CD100 up-Regulation Induced by Interferon-α on B Cells Is Related to Hepatitis C Virus Infection

Objectives: CD100, also known as Sema4D, is a member of the semaphorin family and has important regulatory functions that promote immune cell activation and responses. The role of CD100 expression on B cells in immune regulation during chronic hepatitis C virus (HCV) infection remains unclear. Materials and Methods: We longitudinally investigated the altered expression of CD100, its receptor CD72, and other activation markers CD69 and CD86 on B cells in 20 chronic HCV-infected patients before and after treatment with pegylated interferon-alpha (Peg-IFN-α) and ribavirin (RBV) by flow cytometry. Results: The frequency of CD5+ B cells as well as the expression levels of CD100, CD69 and CD86 was significantly increased in chronic HCV patients and returned to normal in patients with sustained virological response after discontinuation of IFN-α/RBV therapy. Upon IFN-α treatment, CD100 expression on B cells and the two subsets was further up-regulated in patients who achieved early virological response, and this was confirmed by in vitro experiments. Moreover, the increased CD100 expression via IFN-α was inversely correlated with the decline of the HCV-RNA titer during early-phase treatment. Conclusions: Peripheral B cells show an activated phenotype during chronic HCV infection. Moreover, IFN-α therapy facilitates the reversion of disrupted B cell homeostasis, and up-regulated expression of CD100 may be indirectly related to HCV clearance

High levels of exfoliated fragments following glycocalyx destruction in hemorrhagic fever with the renal syndrome are associated with mortality risk

BackgroundThe glycocalyx is a gel-like structure that covers the luminal side of vascular endothelial cells. It plays an important role in maintaining the integrity of the vascular endothelial barrier structure. However, the presence or absence of glycocalyx destruction in hemorrhagic fever with renal syndrome (HFRS) and its specific mechanism and role is still unclear.MethodsIn this study, we detected the levels of exfoliated glycocalyx fragments, namely, heparan sulfate (HS), hyaluronic acid (HA), and chondroitin sulfate (CS), in HFRS patients and investigated their clinical application value on the evaluation of disease severity and prognosis prediction.ResultsThe expression of exfoliated glycocalyx fragments in plasma was significantly increased during the acute stage of HFRS. The levels of HS, HA, and CS in HFRS patients during the acute stage were significantly higher than in healthy controls and convalescent stages of the same type. HS and CS during the acute stage gradually increased with the aggravation of HFRS, and both fragments showed a significant association with disease severity. In addition, exfoliated glycocalyx fragments (especially HS and CS) showed a significant correlation with conventional laboratory parameters and hospitalization days. High levels of HS and CS during the acute phase were significantly associated with patient mortality and demonstrated an obvious predictive value for the mortality risk of HFRS.ConclusionGlycocalyx destruction and shedding may be closely associated with endothelial hyperpermeability and microvascular leakage in HFRS. The dynamic detection of the exfoliated glycocalyx fragments may be beneficial for the evaluation of disease severity and prognosis prediction in HFRS

HMGB-1 as a Novel Predictor of Disease Severity and Prognosis in Patients with Hemorrhagic Fever with Renal Syndrome

Objective. To examine the predictive capacity of the high mobility group box protein-1 (HMGB-1) for disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS). Methods. One hundred and five HFRS patients and 28 controls were studied. The concentrations of HMGB-1 in the blood were measured with a commercially available ELISA. The levels of white blood cells (WBC), platelets (PLT), hematocrit (HCT), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (Scr), and uric acid (UA) were routinely tested in the same time frame. Results. The levels of HMGB-1 increased with the severity of the disease ( < 0.001). HMGB-1 was positively correlated with WBC and BUN and negatively correlated with PLT, ALB, and UA ( < 0.001). HMGB-1 showed statistical significance for predicting prognosis (AUC = 0.800, < 0.001). The sensitivity and specificity of HMGB-1, WBC, PLT, and ALB used in combination for predicting outcome were better than those of single analyses (AUC = 0.892, < 0.001). Conclusions. HMGB-1 can be considered a novel biomarker for severity and outcome in patients with HFRS. The use of HMGB-1, WBC, PLT, and ALB in combination to predict the outcome in patients with HFRS exhibited an acceptable level of diagnostic capability

