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Functional study of p38 mitogen-activated protein kinase based on cell-penetrating peptide delivery system

Journal of Geriatric Cardiology 2009年第2期6卷 108-114页

作者： Liping Yang Yongming Yao Zhiyong Sheng Xiaomei Zhu Yong Jiang Department of Microbiology and Immunology the Burns Institute First Hospital Affiliated to the Chinese PLA GeneralHospital Beijing 100048 P.R. China

Objective p38 Mitogen-activated protein kinase （MAPK） is a crossing center of various pathways. In this study, protein transduction system based on human immunodeficiency virus （HIV）-1 transactivator of transcription （TAT）, which is an efficient delivery peptide of the foreign proteins into cells, was employed to study p38 MAPK functions in eukaryotic cells. Methods p38 And its dominant negative form, p38AF, were constructed into pET-His-TAT vector correctly to verify that the recombinant plasmids were well-founded through restriction enzyme digestion and DNA sequencing. The two proteins, His-TAT-p38 and His-TAT-p38AF, were expressed and purified in Escherichia coli by SDS-PAGE. Then they were incubated with ECV304 cells respectively and readily transduced into cells in a time-dependent and dose-dependent manner. The cells were stimulated by sorbitol. Activating transcription factor （ATF） 2 phosphorylation level was checked using Western blot to assess the activity of endogenous p38. Results Compared with controls, it was found that His-TAT-p38 increased the level ofATF2 phosphorylation in sorbitol-stimulated ECV304 cells, while His-TAT-p38AF inhibited it, indicating p38 MAPK protein delivery system based on TAT was constructed successfully. TAT-p38 and its dominant negative form possessed high biological activity after transduction into ECV304 cells by TAT protein delivery system. The results showed that p38AF fused with TAT could inhibit the transduction of endogenous p38 signal pathway in part, and other pathway might regulate p38 phosphorylation. Conclusions Our study provides a novel pathway to inhibit p38 signal pathway and establish a new method to study p38 function.

关键词： human immunodeficiency virus-1 transactivator of transcription p38 mitogen-activated protein kinase protein transduction: sorbitol

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Heterogeneity of HIV-1 latent reservoirs

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Chinese Medical Journal 2020年第23期133卷 2867-2873页

作者： Jia-Cong Zhao Kai Deng Institute of human Virology Key Laboratory of Tropical Disease Control of Ministry of EducationZhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China Department of Immunology Zhongshan School of MedicineSun Yat-Sen UniversityGuangzhouGuangdong 510080China

Antiretroviral therapy(ART)can effectively inhibit human immunodeficiency virus-1(HIV-1)replication,but is not curative due to the existence of a stable viral latent reservoir harboring replication-competent *** order to reduce or eliminate the HIV-1 latent reservoir,characteristics of the latently infected cells need to be intensively studied,and a comprehensive understanding of the heterogenous nature of the latent reservoir will be critical to develop novel therapeutic ***,we discuss the different cell types and mechanisms contributing to the complexity and heterogeneity of HIV-1 latent reservoirs,and summarize the key challenges to the development of cure strategies for acquired immunodeficiency syndrome(AIDS).

关键词： Clonal expansion Heterogeneity human immunodeficiency virus-1 HIV-1 Integration sites Latent reservoirs

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Low rate of pre-exposure prophylaxis and post-exposure prophylaxis uptake and high prevalence of transmitted drug resistance among newly diagnosed primary HIV infections in Shenzhen, China: a real-world retrospective study

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Chinese Medical Journal 2022年第22期135卷 2730-2737页

作者： Qiaoli Peng Xiaoning Liu Xian Tang Qiuyue Zhang Jin Zhao Chenli Zheng Fang Zhao Yang Zhou Lukun Zhang Liqin Sun Haitao Zhang Xinyun Jia Ying Song Tingzhi Cao Siyuan Wang Man Rao Zhiwei Chen Hui Wang Yun He National Clinical Research Center for Infectious Diseases HKU AIDS Institute Shenzhen Research LaboratoryThe Third People's Hospital of Shenzhen and The Second Affiliated Hospital of Southern University of Science and TechnologyShenzhenGuangdong 518112China National Heart and Lung Institute Faculty of MedicineImperial College LondonLondonUnited Kingdom Shenzhen Center for Disease Control and Prevention ShenzhenGuangdong 518073China Department of Microbiology AIDS InstituteLi Ka Shing Faculty of MedicineThe University of Hong KongHong Kong 999077China

Background: Understanding the characteristics of newly diagnosed primary human deficiency virus-1 (HIV-1) infection in the context of the post-antiretroviral therapy era and HIV drug prophylaxis is essential for achieving the new target of 95-95-95-95 by 2025. This study reported the characteristics of newly diagnosed primary HIV-1 infection in ***: This is a real-world retrospective study. Eighty-seven newly diagnosed primary HIV-1-infected patients were recruited from January 2021 to March 2022 at the Third People’s Hospital of Shenzhen. Demographic, epidemiological, diagnostic, drug resistance, and medical data were described and ***: Overall, 96.6% (84/87) of the newly identified primary HIV-1-infected patients were male, including 88.5% (77/87) men have sex with men (MSM), with a median age of 29.0 years (Q_(1)-Q_(3): 24.0-34.0 years);of these, 85.1% (74/87) reported high-risk sexual behaviors with casual partners. The rate of condom usage was only 28.7% (25/87). The overall rate of pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) was 8.0% (7/87, including 4 PrEP and 3 PEP cases) around the potential exposure, although 41.4% of the patients had prior awareness of such interventions. Moreover, only 19.5% (17/87) had previously used PrEP or PEP. Of those, 58.8% (10/17) of the patients obtained drugs from the internet, and only 35.3% (6/17) reported good compliance. A total of 54.0% (47/87) of subjects were diagnosed by the HIV nucleic acid test. Acute retroviral syndrome appeared in 54.0% (47/87) of patients. The prevalence of transmitted drug resistance (TDR) mutation was 33.9% (19/56), including 6 (10.7%) against nucleoside reverse transcriptase inhibitor (NRTI) plus non-nucleoside reverse transcriptase inhibitor (NNRTI), 8 (14.3%) against NNRTI, and 5 (8.9%) against protease inhibitor (PI) ***: Owing to the low utilization rate and incorrect usage of PrEP and PEP, massive efforts are needed to promote H

关键词： Antiretroviral therapy Drug resistance human immunodeficiency virus-1 Post-exposure prophylaxis Pre-exposure prophylaxis

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