糖尿病与细胞焦亡

细胞焦亡是不同于坏死与凋亡的另一种细胞死亡形式。对于机体而言细胞焦亡有助于维持内环境稳态,但是过度的细胞焦亡会引发机体疾病状态,糖尿病就是其中之一。糖尿病前期、糖尿病的代谢产物和肠道菌群变化会引起细胞焦亡的发生,而细胞焦亡进一步促使胰岛β细胞数量减少和胰岛素靶器官的胰岛素抵抗形成,加重糖尿病病情的发展和并发症的发生。以细胞焦亡为基础的治疗方法虽然越来越被关注,但有待进一步研究。     

硫氢化钠通过抑制经典细胞焦亡信号通路减轻巨噬细胞焦亡

目的：探讨硫化氢（hydrogen sulfide,H2S）供体硫氢化钠（sodium hydrosulfide,NaHS）对巨噬细胞焦亡的作用。方法：人髓系白血病单核细胞THP-1经佛波酯刺激并分化为巨噬细胞后,采用不同浓度的氧化低密度脂蛋白（oxidized low-density lipoprotein,ox-LDL）和NaHS对其进行干预,并分为空白对照组、ox-LDL刺激组和NaHS+ox-LDL干预组。采用CCK-8法检测THP-1巨噬细胞活力;采用油红O染色和光镜分别观察THP-1巨噬细胞脂质蓄积和焦亡细胞形态;采用Hoechst 33342/碘化丙啶（propidium iodide,PI）荧光染色和乳酸脱氢酶（lactate dehydrogenase,LDH）活性检测评估细胞焦亡程度;采用H2S检测试剂盒测定细胞内的H2S水平;采用试剂盒测定细胞中的caspase-1活性;采用Western blot分析细胞中焦亡关键蛋白的表达水平。结果：与空白对照组相比,ox-LDL(100和150 mg/L)可显著增加THP-1巨噬细胞中的PI阳性细胞比例、LDH释放、casp...     

细胞焦亡与原发性肝癌研究进展

细胞焦亡是一种不同于凋亡、自噬的程序性细胞死亡方式。其特征是在Gasdermin介导下,细胞膜发生破裂,之后释放细胞内容物和促炎因子,进而导致细胞死亡。细胞焦亡炎症通路包括由Caspase-1活化的经典通路和Caspase-4/-5/-11介导的非经典通路。细胞焦亡与原发性肝癌(primary liver cancer,PLC)的发生、发展联系密切,该文就细胞焦亡的发生机制及其在PLC的早期诊断、治疗、预后及药物开发等相关领域中的研究进展作简要综述。     

程序性细胞坏死及细胞焦亡信号通路研究进展概述

细胞死亡是生命活动中一个非常重要的事件,真核生物可因物理损伤刺激导致细胞死亡,因特异信号通路介导的程序性细胞死亡近年来得到越来越多的关注。目前程序性细胞死亡主要存在以下3种方式:凋亡(apoptosis)、程序性坏死(necroptosis)、细胞焦亡(pyroptosis)。程序性坏死和细胞焦亡是近年来才发现的新的细胞程序性死亡方式,在细菌或病毒感染宿主细胞过程中起着关键作用。这两种细胞死亡都是细胞裂解型死亡,但其信号通路存在明显差异。本文就这两种程序性细胞死亡的形态学特征、信号转导通路及其在病原体感染过程中的作用等方面的研究进展作一综述。     

细胞焦亡与肾脏疾病

细胞焦亡是一种区别于细胞凋亡的病理性自杀方式,主要由半胱氨酸蛋白酶1（Caspase-1）和/或半胱氨酸蛋白酶4/5/11（Caspase-4/5/11）依赖性介导,伴随产生大量炎性因子,致使细胞程序性死亡。细胞焦亡信号传导途径主要包括经典焦亡途径和非经典焦亡途径,炎性小体生成和打孔蛋白Gasdermin D（GSDM...     

