The present study aimed to assess the effects of therapy with adiponectin (APN) gene-modified adipose-derived stem cells (ADSCs) on pulmonary arterial hypertension (PAH) in rats and the underlying cellular and molecular mechanisms. ADSCs were successfully isolated from the rats and characterized. ADSCs were effectively infected with the green fluorescent protein (GFP)-empty (ADSCs-V) or the APN-GFP (ADSCs-APN) lentivirus and the APN expression was evaluated by ELISA. Sprague-Dawley rats were administered monocrotaline (MCT) to develop PAH. The rats were treated with MCT, ADSCs, ADSCs-V and ADSCs-APN. Then ADSCs-APN in the lung were investigated by confocal laser scanning microscopy and western blot analysis. Engrafted ADSCs in the lung were located around the vessels. Mean pulmonary arterial pressure (mPAP) and the right ventricular hypertrophy index (RVHI) in the ADSCs-APN-treated mice were significantly decreased as compared with the ADSCs and ADSCs-V treatments. Pulmonary vascular remodeling was assessed. Right ventricular (RV) function was evaluated by echocardiography. We found that pulmonary vascular remodeling and the parameters of RV function were extensively improved after ADSCs-APN treatment when compared with ADSCs and ADSCs-V treatment. Pulmonary artery smooth muscle cells (PASMCs) were isolated from the PAH rats. The antiproliferative effect of APN on PASMCs was assayed by Cell Counting Kit-8. The influence of APN and specific inhibitors on the levels of bone morphogenetic protein (BMP), adenosine monophosphate activated protein kinase (AMPK), and small mothers against decapentaplegia (Smad) pathways was detected by western blot analysis. We found that APN suppressed the proliferation of PASMCs isolated from the PAH rats by regulating the AMPK/BMP/Smad pathway. This effect was weakened by addition of the AMPK inhibitor (compound C) and BMP2 inhibitor (noggin). Therefore, combination treatment with ADSCs and APN effectively attenuated PAH in rats by inhibiting PASMC proliferation and regulating the AMPK/BMP/Smad pathway.
Background/Aims: Acute respiratory tract infection (ARTI) is the most common reason for outpatient physician office visits. Although powerful and significant in the treatment of infections, antibiotics used for ARTI inappropriately have been an important contributor to antibiotic resistance. We previously reported that Shufeng Jiedu Capsule (SJC) can effectively amplify anti-inflammatory signaling during infection. In this study, we aimed to systematically explore its composition and the mechanism of its effects in ARTI. Methods: Pseudomonas aeruginosa (PAK) strain was used to generate a mouse model of ARTI, which were then treated with different drugs or compounds to determine the corresponding anti-inflammatory roles. High-performance liquid chromatography-quadrupole time of flight-tandem mass spectrometry. was conducted to detect the chemical compounds in SJC. RNAs from the lung tissues of mice were prepared for microarray analysis to reveal globally altered genes and the pathways involved after SJC treatment. Results: SJC significantly inhibited the expression and secretion of inflammatory factors from PAK-induced mouse lung tissues or lipopolysaccharide-induced peritoneal macrophages. Verbenalin, one of the bioactive compounds identified in SJC, also showed notable anti-inflammatory effects. Microarray data revealed numerous differentially expressed genes among the different treatment groups; here, we focused on studying the role of GPR18. We found that the anti-inflammatory role of verbenalin was attenuated in GPR18 knockout mice compared with wild-type mice, although no statistically significant difference was observed in the untreated PAK-induced mice types. Conclusion: Our data not only showed the chemical composition of SJC, but also demonstrated that verbenalin was a significant anti-inflammatory compound, which may function through GPR18.
