COX．2介导的TH2类细胞因子与重症肝炎的关系研究

目的：探讨重症肝炎与COX-2的关系,为临床防治重症肝炎提供新的治疗理论和方法。方法：用FH643A-γ测量仪检测50例肝病患者和25例正常对照血清中PGs代谢产物TXB2、6-keto-PGF1α的水平。结果：各组肝病患者血清中TXB2和6-keto-PGFlet的表达水平均明显高于正常人（P〈0．001）,并且随着病情的好转,T／6-K比值明显下降,但肝病患者各组间细胞因子水平无显著性差异（p〉0．05）。结论：检测重症肝炎患者血清TXB2、6-keto—PGF1α的水平和T／6-K比值不仅对揭示肝病发生发展过程有一定的实用价值．而且对监测病情转归和预后有重要临床意义。     

COX-2与糖尿病并发症关系研究进展

糖尿病是一种慢性、低度炎症性疾病。多种因素刺激下,环氧化酶COX-2在胰岛及多种组织中高水平表达。它通过与炎症因子和炎症介质,如一氧化氮、核因子-κB、前列腺素E等相互作用,对相应组织产生作用,从而促进了糖尿病并发症的发生和发展。对COX-2的研究可进一步揭示糖尿病并发症发生的分子机制,为预防和治疗糖尿病并发症提供新的思路。     

8例胆道周围感染与小儿亚急性重症肝炎关系的临床分析

对8例小儿亚急性重症肝炎合并胆道周围感染进行了临床分析。其结果,8例胆道周围感染的B型超声图像均有特征性显示。其中以壁厚、呈双边征,胆囊水肿显示率最高;8例胆道周围感染中,血象仅有1例在正常范围内,余均超过正常范围,白细胞升高者占盯．5％,8例血象75％以中性粒细胞升高为主。 认为,（1）胆道周围感染与肝脏病变互为因果。感染是小儿重型病毒性肝炎致死的重要原因之一;（2）继发感染在重症肝炎时易被忽视。感染灶不易被发现,临床表现多不典型。B超图像特征性显示,对胆道周围感染的诊断有很大的临床实用价值。     

COX-2与VEGF-C在大肠癌中的表达及与预后的关系

目的探讨COX-2与VEGF-C在大肠癌组织中的表达及与临床病理因素之间的关系。方法运用免疫组化方法检测54例大肠癌组织中COX-2与VEGF-C的表达。结果COX-2和VEGF-C蛋白在大肠癌中的表达阳性率分别为72．22％（39／54）和64．81％（35／54）,COX-2与VEGF-C表达之间存在显著的相关性（P〈0．001）;在伴有淋巴结转移的大肠腺癌中,COX-2与VEGF-C的阳性表达率分别为87．5g（21／24）和91．67％（22／24）,转移组与非转移组相比较均有显著性差异（P＜0．05）;COX-2蛋白表达与肿瘤大小、浸润深度、Duke’s分期呈负相关（P〈0．05）,与组织分化、性别、年龄等临床病理因素无关（P〉0.05）。VEGF-C表达与浸润深度、Duke’s分期呈负相关（P〈0．05）,与组织分化、性别、年龄、肿瘤大小等临床病理因素无关（P〉0．05）。结论COX-2蛋白与VEGF-C共表达可增加大肠癌转移和侵袭能力,其检测有助于大肠癌恶性程度评价及临床预后的判断。     

重症肝炎血浆置换术前护理问题分析与对策

目的：通过分析重症肝炎病人行血浆置换术的护理问题,提出相应的护理对策,减少手术的危险性。方法：通过沟通、观察、查阅病例。收集要钉血浆置换治疗的16例重症肝炎病人的资料,包括身体状况、心理、文化、社会、经济等。提出现存的或潜在的护理问题。寻求问题原因,经分析后进行护理帮助,做到了从生物一心理一社会医学模式的整体进行评估和护理。结果：10例重症肝炎病人在行血浆王换术前较以往病人情绪稳定,6例肝性脑病病人家属能周到的照顾病人,积极配合治疗。16例病人都能顺利完成血浆置换,提高了病人的治愈率。结论：重症肝炎病人行血浆置换前,实施积极有效的护理措施。较以前无护理措施者或肤浅的指导能降低手术危险性,使手术得以顺利进行。     

