Global prevalence of diet low in calcium and the disease burden: results from the Global Burden of Disease Study 2019.

BACKGROUND: Due to the essential role of calcium in vital biological functions, diet low in calcium (DLC) is associated with various diseases. However, there is a lack of study about the current prevalence and health burden due to DLC using reliable data sources. METHODS: We used data from the Global Burden of Disease study 2019 (GBD 2019) to estimate the prevalence and health burden of DLC in 204 countries from 1990 to 2019, by age, sex, and sociodemographic index (SDI). The estimates were produced in DisMod-MR 2.1, a Bayesian meta-regression tool. Summary exposure value (SEV) was used to show the prevalence of DLC, while diseases adjusted life year (DALY) was used to represent the disease burden. The disease burden was estimated for DLC-induced colorectal cancer. Spearman Rank Order correlation was used for correlation analysis, and estimated annual percentage (EAPC) was used to reflect the temporal trends. RESULTS: From 1990 to 2019, the global prevalence of DLC decreased (EAPC of SEV, -0.47; 95% CI, -0.5 to -0.43), but have increased in Oceania region and in many countries, such as United Arab Emirates, New Zealand, Japan, and France. The global DALYs associated with low in calcium were estimated to be 3.14 million (95% uncertainty interval (UI), 2.25-4.26 million) in 2019, with an age standardized rate of 38.2 (95% UI, 27.2-51.8) per 100,000. Unlike the prevalence, the global age standardized DALY rates has remained unchanged (EAPC, -0.03; 95% CI, -0.12 to 0.07), but has increased in over 80 of the 204 countries, located mainly in Asia, Africa, and South America. In all years and regions, the age standardized SEV and DALY rates were higher in male people than that in female people. The prevalence (rho = -0.823; P < 0.001) and disease burden (rho = -0.433; P < 0.001) associated with diet in low calcium were strongly correlated to SDI. The prevalence decreased with age, but the DALY rates increased with age and peaked at about 90 years. The prevalence of DLC has decreased worldwide and in most countries, but the disease burden of DLC induced colorectal cancer has increased in over 40% of countries worldwide. CONCLUSION: Countries with low sociodemographic level and male people are more likely to experience the risk of DLC and related disease burden. Related measures in improve dietary calcium intake are in need to address diet in low calcium related health problems.

PRR34-AS1 promotes mitochondrial division and glycolytic reprogramming in hepatocellular carcinoma cells through upregulation of MIEF2.

LncRNA PRR34-AS1 overexpression promotes the proliferation and invasion of hepatocellular carcinoma (HCC) cells, but whether it affects HCC energy metabolism remains unclear. Mitochondrial division and glycolytic reprogramming play important roles in tumor development. In this study, the differential expression of PRR34-AS1 is explored via TCGA analysis, and higher levels of PRR34-AS1 are detected in patients with liver cancer than in healthy individuals. A series of experiments, such as CCK-8, PCR, and immunofluorescence staining, reveal that the proliferation, invasion, glycolysis, and mitochondrial division of PRR34-AS1-overexpressing hepatoma cells are significantly promoted. TCGA analysis and immunohistochemistry reveal high expression of the mitochondrial dynamin MIEF2 in liver cancer tissues. Dual-luciferase reporter assays confirm that miR-498 targets and binds to mitochondrial elongation factor 2 (MIEF2). In addition, we show that PRR34-AS1 can sponge miR-498. Therefore, we further investigate the effects of the lncRNA PRR34-AS1/miR-498/MIEF2 axis on the growth, glucose metabolism, and mitochondrial division in hepatocellular carcinoma cells. A series of experiments are performed on hepatocellular carcinoma cells after different treatments. The results show that the proliferative activity, invasive ability, and glycolytic level of hepatocellular carcinoma cells are decreased in HCC cells with low PRR34-AS1 expression, and the miR-498 expression level is increased in these cells. Inhibition of miR-498 or overexpression of MIEF2 restored the proliferative activity, invasive ability, glycolysis, and mitochondrial division in hepatocellular carcinoma cells. Thus, PRR34-AS1 regulates MIEF2 by sponging miR-498, thereby promoting mitochondrial division, mediating glycolytic reprogramming and ultimately driving the growth and invasion of HCC cells. Furthermore, in vivo mouse experiments yield results similar to those of the in vitro experiments, verifying the above results.

