Targeting Pyruvate Kinase M2 and Hexokinase II, Pachymic Acid Impairs Glucose Metabolism and Induces Mitochondrial Apoptosis.

Pachymic acid (PA), a triterpenoid from Poria cocos, has various pharmacological effects, including anti-inflammatory, anti-cancer, anti-aging, and insulin-like properties. PA has gained considerable research attention, but the mechanism of its anti-cancer effects remains unclear. In this study, pyruvate kinase M2 (PKM2) was discovered as a PA target via the drug affinity responsive target stability. Molecular docking and enzyme assay revealed that PA is a competing activator of PKM2, and mimics the natural activator, fructose-1,6-bisphosphate. PKM2 activation should augment the flux of glycolysis. However, decreased glucose uptake and lactate production after PA treatment was observed in SK-BR-3 breast carcinoma cells, indicating a blockage or downregulation of glycolysis. The potential of previously reported triterpenoids in blocking hexokinase II (HK2) activity inspired us to investigate the inhibition effect of PA on HK2 activity. Molecular docking and enzyme assay confirmed that PA was an inhibitor of HK2, with an IC50 of 5.01 µM. The possible consequences of glycometabolic regulation by PA, such as dissociation of HK2 from the mitochondria, release of mitochondrial cytochrome (Cyt) c, depletion of ATP, and generation of reactive oxygen species, were further validated. Furthermore, the details of the possible linkage of targeting PKM2 and HK2 with previously reported actions of PA were discussed. The results of our study provided valuable information on the anti-cancer mechanisms of PA.

Hypomethylation of the Angiotensin II Type I Receptor (AGTR1) Gene Along with Environmental Factors Increases the Risk for Essential Hypertension.

OBJECTIVES: The present study aimed to evaluate the hypertension status of community residents, analyze environmental and epigenetic factors, and propose prevention measures for hypertension. METHODS: In our study, different methylation levels were distinguished utilizing melting temperature (Tm) values in both the case and the control group. Multiple logistic regression analysis was used to estimate the risk of having essential hypertension (EH) between hypertensive and nonhypertensive participants. A receiver-operating characteristic curve was used to analyze Tm cutoff levels of methylation. RESULTS: The average DNA Tm was 71.784 with a standard deviation of 0.210. The Tm value of community residents (Fujian, China) was inversely correlated with systolic and diastolic blood pressure. Student t test analysis showed a clear separation in Tm expression levels between the hypertensive and the control group (p < 0.05). The Tm value was lower in the hypertension group than in the normotensive group. Multivariate regression analysis showed that high levels of DNA methylation were a protective factor in hypertension with adjustment of demographic and environmental factors, whereas when the Tm value increased by 0.1 units, the risk of hypertension was reduced by 0.652 times. Patients that smoked and consumed an irregular diet demonstrated a lower degree of methylation in the presence of hypertension. CONCLUSIONS: DNA methylation affects the risk for the development of hypertension; therefore, epigenetic markers could be used to measure hypertension levels to help elucidate the pathogenesis of EH.

[A study of sub-healthy status of community residents and its relevant factors in Fuzhou City].

OBJECTIVE: To evaluate the sub-healthy status of community residents and its main relevant factors. METHODS: The proportional stratified random sampling was selected to take the sample of 5000 community residents from two communities in Fujian province. The sub-healthy status and its main influence factors were measured with the method of physical examination and questionnaire. RESULTS: The women, the oldest group (≥60 years old) and the divorce/widowed group were found to have the higher scores of sub-health status than others (P <0. 05). Multivariate analysis showed that female, age, education level and irregular eating were the main risk factors for the three dimensions of sub-health status. Divorced or widowed statue was unfavorable factors for physical and psychological sub-health status. Quit smoking was found to be significant risk factor for psychological and social sub-health status. Body mass index (BMI) was related to physical sub-health status, alone. While physical exercise was the main protective factor for sub-health status. CONCLUSION: Improving behavioral habits, maintaining stable family, maintaining normal BMI may be important to prevent sub-health status among community residents.

Study on removal of copper ions from aqueous phase by modified sepiolite flocs method.

With the improvement of environmental protection and standards, the recovery and recycling of copper ions released from industrial wastewater discharge has aroused sufficient research interest. A new adsorbent (ABsep) derived from natural sepiolite (Sep) by modification technology of hexadecyltrimethoxysilane (HDTMS) or tetraethylorthosilicate (TEOS) and flocs separation method for adsorption of Cu2+ in wastewater have been investigated in this paper. The changes of crystal structure and physicochemical properties of Sep during modification process showed that HDTMS and TEOS were loaded onto the Sep surface without inserting into the Sep interlayer structure. The adsorption experimental results presented a smaller amount of ABsep (1 g/L) achieved 97.5% removal of 50 mg/L Cu2+ at pH 6 and temperature of 298 K within a shorter contact time (50 min). It is interesting the adsorption process of Cu2+ on ABsep was spontaneous and exothermic, with physical adsorption dominating, as result of combination of physical adsorption, electrostatic gravitational force, and chemical reaction. Because of good physical-chemical adsorption performance of ABsep surface to Cu2+, high removal rates of Cu2+ from aqueous phase could be achieved after three adsorption regeneration cycles, this indicated the ABsep was expected to be a promising adsorbent of Cu2+ removal for wastewater treatment.

A study on workplace violence and its effect on quality of life among medical professionals in China.

The present study was conducted to investigate workplace violence and to examine how it is associated with quality of life (QOL) among medical professionals in China. A total of 2,464 medical professionals were selected from Fujian Province and Henan Province by using stratified cluster-sampling method. A Chinese version of the workplace violence scale was used to measure the incidence of workplace violence. The Short Form-36 Health Survey was employed to assess their QOL. Approximately 50% of the participants reported at least one type of workplace violence occurring in the previous 12 months. The multivariate analysis demonstrated workplace violence as a significant predictor for QOL among medical professionals, after controlling for other potential predictors. It suggests that the implementation of violence prevention policies and strategies to reduce workplace violence may improve QOL of medical professionals in China.