IF 10.7

MedComm Pub Date : 2026-04-12 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70729

Shuning Zhang, Jingmin Li, Meihuan Chen, Hailong Huang

{"title":"Post-translational Modifications in Proteins: Prediction Methods, Biological Functions, and Diseases.","authors":"Shuning Zhang, Jingmin Li, Meihuan Chen, Hailong Huang","doi":"10.1002/mco2.70729","DOIUrl":"https://doi.org/10.1002/mco2.70729","url":null,"abstract":"Posttranslational modifications (PTMs) act as rapid, reversible switches that reshape protein activity, stability, and interactome, thereby governing virtually every physiological cue from signal transduction to epigenetic memory. Mass spectrometry-based proteomics has considerably extended our knowledge about the occurrence and dynamics of PTMs. Pinpointing disease- or physiology-specific PTM sites remains an open challenge. As a biological process with well-defined stage-specific markers and a precise endpoint, erythropoiesis is orchestrated by the complex interplay of multiple PTM-regulatory networks, making it an ideal model for dissecting the spatiotemporal dynamics, quantitative thresholds, and crosstalk of PTMs. This review delineates the applications, detection, and prediction technologies of PTMs, with an emphasis on the mechanisms of phosphorylation, ubiquitination, methylation, SUMOylation, glycosylation, and acetylation in both physiological and pathological processes. Dissecting PTM circuitry driving erythroid specification and maturation, we show how its perturbation triggers disease, clarifying PTM roles. Additionally, we have investigated the progress made in the clinical translation and drug development of the PTMs field, emphasizing the potential of PTMs in the field of precision medicine as well as the existing challenges. This review aims to provide new insights and perspectives for the study of PTMs.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 ","pages":"e70729"},"PeriodicalIF":10.7,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070201/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679817","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

Epilepsy: Molecular Pathogenesis and Emerging Therapies. 癫痫：分子发病机制和新兴疗法。

IF 10.7

MedComm Pub Date : 2026-04-12 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70735

Wanbin Huang, Jiabin Zong, Yu Zhang, Ming Li, Songqing Pan, Zheman Xiao

{"title":"Epilepsy: Molecular Pathogenesis and Emerging Therapies.","authors":"Wanbin Huang, Jiabin Zong, Yu Zhang, Ming Li, Songqing Pan, Zheman Xiao","doi":"10.1002/mco2.70735","DOIUrl":"https://doi.org/10.1002/mco2.70735","url":null,"abstract":"Epilepsy is a prevalent and often severe neurological disorder with significant economic and societal impacts. Despite adequate trials with two or more antiseizure medications (ASMs), approximately one-third of patients continue to experience drug-resistant epilepsy. Surgery remains the most effective treatment for patients with drug-resistant focal epilepsy, yet it may be underutilized. Given the unsatisfactory clinical outcomes, it is imperative to investigate the molecular pathogenesis of epilepsy and to develop novel therapeutic strategies. This review systematically outlines the advances in understanding the etiology and molecular pathogenesis of epilepsy. These advances have identified diverse therapeutic targets, stimulating the development of emerging therapies, including novel ASM, minimally invasive surgery, neurostimulation, focused ultrasound, nanomedicine, gamma-aminobutyric acid (GABA)ergic cell therapy, and gene therapy. Additionally, the review comprehensively evaluates emerging therapies for epilepsy from different perspectives by integrating findings from both preclinical and clinical studies. These innovative approaches offer the potential for long-term seizure control. A great deal of future research is still needed to overcome current shortcomings. This work provides a cohesive framework that bridges molecular mechanisms with therapeutic applications. Such efforts may provide novel ideas and optimizing approaches in the field, ultimately advancing the precision and effectiveness of epilepsy treatments in the future.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 ","pages":"e70735"},"PeriodicalIF":10.7,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070203/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679646","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

Targeted Therapies for Each Subtype of Breast Cancer. 针对乳腺癌各亚型的靶向治疗。

IF 10.7

MedComm Pub Date : 2026-04-12 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70733

