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"Kumar, Dharmendra"
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Arsenic contamination in the environment : the issues and solutions
This book provides an overview to researchers, graduate, and undergraduate students, as well as academicians who are interested in arsenic. It covers human health risks and established cases of human ailments and sheds light on prospective control measures, both biological and physico-chemical. Arsenic (As) is a widely distributed element in the environment having no known useful physiological function in plants or animals. Historically, this metalloid has been known to be used widely as a poison. Effects of arsenic have come to light in the past few decades due to its increasing contamination in several parts of world, with the worst situation being in Bangladesh and West Bengal, India. The worrying issue is the ingestion of arsenic through water and food and associated health risks due to its carcinogenic and neurotoxic nature. The impact of the problem is widespread, and it has led to extensive research on finding both the causes and solutions. These attempts have allowed us to understand the various probable causes of arsenic contamination in the environment, and at the same time, have provided a number of possible solutions. It is reported that more than 200 mineral species contain As. Generally, As binds with iron and sulfur to form arsenopyrite. According to one estimate from the World Health Organization (WHO), contextual levels of As in soil ranges from 1 to 40 mg kg-1. Arsenic toxicity is related to its oxidation state which is present in the medium. As is a protoplastic toxin, due to its consequence on sulphydryl group it interferes in cell enzymes, cell respiration and in mitosis. Exposure of As may occur to humans via several industries, such as refining or smelting of metal ores, microelectronics, wood preservation, battery manufacturing, and also to those who work in power plants that burn arsenic-rich coal.
Book
TNBC: Potential Targeting of Multiple Receptors for a Therapeutic Breakthrough, Nanomedicine, and Immunotherapy
Triple-negative breast cancer (TNBC) is a heterogeneous, recurring cancer associated with a high rate of metastasis, poor prognosis, and lack of therapeutic targets. Although target-based therapeutic options are approved for other cancers, only limited therapeutic options are available for TNBC. Cell signaling and receptor-specific targets are reportedly effective in patients with TNBC under specific clinical conditions. However, most of these cancers are unresponsive, and there is a requirement for more effective treatment modalities. Further, there is a lack of effective biomarkers that can distinguish TNBC from other BC subtypes. ER, PR, and HER2 help identify TNBC and are widely used to identify patients who are most likely to respond to diverse therapeutic strategies. In this review, we discuss the possible treatment options for TNBC based on its inherent subtype receptors and pathways, such as p53 signaling, AKT signaling, cell cycle regulation, DNA damage, and programmed cell death, which play essential roles at multiple stages of TNBC development. We focus on poly-ADP ribose polymerase 1, androgen receptor, vascular endothelial growth factor receptor, and epidermal growth factor receptor as well as the application of nanomedicine and immunotherapy in TNBC and discuss their potential applications in drug development for TNBC.
Journal Article
Concepts and techniques of graph neural network
\"This book will aim to provide stepwise discussion; exhaustive literature review; detailed analysis and discussion; rigorous experimentation results, application-oriented approach that will be demonstrated with respect to applications of Graph Neural Network (GNN). It will be written to develop the understanding of concepts and techniques on GNN and to establish the familiarity of different real applications in various domains for GNN. Moreover, it will also cover the prevailing challenges and opportunities\"-- Provided by publisher.
Book
The Potential Application of Endophytes in Management of Stress from Drought and Salinity in Crop Plants
Endophytic microorganisms present inside the host plant play an essential role in host fitness, nutrient supply and stress tolerance. Endophytes are often used in sustainable agriculture as biofertilizers, biopesticides and as inoculants to mitigate abiotic stresses including salinity, drought, cold and pH variation in the soil. In changing climatic conditions, abiotic stresses create global challenges to achieve optimum crop yields in agricultural production. Plants experience stress conditions that involve endogenous boosting of their immune system or the overexpression of their defensive redox regulatory systems with increased reactive oxygen species (ROS). However, rising stress factors overwhelm the natural redox protection systems of plants, which leads to massive internal oxidative damage and death. Endophytes are an integral internal partner of hosts and have been shown to mitigate abiotic stresses via modulating local or systemic mechanisms and producing antioxidants to counteract ROS in plants. Advancements in omics and other technologies have been made, but potential application of endophytes remains largely unrealized. In this review article, we will discuss the diversity, population and interaction of endophytes with crop plants as well as potential applications in abiotic stress management.
