivo</em> experiments to investigate the impact of CELF2 expression levels on bladder cancer cell proliferation and migration.</div></div><div><h3>Key findings</h3><div>CELF2 expression was downregulated in bladder cancer and positively correlated with the progression-free interval in patients. Increased CELF2 expression suppressed the proliferation and migration of bladder cancer cells. Furthermore, CELF2 was bound to AU-rich motifs in the 3′-UTR of <em>CXCL5</em>, reducing its stability, inhibiting CXCL5/CXCR2/AKT signaling, and repressing bladder cancer progression. Finally, we developed a prognostic model that revealed <em>CELF2</em> and <em>CXCL5</em> as independent prognostic factors for progression-free intervals in patients with bladder cancer.</div></div><div><h3>Significance</h3><div>CELF2 reduced the stability of <em>CXCL5</em> and suppressed the proliferation and migration of bladder cancer cells by inhibiting p-AKT expression. The findings of this study highlight CELF2 as a potential therapeutic target for bladder cancer treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123585"},"PeriodicalIF":5.2,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724438","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The role of RAB12 in inhibiting osteogenic differentiation and driving metabolic dysregulation in osteoporosis RAB12在骨质疏松症中抑制成骨分化和驱动代谢失调中的作用

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-25 DOI: 10.1016/j.lfs.2025.123590

Pengfei Ji , Quanfeng Li , Yunhui Zhang , Jiahao Jin , Yibin Zhang , Zihao Yuan , Guozhen Shen , Qian Cao , Yanfeng Wu , Peng Wang , Wenjie Liu

{"title":"The role of RAB12 in inhibiting osteogenic differentiation and driving metabolic dysregulation in osteoporosis","authors":"Pengfei Ji , Quanfeng Li , Yunhui Zhang , Jiahao Jin , Yibin Zhang , Zihao Yuan , Guozhen Shen , Qian Cao , Yanfeng Wu , Peng Wang , Wenjie Liu","doi":"10.1016/j.lfs.2025.123590","DOIUrl":"10.1016/j.lfs.2025.123590","url":null,"abstract":"<div><h3>Aims</h3><div>The osteogenic differentiation of mesenchymal stem cells (MSCs) is crucial in osteoporosis, and the metabolic level of the bone microenvironment directly affects metabolic dysregulation in postmenopausal women. RAB12 is a member of the small GTPase Rab family proteins, known to play an important role in autophagy. However, the role of RAB12 in the osteogenic differentiation of osteoporotic hMSCs remains unclear.</div></div><div><h3>Materials and method</h3><div>Immunohistochemical staining was used to validate the high expression of RAB12 in aged osteoporotic mouse models and ovariectomized (OVX) mouse models. Co-immunoprecipitation (Co-IP) and LC-MS/MS were employed to explore downstream proteins that may interact with RAB12. Adenovirus containing RAB12 siRNA sequences was injected into the tail vein of OVX osteoporotic mice to analyze the impact of the RAB12/PCBP1/GLUT1 axis on MSC osteogenic differentiation.</div></div><div><h3>Key findings</h3><div>We found that RAB12 expression is upregulated in elderly osteoporotic patients and in osteoporotic mouse models. RAB12 negatively regulates the osteogenic differentiation of hMSCs both in vivo and in vitro. RAB12 interacts with the PCBP1 protein, affecting its autophagic degradation when its expression levels change. RAB12 regulates the transcriptional level of GLUT1 by influencing the autophagic degradation of PCBP1, thereby affecting MSC's regulation of glucose uptake, which in turn impacts MSC osteogenic differentiation and metabolic changes.</div></div><div><h3>Significance</h3><div>RAB12 negatively regulates osteogenic differentiation through the PCBP1/GLUT1 axis, affecting glucose metabolism levels in the bone microenvironment. RAB12 may serve as a potential target for the treatment of osteoporosis and postmenopausal metabolic dysregulation.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123590"},"PeriodicalIF":5.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143724439","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Engineered promoter-free insulin-secreting cells provide closed-loop glycemic control 不含启动子的工程胰岛素分泌细胞可提供闭环血糖控制。

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-25 DOI: 10.1016/j.lfs.2025.123587

Yumin Li , Cong He , Doulathunnisa Ahamed Younis , Chengming Ni , Rui Liu , Zilin Sun , Hao Lin , Yuxin Wang , Pengyu Zhu , Zhongdang Xiao , Bo Sun

