MedComm最新文献

{"title":"Integrated Analysis of the Anoikis-Related Signature Identifies Rac Family Small GTPase 3 as a Novel Tumor-Promoter Gene in Hepatocellular Carcinoma","authors":"Dong Wu,&nbsp;Ze-Kun Liu,&nbsp;Ying Sun,&nbsp;Chu-Heng Gou,&nbsp;Run-Ze Shang,&nbsp;Meng Lu,&nbsp;Ren-Yu Zhang,&nbsp;Hao-Lin Wei,&nbsp;Can Li,&nbsp;Ying Shi,&nbsp;Cong Zhang,&nbsp;Yu-Tong Wang,&nbsp;Ding Wei,&nbsp;Zhi-Nan Chen,&nbsp;Huijie Bian","doi":"10.1002/mco2.70125","DOIUrl":"https://doi.org/10.1002/mco2.70125","url":null,"abstract":"<p>Anoikis resistance in hepatocellular carcinoma (HCC) cells boosts survival and metastasis. This study aimed to establish an anoikis-related genes (ARGs)-based model for predicting HCC patients’ outcomes and investigate the clinicopathological significance and function of crucial ARGs. The transcriptional expression patterns for HCC cohorts were compiled from TCGA, GEO and ICGC. Univariate and LASSO multivariate analyses were performed to screen for prognostic ARGs. Gain- and loss-of-function studies, RNA sequencing, and mass spectrometry were employed to elucidate the underlying mechanisms of ARGs in HCC. We established a five-gene ARGs risk model for HCC prognosis, with an AUC value of 0.812 for 1-year survival. Among the five genes, Rac family small GTPase 3 (RAC3) was upregulated in HCC relative to adjacent normal tissues and negatively correlated to overall survival and disease-free survival of patients with HCC. Silence of RAC3 in HCC cells resulted in an increased cell apoptosis and diminished cell proliferation and invasion. Mechanistically, we uncovered that RAC3 binding with SOX6 propelled the advancement of HCC cells through NNMT-mediated stimulation of the cAMP/MAPK/Rap1 signaling. In particular, EHop-016, a small molecule inhibitor targeting RAC3, significantly suppressed HCC progression.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70125","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689366","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":"ATP11B Modulates Microglial Lipid Metabolism and Alleviates Alzheimer's Disease Pathology","authors":"Yuchen Zhang,&nbsp;Shibo Zhang,&nbsp;Xuyu Zhao,&nbsp;Peiru Wu,&nbsp;Yiwei Ying,&nbsp;Lingling Wu,&nbsp;Junyi Zhuang,&nbsp;Zixin Chen,&nbsp;Yufan Chao,&nbsp;Xin Dong,&nbsp;Robert Chunhua Zhao,&nbsp;Jiao Wang","doi":"10.1002/mco2.70139","DOIUrl":"https://doi.org/10.1002/mco2.70139","url":null,"abstract":"<p>Abnormal lipid metabolism in microglia leads to the formation of pathological lipid droplets (LDs), a phenomenon also observed in neurodegenerative diseases such as Alzheimer's disease (AD). The abnormal accumulation of LDs disrupts normal cellular function and exacerbates the pathological process of AD. ATP11B is a P4-ATPase and the expression of <i>Atp11b</i> changes in the brain of patients with AD and diseases of lipid metabolism. The present study aimed to explore the regulatory role of ATP11B in microglial lipid metabolism and assess the potential of ATP11B as a therapeutic target for AD. <i>Atp11b</i> deficiency caused excessive fatty acid uptake and activated the PPAR signaling pathway, resulting in abnormal synthesis of neutral lipids and mitochondrial energy metabolism in microglia. Further results showed that <i>Atp11b</i> deficiency led to the accumulation of pathological LDs in microglia and AD mice. Conversely, overexpression of <i>Atp11b</i> alleviated exploratory behavior impairment, learning and memory impairment, LD accumulation, beta-amyloid (Aβ) deposition, and inflammatory response in the brain of AD mice. These findings provide important clues for a better understanding of the pathogenesis of AD and for developing novel therapeutic strategies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70139","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143689367","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":"Subsequent Survival and Loss of Lifetime for Patients With Progression-Free 24 Months After Treatment in Nasopharyngeal Carcinoma: A Comprehensive Nationwide Population-Based Analysis","authors":"Yang Liu,&nbsp;Yaqian Han,&nbsp;Mei Feng,&nbsp;Ye Zhang,&nbsp;Kai Wang,&nbsp;Yuan Qu,&nbsp;Xuesong Chen,&nbsp;Jianghu Zhang,&nbsp;Jingwei Luo,&nbsp;Runye Wu,&nbsp;Ye-Xiong Li,&nbsp;Xiaodong Huang,&nbsp;Qiuyan Chen,&nbsp;Jingbo Wang,&nbsp;Junlin Yi","doi":"10.1002/mco2.70143","DOIUrl":"10.1002/mco2.70143","url":null,"abstract":"<p>Currently, there