MedComm最新文献_第10页

Dynamic Changes of Neutrophil Nuclear Membrane CD63 as a Potential Biomarker for Early Adjunctive Diagnosis and Prognostic Evaluation of Sepsis in Critically Ill Patients: A Prospective Cohort Study 中性粒细胞核膜CD63作为危重症患者早期辅助诊断和预后评估的潜在生物标志物的动态变化：一项前瞻性队列研究

IF 14.1

MedComm Pub Date : 2026-09-16 DOI: 10.1002/mco2.71007

Xingxin Gao, Min Zhang, Linbin Li, Haihua Lyu, Zhihao Liu, Xucheng Wei, Dehui Li, Yiming Shao

{"title":"Dynamic Changes of Neutrophil Nuclear Membrane CD63 as a Potential Biomarker for Early Adjunctive Diagnosis and Prognostic Evaluation of Sepsis in Critically Ill Patients: A Prospective Cohort Study","authors":"Xingxin Gao, Min Zhang, Linbin Li, Haihua Lyu, Zhihao Liu, Xucheng Wei, Dehui Li, Yiming Shao","doi":"10.1002/mco2.71007","DOIUrl":"10.1002/mco2.71007","url":null,"abstract":"Sepsis has high intensive care unit mortality because biomarkers for early reversible pathological events are lacking. Targeted nuclear degranulation, the rate-limiting step in neutrophil extracellular trap formation, refers to azurophilic granule fusion with the nuclear membrane. As an exclusive granule membrane marker, CD63 enrichment in nuclear membranes directly reflects this early pathogenic process. We developed a flow cytometry assay to quantify nuclear membrane CD63 (nmCD63) and validated its clinical utility in a two-center prospective cohort with strict independent external validation. Assay protocols, diagnostic cutoffs, and combined models were established for the derivation cohort (n = 180) and applied without recalibration to the validation cohort (n = 76) comprising 256 participants. nmCD63 levels increased progressively with disease severity. They differentiated non-infectious systemic inflammation from non-severe infections (area under the curve [AUC] = 0.794) and outperformed C-reactive protein and procalcitonin levels. Combined with the Sequential Organ Failure Assessment score, nmCD63 achieved an AUC of 0.943 for identifying sepsis in patients with a confirmed infection. Dynamic nmCD63 shifts preceded changes in all conventional biomarkers, and 7-day trajectories enabled reliable prognostic stratification. This study translates targeted nuclear degranulation as a practical biomarker with dual diagnostic and prognostic value for sepsis in critically ill patients.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13583469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148993357","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

Inhibition of COX-2-Mediated Arachidonic Acid Metabolism by FGF21-PPARα Axis Alleviates Liver Steatosis FGF21-PPARα轴抑制cox -2介导的花生四烯酸代谢减轻肝脏脂肪变性

IF 14.1

MedComm Pub Date : 2026-09-15 DOI: 10.1002/mco2.70999

Guangsen Xu, Tingting Pan, Guiyun Wang, Feng Qiu, Junlin Leng, Qiyang Feng, Yongguo Xue, Ye Wang, Junwei Zheng, Huiying Lu, Bingyan Han, Suntao Wang, Jie Du, Jiaojian Lv, Baile Wang, Xuebo Pan