{"title":"Engineered promoter-free insulin-secreting cells provide closed-loop glycemic control","authors":"Yumin Li , Cong He , Doulathunnisa Ahamed Younis , Chengming Ni , Rui Liu , Zilin Sun , Hao Lin , Yuxin Wang , Pengyu Zhu , Zhongdang Xiao , Bo Sun","doi":"10.1016/j.lfs.2025.123587","DOIUrl":"10.1016/j.lfs.2025.123587","url":null,"abstract":"<div><div>Diabetes mellitus is currently a priority health issue worldwide, but existing therapies suffer from insufficient donors, inability to provide glucose-dependent endogenous insulin secretion, transplantation risks, and immune rejection. Especially, reported engineered cells are mostly promoter-induced glucose-independent insulin producing cells. Here we constructed a closed-loop of insulin secretion with glucose-dependent IRES to achieve glucose-sensitive endogenous insulin secretion. Those cells successfully reversed hyperglycemia in diabetic mice for at least 60 days after transplantation without any significant immune rejection, demonstrating that our constructed engineered cellular grafts have good biocompatibility. Our findings hold great promise in the field of diabetes treatment and provide a new, glucose-dependent genetic engineering approach to insulin production, which is expected to solve many of the current problems faced in the clinical treatment of diabetes mellitus.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"371 ","pages":"Article 123587"},"PeriodicalIF":5.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730496","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

BTN3A2 interacted with MFGE8 to alleviate preeclampsia by promoting ferroptosis and inhibiting angiogenesis BTN3A2与MFGE8相互作用，通过促进铁下垂和抑制血管生成来缓解子痫前期

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-25 DOI: 10.1016/j.lfs.2025.123584

Xi Yuan , Qi Wang , Caihong Hu , Wenjing Yong , Ping Li

{"title":"BTN3A2 interacted with MFGE8 to alleviate preeclampsia by promoting ferroptosis and inhibiting angiogenesis","authors":"Xi Yuan , Qi Wang , Caihong Hu , Wenjing Yong , Ping Li","doi":"10.1016/j.lfs.2025.123584","DOIUrl":"10.1016/j.lfs.2025.123584","url":null,"abstract":"<div><h3>Aims</h3><div>Preeclampsia (PE) is a major cause of maternal and perinatal morbidity and mortality and is characterized by placental ischemia. Angiogenic disorders and ferroptosis are key mechanisms in PE; however, their relationship remains unclear. The butyrophilin 3A (BTN3A) family member BTN3A2 is involved in the progression of many cancers; however, its role in PE angiogenesis and ferroptosis is unclear. In this study, we investigated the role of BTN3A2 in PE angiogenesis and ferroptosis.</div></div><div><h3>Materials and methods</h3><div>Placental tissues were collected from healthy individuals and PE patients to explore the correlation between ferroptosis and angiogenesis. Human umbilical vein endothelial cells (HUVECs) were subjected to hypoxia, ferrostatin-1, Erastin, and gene manipulations (oe-BTN3A2, si-BTN3A2, and si-milk factor-globule-EFG factor 8 (MFGE8)) to elucidate the underlying mechanisms. Finally, a rat model of PE was established by intraperitoneal injection of Nomega-nitro-L-arginine methyl ester to verify the effects of BTN3A2 on angiogenesis.</div></div><div><h3>Key findings</h3><div>Placental ferroptosis was negatively correlated with angiogenesis in PE. Clone number, migration, and tube number decreased in HUVECs after hypoxic exposure, and these effects were reversed by ferrostatin-1. BTN3A2 was increased in PE placentae and inhibited the viability of hypoxic HUVECs by inducing ferroptosis. Mechanistically, BTN3A2 interacted with MFGE8, and BTN3A2 promoted hypoxia-induced ferroptosis in HUVECs by downregulating MFGE8. Additionally, BTN3A2 knockdown promoted placental angiogenesis and improved the prognosis in PE rats.</div></div><div><h3>Significance</h3><div>BTN3A2 interacted with MFGE8 to alleviate PE by promoting ferroptosis and inhibiting angiogenesis. Therefore, it may serve as a potential therapeutic target for the diagnosis and treatment of PE.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123584"},"PeriodicalIF":5.2,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparing the effectiveness of Rosuvastatin and Atorvastatin on changes in LDL, TG and HDL: A systematic review and meta-analysis 比较瑞舒伐他汀和阿托伐他汀对低密度脂蛋白、总胆固醇和高密度脂蛋白变化的有效性：系统回顾和荟萃分析

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-24 DOI: 10.1016/j.lfs.2025.123576

