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Nickle-cobalt alloy nanocrystals inhibit activation of inflammasomes

National science Review 2023年第8期10卷 211-221页

作者： Jun Lin Liang Dong Yi-Ming Liu Yi hu Chen {1. Ke Liu Liu Liu Yong-Hong Song Mei Sun Xing-Cheng Xiang Kun Qu Yang Lu Long-Ping Wen Shu-Hong Yu department of Neurosurgery The First Affiliated Hospital of USTC School of Basic Medical SciencesDivision of Molecular Medicine Department of Chemistry Institute of Biomimetic Materials&Chemistry Division of Nanomaterials&Chemistry Hefei National Research Center for Physical Sciences at the Microscale University of Science and Technology of China The Cancer Hospital of the university of Chinese Academy of {1.s(zhejiang Cancer Hospital) Institute of Basic Medicine and Cancer(IBMC) Chinese Academy of Sciences Anhui Province Key Laboratory of Advanced Catalytic Materials and Reaction Engineering School of Chemistry and Chemical EngineeringHefei University of Technology The WUT-AMU Franco-Chinese Institute Wuhan University of Technology Institute of Artificial Intelligence Hefei Comprehensive National Science Center

Activation of inflammasomes—immune system receptor sensor complexes that selectively activate inflammatory responses—has been associated with diverse human diseases, and many nanomedicine studies have reported that structurally and chemically diverse inorganic nanomaterials cause excessive inflammasome activation. Here, in stark contrast to reports of other inorganic nanomaterials, we find that nickel-cobalt alloy magnetic nanocrystals(NiCo NCs) actually inhibit activation of NLRP3, NLRC4 and AIM2 inflammasomes. We show that NiCo NCs disrupt the canonical inflammasome ASC speck formation process by downregulating the lncRNA Neat1. and experimentally confirm that the entry of NiCo NCs into cells is required for the observed inhibition of inflammasome activation. Furthermore, we find that NiCo NCs inhibit neutrophil recruitment in an acute peritonitis mouse model and relieve symptoms in a colitis mouse model, again by inhibiting inflammasome activation. Beyond demonstrating a highly surprising and apparently therapeutic impact for an inorganic nanomaterial on inflammatory responses, our work suggests that nickel-and cobalt-containing nanomaterials may offer an opportunity to design anti-inflammatory nanomedicines for the therapeutics of macrophage-mediated diseases.

关键词： inflammasome nickel-cobalt nanoparticle Neat1 colitis NLRP3

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Effects of Benzo(a)pyrene on the Contractile Function of the Thoracic Aorta of Sprague-dawley Rats

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Biomedical and Environmental sciences 2012年第5期25卷 549-556页

作者： GAN Tie Er XIAO Su Ping jiang Ying {1. {1. WU Yi {1.a DUERKSEN-{1.GHES Penelope J SHENG Jian Zhong YANG Jun First Affiliated Hospital State Key Laboratory for Diagnosis and Treatment of Infectious DiseasesZhejiang UniversityHangzhou 310003ZhejiangChina department of Pathology and Pathophysiology Zhejiang University School of MedicineHangzhou 310058ZhejiangChina department of Basic {1. Division of BiochemistryLoma Linda University School of MedicineLoma LindaCA 92354USA department of Toxicology Hangzhou Normal University School of Public HealthHangzhou 310036ZhejiangChina

Abstract Objective To evaluate the possible vascular effects of an environment carcinogen benzo（a）pyrene （BaP）. Methods The cytotoxicit of BaP and rat liver S9 （0.25 mg/mL）-activated BaP were examined by MTT assay. Thoracic aortic rings were dissected from Sprague-Dawley rats. Contraction of aortic rings was induced by 60 mmol/L KCl or 1.-6 mol/L phenylephrine （PE） in an ex-vivo perfusion system after BaP （1.0 tlmol/L） incubation for 6 h. [Ca^2＋]i was measured using Fluo-4/AM. For in-vivo treatment, rats were injected with BaP for 4 weeks （1. mg/kg, weekly, i.p.）. Results BaP （1.500 μm） did not significantly affect cell viability; S9-activated BaP stimulated cell proliferation. BaP did not affect the contractile function of endothelium-intact or -denuded aortic rings. BaP did not affect ATP-induced （[Ca2＋]i） increases in human umbilical vein endothelial cells. In BaP-treated rats, heart rate and the number of circulating inflammatory cells were not affected. Body weight decreased while blood pressure increased significantly. The maximum aortic contractile responses to PE and KCI and the maximum aortic relaxation response to acetylcholine were significantly decreased by 25.0%, 34.2%, and 1..4%, respectively. Conclusion These results suggest, in accordance with its DNA-damaging properties, that metabolic activation is a prerequisite for BaP-induced cardiovascular toxicity.

