Inhibitory effect of probiotic Bacillus spp. isolated from the digestive tract of Rhynchocypris Lagowskii on the adhesion of common pathogenic bacteria in the intestinal model.

Diseases of fish caused by pathogenic bacteria are an important constraint on aquaculture production. Antibiotics have been widely used to control infectious diseases, but this has led to the emergence of drug-resistant bacteria and affected human health. In this context, probiotics are used as an alternative to antibiotics for the prevention and control of diseases in aquaculture. The aim of this study was to obtain probiotic candidate strains of Bacillus spp. from the gut of Rhynchocypris Lagowskii. Strains were screened by enzyme-producing ability, antagonism assay and antibiotic susceptibility. The safety of the strains to host fish has also been established. The isolated Bacillus licheniformis (LSG1-1) and Bacillus subtilis (LSG2-1) were characterized and performed well in tolerance experiments. In addition, LSG1-1 and LSG2-1 were detected to have higher self-aggregation ability and surface hydrophobicity. In the in vitro adhesion model, LSG1-1 and LSG2-1 showed good adhesion ability and had obvious adhesion inhibitory effect on three pathogens of Aeromonas. Based on the characteristics observed so far, Bacillus licheniformis LSG1-1 and Bacillus subtilis LSG2-1 could form potential probiotic candidates in the digestive tract of R. lagowskii to help combat diseases in aquaculture.

IL-17 is necessary for host protection against acute-phase Trypanosoma cruzi infection.

IL-17A is a key cytokine that induces inflammatory responses through the organized production of inflammatory cytokines, such as IL-6, TNF-alpha, and GM-CSF, and induces neutrophil migration. The roles of IL-17A in infection of intracellular protozoan parasites have not been elucidated, although augmented immune responses by IL-17A are important for the resolution of some bacterial and fungal infections. Therefore, we experimentally infected IL-17A-deficient (IL-17A(-/-)) mice with Trypanosoma cruzi. IL-17A(-/-) mice had a lower survival rate and prolonged worse parasitemia compared with control C57BL/6 wild-type (WT) mice postinfection. In the infected IL-17A(-/-) mice, multiple organ failure was observed compared with WT mice, as reflected by the marked increase in serologic markers of tissue injury, such as aspartate aminotransferase, which resulted in increased mortality of IL-17A(-/-) mice. Expression of cytokines, such as IFN-gamma, IL-6, and TNF-alpha, was lower in liver-infiltrating cells from the IL-17A(-/-) mice compared with WT mice. A similar defect was observed in the expression of neutrophil enzymes, such as myeloperoxidase and lipoxygenase, whereas cellular infiltration into the infected tissues was not affected by IL-17A deficiency. These results suggested that the efficient activation of immune-related cells critical for the killing of T. cruzi was impaired in the absence of IL-17A, resulting in the greater susceptibility of those mice to T. cruzi infection. From these results, we conclude that IL-17A is important for the resolution of T. cruzi infection.

Dengue vaccine: an update.

Introduction: Dengue virus is a global health threat, with approximately 390 million dengue infections annually. Efficient vaccines for dengue prevention are currently lacking. This review aims to summarize the current progress in dengue vaccine development.Area covered: This article discusses recent dengue vaccine developments based on the published literature and ClinicalTrials.gov website up to December 2020.Expert opinion: The first live-attenuated chimeric yellow-fever/tetravalent dengue vaccine (CYD-TDV), Dengvaxia, has been licensed in several countries. However, the low efficacy of this vaccine was observed in children and dengue-naïve individuals. It also increased the risk of severe dengue in people who had not been exposed to dengue. The heterologous prime-boost regimen of sequential immunization with DENVax and Dengvaxia covers four serotypes of immunogenicity, eliminating the effect of ADE. Moreover, a heterologous prime-boost regimen that combines inactivated vaccines with alum and live attenuated vaccines might increase the immunogenic response. The lack of an ideal animal model is an obstacle to the development of dengue vaccines, and the macaque model may be considered for similar immunologic responses in humans.

Generation and characterization of B7-H4/B7S1/B7x-deficient mice.

