Browsing by Author "Abha Mishra"

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2-Hydroxyestradiol-17β-induced oocyte maturation in catfish (Heteropneustes fossilis) involves protein kinase C and its interaction with protein phosphatases
(Elsevier Inc., 2006) Abha Mishra; Keerikkattil Paily Joy
In vitro effects of phorbol 12-myristate 13-acetate (PMA), a protein kinase C (PKC) activator, calphostin C (PKC inhibitor) and okadaic acid [OA, a protein phosphatase (PP; PP1 and PP2A) inhibitor] on 2-hydroxyestradiol-17β (2-OHE2)-induced oocyte maturation were investigated in the catfish Heteropneustes fossilis. Incubations of postvitellogenic follicles with PMA or OA alone did not induce oocyte maturation. However, co-incubations with 2-OHE2 and PMA (0.05, 0.5 and 5 μM) or 2-OHE2 and OA (0.5, 1.0 or 2.0 μM) increased germinal vesicle breakdown (GVBD) significantly over that of 2-OHE2. Incubation of follicles with calphostin C elicited varied effects on GVBD, low (0.005 and 0.01 μM) and high (5.0 and 10.0 μM) concentrations did not affect GVBD, but medium concentrations (0.05, 0.1, 0.5, 1.0 and 2.5 μM) stimulated it. The medium concentrations elicited a biphasic stimulatory response with peak GVBD at 0.1 μM (54%). Calphostin C (≥ 2.5 μM) inhibited the 2-OHE2-induced GVBD in a concentration-dependent manner during the 24 h incubation. Pre- or post-treatment with calphostin C inhibited the steroid-induced GVBD only at 6 h. In co-incubation studies, both PMA and OA reversed the inhibitory effect of calphostin C: the former partially and the latter fully. The results of the present study show that PKC appears to modulate the 2-OHE2-induced oocyte maturation. The OA-sensitive PP may be involved in the PKC modulation of steroid-induced oocyte maturation. © 2006 Elsevier Inc. All rights reserved.
Advancements in Nano-Mediated Biosensors: Targeting Cancer Exosome Detection
(Springer, 2024) Abhay Dev Tripathi; Yamini Labh; Soumya Katiyar; Vivek K. Chaturvedi; Pooja Sharma; Abha Mishra
Cancer-derived exosomes, a subset of extracellular vesicles, carry vital information about tumor progression, metastasis, and drug resistance, making them attractive targets for cancer diagnostics and therapeutics. The identification of these cancer exosomes with high sensitivity and specificity has enormous promise for early diagnosis and prognosis. Nano-mediated biological sensors are establishing themselves as innovative techniques for detecting cancer exosomes based on the distinctive physicochemical attributes of nanomaterials to improve detection sensitivity and specificity. This article presents an overview of the recent developments in nano-mediated biosensors directed particularly toward the detection of cancer exosomes. The development of ultrasensitive sensors has been enhanced by using nanomaterials such as magnetic nanoparticles, quantum dots, and gold nanoparticles. Surface modifications of these nanomaterials by conjugating the cancer-specific antibodies or aptamers facilitate target recognition and binding of cancer exosomes, thus increasing the sensitivity of detection. This review compiles different detection techniques, including SERS, Electrochemical, SPR, Chemiluminescence, and Fluorescence-based biosensor detection, in combination with different nanomaterials that are currently being researched or utilized as biosensors. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
An in vitro study on noradrenergic modulation of final oocyte maturation in the catfish Heteropneustes fossilis
(Elsevier Inc., 2018) Abha Mishra; Radha Chaube; K.P. Joy
