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Aim To investigate the effects of astragalus polysaccharide and hirudin combined intervention on lipid accumulation, mitochondrial membrane potential and apoptosis-related proteins in macrophages induced by oxidized low density lipoprotein (ox-LDL). Methods RAW264. 7 cells were incubated with 100 mg/ L ox-LDL for 24 h to establish a foam-cell model, which were treated by astragalus polysaccharide and hirudin after dose optimization. The control group, model group, astragalus polysaccharide group, hirudin group and the combined intervention of the two drugs group were established. Oil red O staining and oxidase method were used to detect the cholesterol contents in macrophages induced by ox-LDL, flow cytometry was used to detect the early apoptosis rate, late apoptosis rate and total apoptosis rate of macrophages, the changes of mitochondrial membrane potential were detected by laser confocal microscopy, Western blot was used to detect the expression levels of anti-apoptotic protein Bcl-2, proapoptotic protein Caspase-3 and Bax. Results The contents of cholesterol in macrophages of the astragalus polysaccharide and hirudin combined intervention group were decreased than those in the hirudin group or astragalus polysaccharide group significantly (P<0.05). Compared with the model group, the astragalus polysaccharide and hirudin combined intervention could reduce the early apoptosis rate and total apoptosis rate of macrophages induced by ox-LDL (P<0.01), increase the mitochondrial membrane potential of macrophages (P<0.01), reduce the expressions of Caspase-3 and Bax, and increase the expression of Bcl-2 protein (P< 0.05) significantly. Conclusions The astragalus polysaccharide and hirudin combined intervention in reducing lipid accumulation in macrophages is superior to drug treatment alone. The combined treatment of the two drugs can reduce the apoptosis rate of macrophages induced by ox-LDL. Its mechanism may be related to regulate mitochondrial membrane potential and regulate the expressions of proapoptotic protein Caspase-3, Bax and anti-apoptotic protein Bcl-2. [ABSTRACT FROM AUTHOR]

The entropy of the flow field could not keep constant due to a strong exothermic reaction of aluminum powders during the post-detonation expansion of the aluminized explosives. Therefore, a non-isentropic model incorporating the aluminum oxidation in the detonation products was established. To solve the non-isentropic expansion process analytically, it was assumed that the whole expansion process was divided into several time ranges and the flow field was isentropic in each time range. Besides, the method of characteristic line was applied to theoretically calculate the velocity of the metal plate driven by aluminized explosives. Moreover, the effects on the pressure, density, sound speed, and temperature of detonation products due to the change of the entropy were analyzed. Finally, the metal plate-pushing tests were conducted to measure the velocity of metal plate driven by aluminized explosives through the Photonic Doppler Velocimetry system, and the degree of aluminum reaction was calculated indirectly from the test results. By comparing the results based on the isentropic model and novel non-isentropic model, it was proved that the non-isentropic model could more correctly describe the driving process of detonation products of aluminized explosives. [ABSTRACT FROM AUTHOR]

