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Jain M, Yadav P, Joshi B, Joshi A, Kodgire P Ref: Applied Microbiology & Biotechnology, 105:389, 2021 : PubMed ESTHER: Jain_2021_Appl.Microbiol.Biotechnol_105_389 PubMedSearch: Jain 2021 Appl.Microbiol.Biotechnol 105 389 PubMedID: 33191461 Abstract Indiscriminate use of organophosphorus (OP)-based insecticides is a great concern to human health because of bioaccumulation-induced health hazards. Potentially fatal consequences and limited treatment methods of OP poisoning necessitate the need for the development of reliable, selective, cost-effective, and sensitive methods of OP detection. To tackle this issue, the development of effective devices and methods is required to sensitively detect as well as degrade OPs. Enzymatic sensor systems have gained popularity due to high catalytic activity, enhanced detection limits, and high sensitivity with the environmentally benign operation. Organophosphorus acid anhydrolase (OPAA) from Alteromonas sp. JD6.5 is capable of hydrolyzing the P-F, P-O, P-S, and P-CN bonds, in OPs, including nerve agents of the G/V-series. Several mutants of OPAA are reported which have greater activity against various OPs. In this study, recombinant expression of the OPAA-FL variant in Escherichia coli was performed, purified, and subsequently tested for activity against ethyl paraoxon. OPAA-FL variant showed its optimum activity at pH 8.5 and 50 degreesC. Colorimetric and fluorometric assays were used for estimation of ethyl paraoxon based on p-nitrophenol and fluorescein isothiocyanate (FITC) fluorescence intensity, respectively. Colorimetric and fluorometric assay estimation indicates that ethyl paraoxon can be estimated in the linear range of 0.01 to 1 mM and 0.1 to 0.5 mM, with LOD values 0.04 mM and 0.056 mM, respectively. Furthermore, the OPAA-FL variant was immobilized into alginate microspheres for colorimetric detection of ethyl paraoxon and displayed a linear range of 0.025 to 1 mM with a LOD value of 0.06 mM. KEY POINTS: Biosensing of paraoxon with purified and encapsulated OPAA-FL variant. Colorimetric and fluorometric biosensing assay developed using OPAA-FL variant for paraoxon. First report on alginate encapsulation of OPAA-FL variant for biosensing of paraoxon. Graphical abstract. Title: Biofabricated zinc oxide nanoparticles impair cognitive function via modulating oxidative stress and acetylcholinesterase level in mice Yadav E, Yadav P Ref: Environ Toxicol, 36:572, 2021 : PubMed ESTHER: Yadav_2021_Environ.Toxicol_36_572 PubMedSearch: Yadav 2021 Environ.Toxicol 36 572 PubMedID: 33247493 Abstract Current work was designed to explore the effect of ZnO nanoparticles (ZnONP) biofabricated by using Trianthema portulacastrum (TP) leaves extract on mice brain hippocampus. ZnO nanoparticles of TP leaves (ZnOTP) were synthesized by co-precipitation method and further characterized by using various techniques such as UV-Vis spectrophotometer, Field Emission Scanning Electron Microscopy (FESEM), Fourier Transform Infrared (FTIR), and Energy Dispersive X-ray (EDX). ZnOTP were evaluated for in vitro antioxidant activity, in vivo behavior models (for assessment of cognitive ability), acetylcholinesterase (AChE) activity along with other neurotransmitters content determination, estimation of various oxidative stress parameters and analysis of zinc content in the brain as well as plasma. Histopathological evaluation of the brain hippocampus of each group was performed to corroborate the statistical results. Spherical ZnOTP of 10 to 20nm size embedded with different phytoconstituents of TP was confirmed. Results of our study revealed a significant memory deficit in mice treated with ZnOTP. Neuronal degeneration was also observed via a significant increase in AChE activity and oxidative stress levels in the brain of mice administered with ZnOTP. Exposure of ZnOTP was also found responsible for modulation of neurotransmission in hippocampus area. Further, ZnOTP disturbed the zinc homeostasis in hippocampus via elevation of zinc content in brain as well as plasma. Histopathology of hippocampus supported the damaging impact of ZnOTP by an increase in vacuolated cytoplasm and focal gliosis in groups treated with ZnOTP. Results demonstrated the neurotoxic effect of ZnOTP on brain hippocampus via cognitive impairment by alteration of neurotransmitter level, zinc content and oxidative stress. Title: Advances in detection of hazardous organophosphorus compounds using organophosphorus hydrolase based biosensors Jain M, Yadav P, Joshi A, Kodgire P Ref: Crit Rev Toxicol, :1, 2019 : PubMed ESTHER: Jain_2019_Crit.Rev.Toxicol__1 PubMedSearch: Jain 2019 Crit.Rev.Toxicol 1 PubMedID: 31268806 Abstract Agricultural advancements focusing on increasing crop production have led to excessive usage of insecticides and pesticides, resulting in leaching and accumulation of these highly toxic chemicals in soil, water, and the food-chain. Organophosphorus (OP) compounds are the most commonly used insecticides and pesticides, which cause a wide range of long-lasting and life-threatening conditions. Due to the acute toxicity and long-term side effects of OP compounds, their timely, on-the-spot and rapid detection has gained importance, for efficient healthcare management. In this respect, several OP degrading enzymes have gained the spotlight in developing the enzyme-based biosensors, owing to their high activity and broad specificity. Among these enzymes, organophosphorus hydrolase (OPH) has emerged as a promising candidate for the detection of OP compounds, due to its ability to act on a broad range of substrates having a variety of bonds, like P horizontal line F, P horizontal line O, P horizontal line S, and P horizontal line CN. Various techniques employing OPH in free/immobilized/conjugated forms into sensing devices were reported to accurately detect OP compounds. The transduction mechanisms of bio-sensing are electrochemical, optical as well as novel methods like magnetoelastic/surface plasmon resonance. Furthermore, to improve the detection limits and sensitivity, nanoparticles and quantum dots are often employed in conjunction with OPH. Here, we highlight the recent advances in sensing OP compounds using OPH based biosensors, compare specifications of sensing methods, and evaluate the influence of different materials used in developing sensors. This review will also enable researchers to design and configure highly sensitive and accurate sensing systems, leading to the development of point-of-care devices for real-time analysis. Title: Carboxypeptidase in prolyl oligopeptidase family: Unique enzyme activation and substrate-screening mechanisms Yadav P, Goyal VD, Gaur NK, Kumar A, Gokhale SM, Jamdar SN, Makde RD Ref: Journal of Biological Chemistry, 294:89, 2019 : PubMed ESTHER: Yadav_2019_J.Biol.Chem_294_89 PubMedSearch: Yadav 2019 J.Biol.Chem 294 89 PubMedID: 30409909 Gene_locus related to this paper: deira-DR0165 Abstract Serine peptidases of the prolyl oligopeptidase (POP) family are of substantial therapeutic importance because of their involvement in diseases such as diabetes, cancer, neurological diseases, and autoimmune disorders. Proper annotation and knowledge of substrate specificity mechanisms in this family are highly valuable. Although endopeptidase, dipeptidyl peptidase, tripeptidyl peptidase, and acylaminoacyl peptidase activities have been reported previously, here we report the first instance of carboxypeptidase activity in a POP family member. We determined the crystal structures of this carboxypeptidase, an S9C subfamily member from Deinococcus radiodurans, in its active and inactive states at 2.3-A resolution, providing an unprecedented view of assembly and disassembly of the active site mediated by an arginine residue. We observed that this residue is poised to bind substrate in the active structure and disrupts the catalytic triad in the inactive structure. The assembly of the active site is accompanied by the ordering of gating loops, which reduces the effective size of the oligomeric pore. This prevents the entry of larger peptides and constitutes a novel mechanism for substrate screening. Furthermore, we observed structural adaptations that enable its carboxypeptidase activity, with a unique loop and two arginine residues in the active site cavity orienting the peptide substrate for catalysis. Using these structural features, we identified homologs of this enzyme in the POP family and confirmed the presence of carboxypeptidase activity in one of them. In conclusion, we have identified a new type within POP enzymes that exhibits not only unique activity but also a novel substrate-screening mechanism. Title: Molecular Docking and Cognitive Impairment Attenuating Effect of Phenolic Compound Rich Fraction of Trianthema portulacastrum in Scopolamine Induced Alzheimer's Disease Like Condition Yadav E, Singh D, Debnath B, Rathee P, Yadav P, Verma A Ref: Neurochem Res, 44:1665, 2019 : PubMed ESTHER: Yadav_2019_Neurochem.Res_44_1665 PubMedSearch: Yadav 2019 Neurochem.Res 44 1665 PubMedID: 30949934 Abstract Dementia is considered as the frequent cause of neurodegenerative mental disorder such as Alzheimer's disease (AD) amongst elderly people. Free radicals as well as cholinergic deficit neurons within nucleus basalis magnocellularis demonstrated to attribute with aggregation of beta amyloid which further acts as an essential hallmark in AD. Various phenolic phytoconstituents exists in Trianthema portulastrum (TP) leaves have been reported as active against various neurological disorders. The current investigation was undertaken to evaluate the antiamnesic potential of butanol fraction of TP hydroethanolic extract (BFTP) by utilizing rodent models of elevated plus maze (EPM) and Hebbs William Maze (HWM) along with in vitro and in vivo antioxidant as well as acetylcholinesterase (AChE) inhibition