A New Insight into Hepatitis C Vaccine Development

Chronic hepatitis C virus (HCV) infection remains a serious burden to public health worldwide. Currently, HCV-infected patients could undergo antiviral therapy by giving pegylated IFN-α with ribavirin. However, this therapy is only effective in around 50% of patients with HCV genotype 1, which accounts for more than 70% of all HCV infection, and it is not well tolerated for most patients. Moreover, there is no vaccine available. The efforts on identifying protective immunity against HCV have progressed recently. Neutralizing antibodies and robust T cell responses including both CD4+ and CD8+ have been shown to be related to the clearance of HCV, which have shed lights on the potential success of HCV vaccines. There are many vaccines developed and tested before entering clinical trials. Here, we would first discuss strategies of viral immune evasion and correlates of protective host immunity and finally review some prospective vaccine approaches against chronic HCV infection

Location – Positioning Tregs to the right place at the right time

After a fruitless pursuit for suppressor cells spanning 1970s to mid-80s, the identification of CD4+CD25+ T cellsas a specific T-cell lineage with immune regulatory function in the 1990s has revived the theory of active immune tolerance and uncovered a brand-new avenue for immunologic research. Tregs have been shown to play a crucial role both in health and diseases. Whilst tremendous advance has been made in our understanding of the expanding varieties of effector mechanisms exploited by Tregs, the migration phenotypes as well as the anatomic sites where Tregs exert immune regulation are scarcely investigated. Migration of Tregs to either the lymph nodes or peripheral tissues has been shown to be exclusively indispensable in Treg-mediated immune regulation in a variety of experimental models with specific gene-targeted mice. The once seemingly paradoxical findings are partly reconciled by later discovery of various Treg subsets with distinct migration/homing property as well as the inflammatory stage when Tregs come into play along an immune reaction. In our recent study, we investigated the migration characteristics of Treg cells by using the endothelial cell-based shear-stress flow assay that resembles the intravascular blood flow system. We found that both FoxP3-expressing Tregs and anergic T cells generated by blockage of costimulation factors, CD80 and CD86, exhibited a significantly decreased adhesion to endothelial cells as compared to antigen-activated effector T cells (66~88 % reduction). The less migration phenotype hinted inefficient tissue trafficking of the Tregs and suggested the lymph nodes as the anatomic site where Tregs optimally exerted immune regulation. To this speculation, an essential role of Treg lymph node positioning in exerting immune suppression was demonstrated by the inability of adoptively transferred Tregs to prevent footpad inflammation after blockage of lymph node entry of these Tregs by CCR7 or CD62L Ab. Therapeutic modality targeting leukocyte migration has been a mainstay alternative for immunologic diseases. Important messages have arisen for treatments of this kind and Treg-based cell therapy that whilst inflammatory response can be harnessed by modulating the migration property of leukocytes, the relationship between Treg migration phenotypes and their immune regulatory function should always be taken into consideration

Effects of overexpression of IL-10, IL-12, TGF-β and IL-4 on allergen induced change in bronchial responsiveness

BACKGROUND: An increasing prevalence of allergic diseases, such as atopic dermatitis, allergic rhinitis and bronchial asthma, has been noted worldwide. Allergic asthma strongly correlates with airway inflammation caused by the unregulated production of cytokines secreted by allergen-specific type-2 T helper (Th2) cells. This study aims to explore the therapeutic effect of the airway gene transfer of IL-12, IL-10 and TGF-β on airway inflammation in a mouse model of allergic asthma. METHODS: BALB/c mice were sensitized to ovalbumin (OVA) by intraperitoneal injections with OVA and challenged by nebulized OVA. Different cytokine gene plasmids or non-coding vector plasmids were instilled daily into the trachea up to one day before the inhalatory OVA challenge phase. RESULTS: Intratracheal administration of IL-10, IL-12 or TGF-β can efficiently inhibit antigen-induced airway hyper-responsiveness and is able to largely significantly lower the number of eosinophils and neutrophils in bronchoalveolar lavage fluid of ovalbumin (OVA) sensitized and challenged mice during the effector phase. Furthermore, the effect of IL-10 plasmids is more remarkable than any other cytokine gene plasmid. On the other hand, local administration of IL-4 gene plasmids before antigen challenge can induce severe airway hyper-responsiveness (AHR) and airway eosinophilia. CONCLUSION: Our data demonstrated that anti- inflammatory cytokines, particularly IL-10, have the therapeutic potential for the alleviation of airway inflammation in murine model of asthma

Type I IL-1 Receptor (IL-1RI) as Potential New Therapeutic Target for Bronchial Asthma

