Enhancing growth, vitality, and aromatic richness: unveiling the dual magic of silicon dioxide and titanium dioxide nanoparticles in Ocimum tenuiflorum L.

Ocimum tenuiflorum, commonly known as "Holy basil," is renowned for its notable medicinal and aromatic attributes. Its unique fragrance attributes to specific volatile phytochemicals, primarily belonging to terpenoid and/or phenylpropanoid classes, found within their essential oils. The use of nanoparticles (NPs) in agriculture has attracted attention among plant researchers. However, the impact of NPs on the modulation of morpho-physiological aspects and essential oil production in medicinal plants has received limited attention. Consequently, the present study aimed to explore the effect of silicon dioxide (SiO2) and titanium dioxide (TiO2) nanoparticles at various concentrations (viz., DDW (control), Si50+Ti50, Si100+Ti50, Si100+Ti100, Si200+Ti100, Si100+Ti200 and Si200+Ti200 mg L-1) on growth, physiology and essential oil production of O. tenuiflorum at 120 days after planting (DAP). The results demonstrated that the combined application of Si and Ti (Si100+Ti100 mg L-1) exhibited the most favourable outcomes compared to the other combinational treatments. This optimal treatment significantly increased the vegetative growth parameters (root length (33.5%), shoot length (39.2%), fresh weight (62.7%) and dry weight (28.5%)), photosynthetic parameters, enzymatic activities (nitrate reductase and carbonic anhydrase), the overall area of PGTs (peltate glandular trichomes) and essential oil content (172.4%) and yield (323.1%), compared to the control plants. Furthermore, the GCMS analysis showed optimal treatment (Si100+Ti100) significantly improved the content (43.3%) and yield (151.3%) of eugenol, the primary active component of the essential oil. This study uncovers a remarkable and optimal combination of SiO2 and TiO2 nanoparticles that effectively enhances the growth, physiology, and essential oil production in Holy basil. These findings offer valuable insights into maximizing the potential benefits of its use in industrial applications.

Combined application of SiO2 and TiO2 nanoparticles enhances growth characters, physiological attributes and essential oil production of Coleus aromatics Benth.

Nanoparticles (NPs) have gained considerable interest among researchers in the field of plant biology, particularly in the agricultural sector. Among the numerous NPs, the individual application of silicon (Si) or titanium (Ti), in their oxide forms, had a positive influence on growth, physiochemical and yield attributes of plants. However, the synergetic application of both these NPs has not been studied yet. Therefore, the current study was aimed to investigate the effect of combined application of silicon dioxide (SiO2) and titanium dioxide (TiO2) NPs on the growth characters, physiological parameters, and essential oil quality and production of Coleus aromatics Benth. Aqueous solutions of nanoparticles were applied to the foliage of the plants at varying combinations (Si50+Ti50, Si100+Ti50, Si100+Ti100, Si200+Ti100, Si100+Ti200 and Si200+Ti200 mg L-1). Various morpho-physiological, biochemical and yield attributes were assessed at 120 days after planting. The results demonstrated that both Si and Ti NPs improved the growth and photosynthetic efficiency in a dose dependent manner. The best results were obtained by the combined application of Si100+Ti100 mg L-1, and thereafter, the values declined progressively. The maximum improvement in fresh weight (39.5 %) and dry weight (40.8 %) of shoot, fresh weight (45.7 %) and dry weight (49.4 %) of root was observed as compared to respective controls. Moreover, the exogenous application of Si100+Ti100 mg L-1 increased photosynthetic attributes such as total content of chlorophyll (41.7 %), carotenoids (43.7 %), chlorophyll fluorescence (7.1 %), and carbonic anhydrase (23.8 %). All of these contributed to the highest accumulation in the content (129.0 %) and yield (215.5 %) of essential oil (EO), in comparison to the control. Thus, results encouraged the use of SiO2 and TiO2 NPs to be applied in combined form to boost the essential oil production of Coleus aromaticus. The findings of this study may serve agronomists to determine the optimal concentrations of NPs for enhanced production of bioactive compounds with a wide range of industrial applications.

