Protein as the allergens could lead to allergy. In addition, a widespread class of allergens were known as glycans of N-glycoprotein. N-glycoprotein contained oligosaccharide linked by covalent bonds with protein. Recently,studies implicated that allergy was associated with glycans of heterologous N-glycoprotein found in food, inhalants, insect toxins, etc. The N-glycan structure of N-glycoprotein allergen has exerted an influence on the binding between allergens and IgE, while the recognition and presentation of allergens by antigen-presenting cells (APCs) were also affected. Some researches showed thatN-glycan structure of allergen was remodeled by N-glycosidase, such as cFase I, gpcXylase, as binding of allergen and IgE partly decreased. Thus, allergic problems caused by N-glycoproteins could potentially be solved by modifying or altering the structure ofN-glycoprotein allergens, addressing the root of the issue. Mechanism of N-glycans associated allergy could also be elaborated through glycosylation enzymes, alterations of host glycosylation. This article hopes to provide a separate insight for glycoimmunology perspective, and an alternative strategy for clinical prevention or therapy of allergic diseases.

Antineoplastic Combined Chemotherapy Protocols ; Bortezomib/therapeutic use* ; Dexamethasone ; Humans ; Multiple Myeloma/drug therapy* ; Treatment Outcome

BACKGROUNDPlasmacytoid dendritic cells (pDCs) and cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to explore the frequency and function of pDC and serum cytokine network profiles in patients with acute or chronic HBV infection.

METHODSThe healthy individuals (HI group), hepatitis B envelope antigen (HBeAg)-positive chronic HBV patients in immune tolerance (IT) phase (IT group), HBeAg-positive chronic HBV patients (CHB group), and acute HBV patients (AHB group) were enrolled in this study. The frequency of cluster of differentiation antigen 86 (CD86) + pDC and the counts of CD86 molecular expressed on surface of pDC were tested by flow cytometer. The quantitative determinations of cytokines, including Fms-like tyrosine kinase 3 ligand (Flt-3L), interferon (IFN)-α2, IFN-γ, interleukin (IL)-17A, IL-6, IL-10, transforming growth factor (TGF)-β1 and TGF-β2, were performed using Luminex multiplex technology.

RESULTSIn this study, there were 13 patients in HI group, 30 in IT group, 50 in CHB group, and 32 in AHB group. Compared with HI group, HBV infected group (including all patients in IT, CHB and AHB groups) had significantly higher counts of CD86 molecular expressed on the surface of pDC (4596.5 ± 896.5 vs. 7097.7 ± 3124.6; P < 0.001). The counts of CD86 molecular expressed on the surface of pDC in CHB group (7739.2 ± 4125.4) was significantly higher than that of IT group (6393.4 ± 1653.6, P = 0.043). Compared with IT group, the profile of cytokines of Flt-3L, IFN-γ, and IL-17A was decreased, IFN-α2 was significantly increased (P = 0.012) in CHB group. The contents of IL-10, TGF-β1, and TGF-β2 in AHB group were significantly increased compared with IT and CHB groups (all P < 0.05).

CONCLUSIONSThis study demonstrated that the function of pDC was unaffected in HBV infection. The enhanced function of pDC and IFN-α2 might involve triggering the immune response from IT to hepatitis active phase in HBV infection. Acute patients mainly presented as down-regulation of the immune response by enhanced IL-10 and TGF-β.

Background: Cytokines play an important role in occurrence and recovery of hepatitis B virus (HBV) infection. The aim of this study was to investigate the changes of cytokines concentration and its correlation to alanine aminotransferase (ALT), HBV deoxyribonucleic acid (HBV-DNA), hepatitis B envelope antigen (HBeAg), and HBV surface antigen (HBsAg) in the development of chronic hepatitis B (CHB). Methods: Thirteen healthy individuals (HI), 30 chronic HBV-infected patients in immune tolerant (IT) phase, and 55 CHB patients were enrolled between August 2015 and May 2017. The peripheral blood samples were collected from all individuals. The levels of interferon (IFN)-α2, interleukin (IL)-10, transforming growth factor (TGF)-β1, HBV-DNA, HBsAg, and HBeAg and liver function were measured. The quantitative determinations of cytokines levels, including IFN-α2, IL-10, and TGF-β1 were performed using Luminex multiplex technology. The correlation of cytokines to ALT, HBV-DNA, HBsAg, and HBeAg was analyzed by linear regression analysis. Results: IFN-α2 levels were similar between HI and IT groups (15.35 [5.70, 67.65] pg/ml vs. 15.24 [4.07, 30.73] pg/ml, Z = -0.610, P = 0.542), while it elevated significantly in CHB group (35.29 [15.94, 70.15] pg/ml vs. 15.24 [4.07, 30.73] pg/ml; Z = -2.522, P = 0.012). Compared with HI group (3.73 [2.98, 11.92] pg/ml), IL-10 concentrations in IT group (5.02 [2.98, 10.11] pg/ml), and CHB group (7.48 [3.10, 18.00] pg/ml) slightly increased (χ = 2.015, P = 0.365), and there was no significant difference between IT and CHB group (Z = -1.419, P = 0.156). The TGF-β1 levels among HI (3.59 ± 0.20 pg/ml), IT (3.62 ± 0.55 pg/ml), and CHB groups (3.64 ± 0.30 pg/ml) were similar (χ = 2.739, P = 0.254). In all chronic HBV-infected patients (including patients in IT and CHB groups), the elevation of IFN-α2 level was significantly associated with ALT level (β= 0.389, t = 2.423, P = 0.018), and was also negatively correlated to HBV-DNA load (β = -0.358, t = -2.308, P = 0.024), HBsAg (β = -0.359, t = -2.288, P = 0.025), and HBeAg contents (β = -0.355, t = -2.258, P = 0.027). However, when both ALT level and cytokines were included as independent variable, HBV-DNA load, HBsAg, and HBeAg contents were only correlated to ALT level (β = -0.459, t = -4.225, P = 0.000; β = -0.616, t = -6.334, P = 0.000; and β = -0.290, t = -2.433, P = 0.018; respectively). Conclusions IFN-α2 elevation was associated with ALT level in patients with chronic HBV infection. However, in CHB patients, only ALT level was correlated to HBV-DNA, HBsAg and HBeAg contents.
Adult ; Alanine Transaminase ; blood ; Antigens, Surface ; Case-Control Studies ; Cytokines ; blood ; DNA, Viral ; Female ; Hepatitis B ; Hepatitis B Surface Antigens ; analysis ; Hepatitis B e Antigens ; Hepatitis B virus ; Hepatitis B, Chronic ; blood ; immunology ; Humans ; Male ; Young Adult

