Carvacrol protects against carbonyl osmolyte-induced structural modifications and aggregation to serum albumin: Insights from physicochemical and molecular interaction studies.

The robust use of osmolytes (i.e., polyols and sugars) in the key therapeutic regimens/formulations has questioned their impact beyond the stability of therapeutic proteins as these osmolytes trigger structural alterations into proteins including misfolding and subsequent aggregation into amyloid fibrils. Therefore, the current study is the first to delineate the inhibitory effect of carvacrol (CRV) on the carbonyl osmolyte-induced aggregation as well as structural alterations to the bovine serum albumin (BSA) via a set of physicochemical as well as artificial intelligence (AI)-based molecular docking studies. Our initial findings from physicochemical investigations revealed that CRV exhibits substantial protection to BSA under carbonyl osmolyte stress as evident by the compromised hyperchromicity, Schiff's bases, carbonyl and hydroxymethyl furfural content, reduced fluorescent signals, low Rayleigh scattering and prevention of covalent modifications at Lys and Arg residues. The protection against aggregate formation by CRV was further confirmed through the reduced amyloid-specific congo red absorbance as well as fluorescent signals recorded after adding the fibril-specific extrinsic fluorophore probes (i.e., ThT and ANS). The AI-based molecular docking analysis further revealed that CRV (ΔG: -4.96 kcal/mol) competes with d-fructose (ΔG: -4.40 kcal/mol) to mask the Lys and Arg residues to restrict the osmolyte-mediated protein modifications. In conclusion, CRV exhibits substantial protective impact against carbonyl osmolyte-induced structural alterations and protein misfolding and aggregation.

Glyoxal induced glycative insult suffered by immunoglobulin G and fibrinogen proteins: A comparative physicochemical characterization to reveal structural perturbations.

Glycation of proteins results in structural alteration, functional deprivation, and generation of advanced glycation end products (AGEs). Reactive oxygen species (ROS) that are generated during in vivo autoxidation of glucose induces glycoxidation of intermediate glycation-adducts, which in turn give rise to aldehyde and/or ketone groups containing dicarbonyls or reactive carbonyl species (RCS). RCS further reacts non-enzymatically and starts the glycation-oxidation vicious cycle, thus exacerbating oxidative, carbonyl, and glycative stress in the physiological system. Glyoxal (GO), a reactive dicarbonyl that generates during glycoxidation and lipid peroxidation, contributes to glycation. This in vitro physicochemical characterization study focuses on GO-induced glycoxidative damage suffered by immunoglobulin G (IgG) and fibrinogen proteins. The structural alterations were analyzed by UV-vis, fluorescence, circular dichroism, and Fourier transform infrared (FT-IR) spectroscopy. Ketoamines, protein carbonyls, hydroxymethylfurfural (HMF), free lysine, free arginine, carboxymethyllysine (CML), and protein aggregation were also quantified. Structural perturbations, increased concentration of ketoamines, protein carbonyls, HMF, and malondialdehyde (MDA) were reported in glycated proteins. The experiment results also validate increased oxidative stress and AGEs formation i.e. IgG-AGEs and Fib-AGEs. Thus, we can conclude that AGEs formation during GO-mediated glycation of IgG and fibrinogen could hamper normal physiology and might play a significant role in the pathogenesis of diabetes-associated secondary complications.

Balance Enhancement in Older Adults: Is Functional-Task Training Better Than Resistance Training in Enhancing Balance in Older Adults?

Background and purpose The effects of various exercise training programs on balance in older adults are well established. This study aimed to compare the effect of functional-task training with resistance training in improving balance performance in older adults. Methods A total of 100 community-dwelling older adults aged 65 years and above were randomly allocated into two groups: functional-task training (FTT) group and resistance training (RT) group. The FTT group (n = 50) performed functional task exercises and the RT group (n = 50) performed resistance exercises three times a week for 12 weeks. Balance was evaluated before and after the trial using the Berg Balance Scale (BBS) and the Timed Up and Go (TUG) test. Results A total of 87 subjects who completed the study were analyzed. Both the groups showed a significant change in BBS and TUG test (p < 0.05) from baseline to 12 weeks. However, post-intervention analysis between the groups showed a significant difference in both the BBS and TUG test (p < 0.05), i.e. improvement in the FTT group was better than the RE group at the end of training. Conclusion Both the FTT and RT were effective in improving balance. However, the improvement achieved by the FTT group was better than the RT group.