MedComm最新文献

{"title":"Global Lactylome Reveals Lactylation-Dependent Mechanisms Underlying CXC Motif Chemokine Ligand 12 Expression in Pulmonary Endothelium During Acute Respiratory Distress Syndrome","authors":"Xu Liu,&nbsp;Haofei Wang,&nbsp;Weijie Ni,&nbsp;Xuecheng Dong,&nbsp;Mingzhu Zheng,&nbsp;Wei Chang","doi":"10.1002/mco2.70344","DOIUrl":"https://doi.org/10.1002/mco2.70344","url":null,"abstract":"<p>Acute respiratory distress syndrome (ARDS) is a life-threatening condition affecting millions of people worldwide. The severity of ARDS is associated with the dysfunction of pulmonary endothelial cells (PECs). Metabolic reprogramming is characterized by enhanced glycolysis and lactate accumulation, which play a critical role in this process. Here, we showed that lactate levels in the lungs of patients with ARDS were associated with disease severity and prognosis. Lactate promoted PEC dysfunction and drove experimental ARDS progression via lysine lactylation (Klac), a recently described posttranslational modification. Suppression of lactate-induced lactylation mitigated the development of ARDS and inhibited the release of chemokines, particularly CXC motif chemokine ligand 12 (CXCL12), from PECs. Through quantitative lactylome analysis, we identified hyperlactylation at K193 of Enolase 1 (Eno1), a glycolytic enzyme with RNA-binding capacity, as a previously unknown mechanism promoting CXCL12 production in PECs. Under homeostatic conditions, Eno1 could bind and inhibit the translation of CXCL12 mRNA, whereas increased glycolysis and accumulated lactate drove K193 hyperlactylation of Eno1 to release CXCL12 mRNA for accelerated translation. In addition, K193 hyperlactylation enhanced Eno1 enzymatic activity, further amplifying glycolysis. These findings establish Klac as a link between glycolytic reprogramming and PEC dysfunction, offering a new therapeutic target for ARDS.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70344","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144914984","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":"Hepatitis B Virus Assembly: Cryo-Electron Microscopy Reveals Structure of the Surface Antigen","authors":"Guobao Li,&nbsp;Jiaxin Cui,&nbsp;Jifeng Nie","doi":"10.1002/mco2.70348","DOIUrl":"https://doi.org/10.1002/mco2.70348","url":null,"abstract":"&lt;p&gt;In a recent study published in &lt;i&gt;Science&lt;/i&gt;, Wang et al. provided novel insights into the assembly of the hepatitis B virus (HBV) by utilizing cryo-electron microscopy (cryo-EM) [&lt;span&gt;1&lt;/span&gt;]. Through reconstruction of &lt;i&gt;D&lt;/i&gt;&lt;sub&gt;2&lt;/sub&gt;(222)- and &lt;i&gt;D&lt;/i&gt;&lt;sub&gt;4&lt;/sub&gt;(422)-like quasisymmetric subviral particles (SVPs) combined with near atomic-level determination of HBsAg topology, they elucidated how HBsAg dimers polymerize into higher-order architectures—enabling SVP formation and coordinated interactions with HBV nucleocapsids to assemble infectious virions.&lt;/p&gt;&lt;p&gt;The World Health Organization (WHO) estimates that approximately 254 million people were living with chronic hepatitis B in 2022. Viral hepatitis caused 1.3 million deaths globally, with HBV accounting for 83% of the fatalities. As a member of the &lt;i&gt;Hepadnaviridae&lt;/i&gt; family, HBV generates non-infectious spherical SVPs (17–22 nm in diameter), filamentous SVPs (22 nm in diameter), and infectious Dane particles (∼44 nm in diameter) during its life cycle. Notably, SVPs can outnumber Dane particles by up to 10,000-fold, contributing to immune tolerance and the persistence of chronic infection. Deciphering the architecture and assembly of HBV particles remains crucial for understanding viral morphogenesis. However, the acquisition of SVPs and their HBsAg-mediated structural heterogeneity present significant barriers to high-resolution structural elucidation of distinct SVP subtypes. Elucidating HBsAg conformation is essential for rational vaccine design, neutralizing epitope mapping, and HBV therapeutics development.