MOLECULAR DOCKING STUDIES FOR THE COMPARATIVE ANALYSIS OF DIFFERENT BIOMOLECULES TO TARGET HYPOXIA INDUCIBLE FACTOR-1α

Objective: Hypoxia plays a significant role in governing many vital signalling molecules in the central nervous system (CNS). Hypoxic exposure has also been depicted as a stimulus for oxidative stress, increase in lipid peroxidation, DNA damage, blood-brain dysfunction, impaired calcium (Ca2+) homoeostasis and agglomeration of oxidized biomolecules in neurons, which act as a novel signature in diverse neurodegenerative and oncogenic processes. On the contrary, the presence of abnormally impaired expression of HIF-1α under hypoxic insult could serve as an indication of the existence of tumors and neuronal dysfunction as well. For instance, under hypoxic stress, amyloid-β protein precursor (AβPP) cleavage is triggered due to the higher expression of HIF-1α and thus leads to synaptic loss. The objective of this research is to perform comparative studies of biomolecules in regulating HIF-1α activity based on in silico approaches that could establish a potential therapeutic window for the treatment of different abnormalities associated with impaired HIF-1α.Methods: We employed various in silico methods such as drug-likeness parameters namely Lipinski filter analysis, Muscle tool, SWISS-MODEL, active site prediction, Auto Dock 4.2.1 and LigPlot1.4.5for molecular docking studies.Results: 3D structure of HIF-1α was generated and Ramachandran plot obtained for quality assessment. RAMPAGE displayed 99.5% of residues in the most favoured regions. 0% residues in additionally allowed and 0.5% disallowed regions of the HIF-1α protein. Further, initial screenings of the molecules were done based on Lipinski's rule of five. Cast P server used to predict the ligand binding site suggests that this protein can be utilised as a potential drug target. Finally, we have found Naringenin to be most effective amongst three biomolecules in modulating HIF-1α based on minimum inhibition constant, Ki and highest negative free energy of binding with the maximum interacting surface area during docking studies.Conclusion: The present study outlines the novel potential of Biomolecules in regulating HIF-1α activity for the treatment of different abnormalities associated with impaired HIF-1α

BIOMOLECULES MEDIATED TARGETING OF VASCULAR ENDOTHELIAL GROWTH FACTOR IN NEURONAL DYSFUNCTION: AN IN SILICO APPROACH

Objective: Neurodegenerative diseases are a debilitating age-related disorder manifested by memory loss, impaired motor activity, and loss of muscle tone due to the accumulation of toxic metabolites in the brain. Despite the knowledge of factors causing neurodegenerative disorders, it remains irreversible and incurable. Growing evidence have currently advocated the physiological and pathological contribution of hypoxia-induced vascular endothelial growth factor (VEGF) in neuronal loss. The objective of this research report highlights biomolecules mediated targeting of VEGF activity based on in silico approaches that could establish a potential therapeutic window for the treatment of different abnormalities associated with impaired VEGF.Methods: We employed various in silico methods such as drug-likeness parameters, namely, Lipinski filter analysis, Pock Drug tool for active site prediction, AUTODOCK 4.2.1, and LigPlot1.4.5 for molecular docking studiesResults: Three-dimensional structure of VEGF was generated and Ramachandran plot obtained for quality assessment. RAMPAGE displayed 99.5% of residues in the most favored regions, 0.5% residues in additionally allowed, and no residues in disallowed regions in VEGF, showing that stereochemical quality of protein structure is good. Further, initial screenings of the molecules were done based on Lipinski's rule of five. Finally, we have found Naringenin to be most effective among three biomolecules in modulating VEGF activity based on minimum inhibition constant, Ki, and highest negative free energy of binding with the maximum interacting surface area during docking studies.Conclusion: The present study outlines the novel potential of biomolecules in regulating VEGF activity for the treatment of different abnormalities associated with impaired VEGF

Giant Arcuate Lupus Vulgaris with Rapid Progression:A Case Report

Lupus vulgaris is the commonest form of cutaneous tuberculosis. It is a chronic and slowly progressive disease. It can be transmitted either through hematogenous or lymphatic spread but most commonly through contiguous extension.There are many reports on different form of lupus vulgaris but there are only a few reports on large sized lupus vulgaris. Here, we report a case of 75-year-old man with a giant lupus vulgaris rapidly progressing in just two year's duration

Cytokinin and abiotic stress tolerance -What has been accomplished and the way forward?

