Effect of non-enzymatic glycosylation in the epigenetics of cancer.

The non-enzymatic glycosylation or non-enzymatic covalent modifications (NECMs) or glycation of cellular proteins result in the generation and accumulation of advanced glycation end products (AGEs) that are associated with the epigenetics of cancer. Epigenetic modifications are inheritable changes without alterations in the sequences of DNA. Glycation-mediated epigenetic mechanisms change the accessibility of transcriptional factors to DNA via rearrangement or modification in the chromatin structure and collaborate with gene regulation in the pathogenesis of cancer. Epigenetic mechanisms play a critical role in sustaining the tissue-specific gene expression. Distraction from normal epigenetic mechanism results in alteration of gene function, initiation and progression of cancer, and cellular malignant transformation. Epigenetic modifications on DNA and histones control enzymatic expressions of corresponding metabolic pathways, which in turn influence epigenetic regulation. Glycation of histones due to persistent hyperglycemia results in histone-histone and histone-DNA cross-linking in chromatin by compromising the electrostatic interactions, that affect the dynamic architecture of chromatin. Histone proteins are highly prone to glycation due to their basic nature and long half-lives, but the exact role of histone glycation in the epigenetics of cancer is still in the veil. However, recent studies have suggested the role of histone glycation mediated epigenetic modifications that affect cellular functioning by altering the gene expressions of related metabolic pathways. Moreover, dicarbonyls-induced NECMs of histones perturb the architecture of chromatin and transcription of genes via multiple mechanisms. Contrary to the genetic causes of cancer, a possible reversal of glycation-mediated epigenetic modifications might open a new realm for therapeutic interventions. In this review, we have portrayed a mechanistic link between histone glycation and cancer epigenetics.

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.

Nonenzymatic glycosylation of isolated human immunoglobulin-G by D-ribose.

Glycation is vital in terms of its damaging effect on macromolecules resulting in the formation of end products, which are highly reactive and cross-linked irreversible structures, known as advanced glycation end products (AGEs). The continuous accumulation of AGEs is associated with severe diabetes and its associated ailments. Saccharides with their reducing ends can glycate amino acid side chains of proteins, among them glucose is well-known for its potent glycating capability. However, other reducing sugars can be more reactive glycating agents than glucose. The D-ribose is a pentose sugar-containing an active aldehyde group in its open form and is responsible for affecting the biological processes of the cellular system. D-ribose, a key component of many biological molecules, is more reactive than most reducing sugars. Protein glycation by reducing monosaccharides such as D-ribose promotes the accelerated formation of AGEs that could lead to cellular impairments and dysfunctions. Also, under a physiological cellular state, the bioavailability rate of D-ribose is much higher than that of glucose in diabetes, which makes this species much more active in protein glycation as compared with D-glucose. Due to the abnormal level of D-ribose in the biological system, the glycation of proteins with D-ribose needs to be analyzed and addressed carefully. In the present study, human immunoglobulin G (IgG) was isolated and purified via affinity column chromatography. D-ribose at 10 and 100 mM concentrations was used as glycating agent, for 1-12 days of incubation at 37°C. The postglycation changes in IgG molecule were characterized by UV-visible and fluorescence spectroscopy, nitroblue tetrazolium assay, and various other physicochemical analyses for the confirmation of D-ribose mediated IgG glycation.

Metformin encapsulated gold nanoparticles (MTF-GNPs): A promising antiglycation agent.

