IF 10.7

MedComm Pub Date : 2025-03-04 DOI: 10.1002/mco2.70110

Wen Hu, Jiayong Zhu, Qi Zhang, Xiaoqian Lu, Luting Yu, Bin Li, Liaobin Chen, Hui Wang

{"title":"Cholesterol-27α-hydroxylase inhibitor nilvadipine can effectively treat cholestatic liver injury in adult offspring induced by prenatal dexamethasone exposure","authors":"Wen Hu, Jiayong Zhu, Qi Zhang, Xiaoqian Lu, Luting Yu, Bin Li, Liaobin Chen, Hui Wang","doi":"10.1002/mco2.70110","DOIUrl":"https://doi.org/10.1002/mco2.70110","url":null,"abstract":"Prenatal dexamethasone exposure (PDE) can increase offspring susceptibility to various diseases. However, the pathogenesis and early prevention for PDE offspring prone to cholestatic liver injury have been unclear. In this study, we collected human umbilical cord blood from neonates with prenatal dexamethasone therapy, showing increased primary unconjugated bile acid levels in utero. PDE increased blood primary bile acid levels, enhanced endoplasmic reticulum stress, and led to cholestatic liver injury in adulthood in rats, which is accompanied by the persistent increase of H3K14ac level in cholesterol 27α-hydroxylase (CYP27A1) promoter and its expression before and after birth. In vitro, dexamethasone activates glucocorticoid receptors, binding to the CYP27A1 promoter, and promotes its transcriptional expression. Through the miR-450b-3p/SIRT1 pathway, it increased the H3K14ac level of the CYP27A1 promoter to enhance its transcription, which continues after birth. Finally, nilvadipine effectively reversed cholestatic liver injury induced by PDE. This study confirmed PDE could cause cholestatic liver injury, and innovatively proposed its early intervention target (CYP27A1) and effective drug (nilvadipine), providing a theoretical and experimental basis for guiding rational drug use during pregnancy, and preventing and treating the fetal-originated cholestatic liver injury.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70110","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143554293","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

Liver Metastasis in Cancer: Molecular Mechanisms and Management 肝癌的肝转移：分子机制和管理

IF 10.7

MedComm Pub Date : 2025-02-27 DOI: 10.1002/mco2.70119

Wenchao Xu, Jia Xu, Jianzhou Liu, Nanzhou Wang, Li Zhou, Junchao Guo

{"title":"Liver Metastasis in Cancer: Molecular Mechanisms and Management","authors":"Wenchao Xu, Jia Xu, Jianzhou Liu, Nanzhou Wang, Li Zhou, Junchao Guo","doi":"10.1002/mco2.70119","DOIUrl":"https://doi.org/10.1002/mco2.70119","url":null,"abstract":"Liver metastasis is a leading cause of mortality from malignant tumors and significantly impairs the efficacy of therapeutic interventions. In recent years, both preclinical and clinical research have made significant progress in understanding the molecular mechanisms and therapeutic strategies of liver metastasis. Metastatic tumor cells from different primary sites undergo highly similar biological processes, ultimately achieving ectopic colonization and growth in the liver. In this review, we begin by introducing the inherent metastatic-friendly features of the liver. We then explore the panorama of liver metastasis and conclude the three continuous, yet distinct phases based on the liver's response to metastasis. This includes metastatic sensing stage, metastatic stress stage, and metastasis support stage. We discuss the intricate interactions between metastatic tumor cells and various resident and recruited cells. In addition, we emphasize the critical role of spatial remodeling of immune cells in liver metastasis. Finally, we review the recent advancements and the challenges faced in the clinical management of liver metastasis. Future precise antimetastatic treatments should fully consider individual heterogeneity and implement different targeted interventions based on stages of liver metastasis.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70119","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513825","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

Noninvasive Quantification of Hepatic Steatosis Using Ultrasound-Derived Fat Fraction (CHESS2303): A Prospective Multicenter Study 超声脂肪分数无创定量肝脂肪变性（CHESS2303）：一项前瞻性多中心研究

