Life sciences最新文献_第9页

Melatonin protects against particulate matter-induced ovarian dysfunction by activating the Nrf2 signaling pathway to alleviate ferroptosis 褪黑素通过激活Nrf2信号通路来缓解铁氧化，从而保护卵巢免受微粒物质诱发的卵巢功能障碍的影响。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-04 DOI: 10.1016/j.lfs.2024.123200

Xiaoyuan Zhang , Xiaxia Man , Qi Zhang , Laiyu Zhu , Lu Chen , Chao Zhu , Xinxin Ci , Xiaowei Yu

{"title":"Melatonin protects against particulate matter-induced ovarian dysfunction by activating the Nrf2 signaling pathway to alleviate ferroptosis","authors":"Xiaoyuan Zhang , Xiaxia Man , Qi Zhang , Laiyu Zhu , Lu Chen , Chao Zhu , Xinxin Ci , Xiaowei Yu","doi":"10.1016/j.lfs.2024.123200","DOIUrl":"10.1016/j.lfs.2024.123200","url":null,"abstract":"<div><div>Accumulating evidence suggests that exposure to ambient airborne PM2.5 increases the risk of primary ovarian insufficiency (POI). However, whether ferroptosis, a newly discovered type of cell death involved in PM2.5-induced lung injury and fibrosis, is involved in PM2.5-induced POI has not been determined. This study aimed to verify the involvement of PM2.5-induced ferroptosis in ovarian dysfunction and further demonstrate that melatonin inhibits ferroptosis by activating the Nrf2 signaling pathway to ameliorate POI in vivo and in vitro. In our study, PM2.5 promoted iron accumulation and induced lipid peroxidation, thus contributing to ferroptosis in KGN cells and ovaries. However, these effects were eliminated and enhanced in Nrf2-overexpressing and Nrf2-knockdown cells, respectively. In addition, melatonin and ferrostatin-1 (Fer-1) inhibited ferroptosis by activating the NRF2 signaling pathway, as evidenced by the silencing of Nrf2 in vivo and in vitro. Mechanistically, Nrf2-knockout mice were more susceptible to ferroptosis and PM2.5-induced POI than control mice. Moreover, melatonin suppressed changes in morphological and biochemical indicators related to ferroptosis, such as MDA and GSH depletion and GPX4 and XCT downregulation, by enhancing Nrf2 signaling. Here, we first reported that PM2.5 triggered ferroptosis by increasing ROS levels, lipid peroxidation and glutathione depletion. Notably, melatonin significantly decreased ferroptosis levels and improved ovarian function by activating the NRF2 signaling pathway in vivo and in vitro.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123200"},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591100","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

Simvastatin ameliorates adverse pregnancy by inhibiting glycolysis-related NETs in obstetrical antiphospholipid syndrome 辛伐他汀通过抑制产科抗磷脂综合征中与糖酵解相关的NET，改善不良妊娠。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-04 DOI: 10.1016/j.lfs.2024.123215

Ruiheng Huo , Qipeng Sun , Qingfeng Lv , Yuan Wang , Weiyi Qi , Meihua Zhang , Lei Li , Xietong Wang

{"title":"Simvastatin ameliorates adverse pregnancy by inhibiting glycolysis-related NETs in obstetrical antiphospholipid syndrome","authors":"Ruiheng Huo , Qipeng Sun , Qingfeng Lv , Yuan Wang , Weiyi Qi , Meihua Zhang , Lei Li , Xietong Wang","doi":"10.1016/j.lfs.2024.123215","DOIUrl":"10.1016/j.lfs.2024.123215","url":null,"abstract":"<div><h3>Aims</h3><div>Some patients with Obstetric Antiphospholipid Syndrome (OAPS) still experience miscarriage and placental dysfunction after routine treatment, which is related to an abnormal increase in neutrophil extracellular traps (NETs). The labeling of statins has been revised to remove the contraindication for use during pregnancy. Our aim is to investigate the effect of Simvastatin on pregnancy outcomes in OAPS and its correlation mechanisms with NETs.</div></div><div><h3>Main methods</h3><div>The effect of Simvastatin on pregnancy outcomes was observed. The effect of simvastatin on the function and apoptosis of neutrophils has evaluated. The effect of Simvastatin to NETs and the changes in oxidative stress levels were observed. Different groups of NETs were extracted to intervene the HTR8-Svneo.RNA-seq analysis of the mechanism of which Simvastatin reduces NETs. Seahorse experiment detected the effect of Simvastatin on neutrophil glycolysis levels. Fluorescence co-localization and flow cytometry and Co-IP were used to verify relevant mechanisms.</div></div><div><h3>Key findings</h3><div>In the OAPS mice, Simvastatin can reduce embryo absorption rate, reshape placental blood flow perfusion. Simultaneously reducing the production of NETs both in vivo and <em>vitro</em>, remolding oxidative stress. Simvastatin can improve neutrophil dysfunction caused by aPL-IgG. The reduction of NETs improved HTR8-Svneo's dysfunction. The intervention of Simvastatin on neutrophils under the stimulation of aPL-IgG showed a signature in glycolytic. The key rate limiting enzyme PKM2 in glycolysis interacts with Cit-H2b and PI3K/AKT signaling pathway.</div></div><div><h3>Significance</h3><div>Our study providing basic theoretical support for the treatment of OAPS with Simvastatin.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123215"},"PeriodicalIF":5.2,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591102","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}