Inhibition of TRF2 Accelerates Telomere Attrition and DNA Damage in Naïve CD4 T Cells During HCV Infection

T cells play a crucial role in viral clearance and vaccine responses; however, the mechanisms that regulate their homeostasis during viral infections remain unclear. In this study, we investigated the machineries of T-cell homeostasis and telomeric DNA damage using a human model of hepatitis C virus (HCV) infection. We found that naïve CD4 T cells in chronically HCV-infected patients (HCV T cells) were significantly reduced due to apoptosis compared with age-matched healthy subjects (HSs). These HCV T cells were not only senescent, as demonstrated by overexpression of aging markers and particularly shortened telomeres; but also DNA damaged, as evidenced by increased dysfunctional telomere-induced foci (TIF). Mechanistically, the telomere shelterin protein, in particular telomeric repeat binding factor 2 (TRF2) that functions to protect telomeres from DNA damage, was significantly inhibited posttranscriptionally via the p53-dependent Siah-1a ubiquitination. Importantly, knockdown of TRF2 in healthy T cells resulted in increases in telomeric DNA damage and T-cell apoptosis, whereas overexpression of TRF2 in HCV T cells alleviated telomeric DNA damage and T-cell apoptosis. To the best of our knowledge, this is the first report revealing that inhibition of TRF2 promotes T-cell telomere attrition and telomeric DNA damage that accelerates T-cell senescent and apoptotic programs, which contribute to naïve T-cell loss during viral infection. Thus, restoring the impaired T-cell telomeric shelterin machinery may offer a new strategy to improve immunotherapy and vaccine response against human viral diseases

The Safety of Baduanjin Exercise: A Systematic Review

Objectives. Baduanjin exercise is a form of Qigong exercise therapy that has become increasingly popular worldwide. The aims of the current systematic review were to summarize reported adverse events potentially associated with Baduanjin exercise based on currently available literature and to evaluate the quality of the methods used to monitor adverse events in the trials assessed. Methods. The English databases PubMed, Cochrane library, and EMbase were searched from inception to October 2020 using the keywords “Baduanjin” or “eight session brocade.” Only studies that included Baduanjin exercise therapy were included. Results. Forty-seven trials with a total of 3877 participants were included in this systematic review. Twenty-two studies reported protocols for monitoring adverse events, and two studies reported the occurrence of adverse events during training. The adverse events reported included palpitation, giddiness, knee pain, backache, fatigue, nervousness, dizziness, shoulder pain, chest tightness, shortness of breath, and muscle ache. Conclusions. Only two studies reported adverse events that were potentially caused by Baduanjin exercise. Adverse events related to Baduanjin exercise in patients with chronic fatigue syndrome may include muscle ache, palpitation, giddiness, knee pain, backache, fatigue, nervousness, dizziness, shoulder pain, chest tightness, and shortness of breath. Further studies conducted in accordance with the Consolidated Standards of Reporting Trials statement guideline incorporating monitoring of adverse events are recommended. Additional clinical trials in which Baduanjin exercise is used as a main intervention are needed, and further meta-analysis may be required to assess its safety and reach more informed conclusions in this regard in the future

Lung ultrasound findings in patients with COVID-19 pneumonia

Since December 2019, the outbreak of pneumonia caused by a new coronavirus [1], which was later identified as coronavirus disease 2019 (COVID­19), has infected more than 410,000 patients globally according to the situation report of World Health Organization. Lung ultrasound is an important tool for the diagnosis and follow-up of pneumonia in neonates, children, and adults [2,3,4]. Recent CT reports demonstrated that most of the lesions were distributed peripherally in the lung, which facilitates detection by lung ultrasound [5, 6]. In this study, we characterize the lung ultrasound findings COVID-19 pneumonia, and study the relationship between the ultrasound findings and clinical severity and the time-course of disease progress. Bedside lung ultrasound was performed to detect B-lines, lung consolidation, and pleural line abnormalities at 5 areas in each lung. Vascular ultrasound was also performed to detect potential deep vein thrombosis

HMGB-1 as a Novel Predictor of Disease Severity and Prognosis in Patients with Hemorrhagic Fever with Renal Syndrome