IF 10.7

MedComm Pub Date : 2025-02-27 DOI: 10.1002/mco2.70123

Yunlin Huang, Jia Li, Chuan Liu, Danlei Song, Chuanlong Zhu, Yongfeng Ren, Jiaojian Lv, Longfeng Jiang, Rong Shan, Hao Wang, Zhou Wang, Siqin Long, Fan Jiang, Xiang Xie, Liren Lu, Ruixiang Qi, Pengfei Rong, Chuxiao Shao, Wang Yao, Youfang Gao, Wenping Wang, Juan Cheng, Vincent Wai-Sun Wong, Ying Wang, Wai-Kay Seto, Yi Dong, Christoph F. Dietrich, Xiaolong Qi

{"title":"Noninvasive Quantification of Hepatic Steatosis Using Ultrasound-Derived Fat Fraction (CHESS2303): A Prospective Multicenter Study","authors":"Yunlin Huang, Jia Li, Chuan Liu, Danlei Song, Chuanlong Zhu, Yongfeng Ren, Jiaojian Lv, Longfeng Jiang, Rong Shan, Hao Wang, Zhou Wang, Siqin Long, Fan Jiang, Xiang Xie, Liren Lu, Ruixiang Qi, Pengfei Rong, Chuxiao Shao, Wang Yao, Youfang Gao, Wenping Wang, Juan Cheng, Vincent Wai-Sun Wong, Ying Wang, Wai-Kay Seto, Yi Dong, Christoph F. Dietrich, Xiaolong Qi","doi":"10.1002/mco2.70123","DOIUrl":"https://doi.org/10.1002/mco2.70123","url":null,"abstract":"Ultrasound-derived fat fraction (UDFF) is designed to assess the hepatic fat content quantitatively. A multicenter study that verifies the diagnostic performance of UDFF for detecting hepatic steatosis has not yet been reported. This study aimed to evaluate the performance of UDFF for diagnosing and grading hepatic steatosis. Participants referred for assessment of hepatic steatosis were prospectively recruited from eight hospitals. All participants underwent UDFF and magnetic resonance imaging proton density fat fraction (MRI-PDFF) examinations. MRI-PDFF was used as the reference for diagnosing hepatic steatosis. From January 2023 to July 2023, a total of 300 participants were included. The median body mass index was 25.4 kg/m2 (interquartile range: 22.7–28.1). UDFF values were positively correlated with MRI-PDFF (R = 0.80, p < 0.001). Using MRI-PDFF ≥ 5%, ≥ 15%, and ≥ 25% as the reference standard for detecting mild, moderate, and severe hepatic steatosis, the best cutoff values of UDFF were 7.6% (area under the receiver operating characteristic curves [AUC] = 0.90), 15.9% (AUC = 0.90), and 22.3% (AUC = 0.91), respectively. Thus, UDFF has excellent diagnostic performance in detecting and grading hepatic steatosis.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70123","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143513827","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

Targeting WDPF domain of Hsp27 achieves a broad spectrum of antiviral 靶向Hsp27的WDPF结构域可实现广谱抗病毒

IF 10.7

MedComm Pub Date : 2025-02-26 DOI: 10.1002/mco2.70032

Mandi Wu, Wei Li, Houying Leung, Yiran Wang, Qianya Wan, Peiran Chen, Cien Chen, Yichen Li, Xi Yao, Ming-Liang He

