Overview of the microbiota in the gut-liver axis in viral B and C hepatitis

Viral B and C hepatitis are a major current health issue, both diseases having a chronic damaging effect on the liver and its functions. Chronic liver disease can lead to even more severe and life-threatening conditions, such as liver cirrhosis and hepatocellular carcinoma. Recent years have uncovered an important interplay between the liver and the gut microbiome: the gut-liver axis. Hepatitis B and C infections often cause alterations in the gut microbiota by lowering the levels of ‘protective’ gut microorganisms and, by doing so, hinder the microbiota ability to boost the immune response. Treatments aimed at restoring the gut microbiota balance may provide a valuable addition to current practice therapies and may help limit the chronic changes observed in the liver of hepatitis B and C patients. This review aims to summarize the current knowledge on the anato-functional axis between the gut and liver and to highlight the influence that hepatitis B and C viruses have on the microbiota balance, as well as the influence of treatments aimed at restoring the gut microbiota on infected livers and disease progression.     

Leflunomide: an immunosuppressive drug with multiple effects on T cell function

Abstract

Leflunomide has recently been introduced as a new treatment for rheumatoid arthritis. Although its immunosuppressive effect has been well demonstrated in experimentally induced autoimmune diseases and in organ transplant rejection in animal models, the exact mechanisms mediating its immunomodulatory effect are not fully understood. As T cells play a central role in the orchestration of immune responses in both physiological and pathological conditions, it has been proposed that the ability of leflunomide to suppress inappropriate and unwanted immunity is related to a functional inhibition of T cells. A precise knowledge of the mechanisms of leflunomide's action on T cells is therefore necessary. As the clinical effect of leflunomide has been well described elsewhere, this review will focus on, and will discuss, current data on the different aspects of leflunomide's effect on T cell function.     

Adsorption of Surfactant to Bronchial Epithelium: Possible Role of Receptor ‘Unmasking’ in Asthma

Background.?In a recent study in animals it has been shown how surface-active phospholipid (SAPL) in the form of a commercially available micronized (5 µmφ) dry powder (ALEC^T/Pumactant^T) was able to reduce afferent neural feedback to the brainstem in response to a methacholine challenge by the same order of magnitude as drugs commonly prescribed for asthma. The underlying theory assumed that adsorption of SAPL to bronchial epithelium masked irritant receptors eliciting the bronchoconstrictor reflex, thus providing a barrier to noxious stimuli entering the lungs. Objective.?To test the underlying assumption that SAPL was actually adsorbed (i.e., bound to bronchial epithelium), especially the major and most surface-active component of lung surfactant, namely dipalmitoyl phosphatidylcholine (DPPC). A secondary objective was to investigate any role of phosphatidylglycerol (PG) in promoting the adsorption of DPPC. Methods.?Radiolabeled DPPC dispersed ultrasonically in saline was used to incubate excised sections of porcine bronchial epithelium. The adsorbed DPPC was then quantified by rigorously rinsing the tissue of adhering fluid and then digesting it for β-scintillation counting. Each test (n = 8 runs) was repeated for ratios of DPPC:PG of 9:1, 7:3 (as per ALEC^T/Pumactant^T) and 1:1 for both dipalmitoyl PG (DPPG) and EggPG (as incorporated in ALEC^T/Pumactant^T). Results.?Despite rigorous rinsing postincubation, bronchial epithelium was found to adsorb DPPC at a level roughly equivalent to one close-packed monolayer; whereas both DPPG and EggPG promoted the adsorption of DPPC in a dose-dependent manner, reaching an approximate threefold increase for 7:3 DPPC:PG. Conclusion.?DPPC adsorbs to bronchial epithelium in amounts necessary for the masking of receptors, and this adsorption (probably chemisorption) is quite strongly promoted by PG either in its indigenous state (DPPG) or in the form (EggPG) used in ALEC^T to suppress the sensitivity of bronchial irritant receptors in our previous study and in clinical trials just completed.     

