麦角甾酮对小鼠急性酒精性肝损伤及肠道菌群群落组成的影响

目的 研究麦角甾酮对酒精引起的小鼠急性肝损伤的作用及其对肠道菌群群落组成的影响。方法 将C57BL/6小鼠随机分成空白组、模型组、甘草酸二铵组(60 mg?kg-1)、麦角甾酮低剂量组(30 mg?kg-1)、麦角甾酮高剂量组(60 mg?kg-1),每组10只。除空白组、模型组外,其余组按相应剂量灌胃10 d。第9-10 d,除空白组外的其他组均以每剂量12h的间隔灌胃2剂的50%酒精(10 mL?kg-1)诱导造模。ELISA检测血清中天冬氨酸转氨酶(AST)、γ-谷氨酰转肽酶(γ-GT)和肝脏中的谷丙转氨酶(ALT)、前白蛋白(PA)、丙二醛(MDA)、超氧化物歧化酶(SOD)的水平,苏木精-伊红染色法(HE)观察肝组织病理变化,并使用16S rRNA基因测序分析技术分析了麦角甾酮对小鼠肠道菌群的影响。结果 麦角甾酮可显著降低小鼠血清中AST、γ-GT和肝组织中ALT和MDA的水平,显著升高肝组织中PA和SOD的水平,并可调节酒精引起肠道菌群中门水平和属水平菌群丰富度的变化。结论 麦角甾酮对小鼠酒精诱导的急性肝损伤具有保护作用,并且可通过调节肠道菌群来改善肝损伤。     

Effect of high volume hemofiltration on CHOP protein from a canine model of multiple organ dysfunction syndrome

Objective To observe the effect of high volume hemofiltration (HVHF) on the expression of CCAAT enhancer binding protein(CHOP) during the treatment of multiple organ dysfunction syndrome (MODS). To investigate the role of CHOP protein act in apoptosis pathway mediated by the endoplasmic reticulum stress. Methods Twelve Beagle dogs were subjected to hemorrhagic shock plus resuscltation and endotixemia to establish MODS model, then they were randomly divided into two groups: HVHF group (n=6) and MODS group (n=6). After endotoxin injection completed, the HVHF group received HVHF treatment for 24 hours; MODS group did not receive. Vivo experiments: Blood samples were obtained at different time points(before operation, 0 h, 6 h, 12 h, 24 h after the injection of endotoxin). The dogs were killed and the tissue samples from lung, liver and kidney were took, then the expression of CHOP mRNA was determined. Vitro experiments: human umbilical vein endothelial cells (HUVECs) were induced by two groups’ blood samples to establish the apoptosis model. Gene expression, protein quantification and cell apoptosis rate were determined before and after the interference. Results Vivo experiments: The levels of CHOP mRNA from lung, liver and kidney had no significant difference between the two groups (P＞0.05). Vitro experiments: (1)The expression of CHOP mRNA: Compared with MODS group, the expression levels of CHOP mRNA were significantly decreased in HVHF group at 6 h, 24 h after the injection of endotoxin (P＜0.05). Compared with before, the expression levels of CHOP mRNA in the two groups were both significantly decreased after CHOP siRNA interference (P＜0.05). (2)The expression of CHOP protein: Compared with MODS group, the expression levels of CHOP protein were significantly decreased in HVHF group at each time points (P＜0.05). Compared with before, the expression levels of CHOP protein in the two groups were both significantly decreased after CHOP siRNA interference(P＜0.05). (3)Endothelial cell apoptosis rate: Compared with the preoperative rate, the two group’s endothelial cell apoptosis rate was decreased significantly at each time points(P＜0.05). Compared with MODS group, the endothelial cell apoptosis rate was significantly decreased in HVHF group at each time points(P＜0.05). Compared with before, the endothelial cell apoptosis rate in the two groups was both significantly decreased after CHOP siRNA interference(P＜0.05). Conclusion In the treatment of MODS process, HVHF can reduce endothelial cell apoptosis which may be related to the inhibition of CHOP mRNA expression and protein synthesis.     

MHC捕获测序探寻慢性肾功能衰竭的致病基因

目的 研究慢性肾功能衰竭患者人类白细胞抗原(HLA)基因,以获得慢性肾功能衰竭的致病突变.方法 使用新的MHC捕获技术结合新一代高通量测序技术对15例慢性肾功能衰竭患者和15名健康对照的HLA区域基因进行捕获测序.结果 慢性肾功能衰竭的致病与HLA-A* 02∶01∶01、B*15∶01∶01和DRB1* 09∶01∶02关联,且这三个基因相互独立与慢性肾功能衰竭关联.结论 HLA-A*02∶01∶01、B* 15∶01∶01和DRB1* 09∶01∶02与慢性肾功能衰竭相关.采用MHC基因捕获技术结合下一代高通量测序技术研究慢性肾功能衰竭的基因易感性是可行的.     