The IL-1R/TLR family has been receiving considerable attention as potential regulators of inflammation through their ability to act as either activators or suppressors of inflammation. Asthma is a chronic inflammatory disease characterized by airway hyperresponsiveness, allergic inflammation, elevated serum total, allergen-specific IgE levels, and increased Th2 cytokine production. The discovery that the IL-1RI–IL-1 and ST2–IL-33 pathways are crucial for allergic inflammation has raised interest in these receptors as potential targets for developing new therapeutic strategies for bronchial asthma. This paper discusses the current use of neutralizing mAb or soluble receptor constructs to deplete cytokines, the use of neutralizing mAb or recombinant receptor antagonists to block cytokine receptors, and gene therapy from experimental studies in asthma. Targeting IL-1RI–IL-1 as well as ST2–IL-33 pathways may promise a disease-modifying approach in the future

Juvenile Dermatomyositis: A 20-year Retrospective Analysis of Treatment and Clinical Outcomes

BackgroundJuvenile dermatomyositis is a rare childhood multisystem autoimmune disease involving primarily the skin and muscles, and it may lead to long-term disability. This study aimed to describe the clinical course of juvenile dermatomyositis and determine if any early clinical or laboratory features could predict outcome.MethodsMedical charts of patients aged ≤18 years and diagnosed with juvenile dermatomyositis (according to the criteria of Bohan and Peter) at the Pediatric Department, National Taiwan University Hospital, between 1989 and 2009 were reviewed. The endpoints for disease assessment were complete clinical response and complete clinical remission. Cox's proportional hazards model was fitted to identify important predictors of complete clinical remission.ResultsA total of 39 patients with juvenile dermatomyositis were reviewed. Two-thirds were females, and the mean age at disease onset was 81.97 ± 46.63 months. The most common initial presentations were Gottron's papule (82.1%) and muscle weakness (82.1%). After excluding one patient with an incomplete record, the remaining 31 patients who had muscle weakness were analyzed; among them, 22 (70.97%) achieved complete clinical response, but only six (19.4%) achieved complete clinical remission. Multivariate analysis showed that female sex, negative Gowers' sign at disease onset, and positive photosensitivity at disease onset were favorable factors to achieve complete clinical remission. Moreover, covariate-adjusted survival curves were drawn for making predictions of complete clinical remission. Only 13 (33.33%) patients were symptom free at the end of follow up, whereas the other 26 suffered from different kinds of complications. None of them developed malignancy, but two (5.13%) patients died during the follow-up period.ConclusionFactors such as male sex and Gowers' sign were unlikely to favor the achievement of complete clinical remission in juvenile dermatomyositis. Certain complications cannot be avoided, and thus more effective treatments and monitoring strategies are needed for better control of juvenile dermatomyositis

The effect of caffeic acid phenethyl ester on the functions of human monocyte-derived dendritic cells

<p>Abstract</p> <p>Background</p> <p>Propolis, an ancient herbal medicine, has been reported the beneficial effect both in asthma patients and murine model of asthma, but the mechanism was not clearly understood. In this study, the effect of caffeic acid phenethyl ester (CAPE), the most extensively studied components in propolis, on the functions of human monocyte-derived dendritic cells (MoDCs) was investigated.</p> <p>Results</p> <p>CAPE significantly inhibited IL-12 p40, IL-12 p70, IL-10 protein expression in mature healthy human MoDCs stimulated by lipopolysaccharides (LPS) and IL-12 p40, IL-10, IP-10 stimulated by crude mite extract. CAPE significantly inhibited IL-10 and IP-10 but not IL-12 expression in allergic patients' MoDCs stimulated by crude mite extract. In contrast, the upregulation of costimulatory molecules in mature MoDCs was not suppressed by CAPE. Further, the antigen presenting ability of DCs was not inhibited by CAPE. CAPE inhibited IκBα phosphorylation and NF-κB activation but not mitogen-activated protein kinase (MAPK) family phosphorylation in human MoDCs.</p> <p>Conclusion</p> <p>These results indicated that CAPE inhibited cytokine and chemokine production by MoDCs which might be related to the NF-κB signaling pathway. This study provided a new insight into the mechanism of CAPE in immune response and the rationale for propolis in the treatment of asthma and other allergic disorders.</p

X-linked hyper-IgM syndrome with CD40LG mutation: Two case reports and literature review in Taiwanese patients