{"title":"Inhibition of COX-2-Mediated Arachidonic Acid Metabolism by FGF21-PPARα Axis Alleviates Liver Steatosis","authors":"Guangsen Xu, Tingting Pan, Guiyun Wang, Feng Qiu, Junlin Leng, Qiyang Feng, Yongguo Xue, Ye Wang, Junwei Zheng, Huiying Lu, Bingyan Han, Suntao Wang, Jie Du, Jiaojian Lv, Baile Wang, Xuebo Pan","doi":"10.1002/mco2.70999","DOIUrl":"https://doi.org/10.1002/mco2.70999","url":null,"abstract":"Metabolic dysfunction-associated steatotic liver disease (MASLD) is associated with disturbances in arachidonic acid (AA) metabolism; however, the role and regulation of cyclooxygenase-2 (COX-2), a key enzyme in AA metabolism, during disease progression remain incompletely understood. Here, we identify fibroblast growth factor 21 (FGF21) as a previously unrecognized suppressor of hepatic COX-2 in MASLD. Although both FGF21 and COX-2 were elevated in steatotic livers, FGF21 deficiency further augmented hepatic COX-2 expression in mice fed with a high-fat diet, leading to dysregulated AA metabolism, excessive prostaglandin E2 (PGE2) production, aggravated inflammation, oxidative stress, and fibrosis. Conversely, adeno-associated virus (AAV)-mediated restoration of FGF21 normalized COX-derived AA metabolites, suppressed COX-2 activation, and ameliorated hepatic injury. Pharmacological inhibition of COX-2 partially recapitulated the protective effects of FGF21 but failed to reverse fibrosis, suggesting that COX-2 contributes to disease progression but is not sufficient to account for fibrosis. Mechanistically, FGF21 suppressed COX-2 through a PPARα-dependent pathway, whereas ERK1/2 phosphorylation acted upstream of the FGF21/PPARα axis. In patients with MASLD, circulating PGE2 was positively associated with liver injury after adjustment for body mass index and hepatic steatosis. Collectively, the FGF21-PPARα-COX-2 axis represents a critical regulator of AA metabolic remodeling and a potential therapeutic target for MASLD.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70999","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962570","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

Cooccurrence of Homologous Recombination Deficiency and Mismatch Repair Deficiency in Colorectal Cancer 结直肠癌中同源重组缺陷和错配修复缺陷的共同发生

IF 14.1

MedComm Pub Date : 2026-09-15 DOI: 10.1002/mco2.70991

Xu Zhang, Hao Xu, Kailai Wang, Wangxiong Hu

{"title":"Cooccurrence of Homologous Recombination Deficiency and Mismatch Repair Deficiency in Colorectal Cancer","authors":"Xu Zhang, Hao Xu, Kailai Wang, Wangxiong Hu","doi":"10.1002/mco2.70991","DOIUrl":"https://doi.org/10.1002/mco2.70991","url":null,"abstract":"Homologous recombination deficiency (HRD) in colorectal cancer (CRC) remains largely unexplored. In contrast, mismatch repair deficiency (dMMR) occurs in ∼15% of patients with CRC. Although HRD and dMMR have historically been regarded as mutually exclusive, emerging evidence suggests that this mutual exclusivity may not be absolute. Here, we conducted a retrospective cohort study utilizing genomic and transcriptomic data to define HRD status in a Chinese dMMR CRC cohort (n = 99). Multiple machine learning approaches were employed to analyze the expression profiles of these tumors and to develop a classifier distinguishing HRD from homologous recombination proficiency (HRP) in dMMR CRCs. In the Chinese dMMR CRC cohort, 66% of tumors were classified as HRD. Compared with the HRP group, the HRD group had a significantly higher tumor mutational burden and better outcomes. The derived expression signature, comprising eight genes, successfully predicted HRD status in dMMR tumors with high accuracy in the training set (AUC = 0.88, Naïve Bayes) and the test set (AUC = 0.87). In this study, a subset of dMMR CRC tumors with co-occurring HRD was identified, which may have potential implications for patient stratification and the application of targeted therapies, such as PARP inhibitors, in this molecular subgroup.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70991","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962568","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

Neutrophil Extracellular Traps in Atherosclerosis and Cardiovascular Disease 动脉粥样硬化和心血管疾病中的中性粒细胞胞外陷阱

IF 14.1

MedComm Pub Date : 2026-09-15 DOI: 10.1002/mco2.70912

Ji Zhang, Fangjiaqi Wei, Mengdi Qu, Yuwen Shao, Tingye Xu, Darko Stojkov, Hans-Uwe Simon, Ben Huang, Changhong Miao, Hao Zhang

