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Aspartoacylase suppresses prostate cancer progression by blocking LYN activation

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Military Medical Research 2024年第2期11卷 180-205页

作者： Hong Weng Kang-Ping Xiong Wang Wang Kai-Yu Qian Shuai Yuan Gang Wang Fang Yu Jun Luo Meng‑Xin Lu Zhong‑Hua Yang Tao Liu Xing Huang Hang Zheng Xing-Huan Wang Department of Urology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Evidence‑Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071China Department of Biological Repositories Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Key Laboratory of Tumor Biological Behaviors Wuhan 430071China Department of Pathology Zhongnan Hospital of Wuhan UniversityWuhan 430071China Center for Pathology and Molecular Diagnostics Wuhan UniversityWuhan 430071China Wuhan Research Center for Infectious Diseases and Cancer Chinese Academy of Medical SciencesWuhan 430071China

Background:Globally,despite prostate cancer(PCa)representing second most prevalent malignancy in male,the precise molecular mechanisms implicated in its pathogenesis remain unclear.Consequently,elucidating the key molecular regulators that govern disease progression could substantially contribute to the establishment of novel therapeutic strategies,ultimately advancing the management of PCa.Methods:A total of 49 PCa tissues and 43 adjacent normal tissues were collected from January 2017 to December 2021 at zhongnan hospital of Wuhan University.The advanced transcriptomic methodologies were employed to identify differentially expressed mRNAs in PCa.The expression of aspartoacylase(ASPA)in PCa was thoroughly evaluated using quantitative real-time PCR and Western blotting techniques.To elucidate the inhibitory role of ASPA in PCa cell proliferation and metastasis,a comprehensive set of in vitro and in vivo assays were conducted,including orthotopic and tumor-bearing mouse models(n=8 for each group).A combination of experimental approaches,such as Western blotting,luciferase assays,immunoprecipitation assays,mass spectrometry,glutathione S-transferase pulldown experiments,and rescue studies,were employed to investigate the underlying molecular mechanisms of ASPA's action in PCa.The Student‘s t-test was employed to assess the statistical significance between two distinct groups,while one-way analysis of variance was utilized for comparisons involving more than two groups.A two-sided P<0.05 was deemed to indicate statistical significance.Results:ASPA was identified as a novel inhibitor of PCa progression.The expression of ASPA was found to be significantly down-regulated in PCa tissue samples,and its decreased expression was independently associated with patients’prognosis(HR=0.60,95%CI 0.40–0.92,P=0.018).Our experiments demonstrated that modulation of ASPA activity,either through gain-or loss-of-function,led to the suppression or enhancement of PCa cell proliferation,migration,and invasion,respectively.The inhibitory

关键词： Prostate cancer Aspartoacylase LYN JNK AP-1 C-Jun Phosphorylation

Meta Analysis of Non-penetrating Trabecular Surgery versus Trabeculectomy for the Treatment of Open Angle Glaucoma

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2011年第2期31卷 264-270页

作者：柯敏郭敬钱志刚 Department of Ophthalmology Zhongnan Hospital Wuhan University

This study compared the efficacy of non-penetrating trabecular surgery and trabeculectomy for the treatment of open angle glaucoma. We searched the Cochrane Library, PUBMED （1966 to 2009）, Embase （1980 to 2009） and CMB-disk （1979 to 2009） for the randomized clinical trials （RCT） concerning the two treatment strategies. The reports, including the papers listed in bibliographies, were evaluated against a set of quality criteria and the RCTs that satisfied the criteria were selected and subjected to Meta analysis by employing the Cochrane Collaboration＇s RevMan 4.5 software package. A total of nine RCTs were included in the study. The analyses of the reports showed that, 12 months after surgery, there was significant difference in the reduction of interocular pressure （IOP） between non-penetrating trabecular surgery and trabeculectomy （Z=6.05 P0.00001）. There also existed statistically significant difference in the reduction of IOP at the censored time between the two procedures （Z=4.92, P0.00001）. Difference in the success rate was also found between the two surgeries （Z=3.82, P=0.0001）. It is concluded that, compared with the non-penetrating trabeculectomy, the traditional trabeculectomy could reduce IOP more and had higher success rate while the non-penetrating trabecular surgery is associated with lower postoperative complications.