The post-detonation burning effect of aluminum (Al) powder plays an important role during the expansion of detonation products (DPs) of aluminized explosives (AEs). Lithium fluoride (LiF) is an inert substitute for Al, and hence, a comparison of the performance of composite explosives based on cyclotrimethylenetrinitramine (RDX), such as RDX/Al and RDX/LiF, clearly illustrates its contribution to accelerating ability due to Al oxidation. A series of metal plate tests is conducted to measure the velocity history of a metal plate driven by RDX/Al and RDX/LiF through a photonic Doppler velocimetry system with 5%, 15%, and 25% Al or LiF contents. The detonation and expansion process of the AEs is generally divided into two stages: the detonation zone (DZ) and the post-detonation zone (PDZ). In the DZ, the Al powder remains inert, while it absorbs the detonation energy from pure explosives. Therefore, the equivalent inert dilution model is established and the equivalent inert dilution coefficient of the Al powder is introduced. In the PDZ, the Al powder reacts with DPs, and the Al oxidation reaction results with a change in entropy related to the reaction degree of the Al powder. Based on the local isentropic assumption, as well as the function of the reaction degree of the Al powder, a non-isentropic model is established. The method of the non-linear characteristic line is applied to theoretically calculate the metal plate velocity based on the non-isentropic model. In addition, the theoretical results show good agreement with the metal plate test results with an acceptable error (less than 10%), indicating that the non-isentropic model can be effectively applied to analyze the accelerating ability of the AEs. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: Moderate autophagy plays a positive role in the prevention of atherosclerosis. Aberrant promoter methylation of autophagic genes can affect autophagy. Shen-Yuan-Dan Capsule (SYDC), a traditional Chinese medicine, can prevent atherosclerosis in high-fat-fed mice. However, its precise mechanism remains unclear. This study investigated the mechanism of SYDC in ameliorating atherosclerosis in a mice model., Methods: After 6 weeks of a high-fat diet, apolipoprotein E knockout (apoE -/- ) mice were randomly grouped into control, Lipitor, and SYDC groups (n = 10). The mice were intragastrically administered with the respective drugs for 6 weeks. The expressions of Beclin1 and Atg5-Atg12 complex in atherosclerotic plaques of the mice were measured. The levels of 5-mC and DNA methyltransferase 1 (DNMT1) in the plasma of the mice were determined. The average methylation rate of CpG islands in the promoter region of autophagy-related protein (Atg13) and the mRNA expression of Atg13 in the aortas of the mice were determined., Results: SYDC up-regulated the expressions of Atg5-Atg12 complex and Beclin-1 in atherosclerotic plaques (p < 0.01). Moreover, SYDC decreased the 5-mC and DNMT1 levels in plasma and atherosclerotic plaques of the mice (p < 0.01), and also decreased the average methylation rate of CpG islands in the promoter region of Atg13 and increased the mRNA levels of Atg13 in the aortas of atherosclerotic mice (p < 0.01)., Conclusions: SYDC attenuates atherosclerosis by promoting autophagy, probably through regulating genomic DNA methylation and Atg13 promoter demethylation.

Background: Shen-Yuan-Dan Capsule (SYDC), a traditional Chinese medicine, is proposed to have the capacity to prevent angina pectoris. However, the effects and the related mechanisms of SYDC on atherosclerosis (AS) are still unknown. This study was designed to investigate the effects of SYDC on AS and inflammatory reaction in the apoliprotein E-knockout (ApoE -/- ) mice fed with a high-fat diet., Methods: Thirty eight-week-old male ApoE -/- mice were randomly divided into three groups (n = 10) 6 weeks after being fed with a high-fat diet: the control group, the lipitor group, and the SYDC group. The hearts were collected for hematoxylin and eosin (HE) or Van Gieson (VG) staining, and the aortas were collected for quantitative reverse transcription polymerase chain reaction (RT-PCR) and western-blotting., Results: The data showed that the levels of total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), atherosclerotic indexes (AI) and the corrected areas of atherosclerotic plaque of the mice on SYDC group were significantly decreased compared with those of the mice in the control group (p < 0.01, p < 0.05). SYDC can significantly increase collagen proportion in plaques as compared to the untreated mice (p < 0.01). In addition, the messenger ribonucleic acid (mRNA) expressions of insulin receptor substrate 1 (IRS-1), PI3K, Akt, NF-κB and tumor necrosis factor-α (TNF-α) in the mice fed with a high-fat diet were significantly reduced by SYDC (p < 0.05, p < 0.01)., Conclusions: SYDC can exert an anti-atherosclerotic effect on ApoE -/- mice fed with a high-fat diet. The action mechanism of SYDC was attributed to its ability to inhibit inflammatory reaction by regulating IRS-1/PI3K/Akt/NF-κB signaling pathway.

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.

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 Ca 2+ current ( I Ca-L ) in HF mice by the downregulation of Ca 2+ /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 I Ca-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 I Ca-L kinetics. AG treatment attenuated this electrical remodeling, supported by AG-related shortened repolarization time, decreased peak I Ca-L , accelerated I Ca-L inactivation, and positive frequency-dependent I Ca-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 I Ca-L remodeling by downregulating CaMKII.