8例胆道周围感染与小儿亚急性重症肝炎关系的临床分析

对8例小儿亚急性重症肝炎合并胆道周围感染进行了临床分析。其结果,8例胆道周围感染的B型超声图像均有特征性显示,其中以壁厚、呈双边征,胆囊水肿显示率最高;8例胆道周围感染中,血象仅有1例在正常范围内,余均超过正常范围,白细胞升高者占87.5%,8例血象75%以中性粒细胞升高为主。认为,(1)胆道周围感染与肝脏病变互为因果。感染是小儿重型病毒性肝炎致死的重要原因之一;(2)继发感染在重症肝炎时易被忽视,感染灶不易被发现,临床表现多不典型。B超图像特征性显示,对胆道周围感染的诊断有很大的临床实用价值。     

甘草总黄酮对慢性浅表性胃炎患者胃粘膜COX-1和COX-2表达的影响

目的：探究甘草总黄酮对慢性浅表性胃炎患者胃粘膜COX-1 及COX-2 表达的影响。方法：选取我院2014 年1 月-2014 年 12 月收治的慢性期浅表性胃炎患者48 例,随机分为两组,其中对照组24 例给予阿莫西林口服治疗,实验组24 例予以甘草黄酮 提取物口服治疗。观察并比较两组患者的临床疗效及胃粘膜COX-1 和COX-2 的阳性率。结果：与实验前相比,治疗后两组 COX-1 阳性率显著升高（P<0.05）;与对照组相比,实验组升高更明显,差异具有统计学意义（P<0.05）;治疗后两组COX-2 阳性率 显著降低（P<0.05）;与对照组相比,实验组降低更明显,差异具有统计学意义（P<0.05）;治疗后两组患者胃粘膜细胞凋亡指数明显 降低（P<0.05）;与对照组相比,实验组下降更明显,差异具有统计学意义（P<0.05）;与对照组有效率比较,实验组较高,差异具有统 计学意义,（P<0.05）。结论：甘草总黄酮可以改善慢性浅表性胃炎患者的临床症状。     

重症肝炎血浆置换术前护理问题分析与对策

目的:通过分析重症肝炎病人行血浆置换术的护理问题,提出相应的护理对策,减少手术的危险性。方法:通过沟通、观察、查阅病例,收集要行血浆置换治疗的16例重症肝炎病人的资料,包括身体状况、心理、文化、社会、经济等,提出现存的或潜在的护理问题,寻求问题原因,经分析后进行护理帮助,做到了从生物-心理-社会医学模式的整体进行评估和护理。结果:10例重症肝炎病人在行血浆置换术前较以往病人情绪稳定,6例肝性脑病病人家属能周到的照顾病人,积极配合治疗。16例病人都能顺利完成血浆置换,提高了病人的治愈率。结论:重症肝炎病人行血浆置换前,实施积极有效的护理措施,较以前无护理措施者或肤浅的指导能降低手术危险性,使手术得以顺利进行。     

肺癌化学预防和治疗的新途径——COX-2

肺癌的发生包含基因突变、凋亡受阻、增殖失控、转移侵袭、血管生成等一系列过程.表皮细胞向间叶细胞化生是癌变的一个重要过程,它的发生是由于人体内解除控制的炎症反应,从而导致细胞免疫的削弱和恶性肿瘤的发生.基于肿瘤细胞存在免疫抑制性,如何提高人体的免疫反应成为我们研究的重点.环氧合酶-2(COX-2)及其下游信号转导可能成为肺癌的化学预防和治疗的途径.COX-2抑制剂作为肺癌患者化疗的辅助用药和预防支气管肺癌发生的作用等大量临床实验正在进行.随着对炎症反应和肺癌发生的分子机制的认识,我们发现了新的药物来逆转或阻止突变,为肺癌的化学预防和治疗提供了方向.     

原发性翼状胬肉中COX-2与iNOS的表达及相关研究

目的:探讨环氧合酶2(COX-2)与诱导型一氧化氮合酶(iNOS)在原发性翼状胬肉中的表达及其在发生发展过程中的作用.方法:原发性翼状胬肉组织与对照组的正常结膜组织标本均取自石河子大学第一附属医院眼科行手术治疗的患者,采用免疫组织化学Elivision法分别检测56例原发性翼状胬内、20例正常结膜中COX-2、iNOS的表达;脱氧核苷酸末端转移酶介导的脱氧尿苷三磷酸末端标记法(terminal deoxynucleotidyl transferase mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling,TUNEL),检测不同时期原发性翼状胬肉细胞中凋亡细胞的表达.结果:56例原发性翼状胬肉中COX-2的阳性表达率,静止期为50%,进行期为87.5%,正常结膜为0(0/20).iNOS的阳性表达率,静止期为50%,进行期为92.5%,正常结膜50%.COX-2、iNOS阳性表达在原发性翼状胬肉与正常结膜两组间差异有显著意义,P＜0.001.正常结膜对照组无凋亡细胞表达,静止期和进行期胬肉组织中均出现凋亡细胞,凋亡细胞的表达在静止期和进行期2组间的表达有明显差异(P＜0.05)).结论:COX-2、iNOS在翼状胬肉中的表达,提示COX-2、iNOS可促进新生血管形成,可能与翼状胬肉的发生、发展以及术后复发有关,细胞凋亡在翼状胬肉的发生中起重要作用,COX-2、iNOS抑制剂以及细胞凋亡的调控可望成为降低翼状胬肉复发率新的依据.     

