Life sciences最新文献

Molecular insights into the causal role of TG/IDL in rheumatoid arthritis: Integrating Mendelian randomization and single-cell RNA sequencing. TG/IDL在类风湿关节炎中的因果作用：整合孟德尔随机化和单细胞RNA测序。

IF 5.1 2区医学

Life sciences Pub Date : 2025-10-15 Epub Date: 2025-08-05 DOI: 10.1016/j.lfs.2025.123883

Qing Meng, BiYong Deng, Ding Liu

{"title":"Molecular insights into the causal role of TG/IDL in rheumatoid arthritis: Integrating Mendelian randomization and single-cell RNA sequencing.","authors":"Qing Meng, BiYong Deng, Ding Liu","doi":"10.1016/j.lfs.2025.123883","DOIUrl":"10.1016/j.lfs.2025.123883","url":null,"abstract":"<p><strong>Aims: </strong>Triglycerides in intermediate-density lipoproteins (TG/IDL) have been implicated in rheumatoid arthritis (RA) pathogenesis, but their causal relationship and underlying molecular mechanisms remain unclear. This study integrates Mendelian randomization (MR) and single-cell RNA sequencing (scRNA-seq) to identify key genes mediating the link between TG/IDL and RA.</p><p><strong>Materials and methods: </strong>GWAS datasets and MR analysis were utilized to establish TG/IDL as a risk factor for RA. scRNA-seq of RA synovial tissue was conducted to examine cellular heterogeneity and identify differentially expressed genes (DEGs). Integration of MR and scRNA-seq data pinpointed key genes, which were validated through functional studies in collagen-induced arthritis (CIA) mouse models and fibroblast-like synoviocyte (FLS) cultures.</p><p><strong>Key findings: </strong>MR analysis confirmed TG/IDL as a risk factor for RA (OR = 1.001, p = 0.027). scRNA-seq identified seven distinct cell types and highlighted ABCA1, PLTP, and GAS6 as key genes. Overexpression of these genes in CIA mice and FLS cultures reduced inflammation, suppressed cell migration, and inhibited signaling pathways (p65, MAPK, JNK), validating their therapeutic potential.</p><p><strong>Significance: </strong>This study establishes a molecular link between TG/IDL and RA, identifies novel therapeutic targets, and provides insights into lipid metabolism's role in RA, paving the way for innovative treatment strategies.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"123883"},"PeriodicalIF":5.1,"publicationDate":"2025-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775776","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

Diabetic kidney disease and aging: Focus on gut microbiota. 糖尿病肾病和衰老：关注肠道微生物群。

IF 5.1 2区医学

Life sciences Pub Date : 2025-10-06 DOI: 10.1016/j.lfs.2025.123999

Jin Rong, Yuanhua Dai, Bo Zhang, Yuxi Li, Kexu Chen, Hanfei Li, Tingting Zhao, Shunmei Liu

引用次数: 0

`Integrated multi-modal dissection of IVIg-mediated immune reprogramming in lupus mice 狼疮小鼠ivig介导的免疫重编程的综合多模态解剖

IF 5.1 2区医学

Life sciences Pub Date : 2025-10-03 DOI: 10.1016/j.lfs.2025.123997

Xin Yuan , Pan Sun , Tong Wang , Wei Zhang , Peng Jiang , Hong Liang , Xiaochen Yan , Tiancheng Chu , Xi Du , Shengliang Ye , Li Ma , Ping Fu , Zongkui Wang , Changqing Li

{"title":"`Integrated multi-modal dissection of IVIg-mediated immune reprogramming in lupus mice","authors":"Xin Yuan , Pan Sun , Tong Wang , Wei Zhang , Peng Jiang , Hong Liang , Xiaochen Yan , Tiancheng Chu , Xi Du , Shengliang Ye , Li Ma , Ping Fu , Zongkui Wang , Changqing Li","doi":"10.1016/j.lfs.2025.123997","DOIUrl":"10.1016/j.lfs.2025.123997","url":null,"abstract":"<div><div>Intravenous immunoglobulin (IVIg) is widely used to treat autoimmune diseases, yet its precise mechanisms of action in systemic lupus erythematosus remain incompletely understood. Here, we employed an integrated multi-modal approach combining single-cell RNA sequencing, quantitative proteomics, flow cytometry, immunofluorescence, enzyme-linked immunosorbent assay, and histopathological analysis to investigate IVIg-induced immune reprogramming in MRL/lpr lupus-prone mice. IVIg treatment markedly alleviated disease manifestations, including splenomegaly, proteinuria, renal injury, and systemic autoantibody production. Histological examination of the spleen and kidney showed decreased lymphoid hyperplasia, glomerular inflammation, and tissue damage in IVIg-treated mice. At the immune-cell level, IVIg was associated with alterations in T and B cell activation states, partial restoration of immune repertoire diversity, and shifts in dendritic cell populations. Collectively, our integrated analyses suggest that IVIg treatment is correlated with broad immunomodulatory changes in splenic immune composition in lupus-prone mice.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 123997"},"PeriodicalIF":5.1,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227683","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

