MedComm最新文献

{"title":"Obesity Biomarkers: Exploring Factors, Ramification, Machine Learning, and AI-Unveiling Insights in Health Research","authors":"Ankita Awari,&nbsp;Deepika Kaushik,&nbsp;Ashwani Kumar,&nbsp;Emel Oz,&nbsp;Kenan Çadırcı,&nbsp;Charles Brennan,&nbsp;Charalampos Proestos,&nbsp;Mukul Kumar,&nbsp;Fatih Oz","doi":"10.1002/mco2.70169","DOIUrl":"https://doi.org/10.1002/mco2.70169","url":null,"abstract":"<p>Biomarkers play a pivotal role in the detection and management of diseases, including obesity—a growing global health crisis with complex biological underpinnings. The multifaceted nature of obesity, coupled with socioeconomic disparities, underscores the urgent need for precise diagnostic and therapeutic approaches. Recent advances in biosciences, including next-generation sequencing, multi-omics analysis, high-resolution imaging, and smart sensors, have revolutionized data generation. However, effectively leveraging these data-rich technologies to identify and validate obesity-related biomarkers remains a significant challenge. This review bridges this gap by highlighting the potential of machine learning (ML) in obesity research. Specifically, it explores how ML techniques can process complex data sets to enhance the discovery and validation of biomarkers. Additionally, it examines the integration of advanced technologies for understanding obesity mechanisms, assessing risk factors, and optimizing treatment strategies. A detailed discussion is provided on the applications of ML in multi-omics analysis and high-throughput data integration for actionable insights. The academic value of this review lies in synthesizing the latest technological and analytical innovations in obesity research. By providing a comprehensive overview, it aims to guide future studies and foster the development of targeted, data-driven strategies in obesity management.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70169","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144339115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Associations of Plasma and CSF Osteocalcin Levels With CSF ATN Biomarkers and Cognitive Functions in Alzheimer's Disease","authors":"Xian-Le Bu,&nbsp;Zhuo-Ting Liu,&nbsp;Jia-Yan Xin,&nbsp;Mei Huang,&nbsp;Yu-Di Bai,&nbsp;Jin Zhou,&nbsp;Yun-Yu Bao,&nbsp;Jiang-Hui Li,&nbsp;Zhi-Hao Liu,&nbsp;Gui-Hua Zeng,&nbsp;An-Yu Shi,&nbsp;Dong-Wan Chen,&nbsp;Yu-Jie Lai,&nbsp;Yang Chen,&nbsp;Fan Zeng,&nbsp;Jun Wang,&nbsp;Qing-Qing Tao,&nbsp;Zhi-Ying Wu,&nbsp;Yan-Jiang Wang","doi":"10.1002/mco2.70255","DOIUrl":"https://doi.org/10.1002/mco2.70255","url":null,"abstract":"<p>Animal studies have shown that osteocalcin (OCN), a hormone derived from bone, plays a vital role in brain development and cognitive function. However, its potential connection to Alzheimer's disease (AD) pathology in humans remains largely unexplored. This cross-section study included 238 cognitively unimpaired participants, 26 mild cognitive impairment (MCI) patients, 54 AD dementia patients, and 32 patients with non-AD neurodegenerative diseases. Plasma and cerebrospinal fluid (CSF) levels of OCN were measured by enzyme-linked immunosorbent assay kits. In the clinical diagnosis-based subgroup, plasma and CSF levels of OCN were significantly higher in MCI and AD dementia compared with cognitively unimpaired participants. In the ATN framework-based subgroup, plasma and CSF OCN levels were significantly elevated in Aβ-positive participants, including those in the preclinical stage of AD. Both plasma and CSF OCN levels were negatively correlated with CSF Aβ42 and positively correlated with CSF total-tau and phosphorylated-tau181/Aβ42. In addition, OCN mediated the relationship between Aβ pathology and tau pathology. Notably, OCN levels in plasm and CSF were also negatively associated with cognitive functions. This study provides clinical evidence linking OCN to AD, suggesting that OCN may be associated with brain Aβ deposition, tau hyperphosphorylation and neurodegeneration.