Ubiquitin Regulation: The Histone Modifying Enzyme\u27s Story

Histone post-translational modifications influence many fundamental cellular events by regulating chromatin structure and gene transcriptional activity. These modifications are highly dynamic and tightly controlled, with many enzymes devoted to the addition and removal of these modifications. Interestingly, these modifying enzymes are themselves fine-tuned and precisely regulated at the level of protein turnover by ubiquitin-proteasomal processing. Here, we focus on recent progress centered on the mechanisms regulating ubiquitination of histone modifying enzymes, including ubiquitin proteasomal degradation and the reverse process of deubiquitination. We will also discuss the potential pathophysiological significance of these processes

The Landscape of Histone Modification in Cancer Metastasis

Metastasis represents one of the most devastating aspects of cancer. Epithelial to mesenchymal transition (EMT) has been shown to play a critical role in tumorigenic metastasis. During metastatic progression, both genetic and epigenetic modifications endow cancer cells with properties that modulate the capacity for metastatic success. Histone modification is profoundly altered in cancer cells and contributes to cancer metastasis by controlling different metastatic phenotypes. Here, we first review histone modifications and discuss their roles in EMT and metastasis, with a particular focus on histone methylation and acetylation. Second, we review the major histone modification enzymes that control chromatin in cancer metastasis. Third, we discuss the transcriptional regulation concerted by these enzymes with EMT transcription factors at different molecular layers. Finally, we discuss pharmacologic manipulation of histone modification enzymes for metastasis treatment. A comprehensive understanding of histone modification in metastasis will not only provide new insights into our knowledge of cancer progression and metastasis, but also offer a novel approach for the development of innovative therapeutic strategies

Association of blood pressure with development of metabolic syndrome components: a five-year retrospective cohort study in Beijing

Background: Raised blood pressure (BP) is associated with the incidence of metabolic syndrome (MetS). It is unknown if subjects with different BP levels may develop certain components of MetS over time. We investigated the incidence of MetS relative to different levels of BP over a 5-year period in a Chinese population in Tongren Hospital, Beijing. Methods: During the period of 2006–2011, we recruited 2,781 participants with no MetS, or self-reported type 2 diabetes, dyslipidemia, hypertension, or cardiovascular disease at baseline. Association rule was used to identify the transitions of MetS components over time. Results: The incidence of MetS at follow-up was 9.74% for men and 3.21% for women in the group with optimal BP; 10.29% and 7.22%, respectively, in the group with normal BP; 10.49% and 10.84%, respectively, in the group with high-normal BP; and 14.48% and 23.21%, respectively in the group with high BP. The most common transition was from healthy to healthy in the groups with optimal or normal BP (17.9–49.3%), whereas in the high-normal BP group, 16.9-22.1% of subjects with raised BP returned to healthy status or stayed unchanged, while 13.8-21.4% of people with high BP tended to develop raised fasting glucose levels. Conclusions: The incidence of MetS increased in parallel with the increase in BP. People with optimal and normal BP levels were less susceptible to developing MetS over time, whereas abnormal BP seemed to be a pre-existing phase of MetS. High-normal BP was a crucial status for MetS prevention

Plasma Clearance of Lovastatin Versus Chinese Red Yeast Rice in Healthy Volunteers

Objectives: It is now accepted that inhibition of cholesterol biosynthesis is effective in the primary and secondary prevention of heart disease. However, the perceived side-effects on muscle and liver reduce the general acceptance of statin drug therapy as well as compliance over the long term, which is necessary for prevention efforts to be successful. Chinese red yeast rice (CRYR) is a supplement containing lovastatin (monacolin K), eight other monacolins, pigments, tannins, and other phytochemicals. The authors previously reported on a double- blind placebo-controlled trial of CRYR supplement in 80 individuals demonstrating a significant decrease in cholesterol levels from 250 mg/dL to 210 mg/dL over 8 weeks independent of diet. The current study compared the pharmacokinetics of CRYR with lovastatin at the same bioeffective dose for lowering cholesterol. Methods: Eleven (11) healthy volunteers were randomized to a crossover study taking 2400 mg CRYR or 20 mg of lovastatin. Results: The Cmax and area under the curve (AUC) of lovastatin were 22.42 ng/mL, and 80.47 higher than CRYR (p = 0.001 and 0.002, respectively). The Cmax for lovastatin hydroxy-acid was 36.63 ng/mL higher than the Cmax of CRYR hydroxy-acid (p = 0.001). The AUC of lovastatin hydroxy-acid was 258.5 greater than that of CRYR (p = 0.001). Conclusions: The results suggested that the effect of CRYR on the cholesterol concentration might be caused by the additive and/or synergistic effects of monacolin K with other monacolins and substances in CRYR. It may lead to the ultimate development of a botanical supplement based on CRYR

Fractal characteristics of pore structures on different coal structures and its research significance