Aim: To investigate the association between uric acid (UA) and endothelial function in Chinese hypertensive patients with Metabolic Syndrome (MS).Methods: 615 hypertensive patients were enrolled, all hypertensives were divided into two groups: hypertensives with MS (MS group, n=239) and hypertensives without MS (NMS group, n=376). 87 age-and sex-matched normotensives served as controls (NC group). Flow-mediated (endothelium-dependent) dilatations (FMD), nitroglycerin-induced (endothelium-independent) dilatation (EID) in the brachial artery were assessed by highresolution ultrasonography. UA was detected by urease indophenol. .58)%, p<0.001) among groups. After stratification of gender, lower FMD was only seen in male hypertensives with MS accompanied by hyperuricemia <60 years old ((9.98 ± 5.78)% vs (7.12 ± 4.49)%, p<0.05); Pearson correlation analysis showed that the FMD was negatively correlated with UA (r=-0.314, p<0.01); Finally, logistic regression analysis showed that a 50 µmol/L increase in UA levels carried a 41.1% higher risk for endothelial dysfunction in this cohort. Conclusions: A higher UA level is related to poorer endothelial function in hypertensives with MS. Increased UA can be used as an alternative indicator for monitoring endothelial function and preventing vascular damage in male hypertensives with MS aged less than 60 years old.Keywords: Uric acid; Endothelial dysfunction; Hypertension; Metabolic syndrome
InstructionRecently, several studies have indicated that uric acid (UA), the circulating end-metabolite of purine nucleotides of mankind, is associated with subsequent cardiovascular diseases [1,2]. However, it remains controversial whether UA is a relevant and independent risk factor for cardiovascular disease and the mechanisms by which UA results in target organ injury are still unknown. Increasing data suggest that UA is associated with endothelial dysfunction [3,4], which is characteristic of patients with essential hypertension [5]. It is well recognized that endothelial dysfunction is an early stage in atherogenesis and associates with poor cerebro-cardiovascular outcomes [6]. It has been shown that UA disturbs endothelial function by disrupting nitric oxide (NO) synthesis, inhibiting NO bioavailability and activating the renin-angiotensin system.Metabolic syndrome (MS) is believed to be a clustering of abnormalities of several cardiovascular risk factors in an individual including abdominal obesity, hypertension, and dyslipidemia, including low HDL-C, high LDL-C and hyperglycemia. MS is often associated with elevated UA levels [7] and endothelial dysfunction [8,9]. The prevalence of MS has been increasing in recent years in China. A recent epidemiological study showed that the prevalence of MS among Chinese men and women aged 35 to 64 years old was 9.8% and 17.8%, respectively [10]. As is known to all, MS is quite common in patients with primary hypertension and carries much higher risk of cardiovascular events. It was reported that nearly 90% of Chinese hypertensives were ...
Most components of Shen-su-yin (SSY), an herbal formula, have anti-inflammatory and antioxidant activities. The present study was designed to investigate potential effects and mechanisms of SSY on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in rats. 48 rats were randomly divided into 4 groups: control (Ctrl) group, LPS-induced ALI group, low- (SSY-LD) and high- (SSY-HD) dose SSY-treated ALI group. SSY was administered to SSY-treated rats immediately after LPS induction. After 24 hours, blood gas analysis and lactate determination were performed; and bronchoalveolar lavage fluid was collected for detecting protein concentration and levels of cytokines. Lung tissues were obtained for Western blot analysis, histopathological analysis, wet-to-dry weight ratio calculation and measurement of oxidative stress levels. SSY improved oxygenation index and mean arterial pressure, decreased levels of lactate and heart rate, alleviated lung histopathology indexes including lung injury score, wet-to-dry weight ratio and exudation of protein as well as inflammatory cells in ALI rats. Furthermore, SSY reduced levels of pro-inflammatory and oxidative mediums, while increasing levels of anti-inflammatory cytokine and anti-oxidative activity in lung tissues. SSY also suppressed NF-κB signalling pathway and further activated Keap1-Nrf2-ARE signalling pathway activated by LPS. Moreover, all the effects caused by SSY in the SSY-HD group were more encouraging than those in the SSY-LD group. The results indicate that the preventive use of SSY can alleviate ALI through the anti-inflammatory and antioxidant effects mediated by inhibition of NF-κB signalling pathway and activation of Keap1-Nrf2-ARE signalling pathway, and the effect of high dose is better.
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