细胞焦亡调控与炎症和肿瘤病理机制的关系

细胞焦亡是近年来的研究热点,且在多种疾病中发挥关键作用,在机体炎症反应和免疫反应中普遍存在。该文回顾性综述近年来有关细胞焦亡机制及相关疾病的最新文献,系统而全面地阐述细胞焦亡研究的最新进展。     

细胞焦亡：程序性死亡研究新热点

细胞焦亡(Pyroptosis)是一种以促炎性为特点的细胞程序性死亡方式,分为依赖半胱氨酸蛋白酶-1(Caspase-1)的经典细胞焦亡途径和依赖半胱氨酸蛋白酶-4/5/11(Caspase-4/5/11)的非经典细胞焦亡途径。研究表明细胞焦亡广泛参与到多种疾病的发生发展中。最近研究人员发现GSDMD和Pannexin-1可能是介导细胞焦亡的关键物质,但具体机制和相互关系仍有待进一步深入研究。     

心肌缺血再灌注损伤中细胞焦亡的研究进展

细胞焦亡是近年来发现并被证实的一种新的细胞程序性死亡方式,它的特征是依赖半胱氨酸天冬氨酸酶1(cysteinyl aspartate specific proteinase 1,caspase-1)并伴随大量炎症因子的释放。细胞焦亡参与了包括感染性疾病在内的多种疾病的病理生理过程。作为一种新的调节性细胞死亡方式,近年来...     

Research progresses of molecular mechanism of pyroptosis and its related diseases

Pyroptosis is a newly discovered untypical form of programmed cell death by inflammatory response, which is dependent on the classic pathway of Caspase-1 and the non-canonical pathway of Caspase-11 in mice or orthologue Caspase-4/-5 in Humans. It has been found that the Gasdermin family of protein is a key molecule in the formation of membrane pores of pyroptosis. After being cleaved by inflammatory caspases, it releases a N-terminal fragment with perforating activity to trigger pyroptosis. That pyroptosis is closely related to the occurrence and development of certain diseases. Now, the molecular mechanism of pyroptosis and pyroptosis-related diseases are reviewed.     

Chronic HIV encephalitis — I. cerebrospinal fluid diagnosis

Summary To establish a reliable procedure for the early detection of central nervous system involvement in HIV infection, paired cerebrospinal fluid and serum samples of 59 patients were analysed. Fifteen were HIV antibody positive without clinical symptoms (stage I), 12 had lymphadenopathy syndrome or AIDS-related complex (stage II), and 32 had AIDS (stage III). Intrathecal synthesis of HIV antibodies was determined by a modified ELISA. Antibodies in CSF and serum were evaluated at identical immunoglobulin G levels to correct for the actual blood-CSF-barrier permeability. A CSF/serum quotient above 1.5 is indicative of intrathecal antibody synthesis, which was found in 47% of the patients in stage I, 67% in stage II, and 84% in stage III. These findings indicate an early and frequent invasion of the CNS.Abbreviations ABTS (2,2-azino-di-(3-ethylbenz-thiazolino-sulfonate)) - CMV Cytomegalovirus - CNS Central nervous system - CSF Cerebrospinal fluid - CT Computerized tomography - ELISA Enzyme linked immunosorbent assay - HIV Human immunodeficiency virus - HSV Herpes simplex virus - IQ Intelligence quotient - MRI Magnetic resonance imaging - VZV Varicella/Zoster virus     

Evidence for different immune responses to HIV in CSF and serum?

Summary A case of acquired immune deficiency syndrome (AIDS) and a case of AIDS-related complex (ARC) are described. In both instances comparative Western blot analysis of cerebrospinal fluid (CSF) and serum samples show evidence of qualitative differences in antibody-binding patterns to viral polypeptides.Abbreviations ABTS [2.2-azino-di-(3-ethyl-benzthiazoline sulfonate (6))] - AIDS Acquired immune deficiency syndrome - ARC AIDS-related complex - BCIP 5-Bromo-4-chloro-3-in-dolylphosphate - CT Computerized tomography - CMV Cytomegalo virus - CNS Central nervous system - CSF Cerebrospinal fluid - EEG Electroencephalogram - ELISA Enzyme linked immunosorbent assay - HIV Human immune deficiency virus - NBT Nitro blue tetrazolium - n.d. not determined - TPHA Treponema pallidum hemagglutination assay - VDRL Venereal Disease Research Laboratories Test     

Cell cycling in HIV infection: analysis of in vivo activated lymphocytes.

