2021
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Journal Article
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Dr. Bipin G. Nair, M, V., and J, N., “Anacardic acid-mediated regulation of osteoblast differentiation involves mitigation of inflammasome activation pathways”, Molecular and Cellular Biochemistry, vol. 476(2):1-11, 2021.[Abstract]
Disruption of the finely tuned osteoblast–osteoclast balance is the underlying basis of several inflammatory bone diseases, such as osteomyelitis, osteoporosis, and septic arthritis. Prolonged and unrestrained exposure to inflammatory environment results in reduction of bone mineral density by downregulating osteoblast differentiation. Earlier studies from our laboratory have identified that Anacardic acid (AA), a constituent of Cashew nut shell liquid that is used widely in traditional medicine, has potential inhibitory effect on gelatinases (MMP2 and MMP9) which are over-expressed in numerous inflammatory conditions (Omanakuttan et al. in Mol Pharmacol, 2012 and Nambiar et al. in Exp Cell Res, 2016). The study demonstrated for the first time that AA promotes osteoblast differentiation in lipopolysaccharide-treated osteosarcoma cells (MG63) by upregulating specific markers, like osteocalcin, receptor activator of NF-κB ligand, and alkaline phosphatase. Furthermore, expression of the negative regulators, such as nuclear factor-κB, matrix metalloproteinases (MMPs), namely MMP13, and MMP1, along with several inflammatory markers, such as Interleukin-1β and Nod-like receptor protein 3 were downregulated by AA. Taken together, AA expounds as a novel template for development of potential pharmacological therapeutics for inflammatory bone diseases
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2021
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Journal Article
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Dr. Bipin G. Nair, Gondkar, K., Gajanan Sathe, Joshi, N., Akhilesh Pandey, and Kumar, P., “Integrated Proteomic and Phosphoproteomics Analysis of DKK3 Signaling Reveals Activated Kinase in the Most Aggressive Gallbladder Cancer”, Cells, vol. 10(3), 511, 2021.[Abstract]
DKK3 is a secreted protein, which belongs to a family of Wnt antagonists and acts as a potential tumor suppressor in gallbladder cancer. To further understand its tumor suppressor functions, we overexpressed DKK3 in 3 GBC cell lines. We have employed high-resolution mass spectrometry and tandem mass tag (TMT) multiplexing technology along with immobilized metal affinity chromatography to enrich phosphopeptides to check the downstream regulators. In this study, we reported for the first time the alteration in the phosphorylation of 14 kinases upon DKK3 overexpression. In addition, we observed DKK3 induced hyper phosphorylation of 2 phosphatases: PPP1R12A and PTPRA, which have not been reported previously. Canonical pathway analysis of altered molecules indicated differential enrichment of signaling cascades upon DKK3 overexpression in all the 3 cell lines. Protein kinase A signaling, Sirtuin signaling pathway, and Cell Cycle Control of Chromosomal Replication were observed to be differentially activated in the GBC cell lines. Our study revealed, DKK3 overexpression has differential effect based on the aggressive behavior of the cell lines. This study expands the understanding of DKK3-mediated signaling events and can be used as a primary factor for understanding the complex nature of this molecule.
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2021
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Journal Article
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Dr. Bipin G. Nair, Divya Nedungadi, Divya Nair, Mishra, N., and Dr. Sudarslal S., “Identification of carbonylated proteins from monocytic cells under diabetes‐induced stress conditions”, Biomedical Chromatography, vol. e5065, 2021.[Abstract]
Diabetes is a metabolic disorder characterized by the presence of elevated glucose in the blood and enhanced oxidative stress. It affects the cellular homeostasis that lead to the development of micro‐and macro‐vascular complications. Monocytes are the primary immune cells present in the circulatory system. Under high glucose conditions, the cells undergo oxidative stress and secrete reactive oxygen species. The enhanced release of reactive species are known to modify biomolecules like proteins and nucleic acids. Protein carbonylation, one of the most harmful and irreversible protein modifications, is considered as a key player in the progression of diabetes and associated complications. Hence, the present study explores the identification of carbonylated proteins from the monocytes under diabetic stress and determination of their site of modifications. Combined avidin affinity chromatography and bottom‐up proteomics experiments identified thirteen consistently expressed carbonylated proteins. Most of the identified proteins were reported to have altered functions under diabetic conditions that contribute to the development of diabetes associated inflammations and complications. We were able to determine oxidative stress‐induced modifications on Lys, Val, Ile, Cys, Thr and Asp residues.