Cancer burden attributable to risk factors, 1990-2019: A comparative risk assessment.

An up-to-date comprehensive assessment of the cancer burden attributable to risk factors is essential for cancer prevention. We analyzed the population attributable fraction (PAF) of cancer disability-adjusted life years (DALYs) attributable to 11 level 2 risk factors using data from the Global Burden and Disease Study (GBD) 2019. We highlighted that almost half of the cancer DALYs can be preventable by modifying relevant risk factors. The attributable cancer DALYs increased by 60.42%-105.0 million from 1990 to 2019. Tobacco, dietary risks, alcohol use, high body-mass index, and air pollution were the top five risk factors. The PAFs attributable to high fasting plasma glucose, high body-mass index, and low physical activity have increased worldwide from 1990 to 2019. Unsafe sex was the leading risk factor for women before age of 54. Tailored prevention programs targeted at specific populations should be scaled up to reduce the cancer burden in the future.

miR-33a-5p Targets RAP2A to Mediate the Sensitivity of Gastric Cancer Cells to 5-FU.

Objective: The objective of this study is to explore the effects of microRNA-33a-5p (miR-33a-5p)-ras-related protein Rap-2a (RAP2A) on biological functions of gastric cancer (GC) and to find the potential functional mechanism. Methods: We measured the miR-33a-5p expression in 30 GC tissues and cellular level and 30 adjacent normal tissues as control. Besides, the expression of miR-33a-5p was checked at cell level as well. To screen the possible targets of miR-33a-5p, prediction software was used and gene RAP2A attracted our attention. Through a series of experiments including real-time polymerase chain reaction (qRT-PCR), luciferase assay, and western blotting (WB), we verified RAP2A as a potential target of miR-33a-5p. The impacts of miR-33a-5p and RAP2A on biological functions of GC cell lines (BGC-823 and MGC-803) were analyzed by subsequent experiments. Cell invasion was tested by invasion assays. Cell proliferation was measured by cell counting kit-8 (CCK-8) assay. Cell clone was measured by clone formation assays. Finally, the expression of RAP2A protein was analyzed by WB assay. Results: We found miR-33a-5p was expressed lowly in GC tissues and cells. Overexpression of miR-33a-5p in BGC-823 and MGC-803 cells greatly inhibited the cell invasion and colony number. Furthermore, compared to sh-control (shControl), RAP2A knockdown (sh-RAP2A/shRAP2A) raised the sensitivity of GC cells to 5-FU significantly, characterized as reducing cell apoptosis. Conclusions: The expression of miR-33a-5p was lower in GC cell lines and tissues obviously, indicating that miR-33a-5p served as the antitumor gene in GC. The expression of RAP2A regulated negatively the sensitivity of GC cells to 5-FU. According to our in vitro experiments, miR-33a-5p/RAP2A was likely to become a new therapeutic target for GC.

Disassociation between left ventricular mechanical and electrical properties in ischemic rat heart after G-CSF treatment.

OBJECTIVE: The effect of granulocyte colony-stimulating factor (G-CSF) on post-infarct ventricular remodeling remains controversial. We hypothesized that the timing of G-CSF administration after myocardial ischemia plays an important role in determining its efficacy. METHODS: Rat myocardial ischemia was induced by 60 min coronary ligation and reperfusion. Surviving animals received G-CSF after 1 h (E-G) or 24 h (D-G) of reperfusion randomly at 100 µg/kg/d for five consecutive days. 7 days or 3 months post-ischemia, rat hearts were quickly removed for ex vivo electrophysiological measurements or histological analysis (collagen disposition and angiogenesis) and metalloproteinase-2 and -9 activity assays (gelatin zymography). Left ventricular (LV) invasive hemodynamic analysis was performed in 3-month recovery animals before sacrifice. RESULTS: At 3 months post ischemia, LV mechanical remodeling was further impaired with early G-CSF administration (0.65 ± 0.17%, 13.21 ± 7.36 mmHg, -4,684 ± 1,560 mmHg/s) compared with the control group (0.28 ± 0.12%, 6.45 ± 3.43 mmHg, -6,267 ± 1,111 mmHg/s) and D-G group (0.34 ± 0.12%, 7.90 ± 5.33 mmHg, -6,227 ± 1,075 mmHg/s) as shown by increased expansion index (P < 0.01), deterioration of myocardial function with increased LVDP (P < 0.05), and decreased -dP/dt (max) (P < 0.05). By contrast, there was a significant increase in electrical properties including monophasic action potential (MAP) 90 dispersion (12.58 ± 4.46 vs. 30.56 ± 6.17 ms at 7 days; 18.54 ± 4.31 vs. 34.78 ± 5.24 ms at 3 months; P < 0.05 for both) and inducibility of ventricular arrhythmias (4.78 ± 1.19 vs. 11.58 ± 2.76 ms at 3 months; P < 0.05) with early G-CSF treatment compared with the control group. CONCLUSIONS: Both early and delayed administrations of G-CSF can improve electrophysiological properties after myocardial ischemia, but have no beneficial effects on LV mechanical remodeling.

