Browsing by Author "Dubey, Uma S."

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Aberrant expression of col14a1, celrs3, and cthrc1 in breast cancer сells
(Experimental oncology, 2023) Dubey, Uma S.
Collagens, which are the major components of the extracellular matrix involved in the regulation of tumor microenvironment, could be differentially expressed in breast cancer (BC) with different transcriptome profiling. Aim: To analyze the transcript level expression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, COL14A1, CTHRC1, and CELRS3 genes and the clinical relevance of their differential expression in BC. Materials and Methods: The transcript level expression of the genes was analyzed using the quantitative real-time PCR (qPCR) in tumor tissue of 60 BC patients. Results: Overexpression of COL1A1, COL5A1, COL10A1, COL11A1, COL12A1, CTHRC, and CELRS3 anddown-regulated expression of COL14A1 were observed. COL14A1 down-regulation was associated with aggressive, basal, and Her-2/neu BC subtypes (p = 0.031). Overexpression of CELSR3 was found to be associated with the older age of the patients (> 55 years, p = 0.049). Further analysis with the TCGA BC data set has shown a concordance in the differential expression of the above genes. Furthermore, overexpression of CTHRC1 was associated with poor overall survival (OS), particularly with poor prognosis (p = 0.00042) for the luminal BC subtype. On the other hand, CELSR3 overexpression was associated with mucinous tumors and poor prognosis in post-menopausal women. In silicotarget prediction identified several BC-associated miRNAs and members of miR-154, -515, and -10 families to perform a likely regulatory role in the above ECM genes. Conclusion: The present study shows that the expression of COL14A1 and CTHRC1 may serve as potential biological markers for the detection of basal BC and the prognosis of survival for patients with the luminal subtype of BC.
Bifurcation and chaotic dynamics in a spatiotemporal epidemic model with delayed optimal control, stochastic process, and sensitivity analysis
(AIP, 2025-03) Dubey, Uma S.; Dubey, Balram
This study introduces an epidemic model with a Beddington–DeAngelis-type incidence rate and Holling type II treatment rate. The Bedding- ton–DeAngelis incidence rate is used to evaluate the effectiveness of inhibitory measures implemented by susceptible and infected individuals. Moreover, the choice of Holling type II treatment rate in our model aims to assess the impact of limited treatment facilities in the context of disease outbreaks. First, the well-posed nature of the model is analyzed, and then, we further investigated the local and global stability analysis along with bifurcation of co-dimensions 1 (transcritical, Hopf, saddle-node) and 2 (Bogdanov–Takens, generalized Hopf) for the system. Moreover, we incorporate a time-delayed model to investigate the effect of incubation delay on disease transmission. We provide a rigorous demonstration of the existence of chaos and establish the conditions that lead to chaotic dynamics and chaos control. Additionally, sensitivity analysis is performed using partial rank correlation coefficient and extended Fourier amplitude sensitivity test methods. Furthermore, we delve into optimal control strategies using Pontryagin’s maximum principle and assess the influence of delays in state and control parame- ters on model dynamics. Again, a stochastic epidemic model is formulated and analyzed using a continuous-time Markov chain model for infectious propagation. Analytical estimation of the likelihood of disease extinction and the occurrence of an epidemic is conducted using the branching process approximation. The spatial system presents a comprehensive stability analysis and yielding criteria for Turing instability. Moreover, we have generated the noise-induced pattern to assess the effect of white noise in the populations. Additionally, a case study has been conducted to estimate the model parameters, utilizing COVID-19 data from Poland and HIV/AIDS data from India. Finally, all theo- retical results are validated through numerical simulations. This article extensively explores various modeling techniques, like deterministic, stochastic, statistical, pattern formation(noise-induced), model fitting, and other modeling perspectives, highlighting the significance of the inhibitory effects exerted by susceptible and infected populations.