关键词： DNA damage Benzo(a)pyrene Cardiovascular toxicity Vascular contraction

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Comparison and development of machine learning for thalidomideinduced peripheral neuropathy prediction of refractory Crohn’s disease in Chinese population

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World Journal of Gastroenterology 2023年第24期29卷 3855-3870页

作者： Jing Mao Kang Chao Fu-Lin jiang Xiao-Ping Ye Ting Yang Pan Li Xia Z{1. Pin-Jin {1. Bai-Jun Zhou Min {1.ang Xiang Gao Xue-Ding Wang Institute of Clinical Pharmacology School of Pharmaceutical SciencesSun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina Guangdong Provincial Key Laboratory of New Drug Design and Evaluation Sun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina department of Gastroenterology The Sixth Affiliated HospitalSun Yat-sen UniversityGuangzhou 510006Guangdong ProvinceChina department of Pharmacy Guangdong Women and Children HospitalGuangzhou 510000Guangdong ProvinceChina

BACKGROUND Thalidomide is an effective treatment for refractory Crohn’s disease(CD).However,thalidomide-induced peripheral neuropathy(TiPN),which has a large individual variation,is a major cause of treatment *** is rarely predictable and recognized,especially in *** is necessary to develop a risk model to predict TiPN *** To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic *** A retrospective cohort of 1.4 CD patients from January 201. to June 2022 was used to establish the *** National Cancer Institute Common Toxicity Criteria Sensory Scale(version 4.0)was used to assess *** 1. clinical features and 1.0 genetic variables,five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve(AUROC),area under the precision-recall curve(AUPRC),specificity,sensitivity(recall rate),precision,accuracy,and F1.*** The top-ranking five risk variables associated with TiPN were interleukin-1. rs1.53248[P=0.0004,odds ratio(OR):8.983,95%confidence interval(CI):2.497-30.90],dose(mg/d,P=0.002),brainderived neurotrophic factor(BDNF)rs2030324(P=0.001.OR:3.1.4,95%CI:1.561.6.434),BDNF rs6265(P=0.001.OR:3.1.0,95%CI:1.546-6.073)and BDNF rs1.0301.4(P=0.001.OR:3.091.95%CI:1.525-5.960).In the training set,gradient boosting decision tree(GBDT),extremely random trees(ET),random forest,logistic regression and extreme gradient boosting(XGBoost)obtained AUROC values>0.90 and AUPRC>*** these models,XGBoost and GBDT obtained the first two highest AUROC(0.90 and 1.,AUPRC(0.98 and 1.,accuracy(0.96 and 0.98),precision(0.90 and 0.95),F1.score(0.95 and 0.98),specificity(0.94 and 0.97),and sensitivity(1..In the validation set,XGBoost algorithm exhibited the best predictive performance with the highest specificity(0.857),accuracy(0.81.),AUPRC(0.86)and AUROC(0.89).ET and GBDT obtained the highest sensitivity(1.and F1.score(0.8)

关键词： Thalidomide-induced peripheral neuropathy Refractory Crohn’s disease Neurotoxicity prediction models Machine learning Gene polymorphisms

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DNA crosslinking and recombination-activating genes 1.2(RAG1.2)are required for oncogenic splicing in acute lymphoblastic leukemia

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Cancer Communications 2021年第11期41卷 1116-1136页