Kourosh Sayehmiri , Masoumeh Shohani , SamiraMis Qavam , Hamed Tavan

{"title":"Comparing the effectiveness of Rosuvastatin and Atorvastatin on changes in LDL, TG and HDL: A systematic review and meta-analysis","authors":"Kourosh Sayehmiri , Masoumeh Shohani , SamiraMis Qavam , Hamed Tavan","doi":"10.1016/j.lfs.2025.123576","DOIUrl":"10.1016/j.lfs.2025.123576","url":null,"abstract":"<div><h3>Aim</h3><div>Elevated levels of LDL and triglycerides, along with low levels of HDL, are key contributors to cardiovascular disease. If the increase of harmful fats is prevented, it will be a great step towards the prevention of diseases. The two drugs atorvastatin and rosuvastatin are the most commonly used drugs to reduce LDL and triglycerides and increase HDL in patients.</div><div>The present study aimed to compare the effectiveness of Rosuvastatin and Atorvastatin on changes in LDL, TG and HDL using a systematic review and meta-analysis method.</div></div><div><h3>Materials and methods</h3><div>The present study was conducted on the basis of the protocol of systematic review and meta-analyses. The ISI, Cochrane Library, Google Scholar, PubMed, Scopus, and Elsevier databases were independently searched by two researchers using Mesh keywords in different regions of the world during 2003 to 2025. Data was analyzed using the STATA software.</div></div><div><h3>Key findings</h3><div>Effectiveness of Atorvastatin on the reduction of LDL was 51.49 mg/dl (42.75–60.23 %, CI =95 %) versus Rosuvastatin with a reduction of 55.66 mg/dl (46.32–65 and CI =95 %). The effectiveness of Atorvastatin on the rise of HDL was 1.85 mg/dl (−3.23–0.46 and CI =95 %) versus Rosuvastatin with a rise of 3.87 mg/dl (2.08–5.66 and CI =95 %); and the effectiveness of atorvastatin on the reduction of TG was 24.76 mg/dl (18.14–31.88 and CI = 95 %) versus the effectiveness of Rosuvastatin with a reduction of 31.98 mg/dl (24. 41–39.55 and CI = 95 %).</div></div><div><h3>Significance</h3><div>According to research results, Rosuvastatin was better than Atorvastatin and decreased triglyceride and LDL and increased HDL in all cases.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123576"},"PeriodicalIF":5.2,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Interferon regulatory factor 1 contributes to metabolic dysfunction associated steatotic liver disease 干扰素调节因子1与脂肪变性肝病相关的代谢功能障碍有关。

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-23 DOI: 10.1016/j.lfs.2025.123575

Xinyue Sun , Zhen Yang , Min Li , Shanwen Gong , Xiulian Miao , Bo Wang , Xiaocen Kong , Qiang Zhu

{"title":"Interferon regulatory factor 1 contributes to metabolic dysfunction associated steatotic liver disease","authors":"Xinyue Sun , Zhen Yang , Min Li , Shanwen Gong , Xiulian Miao , Bo Wang , Xiaocen Kong , Qiang Zhu","doi":"10.1016/j.lfs.2025.123575","DOIUrl":"10.1016/j.lfs.2025.123575","url":null,"abstract":"<div><h3>Aims</h3><div>Non-alcoholic fatty liver disease (NAFLD) or metabolic dysfunction associated steatotic liver disease (MASLD), has reached epidemic levels in multiple regions worldwide and contributes to cirrhosis and hepatocellular carcinoma. We have previously reported that the C<img>C motif chemokine ligand 11 (CCL11) is a key regulator of MASLD. Expression of interferon regulatory factor 1 (IRF1) can be up-regulated by CCL11 treatment in hepatocytes, the relevance of which is not clear. In the present study we investigated the role of IRF1 in NAFLD pathogenesis.</div></div><div><h3>Methods and materials</h3><div>MASLD was investigated in mice fed a high-fat high carbohydrate (HFHC) diet or in the genetically predisposed obese mice (<em>db</em>/<em>db</em>).</div></div><div><h3>Key findings</h3><div>Hepatocytes from CCL11 knockout mice displayed a less severe MASLD phenotype, when treated with palmitic acid (PA), compared to wild type hepatocytes, which could be normalized by IRF1 over-expression. On the contrary, IRF1 knockdown in hepatocytes significantly down-regulated expression of pro-inflammatory mediators and dampened lipid accumulation induced by PA treatment. More importantly, IRF1 knockdown in hepatocytes led to amelioration of MASLD in mice. RNA-seq and CUT&Tag-seq identified pro-MASLD genes, including <em>Osbpl3</em>, <em>Ddit4</em>, and <em>Ccl2</em>, as potential targets for IRF1 in hepatocytes.</div></div><div><h3>Significance</h3><div>Our data reveal a novel regulatory role of IRF1 in MASLD pathogenesis. Targeting IRF1 can be considered as a reasonable approach for MASLD intervention.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123575"},"PeriodicalIF":5.2,"publicationDate":"2025-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143710545","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

M2 macrophage derived exosomal miR-20a-5p ameliorates trophoblast pyroptosis and placental injuries in obstetric antiphospholipid syndrome via the TXNIP/NLRP3 axis M2巨噬细胞来源的外泌体miR-20a-5p通过TXNIP/NLRP3轴改善产科抗磷脂综合征的滋养细胞焦亡和胎盘损伤

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-22 DOI: 10.1016/j.lfs.2025.123561

