0000000000613382
AUTHOR
Aleksandra Gruevska
p53 and p53-related mediators PAI-1 and IGFBP-3 are downregulated in peripheral blood mononuclear cells of HIV-patients exposed to non-nucleoside reverse transcriptase inhibitors.
The improved effectiveness and safety of the combined antiretroviral therapy (cART) has largely diminished mortality and AIDS-defining morbidity of HIV-patients. Nevertheless, chronic age-related diseases in these individuals are more common and their underlying pathogenic mechanisms of these actions seem to involve accelerated aging and enhanced inflammation. The present study explores markers of these processes in a heterogenous Spanish HIV cohort using peripheral blood samples of HIV-patients and matched uninfected controls. We isolated periheral blood mononuclear cells (PBMCs) and i) compared the expression of a panel of 14 genes related to inflammation and senescence in PBMCs of HIV-pa…
Interconnections among inflammation, chronic liver disease and HIV: understanding the hepatoprotective effects of the antiretroviral drug rilpivirine
INTRODUCCIÓN Durante las últimas décadas, la utilización de la terapia antirretroviral combinada (TARc) para combatir la infección por el virus de la inmunodeficiencia humana (VIH) ha convertido esta enfermedad en una patología crónica. A pesar de que la TARc ha mejorado enormemente la calidad de vida de los pacientes, según diversos estudios epidemiológicos, estos pacientes envejecen antes y sufren de enfermedades relacionadas con la edad como cáncer, osteoporosis, enfermedades metabólicas (diabetes mellitus y enfermedad hepática) y patologías neurodegenerativas aparecen a edades más tempranas que la población no infectada. Los mecanismos responsables de este fenómeno aún no se conocen, si…
Apoptosis of Hepatocytes: Relevance for HIV-Infected Patients under Treatment.
Due to medical advances over the past few decades, human immunodeficiency virus (HIV) infection, once a devastatingly mortal pandemic, has become a manageable chronic condition. However, available antiretroviral treatments (cART) cannot fully restore immune health and, consequently, a number of inflammation-associated and/or immunodeficiency complications have manifested themselves in treated HIV-infected patients. Among these chronic, non-AIDS (acquired immune deficiency syndrome)-related conditions, liver disease is one of the deadliest, proving to be fatal for 15–17% of these individuals. Aside from the presence of liver-related comorbidities, including metabolic disturbances and co-infe…
Understanding the implication of autophagy in the activation of hepatic stellate cells in liver fibrosis: are we there yet?
Liver fibrosis (LF) occurs as a result of persistent liver injury and can be defined as a pathologic, chronic, wound-healing process in which functional parenchyma is progressively replaced by fibrotic tissue. As a phenomenon involved in the majority of chronic liver diseases, and therefore prevalent, it exerts a significant impact on public health. This impact becomes even more patent given the lack of a specific pharmacological therapy, with LF only being ameliorated or prevented through the use of agents that alleviate the underlying causes. Hepatic stellate cells (HSCs) are fundamental mediators of LF, which, activated in response to pro-fibrotic stimuli, transdifferentiate from a quies…
Mitophagy in human astrocytes treated with the antiretroviral drug Efavirenz: Lack of evidence or evidence of the lack
Efavirenz (EFV), a first generation non-nucleoside analogue reverse transcriptase inhibitor widely employed in combination antiretroviral therapy regimens over the last 20 years, has been associated with a wide range of neuropsychiatric effects and has also been linked with HIV-associated neurocognitive disorder (HAND). EFV has been reported to alter mitochondrial dysfunction and bioenergetics in different cell types, including astrocytes. Here, we analyzed whether this mitochondrial effect is associated with alterations in autophagy and, more specifically, mitophagy. U251-MG cells were exposed to EFV (10 and 25 μM; 24 h) and the effect was compared with that of CCCP - an uncoupler of the m…
Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.
Type 2 diabetes (T2D) is a very prevalent, multisystemic, chronic metabolic disorder closely related to atherosclerosis and cardiovascular diseases. It is characterised by mitochondrial dysfunction and the presence of oxidative stress. Metformin is one of the safest and most effective anti-hyperglycaemic agents currently employed as first-line oral therapy for T2D. It has demonstrated additional beneficial effects, unrelated to its hypoglycaemic action, on weight loss and several diseases, such as cancer, cardiovascular disorders and metabolic diseases, including thyroid diseases. Despite the vast clinical experience gained over several decades of use, the mechanism of action of metformin i…