引用次数: 0

Mouse liver blood flow is regulated by hepatic stellate cells in response to the sympathetic neurotransmitter norepinephrine 小鼠肝脏血流量受肝脏星状细胞对交感神经递质去甲肾上腺素的调节。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-02 DOI: 10.1016/j.lfs.2024.123214

Naoki Dohi , Momoka Yamaguchi , Kyosuke Iwami , Yukiko K. Kaneko , Shin-ya Saito , Tomohisa Ishikawa

{"title":"Mouse liver blood flow is regulated by hepatic stellate cells in response to the sympathetic neurotransmitter norepinephrine","authors":"Naoki Dohi , Momoka Yamaguchi , Kyosuke Iwami , Yukiko K. Kaneko , Shin-ya Saito , Tomohisa Ishikawa","doi":"10.1016/j.lfs.2024.123214","DOIUrl":"10.1016/j.lfs.2024.123214","url":null,"abstract":"<div><h3>Background</h3><div>There is no clear information on the regulation of liver blood flow by the autonomic nervous system. We conducted this study to investigate whether quiescent hepatic stellate cells (qHSCs) regulate liver blood flow in response to the sympathetic neurotransmitter norepinephrine (NE).</div></div><div><h3>Methods</h3><div>qHSCs isolated from mice were cultured in Dulbecco's modified Eagle medium without fetal bovine serum for 1 day on collagen gel. NE-induced qHSC contraction was evaluated using the quantitative single-cell contraction measurement method that we had developed previously. For the measurement of liver perfusion pressure <em>in situ</em>, a buffer solution was perfused from the portal vein in mice.</div></div><div><h3>Results</h3><div>NE-induced a reversible contraction of qHSCs. This contraction was suppressed by the nonmuscle myosin II inhibitor blebbistatin, the myosin light chain kinase inhibitor ML-9, the Rho kinase inhibitor H-1152, the calmodulin inhibitor W-7, the store-operated calcium channel inhibitor YM-58483, and the IP<sub>3</sub> receptor inhibitor xestospongin C. In contrast, the transient receptor potential C channel inhibitor SKF96365 did not affect the NE-induced contraction.</div></div><div><h3>Conclusion</h3><div>These results suggest that qHSCs contract in response to NE.</div></div><div><h3>New & noteworthy</h3><div>The present study provides direct evidence for the first time that norepinephrine (NE) induces a reversible contraction of isolated single quiescent hepatic stellate cells (qHSCs) and further suggests that the NE-mediated qHSC contraction participates in the regulation of liver blood flow <em>in vivo</em>.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123214"},"PeriodicalIF":5.2,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568489","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

Metabolic disorders, inter-organ crosstalk, and inflammation in the progression of metabolic dysfunction-associated steatotic liver disease 代谢紊乱、器官间串联和炎症在代谢功能障碍相关性脂肪肝进展过程中的作用。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-02 DOI: 10.1016/j.lfs.2024.123211

Shendong Wang , Junhao Yin , Zhaojun Liu , Xin Liu , Ge Tian , Xijian Xin , Yiming Qin , Xiujing Feng

引用次数: 0

Defective macrophage efferocytosis in advanced atherosclerotic plaque and mitochondrial therapy 晚期动脉粥样硬化斑块中巨噬细胞排泄功能缺陷与线粒体疗法。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-02 DOI: 10.1016/j.lfs.2024.123204

Wanling Li , Yaqing Huang , Jun Liu , Yue Zhou , Hongyu Sun , Yonghong Fan , Feila Liu

