Closest horizons of Hsp70 engagement to manage neurodegeneration.

Our review seeks to elucidate the current state-of-the-art in studies of 70-kilodalton-weighed heat shock proteins (Hsp70) in neurodegenerative diseases (NDs). The family has already been shown to play a crucial role in pathological aggregation for a wide spectrum of brain pathologies. However, a slender boundary between a big body of fundamental data and its implementation has only recently been crossed. Currently, we are witnessing an anticipated advancement in the domain with dozens of studies published every month. In this review, we briefly summarize scattered results regarding the role of Hsp70 in the most common NDs including Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS). We also bridge translational studies and clinical trials to portray the output for medical practice. Available options to regulate Hsp70 activity in NDs are outlined, too.

Structural changes of erythrocyte membrane revealed by 3D confocal optical profilometer.

We examined hematological changes influenced by the experimental hypervitaminosis A. The 3D confocal optical profilometer was applied for assessment of the erythrocytes' membrane structural changes influenced by an overdose of vitamin A. The blood smears were evaluated in terms of alterations of geometrical and optical parameters of erythrocytes for two groups of animals: oil base and retinol palmitate (n = 9 animals for each group). The results demonstrate that an overdose of retinol palmitate causes changes in the torus curvature and pallor of discocytes, their surface area and volume. The observed structural malformations of the shape of red blood cells become visible at the earlier preclinical stage of changes in animal state and behavior. With this in mind, the results of the study open a new area of research in the certain dysfunction diagnosis of red blood cells and have a great potential in the further development of new curative protocols.

Cytokines in Abdominal Aortic Aneurysm: Master Regulators With Clinical Application.

Abdominal aortic aneurysm (AAA) is a potentially life-threatening disorder with a mostly asymptomatic course where the abdominal aorta is weakened and bulged. Cytokines play especially important roles (both positive and negative) among the molecular actors of AAA development. All the inflammatory cascades, extracellular matrix degradation and vascular smooth muscle cell apoptosis are driven by cytokines. Previous studies emphasize an altered expression and a changed epigenetic regulation of key cytokines in AAA tissue samples. Such cytokines as IL-6, IL-10, IL-12, IL-17, IL-33, IL-1ß, TGF-ß, TNF-α, IFN-γ, and CXCL10 seem to be crucial in AAA pathogenesis. Some data obtained in animal studies show a protective function of IL-10, IL-33, and canonical TGF-ß signaling, as well as a dual role of IL-4, IFN-γ and CXCL10, while TNF-α, IL-1ß, IL-6, IL-12/IL-23, IL-17, CCR2, CXCR2, CXCR4 and the TGF-ß noncanonical pathway are believed to aggravate the disease. Altogether data highlight significance of cytokines as informative markers and predictors of AAA. Pathologic serum/plasma concentrations of IL-1ß, IL-2, IL-6, TNF-α, IL-10, IL-8, IL-17, IFN-γ, and PDGF have been already found in AAA patients. Some of the changes correlate with the size of aneurysms. Moreover, the risk of AAA is associated with polymorphic variants of genes encoding cytokines and their receptors: CCR2 (rs1799864), CCR5 (Delta-32), IL6 (rs1800796 and rs1800795), IL6R (rs12133641), IL10 (rs1800896), TGFB1 (rs1800469), TGFBR1 (rs1626340), TGFBR2 (rs1036095, rs4522809, rs1078985), and TNFA (rs1800629). Finally, 5 single-nucleotide polymorphisms in gene coding latent TGF-ß-binding protein (LTBP4) and an allelic variant of TGFB3 are related to a significantly slower AAA annual growth rate.