{"title":"Targeting WDPF domain of Hsp27 achieves a broad spectrum of antiviral","authors":"Mandi Wu, Wei Li, Houying Leung, Yiran Wang, Qianya Wan, Peiran Chen, Cien Chen, Yichen Li, Xi Yao, Ming-Liang He","doi":"10.1002/mco2.70032","DOIUrl":"https://doi.org/10.1002/mco2.70032","url":null,"abstract":"Enterovirus A71 (EV-A71) is a positive-sense single-stranded RNA virus, which hijacks host proteins to benefit viral internal ribosome entry site (IRES)-dependent protein translation and further propagation. We demonstrated that serine 78 (S78) phosphorylation of Hsp27 is critical for Hsp27/hnRNP A1 relocalization upon EV-A71 infection. Here, we report that the deletion of WDPF and ACD domains disturbs subcellular localization of Hsp27, resulting in partial nuclear translocation. The domain deletion-induced Hsp27 nuclear translocation fails to direct hnRNP A1 translocation. The 2Apro-induced IRES activity and viral replication are suppressed by the deletion of WDPF or ACD domain. Surprisingly, a peptide (WDPF) dramatically inhibits S78 phosphorylation. Therefore, hnRNP A1 translocation, viral IRES activity, and viral protein translation and propagation are all strongly suppressed by the WDPF peptide, but not by peptide without WDPFR sequence (ΔWDPF). Moreover, the WDPF peptide also has potent antiviral activity on other RNA virus (e.g., coronavirus HCoV-OC43) and DNA virus (e.g., HSV-1 and HBV). Peptide treatment with kinase inhibitor Sorafenib brings an additional inhibitory effect on HCoV-OC43 and HSV-1. Taken together, we uncover a crucial role of WDPF domain in S78 phosphorylation for EV-A71-induced hnRNP A1 nuclear translocation, IRES-dependent viral protein translation, and EV-A71 propagation. Our results explore a new path for target-based pan-antiviral strategy.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70032","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490021","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

Endoscopic Ultrasound-Guided Brachytherapy of Yttrium-90 Implantation Into Pancreas: A Dose-Escalation Pilot Study 超声内镜引导下近距离治疗胰腺植入钇-90：剂量递增先导研究

IF 10.7

MedComm Pub Date : 2025-02-24 DOI: 10.1002/mco2.70117

Yuchong Zhao, Yilei Yang, Buchuan Zhang, Haochen Cui, Luyao Liu, Ronghua Wang, Yunfeng Han, Dongling Zhu, Wenliang Ma, Xinxing Zhang, Jinlin Wang, Si Xiong, Shuya Bai, Xiaohua Zhu, Bin Cheng

{"title":"Endoscopic Ultrasound-Guided Brachytherapy of Yttrium-90 Implantation Into Pancreas: A Dose-Escalation Pilot Study","authors":"Yuchong Zhao, Yilei Yang, Buchuan Zhang, Haochen Cui, Luyao Liu, Ronghua Wang, Yunfeng Han, Dongling Zhu, Wenliang Ma, Xinxing Zhang, Jinlin Wang, Si Xiong, Shuya Bai, Xiaohua Zhu, Bin Cheng","doi":"10.1002/mco2.70117","DOIUrl":"https://doi.org/10.1002/mco2.70117","url":null,"abstract":"Intratumoral brachytherapy enables higher dose treatment and reduces damage to adjacent tissues. We first validated the feasibility and safety of endoscopic ultrasound (EUS)-guided Yttrium-90 (90Y) microspheres implantation in a porcine model. Under EUS guidance, 90Y-loaded microspheres were implanted into the pancreas of 10 miniature pigs. The first pig was implanted with 10 MBq particles. Subsequently, nine pigs were sequentially included in the low- (20 MBq), medium- (40 MBq), and high-dose (60 MBq) groups. Positron emission tomography (PET)/CT imaging was used to check the occurrence of particle displacement postoperatively. After euthanasia, the pancreas and adjacent organs were excised for histological examination and residue radiation detection. The absorbed doses demonstrated safe in the porcine model were further in the xenograft model and KRASLSL/+Trp53FL/FLPtfqaCre/+ mouse model. EUS-guided implantations of 90Y-loaded microspheres were successful in all animals. Two pigs had mild serum amylase elevation in the high-dose group and the abnormal index returned to baseline without interventions. The volume of necrotic lesions ranged from 255.76 to 745.57 mm3. In KPC mouse model, PET/CT imaging demonstrated a significant decrease in maximum standardized uptake value (SUVmax) after 90Y implantation. EUS-guided 90Y-loaded carbon microsphere implantation could serve as a safe and feasible technique at ultrahigh dose for pancreatic cancer brachytherapy.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70117","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481463","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