is little evidence supporting the use of early endpoints to assess primary treatment outcomes in nasopharyngeal carcinoma (NPC). We aim to explore the relationship between 24-month progression-free survival (PFS24) and subsequent overall survival (sOS) as well as loss of lifetime (LoL) in NPC patients. sOS is defined as survival from the 24-month point or progression within 24 months leading to mortality. LoL represents the reduction in life expectancy due to NPC, compared to the general population matched by age, sex, and calendar year. The standardized mortality ratio (SMR) is defined as the ratio of observed mortality to expected mortality. The study included 6315 patients from nonendemic and endemic regions of China. Among them, 5301 patients (83.9%) achieved PFS24, with a 5-year sOS of 90.2% and an SMR of 1.0. Over a 10-year period following treatment, the mean LoL was only 0.01 months/year. For most subgroups, patients achieving PFS24 exhibited comparable sOS and LoL with the general population. However, patients failing to achieve PFS24 showed significantly worse outcomes, with 5-year sOS of 21.9%, SMR of 23.7, and LoL of 6.48 months/year. These notable outcome disparities highlight the importance of PFS24 in NPC risk stratification, patient monitoring, and study design.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923380/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672184","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":"Rational Design, Synthesis, and Biological Assessment of Potential Indole-Capped HDAC6 Inhibitors for Gastric Cancer Suppression","authors":"Ya Gao,&nbsp;Hai-Qian Nie,&nbsp;Hong-Min Liu,&nbsp;Xin-Hui Zhang,&nbsp;Li-Ying Ma","doi":"10.1002/mco2.70158","DOIUrl":"10.1002/mco2.70158","url":null,"abstract":"&lt;p&gt;Dear Editor,&lt;/p&gt;&lt;p&gt;Gastric cancer and gastroesophageal junction cancer have long been among the top killers in the cancer realm [&lt;span&gt;1&lt;/span&gt;]. Moreover, East Asian countries such as China, Japan, and South Korea are known as high-incidence regions for gastric cancer on a global scale. As the limited availability of precision medicine drugs for gastric cancer at present, there is still a need for the development of small molecule compounds targeting novel targets. Accumulating evidence suggests a link between dysregulated histone deacetylase 6 (HDAC6) activity and numerous oncological disorders [&lt;span&gt;2, 3&lt;/span&gt;]. HDAC6 is frequently overexpressed in various malignancies, including primary acute myeloid leukemia, gastric cancer, breast cancer, ovarian cancer, and colorectal cancer, and is strongly associated with unfavorable prognosis [&lt;span&gt;4&lt;/span&gt;]. These findings underscore the pivotal role of HDAC6 as a prominent therapeutic target in the pathogenesis and progression of diverse tumor types.&lt;/p&gt;&lt;p&gt;To develop small molecule inhibitors targeting the HDAC6 enzyme, we relied on the in-house library compounds screening strategy and obtained a lead compound. We then optimized the structure of the lead compound &lt;b&gt;L9&lt;/b&gt;. Among them, enzyme activity assays revealed compound &lt;b&gt;10n&lt;/b&gt; exhibited excellent inhibitory effects on HDAC6 with an IC&lt;sub&gt;50&lt;/sub&gt; value of 3.11 nM. Simultaneously, &lt;b&gt;10n&lt;/b&gt; showed notable selectivity in inhibiting HDAC1, HDAC2, HDAC3, and HDAC8 compared to HDAC6, with selectivity ratios of 133.7-fold, 27.8-fold, 82.8-fold, and 622.22-fold, respectively. Ricolinostat (ACY-1215), one selective HDAC6 inhibitor in the clinical stage, exhibited IC&lt;sub&gt;50&lt;/sub&gt; values of 50, 42, 60, 120, and 5.3 nM for HDAC1, 2, 3, 6, and 8, respectively. The selectivity ratios of HDAC1/6, 2/6, 3/6, and 8/6 are 9.4-fold, 7.9-fold, 11.3-fold, and 22.6-fold, respectively. Compound &lt;b&gt;10n&lt;/b&gt; exhibits greater selectivity against HDAC1, HDAC2, HDAC3, and HDAC8 compared to HDAC6. This indicates that &lt;b&gt;10n&lt;/b&gt; is a significantly selective HDAC6 inhibitor.