Browsing by Author "Ajai Kumar Pandey"

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Comparative evaluation of two intranasal forms of Curcumin: Quantitation and impact on mouse model of asthma
(Elsevier B.V., 2023) Payal Singh; Ruchi Chawla; Ajai Kumar Pandey; J.K. Mishra; Rashmi Singh
Aim of the study: Present study aimed to investigate impact of two different intranasal forms of curcumin on mouse model of asthma and detection of its absorption after different time points of administration. Since the systemic bioavailability of curcumin is very low, therefore, intranasal route of administration has been explored here where systemic absorption of two intranasal forms of curcumin was evaluated. Materials and methods: To explore the possibilities of its absorption and role in amelioration of asthma, two intranasal forms of curcumin, nasal drop and aerosol were administered to control and asthmatic mice. Blood plasma and lungs were collected at different time points of curcumin administration. Separation was done by using isocratic reversed phase high performance liquid chromatography (HPLC). Airway inflammation and oxidative stress parameters like SOD, Catalase, ROS, lipid peroxidation, and total inflammatory cell recruitments were analyzed to study efficacy of two intranasal forms of curcumin. Results: Maximum absorption was noted at 3 hrs of different intranasal forms of curcumin, administration, i.e., nasal drop (1.93 ± 0.050 plasma, 2.87 ± 0.26 in lungs) and aerosol form of curcumin where better absorption was noted in aerosol form as compared to nasal drop (Lungs 3.08 ± 0.12 aerosol, 2.05 ± 0.020 nasal drop) at 1 h. Both, curcumin aerosol and nasal drops were effective in ameliorating oxidative stress (p < 0.05) associated with asthma in mice model. The present study may pave the way towards the development of intranasal curcumin as complementary medication because of its better absorption in plasma and lungs. © 2023 The Author(s)
Damage mechanisms of bisphenols on the quality of mammalian oocytes
(Oxford University Press, 2025) Ashutosh N. Pandey; Pramod Kumar Yadav; Karuppanan V. Premkumar; Meenakshi Tiwari; Mano Mohan Antony; Ajai Kumar Pandey; Shail K. Chaube
The extensive use of bisphenols in the plastics industry globally is a major growing concern for human health. Bisphenol compounds are easily leached out from plastic containers to food, beverages, and drinking water and contaminate the natural environment. Daily exposure of bisphenol compounds increases their load and impairs various organs, including the reproductive system. Bisphenol compounds directly or indirectly affect ovarian functions, such as folliculogenesis, steroidogenesis, oogenesis, and thereby oocyte quality. Bisphenol A (BPA) and its structural analogues act as endocrine disruptors and induce generation of reactive oxygen species (ROS) within the ovary. Excess levels of ROS induce death pathways in follicular steroidogenic cells and affect ovarian steroidogenesis. The reduced level of estradiol-17β impairs follicular growth and development that reduces the number and quality of oocytes. In addition, excess levels of ROS in follicular fluid trigger meiotic instability, which further deteriorates oocyte quality. The high level of ROS generates oxidative stress that triggers various death pathways in germ cells as well as in oocytes, induces follicular atresia, and depletes ovarian reserve. Although growing evidence indicates the destructive effects of bisphenol compounds at the level of ovary, potential effects and underlying mechanisms that deteriorate oocyte quality remain poorly understood. Therefore, this review summarizes the mechanisms by which bisphenols cause damage to the ovary, impair oocyte quality, and affect women's fertility. © The Author(s) 2024. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved.
