School Of Basic And Applied Sciences

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Subject: search.filters.subject.Phytochemical

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    Identification of cancer stemness related miRNA(s) using integrated bioinformatics analysis and in vitro validation
    (Springer Science and Business Media Deutschland GmbH, 2021-09-23T00:00:00) Prajapati, Kumari Sunita; Shuaib, Mohd; Kushwaha, Prem Prakash; Singh, Atul Kumar; Kumar, Shsahank
    The stemness property of cells allows them to sustain their lineage, differentiation, proliferation, and regeneration. MicroRNAs are small non-coding RNAs known to regulate the stemness property of cells by regulating the expression of stem cell signaling pathway proteins at mRNA level. Dysregulated miRNA expression and associated stem cell signaling pathways in normal stem cells give rise to cancer stem cells. Thus, the present study was aimed to identify the miRNAs involved in the regulation of major stem cell signaling pathways. The proteins (n = 36) involved in the signaling pathways viz., Notch, Wnt, JAK-STAT, and Hedgehog which is associated with the stemness property was taken into the consideration. The miRNAs, having binding sites for the targeted protein-encoding gene were predicted using an online tool (TargetScan) and the common miRNA among the test pathways were identified using Venn diagram analysis. A total of 22 common miRNAs (including 8 non-studied miRNAs) were identified which were subjected to target predictions, KEGG pathway, and gene ontology (GO) analysis to study their potential involvement in the stemness process. Further, we studied the clinical relevance of the non-studied miRNAs by performing the survival analysis and their expression levels in clinical breast cancer patients using the TCGA database. The identified miRNAs showed overall poor survival in breast cancer patients. The miR-6844 showed significantly high expression in various clinical subgroups of invasive breast cancer patients compared with the normal samples. The expression levels of identified miRNA(s) were validated in breast normal, luminal A, triple-negative, and stem cells in vitro models using qRT-PCR analysis. Further treatment with the phytochemical showed excellent down regulation of the lead miRNA. Overall the study first time reports the association of four miRNAs (miR-6791, miR-4419a, miR-4251 and miR-6844) with breast cancer stemness. � 2021, King Abdulaziz City for Science and Technology.
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    Phytochemical investigation in vitro anti-mutagenic activity of potentilla fulgens lodd and silico study of flavonoids with CDK-2,CDK-6 receptors
    (Central University of Punjab, 2013) Monga, Prakriti; Jaitak, Vikas
    Plants have been used for thousand years in the treatment of various diseases. Plant secondary metabolites have proved to be an excellent source of new medicinal compounds. They offer protection against variety of chronic diseases including diabetes, cardiovascular diseases, obesity and cancer. Mutation is an important factor that is linked to carcinogenesis. It has been found that occurrence of cancer can be reduced by decreasing the incidence or rate of mutation. Plants are promising source of antimutagens agents which are present in them as secondary metabolites such as flavonoids, alkaloids, terpenoids, glycosides etc. Potentilla fulgens is an important medicinal plant of higher Himalayas that is known globally for its therapeutic importance. A number of antioxidant constituents have been reported from the plant which mainly consists of polyphenolic compounds. It has been observed that diet rich in polyphenolic compounds such as flavonoids can reduce the risk of cancer. P.fulgens reported to have polyphenolic compounds such as flavonoids which are potent bioactive molecules that possess anticarcinogenic effects as they can interfere with initiation, development and progression of cancer by the modulation of cell cycle, apoptosis, and angiogenesis. Anti-mutagenic activity on different fractions of P.fulgens was carried out, which indicates that n-butanol and water fractions of the plant are strongly anti-mutagenic. Inhibitory activity for n-butanol fraction was 60.4% and 35.4% in co-incubation and pre-incubation respectively in TA 98 tester strains while 55.6% and 62.0% inhibition was observed in TA100 tester strains respectively for co and pre-incubation. For water fraction 56.6% and 60.7% inhibitory activity in co-incubation and pre-incubation mode of treatment respectively against TA98 strain and 34.5% and 50.6% inhibition in TA100 strain for co-incubation and pre-incubation treatment respectively. Results specify the importance of P.fulgens as a new source of anti-mutagenic agents. Isolation of molecules from ethyl acetate and n-butanol v fractions led to the characterisation of one molecule namely catechin out of total six isolated molecules. In-silico study of various reported flavonoids were performed on CDK-2, CDK-6 as these receptors are linked to cell cycle and mutation in cell cycle may lead to cancer. In-silico study indicates that natural as well as synthetic flavonoid molecules can be considered as a treatment for cancer by inhibiting CDK-2 and CDK-6 receptors.