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ASF1A-dependent P300-mediated histone H3 lysine 18 lactylation promotes atherosclerosis by regulating EndMT

Acta Pharmaceutica Sinica B 2024年第7期14卷 3027-3048页

作者： Mengdie Dong Yunjia Zhang Minghong Chen Yongkang Tan Jiao Min Xian He Fuhao Liu Jiaming Gu Hong Jiang Longbin Zheng Jiajing Chen Quanwen Yin Xuesong Li Xiang Chen Yongfeng Shao Yong Ji Hongshan Chen Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical Universityand Key Laboratory of Cardiovascular and Cerebrovascular MedicineSchool of PharmacyNational Vaccine Innovation PlatformNanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular Medicine School of PharmacyNanjing Medical UniversityNanjing 211166China Department of Clinical Medicine Nanjing Medical University TIANYUAN Honors SchoolNanjing Medical UniversityNanjing 211166China Department of Anesthesiology Sir Run Run HospitalNanjing Medical UniversityNanjing 211166China Department of Cardiovascular Surgery the First Affiliated Hospital of Nanjing Medical UniversityNanjing 211166China Key Laboratory of Cardiovascular and Cerebrovascular Medicine Key Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineState Key Laboratory of Reproductive MedicineSchool of Pharmacythe Affiliated Suzhou Hospital of Nanjing Medical UniversityGusu SchoolNanjing Medical UniversityNanjing 211166China National Key Laboratory of Frigid Zone Cardiovascular Diseases(NKLFZCD) Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China)College of PharmacyKey Laboratory of Cardiovascular Medicine Research and Key Laboratory of Myocardial IschemiaChinese Ministry of EducationNHC Key Laboratory of Cell Transplantationthe Central Laboratory of the First Affiliated HospitalHarbin Medical UniversityHarbin 150081China Key Laboratory of Targeted Intervention of Cardiovascular Disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjing 211166China Department of Cardiology Huai’an First People’s Hospital Affiliated with Nanjing Medical UniversityHuai’an 223399China

Endothelial-to-mesenchymal transition(EndMT)is a key driver of *** glycolysis is increased in the endothelium of atheroprone areas,accompanied by elevated lactate *** lactylation,mediated by lactate,can regulate gene expression and participate in disease ***,whether histone lactylation is involved in atherosclerosis remains ***,we report that lipid peroxidation could lead to EndMT-induced atherosclerosis by increasing lactatedependent histone H3 lysine 18 lactylation(H3K18la)in vitro and in vivo,as well as in atherosclerotic patients’***,the histone chaperone ASF1A was first identified as a cofactor of P300,which precisely regulated the enrichment of H3K18la at the promoter of SNAI1,thereby activating SNAI1 transcription and promoting *** found that deletion of ASF1A inhibited EndMT and improved endothelial *** analysis based on Apoe^(KO)Asf1a^(ECKO) mice in the atherosclerosis model confirmed the involvement of H3K18la in atherosclerosis and found that endotheliumspecific ASF1A deficiency inhibited EndMT and alleviated atherosclerosis *** of glycolysis by pharmacologic inhibition and advanced PROTAC attenuated H3K18la,SNAI1 transcription,and EndMT-induced *** study illustrates precise crosstalk between metabolism and epigenetics via H3K18la by the P300/ASF1A molecular complex during EndMT-induced atherogenesis,which provides emerging therapies for atherosclerosis.

关键词： Histone lactylation Atherosclerosis Endothelial-tomesenchymal transition ASF1A SNAI1 Endothelial dysfunction Lactate Epigenetic

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Cell-specific mineralocorticoid receptors:future therapeutic targets for stroke?

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Neural Regeneration Research 2016年第8期11卷 1230-1231页

作者： Quynh N.Dinh Grant R.Drummond Christopher G.Sobey Sophocles Chrissobolis Vascular Biology & Immunopharmacology Group Cardiovascular Disease Program and Department of PharmacologyBiomedicine Discovery InstituteMonash University Department of Pharmaceutical and Biomedical Sciences Raabe College of PharmacyOhio Northern University

The mineralocorticoid receptor（MR）,well known to be expressed in renal epithelial cells where it is important in fluid and electrolyte homeostasis,has aldosterone as one of its main *** research in the last 10–15 years indicates that MRs are also expressed outside of the kidney,including in the brain,vasculature and heart,where they contribute to the pathophysiology of disease（Dinh et al.,2012;]aisser and Farman, 2016）.