In vivo, in vitro, and in silico approaches in the detailed study of di-butyl phthalate (DBP), a plasticizer-induced lung fibrosis via Nrf-2/Keap-1/HO-1 pathway and its regulation
(Academic Press Inc., 2025) Payal Singh; Sneha Kumari; Harshika Chakravortty; Ajai Kumar Pandey; Debabrata Dash; Rashmi N. Singh
The alveolar epithelium is a crucial barrier against external threats, yet it becomes a key player in initiating pulmonary fibrosis when compromised. Despite its importance, the intricate relationship between, DBP exposure and alveolar epithelial cell injury ensuing pro-fibrotic effects remains poorly understood. Phthalates, ubiquitous in nature, pose a significant risk to lung health upon inhalation, acting as immune triggers that cause airway inflammation and epithelial damage. We aimed to investigate the impact of intranasal administration of Di-butyl Phthalate (DBP) inhalation, and its probable effects on normal and asthmatic lungs. DBP was administered via intranasal route in normal and OVA-induced asthmatic mice. DBP exposure enhanced oxidative stress and inflammatory parameters, leading to exacerbated asthmatic response and oxidative lung damage. Enhanced accumulation of immune cells, bronchial thickening, and collagen deposition was noted in histopathological investigations of DBP-exposed lung sections. Curcumin, a plant-derived molecule, significantly mitigated DBP-exposed asthma exacerbations by suppressing NF-κB expression and enhancing NRF2 levels via the Nrf-2/Keap-1/HO-1 signaling pathway. FACS analysis revealed increased CD11b+ cells (32 %) in asthmatic mice which were reduced in the curcumin pre-treatment group (10.5 %). Enhanced epithelial to mesenchymal transition (EMT) was noted in mice lungs and A549 cells where E-cadherin expression was reduced as compared to Vimentin, and α-SMA. Apart from aggravated airway inflammation, DBP exposure damages healthy lungs also. MMP-9/TIMP-1 ratios and collagen-1 levels were restored which were enhanced after DBP exposure. Moreover, antioxidant enzyme levels such as NQO-1, HO-1, and Catalase were significantly enhanced (p < 0.01) and comparable to dexamethasone, a conventional corticosteroid. Notably, both dexamethasone and curcumin treatments effectively regulated the stimulation and accumulation of Nrf-2 in the nucleus, promoting antioxidant production and offering potential therapeutic benefits in mitigating pulmonary fibrosis. OVA and DBP alone caused DNA damage in the lung cells where increased percentage of damaged DNA movement in the tail, tail length, tail moment, and olive tail moment indicated severe damage in the DBP and OVA combined exposure strategies. Dexamethasone and Curcumin treatments reduced the extent of the DNA damage indicating anti-inflammatory and ant-oxidative potentials. Moreover, in silico studies are supportive of therapeutic potential of Curcumin and Dexamethasone in DBP-induced lung inflammation and fibrosis. © 2024 Elsevier Inc.
Model-based ensembles: Lessons learned from retrospective analysis of COVID-19 infection forecasts across 10 countries
(Elsevier B.V., 2022) Martin Drews; Pavan Kumar; Ram Kumar Singh; Manuel De La Sen; Sati Shankar Singh; Ajai Kumar Pandey; Manoj Kumar; Meenu Rani; Prashant Kumar Srivastava
Mathematical models of different types and data intensities are highly used by researchers, epidemiologists, and national authorities to explore the inherently unpredictable progression of COVID-19, including the effects of different non-pharmaceutical interventions. Regardless of model complexity, forecasts of future COVID-19 infections, deaths and hospitalization are associated with large uncertainties, and critically depend on the quality of the training data, and in particular how well the recorded national or regional numbers of infections, deaths and recoveries reflect the the actual situation. In turn, this depends on, e.g., local test and abatement strategies, treatment capacities and available technologies. Other influencing factors including temperature and humidity, which are suggested by several authors to affect the spread of COVID-19 in some countries, are generally only considered by the most complex models and further serve to inflate the uncertainty. Here we use comparative and retrospective analyses to illuminate the aggregated effect of these systematic biases on ensemble-based model forecasts. We compare the actual progression of active infections across ten of the most affected countries in the world until late November 2020 with “re-forecasts” produced by two of the most commonly used model types: (i) a compartment-type, susceptible–infected–removed (SIR) model; and (ii) a statistical (Holt-Winters) time series model. We specifically examine the sensitivity of the model parameters, estimated systematically from different subsets of the data and thereby different time windows, to illustrate the associated implications for short- to medium-term forecasting and for probabilistic projections based on (single) model ensembles as inspired by, e.g., weather forecasting and climate research. Our findings portray considerable variations in forecasting skill in between the ten countries and demonstrate that individual model predictions are highly sensitive to parameter assumptions. Significant skill is generally only confirmed for short-term forecasts (up to a few weeks) with some variation across locations and periods. © 2021 The Authors
Nitrogen dioxide as proxy indicator of air pollution from fossil fuel burning in New Delhi during lockdown phases of COVID-19 pandemic period: impact on weather as revealed by Sentinel-5 precursor (5p) spectrometer sensor
(Springer Science and Business Media B.V., 2024) Pavan Kumar; Aishwarya; Prashant Kumar Srivastava; Manish Kumar Pandey; Akash Anand; Jayanta Kumar Biswas; Martin Drews; Manmohan Dobriyal; Ram Kumar Singh; Manuel De la Sen; Sati Shankar Singh; Ajai Kumar Pandey; Manoj Kumar; Meenu Rani
There has been a long-lasting impact of the lockdown imposed due to COVID-19 on several fronts. One such front is climate which has seen several implications. The consequences of climate change owing to this lockdown need to be explored taking into consideration various climatic indicators. Further impact on a local and global level would help the policymakers in drafting effective rules for handling challenges of climate change. For in-depth understanding, a temporal study is being conducted in a phased manner in the New Delhi region taking NO2 concentration and utilizing statistical methods to elaborate the quality of air during the lockdown and compared with a pre-lockdown period. In situ mean values of the NO2 concentration were taken for four different dates, viz. 4th February, 4th March, 4th April, and 25th April 2020. These concentrations were then compared with the Sentinel (5p) data across 36 locations in New Delhi which are found to be promising. The results indicated that the air quality has been improved maximum in Eastern Delhi and the NO2 concentrations were reduced by one-fourth than the pre-lockdown period, and thus, reduced activities due to lockdown have had a significant impact. The result also indicates the preciseness of Sentinel (5p) for NO2 concentrations. © The Author(s), under exclusive licence to Springer Nature B.V. 2023.
