Activity of human erythrocyte gangliosides as a receptor to HVJ

Liposomes could bind and fuse efficiently to human erythrocytes in the presence of HVJ when they contained gangliosides isolated from human erythrocytes. Sialosylparagloboside, which has a terminal sequence of NeuAcα2?3Ga1β1?4GlcNac, has a much higher receptor activity to the virus than GD_1a, GD_1b, GT_1b, and GT_1a, all of which contain the terminal sequence of NeuAcα2?3Galβ1?3GalNAc or NeuAcα2?8NeuAcα2?3Galβ1?3GalNAc. The activity of sialosylparagloboside is comparable to that of glycophorin, a major sialoglycoprotein of human erythrocytes, when compared on the basis of the required amount (as sialic acid) of compounds. The high affinity of sialosylparagloboside to the viral HANA protein is also suggested by the finding that it showed high inhibitory activity against HVJ-mediated binding of glycophorin liposomes to erythrocytes. Sialosylparagloboside was also highly susceptible to the viral sialidase, the other biological function of HANA protein.     

Pathogenesis of antiphospholipid syndrome: recent insights and emerging concepts

Introduction: Even though our understanding of the antiphospholipid syndrome (APS) has improved tremendously over the last decades, we are still not in a position to replace symptomatic anticoagulation by pathogenesis based causal treatments.

Areas covered: Recent years have provided further insights into pathogenetically relevant mechanisms. These include a differentiation of pathogenic subtypes of antiphospholipid antibodies (aPL), novel mechanisms modulating disease activity, for example, extracellular vesicles and microRNA, and novel players in pathogenesis, for example, neutrophils and neutrophil extracellular traps (NETs).

Expert commentary: It is evident that aPL induce a proinflammatory and procoagulant state and recent data suggest that different aPL species activate different signaling pathways which sometimes converge into a common cellular response. This implies that presence of more than one aPL species may disproportionally increase the risk for the major manifestations of APS, that is, thrombosis and fetal loss. Further delineation of the pathogenic mechanisms will hopefully provide clues to causal rather than symptomatic treatments of APS.     

Production and detection of monoclonal anti-idiotype antibodies directed against a monoclonal anti-beta-adrenergic ligand antibody

A new method has been developed to raise monoclonal anti-idiotypic antibodies. Monoclonal anti-idiotypic antibodies were obtained by fusion of NS-1 myeloma cells with splenocytes of mice immunised by intravenous injections of fixed hybridoma cells bearing a monoclonal antibody specific for beta-adrenergic ligands. New screening tests were developed to analyse the resulting hybridoma supernatants for different anti-idiotypic properties. Among 23 hybridoma supernatants recognising the idiotype, 6 were found to inhibit hapten binding and 3 of these recognised beta-adrenergic receptors.     

Protein micelles of human histocompatibility antigens (HLA-A and HLA-B)

Human histocompatibility antigens (HLA-A and -B) are membrane proteins which have large hydrophilic domains outside the cell membrane and a small hydrophobic portion in the lipid bilayer. In this paper we describe optimal conditions for preparing micelles of detergent-solubilized HLA-A2 and -B7 antigens. These homogeneous protein aggregates are water soluble and free of detergent and lipid. Hydrophobic interactions between the intramembraneous portions of the HLA antigens are the driving forces in the formation of these protein micelles. The papain-solubilized fragment of the HLA antigens is not included in the micelle. The average molecular weight of the HLA micelles is around 9 × 10⁵ daltons, which suggests sixteen HLA-A2 and/or HLA-B7 antigenic molecules per protein aggregate. Electron microscopic studies revealed that the most frequent size of the micelles is 12 mm and that HLA-micelles are similar but not identical to micelles from Sindbis Virus glycoproteins (E1 and E2) The HLA-A2 and -B7 micelles retained full antigenic activity as judged by precipitations with allo- and heteroantisera. Such micelles will no doubt be important tools in further studies of the role of histocompatibility antigens.     

Interaction of biodegradable β-whitlockite ceramics with bone tissue: An in vivo study

The biodegradation of different porous β-whitlockite materials are studied by in vivo experiments, radiographie follow-ups and light microscopy observations. The materials were implanted in rabbit tibiae for 16 mnth. Micropores play an important role in the biodegradation rate. The resorbing materials evoke an inflammation with plasma cells. The resorption starts in the medulla, and the phagocytosed particles are removed to the lymph nodes. Normal bone function can be restored after all the implant material is resulted.     

