Integrated bioinformatics approach to unwind key genes and pathways involved in colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the fifth leading cause of death in India. Until now, the exact pathogenesis concerning CRC signaling pathways is largely unknown; however, the diseased condition is believed to deteriorate with lifestyle, aging, and inherited genetic disorders. Hence, the identification of hub genes and therapeutic targets is of great importance for disease monitoring. OBJECTIVE: Identification of hub genes and targets for identification of candidate hub genes for CRC diagnosis and monitoring. MATERIALS AND METHODS: The present study applied gene expression analysis by integrating two profile datasets (GSE20916 and GSE33113) from NCBI-GEO database to elucidate the potential key candidate genes and pathways in CRC. Differentially expressed genes (DEGs) between CRC (195 CRC tissues) and healthy control (46 normal mucosal tissue) were sorted using GEO2R tool. Further, Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed using Cluster Profiler in Rv. 3.6.1. Moreover, protein-protein interactions (PPI), module detection, and hub gene identification were accomplished and visualized through the Search Tool for the Retrieval of Interacting Genes, Molecular Complex Detection (MCODE) plug-in of Cytoscape v3.8.0. Further hub genes were imported into ToppGene webserver for pathway analysis and prognostic expression analysis was conducted using Gene Expression Profiling Interactive Analysis webserver. RESULTS: A total of 2221 DEGs, including 1286 up-regulated and 935down-regulated genes mainly enriched in signaling pathways of NOD-like receptor, FoxO, AMPK signalling and leishmaniasis. Three key modules were detected from PPI network using MCODE. Besides, top 20 high prioritized hub genes were selected. Further, prognostic expression analysis revealed ten of the hub genes, namely IL1B, CD44, Glyceraldehyde-3-phosphate dehydrogenase (GAPDH, MMP9, CREB1, STAT1, vascular endothelial growth factor (VEGFA), CDC5 L, Ataxia-telangiectasia mutated (ATM + and CDH1 to be differently expressed in normal and cancer patients. CONCLUSION: The present study proposed five novel therapeutic targets, i.e., ATM, GAPDH, CREB1, VEGFA, and CDH1 genes that might provide new insights into molecular oncogenesis of CRC.

Green synthesis of Piper nigrum copper-based nanoparticles: in silico study and ADMET analysis to assess their antioxidant, antibacterial, and cytotoxic effects.

Nanobiotechnology is a popular branch of science that is gaining interest among scientists and researchers as it allows for the green manufacturing of nanoparticles by employing plants as reducing agents. This method is safe, cheap, reproducible, and eco-friendly. In this study, the therapeutic property of Piper nigrum fruit was mixed with the antibacterial activity of metallic copper to produce copper nanoparticles. The synthesis of copper nanoparticles was indicated by a color change from brown to blue. Physical characterization of Piper nigrum copper nanoparticles (PN-CuNPs) was performed using UV-vis spectroscopy, FT-IR, SEM, EDX, XRD, and Zeta analyzer. PN-CuNPs exhibited potential antioxidant, antibacterial, and cytotoxic activities. PN-CuNPs have shown concentration-dependent, enhanced free radical scavenging activity, reaching maximum values of 92%, 90%, and 86% with DPPH, H2O2, and PMA tests, respectively. The antibacterial zone of inhibition of PN-CuNPs was the highest against Staphylococcus aureus (23 mm) and the lowest against Escherichia coli (10 mm). PN-CuNPs showed 80% in vitro cytotoxicity against MCF-7 breast cancer cell lines. Furthermore, more than 50 components of Piper nigrum extract were selected and subjected to in silico molecular docking using the C-Docker protocol in the binding pockets of glutathione reductase, E. coli DNA gyrase topoisomerase II, and epidermal growth factor receptor (EGFR) tyrosine to discover their druggability. Pipercyclobutanamide A (26), pipernigramide F (32), and pipernigramide G (33) scored the highest Gibbs free energy at 50.489, 51.9306, and 58.615 kcal/mol, respectively. The ADMET/TOPKAT analysis confirmed the favorable pharmacokinetics, pharmacodynamics, and toxicity profiles of the three promising compounds. The present in silico analysis helps us to understand the possible mechanisms behind the antioxidant, antibacterial, and cytotoxic activities of CuNPs and recommends them as implicit inhibitors of selected proteins.

Antioxidant, Antibacterial, and Anti-diabetic Activity of Green Synthesized Copper Nanoparticles of Cocculus hirsutus (Menispermaceae).

The emergence of new technologies has led to the discovery of the biological properties of nanoparticles through green approach. In the present investigation, we report the potential antibacterial, antioxidant, and anti-diabetic properties of copper nanoparticle (CuNPs) synthesized by reducing 3 mM copper acetate solution with aqueous leaf extract of Cocculus hirsutus. A colour change from deep brown to dark greenish brown indicated the formation of copper nanoparticles. The so-formed CuNPs were characterized by employing UV spectroscopy, FTIR, SEM, and EDX analyses which described sheet-like structure morphology having typical size of 63.46 nm. Later, the synthesized CuNPs efficiency was evaluated against bacterial pathogens, and was found highly toxic to B. subtilis and S. aureus strains. The synthesized CuNPs were examined through H2O2 and PMA assays which demonstrated the highest free radical scavenging activity. Besides, the resulted CuNPs revealed the higher anti-diabetic efficacy in both the [Formula: see text]-amylase and [Formula: see text] -glucosidase inhibition assays (64.5% ± 0.11 and 68.5% ± 0.11, respectively). Finally, our findings report that C. hirsutus can be exploited as a source for green synthesis of CuNPs, having potent in vitro antioxidant, antibacterial, and anti-diabetic properties.

Ascorbic acid is a key participant during the interactions between chloroplasts and mitochondria to optimize photosynthesis and protect against photoinhibition.

The possible role of L-ascorbate (AsA) as a biochemical signal during the interactions between photosynthesis and respiration was examined in leaf discs of Arabidopsis thaliana. AsA content was either decreased as in AsA-deficient vtc1 mutants or increased by treatment with L-galactono-1, 4-lactone (L-GalL, a precursor of AsA; EC 1.3.2.3). In mutants, photosynthesis was extremely sensitive to both antimycin A (inhibitor of the cytochrome c oxidase pathway [COX pathway]) and salicylhydroxamic acid (SHAM, inhibitor of the alternative pathway [AOX pathway]), particularly at high light conditions. Mitochondrial inhibitors lowered the ratio of reduced AsA to total AsA, at high light, indicating oxidative stress in leaf discs. Elevation of AsA by L-GalL decreased the sensitivity of photosynthesis at high light to antimycin A or SHAM, sustained photosynthesis at supraoptimal light and relieved the extent of photoinhibition. High ratios of reduced AsA to total AsA in L-GalL-treated leaf discs suggests that L-GalL lowers oxidative stress. The protection by L-GalL of photosynthesis against the mitochondrial inhibitors and photoinhibition was quite pronounced in vtc1 mutants. Our results suggest that the levels and redox state of AsA modify the pattern of modulation of photosynthesis by mitochondrial metabolism. The extent of the AOX pathway as a percentage of the total respiration in Arabidopsis mesophyll protoplasts was much higher in vtc1 than in wild type. We suggest that the role of AsA becomes pronounced at high light and/or when the AOX pathway is inhibited. While acknowledging the importance of the COX pathway, we hypothesize that AsA and the AOX pathway may complement each other to protect photosynthesis against photoinhibition.