Activation-Induced T Helper Cell Death Contributes to Th1/Th2 Polarization following Murine Schistosoma japonicum Infection

In chronic infectious diseases, such as schistosomiasis, pathogen growth and immunopathology are affected by the induction of a proper balanced Th1/Th2 response to the pathogen and by antigen-triggered activation-induced T cell death. Here, by using S. japonicum infection or schistosome antigens-immunized mouse model, or antigens in vitro stimulation, we report that during the early stage of S. japonicum infection, nonegg antigens trigger Th2 cell apoptosis via the granzyme B signal pathway, contributing to Th1 polarization, which is thought to be associated with worm clearance and severe schistosomiasis. Meanwhile, after the adult worms lay their eggs, the egg antigens trigger Th1 cell apoptosis via the caspase pathway, contributing to Th2 polarization, which is associated with mild pathology and enhanced survival of both worms and their hosts. Thus, our study suggests that S. japonicum antigen-induced Th1 and Th2 cell apoptosis involves the Th1/Th2 shift and favorites both hosts and parasites

What Really Matters for Loneliness Among Left-Behind Children in Rural China: A Meta-Analytic Review

In rural China, left-behind children are likely to suffer chronic loneliness. Research has identified a variety of factors that may be associated with loneliness among these children. A meta-analysis is needed to address the empirical inconsistencies and examine the strength of relations between different factors and loneliness. The current meta-analysis included 51 studies on predictors of loneliness published from 2008 to 2017. Results showed that one individual factor (social anxiety) is a key risk factor for loneliness, whereas eight individual (older age, self-esteem, resilience, extroversion) and contextual factors (family functioning, parent–child relationship, peer relationship, social support) serve as protective factors in predicting loneliness. In addition, boys were more likely to feel lonely than girls. Findings and implications of this study were discussed

The nature and combination of subunits used in epitope-based Schistosoma japonicum vaccine formulations affect their efficacy

<p>Abstract</p> <p>Background</p> <p>Schistosomiasis remains a major public health problem in endemic countries and is caused by infections with any one of three primary schistosome species. Although there are no vaccines available to date, this strategy appears feasible since natural immunity develops in individuals suffering from repeated infection during a lifetime. Since vaccinations resulting in both Th1- and Th2-type responses have been shown to contribute to protective immunity, a vaccine formulation with the capacity for stimulating multiple arms of the immune response will likely be the most effective. Previously we developed partially protective, single Th- and B cell-epitope-based peptide-DNA dual vaccines (PDDV) (T3-PDDV and B3-PDDV, respectively) capable of eliciting immune responses against the <it>Schistosoma japonicum </it>22.6 kDa tegument antigen (Sj22.6) and a 62 kDa fragment of myosin (Sj62), respectively.</p> <p>Results</p> <p>In this study, we developed PDDV cocktails containing multiple epitopes of <it>S. japonicum </it>from Sj22.6, Sj62 and Sj97 antigens by predicting cytotoxic, helper, and B-cell epitopes, and evaluated vaccine potential <it>in vivo</it>. Results showed that mice immunized with a single-epitope PDDV elicited either Tc, Th, or B cell responses, respectively, and mice immunized with either the T3- or B3- single-epitope PDDV formulation were partially protected against infection. However, mice immunized with a multicomponent (3 PDDV components) formulation elicited variable immune responses that were less immunoprotective than single-epitope PDDV formulations.</p> <p>Conclusions</p> <p>Our data show that combining these different antigens did not result in a more effective vaccine formulation when compared to each component administered individually, and further suggest that immune interference resulting from immunizations with antigenically distinct vaccine targets may be an important consideration in the development of multicomponent vaccine preparations.</p

Altered Functional Connectivity in an Aged Rat Model of Postoperative Cognitive Dysfunction: A Study Using Resting-State Functional MRI

BACKGROUND: Postoperative cognitive impairment is a common complication after cardiac and major non-cardiac surgery in the elderly, but its causes and mechanisms remain unclear. The purpose of the current study was to use resting-state functional magnetic resonance imaging (fMRI) to explore changes in the functional connectivity, i.e. the synchronization of low frequency fluctuation (LFF), in an animal model of cognitive impairment in aged rats. METHODS: Aged (22 months) rats were anaesthetized with 40 µg/kg fentanyl and 500 µg/kg droperidol (intraperitoneal) for splenectomy. Cognitive function was assessed using Y maze prior to operation and on postoperative days 1, 3 and 9. To evaluate functional connectivity, resting-state fMRI data were acquired using a 3T MR imaging system with a 4 channel phase array rat head coil. RESULTS: Cognitive function was impaired at postoperative days 1 and 3 compared with preoperative. Significant synchronized LFF was detected bilaterally in the primary somatosensory cortex and hippocampus preoperatively. By contrast, no significant LFF synchronization was detected in the right primary somatosensory cortex and right hippocampus on postoperative days 1 and 3, although the pattern of functional connectivity had become almost normal by day 9. CONCLUSION: Splenectomy performed under neuroleptic anaesthesia triggers a cognitive decline that is associated with altered spontaneous neuronal activity in the cortex and hippocampus