Aiyu Liu, Puchao Peng, Yeke Zhu, Qiuwen Fei, Weiwei Liu, Shizhen Zhang

{"title":"Targeted Therapies for Each Subtype of Breast Cancer.","authors":"Aiyu Liu, Puchao Peng, Yeke Zhu, Qiuwen Fei, Weiwei Liu, Shizhen Zhang","doi":"10.1002/mco2.70733","DOIUrl":"https://doi.org/10.1002/mco2.70733","url":null,"abstract":"Breast cancer (BC) is a clinically heterogeneous malignancy and a leading cause of cancer-related mortality in women worldwide. It is classified into hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-positive, and triple-negative (TNBC) subtypes based on molecular biomarkers. This heterogeneity drives distinct disease progression and treatment responses, making subtype-specific precision therapy indispensable for improving patient outcomes. While estrogen receptor (ER)-targeting agents and anti-HER2 therapies have achieved notable successes, critical challenges remain, including drug resistance, inadequate biomarkers, and limited therapeutic targets for TNBC. This review comprehensively summarizes recent advances in targeted therapies for major BC subtypes: endocrine therapy combined with cyclin-dependent kinase 4/6 (CDK4/6) or phosphatidylinositol 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) inhibitors for HR-positive BC; novel antibody‒drug conjugates (ADCs) such as trastuzumab deruxtecan (T-DXd) and tyrosine kinase inhibitors (TKIs) for HER2-positive BC; and trophoblast cell-surface antigen 2 (Trop-2) ADCs, immunotherapies, and poly-ADP-ribose polymerase (PARP) inhibitors for TNBC. It also discusses cross-subtype therapeutic platforms (ADCs, PI3K/AKT/mTOR pathway) and emerging modalities (chimeric antigen receptor [CAR] T-cell therapy, proteolysis-targeting chimeras [PROTACs]). By analyzing successes, challenges, and translational potential, this review provides a clear framework for clinicians and researchers, advancing personalized treatment optimization and addressing unmet clinical needs in BC precision oncology.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 ","pages":"e70733"},"PeriodicalIF":10.7,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679797","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 Incremental Prognostic Value of Hyperemic Coronary Flow Velocity in Patients with Angina and Nonobstructive Coronary Artery Disease. 冠状动脉血流速度在心绞痛和非阻塞性冠状动脉疾病患者中的增量预后价值。

IF 10.7

MedComm Pub Date : 2026-04-12 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70731

Quande Liu, Guihua Jiang, Mingjun Xu, Jichen Pan, Chenghu Guo, Yichun Zhou, Meng Zhang, Yu Zhang, Yun Zhang, Mengmeng Li, Mei Zhang

{"title":"The Incremental Prognostic Value of Hyperemic Coronary Flow Velocity in Patients with Angina and Nonobstructive Coronary Artery Disease.","authors":"Quande Liu, Guihua Jiang, Mingjun Xu, Jichen Pan, Chenghu Guo, Yichun Zhou, Meng Zhang, Yu Zhang, Yun Zhang, Mengmeng Li, Mei Zhang","doi":"10.1002/mco2.70731","DOIUrl":"https://doi.org/10.1002/mco2.70731","url":null,"abstract":"Risk stratification in patients with angina and nonobstructive coronary arteries (ANOCA) remains suboptimal. Coronary flow velocity reserve (CFVR) is prognostic but susceptible to hemodynamic variability; we evaluated whether hyperemic coronary flow velocity (hCFV) improves risk prediction. We analyzed 246 consecutively enrolled ANOCA patients and an independent validation cohort (n = 135). Transthoracic Doppler of the mid-distal LAD quantified CFVR and hCFV. The primary end point was major adverse cardiovascular events (MACE). During a median follow-up of 28.8 months, 27 patients (10.9%) experienced MACE. Both CFVR and hCFV were significantly associated with MACE. Among patients with CFVR < 2.5, hCFV ≤ 0.44 m/s independently predicted MACE (adjusted HR 6.6, p = 0.001). A combined CFVR-hCFV scheme yielded graded risk of MACE (Group A: CFVR ≥ 2.5; Group B: CFVR < 2.5 with hCFV > 0.44 m/s; Group C: CFVR < 2.5 with hCFV ≤ 0.44 m/s), with Group C exhibiting the highest risk of MACE (35.5% vs. 6.3%, 10.5%, p < 0.01). Adding reduced hCFV to a model including clinical risk factors and CFVR improved prediction (IDI 0.05, p = 0.011; NRI 0.23, p = 0.0023) and was confirmed in the validation cohort. Reduced hCFV provides incremental prognostic value beyond CFVR and offers a practical approach to identify high-risk ANOCA patients.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 ","pages":"e70731"},"PeriodicalIF":10.7,"publicationDate":"2026-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13070199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679792","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

Correction to "HSD17B7 Counters Bone Loss in Estrogen Deficiency via Estrogen Receptor Stabilization and Mediates the Effect of Raloxifene". 更正“HSD17B7通过雌激素受体稳定对抗雌激素缺乏的骨质流失并介导雷洛昔芬的作用”。