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70255","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tet Methylcytosine Dioxygenase 3 Promotes Cardiovascular Senescence by DNA 5-Hydroxymethylcytosine-Mediated Sp1 Transcription Factor Expression","authors":"Yanqi Dang,&nbsp;Jing Ma,&nbsp;Shuang Ling,&nbsp;Shurong Wang,&nbsp;Huining Guo,&nbsp;Jun Liu,&nbsp;Guang Ji,&nbsp;Jin-Wen Xu","doi":"10.1002/mco2.70261","DOIUrl":"https://doi.org/10.1002/mco2.70261","url":null,"abstract":"<p>Cellular senescence is a significant contributor to various age-related diseases. Tet methylcytosine dioxygenase 3 (TET3) is a pivotal regulator of epigenetic modifications, and this study aimed to elucidate its role in cellular senescence. The study utilized replication and paraquat (PQ)-induced senescent endothelial cells, as well as TET3 heterozygous, p53 heterozygous, and PQ-induced senescent mice as experimental models. Senescent endothelial cells were analyzed using hydromethylated DNA immunoprecipitation sequencing, β-galactosidase staining, real-time PCR, western blotting, immunofluorescence staining, dot blot, chromatin immunoprecipitation assay, and luciferase reporter assays. These analyses were conducted following TET3 knockdown and gene overexpression. TET3 is instrumental in the elevation of 5-hydroxymethylcytosine (5-hmC) levels in both replication and PQ-induced senescent endothelial cells, as well as in the cardiovascular systems of PQ-induced aging mice. TET3 significantly promoted cellular senescence in PQ-induced endothelial cells and mice. TET3 facilitates the upregulation of the Sp1 transcription factor (SP1) through 5-hmC modification, leading to a synergistic interaction between SP1 and ETS proto-oncogene 1 that further enhances p53 expression. Moreover, p53 not only promotes cellular senescence in vitro and in vivo but also reciprocally enhances TET3 and 5-hmC levels. These findings underscore the critical role of elevated TET3 and 5-hmC levels in cellular senescence.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70261","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endoplasmic Reticulum Stress in Cancer","authors":"Ruixin Zhou,&nbsp;Wenlong Wang,&nbsp;Baizhao Li,&nbsp;Zhu Li,&nbsp;Juan Huang,&nbsp;Xinying Li","doi":"10.1002/mco2.70263","DOIUrl":"https://doi.org/10.1002/mco2.70263","url":null,"abstract":"<p>Persistent and intense endoplasmic reticulum (ER) stress is widely acknowledged as a hallmark of tumorigenesis. To restore ER homeostasis, cells activate the unfolded protein response (UPR), which is aberrantly regulated in cancer cells. This review provides an in-depth analysis of the mechanisms through which the UPR facilitates tumor progression. The UPR is activated by ER stress sensors such as inositol-requiring enzyme 1 (IRE1α), protein kinase R-like ER-resident kinase (PERK), and activating transcription factor 6 (ATF6). These sensors regulate cancer cell proliferation, immune evasion, metastasis, and drug resistance. We summarize the crosstalk between the UPR and multiple signaling pathways, including mTOR, MAPK, and NF-κB, which collectively promote tumor growth and metastasis. Additionally, we discuss the role of the UPR in modulating the tumor microenvironment to support angiogenesis and immune evasion. We also provide an overview of pharmacological agents targeting specific UPR pathways, such as GRP78 inhibitors, IRE1α inhibitors, PERK inhibitors, and ATF6 inhibitors, with the aim of developing more effective cancer therapies. This comprehensive review highlights the potential of targeting the UPR as a novel strategy for cancer treatment and underscores the need for further research to elucidate the complex interactions between the UPR and cancer progression.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70263","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Mechanism of Omicron Variant-Associated Cardiac Injury in Rhesus Macaques Was Revealed by Proteomic and Phosphoproteomic Analyses","authors":"Tao Ding,&nbsp;Ya-Nan Zhou,&nbsp;Jiang-Feng Liu,&nbsp;Shuai-Yao Lu,&nbsp;Jun-Tao Yang","doi":"10.1002/mco2.70266","DOIUrl":"https://doi.org/10.1002/mco2.70266","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;The Omicron variant of SARS-CoV-2 quickly surpassed the previously dominant Delta variant. Compared to previous variants of concern (VOCs), it was highly mutated, high reinfection, highly transmissible, and rapidly spreading strain. The Omicron variant infected cells that depended on angiotensin-converting enzyme 2 (ACE2). The increased expression of ACE2 in cardiomyocytes made cardiac tissue more susceptible to Omicron variant infection. Myocardial injury was a common comorbidity in patients with SARS-CoV-2 infection and portended a poor prognosis. Consequently, studying myocardial injury caused by the Omicron variant is urgent compared to previous VOCs. To determine how the Omicron variant hijacks protein signaling in different cardiac regions, the cardiac samples were harvested for proteomic and phosphoproteomic analyses (Figure 1A). SARS-CoV-2 RNA was detected in the heart, further suggesting that SARS-CoV-2 can infect the heart tissue directly (Figure 1A). H&amp;E staining revealed myocardial hemorrhage, infiltration of inflammatory cells, and atrophy of myocytes in the infected hearts, and Masson staining revealed significant myocardial fibrosis in the infected hearts, which are characteristic features of human COVID-19 cardiac injury [&lt;span&gt;1&lt;/span&gt;] (Figure 1A).