关键词： aldosterone homeostasis electrolyte outside inflammation deletion neurological protective infarct remodeling

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Nanovoid-confinement and click-activated nanoreactor for synchronous delivery of prodrug pairs and precise photodynamic therapy

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Nano Research 2022年第10期15卷 9264-9273页

作者： Peng Wang Fang Zhou Xia Yin Qingji Xie Guosheng Song Xiao-Bing Zhang Molecular Science and biomedicine Laboratory State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringHunan UniversityChangsha 410082China Key Laboratory of Chemical Biology and Traditional Chinese Medicine(Hunan Normal University) Ministry of EducationChangsha 410082China

Bioorthogonal cleavage reaction-triggered prodrug activation by the pretargeted methods can achieve accurate cancer ***,the click and release efficiency of these methods in vivo is limited by the space-time dislocation of bioorthogonal prodrug-trigger pairs within the tumor area,caused by their asynchronous administration and inconsistent accumulation for most delivery *** herein created a nanovoid-confinement and click-activated(NCCA)core–shell nanoreactor by incorporating prodrugs within zeolitic imidazolate framework-90(ZIF-90)as core and coating tetrazine-based covalent organic framework(COF)as *** surface modification of aptamer polymer,the NCCA nanoreactor enabled the sufficient delivery of photodynamic prodrugs within ***,the core of ZIF-90 was decomposed by tumor acidic environment,inducing the high-efficiency activation of photodynamic prodrugs via nanoconfined bioorthogonal reaction with tetrazine-based COF *** a result,such photodynamic agents are efficiently and safely accumulated into tumor and specifically activated for precise photodynamic therapy of cancer cells and tumor bearing mice with minimizing toxic side *** together,such NCCA nanoreactor clearly demonstrates the critical feasibility to realize the synchronous delivery of both prodrugs and triggers for precise treatment,which most of delivery systems are not able to afford.

关键词： nanoreactor covalent organic framework bioorthogonal reaction prodrug photodynamic therapy

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Protective effects of a polymethoxy flavonoids-rich Citrus aurantium peel extract on liver fibrosis induced by bile duct ligation in mice

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Asian Pacific Journal of Tropical Medicine 2016年第12期9卷 1135-1141页

作者： Seol-Wa Lim Dong-Ryung Lee Bong-Keun Choi Hong-Suk Kim Seung Hwan Yang Joo-Won Suh Kyung Soo Kim Graduate School of biomedicine & Health Sciences Catholic University Nutra Pharm Tech Interdisciplinary program of Biomodulation Myongji University Department of Biotechnology Chonnam National University Center for Nutraceutical and Pharmaceutical Materials Myongji University

Objective: To evaluate the possible protective effect of Citrus aurantium peel extract(CAE) against apoptosis in cholestatic liver fibrosis induced by bile duct ligation in mice. Methods: Male ICR mice were divided to 5 groups: 1) Control group(Sham-operated mice), 2) Cholestatic liver injury group induced by bile duct ligation(BDL), 3) BDL mice treated with silymarin(200 mg/kg) for 4 weeks, 4) BDL mice treated with 50 mg/kg CAE for 4 weeks, 5) BDL mice treated with 200 mg/kg CAE for 4 weeks. Mice were sacrificed and liver fibrosis was evaluated by serum and hepatic tissue biochemistry tests and liver histopathological examination. Effects of CAE on inflammation and apoptosis gene regulation were investigated through real-time PCR. CAE effect on lipid metabolism related signaling was determined by western blot analysis. Results: In BDL mice, administration of CAE for 4 weeks markedly attenuated liver fibrosis based on histopathological alteration. Serum and hepatic tissue biochemistry results revealed that CAE(50 and 200 mg/kg) decreased the levels of alanine transaminase, aspartate transaminase, gamma glutamyl transferase, total bilirubin, nitric oxide, and thiobarbituric acid reactive substances. Real-time PCR and western blot analysis showed that CAE regulated inflammation, apoptosis, and lipid metabolism factors increased by BDL. Interleukin family, tumor necrosis factor α, and related apoptosis factors m RNA levels were increased by BDL treatment. However, these increases were suppressed by CAE administration. In addition, CAE effectively increased phosphorylation of AMPactivated protein kinase, nuclear factor E2-related factor 2, and related cytoprotective proteins. Conclusions: CAE can efficiently regulate BDL-induced liver injury with antioxidant, antiinflammatory, and antiapoptotic activities.

关键词： Liver injury Bile duct ligation Cholestasis Citrus aurantium peel extract Hepatic fibrosis

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Ferroptosis-inducing inorganic arsenic(II)sulfide nanocrystals enhance immune activation

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Nano Research 2023年第7期16卷 9760-9767页

作者： Jingyi Zhang Yue Qin Zhicheng Wang Wei Zhang Shengjin Liu Wei Wei Xiuxiu Wang Jing Zhao Chemistry and biomedicine Innovation Center(ChemBIC) State Key Laboratory of Coordination ChemistrySchool of Chemistry and Chemical EngineeringNanjing UniversityNanjing 210023China School of Life Sciences Nanjing UniversityNanjing 210023China College of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China