&lt;/p&gt;&lt;p&gt;&lt;i&gt;S&lt;/i&gt;ilico docking study revealed that &lt;b&gt;10n&lt;/b&gt; was capable of fitting into the substrate-binding pocket of HDAC6. Additionally, the C═O group was seen to form a hydrogen bond with a Zn&lt;sup&gt;2+&lt;/sup&gt;-bound water molecule, with as O&lt;b&gt;&lt;sup&gt;…&lt;/sup&gt;&lt;/b&gt;H separation of 2.05 Å (Figure 1A). Furthermore, the N-benzylformamide-based linker portion nested in the hydrophobic tunnel and was sandwiched between P583 and P643, forming a clear π–π stacking interaction with P643 (Figure 1A). Additionally, BLI verified that &lt;b&gt;10n&lt;/b&gt; exhibits a high affinity for HDAC6, with a Kd value of 330 ± 180 nM (Figure 1B).&lt;/p&gt;&lt;p&gt;Furthermore, &lt;b&gt;10n&lt;/b&gt; exhibited enhanced cytotoxicity against MGC-803 and MKN-45 cells, with IC&lt;sub&gt;50&lt;/sub&gt; values of 1.067 ± 0.312 and 2.704 ± 0.935 µM at 72 h. EdU incorporation assays and plate clone formation assays were conducted to evaluate the antiproliferative effects of &lt;b&gt;","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11923385/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143672183","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":"Mitigating Early Phosphatidylserine Exposure in a Tmem30a-Dependent Way Ameliorates Neuronal Damages After Ischemic Stroke","authors":"Chuanjie Wu,&nbsp;Jiaqi Guo,&nbsp;Yunxia Duan,&nbsp;Jiachen He,&nbsp;Shuaili Xu,&nbsp;Guiyou Liu,&nbsp;Chen Zhou,&nbsp;Yuchuan Ding,&nbsp;Xianjun Zhu,&nbsp;Xunming Ji,&nbsp;Di Wu","doi":"10.1002/mco2.70140","DOIUrl":"https://doi.org/10.1002/mco2.70140","url":null,"abstract":"<p>Phosphatidylserine (PS) exposes to the outer plasma membrane after a pathological insult (e.g., stroke) but not under normal conditions whereby PS remains within the inner plasma membrane. However, the reversibility and translational potential of PS exposure in damaged cells after stroke are still unknown. Here, we demonstrated that plasma Annexin V, which has a high affinity to membranes bearing PS, was increased in patients with salvage penumbra after endovascular therapy, and associated with early neurological improvement. Moreover, Annexin V treatment could decrease PS exposure and mitigate neurological impairments in transient ischemia/reperfusion mouse models, but not in permanent ischemia. Furthermore, we used a combination of cell, rodent, and nonhuman primate ischemia/reperfusion models and found that transmembrane protein 30A (Tmem30a) was increased in the ischemic penumbra after stroke and imperative for less PS exposure and better neurological functions. Mechanistically, mitigation of PS exposure mediated by Tmem30a/Annexin V connection led to decreased expression of apoptosis and necroptosis markers in neurons of penumbra. Overall, our findings reveal a previously unappreciated role of reducing PS exposure by Annexin V treatment in protecting the penumbra in a clinically relevant ischemia/reperfusion model. Tmem30a is essential for reducing PS exposure in the penumbra after ischemic stroke.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638781","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":"Swimming Exercise Pretreatment Attenuates Postoperative Delirium-Like Behavior in Type 2 Diabetic Rats by Enhancing Mitochondrial Biogenesis Through Activation of SIRT2 Deacetylation","authors":"Kaixi Liu,&nbsp;Lei Chen,&nbsp;Xinning Mi,&nbsp;Qian Wang,&nbsp;Yitong Li,&nbsp;Jingshu Hong,&nbsp;Xiaoxiao Wang,&nbsp;Yue Li,&nbsp;Yanan Song,&nbsp;Yi Yuan,&nbsp;Jie Wang,&nbsp;Dengyang Han,&nbsp;Taotao Liu,&nbsp;Ning Yang,&nbsp;Xiangyang Guo,&nbsp;Zhengqian Li","doi":"10.1002/mco2.70142","DOIUrl":"https://doi.org/10.1002/mco2.70142","url":null,"abstract":"<p>Postoperative delirium (POD) is a common postsurgical complication that seriously affects patients' prognosis and imposes a heavy burden on families and society. Type 2 diabetes mellitus (T2DM) is a major risk factor for POD. The susceptibility mechanisms of POD in T2DM individuals and the role of exercise preconditioning remain unclear. Adult rats with and without T2DM were used to assess the promotive effect of diabetes on postoperative delirium-like behavior. The diabetic rats were also subjected to a swimming exercise program before surgery. The potential beneficial effect of exercise preconditioning on postoperative cognition was evaluated by examining neurobehavior, hippocampal neuroinflammation, mitochondrial morphology, and function in diabetic rats. Finally, underlying mechanisms were further analyzed by exploring the role of the sirtuin family in vivo and in vitro. We found that performing tibial fracture surgery resulted in delirium-like behavior and inhibited hippocampal mitochondrial biogenesis in diabetic rats but not in healthy rats. Preoperative swimming exercise was beneficial in attenuating delirium-like behavior, inhibiting neuroinflammation, and improving mitochondrial biogenesis and function. Preoperative swimming exercise achieved these positive effects by upregulating SIRT2-mediated peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) deacetylation and activating mitochondrial biogenesis in T2DM rats.