Objective. To examine the predictive capacity of the high mobility group box protein-1 (HMGB-1) for disease severity and prognosis of hemorrhagic fever with renal syndrome (HFRS). Methods. One hundred and five HFRS patients and 28 controls were studied. The concentrations of HMGB-1 in the blood were measured with a commercially available ELISA. The levels of white blood cells (WBC), platelets (PLT), hematocrit (HCT), albumin (ALB), blood urea nitrogen (BUN), serum creatinine (Scr), and uric acid (UA) were routinely tested in the same time frame. Results. The levels of HMGB-1 increased with the severity of the disease (P<0.001). HMGB-1 was positively correlated with WBC and BUN and negatively correlated with PLT, ALB, and UA (P<0.001). HMGB-1 showed statistical significance for predicting prognosis (AUC = 0.800, P<0.001). The sensitivity and specificity of HMGB-1, WBC, PLT, and ALB used in combination for predicting outcome were better than those of single analyses (AUC = 0.892, P<0.001). Conclusions. HMGB-1 can be considered a novel biomarker for severity and outcome in patients with HFRS. The use of HMGB-1, WBC, PLT, and ALB in combination to predict the outcome in patients with HFRS exhibited an acceptable level of diagnostic capability

Ag functionalized molybdenum disulfide hybrid nanostructures for selective and sensitive amperometric hydrogen peroxide detection

Ag nanoparticles functionalized flower-like molybdenum disulfide (MoS2) hybrid nanostructures (AgNPs/MoS2) were successfully synthesized by a facile hydrothermal method. The structure and surface morphology were subsequently characterized by scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) techniques. The as-synthesized AgNPs/MoS2 hybrid nanostructures were modified on a glassy carbon electrode (GCE) and further utilized for amperometric hydrogen peroxide (H2O2) detection. The electrochemical behaviors and sensing performance of the AgNPs/MoS2/GCE were studied by cyclic voltammetry (CV) and single-potential amperometry methods. The obtained results have demonstrated that the developed AgNPs/MoS2/GCE amperometric sensor possesses an excellent catalytic performance toward the reduction of H2O2. The as-prepared electrochemical sensor exhibits fast response time of less than 3 s, large linear detection range of 0.025-135.2 mM (R-2=0.998) and high sensitivity of 54.5 mu A.mM(-1). cm(-2). Moreover, the developed H2O2 sensor has shown good anti interference ability, outstanding stability and reproducibility, which represents a great potential for H2O2 detection in practical applications

Role of A20 in Interferon-α-Mediated Functional Restoration of Myeloid Dendritic Cells in Patients With Chronic Hepatitis C

Hepatitis C virus (HCV) infection is a global health problem characterized by a high rate of chronic infection, which may in part be due to a defect in myeloid dendritic cells (mDCs). This defect appears to be remedied by treatment with interferon-α (IFN-α) -based antiviral therapies; however, the molecular mechanisms underlying mDC dysfunction in HCV infection and restoration by IFN-α treatment are unclear. The ubiquitin-editing protein A20 plays a crucial role in controlling the maturation, cytokine production and immunostimulatory function of mDCs. We propose that the expression of A20 correlates with the function of mDCs during HCV infection and IFN-α therapy. In this study, we observed that A20 expression in mDCs isolated from chronically HCV-infected subjects was significantly higher than healthy subjects or subjects achieving sustained virological responses (SVR) following antiviral treatment. Notably, A20 expression in mDCs from HCV patients during IFN-α treatment was significantly lower than for untreated patients, SVR patients, or healthy subjects. Besides, A20 expression in mDCs stimulated by polyI:C differed between HCV patients and healthy subjects, and this difference could be abrogated by the treatment with IFN-α in vitro. Additionally, A20 expression by polyI:C-activated mDCs, with or without IFN-α treatment, negatively correlated with the expression of HLA-DR, CD86 and CCR7, and the secretion of interleukin-12 (IL-12), but positively associated with the production of IL-10. Importantly, silencing A20 expression using small interfering RNAs increased the production of IL-12 in mDCs of chronically HCV-infected individuals. These findings suggest that A20 plays a crucial role in negative regulation of innate immune responses during chronic viral infection