Journal Article
Salinity Stress in Potato: Understanding Physiological, Biochemical and Molecular Responses
Among abiotic stresses, salinity is a major global threat to agriculture, causing severe damage to crop production and productivity. Potato (Solanum tuberosum) is regarded as a future food crop by FAO to ensure food security, which is severely affected by salinity. The growth of the potato plant is inhibited under salt stress due to osmotic stress-induced ion toxicity. Salinity-mediated osmotic stress leads to physiological changes in the plant, including nutrient imbalance, impairment in detoxifying reactive oxygen species (ROS), membrane damage, and reduced photosynthetic activities. Several physiological and biochemical phenomena, such as the maintenance of plant water status, transpiration, respiration, water use efficiency, hormonal balance, leaf area, germination, and antioxidants production are adversely affected. The ROS under salinity stress leads to the increased plasma membrane permeability and extravasations of substances, which causes water imbalance and plasmolysis. However, potato plants cope with salinity mediated oxidative stress conditions by enhancing both enzymatic and non-enzymatic antioxidant activities. The osmoprotectants, such as proline, polyols (sorbitol, mannitol, xylitol, lactitol, and maltitol), and quaternary ammonium compound (glycine betaine) are synthesized to overcome the adverse effect of salinity. The salinity response and tolerance include complex and multifaceted mechanisms that are controlled by multiple proteins and their interactions. This review aims to redraw the attention of researchers to explore the current physiological, biochemical and molecular responses and subsequently develop potential mitigation strategies against salt stress in potatoes.
Journal Article
Molecular dynamic simulations of oxidized skin lipid bilayer and permeability of reactive oxygen species
Lipid peroxidation by reactive oxygen species (ROS) during oxidative stress is non-enzymatic damage that affects the integrity of biological membrane, and alters the fluidity and permeability. We conducted molecular dynamic simulation studies to evaluate the structural properties of the bilayer after lipid peroxidation and to measure the permeability of distinct ROS. The oxidized membrane contains free fatty acid, ceramide, cholesterol, and 5α-hydroperoxycholesterol (5α-CH). The result of unconstrained molecular dynamic simulations revealed that lipid peroxidation causes area-per-lipid of the bilayer to increase and bilayer thickness to decrease. The simulations also revealed that the oxidized group of 5α-CH (-OOH) moves towards the aqueous layer and its backbone tilts causing lateral expansion of the bilayer membrane. These changes are detrimental to structural and functional properties of the membrane. The measured free energy profile for different ROS (H
2
O
2
, HO
2
, HO, and O
2
) across the peroxidized lipid bilayer showed that the increase in lipid peroxidation resulted in breaching barrier decrease for all species, allowing easy traversal of the membrane. Thus, lipid peroxidation perturbs the membrane barrier and imposes oxidative stress resulting into apoptosis. The collective insights increase the understanding of oxidation stress at the atomic level.
Journal Article
Multifaceted bioactivity of brown seaweed-derived fucoidan from the Indian Coastline: A natural health product candidate
Brown seaweeds are rich in bioactive constituents, among which fucoidan a sulphated polysaccharide is particularly noted for its broad-spectrum therapeutic properties. This study explores the multifaceted bioactivity of fucoidan extracted from six brown seaweed species ( Sargassum wightii , Sargassum tenerrimum , Sargassum cinereum , Turbinaria conoides , Padina boergesenii , and Padina tetrastromatica ) collected from the Pudumadam coast, Gulf of mannar region, Tamil Nadu, India. Fucoidan was isolated and structurally characterized using Fourier-transform infrared spectroscopy (FT-IR) and nuclear magnetic resonance (NMR) spectroscopy. The antioxidant capacity of the extracts was assessed through 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl radical scavenging activity (HRSA), and ferric reducing antioxidant power (FRAP) assays, with Sargassum cinereum showing the highest antioxidant activity (IC₅₀: 0.342 ± 0.01 mg/ml for DPPH; 1.26 ± 0.02 mg/ml for HRSA; 33.17 ± 0.02 mM Fe (II)/g for FRAP). In vitro antidiabetic assays demonstrated that fucoidan from Sargassum wightii exhibited the strongest inhibition of α-amylase and α-D-glucosidase (IC₅₀: 0.042 ± 0.02 mg/ml). Additionally, fucoidan from S. wightii displayed significant cytotoxic activity against MCF-7 human breast cancer cells. These findings underscore the therapeutic promise of brown seaweed-derived fucoidan as a multifunctional agent, supporting its potential application in the formulation of natural health products.