The generation of advanced glycation end products (AGEs) through nonenzymatic protein glycation contributes to the pathogenesis of long-lived diabetic problems. Metformin (MTF) is the very first drug having antihyperglycemic effects on type II diabetes mellitus which also possess interaction with dicarbonyl compounds and blocks the formation of AGEs. In the current study, MTF is bioconjugated with glycation-derived synthesized gold nanoparticles (GNPs) of significant size. Additionally, using various biophysical and biochemical approaches, we investigated the antiglycating capacity MTF-GNPs in contrast to MTF against d-ribose-derived glycation of bovine serum albumin. Our key findings via utilizing various assays demonstrated that MTF-GNPs were able to inhibit AGEs development by reducing hyperchromicity, early glycation products, carbonyl content, hydxoxymethylfurfural content, production of fluorescent AGEs, normalizing the loss of secondary structure (i.e., α-helix and ß-sheets) of proteins, elevating the levels of free lysine and free arginine more efficiently compared to pure MTF. Based on these results, we concluded that MTF-GNPs possess a considerable antiglycation property and may be developed as an outstanding anti-AGEs treatment drug. Further in vivo and clinical research are necessary to determine the therapeutic effects of MTF-GNPs against AGE-related and metabolic disorders.

RAGE Inhibitors for Targeted Therapy of Cancer: A Comprehensive Review.

The receptor for advanced glycation end products (RAGE) is a member of the immunoglobulin family that is overexpressed in several cancers. RAGE is highly expressed in the lung, and its expression increases proportionally at the site of inflammation. This receptor can bind a variety of ligands, including advanced glycation end products, high mobility group box 1, S100 proteins, adhesion molecules, complement components, advanced lipoxidation end products, lipopolysaccharides, and other molecules that mediate cellular responses related to acute and chronic inflammation. RAGE serves as an important node for the initiation and stimulation of cell stress and growth signaling mechanisms that promote carcinogenesis, tumor propagation, and metastatic potential. In this review, we discuss different aspects of RAGE and its prominent ligands implicated in cancer pathogenesis and describe current findings that provide insights into the significant role played by RAGE in cancer. Cancer development can be hindered by inhibiting the interaction of RAGE with its ligands, and this could provide an effective strategy for cancer treatment.

Do all roads lead to the Rome? The glycation perspective!

Oxidative, carbonyl, and glycative stress have gained substantial attention recently for their alleged influence on cancer progression. Oxidative stress can trigger variable transcription factors, such as nuclear factor erythroid-2-related factor (Nrf2), nuclear factor kappa B (NF-κB), protein-53 (p-53), activating protein-1 (AP-1), hypoxia-inducible factor-1α (HIF-1α), ß-catenin/Wnt and peroxisome proliferator-activated receptor-γ (PPAR-γ). Activated transcription factors can lead to approximately 500 different alterations in gene expression, and can alter expression patterns of inflammatory cytokines, growth factors, regulatory cell cycle molecules, and anti-inflammatory molecules. These alterations of gene expression can induce a normal cell to become a tumor cell. Glycative stress resulting from advanced glycation end products (AGEs) and reactive dicarbonyls can significantly affect cancer progression. AGEs are fashioned from the multifaceted chemical reaction of reducing sugars with a compound containing an amino group. AGEs bind to and trigger the receptor for AGEs (RAGE) through AGE-RAGE interaction, which is a major modulator of inflammation allied tumors. Dicarbonyls like, GO (glyoxal), MG (methylglyoxal) and 3-DG (3-deoxyglucosone) fashioned throughout lipid peroxidation, glycolysis, and protein degradation are viewed as key precursors of AGEs. These dicarbonyls lead to the carbonyl stress in living organisms, possibly resulting in carbonyl impairment of proteins, carbohydrates, DNA, and lipoproteins. The damage caused by carbonyls results in numerous lesions, some of which are involved in cancer pathogenesis. In this review, the effects of oxidative, carbonyl and glycative stress on cancer initiation and progression are thoroughly discussed, including probable signaling pathways and the effects on tumorigenesis.

Oxidation, glycation and glycoxidation-The vicious cycle and lung cancer.

