Browsing by Author "Varsha Rani"

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Arsenic-induced responses in plants: Impacts on biochemical processes
(wiley, 2022) Sanjay Kumar; Varsha Rani; Simranjeet Singh; Dhriti Kapoor; Daljeet Singh Dhanjal; Ankita Thakur; Mamta Pujari; Praveen C. Ramamurthy; Joginder Singh
Arsenic (As) overaccumulates into plants because of mineralization, mining activities, irrigation with contaminated groundwater, wood preservatives, herbicides, insecticides, and fertilization with solid municipal wastes. The state of arsenic (III) and (V) triggers an overproduction of reactive oxygen species like hydroxyl radical, oxide radical, and hydrogen peroxide, causing oxidative damage of various biochemicals like nucleic acids, proteins, and lipids. These ions also stimulate various enzymes like catalase, ascorbate peroxidase, glutathione reductase, superoxide dismutase, guaiacol peroxidase, and nonenzymatic components like glutathione, ascorbate, carotenoid, and A-tocopherol inside the plants and act as antioxidants. Therefore, the toxicity of arsenic is stated to negatively affect the productivity as well as the quality of plants and impact the well-being and health of animals and humans consuming it. With passing time, plants have started evolving and developing strategies to curb the toxic effect induced by arsenic via mechanisms like accumulation of compatible solutes (mannitol, glycine betaine, sugar, and proline), biosynthesis of polyphenols, compartmentalization, and metal-binding proteins. Moreover, exogenous application of nitric oxide (NO), phosphate, proline, and potassium has been reported to reduce arsenic toxicity substantially. In this chapter, we explored the effects of arsenic on biochemical processes, oxidative stress, carbohydrate metabolism, lipid metabolism, and protein metabolism in arsenic-induced plants. We also discussed some directions to uncover the precise molecular mechanism involved in ameliorating arsenic-induced toxicity responses in different plants. © 2023 John Wiley & Sons, Inc.
Crafting a Molecular Trojan Horse: Sialic Acid-Modified PLGA Nanoparticles for Targeted Lung Cancer Therapy
(American Chemical Society, 2025) Krishan Kumar; Manjit Saini; Varsha Rani; Mohini Mishra; None Priya; None Jatin; Siddharth Tiwari; Brahmeshwar Mishra; Ruchi Chawla
The glycan receptors prominently expressed on the surface of lung cancer cells offers promising targets for drug delivery. The prepared gemcitabine (GB)-loaded PLGA-NPs and sialic acid (Siac)-modified PLGA-NPs exhibited a uniform polydispersity index (PDI) value below 0.3, a particle size under 200 nm, and negative zeta potentials ranging from −17.45 to −21.45 mV. Entrapment efficiency (% EE) and drug loading values exceeded 70% and 8%, respectively. SEM and TEM showed that the particles were uniformly dispersed with a spherical shape. FTIR, XRD, TGA, and DSC analyses indicated the physiochemical stability of the drug within the nanoformulations. Controlled (26.92 to 31.64% within 24 h at pH 7.4) and pH-sensitive (36.80 to 40.25% within 24 h at pH 5.5) GB release were observed for the different formulations of PLGA-NPs. The MTT cytotoxicity assay revealed IC50 values for the GB control, GB-PLGA-NPs, and GB-PLGA-Siac-NPs as 13.65 ± 1.20, 8.14 ± 1.24, and 4.16 ± 1.05 μg/mL, respectively. The Co6-GB-PLGA-Siac-NPs showed significantly higher cellular uptake than that of the Co6-GB control (p < 0.001) and Co6-GB-PLGA-NPs (p < 0.01) respectively. Pharmacokinetic profiles indicated higher AUC values (ng·h/mL) for GB-PLGA-Siac-NPs (8355.07 ± 2006.45) compared to GB-PLGA-NPs (6145.58 ± 969.25) and the GB control (1510.72 ± 81.08), resulting in higher bioavailability of GB-PLGA-Siac-NPs. Biodistribution studies confirmed superior localization of DiD-GB-PLGA-Siac-NPs, indicated by radiant efficiency signal on B[a]P induced lung cancerous tissues relative to DiD-GB-PLGA-NPs after 1 h (p < 0.001), 4 h (p < 0.01), and 12 h (p < 0.001), which could be attributed to their ability to target glycans. In vivo anticancer efficacy in a B[a]P-induced lung cancer mice model depicted that GB-PLGA-Siac-NPs effectively inhibited lung cancer cells and reduced systemic toxicity, as evidenced by the average number of lung cancer cells, body weight values, survival analysis, biochemical parameters associated with organs (such as the liver and kidney), and histopathological analysis. Therefore, GB-loaded Siac-coated PLGA nanoparticles could serve as an efficient vehicle for GB delivery via targeting glycan receptors in lung cancer therapy. © 2025 American Chemical Society.