&lt;/p&gt;&lt;p&gt;Previous studies conducted phosphoproteomic analysis on cardiomyocytes infected with SARS-CoV-2 [&lt;span&gt;2&lt;/span&gt;], finding significant changes in the phosphoproteomes, consistent with the central role of phosphorylation in cellular signal transduction. Thus, we performed the global phosphoproteomic analysis and revealed that differentially expressed phosphoproteins in the four regions were concentrated in the cardiac muscle contraction pathway (Figure 1A), which may be associated with COVID-19-related arrhythmias [&lt;span&gt;3&lt;/span&gt;]. To explore the biological significance, we performed kinase prediction using GPS 5.0 and GSEA. We highlighted key kinases, including CAMK2A and CAMK2G in modulating the phosphosites RYR2_S2031. Furthermore, MYH7 may be involved in the phosphorylation regulation of TNNT2_S72. Although the kinase function of MYH7 required further validation, our findings suggested its potential biological significance (Figure 1A). CAMK2A and CAMK2G exhibited significant activation in the four cardiac regions following Omicron variant infection (Figure 1A). CAMK2 increased RYR2-mediated sarcoplasmic reticulum (SR) calcium leakage by phosphorylating specific RYR2 residues, which trigger cardiac arrhythmias. Thus, the upregulation of phosphorylation at RYR2_S2031 may signal arrhythmia risk following Omicron variant infection. KN-93, a CAMK2 inhibitor, has previously been used in the treatment of ventricular arrhythmias [&lt;span&gt;4&lt;/span&gt;]. The results suggested that CAMK2A and CAMK2G could be potential targets for treating arrhythmias caused by Omicron variant infections.&lt;/p&gt;&lt;p&gt;We plotted the normalized enrichment score (NES) values of kinases to compa","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70266","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interaction Between Microbiota and Immunity: Molecular Mechanisms, Biological Functions, Diseases, and New Therapeutic Opportunities","authors":"Jingjing Zeng,&nbsp;Zimeng He,&nbsp;Guoqing Wang,&nbsp;Yuxin Ma,&nbsp;Feng Zhang","doi":"10.1002/mco2.70265","DOIUrl":"https://doi.org/10.1002/mco2.70265","url":null,"abstract":"<p>The microbiota is pivotal for our health. It includes different phyla like Bacteroidetes, Firmicutes, Actinobacteria, Proteobacteria, Fusobacteria, and Verrucomicrobia. The interaction between microbiota and immunity shares a bidirectional relationship. The microbiota helps to stimulate immunity development. The immunity influences microbial composition in turn. This interaction is critical for maintaining homeostasis, preventing pathogen invasion, and regulating the immune system. Furthermore, this symbiotic relationship is crucial for maintaining overall health and preventing various diseases. The microbiota–immune system contributes to immune system maturation, while the immune system selects for beneficial microbiota composition, thus enhancing our immunity. This review summarizes the molecular mechanisms and biological functions of the interaction between microbiota and immunity, offering solid evidence for the role of microbiota in immune regulation. Notably, the review categorizes microbiota according to phyla and explains disease associations, molecular effectors, and functional outcomes about the microbiota–immune system. We also introduced three core molecular mechanisms of the microbiota–immune systems. Moreover, we detail the progression from target discovery to clinical trial design for bacterial and immune-related diseases. Finally, we propose four therapeutic strategies for diseases.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70265","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144323597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage Signaling Pathways in Health and Disease: From Bench to Bedside Applications","authors":"Yongquan Chi,&nbsp;Haipeng Jiang,&nbsp;Yiyuan Yin,&nbsp;Xinyu Zhou,&nbsp;Yiyouyou Shao,&nbsp;Yongsheng Li,&nbsp;Jianhua Rao","doi":"10.1002/mco2.70256","DOIUrl":"https://doi.org/10.1002/mco2.70256","url":null,"abstract":"<p>Macrophages exhibit remarkable functional plasticity by dynamically polarizing into proinflammatory or antiinflammatory subsets in response to microenvironmental cues. This duality underpins their pivotal roles in immune defense, tissue homeostasis, and disease