MedComm最新文献 - Book学术

Safety, Pharmacokinetics, and Efficacy Study of Porcine and Rabbit Antithymocyte Globulin in the Treatment of Patients With Severe Aplastic Anemia: A Multicenter, Prospective, Randomized, Open-Label Clinical Trial 猪和兔抗胸腺细胞球蛋白治疗严重再生障碍性贫血的安全性、药代动力学和疗效研究：一项多中心、前瞻性、随机、开放标签的临床试验

IF 14.1

MedComm Pub Date : 2026-10-17 DOI: 10.1002/mco2.71084

Yawen Zhang, Yingying Zhang, Yuemin Gong, Yu Sun, Guangsheng He

{"title":"Safety, Pharmacokinetics, and Efficacy Study of Porcine and Rabbit Antithymocyte Globulin in the Treatment of Patients With Severe Aplastic Anemia: A Multicenter, Prospective, Randomized, Open-Label Clinical Trial","authors":"Yawen Zhang, Yingying Zhang, Yuemin Gong, Yu Sun, Guangsheng He","doi":"10.1002/mco2.71084","DOIUrl":"https://doi.org/10.1002/mco2.71084","url":null,"abstract":"Severe aplastic anemia (SAA) is a T lymphocyte-mediated bone marrow failure disorder. Only porcine ATG (p-ATG) and rabbit ATG (r-ATG) are available in mainland China, with the optimal first-line regimen undetermined. This study compared their pharmacokinetics, efficacy, and safety. Ninety-three SAA patients ineligible for transplantation or lacking a suitable donor (p-ATG, n = 55; r-ATG, n = 38) who were receiving immunosuppressive therapy were prospectively enrolled between 2020 and 2024. The primary endpoint was dynamic changes in lymphocyte subsets. Both ATGs peaked on treatment Day 5; r-ATG cleared significantly faster, with comparable peak active concentrations. The p-ATG group showed a stable early neutrophil increase, whereas the r-ATG group had an initial decline, with comparable recovery at 1 month. The r-ATG group exhibited prolonger lymphopenia, lower CD3+/CD4+ T cells, reduced Treg cells, and higher CD19+ B-cell proportions. IL-10 was significantly elevated on day 2 after ATG administration. At 6 months, the CRR was 18.87% with p-ATG and 18.92% with r-ATG; ORR was 69.81% with p-ATG and 56.76% with r-ATG. Two-year ORR and overall survival were similar, with no significant differences in infection or serum sickness. P-ATG and r-ATG have distinct pharmacokinetic and immunomodulatory but comparable efficacy and safety profiles, supporting interchangeable use in clinical practice.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 11","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.71084","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205985","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

Intratumoral and Peritumoral Functional Connectivity Reveals Network-Level Signatures of Glioma 肿瘤内和肿瘤周围功能连接揭示神经胶质瘤的网络水平特征

IF 14.1

MedComm Pub Date : 2026-10-17 DOI: 10.1002/mco2.71083

Hongbo Bao, Yan Bai, Jie Hu, Wencai Ding, Jiacheng Lai, Andrew Zalesky, Ye Ella Tian, Yanmei Tie, Janet Mei, Shengyu Fang, Xing Fan, Licia P. Luna, Craig K. Jones, Jianxun Ren, Weigang Cui, Jiadong Yan, Zeya Yan, Zihan Wang, Renwu Zhang, Zhonghua Lv, Yihang Jiao, Tao Jiang, Peng Liang, Haris I. Sair, Yinyan Wang

