Astilbin promotes the induction of regulatory NK1.1− CD4+ NKG2D+ T cells through the PI3K,STAT3, and MAPK signaling pathways

Astilbin is a potential agent for autoimmune and inflammatory diseases and has a protective effect in mice with DSS-induced colitis. NK1.1⁻ CD4⁺ NKG2D⁺ T cells are a subpopulation of regulatory T cells that produce TGF-β1 and IL-10. Whether astilbin directly promotes the induction of NK1.1⁻ CD4⁺ NKG2D⁺ T cells and whether these astilbin-stimulated T cells exert an immune-regulatory role remain unclear. Here, we show that astilbin efficiently induces the production of NK1.1⁻ CD4⁺ NKG2D⁺ T cells with high expressions of TGF-β1, IL-10, CCR6, and CCR9 in a dose-dependent manner ex vivo. These regulatory T cells also substantially inhibit the activities of CD8⁺ T cells and macrophages. Intraperitoneal injection of astilbin ameliorates the severity of colitis with an increase in the frequency of NK1.1⁻ CD4⁺ NKG2D⁺ T cells in the colon tissue of DSS-treated mice. Moreover, adoptive transfer of NK1.1⁻ CD4⁺ NKG2D⁺ T cells induced by astilbin remarkably protects against the onset of DSS-induced colitis. Finally, the PI3K, STAT3, and MAPK signaling pathways are involved in the induction of NK1.1⁻ CD4⁺ NKG2D⁺ T cells by astilbin. Taken together, our study elucidates a new immune-regulatory mechanism of astilbin by inducing the regulatory NK1.1⁻ CD4⁺ NKG2D⁺ T cells and indicates a potential clinical use of astilbin for patients with inflammatory bowel diseases.     

TIRAP C539T polymorphism contributes to tuberculosis susceptibility: Evidence from a meta-analysis

BackgroundToll-interleukin 1 receptor domain containing adaptor protein (TIRAP), an important adaptor protein downstream of the Toll-like receptor (TLR) 2 and 4 pathways, is highly involved in the activation and coordination of the anti-mycobacterial immune response. We performed a meta-analysis to assess the association between TIRAP C539T polymorphism and tuberculosis (TB) risk.MethodsA systematic literature search for relevant studies up to February 27, 2014 was conducted in PUBMED, EMBASE, Web of science, CNKI, VIP, and Wanfang database. The association between gene and disease was assessed using odds ratios (ORs) with 95% confidence intervals (95%CIs) based on five genetic models.ResultsA total of 16 qualified studies were enrolled in this meta-analysis. The results of pooling all studies detected statistically resistance of TIRAP C539T mutants to TB risk (T vs. C: OR 0.80, 95%CI 0.65–0.97; TC vs. CC: OR 0.71, 95%CI 0.55–0.92; TT + TC vs. CC: OR 0.74, 95% CI 0.58–0.94). Further subgroup analyses by ethnicity also demonstrated reduced risk of TB in European population (T vs. C: OR 0.71, 95%CI 0.52–0.95; TC vs. CC: OR 0.56, 95%CI 0.35–0.91; TT + TC vs. CC: OR 0.61, 95%CI 0.40–0.92), whereas no such effects were observed in other ethnicities.ConclusionThis present meta-analysis suggests TIRAP C539T polymorphism is significantly correlated with reduced risk of TB infection, with stronger effect in European. Additional well-designed, larger-scale epidemiological studies among different ethnicities are needed.     

Erythrocyte miRNA regulators and malarial pathophysiology

Pathophysiology of Plasmodium falciparum and Plasmodium vivax in malaria vis a vis host and the parasite genome interactions has been deciphered recently to present the biology of cerebral malaria, severe anaemia and placental malaria. Small non-coding RNAs have exhibited their potential to be considered as indicators and regulators of diseases. The malarial pathologies and their associated mechanisms mediated by miRNAs and their role in haematopoiesis and red cell-related disorders are elucidated. Evidence of miRNA carrying exosome-like vesicles released during infection, delivering signals to endothelial cells enhancing gene expression, resulting in parasite sequestration and complications leading to pathologies of cerebral malaria are important breakthroughs. Pregnancy malaria showed Plasmodium surface antigen promoted erythrocyte sequestration in the placental intervillous space, provoking disease development and assorted complications. Syncytiotrophoblast-derived microparticles during pregnancy and fetus development may predict pathophysiological progression on account of their altered miRNA cargoes in malaria.     

Is patient reported outcome (PRO) affected by different follow-up regimens in inflammatory bowel disease (IBD)? A one year prospective,longitudinal comparison of nurse-led versus conventional follow-up

ObjectiveSpecialist nurses have become increasingly involved in the management of Inflammatory Bowel Disease (IBD). The objectives of this study were to investigate the impact of nurse-led versus conventional follow-up on patient outcomes, such as quality of life, worries and time from relapse to start of treatment.MethodsPatients completed the Short Form 36 (SF-36), Inflammatory Bowel Disease Questionnaire (N-IBDQ) and the Rating Form of IBD Patient Concerns (RFIPC) at baseline and after 1 year. Socio-demographic and clinical variables were obtained at V1 and V2. In addition the amount of e.g., relapses, hospitalisations, time from relapse to start of treatment, sick-leave, unscheduled visits or telephone calls was recorded during the follow-up period.ResultsA total of 140 patients were included; ulcerative colitis (UC) n = 92, Crohn's disease (CD) n = 48, mean age 46.9 and 40.0 years old, respectively. One hundred and thirty three patients attended the follow-up after 1 year. After 1 year there were no differences between the groups in relation to quality of life, worries, amount of relapse, sick-leave, hospitalisations or surgery. Participants in nurse-led follow-up had a significantly (p < 0.05) shorter interval from the start of a relapse to the start of treatment.ConclusionsNurse-led follow-up of IBD patients produces PRO results comparable to that of gastroenterologists and may shorten the interval from the beginning of a relapse to the start of treatment.     