Calcium chloride linked camel milk deried casein nanoparticles for the delivery of sorafenib in hepatocarcinoma cells
(TSP, 2021) Dubey, Uma S.
Sorafenib, a multikinase inhibitor used for the treatment of hepatocellular carcinoma, is limited by its low oral bioavailability. To overcome this drawback, we have developed novel camel milk casein-derived nanoparticles as a drug delivery system. Camel milk casein is not only biocompatible on oral administration but is actually a dietary protein of pharmaceutical relevance. Casein is used because of its amphiphilic nature, self-assembling property, ability to show sustained release, and capability of encapsulating both hydrophilic and hydrophobic drugs. In this study, camel milk casein nanoparticles loaded with sorafenib were developed and characterized. Characterization of casein nanoparticles was done by dynamic light scattering (DLS), zeta potential analysis, scanning light microscopy (SEM), and FTIR. The drug content in nanoparticle and drug-protein binding studies were conducted by UV spectroscopy. The cytotoxicity and cellular uptake efficiency studies were performed in HepG2 cell lines. It was observed that the cytotoxic effect of sorafenib loaded camel milk casein nanoparticles was more than free sorafenib in HepG2 cells. This work suggests camel milk casein as a suitable drug delivery molecule for sorafenib. In the future, it may also be used in enhancing the efficacy and specific distribution of other water-insoluble anticancer drugs.
Calcium chloride linked camel milk derived casein nanoparticles for the delivery of sorafenib in hepatocarcinoma cells
(Tech Science Press, 2021-09) Dubey, Uma S.
Sorafenib, a multikinase inhibitor used for the treatment of hepatocellular carcinoma, is limited by its low oral bioavailability. To overcome this drawback, we have developed novel camel milk casein-derived nanoparticles as a drug delivery system. Camel milk casein is not only biocompatible on oral administration but is actually a dietary protein of pharmaceutical relevance. Casein is used because of its amphiphilic nature, self-assembling property, ability to show sustained release, and capability of encapsulating both hydrophilic and hydrophobic drugs. In this study, camel milk casein nanoparticles loaded with sorafenib were developed and characterized. Characterization of casein nanoparticles was done by dynamic light scattering (DLS), zeta potential analysis, scanning light microscopy (SEM), and FTIR. The drug content in nanoparticle and drug-protein binding studies were conducted by UV spectroscopy. The cytotoxicity and cellular uptake efficiency studies were performed in HepG2 cell lines. It was observed that the cytotoxic effect of sorafenib loaded camel milk casein nanoparticles was more than free sorafenib in HepG2 cells. This work suggests camel milk casein as a suitable drug delivery molecule for sorafenib. In the future, it may also be used in enhancing the efficacy and specific distribution of other water-insoluble anticancer drugs.
Camel Milk α-lactalbumin As A Potential Anticancer Molecule: A Bioinformatics Analysis
(Research Journal of Pharmaceutical, Biological and Chemical Sciences, 2020) Dubey, Uma S.
α-lactalbumin-Oleic acid complex derived from milk is well known to have anti-cancer properties in many diverse mammalian species including humans, goats and cows. The objective of the current study is to see if α-lactalbumin present in camel’s milk too can serve as a potential anti-cancer molecule in its complex form. A comparative evaluation of α-lactalbumin structure among four mammalian species, viz, Camelusferus, Bostaurus, Homo sapiens, and Capra hircus has been made between the nucleotide sequences and structures of protein. Furthermore, the physico-chemical properties, amino acid composition, position of disulfide bridge formation in these species has been compared. The outcome of the present study suggests the presence of an anti-cancer property in the α-lactalbumin of camel, as has been experimentally observed in the other three species.
Counteracting Microbes
(‎ Nova Science Publishers, 2013) Dubey, Uma S.
