Chemical constituents from Canarium album Raeusch and their anti-influenza A virus activities.

Two new dyhydrophaseic acid glucoside isomers, (1'S, 3'R, 5'S, 8'R, 2Z, 4E)-dihydrophaseic acid-3'-O-ß-D-glucopyranoside (2) and (1'R, 3'S, 5'R, 8'R, 2Z, 4E)-dihydrophaseic acid-3'-O-ß-D-glucopyranoside (4), together with 10 known compounds [myo-inositol (1), 3,4-dihydroxybenzoic acid (3), 3-O-galloyl quinic acid (5), ellagic acid (6), gallic acid (7), ethyl gallate (8), scopoletin (9), ellagic acid-4-O-ß-D-glucopyranoside (10), ellagic acid-4-O-α-L-rhamnopyranoside (11), and isocorilagin (12)] were isolated from the chloroform extract of Canarium album Raeusch fruits by repeated chromatography on macroporous adsorption resin, silica gel, Sephadex LH-20, Toyopearl HW-40F, and reverse-phase C18 columns, etc. Their structures and absolute configurations were determined by comprehensive analysis of 1D- and 2D-nuclear magnetic resonance (NMR), high-resolution electron spray ionization mass spectrometry (HR-ESI-MS), ESI-MS, optical rotation, circular dichroism spectra, and comparison of NMR data with data of known compounds. Bioassay of their anti-influenza virus A activities showed that compounds 9 and 12 displayed a significant inhibitory effect with IC50 values of 22.9 ± 3.7 and 5.42 ± 0.97 µg/ml, respectively.

Tim-1+ B cells suppress T cell interferon-gamma production and promote Foxp3 expression, but have impaired regulatory function in coronary artery disease.

Atherosclerosis and its associated coronary artery disease (CAD) represent another chronic low-grade inflammatory disorder. Regulatory B cells (Bregs) possess essential functions in maintaining peripheral tolerance and inhibiting pathogenic inflammation through IL-10. Here, we investigated one subset of Bregs, Tim-1+ B cell, and its role in atherosclerosis and CAD patients. In healthy individuals, IL-10-producing B cells were predominantly found in the Tim-1+ B cells. Upon stimulation of the B cell receptor (BCR) and Toll-like receptor 9 (TLR-9) by anti-BCR antibodies and CpG, respectively, the Tim-1+ B cells could further upregulate IL-10 expression. In contrast, the Tim-1+ B cells were present at normal frequency in CAD patients, but showed impaired capacity to upregulate IL-10 with or without BCR + CpG stimulation. The stimulated Tim-1+ B cells from healthy individuals also suppressed expression of interferon gamma (IFN-γ), an atherogenic cytokine in T cells, in an IL-10-dependent fashion, and strongly promoted the expression of Foxp3 in naive CD4+ CD45RO- T cells. In contrast, the Tim-1+ B cells from CAD patients were unable to suppress IFN-γ secretion, and only minimally increased the expression of Foxp3 in naive CD4+ CD45RO- T cells. Despite this, the frequency of Tim-1+ B cells in the atherosclerotic lesions from CAD patients was inversely correlated with the frequency of IFN-γ-expressing T cells. Together, these results demonstrated that CAD patients presented an inflammatory disorder in regulatory B cells, which could be used as a therapeutic target.

Complete mitochondrial genome of a German Shepherd (Canis lupus familiaris breed German Shepherd) provides insights into genome-wide sequence variations.

In this work, we report the complete mitochondrial genome sequence of a German shepherd. The total length of the mitogenome was 16,727 bp. It contained the typical structure of 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and a non-coding control region (D-loop region). The arrangement of these genes was the same as that found in other dogs. All the protein initial codons were ATG, except for ND2, ND3 and ND5 starting with ATA. Sequence comparison indicates that D-loop region harbors most sequence variations.

Polymorphism of stromal cell-derived factor-1 selectively upregulates gene expression and is associated with increased susceptibility to coronary artery disease.