作者： Hao Zhang Nuo Cheng Zhihui Li Ling Bai Chengli Fang Yuwen Li Weina Zhang Xue Dong Minghao {1. Yang Liang Su{1. Zhang Jianqing Mi {1. Zhu Yu Zhang Sai-Juan Chen Yajie Zhao Xiang-Qin Weng Weiguo hu Zhu Chen Jinyan huang Guoyu Meng Shanghai Institute of Hematology State Key Laboratory of Medical GenomicsNational Research Center for Translational MedicineRui-Jin HospitalSchool of Medicine and School of Life Sciences and BiotechnologyShanghai JiaoTong UniversityShanghai 200025P.R.China Key Laboratory of Synthetic Biology CAS Center for Excellence in Molecular Plant SciencesChinese Academy of SciencesShanghai 200032P.R.China university of Chinese Academy of {1.s Beijing 100049P.R.China department of Hematologic Oncology State key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer CenterGuangzhouGuangdong 510060P.R.China department of Geriatrics Ruijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025P.R.China Medical Center on Aging of Ruijin Hospital Shanghai Jiao Tong University School of MedicineShanghai 200025P.R.China department of Laboratory Medicine West China HospitalSichuan UniversityChengduSichuan 610044P.R.China Biomedical Big Data Center the First Affiliated HospitalZhejiang University School of MedicineHangzhouZhejiang 310000P.R.China Cancer Center Zhejiang UniversityHangzhouZhejiang 310000P.R.China

Background:Abnormal alternative splicing is frequently associated with *** B-cell acute lymphoblastic leukemia(B-ALL),double homeobox 4 fused with immunoglobulin heavy chain(DUX4/IGH)can lead to the aberrant production of E-26 transformation-specific family related gene abnormal transcript(ERGalt)and other splicing ***,the molecular mechanism underpinning this process remains ***,we aimed to know how DUX4/IGH triggers abnormal splicing in ***:The differential intron retention analysis was conducted to identify novel DUX4/IGH-driven splicing in B-ALL patients.X-ray crystallography,small angle X-ray scattering(SAXS),and analytical ultracentrifugation were used to investigate how DUX4/IGH recognize double DUX4 responsive element(DRE)-DRE *** ERGalt biogenesis and B-cell differentiation assays were performed to characterize the DUX4/IGH crosslinking *** check whether recombination-activating gene 1.2(RAG1.2)was required for DUX4/IGH-driven splicing,the proximity ligation assay,co-immunoprecipitation,mammalian two hybrid characterizations,in vitro RAG1.2 cleavage,and shRNA knock-down assays were ***:We reported previously unrecognized intron retention events in Ctype lectin domain family 1.,member A abnormal transcript(CLEC1.Aalt)and chromosome 6 open reading frame 89 abnormal transcript(C6orf89alt),where also harbored repetitive DRE-DRE ***,X-ray crystallography and SAXS characterization revealed that DUX4 homeobox domain(HD)1.HD2 might dimerize into a dumbbell-shape trans configuration to crosslink two adjacent DRE *** DUX4/IGH-mediated crosslinking abolishes ERGalt,CLEC1.Aalt,and C6orf89alt biogenesis,resulting in marked alleviation of its inhibitory effect on B-cell ***,we also observed a rare RAG1.2-mediated recombination signal sequence-like DNA edition in DUX4/IGH target ***,shRNA knock-down of RAG1.2 in leukemic Reh cells c

关键词： Acute lymphoblastic leukemia alternative splicing DUX4/IGH ERG_(alt) RAG1.2

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One-year status of hepatic venous pressure gradient measurement from 85 hospitals in china

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Portal Hypertension & Cirrhosis 2024年第2期3卷 116-123页