Plant-derived smoke water and karrikinolide (KAR1) enhance physiological activities, essential oil yield and bioactive constituents of Mentha arvensis L.

Introduction: The current study was carried out with the hypothesis that foliar application of plant-derived smoke water (PDSW) and karrikinolide (KAR1) might enhanced the plant growth, physiology, and essential oil production of the Mentha arvensis L. Karrikinolide (KAR1) is one of the most important bioactive constituents of PDSW. Methods: Mint (Mentha arvensis L.) was grown in natural conditions in the net-house. Different concentrations of PDSW (1:125, 1:250, 1:500 and 1:1000 v/v) and KAR1 (10-9 M, 10-8 M, 10-7 M and 10-6 M) were used as foliar-spray treatments, using double-distilled water as control. The PDSW was prepared by burning the dried wheat-straw that acted as a growth-promoting substance. Results: Foliar-spray treatment 1:500 v/v of PDSW and 10-8 M of KAR1 proved optimal for enhancing all morphological, physiological, and essential-oil yield related parameters. In comparison with the control, 1:500 v/v of PDSW and 10-8 M of KAR1 increased significantly (p ≤ 0.05) the height of mint plant (19.23% and 16.47%), fresh weight (19.30% and 17.44%), dry weight (35.36% and 24.75%), leaf area (18.22% and 17.46%), and leaf yield per plant (28.41% and 23.74%). In addition, these treatments also significantly increased the photosynthetic parameters, including chlorophyll fluorescence (12.10% and 11.41%), total chlorophyll content (25.70% and 20.77%), and total carotenoid content (29.77% and 27.18%). Likewise, 1:500 v/v of PDSW and 10-8 M of KAR1 significantly increased the essential-oil content (37.09% and 32.25%), essential oil productivity per plant (72.22% and 66.66%), menthol content (29.94% and 25.42%), menthyl acetate content (36.90% and 31.73%), and menthone content (44.38% and 37.75%). Furthermore, the TIC chromatogram of the GCMS analysis revealed the presence of 34 compounds, 12 of which showed major peak areas. Discussion: Treatment 1: 500 v/v of PDSW proved better than the treatment 10-8 M of KAR1 with regard to most of the parameters studied. The outcome of the study can be used as a recommendation tool for agricultural and horticultural crops, since it costs much lesser than that of KAR1. In fact, the foliar application of PDSW proved economical and played bioactive role at very low concentrations.

Studies on the synergistic action of methylglyoxal and peroxynitrite on structure and function of human serum albumin.

Albumin, an important serum protein, is continuously exposed to various oxidizing/nitrating and glycating agents. Depending upon the nature/concentration of reactive species present, the protein may be glycated, oxidized/nitroxidized or glyco-nitro-oxidized. Peroxynitrite is a powerful nitroxidant and has been reported to damage a wide array of macromolecules. On the other hand, methylglyoxal is a very strong reactive dicarbonyl and a potent precursor for the formation of advanced glycation end products under pathological conditions. In certain pathological conditions albumin may be modified by peroxynitrite and methylglyoxal simultaneously. There is dearth of literature suggests that structural/conformational and functional alteration in albumin upon glycation and oxidation/nitroxidation, however the alterations produced by glyco-nitro-oxidation has not yet been explored. Therefore, in this study, simultaneous effect of glycation and nitroxidation on the structure and conformation, vis-a-vis function of albumin was explored. Glyco-nitro-oxidized albumin showed decreased free amino acid content together with decreased affinity of albumin towards cobalt. Molecular docking model and molecular dynamic simulations showed close interaction and formation of stable complexes between methylglyoxal, peroxynitrite and albumin. Formation of carboxymethyl lysine and 3-nitrotyrosine in glyco-nitro-oxidized albumin were confirmed by MALDI-TOF MS and UP-LC MS. Aggregate formation in glyco-nitro-oxidized albumin was visualized by transmission electron microscopy. On the basis of these results, it may be speculated that, albumin modified with endogenously generated methylglyoxal and peroxynitrite might be a driving factor in the progression of heightened inflammatory autoimmune responses. The work presents a ground to study the role of glyco-nitro-oxidized albumin in the pathogenesis and progression of various autoimmune diseases including rheumatoid arthritis. Communicated by Ramaswamy H. Sarma.