Arsenic(II)sulfide is a stable inorganic arsenic compound with a different valence from arsenic trioxide,and has been widely applied to treat various diseases with low toxic side effects for a long ***,its low solubility and complicated formulations restrict its further applications in modern medical ***,as the tumour with the highest incidence rate among women,the low recurrence risk of breast cancer has been confirmed to be closely related to the high infiltration of immune ***,we synthesized and filtered novel biocompatible PEGylated arsenic(II)sulfide nanocrystals AsS@PEG with a size of 93.14±0.49 nm by the gel method,which displayed excellent anticancer and immune activation activity in breast cancer *** analysis suggested that the AsS@PEG induce ferroptosis in cancer cells and further activate antitumour immune responses via B-cell lymphoma 9-like(BCL9L)protein ***,mechanism studies revealed notable glutathione peroxidase 4(GPX4)downregulation in cancer cells,dendritic cells(DCs)maturation and subsequent effector CD8^(+)T-cells production induced by the AsS@PEG in the tumour *** study highlights biocompatible arsenic(II)sulfide nanocrystals that induce ferroptotic cell death and activate antitumour immune responses,providing insights into the path towards the immunotherapy assisted chemotherapy for breast cancer.

关键词： arsenic sulfide ferroptosis immunogenic cell death(ICD) immune activation

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老年人功能评估简表对死亡率和住院率的预测效能研究

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International Journal of Nursing Sciences 2023年第1期10卷 38-45页

作者： Giuseppe Liotta Grazia Lorusso Olga Madaro Valeria Formosa Susanna Gentili Fabio Riccardi Stefano Orlando Paola Scarcella Leonardo Palombi Department of biomedicine and Prevention University of Rome Tor VergataRomeItaly Postgraduate School of Hygiene and Preventive Medicine University of Rome Tor VergataRomeItaly Community of Sant’Egidio “Long Live the Elderly”ProgramRomeItaly

目的生物-心理-社会衰弱与死亡风险增加和医疗卫生服务利用有关。本研究旨在评估老年人功能评估简表(Short Functional Geriatric Evaluation,SFGE)对老年人死亡率和住院率的预测效能。方法采用回顾性队列研究对参与意大利“老年人长寿... 详细信息

目的生物-心理-社会衰弱与死亡风险增加和医疗卫生服务利用有关。本研究旨在评估老年人功能评估简表(Short Functional Geriatric Evaluation,SFGE)对老年人死亡率和住院率的预测效能。方法采用回顾性队列研究对参与意大利“老年人长寿!”项目的人群进行分析。共纳入8561名75岁以上的意大利社区居民,平均随访时间516.6 d。计算老年人死亡率、住院率、养老机构入住率和SFGE评估的衰弱程度并进行分析。SFGE评分中社会经济相关条目占40%。结果与健康老年人相比,衰弱前期、衰弱和非常衰弱老人死亡(RR分别为1.40、2.78和5.41)、住院(OR分别为1.31、1.67和2.08)和养老机构入住(OR分别为3.63、9.52和10.61)风险显著增加。在仅纳入社会经济条目的模型中得到类似结果。衰弱预测死亡率的受试者工作特征曲线下面积为0.70(95%CI 0.68~0.72),敏感性和特异性分别为83.2%和40.4%。结论SFGE评分通过对老年人衰弱程度进行分层来预测死亡、住院和养老机构入住风险。该评估工具简短、包含社会经济变量等特征使之可作为公众健康大样本筛查工具,将衰弱作为社区老年人照护的核心。

关键词：老年人衰弱老年医学评估意大利问卷调查

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Biological functions and applications of circRNAs—next generation of RNA-based therapy

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Journal of Molecular Cell Biology 2023年第5期15卷 1-6页

作者： Meiling Sun Yun Yang Research and Development Department Shanghai CirCode Biomedicine Co.LtdShanghaiChina

Introduction Circular RNAs(circRNAs)are a unique class of single-stranded RNA molecules that are covalently closed and lack 5 and 3 *** were first discovered in eukaryotic cells>30 years ago,but technical limitations hindered the characterization of circRNAs until the *** advances in high-throughput RNA sequencing(RNA-seq),coupled with circRNA enrichment using RNase R treatment and new bioinformatic tools,have led to the discovery of a large number of circRNAs in various eukaryotic organisms,including mammals,insects.

