Papers by Kulbhushan Tikoo
Journal of Inorganic and Organometallic Polymers and Materials, Jan 12, 2022
Graphene based magnetic nanohybrids have engrossed considerable research curiosity because of the... more Graphene based magnetic nanohybrids have engrossed considerable research curiosity because of their exceptional properties and diverse applications associated with green chemistry. In this regard, a practical, facile and regioselective preparation of 1,2-diamines from N-tosylaziridine/(S)-(+)-2-Benzyl-1-(ptolylsulfonyl)aziridine and aryl amines in the presence of magnetically separable graphene based nanohybrid (CoFe@rGO) has been proposed under mild and solvent free conditions. The FT-IR, FE-SEM, XRD and EDX spectroscopic analysis con rmed the formation of the CoFe@rGO nanohybrids. For unsymmetrical aziridine, nucleophilic attack of aryl amines was observed to take place selectively at the more substituted carbon atom of aziridine ring. Environmentally benign, e cient, shorter reaction time, solvent-free conditions, low catalyst loading, excellent reaction yields and reusability of the catalyst for six consecutive runs without signi cant loss in its activity are the key advantages of this protocol. Synthesis of Graphene based magnetic nanohybrids (CoFe@rGO) using hydrothermal technique. Enhanced catalytic performance owing to large surface areas and active catalytic sites. Magnetically retrievable catalyst displaying great recyclability. Aziridine ring opening reactions with amines under solvent free conditions.
International journal of applied science - research and review, Mar 7, 2019
B alanced nutrition plays an important role in the maintenance of healthy life. Imbalance in any ... more B alanced nutrition plays an important role in the maintenance of healthy life. Imbalance in any of it, results in various metabolic disorders. L-Methionine (L-Met) is one of the essential amino acids which play an important role in variety of cellular processes. Reports suggest that dietary methionine restriction as well as its supplementation both have beneficial effects in animal models. But in long run methionine restriction has prominent adverse effects on bone, immune system and can cause cardiac adverse event (via hyperhomocysteinemia). Here, we report the protective effect of L-Met (0.45% L-Met supplementation in diet) on T2DM induced hyperglycemia, dyslipidemia and other complications. Interestingly, L-Met supplementation also activates hepatic p-AMPK and its downstream signaling molecule SIRT1, mimicking anti-diabetic drug metformin, an AMPK activator. Real Time PCR, results show that L-Met supplementation prevents diabetes induced increase in expression of master regulator FOXO1, hepatic DNMT1 expression and global histone H3K36 di-methylation. Furthermore, FOXO1 regulated genes, involved in hepatic glucose metabolism and lipogenesis are also modulated by L-Met supplementation. Chromatin-immunoprecipitation assay shows that L-Met supplementation decreases the H3k36me2 abundance on FOXO1 promoter. We provide first evidence for the involvement of epigenetic alterations in preventing progression of diabetes by L-Met supplementation.
Recombinant human arginase I (rhArg I) have emerged as a potential candidate for the treatment of... more Recombinant human arginase I (rhArg I) have emerged as a potential candidate for the treatment of varied pathophysiological conditions ranging from arginine-auxotrophic cancer, inflammatory conditions and microbial infection.. However, rhArg I have a low circulatory half-life, leading to poor pharmacokinetic and pharmacodynamic properties, which necessitating the rapid development of modifications to circumvent these limitations. To address this, polyethylene glycol (PEG)ylated-rhArg I variants are being developed by pharmaceutical companies. However, because of the limitations associated with the clinical use of PEGylated proteins, there is a dire need in the art to develop rhArg I variant(s) which is safe (devoid of limitations of PEGylated counterpart) and possess increased circulatory half-life. In this study, we described the generation and characterization of a fused human arginase I (FHA-3) variant having improved circulatory half-life. FHA-3 protein was engineered by fusing ...
Journal of Sol-Gel Science and Technology
Journal of Environmental Chemical Engineering
Biological Trace Element Research
International Journal of Pharmaceutics
Nanomedicine
Aim: To evaluate whether selenium nanoparticles (SeNPs) can stimulate bone formation and inhibit ... more Aim: To evaluate whether selenium nanoparticles (SeNPs) can stimulate bone formation and inhibit the bone loss involved in hyperglycemia-induced osteoporosis. Methods: Rat osteoblastic UMR-106 cells were used for in vitro studies and female Sprague–Dawley rats were used for type 2 diabetes-associated osteoporosis in vivo study. Results: In vitro studies show that SeNPs promote osteoblast differentiation via modulating alkaline phosphatase (ALP) activity, and promoting calcium nodule formation and collagen content. The authors also provide evidence regarding the involvement of the BMP-2/MAPKs/β-catenin pathway in preventing diabetic osteoporosis. Further, in vivo and ex vivo studies suggested that SeNPs can preserve mechanical and microstructural properties of bone. Conclusion: To the best of our knowledge, this study provides the first evidence regarding the therapeutic benefits of SeNPs in preventing diabetes-associated bone fragility.