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70142","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143638726","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":"A Single-Nucleus Transcriptomic Atlas Reveals Cellular and Genetic Characteristics of Alzheimer's-Like Pathology in Aging Tree Shrews","authors":"Liu-Lin Xiong,&nbsp;Rong He,&nbsp;Ruo-Lan Du,&nbsp;Rui-Ze Niu,&nbsp;Lu-Lu Xue,&nbsp;Li Chen,&nbsp;Li-Ren Huangfu,&nbsp;Qiu-Xia Xiao,&nbsp;Jing Li,&nbsp;Yong-Ping Li,&nbsp;Si-Min Zhang,&nbsp;Chang-Yin Yu,&nbsp;Xiao-He Tian,&nbsp;Ting-Hua Wang","doi":"10.1002/mco2.70114","DOIUrl":"https://doi.org/10.1002/mco2.70114","url":null,"abstract":"<p>The lack of natural aging-inducing Alzheimer's disease (AD) model presents a significant gap in the current preclinical research. Here, we identified a unique cohort of 10 naturally aging tree shrews (TSs) displaying distinct Alzheimer's-like pathology (ALP) from a population of 324, thereby establishing a novel model that closely mirrors human AD progression. Using single-nucleus RNA sequencing, we generated a comprehensive transcriptome atlas, revealing the cellular diversity and gene expression changes underlying AD pathology in aged TSs. Particularly, distinct differentiation trajectories of neural progenitor cells were highly associated with AD pathology. Intriguingly, cross-species comparisons among humans, TSs, monkeys, and mice highlighted a greater cellular homogeneity of TSs to primates and humans than to mice. Our extended cross-species analysis by including a direct comparison between human and TS hippocampal tissue under AD conditions uncovered conserved cell types, enriched synaptic biological processes, and elevated excitatory/inhibitory imbalance across species. Cell–cell communication analysis unveiled parallel patterns between AD human and ALP TSs, with both showing reduced interaction strength and quantity across most cell types. Overall, our study provides rich, high-resolution resources on the cellular and molecular landscape of the ALP TS hippocampus, reinforcing the utility of TSs as a robust model for AD research.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 4","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70114","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629762","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":"RETRACTION: ENKUR Recruits FBXW7 to Ubiquitinate and Degrade MYH9 and Further Suppress MYH9-Induced Deubiquitination of β-Catenin to Block Gastric Cancer Metastasis","authors":"","doi":"10.1002/mco2.70160","DOIUrl":"https://doi.org/10.1002/mco2.70160","url":null,"abstract":"<p>J. Liu, Z. Liu, W.i Yan, et al., “ENKUR Recruits FBXW7 to Ubiquitinate and Degrade MYH9 and Further Suppress MYH9-Induced Deubiquitination of β-catenin to Block Gastric Cancer Metastasis,” <i>MedComm</i> 3, no. 4 (2022): e185, https://doi.org/10.1002/mco2.185.</p><p>The above article, published online on 25 November 2022 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the authors; the journal Editors-in-Chief; the Sichuan International Medical Exchange &amp; Promotion Association (SCIMEA); and John Wiley &amp; Sons Australia, Ltd. The retraction has been agreed due to concerns raised by third parties. Further investigation by the publisher has found evidence of image manipulation in Figure 5G. The authors cooperated with the investigation and stated that they were unaware of any manipulation as they did not directly participate in the experiments presented in Figure 5G. They informed the journal that, due to laboratory limitations, an independent company conducted the EMSA experiments and provided them with the digital images of the results instead of original blots. The authors state that they had no reason to doubt the data's authenticity and did not notice irregularities in the images before submission. During the investigation, the authors explained that the company which conducted the EMSA experiments was not the same company stated in the article.