Sulfated modification can enhance the immune-enhancing activity of lycium barbarum polysaccharides

In test in vitro, four sulfated lycium barbarum polysaccharides (sLBPSs) with different degrees of sulfation (DS), sLBPS_0.7, sLBPS_1.1, sLBPS_1.5 and sLBPS_1.9, were added into cultured chicken peripheral lymphocytes and the changes of lymphocytes proliferation were compared by MTT assay taking the non-modified LBPS as control. Two sLBPSs with better efficacy, sLBPS_1.5 and sLBPS_1.9 were selected. In test in vivo, one hundred 14-day-old chickens were averagely divided into five groups randomly. The chickens except blank control group were vaccinated with Newcastle disease vaccine, repeated vaccination at 28 days old. At the same time of the first vaccination, the chickens in three experimental groups were injected with 0.5 mL of sLBPS_1.5, sLBPS_1.9 and LBPS at 4 mg mL⁻¹, in vaccination control group, with 0.5 mL of physiological saline, once a day for three successive days. On days 7, 14, 21 and 28 after the first vaccination, the changes of peripheral lymphocytes proliferation and serum HI antibody titer were determined. The result showed that two sLBPSs could significantly promote lymphocytes proliferation and enhance serum antibody titer. These results indicated that sulfated modification could enhance the immune-enhancing activity of LBPS, which there was a certain relativity with the DS of sulfated polysaccharide. sLBPS_1.5 possessed the best efficacy and would be expected as the component drug of a new-type immunopotentiator.     

NO, but not CO, attenuates anaphylaxis-induced postsinusoidal contraction and congestion in guinea pig liver

The pathophysiology of the hepatic vascular response to anaphylaxis in guinea pig is not known. We studied effects of anaphylaxis on hepatic vascular resistances and liver weight in isolated perfused livers derived from guinea pigs sensitized with ovalbumin. We also determined whether nitric oxide (NO) or carbon monoxide (CO) modulates the hepatic anaphylaxis. The livers were perfused portally and recirculatingly at constant flow with diluted blood. With the use of the double-occlusion technique to estimate the hepatic sinusoidal pressure (Pdo), portal venous resistance (Rpv) and hepatic venous resistance (Rhv) were calculated. An antigen injection caused venoconstriction characterized by an increase in Rpv greater than Rhv and was accompanied by a large liver weight gain. Pretreatment with the NO synthase inhibitor NG-nitro-l-arginine methyl ester, but not the heme oxygenase inhibitor zinc protoporphyrin IX, potentiated the antigen-induced venoconstriction by increasing both Rpv and Rhv (2.2- and 1.2-fold increase, respectively). In conclusion, anaphylaxis causes both pre- and postsinusoidal constriction in isolated guinea pig livers. However, the increases in postsinusoidal resistance and Pdo cause hepatic congestion. Endogenously produced NO, but not CO, modulates these responses.     

A strategy for high-throughput assay development using leads derived from nuclear magnetic resonance-based screening

A strategy is described for the development of high-throughput screening assays against targets of unknown function that involves the use of nuclear magnetic resonance (NMR) spectroscopy. Using this approach, molecules that bind to the protein target are identified from an NMR-based screen of a library of substrates, cofactors, and other compounds that are known to bind to many proteins and enzymes. Once a ligand has been discovered, a fluorescent or radiolabeled analog of the ligand is synthesized that can be used in a high-throughput screen. The approach is illustrated in the development of a high-throughput screening assay against HI-0033, a conserved protein from Haemophilus influenzae whose function is currently unknown. Adenosine was found to bind to HI-0033 by NMR, and fluorescent analogs were rapidly identified that bound to HI-0033 in the submicromolar range. Using these fluorescent compounds, a fluorescence polarization assay was developed that is suitable for high-throughput screening and obtaining detailed structure-activity relationships for lead optimization.     