Ellagic acid protects against deoxyaconitine-induced neurotoxicity by improving mitochondrial function. 鞣花酸通过改善线粒体功能来保护脱氧乌头碱诱导的神经毒性。

IF 5.1 2区医学

Life sciences Pub Date : 2025-10-01 DOI: 10.1016/j.lfs.2025.124007

Wenqi Wang, Jie Guo, Danyang Ye, Ruiguang Wu, Yi Zhang, Yonggang Liu

{"title":"Ellagic acid protects against deoxyaconitine-induced neurotoxicity by improving mitochondrial function.","authors":"Wenqi Wang, Jie Guo, Danyang Ye, Ruiguang Wu, Yi Zhang, Yonggang Liu","doi":"10.1016/j.lfs.2025.124007","DOIUrl":"https://doi.org/10.1016/j.lfs.2025.124007","url":null,"abstract":"<p><p>Ellagic acid (EA), a naturally occurring polyphenol abundant in fruits and nuts, is known for its diverse pharmacological properties, with recent investigations demonstrating its beneficial neuroprotective effects. The clinical application of Aconitum alkaloids, particularly the neurotoxic diester-type alkaloid deoxyaconitine (DA), remains challenging due to incomplete understanding of its toxicological mechanisms. In this study, we systematically investigated the neuroprotective efficacy of EA against DA-induced Caenorhabditis elegans (C. elegans) model. EA alleviated DA-induced neurodegeneration across dopaminergic, serotonergic, glutamatergic, and GABAergic circuits, coupled with reduced ROS levels, lipofuscin deposition, and apoptotic cell death. Mechanistically, EA exerted neuroprotection by attenuating oxidative stress, restoring energy metabolism homeostasis, modulating amino acid and neurotransmitter synthesis/metabolism, ameliorating mitochondrial dysfunction, and activating the insulin/insulin-like growth factor (IIS) signaling pathway and the p38 mitogen-activated protein kinase (MAPK) signaling cascade. Collectively, these findings position EA as a promising adjuvant agent to counteract DA-associated neurotoxicity, thereby expanding the therapeutic window for DA-based clinical applications and making traditional Aconitum-based medicines safer for clinical use.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124007"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225527","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

Retraction notice to "Codelivery of STAT3 and PD-L1 siRNA by hyaluronate-TAT trimethyl/thiolated chitosan nanoparticles suppresses cancer progression in tumor-bearing mice" [Life Sci. 266 (2021) 118847]. “透明质酸- tat三甲基/硫代壳聚糖纳米颗粒共同递送STAT3和PD-L1 siRNA抑制荷瘤小鼠的癌症进展”[生命科学]，266(2021)118847]。

IF 5.1 2区医学

Life sciences Pub Date : 2025-10-01 DOI: 10.1016/j.lfs.2025.124005

Shima Bastaki, Surendar Aravindhan, Nasrin Ahmadpour Saheb, Mahsa Afsari Kashani, Aleksei Evgenievich Dorofeev, Fariba Karoon Kiani, Hediyeh Jahandideh, Farzaneh Beigi Dargani, Mohsen Aksoun, Afshin Nikkhoo, Ali Masjedi, Ata Mahmoodpoor, Majid Ahmadi, Sanam Dolati, Simin Namvar Aghdash, Farhad Jadidi-Niaragh

引用次数: 0

Retraction notice to "The endocannabinoid signaling pathway as an emerging target in pharmacotherapy, earmarking mitigation of destructive events in rheumatoid arthritis" [Life Sci. 257 (2020) 118109]. “内源性大麻素信号通路作为类风湿性关节炎药物治疗的新靶点，特异性缓解破坏性事件”[生命科学，257(2020)118109]。

IF 5.1 2区医学

Life sciences Pub Date : 2025-10-01 DOI: 10.1016/j.lfs.2025.124004

Ishnoor Kaur, Tapan Behl, Simona Bungau, Gokhan Zengin, Arun Kumar, Mohamed A El-Esawi, Gaurav Khullar, Thangavel Venkatachalam, Sandeep Arora

