Biology subjects

Bhowmick, S.

Publications and source records attributed to Bhowmick, S..

5 recordsLinked to original sources

bioRxiv2021

Identifying potential key genes and existing drugs for Multiple sclerosis, Schizophrenia, and Autism- an in silico approach

Nowadays, neurological conditions are a major concern as it not only preys on a patients health but also is a huge economic burden that is placed on the patients family. The diagnosis and treatment of disease sometimes cause methodological limitations. This is mainly common for individuals who have the signs of MS and schizophrenia (SZ). Patients suffering from multiple sclerosis are more likely to develop schizophrenia. Besides, a significant portion of patients who have been diagnosed with Autism Spectrum Disorder (ASD) later acquire the symptoms of Schizophrenia. In this study, we used bioinformatics tools to determine differentially expressed genes (DEGs) in all these diseases, and then we created a protein-protein interaction network using the online software STRING and identified 15 significant genes with the help of Cytohubba a plug-in tool in Cytoscape, the offline software (version3.8.2). We then used a drug-gene interaction database to conduct a drug-gene interaction study of the 15 hub genes and from there we identified 37 FDA-approved drugs. These findings may provide a new and common therapeutic approach for MS, SZ, and ASD therapy.

neuroscience↗

bioRxiv2021

Isolation and characterisation of quercitrin as a potent anti-sickle cell anaemia agent from Alchornea cordifolia.

Alchornea cordifolia Mull. Arg. (commonly known as Christmas Bush) has been used traditionally in Africa to treat sickle cell anaemia (a recessive disease, arising from the S haemoglobin [Hb] allele) but the active compounds are yet to be characterised. Herein we describe the use of sequential fractionation coupled with in vitro anti-sickling assays to purify the active component. Sickling was induced in HbSS genotype blood samples using sodium metabisulphite (Na2S2O5) or incubation in 100 % N2. Methanol extracts of A. cordifolia leaves and its sub-fractions showed >70 % suppression of HbSS erythrocyte sickling. Purified compound demonstrated 87.2 {+/-} 2.39 % significant anti-sickling activity and 93.1 {+/-} 2.69 % erythrocyte sickling-inhibition at 0.4 mg/mL. Nuclear magnetic resonance (NMR) spectra and high-resolution mass spectroscopy identified it as quercitrin (quercetin 3-rhamnoside). Purified quercitrin also inhibited the polymerisation of isolated HbS and stabilized sickle erythrocytes membranes. Metabolomic comparisons of blood samples using flow-infusion electrospray-high resolution mass spectrometry indicated that quercitrin could convert HbSS erythrocyte metabolomes to be similar to HbAA. Sickling was associated with changes in anti-oxidants, anaerobic bioenergy and arachidonic acid metabolism, all of which were reversed by quercitrin. The findings described could inform efforts directed to the development of an anti-sickling drug or quality control assessments of A. cordifolia preparations.

pharmacology and toxicology↗

bioRxiv2021

In-silico analysis: common biomarkers of NDs

Neurodegenerative disorders (NDs) are a class of rapidly rising devastating diseases and the reason behind are might be an improper function of related genes or a mutation in a particular gene or even could be autoimmune also. Parkinsons disease (PD), Multiple sclerosis (MS), Huntingtons disease (HD) are some of the NDs, and still, incurable fully. Apart from the similarities in symptoms, there are common genes that express somehow a differential manner in patients of PDs, MSs, and HDs. A total of 1197 differentially expressed genes (DEGs) are obtained by analyzing the chosen datasets. The protein interactions by STRING online tool and degree sorted hubs obtained through a plug-in in Cytoscape; Cyto-Hubba. Among the sorted hubs KRAS, CREB1, PIK3CA, JAK2 are the ones that are not only common to all the studied datasets of NDs but also in other neurological disorders like Alzheimers. The enriched pathways with biological process, molecular function, cellular component, and KEGG pathway details are obtained and analyzed using Enricher. This paper frames that the obtained hub genes could be potential biomarkers also and a need for further drug design for finding a possible cure.

neuroscience↗

bioRxiv2021

Improved HIV-1 drug resistance mutation prediction using quasispecies reconstruction supported analysis

Accurate and sensitive approaches to detect HIV-1 drug resistance mutations (DRMs) are indispensable for the paradigm of treatment as prevention. While HIV-1 proviral DNA allows sensitive high throughput sequencing (HTS)-based DRM detection, its applicability is limited by presence of defective genomes. This study demonstrates application of quasispecies reconstruction algorithms (QRAs) to improve DRM detection sensitivity from proviral DNA. A robust benchmarking of 5 QRAs was performed with 2 distinct experimental control-datasets including a stringent, novel control: DCPM, simulating in-vivo variant distribution (0.08%-86.5%). Selected QRA was further evaluated for its ability to differentiate DRMs from hypermutated sequences using an in-silico control. PredictHaplo outperformed all others in terms of precision and was selected for further analysis. Near full-genome HTS was performed on proviral DNA from 20 HIV-1C infected individuals, at different stages of ART, from Mumbai, India. DRM detection was performed through residue-wise variation analysis and implementation of QRAs. Both analyses were highly concordant for DRM frequencies >10% (spearman r=0.91, p<0.0001). Phylogenetic association in HTS datasets with shared transmission history could also be demonstrated by PredictHaplo. This study highlights utility of QRAs as an adjunct to traditional residue-wise variation-based DRM detection leading to optimal personalized ART as well as better disease management.

bioinformatics↗

bioRxiv2020

The anti-mycobacterial activity of Artemisia annua L is based on deoxyartemisinin and artemisinic acid

The discovery of antimalarial artemisinin from Artemisia annua L. is an example of how Traditional Chinese Medicine (TCM) may be exploited to meet a recognized need. In this study, we systemically investigated A. annua L. for its antimicrobial activity and assessed it as a source of bioactive natural products for anti-mycobacterial activity. We used a silica gel column to perform antimicrobial activity-guided purification of the A. annua leaf, whose identity was confirmed by rbcL DNA barcoding, and used UHPLC-HRMS and NMR to elucidate the structure of purified active compounds. The antimicrobial activity of crude extracts, isolated compounds and the control artemisinin (Apollo Scientific Ltd) was assessed against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, methicillin-resistant Staphylococcus aureus (MRSA), Mycobacterium smegmatis strains by serial micro dilution method (31.25-1000 g/mL). The isolated compounds were tested for synergistic effects against mycobacterium. Bioactive compounds were purified and identified as deoxyartemisinin and artemisinic acid. Artemisinic acid (MIC 250 g/mL) was more effective in comparison to deoxyartemisinin (MIC 500 g/mL) and artemisinin (MIC 1000 g/mL) against M. smegmatis. We used a molecular docking approach to investigate the interactions between selected anti-mycobacterial compounds and proteins involved in vital physiological functions in M. tuberculosis, namely MtPks13, MtPknB, MtPanK, MtKasA, MtInhA and MtDprE1 and found artemisinic acid showed docking scores superior to the control inhibiters for MtKasA, suggesting it to be a potential nick for further in vitro biological evaluation and anti-TB drug design.

pharmacology and toxicology↗