Infection with HIV results in increased circulating levels of T lymphocytes expressing phenotypic markers of immune activation. In the present study, using three-colour immunofluorescence, we examined the cell cycle status of these activated cells. Activated (HLA-DR+, CD25+ and CD38+) CD4+ and CD8+ T lymphocytes in peripheral blood were analysed for DNA content in 15 HIV+ patients and 10 healthy age- and sex-matched control subjects. As expected, all HIV+ patients had elevated percentage levels of activated CD4+ HLA-DR+, CD4+ CD25+, CD8+ HLA-DR+, CD8+ CD25+ and CD8+ CD38+ T lymphocytes compared with control subjects (P < 0.001 for all). Percentage levels of CD4+ HLA-DR+ and CD8+ HLA-DR+T lymphocytes in the 'proliferative' (S-G2M) phase of the cell cycle were also higher in the HIV+ patients compared with controls (P < 0.001 for both). The percentage levels of proliferative CD4+ CD25+, CD8+ CD25+ and CD8+ CD38+ lymphocytes were, however, similar in HIV+ patients and controls, indicating that the proliferative fraction of cells in vivo was confined to the HLA-DR+ subset and absent from the CD25+ and CD38+ populations. Four HIV+ patients had grossly elevated levels of CD8+ lymphocytes which were CD38+ (> 95%) and confined to the pre-G0-G1 phase of the cell cycle, suggesting these may be cells committed to apoptosis. These observations indicate an increase in the proliferative capacity of HLA-DR+ T lymphocytes in HIV infection in vivo. The reduced DNA content in other populations (e.g. CD38+ CD8+ lymphocytes) of some patients with advanced HIV disease suggests that these cells are apoptotic. Thus our results define both proliferative and apoptotic processes as a spectrum of activation-related events in HIV infection.     

山东地区2003-2011年HIV抗体检测的临床现状及分析

目的 探讨山东地区艾滋病(AIDS)感染现状,为临床AIDS监控及避免院内交叉感染提供依据.方法 2003年1月至2011年12月,采用阿克苏第四代酶免检测试剂及免疫发光第四代检测试剂为399 303例门诊及住院患者行HIV抗体初筛,采用北京万泰酶免检测试剂及硒标快速检测试剂行复检,阳性反应标本报送当地疾控中心采用免疫印迹方法进行确认.结果 129例(129/399 303 =0.3230‰)患者确认为HIV-1抗体阳性,其中门诊患者54例(0.1352‰),住院患者75例(0.1878‰).2003-2011年门诊患者HIV感染检出率分别为0.050‰、0.030‰、0.111‰、0.120‰、0.124‰、0.113‰、0.148‰、0.201‰、0.2152‰;住院患者HIV感染检出率分别为0.150‰、0.089‰、0.138‰、0.144‰、0.104‰、0.132‰、0.197‰、0.329‰、0.313‰;住院患者中内科患者61例、外科患者14例,以青壮年、农民居多.结论 HIV感染率呈逐年增高趋势,住院所检出HIV-1阳性患者的特点,多为艾滋病期的患者,建立入院常规检测很有必要.     

IgA1 is the major immunoglobulin component of immune complexes in the acquired immune deficiency syndrome

Compared to a panel of healthy controls, sera from 13 of 23 (57%) patients with the acquired immune deficiency syndrome (AIDS) were shown to have elevated levels of circulating immune complexes (CIC) containing IgA. Levels of IgG-containing CIC were increased in seven patients (30%); no patients had elevated levels of IgM-containing CIC. Additional experiments showed that in all instances in which IgG CIC were demonstrable, IgA was also present; however, IgA CIC could be found that did not contain IgG. The IgA in the CIC was restricted to the IgA1 subclass. These data suggest selective abnormalities of IgA regulation in AIDS and raise questions as to the role in this disease of the immunoglobulin isotype usually thought to possess different protective mechanisms from those attributed to other isotypes.     

