Screening out molecular pathways and prognostic biomarkers of ultraviolet-mediated melanoma through computational techniques.

PURPOSE: Ultraviolet radiation causes skin cancer, but the exact mechanism by which it occurs and the most effective methods of intervention to prevent it are yet unknown. For this purpose, our study will use bioinformatics and systems biology approaches to discover potential biomarkers of skin cancer for early diagnosis and prevention of disease with applicable clinical treatments. METHODS: This study compared gene expression and protein levels in ultraviolet-mediated cultured keratinocytes and adjacent normal skin tissue using RNA sequencing data from the National Center for Biotechnology Information-Gene Expression Omnibus (NCBI-GEO) database. Then, pathway analysis was employed with a selection of hub genes from the protein-protein interaction (PPI) network and the survival and expression profiles. Finally, potential clinical biomarkers were validated by receiver operating characteristic (ROC) curve analysis. RESULTS: We identified 32 shared differentially expressed genes (DEGs) by analyzing three different subsets of the GSE85443 dataset. Skin cancer development is related to the control of several DEGs through cyclin-dependent protein serine/threonine kinase activity, cell cycle regulation, and activation of the NIMA kinase pathways. The cytoHubba plugin in Cytoscape identified 12 hub genes from PPI; among these 3 DEGs, namely, AURKA, CDK4, and PLK1 were significantly associated with survival (P < 0.05) and highly expressed in skin cancer tissues. For validation purposes, ROC curve analysis indicated two biomarkers: AURKA (area under the curve (AUC) value = 0.8) and PLK1 (AUC value = 0.7), which were in an acceptable range. CONCLUSIONS: Further translational research, including clinical experiments, teratogenicity tests, and in-vitro or in-vivo studies, will be performed to evaluate the expression of these identified biomarkers regarding the prognosis of skin cancer patients.

Drug Repurposing and Systems Biology approaches of Enzastaurin can target potential biomarkers and critical pathways in Colorectal Cancer.

Colorectal cancer (CRC) is a severe health concern that results from a cocktail of genetic, epigenetic, and environmental abnormalities. Because it is the second most lethal malignancy in the world and the third-most common malignant tumor, but the treatment is unavailable. The goal of the current study was to use bioinformatics and systems biology techniques to determine the pharmacological mechanism underlying putative important genes and linked pathways in early-onset CRC. Computer-aided methods were used to uncover similar biological targets and signaling pathways associated with CRC, along with bioinformatics and network pharmacology techniques to assess the effects of enzastaurin on CRC. The KEGG and gene ontology (GO) pathway analysis revealed several significant pathways including in positive regulation of protein phosphorylation, negative regulation of the apoptotic process, nucleus, nucleoplasm, protein tyrosine kinase activity, PI3K-Akt signaling pathway, pathways in cancer, focal adhesion, HIF-1 signaling pathway, and Rap1 signaling pathway. Later, the hub protein module identified from the protein-protein interactions (PPIs) network, molecular docking and molecular dynamics simulation represented that enzastaurin showed strong binding interaction with two hub proteins including CASP3 (-8.6 kcal/mol), and MCL1 (-8.6 kcal/mol), which were strongly implicated in CRC management than other the five hub proteins. Moreover, the pharmacokinetic features of enzastaurin revealed that it is an effective therapeutic agent with minimal adverse effects. Enzastaurin may inhibit the potential biological targets that are thought to be responsible for the advancement of CRC and this study suggests a potential novel therapeutic target for CRC.

An integrated in-silico Pharmaco-BioInformatics approaches to identify synergistic effects of COVID-19 to HIV patients.

BACKGROUND: With high inflammatory states from both COVID-19 and HIV conditions further result in complications. The ongoing confrontation between these two viral infections can be avoided by adopting suitable management measures. PURPOSE: The aim of this study was to figure out the pharmacological mechanism behind apigenin's role in the synergetic effects of COVID-19 to the progression of HIV patients. METHOD: We employed computer-aided methods to uncover similar biological targets and signaling pathways associated with COVID-19 and HIV, along with bioinformatics and network pharmacology techniques to assess the synergetic effects of apigenin on COVID-19 to the progression of HIV, as well as pharmacokinetics analysis to examine apigenin's safety in the human body. RESULT: Stress-responsive, membrane receptor, and induction pathways were mostly involved in gene ontology (GO) pathways, whereas apoptosis and inflammatory pathways were significantly associated in the Kyoto encyclopedia of genes and genomes (KEGG). The top 20 hub genes were detected utilizing the shortest path ranked by degree method and protein-protein interaction (PPI), as well as molecular docking and molecular dynamics simulation were performed, revealing apigenin's strong interaction with hub proteins (MAPK3, RELA, MAPK1, EP300, and AKT1). Moreover, the pharmacokinetic features of apigenin revealed that it is an effective therapeutic agent with minimal adverse effects, for instance, hepatoxicity. CONCLUSION: Synergetic effects of COVID-19 on the progression of HIV may still be a danger to global public health. Consequently, advanced solutions are required to give valid information regarding apigenin as a suitable therapeutic agent for the management of COVID-19 and HIV synergetic effects. However, the findings have yet to be confirmed in patients, suggesting more in vitro and in vivo studies.

Development of an in silico multi-epitope vaccine against SARS-COV-2 by précised immune-informatics approaches.

The coronavirus family has been infecting the human population for the past two decades, but the ongoing coronavirus called SARS-CoV-2 has posed an enigmatic challenge to global public health security. Since last year, the mutagenic quality of this virus is causing changes to its genetic material. To prevent those situations, the FDA approved some emergency vaccines but there is no assurance that these will function properly in the complex human body system. In point of view, a short but efficient effort has made in this study to develop an immune epitope-based therapy for the rapid exploitation of SARS-CoV-2 by applying in silico structural biology and advancing immune information strategies. The antigenic epitopes were screened from the Surface, Membrane, Envelope proteins of SARS-CoV-2 and passed through several immunological filters to determine the best possible one. According to this, 7CD4+, 10CD8+ and 5 B-cell epitopes were found to be prominent, antigenic, immunogenic, and most importantly, highly conserved among 128 Bangladeshi and 110 other infected countries SARS-CoV-2 variants. After that, the selected epitopes and adjuvant were linked to finalize the multi-epitope vaccine by appropriate linkers. The immune simulation disclosed that the engineered vaccine could activate both humoral and innate immune responses. For the prediction of an effective binding, molecular docking was carried out between the vaccine and immunological receptors (TLRs). Strong binding affinity and good docking scores clarified the stringency of the vaccines. Furthermore, MD simulation was performed within the highest binding affinity complex to observe the stability. Codon optimization and other physicochemical properties revealed that the vaccine would be suitable for a higher expression at cloning level. So, monitoring the overall in silico assessment, we anticipated that our engineered vaccine would be a plausible prevention against COVID-19.