Hyper-IgM syndrome (HIGM) is a rare primary immunodeficiency disorder characterized by elevated or normal serum IgM and decreased IgG, IgA, and IgE due to defective immunoglobulin class switching. X-linked HIGM (XHIGM, HIGM1) is the most frequent type, is caused by mutations in the CD40 ligand gene, and is regarded as a combined T and B immunodeficiency. We report an 18-year-old male who was diagnosed initially with hypogammaglobulinemia in infancy, but developed repeated pneumonia, sepsis, cellulitis, perianal abscess, pericarditis, and bronchiectasis despite regular intravenous immunoglobulin replacement therapy. The patient died at age 18 years due to pneumonia and tension pneumothorax. Mutation analysis revealed CD40L gene mutation within Exon 5 at nucleotide position 476 (cDNA 476G > A). This nonsense mutation predicted a tryptophan codon (TGG) change to a stop codon (TGA) at position 140 (W140X), preventing CD40L protein expression. Sequence analysis in the family confirmed a de novo mutation. The second case of 6-month-old male infant presented as Pneumocystis jiroveci pneumonia and acute respiratory distress syndrome. Gene analysis of the CD40L gene revealed G to C substitution in Intron 4 (c.409 + 5G > C) and mother was a carrier. Hematopoietic stem cell transplantation, the only cure for XHIGM, was arranged in the second case

Tai-Chi-Chuan Exercise Improves Pulmonary Function and Decreases Exhaled Nitric Oxide Level in Both Asthmatic and Nonasthmatic Children and Improves Quality of Life in Children with Asthma

Tai-Chi-Chuan (TCC) is an exercise of low-to-moderate intensity which is suitable for asthmatic patients. The aim of our study is to investigate improvements of the lung function, airway inflammation, and quality of life of asthmatic children after TCC. Participants included sixty-one elementary school students and they were divided into asthmatic (n=29) and nonasthmatic (n=32) groups by the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Among them, 20 asthmatic and 18 nonasthmatic children volunteered to participate in a 60-minute TCC exercise weekly for 12 weeks. Baseline and postintervention assessments included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), peak expiratory flow rate (PEFR), fractional exhaled nitric oxide (FeNO) level, and Standardised Pediatric Asthma Quality of Life Questionnaire (PAQLQ(S)). After intervention, the level of FeNO decreased significantly; PEFR and the FEV1/FVC also improved significantly in both asthmatic group and nonasthmatic group after TCC. The asthmatic children also had improved quality of life after TCC. The results indicated that TCC could improve the pulmonary function and decrease airway inflammation in both children with mild asthma and those without asthma. It also improves quality of life in mild asthmatic children. Nevertheless, further studies are required to determine the effect of TCC on children with moderate-to-severe asthma

Peripheral Neuroepithelima:A Case Report

Muchos gobiernos europeos, incluido el de Noruega, tienen políticas educativas ambiciosas en materia de digitalización. Muchas empresas y responsables políticos prestan gran atención al uso de las tecnologías digitales en la educación para satisfacer la futura demanda de una mano de obra competente y cualificada. Entre los investigadores y los legisladores, existe un consenso general al considerar a los docentes profesionales como una figura clave para la aplicación con éxito de las TIC en la escuela, en lo referente a su implementación y su uso, y se han depositado muchas expectativas en ellos. Se supone que el docente profesional debe, hasta cierto punto, decidir de manera autónoma cómo se han de utilizar estas tecnologías digitales en el aula. Este artículo analiza lo que puede significar el concepto de «docente profesional digitalmente competente» en el contexto de la escuela. También argumenta sobre la necesidad de una mejor interpretación de la competencia digital profesional, que tenga en cuenta diversos aspectos sociales y culturales en relación con la tecnología, las escuelas y la profesión docente. Al analizar las condiciones sociales y culturales para implementar la tecnología en un contexto de enseñanza profesional, nos basaremos en el enfoque constructivista de la tecnología, en concreto, la «domesticación de la tecnología»Many European governments, including Norway, have ambitious educational policies regarding digitalisation. Many businesses and policymakers pay great attention to the use of digital technologies in education in order to meet the future demands for a competent and qualified workforce. Among researchers and policymakers, there is a general consensus that the professional teacher is a key figure for the successful implementation of digital technologies in schools. Many expectations have been placed upon professional teachers regarding the implementation and use of digital technologies. The professional teacher is, to a certain degree, supposed to independently decide how digital technologies should be used in the classroom. This paper discusses what the concept of a ‘professional digitally competent teacher’ may mean in the context of schools. It also argues the need for a greater understanding of professional digital competence, one which takes into consideration various social and cultural aspects with regard to technology, schools and the teaching profession. In unpacking the social and cultural conditions for implementing technology in a professional teaching context, I will draw on concepts from the constructivist understanding of technology, namely, the ‘domestication of technology