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ZBTB7A governs estrogen receptor alpha expression in breast cancer

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Journal of Molecular Cell Biology 2018年第4期10卷 273-284页

作者： Mary Ellen Molloy Monika Lewinska Amanda K. Williamson Thanh Thao Nguyen Gamze Kuser-Abali Lu Gong Jiawei Yan John B. Little Pier Paolo Pandolfi Zhi-Min Yuan Department of Environmental Health John B. Little Center for Radiation Sciences Harvard T.H. Chan School of Public Health Boston MA 02215 USA biotech Research and Innovation Centre Department of Health and Medical Sciences University of Copenhagen Copenhagen Denmark Cancer Genetics Program Beth Israel Deaconess Cancer Center Departments of Medicine and Pathology Beth Israel Deaconess Medical Center Harvard Medical School Boston MA 02215 USA

ZBTB7A, a member of the POZ/BTB and Krüppel （POK） family of transcription factors, has been shown to have a context-dependent role in cancer development and progression. The role of ZBTB7A in estrogen receptor alpha （ERα）-positive breast cancer is largely unknown. Approximately 70% of breast cancers are classified as ERα-positive. ERα carries out the biological effects of estrogen and its expression level dictates response to endocrine therapies and prognosis for breast cancer patients. In this study, we find that ZBTB7A transcriptionally regulates ERα expression in ERα-positive breast cancer cell lines by binding to the ESR1 promoter leading to increased transcription of ERα. Inhibition of ZBTB7A in ERα-positive cells results in decreased estrogen responsiveness as demonstrated by diminished estrogen-response element-driven luciferase reporter activity, induction of estrogen target genes, and estrogen-stimulated growth. We also report that ERα potentiates ZBTB7A expression via a post-translational mechanism, suggesting the presence of a positive feedback loop between ZBTB7A and ERα, conferring sensitivity to estrogen in breast cancer. Clinically, we find that ZBTB7A and ERα are often co-expressed in breast cancers and that high ZBTB7A expression correlates with improved overall and relapse-free survival for breast cancer patients. Importantly, high ZBTB7A expression predicts a more favorable outcome for patients treated with endocrine therapies. Together, these findings demonstrate that ZBTB7A contributes to the transcriptional program maintaining ERα expression and potentially an endocrine therapy-responsive phenotype in breast cancer.

关键词： ZBTB7A ERα breast cancer endocrine therapies

Immunogenicity noninferiority study of 2 doses and 3 doses of an Escherichia coli-produced HPV bivalent vaccine in girls vs.3 doses in young women

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Science China(Life Sciences) 2020年第4期63卷 582-591页

作者： Yue-Mei Hu Meng Guo Chang-Gui Li Kai Chu Wen-Gang He Jing Zhang Jian-Xiang Gu Juan Li Hui Zhao Xiang-Hong Wu Bi-Zhen Lin Zhi-Jie Lin Xing-Mei Yao Ya-Fei Li Fei-Xue Wei Yue Huang Ying-Ying Su Feng-Cai Zhu Shou-Jie Huang Hui-Rong Pan Ting Wu Jun Zhang Ning-Shao Xia Jiangsu Provincial center for Disease Control and Prevention Nanjing 210009China The State Key Laboratory of Molecular Vaccinology and Molecular Diagnostics National Institute of Diagnostics and Vaccine Development in Infectious DiseasesCollaborative Innovation Center of Biologic ProductsSchool of Public HealthXiamen UniversityXiamen 361102China National Institute for Food and Drug Control Beijing 102629China Sheyang center for Disease Control and Prevention Sheyang 244300China Xiamen Innovax biotech Company Xiamen 361022China

A new HPV-16/18 bivalent vaccine expressed by the Escherichia coli has been proven to be efficacious in adult women.A randomized,immunogenicity noninferiority study of this candidate vaccine was conducted in December 2015 in *** aged 9–14 years were randomized to receive 2 doses at months 0 and 6(n=301)or 3 doses at months 0,1 and 6(n=304).Girls aged 15–17 years(n=149)and women aged 18–26 years(n=225)received 3 *** objectives included noninferiority analysis of the IgG geometric mean concentration(GMC)ratio(95%CI,lower bound>0.5)to HPV-16 and HPV-18 at month 7 in girls compared with *** the per-protocol set,the GMC ratio of IgG was noninferior for girls aged 9–17 years receiving 3 doses compared with women(1.76(95%CI,1.56,1.99)for HPV-16 and 1.93(95%CI,1.69,2.21)for HPV-18)and noninferior for girls aged 9–14 years receiving 2 doses compared with women(1.45(95%CI,1.25,1.62)for HPV-16 and 1.17(95%CI,1.02,1.33)for HPV-18).Noninferiority was also demonstrated for neutralizing *** immunogenicity of the HPV vaccine in girls receiving 3 or 2 doses was noninferior compared with that in young adult women.