More than a half-century has passed since it was discovered that phytohormone cytokinin (CK) is essential to drive cytokinesis and proliferation in plant tissue culture. Thereafter, cytokinin has emerged as the primary regulator of the plant cell cycle and numerous developmental processes. Lately, a growing body of evidence suggests that cytokinin has a role in mitigating both abiotic and biotic stress. Cytokinin is essential to defend plants against excessive light exposure and a unique kind of abiotic stress generated by an altered photoperiod. Secondly, cytokinin also exhibits multi-stress resilience under changing environments. Furthermore, cytokinin homeostasis is also affected by several forms of stress. Therefore, the diverse roles of cytokinin in reaction to stress, as well as its interactions with other hormones, are discussed in detail. When it comes to agriculture, understanding the functioning processes of cytokinins under changing environmental conditions can assist in utilizing the phytohormone, to increase productivity. Through this review, we briefly describe the biological role of cytokinin in enhancing the performance of plants growth under abiotic challenges as well as the probable mechanisms underpinning cytokinin-induced stress tolerance. In addition, the article lays forth a strategy for using biotechnological tools to modify genes in the cytokinin pathway to engineer abiotic stress tolerance in plants. The information presented here will assist in better understanding the function of cytokinin in plants and their effective investigation in the cropping system

Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies

Excessive exposure to toxic substances or chemicals in the environment and various pathogens, including viruses and bacteria, is associated with the onset of numerous brain abnormalities. Among them, pathogens, specifically viruses, elicit persistent inflammation that plays a major role in Alzheimer's disease (AD) as well as dementia. AD is the most common brain disorder that affects thought, speech, memory and ability to execute daily routines. It is also manifested by progressive synaptic impairment and neurodegeneration, which eventually leads to dementia following the accumulation of Aβ and hyperphosphorylated Tau. Numerous factors contribute to the pathogenesis of AD, including neuroinflammation associated with pathogens, and specifically viruses. The human immunodeficiency virus (HIV) is often linked with HIV-associated neurocognitive disorders (HAND) following permeation through the blood-brain barrier (BBB) and induction of persistent neuroinflammation. Further, HIV infections also exhibited the ability to modulate numerous AD-associated factors such as BBB regulators, members of stress-related pathways as well as the amyloid and Tau pathways that lead to the formation of amyloid plaques or neurofibrillary tangles accumulation. Studies regarding the role of HIV in HAND and AD are still in infancy, and potential link or mechanism between both is not yet established. Thus, in the present article, we attempt to discuss various molecular mechanisms that contribute to the basic understanding of the role of HIV-associated neuroinflammation in AD and HAND. Further, using numerous growth factors and drugs, we also present possible therapeutic strategies to curb the neuroinflammatory changes and its associated sequels.Peer reviewe

TLR-mediated signal transduction and neurodegenerative disorders

A special class of proteins called Toll-like receptors (TLRs) are an essential part of the innate immune system, connecting it to the adaptive immune system. There are 10 different Toll-Like Receptors that have been identified in human beings. TLRs are part of the central nervous system (CNS), showing that the CNS is capable of the immune response, breaking the long-held belief of the brain's "immune privilege" owing to the blood–brain barrier (BBB). These Toll-Like Receptors are present not just on the resident macrophages of the central nervous system but are also expressed by the neurons to allow them for the production of proinflammatory agents such as interferons, cytokines, and chemokines; the activation and recruitment of glial cells; and their participation in neuronal cell death by apoptosis. This study is focused on the potential roles of various TLRs in various neurodegenerative diseases such as Parkinson';s disease (PD) and Alzheimer's disease (AD), namely TLR2, TLR3, TLR4, TLR7, and TLR9 in AD and PD in human beings and a mouse model

An Experience of designing supports in newly opened Belgaon Underground coal mine

Belgaon block is located in the northern most ends of explored coal block of the eastern limb of Wardha Valley Coalfields (WVC). WVC is well known for its complexity like complex geological structures, strata control problems while dealing with thick coal seam, fire and water problem etc. The Belgon mine of SUNFLAG is however separated from Majra block in the south by a down throw fault. Designing of road ways and junction support in newly opened underground coal mine was a challenge due to its complex geology. To arrive at suitable support system, various experiments using cement as well as resin bolting were carried out. The pulls out tests were carried out on rock bolts grouted with cement as well as resin. The proposed paper deals with significance and importance of resin grout over cement and other issues related to strata control etc

Microfluidic Platforms to Unravel Mysteries of Alzheimer's Disease: How Far Have We Come?

Alzheimer’s disease (AD) is a significant health concern with enormous social and economic impact globally. The gradual deterioration of cognitive functions and irreversible neuronal losses are primary features of the disease. Even after decades of research, most therapeutic options are merely symptomatic, and drugs in clinical practice present numerous side effects. Lack of effective diagnostic techniques prevents the early prognosis of disease, resulting in a gradual deterioration in the quality of life. Furthermore, the mechanism of cognitive impairment and AD pathophysiology is poorly understood. Microfluidics exploits different microscale properties of fluids to mimic environments on microfluidic chip-like devices. These miniature multichambered devices can be used to grow cells and 3D tissues in vitro, analyze cell-to-cell communication, decipher the roles of neural cells such as microglia, and gain insights into AD pathophysiology. This review focuses on the applications and impact of microfluidics on AD research. We discuss the technical challenges and possible solutions provided by this new cutting-edge technique to understand disease-associated pathways and mechanisms