{"title":"Intratumoral and Peritumoral Functional Connectivity Reveals Network-Level Signatures of Glioma","authors":"Hongbo Bao, Yan Bai, Jie Hu, Wencai Ding, Jiacheng Lai, Andrew Zalesky, Ye Ella Tian, Yanmei Tie, Janet Mei, Shengyu Fang, Xing Fan, Licia P. Luna, Craig K. Jones, Jianxun Ren, Weigang Cui, Jiadong Yan, Zeya Yan, Zihan Wang, Renwu Zhang, Zhonghua Lv, Yihang Jiao, Tao Jiang, Peng Liang, Haris I. Sair, Yinyan Wang","doi":"10.1002/mco2.71083","DOIUrl":"https://doi.org/10.1002/mco2.71083","url":null,"abstract":"Gliomas are recognized as network-level diseases that remodel functional connectivity across the brain. Using resting-state functional MRI (rs-fMRI) data from 306 patients with pathologically confirmed glioma at two hospitals, we delineated individualized intra- and peritumoral functional networks to quantify tumor-related alterations. Two novel indices—the ratio of intratumoral functional regions (RIFR) and ratio of peritumoral tumor-related regions (RPTR)—were proposed to describe network remodeling. Both indices were related to pathological, structural, functional, cognitive, language, and survival measures. Lower RIFR indicated diminished intratumoral connectivity and worse prognosis, while higher values reflected preserved network integration and longer survival. Models incorporating network features yielded areas under the receiver operating characteristic curve of 0.90 in training and 0.86–0.88 in external validation. Supporting analyses suggested that intratumoral functional regions are associated with distinct molecular and cellular characteristics. These findings suggest that intra- and peritumoral networks reflect biologically and functionally distinct tumor subregions and are associated with network-level alterations, brain function, and patient outcome. Interpretation is limited by the hemodynamic basis of rs-fMRI, incomplete data, and limited intraoperative validation. These findings identify individualized intra- and peritumoral connectivity measures as candidate markers of glioma-associated network remodeling and prognosis that require prospective, multimodal validation.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 11","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.71083","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149205986","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

Bispecific NK-Cell Engager Targeting TP53 Mutation Through Integration of a TCR-mimic Antibody 通过整合tcr模拟抗体靶向TP53突变的双特异性nk细胞接合器

IF 14.1

MedComm Pub Date : 2026-10-15 DOI: 10.1002/mco2.71058

Hanfei Wu, Zhe Zhao, Li Zhang, Xuan Xiong, Mengdie Yang, Weiping Ge, Danyue Zhi, Xiaobin Cao, Chuanqian Yi, Yong Qiao, Junjun Cao, Yan Mei, Shiping Jiao, Quan Liu, Hao Zhou, Zhongjuan Xu, Guangli Suo

{"title":"Bispecific NK-Cell Engager Targeting TP53 Mutation Through Integration of a TCR-mimic Antibody","authors":"Hanfei Wu, Zhe Zhao, Li Zhang, Xuan Xiong, Mengdie Yang, Weiping Ge, Danyue Zhi, Xiaobin Cao, Chuanqian Yi, Yong Qiao, Junjun Cao, Yan Mei, Shiping Jiao, Quan Liu, Hao Zhou, Zhongjuan Xu, Guangli Suo","doi":"10.1002/mco2.71058","DOIUrl":"https://doi.org/10.1002/mco2.71058","url":null,"abstract":"Natural killer (NK) cells are valuable for cancer immunotherapy because they kill tumor cells without prior sensitization or human leukocyte antigen (HLA) restriction. However, their efficacy is often limited by immune-evasion, especially major histocompatibility complex I (MHC-I)-mediated NK cell inhibition. NK cell engagers (NKCEs) can redirect NK cells to tumor for more effective immunotherapy, but most current NKCEs target tumor-associated antigens (TAAs), risking on-target, off-tumor toxicity in clinical applications. Neoantigens, as tumor-specific antigens (TSAs) arising from somatic mutations and presented by MHC-I on tumor cell surfaces, represent ideal tumor-specific target. Here, we engineered NKCEs built on neoantigen-targeting TCR-mimic antibodies (TCRm-Abs) to enhance tumor-specific NK cell-mediated cytotoxicity. Using a high-throughput hydrogel-based microwell single-cell chip (HMSC-chip) coupled with T2 cell-based de-selection, we identified C33-Ab, a functional TCRm-Ab specific for p53R175H/HLA-A*02:01, from ∼500,000 hybridoma cells within 8 weeks. Based on this TCRm-Ab, we constructed a bispecific NKCE (C33×CD16), a single-chain diabody (scDb) linking C33-Ab to an anti-CD16 scFv. C33×CD16 specifically bridges NK cells with p53R175H/HLA-A*02:01-positive cancer cells. It potently enhanced NK cell-mediated cytotoxicity in vitro and antitumor efficacy in vivo upon adoptive NK-cell transfer. This TCRm-Ab-based bispecific NKCE offers a promising strategy for tumor-specific NK cell-mediated immunotherapy by targeting intracellular oncogenic hotspot mutations.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 11","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.71058","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177326","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