Dynamics of an SIR Model with Nonlinear Incidence and Treatment Rate
(AAM, 2015-12) Dubey, Uma S.; Dubey, Balram
In this paper, global dynamics of an SIR model are investigated in which the incidence rate is being considered as Beddington-DeAngelis type and the treatment rate as Holling type II (saturated). Analytical study of the model shows that the model has two equilibrium points (diseasefree equilibrium (DFE) and endemic equilibrium (EE)). The disease-free equilibrium (DFE) is locally asymptotically stable when reproduction number is less than one. Some conditions on the model parameters are obtained to show the existence as well as nonexistence of limit cycle. Some sufficient conditions for global stability of the endemic equilibrium using Lyapunov function are obtained. The existence of Hopf bifurcation of model is investigated by using Andronov-Hopf bifurcation theorem. Further, numerical simulations are done to exemplify the analytical studies.
Effect of elevated temperature on natural killer cell and antibody-dependent cellular eytoboxieity
(HALOCYNTHIA ASSOCIATION, 1998) Dubey, Uma S.
Several studies have shown a direct correlation between temperature and immune response. The effect of elevated temperature on cytotoxic effector functions is not well known. In the present study we have investigated the effect of elevated temperatures (38.5 and 40 °C) on cytotoxicity of lymphokine-activated killer cells (LAK), monocyte cytotoxicity, cytotoxic T lymphocytes (CTL) and tumor necrosis factor (TNF)-mediated cytotoxicity, and compared them with results at 37°C. LAK cell cytotoxicity was inhibited significantly at 40°C (p < 0.01) and there was no marked difference at 38.5°C (p = 0.17) as compared to 37 °C when natural killer (NK)-sensitive K562 cells were used as target. When NK-resistant Raji cells were used as a target, cytotoxicity was inhibited at 40°C (p = 0.33). Monocyte cytotoxicity was enhanced at 40°C (p= 0.19) as well as at 38.5°C (p = 0.38) as compared to 37°C but differences
Epidemiology of breast cancer in Indian women
(Wiley, 2017-02-09) Dubey, Uma S.
Breast cancer has ranked number one cancer among Indian females with age adjusted rate as high as 25.8 per 100,000 women and mortality 12.7 per 100,000 women. Data reports from various latest national cancer registries were compared for incidence, mortality rates. The age adjusted incidence rate of carcinoma of the breast was found as high as 41 per 100,000 women for Delhi, followed by Chennai (37.9), Bangalore (34.4) and Thiruvananthapuram District (33.7). A statistically significant increase in age adjusted rate over time (1982–2014) in all the PBCRs namely Bangalore (annual percentage change: 2.84%), Barshi (1.87%), Bhopal (2.00%), Chennai (2.44%), Delhi (1.44%) and Mumbai (1.42%) was observed. Mortality-to-incidence ratio was found to be as high as 66 in rural registries whereas as low as 8 in urban registries. Besides this young age has been found as a major risk factor for breast cancer in Indian women. Breast cancer projection for India during time periods 2020 suggests the number to go as high as 1797900. Better health awareness and availability of breast cancer screening programmes and treatment facilities would cause a favorable and positive clinical picture in the country.
Evaluation of the cytotoxic activity of sorafenib-loaded camel milk casein nanoparticles against hepatocarcinoma cells
(Wiley, 2024-03) Dubey, Uma S.
Sorafenib, a multikinase inhibitor is used to treat hepatocellular and renal carcinoma. However, a low solubility impedes its bioavailability and thus, effectiveness. This study aims to enhance its effectiveness by using novel camel milk casein nanoparticles as a delivery system. This study evaluates the cytotoxicity of sorafenib encapsulated in camel milk casein nanoparticles against human hepatocarcinoma cells (HepG2 cells) in vitro. Optimal drug loaded nanoparticles were stable for 1 month, had encapsulation efficiency of 96%, exhibited a particle size of 230 nm, zeta potential of −14.4 and poly disparity index of 0.261. Treatment with it led to cell morphology and DNA fragmentation as a characteristic of apoptosis. Flow cytometry showed G1 phase arrest of cell cycle and 26% increased apoptotic cells population upon treatment as compared to control. Sorafenib-loaded casein nanoparticles showed 6-fold increased ROS production in HepG2 cells as compared to 4-fold increase shown by the free drug. Gene and protein expression studies done by qPCR and western blotting depicted upregulation of tumor suppressor gene p53, pro-apoptotic Bax, and caspase-3 along with downregulated anti-apoptotic Bcl-2 gene and protein expression which further emphasized death by apoptosis. It is concluded regarding the feasibility of these casein nanoparticles as a delivery system with enhanced therapeutic outcomes against hepatocellular carcinoma cells.