Stromal cell-derived factor-1 (SDF-1) plays critical roles in vascular development and hematopoiesis. Here, we investigated the function of SDF-1 rs1801157G/A polymorphism in various immune cells and examined its association with susceptibility to coronary artery disease (CAD). Protein and mRNA levels of SDF-1 were tested in peripheral CD4+ T cell, CD8+ T cells, monocytes, and natural killer (NK) T cells from healthy donors with different genotypes of rs1801157G/A polymorphism. Prevalence of the polymorphism was compared between CAD patients and healthy controls. Data revealed that SDF-1 mRNA and protein were detectable in CD4+ T cells, CD8+ T cells, monocytes and NK T cells. Interestingly, both protein level and mRNA level of SDF-1 were significantly increased in the monocytes with rs1801157AA genotype, whereas the same phenomenon was not observed in the other three cell types. Blockage of CD14 completely inhibited the upregulation of SDF-1 in the monocytes with rs1801157AA genotype. Association analysis showed that frequencies of the rs1801157AA genotype and A allele were significantly higher in CAD cases than in controls (odds ratio [OR]=2.28, 95% confidence interval [CI], 1.50-3.29, p<0.0001, and OR=1.46, 95% CI, 1.21-3.73, p<0.0001, respectively). Also, prevalence of rs1801157AA genotype was further increased in cases with ST-elevation myocardial infarction (OR=1.65, 95% CI, 1.04-2.56, p=0.028). Our data suggest a novel pathway for regulating SDF-1 and a new risk factor for CAD.

Evaluation on the efficacy and safety of domestic bivalirudin during percutaneous coronary intervention.

BACKGROUND: Bivalirudin was widely used as an anticoagulant during coronary interventional procedure in western countries. However, it was not available in China before this clinical trial was designed. This randomized, single-blind and multicenter clinical trial aimed to evaluate the efficacy and the safety of domestic bivalirudin during percutaneous coronary intervention (PCI). METHODS: A randomized, single-blind, multicenter trial was designed. Elective PCI candidates in five centers were randomized into a bivalirudin group and a heparin group, which were treated with domestic bivalirudin and non-fractional heparin during the PCI procedure. The efficacy was evaluated by comparing the activated coagulation time (ACT), the procedural success rate (residual stenosis < 20% in target lesions without any coronary artery related adverse events within 24 hours after PCI), and the survival rate without major adverse cardiac events at 30 days after PCI between the two groups. Safety was evaluated by the major/minor bleeding rate. RESULTS: A total of 218 elective PCI patients were randomized into a bivalirudin group (n = 110) and heparin group (n = 108). Except for two patients needing additional dosing in the heparin group, the ACT values of all other patients in both groups were longer than 225 seconds at 5 minutes after the first intravenous bolus. Procedural success rates were respectively 100.0% and 98.2% in the bivalirudin group and heparin group (P > 0.05). Survival rates without major adverse cardiac events at 30 days after PCI were 100.0% in the bivalirudin group and 98.2% in the heparin group (P > 0.05). Mild bleeding rates were 0.9% and 6.9% (P < 0.05) at 24 hours, and 1.9% and 8.8% (P < 0.05) at 30 days after PCI in the bivalirudin group and heparin group respectively. There was one severe gastrointestinal bleeding case in the heparin group. CONCLUSIONS: Domestic bivalirudin is an effective and safe anticoagulant during elective PCI procedures. The efficacy is not inferior to heparin, but the safety is superior to heparin.

Positive effects of treatment of donor cells with aphidicolin on the preimplantation development of somatic cell nuclear transfer embryos in Chinese Bama mini-pig (Sus Scrofa).

To optimize somatic cell nuclear transfer (SCNT) procedures in mini-pigs, the present study was designed to examine the effects of donor cell types and aphidicolin (APC) treatment on in vitro development of reconstructed embryos. Oviduct epithelial cells (OEC), ear fibroblast cells (EFC) and cumulus cells (CC) derived from mini-pigs were treated with serum starvation only or serum starvation followed by treatment of 0.1 µg/mL APC. The reconstructed embryos were cultured for 7 days to evaluate their developmental competency. Cleavage and blastocyst formation rates of reconstructed embryos derived from the OEC by APC treatment were significantly higher than the serum starvation (61.82% vs. 56.25%, 24.55% vs. 17.86%; P < 0.05). The cleavage rate from the EFC was significantly increased by APC treatment compared to serum starvation only (63.36% vs. 57.01%; P < 0.05). In the ooctyes with the CC, the reconstructed embryos could yield high blastocyst formation rate by APC treatment (29.63%; P < 0.05). In the presence of APC, CC gave rise to the highest cleavage and blastocyst formation rates among the three cell types. Therefore, our results suggest that treatment of CC with serum starvation plus APC prior to nuclear transfer is more suitable in SCNT of mini-pigs.