ABSTRACT
Endometriosis is a chronic gynecologic disorder characterized by abnormal growth of endometrium-like tissues in the ectopic regions of the pelvic peritoneum. The pathophysiology of endometriosis is not completely understood; however, excessive endometrial cell proliferation together with resistance to apoptosis facilitates the migration, implantation, and survival of endometrial cells in the distant sites. Endoplasmic reticulum (ER) stress response (also called unfolded protein response) is a cellular defense mechanism triggered by ER stress. When severe enough, the so-called response initiates cell suicide, i.e., apoptosis. Therefore, therapeutic induction of ER stress in endometriotic cells could promote apoptosis and contribute to the management of disease. In this review, we discuss the pathogenic role of ER stress in endometriosis and the most recent findings regarding the induction of ER stress in connection with endometriosis.
Subject(s)
Endometriosis , Humans , Female , Endometriosis/drug therapy , Endometriosis/metabolism , Endometriosis/pathology , Endoplasmic Reticulum Stress/physiology , Unfolded Protein Response , Endometrium/metabolism , Endometrium/pathology , ApoptosisABSTRACT
Triterpene derivatives with an α,ß-alkenenitrile moiety in the five-membered ring A have been synthesized by nitrile anion cyclizations of 1-cyano-2,3-secotriterpenoids. Oxime-containing precursors, 2,3-secointermediates and five-membered ring A products of cyclizations were screened for in vitro antiviral activity against enveloped viruses - influenza A virus and human immunodeficiency virus type I (HIV-1). Lupane ketoxime and the 2,3-secolupane C-3 aldoxime which possess antiviral activities against both influenza A virus (EC50 12.9-18.2 µM) and HIV-1 (EC50 0.06 µM) were the most promising compounds.
Subject(s)
Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Terpenes/chemistry , Terpenes/pharmacology , Cyclization , HIV-1/drug effects , Influenza A Virus, H7N1 Subtype/drug effects , Models, Molecular , Molecular Conformation , Oximes/chemistryABSTRACT
The V3 loop on gp120 from human immunodeficiency virus type 1 (HIV-1) is a focus of many research groups involved in anti-AIDS drug development because this region of the protein is a principal target for neutralizing antibodies and a major determinant for cell tropism and syncytium formation. In this study, the nucleotide sequences of the env gene region coding the V3 loop were determined by DNA sequencing methods for four novel HIV-1 strains that circulate in the countries of Eastern Europe, such as Russia, Belarus, Ukraine, etc. Based on the empirical data obtained, the 3D structures of the V3 loops associated with these viral modifications were generated by computer modeling and then compared to discover similarities in the spatial arrangement of this functionally important site of gp120. Despite the HIV-1 genetic variety, several regions of the V3 loop that contain residues critical for cell tropism were shown to be structurally invariant, which may explain its exceptional role in a co-receptor usage. These data together with those on the biological activity of the V3 individual residues clearly show that these conserved structural motifs of gp120 represent potential HIV-1 weak points most suitable for therapeutic intervention.
Subject(s)
Genetic Variation , HIV Envelope Protein gp120/chemistry , HIV-1/genetics , Amino Acid Sequence , Conserved Sequence , Europe, Eastern , HIV Envelope Protein gp120/metabolism , HIV-1/metabolism , Humans , Models, Molecular , Molecular Dynamics Simulation , Molecular Sequence Data , Protein Conformation , Virus Replication/geneticsABSTRACT
The new HIV-1 recombinant, with a B(gag) A(pol)A(env) structure, is described. This recombinant virus differs from the classical "Kaliningrad" (AF193276.1) virus with an A(gag) B(pol)B(env) structure. The number of new HIV cases in Belarus has been increasing in the past few years. Within the 12 months of 2010, 1069 new cases of HIV infection were registered. Molecular epidemiological investigations have shown that though HIV-1 subtype A (84.5%) still dominates in HIV/AIDS patients, the quantity of CRFs has also increased to 7.1%. Although cases with the CRF03_AB virus were previously described in patients from Belarus, CRF06_cpx and CRF02_AG are described in Belarus for the first time.
Subject(s)
HIV Infections/transmission , HIV-1/isolation & purification , Infectious Disease Transmission, Vertical , Pregnancy Complications, Infectious/virology , Child , Female , Genes, gag , HIV Infections/virology , HIV-1/classification , HIV-1/genetics , Humans , Pregnancy , Recombination, GeneticABSTRACT
To study the molecular epidemiology of HIV-1 in Belarus, where the rapid spread of HIV-1 has been registered since 1996, we obtained HIV-1 sequences from 30 individuals living in five cities in both the main geographic areas of the epidemic (Gomel and Minsk regions) and territories where spreading of the epidemic remains limited (Grodno region). Analysis of env V3 and gag p17/p24 sequences demonstrated that infections in all 12 injecting drug users and 14 of 18 individuals infected through sexual contacts were caused by subtype A viruses that are specific for the epidemic in the former Soviet Union (IDU-A viruses), while the remaining four infections were caused by phylogenetically unrelated to each other subtype B viruses. Extrapolation of these results to the total population of HIV-1-infected individuals in Belarus allowed us to estimate that IDU-A viruses account for nearly 95% of HIV-1 infections in Belarus.