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2021
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Journal Article
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Dr. Bipin G. Nair, Dr. Satheesh Babu T. G., Kumar, G., Nizet, V., Priyanka Somanath, Nair, S., Anil kumar, Haripriyan, J., Shetty, K., D’Silva, J. Rowena, Chatterjee, M., Baswe, M., Gayathri Vijayakumar, Bose, S., Kumar, M. S., and Menon, N. D., “A Novel N4-Like Bacteriophage Isolated from a Wastewater Source in South India with Activity against Several Multidrug-Resistant Clinical Pseudomonas aeruginosa Isolates”, mSphere, vol. 6(1), 2021.[Abstract]
Multidrug-resistant community-acquired infections caused by the opportunistic human pathogen Pseudomonas aeruginosa are increasingly reported in India and other locations globally. Since this organism is ubiquitous in the environment, samples such as sewage and wastewater are rich reservoirs of P. aeruginosa bacteriophages. In this study, we report the isolation and characterization of a novel P. aeruginosa N4-like lytic bacteriophage, vB_Pae_AM.P2 (AM.P2), from wastewater in Kerala, India. AM.P2 is a double-stranded DNA podovirus that efficiently lyses the model strain, PAO1, at a multiplicity of infection as low as 0.1 phage per bacterium and resistance frequency of 6.59 × 10 ⁻⁴ . Synergy in bactericidal activity was observed between AM.P2 and subinhibitory concentrations of the antibiotic ciprofloxacin. Genome sequencing of AM.P2 revealed features similar to those of the N4-like P. aeruginosa phages LUZ7 and KPP21. As judged by two independent assay methods, spot tests and growth inhibition, AM.P2 successfully inhibited the growth of almost 30% of strains from a contemporary collection of multidrug-resistant P. aeruginosa clinical isolates from South India. Thus, AM.P2 may represent an intriguing candidate for inclusion in bacteriophage cocktails developed for various applications, including water decontamination and clinical bacteriophage therapy. IMPORTANCE In India, multidrug resistance determinants are much more abundant in community-associated bacterial pathogens due to the improper treatment of domestic and industrial effluents. In particular, a high bacterial load of the opportunistic pathogen P. aeruginosa in sewage and water bodies in India is well documented. The isolation and characterization of bacteriophages that could target emerging P. aeruginosa strains, representing possible epicenters for community-acquired infections, could serve as a useful alternative tool for various applications, such as phage therapy and environmental treatment. Continuing to supplement the repertoire of broad-spectrum bacteriophages is an essential tool in confronting this problem.
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2021
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Journal Article
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Dr. Bipin G. Nair, Arathi G. Rajendran, Asha Vijayan, Chaitanya Medini, and Dr. Shyam Diwakar, “Computational modelling of cerebellum granule neuron temporal responses for auditory and visual stimuli”, International Journal of Advanced Intelligence Paradigms, vol. Vol.18 No.3, pp.356 - 372, 2021.[Abstract]
Sensorimotor signals from the cerebral cortex modulate the pattern generating metaheuristic capabilities of cerebellum. To better understand the functional integration of multisensory information by the single granule neurons and the role of multimodal information in motor guidance of cerebellum, we have modelled granular layer microcircuit in the cerebellum and analysed the encoding of information during the auditory and visual stimuli. A multi-compartmental granule neuron model comprising of excitatory and inhibitory synapses was used and in vivo like behaviour was modelled with the short and long bursts. The change in intrinsic parameters in the model helped to quantify the effect of spike-time dependent plasticity in the firing of granule neurons. Computer simulations implicate coding correlation of output patterns to temporal excitatory stimuli. We observed the role of induced plasticity and granular layer role in sparse recoding of auditory and visual inputs and the model predict how plasticity mechanisms affect the average amount of information transmitted through the single granule neurons during multimodal stimuli.