作者： Jitao Wang Ting Cui Linpeng Zhang Zhiping Yan Lei Li Jinjun Chen Junhui Sun hua Xiang He Zhu Hao Wu Jiancuo Gengzang Feng Zhang Wei Wu Guohong Cao Wuhua Guo Haibin Shi hui Xue Guangjun huang Qiang Yu Meng Niu huiling Xiang Derun Kong Wei Gou Xuefeng Luo Fuliang He Min Yuan Wei Liu Yong Wang Hongjie hu Xiaoli Zhu Tao Yu Qinxue Sun Wei Qu Ting Lu Deqiang Ma Li Zhang Jun Ma Jun Yang Ketao Mu Xiaoliang Zhu Kai Xiong huiguo Ding Shengjuan Yao Mingsheng huang Fang Wang Zexin Wang Yong huang Jianan Li Hongfeng Yi Birun huang Zhongwei Zhao Duiping Feng Yanming Lei Changlong Hou Wenbo Guo Shirong Liu Gaojun Teng Kangshun Zhu Fan Wu Xiaogang hu Wenfeng Zhang Shaoqi Yang Zhouchao hu Pengfei Pang Shaowu Zhuang Weidong Wang Qingliang Zhu Kunpeng Zhang Chengyu Liu Dongliang Li Chao Ma Hong jiang Xingong Zhao Weixin Ren Zhiwei Wang Lei Yu Fuhuang Lin Chaoguang Yan Feng Wang Lei Yu hui huan Wenyong Shen Shaofei He Chengda Zhang Jinlun Bao jiangtao Liu Jun Wu Jianbo Zhao Jian Zhang Xiaolong Qi Hebei Provincial Key Laboratory of Cirrhosis&Portal Hypertension Xingtai People's HospitalXingtaiHebeiChina Center of Portal Hypertension Department of RadiologyZhongda HospitalSchool of MedicineSoutheast UniversityNanjingJiangsuChina department of Interventional Therapy Beijing Shijitan Hospital Affiliated to Capital Medical UniversityBeijingChina department of Intervention Taiyuan Third People's HospitalTaiyuanShanxiChina department of Intervention Zhongshan Hospital Affiliated to Fudan UniversityShanghaiChina department of Interventional Medicine The First Hospital of Lanzhou UniversityLanzhouGansuChina department of Infectious Diseases Nanfang Hospital of Southern Medical UniversityGuangzhouGuangdongChina Hepatobiliary and Pancreatic Intervention Center The First Affiliated Hospital of Zhejiang University School of MedicineHangzhouZhejiangChina Interventional Vascular Surgery Hunan Provincial People's HospitalChangshaHunanChina department of Intervention Sixth People's Hospital of ShenyangShenyangLiaoningChina department of Gastroenterology West China Hospital of Sichuan UniversityChengduSichuanChina department of Intervention The Fourth People's Hospital of Qinghai ProvinceXiningQinghaiChina department of Gastroenterology Nanjing Drum Tower HospitalNanjingJiangsuChina department of Gastroenterology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiangChina department of Radiology Shulan(Hangzhou)HospitalHangzhouZhejiangChina department of Intervention Mengchao Hepatobiliary Hospital of Fujian Medical UniversityFuzhouFujianChina department of Interventional Radiology The First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsuChina department of Gastroenterology The First Affiliated Hospital of Xi'an Jiaotong UniversityXi'anShaanxiChina department of Gastroenterology Shandong Provincial Hospital Affiliated to Shandong First Medical UniversityJinanShandongChina department of Interventional Radiology Fifth Medical Center

Aims:Surveys and research on the applications of the hepatic venous pressure gradient(HVPG)are important for understanding the current status and future development of this technology in *** article aimed to investigate the status of hepatic venous pressure gradient measurement in {1. in ***:We investigated the overall status of HVPG technology in {1.-including hospital distribution,hospital level,annual number of cases,catheters used,average cost,indications,and current challenges by using online *** counting the number and percentages of cases of these results,we hope to clarify the current status of HVPG measurements in ***:According to the survey,85 hospitals in {1. used HVPG technology in 2022 distributed across 29 provinces.A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022,of which 281. cases(56.4%)were measured *** average cost of HVPG measurement was 5646.8±2327.9 *** the clinical teams who performed the measurements(sometimes multiple per hospital),94.3%(82/87)used the balloon method,and the majority of the teams(72.4%,63/87)used embolectomy ***:This survey clarified the clinical application status of HVPG in {1. and confirmed that some medical institutions in {1. have established a foundation for this *** is still necessary to continue promoting and popularizing this technology in the future.