关键词： immunobridging noninferiority human papillomavirus vaccine Escherichia coli girls

Recent advances in the diversification of chromones and flavones by direct C-H bond activation or functionalization

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Chinese Chemical Letters 2020年第12期31卷 3073-3082页

作者： Shanghui Tian Tian Luo Yanping Zhu Jie-Ping Wan College of Chemistry and Chemical Engineering Jiangxi Normal UniversityNanchang 330022China School of Pharmacy Key Laboratory of Molecular Pharmacology and Drug EvaluationMinistry of EducationCollaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of ShandongYantai UniversityYantai 264005China

Chromone and flavone are both central backbones of natural products and clinical *** of diversely functionalized chromones and flavones constitutes significant research contents of the modern synthetic science because abundant molecular libraries of such types are crucial in providing candidate compounds for the discovery of new pharmaceuticals and functional *** direct C—H bond activation or functionalization on these heterocyclic backbones provides highly powerful tools for the rapid accesses to densely functionalized chromone and flavone *** the importance of the functionalized chromone and flavone compounds as well as the notable advances in the synthesis of such products by direct C—H activation or functionalization,we review herein the research advances in the C—H bond activation and functionalization reactions of chro mone and flavones,in hope of showing the current states and promise of the research domain.

关键词： Chromones Flavones C—H bond Activation Functionalization

Research Progress on Causes and Pathogenesis of Sensitive Skin

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China Detergent & Cosmetics 2022年第4期7卷 49-55页

作者： Li An Yang Yuanyuan Cistto Bio-Research center Beijing Zhilejie Biotech Co.Ltd.China

The causes and pathogenesis of sensitive skin are relatively ***,the causes and pathogenesis of sensitive skin are summarized based on previous research *** causes of sensitive skin mainly include various external factors,internal factors,and other dermatological *** mechanisms are complex,including skin barrier function injury,changes in epidermal microbial status,abnormal sensory nerve fiber function,activation of TRPV1 channel,neurovascular-immune-inflammatory pathway,transcriptome,*** skin is often induced by multiple *** analysis and discussion of the causes and mechanisms of sensitive skin will be helpful to guide clinical practice.

关键词： sensitive skin skin barrier sensory nerve fiber TRPV1 channel pathogenesis

Recent advances in systemic and local delivery of ginsenosides using nanoparticles and nanofibers

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Chinese Journal of Chemical Engineering 2021年第2期34卷 291-300页

作者： Jing Zhao Zhiguang Duan Xiaoxuan Ma Yannan Liu Daidi Fan Shaanxi Key Laboratory of Degradable Biomedical Materials School of Chemical EngineeringNorthwest UniversityXi’an 710069China Shaanxi R&D center of Biomaterials and Fermentation Engineering School of Chemical EngineeringNorthwest UniversityXi’an 710069China biotech.&Biomed.Research Institute Northwest UniversityXi’an 710069China

Ginsenosides are the main pharmacologically active constituents of ginseng which have been used in East Asian countries for centuries to modulate blood pressure,metabolism and immune *** the technological advances in isolation,purification and mass production,their mechanisms of action are gradually elucidated,providing solid basis for clinical *** extracts(total ginsenosides)and ginsenoside Rg3,CK,Rd have been marketed or entered clinical trials as drugs or dietary *** the proven safety and efficacy of some ginsenosides,their applications are hindered by inferior pharmacokinetics such as low solubility,poor membrane permeability and metabolic *** formulation of drugs and implantable drug depots are effective strategies to improve the pharmacokinetics of therapeutic agents by enhancing solubility,providing protection,facilitating intracellular transport,and enabling sustained and controlled *** mini-review summarizes the recent advances in systemic delivery of ginsenosides using liposomes,micelles,albumin-based nanoparticles,and inorganic nanoparticles,as well as local delivery of ginsenosides by electronspun fibrous membranes and hydrogels.

关键词： Ginsenosides Nanoparticles Nanofibers Drug delivery

Sprayable nanodrug-loaded hydrogels with enzyme-catalyzed semiinter penetrating polymer network(Semi-IPN)for solar dermatitis

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Nano Research 2022年第7期15卷 6266-6277页

作者： Jialing Yao Junfeng Hui Jing Yang Jiaxin Yao Chaoquan Hu Daidi Fan Shaanxi Key Laboratory of Degradable Biomedical Materials Shaanxi R&D Center of Biomaterials and Fermentation EngineeringSchool of Chemical EngineeringNorthwest UniversityXi’an 710069China Nanjing IPE Institute of Green Manufacturing Industry Nanjing 211100China biotech.&Biomed.Research Institute Northwest UniversityXi’an 710069China

Solar dermatitis is an acute or chronic high incidence of skin injury caused by ultraviolet(UV)radiation based on strong sunlight,which seriously endangers people's *** this study,we designed and demonstrated enzyme-catalyzed semi-inter penetrating polymer network(Semi-IPN)sprayable nanodrug-loaded hydrogels based on gelatin,3-(4-hydroxyphenyl)propionic acid(HPA),polyvinyl alcohol(PVA),glycerol,and dexamethasone sodium phosphate(DEXP)for solar *** hydrogels had high water content,excellent biocompatibility,effective encapsulation and sustained release of nanodrugs,antiinflammatory,and strong anti-ultraviolet B(anti-UVB)radiation properties based on glycerol and phenol functional groups,but also controllable spray gelation mode to make them adhere well on the dynamic skin surfaces and achieve continuous transdermal drugs delivery for solar *** sprayable nanodrug-loaded hydrogel systems could be used as a highly effective therapeutic method for solar dermatitis,and also provide a good strategy for designing novel nanodrug-loaded hydrogel delivery systems.