Shilajit Mitigates Diabetes-Induced Testicular Dysfunction in Mice: A Modulation in Insulin Sensitivity, Germ Cell-Junctional Dynamics, and Oxido-Apoptotic Status
(Wiley-VCH Verlag, 2025) Arti Rajpoot; Ajai Kumar Pandey; V. K. Roy; Raghav Kumar Mishra
Diabetes is a chronic metabolic condition that causes testicular damage by high oxidative stress, rendering 35% of afflicted people infertile. Shilajit is a traditional Indian medicine known for its antioxidant, antidiabetic, and aphrodisiac properties. However, its effectiveness on diabetes-induced testicular dysfunction remains unclear. Therefore, the current investigation aimed to determine whether Shilajit could restore testicular functions in diabetic mice. Two days postpartum male Parkes mice received a single intraperitoneal injection of streptozotocin (STZ) (90 mg/kg BW) to induce diabetes. Three months postinjection, the effects of daily Shilajit (100 and 200 mg/kg BW) treatment were evaluated for one spermatogenic cycle in adult diabetic mice, using Empagliflozin (10 mg/kg BW) as a positive control. In STZ-induced diabetic mice, testicular functions were compromised due to disruptions in testosterone biosynthesis, changes in germ-cell ratios, and increased oxidative stress and apoptosis. Shilajit restored glycemic status in diabetic mice by significantly decreasing serum glucose, insulin level, and homeostasis model assessment of insulin resistance (HOMA-IR) value while increasing insulin sensitivity. These effects were comparable to those observed with conventional antidiabetic medication Empagliflozin. Further, Shilajit stimulates steroidogenesis and germ cell dynamics of diabetic mice by increasing the activity of StAR, 3β-HSD, and 17β-HSD enzymes and 1C:2C, 4C:S-Ph, and 1C:4C germ cell ratios, respectively. Shilajit also improves blood–testis barrier (BTB) functioning by increasing expression of ZO-1, Connexin-43, N-Cadherin, and β-catenin as well as oxidative status and apoptosis by modulating NF-E2–related factor 2 (Nrf-2)/heme oxygenase 1 (HO-1) signaling and Bax/Bcl-2 ratio. Subsequently, Shilajit improved the histoarchitecture of testis and epididymis in diabetic mice and recovered both qualitative and quantitative sperm parameters, as seen by higher percentages of sperm motility, viability, and normal sperm morphology as well as increased sperm numbers in cauda epididymis. In summary, Shilajit restores glycemic status, increases insulin sensitivity, stimulates steroidogenesis, and improves testicular functions through Sertoli cell and Nrf-2/HO-1 signaling in STZ-induced diabetic mice. © © 2025 Arti Rajpoot et al. Andrologia published by John Wiley & Sons Ltd.
Short-term statistical forecasts of COVID-19 infections in India
(Institute of Electrical and Electronics Engineers Inc., 2020) Ram Kumar Singh; Martin Drews; Manuel de la Sen; Manoj Kumar; Sati Shankar Singh; Ajai Kumar Pandey; Prashant Kumar Srivastava; Manmohan Dobriyal; Meenu Rani; Preeti Kumari; Pavan Kumar
COVID-19 cases in India have been steadily increasing since January 30, 2020 and have led to a government-imposed lockdown across the country to curtail community transmission with significant impacts on societal systems. Forecasts using mathematical-epidemiological models have played and continue to play an important role in assessing the probability of COVID-19 infection under specific conditions and are urgently needed to prepare health systems for coping with this pandemic. In many instances, however, access to dedicated and updated information, in particular at regional administrative levels, is surprisingly scarce considering its evident importance and provides a hindrance for the implementation of sustainable coping strategies. Here we demonstrate the performance of an easily transferable statistical model based on the classic Holt-Winters method as means of providing COVID-19 forecasts for India at different administrative levels. Based on daily time series of accumulated infections, active infections and deaths, we use our statistical model to provide 48-days forecasts (28 September to 15 November 2020) of these quantities in India, assuming little or no change in national coping strategies. Using these results alongside a complementary SIR model, we find that one-third of the Indian population could eventually be infected by COVID-19, and that a complete recovery from COVID-19 will happen only after an estimated 450 days from January 2020. Further, our SIR model suggests that the pandemic is likely to peak in India during the first week of November 2020. © This work is licensed under a Creative Commons Attribution 4.0 License. For more information, see https://creativecommons.org/licenses/by/4.0/