Trypanosoma is a human parasite severely affecting poor tropical areas.However,current frontline drugs for Trypanosoma treatment have severe side-effects with decreased effectiveness.Based on the fact that aminoacyl-tRNA synthetase is a bonafide drug target for several microorganisms,including bacteria and fungi,it is plausible that it may also be effective target of Trypanosoma.The Trypanosoma brucei leucyl-tRNA synthetase(tbLeuRS)was cloned,expressed and purified to develop an in vitro enzymatic assay system.The assay conditions were further optimized for the effective screening of tbLeuRS inhibitors thus establishing an anti-Trypanosoma drug screening system targeting tbLeuRS.The results indicated that this system can be employed for the effective screening of anti-Trypanosoma drugs with satisfactory specificity.In addition,this system can also be used for compound optimization,as well as IC50 testing.Using this system a series of compounds are identified that are effective Trypanosoma inhibitors without toxicity to human cells.Therefore,targeting tbLeuRS may represent a new venue for the development of anti-Trypanosoma drugs.

Objective:To develop a catalytic system for the asymmetric Morita-Baylis-Hillman ( MBH) reaction of conjugated ni-troalkene with activated aldehyde, and screen out the chiral catalysts with high activity and enantioselectivity. Methods: Totally 21 chiral organocatalysts were applied in the asymmetric MBH reaction ofβ-nitrostyrene with ethyl glyoxylate, and the ee value was deter-mined by chiral HPLC. The effects of temperature, solvent and substrate ratio on the catalytic reaction were investigated. Results: In the presence of cinchona alkaloid catalyst (DHQ)2AQN, β-nitrostyrene reacted with ethyl glyoxylate in toluene at 0℃ affording the MBH adduct in 60% yield with good enantioselectivity (up to 56.9% ee). Conclusion: The bis-cinchona alkaloids with aromatic bridging group are the efficient catalysts for the asymmetric MBH reaction ofβ-nitrostyrene with ethyl glyoxylate, and moderate isolated yield and enantioselectivity are obtained.

OBJECTIVETo investigate the effect of augmentative locking compression plate combined with bone graft in treating aseptic femoral shaft nonunion after intramedullary nailing.

METHODSTwenty-one cases with aseptic femoral shaft nonunion after intramedullary nailing from January 2007 to January 2013 were treated,including 18 males and 3 females with a mean age of 37.7 years (ranged from 23 to 64 years). The mean period of nonunion after surgery was 23.9 months (ranged from 9 to 62 months). According to Weber-Cech classification,10 of those 21 cases were hypertrophic nonunion,7 were atrophic, and 4 had oligotrophic fracture nonunion. All patients retained the original intramedullary nail, and applied with augmentation plating of 6 to 8 holes locking compression plate, unicortical fixation with 2 to 3 locking screws in the proximal or distal end, with simultaneous autologous iliac bone grafting. After treatment,all patients were allowed to partial weight-bearing until full weight-bearing according to the radiological results. All patients were followed up and were evaluated with clinical and imaging results.

RESULTSAll patients were followed up from 8 to 24 months, averaged (13.5±3.5) months,which showed clinical union at 4 to 8 months, averaged (6.0±1.0) months and radiological solid union at 7 to 12 months, averaged (9.1±1.5) months. No such complications as infection,hardware loosening or breaking were found.

CONCLUSIONAugmentative locking compression plate(LCP) combined with bone graft for aseptic femoral shaft nonunion after intramedullary nail has a satisfied clinical efficacy. It's an useful and simple method.

Adult ; Bone Nails ; adverse effects ; Bone Plates ; Bone Transplantation ; Female ; Femoral Fractures ; complications ; surgery ; Follow-Up Studies ; Fracture Fixation, Intramedullary ; adverse effects ; Fractures, Ununited ; complications ; surgery ; Humans ; Male ; Middle Aged ; Postoperative Complications ; etiology ; surgery ; Treatment Outcome ; Young Adult

OBJECTIVE To investigate the protective effect of Codonopsis Pilosula Polysaccharide (CPPS) on improving of the memory consolidation disorder induced by Cycloheximide and its possible mechanisms in mice. METHODS The mice was divided into five groups, as normal control group, cycloheximid model group, piracetam positive control group, CPPS 300 mg · kg- 1 group, and CPPS 150 mg·kg-1 group. The mice respectively were given saline, piracetam, and CPPS for 15 d. The memory consolidation disorder model in mice was established by ip. Cyclohexylamine, and orally administered CPPS(300 mg·kg-1 or 150 mg·kg-1) every day. Then experimental groups were subjected Morris Water Maze test. Western blotting analysis were used to analysis the expression of CaMKⅡ/CREB signaling pathways. RESULTS Morris water maze experiment showed that cyclohexylamine can cause memory consolidation disorder(P<0.01), and giving piracetam and CPPS (300 mg · kg- 1) can improve spatial memory impairment in mice(P<0.05, P<0.01). Western blotting experiment results show that compared with normal control group, CaMKⅡ and CREB contents of brain in model group mice had significant decreased(P<0.001); Compared with model group, CaMK Ⅱ and CREB contents of brain tissue in piracetam and CPPS groups increased significantly(P<0.05,P<0.01,P<0.001). CONCLUSION Cyclo?heximide can induce the memory consolidation disorder, and its effect in mice related to CaMK/CREB signaling pathways. CPPS can improved this memory disorder by influence CaMKⅡ/CREB signaling pathways.