Hongyuan Zhang , Ning Jiang , Mingyang Xu , Die Jing , Tingting Dong , Qian Liu , Qingfeng Lv , Ruiheng Huo , Pengzheng Chen , Lei Li , Xietong Wang

{"title":"M2 macrophage derived exosomal miR-20a-5p ameliorates trophoblast pyroptosis and placental injuries in obstetric antiphospholipid syndrome via the TXNIP/NLRP3 axis","authors":"Hongyuan Zhang , Ning Jiang , Mingyang Xu , Die Jing , Tingting Dong , Qian Liu , Qingfeng Lv , Ruiheng Huo , Pengzheng Chen , Lei Li , Xietong Wang","doi":"10.1016/j.lfs.2025.123561","DOIUrl":"10.1016/j.lfs.2025.123561","url":null,"abstract":"<div><h3>Aim</h3><div>Obstetric antiphospholipid syndrome (OAPS) is a pregnancy-related complication characterized by trophoblast pyroptosis and placental injury induced by antiphospholipid antibodies (aPLs). M2-polarized macrophage-derived exosomes (M2-exos) exert anti-inflammatory, immunomodulatory, and growth-promoting effects in various autoimmune diseases and tumors. However, their role in OAPS is not yet clear. Therefore, in this study, we isolated M2-exos from M2 macrophages and investigated their effects on trophoblast proliferation, death, migration, invasion, and pyroptosis following stimulation using aPLs.</div></div><div><h3>Main methods</h3><div>First, we established an animal model of OAPS and thereafter treated the OAPS mice with exogenous M2-exos via injection through the tail vein. Then to clarify the roles of miR-20a-5p and thioredoxin-interacting protein (TXNIP) in OAPS, we performed gain- or loss-of-function assays, and used GraphPad Prism software to analyze the collected data with statistical significance set at <em>P</em> < 0.05.</div></div><div><h3>Key findings</h3><div>MicroRNAs (miRNAs) sequencing revealed the enrichment of miR-20a-5p in M2-exos, and these M2-exos significantly alleviated aPLs-induced trophoblast dysfunction. Our results also indicated that M2-exos delivered miR-20a-5p to trophoblast cells directly targeted thioredoxin-interacting protein (TXNIP), and thus suppressed the TXNIP/NLRP3 pathway, reduced pyroptosis and inflammation in trophoblast cells, and improved placental function and fetal development.</div></div><div><h3>Significance</h3><div>M2-exos improve pregnancy outcomes in OAPS via the miR-20a-5p/TXNIP/NLRP3 axis, and thus represent as a novel therapeutic approach for aPLs-induced OAPS.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123561"},"PeriodicalIF":5.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143697568","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Deciphering the CREB-NR2B axis: Unraveling the crosstalk of insulin and TGF-β signalling in ameliorating postoperative cognitive dysfunction 破译CREB-NR2B轴：揭示胰岛素和tgf-β信号传导在改善术后认知功能障碍中的串扰。

IF 5.2 2区医学

Life sciences Pub Date : 2025-03-22 DOI: 10.1016/j.lfs.2025.123574

Jiawen Zhou , Xue Han , Ziqi Wei , Yujia Liu , Jiyan Xu , Minhui Xu , Tianjiao Xia , Xiaolei Cheng , Xiaoping Gu

{"title":"Deciphering the CREB-NR2B axis: Unraveling the crosstalk of insulin and TGF-β signalling in ameliorating postoperative cognitive dysfunction","authors":"Jiawen Zhou , Xue Han , Ziqi Wei , Yujia Liu , Jiyan Xu , Minhui Xu , Tianjiao Xia , Xiaolei Cheng , Xiaoping Gu","doi":"10.1016/j.lfs.2025.123574","DOIUrl":"10.1016/j.lfs.2025.123574","url":null,"abstract":"<div><div>Postoperative cognitive dysfunction (POCD) is a significant postoperative complication, particularly in the elderly, linked to inflammation-mediated neural dysfunction. Insulin resistance and disruptions in transforming growth factor beta (TGF-β) signalling are associated with cognitive decline in aging, yet their roles in POCD are not fully understood. Here, we demonstrated that both insulin and TGF-β pathways were disrupted in POCD mouse models, with recombinant insulin and TGF-β treatments improving cognitive outcomes. These treatments reversed neuroinflammation in vitro, while CREB knockdown abrogated the protective effects, both in vivo and in vitro. Mechanistically, CREB was found to mediate the protective effects of insulin and TGF-β in POCD by directly regulating the expression of the cognitive-related protein NR2B. Altogether, our study identifies a key molecular target involved in the critical signalling pathways associated with POCD, offering promising therapeutic strategies for prevention and treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"370 ","pages":"Article 123574"},"PeriodicalIF":5.2,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143692362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0