This study was aimed to elucidate in vitro the effects of endogenous catecholamines: dopamine (DA), noradrenaline (NA) and adrenaline (A), and the β-adrenergic blocker propranolol on induction of final oocyte maturation (FOM) in the catfish Heteropneustes fossilis. With this aim, post vitellogenic follicles from sexually mature gravid female catfish were incubated with each of DA, NA and A in a concentration range of 5–250 μM, and propranolol in a concentration range of 1–200 μg/mL at time points varying from 0 to 30 h). Translucent follicles without germinal vesicle (GV) and opaque follicles with GV were scored separately for the calculation of percentage germinal vesicle breakdown (GVBD), an index of FOM. Data were analyzed by one-way ANOVA and were considered statistically significant when P values were less than 0.05. The analysis of the data showed that the incubation with NA only stimulated GVBD in a concentration - and time-dependent manner. Though the incubation with propranolol decreased total follicular cAMP level significantly at and above 10 μg/mL concentrations, a significant effect of the GVBD increase was noticed at 50 μg/mL or higher. However, the 10 μg/mL concentration of propranolol was effective to inhibit the NA-induced GVBD significantly albeit at a low level (39%). The present study suggests that final oocyte maturation is modulated by NA through a β-adrenergic mechanism, implicating a neural control of oocyte maturation and ovulation in teleosts. © 2018
Anthropogenic drivers shift diatom dominance-diversity relationships and transparent exopolymeric particles production in River Ganga: Implication for natural cleaning of river water
(Indian Academy of Sciences, 2017) Usha Pandey; Jitendra Pandey; Anand V. Singh; Abha Mishra
We studied the relationships among diatom biodiversity, transparent exopolymeric particles (TEP) and water quality at the confluences of four tributaries of River Ganga (Yamuna, Assi, Varuna and Gomti) during low flow. Diatom abundance changed with concurrent shifts in water chemistry with dominance- diversity curves markedly skewed from a log-normal pattern. Canonical correspondence analysis segregated chloride-loving and calcifilous species from N- and P-favoured taxa. Despite pollution-induced reduction of diatom diversity, TEP production continued to rise plausibly due to dominance transference of TEP producers. However, with further increase in nutrient pollution, TEP declined. Since TEP enhances sedimentation removal of carbon, nutrients and heavy metals, the present study confirms one of the fundamental mechanisms that underline the self-purification capacity of River Ganga and has relevance from a biodiversity/river conservation perspective.
Antitumor potential of ivermectin against T-cell lymphoma-bearing hosts
(Springer, 2025) Alok Shukla; Arpit Sharma; Shivani Gupta; Abha Mishra; Amit Kumar Singh
Ivermectin, a broad-spectrum antiparasitic agent from the ivermectin family, has shown promising anticancer potential. Originally developed for veterinary and human use against parasitic infections, ivermectin demonstrated significant antitumor effects in our study against tumor cells (Dalton’s lymphoma cells). A dose-dependent decrease in tumor cell viability was observed following 24-h treatment with ivermectin, with an IC₅₀ value calculated at 10.55 µg/mL. In comparison, the standard anticancer drug cisplatin exhibited a slightly higher cytotoxic potency, with an IC₅₀ of 8.32 µg/mL under the same treatment duration. Flow cytometric analysis revealed that ivermectin induced cell cycle arrest in the G0–G1 phase. Apoptotic tumor cell death was confirmed via Annexin V/PI staining, further supported by nuclear condensation, a hallmark of apoptosis, visualized through both confocal microscopy and flow cytometry. The apoptosis was determined to be mitochondrial-dependent, as evidenced by a decline in mitochondrial membrane potential (ΔΨm) observed through JC-1 assay. The treatment increased DAPI-positive cells and exhibited severe chromatin condensation. Additionally, cell death was validated using Acridine Orange and Propidium Iodide staining, which highlighted increased cell membrane rupture and death through apoptosis and necrosis. Mitochondrial dependent apoptosis further supported by increased ROS production upon ivermectin treatment. Moreover, In vivo, ivermectin treatment led to a substantial reduction in tumor size in tumor-bearing mice, along with normalization of spleen size, body weight, and improvement histopathology of liver. These findings collectively support the therapeutic potential of ivermectin as a repurposed anticancer agent, acting through multiple mechanisms including cell cycle arrest, ROS generation, mitochondrial dysfunction, and apoptosis. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2025.