Financial Development and Environmental Degradation: Promoting Low-Carbon Competitiveness in E7 Economies' Industries.

Emerging countries are approaching economic prosperity. However, the development process has enhanced their ecological footprints, thus promoting low-carbon competitiveness among E7 countries' industries. Therefore, it is essential to identify the factors that affect a country's ecological footprint (EF) in order to safeguard the environment. This study explored the effect of financial development, human capital, and institutional quality on the EF of emerging countries. Furthermore, we explored the effect of financial development on the EF of emerging countries through the human capital channel. In addition, we investigated the role of institutional quality in the financial development-EF nexus. Using panel data from 1990 to 2018, we employed the cross-sectional autoregressive distributed lag (CS-ARDL) technique to conduct a short-term and long-term empirical analysis. The empirical outcomes revealed that financial development degrades ecological quality by raising the EF. The findings further demonstrated that human capital and institutional quality reduce the EF. Moreover, financial development fosters environmental sustainability through the channel of human capital. Additionally, institutional quality reduces the negative ecological impacts of financial development. The causality analysis suggested that any policy related to financial development, human capital, and institutional quality will affect the EF. However, the inverse conclusion was not sustained. Based on these findings, emerging economies should increase their environmental sustainability by promoting human capital and effectively using financial resources.

N-OH-AABP Modifications in Human DNA May Lead to Auto-Antibodies in Bladder Cancer Subjects.

4-Aminobiphenyl (4-ABP) and other related arylamines have emerged to be responsible for human urinary bladder tumors and cancers. Hemoglobin-ABP adducts have been recognized in the blood of smokers, and it builds up in the circulatory system over the period of years that might lead to a bladder tumor. N-hydroxy-Acetyl 4-Aminobiphenyl (N-OH-AABP) is one of the reactive forms of 4-ABP which has a potential to initiate tumor growth and causes cancer rapidly. In the present study, commercially available human DNA was modified by N-OH-AABP, and its modifications were analyzed biophysically from fluorescence spectroscopy and thermal denaturation studies. Further, Sera and IgG from bladder cancer patients' blood were assessed for affinity to native and N-OH-AABP modified human DNA using ELISA. The study showed N-OH-AABP caused damage in the structure of the DNA macromolecule and the perturbations resulting from damage leads to change in the Tm of the DNA molecule. Bladder cancer auto-antibodies, particularly in smoker group, showed preferential binding to N-OH-AABP modified human DNA. This study shows that N-OH-AABP modified DNA could be an antigenic stimulus for the generation of autoantibodies in the sera of bladder cancer patients.

Nanotized kinetin enhances essential oil yield and active constituents of mint via improvement in physiological attributes.