Rho GTP酶参与肿瘤调控的下游效应蛋白

小G蛋白Rho家族是一类能结合GTP的蛋白质,在哺乳动物细胞的信号转导系统中发挥着“分子开关”样的重要作用。Rho蛋白通过其下游效应蛋白介导发挥多种生物学效应,包括调控细胞骨架重组、黏附和运动等。近年来,Rho蛋白在肿瘤细胞的增殖、分化、凋亡和转移的调控中的作用渐受重视。该文就介导RhoGTP酶调控肿瘤发生发展的几个下游蛋白作一介绍。     

COX-2在乙肝病毒X蛋白（HBx）促进肝癌细胞和肝细胞增殖中的作用

乙型肝炎病毒（hepatitis B virus, HBV）X蛋白（HBx）对肝癌的发生发展具有十分重要的作用．大量研究结果表明,与花生四烯酸代谢相关的磷脂酶COX-2与肿瘤细胞的增殖密切相关．为了阐明COX-2在HBx促进肝细胞增殖中的作用,在前期应用基因芯片方法检测发现稳定转染HBx 基因的肝癌细胞H7402-X中COX-2基因表达明显上调的基础上,本研究应用免疫印迹技术在蛋白表达水平上获得了相同的结果．进而,应用COX-2的特异性抑制剂Indo分别作用H7402-X细胞和L-O2-X细胞（稳定转染HBx 基因的人永生化L-O2肝细胞）,观察HBx蛋白是否通过COX-2促进肝癌细胞或肝细胞增殖．BrdU掺入实验和流式细胞仪检测结果显示,50 μmol/L的Indo可明显抑制H7402-X细胞和L-O2-X细胞的增殖．本研究结果提示,HBx可通过COX-2所介导的花生四烯酸代谢促进肝癌细胞和肝细胞增殖．     

细胞因子在脑缺血损伤中的作用研究进展

脑缺血一旦发生,往往引起不同程度的脑损伤。缺血脑组织会产生一系列复杂的病理生理学改变。一组称为细胞因子的多肽调节物质在脑缺血损伤过程中起着关键的作用。包括神经细胞在内的多种细胞能够产生和分泌细胞因子,它们的表达时相性和作用各不相同。脑缺血引起TNF-α、IL-1、IL-6、IL-8、IL-10和FKN等多种细胞因子的表达和释放,进而触发有关损伤和修复的应答。这些参与脑缺血损伤的细胞因子能通过复杂的细胞因子网络对中枢神经系统发挥着毒性或保护效应。探究它们在脑缺血损伤中的确切作用将有助于神经系统疾病的临床治疗。现对几种关键的细胞因子综述如下。     

细胞因子在类风湿关节炎发病机制中的作用

机体的免疫细胞和非免疫细胞合成和分泌的小分子多肽类因子统称为细胞因子。随着对类风湿关节炎（RA）的病因及发病机制的深入研究,发现细胞因子在RA发病过程中起重要作用。简要综述了细胞因子在RA发病中的促炎、抗炎作用,及细胞因子间的相互作用。     

The Metalloprotease ADAM12 Regulates the Effector Function of Human Th17 Cells

A key modulator of immune homeostasis, TGFβ has an important role in the differentiation of regulatory T cells (Tregs) and IL-17-secreting T cells (Th17). How TGFβ regulates these functionally opposing T cell subsets is not well understood. We determined that an ADAM family metalloprotease called ADAM12 is specifically and highly expressed in both Tregs and CCR6+ Th17 cells. ADAM12 is induced in vitro upon differentiation of naïve T cells to Th17 cells or IL-17-secreting Tregs. Remarkably, silencing ADAM12 expression in CCR6+ memory T cells enhances the production of Th17 cytokines, similar to suppressing TGFβ signaling. Further, ADAM12 knockdown in naïve human T cells polarized towards Th17/Treg cells, or ectopically expressing RORC, greatly enhances IL-17-secreting cell differentiation, more potently then inhibiting TGFβ signals. Together, our findings reveal a novel regulatory role for ADAM12 in Th17 cell differentiation or function and may have implications in regulating their aberrant responses during immune pathologies.     