studies. Molecular docking studies were also performed for evaluation of molecular interaction of existed phenolic compounds in BFTP. In vitro antioxidant study revealed concentration dependant strong ability of BFTP to inhibit free radicals. In vitro AChE inhibition study showed competitive type of inhibition kinetics. BFTP significantly reversed (p < 0.005 versus scopolamine) the damaging effect of scopolamine by reducing TL (Transfer Latency) and TRC (Time taken to recognize the reward chamber) in the EPM and HWM, respectively. BFTP also contributed towards increased (p < 0.005 versus scopolamine) enzymatic antioxidant as well as hippocampal acetylcholine (ACh) levels. Histological studies also supported the results as BFTP pretreated mice significantly reversed the scopolamine induced histological changes in hippocampal region. Docking studies confirmed chlorogenic acid has the most significant binding affinity towards AChE. This research finding concludes that BFTP could be a beneficial agent for management of cognition and behavioral disorders associated with AD. Title: Comparative Evaluation of Prosopis cineraria (L.) Druce and Its ZnO Nanoparticles on Scopolamine Induced Amnesia Yadav E, Singh D, Yadav P, Verma A Ref: Front Pharmacol, 9:549, 2018 : PubMed ESTHER: Yadav_2018_Front.Pharmacol_9_549 PubMedSearch: Yadav 2018 Front.Pharmacol 9 549 PubMedID: 29875670 Abstract Over recent years, utilization of green synthesized nanomaterials has been widely growing on human body because of its special properties. With the increasing acceptance of nanoparticle approach for various clinical treatments, the biosafety and toxicological effects on the vital organs such as central nervous system, have received more concern. Main focus of this study was to evaluate acute exposure of n-butanol fraction of Prosopis cineraria (L.) Druce hydroethanolic extract (BuPC) and green synthesized zinc oxide nanoparticles of BuPC (ZnOPC) on spatial cognition behavior, and to assess underlying mechanism by estimation of enzymatic antioxidative status along with acetylcholinesterase (AChE) activity in mice brain. Strongest in vitro antioxidant and AChE inhibitory activity exhibiting fraction, BuPC, was examined for inhibition kinetic study by Lineweaver-Burk and Dixon plots. BuPC was further used for fabrication ZnOPC and characterized by UV-visible spectroscopy, Fourier Transform Infrared (FTIR), Field Emission Scanning Electron Microscopy (FESEM), Energy Dispersive X ray (EDX), and Dynamic Light Scattering (DLS) analysis. Old male swiss albino mice were randomly divided into seven groups and treated for 21 days. Subsequently spatial memory was determined by two behavioral models [Elevated plus maze (EPM) and Hebbs William maze (HWM)] and supernatant of brain homogenate was analyzed for enzymatic antioxidant level and AChE inhibitory activity. Zinc content of blood plasma and brain was estimated. Results showed prolonged transfer latency (TL) and time taken to reach reward chamber (TRC) by scopolamine was not ameliorated by the ZnOPC group, whereas BuPC group showed significant reduction in scopolamine induced increase in TL and TRC compared to control and scopolamine treated groups. ZnOPC alleviated enzymatic antioxidant activity and AChE as compared to donepezil and BuPC treated groups. Study concludes that ZnOPC attenuated spatial learning and memory by increase in oxidative stress and decrease in AChE activity at both dose levels. Our results suggest that BuPC exhibited a strong neuroprotective effect on cognitive deficit mice and it may be employed as a strong substance for the treatment of dementia whereas the green synthesized ZnOPC was not proficient to reverse the memory impairment induced by scopolamine. Title: Expression, purification, crystallization and preliminary X-ray diffraction analysis of acylpeptide hydrolase from Deinococcus radiodurans Are VN, Ghosh B, Kumar A, Yadav P, Bhatnagar D, Jamdar SN, Makde RD Ref: Acta Crystallographica F Struct Biol Commun, 70:1292, 2014 : PubMed ESTHER: Are_2014_Acta.Crystallogr.F.Struct.Biol.Commun_70_1292 PubMedSearch: Are 2014 Acta.Crystallogr.F.Struct.Biol.Commun 70 1292 PubMedID: 25195912 Gene_locus related to this paper: deira-DR0165 Abstract Acylpeptide hydrolase (APH; EC 3.4.19.1), which belongs to the S9 family of serine peptidases (MEROPS), catalyzes the removal of an N-acylated amino acid from a blocked peptide. The role of this enzyme in mammalian cells has been suggested to be in the clearance of oxidatively damaged proteins as well as in the degradation of the beta-amyloid peptides implicated in Alzheimer's disease. Detailed structural information for the enzyme has been reported from two thermophilic archaea; both of the archaeal APHs share a similar monomeric structure. However, the mechanisms of substrate selectivity and active-site accessibility are totally different and are determined by inter-domain flexibility or the oligomeric structure. An APH