{"title":"Defective macrophage efferocytosis in advanced atherosclerotic plaque and mitochondrial therapy","authors":"Wanling Li , Yaqing Huang , Jun Liu , Yue Zhou , Hongyu Sun , Yonghong Fan , Feila Liu","doi":"10.1016/j.lfs.2024.123204","DOIUrl":"10.1016/j.lfs.2024.123204","url":null,"abstract":"<div><div>Atherosclerosis (AS) is a chronic inflammatory disease primarily affecting large and medium-sized arterial vessels, characterized by lipoprotein disorders, intimal thickening, smooth muscle cell proliferation, and the formation of vulnerable plaques. Macrophages (MΦs) play a vital role in the inflammatory response throughout all stages of atherosclerotic development and are considered significant therapeutic targets. In early lesions, macrophage efferocytosis rapidly eliminates harmful cells. However, impaired efferocytosis in advanced plaques perpetuates the inflammatory microenvironment of AS. Defective efferocytosis has emerged as a key factor in atherosclerotic pathogenesis and the progression to severe cardiovascular disease. Herein, this review probes into investigate the potential mechanisms at the cellular, molecular, and organelle levels underlying defective macrophage efferocytosis in advanced lesion plaques. In the inflammatory microenvironments of AS with interactions among diverse inflammatory immune cells, impaired macrophage efferocytosis is strongly linked to multiple factors, such as a lower absolute number of phagocytes, the aberrant expression of crucial molecules, and impaired mitochondrial energy provision in phagocytes. Thus, focusing on molecular targets to enhance macrophage efferocytosis or targeting mitochondrial therapy to restore macrophage metabolism homeostasis has emerged as a potential strategy to mitigate the progression of advanced atherosclerotic plaque, providing various treatment options.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123204"},"PeriodicalIF":5.2,"publicationDate":"2024-11-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568209","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

Recent pharmacological insights on abating toxic protein species burden in neurological disorders: Emphasis on 26S proteasome activation 关于减轻神经系统疾病中有毒蛋白质负担的最新药理学见解：重点关注 26S 蛋白酶体的激活。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-01 DOI: 10.1016/j.lfs.2024.123206

Mahmoud A. Desouky, Haidy E. Michel, Doaa A. Elsherbiny, Mina Y. George

{"title":"Recent pharmacological insights on abating toxic protein species burden in neurological disorders: Emphasis on 26S proteasome activation","authors":"Mahmoud A. Desouky, Haidy E. Michel, Doaa A. Elsherbiny, Mina Y. George","doi":"10.1016/j.lfs.2024.123206","DOIUrl":"10.1016/j.lfs.2024.123206","url":null,"abstract":"<div><div>Protein homeostasis (proteostasis) refers to the plethora of mechanisms that safeguard the proper folding of the newly synthesized proteins. It entails various intricately regulated cues that demolish the toxic protein species to prevent their aggregation. The ubiquitin-proteasome system (UPS) is recognized as a salient protein degradation system, with a substantial role in maintaining proteostasis. However, under certain circumstances the protein degradation capacity of the UPS is overwhelmed, leading to the accumulation of misfolded proteins. Several neurodegenerative disorders, such as Alzheimer's disease, Parkinson's disease, Huntington disease, and amyotrophic lateral sclerosis are characterized with the presence of protein aggregates and proteinopathy. Accordingly, enhancing the 26S proteasome degradation activity might delineate a pioneering approach in targeting various proteotoxic disorders. Regrettably, the exact molecular approaches that enhance the proteasomal activity are still not fully understood. Therefore, this review aimed to underscore several signaling cascades that might restore the degradation capacity of this molecular machine. In this review, we discuss the different molecular components of the UPS and how 26S proteasomes are deleteriously affected in many neurodegenerative diseases. Moreover, we summarize different signaling pathways that can be utilized to renovate the 26S proteasome functional capacity, alongside currently known druggable targets in this circuit and various classes of proteasome activators.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123206"},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568495","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

Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: The role of EGFR signaling and placental syncytiotrophoblast 探索妊娠期糖尿病大畸形的分子基础：表皮生长因子受体信号转导和胎盘合体滋养细胞的作用。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-01 DOI: 10.1016/j.lfs.2024.123207

Peng Xu , Zewen Sun , Shu Zheng , Lin Pan , Shuai Dong , Jin He , Peng Chen , Chang Shu