Often mint (Mentha arvensis L.) faces unforeseen limitations, resulting in a low yield and quality of essential oil (EO), especially menthol content necessitating the need to explore the potential of modern technology to overcome this predicament. One of such techniques is the use of nanomaterials. The bulk (un-nanotized) form of PGRs (plant growth regulators) has been considered as a potential tool for crop improvement. Utilizing the top-down approach of nanotization, bulk PGR kinetin was ball-milled to the nano-scale range. A pot experiment was conducted on mint applying bulk- and nano-kinetin through foliar application. The concentrations of spray-treatments included 0 (de-ionized water, control), 10, 20, and 30 µM of bulk-as well as nanotized-kinetin. Both forms of kinetin manifested their patterns in the plant. Treatment N2 (20 µM of nanotized-kinetin) excelled in all other treatments for most of the parameters studied. As compared with De-ionized water-spray control, it resulted in the highest improvement in photosynthetic efficiency, Carbonic anhydrase activity, EO content (46.6 %), EO yield (50.8 %), and density as well as the diameter of PGTs (peltate glandular trichomes). Treatment N2, equalled by treatment B2 (20 µM of bulk-kinetin), maximally improved the menthol yield. The highest content and yield of EO, as a result of N2 application, was attributed to its manifestation in terms of the improved photosynthetic machinery, enzyme activity, and vigour (density and diameter) of PGTs. Since treatment N2 increased the most desirable EO-traits, viz. content and yield of EO along with yield of menthol, it might be recommended for successful production of mint.

Characterization of Glyoxal Modified LDL: Role in the Generation of Circulating Autoantibodies in Type 2 Diabetes Mellitus and Coronary Artery Disease.

AIMS: This study aims to investigate the role of glyoxal modified LDL in the immunopathology of diabetes and cardiovascular disease. BACKGROUND: Glycoxidation of proteins is widely studied in relation to diabetes and cardiovascular disease. OBJECTIVE: This study probed the glyoxal mediated modifications in LDL, analyzed the immunogenicity of the glycated LDL and ascertained the presence of circulating antibodies against modified LDL in patients with type 2 diabetes mellitus (T2DM), coronary artery disease (CAD) and patients with both (T2DM+CAD). METHODS: Glyoxal mediated modifications in LDL were studied by multiple spectroscopic techniques, high-performance liquid chromatography and electron microscopy. Immunization studies were carried in New Zealand rabbits. The presence of antibodies against glyoxal modified LDL in immunized rabbits and human subjects was analyzed by ELISA. RESULTS: Glyoxal altered the structural integrity of LDL and led to the formation of AGEs. It decreased the alpha-helix content of LDL; increased ß sheet formation, increased carbonyl content and decreased free lysine and arginine content. Modified LDL showed aggregation, generation of of Nε- (Carboxymethyl) lysine and the formation of amorphous type aggregates. It exhibited high antigenicity and generated a specific immune response that shared common antigenic determinants with other glycated proteins. Direct binding data showed the presence of anti-glyoxal modified LDL antibodies in patients with T2DM, CAD and patients with both T2DM and CAD. Further analysis in competitive binding assay revealed specific binding characteristics of auto-antibodies. Sera from patients with T2DM+CAD exhibited the highest binding with glyoxal modified LDL. CONCLUSION: Glyoxal-modified LDL has neo-antigenic determinants that cause the generation of circulating antibodies in diabetes and coronary artery disease. The study might have potential relevance in biomarker development.

Recent advances in histone glycation: emerging role in diabetes and cancer.

Ever increasing information on genome and proteome has offered fascinating details and new opportunities to understand the molecular biology. It is now known that histone proteins surrounding the DNA play a crucial role in the chromatin structure and function. Histones undergo a plethora of posttranslational enzymatic modifications that influence nucleosome dynamics and affect DNA activity. Earlier research offered insights into the enzymatic modifications of histones; however, attention has been diverted to histone modifications induced by by-products of metabolism without enzymatic engagement in the last decade. Nonenzymatic modifications of histones are believed to be crucial for epigenetic landscape, cellular fate and for role in human diseases. Glycation of histone proteins constitutes the major nonenzymatic modifications of nuclear proteins that have implications in diabetes and cancer. It has emerged that glycation damages nuclear proteins, modifies amino acids of histones at crucial locations, generates adducts affecting histone chromatin interaction, develops neo-epitopes inducing specific immune response and impacts cell function. Presence of circulating antibodies against glycated histone proteins in diabetes and cancer has shown immunological implications with diagnostic relevance. These crucial details make histone glycation an attractive focus for investigators. This review article, therefore, makes an attempt to exclusively summarize the recent research in histone glycation, its impact on structural integrity of chromatin and elaborates on its role in diabetes and cancer. The work offers insights for future scientists who investigate the link between metabolism, biomolecular structures, glycobiology, histone-DNA interactions in relation to diseases in humans.