Treatment of Induced Murine SLE with a Peptide Based on the CDR3 of an Anti-DNA Antibody Reverses the Pattern of Pathogenic Cytokines

A peptide based on the complementarity determining region (CDR) 3 of a pathogenic anti-DNA monoclonal antibody that bears the 16/6 idiotype (Id) was shown previously to be a dominant T-cell epitope in experimental SLE, and to be capable of inhibiting SLE-associated responses. When injected, concomitant with active immunization with the pathogenic human anti-DNA, 16/6 Id + mAb, pCDR3 inhibited the proliferation of LN-derived T cells stimulated in vitro with the 16/6 Id mAb. The inhibition of the specific proliferative responses could be reversed by the addition of exogenous IL-2 to the cultures. Analysis of secreted cytokine profile in supernatants of these cultures demonstrated that pCDR3 treatment reduced significantly the levels of both IL-2 and IFN- &#110 that were elevated further in cells of the 16/6 Id-immunized mice. The CDR3-based peptide was shown here to immunomodulate in vivo experimental SLE, induced by the human anti-DNA 16/6 Id + antibody. The beneficial effects of pCDR3 on the clinical manifestations of SLE were associated with downregulation of the Th1-type (IL-2, IFN- &#110 ) and proinflammatory (TNF- &#102 ) cytokines, whereas the immunosuppressive cytokine TGF- &#103 was up regulated.     

B 和 T 淋巴细胞衰减因子激活在休克／脓毒症诱导的急性肺损伤中的作用

目的：探讨B和T淋巴细胞衰减因子（ B and T lymphocyte attenuator , BTLA）激活在休克／脓毒症诱导的急性肺损伤（ ALI）中的作用。方法24只雄性C57BL／6小鼠随机平均分为三组：对照组、ALI模型组和6A6（BTLA激动性抗体）干预组。采用Western blot 观察对照组和ALI模型组肺组织BTLA蛋白的表达变化,并测定和比较三组小鼠支气管肺泡灌洗液蛋白浓度, ELISA方法测定肺组织促炎症细胞因子、趋化因子水平及肺组织髓过氧化物酶活性,TUNEL染色评估肺组织细胞凋亡情况;肺组织切片HE染色了解肺组织病理学改变。另外45只小鼠随机平均分为如上三组观察10 d生存率。结果 BTLA在ALI模型组肺组织中表达较对照组明显升高。与ALI模型组比较,6A6干预组小鼠支气管肺泡灌洗液蛋白浓度升高,肺部TNF－α和MIP－2、MCP－1水平升高,肺组织MPO活性增加（P均＜0.05）。 TUNEL染色显示,6A6干预组小鼠肺细胞凋亡较ALI模型组增加。 HE染色显示,6A6干预组较ALI模型组小鼠肺组织病理学形态损伤加重。6A6干预组较ALI模型组小鼠死亡率显著升高。结论 BTLA在休克／脓毒症诱导的ALI肺组织中表达升高。 BTLA激活使脓毒症诱导的ALI小鼠肺通透性增高,肺部炎症因子和趋化因子水平升高,肺部中性粒细胞募集增加,肺细胞凋亡增加,肺组织病理学形态损伤加重,导致ALI小鼠死亡率增加。     

芝芪菌质提取物免疫活性研究

目的 探究芝芪菌质及其各部位免疫活性。 方法 芝芪菌质为灵芝菌丝-黄芪药渣的固体发酵复合体。通过小鼠碳粒廓清实验,鸡红细胞吞噬功能实验,小鼠血清溶血素、免疫球蛋白M(IgM)和免疫球蛋白G(IgG)的含量检测,以及小鼠脾淋巴细胞增殖实验,筛选了芝芪菌质水提液,芝芪菌质水浸液,芝芪菌质水提液经大孔树脂分离的部位(水洗脱液、40%乙醇洗脱液和95%乙醇洗脱液)的非特异性和特异性免疫活性。 结果 碳粒廓清实验中,K值最高为水浸液和水提液组的0.23,α值最高为水提液组的2.44。吞噬指数最高为水浸液和水提液组的0.36,鸡红细胞吞噬百分率最佳为水浸液组的47.25%。小鼠溶血素含量最高为水洗脱组的0.4。IgM含量最高为水提液组的34.19 mg·L-1,而IgG最高则是水浸液组的44.50 mg·L-1。淋巴细胞增殖指数最高为40%乙醇洗脱液组的1.23。 结论 芝芪菌质水提液、芝芪菌质水浸液和40%乙醇洗脱液具有显著的免疫增强功效,为芝芪菌质制成增强人体抵抗力的功能性食品及药品提供实验数据和理论参考。     

倍芪腹泻贴微生物限度检查方法的适用性试验

目的 建立倍芪腹泻贴微生物限度检查方法。 方法 按照《中国药典》2015年版四部﹝通则1105和通则1106﹞的具体规定,采用平皿法、稀释法、薄膜过滤法及方法联用对倍芪腹泻贴进行微生物限度方法适用性试验。 结果 需氧菌总数、真菌和酵母菌总数计数方法适用性试验中各试验菌回收比值均不小于0.9,控制菌方法适用性试验均检出金黄色葡萄球菌和铜绿假单胞菌。 结论 该试验方法可用于倍芪腹泻贴的微生物限度检查。