引用次数: 0

HSPB6 based on integrative multi-omics analysis can suppress colorectal cancer progression by downregulating HSPA6 expression through the JNK-JUND axis. 基于整合多组学分析的HSPA6可以通过JNK-JUND轴下调HSPA6的表达，从而抑制结直肠癌的进展。

IF 5.1 2区医学

Life sciences Pub Date : 2025-10-01 DOI: 10.1016/j.lfs.2025.124001

Yukun Cao, Yue Yu, Tian Tian, Qingzhen Fu, Ning Zhao, Chao Qu, Yan Dong, Sichen Li, Tianxue Xu, Binbin Cui, Fan Wang, Yashuang Zhao

{"title":"HSPB6 based on integrative multi-omics analysis can suppress colorectal cancer progression by downregulating HSPA6 expression through the JNK-JUND axis.","authors":"Yukun Cao, Yue Yu, Tian Tian, Qingzhen Fu, Ning Zhao, Chao Qu, Yan Dong, Sichen Li, Tianxue Xu, Binbin Cui, Fan Wang, Yashuang Zhao","doi":"10.1016/j.lfs.2025.124001","DOIUrl":"10.1016/j.lfs.2025.124001","url":null,"abstract":"<p><strong>Aims: </strong>Colorectal cancer (CRC) remains one of the most common malignancies worldwide characterized by poor prognosis, and its mechanism is unclear. Small heat shock protein 6 (HSPB6) plays an important role in cardiovascular diseases. However, the role of HSPB6 in CRC remain poorly understood.</p><p><strong>Materials and methods: </strong>We performed whole-genome methylation, RNA sequencing and proteomics analysis, combined with external database, to identify and validate the role of HSPB6 in CRC. We detected HSPB6 in CRC through in vitro and in vivo experiments. The downstream regulatory mechanism of HSPB6 was explored using RNA sequencing and immunoprecipitation mass spectrometry. The drug sensitivity assay conducted to evaluate the effect of HSPB6 expression on chemosensitivity.</p><p><strong>Key findings: </strong>HSPB6 was hypermethylated and downregulated in CRC tissues, and its expression level was correlated with poor patient prognosis. Both the methylation and expression of HSPB6 showed high diagnostic value. Overexpression of HSPB6 inhibited proliferation, migration and invasion of CRC cells and suppress tumor growth in mice. HSPB6 directly interacted with Heat shock protein family A member 6 (HSPA6), leading to inhibition of the JNK-JUND axis. Additionally, HSPB6 overexpression increased sensitivity to oxaliplatin.</p><p><strong>Significance: </strong>HSPB6 may serve as a valuable diagnostic and prognostic biomarker, and as a putative tumor suppressor in CRC by downregulating HSPA6 and inhibiting the JNK-JUND signaling axis. Our findings suggest a novel therapeutic strategy for CRC patients exhibiting high HSPB6 expression, particularly in the context of oxaliplatin treatment.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124001"},"PeriodicalIF":5.1,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145225522","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

Retraction notice to "Silencing STAT3 enhances sensitivity of cancer cells to doxorubicin and inhibits tumor progression" [Life Sci. 275 (2021) 119369]. “沉默STAT3增强肿瘤细胞对阿霉素的敏感性并抑制肿瘤进展”的撤回通知[生命科学]. 275(2021)119369]。

IF 5.1 2区医学

Life sciences Pub Date : 2025-10-01 DOI: 10.1016/j.lfs.2025.124003

Navneet Joshi, Farnaz Hajizadeh, Ehsan Ansari Dezfouli, Angelina Olegovna Zekiy, Mohsen Nabi Afjadi, Seyedeh Mahboubeh Mousavi, Mohammad Hojjat-Farsangi, Vahid Karpisheh, Ata Mahmoodpoor, Hadi Hassannia, Sanam Dolati, Hamed Mohammadi, Mehdi Yousefi, Farhad Jadidi-Niaragh

引用次数: 0

Horizontal gene transfers differentially shape the functional potential of the infant gut metagenome. 水平基因转移不同地塑造了婴儿肠道宏基因组的功能潜力。