Withdrawal Notice: Characterization of Glyoxal Modified LDL: Role in the Generation of Circulating Autoantibodies in Type 2 Diabetes Mellitus and Coronary Artery Disease

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Glycoxidation of LDL Generates Cytotoxic Adducts and Elicits Humoral Response in Type 2 Diabetes Mellitus.

This study elucidates the immunological implications of methylglyoxal (MGO) modified LDL in diabetes type 2 patients (T2DM). Under in-vitro modifications, MGO altered the tertiary structure of LDL. TNBS and phenanthrenequinone assays confirmed lysine and arginine residues as main targets of MGO in LDL. HPLC and LCMS studies confirmed the generation of Nϵ-(carboxymethyl) lysine in the modified protein. Comet assay showing increased tail length of DNA in lymphocytes inferred the cytotoxicity of MGO-LDL. The easy penetration of MGO-LDL into the nucleus is possibly a consequence of its reduced size, post-modification, as observed from the studies on hydrodynamic radii studies in DLS experiments. MGO-LDL was found to be more immunogenic, as compared to native LDL, in immunological studies conducted on experimental rabbits. Our results reflect the presence of neo-antigenic determinants on modified LDL. Competitive inhibition ELISA suggested the presence of neo-epitopes with marked immunogenicity eliciting specific immune response. Binding studies on purified IgG confirmed the enhanced and specific immunogenicity of MGO-LDL. Studies on interaction of MGO-LDL with the circulating auto-antibodies from T2DM patients showed high affinity of serum-antibodies towards MGO-LDL. This study suggests a potent role of glycoxidatively modified LDL in the generation of auto-immune response in T2DM patients.

Gamma rays induced acquisition of structural modification in chitosan boosts photosynthetic machinery, enzymatic activities and essential oil production in citronella grass (Cymbopogon winterianus Jowitt).

Oligomers derived through irradiation of marine polysaccharides have generated a lot of interest of plant biologists as the application of these molecules has yielded positive results regarding various plant processes. To comprehend the previously established growth-promoting activity of irradiated chitosan (ICH) and to gain insight of the structure-property relationship, gamma rays induced structural changes were analyzed using techniques such as Fourier Transform Infrared (FT-IR) spectroscopy, Ultraviolet-visible (UV-Vis) spectroscopy, 13C-Nuclear Magnetic Resonance (NMR) spectroscopy and Scanning Electron Microscopy (SEM). Moreover, to study the bioactivity of ICH samples a pot experiment was conducted on citronella grass (Cymbopogon winterianus) to access its response to foliar application of various levels (40, 60, 80 and 100 mg L-1) of ICH in terms of growth, physiological attributes and essential oil (EO) production. The application of ICH at 80 mg L-1(ICH-80) resulted in the maximum values of most of the attributes studied. Due to this treatment, the maximum improvement in the content (29.58%) and yield (90.81%) of EO in Cymbopogon winterianus were achieved. Gas chromatography-mass spectrometry (GC-MS) analysis revealed that ICH-80 also increased the content of citronellal (14.81%) and geraniol (18.15%) of the EO as compared to the control.

Elucidating the inhibitory potential of Vitamin A against fibrillation and amyloid associated cytotoxicity.