progression; however, the molecular mechanisms governing their polarization and crosstalk across various pathologies remain incompletely defined. This review systematically delineates macrophage biology, emphasizing the interplay between subset-specific signaling networks and their context-dependent activation in both health and disease. The heterogeneity of macrophages is characterized by detailing the distinctions between tissue-resident and monocyte-derived origins, as well as their polarization states. Core pathways regulating phagocytosis, tissue repair, immune modulation, and neuroprotection are dissected, along with their dysregulation in autoimmune disorders, neurodegeneration, cancers, and cardiovascular diseases. Notably, microenvironmental factors such as damage-associated molecular patterns, pathogen-associated molecular patterns, and metabolic intermediates dynamically reshape macrophage phenotypes through NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome activation or signal transducer and activator of transcription (STAT)-mediated transcriptional control. Preclinical and clinical evidence underscores potential therapeutic targets and emerging strategies. The significance of this review lies in its integrative analysis of signaling crosstalk, paradoxical pathway roles, and translational implications for precision therapies. These insights into macrophage functions and signaling pathways provide a robust foundation for future disease intervention and personalized medicine.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70256","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autoimmune Diseases: Molecular Pathogenesis and Therapeutic Targets","authors":"Xiaoshuang Song,&nbsp;Hantian Liang,&nbsp;Fang Nan,&nbsp;Wenjing Chen,&nbsp;Junyao Li,&nbsp;Liu He,&nbsp;Yiping Cun,&nbsp;Zhenhong Li,&nbsp;Wei Zhang,&nbsp;Dunfang Zhang","doi":"10.1002/mco2.70262","DOIUrl":"https://doi.org/10.1002/mco2.70262","url":null,"abstract":"<p>Autoimmune diseases are a set of disorders in which the immune system attacks one's own tissues, leading to chronic inflammation, tissue damage, and systemic dysfunction. Affecting approximately 10% of the global population, these diseases impose significant health and economic burdens worldwide. The pathogenesis of autoimmune diseases is complex, involving not only genetic predisposition (e.g., human leukocyte antigen variants), environmental triggers (e.g., infections), and a dysregulated immune response but also various interacting components that contribute to the development of diverse clinical phenotypes. This review provides a comprehensive overview of common autoimmune diseases, covering their clinical manifestations, pathogenic mechanisms, and diagnostic approaches such as disease-specific autoantibodies. We also explore current therapeutic strategies, including commonly used broad-spectrum anti-inflammatory drugs, recent molecular-targeted therapies (e.g., Janus kinase inhibitors, monoclonal antibodies), and emerging cellular therapies such as chimeric antigen receptor T cells therapy and regulatory T-cell adoptive transfer. Incorporating knowledge from preclinical and clinical studies, this review synthesizes relevant information to inform about autoimmune diseases, bridge the gap from lab to clinic, and promote future advances through exploring precision medicine applications to meet clinical needs.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70262","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic Subtype-Based International Prognostic Index Prognostic Model in Diffuse Large B-Cell Lymphoma","authors":"Lan Mi,&nbsp;Jili Deng,&nbsp;Jiayue Qin,&nbsp;Chen Zhang,&nbsp;Lixia Liu,&nbsp;Shunli Yang,&nbsp;Libin Chen,&nbsp;Hua-Jun Wu,&nbsp;Haojie Wang,&nbsp;Jun Zhu,&nbsp;Hong Chen,&nbsp;Feng Lou,&nbsp;Shanbo Cao,&nbsp;Yuqin Song,&nbsp;Weiping Liu","doi":"10.1002/mco2.70190","DOIUrl":"https://doi.org/10.1002/mco2.70190","url":null,"abstract":"<p>Molecular subtyping in diffuse large B-cell lymphoma (DLBCL) leads to facilitating drug selection. However, an integrated prognostic model based on molecular subtyping and clinical features has not been well established. Here, we retrospectively performed whole genome sequencing, whole exome sequencing, and fluorescence in situ hybridization in newly diagnosed DLBCLs, established a simplified LymphType algorithm for classification evaluation, and proposed a new integrated prognostic stratification system, combined molecular subtypes and International Prognostic Index (IPI) scoring system in our in-house sequencing cohort (<i>N</i> = 100), and validated in three public