关键词： application status hepatic vein pressure gradient questionnaire survey

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Ambulatory blood pressure profile and stroke recurrence

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Stroke & Vascular Neurology 2021年第3期6卷 352-358,I0006-I0008页

作者： Jie Xu Fei jiang Anxin Wang {1.i Zhi Yuan Gao Junping Tian Jinglin Mo Zimo Chen An-Ding Xu Benyan Luo Bo {1. Yuqing Zhang Xingquan Zhao Yilong Wang Hao Li Haipeng Shen Yongjun Wang department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina china National Clinical Research Center for Neurological Diseases(NCRCND) Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of Statistics and Actuarial {1.s University of Hong KongHong KongChina Biostatistics and Clinical Research Methodology Unit Faculty of MedicineUniversity of Hong KongHong KongChina department of Neurology The First Affiliated Hospital of Zhengzhou UniversityZhengzhouHenanChina department of Cardiology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina department of Neurology and Stroke Center The First Affiliated Hospital of Jinan UniversityGuangzhouGuangdongChina department of Neurology and Brain Medical Centre The First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhouZhejiangChina department of Neurology Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubeiChina Division of Hypertension National Center for Cardiovascular Disease ChinaFuwai HospitalBeijingChina Faculty of Business and Economics University of Hong KongHong KongChina

Objectives To establish a new ambulatory blood pressure(ABP)parameter(24-hour ABP profile)and evaluated its performance on stroke outcome in ischaemic stroke(IS)or transient ischaemic attack(TIA)*** The prospective cohort consisted of 1.96 IS/TIA patients enrolled for ABP monitoring and a 3-month follow-up for stroke recurrence as *** groups of systolic blood pressure(SBP)were identified via an advanced functional clustering method,and the associations of the profile groups and conventional ABP parameters with stroke recurrence were examined in a Cox proportional hazards *** Three discrete profile groups(n=604,781.and 61. in profiles 1.2 and 3,respectively)in 24-hour ambulatory SBP were *** 1.resembled most to the normal diurnal blood pressure pattern;profile 2 also dropped at night,but climbed earlier and with higher morning surge;while profile 3 had sustained higher nocturnal SBP without significant nocturnal SBP *** incidence of stroke recurrence was 2.9%,3.9%and 5.5%in profiles 1.2 and 3,*** adjustment for covariates,profile 3 was significantly associated with higher risk of stroke recurrence with profile 1.as reference(HR 1.76,95%CI:1.00 to 3.09),while no significant difference was observed between profiles 2 and 1.HR 1.22,95%CI:0.66 to 2.25).None of conventional ABP parameters showed significant associations with the *** Ambulatory 24-hour SBP profile is associated with short-term stroke *** of ABP may help improve identification of stroke recurrence by capturing the additive effects of individual ABP parameters.

关键词： sustained Profiles recurrence

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Aging-elevated inflammation promotes DNMT3A R878H-driven clonal hematopoiesis

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Acta Pharmaceutica Sinica B 2022年第2期12卷 678-691页

作者： Min Liao Ruiqing Chen Yang Yang Hanqing He Liqian Xu Yuxuan jiang Zhenxing Guo Wei He Hong jiang Jianwei Wang School of pharmaceutical {1.s Tsinghua UniversityBeijing 100084China Kidney Disease Center the First Affiliated HospitalCollege of MedicineZhejiang UniversityHangzhou 310003China department of Hematology/Oncology First Hospital of Tsinghua UniversityBeijing 100016China

Aging-elevated DNMT3A R882H-driven clonal hematopoiesis(CH)is a risk factor for myeloid malignancies remission and overall *** some studies were conducted to investigate this phenomenon,the exact mechanism is still under *** this study,we observed that DNMT3 A R878 H bone marrow cells(human allele:DNMT3 A R882 H)displayed enhanced reconstitution capacity in aged bone marrow milieu and upon inflammatory ***3 A R878 H protects hematopoietic stem and progenitor cells from the damage induced by chronic inflammation,especially TNFa ***,we identified that RIPK1.RIPK3-MLKL-mediated necroptosis signaling was compromised in R878 H cells in response to proliferation stress and TNFa ***,we elucidated the molecular mechanism driving DNMT3 A R878 H-based clonal hematopoiesis,which raises clinical value for treating DNMT3 A R882 H-driven clonal hematopoiesis and myeloid malignancies with aging.