{"title":"Exploring the molecular underpinnings of macrosomia in gestational diabetes mellitus: The role of EGFR signaling and placental syncytiotrophoblast","authors":"Peng Xu , Zewen Sun , Shu Zheng , Lin Pan , Shuai Dong , Jin He , Peng Chen , Chang Shu","doi":"10.1016/j.lfs.2024.123207","DOIUrl":"10.1016/j.lfs.2024.123207","url":null,"abstract":"<div><div>Macrosomia, which is frequently associated with gestational diabetes mellitus (GDM), is linked to maternal glycemic control during gestation. When GDM is complicated by macrosomia (GDMM), the placenta exhibits increased mass, underscoring its role as a critical nexus for maternal-fetal nutrient exchange. Despite this recognized correlation, the underlying mechanisms propelling placental hypertrophy have remained elusive. Our study leveraged single-cell RNA transcriptome sequencing of GDMM placental tissues to pinpoint the specific syncytiotrophoblast (SCT) subsets that regulate placental dimensions. Notably, we observed pronounced upregulation of the epidermal growth factor receptor (EGFR) and its corresponding ligands, with a particular emphasis on the autoregulatory cascade involving the glycoprotein hormone alpha subunit (CGA), EGFR, and the transcription factor GATA binding protein 2 (GATA2), as well as perturbations in hormonal homeostasis within the SCT. Furthermore, our cell interaction analysis revealed an enhanced interplay between myeloid cells and SCT3, augmenting the EGFR signaling pathway. These molecular exchanges underscore the pivotal role of the placental immune microenvironment in the etiology of macrosomia, shedding light on the pathophysiology of GDMM and paving the way for novel therapeutic approaches.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123207"},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568292","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}

引用次数: 0

AMP kinase: A promising therapeutic drug target for post-COVID-19 complications AMP 激酶：有希望成为治疗 COVID-19 后并发症的药物靶点。

IF 5.2 2区医学

Life sciences Pub Date : 2024-11-01 DOI: 10.1016/j.lfs.2024.123202

Mohammad Saquib Ashraf , Kanika Tuli , Shadman Moiz , Satish Kumar Sharma , Deepa Sharma , Mohd Adnan

{"title":"AMP kinase: A promising therapeutic drug target for post-COVID-19 complications","authors":"Mohammad Saquib Ashraf , Kanika Tuli , Shadman Moiz , Satish Kumar Sharma , Deepa Sharma , Mohd Adnan","doi":"10.1016/j.lfs.2024.123202","DOIUrl":"10.1016/j.lfs.2024.123202","url":null,"abstract":"<div><div>The COVID-19 pandemic, caused by SARS-CoV-2, has resulted in severe respiratory issues and persistent complications, particularly affecting glucose metabolism. Patients with or without pre-existing diabetes often experience worsened symptoms, highlighting the need for innovative therapeutic approaches. AMPK, a crucial regulator of cellular energy balance, plays a pivotal role in glucose metabolism, insulin sensitivity, and inflammatory responses. AMPK activation, through allosteric or kinase-dependent mechanisms, impacts cellular processes like glucose uptake, fatty acid oxidation, and autophagy. The tissue-specific distribution of AMPK emphasizes its role in maintaining metabolic homeostasis throughout the body. Intriguingly, SARS-CoV-2 infection inhibits AMPK, contributing to metabolic dysregulation and post-COVID-19 complications. AMPK activators like capsaicinoids, curcumin, phytoestrogens, cilostazol, and momordicosides have demonstrated the potential to regulate AMPK activity. Compounds from various sources improve fatty acid oxidation and insulin sensitivity, with metformin showing opposing effects on AMPK activation compared to the virus, suggesting potential therapeutic options. The diverse effects of AMPK activation extend to its role in countering viral infections, further highlighting its significance in COVID-19. This review explores AMPK activation mechanisms, its role in metabolic disorders, and the potential use of natural compounds to target AMPK for post-COVID-19 complications. Also, it aims to review the possible methods of activating AMPK to prevent post-COVID-19 diabetes and cardiovascular complications. It also explores the use of natural compounds for their therapeutic effects in targeting the AMPK pathways. Targeting AMPK activation emerges as a promising avenue to mitigate the long-term effects of COVID-19, offering hope for improved patient outcomes and a better quality of life.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123202"},"PeriodicalIF":5.2,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142568113","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

DDIT4 promotes erythroid differentiation and coordinates with SIPA1 to regulate erythroid proliferation in bone marrow of high altitude erythrocytosis DDIT4 可促进红细胞分化，并与 SIPA1 相互配合，调节高海拔红细胞增多症骨髓中红细胞的增殖。

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-31 DOI: 10.1016/j.lfs.2024.123212