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2020
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Journal Article
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A. Sreekumar, Navaneeth, P., Suneesh, P. Vasu, Dr. Bipin G. Nair, and Dr. Satheesh Babu T. G., “A graphite pencil electrode with electrodeposited Pt-CuO for nonenzymatic amperometric sensing of glucose over a wide linear response range”, Microchimica Acta, vol. 187, p. 113, 2020.[Abstract]
A disposable nonenzymatic glucose sensor was obtained by pulsed electrodeposition of Pt-CuO on a graphite pencil electrode (GPE). The morphology of the modified GPE was studied using SEM, and the chemical composition of the coating was examined by EDAX and XRD. The electrochemical response of the modified GPE was compared with individual copper- and platinum-modified GPEs. The electrodeposition parameters were optimized with respect to the electrocatalytic activity of the deposits towards glucose oxidation. Best operated at a working potential of 0.6 V vs. Ag/AgCl, the sensor has a sensitivity of 2035 μA mM−1 cm−2, a 0.1 μM detection limit and a wide linear response range that extends up to 25 mM. It is highly selective for glucose in the presence of various exogenous and endogenous interfering species. Eventhough the requirement of alkaline medium for sensing is a limitation, easy fabrication procedure, very high sensitivity and selectivity, wide analytical range, and disposable sensor characteristics show potential application towards blood glucose determination.
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2020
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Journal Article
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A. K. Ravi, Navaneeth, P., Suneesh, P. Vasu, Dr. Bipin G. Nair, and Dr. Satheesh Babu T. G., “Manganese dioxide based electrochemical sensor for the detection of nitro-group containing organophosphates in vegetables and drinking water samples”, Journal of Electroanalytical Chemistry, p. 113841, 2020.[Abstract]
The widespread use of organophosphates in agricultural farms for pest control has raised serious concerns over the quality of food and water available to the common public. As an effort to fabricate a sensitive, selective, cost-effective and non-toxic sensor to detect nitro-group containing organophosphates in and vegetable washings, a simple manganese dioxide based sensor was developed. α-Manganese dioxide nano-rods were electrodeposited on platinum disk electrode (MnO2/Pt) and is employed to detect 4-nitrophenyl phosphate (4-NPP). 4-NPP is a model compound that well represents widely used nitro-group containing organophosphates such methyl parathion, parathion, fenitrothion, methyl paraoxon and paraoxon in aqueous medium. Determination of 4-NPP at nanomolar levels was achieved using the fabricated sensor using cyclic voltammetry. The developed sensor was found to show a linear response in the concentration range 100 nM to 900 nM with a Limit of Detection (LOD) of 10 nM and a high sensitivity of 11.68 μA μM−1. The sensor showed good selectivity against many of common inorganic ions and two of the major organophosphates: Quinalphos and Dimethoate but the selectivity is poor among other nitro-group containing aromatics.
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2020
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Journal Article
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V. S. Vargis, Vasu, S. P., Sree, R. J., Dr. Bipin G. Nair, and Dr. Satheesh Babu T. G., “Peroxidase Labeled Antibody Conjugated Gold Nanoparticles for Ultrasensitive Voltammetric Immunosensing”, IEEE Sensors Journal, vol. 20, pp. 1142-1149, 2020.[Abstract]
An electrochemical immunosensing platform capable of detecting Immunoglobulin G (IgG) concentration as low as femtograms was developed based on signal amplification strategy. The immunosensing platform was fabricated using self-assembled monolayers (SAM) of 11- mercaptoundecanoic acid (MUDA) on a gold disc electrode. The covalent immobilization of antibody was achieved through the bonding of a carboxyl group of MUDA and amino group of antibody using [1-ethyl-3-(3-dimethylaminopropyl) carbodiimide] (EDC) and N-hydroxysuccinimide (NHS) chemistry. The formation of SAM and antibody immobilization was analyzed using cyclic voltammetry and electrochemical impedance spectroscopy. The gold nanoparticles conjugated with horseradish peroxidase-labeled secondary antibodies were used as nanolabels, to increase the sensitivity and catalytic efficiency of the immunosensor. The sandwich immunocomplex formed on the electrode surface produced an electrocatalytic response through the reduction of hydrogen peroxide in the presence of thionin. The fabricated immunosensor exhibited two linear ranges that included IgG concentrations of 10 fg mL−1 to 0.1 ng mL−1 and 0.1 to 100 ng mL−1 respectively.
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