IF 10.7

MedComm Pub Date : 2026-04-12 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70740

引用次数: 0

Osteoarthritis: Epidemiology, Pathogenesis, and Treatment. 骨关节炎：流行病学、发病机制和治疗。

IF 10.7

MedComm Pub Date : 2026-04-09 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70727

Tianrui Chen, Wenlong Chen, Tianpeng Xu, Hong Wang, Yuheng Zhang, Li Wang, Sijie Zhu, Huaqiang Tao, Xing Yang

{"title":"Osteoarthritis: Epidemiology, Pathogenesis, and Treatment.","authors":"Tianrui Chen, Wenlong Chen, Tianpeng Xu, Hong Wang, Yuheng Zhang, Li Wang, Sijie Zhu, Huaqiang Tao, Xing Yang","doi":"10.1002/mco2.70727","DOIUrl":"https://doi.org/10.1002/mco2.70727","url":null,"abstract":"Osteoarthritis (OA) is the most common chronic joint disorder and a major cause of disability worldwide. Once regarded as a consequence of cartilage wear, OA is now recognized as a complex whole-joint disease involving coordinated pathological changes in articular cartilage, synovium, and subchondral bone. Disease progression is driven by chronic low-grade inflammation, metabolic dysregulation, oxidative stress, and abnormal cellular responses to mechanical stress. These processes are mediated by interconnected signaling networks that regulate inflammatory responses, extracellular matrix (ECM) metabolism, and tissue remodeling. Epigenetic mechanisms, such as DNA methylation, histone modifications, and noncoding RNAs, are increasingly recognized as regulators of OA-related gene expression. However, how signaling networks integrate with epigenetic regulation, particularly histone methylation, remains incompletely understood. In this review, we summarize the epidemiological burden and major risk factors of OA, describe pathological remodeling across joint tissues, and discuss key signaling pathways involved in OA pathogenesis before outlining epigenetic mechanisms. We also highlight the role of histone methylation in inflammation, metabolic imbalance, and tissue remodeling, and summarize current nonpharmacological, pharmacological, injectable, and surgical treatment strategies. Together, this review provides an integrated overview of the epidemiology, pathogenesis, and treatment of OA.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 ","pages":"e70727"},"PeriodicalIF":10.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679568","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 Histone-Lysine N-Methyltransferase (KMT2) Family in Health and Disease. 组蛋白-赖氨酸n -甲基转移酶（KMT2）家族在健康和疾病中的作用。

IF 10.7

MedComm Pub Date : 2026-04-09 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70728

Qiu Wang, Zunjie Bo, Ya Zhang, Yun Chen, Zhiyu Wang, Shuangmei Tong, Ajing Xu, Jian Zhang, Yan Liu

{"title":"The Histone-Lysine N-Methyltransferase (KMT2) Family in Health and Disease.","authors":"Qiu Wang, Zunjie Bo, Ya Zhang, Yun Chen, Zhiyu Wang, Shuangmei Tong, Ajing Xu, Jian Zhang, Yan Liu","doi":"10.1002/mco2.70728","DOIUrl":"https://doi.org/10.1002/mco2.70728","url":null,"abstract":"The histone-lysine N-methyltransferase (KMT2) family is a central epigenetic regulator whose dysfunction drives diverse human diseases through distinct molecular mechanisms. In acute leukemias, KMT2A rearrangements aberrantly recruit transcriptional cofactors, activating oncogenic gene programs; in solid tumors, loss-of-function mutations in KMT2C/D disrupt enhancer-mediated regulatory networks, compromising cellular identity and genome stability; in neurodevelopmental disorders, germline haploinsufficiency of KMT2A/B/D impairs developmental epigenetic programming. Despite increasingly comprehensive understanding of the pathogenic mechanisms involving KMT2 family members, a unified framework translating these molecular insights into effective, subtype-specific therapeutic strategies has been lacking. This review comprehensively deconstructs these pathogenic pathways and explores how mechanistic insights are being translated into novel therapeutic strategies, including direct targeting of oncogenic transcriptional complexes, exploiting vulnerabilities from tumor suppressor loss, and modulating the tumor immune microenvironment. We systematically synthesize recent clinical advances, from small-molecule inhibitors against protein-protein interactions (e.g., menin-KMT2A), to targeted degraders (PROTACs), epigenetic readers/writers inhibitors (e.g., BET, LSD1, DOT1L), and rational combination regimens with chemotherapy or immunotherapy. By integrating the biological characteristics of KMT2 with translational medicine and clinical evidence, this study provides a framework for advancing precision medicine approaches based on the molecular subtypes driven by KMT2.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 ","pages":"e70728"},"PeriodicalIF":10.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679808","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 a First-in-Class Murine Double Minute 2-Recruiting Positive Transcription Elongation Factor B PROTAC Degrader With Selective Antitumor Activity. 一类具有选择性抗肿瘤活性的小鼠双分钟2招募阳性转录延伸因子B PROTAC降解物的发现。

