Browsing by Author "Amarish Kumar Yadav"

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Biphasic ROS accumulation and programmed cell death in a cyanobacterium exposed to salinity (NaCl and Na2SO4)
(Elsevier B.V., 2017) Prashant Swapnil; Amarish Kumar Yadav; Saurabh Srivastav; Naveen K Sharma; Saripella Srikrishna; Ashwani K Rai
High salinity increases antioxidative activities in plants; however, their significance for overall plant salt tolerance remains to be established. This work provided in vivo evidence of salinity induced biphasic reactive oxygen species (ROS) accumulation evoking oxidative stress in the cyanobacterium Anabaena fertilissima. First, a transient increase in ROS (intense and short-lived) was observed within 5 min of salt exposure, which peaked within 15 min and reached basal level by 2 h. This was followed by a second relatively long-lived and low magnitude ROS accumulation that started at 4 h of salt stress, attained its maximal at 6 h, followed by a gradual decline but did not attain the basal level by the end of experimentation (12 h). Phase I ROS accumulation timing corresponded to the reaction of cyanobacterial cells to the salt stress, while altered photosynthetic and respiratory parameters corresponded with the phase II ROS generation. Relatively lower magnitude of ROS generation during phase II may be attributed to the rapid activation of robust antioxidative systems in cyanobacteria. Consequently, ROS generation lead to the activation of programmed cell death (PCD) undergoing various apoptotic stages such as externalization of phosphatidylserine, DNA laddering and loss of plasma membrane integrity. A. fertilissima exposed to salt in the presence of SO4¯ was relatively better equipped to deal with salt stress. © 2017 Elsevier B.V.
Cancer Drug Development Using Drosophila as an in vivo Tool: From Bedside to Bench and Back
(Elsevier Ltd, 2016) Amarish Kumar Yadav; Saripella Srikrishna; Subash Chandra Gupta
The fruit fly Drosophila melanogaster has been used for modeling cancer and as an in vivo tool for the validation and/or development of cancer therapeutics. The impetus for the use of Drosophila in cancer research stems from the high conservation of its signaling pathways, lower genetic redundancy, short life cycle, genetic amenability, and ease of maintenance. Several cell signaling pathways in Drosophila have been used for cancer drug development. The efficacy of combination therapy and uptake/bioavailability of drugs have also been studied. Drosophila has been validated using several FDA-approved drugs, suggesting a potential application of this model in drug repurposing. The model is emerging as a powerful tool for high-throughput screening and should significantly reduce the cost and time associated with drug development. In this review we discuss the applications of Drosophila in cancer drug development. The advantages and limitations of the model are discussed. © 2016 Elsevier Ltd
Correction: Fluorescein hydrazone-based supramolecular architectures, molecular recognition, sequential logic operation and cell imaging (RSC Adv. (2017) 7 (2264-2272) DOI: 10.1039/C6RA26255D)
(Royal Society of Chemistry, 2017) Kamini Tripathi; Abhishek Rai; Amarish Kumar Yadav; Saripella Srikrishna; Niraj Kumari; Lallan Mishra
Correction for ‘Fluorescein hydrazone-based supramolecular architectures, molecular recognition, sequential logic operation and cell imaging’ by Kamini Tripathi et al., RSC Adv., 2017, 7, 2264-2272. © The Royal Society of Chemistry.
Fluorescein hydrazone-based supramolecular architectures, molecular recognition, sequential logic operation and cell imaging
(Royal Society of Chemistry, 2017) Kamini Tripathi; Abhishek Rai; Amarish Kumar Yadav; Saripella Srikrishna; Niraj Kumari; Lallan Mishra
A fluorescein hydrazone (FDNS) is prepared by the coupling of fluorescein hydrazide with 3,5-dinitrosalicylaldehyde. It is well characterized using spectroscopic (IR, UV-visible, 1H, 13C NMR, ESI-MS) techniques and X-ray crystallography. FDNS is embedded with several H-bonding domains which provide interesting intra and inter molecular H-bonded networks. Its crystal packing along the b crystallographic axis using H-bonding interactions provides a fascinating helical structure. It detects Cu2+ ions selectively over many relevant ions and displays a novel peak at λmax = 495 nm. The significant enhancement in its fluorescence is observed with a peak at λem = 517 nm on addition of Hg2+ ions, which is quenched upon the addition of S2− ions. The sensing of Hg2+ ions by FDNS follow a hydrolysis pathway whereas the binding of Cu2+ ions with FDNS provides a colour change. The addition of a solution of tetrabutylammoniumcyanide in methanol to a corresponding solution of FDNS caused a turn to a green colour immediately. But on keeping the solution at room temperature for 72 h, red coloured crystals are obtained. The crystals were authenticated by X-ray crystallography. It was found to be a new compound FKCN in which a tetrabutylammonium cation is co-crystallized with deprotonated FDNS. Its supramolecular assembly via H-bonding provides an interesting ladder type architecture. FDNS displays chronological logic gate-based detection of several ions (Cu2+, Hg2+, EDTA, and S2−) at ppm levels. The real sample analysis, live cell imaging and portable paper strip based detection of Cu2+ and Hg2+ ions via an obvious colour change endows FDNS with great economic significance in recognition processes. © The Royal Society of Chemistry.
