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Objective

The purpose of this study was to investigate whether rapamycin inhibits the development of thoracic aortic aneurysm and dissection (TAAD) in mice.

Methods

Three-week-old C57BL/6J male mice were fed a normal diet and randomized into a control group (n = 6), β-aminopropionitrile fumarate (BAPN) group (Gp A; n = 15), BAPN plus rapamycin (5 mg) group (Gp B; n = 8), and BAPN plus rapamycin (10 mg) group (Gp C; n = 8). Gp A, Gp B, and Gp C were administered BAPN (1 g/kg/d) for 4 weeks. One week after BAPN administration, Gp B and Gp C were treated with rapamycin (5 mg/kg/d or 10 mg/kg/d) through gavage for 21 days. Thoracic aortas were harvested for Western blot and immunofluorescence staining at day 14 and for morphologic and histologic analyses at day 28.

Results

BAPN treatment induced TAAD formation in mice. The incidence of TAAD in control, Gp A, Gp B, and Gp C mice was 0%, 80%, 25%, and 37.5%, respectively. Smaller thoracic aortic diameters (ascending aorta and arch) were observed in Gp B and Gp C mice than in Gp A mice (Gp B vs Gp A: ascending aorta, ex vivo, 1.07 ± 0.21 mm vs 1.80 ± 0.67 mm [P < .05]; aortic arch, ex vivo, 1.51 ± 0.40 mm vs 2.70 ± 1.06 mm [P < .05]; Gp C vs Gp A: ascending aortas, ex vivo, 1.10 ± 0.33 mm vs 1.80 ± 0.67 mm [P < .05]; aortic arch, ex vivo, 1.55 ± 0.56 mm vs 2.70 ± 1.06 mm [P < .05]). TAAD mice exhibited elastin fragmentation, abundant inflammatory cell infiltration, and significantly increased matrix metalloproteinase production in the aorta, and rapamycin treatment alleviated these changes. The protein levels of p-S6K and p-S6 in TAAD aortic tissues increased significantly, whereas they were suppressed by rapamycin.