Design, fabrication, optimization and characterization of memantine-loaded biodegradable PLGA nanoscaffolds for treatment of Alzheimer’s disease
(Institute of Physics, 2022) Varsha Rani; Ruchi Chawla
This study aimed to design and develop nanoscaffolds for the controlled release of memantine by non-solvent-induced phase separation (N-TIPS) method. The development and optimization of nanoscaffolds was performed by Box-Behnken Design in which two independent formulation variables and one independent process variable: poly(lactic-co-glycolic acid) (PLGA) (X 1), Pluronics F-127 (X 2), and rotation speed (X 3) were used. The design provided 15 formulation designs which were prepared to determine the response: percentage porosity (Y 1) and drug loading (Y 2). Polynomial equations were generated and analyzed statistically to establish a relationship between independent and dependent variables and develop an optimal formulation with maximized porosity (%) and drug loading (%). The optimized formulation batch was prepared using 19.18% w/v PLGA, 4.98% w/v Pluronics at 500 rpm rotation speed and exhibited drug loading of 11.66% and porosity of 82.62%. Further, correlation between the independent and dependent variables were established and statistically analyzed by using model generated mathematical regression equations, ANOVA, residual plots, interaction plot, main effect plot, contour plot and response surface designs. The analysis of model showed the significant individual effect of PLGA and significant interactive effect of Pluronics F-127 and rotation speed on drug loading and porosity. Further, its physicochemical characterization, and in-vitro (drug release kinetics, and PAMPA study), ex-vivo (enzyme inhibition assay and pro-inflammatory cytokines study) and in-vivo (neurobehavioral and histological study) studies were performed to evaluate the potential of memantine-loaded nanoscaffolds in the treatment of Alzheimer’s disease (AD). © 2022 IOP Publishing Ltd.
Factorial Design-Based Nanocarrier Mediated Formulation of Efavirenz and Its Characterization
(World Scientific, 2022) Ruchi Chawla; Venkatanaidu Karri; Varsha Rani; Mohini Mishra; Krishan Kumar
Efavirenz (EFV) suffers from poor aqueous solubility which results in low bioavailability of the drug. Nanocarrier-based drug delivery systems offer a suitable alternative for improving the physico-chemical properties of the drug and hence its efficacy. Nanosuspension (NS) of EFV was formulated by solvent-anti solvent precipitation method using PVP K-30 as stabilizer and sodium lauryl sulphate (SLS) as the wetting agent. Multi-level factorial design was applied to select the optimal formulation which was further characterized. The optimal batch exhibited mean particle size of 305nm and polydispersity index (PDI) of 0.345. Solid-state characterization studies of the NS conducted using scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction, and differential scanning calorimetry (DSC) revealed compatibility between the drug and the excipients and modest alteration in the crystallinity of the drug. There was progressive increase in the solubility of the drug when incorporated in NS from 17.39μg/ml to 256μg/ml. Further, drug release studies showed significantly better and controlled drug release pattern in comparison to the free drug due to the presence of nanosized particles in the formulation. © 2022 World Scientific Publishing Company.