Evolution Of Classification Of Bladder (Urothelial) Cancer Bladder Cancer Classification
(NICPD, 2015) Dubey, Uma S.
The classification of bladder tumors has undergone a change over the years but still has not achieved success in predicting the behavior. The correct cellular classification of a tumor helps initiate appropriate treatment. Recently functional, genomic and proteomic data have been of help in aiding prognosis and modifying the treatment in many cancers. However, this data is not routinely integrated into the classification, and treatment protocols in bladder carcinoma hinge on grade and depth of invasion. An in depth understanding of the implication of grade, stage, molecular features on survival is necessary to understand the behavior of the tumor. The classification of Urothelial cancer has undergone a lot of change in terminology over the past century but we have still not identified markers (both morphologic and molecular) for preventing recurrences. It is believed that the treatment protocols should be based on a combination of these and we still have to conduct large-scale follow-up studies to identify these parameters. We present here the changes in bladder cancer classifications over the past century and the implications thereof in this review
Gene deleted live attenuated Leishmania vaccine candidates against visceral leishmaniasis elicit pro-inflammatory cytokines response in human PBMCs
(Nature, 2016) Dubey, Uma S.
Currently no effective vaccine is available for human visceral leishmaniasis(VL) caused by Leishmania donovani. Previously, we showed that centrin1 and p27gene deleted live attenuated Leishmania parasites (LdCen1−/− and Ldp27−/−) are safe, immunogenic and protective in animal models. Here, to assess the correlates of protection, we evaluated immune responses induced by LdCen1−/− and Ldp27−/− in human blood samples obtained from healthy, healed VL (HVL), post kala-azar dermal leishmaniasis(PKDL) and VL subjects. Both parasites infected human macrophages, as effectively as the wild type parasites. Further, LdCen1−/− and Ldp27−/− strongly stimulated production of pro-inflammatory cytokines including, IL-12, IFN-γ, TNF-α, IL-2, IL-6 and IL-17 in the PBMCs obtained from individuals with a prior exposure to Leishmania (HVL and PKDL). There was no significant stimulation of anti-inflammatory cytokines (IL-4 and IL-10). Induction of Th1 biased immune responses was supported by a remarkable increase in IFN-γ secreting CD4+ and CD8+ T cells and IL-17 secreting CD4+ cells in PBMCs from HVL cases with no increase in IL-10 secreting T cells. Hence, LdCen1−/− and Ldp27−/− are promising as live vaccine candidates against VL since they elicit strong protective immune response in human PBMCs from HVL, similar to the wild type parasite infection, mimicking a naturally acquired protection following cure.
Impact of chemo-immunotherapy on tumour-immune interactions: a non-autonomous model of tumor necrosis factor and T cell dynamics
(2025) Dubey, Uma S.; Dubey, Balram
This study explores the interaction between cancer cells, helper T cells, cytotoxic T cells, and tumour necrosis factors in chemotherapy and immunotherapy treatment in the microenvironment [1]. The goal is to analyze the connection of helper and cytotoxic T-cell levels with the anti-tumour immune response and the impact of various dosing regimens when combined with immunotherapy and chemotherapy. These protocols aim to shorten the interval between treatment cycles from three to two weeks or less to prevent tumour regrowth and maximize its cell elimination by treatment. Motivated by clinical trials, we thoroughly compare procedures involving two medications supplied sequentially or simultaneously in a non-autonomous system. We discussed the positivity and boundedness of the model. Further, we analyze the biologically valid equilibria and investigate their local stability properties, examining transcritical, saddle-node, Hopf, and Bogdanov-Takens bifurcations numerically and analytically [2]. Furthermore, direction and stability conditions for periodic solutions are determined.