关键词： limitations therapy circRNA

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COVID-19 and liver dysfunction in children:Current views and new hypotheses

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World Journal of Hepatology 2023年第3期15卷 353-363页

作者： Yang-Fang Yun Zhi-Yuan Feng Jing-Jing Zhang State Key Laboratory of Analytical Chemistry for Life Science School of Chemistry and Chemical EngineeringChemistry and Biomedicine Innovation CenterNanjing UniversityNanjing 210023Jiangsu ProvinceChina

Coronavirus disease 2019(COVID-19)poses an extremely serious global impact on public healthcare for individuals of all ages,including *** evidence has shown that liver abnormalities are commonly found in children with COVID-19,and age-related features in innate and adaptive response have been ***,there are few reports and studies on COVID-19 related liver injury in children,and the data are *** that many contradictions have *** situation is not only due to the serious ethical issues in studying pediatric patients with COVID-19,but also because of the short duration and wide coverage of the COVID-19 epidemic,the severity and complexity of clinical cases varied,as did the inclusion criteria for case reporting and patient ***,we totaled the incidences,characteristics and pathomechanism of liver injury in children since the COVID-19 *** etiology of COVID-19-related liver injury is divided into three categories:(1)The direct mechanism involves severe acute respiratory syndrome coronavirus 2 binding to angiotensin-converting enzyme 2 in the liver or bile duct to exert direct toxicity;(2)the indirect mechanisms include an inflammatory immune response and hypoxia;and(3)COVID-19-related treatments,such as mechanical ventilation and antiviral drugs,may cause liver *** summary,this minireview provides fundamental insights into COVID-19 and liver dysfunction in children.

关键词： COVID-19 SARS-CoV-2 Children Liver injury Inflammatory immune response Cytokine storm

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Versatile graphitic nanozymes for magneto actuated cascade reaction-enhanced treatment of *** biofilms

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Nano Research 2022年第11期15卷 9800-9808页

作者： Qian Dong Zhaoqian Li Jieqiong Xu Quan Yuan Long Chen Zhuo Chen Molecular Science and biomedicine Laboratory(MBL) State Key Laboratory of Chemo/Biosensing and ChemometricsCollege of Chemistry and Chemical EngineeringCollege of BiologyAptamer Engineering Center of Hunan ProvinceHunan UniversityChangsha 410082China Faculty of Science and Technology University of MacaoTaipaMacao 999078China

Pathogenic oral biofilms especially acid-producing ones cause a variety of oral diseases such as dental *** that bacteria are embedded within the biofilms matrix to prevent the penetration of therapeutic drugs,people have explored the applications of nanoparticles to treat oral ***,current nanoparticle-mediated eradication has not achieved the precise treatment of biofilms,and the stabilities of nanoparticles go on strike because of acidic environment leading to poor therapeutic ***,we design an integrated nanozyme,CoPt@graphene@glucose oxidase(CoPt@G@GOx),which has cascade reaction activity with two-step *** peroxide(H_(2)O_(2))produced through the glucose oxidation by GOx serves as the substrate for peroxidase-mimic CoPt@G to produce highly toxic hydroxyl radical under acidic *** to the simple mixture of GOx and CoPt@G,CoPt@G@GOx shows around fourfold catalytic effect ***,CoPt@G@GOx can precisely target the location of the biofilms,which ensures the minimal impact on normal *** on the advantage of the magneto-actuated cascade catalytic activity,CoPt@G@GOx reveals a superior antibacterial ability in the Streptococcus mutans biofilms ***,our results provide an easy and effective method to exploit bifunctional nanozyme as a novel topical agent to prevent the prevalent biofilm-induced oral disease.

关键词： nanozyme biofilm magnetic targeting platinum antibacterial effect

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Advanced strategies in the application of gelatin-based bioink for extrusion bioprinting

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生物设计与制造(英文) 2023年第5期6卷 586-608页

作者： Jirong Yang Huimin He Duo Li Qian Zhang Lizhi Xu Changshun Ruan Research Center for Human Tissue and Organs Degeneration Institute of Biomedicine and BiotechnologyShenzhen Institute of Advanced TechnologyChinese Academy of SciencesShenzhen 518055China Department of Mechanical Engineering The University of Hong KongHong Kong SARChina University of Chinese Academy of Sciences Beijing 100049China

The signiﬁcance of bioink suitability for the extrusion bioprinting of tissue-like constructs cannot be ***,derived from the hydrolysis of collagen,not only can mimic the extracellular matrix to immensely support cell function,but also is suitable for extrusion under certain ***,gelatin has been recognized as a promising bioink for extrusion ***,the development of a gelatin-based bioink with satisfactory printability and bioactivity to fabricate complex tissue-like constructs with the desired physicochemical properties and biofunctions for a speciﬁc biomedical application is still in its ***,in this review,we aim to comprehensively summarize the state-of-the-art methods of gelatin-based bioink application for extrusion ***ﬁrstly outline the properties and requirements of gelatin-based bioinks for extrusion bioprinting,highlighting the strategies to overcome their main limitations in terms of printability,structural stability and cell ***,the challenges and prospects are further discussed regarding the development of ideal gelatin-based bioinks for extrusion bioprinting to create complex tissue-like constructs with preferable physicochemical properties and biofunctions.

关键词： Gelatin-based bioink Extrusion bioprinting Tissue-like construct

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