IF 10.7

MedComm Pub Date : 2025-08-25 DOI: 10.1002/mco2.70324

Xiatong Huang, Wenjun Qiu, Yuyun Kong, Qiyun Ou, Qianqian Mao, Yiran Fang, Zhouyang Fan, Jiani Wu, Xiansheng Lu, Wenchao Gu, Peng Luo, Junfen Wang, Jianping Bin, Yulin Liao, Min Shi, Zuqiang Wu, Huiying Sun, Yunfang Yu, Wangjun Liao, Dongqiang Zeng

{"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, Wenjun Qiu, Yuyun Kong, Qiyun Ou, Qianqian Mao, Yiran Fang, Zhouyang Fan, Jiani Wu, Xiansheng Lu, Wenchao Gu, Peng Luo, Junfen Wang, Jianping Bin, Yulin Liao, Min Shi, Zuqiang Wu, Huiying Sun, Yunfang Yu, Wangjun Liao, Dongqiang Zeng","doi":"10.1002/mco2.70324","DOIUrl":"https://doi.org/10.1002/mco2.70324","url":null,"abstract":"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.","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}

引用次数: 0

Activated Interferon-γ-Positive T Lymphocytes and Cytokine Signatures in Patients With Postinfectious Cough 感染后咳嗽患者活化干扰素-γ阳性T淋巴细胞和细胞因子特征

IF 10.7

MedComm Pub Date : 2025-08-24 DOI: 10.1002/mco2.70340

Zheng Deng, Tongtong Song, Wenbin Ding, Wei Luo, Jiaxing Xie, Haodong Wu, Nanshan Zhong, Kefang Lai

{"title":"Activated Interferon-γ-Positive T Lymphocytes and Cytokine Signatures in Patients With Postinfectious Cough","authors":"Zheng Deng, Tongtong Song, Wenbin Ding, Wei Luo, Jiaxing Xie, Haodong Wu, Nanshan Zhong, Kefang Lai","doi":"10.1002/mco2.70340","DOIUrl":"https://doi.org/10.1002/mco2.70340","url":null,"abstract":"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.","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}

引用次数: 0

Human Umbilical Cord Blood Plasma-Derived Exosomal miR-410-3p Alleviates Liver Injury by Regulating the Mitochondria-Mediated Antiapoptotic Signaling 人脐带血源性外泌体miR-410-3p通过调节线粒体介导的抗凋亡信号缓解肝损伤

IF 10.7

MedComm Pub Date : 2025-08-24 DOI: 10.1002/mco2.70339

Lin Zhang, Yushuang Ren, Dongsheng Su, Qingyuan Jiang, Huan Peng, Fuyi Cheng, Hantao Zhang, Xue Bai, Xiao Wei, Weixiao Yang, Pusong Zhao, Yixin Ye, Gang Shi, Hongxin Deng

{"title":"Human Umbilical Cord Blood Plasma-Derived Exosomal miR-410-3p Alleviates Liver Injury by Regulating the Mitochondria-Mediated Antiapoptotic Signaling","authors":"Lin Zhang, Yushuang Ren, Dongsheng Su, Qingyuan Jiang, Huan Peng, Fuyi Cheng, Hantao Zhang, Xue Bai, Xiao Wei, Weixiao Yang, Pusong Zhao, Yixin Ye, Gang Shi, Hongxin Deng","doi":"10.1002/mco2.70339","DOIUrl":"https://doi.org/10.1002/mco2.70339","url":null,"abstract":"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.","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}

引用次数: 0

Discovery of RNA-Targeting Small Molecules: Challenges and Future Directions rna靶向小分子的发现：挑战与未来方向

IF 10.7

MedComm Pub Date : 2025-08-24 DOI: 10.1002/mco2.70342

Zhengguo Cai, Hongli Ma, Fengcan Ye, Dingwei Lei, Zhenfeng Deng, Yongge Li, Ruichu Gu, Han Wen

