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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. [ABSTRACT FROM AUTHOR]

Biosynthetic procedure is one of the best alternatives, inexpensive and ecologically sound for the synthesis of titanium dioxide (TiO2) nanoparticles using a methanolic extract of medicinal plant. The main prospect of this study was to investigate the antiglycation activity of the TiO2 nanoparticles (TNP) prepared by ethanolic leaf extract of the Coleus scutellarioides. In this study, biosynthesized TNP characterized with UV‐Visible spectroscopy, X‐ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscope. These TNP were further investigated with respect to their antiglycation property and it was checked in the mixture of d‐ribose glycated bovine serum albumin (BSA) by measuring ketoamine, carbonyl content, Advanced glycation end products (AGEs) and aggregation of protein instigated by glycation process. The inhibitory effect of TNP to restore the structure of BSA in presence of d‐ribose were also characterize by biophysical techniques mentioned above. Therefore, the findings of this study suggest repurposing of TNP for its antiglycation property that could be helpful in prevention of glycation instigated AGEs formation and structural loss of proteins. Significance statement: Provide a low cost green synthesis method for the synthesis of biologically active titanium dioxide (TiO2) nanoparticles.Provide the structural characterization of green synthesized TiO2 nanoparticles (TNP).An insight to identify the TNP as significant glycation inhibitor.Study suggest antiglycation potential detection of plant based TNP as possible therapeutic invention for hyperglycemia assisted diabetes and associated diseases. [ABSTRACT FROM AUTHOR]

Apolipoprotein A1 (ApoA1) is a prominent component of the “good cholesterol” and facilitates its functioning. Its misfolding is a critical risk factor for several diseases, such as cardiovascular diseases, Alzheimer’s, diabetes and hereditary amyloidoses. Several naturally occuring mutants of ApoA1 are also associated with amyloidoses. The structural correlations between amyloidosis and protein stability are largely unknown forApoA1. In this study, a sequence-based bioinformatics and molecular modeling approach was adopted to investigate the structural manifestations of selected ApoA1 mutations and their association with the amyloid-forming potential of the protein. Based on in silico analyses, we predicted the structure and aggregation propensities of the fibrilogenic ApoA1 polypeptides. Physico-chemical characterization using several parameters revealed the polypeptidesto be unstable and having anacidic nature. Secondary structure was also predicted along with different motifs. Because the three-dimensional structures for the mature wild type (WT) ApoA1 and its selected mutants were not available in the Protein Data Bank, we developed homology models using Modeller 9.10. The model was validated using RAMPAGE. The order of WT and the selected mutants in the formation of amyloid fibrils (L170P>WT = P143R) correlates with the involvement of protein in amyloidosis and directly with the strength of the protein–lipid association, which increases with the increasing protein hydrophobicity. However, this pattern was not observed in in silico prediction of proteolytically susceptible residues. We conclude that the amyloid-forming propensity and its stability is rooted in the hydrophobicity of Apo A1. The generated model would pavethe way for detailed in vitro and in vivo studies. [ABSTRACT FROM AUTHOR]

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., (Copyright © 2024. Published by Elsevier Inc.)

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-β-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.

Impaired awareness of glycation biology in cancer initiation and progression is one of the fundamental reasons for its meticulous investigation of the molecules involved in signalling pathway. Glycation of biological macromolecules results in the progression of advanced glycation end-products (AGEs) that proliferates the process of carcinogenesis by activation of transcription factors and release of cytokines. The receptor for advanced glycation end-products (RAGEs) with the binding of its different ligands like; AGEs, HMGB1 and S100 activate the signalling arrays. The activation of downstream signalling pathway ultimately leads to the pathophysiological conditions of diabetes, ageing, neurological disorders and cancers as well as a result of the activation of transcription factors which is discussed in the main body text of this review. However, there might be a likelihood of the positive effect of the HMGB1 and S100 proteins in cancer. Still, some untouched mechanisms might be responsible for the establishment of the function of AGE-RAGE or AGE-sRAGE axis activation that leads to the friend-foe association with the cancers. The levels of RAGE and s-RAGE may be a useful biomarker of ligand-RAGE pathway activation and cancer. Thus, the possibility of providing a potential complement to carcinogenesis is very high which might be an interesting target for therapeutic interventions. This article is an insightful assessment on AGE, RAGE and s-RAGE for its possible role in cancer onset and progression. The novel therapeutic targets for cancer prevention or inhibition are also explained in brief in relation to AGE and RAGE., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

The available data suggest that among cellular constituents, proteins are the major target for oxidation primarily because of their quantity and high rate of interactions with ROS. Proteins are susceptible to ROS modifications of amino acid side chains which alter protein structure. Among the amino acids, Cysteine (Cys) is more prone to oxidation by ROS because of its high nucleophilic property. The reactivity of Cys with ROS is due to the presence of thiol group. In the oxidised form, Cys forms disulfide bond, which are primary covalent cross-link found in proteins, and which stabilize the native conformation of a protein. Indirect evidence suggests that thiol modifications by ROS may be involved in neurodegenerative disorders, but the significance and precise extent of the contributions are poorly understood. Here, we review the role of oxidized Cys in different pathological consequences and its biochemistry may increase the research in the discovery of new therapies. The purpose of this review is to re-examine the role and biochemistry of oxidised Cys residues.