Antiviral and Antimicrobial Potentiality of Nano Drugs
(Elsevier, 2018) Kushagri Singh; Abha Mishra; Deepankar Sharma; Kavita Singh
Despite different existing potential antimicrobial agents, microbial (bacterial and viral) infections are still an important challenge to the pharmaceutical industry today. Therefore, it is required to develop another bactericidal route to destroy some microorganisms that have become resistant toward antibiotics and antiviral infections. Accordingly, attention is concentrating especially on novel as well as emerging nanotechnology-based materials in the field of antimicrobial therapy. This chapter discusses the antimicrobial activities of numerous nanoparticles such as carbon-based nanoparticles like carbon nanotubes, fullerenes, graphene oxides, and metallic nanoparticles together with polymeric chitosan nanoparticles as an antimicrobial agent, their mode of action, nanoparticle effect on drug-resistant bacteria, and the risks attendant with their use as antimicrobial agents to tissues of human cells. The importance of metallic nanoparticles such as silver nanoparticles as an antiviral agent was also investigated. © 2019 Elsevier Inc. All rights reserved.
Artificial intelligence-driven optimization of biohydrogen production: ANN-GA, RSM, and python synergy for novel Alcaligenes ammonioxydans utilizing sugarcane bagasse
(Elsevier Ltd, 2025) Shruti Sharadrao Raut; Arpit Sharma; Ankit Keshariya; Vansh Agarwal; Rohit Kumar; Abha Mishra
Biohydrogen (bioH2) production through dark fermentation presents a promising and sustainable alternative to fossil fuels, especially when utilizing lignocellulosic agricultural residues. In this study, sugarcane bagasse (SB) was selected as the feedstock due to its high carbohydrate content, abundant availability, and low cost, making it an ideal substrate for microbial bioH2 production. A newly isolated and efficient bioH2-producing bacterium, Alcaligenes ammonioxydans SRAM was employed to ferment the pretreated bagasse under anaerobic conditions. To optimize bioH2 yield, four critical process parameters substrate concentration, inoculum ratio, acid pretreatment concentration, and pH were systematically investigated using a Central Composite Design (CCD). Two advanced modelling approaches, Response Surface Methodology (RSM) and Artificial Neural Networks (ANN), were used to develop predictive frameworks based on the experimental data. ANN models were developed in MATLAB and Python, demonstrating superior performance over RSM by accurately capturing complex nonlinear interactions with significantly lower prediction errors. To enhance the optimization process, the ANN model was further integrated with a Genetic Algorithm (GA), resulting in a hybrid ANN-GA model implemented in Python. This hybrid approach effectively determined the optimal conditions for maximum bioH2 production, achieving a minimal prediction error of 0.02. The optimized parameter set included a substrate concentration of 48.98 g/L, an inoculum ratio of 8.21 % v/v, an acid concentration of 3.56 % v/v, and a pH of 7.02. This study clearly highlights the potential of A. ammonioxydans SRAM for high-efficiency bioH2 production and presents a robust ANN-GA-based optimization framework for enhancing bioH2 yields from SB, advancing the transition to renewable energy sources. © 2025 Elsevier Ltd
Cadmium sulfide nanoparticles (CdSNPs) modulate key oncogenic pathways in PA1 ovarian cancer cells: Insights from transcriptomic analysis
(Elsevier Ltd, 2025) Aditi Bhatnagar; Abhay Dev Tripathi; Sonali Kumari; Abha Mishra
Transcriptomics has become a useful tool for comparing the levels of gene expression in healthy and malignant cells, holding potential for the discovery of new cancer therapies. This study used RNA-sequencing and transcriptome analysis on the PA1 ovarian cancer cell line to examine the potential of Cadmium Sulfide Nanoparticles (CdSNPs) as a therapeutic agent. A total of 5.42 Gb of high-quality reads was estimated based on the findings of gene expression techniques, comprising 2.25 Gb of treated PA1 cells and 3.17 Gb of control cells. Of these, 1641 genes with padj<0.001 and log2 foldchange >2 were found to be significantly regulated DEGs (differentially expressed genes). Analysis of gene ontology (GO) assays demonstrates the molecular mechanism behind CdSNPs anticancer effects. GO:0006915, GO:0012501, GO:1903561, and GO:0070588 are a few significant highlights of elevated GO (enriched DEGs) that are involved in apoptotic pathways, extracellular vesicles, programmed cell death, and Ca++ signaling. KEGG analysis elucidated that up and downregulated DEGs were enriched in a few pathways: calcium signaling pathway, Apoptosis, and TNF signaling pathway. Important pathways like MAP kinase, JAK/STAT, cAMP, and folate biosynthesis, showed inhibitory effects on ovarian cancer cell proliferation. The results of this work provide insight into possible therapeutic approaches employing CdSNPs and encourage additional research using a variety of cell lines and in vivo models to improve ovarian cancer treatment. © 2025
Catechin isolated from faba beans (Vicia faba L.): insights from oxidative stress and hypoglycemic effect in yeast cells through confocal microscopy, flow cytometry, and in silico strategy
(Taylor and Francis Ltd., 2022) Dhiraj Kumar Choudhary; Navaneet Chaturvedi; Amit Singh; Abha Mishra
The present aim of this investigation was to evaluate the effect of catechin from faba beans on oxidative stress and glucose uptake in yeast cells. Flow cytometry approach indicated that 2-NBDG (1.98 ± 0.37) seed extract had a lower relative fluorescence signal than methanol (5.98 ± 0.67) and acetone seed extract (4.43 ± 0.55). In comparison to the control and seed extract, H2O2 exposure increased the apoptosis rate of yeast cells from 8.20% to 64.80%. Yeast cells incubated with H2O2 produced significantly more ROS intensity (162 ± 4.32, p < 0.05) than control cells (118 ± 2.52, p < 0.05) and less than seed extract-treated cells. Molecular dynamics simulation studies were performed for cat:α-amylase (catechin-α-amylase complex) which revealed the stable and mixed mode of inhibition during a simulation. The synergistic action of polyphenols or catechin present in seed extract may be responsible for the anti-oxidative stress and hypoglycaemic effects. The findings of this study may provide insight into the further development of a novel antidiabetic drug for T2DM. Communicated by Ramaswamy H. Sarma. © 2021 Informa UK Limited, trading as Taylor & Francis Group.
Characterization, inhibitory activity and mechanism of polyphenols from faba bean (gallic-acid and catechin) on α-glucosidase: insights from molecular docking and simulation study
(Taylor and Francis Inc., 2020) Dhiraj Kumar Choudhary; Navaneet Chaturvedi; Amit Singh; Abha Mishra
The chemo-profiling of ethanolic extract of faba beans seeds was performed and explored as an α-glucosidase inhibitor. The inhibition of α-glucosidase is one of the alternatives approach to control postprandial hyperglycemia by, resulting in the delay of the carbohydrate digestion of absorbable monosaccharides. Ethanolic seed extract showed phenolic compounds, flavonoid such as gallic acid (m/z [M– H] = 169.0124,C7H6O5) ellagic acid derivatives epigallocatechin (m/z [M– H = 305.0644,C15H14O7),catechin (m/z [M– H] = 289.0656,C15H14O6), epigallocatechin gallate (m/z [M– H] = 457.0578,C22H18O11) and epicatechin monogallate (m/z [M– H] = 441.081, C22H18O10). The extract was found to exert inhibitory activity (88.28 ± 2.67%) (IC50 value of 2.30 ± 0.032 mg/mL) with a mixed mode of inhibition (Km, apparent = 0.54 ± 0.020 mM and Vmax, apparent 0.136 ± 0.04 mM/min). Molecular docking studies of gallic acid and catechin on α-glucosidase proposed productive binding modes having binding energy (−6.58 kcal/mol and −7.25 kcal/mol) with an effective number of hydrogen bonds and binding energy. Tyr63, Arg197, Asp198, Glu 233, Asn324, Asp 326 of α-glucosidase participated in binding events with gallic acid and catechin. Molecular dynamics simulation studies were performed for both complexes i.e. gal:α-glucosidase and cat:α-glucosidase along with apo state of α-glucosidase, which revealed stable systems during the simulation. These findings of the present study may give an insight into the further development of the novel antidiabetic drug from the seeds of faba beans. © 2019, © 2019 Taylor & Francis Group, LLC.