IF 5.1 2区医学

Life sciences Pub Date : 2025-09-30 DOI: 10.1016/j.lfs.2025.124006

Umme Habiba, Muneebah Noor, Masood Ur Rehman Kayani, Lisu Huang

{"title":"Horizontal gene transfers differentially shape the functional potential of the infant gut metagenome.","authors":"Umme Habiba, Muneebah Noor, Masood Ur Rehman Kayani, Lisu Huang","doi":"10.1016/j.lfs.2025.124006","DOIUrl":"10.1016/j.lfs.2025.124006","url":null,"abstract":"<p><p>Horizontal gene transfer (HGT) is a major driver of microbial evolution, influencing the metabolic potential of microbial communities. Despite its significance, the consequences of HGT in shaping the microbial metabolic potential remain poorly understood, particularly in complex environments such as the human gut. This study aimed to assess the impact of HGT in infant gut microbiome from Caesarean section (CSD) and vaginal delivery (VD) groups during the first year of life. At Month 0, CSD infants exhibited a higher number of HGT events than VD infants. However, the numbers converged around Month 2 and remained comparable until Month 9, with no significant differences between groups (p > 0.05). HGT in VD was primarily driven by Coprococcus catus and Ruminococcus sp_5_1_39BFAA, while in CSD, Salmonella enterica and Klebsiella pneumoniae were dominant donors and acceptors. Functional analysis revealed that HGT in VD enriched genes related to carbohydrate metabolism and immune responses, whereas CSD was enriched for metabolic processes and biofilm formation. Additionally, HGT events were associated with Neonatal Intensive Care Unit Admission and diet transitions. These results suggest that HGT events in the VD and CSD groups differently shape the functional potential of the infant gut microbiome, with possible health implications that require further investigation. However, experimental validation is needed to establish a causal link.</p>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":" ","pages":"124006"},"PeriodicalIF":5.1,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145213143","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

Progesterone receptor membrane component 1 accelerates liver fibrosis by interacting with transforming growth factor β receptor 黄体酮受体膜组分1通过与转化生长因子β受体相互作用加速肝纤维化。

IF 5.1 2区医学

Life sciences Pub Date : 2025-09-29 DOI: 10.1016/j.lfs.2025.124000

Moeka Mukae , Je-Won Ko , Hyo-Jung Kwun , In-Jeoung Baek , Sang R. Lee , Eui-Ju Hong

{"title":"Progesterone receptor membrane component 1 accelerates liver fibrosis by interacting with transforming growth factor β receptor","authors":"Moeka Mukae , Je-Won Ko , Hyo-Jung Kwun , In-Jeoung Baek , Sang R. Lee , Eui-Ju Hong","doi":"10.1016/j.lfs.2025.124000","DOIUrl":"10.1016/j.lfs.2025.124000","url":null,"abstract":"<div><h3>Aims</h3><div>Transforming growth factor-beta (TGF-β) is a central driver of hepatic stellate cell (HSC) activation via SMAD signaling, ultimately contributing to liver fibrosis and cirrhosis. While progesterone receptor membrane component 1 (Pgrmc1), a non-canonical progesterone receptor, has been implicated in liver metabolism, its role in liver fibrosis remains poorly understood.</div></div><div><h3>Main methods</h3><div>To investigate the involvement of PGRMC1 in liver fibrosis, we analyzed public Gene Expression Omnibus (GEO) datasets from cirrhotic patients. A carbon tetrachloride (CCl₄)-induced liver fibrosis model was established in wild-type and Pgrmc1-knockout (KO) mice. Additionally, primary hepatocytes and Lx-2 cells were used to explore cell-type specific signaling pathways.</div></div><div><h3>Key findings</h3><div>Public dataset analysis revealed that higher PGRMC1 expression is associated with cirrhosis development and shorter survival in cirrhotic patients. In a CCl₄-induced model, Pgrmc1-KO mice exhibited significant resistance to liver fibrosis with suppression of TGF-β signaling. However, Pgrmc1-KO primary hepatocytes were prone to CCl₄-induced apoptosis. Instead, PGRMC1 knockdown significantly reduced TGF-β receptor (TGF-βR) protein levels and SMAD phosphorylation. Inhibition of TGF-βR1 abrogated the reduction in SMAD phosphorylation observed in PGRMC1-knockdown cells and co-immunoprecipitation assay revealed the interaction between PGRMC1 and TGF-βR.</div></div><div><h3>Significance</h3><div>Collectively, our findings demonstrate that PGRMC1 plays a crucial role in liver fibrosis progression by regulating TGF-βR, highlighting its potential as a promising therapeutic target for antibody-based treatment.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"381 ","pages":"Article 124000"},"PeriodicalIF":5.1,"publicationDate":"2025-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145206781","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