In the last three decades, there has been a considerable improvement in human immunodeficiency virus (HIV) therapy. Acquired immunodeficiency syndrome (AIDS) is no longer a common cause of death for people living with HIV (PLWH) in developed countries, and co-infections with hepatitis viruses can be effectively managed. However, metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD) are emerging threats these days, especially as the HIV-positive population gets older. The factors for MASLD development in PLWH are numerous, including non-specific (common for both HIV-positive and negative) and virus-specific. We focus on what is known for both, and in particular, on the burden of antiretroviral therapy (ART) for metabolic health and liver damage. We review data on contemporary drugs, including different groups and some particular agents in those groups. Among current ART regimens, the switch from tenofovir disoproxil fumarate (TDF) to tenofovir alafenamide fumarate (TAF) and particularly its combination with integrase inhibitors (INSTIs) appear to have the most significant impact on metabolic disturbances by increasing insulin resistance, which over the years promotes the evolution of the cascade leading to metabolic syndrome (MetS), MASLD, and eventually metabolic dysfunction-associated steatohepatitis (MASH).
The extracts from fruits of Chaenomeles japonica (Thunb.) Lindl. ex Spach (CJE), Cornus mas L. (CME), and Hippophaё rhamnoides L. (HRE) are known inhibitors of a variety of eukaryotic hydrolases, engaged in the digestion of fats and polysaccharides. However, there are no data on their potential interaction with the bacterial hydrolases participating in the replication of microbial nucleic acids. This analysis predicted the interaction of the most abundant constituents of HRE, CJE, and CME with the bacterial nucleases. The analysis covered the molecular docking of isorhamnetin glycosides, procyanidins C1 and B2, epicatechin, loganic acid, and cornuside with bacterial enzymes (Escherichia coli endonuclease 1, colicin E9, and ribonuclease H; or Staphylococcus aureus thermonuclease and nuclease SbcCD). The suggested complexes have been subjected to molecular mechanics with generalized Born and surface area solvation (MM/GBSA) calculations. The second aim was the in vitro evaluation of the influence of the CJE, HRE, and CME on the metabolic activity of bacterial biofilm of selected microbial strains, as well as fibroblasts (L929) and adenocarcinoma intestinal cells (Caco-2) toxicity. Among all extracts, CME showed the most relevant effect on the survival of planktonic cells and biofilm of E. coli and Pseudomonas aeruginosa. As a result of in silico studies, most virtual hits were predicted to inhibit the proteins under investigation, except for procyanidin C1. Further research on the direct interaction of phytochemicals and selected enzymes in vitro is required and challenged.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) have been important factors leading to morbidity and mortality. Despite the emergence of new variants, such as Omicron, which can cause milder illness than e.g. Delta, there is a group...