关键词： open angle glaucoma non-penetrating trabecular surgery sclerectomy viscocanalostomy trabeculectomy

Role of Protein Kinase C in the Activation of Store-operated Ca^(2+) Entry in Airway Smooth Muscle Cells

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2012年第3期32卷 303-310页

作者：高亚东邹进晶耿爽郑君文杨炯 Department of Respiratory Medicine Zhongnan HospitalWuhan University

Store-operated Ca2＋ channels （SOCs） are plasma membrane Ca2＋ permeable channels activated by depletion of intracellular Ca2＋ store. Ca2＋ entry through SOCs is known as store-operated Ca2＋ entry （SOCE）, which plays an important role in the functional regulation of airway smooth muscle cells （ASMCs）. Protein kinase C （PKC） has been shown to have an activating or inhibiting effect on SOCE, depending on cell types and PKC isoforms that are involved. In ASMCs, the effect of PKC on SOCE has not been elucidated so far. In this study, the role of PKC in the activation of SOCE in rat ASMCs was examined by using Ca2＋ fluorescence imaging technique. The results showed that acute application of PKC activators PMA and PDBu did not affect SOCE induced by the sarcoplasmic reticulum Ca2＋-ATPase （SERCA） inhibitor thapsigargin. The non-selective PKC inhibitor chelerythrine significantly inhibited thapsigargin- and bradykinin-induced SOCE. RT-PCR assay identified PKCα, δ and ε isoforms in rat ASMCs. PKCα-selective inhibitor G6976 and PKCε-inhibiting peptide Epsilon-V1-2 had no effect on SOCE; by contrast, PKCδ-selective inhibitor rottlerin attenuated SOCE dramatically, suggesting that PKCδ was the major PKC isoform involved in the activation of SOCE in ASMCs. Moreover, PKC down-regulation by extended exposure to high doses of PMA or PDBu also reduced SOCE, confirming the essential role of PKC in the activation of SOCE in ASMCs. In addition, PKC down-regulation did not influence the expression of stromal interaction molecule 1 （STIM1） and Orai1, two elementary molecules in the regulation and activation of SOCs. These results identified PKCδ as an essential PKC isoform involved in the activation of SOCE, and confirmed that PKC regulates the function of ASMCs in a SOCE-dependent manner.

关键词： airway smooth muscle cells protein kinase C store-operated Ca2＋ entry

The generation and use of animal models of osteosarcoma in cancer research

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Genes & Diseases 2024年第2期11卷 664-674页

作者： Feifei Pu Haoyu Guo Deyao Shi Fengxia Chen Yizhong Peng Xin Huang Jianxiang Liu Zhicai Zhang Zengwu Shao Department of Orthopedics Wuhan Hospital of Traditional Chinese and Western Medicine (Wuhan No.1 Hospital)Tongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Orthopedics Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Radiation and Medical Oncology Zhongnan HospitalWuhan UniversityWuhanHubei 430071China Hubei Cancer Clinical Study Center Zhongnan HospitalWuhan UniversityWuhanHubei 430071China

Osteosarcoma is the most common malignant bone tumor affecting children and adolescents.Currently,the most common treatment is surgery combined with neoadjuvant chemotherapy.Although the survival rate of patients with osteosarcoma has improved in recent years,it remains poor when the tumor(s)progress and distant metastases develop.Therefore,better animal models that more accurately replicate the natural progression of the disease are needed to develop improved prognostic and diagnostic markers,as well as targeted therapies for both primary and metastatic osteosarcoma.The present review described animal models currently being used in research investigating osteosarcoma,and their characteristics,advantages,and disadvantages.These models may help elucidate the pathogenic mechanism(s)of osteosarcoma and provide evidence to support and develop clinical treatment strategies.

关键词： Animal model Cancer Osteosarcoma Pathogenic mechanism Translational research

Protein lipidation in health and disease:molecular basis,physiological function and pathological implication

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1423-1465页

作者： Yuan Yuan Peiyuan Li jianghui Li Qiu Zhao Ying Chang Xingxing He Department of Gastroenterology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanChina Department of Gastroenterology Zhongnan Hospital of Wuhan UniversityWuhanChina Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases WuhanChina

Posttranslational modifications increase the complexity and functional diversity of proteins in response to complex external stimuli and internal changes.Among these,protein lipidations which refer to lipid attachment to proteins are prominent,which primarily encompassing five types including S-palmitoylation,N-myristoylation,S-prenylation,glycosylphosphatidylinositol(GPl)anchor and cholesterylation.Lipid attachment to proteins plays an essential role in the regulation of protein trafficking,localisation,stability,conformation,interactions and signal transduction by enhancing hydrophobicity.Accumulating evidence from genetic,structural,and biomedical studies has consistently shown that protein lipidation is pivotal in the regulation of broad physiological functions and is inextricably linked to a variety of diseases.Decades of dedicated research have driven the development of a wide range of drugs targeting protein lipidation,and several agents have been developed and tested in preclinical and clinical studies,some of which,such as asciminib and lonafarnib are FDA-approved for therapeutic use,indicating that targeting protein lipidations represents a promising therapeutic strategy.Here,we comprehensively review the known regulatory enzymes and catalytic mechanisms of various protein lipidation types,outline the impact of protein lipidations on physiology and disease,and highlight potential therapeutic targets and clinical research progress,aiming to provide a comprehensive reference for future protein lipidation research.