SIRT1 Alleviates Mitochondrial Fission and Necroptosis in Cerebral Ischemia/Reperfusion Injury via SIRT1–RIP1 Signaling Pathway SIRT1通过SIRT1 - rip1信号通路缓解脑缺血再灌注损伤线粒体分裂和坏死下垂

IF 10.7

MedComm Pub Date : 2025-02-24 DOI: 10.1002/mco2.70118

Xuan Wei, Hanjing Guo, Guangshan Huang, Haoyue Luo, Lipeng Gong, Pan Meng, Jiyong Liu, Wenli Zhang, Zhigang Mei

{"title":"SIRT1 Alleviates Mitochondrial Fission and Necroptosis in Cerebral Ischemia/Reperfusion Injury via SIRT1–RIP1 Signaling Pathway","authors":"Xuan Wei, Hanjing Guo, Guangshan Huang, Haoyue Luo, Lipeng Gong, Pan Meng, Jiyong Liu, Wenli Zhang, Zhigang Mei","doi":"10.1002/mco2.70118","DOIUrl":"https://doi.org/10.1002/mco2.70118","url":null,"abstract":"Programmed cell death, including necroptosis, plays a critical role in the pathogenesis of cerebral ischemia/reperfusion injury (CIRI). Silent information regulator 1 (SIRT1) has been identified as a potential therapeutic target for CIRI, yet its precise role in regulating necroptosis remains controversial. Furthermore, the potential interaction between SIRT1 and receptor-interacting protein kinase 1 (RIP1) in this context is not fully understood. Sanpian Decoction (SPD), a classical traditional herbal formula, was previously shown to enhance SIRT1 expression in our studies. Our findings demonstrated that, both in vivo and in vitro, CIRI was associated with a decrease in SIRT1 levels and phosphorylated dynamin-related protein 1 (p-DRP1) at Ser637, alongside an increase in RIP1 and other necroptosis-related proteins. Co-immunoprecipitation and immunofluorescence analyses revealed a weakened interaction between SIRT1 and RIP1. Furthermore, abnormal mitochondrial fission and dysfunction were mediated through the phosphoglycerate mutase 5–DRP1 pathway. Notably, SPD treatment improved neurological outcomes and reversed these pathological changes by enhancing the SIRT1–RIP1 interaction. In conclusion, this study suggests that SIRT1 is a promising therapeutic target for CIRI, capable of inhibiting necroptosis and mitigating mitochondrial fission via the SIRT1–RIP1 pathway. SPD exhibits therapeutic potential by activating SIRT1, thereby attenuating necroptosis and mitochondrial fission during CIRI.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70118","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143481464","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

Sepsis: the evolution of molecular pathogenesis concepts and clinical management 脓毒症：分子发病概念的演变与临床管理

IF 10.7

MedComm Pub Date : 2025-02-23 DOI: 10.1002/mco2.70109

Zhongxue Feng, Lijun Wang, Jing Yang, Tingting Li, Xuelian Liao, Yan Kang, Fei Xiao, Wei Zhang