Genome-wide identification of nuclear factor -Y (NF–Y) transcription factor family in finger millet reveals structural and functional diversity
(Elsevier Ltd, 2024) Varsha Rani; Vinay Kumar Singh; D.C. Joshi; Rajesh Singh; Dinesh Yadav
The Nuclear Factor Y (NF–Y) is one of the widely explored transcription factors (TFs) family for its potential role in regulating molecular mechanisms related to stress response and developmental processes. Finger millet (Eleusine coracana (L.) Gaertn) is a hardy and stress-tolerant crop where partial efforts have been made to characterize a few transcription factors. However, the NF–Y TF is still poorly explored and not well documented. The present study aims to identify and characterize NF–Y genes of finger millet using a bioinformatics approach. Genome mining revealed 57 EcNF-Y (Eleusine coracana Nuclear Factor-Y) genes in finger millet, comprising 18 NF-YA, 23 NF-YB, and 16 NF-YC genes. The gene organization, conserved motif, cis-regulatory elements, miRNA target sites, and three-dimensional structures of these NF-Ys were analyzed. The nucleotide substitution rate and gene duplication analysis showed the presence of 7 EcNF-YA, 10 EcNF-YB, and 8 EcNF-YC paralogous genes and revealed the possibilities of synonymous substitution and stabilizing selection during evolution. The role of NF-Ys of finger millet in abiotic stress tolerance was evident by the presence of relevant cis-elements such as ABRE (abscisic acid-responsive elements), DRE (dehydration-responsive element), MYB (myeloblastosis) or MYC (myelocytomatosis). Twenty-three isoforms of miR169, mainly targeting a single NF–Y gene, i.e., the EcNF-YA13 gene, were observed. This interaction could be targeted for finger millet improvement against Magnaporthe oryzae (blast fungus). Therefore, by this study, the putative functions related to biotic and abiotic stress tolerance for many of the EcNF-Y genes could be explored in finger millet. © 2024
Identification and characterization of Eco-miR 169-EcNF-YA13 gene regulatory network reveal their role in conferring tolerance to dehydration and salinity stress in finger millet
(Nature Research, 2025) Varsha Rani; Sumi Rana; Mehanathan Muthamilarasan; Dinesh Chandra Joshi; Ramwant Kumar Gupta; Rajesh Kumar Singh; D. L. Yadav
The finger millet (Eleusine coracana (L.) Gaertn) genome, comprised 166 conserved microRNAs (miRNAs) belonging to 39 families and three novel miRNAs. The miR169 is one of the most conserved miRNA families, while Eco_N1 is a species-specific miRNA prevalent in finger millet. Its members regulate the expression of genes encoding the Nuclear Factor-Y subunit A (NF-YA) via transcript cleavage. However, the role of miRNA genes in regulating the expression of NF-YA transcription factors in finger millet needs to be deciphered. The present study characterized 166 conserved and novel miRNAs (Eco_N1, Eco_N2 and Eco_N3). Further, secondary structures were predicted, and the potential miR genes targeting the NF-YA transcription factors regulating abiotic stress tolerance were analysed. Twenty-three Eco-miR169 members and one Eco_N1 miRNA targeting EcNF-YA13 were identified in the finger millet genome. The presence of relevant cis-elements such as ABRE (abscisic acid-responsive elements), DRE (dehydration-responsive element), and MYB (myeloblastosis) indicates that the target of Eco-miR169 might be involved in abiotic stress responses. The tissue-specific RNA-seq transcriptomic expression pattern of Eco-miR169 showed variable fold of expression in seedlings compared to the control. At the same time, the expression of EcNF-YA13 (target genes of Eco-miR169 members and Eco_N1) presented a downregulated trend under salinity and dehydration conditions compared to the control. Tissue-specific RNA-seq followed by expression analysis confirmed the antagonistic effect of Eco-miR genes on EcNF-YA13. In a nutshell, the results of this study could be utilized as a platform for further exploration and characterization of finger millet Eco-miR169-EcNF-YA13gene regulatory network. © The Author(s) 2025.
Intranasal micellar curcumin for the treatment of chronic asthma
(Editions de Sante, 2022) Ruchi Chawla; Bhupendra Sahu; Mohini Mishra; Varsha Rani; Rashmi Singh
Curcumin is a natural phytoconstituent obtained from the rhizomes of Curcuma longa (turmeric) and is known for its diverse anti-oxidant and anti-inflammatory benefits, but its clinical utility is limited by its poor aqueous solubility and rapid metabolism, which ultimately affects its bioavailability. The present study is focused on the formulation of curcumin loaded micellar dispersion for intranasal delivery for the treatment of chronic asthma. Micellar dispersion was prepared by film formation method using poly-(ethylene oxide)-block-distearoyl phosphatidyl-ethanolamine (mPEG5000-DSPE) as lipid surfactant and characterized for its physic-chemical properties. The curcumin micelles were evaluated for their anti-asthmatic action in ovalbumin (OVA)-induced allergic asthma model in male wistar rats against standard drug dexamethasone. The micelles showed mean particle size in the range of 20.03 nm–26.48 nm. The micellar dispersion exhibited negative zeta potential in the range of −26.22 to −25.52 mV. Incorporation of curcumin into micelles helped in enhancing the solubility of curcumin besides providing it protection against degradation. In vitro studies showed sustained relase of curcumin up to 36 h. A 14- fold increase in the bioaviability of the curcumin was measured when administered as micelles. In addition, 4.4- fold higher concentration of drug was measured in the lungs for micellar curcumin. Comparable reduction in the levels of intracellular ROS was observed for i.n. curcumin-micelles (approx.57.6%) and dexamethasone (59.3%). Also, micellar curcumin produced significant supression (p < 0.05) in the release of nitric oxide. Through the present study, we can suggest the potential application of curcumin micelles in the treatment of asthma. © 2021 Elsevier B.V.