Folic Acid Supplementation Ameliorates Oxidative Stress, Metabolic Functions and Developmental Anomalies in a Novel Fly Model of Parkinson’s Disease
(Springer New York LLC, 2015) Saurabh Srivastav; Sandeep Kumar Singh; Amarish Kumar Yadav; Saripella Srikrishna
Mutations in parkin cause early-onset Parkinson’s disease. Studies involving Drosophila model have emphasised mitochondrial dysfunction as a critical event in disease pathogenesis. In this context, we employed a novel recessive allele of parkin, parkc00062, for the current study. The piggyBac insertion at 3rd intron of parkin in parkc00062 was confirmed by PCR. Homozygous parkc00062 has diminished levels of truncated parkin transcript with no detectable protein as confirmed by qRT-PCR and western blot analysis, respectively. The homozygous parkc00062 displayed severe developmental anomalies involving reduced body size, ~45 % pupal lethality, high mortality with locomotory defect, elevated oxidative stress, low metabolic active cell status with low mitochondrial respiration as reflected from reduced ATP levels. Further, folic acid therapeutic potential was analysed in parkc00062. Here we show that dietary folic acid provided protection against disparities involving pupal lethality, high mortality, locomotory defect, elevated oxidative stress and low metabolic active cell status associated with parkc00062. Further mitochondrial respiration was enhanced as reflected from improved ATP levels in folate supplemented parkc00062. To corroborate mitochondrial functioning further our analysis regarding transcript status of p53 and spargel by qRT-PCR, revealed down regulation of p53 and up regulation of spargel in folate supplemented parkc00062, which was originally vice a versa. Our data thus support the potential of FA in alleviating the disparities associated with parkin loss of function in fly model. Further, FA role in alleviating mitochondrial dysfunction is encouraging to further explore FA mechanistic role to be utilized as potential therapeutics for parkin mediated neurodegenerative diseases. © 2015, Springer Science+Business Media New York.
Folic acid supplementation rescues anomalies associated with knockdown of parkin in dopaminergic and serotonergic neurons in Drosophila model of Parkinson's disease
(Academic Press Inc., 2015) Saurabh Srivastav; Sandeep Kumar Singh; Amarish Kumar Yadav; Saripella Srikrishna
parkin loss associated early-onset of Parkinson's disease, involves mitochondrial dysfunction and oxidative stress as the plausible decisive molecular mechanisms in disease pathogenesis. Mitochondrial dysfunction involves several up/down regulation of gene products, one of which being p53 is found to be elevated. Elevated p53 is involved in mitochondrial mediated apoptosis of neuronal cells in Parkinson's patients who are folate deficient as well. The present study therefore attempts to examine the effect of Folic acid (FA) supplementation in alleviation of anomalies associated with parkin knockdown using RNAi approach, specific to Dopaminergic (DA) neurons in Drosophila model system. Here we show that FA supplementation provide protection against parkin RNAi associated discrepancies, thereby improves locomotor ability, reduces mortality and oxidative stress, and partially improves Zn levels. Further, metabolic active cell status and ATP levels were also found to be improved thereby indicating improved mitochondrial function. To corroborate FA supplementation in mitochondrial functioning further, status of p53 and spargel was checked by qRT-PCR. Here we show that folic acid supplementation enrich mitochondrial functioning as depicted from improved spargel level and lowered p53 level, which was originally vice versa in parkin knockdown flies cultured in standard media. Our data thus support the potential of folic acid in alleviating the behavioural defects, oxidative stress, augmentation of zinc and ATP levels in parkin knock down flies. Further, folic acid role in repressing mitochondrial dysfunction is encouraging to further explore its possible mechanistic role to be utilized as potential therapeutics for Parkinson's disease. © 2015 Elsevier Inc. All rights reserved.
Knockdown of APPL mimics transgenic Aβ induced neurodegenerative phenotypes in Drosophila
(Elsevier Ireland Ltd, 2017) Sandeep Kumar Singh; Saurabh Srivastav; Amarish Kumar Yadav; Saripella Srikrishna
A variety of Drosophila mutant lines have been established as potential disease-models to study various disease mechanisms including human neurodegenerative diseases like Alzheimer's disease (AD), Huntington's disease (HD) and Parkinson's disease (PD). The evolutionary conservation of APP (Amyloid Precursor Protein) and APPL (Amyloid Precursor Protein-Like) and the comparable detrimental effects caused by their metabolic products strongly implies the conservation of their normal physiological functions. In view of this milieu, a comparative analysis on the pattern of neurodegenerative phenotypes between Drosophila APPL-RNAi line and transgenic Drosophila line expressing eye tissue specific human Aβ (Amyloid beta) was undertaken. Our results clearly show that Drosophila APPL-RNAi largely mimics transgenic Aβ in various phenotypes which include eye degeneration, reduced longevity and motor neuron deficit functions, etc. The ultra-structural morphological pattern of eye degeneration was confirmed by scanning electron microscopy. Further, a comparative study on longevity and motor behaviour between Aβ expressing and APPL knockdown lines revealed similar kind of behavioural deficit and longevity phenotypes. Therefore, it is suggested that APPL-knockdown approach can be used as an alternative approach to study neurodegenerative diseases in the fly model. To the best of our knowledge this is the first report showing comparable phenotypes between APPL and Aβ in AD model of Drosophila. © 2017 Elsevier B.V.
