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31.
《Annals of hepatology》2020,19(4):411-416
Introduction and objectivesResearch in the last few years has proven that inhibition of fatty acid synthase (FASN) suppresses the migration and invasion of hepatoma carcinoma cells. This study aims to explore the effect of fatty acid synthase knockdown on the apoptosis and proliferation of HepG2 cells.Materials and methodsThe human liver cancer cell line HepG2 was cultured and then transfected with FASN-specific siRNA and negative control RNAi. After 48 h, cells and protein lysates were used for western blotting, CCK-8 (cell counting kit-8) assays, flow cytometry and other tests. To assess cell apoptosis, Bax, Bcl-2 and caspase-3 were detected; to assess proliferation, CDK4 (cyclin-dependent kinases 4) and P21 were detected; and to determine the signaling pathway involved, β-catenin and C-myc were also detected.ResultsInhibition of FASN in HepG2 cells can decrease proliferation and promote apoptosis. Flow cytometry and CCK-8 assays demonstrated that the apoptosis rate of FASN-specific siRNA-transfected cells was significantly increased compared to that of the control cells (p < 0.01). In addition, the cell cycle analysis revealed that FASN-specific siRNA-transfected cells induced G1 phase arrest (p < 0.05), but an increasing trend in G2 (p < 0.05).Compared with expression in negative RNAi-transfected cells, the expression of Bcl-2 and CDK-4 was reduced and the expression of Bax, caspase-3 and P21 was increased in FASN-specific siRNA-transfected cells (p < 0.05). Regarding the signaling pathway, the expression of β-catenin and C-myc was significantly reduced when compared to that in negative control cells (p < 0.05).ConclusionsInhibition of FASN suppressed the cell survival of HepG2 cells by inhibiting the β-catenin/C-myc pathway. This result suggests the potential treatment value of FASN for hepatoma carcinoma (HCC). 相似文献
32.
目的:观察血府逐瘀汤合温胆汤加减联合西药治疗高血压颈动脉硬化的效果。方法:选取2017年6月至2018年6月聊城市中医院收治的高血压颈动脉硬化患者92例作为研究对象,按照随机数字表法随机分为对照组与观察组,每组46例。对照组患者给予左旋氨氯地平+阿托伐他汀口服,观察组在对照组基础上加用血府逐瘀汤合温胆汤加减口服。观察患者血压、血脂控制情况,测定颈动脉内膜中层厚度(IMT)、斑块面积、血管皮内皮功能、血清蛋白酶分子水平。结果:与对照组比较,观察组治疗后的血压SBP、DBP及血脂TG、TC、LDL-C等指标更低(P<0.05);颈动脉粥样硬化斑块IMT厚度、斑块面积明显缩小(P<0.05),血管内皮功能指标ET-1、AngⅡ、TXB2水平明显降低,NO水平明显升高(P<0.05);血清CatK、MMP-9水平明显降低(P<0.05);观察组不良反应发生率8.70%明显低于对照组不良反应发生率21.74%(P<0.05)。结论:血府逐瘀汤合温胆汤加减联合西药更利于控制高血压颈动脉硬化患者的血压,调节脂质代谢,改善血管内皮功能,降低血清蛋白酶分子的含量,用药安全。 相似文献
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目的优化1,8-桉叶油素(1,8-cineole,1,8-Cin)自微乳给药系统(1,8-cineole self-microemulsion drug delivery system,1,8-Cin-SMEDDS)处方,对其进行表征并进行细胞摄取考察。方法通过绘制伪三元相图,确定1,8-Cin-SMEDDS有效自乳化区域,进行初步处方筛选。以粒径和载药量为指标,采用星点设计-效应面法对1,8-Cin-SMEDDS处方进行优化并验证。荧光显微镜观察高糖损伤的人脐静脉内皮细胞(HUVEC)对1,8-Cin-SMEDDS的摄取情况。结果 1,8-Cin-SMEDDS的最佳处方是大豆油(7.5%)与1,8-Cin(22.5%)为混合油相,HS15(56%)为乳化剂,乙醇(14%)为助乳化剂,滴加纯水至8m L得半透明略带蓝色乳光液体。透射电镜观察其外观呈球形液滴,激光粒度Zeta电位测定仪测得平均粒径为(131.68±1.44)nm,Zeta电位为(-10.03±1.63)m V;HPLC法测得包封率为(99.890±0.012)%,载药量为(224.750±0.028)mg/g。HUVEC细胞摄取实验结果表明,细胞对1,8-Cin-SMEDDS的摄取高于游离1,8-Cin。结论 1,8-Cin-SMEDDS制备方法简便,重复性好,所得1,8-Cin-SMEDDS外观良好,包封率高,理化性质稳定,且能促进细胞摄取。 相似文献
35.
Macrophages are the most abundant immune cells in the lung, which play an important role in COPD. The anti-inflammatory and anti-oxidation of ergosterol are well documented. However, the effect of ergosterol on macrophage polarization has not been studied. The objective of this work was to investigate the effect of ergosterol on macrophage polarization in CSE-induced RAW264.7 cells and Sprague-Dawley (SD) rats COPD model. Our results demonstrate that CSE-induced macrophages tend to the M1 polarization via increasing ROS, IL-6 and TNF-α, as well as increasing MMP-9 to destroy the lung construction in both RAW264.7 cells and SD rats. However, treatment of RAW264.7 cells and SD rats with ergosterol inhibited CSE-induced inflammatory by decreasing ROS, IL-6 and TNF-α, and increasing IL-10 and TGF-β, shuffling the dynamic polarization of macrophages from M1 to M2 both in vitro and in vivo. Ergosterol also decreased the expression of M1 marker CD40, while increased that of M2 marker CD163. Moreover, ergosterol improved the lung characters in rats by decreasing MMP-9. Furthermore, ergosterol elevated HDAC3 activation and suppressed P300/CBP and PCAF activation as well as acetyl NF-κB/p65 and IKKβ, demonstrating that HDAC3 deacetylation was involved in the effect of ergosterol on macrophage polarization. These results also provide a proof in immunoregulation of ergosterol for therapeutic effects of cultured C. sinensis on COPD patients. 相似文献
36.