关键词： Lipid ation primarily

Curcumin regulated shift from Th1 to Th2 in trinitrobenzene sulphonic acid-induced chronic colitis

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Acta Pharmacologica Sinica 2006年第8期27卷 1071-1077页

作者： Ming ZHANG~(3,4) Chang-sheng DENG~1 Jia-ju ZHENG~2 Jian XIA~1 ~1Department of Gastroenterology,zhongnan hospital of Wuhan University,Wuhan 430071,China ~2Municipal hospital of Suzhou,Suzhou 215008,China ~3Department of Gastroenterology,Drum Tower hospital of Nanjing,Nanjing 210008,China Department of Gastroenterology Drum Tower Hospital of Nanjing Nanjing China Department of Gastroenterology Zhongnan Hospital of Wuhan University Wuhan China Municipal hospital of Suzhou Suzhou China

Aim:To investigate the therapeutic effects of curcumin（Cur）on trinitrobenzenesulphonic acid（TNBS）-induced colitis and the effects of Cur on the balance ofTh1/Th2 cytokines.Methods:Colitis was induced by TNBS and treated with Cur(30mg.kg-1·d-1,ip),dexamethasone(Dex,2 mg·kg-1·d-1),or Cur plus dexamethasone(Cur+Dex,30 mg.kg-1·d-1Cur ip+2 mg.kg-1·d-1Dex,ip).mRNA in colon mucosawere detected by real-time quantitative polymerase chain reaction.Intracellularcytokines were detected by flow cytometry and concentrations of cytokines insera were detected by enzyme-linked immunosorbent analysis.Results:Both Curand Dex improved body weight loss,ameliorated histological images and de-creased macroscopic score and myeloperoxidase activity.Cur decreased the ex-pression of Th1 cytokines（IL-12,IFN-γ,TNF-α,IL-1）and increased the expres-sion of Th2 cytokines（IL-4 and IL-10）in colon mucosa.Cur also increased theproportion of IFN-γ/IL-4 in splenocytes and circulation.Dex and Cur+Dex de-creased the expression of Th1 cytokines but could not increase the expression ofTh2 cytokines and the proportion of IFN-γ/IL-4.Conclusion:Cur exerted thera-peutic effects on colitis by regulating the shift from Th1 to Th2.

关键词： colitis curcumin IL-4 IL-12 Th1 Th2

Updating the diagnostic criteria of COVID-19 “suspected case” and “confirmed case” is necessary

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Military Medical Research 2020年第4期7卷 507-509页

作者： Yun-Yun Wang Ying-Hui Jin Xue-Qun Ren Yi-Rong Li Xiao-Chun Zhang Xian-Tao Zeng Xing-Huan Wang the zhongnan hospital of Wuhan University Novel Coronavirus Management and Research Team Center for Evidence-Based and Translational Medicine Zhongnan Hospital of Wuhan UniversityWuhan 430071HubeiChina Institute of Evidence-Based Medicine and Knowledge Translation Henan UniversityKaifeng 475000HenanChina Department of Clinical Laboratory Zhongnan Hospital of Wuhan UniversityWuhan 430071HubeiChina Leishenshan hospital of Wuhan Wuhan 430200HubeiChina Department of Radiology Zhongnan Hospital of Wuhan UniversityWuhan 430071HubeiChina 不详

On 6 February 2020,our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus(2019-nCoV)infection,and this guideline provided our experience and make well reference for fighting against this pandemic worldwide.However,the coronavirus disease 2019(COVID-19)is a new disease,our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience;hence,the strategies of diagnosis and treatment are also continually updated.In this letter,we answered one comment on our guideline and provided the newest diagnostic criteria of"suspected case"and"confirmed case"according to the latest Diagnosis and Treatment Guidelines for COVID-19(seventh version)that issued by the National Health Committee of the People’s Republic of China.