&lt;/p&gt;&lt;p&gt;HBsAg is translated from a single open reading frame encoding three co-terminal isoforms: small (S-), medium (M-), and large (L-) HBsAg (Figure 1A). Among these, S-HBsAg constitutes the predominant component in both SVPs and infectious Dane particles. Wang et al. expressed S-HBsAg in human embryonic kidney 293 (HEK293) and Chinese hamster ovary (CHO) cells, generating SVPs morphologically analogous to native virions. HEK293-derived SVPs were purified by affinity chromatography, whereas CHO-derived SVPs were isolated via sucrose gradient centrifugation. Both populations underwent size-exclusion chromatography to exclude aggregates and isolate monodisperse particles, ensuring sample homogeneity for cryo-EM. After data acquisition and analysis, two monodisperse populations of quasi-spherical SVPs with a diameter of 22 nm were identified. Single-particle reconstruction revealed two distinct icosahedral symmetry classes: &lt;i&gt;D&lt;/i&gt;&lt;sub&gt;2&lt;/sub&gt;(222) and &lt;i&gt;D&lt;/i&gt;&lt;sub&gt;4&lt;/sub&gt;(422) (referred to as “D2” and “D4,” respectively). By applying symmetry constraints and a custom orientation transformation script, the authors achieved a 3.7 Å resolution structure of S-HBsAg. It comprises two N-terminal transmembrane α-helices (TH1 and TH2) and four C-terminal membrane-embedded α-helices (EH1–EH4) (Figure 1B). The protein integrates into the lipid bilayer with the cytoplasmic lo","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70348","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910088","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":"Chimeric Antigen Receptor-Macrophage Therapy Enters the Clinic: The First-in-Human Trial for HER2+ Solid Tumors","authors":"Wenxue Ma,&nbsp;Catriona Jamieson","doi":"10.1002/mco2.70374","DOIUrl":"https://doi.org/10.1002/mco2.70374","url":null,"abstract":"&lt;p&gt;In a recent study published in Nature Medicine (2025), Reiss et al. [&lt;span&gt;1&lt;/span&gt;] reported the first-in-human Phase 1 trial of CT-0508, a chimeric antigen receptor macrophage (CAR-M) therapy targeting HER2-overexpressing solid tumors. This trial demonstrated safety, feasibility, and early immune activity in heavily pretreated patients, marking the first clinical validation of macrophage-based immunotherapy. This milestone highlights the potential of engineered macrophages to overcome tumor microenvironment (TME)-mediated resistance, signaling a paradigm shift for treating solid tumors refractory to current therapies.&lt;/p&gt;&lt;p&gt;Fourteen patients with HER2-overexpressing tumors, including breast, gastroesophageal, and salivary duct carcinomas, were enrolled and received CT-0508 without prior lympho-depleting chemotherapy. Two dosing regimens were explored: fractionated (Group 1) and bolus (Group 2). CAR-Ms were generated from autologous monocytes using a replication-incompetent adenoviral vector (Ad5.F35), achieving high viability, purity, and CAR expression across all manufactured products. Preclinical assays demonstrated HER2-specific cytotoxicity, phagocytosis, and secretion of proinflammatory cytokines upon antigen engagement.&lt;/p&gt;&lt;p&gt;Clinically, CT-0508 exhibited a favorable safety profile. No dose-limiting toxicities, Grade ≥3 cytokine release syndrome (CRS), or immune effector cell-associated neurotoxicity syndrome (ICANS) were observed. Grade 1–2 CRS occurred in nine patients and was managed without corticosteroids or intensive supportive care. Importantly, the trial avoided the use of lympho-depleting regimens such as cyclophosphamide or fludarabine, which are standard in CAR-T therapies, thereby supporting a more tolerable, outpatient-based delivery model. This distinction represents a major advantage in the solid tumor space, where toxicity concerns and logistical burdens have limited broader access to cell therapy.