Members of the B7 family of cosignaling molecules regulate T-cell proliferation and effector functions by engaging cognate receptors on T cells. In vitro and in vivo blockade experiments indicated that B7-H4 (also known as B7S1 or B7x) inhibits proliferation, cytokine production, and cytotoxicity of T cells. B7-H4 binds to an unknown receptor(s) that is expressed on activated T cells. However, whether B7-H4 plays nonredundant immune regulatory roles in vivo has not been tested. We generated B7-H4-deficient mice to investigate the roles of B7-H4 during various immune reactions. Consistent with its inhibitory function in vitro, B7-H4-deficient mice mounted mildly augmented T-helper 1 (Th1) responses and displayed slightly lowered parasite burdens upon Leishmania major infection compared to the wild-type mice. However, the lack of B7-H4 did not affect hypersensitive inflammatory responses in the airway or skin that are induced by either Th1 or Th2 cells. Likewise, B7-H4-deficient mice developed normal cytotoxic T-lymphocyte reactions against viral infection. Thus, B7-H4 plays a negative regulatory role in vivo but the impact of B7-H4 deficiency is minimal. These results suggest that B7-H4 is one of multiple negative cosignaling molecules that collectively provide a fine-tuning mechanism for T-cell-mediated immune responses.

MicroRNA-524 inhibits the progress of glioma via the direct targeting of NCF2.

In recent years, a large amount of research has reported that microRNA (miRNA) dysregulation is closely related to glioma progression. miR-524, a member of the miRNA family, has been confirmed to be involved in many human diseases, including glioma. However, the role and molecular mechanism of miR-524 in glioma have not been clarified. In our study, we showed that miR-524 expression was significantly decreased in glioma and was associated with glioma recurrence. Next, we performed a series of assays and confirmed that the upregulation of miR-524 suppressed glucose uptake, proliferation, migration and invasion in glioma cell lines. Then, through bioinformatics software and a dual luciferase assay, we demonstrated that NCF2 was a target gene of miR-524. In addition, we found that NCF2 reintroduction restored the inhibitor effect of miR-524 on glioma progression. These results elucidate the mechanism of miR-524 in glioma development and provide a potential therapeutic strategy for glioma patients.

Amelioration of delayed-type hypersensitivity responses by IL-27 administration.

Interleukin (IL-) 27 is a member of the IL-12 cytokine family. Although recent analyses of WSX-1 (IL-27 receptor alpha chain)-deficient mice as well as in vitro studies using recombinant IL-27 revealed the immunosuppressive function of IL-27, in vivo role and therapeutic potential of IL-27 remain poorly elucidated. Here we investigated the effect of IL-27 administration on delayed-type hypersensitivity (DTH). While WSX-1-deficient mice showed higher DTH responses as shown by the degree of footpad swelling, administration of IL-27 significantly ameliorated the footpad swelling. Since the activation status of the draining lymph node cells were not affected by IL-27 deficiency, it was suggested that IL-27 affected the effector phase of the response. These results collectively indicate that IL-27 has a suppressive effect on activated T cells in the experimental model and also has a therapeutic potential for some diseases caused by immune disorder.

Sequencing of PCR amplified HBV DNA pre-c and c regions in the 2.2.15 cells and antiviral action by targeted antisense oligonucleotide directed against sequence.

AIM:To study the specific inhibition of HBV gene expression by liver-targeting antisense oligonucleotide (ASON) directed against pre-c and cregious in a sequence specific manner.METHODS:According to the result of direct sequencing of PCR amplified products, a 16 mer phosphorothioate analogue of the antisense oligonucleotide (PS-ASOn) directed against the HBV U-5-like region was synthesized and then linked with one live-targeting ligand, the galactosylated poly-L-lysine.Their effect on the expression of HBV gene was observed using the 2.2.15 cells.RESULTS:HBV DNA in the 2.2.15 cells was from HBV with surface antigen subtype ayw 1 by sequencing so that antisense oligonucleotides could bind specifically to the target sequence through base piring. Under the same experimental conditions, the inhibitory rates of PS-ASON to HBsAg and HBeAg were 70% and 58% at a concentration of 10&mgr;mol/L, while by ligand-PS-ASON they were 96% and 82%, the amount of HBV DNA in cultured supernatant and cells was reduced significantly. An unrelated sequence oligonucleotide showed no effectiveness. All the oligonucleotides had no cytotoxicity.CONCLUSION:Antisense oligonucleotides complexed by the liver-targeting ligand can be targeted to cells via asialoglycoprotein receptors, resulting in supecific inhibition of HBV gene expression and replication.