Protein aggregation and amyloid fibrillation are associated with many serious human pathophysiologies like Alzheimer's, Parkinson's diseases, type II diabetes etc. A powerful strategy for controlling and understanding amyloid protein aggregation is the modulation of protein self-assembly. In this study, anti-fibrillation activity of vitamin A (VA) and its effect on the kinetics of amyloid formation of Aß-42 peptide was investigated by employing various spectroscopic, imaging and computational approaches. The present data of Thioflavin T (ThT) fluorescence assay, circular dichroism (CD), dynamic light scattering assay, transmission electron microscopy and cell cytotoxicity assay demonstrated that vitamin A significantly inhibits fibril formation. Our experimental studies inferred that Vitamin A protects human neuroblastoma cell line (SH-SY5Y) and the neuroprotective effect against amyloid induced cytotoxicity is through modification of the amyloid formation towards formation of nontoxic aggregates. Molecular docking demonstrated that vitamin A interacts with Aß-42 through hydrophobic interactions as well as hydrogen bonding. Therefore, the study signifies the role of vitamin A as a potential molecule in preventing Aß-42 aggregation and associated pathophysiology. Hence, Vitamin A and related compounds can thus act as effective inhibitors in the therapeutic development to combat systemic amyloidosis.

Nitroxidized-Albumin Advanced Glycation End Product and Rheumatoid Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease whose major clinical consequence is inflammation of small joints and contiguous structures. Oxidative and nitrosative stress along with increased formation of advanced glycation end products (AGEs) play an important role in the disease process. Generation of reactive species during glycation of proteins further adds to the oxidative and nitrosative stress. Albumin, being the most abundant plasma protein, is frequently targeted by different oxidizing and nitrating agents, including peroxynitrite (OONO-) anion. Albumin is also targeted and modified by dicarbonyl metabolites (glyoxal and methylglyoxal) which are formed in oxidative and non-oxidative processes during the synthesis of AGEs. The endogenously formed OONO- and dicarbonyls may modify plasma albumin including those albumin that have travelled or migrated to synovial cells and caused nitration, oxidation, and glycation. These modifications may produce crosslinks, aggregate in albumin and confer immunogenicity. Simultaneous modification of albumin by OONO- and dicarbonyls may generate nitroxidized-AGE-albumin which may persist in circulation for a longer duration compared to native albumin. Nitroxidized-AGE-albumin level (or serum autoantibodies against nitroxidized- AGE-albumin) along with other pre-clinical features may help predict the likely onset of RA.

DARK Classics in Chemical Neuroscience: Opium, a Friend or Foe.

Opium has found great use medicinally for its analgesic properties and has been witnessed as one of the most popular medications used in psychiatry. Opium derivatives have been shown as efficacious for relieving pain and the treatment of epileptic seizures, but progressive research toward their use in the treatment of neurodegenerative diseases remain elusive. To gain more insight into the other properties of opium such as anti-inflammatory properties, herein we discuss basic information regarding opium, opium content and mechanism of action, pharmacology of opium derivatives, the role of opium in the prevention of neurodegeneration, and adverse effects of opium derivatives on neuronal health.

Structural re-arrangement of depolymerized sodium alginate enriches peltate glandular trichomes and essential oil production of spearmint.

Over the past decade, radiation-degraded polysaccharides have been used as regulators of growth and development in several crop plants. In quest of the possible reasons of previously established growth-promotion activity of irradiated sodium alginate (ISA), structural parameters of irradiated and un-irradiated sodium alginate were analysed using Ultraviolet-visible spectroscopy (UV-vis) and Fourier Transform Infrared spectroscopic (FT-IR) studies to develop an understanding of structure-property relationship. Using foliar application, response to graded concentrations of ISA was tested in terms of yield and quality attributes of spearmint (Mentha spicata L.). Among different concentrations of ISA [0 (control), 40, 80, 120 and 160mgL-1], 80mgL-1 proved to be the optimum foliar-spray treatment for most of the parameters studied including peltate glandular-trichomes density, which was increased from 20 to 44mm-2. Measurements made at 150days after planting revealed that foliar application of ISA at 80mgL-1 increased the content and yield of spearmint essential oil (EO) by 36.0 and 122.6%, respectively, in comparison to the control. Compared to the control, gas chromatography mass spectrometry (GC-MS) analysis revealed an increase of 18.7% in the carvone content and a decrease of 15.7% in limonene content of the spearmint EO.

