Steroidal alkaloid cortistatin is a promising marine natural compound isolated from marine sponges Corticium simplex. Experimental studies and clinical evidence have shown that cortistatin and its derivatives have a curative effect in patients with autoimmune disorders, HIV infection and several types of cancer. The objective of our study was to examine the potential cancer-related therapeutic objectives of Cortistatin using a network pharmacology method, which is a computational approach, including inverse pharmacophore research, enrichment analysis, molecular docking and dynamics study. Systematic protocol also involves the assessment of ADMET parameters to define the pharmacokinetic profile of cortistatin. Inverse pharmacophore search method was used for computational target fishing and target proteins were ranked based on the graph theory approach. Cancer target proteins, namely HSP90, EGFR, CDK2, MMP13, MAPK13, AR, ESR1, PTPN11 and SRC, were classified as top-ranking proteins according to graph theory parameters, namely MCC, DMNC, MNC, Degree(Local-based methods), EPC, Bottleneck, Eccentricity, Closeness, Radiality, Betweenness, Stress(Global-based methods) and Clustering Coefficient. Enrichment assessment established on Gene Ontology and pathway analysis of these proteins that play a vital role in cancer pathways, FaxO Signalling pathways, Ras Signalling pathways and tyrosine metabolism. Molecular docking and dynamic simulation studies of cortistatin with proposed target proteins were found to be stable and conformers generated after 3ns were consistent with stable inter-molecular interactions. The current study summarized here would provide a broad perspective on the therapeutic potential of cortistatin and provide new insights into the future development of cancer therapy strategies.
Purpose β-Carotene is the most appropriate and significant precursor of vitamin A. Synthetic carotene supplements have been known to pose a threat to human health, making natural sources such as the indefensible choice for the production and extraction of carotene. Design/methodology/approach This study considers Blakeslea trispora, a filamentous fungus, as a source of production of carotenoids by fermentation and wet and dry mycelium were used to analyse and obtain better extraction results. Findings In this study, natural oils such as soy oil and cottonseed oil were incorporated into fermentation media to increase the production of carotene. For the optimization process, Plackett–Burman and one-factor-at-a-time (OVAT) models were identified as being of great value. Originality/value OVAT was carried out for corn starch because it plays a major role in the production of carotene and the corn starch at 30 g/L concentration has shown the maximum activity of 3.48 mg/gm. After optimizing process variables, submerged fermentation was eventually carried out under highly controlled media conditions. The resulting product was quantified using UV spectroscopy and extraction of carotene has been observed in the presence of various solvents. Among a range of solvents used, the methylene Di chloride produced-carotene at 86% recovery at a significantly lower temperature of 35°C.
This study is an evaluative effort to analyse different physiological parameters and rheological properties observed during the fermentative production of cyclosporin A. Tolypocladium inflatum culture was used for seed development. For production fermentation, the mature seed was inoculated at specific transfer parameters. At each stage of the current study, pH, PMV and sugar consumption were keenly analysed and recorded. Different aeration rates and agitation speeds were evaluated during various stages of growth. Based on several experiments, the most optimised parameters were included for further analysis. The maximum productivity obtained was 8.3 g/L. Further, different kinds of solvents were studied to extract crude from the fermentation broth. Solvents required at various stages of downstream processing were analysed for best recovery with minimal product loss. Finally, the product was obtained with 80.58% recovery. Keywords: cyclosporin A, Tolypocladium inflatum, fermentation, seed, pH, PMV, extraction, downstream processing
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