homologue from a bacterium, Deinococcus radiodurans (APHdr), has been crystallized using microbatch-under-oil employing the random microseed matrix screening method. The protein crystallized in space group P21, with unit-cell parameters a = 77.6, b = 189.6, c = 120.4 A, beta = 108.4 degrees . A Matthews coefficient of 2.89 A(3) Da(-1) corresponds to four monomers, each with a molecular mass of approximately 73 kDa, in the asymmetric unit. The APHdr structure will reveal the mechanisms of substrate selectivity and active-site accessibility in the bacterial enzyme. It will also be helpful in elucidating the functional role of this enzyme in D. radiodurans. Title: Plant toxin abrin induced oxidative stress mediated neurodegenerative changes in mice Bhasker AS, Sant B, Yadav P, Agrawal M, Lakshmana Rao PV Ref: Neurotoxicology, 44:194, 2014 : PubMed ESTHER: Bhasker_2014_Neurotoxicol_44_194 PubMedSearch: Bhasker 2014 Neurotoxicol 44 194 PubMedID: 25010655 Abstract Abrin is a potent plant toxin. It is a heterodimeric protein toxin which is obtained from the seeds of Abrus precatorius plant. At cellular level abrin causes protein synthesis inhibition by removing the specific adenine residue (A4324) from the 28s rRNA of the 60S - ribosomal subunit. In the present study we investigated the role of oxidative stress in neurotoxic potential and demyelinating effects of abrin on brain. The mechanism by which abrin induces oxidative damage and toxicity in brain are relatively unknown. Animals were exposed to 0.4 and 1.0 LD50 abrin dose by intraperitoneal route and observed for 1 and 3 day post-toxin exposure. Oxidative stress occurred in brain due to abrin was confirmed in terms of increased reactive oxygen species (ROS), glutathione depletion and increased lipid peroxidation. Significant increase in blood and brain ROS was observed at day 3, 1 LD50. Abrin induced changes in the neurotransmitters (5-hydroxy tryptamine, norepinephrine, dopamine and monoamine oxidase) levels were evaluated by spectroflourometry. Increase in the levels of 5-HT and NE was observed after abrin exposure. MAO activity was found to be decreased in abrin exposed animals compared to control. Significant inhibition in the activity of acetylcholine esterase enzyme in brain and serum was reported for both the doses and time points. Western blot analysis of iNOS expression indicated that abrin treatment resulted in dose and time dependent increase. Furthermore, protein expression of myelin basic protein (MBP) was down regulated in a dose and time dependent manner. Brain histopathology was carried out and cortical brain region showed demyelination after abrin exposure. Results confirmed that abrin poisoning leads to neurodegeneration and neurotoxicity mediated through oxidative stress, AChE inhibition, lipid peroxidation and decrease in MBP levels. Title: Effects of combined exposure to dichlorvos and monocrotophos on blood and brain biochemical variables in rats Dwivedi N, Bhutia YD, Kumar V, Yadav P, Kushwaha P, Swarnkar H, Flora SJ Ref: Hum Exp Toxicol, 29:121, 2010 : PubMed ESTHER: Dwivedi_2010_Hum.Exp.Toxicol_29_121 PubMedSearch: Dwivedi 2010 Hum.Exp.Toxicol 29 121 PubMedID: 20026515 Abstract Dichlorvos (DDVP) and monocrotophos (MC) are systemic insecticides and known to produce cholinergic and non-cholinergic effects. Individual toxic effects of these chemicals are known but their combined effects have not been studied. We studied the effect of concomitant exposure to DDVP and MC on selected biochemical variables suggestive of liver damage, changes in whole brain biogenic amines levels, acetylcholinesterase (AchE) and monoamine oxidase (MAO) activities in rats. Female rats were exposed to DDVP (2.5 mg/kg subcutaneously) and MC (1.8 mg/kg oral) either individually or in combination for 4 weeks. We observed significant decrease in more pronounced depletion in norepinephrine (NE) and dopamine (DA) levels during co-exposure to DDVP and MC. Brain AChE activity increased and activity of MAO showed significant depletion on co-exposure to DDVP and MC. Brain glutathione (GSH) and oxidized glutathione (GSSG) ratio decreased significantly during exposure to DDVP or MC while co-exposure to these toxicants led to a more pronounced depletion of GSH: GSSG ratio. Serum aspartate amino transferase (AST) and alkaline phosphatase (ALP) activities increased significantly on exposure to MC suggesting liver injury, while DDVP alone had no effect on these variables. There were no effects of DDVP and MC exposure on haematological biochemical variables except for depletion in serum glucose level after MC exposure which was more pronounced DDVP + MC during co-exposure. It can be concluded that only moderate synergistic effects occur between MC and DDVP during co-exposure. A more detailed study with variable doses, prolonged exposure and alterations in different brain regions is recommended. | |||||||
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