Effects of intramyocardial injection of platelet-rich plasma on the healing process after myocardial infarction.

OBJECTIVE: Platelet activation and subsequent release of granules containing a variety of growth factors, at the site of injury, is crucial for the wound healing process. We postulated that a platelet-mediated paracrine effect may accelerate the healing process after myocardial infarction. METHODS: Allogenic platelet-rich and platelet-poor plasma (PRP and PPP) were collected from 15 healthy male Wistar rats. After thrombin activation, the level of vascular endothelial growth factor (VEGF) in PRP and PPP was measured by enzyme-linked immunosorbent assay. A rat model of myocardial infarction was induced by permanent ligation of the left anterior descending artery, and thrombin-activated PRP and PPP, respectively, were injected into the ischemic region. Seven days and 28 days after operation, surviving rats were killed. Ex-vivo left ventricular pressure-volume relationship was performed to evaluate passive diastolic function. Collagen analysis was performed by picrosirius red staining plus polarized microscopy. Angiogenesis and arteriogenesis were evaluated by immunofluorescent staining. RESULTS: After thrombin activation, VEGF level in PRP was significantly higher than that in PPP (187.5+/-45.5 vs. 30.1+/-7.8 pg/ml, P<0.01). Injection of thrombin-activated PRP into the infarcted area resulted in improvement of ventricular remodeling and accelerated healing, as demonstrated by limitation of ventricular expansion, attenuation of myocardial hypertrophy in the noninfarct region, facilitation of angiogenesis and arteriogenesis in the infarct. CONCLUSION: Injection of thrombin-activated PRP could modulate favorably the postinfarction remodeling process. Platelet-released VEGF may participate in this protective effect.

Neural remodeling may partly contribute to the abnormality of excitation-contraction coupling in heart failure.

Heart failure (HF) is a major and growing public health problem in the world. About 50% of deaths in HF occur suddenly due to malignant arrhythmia. Therefore, exploring the further mechanisms of chronic HF and finding new therapy targets are essential for the progression of HF treatment. Recently, some published papers suggested that myocardial neural remodeling and abnormal excitation-contraction (EC) coupling might partly contribute to the development of HF and sudden cardiac death. Even though a few studies have demonstrated that the sympathetic nerve system (SNS) may have significant impact on the functional states of myocardial EC coupling through the beta-adrenergic signaling pathway, so far, it still remains unknown that whether neural remodeling affects the EC coupling. Studies from Marks' group demonstrated that 70% of cardiac ryanodine receptors (RyR2), which located on the sarcoplasmic reculum (SR) controlling intracellular Ca(2+) release and muscle contraction in the heart, from failing hearts were abnormal and only 15% exhibited the most severe defects. In addition, Litwin et al. observed that temporal and spatial heterogeneities in local Ca(2+) release events in a rabbit model of HF after myocardial infarction. Because some studies have demonstrated that chronic SNS hyperactivity in HF led to protein kinase A (PKA) hyperphosphorylation of RyR2 in the heart, and the myocardial sympathetic nerve distribution become heterogeneous in the setting of HF. Thus, it is reasonable for us to propose the hypothesis that neural remodeling may partly account for the abnormality of EC coupling in HF.

Increased levels of interleukin-6 and matrix metalloproteinase-9 are of cardiac origin in acute coronary syndrome.