关键词： Aging Inflammation DNMT3A R882H Clonal hematopoiesis Hematopoietic stem cells Necroptosis TNFα

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Efficacy of a Chinese herbal formula on hepatitis B e antigenpositive chronic hepatitis B patients

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World Journal of Gastroenterology 2020年第30期26卷 4501-4522页

作者： Yu-Feng Xing Chun-Shan Wei Tian-Ran Zhou Dan-Ping huang Wei-Chao Zhong Bin Chen hua Jin Xiao-Yu hu Zhi-Yun Yang Qing He Kai-Ping jiang Jun-Min jiang Zhen-Bin hu Xin Deng Fan Yang Feng-Yi Li Gang Zhao Li-Chun Wang Yu-Qiang Mi Zuo-Jiong Gong Peng Guo Jian-hua Wu Wei-Qun Shi Hong-Zhi Yang Da-Qiao Zhou Guang-Dong Tong department of Hepatology Shenzhen Traditional Chinese Medicine HospitalThe Fourth Clinical Medical College of Guangzhou University of Chinese MedicineShenzhen 518033Guangdong ProvinceChina department of Hepatology The First Hospital of Hunan University of Chinese MedicineChangsha 410007Hunan ProvinceChina department of Integrated Traditional and Western Medicine on Liver Diseases Beijing Youan HospitalCapital Medical UniversityBeijing 100069China department of Infectious Disease The Affiliated Hospital of Chengdu University of Traditional Chinese MedicineChengdu 610032Sichuan ProvinceChina department of Integrated Traditional and Western Medicine on Liver Diseases Beijing Ditan HospitalCapital Medical UniversityBeijing 100015China The First department of Hepatology Shenzhen No.3 People’s HospitalShenzhen 518100Guangdong ProvinceChina department of Hepatology Foshan Hospital of Traditional Chinese MedicineFoshan 528000Guangdong ProvinceChina department of Hepatology Guangdong Hospital of Traditional Chinese MedicineGuangzhou 510006Guangdong ProvinceChina department of Hepatology The First Affiliated Hospital of Guangxi University of Chinese MedicineNanning 530012Guangxi ProvinceChina department of Hepatology Ruikang HospitalGuangxi University of Chinese MedicineNanning 530012Guangxi ProvinceChina hubei Provincial Hospital of Traditional Chinese Medicine Wuhan 430060Hubei ProvinceChina Treatment and Research Center of Infectious Disease 302 Military Hospital of ChinaBeijing 100039China department of Hepatology Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201204China Center of Infectious Disease Huaxi HospitalSichuan UniversityChengdu 610044Sichuan ProvinceChina department of Infectious Disease Tianjin Infectious Disease HospitalTianjin 300192China department of Infectious Disease Hubei People’s HospitalWuhan 430060Hubei ProvinceChina department of Hepatology Xiyuan HospitalChina Academy of Chinese Medical ScienceBeijing 100080China C

BACKGROUND No guideline recommends antiviral therapy for hepatitis B e antigen(HBeAg)-positive chronic hepatitis B patients with persistently normal alanine aminotransferase levels and a high hepatitis B virus(HBV)DNA viral *** To evaluate the feasibility and safety of a Chinese herbal formula as a therapeutic option for chronic HBV *** In total,395 patients(30–65 years old)with confirmed HBeAg-positive chronic hepatitis B infection and persistently normal alanine aminotransferase were randomized to receive either Chinese herbal formula or placebo for 96 *** to evaluate therapeutic efficacy included:(1.HBV DNA levels decreased to less than 4 log1. IU/mL at weeks 48 and 96;and(2)HBeAg clearance and seroconversion rates at weeks 48 and *** HBV DNA levels≤4 log1. IU/mL were 1..05%at week 48 and 1..59%at week 96 in the treatment *** HBeAg clearance and conversion rates were 8.54%and 8.04%at week 48 and 1..08%and 1..57%at week 96,***,HBV DNA levels≤4 log1. IU/mL were 2.55%and 2.55%at weeks 48 and 96,respectively,and the HBeAg clearance rates were 3.06%and 5.61.at weeks 48 and 96,respectively,in the control *** quantitative hepatitis B surface antigen and HBeAg levels at baseline and changes during the treatment period as well as the alanine aminotransferase elevation at weeks 1. and 24 were strong predictors of HBeAg *** High rates of HBV DNA reduction,HBeAg clearance and seroconversion could be achieved with Chinese herbal formula treatments,and the treatments were relatively safe for HBeAg-positive chronic hepatitis B-infected patients with persistently normal alanine *** ability of the compound to modulate host immune function probably contributed to this effect.