{"title":"Discovery of RNA-Targeting Small Molecules: Challenges and Future Directions","authors":"Zhengguo Cai, Hongli Ma, Fengcan Ye, Dingwei Lei, Zhenfeng Deng, Yongge Li, Ruichu Gu, Han Wen","doi":"10.1002/mco2.70342","DOIUrl":"https://doi.org/10.1002/mco2.70342","url":null,"abstract":"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.","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}

引用次数: 0

Identification of c-Met on Tumor Cells as a Novel Receptor for B7-H3 Entails Implications for Cancer Cell Stemness and Targeted Therapy 肿瘤细胞上c-Met作为B7-H3新受体的鉴定对肿瘤细胞干细胞和靶向治疗具有重要意义

IF 10.7

MedComm Pub Date : 2025-08-22 DOI: 10.1002/mco2.70332

Lei Cao, Yunyun Xu, Yizhou Hu, Xue Huang, Fengqing Fu, Shenghua Zhan, Lili Huang, Yangyang Feng, Ylivinkka Irene, Huini Li, Varjosalo Markku, Keski-Oja Jorma, Guangbo Zhang, Binfeng Lu, Jian Wang, Wanli Liu, Xueguang Zhang

{"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, Yunyun Xu, Yizhou Hu, Xue Huang, Fengqing Fu, Shenghua Zhan, Lili Huang, Yangyang Feng, Ylivinkka Irene, Huini Li, Varjosalo Markku, Keski-Oja Jorma, Guangbo Zhang, Binfeng Lu, Jian Wang, Wanli Liu, Xueguang Zhang","doi":"10.1002/mco2.70332","DOIUrl":"https://doi.org/10.1002/mco2.70332","url":null,"abstract":"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.","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}

引用次数: 0

Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets 星形胶质细胞在神经系统疾病中的活性和异质性：分子机制和治疗靶点

IF 10.7

MedComm Pub Date : 2025-08-22 DOI: 10.1002/mco2.70329

Shijie Mao, Rui Qiao, Qi Wang, Ling Shen, Daxing Li, Xinchen Huo, Jindou Wang, Kunxuan Liu, Wenjing Chen, Tianhao Zhu, Beicheng Zhang, Shuo Leng, Ying Bai

{"title":"Activity and Heterogeneity of Astrocytes in Neurological Diseases: Molecular Mechanisms and Therapeutic Targets","authors":"Shijie Mao, Rui Qiao, Qi Wang, Ling Shen, Daxing Li, Xinchen Huo, Jindou Wang, Kunxuan Liu, Wenjing Chen, Tianhao Zhu, Beicheng Zhang, Shuo Leng, Ying Bai","doi":"10.1002/mco2.70329","DOIUrl":"https://doi.org/10.1002/mco2.70329","url":null,"abstract":"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.","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}

引用次数: 0

Nanocarrier-Based Systems for Targeted Delivery: Current Challenges and Future Directions 靶向递送的纳米载体系统：当前的挑战和未来的方向

IF 10.7

MedComm Pub Date : 2025-08-21 DOI: 10.1002/mco2.70337

Zichen Xu, Yongyi Xie, Wenjie Chen, Wei Deng

{"title":"Nanocarrier-Based Systems for Targeted Delivery: Current Challenges and Future Directions","authors":"Zichen Xu, Yongyi Xie, Wenjie Chen, Wei Deng","doi":"10.1002/mco2.70337","DOIUrl":"https://doi.org/10.1002/mco2.70337","url":null,"abstract":"Nanomaterials have become promising platforms in the field of drug and gene delivery, offering unique advantages over traditional therapeutic approaches. Their tunable physicochemical properties enable improved pharmacokinetics and therapeutic performance. A wide range of nanocarriers, including lipid-based, polymer-based, and hybrid systems, have been rapidly developed and are attracting increasing attention in both preclinical and clinical research. However, despite promising preclinical outcomes, these systems still encounter critical challenges in achieving precise delivery to specific tissues, cells, and intracellular compartments. This review provides a comprehensive assessment of recent advances in the design and application of nanocarriers for targeted delivery, with emphasis on strategies designed for nuclear targeting. In the context of nuclear targeting, it explores passive approaches involving modulation of particle size, morphology, and surface charge, alongside active targeting strategies incorporating nuclear localization signals and other ligands. In addition to highlighting progress, the review examines the limitations associated with delivery efficiency, off-target effects, and barriers to clinical translation. By addressing both advances and ongoing challenges, this review provides valuable insights into the design and engineering of targeted nanocarriers. These developments are crucial for unlocking the full potential of precision nanomedicine.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70337","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144885330","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}