The occurrence and production of coalbed methane is related to the development degree of pore system in coal reservoirs. The pore structure characteristics of original structural coal seam will change significantly after damage and deformation, thus affecting the adsorption/desorption and diffusion process of coalbed methane. Through the low-temperature liquid N2 and low-pressure CO2 adsorption analysis and isothermal adsorption experiments on coal with different structures from the No. 3 coal seam in Zhaozhuang coalfield in Qinshui Basin, the variation laws of pore structure and adsorption of coals with various destructive strengths were analyzed. Applying experimental data and numerical fractal modeling, the pore fractal characteristics of coal with different structures and their effects on methane adsorption and diffusion in coal were revealed. The results shown that with the increase of the destructive intensity of coal structures, the specific surface area and pore volume of coal increased, the proportion of 50-300 nm pores gradually decreased, the micropores and mesopores of 2-50 nm and ultra-micropores of less than 2 nm increased. As the main adsorption pores in coal, the ultra-micropores size was mainly distributed in 0.45-0.65 nm and 0.80-1.0 nm. The adsorption amount of N2, CO2 and CH4 increased with the increasing destructive degree of coal structure. The order of adsorption capacity from large to small was: intact coal>mylonitic coal > granulated coal > cataclastic coal. The fractal dimensions of the micro-, meso- and macro-porous structures indicated that the pore structure of tectonically deformed coals will be simplified. Coal with a higher damage intensity had a rougher pore surface (corresponding to a higher D1) and a more homogeneous pore size distribution (corresponding to a lower D2). The fractal dimension of ultra-microporous (Dm) gradually increased with the increasing structural destruction intensity of coal, and was positively correlated with Langmuir constant (VL) and the corresponding specific surface area, indicating that the increase of coal surface roughness led to the increase of specific surface area, which provided more adsorption points with high adsorption potential for gas adsorption and enhanced the adsorption capacity of coal. The effective diffusion coefficient and pore volume were positively correlated with the fractal dimensions D1 and negatively correlated with D2, which indicated better pore connectivity, increased pore volume, improved gas inlet and outlet efficiency, and enhanced gas diffusion efficiency of destroyed intact coal

Association between γ-glutamyl transferase and metabolic syndrome: A cross-sectional study of an adult population in Beijing

The relationship between liver enzymes and clustered components of metabolic syndrome (MetS) is explored and the predictive power of γ-glutamyl transferase (GGT) for the diagnosis of MetS in an adult population in Beijing is investigated. A total of 10,553 adults aged 20-65 years who underwent health examinations at Beijing Tongren Hospital in 2012 were enrolled in the study. Multivariate logistic regression analysis is conducted to determine the associations between the levels of various liver enzymes and clustered components of MetS. A receiver operating characteristic analysis is used to determine the optimal cut-off value of GGT for the diagnosis of MetS. A high level of GGT is found to be positively associated with clustered components of MetS in both men and women after adjusting for age, body mass index (BMI), history of alcoholic fatty liver, and the presence of taking anti-hypertensive, anti-dyslipidemic, and anti-diabetic drugs. Among all components of MetS, GGT is more predictive of triglyceride, and BMI. The area-under-the-curve values of GGT for discriminating MetS from normal metabolic status in men and women are 0.73 and 0.80, respectively. The optimal cut-off value of GGT for men is 31.50 U/L, demonstrating a sensitivity of 74.00% and specificity of 62.00%. For women, it is 19.50 U/L (sensitivity 76.00% and specificity 70.00%). GGT is therefore recommended as a useful diagnostic marker for MetS, because the test is inexpensive, highly sensitive, and frequently encountered in clinical practice

Progress and challenge of food microbiological risk assessment in China

In the recent 10 years, China has carried out the construction of food safety risk assessment system including microbiological risk assessment (MRA) in accordance with the Food Safety Law, and has made significant progress in the work system and technical system of MRA, which has become an important basis for the risk assessment of foodborne pathogens in China. With the change of food supply chain in the global post epidemic era and the rapid development of new technologies as well as the increasing demand for the modernization of food safety management in China, it will become the main challenge for the construction of food MRA to build assessment model based on China’s dietary consumption behavior, improve the implementation ability and quality of risk assessment, and realize the application of modern technologies in risk assessment

Substantially enhanced plasticity of bulk metallic glasses by densifying local atomic packing

Common wisdom to improve ductility of bulk metallic glasses (BMGs) is to introduce local loose packing regions at the expense of strength. Here the authors enhance structural fluctuations of BMGs by introducing dense local packing regions, resulting in simultaneous increase of ductility and strength

Photoacoustic Identification of Laser-induced Microbubbles as Light Scattering Centers for Optical Limiting in Liquid Suspension of Graphene Nanosheets

Liquid suspensions of carbon nanotubes, graphene and transition metal dichalcogenides have exhibited excellent performance in optical limiting. However, the underlying mechanism has remained elusive and is generally ascribed to their superior nonlinear optical properties such as nonlinear absorption or nonlinear scattering. Using graphene as an example, we show that photo-thermal microbubbles are responsible for the optical limiting as strong light scattering centers: graphene sheets absorb incident light and become heated up above the boiling point of water, resulting in vapor and microbubble generation. This conclusion is based on direct observation of bubbles above the laser beam as well as a strong correlation between laser-induced ultrasound and optical limiting. In-situ Raman scattering of graphene further confirms that the temperature of graphene under laser pulses rises above the boiling point of water but still remains too low to vaporize graphene and create graphene plasma bubbles. Photo-thermal bubble scattering is not a nonlinear optical process and requires very low laser intensity. This understanding helps us to design more efficient optical limiting materials and understand the intrinsic nonlinear optical properties of nanomaterials