关键词： Chronic hepatitis B Chinese Herbal Formula treatment Hepatitis B e antigen clearance Hepatitis B e antigen seroconversion Hepatitis B virus DNA reduction Clinical trial

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Screening and verifying potential NTCP inhibitors from herbal medicinal ingredients using the LLC-PK1.cell model stably expressing human NTCP

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Chinese Journal of Natural Medicines 2016年第7期14卷 549-560页

作者： SHEN Zhuo-Wei LUO Meng-Yue hu Hai-Hong ZHOU hui jiang hui-Di YU Lu-Shan ZENG Su Institute of Drug Metabolism and pharmaceutical Analysis Zhejiang Province Key Laboratory of Anti-Cancer Drug ResearchCollege of Pharmaceutical Sciences Zhejiang University

NTCP is specifically expressed on the basolateral membrane of hepatocytes, participating in the enterohepatic circulation of bile salts, especially conjugated bile salts, to maintain bile salts homeostasis. In addition, recent studies have found that NTCP is a functional receptor of HBV and HDV. Therefore, it is important to study the interaction between drugs and NTCP and identify the inhibitors/substrates of NTCP. In the present study, a LLC-PK1.cell model stably expressing human NTCP was established, which was simple and suitable for high throughput screening, and utilized to screen and verify the potential inhibitors of NTCP from 1.2 herbal medicinal ingredients. The results showed that ginkgolic acid(GA)(1. : 0), GA(1. : 1., GA(1. : 1., erythrosine B, silibinin, and emodin have inhibitory effects on NTCP uptake of TCNa in a concentration-dependent manner. Among them, GA(1. : 0) and GA(1. : 1. exhibited the stronger inhibitory effects, with IC_(50) values being less than 8.3 and 1..5 mmol·L^(-1., respectively, than the classical inhibitor, cyclosporin A(CsA)(IC_(50) = 20.33 mmol·L^(-1.). Further research demonstrated that GA(1. : 0), GA(1. : 1., GA(1. : 1., silibinin, and emodin were not substrates of NTCP. These findings might contribute to a better understanding of the disposition of the herbal ingredients in vivo, especially in biliary excretion.

关键词： Herbal medicinal ingredients human NTCP Inhibitor Transport Biliary excretion

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A New Approach to the Synthesis of Bergapten

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Chemical Research in Chinese Universities 2022年第6期38卷 1492-1496页

作者： CAI Xiaoqing JI Dongxin LIU Jiageng hu Maolin JIN Zhimin College of Chemistry and Materials Engineering Wenzhou UniversityWenzhou325035P.R.China College of pharmaceutical {1.s Zhejiang University of TechnologyHangzhou310014P.R.China department of Chemistry Zhejiang UniversityHangzhou310027P.R.China

In this study, bergapten was synthesized in a yield of 55% from phloroglucinol as starting material, via a novel approach including monomethylation, Hoesch reaction, acetylation, deacetoxylation, Pechmann condensation and 2,3-dichloro-5,6-dicyano-1.4-benzoquinone(DDQ) dehydrogenation. With the adoption of the acetylation of enol tautomer, the deacetoxylation and the DDQ dehydrogenation, the novel approach differs greatly from the processes reported previously, though the starting material was the same or similar to those used on previous synthetic processes. The newly adopted reaction underwent easily, affording all reactions in high yields, especially acetylation and deacetoxylation and DDQ dehydrogenation in almost quantitative yields, ensuring a final yield higher than those previously reported.

关键词： Bergapten Enol tautomerism Acetylation Deacetoxylation 2,3-Dichloro-5,6-dicyano-1.4-benzoquinone (DDQ)dehydrogenation

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