OBJECTIVES: To investigate the association between inflammatory mediators, matrix degrading enzymes and acute coronary syndrome (ACS) and the impact of early reperfusion therapy on circulating biomarkers. DESIGN: Peripheral serum levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) and matrix metalloproteinase-9 (MMP-9) were determined in 134 patients with ACS. These biomarkers were serially monitored in ten patients with intravenous thrombolytic therapy (IVT). RESULTS: Serum levels of IL-6, hs-CRP and MMP-9 were higher in unstable angina (UA) and myocardial infarction (MI) groups than in control or SA group (p<0.05). Peripheral IL-6 level in patients with MI was greater after percutaneous coronary intervention (PCI) (p<0.01) or IVT (p<0.05). Serial concentration determination revealed marked elevation of serum IL-6 and MMP-9 levels, both reaching peak values (like creatine kinase-MB). CONCLUSIONS: Elevated levels of IL-6, hs-CRP and MMP-9 provide a link between inflammation, matrix degradation and the development and progression of ACS. IL-6 and MMP-9 appear to be released mainly from vulnerable plaque or necrotic myocardium during the acute phase of MI.

Enhancement of endogenous defenses against ROS by supra-nutritional level of selenium is more safe and effective than antioxidant supplementation in reducing hypertensive target organ damage.

Hypertension-induced target organ damage (TOD), is one of the leading causes of morbidity and mortality. Reactive oxygen species (ROS) play an important role in the pathogenesis and development of hypertension. It has been suggested that hypertension-induced TOD is related to the level of oxidative stress, but is in part independent of the level of blood pressure. Therefore, in addition to anti-hypertensive drug therapy, novel strategies against ROS, will provide additional benefits to patient with hypertension. Vitamin E has long been supplemented as an effective antioxidant. However, the potential hazardous effects of vitamin E supplementation as antioxidant revealed by recent studies make its clinical and routine use prudent. Therefore, novel approaches capable of enhancing endogenous system to defend against ROS are required. Here, we propose that enhancement of intrinsic defenses against ROS by supra-nutritional level of selenium is more safe and effective than antioxidant supplementation in reducing hypertensive target organ damage, owing to its role in activating and constitution of native vital proteins and/or enzymes against oxidative stress, and the fact that scarcity of selenium can not be supplemented by normal food, and potentially extra benefits by supra-normal intake.

[Analysis of factors correlated to death and reinfarction in patients with acute myocardial infarction].

OBJECTIVE: To identify the predictors of death and reinfarction in patients with acute myocardial infarction (AMI) treated with urokinase (UK) thrombolysis or percutaneous transluminal coronary angioplasty (PTCA). METHODS: In ambispective cohort study, 97 cases of AMI were treated with UK thrombolytic therapy, while 93 cases of AMI were treated with PTCA. The patients' data about clinical outcome during hospital and follow-up periods were collected. Death and reinfarction were defined as adverse event. To analyze the correlative factors and independent predictors of death and reinfarction, the spearman rank correlation and multivariate logistic regression modeling were performed. RESULTS: During hospital,incidences of adverse event were 15.46 percent and 6.45 percent in UK and PTCA groups respectively. In follow-up period, they were 30.93 percent and 9.68 percent respectively. Age, Q wave leads, Kill ip class, heart failure in hospital, the history of hypertension and myocardial infarction were positive correlation with adverse event, whereas history of smoking, systolic blood pressure and ejection fraction (EF) showed negative correlation with the adverse event. The interventional therapy, associated with lower mortality and reinfarction rate, was the independent predictor for adverse event in UK and PTCA groups during hospital and follow-up periods. Furthermore, it was the only independent predictor for PTCA group. In UK group, the adverse event also was independently predicted by age, heart failure and Q wave leads in hospital and by age, heart failure during follow-up period. There was negative correlation between preinfarction angina and adverse event, and positive correlation between thrombolysis and adverse event inpatients undergone rescue PTCA. CONCLUSION: Interventional therapy is crucial independent predictor for adverse event of patients suffering from AMI. The adverse event is also predicted by age, Q wave leads and heart failure. The history of preinfarction angina is negative correlation with the adverse event in hospital, due to, maybe, myocardium ischemia preconditioning.