IF 10.7

MedComm Pub Date : 2026-04-09 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70723

Xian Guan, Long Xie, Hanjun Guo, Lin Ma, Jiawei Zhou, Lisong Luo, Hao Yang, Yuanfang Wu, Jiangyu Liu, Yue Wang, Xingze Huang, Jiyang Liu, Ying Zhang, Wenhao Chen, Ye Chen, Liang Xu, Xin Han

{"title":"Discovery of a First-in-Class Murine Double Minute 2-Recruiting Positive Transcription Elongation Factor B PROTAC Degrader With Selective Antitumor Activity.","authors":"Xian Guan, Long Xie, Hanjun Guo, Lin Ma, Jiawei Zhou, Lisong Luo, Hao Yang, Yuanfang Wu, Jiangyu Liu, Yue Wang, Xingze Huang, Jiyang Liu, Ying Zhang, Wenhao Chen, Ye Chen, Liang Xu, Xin Han","doi":"10.1002/mco2.70723","DOIUrl":"https://doi.org/10.1002/mco2.70723","url":null,"abstract":"The positive transcription elongation factor b (P-TEFb) complex, composed of CDK9 and cyclin T isoforms (T1, T2a and T2b), is critical for gene transcription, positioning CDK9 as a very promising oncology target. However, the development of selective and clinically effective small-molecule CDK9 inhibitors has proven challenging. To overcome this limitation, we designed a series of highly efficient and selective P-TEFb degraders by conjugating the CDK9 inhibitor SNS032 with the mouse double minute 2 (MDM2) ligand RG7388. Our lead compound, 13 (dCDK9-010), recruits the MDM2 E3 ligase to induce proteasome-dependent degradation of CDK9 and all cyclin T isoforms across diverse cancer models. dCDK9-010 potently inhibits RNA polymerase II carboxy-terminal repeat domain phosphorylation and blocks MDM2-mediated p53 degradation, resulting in concurrent p53 pathway activation. This dual mechanism drives selective cytotoxicity in TP53 wild-type cancer cells, sparing TP53-mutant or nonmalignant cells. In murine xenograft models of lung cancer and Ewing sarcoma, intravenous dCDK9-010 administration significantly inhibited tumor growth while demonstrating an excellent safety profile. Collectively, this study establishes dCDK9-010 as a first-in-class, selective MDM2-recruiting P-TEFb degrader. By enabling the elimination of the entire P-TEFb complex, this MDM2-recruiting degradation strategy expands the toolkit for targeting CDK9 and represents a promising new therapeutic paradigm for TP53 wild-type cancers.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 ","pages":"e70723"},"PeriodicalIF":10.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066720/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679592","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

Oncolytic Therapy: Delivery System and New Therapeutic Strategies for Cancer. 溶瘤治疗：肿瘤的输送系统和新的治疗策略。

IF 10.7

MedComm Pub Date : 2026-04-09 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70725

Sikan Jin, Yi Zhang, Ziling Zhou, Yaqi Zhang, Ting Yu, Rui Xu, Lin Xu, Jidong Zhang, Longze Zhang, Shan Yang, Xianyao Wang

{"title":"Oncolytic Therapy: Delivery System and New Therapeutic Strategies for Cancer.","authors":"Sikan Jin, Yi Zhang, Ziling Zhou, Yaqi Zhang, Ting Yu, Rui Xu, Lin Xu, Jidong Zhang, Longze Zhang, Shan Yang, Xianyao Wang","doi":"10.1002/mco2.70725","DOIUrl":"https://doi.org/10.1002/mco2.70725","url":null,"abstract":"Oncolytic virotherapy is an emerging cancer immunotherapy that combines selective tumor cell lysis with activation of systemic antitumor immunity. Various DNA- and RNA-based oncolytic viruses (OVs) have demonstrated favorable safety profiles and therapeutic activity across different malignancies. Despite these advancements, clinical efficacy remains inconsistent because of several biological barriers, including rapid immune clearance, insufficient tumor targeting, limited intratumoral spread, and the immunosuppressive tumor microenvironment (TME). In this review, we examine the key mechanisms of OV infection, tumor selectivity, and virus-induced antitumor immune responses. It also explores the factors that limit therapeutic efficacy, particularly host antiviral immunity, structural barriers within solid tumors, and the immunosuppressive networks in the TME. To address these challenges, a range of strategies have been developed, with a focus on optimizing viral delivery. Current approaches, such as cell-based carriers, extracellular vesicle-mediated transport, and nanomaterial-assisted delivery systems, aim to enhance tumor targeting, protect viral integrity, and improve intratumoral distribution. Additionally, combination therapies designed to enhance antitumor immunity and reshape the TME are outlined, including immune checkpoint blockade, chemoradiotherapy, and metabolic modulation. Collectively, these advancements transform OVs from standalone cytolytic agents into adaptable immunotherapeutic platforms, with their effectiveness determined by the delivery method, microenvironmental conditions, and therapeutic integration.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 ","pages":"e70725"},"PeriodicalIF":10.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066727/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679627","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

