Heterogeneity of hepatocellular carcinoma contributes to cancer progression

Hepatocellular carcinoma (HCC) is a highly heterogeneous disease displaying differences in angiogenesis, extracellular matrix proteins, the immune microenvironment and tumor cell populations. Additionally, genetic variations and epigenetic changes of HCC cells could lead to aberrant signaling pathways, induce cancer stem cells and enhance tumor progression. Thus, the heterogeneity in HCC contributes to disease progression and a better understanding of its heterogeneity will greatly aid in the development of strategies for the HCC treatment.     

Interferon-gamma release assays in tuberculous uveitis: a comprehensive review

Tuberculous uveitis (TBU) comprises a broad clinical spectrum of ocular manifestations, making its diagnosis challenging. Ophthalmologists usually require evidence from investigations to confirm or support a clinical diagnosis of TBU. Since direct isolation of the causative organism from ocular specimens has limitations owing to the small volume of the ocular specimens, resultant test positivities are low in yield. Immunodiagnostic tests, including the tuberculin skin test and interferon-gamma release assays (IGRAs), can help support a clinical diagnosis of TBU. Unlike the tuberculin skin test, IGRAs are in vitro tests that require a single visit and are not affected by prior Bacillus Calmette-Guerin vaccination. Currently, available IGRAs consist of different techniques and interpretation methods. Moreover, newer generations have been developed to improve the sensitivity and ability to detect active tuberculosis. This narrative review collates salient practice points as a reference for general ophthalmologists, such as evidence for the utilization of IGRAs in patients with suspected TBU, and summarizes basic knowledge and details of clinical applications of these tests in a clinical setting.     

The influence of a targeted deletion of the IFNgamma gene on emotional behaviors

Evidence suggests that interferon-gamma (IFNgamma) plays an important role in CNS function and development. While the paucity of agents that selectively modify IFNgamma production or interaction with its receptors makes analyses of its potential behavioral relevance difficult, mice with null mutations of the IFNgamma gene have been used to investigate the potential role of IFNgamma in emotional behaviors. C57Bl/6 (B6) mice with null mutations of the IFNgamma gene (IFNgamma (-/-)) showed significantly increased emotionality compared to the wild-type (IFNgamma (+/+)) B6 mice. This was manifested in performance in the elevated plus maze as well as increased defecation scores and decreased locomotor activity both in novel environments and following a sonic stimulus. In contrast, the general level of emotionality of both IFNgamma (+/+) and (-/-) BALB/c (C) mice was substantially greater than that of either of the B6 mouse groups. While C IFNgamma (-/-) showed increased immobility in response to novelty, other indices of emotionality of C IFNgamma (-/-) mice were not significantly different from those of the C IFNgamma (+/+) mice. In summary, the lack of IFNgamma appears to contribute to increased emotionality, but the basal behaviors of the parental strain (e.g., BALBc) may overshadow the expression of this emotionality. While mice with null mutations of the IFNgamma gene may be useful tools for investigating the role of IFNgamma in brain function and behavior, the influence of the parent strain genome(s) on the behaviors in question must be taken into account.     

HBV-specific immune defect in chronic hepatitis B (CHB) is correlated with a dysregulation of pro- and anti-inflammatory cytokines

The aim of this study was to examine the immunomodulating effects of rhIL-12 on the immune response induced by hepatitis B virus (HBV) antigens in clinical subgroups of patients with HBV infection. Peripheral blood mononuclear cells (PBMC) of 80 patients were stimulated with HBsAg, HBcAg, pre-S1Ag and tetanus toxoid in the absence or presence of IL-12 (0.01, 0.1 and 1 ng/ml). Stimulation by anti-CD3+ anti-CD28 and lipopolysaccharide (LPS) were used as controls. Proliferation and cytokine production were determined by 3H-thymidine uptake and ELISA after 72 h. After stimulation with HBV antigens only, production of tumour necrosis factor-alpha (TNF-alpha) or IL-10 was observed in all patients, while interferon-gamma (IFN-gamma) was detectable in only 27 patients. After costimulation with IL-12 and HBV antigens, however, large amounts of IFN-gamma were found in all patients, while HBV-induced IL-10 production remained mostly unchanged. When clinical subgroups including patients with compensated liver cirrhosis were compared, PBMC from patients with HBeAg+ hepatitis showed the lowest capacity to produce IFN-gamma after HBV antigen-positive IL-12. These data suggest that the ability of IL-12 to enhance IFN-gamma production against HBV antigens is correlated with the presence of HBeAg and is not impaired in patients with advanced liver disease. In addition, IL-12 and IL-10 production by antigen-presenting cells may be a critical factor that determines the efficacy of the immune response against the hepatitis B virus.     

Differences in the anti-inflammatory effects of theophylline and pentoxifylline: important for the development of asthma therapy?