Even in the era of novel targeted agents, switching to a second-line nonsteroidal antiandrogen (NSAA) is still widely used in treating metastatic castration-resistant prostate cancer (mCRPC), especially in undeveloped countries. However, whether prior treatment with a second-line NSAA would impact the efficacy of abiraterone acetate (Abi) remains uncertain. In the current study, 87 mCRPC patients treated with Abi were analyzed. Among them, 21 were treated with a second-line NSAA (from bicalutamide to flutamide) before receiving abiraterone, while the remaining 66 received Abi directly. Therapeutic efficacy of Abi was compared between those with and without prior second-line NSAA using Kaplan-Meier curves, log-rank test, and Cox regression models. The therapeutic efficacy of Abi was similar between those with or without the prior switching treatment of flutamide, in terms of either prostate-specific antigen progression-free survival (PSA-PFS, 5.5 vs 5.6 months, P = 0.967), radiographic progression-free survival (rPFS, 12.8 vs 13.4 months, P = 0.508), overall survival (OS, not reached vs 30.6 months, P = 0.606), or PSA-response rate (71.4% [15/21] vs 60.6% [40/66], P = 0.370). This is the first time that the impact of prior switching of treatment to a second-line NSAA on the efficacy of Abi in mCRPC patients has been addressed. Our data support that, use of prior sequential bicalutamide and flutamide does not seem to preclude response to abiraterone, although larger cohort studies and, ideally, a randomized controlled trial are needed. These findings will facilitate doctors' decision-making in the treatment of mCRPC patients, especially for those with previous experience of switching NSAA second-line treatments in the clinic.
Abiraterone Acetate/therapeutic use* ; Aged ; Aged, 80 and over ; Androgen Antagonists/therapeutic use* ; Anilides/therapeutic use* ; Antineoplastic Agents, Hormonal/therapeutic use* ; Disease-Free Survival ; Female ; Flutamide/therapeutic use* ; Humans ; Kaplan-Meier Estimate ; Male ; Nitriles/therapeutic use* ; Nonsteroidal Anti-Androgens/therapeutic use* ; Prostate-Specific Antigen/analysis* ; Prostatic Neoplasms, Castration-Resistant/drug therapy* ; Retrospective Studies ; Survival Analysis ; Tosyl Compounds/therapeutic use* ; Treatment Outcome

Objective:To investigate the role of pro-inflammatory cytokine IL-17 involved in the pathogenesis of cytomegalovirus hepatitis in vivo.Methods:First of all,disseminated infection model was established.Then,mice were randomly divided into 4 groups:normal control group,MCMV-infected control group,IL-17 blockade group,and isotype control group.Mice were sacrificed on day 7 after infection.The levels of IL-17 protein were detected by Western blot.Hematoxylin eosin (HE) staining was performed to evaluate the pathologic change of the liver.Serum ALT levels were detected by a Roche DPPI biochemical analyzer.The level of serum IL-17 was measured by double antibody sandwich ELISA.The expressions of mRNA of IL-17R,IFN-γand IL-10 in liver were detected by RT-PCR.Results:Compared with MCMV-infected mice and isotype control,the blockade of IL-17 inhibited the expression of IL-17 protein in liver (P＜0.05).The degree of liver damage reduced obviously.The serum ALT was significantly lower [(146±15)vs (102±11)vs (37±12),P＜0.05].The level of serum IL-17 was relatively reduced[(719.76±6.06)vs (722.1±4.62) vs (707.53 ±8.58),P＜0.05].The expression of IFN-γmRNA [(0.56± 0.06)vs (0.55±0.13)vs (0.96±0.2),P＜0.05] and IL-10 mRNA[(0.55±0.073) vs (0.51 ±0.07) vs (0.903 ±0.18),P＜0.05] increased significantly,while that of IL-17R did not change apparently[(0.81±0.16)vs (0.89±0.38) vs (0.87±0.23),P＞0.05].Conclusion:The increased expression of pro-inflammatory cytokine IL-17 is involved in the pathogenesis of immune injury in cytomegalovirus hepatitis.The blockade of IL-17 is helpful to relieve the liver damage and improve the liver function.