The combine effect of oxidative and glycative stress predisposed to glycoxidation, and their outcomes that play critical role in lung cancer have been examined in different ways. The therapeutic approaches for lung cancer are still unsatisfactory. We observe some unclear and decisive pathways which might play an important role in targeting lung cancer. The roadmap of signaling pathway includes p38 MAPK, NF-ƙB, TNF-α and AGE-RAGE binding affinity play role in the cell growth, proliferation, apoptosis inhibition and metastasis. The goal of this review is to achieve a new signaling map inside the lung cancer which is mediated by glycoxidative products mainly reactive dicarbonyls and advanced glycation end products (AGEs). Additionally, AGE-RAGE binding critically regulates the suppression and promotion of lung cancer via inhibition and activation of different signaling pathways. Hence, this review suggests the role of oxidation, glycation, and glycoxidation in lung cancer.

Social exclusion, mental health and suicidal ideation among adults with hearing loss: protective and risk factors.

OBJECTIVE: To investigate social exclusion, mental health and demographic characteristics as risk and protective factors of suicidal ideation among adults with hearing loss. . METHODS: This analytical, cross-sectional study was conducted in Lahore, Pakistan, from June 2016 to January 2017, and comprised people with hearing loss. Multistage proportionate stratified sampling procedure was used. Mental Health Inventory, Social Exclusion Scale and Suicidal Ideation Attributes Scale were administered to the participants. RESULTS: Of the 415 subjects, 246(59.3%) were males and 169(40.8%) females. Suicidal ideation was significantly and positively related to social exclusion (p<0.001), psychological distress (p<0.001), age (p<0.001)) and severity of hearing loss (p<0.05), whereas a significant negative relationship of suicidal ideation (p<0.05) was observed with psychological well-being. Hierarchical regression analysis indicated social exclusion (p<0.001), psychological distress (p<0.001), age (p<0.001), severity of hearing loss (p<0.001) and gender (p<0.001) as significant positive predictors (risk factors), whereas psychological well-being (p<0.05)) was a significant negative predictor (protective factor) of suicidal ideation. CONCLUSIONS: Social exclusion, psychological distress, severity of hearing loss and age were risk factors, whereas psychological well-being was a protective factor regarding suicidal ideation.

Non-suicidal self-injury among children with hearing loss and intellectual disability.

OBJECTIVE: To find the prevalence and to identify the predictors of non-suicidal self-injury among school-going children.. METHODS: This cross-sectional study was conducted at the University of Gujrat, Gujrat Pakistan, from September 2015 to October 2016, and comprised children with intellectual disability and hearing loss. Participants were recruited from schools for special children located in Gujranwala, Jhelum and Gujrat. Multistage stratified sampling technique was used. RESULTS: Of the 325 children, 178(50.4%) had intellectual disability and 175(49.6%) had hearing loss. Findings indicated that the prevalence of self-injurious behaviour was higher in children with intellectual disability 48(27%) compared to their counterparts with hearing loss 3(2%). Neural network, when administered on whole data set, indicated type of disability 0.474(100%), education/training 0.99(20.9%) and access of counselling 0.114(24%) as important predictors of non-suicidal self-injury in both groups. On the other hand, the degree of disability (hearing loss 0.42[100%]; intellectual disability 0.32[100%]), education/ training (hearing loss 0.18[43%]; intellectual disability 0.27[84.5%]) and access of counselling (hearing loss 0.175[41.8%]; intellectual disability 0.256[78.7%]) were important predictors of non-suicidal self-injury among the participants, when neural network was run on the split files on the basis of disability. CONCLUSIONS: The prevalence of non-suicidal self-injury among children with intellectual disability was higher as compared to those with hearing loss.

Prevalence and Predictors of Non-Suicidal Self-Injury among Children with Autism Spectrum Disorder.

