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

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

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

The Cassiopeia Filament: A Blown Spur of the Local Arm

We present wide-field and high-sensitivity CO(1-0) molecular line observations toward the Cassiopeia region, using the 13.7m millimeter telescope of the Purple Mountain Observatory (PMO). The CO observations reveal a large-scale highly filamentary molecular cloud within the Galactic region of 132\fdg0\,$\geq$\,$l$\,$\geq$\,122\fdg0 and -1\fdg0\,$\leq$\,$b$\,$\leq$\,3\fdg0 and the velocity range from approximately +1 to +4 km/s. The measured length of the large-scale filament, referred to as the Cassiopeia Filament, is about 390 pc. The observed properties of the Cassiopeia Filament, such as length, column density, and velocity gradient, are consistent with those synthetic large-scale filaments in the inter-arm regions. Based on its observed properties and location on the Galactic plane, we suggest that the Cassiopeia Filament is a spur of the Local arm, which is formed due to the galactic shear. The western end of the Cassiopeia Filament shows a giant arc-like molecular gas shell, which is extending in the velocity range from roughly -1 to +7 km/s. Finger-like structures, with systematic velocity gradients, are detected in the shell. The CO kinematics suggest that the large shell is expanding at a velocity of ~6.5 km/s. Both the shell and finger-like structures outline a giant bubble with a radius of ~16 pc, which is likely produced by stellar wind from the progenitor star of a supernova remnant. The observed spectral linewidths suggest that the whole Cassiopeia Filament was quiescent initially until its west part was blown by stellar wind and became supersonically turbulent.Comment: 46 pages, 19 figures, to be published by the A