The PIEZO1/CISD1/IP3R Mechanotransduction Axis Drives Macrophage Mitochondrial Dysfunction and Inflammatory Activation in Pulmonary Fibrosis PIEZO1/CISD1/IP3R机械转导轴驱动肺纤维化中巨噬细胞线粒体功能障碍和炎症激活

IF 14.1

MedComm Pub Date : 2026-10-15 DOI: 10.1002/mco2.71080

Yungeng Wei, Chao Xie, Xiangsheng Yang, Xiao Xiao Tang

{"title":"The PIEZO1/CISD1/IP3R Mechanotransduction Axis Drives Macrophage Mitochondrial Dysfunction and Inflammatory Activation in Pulmonary Fibrosis","authors":"Yungeng Wei, Chao Xie, Xiangsheng Yang, Xiao Xiao Tang","doi":"10.1002/mco2.71080","DOIUrl":"https://doi.org/10.1002/mco2.71080","url":null,"abstract":"Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal interstitial lung disease characterized by excessive extracellular matrix (ECM) deposition and elevated tissue stiffness. While aberrant mechanotransduction is increasingly recognized as a key driver of fibrotic progression, the mechanisms by which mechanical cues orchestrate macrophage dysfunction remain poorly elucidated. Here, we identify the mechanosensitive ion channel PIEZO1 as a key mediator coupling matrix stiffening to macrophage inflammatory activation in pulmonary fibrosis. We demonstrate that PIEZO1 is substantially upregulated in fibrotic lungs, and that its activation drives intracellular calcium overload via the CISD1/IP3R signaling axis. This process elicits aberrant opening of the mitochondrial permeability transition pore (MPTP), causing mitochondrial dysfunction and augmented pro-inflammatory macrophage polarization. Conversely, PIEZO1 inhibition suppresses the CISD1/IP3R signaling cascade, alleviates calcium dysregulation, prevents mitochondrial damage, and attenuates inflammatory activation. In vitro CISD1 inhibition ameliorates PIEZO1-driven mitochondrial abnormalities and pro-inflammatory signaling in macrophages. Furthermore, genetic knockdown of CISD1 mitigates mitochondrial abnormalities and attenuates bleomycin (BLM)-induced lung fibrosis in mice. Collectively, these findings identify a previously unrecognized PIEZO1/CISD1/IP3R mechanotransduction axis coupling tissue stiffening to macrophage-mediated inflammation and fibrosis. This study offers mechanistic insights into fibrosis-associated immune dysregulation, highlighting PIEZO1 and CISD1 as promising therapeutic targets for pulmonary fibrosis.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 11","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.71080","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149177327","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

Blocking Extracellular Cyclophilin A-Mediated Adhesion Protects Against Bacterial Infection. 阻断细胞外亲环蛋白a介导的粘附可防止细菌感染。

IF 14.1

MedComm Pub Date : 2026-10-13 eCollection Date: 2026-10-01 DOI: 10.1002/mco2.71063

Xiaoyuan Bai, Heqiao Li, Pengtao Jiao, Yuna Zhao, Xiaoxiao Jia, Han Zhong Pei, Zeqiu Fan, Runshan Lin, He Zhang, Beinan Wang, Xinhai Chen, Yuhai Bi, De Chang, Zhongfa Zhang, Yuxin Chen, Wenjun Liu, Lei Sun

{"title":"Blocking Extracellular Cyclophilin A-Mediated Adhesion Protects Against Bacterial Infection.","authors":"Xiaoyuan Bai, Heqiao Li, Pengtao Jiao, Yuna Zhao, Xiaoxiao Jia, Han Zhong Pei, Zeqiu Fan, Runshan Lin, He Zhang, Beinan Wang, Xinhai Chen, Yuhai Bi, De Chang, Zhongfa Zhang, Yuxin Chen, Wenjun Liu, Lei Sun","doi":"10.1002/mco2.71063","DOIUrl":"https://doi.org/10.1002/mco2.71063","url":null,"abstract":"Bacterial pneumonia remains a leading cause of mortality and morbidity worldwide and is primarily managed through antibiotic therapy. However, the increasing threat of antimicrobial resistance underscores the urgent need for alternative strategies. In this study, we identify extracellular cyclophilin A (eCypA) as a key host factor that promotes the adherence of bacteria such as group A Streptococcus (GAS) and Streptococcus pneumoniae (S. P.). Using single-nucleus RNA sequencing of mouse lung tissue, we demonstrate that eCypA upregulates the expression of integrin/extracellular matrix adhesion receptors, including integrin α5, fibronectin, and mucin, an effect largely mediated by enhancing the transforming growth factor-β (TGF-β) signaling. Mechanistically, eCypA interacts with TGF-β receptor II, acting as a coactivator to increase its binding to TGF-β1 and amplify downstream signaling. Notably, administration of an anti-CypA monoclonal antibody yields both prophylactic and therapeutic effects against GAS-induced lung damage in mice by reducing bacterial adhesion and suppressing proinflammatory cytokine production. Collectively, these findings identify eCypA as a critical regulator of infection exploited by diverse bacteria that rely on integrin/extracellular matrix for adherence, highlighting eCypA as a promising target for host-directed therapies designed to mitigate bacterial attachment and subsequent inflammation.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":"e71063"},"PeriodicalIF":14.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186003","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

