👤 Preeti Ramadoss

Traditional lipid parameters like low-density lipoprotein (LDL), high-density lipoprotein (HDL), and total cholesterol (TC) are commonly used in evaluating cardiovascular risk. Recently, emerging biomarkers such as apolipoprotein B (ApoB) and apolipoprotein A1 (ApoA1) are proposed to provide improved accuracy in assessing atherosclerotic risk. This study examined the association between conventional and novel lipid parameters and plaque burden in statin-naïve acute coronary syndrome (ACS) patients. We enrolled 81 statin-naïve patients with ACS. Each underwent both standard and extended lipid profiling. Coronary angiograms were evaluated using the Gensini score to quantify plaque burden. All participants were followed for 28 days to monitor for major adverse cardiac events (MACE). The average age was 51 years, with males comprising 77%. The ST-segment elevation myocardial infarction (STEMI) was observed in 58% of cases, non-ST-segment elevation myocardial infarction (NSTEMI) in 31%, and unstable angina in 11%. There was a significant correlation between the Gensini score and TC/HDL ratio ( The ratios of TC/HDL, LDL/HDL, and ApoB levels were positively associated with coronary plaque burden. While conventional lipid parameters continue to serve well in cardiovascular risk assessment (CRA), ApoB presents a promising standalone marker for identifying atherogenic risk and may serve as a practical alternative in clinical practice. Show less

Extracellular matrix component derangement is the major event in pathogenesis of Oral submucous fibrosis. Many studies have elaborated the alteration of the matrix components at a cellular and genetic level. However elaborate quantification of the components with varying concentrations of Areca nut extract  and commercial tobacco products have not been done so far. Primary culture of tissues sourced during crown lengthening procedures were used for establishment of fibroblast monoculture and fibroblast / keratinocyte co-culture. Extracts of areca nut, commercial smokeless tobacco products (gutkha and haans) and control CCl4 were tested at concentrations  ranging from 20 μL, 40 μL, 80 μL, 160 μL, 320 μL and time intervals of 12, 24, 48, 72 hours. Collagen quantification by spectrophotometry and SNAI1 gene expression study were done. Extract of areca nut was found to show increased collagen production than commercial tobacco products and closely similar values to CCL4. Kruskal Wallis test was used to analyse the difference in collagen obtained. The mean values of collagen obtained in co-culture were lesser than those obtained in the fibroblast monoculture. SNAI1 gene expression was negative in both the culture experiments. Areca nut extract was found to be more potent as an individual agent. Commercial smokeless tobacco products Gutka and Hans exhibited increased collagen production at higher concentration. These findings further steps up the persuasive ill effects of  tobacco products. Negative SNAI1 gene expression was corroborated to  lack of extracellular environment in the co coculture experiment. Show less

Human colorectal cancer stem cells (CSCs) are tumour initiating cells that can self-renew and are highly tumorigenic and chemoresistant. While genetic mutations associated with human colorectal cancer development are well-known, little is known about how and whether epigenetic factors specifically contribute to the functional properties of human colorectal CSCs. Here we report that the KDM3 family of histone demethylases plays an important role in tumorigenic potential and survival of human colorectal CSCs by epigenetically activating Wnt target gene transcription. The depletion of KDM3 inhibits tumorigenic growth and chemoresistance of human colorectal CSCs. Mechanistically, KDM3 not only directly erases repressive H3K9me2 marks, but also helps to recruit histone methyltransferase MLL1 to promote H3K4 methylation, thereby promoting Wnt target gene transcription. Our results suggest that KDM3 is a critical epigenetic factor in Wnt signalling that orchestrates chromatin changes and transcription in human colorectal CSCs, identifying potential therapeutic targets for effective elimination of CSCs. Show less

Transcriptional coregulators are important components of nuclear receptor (NR) signaling machinery and provide additional mechanisms for modulation of NR activity. Expression of a mutated nuclear corepressor 1 (NCoR1) that lacks 2 NR interacting domains (NCoRΔID) in the liver leads to elevated expression of genes regulated by thyroid hormone receptor (TR) and liver X receptor (LXR), both of which control hepatic cholesterol metabolism. Here, we demonstrate that expression of NCoRΔID in mouse liver improves dietary cholesterol tolerance in an LXRα-independent manner. NCoRΔID-associated cholesterol tolerance was primarily due to diminished intestinal cholesterol absorption as the result of changes in the composition and hydrophobicity of the bile salt pool. Alterations of the bile salt pool were mediated by increased expression of genes encoding the bile acid metabolism enzymes CYP27A1 and CYP3A11 as well as canalicular bile salt pump ABCB11. We have determined that these genes are regulated by thyroid hormone and that TRβ1 is recruited to their regulatory regions. Together, these data indicate that interactions between NCoR1 and TR control a specific pathway involved in regulation of cholesterol metabolism and clearance. Show less