Th1/Th2和Tc1/Tc2与慢性丙型肝炎

CD4 +T细胞根据分泌的细胞因子不同可分为Th1和Th2细胞 ,同样 ,分泌Th1和分泌Th2样细胞因子的CD8+T细胞分别命名为Tc1和Tc2。一般说来 ,Th1细胞促进细胞免疫反应 ,Th2细胞促进体液免疫反应。Th1/Th2以及Tc1/Tc2细胞失衡与丙型肝炎的发病有密切的相关性 ,本文就这方面的有关研究近况作一简述。     

017 Th1/Th2和Tc1/Tc2与慢性丙型肝炎

CD4+T细胞根据分泌的细胞因子不同可分为Th1和Th2细胞,同样,分泌Th1和分泌Th2样细胞因子的CD8+T细胞分别命名为Tc1和Tc2.一般说来,Th1细胞促进细胞免疫反应,Th2细胞促进体液免疫反应.Th1/Th2以及Tc1/Tc2细胞失衡与丙型肝炎的发病有密切的相关性,本文就这方面的有关研究近况作一简述.     

PD-1/PD-L1/PD-L2小分子抑制剂的研究进展

正据世界卫生组织相关数据显示,全球每年大约有880万人死于恶性肿瘤,且增长态势显著,对人类健康造成了严重的威胁。研究显示免疫系统在人体自身稳态的维持中起着关键性作用,特别是近十年来随着较多肿瘤免疫药物被FDA批准上市,该疗法已成为肿瘤治疗领域的焦点。因此,2013年《科学》将其选为当年"最重要的突破"~([1]),2015年又将肿瘤免疫联合治疗列为"最值得关注的四项科学进展"之一。在肿瘤免疫治疗突破性进展中,免疫检查点抑制     

HMGB1对淋巴细胞增殖、凋亡及Th1/Th2、Tc1/Tc2漂移的影响

目的:探索HMGB1是否参与淋巴细胞免疫功能的调节.方法:系列浓度HMGB1单独或与ConA联合刺激培养小鼠脾淋巴细胞.MTT法检测细胞增殖,流式细胞术(FCM)检测细胞凋亡、细胞表面CD3、CD8及细胞内IL-4、IFN-γ表达.结果:(1)HMGB1时间-剂量依赖性调节淋巴细胞增殖,而不影响其凋亡.(2)不同HMGB1浓度和刺激时间不影响淋巴细胞Th1、Th2及Th1/Th2变化,但10 μg/L和100 μg/L HMGB1刺激12～24 h,Th1亚群占优势;培养12～24 h,淋巴细胞Tc1亚群明显减少,Tc2无变化.Tc1/Tc2变化显示,1 μg/L和10 μg/L HMGB1刺激,Tc1亚群占优势.(3)培养12～24 h,上清中IL-2增加,sIL-2R减少,IL-2/sIL-2R比例升高20～50倍,尤以10 μg/L HMGB1刺激明显.结论:低剂量HMGB1可增强淋巴细胞免疫功能.     

The MEK1/2–ERK1/2 Pathway is Activated in Chronic Rhinosinusitis with Nasal Polyps

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common disease that has a considerable impact on the quality of life. Alterations in signalling pathways may contribute to the ongoing inflammation and proliferation in CRSwNP. The MEK1/2–ERK1/2 pathway transmits signals from many extracellular molecules to regulate cellular processes. We examined tissue samples from nasal polyps and the inferior turbinate of patients with CRSwNP and the inferior turbinate from subjects with healthy mucosa. The expressions of MEK1/2, ERK1/2, and their active phosphorylated forms pMEK1/2 and pERK1/2 were analysed using DNA microarray, quantitative real-time PCR, protein array, Western hybridisation, and immunohistochemistry. We detected increased MEK1/2 protein expression in nasal polyps compared to the inferior turbinates of patients with CRSwNP or healthy mucosa. We also found a higher amount of MEK1/2 in the inferior turbinates of patients with CRSwNP compared to those with healthy mucosa. Most importantly, we observed a significant increase in the phosphorylation of MEK1/2 and ERK1/2 in nasal polyps compared to both types of controls. We observed activation of the MEK1/2–ERK1/2 pathway in nasal polyps. Interestingly, we did not see the same activation pattern in different tiers of the MEK1/2–ERK1/2 signalling cascade. One explanation for this result is that the components enhance the complex MEK–ERK cascade in a distinct manner, enabling a wide variety of functions. The MEK1/2–ERK1/2 pathway appears to play a pivotal role in the pathogenesis of CRSwNP.     

