45 research outputs found

    Activated IL-23/IL-17 pathway closely correlates with increased Foxp3 expression in livers of chronic hepatitis B patients

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    <p>Abstract</p> <p>Background</p> <p>Foxp3 protein plays a critical role in mediating the inflammatory response and can inhibit the proinflammatory IL-23/IL-17 pathway. However, the molecular interplay of Foxp3 and the IL-23/IL-17 pathway in patients with chronic hepatitis B (CHB) remains unclear. To this end, we analyzed the expression patterns of Foxp3- and IL-23/IL-17 pathway-related proinflammatory cytokines in 39 patients with acute-on-chronic liver failure, 71 patients with CHB and 32 healthy controls.</p> <p>Results</p> <p>Foxp3 expression was found to be elevated in and mainly expressed by the CD4<sup>+ </sup>T cell sub-population of peripheral blood mononuclear cells and liver tissues of patients with hepatitis B. The intrahepatic expression of Foxp3 strongly correlated with the copies of HBV DNA and the concentration of surface antigen, HBsAg. IL-23/IL-17 pathway-related proinflammatory cytokines were also found to be significantly increased in patients' liver tissues, as compared to healthy controls. Moreover, Foxp3 expression was strikingly correlated with the production of these cytokines in liver tissues of CHB patients.</p> <p>Conclusions</p> <p>The closely-correlated increase of Foxp3 and IL-23/IL-17 pathway activity in HBV-infected livers suggests that the proinflammatory IL-23/IL-17 pathway had not been effectively suppressed by the host immune machinery, such as Treg (Foxp3) cells. Constitutive activation of the IL-23/17 pathway, thus, may support the chronic hepatitis B state.</p

    Effects of Telbivudine Treatment on the Circulating CD4+ T-Cell Subpopulations in Chronic Hepatitis B Patients

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    CD4+ T cells serve as master regulators of the adaptive immune response to HBV. However, CD4+ T-cell subsets are heterogeneous, and it remains unknown how the antiviral agents affect the different CD4+ T cell subtypes. To this end, the expressions of signature transcription factors and cytokines of CD4+ T-cell subtypes were examined in hepatitis B patients before and after treatment with telbivudine. Results showed that, upon the rapid HBV copy decrease induced by telbivudine treatment, the frequencies and related cytokines of Th17 and Treg cells were dramatically decreased, while those for Th2 cells were dramatically increased. No obvious changes were observed in Th1 cell frequencies; although, IFN-γ expression was upregulated in response to telbivudine treatment, suggesting another cell source of IFN-γ in CHB patients. Statistical analyses indicated that Th17 and Tr1 (a Treg subtype) cells were the most sensitive subpopulations of the peripheral blood CD4+ T cells to telbivudine treatment over 52 weeks. Thus, Th17 and Tr1 cells may represent a suitable and effective predictor of responsiveness during telbivudine therapy. These findings not only improve our understanding of hepatitis pathogenesis but also can aid in future development of appropriate therapeutic strategies to control viral hepatitis

    Collective Learning

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    Can Hybrid Synapse be Formed between Rat Spinal Motor Neurons and Major Pelvic Ganglion Neurons

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    The purpose of this study is to determine whether synapses can be formed between spinal motor neurons (SMNs) and major pelvic ganglion (MPG) neurons of a rat in vitro. The green fluorescent protein (GFP)-labelled MPG cells were cultured together with SMNs in a specific medium. The synaptic-like contacts established between SMNs and MPG neurons were studied in co-cultures using morphologic and immunocytochemistry approaches. Phase-contrast observation of co-cultures showed apparent SMNs-MPG neurons contacts as early as three or four days in vitro. We demonstrate some evidence of synaptic contacts between SMNs and MPG neurons in vitro by immunostaining with antibody directed against postsynaptic density protein 95 (PSD-95). We describe the development process of a defined SMNs-MPG neurons co-culture system. The results suggest that the hybrid synapse formation that may occur between SMNs and MPG neurons in vitro played an essential role in the mechanisms of a regenerated bladder with an artificial somatic-autonomic reflex arc

    Domain-Adaptive Emotion Recognition Based on Horizontal Vertical Flow Representation of EEG Signals

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    With the development of cognitive science and brain science, brain-computer interface technology can use Electroencephalogram (EEG) signals to better represent the inner changes of emotions. In this paper, A video-induced emotional stimulation experimental paradigm was designed, and the EEG signals of 15 hearing-impaired subjects under three emotions (positive, neutral, and negative) were collected. Considering the flow diffusion properties of EEG signals, we used the diffusion effect based on horizontal representation and vertical representation forms to obtain the spatial domain features. After EEG preprocessing, the differential entropy feature (DE) in the frequency domain is extracted. The frequency domain features of 62 channels are delivered to two Bi-directional Long Short-Term Memory (BiLSTM) to obtain spatial domain features of horizontal and vertical representations respectively, and then two kinds of domain features are fused by the residual network. The attention mechanism is applied to effectively extract emotional representational information from the fused features. To solve the cross-subject problem of emotion recognition, the domain adaptation method is utilized, and a center alignment loss function is applied to increase the distance of inter-class and reduce the distance of intra-class. According to the experimental results, the average accuracies of 75.89&#x0025; (subject- dependent) and 69.59&#x0025; (cross-subject) are obtained. Moreover, the validation was also performed on the public dataset SEED, achieving average accuracies of 93.99&#x0025; (subject-dependent) and 84.22&#x0025; (cross-subject), respectively

    Impact of a Combined High Cholesterol Diet and High Glucose Environment on Vasculature

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    <div><p>Aims</p><p>Vascular complications are the leading cause of mortality and morbidity in patients with diabetes. However, proper animal models of diabetic vasculopathy that recapitulate the accelerated progression of vascular lesions in human are unavailable. In the present study, we developed a zebrafish model of diabetic vascular complications and the methodology for quantifying vascular lesion formation real-time in the living diabetic zebrafish.</p><p>Methods and Results</p><p>Wild type zebrafish (AB) and transgenic zebrafish lines of <i>fli1:EGFP</i>, <i>lyz:EGFP, gata1:dsRed</i>, double transgenic zebrafish of <i>gata1:dsRed/fli1:EGFP</i> were exposed to high cholesterol diet and 3% glucose (HCD-HG) for 10 days. The zebrafish model with HCD-HG treatment was characterized by significantly increased tissue levels of insulin, glucagon, glucose, total triglyceride and cholesterol. Confocal microscopic analysis further revealed that the diabetic larvae developed clearly thickened endothelial layers, distinct perivascular lipid depositions, substantial accumulations of inflammatory cells in the injured vasculature, and a decreased velocity of blood flow. Moreover, the vascular abnormalities were improved by the treatment of pioglitazone and metformin.</p><p>Conclusion</p><p>A combination of high cholesterol diet and high glucose exposure induces a rapid onset of vascular complications in zebrafish similar to the early atherosclerotic vascular injuries in mammalian diabetic models, suggesting that zebrafish may be used as a novel animal model for diabetic vasculopathy.</p></div
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