Objective To discuss the impact of repeated contrast media exposure on renal function in patients who received coronary angiography ( CAG) or percutaneous coronary intervention ( PCI) within 1 week after CTA of coronary ateries. Methods A total of 258 patients who received CAG or PCI after coronary CTA were divided into the study group ( n=132, patients had CAG/PCI within 1 week after CTA) and the control group ( n=126, patients had CAG/PCI 1-2 weeks after CTA). Serum creatinine, cystatin C and estimated GFR were tested before and on day 1, 2 and 3 after procedures. The occurance of contrast-induced nephropathy ( CIN ) was recorded. Resu1ts The baseline clinical characteristics of the patients between the two groups had no significant difference. Preoperative and postoperative serum creatinine, cystatin C and eGFR values on day 1, 2 and 3 had no significant difference between the two groups (all P﹥0. 05). There was no significant difference in the incidence of CIN between two groups (5. 3% in the study group vs. 4. 8% in the control group, P﹥0. 05 ) . Conc1usions It is safe and feasible for patients with eGFR≥60 ml/( min?1. 73 m2 ) to undergo CAG or PCI within 1 week after coronary CTA.

Genotypic and environmental variation in Cd, Cr, As, Ni and Pb concentrations of grains, and the relationships between these heavy metals and Fe, Zn were investigated using 9 rice genotypes grown in 6 locations for two successive years. Significant genotypic variation was detected in the five heavy metal concentrations in grains, indicating the possibility to reduce the concentration of these heavy metals in grains through breeding approach. The environmental effect varied with metal, with Pb and Ni having greater variation than the other three metals. There was significant genotype-environment (location) interaction of the concentrations of all five heavy metals in grains, suggesting the importance of cultivar choice in producing rice with low heavy metal concentrations in grains for a given location. Correlation analysis showed that Cd and As, Cr and Ni, and As and Pb concentrations in rice grains were closely associated, and that Ni concentration in grains was negatively correlated with Zn concentration.
Arsenic ; analysis ; Cadmium ; analysis ; Chromium ; analysis ; Edible Grain ; chemistry ; genetics ; Environment ; Genetic Variation ; genetics ; Genotype ; Lead ; analysis ; Metals, Heavy ; analysis ; Nickel ; analysis ; Oryza ; chemistry ; genetics ; Soil Pollutants ; analysis

The cholinergic anti-inflammatory pathway (CAP) is a neurophysiological mechanism that regulates the immune system. The CAP inhibits inflammation by suppressing cytokine synthesis via release of acetylcholine in organs of the reticuloendothelial system, including the lungs, spleen, liver, kidneys and gastrointestinal tract. Acetylcholine can interact with alpha7 nicotinic acetylcholine receptors (alpha7 nAchR) expressed by macrophages and other cytokine producing cells, down-regulate pro-inflammatory cytokine synthesis and prevent tissue damage. Herein is a review of the neurophysiological mechanism in which the CAP regulates inflammatory response, as well as its potential interventional strategy for inflammatory diseases.
Acetylcholine ; pharmacology ; Animals ; Humans ; Inflammation ; immunology ; prevention & control ; Myocardial Infarction ; immunology ; Pancreatitis ; immunology ; Receptors, Muscarinic ; physiology ; Receptors, Nicotinic ; physiology ; Reperfusion Injury ; immunology ; Sepsis ; immunology ; Shock, Hemorrhagic ; immunology ; Spleen ; immunology ; innervation ; Vagus Nerve ; physiology ; alpha7 Nicotinic Acetylcholine Receptor

OBJECTIVEAn HPLC-MS/MS assay was established to determine paeoniflorin in rat plasma and be used to investigate the effect of pharmacokinetics of paeoniflorin when co-administrated Radix Angelicae Sinensis and Radix Paeoniae Rubra.

METHODHPLC-MS/MS was performed in the multiple reaction monitoring (MRM) mode using target ions at m/z 450 --> m/z 327 for paeoniflorin and m/z 388 --> m/z 225 for jasminoidin. A single dose of Radix Paeoniae Rubra alone and with Radix Angelicae Sinensis was given to rats by ig, the dosage of paeoniflorin was 294.78 mg x kg(-1). Concentrations of paeoniflorin in rat plasma were determined by HPLC-MS/MS assay and main pharmacokinetic parameters were estimated.