Light and electron microscopic immunocytochemical localization of vasoactive intestinal polypeptide VIP-like activity in the rat small intestine

Vasoactive intestinal polypeptide nerve processes and cell bodies were identified by electron microscopic immunocytochemistry in the rat small intestine. Labeled nerve processes were numerous in the inner circular smooth muscle coat and mainly in the mucosa, but were absent in the longitudinal muscle layer. Submucosal blood vessels were often surrounded by immunoreactive vasoactive intestinal polypeptide positive nerves, in close associations (distance less than 40 mn) to blood vessel basement membranes and to smooth muscle cells. In the ganglia of the myenteric and submucous plexuses, labeled fibers surrounded unstained neural cell bodies. The synaptic vesicles of vasoactive intestinal polypeptide positive terminals were 35-40 nm in diameter and some dense core vesicles (80-120 nm in diameter) were also observed in the same profiles. These observations suggest that vasoactive intestinal polypeptide nerves may participate in regulating smooth muscle activity and local blood flow in the small intestine.     

Gadd45β和Gadd45γ在亚砷酸钠所致的MIHA细胞周期改变中的作用

目的 探索Gadd45β和Gadd45γ在亚砷酸钠所致的MIHA细胞周期改变中的作用,为砷中毒的人群防治提供依据。方法 收集贵州省兴仁县雨樟镇交乐病区砷中毒人群以及格沙屯正常人群分别作为砷中毒组和对照组,实时荧光定量PCR检测各组人群Gadd45β和Gadd45γ基因mRNA表达水平。同时,分别以不同剂量亚砷酸钠、不同时间处理MIHA细胞,流式细胞术测定细胞周期改变情况,实时荧光定量PCR和免疫印迹法分别检测Gadd45β和Gadd45γ基因mRNA表达水平和蛋白表达情况。在上述实验基础上,针对Gadd45β和Gadd45γ基因分别设计的siRNA作用于染砷的MIHA细胞,反向验证Gadd45β和Gadd45γ基因在砷致细胞周期改变过程中的影响。统计学分析采用独立样本t检验比较两组间差异,采用单因素方差比较多组间差异。结果 人群实验研究发现,与对照组相比,砷中毒患者Gadd45β和Gadd45γ基因mRNA表达水平升高（t = 2.576,P = 0.011;t = 2.312,P = 0.022）;MIHA细胞中,随亚砷酸钠染毒剂量、染毒时间增加,细胞G2/M期比例明显升高（F剂量 = 340.136,P＜0.001;F时间 = 49.194,P＜0.001）;在相对较低亚砷酸钠浓度（低于20 μmol/L）、一定时间内（低于48 h）Gadd45β和Gadd45γ基因mRNA和蛋白表达水平随染砷剂量、染砷时间升高而升高,超过该浓度范围和作用时间后,出现表达下降的现象（Gadd45β:F剂量-蛋白 = 37.568,P＜0.001;F剂量- mRNA = 9.771,P＜0.001;F时间-蛋白 = 61.144,P＜0.001;F时间- mRNA = 46.366,P = 0.001;Gadd45γ:F剂量-蛋白 = 12.989,P = 0.001;F剂量- mRNA = 23.613,P＜0.001;F时间-蛋白 = 27.425,P＜0.001;F时间- mRNA = 37.969,P＜0.001）。转染siRNA分别下调Gadd45β和Gadd45γ的表达后,细胞周期都出现G2/M期比例下调（t = 3.053,P = 0.038;t = 14.47,P＜0.001）。结论 砷致Gadd45β和Gadd45γ基因表达水平升高在其诱导MIHA细胞出现G2/M期阻滞过程中发挥重要作用。     

Berberine plays a cardioprotective role by inhibiting macrophage Wnt5a/β-catenin pathway in the myocardium of mice after myocardial infarction

Myocardial infarction (MI) is one of the diseases with high fatality rate. Berberine (BBR) is a monomer compound with various biological functions. And some studies have confirmed that BBR plays an important role in alleviating cardiomyocyte injury after MI. However, the specific mechanism is unclear. In this study, we induced a model of MI by ligation of the left anterior descending coronary artery and we surprisingly found that BBR significantly improved ventricular remodeling, with a minor inflammatory and oxidative stress injury, and stronger angiogenesis. Moreover, BBR inhibited the secretion of Wnt5a/β-catenin pathway in macrophages after MI, thus promoting the differentiation of macrophages into M2 type. In summary, BBR effectively improved cardiac function of mice after MI, and the potential protective mechanism was associated with the regulation of inflammatory responses and the inhibition of macrophage Wnt5a/β-catenin pathway in the infarcted heart tissues. Importantly, these findings supported BBR as an effective cardioprotective drug after MI.