Heterogeneous nuclear ribonucleoprotein K (hnRNPK) is an RNA/DNA-binding protein involved in chromatin remodeling, RNA processing and the DNA damage response. In addition, increased hnRNPK expression has been associated with tumor development and progression. A variety of post-translational modifications of hnRNPK have been identified and shown to regulate hnRNPK function, including phosphorylation, ubiquitination, sumoylation and methylation. However, the functional significance of hnRNPK arginine methylation remains unclear. In the present study, we demonstrated that the methylation of two essential arginines, Arg296 and Arg299, on hnRNPK inhibited a nearby Ser302 phosphorylation that was mediated through the pro-apoptotic kinase PKCδ. Notably, the engineered U2OS cells carrying an Arg296/Arg299 methylation-defective hnRNPK mutant exhibited increased apoptosis upon DNA damage. While such elevated apoptosis can be diminished through addition with wild-type hnRNPK, we further demonstrated that this increased apoptosis occurred through both intrinsic and extrinsic pathways and was p53 independent, at least in part. Here, we provide the first evidence that the arginine methylation of hnRNPK negatively regulates cell apoptosis through PKCδ-mediated signaling during DNA damage, which is essential for the anti-apoptotic role of hnRNPK in apoptosis and the evasion of apoptosis in cancer cells.

Anemia defined as reduced hemoglobin levels of red blood cells may carry less oxygen to skeletal muscle and impair physical performance. Previous studies have shown that exercise intolerance was related to moderate or severe anemia, however, the relationship to mild anemia was unknown. We investigated the cross-sectional association of mild anemia defined as a hemoglobin level of 10.0–13.9 g/dL with physical fitness in 3,666 military young males in Taiwan in 2014. Aerobic fitness was evaluated by 3000-meter run test, and anaerobic fitness was evaluated by 2-minute sit-ups and 2-minute push-ups, respectively. Multiple logistic regressions for the best 10% and the worst 10% performers were used to determine the relationship. There were 343 mild anemic males in whom 47.8% were microcytic anemia and 3,323 non-anemic males for the analysis. The multiple logistic regression shows that as compared with non-anemic males, mild anemic males were more likely to be the worst 10% performers in the 3000-meter run test (odds ratios (OR) and 95% confidence intervals: 1.47, 1.01–2.14) after adjusting for age, service specialty, body mass index, waist size, mean blood pressure, unhealthy behaviors, lipid profiles, and exercise frequency. On the contrary, mild anemic males had higher possibility to be the best 10% performers in the 2-minute push-ups test (OR: 1.48, 1.08–2.04). However, there was no association between mild anemia and 2-minute sit-ups. Our findings suggest that unspecified mild anemia might be associated with lower cardiorespiratory fitness but not with anaerobic fitness in physically active military males.

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We employed a population-based cohort sample to explore the risk of coronary heart disease (CHD) in relation to osteoporosis in an Asian population.We designed a retrospective population-based cohort study from 2000 to 2010 with data obtained from Taiwan's Longitudinal Health Insurance Database. A total of 19,456 patients aged 45 years or older who had no history of CHD and had a diagnosis of osteoporosis were identified as the osteoporosis cohort. The patients in the comparison cohort were randomly selected and frequency matched according to age, sex, and year of index date at a 1:1 ratio. Both cohorts were followed from the index date until a new diagnosis of CHD was made. Baseline variables, comorbidities, and bisphosphonate and estrogen prescriptions were collected.The overall incidence of CHD was 23.5 (per 1000 person-years) for the osteoporosis cohort and 16.7 for the comparison cohort, with a mean follow-up of 6.54 years and 6.63 years, respectively. The hazard ratio (HR) for developing CHD during follow-up was 1.30 (95% confidence interval [CI], 1.23–1.38) for the osteoporosis cohort compared with the comparison cohort after adjusting for age, sex, comorbidities, and estrogen medication. Patients with osteoporosis who received treatment with bisphosphonates or with both bisphosphonates and estrogen exhibited a significantly lower risk for CHD (adjusted HR = 0.37 and 0.23) than those who did not receive either of these 2 medications.The results support an association between osteoporosis and CHD in Asian population.

miRNAs have emerged as important regulators of lipoprotein metabolism. Work over the past few years has demonstrated that miRNAs control the expression of most of the genes associated with high-density lipoprotein (HDL) metabolism, including the ATP transporters, ABCA1 and ABCG1, and the scavenger receptor SRB1. These findings strongly suggest that miRNAs regulate HDL biogenesis, cellular cholesterol efflux, and HDL cholesterol (HDL-C) uptake in the liver, thereby controlling all of the steps of reverse cholesterol transport. Recent work in animal models has demonstrated that manipulating miRNA levels including miR-33 can increase circulating HDL-C. Importantly, antagonizing miR-33 in vivo enhances the regression and reduces the progression of atherosclerosis. These findings support the idea of developing miRNA inhibitors for the treatment of dyslipidaemia and related cardiovascular disorders such as atherosclerosis. This review article focuses on how HDL metabolism is regulated by miRNAs and how antagonizing miRNA expression could be a potential therapy for treating cardiometabolic diseases.

Improved prevention and treatment of cardiovascular diseases (CVD) is one of the challenges in Western societies, where ischemic heart disease and stroke are the leading cause of death. Early epidemiological studies have shown an inverse correlation between circulating high-density lipoprotein cholesterol (HDL-C) and cardiovascular disease (CVD). The cardioprotective effect of HDL is due to its ability to remove cholesterol from plaques in the artery wall to the liver for excretion by a process known as reverse cholesterol transport (RCT). Numerous studies have reported the role that microRNAs (miRNAs) play in the regulation of the different steps in RCT, including HDL biogenesis, cholesterol efflux, cholesterol uptake in the liver and bile acid synthesis and secretion. Due to their ability to control different aspects of HDL metabolism and function, miRNAs have emerged as potential therapeutic targets to combat CVDs. In this review, we summarize the recent advances in the miRNA-mediated control of HDL metabolism. We also discuss how HDL particles serve as carriers of miRNAs and the potential use of HDL-containing miRNAs as CVD biomarkers.

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