{"title":"Neutrophil Extracellular Traps in Atherosclerosis and Cardiovascular Disease","authors":"Ji Zhang, Fangjiaqi Wei, Mengdi Qu, Yuwen Shao, Tingye Xu, Darko Stojkov, Hans-Uwe Simon, Ben Huang, Changhong Miao, Hao Zhang","doi":"10.1002/mco2.70912","DOIUrl":"https://doi.org/10.1002/mco2.70912","url":null,"abstract":"Atherosclerosis is a chronic inflammatory disease of the arterial wall and the leading pathological basis of cardiovascular morbidity and mortality worldwide. Neutrophil extracellular traps (NETs), web-like chromatin structures armed with histones, myeloperoxidase, and serine proteases, have emerged as active participants in vascular inflammation and thrombosis. Under physiological conditions, NETs contribute to host defense and immunothrombosis, but excessive or persistent NET formation drives endothelial injury, plaque progression, and acute coronary events. However, how NETs shift from protective to pathological across the atherosclerotic continuum, and how their individual components cooperate to amplify vascular damage, remain insufficiently understood. This review explores NET homeostasis in the cardiovascular system and the balance between protective and pathological NET release. We then describe the molecular mechanisms of NET formation and the cooperative actions of NET components as an integrated thrombo-inflammatory platform. Next, we discuss stage-specific NET roles throughout atherogenesis, plaque destabilization, and ischemia–reperfusion injury. Finally, we evaluate clinical and translational evidence linking NET biomarkers to cardiovascular outcomes and critically assess precision-targeted NET therapies. This framework highlights NETs as both mechanistic drivers and promising therapeutic targets in atherosclerotic cardiovascular disease.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962571","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

Mucosal-Associated Invariant T Cells in Health and Disease 健康和疾病中粘膜相关的不变性T细胞

IF 14.1

MedComm Pub Date : 2026-09-15 DOI: 10.1002/mco2.70996

Yu Zhao, Feng-Mi Ou, Dan Liang, Yang Gao, Qing-Qing Li, Yi-Qun Kuang

{"title":"Mucosal-Associated Invariant T Cells in Health and Disease","authors":"Yu Zhao, Feng-Mi Ou, Dan Liang, Yang Gao, Qing-Qing Li, Yi-Qun Kuang","doi":"10.1002/mco2.70996","DOIUrl":"https://doi.org/10.1002/mco2.70996","url":null,"abstract":"Mucosal-associated invariant T (MAIT) cells are a population of evolutionarily conserved, unconventional innate-like T lymphocytes that are restricted by major histocompatibility complex Class I-related (MR1) molecules. They can be activated either in a T-cell receptor–MR1- or cytokine-dependent manner. Activated MAIT cells play crucial roles in maintaining homeostasis and the fine regulation of the immune system. This review presents a systematic exploration of the development, biological characteristics, and multiple effects of MAIT cells in health and various diseases. In healthy individuals, MAIT cells maintain mucosal barrier integrity, participate in tissue repair after injury, and prevent excessive inflammation. In microbial infections, MAIT cells eliminate infected cells and modulate immune responses or become pathogenic when overactivated by superantigens. In the context of immune-related diseases, MAIT cells migrate to inflamed tissues and become pathogenic by secreting tissue-damaging cytokines or protective by modulating immune responses. Moreover, MAIT cells have been demonstrated to have therapeutic applications in controlling diseases through their use as cellular adjuvants, their increased activation by engineered bacteria, and their modification with chimeric antigen receptors. This review synthesizes the functional plasticity of MAIT cells in health and disease, highlighting the therapeutic efficacy and limitations of engineered MAIT cells for precise intervention.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70996","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962572","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

Post-Tuberculosis Lung Disease: Clinicopathologic Insights, Diagnosis, Prevention, and Management 结核后肺病：临床病理见解、诊断、预防和管理

