Epigenetic contributions to cancer: Exploring the role of glycation reactions.

Advanced Glycation End-products (AGEs), with their prolonged half-life in the human body, are emerging as potent diagnostic indicators. Early intervention studies, focusing on AGE cross-link breakers, have shown encouraging results in heart failure patients, paving the way for disease progression monitoring and therapy effectiveness evaluation. AGEs are the byproducts of a non-enzymatic reaction where sugars interact with proteins, lipids, and nucleic acids. These compounds possess the power to alter numerous biological processes, ranging from disrupting molecular conformation and promoting cross-linking to modifying enzyme activity, reducing clearance, and impairing receptor recognition. The damage inflicted by AGEs through the stimulation of intracellular signaling pathways is associated with the onset of chronic diseases across various organ systems. This review consolidates the characteristics of AGEs and the challenges posed by their expression in diverse physiological and pathological states. Furthermore, it highlights the clinical relevance of AGEs and the latest research breakthroughs aimed at reducing AGE accumulation.

Identification of Glycoxidative Lesion in Isolated Low-Density Lipoproteins from Diabetes Mellitus Subjects.

Methylglyoxal (MG) is a precursor for advanced glycation end-products (AGEs), which have a significant role in diabetes. The present study is designed to probe the immunological response of native and glycated low-density lipoprotein (LDL) in experimental animals. The second part of this study is to probe glycoxidative lesion detection in low-density lipoproteins (LDL) in diabetes subjects with varying disease duration. The neo-epitopes attributed to glycation-induced glycoxidative lesion of LDL in DM patients' plasma were, analyzed by binding of native and MG-modified LDL immunized animal sera antibodies using an immunochemical assay. The plasma purified human LDL glycation with MG, which instigated modification in LDL. Further, the NewZealand-White rabbits were infused with unmodified natural LDL (N-LDL) and MG-glycatedLDL to probe its immunogenicity. The glycoxidative lesion detection in LDL of DM with disease duration (D.D.) of 5-15 years and D.D. > 15 years was found to be significantly higher as compared to normal healthy subjects (NHS) LDL. The findings support the notion that prolonged duration of diabetes can cause structural alteration in LDL protein molecules, rendering them highly immunogenic in nature. The presence of LDL lesions specific to MG-associated glycoxidation would further help in assessing the progression of diabetes mellitus.

Antiglycation and chemopreventive effects of leaf extracts of Ficus palmata Forssk. found in the Hail region of Saudi Arabia.

The antioxidant and antiglycation activities of the Ficus leaf extracts were evaluated using in vitro assays. The antioxidant activity was determined using the α, α-diphenyl-ß-picrylhydrazyl and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging assays. In vitro ferric reducing activity was evaluated using the ferric reducing antioxidant power assay. The antiglycation potential of the extract was evaluated using dinitrophenylhydrazine, thiobarbituric acid and protein thiol assays. The inhibition of the formation of advanced glycation end products (AGEs) was detected using AGE-specific fluorescence with a fluorescence spectrophotometer. This study was aimed at investigating the potential of Ficus palmata Forssk. leaf extracts, which have abundant bioactive constituents, including polyphenols and flavonoids, in inhibiting glycation and cancer. The results show that the aqueous and methanolic Ficus leaf extracts are rich in phenolic and flavonoid compounds. Both extracts showed potent antioxidant activities. Furthermore, the methanolic extract showed antiglycation activities, as assessed using an in vitro model of bovine serum albumin glycation with D-ribose. The polyphenol- and flavonoid-rich Ficus leaf extracts exhibit antiglycation, chemopreventive and antioxidant activities and have potential for use in the treatment of diseases, such as cancer, which involve oxidative and glycative impairment of cellular proteins.

Differential impact of glycation on apolipoprotein A-I of high-density lipoprotein: a review.

Hyperglycemia is a poorly controlled diabetic condition, affects about 70% of people all round the world. In the year 2015, about 41.5 crore people were diabetic and is expected to reach around 64.3 crore by the year 2040. Cardiovascular diseases (CVDs) are considered as one of the major risk factors that cause more than half of the death of diabetic patients and promote related comorbidities. Atherosclerosis and amyloidosis are the prime factors linked with CVDs. Apolipoprotein A-I (ApoA-I) of HDL has protective action against CVDs, participates in reverse cholesterol transport mechanism and lipid metabolism, but gets easily glycated under prolonged hyperglycemic aura, i.e. glycation. ApoA-I has a potent role in maintenance of glucose level, providing a compelling link between diabetes and CVDs. Increased protein glycation in people with diabetes promotes atherosclerosis, which might play possible role in promotion of protein aggregation by altering the protein structure and its conformation. Here, we intend to investigate the mechanistic behavior of ApoA-I under the menace of glycation and its impact on ApoA-I structure and function that possibly link with aggregation or amyloidosis.

A Study on Multiple Facets of Apolipoprotein A1 Milano.

For several strategies formulated to prevent atherosclerosis, Apolipoprotein A1 Milano (ApoA1M) remains a prime target. ApoA1M has been reported to have greater efficiency in reducing the incidence of coronary artery diseases. Furthermore, recombinant ApoA1M based mimetic peptide exhibits comparatively greater atheroprotective potential, offers a hope in reducing the burden of atherosclerosis in in vivo model system. The aim of this review is to emphasize on some of the observed ApoA1M structural and functional effects that are clinically and therapeutically meaningful that might converge on the basic role of ApoA1M in reducing the chances of glycation assisted ailments in diabetes. We also hypothesize that the nonenzymatic glycation prone arginine amino acid of ApoA1 gets replaced with cysteine residue and the rate of ApoA1 glycation may decrease due to change substitution of amino acid. Therefore, to circumvent the effect of ApoA1M glycation, the related mechanism should be explored at the cellular and functional levels, especially in respective experimental disease model in vivo.