Pathogenic molecular mechanisms in an animal model of fulminant hepatic failure: rabbit hemorrhagic viral disease

In this study we sought to determine whether molecular mechanisms involved in the pathogenesis of fulminant hepatic failure are present in rabbits experimentally infected with rabbit hemorrhagic disease virus (RHDV). The activities of aspartate aminotransferase, alanine aminotransferase, and lactate dehydrogenase, as well as bilirubin concentration, were found to be significantly increased 36 hours after infection. Infected animals also demonstrated significant decreases in factor VII activity, in the Fischer index, and in the deterioration of prothrombin time. The concentration of reduced glutathione was significantly decreased 36 hours after infection, and we noted a marked increase in the ratio of oxidized to reduced glutathione. Infected animals showed progressive decreases in liver activity of the antioxidant enzyme superoxide dismutase. Expression of hepatocyte growth factor and c-met was found to be progressively reduced from 24 hours after infection, during which time we detected no modification in messenger RNA (mRNA) levels of transforming growth factor (TGF)-alpha. TFG-beta 1 was overexpressed 24 and 36 hours after infection, and 36 hours after infection we detected a significant increase in TNF-alpha mRNA levels. Experimental RHDV infection also induced marked activation of nuclear factor-kappaB and a significant increase in inducible nitric oxide synthase mRNA levels from 24 hours after infection. Data obtained from this animal model support its usefulness in the investigation of potential novel therapeutical modalities aimed at neutralizing reactive oxygen species and hepatocyte growth inhibitors or enhancing hepatocyte responsiveness to mitogens.     

自拟消鼽汤协定方对过敏性鼻炎患者中医证候积分及转化生长因子-α、白细胞介素-4水平变化的影响

目的:研究自拟消鼽汤协定方对过敏性鼻炎患者中医证候积分及转化生长因子-α(TGF-α)、白细胞介素-4(IL-4)水平变化的影响。方法:选取我院收治的过敏性鼻炎患者60例作为研究对象,随机分组,各30例。对照组给予西医常规治疗,观察组在对照组基础上给予自拟消鼽汤协定方治疗。比较两组治疗效果、治疗前后中医证候积分、血清炎性因子(TGF-α、IL-4)水平。结果:与对照组总有效率73.33%(22/30)相比,观察组93.33%(28/30)较高(P<0.05);治疗4周后,两组喷嚏、鼻痒、流涕、鼻塞积分较治疗前显著降低,且与对照组相比,观察组较低(P<0.05);治疗4周后,两组血清TGF-α、IL-4水平较治疗前显著降低,且与对照组相比,观察组较低(P<0.05)。结论:自拟消鼽汤协定方治疗过敏性鼻炎患者疗效显著,可明显改善临床症状,减轻炎症反应。     

Protective effects of CVPM on vascular endothelium in rats fed cholesterol diet

BACKGROUND: The cardiovascular protective mixture (CVPM) is a concoction of nine Chinese traditional medicines: Dan-shen root, Szechwan lovge rhizome, Chinese angelica, Hawthorn fruit, Safflower, Peach seed, Red peony root, earthworm, and membranous milkvetch root. These medicines are used to cure cardiovascular disease in China. METHODS: Animal models were established by feeding the Sprague-Dawley (SD) rats with lipid-rich forage. Serum total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) were measured. Malondialdehyde (MDA) content was determined to monitor lipid peroxidation. The 6-keto-prostaglandin F(1alpha)(6-keto-PGF(1alpha)) concentration was measured by radioimmunoassay to investigate the content of prostacyclin (PGI(2)). Electron microscope (JEM-1200EX) was used to observe the microstructure of the vascular endothelium. Rat aortic endothelial cell was cultured to investigate the effect of CVPM on vascular endothelial cell in vitro. RESULTS: CVPM inhibited the accumulation of TC, LDL-C, and MDA in vivo, when the rats were fed with cholesterol diet. CVPM promoted synthesizing and excreting of PGI(2), since it is capable of activating the proliferation of vascular endothelium in vitro. Electron micrographs showed that CVPM had notable protective effect on the vascular endothelium and prevented the shedding of these cells from subendothelial layer. CONCLUSIONS: CVPM could ameliorate the internal environment in which vascular endothelial cells lived, and activate the proliferation of these cells. Through these mechanisms, CVPM protect vascular endothelial cell from being harmed by excess cholesterol in vivo.     

细胞因子TNF-α和血管内皮细胞功能标志物与多器官功能衰竭综合征的关系

目的探讨在多器官功能衰竭综合征(MODS)患者中细胞因子TNF-α和血管内皮细胞功能标志物的变化。方法动态观察MODS及非MODS患者一氧化氮(NO)、内皮素(ET-1)、组织纤溶酶原激活物(t-Pa)、纤溶酶原激活物抑制物-1(PAI-1)、循环内皮细胞(CEC)、肿瘤坏死因子(TNF-α)的浓度,同时给予Marshall评分。结果与非MODS组相比,MODS组、死亡组的TNF-α、ET- 1、PAI-1、CEC、Marshall评分显著升高(P＜0．05),而NO、t-Pa显著降低(P＜0．05)。结论TNF-α作为炎性因子在MODS的进展中起重要作用；在MODS时内皮细胞的损伤表现为ET-1、PAI-1、CEC增加,NO、t-PA减少,Marshall评分对于危重症患者的评估是敏感指标。     