《Journal of Science and Medicine in Sport》2020,23(4):342-346
ObjectivesThe aim of this case control genetic association study was to explore whether two variants within the inducible nitric oxide synthase (iNOS) gene, rs2779249 (C/A) and rs2248814 (A/G), influenced the risk of Achilles tendinopathy in a British population.DesignCandidate gene, case control association study.MethodWe recruited 145 individuals diagnosed with Achilles tendon pathology and 132 asymptomatic controls. All participants were genotyped for the iNOS variants using qPCR and significant associations were discovered using a combination of Chi squared and ANOVA type analysis.ResultsThe CA genotype of the iNOS rs2779249 variant was protective and conformed to a heterozygous advantage model of inheritance as it was overrepresented in the control participants (p = 0.009). In sex specific analysis the protective association persisted in male participants (p = 0.016) but not in females. Unlike the rs2779249 variant, the rs2248814 variant was not associated with Achilles tendinopathy or Achilles tendon rupture.ConclusionThe rs2779249 CA genotype within the human iNOS gene appears to protect individuals from Achilles tendinopathy. This study further supports a genetic contribution to modifying the risk of Achilles tendon problems. The study also infers an important role for nitric oxide in tendon healing and/or degradation. 相似文献
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39.
Understanding the contribution of endothelial cells to the progenitor pools of adult tissues has the potential to inform therapies for human disease.To address whether endothelial cells transdifferentiate into non-vascular cell types,we performed cell lineage tracing analysis using transgenic mice engineered to express a fluorescent marker following activation by tamoxifen in vascular endothelial cadherin promoter-expressing cells(VEcad-CreERT2;B6 Cg-Gt(ROSA)26Sortm9(CAG-tdTomato)Hze).Activation of target-cell labeling following 1.5 months of ad libitum feeding with tamoxifen-laden chow in 4–5 month-old mice resulted in the tracing of central nervous system and peripheral cells that include:cerebellar granule neurons,ependymal cells,skeletal myocytes,pancreatic beta cells,pancreatic acinar cells,tubular cells in the renal cortex,duodenal crypt cells,ileal crypt cells,and hair follicle stem cells.As Nestin expression has been reported in a subset of endothelial cells,Nes-CreERT2 mice were also utilized in these conditions.The tracing of cells in adult Nes-CreERT2 mice revealed the labeling of canonical progeny cell types such as hippocampal and olfactory granule neurons as well as ependymal cells.Interestingly,Nestin tracing also labeled skeletal myocytes,ileal crypt cells,and sparsely marked cerebellar granule neurons.Our findings provide support for endothelial cells as active contributors to adult tissue progenitor pools.This information could be of particular significance for the intravenous delivery of therapeutics to downstream endothelial-derived cellular targets.The animal experiments were approved by the Boise State University Institute Animal Care and Use Committee(approval No.006-AC15-018)on October 31,2018. 相似文献
40.
Mild intrauterine hypoperfusion(MIUH) is a serious pathological event that affects the growth and development of fetuses and offspring. MIUH can lead to growth restriction, low birth weight, neurodevelopmental disorders, and other adverse clinical outcomes. To study the effects of MIUH on learning and memory function in offspring, a model of MIUH was established by placing a coil(length 2.5 mm, diameter 0.24 mm) on the uterine artery and ovarian uterine artery of Sprague-Dawley rats in the second trimester of pregnancy(day 17). Next, 120 mg/kg lithium chloride(the MIUH + Li group) or normal saline(the MIUH group) was injected intraperitoneally into these rats. In addition, 120 mg/kg lithium chloride(the Li group) or normal saline(the SHAM group) was injected intraperitoneally into pregnant rats without coil placement. The Morris water maze was used to detect changes in learning and memory ability in the offspring at 4 weeks after birth. In the MIUH group, the escape latency and journey length before reaching the platform were both increased, and the number of times that the platform was crossed and the activity time in the target quadrant within 90 seconds were both decreased compared with the SHAM group. Immunofluorescence double staining and western blot assays demonstrated that hippocampal nestin and Ki67(both cell-proliferation-related proteins) expression was significantly downregulated in the MIUH group compared with the SHAM group. Furthermore, western blot assays were conducted to investigate changes in related signaling pathway proteins in the brains of offspring rats, and revealed that glycogen synthase kinase 3β(GSK3β) expression was upregulated and β-catenin expression was downregulated in the MIUH group compared with the SHAM group. In addition, compared with the MIUH group, the expression levels of p-GSK3β and β-catenin were upregulated in the MIUH + Li group. These results suggest that MIUH may affect learning and memory function in rat offspring by regulating the GSK3β signaling pathway. The experimental procedures were approved by Animal Ethics Committee of Shengjing Hospital of China Medical University(approval No. 2018 PS07 K) in June 2018. 相似文献