Dynamics of Th17 Cells and Their Role in Schistosoma japonicum Infection in C57BL/6 Mice

Th17 immune cells secrete the IL-17 cytokine and contribute to host defenses against certain infections. Recent studies linked IL-17 with the severity of liver inflammation and suggested that Th17 cells contribute to the pathology in schistosomiasis, a serious disease caused by parasitic worms such as Schistosoma japonicum widespread in vertebrates including humans. However, the role of Th17 cells in protection against S. japonicum infection is still unclear. For the first time, we describe here the changes in Th17 cell levels during S. japonicum infection and suggest that the schistosome egg antigens are primarily responsible for stimulating the generation of host Th17 cells after S. japonicum infection. We further show that the level of Th17 cells in the host is determined by a combination of factors, namely exposure to complex parasitic antigens that either induce or suppress their generation. We also suggest that lowering IL-17 levels may favor the host's protective responses against S. japonicum infection. Our findings help to better understand the relationship between the host and parasite in terms of immune protection and pathology in schistosomiasis and may contribute to the future development of vaccination and therapeutic strategies

Abnormal expression of an ADAR2 alternative splicing variant in gliomas downregulates adenosine-to-inosine RNA editing

BACKGROUND: RNA editing is catalyzed by adenosine deaminases acting on RNA (ADARs). ADAR2 is the main enzyme responsible for recoding editing in humans. Adenosine-to-inosine (A-to-I) editing at the Q/R site is reported to be decreased in gliomas; however, the expression of ADAR2 mRNA was not greatly affected. METHODS: We determined ADAR2 mRNA expression in human glioblastoma cell lines and in normal human glial cells by real-time RT-PCR. We also determined ADAR2 mRNA expression in 44 glioma tissues and normal white matter. After identifying an alternative splicing variant (ASV) of ADAR2 in gliomas, we performed sequencing. We then classified glioblastomas based on the presence (+) or absence (–) of the ASV to determine the correlations between ASV + and malignant features of glioblastomas, such as invasion, peritumoral brain edema, and survival time. RESULTS: There were no significant differences in ADAR2 mRNA expression among human glioblastoma cell lines or in gliomas compared with normal white matter (all p > 0.05). The ASV, which contained a 47-nucleotide insertion in the ADAR2 mRNA transcript, was detected in the U251 and BT325 cell lines, and in some glioma tissues. The expression rate of ASV differed among gliomas of different grades. ASV + glioblastomas were more malignant than ASV – glioblastomas. CONCLUSIONS: ADAR2 is a family of enzymes in which ASVs result in differences in enzymatic activity. The ADAR2 ASV may be correlated with the invasiveness of gliomas. Identification of the mechanistic characterization of ADAR2 ASV may have future potential for individualized molecular targeted-therapy for glioma

Assessment of contamination and drug resistance profiles of non-typhoid Salmonella in pig slaughtering industry in Shandong Province

ObjectiveTo understand the contamination and drug resistance characteristics of non-typhoidal Salmonella （NTS） during pig slaughter.MethodsA total of 170 carcasses and environmental samples were collected from two large-scale pig slaughterhouses in May and August 2021 in Shandong Province， China. Whole genome sequencing （WGS） combined with bioinformatics was used to analyze the data of the NTS isolates.ResultsNTS was detected in 29 of 170 pork samples， detection rate was 17.1%. Salmonella typhimurium was the predominant serotype （58.6%， 17/29） in the samples. The results of the drug sensitivity analysis showed that 29 NTS strains had 15 drug resistance spectra， with the highest rate of tetracycline resistance （100.0%， 29/29）， followed by ampicillin and chloramphenicol （79.3%， 23/29）. The multidrug resistance rate was 86.2% （25/29 patients）. Multilocus sequence typing （MLST） showed that ST19 was the main type， accounting for 48.3% （14/29） of cases. Analysis of drug resistance genes showed that they carried mainly tet（A）， tet（B）， tet（M）， blaTEM-1B， blaCMY-97， floR， cmlA1， etc.ConclusionThe phenomenon of NTS contamination exists in some pig slaughterhouses in Shandong Province. NTS has shown resistance to multiple antibiotics， suggesting that attention should be paid to the prevention of NTS in pig slaughterhouses