Th1/Th2、Tc1/Tc2亚群在乙肝肝硬化患者中的作用

目的 :探讨乙肝肝硬化患者外周血 (PBMC)中CD4 和CD8 T细胞内Th1和Th2类细胞的平衡状态 ,探明Th1、Th2类细胞在乙肝肝硬化中的作用。方法 :乙肝肝硬化患者CD4 T细胞和CD8 T细胞中IFN γ 和IL 4 细胞的百分率 ,观察乙肝肝硬化患者Th1 Th2、Tc1 Tc2比例的变化。结果 :乙肝肝硬化患者PBMC中CD4 ,CD8细胞 ,CD4 CD8比值与健康对照者相比无统计学差异 (P >0 0 5 ) ,Th1细胞及Tc1细胞百分率为 8 8% ,9 0 % ,较健康对照者 7 5 % ,7 7%升高 (P <0 0 5 )。结论 :乙肝肝硬化患者外周血T细胞亚群发生Th1类偏移 ,在乙肝肝硬化的发生和发展中可能起重要作用     

Graves'病患者Th1/Th2免疫应答及性激素对Th1/Th2的影响

Graves'病(GD)是最常见的自身免疫性甲状腺疾病(AI-TD),其发病机理以体液免疫异常为大家所熟知,但细胞因子在GD中的发病作用越来越受到国内外学者的重视,研究的焦点主要侧重于Th1/Tb2细胞平衡紊乱.GD及其他自身免疫性疾病女性显著高发,提示性激素是影响机体免疫功能的重要因素.本文就近年来国内外对GD患者Th1/Th2免疫应答的研究及性激素对Th1/Th2平衡的影响作一综述.     

疾病的T_H1/T_H2模式

疾病的ＴＨ１／ＴＨ２ 模式是指疾病所引起的机体优势免疫应答的类型（ＴＨ１ 型／ＴＨ２ 型）。这种模式可应用于多种疾病，如感染性疾病、过敏性疾病、自身免疫性疾病、流产、移植免疫及恶性肿瘤等，使人们更好地理解疾病的发生发展过程，并有助于发展新型免疫疗法。     

BRCA1/2基因变异解读简明流程

本文提出了一套简明实用的BRCA1/2变异解读流程,为新接触该领域的从业人员提供易于学习和掌握的入门级实践指导。     

HIV-1 /SARS-CoV-2合并感染研究进展

严重急性呼吸综合征冠状病毒2 （severe acute respiratory syndrome coronavirus 2,SARS-CoV-2）感染导致的新型冠状病毒肺炎（coronavirus disease 2019,COVID-19）引发全球大流行。HIV感染者/艾滋病患者是一个特殊人群,由于其免疫系统受损...     

Transforming growth factor-β1 induces glutathione peroxidase-1 and protects from H2O2-induced cell death in colon cancer cells via the Smad2/ERK1/2/HIF-1α pathway

Recent studies have shown that transforming growth factor-β1 (TGF-β1) signaling plays important roles in the redox system in benign and malignant cells. Whether TGF-β mediates an antioxidative damage response in colorectal cancer cells is largely unknown. Herein, using the human colorectal cancer cell lines we found that TGF-β1 induced glutathione peroxidase-1 (GPx-1) expression and enzyme activity, and that the upregulation of GPx-1 by TGF-β1 could protect colorectal cell lines from H2O2-induced oxidation damage. Further, we used loss- and gain-function approaches to elucidate the underlying mechanism and found that TGF-β1 induced GPx-1 through activation of the TGF-β receptor type?I (TGF-βRI)/Smad2/extracellular-signal-regulated kinase 1/2 (ERK1/2)/hypoxia-inducible factor-1α (HIF-1α) signaling pathway. This cascade could be blocked by the TGF-βRI inhibitor or ERK1/2 inhibitor. Taken together, our data demonstrated that TGF-β1 induced GPx-1 expression and enzymatic activity via the TGF-βRI/Smad2/ERK1/2/HIF-1α signaling pathway, suggesting a novel antioxidative protective function of TGF-β1 in colorectal cancer cells.     