{"title":"Sepsis: the evolution of molecular pathogenesis concepts and clinical management","authors":"Zhongxue Feng, Lijun Wang, Jing Yang, Tingting Li, Xuelian Liao, Yan Kang, Fei Xiao, Wei Zhang","doi":"10.1002/mco2.70109","DOIUrl":"https://doi.org/10.1002/mco2.70109","url":null,"abstract":"The mortality rate of sepsis is approximately 22.5%, accounting for 19.7% of the total global mortality. Since Lewis Thomas proposed in 1972 that “it is our response that makes the disease (sepsis)” rather than the invading microorganisms, numerous drugs have been developed to suppress the “overwhelming” inflammatory response, but none of them has achieved the desired effect. Continued failure has led investigators to question whether deaths in septic patients are indeed caused by uncontrolled inflammation. Here, we review the history of clinical trials based on evolving concepts of sepsis pathogenesis over the past half century, summarize the factors that led to the failure of these historical drugs and the prerequisites for the success of future drugs, and propose the basic principles of preclinical research to ensure successful clinical translation. The strategy of targeting inflammatory factors are like attempting to eliminate invaders by suppressing the host's armed forces, which is logically untenable. Sepsis may not be that complex; rather, sepsis may be the result of a failure to fight microbes when the force of an invading pathogen overwhelms our defenses. Thus, strengthening the body's defense forces instead of suppressing them may be the correct strategy to overcome sepsis.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70109","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475337","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

Ferroptosis in Pulmonary Disease and Lung Cancer: Molecular Mechanisms, Crosstalk Regulation, and Therapeutic Strategies 肺疾病和肺癌中的铁下垂：分子机制、串扰调节和治疗策略

IF 10.7

MedComm Pub Date : 2025-02-23 DOI: 10.1002/mco2.70116

Dandan Guo, Songhua Cai, Lvdan Deng, Wangting Xu, Sentao Fu, Yaling Lin, Tong Jiang, Qing Li, Zhijun Shen, Jian Zhang, Peng Luo, Bufu Tang, Ling Wang

{"title":"Ferroptosis in Pulmonary Disease and Lung Cancer: Molecular Mechanisms, Crosstalk Regulation, and Therapeutic Strategies","authors":"Dandan Guo, Songhua Cai, Lvdan Deng, Wangting Xu, Sentao Fu, Yaling Lin, Tong Jiang, Qing Li, Zhijun Shen, Jian Zhang, Peng Luo, Bufu Tang, Ling Wang","doi":"10.1002/mco2.70116","DOIUrl":"https://doi.org/10.1002/mco2.70116","url":null,"abstract":"Ferroptosis is a distinct form of iron-dependent programmed cell death characterized primarily by intracellular iron accumulation and lipid peroxidation. Multiple cellular processes, including amino acid metabolism, iron metabolism, lipid metabolism, various signaling pathways, and autophagy, have been demonstrated to influence the induction and progression of ferroptosis. Recent investigations have elucidated that ferroptosis plays a crucial role in the pathogenesis of various pulmonary disorders, including lung injury, chronic obstructive pulmonary disease, pulmonary fibrosis, and asthma. Ferroptosis is increasingly recognized as a promising novel strategy for cancer treatment. Various immune cells within the tumor microenvironment, including CD8+ T cells, macrophages, regulatory T cells, natural killer cells, and dendritic cells, have been shown to induce ferroptosis in tumor cells and modulate the process through the regulation of iron and lipid metabolism pathways. Conversely, ferroptosis can reciprocally alter the metabolic environment, leading to the activation or inhibition of immune cell functions, thereby modulating immune responses. This paper reviews the molecular mechanism of ferroptosis and describes the tumor immune microenvironment, discusses the connection between ferroptosis and the tumor microenvironment in lung cancer and pulmonary diseases, and discusses the development prospect of their interaction in the treatment of lung cancer and pulmonary diseases.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70116","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475336","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

Hypoxia-Induced O-GlcNAcylation of GATA3 Leads to Excessive Testosterone Production in Preeclamptic Placentas 缺氧诱导的o - glcn酰化GATA3导致子痫前期胎盘过量的睾酮产生

IF 10.7

MedComm Pub Date : 2025-02-23 DOI: 10.1002/mco2.70115

Juan Liu, Yun Yang, Hongyu Wu, Feihong Dang, Xin Yu, Feiyang Wang, Yongqing Wang, Yangyu Zhao, Xiaoming Shi, Wei Qin, Yanling Zhang, Yu-Xia Li, Chu Wang, Xuan Shao, Yan-Ling Wang