关键词： COVID-19 SARS-CoV-2 2019-nCoV Guideline Prevention Diagnosis Treatment Novel coronavirus

Association between Serum Ferritin Levels and Metabolic-associated Fatty Liver Disease in Adults:a Cross-sectional Study Based on the NHANES

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Current Medical Science 2024年第3期44卷 494-502页

作者： Jiang-hui LI Xue-yao MA Yun YI Lu-rao LI Zhi-yong XU Ying CHANG Department of Gastroenterology Zhongnan Hospital of Wuhan UniversityWuhan430071China Hubei Clinical Center and Key Laboratory of Intestinal and Colorectal Diseases Wuhan430071China Endoscopy Center The People’s Hospital of YingshanHuanggang438799China

Objective Ferritin,initially acting as an iron-storage protein,was found to be associated with metabolic diseases.Our study was designed to investigate the association between serum ferritin and metabolic-associated fatty liver disease(MAFLD)using data from the National Health and Nutrition Examination Survey(NHANES)of the United State of America.Methods A cross-sectional study was conducted,enrolling a total of 2145 participants from the NHANES in the 2017–2018 cycles.Hepatic steatosis and liver fibrosis were assessed by ultrasound images and several non-invasive indexes.Multiple regression analysis was conducted to determine the associations between serum ferritin concentration and MAFLD and liver fibrosis.Results The analysis revealed that participants with higher serum ferritin levels(Q3 and Q4 groups)had a higher prevalence of MAFLD than those with the lowest serum ferritin levels[Q3 vs.Q1:OR=2.17(1.33,3.53),P<0.05 in fatty liver index(FLI);Q4 vs.Q1:OR=3.13(1.91,5.13),P<0.05 in FLI].Additionally,participants with the highest serum ferritin levels(Q4 group)displayed a higher prevalence of liver fibrosis[Q4 vs.Q1:OR=2.59(1.19,5.62),P<0.05 in liver stiffness measurement;OR=5.06(1.12,22.94),P<0.05 in fibrosis-4 index],with significantly increased risk observed in participants with concomitant diabetes[OR=7.45(1.55,35.72),P=0.012].Conclusion Our study revealed that elevated serum ferritin levels are associated with a higher prevalence of MAFLD and advanced liver fibrosis in patients.Elevated serum ferritin levels combined with diabetes are important risk factors for liver fibrosis.

关键词： serum ferritin liver fibrosis metabolic-associated fatty liver disease National Health and Nutrition Examination Survey

Method for the extraction of circulating nucleic acids based on MOF reveals cell-free RNA signatures in liver cancer

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National Science Review 2024年第1期11卷 94-106页

作者： Yuqing Sun Haixin Yu Shaoqing Han Ruoxi Ran Ying Yang Yongling Tang Yuhao Wang Wenhao Zhang Heng Tang Boqiao Fu Boshi Fu Xiaocheng Weng Song-Mei Liu Hexiang Deng Shuang Peng Xiang Zhou College of Chemistry and Molecular Sciences Key Laboratory of Biomedical Polymers-Ministry of Education Wuhan University Department of Digestive Surgical Oncology Union Hospital Tongji Medical College Huazhong University of Science and Technology Cancer Center Union HospitalTongji Medical CollegeHuazhong University of Science and Technology Department of Clinical Laboratory Center for Gene Diagnosis and Program of Clinical Laboratory Zhongnan Hospital of Wuhan University College of Chemistry and Materials Science Hubei Engineering University Department of Pharmacology School of Pharmacy China Medical University Taikang Center for Life and Medical Sciences Wuhan University Department of Hematology Zhongnan Hospital of Wuhan University

Cell-free RNA(cf RNA) allows assessment of health, status, and phenotype of a variety of human organs and is a potential biomarker to non-invasively diagnose numerous diseases. Nevertheless, there is a lack of highly efficient and bias-free cf RNA isolation technologies due to the low abundance and instability of cf RNA.Here, we developed a reproducible and high-efficiency isolation technology for different types of cell-free nucleic acids(containing cf RNA and viral RNA) in serum/plasma based on the inclusion of nucleic acids by metal-organic framework(MOF) materials, which greatly improved the isolation efficiency and was able to preserve RNA integrity compared with the most widely used research kit method. Importantly, the quality of cf RNA extracted by the MOF method is about 10-fold that of the kit method, and the MOF method isolates more than three times as many different RNA types as the kit method. The whole transcriptome mapping characteristics of cf RNA in serum from patients with liver cancer was described and a cf RNA signature with six cf RNAs was identified to diagnose liver cancer with high diagnostic efficiency(area under curve = 0.905 in the independent validation cohort) using this MOF method. Thus, this new MOF isolation technique will advance the field of liquid biopsy, with the potential to diagnose liver cancer.

关键词： MOF circulating cell-free RNA biomarker liver cancer diagnosis