The impact of radio-chemotherapy on tumour cells interaction with optimal control and sensitivity analysis
(Elsevier, 2024-03) Dubey, Balram; Dubey, Uma S.
Oncologists and applied mathematicians are interested in understanding the dynamics of cancer-immune interactions, mainly due to the unpredictable nature of tumour cell proliferation. In this regard, mathematical modelling offers a promising approach to comprehend this potentially harmful aspect of cancer biology. This paper presents a novel dynamical model that incorporates the interactions between tumour cells, healthy tissue cells, and immune-stimulated cells when subjected to simultaneous chemotherapy and radiotherapy for treatment. We analysed the equilibria and investigated their local stability behaviour. We also study transcritical, saddle–node, and Hopf bifurcations analytically and numerically. We derive the stability and direction conditions for periodic solutions. We identify conditions that lead to chaotic dynamics and rigorously demonstrate the existence of chaos. Furthermore, we formulated an optimal control problem that describes the dynamics of tumour-immune interactions, considering treatments such as radiotherapy and chemotherapy as control parameters. Our goal is to utilize optimal control theory to reduce the cost of radiotherapy and chemotherapy, minimize the harmful effects of medications on the body, and mitigate the burden of cancer cells by maintaining a sufficient population of healthy cells. Cost-effectiveness analysis is employed to identify the most economical strategy for reducing the disease burden. Additionally, we conduct a Latin hypercube sampling-based uncertainty analysis to observe the impact of parameter uncertainties on tumour growth, followed by a sensitivity analysis. Numerical simulations are presented to elucidate how dynamic behaviour of model is influenced by changes in system parameters. The numerical results validate the analytical findings and illustrate that a multi-therapeutic treatment plan can effectively reduce tumour burden within a given time frame of therapeutic intervention.
The impact of social media advertisements and treatments on the dynamics of infectious diseases with optimal control strategies
(Elsevier, 2024-05) Dubey, Uma S.; Dubey, Balram
The dissemination of public health information through television and social media posts is essential for informing the public about the transmission of contagious diseases, which is crucial in preventing the spread of various infectious diseases. In this paper, we propose a non-linear mathematical model to assess the effect of advertisements through social media in creating awareness and limiting treatment on spreading infectious diseases. These initiatives may alter population behaviour and divide the susceptible population into subgroups. In addition, to comprehend these dynamics better, we use half-saturation constant rates for media coverage and treatment. The model’s well-posedness and feasibility are evaluated. The possible biological equilibrium points are calculated. Local and global stability are carried out. The objective of our study is to produce the model’s bifurcation. Transcritical, Saddle–node, Hopf bifurcation of codimension 1 and Cusp, Generalized-Hopf (Bautin), and Bogdanov–Takens (BT) bifurcation of codimension 2 are studied for this purpose. Due to the limited medical resources and supply efficiency, the model exhibits backward bifurcation, resulting in bistability. Moreover, the occurrence condition for stability and direction of Hopf bifurcation is discussed. This model study demonstrates that the system is significantly influenced by the pace with which awareness programmes are implemented and that raising this value above a threshold may result in continuous oscillation. Sensitivity analysis employs the normalized forward sensitivity index of the basic reproduction number to provide a comprehensive understanding of the effect of various parameters on accelerating and limiting disease spread. Further, the minimum possible cost is determined by formulating an optimal control system based on sensitivity analysis and applying Pontryagin’s maximum principle. Methods of cost-effectiveness, such as ACER and ICER, are used to determine the most cost-effective control intervention strategy among all the strategies. Numerical simulations have been done to support all theoretical findings.