cohorts (<i>N</i> = 1480). Compared with IPI scoring system and classification algorithm model alone, the discrimination ability of prognostic model based on the new integrated model showed best discrimination of overall survival with concordance index value (0.773 vs. 0.724 vs. 0.648). We subsequently established a four-category risk model defined for the integrated prognostic model as follows: low, low-intermediate, high-intermediate, and high risk, demonstrating stronger prognostic separation across all end points (all <i>p </i>&lt; 0.001) in our in-house cohort and three validation cohorts. Collectively, the new feasible integrated prognostic stratification system contributes to accurate prognosis assessment in clinical routine and provides a new basis for the follow-up treatment.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70190","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144300214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Key Roles in the Process of Extravasation and Colonization: Acyl-coenzyme A Synthetase Long-chain Family Member 4 and Polyunsaturated Lipids","authors":"Jiayu Han,&nbsp;Jie Zhang,&nbsp;Yicheng Chen","doi":"10.1002/mco2.70264","DOIUrl":"https://doi.org/10.1002/mco2.70264","url":null,"abstract":"&lt;p&gt;In a recent study published in &lt;i&gt;Cell&lt;/i&gt;, Yilong Zou et al. [&lt;span&gt;1&lt;/span&gt;] revealed dual functions of polyunsaturated fatty acyl (PUFA)-lipid in metastatic cancer cells. Acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4), a PUFA-lipid biosynthesis enzyme, promotes hematogenous metastasis by enhancing membrane fluidity and cell invasiveness. Concurrently, elevated levels of PUFA-lipid induce reliance of cancer cells on enoyl-CoA delta isomerase 1 (ECI1) and enoyl-CoA hydratase 1 (ECH1), enzymes preparing UFAs for β-oxidation. Dual inhibition of ACSL4/ECH1 effectively suppresses tumor metastasis.&lt;/p&gt;&lt;p&gt;The majority of cancer patients succumb to metastatic disease rather than primary tumor burden [&lt;span&gt;2&lt;/span&gt;]. Moreover, metastatic cancers remain largely incurable in clinical settings, ultimately leading to death due to systemic organ failure [&lt;span&gt;2&lt;/span&gt;]. Extravasation, dormancy, and colonization are three major steps of metastasis [&lt;span&gt;2&lt;/span&gt;] alongside other critical processes such as epithelial-to-mesenchymal transition. Factors impacting extravasation include increased cell motility and altered lipid phase behavior. At the same juncture, the metabolism of fatty acid and acyl-CoA plays an extremely significant role in the progression of cancer cell growth and metastasis [&lt;span&gt;3&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;Yilong Zou et al. conducted an analysis utilizing the Cancer Metastasis Map and the Cancer Therapeutics Response Portal to find whether metastatic cancer cells are more sensitive to specific cytotoxic compounds within the cancer cell lines listed in the dataset. These well-established databases serve as invaluable resources for oncology research, offering comprehensive datasets and insights that are worthy of further exploration. The results demonstrated that ovarian cancer cells exhibiting higher metastatic potential displayed increased sensitivity to ferroptosis induction. Subsequently, they utilized clinically collected metastatic samples to validate that ovarian cancer cells with higher metastatic potential showed increased susceptibility to ferroptosis and elevated levels of unsaturated lipids. Notably, emerging evidence indicates that oncogenic driver mutations may simultaneously prime cancer cells for ferroptosis vulnerability in breast and gastric adenocarcinomas [&lt;span&gt;4&lt;/span&gt;].&lt;/p&gt;&lt;p&gt;To investigate the function of PUFA-lipids and ferroptosis-sensitizing factors in metastatic progression, an ovarian cancer metastasis model was established through intraperitoneal injection of GFP-firefly-luciferase-labeled ES-2 cells, a clear-cell carcinoma line derived from malignant ascites of ovarian cancer patients. Utilizing lipidomic analysis, the researchers found that PUFA-lipids increased in pulmonary metastatic lesions, without a corresponding change in the abundance of lipid droplets. This suggested a potential relationship between ferroptosis susceptibility and increased PUFA-lipids. To further minimize variability in","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 7","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70264","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144292575","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}