Perioperative Camrelizumab and Apatinib for High-Risk Resectable Hepatocellular Carcinoma: A Phase II Study. 围手术期Camrelizumab和Apatinib治疗高危可切除肝细胞癌：II期研究

IF 14.1

MedComm Pub Date : 2026-10-13 eCollection Date: 2026-10-01 DOI: 10.1002/mco2.70861

Yunlong Cui, Xu Bao, Ge Yu, Feng Fang, Qiang Li, Han Mu, Chen Liu, Qiang Wu, Wei Zhang, Huikai Li, Ping Chen, Xiaomeng Liu, Hongyuan Zhou, Tianqiang Song

{"title":"Perioperative Camrelizumab and Apatinib for High-Risk Resectable Hepatocellular Carcinoma: A Phase II Study.","authors":"Yunlong Cui, Xu Bao, Ge Yu, Feng Fang, Qiang Li, Han Mu, Chen Liu, Qiang Wu, Wei Zhang, Huikai Li, Ping Chen, Xiaomeng Liu, Hongyuan Zhou, Tianqiang Song","doi":"10.1002/mco2.70861","DOIUrl":"https://doi.org/10.1002/mco2.70861","url":null,"abstract":"The optimal perioperative regimen for resectable hepatocellular carcinoma (HCC) remains undefined. This study evaluated the efficacy and safety of perioperative camrelizumab combined with apatinib in patients with resectable high-risk HCC. In this single-arm, phase II study, 31 patients with resectable HCC and high recurrence risk factors (e.g., large tumor size, multinodularity, and vascular invasion) received neoadjuvant camrelizumab (200 mg every 2 weeks) and apatinib (250 mg daily) for four cycles, followed by surgical resection and adjuvant therapy with the same regimen for up to 1 year. The primary endpoint was major pathological response (MPR), defined as ≤ 50% viable tumor cells in resected specimens. A total of 31 patients were enrolled in the study. Among 26 patients who underwent surgery, the MPR rate was 46.2%. The median disease-free survival (DFS) in patients who underwent surgery was 24.1 months (95% confidence interval [CI]: 14.4-not estimable [NE]). The median progression-free survival (PFS) in all patients was 18.3 months (95% CI: 11.6-NE). In the neoadjuvant setting, Grade 3 or higher adverse events were observed in 12.9% of patients. Perioperative camrelizumab combined with apatinib demonstrated promising efficacy and manageable safety in high-risk resectable HCC.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":"e70861"},"PeriodicalIF":14.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187120","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

Carbon Quantum Dots: From Mechanisms to Biomedical Applications. 碳量子点：从机制到生物医学应用。

IF 14.1

MedComm Pub Date : 2026-10-13 eCollection Date: 2026-10-01 DOI: 10.1002/mco2.71062

Bingxin Fan, Nianqiang Jin, Nuo Jin, Jiayu Shen, Xinliang Duan, Sichen Han, Yao Yuan, Zilin Wang

