The knowledge-integrated network biomarkers discovery for major adverse cardiac events

The mass spectrometry (MS) technology in clinical proteomics is very promising for discovery of new biomarkers for diseases management. To overcome the obstacles of data noises in MS analysis, we proposed a new approach of knowledge-integrated biomarker discovery using data from Major Adverse Cardiac Events (MACE) patients. We first built up a cardiovascular-related network based on protein information coming from protein annotations in Uniprot, protein-protein interaction (PPI), and signal transduction database. Distinct from the previous machine learning methods in MS data processing, we then used statistical methods to discover biomarkers in cardiovascular-related network. Through the tradeoff between known protein information and data noises in mass spectrometry data, we finally could firmly identify those high-confident biomarkers. Most importantly, aided by protein-protein interaction network, that is, cardiovascular-related network, we proposed a new type of biomarkers, that is, network biomarkers, composed of a set of proteins and the interactions among them. The candidate network biomarkers can classify the two groups of patients more accurately than current single ones without consideration of biological molecular interaction.     

单向放射免疫扩散法测定流感灭活疫苗血凝素含量的研究

为改进流感灭活疫苗血凝素含量的测定方法 ,将待测样品经去污剂处理后 ,用WHO标准品作对照进行免疫扩散测定 10个流感灭活疫苗样品血凝素含量。在血凝效价相同的情况下 ,疫苗中三价 (A1,A3,B)血凝素含量存在不同程度的差异。可见 ,单向放射免疫扩散法较血球凝集法更适用于流感灭活疫苗血凝素含量的测定。     

黄曲霉产木聚糖酶条件优化及酶解产物初步分析

一株能利用木糖及丰纤维素水解液产乙醇的黄曲霉Aspergillus flavus Z7具有产木聚糖酶的能力.通过单因素试验和正交试验优化了产酶培养基,得到最佳组分为玉米芯2%,尿素0.2%,酵母膏0.25%,K2HPO4 0.5%,NaNO,0.1%,MgSO4·7H2O 0.1%;单因素试验表明,用纱布代替塑料布密封摇瓶封口能显著提高产酶量;Z7在碱性条件下具有更强的产酶性能,在最优条件下发酵,能产生最大木聚糖酶活122.23IU/ml.通过薄层分析,验证了Z7产生的木聚糖酶具有水解木聚糖生成木糖及木寡糖的能力.     

Hypoxia suppresses KV1.5 channel expression through endogenous 15-HETE in rat pulmonary artery

Hypoxia initiated pulmonary vasoconstriction is due to the inhibition of voltage-gated K(+) (K(V)) channels. But the mechanism is unclear. We have evidence that hypoxia activates 15-lipoxygenase (15-LOX) in distal pulmonary arteries and increases the formation of 15-hydroxyeicosatetraenoate (15-HETE). 15-HETE-induced pulmonary artery constriction to be through the inhibition of K(V) channels (K(V)1.5, K(V)2.1 and K(V)3.4). However, no direct link among hypoxia, 15-HETE and inhibition of K(V) subtypes is established. Therefore, we investigated whether 15-LOX/15-HETE pathway contributes to the hypoxia-induced down-regulation of K(V) channels. As K(V)1.5 channel is O(2)-sensitive, it was chosen in the initial study. We found that inhibition of 15-LOX suppressed the response of hypoxic pulmonary artery rings to phenylephrine. The expressions of K(V)1.5 channel mRNA and protein was robustly up-regulated in cultured PASMC and pulmonary artery after blocking of 15-LOX by lipoxygenase inhibitors in hypoxia. The 15-LOX blockade also partly rescued the voltage-gated K(+) current (I(K(V))). 15-HETE contributes to the down-regulation of K(V)1.5 channel, inhibition of I(K(V)) and increase of native pulmonary artery tension after hypoxia. Hypoxia inhibits K(V)1.5 channel through 15-LOX/15-HETE pathway.     

