Complete Genome Sequence of Hepatitis E Virus from Rabbits in the United States

Hepatitis E virus (HEV) is a single-strand positive-sense RNA virus in the family Hepeviridae. The disease caused by HEV, hepatitis E, is an important public health problem in developing countries of Asia and Africa and is also endemic in many industrialized countries, including the United States. HEV has been identified from several other animal species in addition to humans, including the pig, chicken, mongoose, deer, rabbit, ferret, bat, and fish. Here we report the complete genome sequence of the first strain of HEV from rabbits in the United States. Sequence and phylogenetic analyses revealed that the U.S. rabbit HEV is a distant member of the zoonotic genotype 3 HEV, thus raising a concern for potential zoonotic human infection. A unique 90-nucleotide insertion within the X domain of the ORF1 was identified in the rabbit HEV, and this insertion may play a role in the species tropism of HEV.     

胭脂红景天引种至西藏日喀则其渗透调节物质及保护酶活性的变化

胭脂红景天叶片呈胭脂红色,花开红色,具有极强的耐寒性和耐旱性,是优良的城市绿化植物。为了扩大胭脂红景天的应用范围,丰富恶劣生境的绿化材料,本试验对从哈尔滨引种到西藏日喀则表现良好的胭脂红景天进行了生理适应性研究。结果表明,随着栽植时间的延长,胭脂红景天叶片中丙二醛含量逐渐升高,但增加的幅度较小,脯氨酸含量先降低后升高,SOD、POD、CAT等保护酶的活性均呈先升高后降低的趋势。胭脂红景天可以通过增加体内渗透调节物质含量和提高保护酶活性来调节自身的生理代谢,适应日喀则地区高辐射、干旱等条件。     

Trinorsesquiterpenoids from Inula racemosa

Four trinorsesquiterpenoids (1–4) were isolated from the roots of Inula racemosa and the structures of two new compounds, (4R,5S,10S)-5-hydroxy-11,12,13-trinoreudesm-6-en-8-one (1) and (4R,5R,10R)-4,15-epoxy-11,12,13-trinoreudesman-8-one (3), were elucidated by extensive spectroscopic analysis. Furthermore, the structure of compound 2a should be revised as (4R,5R,10S)-5-hydroxy-11,12,13-trinoreudesm-6-en-8-one (2) and compound 2 showed antiproliferative activity against A549, HepG2, and HT1080 cell lines with IC50 values of 3.71, 5.94, and 3.95 μg/mL, respectively.     

Charge Variants of an Avastin Biosimilar Isolation,Characterization, In Vitro Properties and Pharmacokinetics in Rat

The similarity between a proposed biosimilar product and the reference product can be affected by many factors. This study is designed to examine whether any subtle difference in the distribution of the charge variants of an Avastin biosimilar can affect its in vitro potency and in vivo PK. Here, the acidic, basic and main peak fractions of a biosimilar product were isolated using high-performance cation-exchange chromatography and were subjected to various studies to compare their in vitro properties and in vivo PK profile. A serial of analytical methods, including size exclusion chromatography (SEC), imaged capillary isoelectric focusing (icIEF) capillary zone electrophoresis (CZE) and cation-exchange chromatography (CEX-HPLC) were also used to characterize the isolated charge variants. The kinetics constant was measured using a Biacore X100 system. The study indicates the biosimilar product has a high similarity with avastin in physicochemical properties. The potency in vitro and PK profile in rat of charge variants and biosimilar product are consistent with avastin.     

靶向蛋白质降解技术研究进展

靶向蛋白质降解技术可有效克服DNA敲除、RNA干扰等传统药物靶点确认及干扰策略的局限性。近年来,一系列新型靶向蛋白质降解技术不断涌现,在药物研发领域展现出极好的应用前景。本文综述了靶向蛋白质降解技术的最新研究进展,重点介绍各种技术的作用机制、应用情况、技术优势及目前存在问题,以期为药物靶点确认及新药开发提供有力理论及技术支持。     

The discovery of a novel eight-mRNA-lncRNA signature predicting survival of hepatocellular carcinoma patients