&lt;/p&gt;&lt;p&gt;Although no objective responses (per RECIST v1.1) were observed, four of nine patients (44.5%) with HER2 immunohistochemistry (IHC) 3&lt;sup&gt;+&lt;/sup&gt; tumors achieved stable disease (SD), while all five patients with HER2 IHC 2&lt;sup&gt;+&lt;/sup&gt; tumors exhibited progressive disease (PD). Tumor volume reductions were noted in 41% of measurable lesions, and circulating tumor DNA (ctDNA) levels decreased in 62% of patients, including all those with SD. These molecular and radiographic evidence indicate biological activity, although transient. Interestingly, some patients exhibited ctDNA rebound at later timepoints, raising questions about the durability of response and the potential need for maintenance dosing or sequential therapeutic strategies. These observations reinforce the value of integrating longitudinal molecular monitoring in early-phase trials to better understand the kinetics of response and identify early markers of relapse. A graphical overview summarizing the clinical workflow, immunologic changes, and future directio","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70374","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910089","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":"Mitochondrial Dysfunction in Neurodegenerative Diseases","authors":"Chongyang Chen,&nbsp;Yujie Zhao,&nbsp;Jing Wang,&nbsp;Donghui Pan,&nbsp;Xinyu Wang,&nbsp;Yuping Xu,&nbsp;Junjie Yan,&nbsp;Lizhen Wang,&nbsp;Xifei Yang,&nbsp;Ming Lu,&nbsp;Gong-Ping Liu","doi":"10.1002/mco2.70326","DOIUrl":"https://doi.org/10.1002/mco2.70326","url":null,"abstract":"<p>Mitochondria are indispensable for the normal physiological activities and metabolism of living organisms. The proper function of mitochondria in the brain is crucial for maintaining the normal brain function with high energy demands. There are growing evidences that mitochondrial dysfunction plays a critical role in multiple of neurodegenerative diseases (NDDs), including Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and Huntington's disease. In this review, the research progress and future development trajectory of mitochondrial function in NDDs will be comprehensively summarized, which focusing on mitochondrial physiological function, the mechanisms underlying mitochondrial dysfunction in diverse NDDs, research approaches for exploring mitochondrial function, various strategies for targeted mitochondrial therapy, and the challenges and opportunities encountered in the evaluation of mitochondrial-targeted therapeutic drugs. The feasibility of in vivo mitochondrial imaging and the future perspectives of AI for mitochondria-targeted drug screening are deliberated, which will facilitate the advancement of the comprehension of mitochondrial functional mechanisms in NDDs and the development of future clinical therapeutic drugs. This review shall furnish several insights regarding novel research methodologies and drug developments for researchers engaged in the investigation of mitochondrial dysfunction in NDDs.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70326","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910087","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":"Artificial Intelligence-Based Multimodal Prediction of Postoperative Adjuvant Immunotherapy Benefit in Urothelial Carcinoma: Results From the Phase III, Multicenter, Randomized, IMvigor010 Trial","authors":"Xiatong Huang,&nbsp;Wenjun Qiu,&nbsp;Yuyun Kong,&nbsp;Qiyun Ou,&nbsp;Qianqian Mao,&nbsp;Yiran Fang,&nbsp;Zhouyang Fan,&nbsp;Jiani Wu,&nbsp;Xiansheng Lu,&nbsp;Wenchao Gu,&nbsp;Peng Luo,&nbsp;Junfen Wang,&nbsp;Jianping Bin,&nbsp;Yulin Liao,&nbsp;Min Shi,&nbsp;Zuqiang Wu,&nbsp;Huiying Sun,&nbsp;Yunfang Yu,&nbsp;Wangjun Liao,&nbsp;Dongqiang Zeng","doi":"10.1002/mco2.70324","DOIUrl":"https://doi.org/10.1002/mco2.70324","url":null,"abstract":"<p>While circulating tumor DNA (ctDNA) testing has demonstrated utility in identifying