Alterations in cytotoxic and phenotypic subsets of natural killer cells in acquired immune deficiency syndrome (AIDS)

Testing of cytotoxic function using a panel of natural killer (NK)-sensitive target cells, including a unique herpes simplex virus-infected Raji-cell target, was performed in conjunction with phenotypic cell analysis by dual-color flow cytometry to characterize the NK system. Subjects included in the study were at risk for or infected with the etiologic agent of the acquired immune deficiency syndrome (AIDS), human immunodeficiency virus (HIV). A generalized defect in NK function was temporally correlated with disease manifestations, as evidenced by deficient NK lytic function in patients with AIDS and AIDS-related complex (ARC). Healthy at-risk subjects, including those seropositive for HIV, exhibited robust NK-cell function. Phenotypic analysis revealed that normal proportions of the NK-associated CD16⁺ (Leu11) Leu7^– and CD16⁺(Leu11)Leu7⁺ lymphocyte subsets were maintained throughout the clinical progression of HIV infection. However, the proportion and numbers of cells of the CD8⁺(Leu2)Leu7⁺ subset were increased in AIDS, ARC, and healthy at-risk subjects, including those seronegative for HIV. These results are consistent with a qualitative defect in the NK system in AIDS, perhaps secondary to CD4-cell depletion and a concomitant lack of essential accessory factors. The elevation in CD8⁺(Leu2)/Leu7⁺ cells is not solely the result of HIV infection and may be a general response to viruses and/or other antigenic stimulation.     

Necroptosis,pyroptosis and apoptosis: an intricate game of cell death

Cell death is a fundamental physiological process in all living organisms. Its roles extend from embryonic development, organ maintenance, and aging to the coordination of immune responses and autoimmunity. In recent years, our understanding of the mechanisms orchestrating cellular death and its consequences on immunity and homeostasis has increased substantially. Different modalities of what has become known as ‘programmed cell death’ have been described, and some key players in these processes have been identified. We have learned more about the intricacies that fine tune the activity of common players and ultimately shape the different types of cell death. These studies have highlighted the complex mechanisms tipping the balance between different cell fates. Here, we summarize the latest discoveries in the three most well understood modalities of cell death, namely, apoptosis, necroptosis, and pyroptosis, highlighting common and unique pathways and their effect on the surrounding cells and the organism as a whole.     

Immunobiology of human imunodeficiency virus infection

After the discovery of human immunodeficiency virus (HIV) and its role in the causation of most devastating epidemic acquired immune deficiency syndrome (AIDS), there has been an increasing trend to decipher the mechanism of infection and to understand why it cannot be controlled by our immune system. By evolution, our immune system has been empowered and enough trained to recognize, elicit immune response and remove antigens and pathogens from the body. Simultaneously, HIV has also gained enough mechanism to escape the natural immune response. On one hand, it downregulates HLA class I antigens, which may present viral antigens to specific CD8 + T cells; on the other hand, the viral genome get mutated very readily under the selection pressure of specific cytotoxic T lymphocytes. The high mutation rate and convertibility of its genotype makes it a moving target and poses a prime hurdle in vaccine development. This review explains how HIV enters into the cell, how it resists the host immune response and how HIV manages to escape from it and establish in the human body.     

Neutralizing antibodies as a prognostic indicator in the progression of acquired immune deficiency syndrome (AIDS)-related disorders: A double-blind study

A double-blind longitudinal study for the presence of human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies (NAb) in the sera of 36 patients with acquired immune deficiency syndrome (AIDS), 149 prodromal homosexual subjects, and 33 heterosexual subjects has been carried out. All AIDS patients and 68% of prodromal homosexual subjects (101/149) were found to be HIV-1 antibody positive by Western blot assay. All heterosexual subjects were HIV-1 antibody negative. Neutralizing antibody(s) was determined by testing the protective activity of sera against HIV-1 infection of human T-cell line H9. Study subjects were divided into NAb(+) (antibody titer, >1:40) and NAb(–) (antibody titer, <1:40) groups. During the 24-month observation period 2 of 80 (3%) HIV-1(+) NAb(+) individuals progressed to AIDS and died, as compared to 5 of 21 (24%) of HIV-1(+) NAb(–) subjects who progressed to AIDS. Similarly, among the NAb(+) AIDS patients 8 of 23 (35%) died, while 10 of 13 (77%) of the NAb(–) patients died during the course of the study. In addition, the absence or reduction of HIV-1 p17 and p24 antibodies directed against HIV-1 antigens as well as the low titer or absence of NAb appears to be closely related to the clinical progression of the disease. These studies suggest that a decrease in the virus neutralization capacity of the sera and a decrease or complete loss of HIV-1 p17 and p24 antibodies may be useful as prognostic indicators for the progression of disease in HIV-1-seropositive patients.