Objective:To compare the incidence of peripheral vascular complications during percutaneous coronary intervention (PCI) through femoral artery and radial artery,and to provide reference for clinical diagnosis and treatment.Methods:The clinical data of 780 patients who underwent coronary angiography and interventional therapy in Cardiovascular Center of Nantong First People's Hospital from July 2014 to December 2016 were analyzed,and the incidence of peripheral vascular complications was compared.Results:There were 471 cases through femoral artery and 309 through radial artery.The overall complication rate of femoral artery approach was 13.2％,which was higher than that of radial artery approach (4.5％),and the difference was statistically significant (P＜0.001).The bleeding rate of femoral artery approach was 7.9％,which was higher than that of radial artery approach (2.6％),and the difference was statistically significant (P=0.002).The incidence of major complications (retroperitoneal hematoma,pseudoaneurysm,arteriovenous fistula,and artery dissection) of femoral artery approach was higher than those of radial artery approach (2.1％ vs 0％),but the difference was not statistically significant.Conclusions:The incidence of peripheral vascular complications during PCI of femoral artery approach is higher than those of radial artery approach,and the approach should be considered comprehensively in clinical practice.

BACKGROUNDTumor necrosis factor-α (TNF-α) plays an important role in progressive contractile dysfunction in several cardiac diseases. The cytotoxic effects of TNF-α are suggested to be partly mediated by reactive oxygen species (ROS)- and mitochondria-dependent apoptosis. Glucagon-like peptide-1 (GLP-1) or its analogue exhibits protective effects on the cardiovascular system. The objective of the study was to assess the effects of exenatide, a GLP-1 analogue, on oxidative stress, and apoptosis in TNF-α-treated cardiomyocytes in vitro.

METHODSIsolated neonatal rat cardiomyocytes were divided into three groups: Control group, with cells cultured in normal conditions without intervention; TNF-α group, with cells incubated with TNF-α (40 ng/ml) for 6, 12, or 24 h without pretreatment with exenatide; and exenatide group, with cells pretreated with exenatide (100 nmol/L) 30 mins before TNF-α (40 ng/ml) stimulation. We evaluated apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay and flow cytometry, measured ROS production and mitochondrial membrane potential (MMP) by specific the fluorescent probes, and assessed the levels of proteins by Western blotting for all the groups.

RESULTSExenatide pretreatment significantly reduced cardiomyocyte apoptosis as measured by flow cytometry and TUNEL assay at 12 h and 24 h. Also, exenatide inhibited excessive ROS production and maintained MMP. Furthermore, declined cytochrome-c release and cleaved caspase-3 expression and increased bcl-2 expression with concomitantly decreased Bax activation were observed in exenatide-pretreated cultures.

CONCLUSIONThese results suggested that exenatide exerts a protective effect on cardiomyocytes, preventing TNF-α-induced apoptosis; the anti-apoptotic effects may be associated with protection of mitochondrial function.

Animals ; Apoptosis ; drug effects ; Cells, Cultured ; In Situ Nick-End Labeling ; Membrane Potential, Mitochondrial ; drug effects ; Mitochondria ; drug effects ; Myocytes, Cardiac ; cytology ; drug effects ; Oxidative Stress ; drug effects ; Peptides ; pharmacology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Rats ; Tumor Necrosis Factor-alpha ; pharmacology ; Venoms ; pharmacology

Objective To study the effect of myocardial bridge oppression on blood flow, positive pressure, circumferential stress and shear stress of the coronary artery. Methods The original myocardial bridge simulative device was greatly improved to be able to measure multi-hemodynamic parameters, such as normal stress, circumferential stress and shear stress, so as to exactly simulate real blood dynamics environment with the common effect of several stresses, and comprehensively investigate the relationship between hemodynamics and atherosclerosis of mural coronary artery under the combined effects of several stresses. Results The results from the myocardial bridge simulative device indicated that the hemodynamic abnormalities were mainly located in the proximal end of mural coronary artery, and the mean and oscillation values of normal stress at the proximal end were increased by 27.8% and 139%, respectively, showing a significant increase with the intensification of myocardial bridge oppression. Conclusions It is myocardial oppression that causes the hemodynamic abnormity of proximal coronary artery, which is quite important for understanding the hemodynamic mechanism of coronary atherosclerotic diseases and valuable for studying pathological effects and treatments of the myocardial bridge in clinic.