ABSTRACT
BACKGROUND: The prevalence of cardiovascular disease (CVD) has been continuously increasing, and this trend is projected to continue. CVD is rapidly becoming a significant public health issue. Every year there is a spike in hospital cases of CVD, a critical health concern in lower- and middle-income countries. Based on identification of novel biomarkers, it would be necessary to study and evaluate the diagnostic requirements or CVD to expedite early detection. MAIN BODY: The literature review was written using a wide range of sources, such as well-known medical journals, electronic databases, manuscripts, texts, and other writings from the university library. After that, we analysed the specific markers of CVD and compiled a systematic review. A growing body of clinical research aims to identify people who are at risk for cardiovascular disease by looking for biomolecules. A small number of biomarkers have been shown to be useful and reliable in medicine. Biomarkers can be used for a variety of clinical applications, such as predicting heart disease risk, diagnosing disease, or predicting outcomes. As a result of the ability for a single molecule to act as a biomarker, its usefulness in medicine is expected to increase significantly. CONCLUSIONS: Based on assessing the current trends in the application of CVD markers, we discussed and described the requirements for the application of CVD biomarkers in coronary heart disease, cerebrovascular disease, rheumatic heart disease, and other cardiovascular illnesses. Furthermore, the current review focuses on biomarkers for CVD and the procedures that should be considered to establish the comprehensive nature of the expression of biomarkers for cardiovascular illness.
ABSTRACT
BACKGROUND: Cancer is an outcome of uncontrolled cell division eventually associated with dysregulated epigenetic mechanisms, including DNA methylation. DNA methyltransferase 1 is ubiquitously expressed in the proliferating cells and is essential for the maintenance of DNA methylation. It causes the abnormal silencing of tumor suppressor genes in human cancer which is necessary for proliferation, cell cycle progression, and survival. DNMT1 is involved in tumorigenesis of several cancers, its upregulation potentially upscale the promoter level inactivation of transcription of a tumor inhibitory gene by introducing repressive methylation marks on the CpG islands. This epigenetic perturbation caused by DNMT is targeted for cancer therapeutics. PURPOSE: To demonstrate the proliferative inhibitory potential of brazilin in human breast cancer cell line (MCF-7) with concurrent mitigation of DNMT1 functional expression and to understand its effect on downstream targets like cell cycle inhibitor p21. STUDY DESIGN/ METHODS: The impact of brazilin on the growth and proliferation of the MCF-7 cells was determined using the XTT assay. The global DNA 5-methyl cytosine methylation pattern was analyzed upon brazilin treatment. The gene and protein expression of DNMTs were determined with quantitative RTPCR and western blots respectively. The potential binding sites of transcription factors in the human DNMT1 promoter were predicted using the MatInspector tool on the Genomatix software. The chromatin immunoprecipitation (ChIP) assay was performed to demonstrate the transcription factors occupancy at the promoter. Methylation of promoter CpG islands was determined by the methylation-specific PCR (MSP) upon brazilin treatment. The molecular docking of the human DNMT1 with brazilin (ligand) was performed using the Schrödinger suite. RESULTS: The heterotetracyclic compound brazilin, present in the wood of Caesalpinia sappan, inhibited the proliferation of the human breast cancer cell line (MCF-7) and reduced the DNMT1 expression with a decrease in global DNA methylation. Brazilin, by activating p38 MAPK and elevating p53 levels within the exposed cells. The elevated level of p53 enriched the occupancy at binding sites within 200 bp upstream to the transcription start site in the DNMT1 promoter, resulting in reduced DNMT1 gene expression. Furthermore, the brazilin restored the p21 levels in the exposed cells as the CpGs in the p21 promoter (-128 bp/+17 bp) were significantly demethylated as observed in the methylation-specific PCR (MSP). CONCLUSION: Highly potential anti-proliferative molecule brazilin can modulate the DNMT1 functional expression and restore the cell cycle inhibitor p21expression. We propose that brazilin can be used in therapeutic interventions to restore the deregulated epigenetic mechanisms in cancer.
