Cellular proteins as potential targets for antiretroviral therapy

The review article conducts an in-depth analysis of information gleaned from a comprehensive literature search across Scopus, Web of Science, and MedLine databases. The focal point of this search revolves around the identification and exploration of the mechanisms orchestrated by host cell factors in the replication cycle of the human immunodeficiency virus (HIV-1, Retroviridae: Orthoretrovirinae: Lentivirus: Human immunodeficiency virus-1). The article delves into two primary categories of proteins, namely HIV dependence factors (such as CypA, LEDGF, TSG101) and restriction factors (including SERINС5, TRIM5α, APOBEC3G), providing illustrative examples. The current understanding of the functioning mechanisms of these proteins is elucidated, and an evaluation is presented on the potential development of drugs for treating HIV infection. These drugs aim to either inhibit or stimulate the activity of host factors, offering insights into promising avenues for future research and therapeutic advancements

Determinants of HIV-1 Late Presentation in Patients Followed in Europe

To control the Human Immunodeficiency Virus (HIV) pandemic, the World Health Organization (WHO) set the 90-90-90 target to be reached by 2020. One major threat to those goals is late presentation, which is defined as an individual presenting a TCD4+ count lower than 350 cells/mm3 or an AIDS-defining event. The present study aims to identify determinants of late presentation in Europe based on the EuResist database with HIV-1 infected patients followed-up between 1981 and 2019. Our study includes clinical and socio-demographic information from 89,851 HIV-1 infected patients. Statistical analysis was performed using RStudio and SPSS and a Bayesian network was constructed with the WEKA software to analyze the association between all variables. Among 89851 HIV-1 infected patients included in the analysis, the median age was 33 (IQR: 27.0–41.0) years and 74.4% were males. Of those, 28,889 patients (50.4%) were late presenters. Older patients (>56), heterosexuals, patients originated from Africa and patients presenting with log VL >4.1 had a higher probability of being late presenters (p < 0.001). Bayesian networks indicated VL, mode of transmission, age and recentness of infection as variables that were directly associated with LP. This study highlights the major determinants associated with late presentation in Europe. This study helps to direct prevention measures for this population

THE STRUCTURE-FUNCTIONAL ORGANISATION OF THE PERIPHERAL SECTION OF SIGHT SYSTEM OF THE POND SNALL LUMNAEA STAGNALIS (L.)

For the first time, the complex geometry of the retina, the laminar structure of the crystalline lens, 4 types of the cells such as photoreceptors I and II, pigment, nervous and glial. The structure of the distal section of the optic nerve has been described, where the aco-axonal interactions of the photoreceptors have been shown. For the first time, the contacts of the slot type between the non-identified appendices of the retina cells and the pigment cells have been detected. The position about the morphogenetic uniqueness of photoreceptors I and II, about the existence of the functional sincitia of the pigment cells is being developed. Described have been 2 populations of neurons in the retina. One of them form the distant contacts on a basal plate, the other send the axons into the central nervous system and, probably, perform the function of the pacemakers, controlling the day rhythm. First a special type of desmosomes has been described. It has been established, that the screening pigments are not ommochromes and, with a large part of probability, adhere of melaninesAvailable from VNTIC / VNTIC - Scientific & Technical Information Centre of RussiaSIGLERURussian Federatio