</p><p>Additionally, a significant portion of the article's conclusions are based on experiments on the cell line BGC-823, reported as contaminated [1, 2]. The authors provided the STR profile of the cell line used in their study, and this was found to match the problematic cell line BGC-823 at RRID CVCL_3360. Accordingly, the article must be retracted as the editors and the publisher determined that a significant portion of the article's data is unreliable and consider its conclusions invalid. In light of the concerns identified in the course of the investigation, the authors have agreed to retract the article.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70160","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143594928","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":"Tissue-Resident Memory CD8+ T Cells: Differentiation, Phenotypic Heterogeneity, Biological Function, Disease, and Therapy","authors":"Luming Xu,&nbsp;Lilin Ye,&nbsp;Qizhao Huang","doi":"10.1002/mco2.70132","DOIUrl":"https://doi.org/10.1002/mco2.70132","url":null,"abstract":"<p>CD8+ tissue-resident memory T cells (TRM) are strategically located in peripheral tissues, enabling a rapid response to local infections, which is different from circulating memory CD8+ T cells. Their unique positioning makes them promising targets for vaccines designed to enhance protection at barrier sites and other organs. Recent studies have shown a correlation between CD8+ TRM cells and favorable clinical outcomes in various types of cancer, indicating their potential role in immune checkpoint blockade (ICB) therapies. However, the dual nature of CD8+ TRM cells presents challenges, as their inappropriate activation may lead to autoimmunity and chronic inflammatory conditions. This review highlights significant advancements in the field, focusing on the differentiation pathways and phenotypic heterogeneity of CD8+ TRM cells across different tissues and disease states. We also review their protective roles in various contexts and the implications for vaccine development against infections and treatment strategies for tumors. Overall, this comprehensive review outlines the common features of CD8+ TRM cell differentiation and biological functions, emphasizing their specific characteristics across diverse tissues and disease states, which can guide the design of therapies against infections and tumors while minimizing the risk of autoimmune diseases.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70132","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581583","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":"Pulmonary Hypertension: Molecular Mechanisms and Clinical Studies","authors":"Joseph Adu-Amankwaah,&nbsp;Qiang You,&nbsp;Xiaoer Liu,&nbsp;Jiayi Jiang,&nbsp;Dongqi Yang,&nbsp;Kuntao Liu,&nbsp;Jinxiang Yuan,&nbsp;Yanfang Wang,&nbsp;Qinghua Hu,&nbsp;Rubin Tan","doi":"10.1002/mco2.70134","DOIUrl":"https://doi.org/10.1002/mco2.70134","url":null,"abstract":"<p>Pulmonary hypertension (PH) stands as a tumor paradigm cardiovascular disease marked by hyperproliferation of cells and vascular remodeling, culminating in heart failure. Complex genetic and epigenetic mechanisms collectively contribute to the disruption of pulmonary vascular homeostasis. In recent years, advancements in research technology have identified numerous gene deletions and mutations, in addition to <i>bone morphogenetic protein receptor type 2</i>, that are closely associated with the vascular remodeling process in PH. Additionally, epigenetic modifications such as RNA methylation, DNA methylation, histone modification, and noncoding RNAs have been shown to precisely regulate PH molecular networks in a cell-type-specific manner, emerging as potential biomarkers and therapeutic targets. This review summarizes and analyzes the roles and molecular mechanisms of currently identified genes and epigenetic factors in PH, emphasizing the pivotal role of long ncRNAs in its regulation. Additionally, it examines current clinical and preclinical therapies for PH targeting these genes and epigenetic factors and explores potential new treatment strategies.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70134","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581585","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}