Chitosan nanoparticulate and their applications: A review
(International Journal of Pharma and Bio Sciences, 2015) Kushagri Singh; Abha Mishra
Chitosan has reached a prominent position as the carrier-forming material, as diverse methods can be applied to produce nanoparticles using that excipient. Chitosan polymers are extensively used for the delivery of an active pharmaceutical ingredient. They can form a matrix or membrane that can control the release of a drug over a prolonged period of time or sustained release of drugs, thus avoiding repetitive dosing. Several methods have been developed to produce chitosan nanoparticles, since those have been shown to offer attractive advantages as drug delivery carriers. Chitosan is an effective material for biomedical applications because of their biocompatibility, biodegradability and non-toxicity, apart from their antimicrobial activity and low immunogenicity, which clearly points to an immense potential for future development. This review summarizes the biomedical applications of multifunctional chitosan based nanomaterials in drug delivery and as a support medium for enzyme immobilization.
Complex disruption effect of natural polyphenols on Bcl-2-Bax: Molecular dynamics simulation and essential dynamics study
(Taylor and Francis Ltd., 2015) Sharad Verma; Amit Singh; Abha Mishra
Apoptosis (programmed cell death) is a process by which cells died after completing physiological function or after a severe genetic damage. Apoptosis is mainly regulated by the Bcl-2 family of proteins. Anti apoptotic protein Bcl-2 prevents the Bax activation/oligomerization to form heterodimer which is responsible for release of the cytochrome c from mitochondria to the cytosol in response to death signal. Quercetin and taxifolin (natural polyphenols) efficiently bound to hydrophobic groove of Bcl-2 and altered the structure by inducing conformational changes. Taxifolin was found more efficient when compared to quercetin in terms of interaction energy and collapse of hydrophobic groove. Taxifolin and quercetin were found to dissociate the Bcl-2-Bax complex during 12 ns MD simulation. The effect of taxifolin and quercetin was, further validated by the MD simulation of ligand-unbound Bcl-2-Bax which showed stability during the simulation. Obatoclax (an inhibitor of Bcl-2) had no significant dissociation effect on Bcl-2-Bax during simulation which favored the previous experimental results and disruption effect of taxifolin and quercetin. © 2014 Taylor & Francis.