Food & Function, 2022
Recently, the protective effects of a methionine-rich diet on hepatic oxidative stress and fibros... more Recently, the protective effects of a methionine-rich diet on hepatic oxidative stress and fibrosis have been suggested but not adequately studied.
Molecular Nutrition & Food Research, 2019
The aim of the current study is to evaluate whether L-Methionine supplementation (L-Met-S) improv... more The aim of the current study is to evaluate whether L-Methionine supplementation (L-Met-S) improves type 2 diabetes-induced alterations in glucose and lipid metabolism by modulating one carbon metabolism and methylation status. Methods and Results: Diabetes was induced in male Sprague Dawley rats using high fat diet and low dose streptozotocin. At the end of study, various biochemical parameters, immunoblotting, qRT-PCR and ChIP-qPCR were performed. We provide first evidence that L-Met-S activates p-AMPK and SIRT1, very similar to 'metformin'. L-Met-S improves the altered key one-carbon metabolites in diabetic rats by modulating methionine adenosyl transferase 1A and cystathione β synthase expression. qRT-PCR shows that L-Met-S alleviates diabetes-induced increase in Forkhead transcription factor 1 expression and thereby regulating genes involved in glucose (G6pc, Pdk4, Pklr) and lipid metabolism (Fasn). Interestingly, L-Met-S inhibits the increased expression of DNMT1 and also prevents methylation of histone H3K36me2 under diabetic condition. ChIP assay shows that persistent increase in abundance of histone H3K36me2 on the promoter region of FOXO1 in diabetic rats and it is recovered by L-Met-S. We provide the first evidence that dietary supplementation of L-Met prevents diabetes-induced epigenetic alterations and regulating methionine levels can be therapeutically exploited for the treatment of metabolic diseases.
Expert Opinion on Therapeutic Patents, 2019
Introduction: Seabuckthorn (SBT) has received worldwide attention for therapeutic, nutraceutical ... more Introduction: Seabuckthorn (SBT) has received worldwide attention for therapeutic, nutraceutical and cosmetic purposes. It is used for the treatment of a number of diseases. Hundreds of commercial products containing SBT are available in the market. Areas covered: This review article covers patents on the therapeutic potential of SBT and its chemical constituents. The therapeutic areas covered in this review include cancer, cardiovascular, diabetes, inflammation, anti-oxidant, and anti-microbial. The patents were searched through Sci-finder, Espacenet, Google Patent, and US Patent. Expert opinion: Plant-based drugs have played an important role in the modern drug industry. Since ancient times, SBT has been used to cure several ailments. SBT has emerged as an important plant, which has been investigated for numerous pharmacological properties and shown to be beneficial in a number of therapeutic areas. Several clinical trials have demonstrated the therapeutic potential of SBT for the treatment of many diseases including cardiovascular, inflammation, diabetes, platelet inhibition, etc. There is huge potential for developing standardized herbal products from different parts of SBT.
New Journal of Chemistry, 2018
Tuning the photoactive behavior of transition metal oxide (Ti2O4, V2O5, Zn3O3) cluster units by s... more Tuning the photoactive behavior of transition metal oxide (Ti2O4, V2O5, Zn3O3) cluster units by structural modifications with polythiophene.
Journal of Chemical Technology & Biotechnology, 2018
BACKGROUNDContinual emergence of quinolones in the environment has raised concerns and the reperc... more BACKGROUNDContinual emergence of quinolones in the environment has raised concerns and the repercussions are almost unimaginable. Along with this an increase of antibiotic resistance in microbes has encouraged the pharmaceutical and food industry to create new antimicrobial agents. Nano‐range materials with exceptional antimicrobial properties synthesized via green routes for fluorescence sensing of fluoroquinolones have rarely been reported.RESULTSA facile, eco‐friendly and green approach was utilized for the synthesis of water soluble glutathione (GSH) functionalized CdS quantum dots (QDs) for the selective detection of fluoroquinolones. The prepared QDs exhibited a strong emission peak at 460 nm and the addition of fluoroquinolones caused enhancement and significant blue shift (∼ 50 nm) in the intensity, revealing sensitive and selective detection of fluoroquinolones. The limit of detection was found to be 2.2 µmol L‐1. Also, antimicrobial activities of the QDs were assessed agai...
The level of RNA oxidation in patients with heart failure (HF) and its effect have not been well ... more The level of RNA oxidation in patients with heart failure (HF) and its effect have not been well established. The aim of this study was to investigate the relationship between urinary 8-oxo-7, 8-dihydroguanosine (8-oxo-Gsn), a marker for oxidative stress to RNA and HF. Methods: A total of 191 HF patients from March 2014 to March 2018 and 155 healthy controls were included in this study, and their morning urine was collected. The level of urinary 8-oxo-Gsn was measured by ultra high-performance liquid chromatography mass spectrometry/mass spectrometry and adjusted by urinary creatinine. Heart failure with reduced ejection fraction (HFrEF) was defined as left ventricular ejection fraction (LVEF) <40%. Heart failure with preserved ejection fraction (HFpEF) was defined as LVEF ≥50% with diastolic dysfunction. Results: 8-oxo-Gsn in HF patients was significantly increased compared with age-and sexmatched healthy control subjects [4.20 (3.09-5.77) vs. 2.75 (2.59-2.85), p < 0.001]. The level of 8-oxo-Gsn was positively correlated with age (r = 0.257, p = 0.001) and N-terminal pro brain natriuretic peptide (r = 0.257, p < 0.001) and negatively correlated with diastolic blood pressure (r = -0.147, p = 0.049), hemoglobin (r = -0.181, p = 0.013), and creatinine clearance rate (r = -0.215, p = 0.004). Patients with HFrEF and HFpEF exhibited both the higher levels of 8-oxo-Gsn than control subjects (all p < 0.001) while there was no difference between , p = 0.406]. The level of urinary 8-oxo-Gsn is increased in patients with HF, indicating that HF may be associated with increased oxidative damage to RNA, and urinary 8-oxo-Gsn be useful in the diagnosis and evaluation of HF.