Ipriflavone From Aquilaria malaccensis Lam. Exosome-Like Nanoparticles Targets Prolyl Hydroxylase Domain Protein 2 (PHD2) to Enhance Hypoxia-Inducible Factor-α (HIF-α) Hydroxylation Thereby Alleviating Hypoxia-Induced Gastrointestinal Mucosal Ferroptosis. 黑木香中的丙烯黄酮。外泌体样纳米颗粒靶向脯氨酸羟化酶结构域蛋白2 (PHD2)，增强缺氧诱导因子-α (HIF-α)的羟基化，从而减轻缺氧诱导的胃肠道粘膜铁下沉。

IF 10.7

MedComm Pub Date : 2026-04-09 eCollection Date: 2026-04-01 DOI: 10.1002/mco2.70722

Dezhi Wang, Xingchen Liao, Yilin Wang, Xuexin Wang, Heng Zhang, Jie Zeng, Mingjie Zhang, Xin Wang, Fangli Ren, Yinyin Wang, Meng Li, Wenchen Wang, Qing Lin, Lingyun Gu, Zhijie Chang, Jianqiu Sheng

{"title":"Ipriflavone From Aquilaria malaccensis Lam. Exosome-Like Nanoparticles Targets Prolyl Hydroxylase Domain Protein 2 (PHD2) to Enhance Hypoxia-Inducible Factor-α (HIF-α) Hydroxylation Thereby Alleviating Hypoxia-Induced Gastrointestinal Mucosal Ferroptosis.","authors":"Dezhi Wang, Xingchen Liao, Yilin Wang, Xuexin Wang, Heng Zhang, Jie Zeng, Mingjie Zhang, Xin Wang, Fangli Ren, Yinyin Wang, Meng Li, Wenchen Wang, Qing Lin, Lingyun Gu, Zhijie Chang, Jianqiu Sheng","doi":"10.1002/mco2.70722","DOIUrl":"https://doi.org/10.1002/mco2.70722","url":null,"abstract":"The major challenge in the clinical treatment of gastrointestinal mucosal injury caused by high-altitude hypoxic environments lies in its unclear underlying mechanisms. In the previous study, we found that hypoxia-induced gastric and small intestinal damage was mainly attributable to ferroptosis mediated by hypoxia-inducible factor-α (HIF-α; mainly HIF-1α and HIF-2α). Both plant exosome-like nanoparticles and Aquilaria malaccensis Lam. have been reported to have antioxidant properties. In the present study, orally delivered A. malaccensis Lam. exosome-like nanoparticles (AELNs) reduced HIF-1α expression and alleviated gastric and small intestinal mucosal ferroptosis induced by hypoxia. We analyzed the compositions of AELNs and hypothesized that ipriflavone was the effector component, as it showed the highest abundance of metabolites. Subsequent experiments demonstrated that ipriflavone downregulated polyunsaturated fatty acid-phospholipids, NADPH oxidase 4 (NOX4), and arachidonate 5-lipoxygenase (ALOX5) by inhibiting HIF-α, consequently alleviating hypoxia-induced gastric and small intestinal mucosal ferroptosis. Ipriflavone was found to inhibit HIF-α by targeting prolyl hydroxylase domain protein 2 (PHD2) to induce it to hydroxylate HIF-α. This study highlights that ipriflavone, a potent HIF-α inhibitor, significantly ameliorates the gastric and small intestinal mucosal damage caused by hypoxia and has promise in clinical applications for treating disorders characterized by high levels of HIF-α.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"7 4","pages":"e70722"},"PeriodicalIF":10.7,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13066503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147679655","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