IF 14.1

MedComm Pub Date : 2026-09-15 DOI: 10.1002/mco2.70974

Radha Gopalaswamy, Selvakumar Subbian

{"title":"Post-Tuberculosis Lung Disease: Clinicopathologic Insights, Diagnosis, Prevention, and Management","authors":"Radha Gopalaswamy, Selvakumar Subbian","doi":"10.1002/mco2.70974","DOIUrl":"https://doi.org/10.1002/mco2.70974","url":null,"abstract":"Post-tuberculosis lung disease (PTLD) encompasses a spectrum of chronic pulmonary abnormalities arising from tuberculosis (TB)-associated tissue injury and maladaptive repair, and is emerging as a major contributor to long-term respiratory disability among TB survivors. In this review, we position PTLD within the broader continuum of TB pathobiology, from initial host–pathogen interactions to chronic structural and functional lung sequelae. We examine current definitions, epidemiology, and clinical burden, and present mechanistic insights into the inflammatory, proteolytic, fibrotic, immunometabolic, and vascular pathways that drive persistent lung damage. We further discuss the heterogeneous clinical phenotypes of PTLD, including airflow obstruction, bronchiectasis, restrictive lung disease, pleural complications, chronic pulmonary aspergillosis, and nontuberculous mycobacterial disease, highlighting practical approaches to diagnosis, risk stratification, and management across diverse healthcare settings. We discuss PTLD in children and adolescents, prevention opportunities throughout the TB care cascade, and health-system strategies for integrating post-TB care. Finally, we identify key knowledge gaps in PTLD nosology, biomarkers, therapeutic development, clinical trial design, and implementation science. Recognition of PTLD as a continuation rather than an endpoint of TB is essential for advancing survivorship-focused care and reducing the global burden of chronic respiratory disease after TB.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70974","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962569","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 Co-Ablation Combined With Aintilimab for Metastatic Melanoma to the Liver (CryoCheck-001): A Phase II Trial 联合安替单抗治疗肝脏转移性黑色素瘤的疗效和安全性（CryoCheck-001）：一项II期试验

IF 14.1

MedComm Pub Date : 2026-09-15 DOI: 10.1002/mco2.70997

Lujun Shen, Letao Lin, Shuanggang Chen, Chen Li, Ruizhi Tang, Lin Xie, Yujia Wang, Yunpeng Li, Hongliang Zou, Dandan Li, Xiaoshi Zhang, Weijun Fan

{"title":"Efficacy and Safety of Co-Ablation Combined With Aintilimab for Metastatic Melanoma to the Liver (CryoCheck-001): A Phase II Trial","authors":"Lujun Shen, Letao Lin, Shuanggang Chen, Chen Li, Ruizhi Tang, Lin Xie, Yujia Wang, Yunpeng Li, Hongliang Zou, Dandan Li, Xiaoshi Zhang, Weijun Fan","doi":"10.1002/mco2.70997","DOIUrl":"https://doi.org/10.1002/mco2.70997","url":null,"abstract":"Liver metastasis is a key driver of immune tolerance in melanoma, limiting immune checkpoint inhibitor efficacy. This prospective single-arm phase II trial investigated the efficacy and safety of co-ablation combined with sintilimab for liver-metastatic melanoma (ChiCTR2200061591). Eligible patients received sintilimab (anti-PD-1, 200 mg every 3 weeks) for up to eight cycles alongside co-ablation. The primary endpoint was a 6-month progression-free survival (PFS) rate per Response Evaluation Criteria in Solid Tumors v1.1. Secondary endpoints included overall survival (OS), PFS time, and overall response rate (ORR). Between June 2022 and July 2025, 16 patients were enrolled. Three patients achieved a partial response (ORR 18.75%). The 6-month PFS rate was 31.25% (95% confidence interval [CI]: 15.1–64.6), with a median PFS of 3.94 months (95% CI: 2.77–14.30). The 12- and 24-month OS rates were 53.8% (95% CI: 33.7–86.0) and 28.7% (10.3–80.1), respectively; median OS was 16.67 months (95% CI: 7.50–NR). Grade ≥ 3 treatment-related adverse events occurred in 14 of 16 patients (87.5%), the most common being elevated liver enzyme levels. Co-ablation combined with sintilimab demonstrates a manageable safety profile and encouraging antitumor activity in patients with liver-metastatic melanoma, meriting further evaluation.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 10","pages":""},"PeriodicalIF":14.1,"publicationDate":"2026-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70997","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148962646","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

Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry. 癌症神经科学：从局部神经免疫微环境到全身脑-体回路。

IF 14.1

MedComm Pub Date : 2026-09-11 eCollection Date: 2026-09-01 DOI: 10.1002/mco2.71025

Mingxuan Xie, Yu Zhao, Xinruo Xing, Yuqiang Liu, Jungang Zhao, Maojin Yao, Jun Tang, Jianzhu Zhao

{"title":"Cancer Neuroscience: From Local Neuro-Immune Microenvironments to Systemic Brain-Body Circuitry.","authors":"Mingxuan Xie, Yu Zhao, Xinruo Xing, Yuqiang Liu, Jungang Zhao, Maojin Yao, Jun Tang, Jianzhu Zhao","doi":"10.1002/mco2.71025","DOIUrl":"10.1002/mco2.71025","url":null,"abstract":"Classic oncological models have largely restricted cancer pathogenesis to autonomous genetic mutations within localized cells. Current research, however, reframes solid tumors as structurally integrated \"pseudo-organs\" that rely on host neural networks for survival. This review examines the reciprocal signaling networks connecting nervous, immune, and malignant cells within the tumor microenvironment. At the tissue level, we outline how tumors construct de novo neural architecture via axonogenesis, cellular plasticity, and the assembly of functional neuro-neoplastic synapses. Expanding beyond the local niche, we describe the systemic brain-body circuitry. We specifically address how central nervous system pathways respond to tumor-derived cues and how chronic stress signaling disrupts physiological homeostasis. To explain the associated immune evasion, we analyze how sensory neuropeptides, particularly CGRP and, more broadly, Substance P-NK1R signaling, contribute to immune dysfunction, tumor-promoting inflammation, and therapeutic resistance. Finally, we discuss the clinical implications of these pathways. Rather than relying on nonspecific structural denervation, future therapeutic strategies should focus on targeted \"neural reprogramming\" to uncouple tumors from their neural dependencies and restore antitumor immunity while minimizing neurotoxicity. Ultimately, this review conceptualizes solid tumors as systemically integrated entities, establishing a framework for precision neural reprogramming to overcome immune evasion and therapeutic resistance.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 9","pages":"e71025"},"PeriodicalIF":14.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13563386/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148956942","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

Heat Shock Proteins in Cancer: Mechanisms and Therapeutic Targeting. 热休克蛋白在癌症中的作用：机制和治疗靶向。

IF 14.1

MedComm Pub Date : 2026-09-11 eCollection Date: 2026-09-01 DOI: 10.1002/mco2.70966