Mechanically magnified chitosan-based hydrogel as tissue adhesive and antimicrobial candidate
(Elsevier B.V., 2019) Swati Sharma; Rajesh Kumar; Puja Kumari; Ravindra Nath Kharwar; Amarish Kumar Yadav; Srikrishna Saripella
The present article reports the development of chitosan (CS) based hydrogel series by varying the concentration of cross-linking agent i.e. N,N′-methylenebisacrylamide (MBA) (0.8–1.4 wt%) via free-radical polymerization in aqueous medium. SEM image analysis confirmed the presence of porous 3D-network in the hydrogel. Prepared hydrogel series exhibited good tissue adhesive property along with antimicrobial activity against E. coli, K. pneumonia, S. aureus, C. albicans & M. gypseum bacteria with the good MIC (4–20 mm). The adhesive strength of hydrogel was found 14 kPa, which seems to be quite efficient in tissue adhesiveness applications, which was also validated and tested on Drosophila (Oregon-R) tissues, results were promising. Magnified mechanical strength i.e. storage modulus (G′) and loss modulus (G″) were found 106 Pa and 104 Pa, respectively, which makes the hydrogel a potential candidate in the biomedical field. Moreover, CS hydrogel showed good swelling ratio in aqueous medium up to 390% at room temperature. © 2018
Modeling neurodegenerative diseases using transgenic model of drosophila
(Bentham Science Publishers, 2020) Brijesh Singh Chauhan; Amarish Kumar Yadav; Roshan Fatima; Sangeeta Arya; Jyotsna Singh; Rohit Kumar; Saripella Srikrishna
From the past several decades, neuroscientists have been focusing on understanding the mechanisms of various human neurodegenerative diseases using different models such as Mouse, Rat, Zebrafish, worm and the Drosophila. Among them, the Drosophila, with a short generation time and genetic amenity, has emerged as a vital and prevailing model system to explore multiple aspects of neurodegenerative diseases like Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, etc. In this chapter, we have presented various molecular, genetic and therapeutic approaches employed to model human neurodegenerative diseases using Drosophila. Furthermore, we also present the worldwide prevalence of neurodegenerative diseases, along with a survey of published literatures of research conducted in the last two decades on major neurodegenerative diseases employing transgenic Drosophila, to evaluate where we stand. © 2020 Bentham Science Publishers. All right reserved.
Overview of Alzheimer's disease and some therapeutic approaches targeting A β by using several synthetic and herbal compounds
(Hindawi Publishing Corporation, 2016) Sandeep Kumar Singh; Saurabh Srivastav; Amarish Kumar Yadav; Saripella Srikrishna; George Perry
Alzheimer's disease (AD) is a complex age-related neurodegenerative disease. In this review, we carefully detail amyloid-β metabolism and its role in AD. We also consider the various genetic animal models used to evaluate therapeutics. Finally, we consider the role of synthetic and plant-based compounds in therapeutics. © 2016 Sandeep Kumar Singh et al.
scribble (scrib) knockdown induces tumorigenesis by modulating Drp1-Parkin mediated mitochondrial dynamics in the wing imaginal tissues of Drosophila
(Elsevier B.V., 2019) Amarish Kumar Yadav; Saripella Srikrishna
scrib loss of function is associated with various human-cancers. Most of the human-cancers have been characterized by mitochondrial dysfunction with elevated oxidative stress. However, the role of scrib to mitochondrial dysfunction in cancer has not been investigated earlier. Here, we have shown that scrib knockdown leads to mitochondrial depolarization, fragmentation and perinuclear-clustering along with disruption of the redox homeostasis. Moreover, the scrib abrogated tumor showed the elevation of Drp-1 and reduced expression of Marf, which suggests enhanced mitochondrial-fission. Further, the reduced expression of Parkin and HtrA2 interpret defective mitophagy leading to clustering of fragmented mitochondria and apoptotic inhibition in scrib knockdown tumors. Also, Parkin immunostaining depicted its reduced expression and mislocalization in the tumor cells in comparison to wild type. Moreover, the genetic study revealed the epistatic interactions of parkin and scrib. Thus, for the first time our results suggested that scrib loss induced mitochondrial-dysfunction modulates cancer progression by altering the mitochondrial dynamics regulators. © 2018 Elsevier B.V. and Mitochondria Research Society