IL-17 and IL-23 may play a pathogenic role in an established AR mouse model; with a more pronounced contribution of IL-23 than IL-17.

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.

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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.

Objectives. The study was to investigate the effects and mechanisms of Shen-Yuan-Dan (SYD) pharmacological postconditioning on myocardial ischemia/reperfusion (I/R) injury. Methods. In the in vivo experiment, myocardial injury markers and histopathology staining were examined. In the in vitro experiment, cell viability and cell apoptosis were, respectively, detected by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays and Hoechst 33342 fluorochrome staining. The protein expressions of Bcl-2 and Bax were determined by immunocytochemistry assay. Results. Both low and high doses of SYD protected myocardium against I/R injury in rat model by reducing lactic dehydrogenase (LDH) and creatine kinase-MB (CK-MB) activity and malondialdehyde (MDA) content, increasing superoxide dismutase (SOD) activity and attenuating histopathology injury. Meanwhile, in the in vitro experiment, SYD promoted cell viability and inhibited the cardiomyocyte apoptosis. The level of Bcl-2 protein was restored to the normal level by SYD pharmacological postconditioning. In contrast, the Bax protein level was markedly reduced by SYD pharmacological postconditioning. These effects of SYD were inhibited by LY294002. Conclusions. The results of this study suggested that SYD pharmacological postconditioning has protective effects against myocardial I/R injury in both in vivo and in vitro models, which are related to activating the phosphatidylinositol 3-kinase/Akt (PI3K/Akt) pathway.

ObjectiveTo ascertain the feasibility of using shear wave velocity (SWV) in assessing the stiffness of carotid plaque by supersonic shear imaging (SSI) and explore preliminary clinical value for such evaluation.Materials and MethodsSupersonic shear imaging was performed in 142 patients with ischemic stroke, including 76 males and 66 females with mean age of 66 years (range, 45–80 years). The maximum, minimum, and mean values of SWV were measured for 129 carotid plaques. SWVs were compared between echolucent and echogenic plaques. Correlations between SWVs and serum homocysteine levels were investigated. Based on neurological symptom, the surrogate marker of vulnerable plaque (VP), binary logistic regression was performed and area under curve (AUC) of homocysteine only and homocysteine combing SWVmean was calculated respectively.ResultsEchogenic plaques (n = 51) had higher SWVs than echolucent ones (n = 78) (SWVmin 3.91 [3.24–4.17] m/s vs. 1.51 [1.04–1.94] m/s; SWVmean, 4.29 [3.98–4.57] m/s vs. 2.09 [1.69–2.41] m/s; SWVmax, 4.67 [4.33–4.86] m/s vs. 2.62 [2.32–3.31] m/s all p values < 0.01). Pearson correlation analysis showed that stiffness of plaques was negatively correlated with homocysteine level. R values for SWVmin, SWVmean, and SWVmax were −0.205, −0.213, and −0.199, respectively. Binary logistic regression analysis showed that sex (p = 0.008), low-density lipoprotein (p = 0.015), triglycerides (p = 0.011), SWVmean (p = 0.004), and hyper-homocysteinemia (p = 0.010) were significantly associated with symptomatic ischemic stroke. Receiver operating characteristic curves revealed that SWVmean combing serum homocysteine level (AUC = 0.67) presented better diagnostic value than serum homocysteine only (AUC = 0.60) for symptomatic ischemic stroke.ConclusionSupersonic shear imaging could be used to quantitatively evaluate stiffness of both echolucent and echogenic carotid plaques. More importantly, SWVs of plaques were not only correlated to serum homocysteine level, but also associated with symptomatic ischemic stroke, suggesting that SSI might be useful for understanding more about VP.

Systemic lupus erythematosus (SLE) is a chronic autoimmune and inflammatory disease affecting multiorgans of human body. Independent studies show that SLE patients had higher caries prevalence compared to non-SLE individuals. However, the underlying mechanisms remain unclear. In present study, we enrolled SLE patients to explore potential factors contributing to the susceptibility of SLE patients to dental caries (such as oral hygiene, salivary function, and oral microbial community). Dental examination confirmed SLE patients were more vulnerable to caries. Although subjects in both groups announced similar oral hygiene habits, more dental plaque was found on tooth surfaces of SLE patents as revealed by plaque index. In addition, the salivary function was impaired in SLE group as salivary flow rate, buffering capacity, and pH were lower among SLE subjects compared to healthy controls. Importantly, disturbed microbial community with lower richness and diversity was observed in SLE group, as well as disequilibrium between acidogenic/aciduric pathogens and alkali-generating commensal bacteria. Our data suggest that SLE increases patients' sensitivity to dental caries through imposing stress to both host and oral microbes.