Effect of Tetramethylpyrazine on Atherosclerosis and SCAP/SREBP-1c Signaling Pathway in ApoE −/−

Lipid metabolism dysregulation plays a crucial role in the occurrence of atherosclerosis (As). SCAP/SREBP signaling is the main pathway for regulating lipid metabolism. Tetramethylpyrazine (TMP), a Traditional Chinese Medicine (TCM) for treating angina pectoris, has antiatherosclerotic effects and ameliorates blood lipids disturbance. However, its precise mechanism remains unclear. This study investigated the mechanism of TMP in ameliorating As in mice model. After six weeks of high-fat diet, 30 ApoE−/− mice were randomized (n=10) and treated with Lipitor, TMP, or distilled water for six weeks. The serum blood lipids and insulin levels were measured. The expressions of PAQR3, Insig-1, SCAP, SREBP-1c, IRS-1, PI3K, Akt, and mTORC-1 in the adipose tissues were determined. The results showed that TMP could significantly decrease blood lipids levels, insulin, and corrected plaque area of the ApoE−/− mice as compared to the untreated mice (P<0.05, P<0.01). Moreover, TMP could significantly downregulate the expressions of SCAP, SREBP-1c, PAQR3, IRS-1, PI3K, Akt, and mTORC1 (P<0.01). Thus, TMP may ameliorate lipid metabolism disorder and As by downregulating PAQR3 and inhibiting SCAP/SREBP-1c signaling pathway. In addition, PI3K/Akt/mTORC1 signaling pathway may be involved in this process

Shen-Yuan-Dan Capsule Attenuates Atherosclerosis and Foam Cell Formation by Enhancing Autophagy and Inhibiting the PI3K/Akt/mTORC1 Signaling Pathway

Background and Aim: The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin complex 1 (mTORC1) signaling pathway plays a crucial role in autophagy and inflammation. Our previous studies demonstrated that Shen-Yuan-Dan Capsule (SYDC), a Chinese medicine used for treating angina pectoris, has anti-atherosclerotic and anti-inflammatory effects in mice. However, its effects on autophagy and the PI3K/Akt/mTORC1 signaling pathway remain unclear. This study aimed to explore the effects of SYDC on autophagy and PI3K/Akt/mTORC1 signaling in the apolipoprotein E knockout (ApoE−/−) mouse model and in macrophage-derived foam cells to delineate the underlying mechanism.Methods: After 6 weeks of high-fat diet, ApoE–/– mice were randomly grouped into control, Lipitor, low-SYDC (SYDC-L), middle-SYDC (SYDC-M), and high-SYDC (SYDC-H) groups (n = 10). The mice were intragastrically administered the respective treatment for 6 weeks. Murine RAW264.7 cells were stimulated with oxidized low-density lipoprotein (ox-LDL) (80 µg/ml) for 24 h and then pretreated with SYDC freeze-dried powder for another 24 h. Cells treated with SYDC were co-cultured for 24 h with LY294002, tricirbine, and rapamycin to investigate the effects on the PI3K/Akt/mTORC1 signaling pathway.Results: SYDC ameliorated blood lipid levels, reduced the atherosclerotic index and plaque areas in the aortic root in mice, and inhibited total cholesterol (TC) levels and cholinesterase (ChE)/TC ratios in ox-LDL stimulated macrophages. Moreover, SYDC up-regulated Beclin1 and LC3II/I proteins in mice and in the ox-LDL–stimulated macrophages. Moreover, SYDC inhibited AKT phosphorylation at Ser473 and mTOR phosphorylation at Ser2448 in mice and in ox-LDL–stimulated macrophages. Furthermore, SYDC’s inhibitory of ChE/TC ratios in ox-LDL–stimulated macrophages was not changed by selective inhibition of the PI3K/Akt/mTORC1 pathway.Conclusions: Our results highlight that SYDC treatment attenuates foam cell formation by promoting autophagy via inhibiting activation of the PI3K/Akt/mTORC1 signaling pathway. This study provides new insights into the molecular mechanism underlying SYDC’s therapeutic potential for treating atherosclerosis

Descope of the ALIA mission

The present work reports on a feasibility study commissioned by the Chinese Academy of Sciences of China to explore various possible mission options to detect gravitational waves in space alternative to that of the eLISA/LISA mission concept. Based on the relative merits assigned to science and technological viability, a few representative mission options descoped from the ALIA mission are considered. A semi-analytic Monte Carlo simulation is carried out to understand the cosmic black hole merger histories starting from intermediate mass black holes at high redshift as well as the possible scientific merits of the mission options considered in probing the light seed black holes and their coevolution with galaxies in early Universe. The study indicates that, by choosing the armlength of the interferometer to be three million kilometers and shifting the sensitivity floor to around one-hundredth Hz, together with a very moderate improvement on the position noise budget, there are certain mission options capable of exploring light seed, intermediate mass black hole binaries at high redshift that are not readily accessible to eLISA/LISA, and yet the technological requirements seem to within reach in the next few decades for China