OBJECTIVES: To find the prevalence as well as to identify the predictors as protective and risk factors of Non-Suicidal Self-Injury (NSSI) among children with autism spectrum disorder (ASD). METHODS: In this analytical cross sectional survey 83 children with ASD age range from 8 to 18 years were selected through convenient sampling technique from five special schools of Lahore city. The Urdu form of a standardized tool was used to assess NSSI. RESULTS: Statistical analysis indicated overall point prevalence of NSSI was 33%. Moreover banging/self-beating (47%), scratching (38), pinching (35%), picking scabs (33%), self-biting (32%), pulling hair (30%) and rubbing skin (19%) emerged as common forms of challenging behavior. Further regression analysis showed that age B(1.68*, P<.05), gender B(3.72, P<.001) and severity level of ASD B(1.85***, p<.0001) as risk factors/positive predictors of NSSI. However early intervention (-0.66***, P<.0001) and involvement of parents in counselling (-2.66*, P<.05) emerged as protective factors/negative predictors of NSSI among children with ASD. CONCLUSION: Non-suicidal self-injury is a serious challenge among children with ASD. Early intervention, counselling and parental involvement in managing the children with ASD will not only prevent but reduce the challenging behaviors.

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.

Exploring Kinnow mandarin's hidden potential: Nature's key to antimicrobial and antidiabetic gold nanoparticles (K-AuNPs).

This pioneering study aims to address the paradox of the highly regarded Kinnow mandarin fruit, whose valuable peels have been considered undesired remnants from industrial fruit juice production. The study proposes the utilization of these discarded peels to synthesize ecologically safe gold nanoparticles (K-AuNPs) through a one-pot method. The objectives of this research are to synthesize K-AuNPs using an ecologically safe single-step approach, utilizing discarded Kinnow mandarin fruit peels, and to assess their antibacterial and antidiabetic potential. The validation of K-AuNPs involved various techniques including UV-visible spectroscopy, TEM, DLS, and zeta-potential investigations. The antibacterial activity against Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis was compared to levofloxacin and Kinnow mandarin aqueous peel extract (KAPE). Furthermore, the anti-diabetic efficacy was evaluated through α-amylase and α-glucosidase experiments, comparing K-AuNPs to pure KAPE and the standard inhibitor acarbose. The results confirmed the successful synthesis of K-AuNPs from KAPE, as evidenced by UV-spectral profiles (527 nm), TEM micrographs (∼21 d. nm), dynamic light scattering (65 d.nm), and zeta-potential (-12 mV). The K-AuNPs demonstrated a superior zone of inhibition and lower MIC values against Escherichia coli, Pseudomonas aeruginosa, and Bacillus subtilis, surpassing levofloxacin and KAPE alone. Additionally, the K-AuNPs exhibited potent anti-diabetic efficacy, outperforming both pure KAPE and acarbose at a lower dosage. To sum up, the process of producing K-AuNPs utilizing Kinnow mandarin peel extracts demonstrates a powerful antibacterial and antidiabetic remedy sourced from previously discarded materials. These findings signify a significant leap forward in the domain of natural product exploration, with the potential to fundamentally reshape modern healthcare approaches.

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.

Delafloxacin-Capped Gold Nanoparticles (DFX-AuNPs): An Effective Antibacterial Nano-Formulation of Fluoroquinolone Antibiotic.

New antibiotics are seen as 'drugs of last resort' against virulent bacteria. However, development of resistance towards new antibiotics with time is a universal fact. Delafloxacin (DFX) is a new fluoroquinolone antibiotic that differs from existing fluoroquinolones by the lack of a protonatable substituent, which gives the molecule a weakly acidic nature, affording it higher antibacterial activity under an acidic environment. Furthermore, antibiotic-functionalized metallic nanoparticles have been recently emerged as a feasible platform for conquering bacterial resistance. In the present study, therefore, we aimed at preparing DFX-gold nano-formulations to increase the antibacterial potential of DFX. To synthesize DFX-capped gold nanoparticles (DFX-AuNPs), DFX was used as a reducing and stabilizing/encapsulating agent. Various analytical techniques such as UV-visible spectroscopy, TEM, DLS, FTIR and zeta potential analysis were applied to determine the properties of the synthesized DFX-AuNPs. The synthesized DFX-AuNPs revealed a distinct surface plasmon resonance (SPR) band at 530 nm and an average size of 16 nm as manifested by TEM analysis. In addition, Zeta potential results (-19 mV) confirmed the stability of the synthesized DFX-AuNPs. Furthermore, FTIR analysis demonstrated that DFX was adsorbed onto the surface of AuNPs via strong interaction between AuNPs and DFX. Most importantly, comparative antibacterial analysis of DFX alone and DFX-AuNPs against Gram-negative (Escherichia coli and Pseudomonas aeruginosa) and Gram-positive (Staphylococcus aureus and Bacillus subtilis) verified the superior antibacterial activity of DFX-AuNPs against the tested microorganisms. To sum up, DFX gold nano-formulations can offer a promising possible solution, even at a lower antibiotic dose, to combat pathogenic bacteria.