DDX3X dynamics, glioblastoma's genetic landscape, therapeutic advances, and autophagic interplay
(Springer, 2024) Arpit Sharma; Shruti S. Raut; Alok Shukla; Shivani Gupta; Amit Singh; Abha Mishra
Glioblastoma is one of the most aggressive and deadly forms of cancer, posing significant challenges for the medical community. This review focuses on key aspects of Glioblastoma, including its genetic differences between primary and secondary types. Temozolomide is a major first-line treatment for Glioblastoma, and this article explores its development, how it works, and the issue of resistance that limits its effectiveness, prompting the need for new treatment strategies. Gene expression profiling has greatly advanced cancer research by revealing the molecular mechanisms of tumors, which is essential for creating targeted therapies for Glioblastoma. One important protein in this context is DDX3X, which plays various roles in cancer, sometimes promoting it or otherwise suppressing it. Additionally, autophagy, a process that maintains cellular balance, has complex implications in cancer treatment. Understanding autophagy helps to identify resistance mechanisms and potential treatments, with Chloroquine showing promise in treating Glioblastoma. This review covers the interplay between Glioblastoma, DDX3X, and autophagy, highlighting the challenges and potential strategies in treating this severe disease. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
Discovery of Histone Deacetylase Inhibitor Using Molecular Modeling and Free Energy Calculations
(American Chemical Society, 2022) Abha Mishra; Amit Singh
The histone acetylation-deacetylation at lysine regulates the functions of many cellular proteins. An increased expression of HDAC6 can cause an increased amount of deacetylated histones, which leads to an inhibition of gene expression and has been associated with cancer cell proliferation. The present study screened the ZINC database to find novel HDAC6 inhibitors using virtual high-throughput screening techniques. The docking score, free energy, and binding pattern of the complexes were used to select a best ligand for further study. Molecular dynamic simulations, binding interactions, and the stability of docked conformations were investigated. Several parameters that determine protein-ligand interactions, such as root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), and binding pattern, were observed. Hydrogen bonds were observed at His 573 and Gly 582 after a 150 ns simulation with identified compound ZINC000002845205, and they were similar to known inhibitor Panobinostat. The molecular mechanics with generalised Born and surface area solvation (MM/GBSA) free energy was comparable to known inhibitor Panobinostat. ZINC000002845205 qualifies drug-likeness according to Lipinski's rule-of-five, rule-of-three, and the World Drug Index (WDI)-like rule, but there is one violation in the lead-like rule. © 2022 The Authors.
Discovery of the allosteric inhibitor from actinomyces metabolites to target EGFRCSTMLR mutant protein: molecular modeling and free energy approach
(Nature Research, 2023) Ravi Saini; Sonali Kumari; Aditi Bhatnagar; Amit Singh; Abha Mishra
EGFR (epidermal growth factor receptor), a surface protein on the cell, belongs to the tyrosine kinase family, responsible for cell growth and proliferation. Overexpression or mutation in the EGFR gene leads to various types of cancer, i.e., non-small cell lung cancer, breast, and pancreatic cancer. Bioactive molecules identified in this genre were also an essential source of encouragement for researchers who accomplished the design and synthesis of novel compounds with anticancer properties. World Health Organization (WHO) report states that antibiotic resistance is one of the most severe risks to global well-being, food safety, and development. The world needs to take steps to lessen this danger, such as developing new antibiotics and regulating their use. In this study, 6524 compounds derived from Streptomyces sp. were subjected to drug-likeness filters, molecular docking, and molecular dynamic simulation for 1000 ns to find new triple mutant EGFRCSTMLR (EGFR-L858R/T790M/C797S) inhibitors. Docking outcomes revealed that five compounds showed better binding affinity (− 9.074 to − 9.3 kcal/mol) than both reference drug CH7233163 (− 6.11 kcal/mol) and co-crystallized ligand Osimertinib (− 8.07 kcal/mol). Further, molecular dynamic simulation confirmed that ligand C_42 exhibited the best interaction at the active site of EGFR protein and comprised a better average radius of gyration (3.87 Å) and average SASA (Solvent Accessible Surface Area) (82.91 Å2) value than co-crystallized ligand (4.49 Å, 222.38 Å2). Additionally, its average RMSD (Root Mean Square Deviation) (3.25 Å) and RMSF (Root Mean Square Fluctuation) (1.54 Å) values were highly similar to co-crystallized ligand (3.07 Å, 1.54 Å). Compared to the reference ligand, it also demonstrated conserved H-bond interactions with the residues MET_793 and GLN_791 with strong interaction probability. In conclusion, we have found a potential drug with no violation of the rule of three, Lipinski's rule of five, and 26 other vital parameters having great potential in medicinal and pharmaceutical industries applications and can overcome synthetic drug issues. © 2023, The Author(s).