IL-6、TNF-α、CRP在急性脑梗死患者血清中的表达及临床意义

目的检测白介素-6(IL-6)、肿瘤坏死因子-α(TNF-α)、C反应蛋白(CRP)在急性脑梗死患者血清中的表达并分析其临床意义。方法2015年5月至2017年8月,选取100例急性脑梗死患者、100例健康体检者,分别设为观察组、对照组。观察组依据病情轻重、病灶大小分为重、中、轻度组,大、中、小灶组。对比组间IL-6、TNF-α、CRP表达情况。结果观察组血清IL-6、TNF-α、CRP水平明显高于对照组(P<0.05)。不同病情、病灶组间的血清IL-6、TNF-α、CRP水平比较,差异有统计学意义(P<0.05)。血清IL-6、TNF-α水平:重度组>中度组>轻度组(P<0.05);血清CRP水平:重度组>中、轻度组(P<0.05)。血清IL-6、CRP水平:大灶组>中灶组>小灶组(P<0.05);血清TNF-α水平:大灶组>中、小灶组(P<0.05)。结论IL-6、TNF-α、CRP在急性脑梗死患者血清中高表达,可能参与疾病的发生发展,临床应给予重视。     

核转录因子-κB诱导肿瘤坏死因子-α在肝肺综合征大鼠肺血管内巨噬细胞中的表达及吡咯醛二硫氨基甲酸对其表达的影响

目的 探讨核转录因子-κB(NF-κB)及肿瘤坏死因子-α(TNF-α)在大鼠肺血管内巨噬细胞(PIM)内的表达及吡咯醛二硫氨基甲酸(PDTC)对其表达的影响.方法 SD大鼠随机分4组:对照组、PDTC对照组、CCI4组、CCI4+PDTC组.取动脉血作血气分析,静脉血测内毒素和肝功能.取肠系膜淋巴结作细菌培养.应用免疫组化方法 观察PIM的粘附、聚集情况,以及TNF-α和NF-κB的蛋白表达和定位.非放射性凝胶电泳阻滞实验(EMSA)检测NF-κB活性,SYBR Green I实时定量PCR方法 检测肺组织中TNF-α的mRNA表达.结果 CCl4组发展成肝肺综合征(HPS)模型,表现为PaO2、PaCO2降低和肺泡一动脉血氧分压(A-aDO2)升高,肝功能异常,内毒素血症.CCl4组肠系膜淋巴结培养阳性率为62.5%(5/8),与CCl4+PDTC组的66.7%(6/9)比较差异无统计学意义(P>0.05).CCl4组超过10个巨噬细胞的血管为60.8%(292/480),而CCl4+PDTC组仅为19.6%(106/540),两组比较差异有统计学意义(P<0.01).对照组和PDTC对照组中肺血管内无巨噬细胞聚集.免疫组化染色NF-κB和TNF-α蛋白均在CCl4组的PIM中表达.CCl4组的NF-κB活性和TNF-α的mRNA表达明显高于对照组、PDTC对照组和CCl4+PDTC组(均P<0.05).结论 NF-κB诱导PIM内TNF-α表达在HPS中发挥重要作用,PDTC通过抑制PIM中NF-κB的活性,降低PIM活性以及其中TNF-α表达,从而改善HPS.     

α－干扰素加冷冻治疗慢性宫颈炎疗效分析

精制人白细胞α－干扰素治疗妇科宫颈糜烂４１３３例，Ｉ°１７９４例，治愈率８５．４５％，有效率９８．２２％；Ⅱ°２１４３例，治愈率７９．６１％，有效率９３．２３％；Ⅲ°１９６例，治愈率３５．７１％，有效率５３．０６％。α－干扰素对轻度及中度糜烂疗效显著，对重度疗效较差。α－干扰素对轻度及中度疗效与冷冻、激光、微波、电的术疗效无显著差异，且副作用少，对重度糜烂采用α－干扰素和冷冻联合治疗疗效明显。     

Resveratrol inhibits hypoxia-induced metastasis potential enhancement by restricting hypoxia-induced factor-1α expression in colon carcinoma cells

Resveratrol has been shown recently to exhibit antimetastatic effect on various human solid tumors. However, the possible molecular mechanism for its antimetastatic action needs to be elucidated. In this study, we investigated the effect of resveratrol on metastasis potential of colon carcinoma cells under normoxia and hypoxia in vitro. These results showed that, resveratrol can restrict the migration, adhesion, invasion and MMP-9 and MMP-2 secretion in Lovo cells cultured under normoxia and hypoxia. Hypoxia and iron chelator 2,2′-dipyridyl treatment can stimulate the invasion and migration enhancement of Lovo cells, while resveratrol exhibited substantial resistance on the metastasis potential stimulation by inhibiting the mRNA expression of VEGF and MMP-9 in colon carcinoma cells under normoxia and hypoxia, reducing HIF-1α protein expression under hypoxia. Also, iron chelator 2,2′-dipyridyl treatment showed approximately the same effect on metastasis potential as Lovo cells cultured under hypoxia. These data demonstrated that, the antimetastatic effect of resveratrol under hypoxia were associated with the restriction of HIF-1α protein expression and stabilization, which could be a promising drug target for resveratrol in the development of an effective chemopreventive and anticancer therapy in human tumors.     

High levels of soluble GPR56/ADGRG1 are associated with positive rheumatoid factor and elevated tumor necrosis factor in patients with rheumatoid arthritis

Background

GPR56/ADGRG1 is a member of the adhesion-class G protein-coupled receptor (aGPCR) family important in brain development, oncogenesis and tumor metastasis. Like other aGPCRs, GPR56 is cleaved at the GPCR proteolysis site (GPS) motif into an N-terminal fragment (NTF) and a C-terminal fragment (CTF). Existence of soluble GPR56 (sGPR56) has been shown in vitro, however the underlying mechanism and its pathophysiologic role remains undetermined.