Cefotaxime Mediated Synthesis of Gold Nanoparticles: Characterization and Antibacterial Activity.

Cefotaxime (CTX) is a third-generation cephalosporin antibiotic with broad-spectrum activity against Gram negative and Gram positive bacteria. However, like other third-generation cephalosporin antibiotics, its efficacy is declining due to the increased prevalence of multidrug-resistant (MDR) pathogens. Recent advances in nanotechnology have been projected as a practical approach to combat MDR microorganisms. Therefore, in the current study, gold nanoparticles (AuNPs) were prepared using cefotaxime sodium, which acted as a reducing and capping agent, besides having well-established antibacterial activity. The synthesized cefotaxime-loaded gold nanoparticles (C-AuNPs) were characterized by UV-Visible spectroscopy, FTIR, TEM and DLS. In addition, the in vitro antibacterial activity of C-AuNPs was assessed against both Gram-positive and Gram-negative bacteria. UV-Visible spectroscopy verified the formation of C-AuNPs, while TEM and DLS verified their nano-size. In addition, CTX loading onto AuNPs was confirmed by FTIR. Furthermore, the colloidal stability of the synthesized C-AuNPs was ascribed to the higher net negative surface charge of C-AuNPs. Most importantly, the synthesized C-AuNPs showed superior antibacterial activity and lower minimum inhibitory concentration (MIC) values against Gram-negative (Escherichia coli, Klebsiella oxytoca, Pseudomonas aeruginosa) and gram-positive (Staphylococcus aureus) bacteria, compared with pure CTX. Collectively, CTX was successfully adopted, as reducing and capping agent, to synthesize stable, nano-sized spherical C-AuNPs. Furthermore, loading CTX onto AuNPs could efficiently restore and/or boost the antibacterial activity of CTX against resistant Gram-negative and Gram-positive bacteria.

A Comparative Antibacterial, Antioxidant, and Antineoplastic Potential of Rauwolfia serpentina (L.) Leaf Extract with Its Biologically Synthesized Gold Nanoparticles (R-AuNPs).

