Metabolomic analysis of amino acid and fat metabolism in rats with l-tryptophan supplementation

Tryptophan (TRP) is an important precursor for several neurotransmitters and metabolic regulators, which play a vital role in regulating nutrient metabolism. The purpose of this study was to investigate the effects of tryptophan supplementation on the biochemical profiles, intestinal structure, liver structure and serum metabolome in rats. Rats received daily intragastric administration of either tryptophan at doses of 200 mg/kg body weight per day or saline (control group) for 7 days. TRP supplementation had a tendency to decrease the body weight of rats (P > 0.05). The levels of urea and CHO in serum were decreased in the TRP-supplemented group rats compared with control group rats (P < 0.05). TRP supplementation increased the villus height and the ratio of villus height to crypt depth in the jejunum compared to control group rats (P < 0.05). Metabolic effects of tryptophan supplementation include: (1) increases in the serum concentrations of lysine, glycine, alanine, glutamate, glutamine, citrulline, methionine, tyrosine, 1-methylhistidine, and albumin, and decreases in the concentrations of serum branched-chain amino acid (isoleucine, valine and leucine); (2) decreases in the serum concentrations of formate and nitrogenous products (trimethylamine, TMAO, methylamine and dimethylamine), and in the contraction of trimethylamine in feces; (3) decreases in serum levels of lipids, low density lipoprotein, very low density lipoprotein, together with the elevated ratio of acetoacetate to β-hydroxybutyrate. The results indicate that tryptophan supplementation reduced the catabolism of dietary amino acids and promoted protein synthesis in rats, promoted the oxidation of fatty acid and reduced fat deposition in the body of rats.     

抑制T细胞增殖的抗CD45单克隆抗体的建立

目的寻找能调节T细胞功能的相关分子,进行与T细胞介导的自身免疫性疾病相关的研究。方法从BALB/c小鼠骨髓中收集树突状细胞,免疫Wistar大鼠,进行细胞融合,建立杂交瘤细胞系。筛选得到很多株能调节T细胞功能的杂交瘤细胞系,对其中一株最能抑制T细胞增殖的杂交瘤细胞系进行了进一步的深入研究。结果显示其目标分子是CD45,同时增殖实验结果显示该抗体能显著抑制T细胞增殖反应。结论抗CD45单克隆抗体能有效抑制T细胞增殖,有望将本抗体用于T细胞介导的自身免疫性疾病的相关预防及治疗中。     

F10蛋白及mRNA在部分正常组织及癌组织中的表达

目的:了解F10基因在部分正常组织及肿瘤组织中的表达情况。方法:利用原位杂交和免疫组化方法对F10在部分正常组织和肿瘤组织中的mRNA和蛋白表达情况进行分析。结果:F10基因不仅在腺癌组织中表达呈阳性,在鳞癌组织中表现出较腺癌更强的强阳性,并且在正常组织中也有一定的表达。结论:F10是一个在多种组织普遍表达的细胞内蛋白,其功能可能与物质转运相关。     

原发性肝癌患者术后两种营养支持的疗效对比及对免疫功能的影响研究

目的:研究原发性肝癌患者术后两种营养支持的疗效及对免疫功能的影响。方法:病例选自2010年10月至2012年11月在我院就诊治疗的90例经诊断为原发性肝癌并进行肝部分切除的患者,随机分为EN组和PN组,每组各45例,分别进行肠内和肠外营养支持治疗,观察术前及术后患者的营养状况、住院时间、肠道功能恢复时间、并发症情况及免疫功能的变化,经统计学处理,探讨两种不同营养支持疗法的临床疗效及对免疫功能的影响。结果:相对于PN组,EN组患者术后营养明显改善,胃肠道功能恢复相对较快,免疫功能明显提高,术后并发症明显减少,且P0.05。差异具有统计学意义。结论:早期EN比PN更能改善肝癌病人术后肠道功能及营养状况,降低术后并发症,提高患者的免疫功能,有利于患者术后恢复。     

Synthesis and evaluation of a series of 2-substituted-5-thiopropylpiperazine (piperidine)-1,3,4-oxadiazoles derivatives as atypical antipsychotics

Background

It is important to develop novel antipsychotics that can effectively treat schizophrenia with minor side-effects. The aim of our work is to develop novel antipsychotics that act on dopamine D₂ and D₃, serotonin 5-HT_1A and 5-HT_2A receptors with low affinity for the serotonin 5-HT_2C and H₁ receptors, which can effectively cure positive symptoms, negative symptoms and cognitive impairment without the weight gain side-effect.