Astragalus Granule Prevents Ca 2+

Background. Astragalus was broadly used for treating heart failure (HF) and arrhythmias in East Asia for thousands of years. Astragalus granule (AG), extracted from Astragalus, shows beneficial effect on the treatment of HF in clinical research. We hypothesized that administration of AG prevents the remodeling of L-type Ca2+ current (ICa-L) in HF mice by the downregulation of Ca2+/calmodulin-dependent protein kinase II (CaMKII). Methods. HF mice were induced by thoracic aortic constriction (TAC). After 4 weeks of AG treatment, cardiac function and QT interval were evaluated. Single cardiac ventricular myocyte was then isolated and whole-cell patch clamp was used to record action potential (AP) and ICa-L. The expressions of L-type calcium channel alpha 1C subunit (Cav1.2), CaMKII, and phosphorylated protein kinase A (p-PKA) were examined by western blot. Results. The failing heart manifested distinct electrical remodeling including prolonged repolarization time and altered ICa-L kinetics. AG treatment attenuated this electrical remodeling, supported by AG-related shortened repolarization time, decreased peak ICa-L, accelerated ICa-L inactivation, and positive frequency-dependent ICa-L facilitation. In addition, AG treatment suppressed the overexpression of CaMKII, but not p-PKA, in the failing heart. Conclusion. AG treatment protected the failing heart against electrical remodeling and ICa-L remodeling by downregulating CaMKII

Roles and mechanisms of renalase in cardiovascular disease: a promising therapeutic target

Cardiovascular disease (CVD) is prevalent worldwide and remains a leading cause of death. Although substantial progress has been made in the diagnosis and treatment of CVD, the prognosis remains unsatisfactory. Renalase is a newly discovered cytokine that is synthesized by the kidney and then secreted into blood. Numerous studies have suggested the efficacy of renalase in treating CVD by metabolizing catecholamines in the circulatory system. As a new biomarker of heart disease, renalase is normally recognized as a signalling molecule that activates cytoprotective intracellular signals to lower blood pressure, protect ischaemic heart muscle and promote atherosclerotic plaque stability in CVD, which subsequently improves cardiac function. Due to its important regulatory role in the circulatory system, renalase has gradually become a potential target in the treatment of CVD. This review summarizes the structure, mechanism and function of renalase in CVD, thereby providing preclinical evidence for alternative approaches and new prospects in the development of renalase-related drugs against CVD. [Abstract copyright: Copyright © 2020 The Author(s). Published by Elsevier Masson SAS.. All rights reserved.

Study on the Decoupling Relationship and Rebound Effect between Economic Growth and Carbon Emissions in Central China

The central area is the core region of China&rsquo;s economic development. Under the current goal of carbon emission reduction, the analysis of the decoupling relationship between economic growth and carbon emissions and the carbon rebound effect will help us to formulate corresponding policies, achieve a carbon peak at an early date, and ensure high-quality economic development. Based on the energy consumption data from 2000 to 2019, the carbon emission of six provinces of the central region was calculated. The Tapio decoupling model was used to learn about the decoupling index. And then, by calculating the contribution rate of technological progress to both economic growth and carbon emission intensity, the carbon saving amount and carbon rebound amount can be calculated, and the rebound effect value of carbon emission is obtained. The results show that the economy in central China presents a trend of growth. In contrast, the carbon emission of each province shows a gradient structure with a large difference, and the economic growth and carbon emission show a weak decoupling in the past five years. We further analyzed the rebound effect of carbon emissions and found that 30% of the years in the central region have a rebound effect with values of more than one. Finally, this study puts forward policy suggestions for the early realization of carbon peaks and high-quality economic development in the central region

Carbon Emissions in the Yellow River Basin: Analysis of Spatiotemporal Evolution Characteristics and Influencing Factors Based on a Logarithmic Mean Divisia Index (LMDI) Decomposition Method

The &ldquo;14th Five-Year Plan&rdquo; period is a critical period and a window to obtain emission peak and carbon neutrality in China. The Yellow River Basin, a vital location for population activities and economic growth, is significant to China&rsquo;s emission peak by 2030. Analyzing carbon emissions patterns and decomposing the influencing factors can provide theoretical support for reducing carbon emissions. Based on the energy consumption data from 2000&ndash;2019, the method recommended by Intergovernmental Panel on Climate Change (IPCC) is used to calculate the carbon emissions in the Yellow River Basin. The Logarithmic Mean Divisia Index (LMDI) decomposition method decomposes the influence degree of each influencing factor. The conclusions are as follows: First, The Yellow River Basin has not yet reached the peak of carbon emissions. Regional carbon emissions trends are different. Second, Shandong, Shanxi, Henan and Inner Mongolia consistently ranked in the top four in total carbon emissions, with low carbon emission efficiency. Third, Economic development has the most significant contribution to carbon emissions; other factors have various effects on nine provinces

Carbon Emissions in the Yellow River Basin: Analysis of Spatiotemporal Evolution Characteristics and Influencing Factors Based on a Logarithmic Mean Divisia Index (LMDI) Decomposition Method

The “14th Five-Year Plan” period is a critical period and a window to obtain emission peak and carbon neutrality in China. The Yellow River Basin, a vital location for population activities and economic growth, is significant to China’s emission peak by 2030. Analyzing carbon emissions patterns and decomposing the influencing factors can provide theoretical support for reducing carbon emissions. Based on the energy consumption data from 2000–2019, the method recommended by Intergovernmental Panel on Climate Change (IPCC) is used to calculate the carbon emissions in the Yellow River Basin. The Logarithmic Mean Divisia Index (LMDI) decomposition method decomposes the influence degree of each influencing factor. The conclusions are as follows: First, The Yellow River Basin has not yet reached the peak of carbon emissions. Regional carbon emissions trends are different. Second, Shandong, Shanxi, Henan and Inner Mongolia consistently ranked in the top four in total carbon emissions, with low carbon emission efficiency. Third, Economic development has the most significant contribution to carbon emissions; other factors have various effects on nine provinces