RESULTThe mainly pharmacokinetic parameters of paeoniflorin when administrated Radix Paeoniae Rubra only were as follows: C(max) (1.55 +/- 0.53) mg x L(-1), T(max) (0.9 +/- 0.3) h, t 1/2 (1.51 +/- 0.63) h, MRT (3.08 +/- 0.74) h, AUC(0 --> tau) (4.68 +/- 0.85) mg x h(-1) x L(-1). When the two drugs administrated together, the corresponding parameters were (0.93 +/- 0.42) mg x L(-1), (1.5 +/- 0.8) h, (3.08 +/- 1.79) h, (5.19 +/- 1.95) h, (3.36 +/- 0.56) mg x h(-1) x L(-1), respectively. The parameters of C(max), AUC(0 --> tau) and MRT were significantly changed (P < 0.05).

CONCLUSIONRadix Angelicae Sinensis can significantly affect the pharmacokinetics of paeoniflorin, the principal component of Radix Paeoniae Rubra.

Animals ; Benzoates ; administration & dosage ; blood ; pharmacokinetics ; Bridged-Ring Compounds ; administration & dosage ; blood ; pharmacokinetics ; Chromatography, High Pressure Liquid ; methods ; Drugs, Chinese Herbal ; metabolism ; pharmacokinetics ; Glucosides ; administration & dosage ; blood ; pharmacokinetics ; Humans ; Male ; Monoterpenes ; Paeonia ; chemistry ; Rats ; Rats, Sprague-Dawley ; Tandem Mass Spectrometry ; methods

Objective To investigate the imaging characteristics of both intra- and extrathoracic sarcoidosis on 18F-FDG PET/CT.Methods From 2007 Aug.to 2009 Nov.,22 patients( 10 males,12 females) with sarcoidosis,confirmed by pathological study and clinical follow-up,underwent 18 F-FDG PET/CT imaging.The imaging patterns of intrathoracic and extrathoracic lesions were analyzed.The patterns were classified as the typical or atypical ( symmetrical or asymmetrical FDG accumulation and enlargement of hilar lymph nodes) based on PET and CT separately.Nonparametric McNemar test,independent t-test and Fisher exact test were applied for statistical analysis.Results For typical pattern vs atypical pattem identification,PET was significantly different from CT ( 18 and 4 vs 12 and 10,P =0.031 ).In those with atypical pattern demonstrated by CT alone at hilar region,PET showed either symmetrical or asymmetrical accumulation of FDG.Except for mediastinal lymph nodes involvement,lung parenchyma was the second common site ( 19/22,86.4％ ),followed by lymph nodes at abdomen and (or) pelvis ( 12/22,54.5％ ).Conclusion The imaging characteristics of both intra- and extrathoracic sarcoidosis on 18F-FDG PET/CT may be helpful for the diagnosis of atypical sarcoidosis on CT image alone.

OBJECTIVECT120B gene is a splicing variant of CT120A, which deletes 96 nucleotides and leads to an in-frame loss of 32 amino acids between the codon 136 and 167 as compared with CT120A. This study was undertaken to assess the effects of CT120B expression on lung cancer cell growth and to explore the gene expression profiles.

METHODSCT120B cDNA was transfected into the human lung adenocarcinoma SPC-A-1 cells, and stable cell lines overexpressing CT120B were established. CCK-8 assay and tumorigenecity in a xenograft model were performed to analyze cell proliferation in vitro and in vivo. The differential gene expression induced by overexpressed CT120B was investigated using Atlas cDNA expression array. Flow cytometry was performed to analyze cell cycle and cell apoptosis.

RESULTSOverexpression of CT120B in SPC-A-1 cells resulted in a reduced cell growth rate in vitro, and decrease of the tumorigenicity in nude mice. A total of 38 genes were identified as differential expressions with more than a 2.0-fold change by Atlas cDNA expression array analysis, including downregulated cyclin E1, cdk 2, c-kit, CXCR4 and upregulated caspase 8 gene. Overexpression of CT120B also induced G1 phase arrest, but had no effect on cell apoptosis.

CONCLUSIONThe G1 cell cycle arrest, but not apoptosis, underlay the growth inhibitory activities of CT120B. The down-regulation of c-kit and CXCR4 expression might also contribute to the suppressive effects on cell growth of CT120B.

Adenocarcinoma ; metabolism ; pathology ; Animals ; Cell Line, Tumor ; Cell Proliferation ; DNA, Complementary ; genetics ; G1 Phase ; Gene Expression Profiling ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Male ; Membrane Proteins ; genetics ; metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Neoplasm Proteins ; genetics ; metabolism ; Neoplasm Transplantation ; Oligonucleotide Array Sequence Analysis ; Proto-Oncogene Proteins c-kit ; metabolism ; Receptors, CXCR4 ; metabolism ; Transfection