Methodology/Principal Findings

A series of 2-substituted-5-thiopropylpiperazine (piperidine) -1,3,4-oxadiazoles derivatives have been synthesized and the target compounds were evaluated for binding affinities to D₂, 5-HT_1A and 5-HT_2A receptors. Preliminary results indicated that compounds 14, 16 and 22 exhibited high affinities to D₂, 5-HT_1A and 5-HT_2A receptors among these compounds. Further binding tests showed that compound 22 had high affinity for D₃ receptor, and low affinity for serotonin 5-HT_2C and H₁ receptors. In addition, compound 22 inhibited apomorphine-induced climbing behavior and MK-801-induced hyperactivity with no extrapyramidal symptoms liability in mice. Moreover, compound 22 exhibited acceptable pharmacokinetic properties.

Conclusions/Significance

Compound 22 showed an atypical antipsychotic activity without liability for extrapyramidal symptoms. We anticipate compound 22 to be useful for developing a novel class of drug for the treatment of schizophrenia.     

Genome-Wide Association Study Dissects the Genetic Architecture of Seed Weight and Seed Quality in Rapeseed (Brassica napus L.)

Association mapping can quickly and efficiently dissect complex agronomic traits. Rapeseed is one of the most economically important polyploid oil crops, although its genome sequence is not yet published. In this study, a recently developed 60K Brassica Infinium^® SNP array was used to analyse an association panel with 472 accessions. The single-nucleotide polymorphisms (SNPs) of the array were in silico mapped using ‘pseudomolecules’ representative of the genome of rapeseed to establish their hypothetical order and to perform association mapping of seed weight and seed quality. As a result, two significant associations on A8 and C3 of Brassica napus were detected for erucic acid content, and the peak SNPs were found to be only 233 and 128 kb away from the key genes BnaA.FAE1 and BnaC.FAE1. BnaA.FAE1 was also identified to be significantly associated with the oil content. Orthologues of Arabidopsis thaliana HAG1 were identified close to four clusters of SNPs associated with glucosinolate content on A9, C2, C7 and C9. For seed weight, we detected two association signals on A7 and A9, which were consistent with previous studies of quantitative trait loci mapping. The results indicate that our association mapping approach is suitable for fine mapping of the complex traits in rapeseed.     

Molecular mechanisms of two-component system RhpRS regulating type III secretion system in Pseudomonas syringae

Pseudomonas syringae uses the two-component system RhpRS to regulate the expression of type III secretion system (T3SS) genes and bacterial virulence. However, the molecular mechanisms and the regulons of RhpRS have yet to be fully elucidated. Here, we show that RhpS functions as a kinase and a phosphatase on RhpR and as an autokinase upon itself. RhpR is phosphorylated by the small phosphodonor acetyl phosphate. A specific RhpR-binding site containing the inverted repeat (IR) motif GTATC-N₆-GATAC, was mapped to its own promoter by a DNase I footprint analysis. Electrophoretic mobility shift assay indicated that P-RhpR has a higher binding affinity to the IR motif than RhpR. To identify additional RhpR targets in P. syringae, we performed chromatin immunoprecipitation followed by high-throughput DNA sequencing (ChIP-seq) and detected 167 enriched loci including the hrpR promoter, suggesting the direct regulation of T3SS cascade genes by RhpR. A genome-wide microarray analysis showed that, in addition to the T3SS cascade genes, RhpR differentially regulates a large set of genes with various functions in response to different growth conditions. Together, these results suggested that RhpRS is a global regulator that allows P. syringae to sense and respond to environmental changes by coordinating T3SS expression and many other biological processes.     

Apparent Diffusion Coefficient (ADC) Value: A Potential Imaging Biomarker That Reflects the Biological Features of Rectal Cancer

Objective

We elected to analyze the correlation between the pre-treatment apparent diffusion coefficient (ADC) and the clinical, histological, and immunohistochemical status of rectal cancers.

Materials and Methods

Forty-nine rectal cancer patients who received surgical resection without neoadjuvant therapy were selected that underwent primary MRI and diffusion-weighted imaging (DWI). Tumor ADC values were determined and analyzed to identify any correlations between these values and pre-treatment CEA or CA19-9 levels, and/or the histological and immunohistochemical properties of the tumor.

Results

Inter-observer agreement of confidence levels from two separate observers was suitable for ADC measurement (k  =  0.775). The pre-treatment ADC values of different T stage tumors were not equal (p  =  0.003). The overall trend was that higher T stage values correlated with lower ADC values. ADC values were also significantly lower for the following conditions: tumors with the presence of extranodal tumor deposits (p  =  0.006) and tumors with CA19-9 levels ≥ 35 g/ml (p  =  0.006). There was a negative correlation between Ki-67 LI and the ADC value (r  =  −0.318, p  =  0.026) and between the AgNOR count and the ADC value (r  =  −0.310, p  =  0.030).

Conclusion

Significant correlations were found between the pre-treatment ADC values and T stage, extranodal tumor deposits, CA19-9 levels, Ki-67 LI, and AgNOR counts in our study. Lower ADC values were associated with more aggressive tumor behavior. Therefore, the ADC value may represent a useful biomarker for assessing the biological features and possible relationship to the status of identified rectal cancers.