Yu Cui , Xiao-yin Zhou , Xiao-xu Li , Yi-dong Yang , Cheng-zhong Yang , De-wei Chen , Jian Huang , Yu-qi Gao

{"title":"DDIT4 promotes erythroid differentiation and coordinates with SIPA1 to regulate erythroid proliferation in bone marrow of high altitude erythrocytosis","authors":"Yu Cui , Xiao-yin Zhou , Xiao-xu Li , Yi-dong Yang , Cheng-zhong Yang , De-wei Chen , Jian Huang , Yu-qi Gao","doi":"10.1016/j.lfs.2024.123212","DOIUrl":"10.1016/j.lfs.2024.123212","url":null,"abstract":"<div><div>Erythrocytosis moderately enhances the oxygen-carrying capacity of the blood and is considered a characteristic response of individuals adapting from low-altitude regions to high-altitude regions. Nevertheless, erythrocytosis can also turn excessive and result in maladaptive syndromes, such as high altitude polycythemia (HAPC). The increased differentiation or proliferation of erythroid cells in the bone marrow may be a crucial factor leading to accumulation of peripheral erythroid cells. However, the mechanism of erythroid regulation within the bone marrow of high-altitude erythrocytosis remains insufficiently systematically observed. We utilized single-cell transcription sequencing to characterize bone marrow cells following chronic hypoxic exposure and found that bone marrow erythrocytosis is associated with the accumulation of Baso-E, Poly-E, and Ortho-E cells at the terminal stage of erythroid lineage differentiation. Through analysis of differential gene expression and localization in differentiated cells within the erythroid lineage, we confirmed that DDIT4 expression was localized in advanced differentiated erythroblast including Baso-E, Poly-E and Ortho-E, its expression was significantly enhanced by hypoxia exposure. We demonstrated that overexpression of DDIT4 could promote K562 cell differentiation, and through the IP pull-down interaction protein profile, we found that DDIT4 might participate in regulating the cell cycle by interacting with SIPA1 to promote the proliferation of erythroid cells and may be involved in HAPC.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123212"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564459","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

GraphCVAE: Uncovering cell heterogeneity and therapeutic target discovery through residual and contrastive learning GraphCVAE：通过残差和对比学习发现细胞异质性和治疗靶点

IF 5.2 2区医学

Life sciences Pub Date : 2024-10-31 DOI: 10.1016/j.lfs.2024.123208

Zhiwei Zhang, Mengqiu Wang, Ruoyan Dai, Zhenghui Wang, Lixin Lei, Xudong Zhao, Kaitai Han, Chaojing Shi, Qianjin Guo

{"title":"GraphCVAE: Uncovering cell heterogeneity and therapeutic target discovery through residual and contrastive learning","authors":"Zhiwei Zhang, Mengqiu Wang, Ruoyan Dai, Zhenghui Wang, Lixin Lei, Xudong Zhao, Kaitai Han, Chaojing Shi, Qianjin Guo","doi":"10.1016/j.lfs.2024.123208","DOIUrl":"10.1016/j.lfs.2024.123208","url":null,"abstract":"<div><div>Advancements in Spatial Transcriptomics (ST) technologies in recent years have transformed the analysis of tissue structure and function within spatial contexts. However, accurately identifying spatial domains remains challenging due to data sparsity and noise. Traditional clustering methods often fail to capture spatial dependencies, while spatial clustering methods struggle with batch effects and data integration. We introduce GraphCVAE, a model designed to enhance spatial domain identification by integrating spatial and morphological information, correcting batch effects, and managing heterogeneous data. GraphCVAE employs a multi-layer Graph Convolutional Network (GCN) and a variational autoencoder to improve the representation and integration of spatial information. Through contrastive learning, the model captures subtle differences between cell types and states. Extensive testing on various ST datasets demonstrates GraphCVAE's robustness and biological contributions. In the dorsolateral prefrontal cortex (DLPFC) dataset, it accurately delineates cortical layer boundaries. In glioblastoma, GraphCVAE reveals critical therapeutic targets such as TF and NFIB. In colorectal cancer, it explores the role of the extracellular matrix in colorectal cancer. The model's performance metrics consistently surpass existing methods, validating its effectiveness. GraphCVAE's advanced visualization capabilities further highlight its precision in resolving spatial structures, making it a powerful tool for spatial transcriptomics analysis and offering new insights into disease studies.</div></div>","PeriodicalId":18122,"journal":{"name":"Life sciences","volume":"359 ","pages":"Article 123208"},"PeriodicalIF":5.2,"publicationDate":"2024-10-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564460","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