International Journal of Pharmaceutics, 2015
The aim of the present study was to establish the potential of rifampicin loaded phospholipid lip... more The aim of the present study was to establish the potential of rifampicin loaded phospholipid lipospheres carrier for pulmonary application. Lipospheres were prepared with rifampicin and phospholipid in the ratio of 1:1 using spray drying method. Further, lipospheres were evaluated for flow properties and surface area measurement. The formulated lipospheres were evaluated in vitro for aerodynamic characterization and in vivo for lung pharmacokinetics and biodistribution studies in Sprague Dawley rats. Powder flow properties finding suggested the free flowing nature of the lipospheres. In vitro aerosol performance study indicated more than 80±5% of the emitted dose (ED) and 77.61±3% fine particles fraction (FPF). Mass median aerodynamic diameter (MMAD) and geometric standard deviation (GSD) were found to be 2.72±0.13µm and 3.28±0.12, respectively. In-vitro aerosol performance study revealed the higher deposition at 3, 4 and 5 stages which simulates the trachea-primary bronchus, secondary and terminal bronchus of the human lung, respectively. The drug concentration from nebulized lipospheres in the nontargeted tissues was lesser than from rifampicin-aqueous solution. The pulmonary pharmacokinetic study demonstrated improved bioavailability, longer residence of drug in the lung and targeting factor of 8.03 for lipospheres as compared to rifampicin-aqueous solution. Thus, the results of the study demonstrated the potential of rifampicin lipospheres formulation would be of use as an alternative to existing oral therapy.
Journal of Molecular Recognition, 2014
The present study involves molecular docking, molecular dynamics (MD) simulation studies, and Cac... more The present study involves molecular docking, molecular dynamics (MD) simulation studies, and Caco-2 cell monolayer permeability assay to investigate the effect of structural modifications on PepT1-mediated transport of thyrotropin releasing hormone (TRH) analogs. Molecular docking of four TRH analogs was performed using a homology model of human PepT1 followed by subsequent MD simulation studies. Caco-2 cell monolayer permeability studies of four TRH analogs were performed at apical to basolateral and basolateral to apical directions. Inhibition experiments were carried out using Gly-Sar, a typical PepT1 substrate, to confirm the PepT1-mediated transport mechanism of TRH analogs. P app of the four analogs follows the order: NP-1894 < NP-2378 < NP-1896 < NP-1895. Higher absorptive transport was observed in the case of TRH analogs, indicating the possibility of a carrier-mediated transport mechanism. Further, the significant inhibition of the uptake of Gly-Sar by TRH analogs confirmed the PepT1-mediated transport mechanism. Glide docking scores of all the four analogues were in good agreement with their transport rates, suggesting the role of substrate binding affinity in the PepT1-mediated transport of TRH analogs. MD simulation studies revealed that the polar interactions with amino acid residues present in the active site are primarily responsible for substrate binding, and a downward trend was observed with the increase in bulkiness at the N-histidyl moiety of TRH analogs. Copyright
Protein Expression and Purification, 2013
An integral component of NF-κB signalling is NEMO, NF-κB essential modulator, a regulatory protei... more An integral component of NF-κB signalling is NEMO, NF-κB essential modulator, a regulatory protein of the IκB kinase (IKK) complex. Post-translational modifications of NEMO, including phosphorylation, SUMOylation, and ubiquitination are critical events during stimuli induced NF-κB activation. Here we demonstrate a method to detect post-translational modifications of NEMO using cells stably expressing polyhistidine tagged NEMO which allows for high-affinity purification of NEMO following rapid denaturing lysis and characterization by MS/MS. We identified a previously uncharacterized basal phosphorylation of NEMO at Serine 387 and tested the biological significance of this phosphorylation through a somatic genetic complementation analysis using the NEMO mutants S387A, S388D, and P388I in 1.3E2 NEMO-deficient murine pre-B cells. NF-κB signalling induced by bacterial lipopolysaccharide, Interleukin-1ß or the DNA damaging agent etoposide was not perturbed by these mutations of NEMO. Thus, S387 phosphorylation of NEMO is not a general requirement to mediate efficient NF-κB signalling and therefore may have cell type and/or stimulus-specific activity in vivo.
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Papers by Kulbhushan Tikoo