Biology subjects

Bhattacharya, S. S.

Publications and source records attributed to Bhattacharya, S. S..

3 recordsLinked to original sources

bioRxiv2025

In Silico Investigation Reveals a Potential Functional Role for Human Microbiome in Chronic Obstructive Pulmonary Disease

Chronic Obstructive Pulmonary Disease (COPD) is a progressive enervating lung disease characterized by chronic inflammation, airway inhibition and unrecoverable structural damage to the lungs. While traditionally associated with environmental factors similar as cigarette smoke and air pollution as well as genetic factors, recent revelations has increasingly indicative of the role of microbiomes in the modulation of this disease. This study explores the structural and functional relations between microbial proteins and human proteins involved in COPD using in-silico bioinformatic tools. Several critical human proteins involved in COPD pathogenesis such as MMP 1, MMP 2, MMP 14, TNF-, TGF-{beta} were evaluated for the presence of microbial homologous proteins using BLAST analysis in the microbial database. The results revealed significant structural homology with microbial proteins from species including E. coli, K.pneumonia, Bacillus thuringiensis, Bifidobacterium samirii. This microbial protein may impact COPD progression through mechanisms similar as molecular belittlement and modulation of host vulnerable responses. Further molecular docking simulations were conducted using the herbal drug oleanolic acid known for their anti-inflammatory effect and can be potentially used in the treatment of COPD. Results demonstrated favourable interactions between these composites and both human and microbial proteins, indicating therapeutic potential of the compounds. For case oleanolic acid showed strong interaction with TNF- and its microbial homolog. Also phylogenetic tree construction using Clustal Omega handed perceptivity into the evolutionary connections between the bacteria hosting homologous proteins, suggesting possible ancestral links and participated functional pathway applicable to COPD pathology. The finding emphasize the possibility of microbiome deduced proteins to act as modifiers in COPD progression as well as the therapeutic potential of the herbal compounds in targeting both host and microbial factors, which need to be further ascertained by in vitro, in vivo, as well as clinical studies. This novel in silico approach offers a unique prospective on COPD treatment by integrating microbiome and phytotherapy laying the groundwork for future personalized therapeutic strategies targeting both microbial and host inflammatory pathways.

bioinformatics↗

bioRxiv2021

A Nanoceutical Agent for Chemoprevention of Bilirubin Encephalopathy

BackgroundTargeted degradation of bilirubin in vivo may enable safer and more effective approach to manage incipient bilirubin encephalopathy consequent to severe neonatal hyperbilirubinemia (SNH). This report builds on the use of a spinel structured mixed-valence transition metal oxide (trimanganese tetroxide) nanoparticle duly functionalized with biocompatible ligand citrate (C-Mn3O4 NP) having the ability to degrade bilirubin without photo-activation. MethodThe efficiency of C-Mn3O4 NP in in vivo degradation of serum bilirubin and amelioration of severe bilirubin encephalopathy and associated neurobehavioral changes was evaluated in C57BL/6j animal model of SNH. ResultsOral single dose (0.25 mg kg-1 body weight) of the NPs efficiently reduced serum bilirubin levels (both conjugated and unconjugated) in study mice. It prevents bilirubin-induced neurotoxicity with reduction of SNH as observed by neurobehavioral and movement studies of SNH-mice. Pharmacokinetic data suggests intestinal reabsorption of the NPs and explain sustainable action. Biodistribution, pharmacokinetics, and biocompatibility of the NPs were tested during sub-chronic exposure. ConclusionThus, we report preliminary studies that explore an affordable chemoprevention mechanism to acutely prevent or minimize bilirubin neurotoxicity in newborn infants. IMPACT STATEMENTO_LIDespite several attempts, no pharmaco-therapeutics are available for the treatment of severe neonatal hyperbilirubinemia (SNH) and associated neurotoxicity. C_LIO_LIOur newly developed nanodrug, citrate functionalized Mn3O4 nanoparticles (C-Mn3O4 NPs), can efficiently ameliorate SNH and associated neurotoxicity as investigated in preclinical rodent model. C_LIO_LIChemoprevention effect of the nanodrug is found to be safe and sustainable. C_LIO_LIIf successfully translated into clinical trials, C-Mn3O4 NPs could become the first drug to treat SNH. C_LI

pharmacology and toxicology↗

bioRxiv2020

Incorporation of a Biocompatible Nanozyme in Cellular Antioxidant Enzyme Cascade Reverses Huntington's Like Disorder in Preclinical Model

The potentiality of nano-enzymes in therapeutic use has directed contemporary research to develop a substitute for natural enzymes, which are suffering from several disadvantages including low stability, high cost, and difficulty in storage. However, inherent toxicity, inefficiency in the physiological milieu, and incompatibility to function in cellular enzyme networks limit the therapeutic use of nanozymes in living systems. Here, we have shown that citrate functionalized manganese-based biocompatible nanoscale material (C-Mn3O4 NP) efficiently mimics glutathione peroxidase enzyme in the physiological milieu and easily incorporates into the cellular multienzyme cascade for H2O2 scavenging. A detailed computational study reveals the mechanism of the nanozyme action. We further established the in vivo therapeutic efficacy of C-Mn3O4 nanozyme in a preclinical animal model of Huntingtons disease, a prevalent progressive neurodegenerative disorder, which has no effective medication till date. SUMMARYAlthough, nano-enzymes have shown lots of promises in the management of several diseases, two major concerns limit their clinical translation. Apart from the inherent toxicity of the constituent materials (e.g., cerium, vanadium, gold, etc.), activities of contemporary nanozymes are often inhibited in physiological milieu. Furthermore, most of them are incapable of incorporation into the cellular metabolic networks for functioning in tandem and parallel with natural enzymes, a major criteria for potential therapeutics. Here, we have shown that citrate-functionalized spherical Mn3O4 nanoparticles can efficiently mimic glutathione peroxidase (GPX) enzyme without the limitations of contemporary nanozymes, and effectively manage neurodegenerative Huntingtons disease in preclinical animal model. The choice of the material in the nanozyme lies on the fact that Mn is an essential micronutrient for mammals, and the stabilizing ligand citrate helps the nanoparticles to cross the blood-brain-barrier to reach brain. We have shown that the nanozyme can easily be incorporated in cellular antioxidant enzyme cascade. The specificity and efficacy of the nanozyme in the cascade was significantly higher compared to other reported nanozymes. We have justified our experimental findings with a detailed computational study. Understanding the mode of operation and management of Huntingtons disease in preclinical animal trial using a biocompatible (non-toxic) nanozyme as a part of the metabolic network may uncover a new paradigm in nanozyme based therapeutic strategy.

pharmacology and toxicology↗