关键词： enzyme-catalyzed semi-inter penetrating polymer network(Semi-IPN) sprayable hydrogel nanodrug-loaded solar dermatitis

An Immunocompetent Patient with High Neutralizing Antibody Titers Who Shed COVID-19 Virus for 169 days——China,2020

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China CDC weekly 2021年第32期3卷 688-691,I0003-I0008页

作者： Li Li Siqi Li Yang Pan Ling Qin Siyuan Yang Dawei Tan Yaling Hu Maria Deloria Knoll Xiaoli Wang Linghang Wang Quanyi Wang Beijing Ditan Hospital Capital Medical UniversityBeijingChina Johns Hopkins Bloomberg School of Public Health BaltimoreMarylandUSA Beijing center for Disease Control and Prevention BeijingChina Biomedical Information center of Beijing YouAn Hospital Capital Medical UniversityBeijingChina Sinovac biotech Co LtdBeijingChina

Few reports are available about prolonged shedding of coronavirus disease(COVID-19)virus,also known as severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),by immunocompetent *** report a case of an infected,immunocompetent person with 169 days of COVID-19 virus shedding during which time he had two brief periods when he tested negative for COVID-19 followed by again testing *** describe relevant clinical,immunological,and genomic *** found that continuous and prolonged viral replication and infectivity existed in an immunocompetent COVID-19 patient,despite having high neutralizing antibody titers.

关键词： Antibody acute respiratory

Recent advances in developing small-molecule inhibitors against SARS-CoV-2

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Acta Pharmaceutica Sinica B 2022年第4期12卷 1591-1623页

作者： Rong Xiang Zhengsen Yu Yang Wang Lili Wang Shanshan Huo Yanbai Li Ruiying Liang Qinghong Hao Tianlei Ying Yaning Gao Fei Yu Shibo Jiang College of Life Sciences Hebei Agricultural UniversityBaoding 071001China Research center of Chinese Jujube Hebei Agricultural UniversityBaoding 071001China Key Laboratory of Medical Molecular Virology(MOE/NHC/CAMS) School of Basic Medical SciencesShanghai Institute of Infectious Diseases and BiosecurityFudan UniversityShanghai 200032China Beijing Pharma and biotech center Beijing 100176China

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire *** though several COVID-19 vaccines are currently in distribution worldwide,with others in the pipeline,treatment modalities lag ***,researchers have been working hard to understand the nature of the virus,its mutant strains,and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic *** the research continues,we now know the genome structure,epidemiological and clinical features,and pathogenic mechanism of ***,we summarized the potential therapeutic targets involved in the life cycle of the *** the basis of these targets,small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.

关键词： SARS-CoV-2 COVID-19 Therapeutic Prophylactic Small-molecule inhibitors

Modeling the Long-term Antibody Response and Duration of Immune Protection Induced by an Inactivated,Preservative-free Hepatitis A Vaccine(Healive)in Children

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Biomedical and Environmental Sciences 2020年第7期33卷 484-492页

作者： YU Yong Pei CHEN Jiang Ting JIANG Zhi Wei WANG Ling YU Cheng Kai YAN Xiao Yan YAO Chen XIA Jie Lai College of Military Preventive Medicine the Fourth Military Medical UniversityXi'an 710032ShaanxiChina Peking University^Clinical Research Institute Peking University Health Science CenterBeijing 100191China Sinovac biotech Beijing 100089China Beijing Keytech Statistical Consulting Beijing 100020China

Objective Long-term seroprotection via the hepatitis A vaccine is essential for the prevention of disease from the hepatitis A virus(HAV).Due to documented difficulties during decade-long follow-ups after receiving vaccines,statistical-modeling approaches have been applied to predict the duration of immune *** Based on five-year follow-up data from a randomized positive-controlled trial among Chinese children(1–8 years old)following a 0,6 months vaccination schedule,a power-law model accounting for the kinetics of B-cell turnover,as well as a modified power-law model considering a memory-B-cell subpopulation,were fitted to predict the long-term immune responses induced by HAV vaccination(Healive or Havrix).Anti-HAV levels of each individual and seroconversion rates up to 30 years after vaccination were *** A total of 375 participants who completed the two-dose vaccination were included in the *** models predicted that,over a life-long period,participants vaccinated with Healive would have close but slightly higher antibody titers than those of participants vaccinated with ***,consistent with previous studies,more than 90%of participants were predicted to maintain seroconversion for at least 30 ***,the modified power-law model predicted that the antibody titers would reach a plateau level after nearly 15 years *** Based on the results of our modeling,Healive may adequately induce long-term immune responses following a 0,6 months vaccination schedule in children via induction of memory B cells to provide stable and durable immune protection.

关键词： Hepatitis A Inactivated hepatitis A vaccine Modeling Antibody persistence Long-term follow-up