RNA-seq analysis of A549 cells treated with chrysin or nifurtimox
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE193541 | GEO | 2022/03/01
REPOSITORIES: GEO
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Project description:RNA-seq analysis of A549 cells treated with chrysin or nifurtimox
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Project description:There is no known single therapeutic drug for treating hypercholesterolemia that comes with negligible systemic side effects. In the current study, using next generation RNA sequencing approach in mouse embryonic fibroblasts we discovered that two structurally related flavonoid compounds, Apigenin and Chrysin exhibited moderate blocking ability of multiple transcripts that regulate rate limiting enzymes in the cholesterol biosynthetic pathway. The observed decrease in cholesterol biosynthesis pathway correlated well with an increase in transcripts involved in generation and trafficking of ketone bodies as evident by the upregulation of Bdh1 and Slc16a6 transcripts. Impact statement - The hypocholesterolemic potential of Apigenin and Chrysin at higher concentrations along with their ability to generate ketogenic substrate especially during embryonic stage is useful or detrimental for embryonic health is not clear and still debatable. Our findings will set the stage for translating this information to whole animal and clinical studies that could shed light to the existing information regarding safe use of Apigenin and Chrysin, specifically to embryonic health.
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Project description:Anticancer drug sagopilone in lung cancer line A549. We performed gene expression analysis of lung cancer cell line A549 treated with sagopilone and paclitaxel. The aim was to analyse gene expression differences between the two drugs in two different concentrations. A549 cells were treated with medium containing either 2.5 nM sagopilone, 40 nM sagopilone, 4 nM paclitaxel or 40 nM paclitaxel, respectively, vehicle (ethanol 0.1%), or were left untreated for 18 hours. The two different concentrations were chosen according the phenotypes they have caused in A549 cells. Treatment with 2.5 nM sagopilone, 4 nM paclitaxel induced an aneuploid cell population, whereas treatment with 40 nM sagopilone and 40 nM paclitaxel induced mitotic arrest.
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Project description:Pulmonary arterial hypertension (PAH) is a debilitating progressive disease characterized by high blood pressure in the pulmonary artery. Chrysin (5,7-dihydroxyflavone) is a phytochemical, which is a flavonoid widely present in plant sources. It is known that right ventricular dysfunction is the worst mortality predictor in patient with PAH. Recent studies have shown that chrysin improves hemodynamic parameters including right ventricular pressure, right ventricular hypertrophy, and pulmonary vascular remodeling in a rat model of chronic hypoxia-induced pulmonary hypertension. On the other hand, trimetazidine (TMZ) is an anti-ischemic agent widely used in the treatment of coronary artery disease. It has been reported that trimetazidine therapy for 3 months on top of standard PAH regime significantly improve right ventricular ejection fraction and functional capacity in patient with PAH. However, the effects of chrysin or trimetazidine on gene expression in lung of patient with PAH. Here, we performed that a comprehensive analysis of gene expression changes in lung tissues of sugen-received rats under hypoxic conditions, which is a model of PAH with chrysin or trimetazidine treatment using RNA sequencing (RNA-seq).
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Project description:Pulmonary arterial hypertension (PAH) is a progressive disease characterized by pulmonary vascular remodeling leading to increased pulmonary vascular resistance and right ventricular (RV) hypertrophy, resulting in RV failure. RV dysfunction is a complex process that leads to cardiomyocyte hypertrophy, fibrosis, inflammation, angiogenesis, and metabolic changes. In patient with PAH, the adaptation of the RV to high pulmonary arterial pressures is the most important determinant of prognosis. However, the underlying molecular mechanism of adverse RV remodeling and dysfunction is poorly understood, and there are no currently approved therapies that improve RV function. Chrysin (5,7-dihydroxyflavone) is a phytochemical, which is a flavonoid widely present in plant sources. In various experimental models chrysin has shown to exert cardio-protective effects through its antioxidant and anti-inflammatory effects. In this study, we performed a comprehensive analysis of gene expression changes in heart tissues of rats under hypoxic conditions with chrysin treatment using RNA sequencing (RNA-seq).
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Project description:In the current study, we investigated the modulatory effect of epigallocatechin gallate (EGCG, an active derivative of green tea) on cellular miRNA expression and cell cycle proliferation in NSCLCs (A549). As the IC50 value of EGCG is approximately 304 μM, our studies support the resistance of A549 lung cancer cell by EGCG. In addition, it was interesting to observe its G0/G1 cell cycle arrest activity at 40μM EGCG treatment. So, in the present study, next-generation sequencing (NGS) was used to study the miRNA expression between the cancer control and EGCG-treated samples. A549 cells were treated with 40 μM and 100 μM EGCG. NGS was employed to study the differential expression of novel and known miRNAs. The data generated was analysed with computational approach to study and correlate the expression profiles of both known and novel miRNAs. Differential expression of known miRNAs was observed between control and EGCG-treated samples. Some putative novel miRNA sequences were also observed in the current study. The differential expression levels of putative novel miRNA sequences were estimated by counting the number of reads in the given dataset. Together the analysis of these miRNA profiles revealed log2-fold modulation in the expression levels. We detected 344, 337, and 346 number of known mature miRNAs in control, 40 μM EGCG treated, and 100 μM EGCG treated samples, respectively. We also reported 119, 126, and 125 number of putative novel mature miRNA sequences in control, 40 μM EGCG treated, and 100 μM EGCG treated samples, respectively. In conclusion, the analysis demonstrates that EGCG is actively involved in miRNA modulation in NSCLCs, which further attests to its chemoprotective role and could play a major role in therapeutic applications.
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