“Millet Models” for harnessing nuclear factor-Y transcription factors to engineer stress tolerance in plants: current knowledge and emerging paradigms
(Springer Science and Business Media Deutschland GmbH, 2023) Varsha Rani; D.C. Joshi; Priyanka Joshi; Rajesh Singh; Dinesh Yadav
Main conclusion: The main purpose of this review is to shed light on the role of millet models in imparting climate resilience and nutritional security and to give a concrete perspective on how NF-Y transcription factors can be harnessed for making cereals more stress tolerant. Abstract: Agriculture faces significant challenges from climate change, bargaining, population, elevated food prices, and compromises with nutritional value. These factors have globally compelled scientists, breeders, and nutritionists to think of some options that can combat the food security crisis and malnutrition. To address these challenges, mainstreaming the climate-resilient and nutritionally unparalleled alternative crops like millet is a key strategy. The C4 photosynthetic pathway and adaptation to low-input marginal agricultural systems make millets a powerhouse of important gene and transcription factor families imparting tolerance to various kinds of biotic and abiotic stresses. Among these, the nuclear factor-Y (NF-Y) is one of the prominent transcription factor families that regulate diverse genes imparting stress tolerance. The primary purpose of this article is to shed light on the role of millet models in imparting climate resilience and nutritional security and to give a concrete perspective on how NF-Y transcription factors can be harnessed for making cereals more stress tolerant. Future cropping systems could be more resilient to climate change and nutritional quality if these practices were implemented. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
Molecular docking insights into nuclear factor Y (NF-Y) transcription factor and pyrabactin resistance 1 (PYL) receptor proteins reveal abiotic stress regulation in finger millet
(Elsevier B.V., 2024) Varsha Rani; Vinay Kumar Singh; D.C. Joshi; Rajesh Singh; Dinesh Yadav
Finger Millet (Eleusine coracana - (L.) Gaertn), is an important nutraceutical crop with the potential for imparting food and nutritional security. These plants have a comparatively higher tolerance for several abiotic stresses like drought, salinity, and heat. Several players including Transcription Factor (TF) like Nuclear Factor Y (NF-Y) might be associated with this enhanced level of tolerance. Further, it is unclear how phytohormones like Abscisic acid (ABA) regulate the expression of NF-Y, whether in ABA-dependent or ABA-Independent pathway. The interaction of PYL (Pyrabactin resistance1-like) receptor proteins with Nuclear Factor Y (NF-Y) Transcription Factor in the presence of phytohormones like abscisic acid (ABA) provides one insight related to the enhanced tolerance towards abiotic stresses under ABA-dependent signaling in finger millet crop. A total of three PYL receptors of finger millet designated as EcPYL1, EcPYL5, and EcPYL9 were retrieved in the finger millet genome. These receptors were modeled through the SWISS-MODEL using templates 5gwo and 3wg8 and docked with ABA. The best-docked protein-ligand complex PYL5-ABA (binding energy ΔG = -8.8 kcal mol-1) was found to be most stable at the 50ns MD simulation study. Further protein-protein interaction between PYL5 and NF-YA2/B3/C1 sub-family members showed a good interaction. This clearly indicates the possibility of the NF-Y-PYL module in the ABA transduction pathway, which performs a crucial role in the expression of stress-responsive genes. These studies reveal the intricate relationship between the ABA, PYL receptors of finger millet, and NF-Y transcription factor in regulating the stress-responsive genes and provide an insight into the abiotic stress tolerance mechanisms, which can be targeted for crop improvement. © 2024 The Authors
Nanoparticulate Carriers-Versatile Delivery Systems
(wiley, 2021) Ruchi Chawla; Varsha Rani; Mohini Mishra
Recently, significant efforts have been made on the development of biocompatible and biodegradable nanoparticulate carrier systems like polymeric nanoparticles, solid lipid nanoparticles, liposomes, etc. for delivery of drugs because of their potential benefits such as enhanced drug permeability, cell adhesion, cytotoxicity and cell attachment, improved bioavailability, reduced systemic toxicity, reduced local irritation, predictable gastric emptying, and improved pharmacokinetic behavior in comparison to conventional (monolithic) formulations. The sub-cellular and sub-micron size of nanoparticles facilitates trafficking and sorting into deep tissues through capillaries or fenestrations and also into different intracellular compartments such as macrophages, dendritic cells, etc. The delivery to target site and tissues can be controlled by engineering the polymer/lipid characteristics for their molecular weight, size, aqueous solubility, etc. The nanoparticulate carriers can be targeted both actively and passively. Conjugation with receptor-specific ligands results in active targeting with potential delivery of drugs to the target tissue. Autophagy is an example of passive targeting mechanism in which circulating cytoplasmic cells or organelles engulf the drug carriers (like in tuberculosis). Besides use of nanocarriers for delivery of drugs, they can also be used for delivery of DNA in gene therapy and administer proteins, peptides, and genes via peroral route. Thus, the nanoparticulate drug carriers have versatile applications in drug delivery and treatment of diseases. © 2021 Scrivener Publishing LLC.