Antiasthma drugs are now being re-evaluated for their anti-inflammatory effects. Theophylline is an immunomodulator; however, weak effects and the narrow therapeutic window make it a controversial drug. We compared the immunomodulatory potencies of theophylline with those of the xanthines pentoxifylline (POF) and A802715. Using a whole-blood, cell-culture system, we studied the effects on the release of tumor necrosis factor-alpha (TNF-a), interferon-gamma (IFN-γ), and interleukin-6 (IL-6) in six healthy subjects, and, in granulocyte suspensions, the effects on the release of reactive oxygen species (ROS). We also studied the influence of a 14-day treatment with theophylline or POF on the release of the cytokines named above in 14 asthmatics. We found that equimolar concentrations of A802715 most effectively inhibit ROS generation, followed by POF; the effects of theophylline were weakest. A802715-inhibited release of TNF-a was four times as potent as that of theophylline, and POF two times as potent. Inhibition of IFN-γ by A802715 was three times as potent, and by POF two times. Neither drug influenced IL-6 release. After a 14-day treatment of asthmatics, POF proved to inhibit TNF-a release more effectively (by 44.3%) than theophylline (7.5%). It is concluded that study of xanthine derivatives in asthmatics might help the development of asthma therapy POF seems to be an especially promising candidate.     

再生障碍性贫血患者细胞免疫指标的观察

采用酶免疫和放射免疫法分析了再生障碍性贫血(AA)患者外周血T淋巴细胞亚群、血清肿瘤坏死因子(TNF)、γ-干扰素(IFN-γ)和IL-2水平,以及患者外周血单个核细胞体外诱生的上述细胞因子水平。结果表明:患者CD4/CD8细胞比值降低或倒置(P<0.001),血清TNF和IFN-γ水平显著增高(P<0.01),外周血单个核细胞诱生的TNF、IFN-γ和IL-2水平均明显高于正常对照(P<0.01)。提示T淋巴细胞亚群比例失调和TNF、IFN-γ等造血负调控因子的过量分泌可能与AA的发病机制有关。     

Cytokine-targeted therapy for the management of solid organ transplant recipients

IntroductionThe number of solid organ transplants completed annually continues to trend upwards each year. Despite this, maintenance immunosuppression available on the market has remained relatively stagnant. Standard triple immunosuppression, composed typically of tacrolimus, mycophenolate, and steroids, lead to many side effects that limit the use of these medications. Tacrolimus, specifically, causes nephrotoxicity that can lead to renal dysfunction requiring a kidney transplant down the road. Alternative therapies for the management of immunosuppression need to be identified to try to mitigate these adverse effects.BodyCytokines are responsible for facilitating T cell differentiation and lead to the activation of inflammatory mediators that can contribute to graft damage and ultimately rejection. IL-4, IL-6, IL-12/23, and IL-15 are attractive targets for medications to try to ameliorate graft rejection. Various cytokine-targeted medications are currently available on the market for the treatment of inflammatory and autoimmune conditions such as rheumatoid arthritis, psoriatic arthritis, Crohn’s, and multiple sclerosis.ConclusionThis article reviews cytokine involvement in alloimmunity and the potential role cytokine-targeted therapy may play in prevention of allograft rejection in solid organ transplant recipients.     

3种检测方法在儿童活动性结核病诊断中的应用

目的 评价γ-干扰素释放试验(IGRA)、结核菌素皮肤试验(TST)及结核抗体(TB-Ab)检测对儿童活动性结核病的临床诊断价值,并分析IG RA及T S T在不同年龄患儿中的应用价值.方法 收集该院就诊的疑似结核患儿367例资料,其中临床诊断结核病患儿113例,非结核病患儿254例.分析3种方法的灵敏度、特异度、一致...     

γ-干扰素体外释放试验在结核病诊断中的价值

目的探讨γ-干扰素(γ-IFN)体外释放试验(IGRA)对诊断结核病的临床价值。方法 479例结核病患者纳入结核病组,42例体检健康者纳入对照组。两组被试均行IGRA、蛋白芯片法检测,采用抗酸染色(AFB)检测结核病患者痰液中的抗酸杆菌。比较IGRA与蛋白芯片法对结核病的诊断效能及在肺结核与肺外结核中的检测效果,并比较IGRA对AFB阳性和阴性的肺结核和肺外结核患者的检测效果。结果IGRA和结核分枝杆菌蛋白芯片法敏感度分别为89.56%(429/479)和76.20%(365/479),特异度分别为100.00%(42/42)和88.10(37/42),准确率分别为90.40%(471/521)和77.16%(402/521)。418例肺结核患者中AFB阳性127例,AFB阴性者291例,其中AFB阳性肺结核患者中IGRA阳性率为93.70%(119/127),AFB阴性肺结核患者阳性率为88.66%(258/291);肺外结核61例患者AFB均阴性,IGRA和结核分枝杆菌蛋白芯片阳性率分别为85.25%(52/61)和68.85%(42/61)。结论 IGRA与结核分枝杆菌蛋白芯片法相比,对结核病诊断有较高的敏感度与特异度,尤其是对AFB阴性的结核病有较高的检出率,值得临床推广应用。