muscle-invasive urothelial carcinoma (MIUC) patients likely to benefit from adjuvant immunotherapy, the prognostic value of transcriptome data from surgical specimens remains underexplored. Using transcriptomic and ctDNA data from the IMvigor010 trial, we developed an artificial intelligence (AI)-driven biomarker to predict immunotherapy response in urothelial carcinoma, termed UAIscore. Patients with high UAIscore had significantly better outcomes in the atezolizumab arm versus the observation arm. Notably, the predictive performance of the UAIscore consistently outperformed that of ctDNA, tTMB, and PD-L1, highlighting its value as an independent biomarker. Moreover, combining ctDNA, tTMB, and PD-L1 with the UAIscore further improved predictive accuracy, underscoring the importance of integrating multi-modality biomarkers. Further analysis of molecular subtypes revealed that the luminal subtype tends to be sensitive to adjuvant immunotherapy, as it may exhibit the highest level of immune infiltration and the lowest degree of hypoxia. Remarkably, we elucidated the role of the NF-κB and TNF-α pathways in mediating immunotherapy resistance within the immune-enriched tumor microenvironment. These findings stratify patients likely to respond to adjuvant immunotherapy, concurrently providing a mechanistic rationale for combination therapies to augment immunotherapy efficacy in urothelial carcinoma.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70324","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144897406","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":"Activated Interferon-γ-Positive T Lymphocytes and Cytokine Signatures in Patients With Postinfectious Cough","authors":"Zheng Deng,&nbsp;Tongtong Song,&nbsp;Wenbin Ding,&nbsp;Wei Luo,&nbsp;Jiaxing Xie,&nbsp;Haodong Wu,&nbsp;Nanshan Zhong,&nbsp;Kefang Lai","doi":"10.1002/mco2.70340","DOIUrl":"https://doi.org/10.1002/mco2.70340","url":null,"abstract":"<p>Postinfectious subacute cough (PISC) and postinfectious chronic cough (PICC) are triggered by respiratory infections, which induce adaptive immunity. The expression of T-lymphocyte subsets and cytokine signatures remains elusive in these patients. Here, we recruited 40 healthy controls, 64 PICC patients, 65 PISC patients, and 20 recovered individuals with postinfectious subacute cough (R-PISC). As cough and airway inflammation resolved in R-PISC subjects, sputum lymphocytes dropped substantially. Both PICC and PISC patients had an increase in blood activated interferon-γ (IFN-γ)⁺ T-lymphocytes, which were decreased in R-PISC subjects. Elevated cough sensitivity, higher proportions of activated IFN-γ⁺ T-lymphocytes, and CD8⁺/CD4⁺ T-lymphocyte ratios, as well as elevated concentrations of uric acid, IFN-γ, tumor necrosis factor-α (TNF-α), IFN-α, IFN-β, and interleukin-10 in sputa, were observed in PICC and PISC patients but normalized in R-PISC subjects. Correlation analyses and logistic regression models identified activated IFN-γ⁺ T-lymphocytes and these cytokines in sputa as biomarkers for predicting cough risk. PICC patients exhibited greater cough severity, elevated activated IFN-γ⁺ T-lymphocytes, and TNF-α concentrations in sputa compared to PISC patients. Overall, postinfectious cough patients exhibit airway inflammatory signatures characterized by activated IFN-γ⁺ T-lymphocytes and elevated levels of IFN-γ, TNF-α, IFN-α, IFN-β, and interleukin-10, which are valuable for effective treatment options.