{"title":"Carbon Quantum Dots: From Mechanisms to Biomedical Applications.","authors":"Bingxin Fan, Nianqiang Jin, Nuo Jin, Jiayu Shen, Xinliang Duan, Sichen Han, Yao Yuan, Zilin Wang","doi":"10.1002/mco2.71062","DOIUrl":"https://doi.org/10.1002/mco2.71062","url":null,"abstract":"Carbon quantum dots (CQDs) have emerged as promising nanomaterials for biomedical applications, including bioimaging, drug delivery, biosensing, and tissue regeneration, owing to their favorable biocompatibility, tunable physicochemical properties, and diverse biological activities. Despite accumulating evidence of their regenerative potential, the mechanisms by which CQDs regulate complex tissue regeneration remain insufficiently integrated. In this Review, we synthesize recent advances in the biomedical applications of CQDs, with particular emphasis on material selection for specific disease contexts and their direct and indirect regulatory roles in tissue regeneration. We examine how CQDs modulate cellular functions, angiogenesis, stem cell differentiation, the immune microenvironment, and redox homeostasis through molecular pathways, and how their physicochemical properties shape these biological effects and regenerative outcomes. We further discuss emerging strategies for functional optimization, including multifunctional and stimuli-responsive CQD systems. Finally, we critically assess key translational barriers, including structural characterization, biological evaluation, safety assessment, material standardization, and manufacturing consistency. By linking CQDs' properties to molecular mechanisms and regenerative outcomes, this Review provides a conceptual framework for the rational design of CQDs and the development of more effective regenerative therapies.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":"e71062"},"PeriodicalIF":14.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186390","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

Network Biology: Current Status, Applications, Challenges, and Future Prospects. 网络生物学：现状、应用、挑战和未来展望。

IF 14.1

MedComm Pub Date : 2026-10-13 eCollection Date: 2026-10-01 DOI: 10.1002/mco2.71065

Xinmeng Li, Laizhong Zhang, Yawen Ding, Kai Li, Shiyuan Chang, Linsen Pei, Zhengwei Li, Zhenzhen Chen

{"title":"Network Biology: Current Status, Applications, Challenges, and Future Prospects.","authors":"Xinmeng Li, Laizhong Zhang, Yawen Ding, Kai Li, Shiyuan Chang, Linsen Pei, Zhengwei Li, Zhenzhen Chen","doi":"10.1002/mco2.71065","DOIUrl":"https://doi.org/10.1002/mco2.71065","url":null,"abstract":"Network biology provides a systems-level framework for understanding how interactions among molecular components, cells, microbial communities, tissues, and organs generate biological function and disease phenotypes. Recent advances in multiomics, single-cell and spatial profiling, network inference, organoid and organ-on-chip technologies, computational modeling, and artificial intelligence have shifted the field from static molecular maps toward dynamic, multiscale, and predictive network models. Major branches include molecular interaction networks, intracellular regulatory networks, single-cell and multicellular networks, microbial networks, disease networks, and interorgan interaction networks. Experimental and computational approaches are compared with respect to network reconstruction, causal validation, and cross-scale integration. Biomedical applications span disease classification, biomarker discovery, therapeutic-target identification, drug-response prediction, regenerative medicine, and precision healthcare. Particular emphasis is placed on interorgan interaction networks, in which carrier, route, range, timescale, recipient specificity, directionality, and feedback are treated as distinct mechanistic dimensions while mechanistic confidence is distinguished from translational maturity. Persistent challenges include incomplete context-specific network reconstruction, uncertain causal directionality, limited cross-scale integration, model interpretability, and insufficient clinical validation. Further progress will depend on integrating longitudinal and perturbation-resolved measurements with human-relevant experimental systems and multiscale computational models that quantify uncertainty and support prospective validation of patient-specific predictions.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":"e71065"},"PeriodicalIF":14.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187062","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

Advanced Glycation End Products: From Pathogenesis to Treatment. 晚期糖基化终产物：从发病机制到治疗。

IF 14.1

MedComm Pub Date : 2026-10-13 eCollection Date: 2026-10-01 DOI: 10.1002/mco2.71073

Tak-Ho Lo, Junying Zou, Jingyi Zhang, Kaijun Lin, Minhui Zhu, Shuangqi Lu, Xin Liu, Mengyao Wu