Dual inhibition of chaperoning process by taxifolin: Molecular dynamics simulation study
(2012) Sharad Verma; Amit Singh; Abha Mishra
Hsp90 (heat shock protein 90), a molecular chaperone, stabilizes more than 200 mutated and over expressed oncogenic proteins in cancer development. Cdc37 (cell division cycle protein 37), a co-chaperone of Hsp90, has been found to facilitate the maturation of protein kinases by acting as an adaptor and load these kinases onto the Hsp90 complex. Taxifolin (a natural phytochemical) was found to bind at ATP-binding site of Hsp90 and stabilized the inactive "open" or "lid-up" conformation as evidenced by molecular dynamic simulation. Furthermore, taxifolin was found to bind to interface of Hsp90 and Cdc37 complex and disrupt the interaction of residues of both proteins which were essential for the formation of active super-chaperone complex. Thus, taxifolin was found to act as an inhibitor of chaperoning process and may play a potential role in the cancer chemotherapeutics. © 2012 Elsevier Inc.
Enhanced sustained release of furosemide in long circulating chitosan-conjugated PLGA nanoparticles
(Wolters Kluwer Medknow Publications, 2019) Sapna Kashyap; Amit Singh; Abha Mishra; Vikas Singh
Furosemide (FSM) is commonly used in the treatment of edema associated with congestive cardiac failure, cirrhosis of the liver, renal disease, including the nephrotic syndrome and hypertension. However, in ascites, it is clinically limited due to its frequent dosing and short biological half-life and its prolonged-release preparations are not available. Therefore, the main objective behind the present research work is to develop chitosan coated and conjugated poly (lactic-co-glycolic acid) (PLGA) nanocarriers, to sustain the delivery of FSM with improved systemic circulation. Emulsion-solvent evaporation technique was used for the preparation of nanoparticles. In-vivo pharmacokinetic study showed 2.6, 3.10, and 4.30 folds enhancement in relative availability of FSM for FSM-PLGA, FSM-chitosan-coated-PLGA and FSM-chitosan-conjugated-PLGA nanoparticles, respectively than FSM. The present research work concluded that FSM loaded chitosan conjugated PLGA nanoparticles could enhance the systemic circulation of FSM with improved pharmacokinetics parameters. © 2019 Medknow Publications.All rights reserved.
Fisetin 8-C-glucoside as entry inhibitor in SARS CoV-2 infection: molecular modelling study
(Taylor and Francis Ltd., 2022) Abha Mishra; Upinder Kaur; Amit Singh
Coronaviruses are RNA viruses that infect varied species including humans. TMPRSS2 is gateway for SARS CoV-2 entry into the host cell. It causes proteolytic activation of spike protein and discharge of the peptide into host cell. The TMPRSS2 inhibition could be one of the approaches to stop the viral entry, therefore, interaction pattern and binding energies for Fisetin and TMPRSS2 have been explored in the present study. TMPRSS2 peptide was used for homology modelling and then for further study. Molecular docking score and MMGBSA Binding energy of Fisetin was better than Nafamostat, a known inhibitor of TMPRSS2. Post docking MM-GBSA free energy for Fisetin and Nafamostat was −42.78 and −21.11 kcal/mol, respectively. Fisetin forms H bond with Val 25, His 41, Lys 42, Lys 45, Glu 44, Ser186. Nafamostat formed H bonds with Lys 85, Asp 90, Asp 203. RMSD plots of TMPRSS2, TMPRSS2-Fisetin and TMPRSS2-Nafamostat complex showed stable profile with very small fluctuation during entire simulation of 150 ns. Significant decrease in TMPRSS2-Fisetin and TMPRSS2-Nafamostat complex fluctuation occurred around His 41, Glu 44, Gly 136, Ser 186 in RMSF study. During simulation Fisetin interaction was observed with residues Val 25, His 41, Glu 44, Lys 45, Lys 87, Gly 136, Gln 183, Ser 186 likewise interaction of Nafamostat with Lys 85, Asp 90, Asn 163, Asp 203 and Ser 205. Post simulation MM-GBSA free energy was found to be −51.87 ± 4.3 and −48.23 ± 4.39 kcal/mol for TMPRSS2 with Fisetin and Nafamostat, respectively. Communicated by Ramaswamy H. Sarma. © 2020 Informa UK Limited, trading as Taylor & Francis Group.