{"title":"Hypoxia-Induced O-GlcNAcylation of GATA3 Leads to Excessive Testosterone Production in Preeclamptic Placentas","authors":"Juan Liu, Yun Yang, Hongyu Wu, Feihong Dang, Xin Yu, Feiyang Wang, Yongqing Wang, Yangyu Zhao, Xiaoming Shi, Wei Qin, Yanling Zhang, Yu-Xia Li, Chu Wang, Xuan Shao, Yan-Ling Wang","doi":"10.1002/mco2.70115","DOIUrl":"https://doi.org/10.1002/mco2.70115","url":null,"abstract":"The maintenance of endocrine homeostasis in the placenta is crucial for ensuring successful pregnancy. An abnormally elevated production of placental testosterone (T0) has been documented in patients with early-onset preeclamptic (E-PE). However, the underlying mechanisms remain unclear. In this study, we found that E-PE placentas exhibited significantly increased expressions of 3β-HSD1 (3β-Hydroxysteroid Dehydrogenase 1) and 17β-HSD3 (17β-Hydroxysteroid Dehydrogenase 3), the rate-limiting enzymes for T0 synthesis. This was strongly correlated with an elevated level of O-linked N-acetylglucosaminylation (O-GlcNAcylation) of GATA3 (GATA binding protein 3). In human trophoblast cells, O-linked-N-acetylglucosamine (O-GlcNAc) modification of GATA3 on Thr322 stabilized the protein and enhanced the transcriptional regulation of 3β-HSD1 and 17β-HSD3, thereby increasing T0 production. Hypoxia, a well-established pathological factor in PE, significantly enhanced the O-GlcNAcylation of GATA3 in human trophoblast cells. Our findings suggest that hypoxia-induced overactive O-GlcNAcylation of GATA3 contributes to the exacerbated T0 production in E-PE placentas. These findings provide a new perspective on the pathogenesis of E-PE from the standpoint of posttranslational regulation and may illuminate novel therapeutic strategies for adverse pregnancy outcomes such as E-PE.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70115","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143475573","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

Protein palmitoylation: biological functions, disease, and therapeutic targets 蛋白棕榈酰化：生物学功能、疾病和治疗靶点

IF 10.7

MedComm Pub Date : 2025-02-21 DOI: 10.1002/mco2.70096

Yan-Ran Qian, Yu-Jia Zhao, Feng Zhang

{"title":"Protein palmitoylation: biological functions, disease, and therapeutic targets","authors":"Yan-Ran Qian, Yu-Jia Zhao, Feng Zhang","doi":"10.1002/mco2.70096","DOIUrl":"https://doi.org/10.1002/mco2.70096","url":null,"abstract":"Protein palmitoylation, a reversible post-translational lipid modification, is catalyzed by the ZDHHC family of palmitoyltransferases and reversed by several acyl protein thioesterases, regulating protein localization, accumulation, secretion, and function. Neurological disorders encompass a spectrum of diseases that affect both the central and peripheral nervous system. Recently, accumulating studies have revealed that pathological protein associated with neurological diseases, such as β-amyloid, α-synuclein, and Huntingtin, could undergo palmitoylation, highlighting the crucial roles of protein palmitoylation in the onset and development of neurological diseases. However, few preclinical studies and clinical trials focus on the interventional strategies that target protein palmitoylation. Here, we comprehensively reviewed the emerging evidence on the role of protein palmitoylation in various neurological diseases and summarized the classification, processes, and functions of protein palmitoylation, highlighting its impact on protein stability, membrane localization, protein–protein interaction, as well as signal transduction. Furthermore, we also discussed the potential interventional strategies targeting ZDHHC proteins and elucidated their underlying pathogenic mechanisms in neurological diseases. Overall, an in-depth understanding of the functions and significances of protein palmitoylation provide new avenues for investigating the mechanisms and therapeutic approaches for neurological disorders.","PeriodicalId":94133,"journal":{"name":"MedComm","volume":"6 3","pages":""},"PeriodicalIF":10.7,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/mco2.70096","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143456070","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

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