Conclusions

Rapamycin suppressed TAAD formation, probably by inhibition of mechanistic target of rapamycin signaling and reduction of inflammatory cell infiltration and matrix metalloproteinase 9 production. Targeting of the mechanistic target of rapamycin signaling pathway using rapamycin may be a favorable modulation for the clinical treatment of TAAD.  相似文献   
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Background and study aimsNon-invasive biomarkers of inflammatory bowel diseases (IBD) are of critical importance. Here, we evaluated the S100A8 and S100A9 mRNA expression, as the heterodimers of calprotectin, in the blood leucocytes of IBD patients to find how their expression associates with the disease characteristics.Patients and methodsIn this cross-sectional study, 59 IBD patients and 30 healthy subjects were included. The flare and remission phases of disease were identified in 46 and 13 patients, respectively. Blood leucocytes were isolated, and the S100A8 and S100A9 mRNA expression were evaluated in the isolated leucocytes using relative quantification real-time PCR.ResultsThe mean S100A8 and S100A9 mRNA expression were significantly higher in IBD patients than in the controls (p = 0.03 and p = 0.02, respectively). The mean S100A8 and S100A9 mRNA expression were significantly higher in the flare phase of the disease compared with the remission phase (p = 0.01 and p = 0.007, respectively). S100A8 distinguished IBD patients from controls with the sensitivity and specificity of 73% and 64%, and flare phase of disease from remission with the sensitivity and specificity of 67% and 62%. On the other hand, S100A9 distinguished IBD patients from controls with the sensitivity and specificity of 81% and 70%, and flare phase of disease from remission with the sensitivity and specificity of 68% and 64%.ConclusionThe S100A8 and S100A9 mRNA are differentially expressed in blood leucocytes of IBD patients compared to healthy controls as well as active versus quiescent disease. Thus, they can be potentially used as a blood-based biomarker in the monitoring of IBD.  相似文献   
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目的观察养阴清肺汤治疗急性放射性口腔炎的临床疗效及其对患者免疫功能和炎症细胞因子的影响。方法患者100例,按照随机数字表法分为治疗组与对照组各50例,两组均采用西医常规治疗,治疗组在对照组治疗基础上加用养阴清肺汤,两组疗程均持续到放疗结束后2~4周。观察两组临床疗效,治疗前后两组唾液中γ-干扰素(IFN-γ)、肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)及白细胞介素-8(IL-8)水平及两组治疗前后免疫功能指标(CD3^+、CD4^+、CD8^+、CD4^+/CD8^+)的变化情况。结果治疗组总有效率为92.00%,显著高于对照组的76.00%(P<0.05)。治疗组症状体征、唾液炎症细胞因子、相关免疫功能指标恢复程度均优于对照组(P<0.05)。结论养阴清肺汤可有效缓解急性放射性口腔炎的疼痛和黏膜损伤程度,加速患者伤口愈合,有效抑制急性放射性口腔炎的相关炎症细胞因子。  相似文献   
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《Vaccine》2020,38(50):8024-8031
Background and aimsChildren with inflammatory bowel disease (IBD) and autoimmune hepatitis (AIH) receiving immunosuppressive treatment are at risk for severe varicella zoster virus (VZV)-induced disease. This study evaluated vaccination of susceptible patients with stable disease and documented immunoreactivity without interruption of their current immunosuppression (IS).MethodsThis prospective multicentre observational study used a prevaccination checklist to select patients with low-intensity and high-intensity IS for VZV vaccination. Tolerability and safety after immunization were assessed by questionnaire. The immune response was measured by the VZV-IgG concentration, relative avidity index (RAI), and specific lymphocyte proliferative response.ResultsA total of 29 VZV vaccinations were performed in 17 seronegative patients aged 3–16 years (IBD n = 15, AIH n = 2). Eight patients received high-intensity immunosuppression, another six low-intensity immunosuppression, and three patients interrupted IS before VZV vaccination.All 29 vaccinations were well tolerated; only minor side effects such as fever and abdominal pain, were reported in two patients. One patient experienced a flare of Crohn’s disease the day after vaccination.The VZV-IgG-concentration increased significantly (p = 0.018) after vaccination, and a specific lymphocyte response towards VZV in vitro was detected in all tested patients which correlated with the RAI (r = 0.489; p = 0.078).ConclusionsVZV vaccination was well tolerated, safe and immunogenic in children receiving ongoing IS due to IBD and AIH. Ensuring immunoreactivity by clinical and laboratory parameters, rather than the type and dosage of IS, is a reasonable approach to decide on live-attenuated virus vaccinations in immunosuppressed children (German clinical trials DRKS00016357).  相似文献   
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目的:探讨黄芪建中汤治疗胃溃疡脾胃虚寒型的可能作用机理。方法:将2013年1月至2016年1月收治的符合入组标准的虚寒型胃溃疡患者分为对照组和观察组各100例,对照组给予常规四联疗法(奥美拉唑+阿莫西林+克拉霉素+替硝唑),观察组在此基础上服用加味黄芪建中汤加减,2组均以8周为1个疗程,比较2组患者的总有效率、血清胃泌素(GAS)、胃动素(MTL)、血清白介素-6(IL-6)、白介素-8(IL-8)、白介素-4(IL-4)、白介素-17(IL-17)、肿瘤坏死因子(TNF-a)水平变化及复发率。结果:观察组总有效率98.0%高于对照组,治疗后观察组患者血清IL-6、IL-8、IL-17、TNF-a水平值均低于治疗前,且低于对照组治疗后,而观察组IL-4水平值明显高于治疗前及对照组治疗后;治疗后观察组GAS和MTL水平值均明显低于治疗前及对照组治疗后,观察组中医症状积分低于对照组治疗后。结论:黄芪建中汤加减联合常规四联疗法治疗虚寒型胃溃疡效果确切,并能够提高IL-4表达水平,降低IL-6、IL-8、IL-17及TNF-a水平。  相似文献   
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摘 要 目的:探讨黄芪汤加减治疗慢性阻塞性肺疾病急性加重期(AECOPD)的临床疗效。方法:采用随机数字表法将166例AECOPD患者随机分为常规组和观察组各83例。常规组采用常规西医方法治疗,观察组在常规组的基础上给予黄芪汤加减治疗。观察两组治疗前后第1秒用力呼气量(FEV1)、用力肺活量(FVC)、FEV1占FVC的百分比(FEV1/FVC%)、动脉血氧分压(PaO2)、动脉血二氧化碳分压(PaCO2)、肿瘤坏死因子 α(TNF α)、白细胞介素 1β(IL 1β)、白细胞介素 6(IL 6)水平。结果:两组治疗后FEV1、FEV1/FVC、PaO2水平与治疗前相比较均显著升高(P<0.05),且观察组与同期常规组相比较均显著升高(P<0.05);两组治疗后PaCO2、TNF α、IL 1β、IL 6水平与治疗前相比较均显著降低(P<0.05),且观察组与同期常规组相比较均显著降低(P<0.05)。结论:黄芪汤加减治疗AECOPD可降低患者炎症反应水平,改善动脉血气和肺功能,提高治疗效果,值得临床应用。  相似文献   
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