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70340","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894235","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":"Human Umbilical Cord Blood Plasma-Derived Exosomal miR-410-3p Alleviates Liver Injury by Regulating the Mitochondria-Mediated Antiapoptotic Signaling","authors":"Lin Zhang,&nbsp;Yushuang Ren,&nbsp;Dongsheng Su,&nbsp;Qingyuan Jiang,&nbsp;Huan Peng,&nbsp;Fuyi Cheng,&nbsp;Hantao Zhang,&nbsp;Xue Bai,&nbsp;Xiao Wei,&nbsp;Weixiao Yang,&nbsp;Pusong Zhao,&nbsp;Yixin Ye,&nbsp;Gang Shi,&nbsp;Hongxin Deng","doi":"10.1002/mco2.70339","DOIUrl":"https://doi.org/10.1002/mco2.70339","url":null,"abstract":"<p>Severe liver injury is a life-threatening condition with high mortality and limited therapeutic options. Extensive research on heterochronic parabiosis has highlighted the potent regenerative repair capabilities of young blood in tissue regeneration. However, it remains unclear whether younger blood, specifically umbilical cord blood, can offer similar benefits for tissue repair. In this study, we demonstrate that exosomes derived from umbilical cord blood plasma (CBP-Exos) exhibit significant therapeutic effects in both acute and chronic liver injury models, outperforming exosomes from young peripheral blood plasma. Treatment with CBP-Exos notably reduced liver necrosis, lipid peroxidation, and apoptosis in liver tissues of acute liver injury (ALI) mice. Mechanistically, miR-410-3p, derived from CBP-Exos, directly targets the proapoptotic gene Bim for posttranscriptional degradation. The downregulation of Bim facilitates the activation of mitochondrial-mediated Bcl2-CytoC antiapoptotic signaling, resulting in the restoration of mitochondrial structure and function, thereby inhibiting hepatocyte apoptosis and oxidative stress. Furthermore, overexpression of miR-410-3p significantly improved liver function in ALI mice. These findings identify the therapeutic effects of CBP-Exos are attributed to the miR-410-3p/Bcl2/CytoC axis, laying a foundation for the clinical application of CBP-Exos and miR-410-3p in liver diseases.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70339","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894234","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":"Discovery of RNA-Targeting Small Molecules: Challenges and Future Directions","authors":"Zhengguo Cai,&nbsp;Hongli Ma,&nbsp;Fengcan Ye,&nbsp;Dingwei Lei,&nbsp;Zhenfeng Deng,&nbsp;Yongge Li,&nbsp;Ruichu Gu,&nbsp;Han Wen","doi":"10.1002/mco2.70342","DOIUrl":"https://doi.org/10.1002/mco2.70342","url":null,"abstract":"<p>RNA-targeting small molecules represent a transformative frontier in drug discovery, offering novel therapeutic avenues for diseases traditionally deemed undruggable. This review explores the latest advancements in the development of RNA-binding small molecules, focusing on the current obstacles and promising avenues for future research. We highlight innovations in RNA structure determination, including X-ray crystallography, nuclear magnetic resonance spectroscopy, and cryo-electron microscopy, which provide the foundation for rational drug design. The role of computational approaches, such as deep learning and molecular docking, is emphasized for enhancing RNA structure prediction and ligand screening efficiency. Additionally, we discuss the utility of focused libraries, DNA-encoded libraries, and small-molecule microarrays in identifying bioactive ligands, alongside the potential of fragment-based drug discovery for exploring chemical space. Emerging strategies, such as RNA degraders and modulators of RNA–protein interactions, are reviewed for their therapeutic promise. Specifically, we underscore the pivotal role of artificial intelligence and machine learning in accelerating discovery and optimizing RNA-targeted therapeutics. By synthesizing these advancements, this review aims to inspire further research and collaboration, unlocking the full potential of RNA-targeting small molecules to revolutionize treatment paradigms for a wide range of diseases.