Proliferating effect of radiolytically depolymerized carrageenan on physiological attributes, plant water relation parameters, essential oil production and active constituents of Cymbopogon flexuosus Steud. under drought stress.

Carrageenan has been proved as potent growth promoting substance in its depolymerized form. However, relatively little is known about its role in counteracting the adverse effects of drought stress on plants. In a pot experiment, lemongrass (Cymbopogon flexuosus Steud.), grown under different water stress regimes [(100% field capacity (FC), 80% FC and 60% FC)], was sprayed with 40, 80 and 120 mg L-1 of gamma irradiated carrageenan (ICA). Foliar application of ICA mitigated the harmful effects of drought stress to various extents and improved the biochemical characteristics, quality attributes and active constituents (citral and geraniol) of lemongrass significantly. Among the applied treatments, ICA-80 mg L-1 proved the best in alleviating detrimental effects of drought. However, drought stress (80 and 60% FC), irrespective of the growth stages, had an adverse impact on most of the studied attributes. Generally, 60% FC proved more deleterious than 80% FC. At 80% FC, application of ICA-80 mg L-1 elevated the essential oil (EO) content by 18.9 and 25%, citral content by 7.33 and 8.19% and geraniol content by 9.2 and 8.9% at 90 and 120 days after planting (DAP), respectively, as compared to the deionized-water (DW) spray treatment (80% FC+ DW). Whereas, at 60% FC, foliar application of 80 mg L-1 ICA significantly augmented the EO content by 15.4 and 17.8% and active constituents viz. citral and geraniol, by 5.01 and 5.62% and by 6.06 and 5.61% at 90 and 120 DAP, respectively, as compared to the control (water-spray treatment).

Neo-Epitopes Generated on Hydroxyl Radical Modified GlycatedIgG Have Role in Immunopathology of Diabetes Type 2.

Glycoxidation plays a crucial role in diabetes and its associated complications. Among the glycoxidation agents, methylglyoxal (MG) is known to have very highglycationpotential witha concomitant generation of reactive oxygen species (ROS) during its synthesis and degradation. The presentstudy probes the MG and ROSinduced structural damage to immunoglobulin G (IgG) and alterations in its immunogenicity in diabetes type 2 patients (T2DM). Human IgG was first glycated with MG followed by hydroxyl radical (OH•) modification. Glycoxidation mediated effects on IgG were evaluated by various physicochemical techniques likeultraviolet (UV) and fluorescence spectroscopy, 8-anilinonaphthalene-1-sulfonic acid (ANS) binding studies, carbonyl andfree sulfhydryl groups assay, matrix assisted laser desorption ionization mass spectrometry-time of flight (MALDI-TOF), red blood cell (RBC) haemolysis assay, Congored (CR) staining analysis and scanning electron microscopy (SEM). The results revealed hyperchromicityin UV, advanced glycation end product (AGE)specific and ANS fluorescence, quenching in tyrosine and tryptophan fluorescence intensity,enhanced carbonyl content,reduction in free sulfhydryl groups,pronounced shift in m/z value of IgGand decrease in antioxidant activity in RBC induced haemolysis assayupon glycoxidation. SEM and CRstaining assay showed highly altered surface morphology in glycoxidised sample as compared to the native. Enzyme linked immunosorbent assay (ELISA) and band shift assay were performed to assess the changes in immunogenicity of IgG upon glyoxidation and its role in T2DM. The serum antibodies derived from T2DM patients demonstrated strong affinity towards OH• treated MG glycatedIgG (OH•-MG-IgG) when compared to native IgG (N-IgG) or IgGs treated with MG alone (MG-IgG) or OH• alone (OH•-IgG). This study shows the cumulating effect of OH• on the glycation potential of MG. The results point towards the modification of IgG in diabetes patients under the effect of glycoxidative stress, leading to the generation of neo-epitopes on theIgG molecule and rendering it immunogenic.

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.