Journal Article
B Cell Lymphoma 2: A Potential Therapeutic Target for Cancer Therapy
Defects in the apoptosis mechanism stimulate cancer cell growth and survival. B cell lymphoma 2 (Bcl-2) is an anti-apoptotic molecule that plays a central role in apoptosis. Bcl-2 is the founding constituent of the Bcl-2 protein family of apoptosis controllers, the primary apoptosis regulators linked with cancer. Bcl-2 has been identified as being over-expressed in several cancers. Bcl-2 is induced by protein kinases and several signaling molecules which stimulate cancer development. Identifying the important function played by Bcl-2 in cancer progression and development, and treatment made it a target related to therapy for multiple cancers. Among the various strategies that have been proposed to block Bcl-2, BH3-mimetics have appeared as a novel group of compounds thanks to their favorable effects on many cancers within several clinical settings. Because of the fundamental function of Bcl-2 in the regulation of apoptosis, the Bcl-2 protein is a potent target for the development of novel anti-tumor treatments. Bcl-2 inhibitors have been used against several cancers and provide a pre-clinical platform for testing novel therapeutic drugs. Clinical trials of multiple investigational agents targeting Bcl-2 are ongoing. This review discusses the role of Bcl-2 in cancer development; it could be exploited as a potential target for developing novel therapeutic strategies to combat various types of cancers. We further highlight the therapeutic activity of Bcl-2 inhibitors and their implications for the therapeutic management of cancer.
Journal Article
SARS-CoV-2: Emergence of New Variants and Effectiveness of Vaccines
The emergence of SARS-CoV-2 variants may cause resistance at the immunity level against current vaccines. Some emergent new variants have increased transmissibility, infectivity, hospitalization, and mortality. Since the administration of the first SARS-CoV-2 vaccine to a human in March 2020, there is an ongoing global race against SARS-CoV-2 to control the current pandemic situation. Spike (S) glycoprotein of SARS-CoV-2 is the main target for current vaccine development, which can neutralize the infection. Companies and academic institutions have developed vaccines based on the S glycoprotein, as well as its antigenic domains and epitopes, which have been proven effective in generating neutralizing antibodies. The effectiveness of SARS-CoV-2 vaccines and other therapeutics developments are limited by the new emergent variants at the global level. We have discussed the emergent variants of SARS-CoV-2 on the efficacy of developed vaccines. Presently, most of the vaccines have been tremendously effective in severe diseases. However, there are still noteworthy challenges in certifying impartial vaccines; the stories of re-infections are generating more stressful conditions, and this needs further clinical evaluation.
Journal Article
TRPγ regulates lipid metabolism through Dh44 neuroendocrine cells
Understanding how the brain controls nutrient storage is pivotal. Transient receptor potential (TRP) channels are conserved from insects to humans. They serve in detecting environmental shifts and in acting as internal sensors. Previously, we demonstrated the role of TRPγ in nutrient-sensing behavior (Dhakal et al., 2022). Here, we found that a TRPγ mutant exhibited in Drosophila melanogaster is required for maintaining normal lipid and protein levels. In animals, lipogenesis and lipolysis control lipid levels in response to food availability. Lipids are mostly stored as triacylglycerol in the fat bodies (FBs) of D. melanogaster . Interestingly, trpγ deficient mutants exhibited elevated TAG levels and our genetic data indicated that Dh44 neurons are indispensable for normal lipid storage but not protein storage. The trpγ mutants also exhibited reduced starvation resistance, which was attributed to insufficient lipolysis in the FBs. This could be mitigated by administering lipase or metformin orally, indicating a potential treatment pathway. Gene expression analysis indicated that trpγ knockout downregulated brummer , a key lipolytic gene, resulting in chronic lipolytic deficits in the gut and other fat tissues. The study also highlighted the role of specific proteins, including neuropeptide DH44 and its receptor DH44R2 in lipid regulation. Our findings provide insight into the broader question of how the brain and gut regulate nutrient storage.
Journal Article