Substantial Conformational Change Mediated by Charge-Triad Residues of the Death Effector Domain in Protein-Protein Interactions

Protein conformational changes are commonly associated with the formation of protein complexes. The non-catalytic death effector domains (DEDs) mediate protein-protein interactions in a variety of cellular processes, including apoptosis, proliferation and migration, and glucose metabolism. Here, using NMR residual dipolar coupling (RDC) data, we report a conformational change in the DED of the phosphoprotein enriched in astrocytes, 15 kDa (PEA-15) protein in the complex with a mitogen-activated protein (MAP) kinase, extracellular regulated kinase 2 (ERK2), which is essential in regulating ERK2 cellular distribution and function in cell proliferation and migration. The most significant conformational change in PEA-15 happens at helices α2, α3, and α4, which also possess the highest flexibility among the six-helix bundle of the DED. This crucial conformational change is modulated by the D/E-RxDL charge-triad motif, one of the prominent structural features of DEDs, together with a number of other electrostatic and hydrogen bonding interactions on the protein surface. Charge-triad motif promotes the optimal orientation of key residues and expands the binding interface to accommodate protein-protein interactions. However, the charge-triad residues are not directly involved in the binding interface between PEA-15 and ERK2.     

Profile of Central and Effector Memory T Cells in the Progression of Chronic Human Chagas Disease

Background

Chronic Chagas disease presents several different clinical manifestations ranging from asymptomatic to severe cardiac and/or digestive clinical forms. Several studies have demonstrated that immunoregulatory mechanisms are important processes for the control of the intense immune activity observed in the chronic phase. T cells play a critical role in parasite specific and non-specific immune response elicited by the host against Trypanosoma cruzi. Specifically, memory T cells, which are basically classified as central and effector memory cells, might have a distinct migratory activity, role and function during the human Chagas disease.

Methodology/Principal Findings

Based on the hypothesis that the disease severity in humans is correlated to the quality of immune responses against T. cruzi, we evaluated the memory profile of peripheral CD4⁺ and CD8⁺ T lymphocytes as well as its cytokine secretion before and after in vitro antigenic stimulation. We evaluated cellular response from non-infected individuals (NI), patients with indeterminate (IND) or cardiac (CARD) clinical forms of Chagas disease. The expression of CD45RA, CD45RO and CCR7 surface molecules was determined on CD4⁺ and CD8⁺ T lymphocytes; the pattern of intracellular cytokines (IFN-γ, IL-10) synthesized by naive and memory cells was determined by flow cytometry. Our results revealed that IND and CARD patients have relatively lower percentages of naive (CD45RA^high) CD4⁺ and CD8⁺ T cells. However, statistical analysis of ex-vivo profiles of CD4⁺ T cells showed that IND have lower percentage of CD45RA^high in relation to non-infected individuals, but not in relation to CARD. Elevated percentages of memory (CD45RO^high) CD4⁺ T cells were also demonstrated in infected individuals, although statistically significant differences were only observed between IND and NI groups. Furthermore, when we analyzed the profile of secreted cytokines, we observed that CARD patients presented a significantly higher percentage of CD8⁺CD45RA^high IFN-γ-producing cells in control cultures and after antigen pulsing with soluble epimastigote antigens.

Conclusions

Based on a correlation between the frequency of IFN-γ producing CD8+ T cells in the T cell memory compartment and the chronic chagasic myocarditis, we propose that memory T cells can be involved in the induction of the development of the severe clinical forms of the Chagas disease by mechanisms modulated by IFN-γ. Furthermore, we showed that individuals from IND group presented more T_CM CD4⁺ T cells, which may induce a regulatory mechanism to protect the host against the exacerbated inflammatory response elicited by the infection.     

The role of IL-10 in crossregulation of TH1 and TH2 responses

The identification of helper T (T_H)-cell subsets has greatly improved understanding of the regulation of immune effector functions. In addition to controlling humoral and delayed-type hypersensitivity responses, these subsets crossregulate by secreting mutually inhibitory cytokines. In this review, Tim Mosmann and Kevin Moore examine these phenomena and in particular the role of interleukin 10, a cytokine secreted by T_H2 cells that inhibits T_H1-cell function.