Significant reduction in notification and seroprevalence rates of hepatitis B virus infection among the population of Zhejiang Province,China, aged between 1 and 29 years from 2006 to 2014

Background and objectiveThe Chinese government integrated hepatitis B vaccination into the national immunization program in 1992, when the hepatitis B birth dose was introduced in China. Zhejiang province is a relatively developed area in eastern China and was an area with high endemicity for hepatitis B virus (HBV) infection via mother-to-child transmission. The hepatitis B vaccine vaccination rates for the birth dose and 3- dose schedule in Zhejiang Province since 1992 have both remained above 90% [1]. The results of two hepatitis B seroepidemiological surveys conducted in 2006 and 2014, respectively, to evaluate the rates of notification and seroprevalence of HBV infection among the population of Zhejiang Province, China, aged between 1 and 29 years.MethodsData on the notification rates of HBV infection in Zhejiang province from 2006 to 2014 were obtained from the National Notifiable Disease Reporting System (NNDRS). The prevalence rate of HBV serological markers and the rate of immunization coverage were compared between surveys.ResultsThe reported notification rates in people aged between 1 and 29 years according to the NNDRS decreased approximately 4.88 times from 2006 to 2014. The prevalence of HBsAg decreased from 2.16% in 2006 to 1.05% in 2014, while the prevalence of anti-HBc decreased from 7.13% to 5.49%. The anti-HBc seroprevalence in the 15–29-year-old age group was significantly higher than that in all the other age groups both in the 2006 and 2014 serosurveys. The rate of anti-HBs seroprevalence in those aged between 1 and 14 years was maintained at a high level between 2006 and 2014.ConclusionsThe rate of hepatitis B reported and the rate of HBsAg positivity decreased significantly in Zhejiang province by maintaining the high-level coverage rate of the hepatitis B timely birth dose and three-dose schedule. While additional efforts are needed to achieve the goal of elimination.     

Why is autophagy important for melanoma? Molecular mechanisms and therapeutic implications

As the principle lysosomal mediated mechanism for the degradation of aged or damaged organelles and proteins, autophagy (self-eating) is generally considered a pro-survival process activated by cells to sustain life in presence of adverse environmental conditions such as nutrient shortage and/or in presence of cytotoxic compounds [1]. Upon activation, cytoplasmic material is sequestered into double-membrane vesicles (autophagosomes) then targeted for degradation by fusion with lysosomes (autolysosomes); metabolic activity and cell survival are consequently sustained by recycling the degradation products. Basal autophagy occurs in almost all cell types, though at different degree, as a finely regulated “quality control” process to prevent cell damage, for the demolition of cellular structures during cell/tissue remodelling, and to ensure the maintenance of cellular homeostasis through recycling cellular components/molecules [2], [3].Autophagy is stimulated in response to both physiological and pathological conditions such as starvation, hypoxia and low energy, pathogen infection and protein aggregates.Although it's clear that autophagy is also involved in cancer, its role, however, is complex since it can both suppress and promote tumorigenesis [4]. Consequently, it is generally accepted that while autophagy is used by advanced stage cancers to maintain tumour survival, loss of autophagy in earlier stages is associated with tumour development.Accordingly, it is now apparent that aberrant control of autophagy is among key hallmarks of cancer, with several studies now demonstrating this process is deregulated also in melanoma [5], [6].     

MicroRNA-34家族的功能及应用研究进展

MicroRNA-34(miR-34)家族包括 miR-34a、miR-34b、miR-34c，与人体正常发育及多个器官功能的维持密切相关。miR-34的表达受抑癌基因p53和长链非编码RNA（long non-coding RNAs, lncRNAs）的调控，其表达失衡会导致一系列疾病的发生发展。miR-34 与肿瘤发生发展密切相关，主要通过阻碍细胞周期、诱导细胞凋亡与自噬、抑制上皮-间充质转化、阻止细胞迁移与侵袭等机制发挥抑癌作用。不断有新的证据表明miR-34在神经修复与心脏保护中也发挥着重要作用。miR-34功能的发挥主要涉及NF-κB、Notch等多个信号通路，基于miR-34 表达的调控有利于部分疾病的控制和转归，是潜在的临床诊治靶标，具有广阔的临床应用前景。因此，本文就miR-34家族得功能及应用进展作一综述，为后续研究提供参考。     

Replacement Therapy for Hemophilia Patients Undergoing Cardiac Surgery: Report of Three Cases

Hemophilia is an X-linked recessive inherited bleeding disorder. Despite the improved treatment in recent years with the advent of replacement therapies, the progression of atherosclerosis is not slowed down after the reduction of clotting factors in hemophilia. As life expectancy increases, more hemophilia patients will suffer from age-related cardiovascular diseases. Since cardiac surgery needs heparinization and cardiopulmonary bypass (CPB), it is extremely challenging to balance hemostasis and coagulation in patients with hemophilia. Here we report three cases of hemophilia patients who underwent cardiac surgery successfully.