Rauwolfia serpentina (R. serpentina), belonging to the family Apocynaceae, is a renowned medicinal herb for its different pharmacological activities such as antibacterial, antifungal, anti-inflammatory, and antiproliferative characteristics. This study has done a comparative assessment of the antibacterial, antioxidant, and anti-cancer activity of R. serpentina aqueous leaf extract (RSALE) with encapsulated gold nanoparticles (R-AuNPs). The R-AuNPs are prepared so that they are significant in size, monodispersed, and extremely stable. Their characterization was done by numerous parameters, including UV-visible spectroscopy (528 nm), transmission electron microscopy (~17 d. nm), dynamic light scattering (~68 d. nm), and zeta-potential (~-17 mV). Subsequently, a potent antibacterial activity was depicted via RSALE and R-AuNPs when examined by disc diffusion against various Gram-positive and Gram-negative bacterial strains. The obtained zones of inhibition of RSALE (100 mg/mL) were 34 ± 0.1, 35 ± 0.1, 28.4 ± 0.01, and 18 ± 0.01, although those of R-AuNPs (15 mg/mL) were 24.4 ± 0.12, 22 ± 0.07, 20 ± 0.16, and 17 ± 0.3 against Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Bacillus subtilis (MTCC 8114), and Streptococcus pyogenes (ATCC 19615), respectively. However, no zone of inhibition was obtained when tested against Proteus vulgaris (MTCC 1771). Furthermore, the obtained MIC values for Staphylococcus aureus were 0.91, 0.61, and 1.15 mg/mL; for Escherichia coli, 0.79, 0.36, and 1.02 mg/mL; for Bacillus subtilis 0.42, 0.27, and 0.474 mg/mL; and for Streptococcus pyogenes, 7.67, 3.86, and 8.5 mg/mL of pure RSALE, R-AuNPs, and Amoxicillin (control), respectively, incorporating that R-AuNPs have been shown to have a 1.4-fold, 2.1-fold, 1.5-fold, and 1.9-fold enhanced antibacterial activity in contrast to pure RSALE tested against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Streptococcus pyogenes, and Proteus vulgaris, respectively. Additionally, an enhanced antioxidant potential was detected in R-AuNPs compared to RSALE evaluated by the 2,2-Diphenyl-1-Picryl Hydrazyl Radical Scavenging (DPPH) Ferric reducing antioxidant power (FRAP) assay. The determined IC 50 values of RSALE and R-AuNPs were 0.131 ± 0.05 and 0.184 ± 0.02 mg/mL, and 0.110 ± 0.1 and 0.106 ± 0.24 mg/mL via the FRAP and DPPH assays, respectively. In addition, the anti-cancer activity against the human cervical cancer (Hela) cell line was evaluated, and the MTT assay results revealed that R-AuNPs (IC50 88.3 µg/mL) had an enhanced anti-cancer potential in contrast to RSALE (171.5 µg/mL). Subsequently, the findings of this study indicated that R. serpentina leaves and their nanoformulation can be used as a potent source for the treatment of the above-mentioned complications and can be used as a possible agent for novel target-based therapies for the management of different ailments.

2'-Deoxyribose Mediated Glycation Leads to Alterations in BSA Structure Via Generation of Carbonyl Species.

The non-enzymatic glycosylation is a very common phenomenon in the physiological conditions which is mediated by distinct chemical entities containing reactive carbonyl species (RCS) and participates in the modification of various macromolecules particularly proteins. To date, various carbonyl species, i.e., glucose, fructose, D-ribose and methylglyoxal have been used frequently to assess the in-vitro non-enzymatic glycosylation. Similarly, 2'-Deoxyribose is one of the most abundant reducing sugar of the living organisms which forms the part of deoxyribonucleic acid and may react with proteins leading to the production of glycation intermediates, advanced glycation end products (AGEs) and highly reactive RCS. Thymidine phosphorylase derived degradation of thymidine contributes to the formation of 2'-Deoxyribose, therefore, acting as a major source of cellular 2'- Deoxyribose. Since albumin is a major serum protein which plays various roles including binding and transporting endogenous and exogenous ligands, it is more prone to be modified through different physiological modifiers; therefore, it may serve as a model protein for in-vitro experiments to study the effect of 2'Deoxyribose mediated modifications in the protein. In this study, Bovine Serum Albumin (BSA) was glycated with 50 and 100 mM 2'-Deoxyribose followed by examining secondary and tertiary structural modifications in BSA as compared to its native (unmodified) form by using various physicochemical techniques. We evident a significant modification in 2'-Deoxyribose-glycated BSA which was confirmed through increased hyperchromicity, keto amine moieties, carbonyl and hydroxymethylfurfural content, fluorescent AGEs, altered secondary structure conformers (α helix and ß sheets), band shift in the amide-I region and diminished free lysine and free arginine content. These modifications were reported to be higher in 100 mM 2'-Deoxyribose-glycated BSA than 50 mM 2'- Deoxyribose-glycated BSA. Our findings also demonstrated that the rate of glycation is positively affected by the increased concentration of 2'-Deoxyribose. The results of the performed study can be implied to uncover the phenomenon of serum protein damage caused by 2'-Deoxyribose leading towards diabetic complications and the number of AGE-related diseases.

Protein oxidation: an overview of metabolism of sulphur containing amino acid, cysteine.

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.