THE SET OF ANTI-RECESSIONARY MEASURES OF THE ENERGY POLICY OF INDUSTRIAL ENTERPRISES IN THE RESOURCE-SAVING SPHERE

Цель: ознакомление научной общественности с результатами авторского исследования в области антикризисного управления промышленными предприятиями. Методология проведения работы: исследование выполнено с позиций актуальных научных методологических подходов в области антикризисного управления. Результаты исследования: представлена авторская трактовка понятий «антикризисное управление»и «антикризисная энергетическая политика»;выявлены проблемные участки в энергосистемах Самарской и Оренбургской областях и мероприятия по устранению рисков; представленкомплекс антикризисных мероприятийс учетом факторов и форм кризисных явлений на предприятиях электроэнергетического комплекса. Область применения результатов: могут быть использованы при разработки элементов антикризисной политики профильных промышленных предприятий.Objective: scientific community familiarization with the results of author’s research in the field of anti-crisis management by the industrial enterprises. Work performance methodology: the research is execu-ted from the positions of actual scientific methodological approaches in the field of anti-crisis management. Research results: the author’s treatment of the concepts «anti-crisis management» and «anti-recessionary energy policy» is presented; the problem areas in the energy systems of Samara and Orenburg regions and the risk elimination measures are revealed; the set of anti-recessionary measures with account of the factors and forms of the crisis phenomena at the electric power complex enterprises is introduced. Application field of the results: can be used in the deve-lopment of the elements of anti-recessionary policy of the profile industrial enterprises

Podocyte injury in diabetes mellitus

The mechanisms of podocyte injury and their correlation with metabolic and haemodynamic disorders in diabetes mellitus are considered in detail; the results of the last experimental and clinical studies on this problem are presented in this review. Authors shined the biomarkers, reflecting expressiveness of podocytopathy and structural and functional glomerular changes at diabetic nephropathy. Modern possibilities of treatment for their correction to prevent diabetic nephropathy progression are discussed

Podocyte injury in diabetes mellitus

The mechanisms of podocyte injury and their correlation with metabolic and haemodynamic disorders in diabetes mellitus are considered in detail; the results of the last experimental and clinical studies on this problem are presented in this review. Authors shined the biomarkers, reflecting expressiveness of podocytopathy and structural and functional glomerular changes at diabetic nephropathy. Modern possibilities of treatment for their correction to prevent diabetic nephropathy progression are discussed

A uniquely prevalent nonnucleoside reverse transcriptase inhibitor resistance mutation in Russian subtype A HIV-1 viruses

BACKGROUND: The subtype A variant in the Former Soviet Union (A(FSU)) causes most of Russia's HIV-1 infections. However, the spectrum of drug-resistance mutations (DRMs) in antiretroviral experienced patients with this variant has not been studied. METHODS: Between 2010 and 2013, genotypic resistance testing was performed on plasma samples from 366 antiretroviral-experienced patients in Siberia. RESULTS: Three-hundred patients (82%) had subtype A(FSU) and 55 (15%) had CRF02_AG viruses. The pattern of DRMs was consistent with patient antiretroviral history with one exception. G190S was the most common nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation, occurring in 55 (33%) subtype A(FSU) viruses from 167 NNRTI-experienced patients compared with none of 37 CRF02_AG viruses from NNRTI-experienced patients (P < 0.001). The next most common subtype A(FSU) NNRTI-resistance mutation, K103N, occurred in 25 (15%) viruses. Wild-type glycine (G) at position 190 is encoded by GGC in more than 99% of published A(FSU) strains. By contrast, G190 is encoded by GGA or GGG in 97% of other subtypes and in subtype A strains outside of the FSU. Therefore, G190S results from a single G→A transition: G (GGC) → S (AGC) almost exclusively in subtype A(FSU) viruses. CONCLUSION: The predisposition of subtype A(FSU) to G190S is concerning because G→A is the most common HIV-1 mutation and because G190S causes higher levels of nevirapine and efavirenz resistance than K103N. This study exemplifies the need for characterizing the genetic mechanisms of resistance in diverse populations and warrants studies to verify that NRTI/NNRTI regimens are as efficacious in treating subtype A(FSU) as viruses belonging to other subtypes.status: publishe

Pre-existing singleton E138A mutations in the reverse transcriptase gene do not affect the efficacy of first-line antiretroviral therapy regimens using rilpivirine in human immunodeficiency virus-infected patients

: General consensus suggests that even singleton E138A mutations in HIV reverse transcriptase at baseline are associated with resistance to rilpivirine (RPV). We detected 11 pre-existing E138A carriers treated with RPV in the pan European EuResist database. However, all 11 patients presented with full virological efficacy for first-line RPV-based ART regimens