Sheng Ma, Chen-Qian Liu, Si-Yang Ma, Shao-Gang Wang, Qi-Dong Xia, Meng-Yao Xu

{"title":"Heat Shock Proteins in Cancer: Mechanisms and Therapeutic Targeting.","authors":"Sheng Ma, Chen-Qian Liu, Si-Yang Ma, Shao-Gang Wang, Qi-Dong Xia, Meng-Yao Xu","doi":"10.1002/mco2.70966","DOIUrl":"10.1002/mco2.70966","url":null,"abstract":"Heat shock proteins (HSPs) are molecular chaperones that couple proteostasis to cancer metabolic reprogramming under oncogenic and microenvironmental stress. This Review integrates structural, biochemical, preclinical, and clinical evidence on HSP90, HSP70, HSP60, HSP40, HSP110, and small HSPs. We explain how ATPase cycles, chaperonin cages, co-chaperone networks, and organelle-specific localization stabilize metabolic enzymes, glucose transporters, hypoxia-responsive factors, and electron-transport-chain components, thereby coordinating glycolysis, mitochondrial bioenergetics, redox homeostasis, lipid metabolism, and metabolic plasticity. These mechanisms enable tumor survival and therapy resistance but also create context-dependent vulnerabilities. We critically evaluate pan-HSP and isoform-selective inhibitors, disruption of chaperone-client or co-chaperone interfaces, HSP-directed immunotherapies, and biomarker-guided combinations with metabolic or immune therapies. Clinical translation remains limited by systemic toxicity, compensatory heat-shock responses, tumor-type heterogeneity, and the absence of validated predictive biomarkers. We also assess circulating HSPs, cryo-EM analysis of chaperone complexes, and AI-assisted ligand design as routes for biomarker development and selective drug discovery. By linking chaperone architecture and client specificity to metabolic outputs and cancer phenotypes, this Review establishes a framework for differentiating actionable HSP dependencies from observational associations. It further defines priorities for patient stratification and precision oncology, supporting the development of selective and tractable strategies that target proteostasis-metabolism coupling.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 9","pages":"e70966"},"PeriodicalIF":14.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957583","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

SKP2 Regulates Pulmonary Inflammatory Injury Triggered by Bacterial Infection Through p27-Mediated Degradation of FOXN3. SKP2通过p27介导的FOXN3降解调控细菌感染引发的肺部炎性损伤。

IF 14.1

MedComm Pub Date : 2026-09-11 eCollection Date: 2026-09-01 DOI: 10.1002/mco2.70963

Jinjin Yu, Xinghong Hu, Huanhuan Wang, Jingyu Yu, Lele Jin, Yingke Li, Jihong Zhou, Xinxing Zhu, Emmanuel Jairaj Moses, Chunfu Zheng, Yong Zhang, Wei Li

{"title":"SKP2 Regulates Pulmonary Inflammatory Injury Triggered by Bacterial Infection Through p27-Mediated Degradation of FOXN3.","authors":"Jinjin Yu, Xinghong Hu, Huanhuan Wang, Jingyu Yu, Lele Jin, Yingke Li, Jihong Zhou, Xinxing Zhu, Emmanuel Jairaj Moses, Chunfu Zheng, Yong Zhang, Wei Li","doi":"10.1002/mco2.70963","DOIUrl":"10.1002/mco2.70963","url":null,"abstract":"Excessive inflammatory responses are a primary driver of acute lung injury, yet the underlying molecular mechanisms remain incompletely understood. In this study, we identify SKP2, an E3 ubiquitin ligase, as a critical negative regulator of pulmonary inflammation during methicillin-resistant Staphylococcus aureus (MRSA) infection. Mechanistically, SKP2 promotes the degradation of its direct substrate p27kip1 (p27), which functions as an activator of a noncanonical NF-κB signaling pathway. We further demonstrate that p27 facilitates the recruitment of p38 kinase to heterogeneous nuclear ribonucleoprotein-U (hnRNPU), leading to direct phosphorylation of the transcriptional repressor FOXN3 at serine residues 83 and 85. This dual phosphorylation event triggers subsequent proteasomal degradation of FOXN3, thereby relieving transcriptional repression and enabling NF-κB-driven activation of pro-inflammatory genes. In vivo, genetic ablation of Skp2 worsens pulmonary inflammatory injury, elevates neutrophil infiltration, and significantly reduces survival in MRSA-infected mice, and these effects are greatly rescued by concurrent p27 depletion. Collectively, our findings uncover the SKP2-p27-FOXN3 axis as a pivotal regulatory module in pulmonary inflammation and suggest that targeting this axis may offer a promising therapeutic strategy for bacterial infection-induced lung injury.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 9","pages":"e70963"},"PeriodicalIF":14.1,"publicationDate":"2026-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13570262/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148957689","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