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70342","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894236","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":"Identification of c-Met on Tumor Cells as a Novel Receptor for B7-H3 Entails Implications for Cancer Cell Stemness and Targeted Therapy","authors":"Lei Cao,&nbsp;Yunyun Xu,&nbsp;Yizhou Hu,&nbsp;Xue Huang,&nbsp;Fengqing Fu,&nbsp;Shenghua Zhan,&nbsp;Lili Huang,&nbsp;Yangyang Feng,&nbsp;Ylivinkka Irene,&nbsp;Huini Li,&nbsp;Varjosalo Markku,&nbsp;Keski-Oja Jorma,&nbsp;Guangbo Zhang,&nbsp;Binfeng Lu,&nbsp;Jian Wang,&nbsp;Wanli Liu,&nbsp;Xueguang Zhang","doi":"10.1002/mco2.70332","DOIUrl":"https://doi.org/10.1002/mco2.70332","url":null,"abstract":"<p>The immune checkpoint molecule B7-H3 is upregulated in many solid tumors, and B7-H3-targeted immunotherapies are in clinical trials. Recently, a growing body of research has highlighted the presence of tumor cell intrinsic while immune cell-independent functions of B7-H3 in tumorigenesis and cancer cell stemness. However, its receptors and mechanisms of action on cancer cells remain poorly understood. Here, we report that c-Met, a canonical oncogenic receptor tyrosine kinase on cancer cells, is identified as a novel binding protein for B7-H3. The binding between c-Met and B7-H3 directly activates the c-Met/STAT3 signaling cascade, promoting cancer cell stemness in both colorectal cancer and glioblastoma-derived tumor cells. More importantly, we evaluated the translational implications of this discovery by screening a high-affinity antibody designed to selectively disrupt the interaction between B7-H3 and c-Met, demonstrating strong anti-tumor activities, surpassing that of the B7-H3-specific antibody lacking the blocking capability. Combination therapy of this newly developed interaction blocking antibody with c-Met inhibitor results in significantly improved therapeutic effects in inhibiting tumor growth. These findings shed light on previously undisclosed interaction of B7-H3 to c-Met on cancer cells, thereby indicating a new mechanism of cancer cell stemness and intervention pathway of molecular targeted therapy.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70332","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144888478","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":"Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets","authors":"Shijie Mao,&nbsp;Rui Qiao,&nbsp;Qi Wang,&nbsp;Ling Shen,&nbsp;Daxing Li,&nbsp;Xinchen Huo,&nbsp;Jindou Wang,&nbsp;Kunxuan Liu,&nbsp;Wenjing Chen,&nbsp;Tianhao Zhu,&nbsp;Beicheng Zhang,&nbsp;Shuo Leng,&nbsp;Ying Bai","doi":"10.1002/mco2.70329","DOIUrl":"https://doi.org/10.1002/mco2.70329","url":null,"abstract":"<p>Astrocytes, the most prevalent glial cells in the central nervous system (CNS), play crucial roles in maintaining CNS homeostasis and responding to various pathological stimuli. They play key roles in neural development, neurotransmission, neuroinflammation, metabolic support, and tissue repair. Recent advancements in single-cell sequencing have revealed the remarkable heterogeneity of astrocytes, with distinct subpopulations differentially contributing to disease progression in neurological disorders, including Alzheimer's disease, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, ischemic stroke, intracerebral hemorrhage, and multiple sclerosis. In addition, they play an important role in various behavioral neuropsychiatric disorders. This review highlights the dual roles of astrocytes in disease progression, driven by their diverse molecular profiles and functions. It outlines the key molecular mechanisms underlying astrocyte heterogeneity and their impact on neuroinflammation, neuronal support, and ionic balance regulation. Additionally, the review discusses potential therapeutic strategies targeting astrocytes to modulate these processes, aiming to improve treatment outcomes in neurological diseases. By elucidating the specific roles of astrocyte subsets in disease, this review seeks to advance the development of precision medicine for astrocyte-related neurological disorders.</p>","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70329","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144891760","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}