The level of Hsp27 in lymphocytes is negatively associated with a higher risk of lung cancer

Heat shock proteins (Hsps) can protect cells, organs, and whole organisms against damage caused by abnormal environmental hazards. Some studies have reported that lymphocyte Hsps may serve as biomarkers for evaluating disease status and exposure to environmental stresses; however, few epidemiologic studies have examined the associations between lymphocyte Hsps levels and lung cancer risk. We examined lymphocyte levels of Hsp27 and Hsp70 in 263 lung cancer cases and age- and gender-matched cancer-free controls by flow cytometry. Multivariate logistic regression models were used to estimate the association between lymphocyte Hsps levels and lung cancer risk. Our results showed that Hsp27 levels were significantly lower in lung cancer cases than in controls (16.5 vs 17.8 mean fluorescence intensity, P < 0.001). This was not observed for Hsp70 levels. Further stratification analysis revealed that lymphocyte Hsp27 levels were negatively associated with lung cancer risk especially in males and heavy smokers. There was a statistical trend of low odd ratios (95% confidence intervals) and upper tertile levels of Hsp27 [1.000, 0.904 (0.566–1.444) and 0.382 (0.221–0.658, P _trend = 0.001) in males and 1.000, 0.9207 (0.465–1.822) and 0.419 (0.195–0.897, P _trend = 0.036) in heavy smokers] after adjustment for confounding factors. These results suggest that lower lymphocyte Hsp27 levels might be associated with an increased risk of lung cancer. Our findings need to be validated in a large prospective study. Feng Wang and Maohui Feng contributed equally to this work.     

Patt1, a novel protein acetyltransferase that is highly expressed in liver and downregulated in hepatocellular carcinoma,enhances apoptosis of hepatoma cells

Protein acetylation is increasingly recognized as an important post-translational modification. Although a lot of protein acetyltransferases have been identified, a few putative acetyltransferases are yet to be studied. In this study, we identified a novel protein acetyltransferase, Patt1, which belongs to GNAT family. Patt1 exhibited histone acetyltransferase activity and auto-acetylation activity. Deletion and mutation analysis of the predicted acetyltransferase domain in Patt1 showed that the conserved Glu139 was an important residue for its protein acetyltransferase activity. Furthermore, we found that Patt1 was highly expressed in liver and significantly downregulated in hepatocellular carcinoma tissues. In addition, we showed that overexpression of Patt1 enhanced the apoptosis of hepatoma cells dependent on its acetyltransferase activity, whereas knockdown of Patt1 significantly protected Chang liver cells from apoptosis. These data suggest that Patt1 might be involved in the development of hepatocellular carcinoma, and could be served as a potential therapy target for hepatocellular carcinoma.     

Conditional random pattern model for copy number aberration detection

Background  

DNA copy number aberration (CNA) is very important in the pathogenesis of tumors and other diseases. For example, CNAs may result in suppression of anti-oncogenes and activation of oncogenes, which would cause certain types of cancers. High density single nucleotide polymorphism (SNP) array data is widely used for the CNA detection. However, it is nontrivial to detect the CNA automatically because the signals obtained from high density SNP arrays often have low signal-to-noise ratio (SNR), which might be caused by whole genome amplification, mixtures of normal and tumor cells, experimental noise or other technical limitations. With the reduction in SNR, many false CNA regions are often detected and the true CNA regions are missed. Thus, more sophisticated statistical models are needed to make the CNAs detection, using the low SNR signals, more robust and reliable.     

Synthesis and anti-tumor evaluation of new trisulfide derivatives

New bis-aromatic and heterocyclic trisulfide derivatives 5, 7-10 were synthesized by optimizing lead dibenzyl trisulfide natural product (4) to evaluate their anti-tumor activities. Five compounds 5-7, 9, and 10 exhibited potent anti-tumor activities against eight different tumor cell lines with low cytotoxicity against HepG2. Initial SAR was discussed, and MOA of these anti-microtubule agents was suggested based on cell kinetic response patterns observed on RT-CES system.     

Design, synthesis, and anti-inflammatory activity both in vitro and in vivo of new betulinic acid analogues having an enone functionality in ring A

Fifteen new betulinic acid analogues were designed, synthesized, and tested for anti-inflammatory activity. Many of these analogues effectively suppress nitric oxide (NO) production in RAW cells stimulated with interferon-γ. Analogue 10 is highly and orally active in vivo for induction of the anti-inflammatory and cytoprotective enzyme, heme oxygenase-1.