Negatively charged liposomes of sertraline hydrochloride: Formulation, characterization and pharmacokinetic studies
(Editions de Sante, 2020) Tejpratap Chauhan; Varsha Rani; Bhupendra Sahu; Adity Sharma; Subhash Chand Kheruka; Sanjay Gambhir; Veeresh Dube; Lalit M. Aggarwal; Ruchi Chawla
The present study was carried out with an objective to study the extent of delivery of negatively charged liposomes of sertraline hydrochloride to brain via intravenous route for treatment of depressive –like symptoms. Liposomes of sertraline hydrochloride were formulated by film hydration technique using cholesterol, hydrogenated soya phosphatidylcholine-L-α-phosphatidylcholine, and distearoyl phosphatidyl glycerol sodium. Uniform sized vesicles with porous surface morphology with vesicle size of 151.59 nm were prepared. Radioactive imaging performed using 99mTcO4 showed ~5% of uptake of labelled liposomes in brain within 2 h of administration. On administration of liposomes and free drug suspension, approximately, 205.06 ng/ml and 87.18 ng/ml of sertraline were estimated in brain at 36 h. The liposomes can be transported by transcelluar transport which includes phagocytosis and the use of phosphatidylcholine enhances macrophage internalization and delivery to brain. The study indicated significantly higher concentration of sertraline in brain after 36 h, on administration of liposomes as compared to free sertraline suspension. © 2020 Elsevier B.V.
Regulation of Transcription Factors in Abscisic Acid-Mediated Signaling Under Abiotic Stresses
(CRC Press, 2025) Varsha Rani; Ramwant Kumar Gupta; Manoj Kumar Yadav; Rajesh Kumar Singh; D. L. Yadav
Abiotic stresses like drought, salinity, heat, cold, and osmotic pressure have adverse effects on a plant’s growth and development. The stress response in plants is mediated by several signaling pathways, mediated by the intervention of different phytohormones. The phytohormones that are linked to biotic and abiotic stresses are salicylic acid, jasmonic acid, auxin, abscisic acid, and gibberellin. The role of auxins, cytokinins, ethylene, gibberellins, brassinosteroids, and jasmonic acid has been studied in the context of developing abiotic stress-tolerant plants by metabolic engineering. The phytohormone abscisic acid (ABA) is a key hormone known to be involved in the regulation of abiotic stresses. ABA regulates osmolytes and detoxifies reactive oxygen species (ROS) as part of stress signaling pathways. During abiotic stress, signaling and plant response, phytohormones induce the expression of the transcription factors that regulate stress-responsive genes. Over the past few years, several transcription factors (TF) have been identified and are essential for regulating plant responses to these stresses. Activation of these TF can be ABA-dependent or independent in nature. In plants, several transcription factors like NAC, NAM, NF-Y, WRKY, bZIP, MYC, MYB, NAM, DREB, AP2, YABBY, Zinc finger, and their cis-acting elements regulate abiotic stresses in association with different plant hormones. This chapter highlights the ABA-dependent and independent transcription factors responsible for abiotic stress tolerance and their regulatory mechanisms. © 2026 selection and editorial matter, Kapil Gupta, Keshawanand Tripathi, Amit Joshi, and Dinesh Yadav.