引用次数: 0

Spatiotemporal Dynamics of Central Nervous System Diseases: Advancing Translational Neuropathology via Single-Cell and Spatial Multiomics 中枢神经系统疾病的时空动态：通过单细胞和空间多组学推进转化神经病理学

IF 10.7

MedComm Pub Date : 2025-08-19 DOI: 10.1002/mco2.70328

Mingkai Xia, Quan Liu, Wenli Zhang, Jinwen Ge, Zhigang Mei

{"title":"Spatiotemporal Dynamics of Central Nervous System Diseases: Advancing Translational Neuropathology via Single-Cell and Spatial Multiomics","authors":"Mingkai Xia, Quan Liu, Wenli Zhang, Jinwen Ge, Zhigang Mei","doi":"10.1002/mco2.70328","DOIUrl":"https://doi.org/10.1002/mco2.70328","url":null,"abstract":"Central nervous system (CNS) diseases, a leading cause of global disability and mortality, encompass a wide range of brain disorders such as stroke, Alzheimer's disease, Parkinson's disease, and so on. These diseases are characterized by dynamic cellular heterogeneity and disrupted intercellular crosstalk, yet their molecular drivers remain incompletely resolved. Single-cell RNA sequencing (scRNA-seq) dissects transcriptional diversity at cellular resolution, while spatial transcriptomics (ST) maps niche-specific interactions within tissue architecture—complementary approaches that have revealed disease-associated subpopulations, neural–glial communication, and microenvironmental remodeling. However, standalone omics layers inadequately capture the genetic, epigenetic, and functional cascades underlying CNS pathologies. Here, we highlight the transformative potential of integrating scRNA-seq and ST with multiomic profiling to delineate spatially orchestrated molecular networks. Such multiomic convergence enables systematic deconstruction of molecular mechanisms and intercellular communication across disease progression. By correlating these signatures with clinical phenotypes, this strategy accelerates biomarker discovery, patient stratification, and therapeutic target identification. We further discuss challenges in data harmonization, subcellular spatial resolution, and computational scalability that must be addressed to realize personalized CNS medicine. This synthesis advocates for interdisciplinary frameworks to translate multiomic insights into mechanistically grounded diagnostics and therapies, ultimately bridging the gap between molecular discovery and precision clinical intervention.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70328","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869774","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}

引用次数: 0

VEGF Signal Complexity Confers Resistance to Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel in EGFR-Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer egfr -酪氨酸激酶抑制剂耐药非小细胞肺癌患者对阿特唑单抗、贝伐单抗、卡铂和紫杉醇的耐药

IF 10.7

MedComm Pub Date : 2025-08-19 DOI: 10.1002/mco2.70335

Sehwa Hong, Namhee Yu, Ju Young Cho, Geon Kook Lee, Beung-Chul Ahn, Youngjoo Lee, Hanna Sim, Bo Ram Song, Mihwa Hwang, Sunshin Kim, Jung-Hyun Kim, Charny Park, Ji-Youn Han