The Impact of Stubble Burning on Air Quality and Anaerobic Biogas Plants as a Viable Solution – An Opportunity Analysis for Punjab, India
(IJEP, 2022-10) Dubey, Uma S.
Stubble burning and its resultant pollutants have adversely affected the environment and posed serious health hazards. It is very important to understand the situation from the farmer’s perspective and from the perspective of conserving the environment. In the present study, a critical analysis of stubble burning and its effects on the neighbouring city of Delhi has been done with the help of satellite imagery and simultaneously analysing the air quality index. The effect of pollutant dispersion on neighbouring areas has been studied at the time point when stubble burning takes place and over the following time intervals in the adjoining area. Furthermore, this study conducts an economic analysis of biogas plant establishment, biogas and biofertilizer generation from stubble and its sale. Thus, this study provides an opportunity analysis on how the stubble can be put to better use to produce utilizable cooking gas and fertilisers, which can directly benefit farmers, besides being economically and environmentally rewarding. The paper concludes with policy-related suggestions including setting up of corporative societies including the farmers as participants.
Isolation and characterization of bioactive lactoferrin from camel milk by novel pH-dependent method for large scale production
(Elsevier, 2022-12) Dubey, Uma S.
The present article exemplifies a novel method to isolate highly purified bioactive lactoferrin from camel milk. Cytotoxicity of lactoferrin against the Hela cells was used to evaluate its bioactivity. SDS-PAGE and LC-MS analysis was done for its identification and characterization. The purified camel milk lactoferrin was found to be 708 amino acids in length with a molecular weight of 77.3 kDa and a pI value of 8.24. This pH-dependent isolation procedure ensures the retention of bioactive lactoferrin from camel milk. The importance of the present work lies in its simplicity and scalability for manufacturing bioactive lactoferrin at an industrial level.
A MATHEMATICAL MODEL FOR THE EFFECT OF TOXICANT ON THE IMMUNE SYSTEM
(World Scientific, 2007) Dubey, Uma S.; Dubey, Balram
In this paper, a nonlinear mathematical model is proposed and analyzed to study the effect of environmental toxicant on the immune response of the body. Criteria for local stability, instability and global stability are obtained. It is shown that the immune response of the body decreases as the concentration of environmental toxicant increases, and certain criteria are obtained under which it settles down at its equilibrium level. In the absence of toxicant, an oscillatory behavior of immune system and pathogenic growth is observed. However, in the presence of toxicant, oscillatory behavior is not observed. These studies show that the toxicant may have a grave effect on our body's defense mechanism.
A mathematical model for the effect of toxicant on the immune system
(World Scientific, 2007) Dubey, Balram; Dubey, Uma S.
In this paper, a nonlinear mathematical model is proposed and analyzed to study the effect of environmental toxicant on the immune response of the body. Criteria for local stability, instability and global stability are obtained. It is shown that the immune response of the body decreases as the concentration of environmental toxicant increases, and certain criteria are obtained under which it settles down at its equilibrium level. In the absence of toxicant, an oscillatory behavior of immune system and pathogenic growth is observed. However, in the presence of toxicant, oscillatory behavior is not observed. These studies show that the toxicant may have a grave effect on our body's defense mechanism.
Medicinal potential of Camel milk lactoferrin
(Intecopen, 2022) Dubey, Uma S.
Camel milk is a rich source of protein with well-recognized medicinal properties to treat various diseases. The objective of this work is to understand the role of camel milk lactoferrin in immunomodulation and in disease treatment. It has been found that camel milk lactoferrin is a very suitable nutraceutical agent by virtue of its bioac- tivity, immuno-compatibility, and safety. It can be used for the treatment of infec- tious, metabolic, and neurodegenerative diseases, besides cancer. It is a cost-effective biomolecule that also has high relative abundance and bioavailability.