Abnormal phosphorylation / dephosphorylation and Ca2+ dysfunction in heart failure.

Heart failure (HF) can be caused by a variety of causes characterized by abnormal myocardial systole and diastole. Ca2+ current through the L-type calcium channel (LTCC) on the membrane is the initial trigger signal for a cardiac cycle. Declined systole and diastole in HF are associated with dysfunction of myocardial Ca2+ function. This disorder can be correlated with unbalanced levels of phosphorylation / dephosphorylation of LTCC, endoplasmic reticulum (ER), and myofilament. Kinase and phosphatase activity changes along with HF progress, resulting in phased changes in the degree of phosphorylation / dephosphorylation. It is important to realize the phosphorylation / dephosphorylation differences between a normal and a failing heart. This review focuses on phosphorylation / dephosphorylation changes in the progression of HF and summarizes the effects of phosphorylation / dephosphorylation of LTCC, ER function, and myofilament function in normal conditions and HF based on previous experiments and clinical research. Also, we summarize current therapeutic methods based on abnormal phosphorylation / dephosphorylation and clarify potential therapeutic directions.

The association between blood heavy metals and gallstones: A cross-sectional study.

BACKGROUND AND AIMS: Exposure to heavy metals has been widely recognized as a risk factor for human health. However, there is limited information on the effects of blood heavy metals on gallstones. This study aims to investigate the relationship between blood heavy metals and gallstones using data from the National Health and Nutrition Examination Survey (NHANES). METHODS: 7192 participants aged 20 years or older with complete information were included in the study. Serum concentrations of heavy metals were determined by inductively coupled plasma kinetic reaction cell mass spectrometry. Gallstones were presented by standard questionnaires. Logistic regression, nonlinear, subgroup, and sensitivity analyses were used to estimate the association between blood heavy metals and gallstones. RESULTS: Multivariate logistic regression showed that the highest quintile of blood selenium (Se) was associated with a higher risk of gallstones compared with the lowest quintile (OR = 1.66, 95% CI: 1.16-2.36), particularly in individuals who were under 65 years of age, females, non-Hispanic Whites, non-drinkers, obese, and had a college education or higher. There was no correlation between blood cadmium (Cd), mercury (Hg), lead (Pb), manganese (Mn), and gallstones in the total population. Restricted cubic spline curves showed that a negative correlation was observed between blood Cd (OR = 0.84, 95% CI: 0.710-1.00), Hg (OR = 0.87, 95% CI: 0.78-0.97) and gallstones when Cd < 0.302 µg/L and Hg < 3.160 µg/L. CONCLUSIONS: Blood Se was an independent risk factor for gallstones, particularly in individuals under 65 years old, females, non-Hispanic Whites, non-drinkers, obese, and had a college education or higher. Furthermore, blood Cd and Hg were associated with a reduced risk of gallstones within a certain range.

Effect of transjugular intrahepatic portosystemic shunt on transarterial chemoembolization for hepatocellular carcinoma: a systematic review and meta-analysis.

PURPOSE: Hepatocellular carcinoma (HCC) usually occurs accompanied by portal hypertension. Transcatheter arterial chemoembolization (TACE) is recommended as an effective treatment in HCC. Recent studies had conflicting results regarding the effectiveness and safety of TACE for HCC in patients with transjugular intrahepatic portosystemic shunt (TIPS). This meta-analysis aimed to evaluate the influence of TIPS on the effectiveness and safety of TACE for patients with HCC. METHODS: A comprehensive search of studies among PubMed, Web of Science and Cochrane Library was conducted, from the earliest publishing date to January 27th, 2020. Statistical analyses were all performed using the Stata 13.0 software. I2 index statistic was used to assess heterogeneity. RESULTS: Six studies with a total of 536 patients with HCC were included in the analysis. The pooled response rate was 51% (95% CI: 25% to 77%) with a significant heterogeneity (I2=93.3%, p < 0.001). The TACE + TIPS group had an inferior response rate than the non-TIPS group, but the difference had no statistical significance (p = 0.171) and heterogeneity was low (I2=0.00%, p = 0.490). Pooled hepatic failure rate was 8.8% (95% CI: 5.2% to 12.4%) with low heterogeneity (I2=0.0%, p = 0.747). But the pooled hepatic failure rate increased to 12.7% (95% CI: 5.7% to 19.7%) with low heterogeneity (I2=11.5%, p = 0.323) if the patients who received TIPS after TACE were excluded. CONCLUSION: TIPS does not influence the effectiveness of TACE, but attention should be paid to the risk of hepatic failure.