{"title":"Advanced Glycation End Products: From Pathogenesis to Treatment.","authors":"Tak-Ho Lo, Junying Zou, Jingyi Zhang, Kaijun Lin, Minhui Zhu, Shuangqi Lu, Xin Liu, Mengyao Wu","doi":"10.1002/mco2.71073","DOIUrl":"https://doi.org/10.1002/mco2.71073","url":null,"abstract":"Advanced glycation end products (AGEs) are chemically heterogeneous modifications generated through nonenzymatic glycation, glycoxidation, and carbonyl stress. Their accumulation increases during aging and is accelerated by hyperglycemia, oxidative stress, inflammation, exogenous exposure, and impaired renal clearance. Although AGE biology has often been framed around the AGE-RAGE-oxidative stress axis, current evidence supports a broader systems-level model in which AGE burden reflects the balance among formation, detoxification, tissue retention, and clearance. This review summarizes AGE chemistry, endogenous and exogenous sources, detoxification pathways, receptor systems, and mechanisms of AGE-mediated tissue injury. We distinguish two complementary pathogenic routes: receptor-independent structural damage, including protein dysfunction, proteostatic stress, extracellular matrix crosslinking, and altered tissue mechanics; and receptor-dependent signaling, mainly through RAGE-mediated redox-inflammatory amplification. We then examine the clinical relevance of AGEs in diabetes, cardiovascular disease, chronic kidney disease, neurovascular and retinal dysfunction, fibrosis, and aging-related tissue decline. Particular attention is given to compartment-specific biomarker interpretation, because circulating free adducts, protein-bound AGEs, tissue autofluorescence, dietary AGE estimates, and dicarbonyl stress markers are not interchangeable. Finally, we evaluate therapeutic strategies and propose a framework that matches each intervention to the relevant mechanism and can be tested clinically. In doing so, the review clarifies major conceptual and methodological uncertainties in AGE research and provides a foundation for more rigorous biomarker interpretation, study design, and clinical translation.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":"e71073"},"PeriodicalIF":14.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13660708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149187284","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

Efficacy and Safety of Fruquintinib Plus TAS-102 in Patients With Previously Treated Metastatic Colorectal Cancer: Results From a Single-Arm, Multi-Center, Phase II Study. fruquininib + TAS-102治疗转移性结直肠癌的疗效和安全性：来自单组、多中心、II期研究的结果

IF 14.1

MedComm Pub Date : 2026-10-13 eCollection Date: 2026-10-01 DOI: 10.1002/mco2.71070

Jianjun Peng, Yong Li, Ling Huang, Jianhua Liu, Jianjun Xiao, Derong Xie, Wei Wang, Zongcheng Zhang, Chengyin Weng, Xiaoshu Chai, Huifen Li, Xiaomei Jiang, Yan Qian, Risheng Zhao, Sile Chen, Zhimin Jiang, Lingdan Le, Xueqin Li, Jianting Long, Haibo Zhang, Chuangqi Chen, Shirong Cai

{"title":"Efficacy and Safety of Fruquintinib Plus TAS-102 in Patients With Previously Treated Metastatic Colorectal Cancer: Results From a Single-Arm, Multi-Center, Phase II Study.","authors":"Jianjun Peng, Yong Li, Ling Huang, Jianhua Liu, Jianjun Xiao, Derong Xie, Wei Wang, Zongcheng Zhang, Chengyin Weng, Xiaoshu Chai, Huifen Li, Xiaomei Jiang, Yan Qian, Risheng Zhao, Sile Chen, Zhimin Jiang, Lingdan Le, Xueqin Li, Jianting Long, Haibo Zhang, Chuangqi Chen, Shirong Cai","doi":"10.1002/mco2.71070","DOIUrl":"https://doi.org/10.1002/mco2.71070","url":null,"abstract":"The clinical efficacy of currently available third- and later-line treatment regimens for patients with metastatic colorectal cancer (mCRC) remains suboptimal. This study was designed to investigate fruquintinib plus TAS-102 regimen in this patient population. This study was a prospective, multi-center, single-arm phase II trial. A total of 50 patients with mCRC who had experienced treatment failure to at least two standard therapies were enrolled. The primary endpoint was progression-free survival (PFS) and secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), and safety. Survival outcomes were estimated using the Kaplan-Meier method. With a median follow-up duration of 25.1 months, the median PFS was 6.07 months (95% CI: 4.07-7.87) and the median OS was 14.10 months (95% CI: 9.84-23.28). The ORR was 10.0% (95% CI: 3.3-21.8), with a DCR of 66.0% (95% CI: 51.2-78.8). All the patients experienced treatment-related adverse events (TRAEs), with 68.0% reporting grade ≥ 3 TRAEs. No serious adverse events (AEs), deaths, or new safety concerns were reported. In conclusion, fruquintinib combined with TAS-102 showed preliminary anti-tumor activity with a manageable safety profile in patients with refractory mCRC, which highlights its potential as a viable later-line therapeutic option. Trial Registration: NCT05004831.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":"e71070"},"PeriodicalIF":14.1,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13659284/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186409","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}

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