Increasing evidence indicates that the expressions of messenger RNAs (mRNAs) and long non-coding RNAs (lncRNAs) undergo a frequent and aberrant change in carcinogenesis and cancer development. But some research was carried out on mRNA-lncRNA signatures for prediction of hepatocellular carcinoma (HCC) prognosis. We aimed to establish an mRNA-lncRNA signature to improve the ability to predict HCC patients’ survival. The subjects from the cancer genome atlas (TCGA) data set were randomly divided into two parts: training data set (n = 246) and testing data set (n = 124). Using computational methods, we selected eight gene signatures (five mRNAs and three lncRNAs) to generate the risk score model, which were significantly correlated with overall survival of patients with HCC in both training and testing data set. The signature had the ability to classify the patients in training data set into a high-risk group and low-risk group with significantly different overall survival (hazard ratio = 4.157, 95% confidence interval = 2.648-6.526, P < 0.001). The prognostic value was further validated in testing data set and the entire data set. Further analysis revealed that this signature was independent of tumor stage. In addition, Gene Set Enrichment Analysis suggested that high risk score group was associated with cell proliferation and division related pathways. Finally, we developed a well-performed nomogram integrating the prognostic signature and other clinical information to predict 3- and 5-year overall survival. In conclusion, the prognostic mRNAs and lncRNAs identified in our study indicate their potential role in HCC biogenesis. The risk score model based on the mRNA-lncRNA may be an efficient classification tool to evaluate the prognosis of patients’ with HCC.     

Roseomonas alkaliterrae sp. nov., isolated from an alkali geothermal soil sample in Tengchong,Yunnan, south-west China

An alkalitolerant, thermotolerant and Gram-stain negative bacterium, designated strain YIM 78007^T, was isolated from an alkaline geothermal soil sample from Hehua hot spring, Tengchong, Yunnan province, south-west China. Cells of strain YIM 78007^T were observed to be aerobic and short rod-shaped. The colonies were observed to be orange-red, convex and circular. 16S rRNA gene sequence-based phylogenetic analysis showed that strain YIM 78007^T clustered with members of the genus Roseomonas (with similarities from 97.2 to 92.2 %). Optimal growth of strain YIM 78007 occurs at 40–50 °C and pH 8.0–10.0. The predominant ubiquinone was identified as Q-10 and the major fatty acids were identified as C_18:1 ω7c and C_16:0. The polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two unidentified aminolipids and one unknown phospholipid. The G + C content of the genomic DNA was determined to be 63 mol %. The levels of DNA–DNA hybridization relatedness between strain YIM 78007^T and its closet neighbours (Roseomonas lacus JCM 13283^T and Roseomonas terrae JCM 14592^T) were well below the threshold required for the proposal of a novel species. The results of physiological and biochemical characteristics, the phylogenetic analysis, as well as low DNA–DNA hybridization values, allowed the phenotypic and genotypic differentiation of strain YIM 78007^T from its closest phylogenetic neighbours. Therefore, strain YIM 78007^T is considered to represent a novel species of the genus Roseomonas, for which the name Roseomonas alkaliterrae sp. nov. is proposed. The type strain is YIM 78007^T (=BCRC 80644^T = JCM 19656^T).     

Urotensin II increases foam cell formation by repressing ABCA1 expression through the ERK/NF-κB pathway in THP-1 macrophages

Objective

Foam cell formation in the arterial wall plays a key role in the development of atherosclerosis. Recent studies showed that Urotensin II (U II) is involved in the pathogenesis of atherosclerosis. Here we examined the effects of human U II on ATP-binding cassette transporter A1 (ABCA1) expression and the underlying mechanism in THP-1 macrophages.

Methods and results

Cultured THP-1 macrophages were treated with U II, followed by measuring the intracellular lipid contents, cholesterol efflux and ABCA1 levels. The results showed that U II dramatically decreased ABCA1 levels and impaired cholesterol efflux. However, the effects of U II on ABCA1 protein expression and cellular cholesterol efflux were partially reversed by inhibition of extracellular signal regulated kinase 1/2 (ERK1/2) and nuclear factor kappa B (NF-κB) activity, suggesting the potential roles of ERK1/2 and NF-κB in ABCA1 expression, respectively.

Conclusion

Our current data indicate that U II may have promoting effects on the progression of atherosclerosis, likely through suppressing ABCA1 expression via activation of the ERK/NF-κB pathway and reducing cholesterol efflux to promote macrophage foam cell formation.