Th1/Th2与慢性乙型肝炎

慢性乙型肝炎发病机制复杂 ,与机体的免疫状态密切相关 ,CD4 + Th细胞是机体的重要调节细胞 ,根据其产生细胞因子的不同分为Th1和Th2亚型 ,分别参与调节细胞免疫和体液免疫 ,Th1和Th2可相互调节 ,影响免疫应答的格局 ,Th1 Th2在多种感染性疾病中发挥重要作用 ,慢性乙肝患者存在Th1 Th2失衡 ,本文就Th1 Th2与慢性乙肝的关系研究进展进行简述。     

gr/gr-DAZ1/DAZ2基因缺失与男性不育

目的 研究中国人群中gr/gr-DAZ1/DAZ2缺失与男性不育的关系。方法 应用PCR和RFLP分析的方法，在364例男性不育患者和287个正常男性中，对gr/gr-DAZ1/DAZ2基因缺失进行调查。结果 在男性不育患者和正常男性中均发现gr/gr-DAZ1/DAZ2基因缺失，但男性不育患者中的缺失频率显著高于正常男性（9.3% vs. 2.8%, P<0.001）。结论gr/gr-DAZ1/DAZ2基因缺失不是中国人群男性不育的直接致病遗传因素，而是一个发病的风险因子，尚不足以作为男性不育基因诊断的指标。     

Type 1 1/2 diabetes: myth or reality?

The disease process in classical Type 1 diabetes patients (IDDM) is believed to be autoimmune. In contrast, the disease process in classical Type 2 diabetes patients (NIDDM) is not autoimmune and a decreased sensitivity to insulin action is the main abnormality. The clinical distinction of Type 1 diabetes versus Type 2 diabetes is recognized to be imperfect and has limitations. There is a group of individuals (Type 1 1/2 diabetes), who present like typical NIDDM, but have some of the immunological and clinical features of IDDM. We review the current medical literature on Type 1 1/2 diabetes with special reference to its clinical characteristics, natural history and pathophysiology. Since the distinction between these two forms of diabetes may have important therapeutic implications especially with regards to the benefits of insulin therapy in patients with Type 1 1/2 diabetes and because of the need for uniformity in its diagnosis we recommend that both clinical plus biochemical criteria (the presence of ICA and/or GAD Ab, HLA typing and tests to quantify beta cell function) be used to make a diagnosis. Comparative studies in the area of cytokine production, T cell reactivity and autoantibody clustering between classic Type 1 diabetes and Type 1 1/2 diabetes patients are needed as are studies with the animal model of Type 1 1/2 diabetes, Psammomys obesus.     

肺动脉高压患者肺组织S1PR1/2/3的表达

目的探讨肺动脉高压患者肺组织1-磷酸鞘氨醇受体1/2/3(sphingosine-1-phosphate receptor1/2/3,S1PR1/2/3)的表达变化,为肺动脉高压发病机制的深入研究奠定基础。方法人的肺组织来源于黑龙江省医院,其中对照组取自右下肺叶球形性变实施肺叶切除患者的肺组织,病变组取自患有特发性肺动脉高压尸检患者的肺组织,应用免疫印迹及实时定量PCR技术检测S1PR1/2/3的表达变化。结果原发性肺动脉高压患者肺组织S1PR1/2/3蛋白的光密度值分别为2.00±0.03,0.86±0.13,0.94±0.03,m RNA的绝对定量值分别为3.90±0.42,2.50±0.37,92.08±11.26,较对照组蛋白的光密度值(0.88±0.29,0.27±0.07,0.54±0.06)及m RNA的绝对定量值(1.44±0.33,1.12±0.15,1.63±0.56)明显增高(P0.01)。结论原发性肺动脉高压患者肺组织S1PR1/2/3的表达上调,提示S1PR1/2/3在肺动脉高压发病过程中可能发挥了重要的作用。     