{"title":"VEGF Signal Complexity Confers Resistance to Atezolizumab, Bevacizumab, Carboplatin, and Paclitaxel in EGFR-Tyrosine Kinase Inhibitor-Resistant Non-Small Cell Lung Cancer","authors":"Sehwa Hong, Namhee Yu, Ju Young Cho, Geon Kook Lee, Beung-Chul Ahn, Youngjoo Lee, Hanna Sim, Bo Ram Song, Mihwa Hwang, Sunshin Kim, Jung-Hyun Kim, Charny Park, Ji-Youn Han","doi":"10.1002/mco2.70335","DOIUrl":"https://doi.org/10.1002/mco2.70335","url":null,"abstract":"Atezolizumab, bevacizumab, carboplatin, and paclitaxel (ABCP) therapy is beneficial for epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI)-resistant non-small cell lung cancer (NSCLC); however, the resistance mechanisms are not fully understood. In this study, we conducted a single-cell RNA-sequencing analysis of EGFR-TKI-resistant NSCLC patients grouped into ABCP responders and non-responders. VEGFA was overexpressed in ABCP responders, whereas VEGFC was upregulated in non-responders. VEGFA and VEGFC had exclusive distributions and interactions, suggesting their distinct roles. VEGFA facilitated the proliferation of responder tumor subcluster cells, whereas VEGFC secreted from non-responder tumor cells interacted with tumor microenvironment cells. VEGFC predominantly cooperated with drug resistance pathways such as fibroblast growth factor signaling and YAP-TAZ regulation, whereas VEGFA coordinated several oncogenic signaling pathways. VEGFC expression was the most significant prognostic marker (hazard ratio, 1.8 [95% confidence interval, 1.1–3.0], p = 0.015). Both VEGFA and VEGFC inhibition effectively suppressed tumor growth, suggesting that VEGF signaling complexity hampers the response to ABCP. In conclusion, combinatorial targeting of both ligands (VEGFA and VEGFC) or their receptors (VEGFR2 and KDR) may enhance the clinical benefit of ABCP in EGFR-TKI-resistant NSCLC patients.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70335","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869770","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}

引用次数: 0

Heavy Metals Toxicity: Mechanism, Health Effects, and Therapeutic Interventions 重金属毒性：机制、健康影响和治疗干预

IF 10.7

MedComm Pub Date : 2025-08-19 DOI: 10.1002/mco2.70241

Yu-feng Cheng, Yu-jia Zhao, Ce Chen, Feng Zhang

{"title":"Heavy Metals Toxicity: Mechanism, Health Effects, and Therapeutic Interventions","authors":"Yu-feng Cheng, Yu-jia Zhao, Ce Chen, Feng Zhang","doi":"10.1002/mco2.70241","DOIUrl":"https://doi.org/10.1002/mco2.70241","url":null,"abstract":"Heavy metals (HMs), such as chromium, arsenic, cadmium, mercury, and lead, constitute a class of environmental pollutants with significant toxicity that pose a serious threat to human health. This review provides a comprehensive overview of the biochemical properties of HMs, and their effects at the cellular, molecular, and genetic levels. HMs exert their toxic effects by interfering with various intracellular biochemical processes, including enzyme activity, protein synthesis, and energy metabolism. Furthermore, they can disrupt the integrity of cell membranes and affect cellular signaling, leading to cellular dysfunction and death. At the molecular and genetic levels, HMs can cause DNA damage and induce gene mutations, thereby affecting genetic transmission and expression. Then, the effects of HMs on the nervous system, kidneys, cardiovascular system, reproduction, and cancer risk are discussed. Therapeutic strategies, such as chelation therapy, antioxidants and free radical scavengers, supportive therapy, and prevention and reduction of exposure, have been shown to mitigate the toxic effects of HMs. Last, based on the current findings on the mechanisms of HMs, future research directions are prospected. Through multidisciplinary cooperation and integrated interventions, it is expected that the health risks posed by HMs can be alleviated. Future research needs to further elucidate the mechanisms of HMs toxicity, develop more effective treatments, and strengthen preventive and control measures.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 9","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70241","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144869773","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}

引用次数: 0

MedComm最新文献