Folate-Mediated Targeting and Controlled Release: PLGA-Encapsulated Mesoporous Silica Nanoparticles Delivering Capecitabine to Pancreatic Tumor
(American Chemical Society, 2024) Abhay Dev Tripathi; Yamini Labh; Soumya Katiyar; Anurag Kumar Singh; Vivek K. Chaturvedi; Abha Mishra
The discovery of specifically tailored therapeutic delivery systems has sparked the interest of pharmaceutical researchers considering improved therapeutic effectiveness and fewer adverse effects. The current study concentrates on the design and characterization of PLGA (polylactic-co-glycolic acid) capped mesoporous silica nanoparticles (MSN)-based systems for drug delivery for pH-sensitive controlled drug release in order to achieve a targeted drug release inside the acidic tumor microenvironment. The physicochemical properties of the nanoformulations were analyzed using TEM, zeta potential, AFM, TGA, FTIR, and BET analyses in addition to DLS size. The final formed PLGA-FoA-MSN-CAP and pure MSN had sizes within the therapeutic ranges of 164.5 ± 1.8 and 110.7 ± 2.2, respectively. Morphological characterization (TEM and AFM) and elemental analysis (FTIR and XPS) confirmed the proper capping and tagging of PLGA and folic acid (FoA). The PLGA-coated FoA-MSN exhibited a pH-dependent controlled release of the CAP (capecitabine) drug, showing efficient release at pH 6.8. Furthermore, the in vitro MTT test on PANC1 and MIAPaCa-2 resulted in an IC50 value of 146.37 μg/ml and 105.90 μg/ml, respectively. Mitochondrial-mediated apoptosis was confirmed from the caspase-3 and annexin V/PI flow cytometry assay, which displayed a cell cycle arrest at the G1 phase. Overall, the results predicted that the designed nanoformulation is a potential therapeutic agent in treating pancreatic cancer. © 2024 American Chemical Society.
Formulation, optimization, and in vitro–in vivo characterization of furosemide-loaded poly lactic-co-glycolic acid nanoparticles for sustained delivery
(BRNSS Publication Hub, 2018) Sapna Kashyap; Amit Singh; Abha Mishra; A.M. Godbole
Objective: In this study, the authors developed furosemide-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) for sustained delivery of furosemide. Materials and Methods: Furosemide-loaded PLGA-NPs were prepared by emulsion solvent evaporation method and characterized for particle size and size distribution, zeta potential, surface morphology, drug encapsulation efficiency, and drug release profile. In vivo study was performed in Charles Foster rats. Results: In vitro characterizations of the furosemide-loaded PLGA NPs showed that the mean particle sizes of the NPs ranged from 98.3 nm to 300.3 nm, the zeta potential values were in the range of −13.0–−27.1 mV, the encapsulation efficiencies were between 61.0 and 73.4%, and the drug release from the formulation was in the range of 40.3–80.7%. Scanning electron micrographs showed that the fabricated particles were spherical in shape. Urine output at the predetermined time showed a sustained effect of drug in PLGA NPs. Conclusion: The fabricated furosemide-loaded PLGA NPs were able to improve the sustained effect of the drug as indicated in in vitro–in vivo results. © 2018 BRNSS Publication Hub. All rights reserved.