Putative stemness markers octamer-binding transcription factor 4, sex-determining region Y-box 2, and NANOG in non-small cell lung carcinoma: A clinicopathological association

Background: The promising improvement in the clinical outcome of lung cancer can be possibly achieved by identification of the molecular events that underlie its pathogenesis. Cancer stem cell (CSC) being one of the subsets of tumor majorly participates in drug resistance and treatment failure because of the moderate cell cycle, lower proliferation, and increased expression of DNA repair and anti-apoptosis genes. Although many putative CSC markers exist, a precise characterization for non-small cell lung cancer is of utmost importance due to increased mortality rate and lack of targeted therapies. Hence, the article focuses on the expression of stemness-associated markers, namely octamer-binding transcription factor 4 (OCT4), NANOG, and sex-determining region Y-box 2 (SOX2) in non-small cell lung cancer (NSCLC) patients. Methods: The expression of OCT4, NANOG, and SOX2 were evaluated in 32 histopathologically confirmed NSCLC tissues using real-time polymerase chain reaction. The obtained expression was correlated with clinical and pathological manifestations using the statistical test such as Student's t-test and Pearson correlation in varied statistical software. Results: Results showed a significantly higher expression of OCT4 and NANOG compared to SOX2 in the tumor tissues. When the expression of these markers was correlated with the clinical parameters, higher expression was seen in males, patients with age above 60 years, and in adenocarcinoma subtype. In correlation with the habit, higher expression of OCT4 and SOX2 was observed in habituated patients. Expression of NANOG and OCT4 was higher even in patients with poor differentiation. Conclusion: The expression and prognostic significance of CSC markers obviously vary depending on histological NSCLC subtype. Importantly, our findings suggest that OCT4, SOX2, and NANOG network together may be promising for ongoing targeted therapies in specific NSCLC subgroups

Preparation of Coronavirus nosodes sourced from a clinical sample of SARS-Cov-2 positive patient, inactivated strain, and spike glycoprotein

IntroductionNosodes, the homeopathicpreparationssourcedfrom biological materials including clinical samples, cultures of organisms, and diseased tissues have been in use against the source-specific infections as well as other diseases. The nosodes have demonstrated some efficacy in managing epidemics, such as influenza, dengue, and leptospirosis.This article presents the need and process of development ofnosodes from the SARS-CoV-2 to explore its prophylactic and therapeutic potentials against certain related viral diseases.Materials and methodsA clinical sample of SARS-Cov-2 positive patient,based on the cycle threshold (CT) value of the qRT-PCR, heat-inactivated SARS-CoV-2, and spike glycoprotein all were processed for making nosodesas per the method described in Homoeopathy Pharmacopoeia of India.Molecular tests, such as qRT-PCR and sterility tests were performed to establish the live organisms, RNA material, and the absence of contamination.ResultsThree variants of CoronavirusNosodewere developed using a clinical sample,heat-inactivatedSARS-CoV-2, and spike glycoprotein.In potencies 3c and above, no detectableSARS-CoV-2 RNA material was found by PCR.The analytical results for nosodes were reported as compliant for sterility testing as per the IP.ConclusionThree variants of Coronavirus nosodes were preparedwhich need to be evaluated further through pre-clinical and clinical studies.(AU)

In-silico analysis of heat shock protein 47 for identifying the novel therapeutic agents in the management of oral submucous fibrosis.

Background: Heat shock proteins-47 (HSP47) is a collagen specific molecular chaperone, involved in the processing and/or secretion of procollagen. It seems to be regularly upregulated in various fibrotic or collagen disorders. Hence, this protein can be a potential target for the treatment of various fibrotic diseases including oral submucous fibrosis (OSF), which is a collagen metabolic disorder of oral cavity and whose etiopathogeneic mechanism and therapeutic protocols are still not well documented. Aim: The aim of this study is to identify the novel therapeutic agents using in-silico methods for the management of OSF. Objectives: The objectives of this study are to identify the binding sites of HSP47 on the collagen molecule and to identify the lead compound with anti-HSP47 activity from the library of natural compounds, using in-silico methodology. Materials and Methods: The web-based and tool based in-silico analysis of the HSP47 and collagen molecules are used in this study. The crystal structure of collagen and HSP47 were retrieved from Protein Data Bank website. The binding site identification and the docking studies are done using Molegro Virtual Docker offline tool. Results: Out of the 104 Natural compounds, six ligands are found to possess best binding affinity to the binding amino acid residues. Silymarin binds with the 4AU2A receptor and the energy value are found to be −178.193 with four Hbonds. The other best five natural compounds are hesperidin, ginkgolides, withanolides, resveratrol, and gingerol. Our findings provide the basis for the in-vitro validation of the above specified compounds, which can possibly act as "lead" molecules in designing the drugs for OSF. Conclusion: HSP47 can be a potential candidate to target, in order to control the production of abundance collagen in OSF. Hence, the binding sites of HSP47 with collagen are identified and some natural compounds with a potential to bind with these binding receptors are also recognized. These natural compounds might act as anti-HSP47 lead molecules in designing novel therapeutic agents for OSF, which are so far unavailable.

A review of proteomics in cancer research.

The most functional compartment encoded by the genome is proteome. Therefore study of proteome i.e. proteomics is the promising approach in identification, separation and quantitation of functional changes. It aims to gain a comprehensive understanding of the expressions, modifications, interactions, and regulation of proteins in cells. The power of two-dimensional electrophoresis and advances in mass spectrometric techniques, combined with sequence data base correlation, has enabled speed and accuracy in identification of proteins in complex mixtures. Therefore, proteomics may provide a better understanding of the molecular basis of cancer growth, with identification of potential pathological markers and therapeutic targets. Tobacco related cancers are the major health hazard in Asian countries; the proteomics approach should be employed for understanding the underlying disease processes and hopefully reveal important clues for identifying high risk individuals and early changes during malignant transformation.