ABSTRACT
From the process of human immunodeficiency virus-1 (HIV-1) invading cells, the combination of gp120 and CD4 is the first step for HIV-1 to invade cells. Interfering with this process can prevent HIV from recognizing target cells and inhibit virus replication. Therefore, HIV-1 gp120 is an important part of the HIV-1 life cycle. Fostesavir, a phosphatate prodrug derived from the gp120 inhibitor BMS-626529 modified by the prodrug strategy, was approved for the treatment of adult patients with multidrug resistant HIV-1 infection by the US FDA and the European Medicines Agency in 2020 and 2021, respectively. In this review, we focus on the research progress of small molecule inhibitors targeting the interaction of gp120-CD4 from the perspective of medicinal chemistry, in order to provide reference for the subsequent research of gp120 inhibitors.
ABSTRACT
Mechanical stimulus is critical to cardiovascular development during embryogenesis period.The mechanoreceptors of endocardial cells and cardiac myocytes may sense mechanical signals and initiate signal transduction that induce gene expression at a cellular level,and then translate molecular-level events into tissue-level deformations,thus guiding embryo development.This review summarizes the regulatory roles of mechanical signals in the early cardiac development including the formation of heart tube,looping,valve and septal morphogenesis,ventricular development and maturation.Further,we discuss the potential mechanical transduction mechanisms of platelet endothelial cell adhesion molecule 1-vascular endothelial-cadherin-vascular endothelial growth factor receptor 2 complex,primary cilia,ion channels,and other mechanical sensors that affect some cardiac malformations.
Subject(s)
Animals , Humans , Heart/embryology , Mechanotransduction, Cellular , Myocytes, Cardiac/physiology , Vascular Endothelial Growth Factor A/metabolismABSTRACT
Objective To summarize the design and implementation of standard work flow of sanitation and epidemic prevention work in the anti-Ebola mission in Liberia, so as to provide reference for treating infectious diseases in the future. Methods The working practice for sanitation and epidemic prevention in Chinese Ebola Treatment Unit in Liberia, including the organizational operation mode, work flow, quality control, and the improvement of the performance were reviewed. Then the importance of sanitation and epidemic prevention was analyzed and the experience and lessons were summarized. Results Deployed in Liberia for the mission of treating Ebola virus disease, the Medical Team of the Chinese People's Liberation Army (PLA) successfully achieved the goal of "win the war, zero infection", in which the sanitary and epidemic prevention work had played an important role. Conclusion The sound organization and management, excellent material preparation, reasonable arrangement of work flow, strict quality control and the continuous improvement of problems were the keys for successful sanitary and epidemic prevention work in the Chinese Ebola Treatment Unit in Liberia.
ABSTRACT
A dominant H-2d restricted Th epitope P34 was found to be contained in recombinant particulate hepatitis E virus (HEV) vaccine HEV 239. In this paper, the cellular immune response induced in P34 immunized BALB/c mice were studied and the priming effect of P34 was characterized. Groups of BALB/c mice were subcutaneously (s. c.) immunized with P34, splenocytes were then stimulated with P34 and HEV 239 protein, cellular immune response was assayed by IFN-gamma-ELISPOT, flow cytometry and T cell proliferation experiments. Results showed that P34 immunized BALB/c splenocytes responsed to P34 and HEV 239 protein stimulation in IFN-gamma-ELISPOT, flow cytometry and T cell proliferation experiments. After depletion of the CD4+ T cells from the immunized splenocytes by magnetic separation, the response decreased to the background level while almost no influence was observed after CD8 + T cells depletion which showed that the cells responsible for IFN-gamma secretion were mainly CD4+ T cells. Then mice were primed with P34 and boosted with its vector protein, E2, the E2 specific antibody titer were assayed. Results showed that after P34 priming, some of the 10 microg, 20 microg E2 boosted mice could develop anti-E2 antibody 1 week later and all the mice had detectable antibody 3 weeks after boosting. In the control peptide P18 priming group, even after boosting with 20 microg E2, anti-E2 antibody couldn't be detected until the end of this experiment. The results showed that priming with P34 epitope could increase the immunogenicity of its vector protein, E2, in BALB/c mice.