Identification of a Toll-Like Receptor 1 in Guinea Fowl (Agelastes niger)

Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns, thus playing important roles in host defense. This study determined the first sequence of a TLR1 type 1 in the guinea fowl (GFTLR1). The open reading frame of GFTLR1 type 1 contains 2,115 nucleotides and encodes 705 amino acids. Amino acid analysis indicated that GFTLR1 type 1 shares 92.3?% homology with the green jungle fowl, 92.1?% with the chicken, 90.4?% with the turkey, and 84.4?% with Cooper's hawk. Genetic patterns were identified within the TLR1 type 1 of the chicken and the guinea fowl. GFTLR1 type 1 was found to have 92 polymorphic amino acid sites, of which 16 were in the leucine-rich repeat (LRR) domain, 3 in a C-terminal LRR domain, and 6 in a Toll/interleukin-1 receptor domain. The data showed that avian TLR1 type 1 genes are under purifying selection and highly conserved, because dN/dS was less than 1.     

Colorectal Cancer with Residual Polyp of Origin: A Model of Malignant Transformation

The majority of colorectal cancers (CRCs) arise from adenomatous polyps. In this study, we sought to present the underrecognized CRC with the residual polyp of origin (CRC RPO +) as an entity to be utilized as a model to study colorectal carcinogenesis. We identified all subjects with biopsy-proven CRC RPO + that were evaluated over 10 years at Mayo Clinic, Rochester, MN, and compared their clinical and pathologic characteristics to CRC without remnant polyps (CRC RPO −). Overall survival and disease-free survival overlap with an equivalent hazard ratio between CRC RPO + and RPO − cases when age, stage, and grade are adjusted. The somatic genomic profile obtained by whole genome sequencing and the gene expression profiles by RNA-seq for CRC RPO + tumors were compared with that of age -and gender-matched CRC RPO − evaluated by The Cancer Genome Atlas. CRC RPO + cases were more commonly found with lower-grade, earlier-stage disease than CRC RPO −. However, within the same disease stage and grade, their clinical course is very similar to that of CRC RPO −. The mutation frequencies of commonly mutated genes in CRC are similar between CRC RPO + and RPO − cases. Likewise, gene expression patterns are indistinguishable between the RPO + and RPO − cases. We have confirmed that CRC RPO + is clinically and biologically similar to CRC RPO − and may be utilized as a model of the adenoma to carcinoma transition.     

Photosynthetic characterization and expression profiles of sugarcane infected by Sugarcane mosaic virus (SCMV)

Photosynthesis Research - Sugarcane mosaic virus (SCMV), belonging to genus Potyvirus, family Potyviridae, is a severe pathogen of several agricultural important crops, mainly sugarcane. Due to...     

Effects of Pb2+ on the transient outward potassium current in acutely dissociated rat hippocampal neurons

Modulation of the voltage-dependent transient outward potassium current (IA) by Pb2+ was studied in acutely dissociated rat hippocampal pyramidal cells from the CA1 region at postnatal ages 7-14 days using the conventional whole-cell patch-clamp technique. In the presence of different concentrations of external Pb2+, the initial delay and activation time of IA were concentration-dependently lengthened. In particular, the initial delay was even longer in 1 mM Pb2+, showing no signs of saturation. Pb2+ also slowed the inactivation of IA, for decay time constants in the presence of Pb2+ were increased under the same experimental protocols. The activation curves, which were reasonably fitted by a single Boltzmann function, illustrated that Pb2+ increased the voltage threshold of IA and shifted the normalized activation current-voltage curves to more depolarizing voltage commands. Moreover, Pb2+ significantly affected the steady-state inactivation of IA. The application of Pb 2+ made the curves of the steady-state inactivation of IA shift to more depolarizing voltages with little change in the slopes factors. In brief, the results demonstrated that Pb2+ is a dose- and voltage-dependent, reversible blocker of IA currents of hippocampal CA1 neurons. The observations were fitted by the revised "Kuo and Chen type model", which postulates a Pb2+-selective site near the pore of the IA channel and that modulation of the IA channel by Pb2+ is the result of the competitive influences of Pb2+ on opening and inactivating different pathways.