CSF1通过CSF1R/PLCG2/ERK/Nrf2信号通路减少缺氧缺血性脑病大鼠神经元凋亡

目的:探讨集落刺激因子1(CSF1)通过CSF1受体(CSF1R)减轻缺氧缺血性脑病(HIE)大鼠神经元凋亡的下游信号通路.方法:采用原代大鼠皮质神经元建立氧糖剥夺(OGD)神经元损伤模型,重组人CSF1(rh-CSF1)干预该模型,通过CCK-8和MTT检测细胞活力,测定LDH漏出,Western blot检测CSF...     

Electroacupuncture delays articular cartilage degeneration in osteoarthritis via ras-raf-mek1/2-erk1/2 signaling pathway北大核心

BACKGROUND: Previous studies have found that electroacupuncture can delay articular cartilage degeneration mediated by JAK-STAT signaling pathway through upregulating the expression level of transforming growth factor β1 as well as mRNA expression levels of STAT3, Smad3 and LepR. In the meanwhile, electroacupuncture can inhibit the mRNA expression of p38 and Fas mRNA mediated by MAPK signaling pathways, further inhibiting the apoptosis of chondrocytes. OBJECTIVE: To explore the effect of electroacupuncture on the degeneration of articular cartilage in rats with knee osteoarthritis based on Ras-Raf-MEK1/2-ERK1/2 signaling pathway. METHODS: 120 male healthy Sprague-Dawley rats aged 2 months olds were selected and randomly divided into normal, model, 15-minite electroacupuncture and 30-minute electroacupuncture groups (n=30 per group). The rats in the latter three groups received the intra-articular injection of 4% papain bilaterally, and the remaining rats received no intervention. At 2 weeks after modeling, the latter two groups were respectively given 15-and 30-minute electroacupuncture, five times weekly for consecutive 12 weeks. The morphology of the cartilage was observed by hematoxylin-eosin staining, the expression level of interleukin-1β in the synovium was detected by ELISA assay, and the protein expression levels of Ras, Raf, MEK1/2, ERK1/2, C-MYC, C-FOS, and C-JUN were detected by western blot analysis. RESULTS AND CONCLUSION: Hematoxylin-eosin staining showed that: in the model group, the cartilage surface was rough, the cartilage layer became thinner, and the cartilage structure was damaged with incomplete tidal line; in the 15and 30-minute electroacupuncture groups, the cartilage structure was complete with clear layers and complete tidal line. ELISA showed that the expression level of interleukin-1β in the model group was significantly higher than that in the normal group (P < 0.01), and the level in the 15-and 30-minute electroacupuncture groups was significantly lower than that in the model group (P < 0.05). Western blot assay found that compared with the normal group, the protein expression levels of Ras, Raf, MEK1/2, ERK1/2, C-MYC, C-FOS, and C-JUN were increased in the model group. However, all above protein levels except ERK1/2 in the 15-and 30-minute electroacupuncture groups were significantly lower than those in the model group (P < 0.01, P < 0.05). To conclude, electroacupuncture inhibits the degeneration of articular cartilage in osteoarthritis via Ras-Raf-MEK1/2-ERK1/2 signaling pathway and downregulating the expression level of interleukin-1β. © 2017, Journal of Clinical Rehabilitative Tissue Engineering Research. All rights reserved.     

Th1/Th2细胞与纤维化疾病

纤维化可以发生在不同组织器官和系统，是细胞外基质成分过度积聚、组织瘢痕形成的过程，是致病和致死的主要原因。纤维化疾病中Th1细胞/Th2细胞对纤维增生的反应失衡有重要影响。随着IFNγ对Th1细胞的免疫反应作用研究的深入，IL-4拮抗剂、IL-5和IL-13已经被用于纤维化疾病的治疗。这些细胞因子拮抗剂在临床试验中发挥着重要作用。