Body mass index as a predictor of hypertension incidence among initially healthy normotensive women

BACKGROUND: Few prospective studies have evaluated the risk for incident hypertension (HTN) across the normal range of body mass index (BMI). Even fewer studies included body composition and fat distribution measurements in their analyses. In the Aerobics Center Longitudinal Study, we examined HTN risk in women across a wide spectrum of baseline BMI (kg/m(2)) values and also studied waist circumference (WC, cm), percent body fat, fat mass (FM, kg), and fat-free mass (FFM, kg) on incident HTN in subgroup analyses. METHODS: A total of 5,296 healthy normotensive women between 20 and 77 years of age completed a baseline examination during 1971-2004, and were followed for HTN incidence. Incident HTN was identified using mail-back surveys. RESULTS: A total of 592 women reported HTN during a mean 16.7 years of follow-up. Higher BMI, even within the "normal" range, was associated with greater risk of HTN. Compared with women in the lowest fifth of BMI (18.5-20.0 kg/m(2)), the hazard ratios (HRs) (95% confidence interval (CI)) of developing HTN for women with a BMI of 20.1-21.2, 21.3-22.5, 22.6-24.7, and >24.7 were 1.19 (0.89-1.60), 1.33 (0.99-1.78), 1.36 (1.03-1.81), and 2.01 (1.52-2.66), respectively (P(trend) < 0.001). In a subgroup (n = 3,189) with complete data on all the five adiposity measures, significant positive associations with HTN were seen across incremental fifths of BMI, percent body fat, and FM (P(trend) < 0.05 each), but not WC and FFM. CONCLUSIONS: Clinicians should emphasize the importance of weight management for the primary prevention of HTN in women.     

Upregulation of cell surface estrogen receptor alpha is associated with the mitogen-activated protein kinase/extracellular signal-regulated kinase activity and promotes autophagy maturation

Recently, accumulating evidence has implicated the dysregulation of autophagy as underlying the pathophysiology of several neurodegenerative diseases. The human neuronal cell line SH-SY5Y was exposed to 1-Methyl-4-phenylpyridinium (MPP⁺). The mechanism is that the sustained activation of the MAPK/ERK pathway by MPP⁺ alters autophagy selectively at the maturation step, significant increasing in autophagy formation and delaying in autophagy degradation in SHSY5Y cells. In this study, we provided evidences that estrogen was capable of promoting SHSY5Y cells survival in MPP⁺-treated group. In particular, the up-regulation of mERα, but not mERβ, was associated with a rapid and transient activation of ERK phosphorylation compatible with promoting autophagy maturation. The up-regulation of mERα changed the sustained activation of ERK phosphorylation in MPP⁺-treated group into a temporary activation. Taken together, these findings strongly support that the expression of mERα promotes the maturation of autophagosomes into functional autolysosomes by regulating ERK, determining SHSY5Y cells survival.     

Synergistic effects of snail and quercetin on renal cell carcinoma Caki-2 by altering AKT/mTOR/ERK1/2 signaling pathways

Renal cell carcinoma has become the most common subtype of kidney cancer, and has the highest propensity to manifest as metastatic disease. Because of lack of knowledge in events that correlated with tumor cell migration and invasion, few therapeutic options are available. Therefore, in current study, we explore the anti-tumoral effect of a potential chemopreventive natural product, quercetin, combined with anti-sense oligo gene therapy (inhibiting Snail gene). We found that either one of them had the remarkable effects in suppressing cell proliferation and migration, inducing cell cycle arrest and apoptosis in a ccRCC cell line, Caki-2 cells. The combination of both means provides even strong suppressive effects toward these ccRCC cells. Our study, for the first time, provides the possibility of using a novel treatment for renal cancer, by combining natural product and gene therapy.     

Ipsilateral breast metastasis from a pulmonary adenocarcinoma: a case report and a focused review of the literature

Metastases to the breast from extramammary malignancies are extremely rare. Ruling out the diagnosis of primary breast tumor is important in order to decide on clinical management and predict prognosis. We report a case of metastasis to the breast from a pulmonary adenocarcinoma, with extensive micropapillary component, diagnosed concomitantly with the primary tumor. A 52 year-old female patient presented with mammary gland tingling and dyspnea accompanied with fatigued of 4 months duration and a nodular shadows in the front of the upper lobe was found on a chest computed tomography (CT) scan. The original clinical diagnosis was right breast cancer with lung and bone metastasis, or breast and lung double primary cancers. In addition,on physical examination a poorly defined mass was noted in the upper outer quadrant of the right breast. The patient underwent thoracocentesis and breast biopsy. By imageology, cytology, histology and immunohistochemistry, we diagnosed primary lung cancer with metastases to the right breast and bone. The metastatic anatomic sites demonstrated histologically extensive micropapillary component, which is recently recognized as an important prognostic factor. The patient was administered 4 cycles of cisplatin and docetaxel, although no clinical response was seen, the patient is still alive 9 months after diagnosis. The result of immunohistochemistry is a useful supplement in differential diagnosis.