亚临床型生殖器疱疹排毒与血清抗体检测及与药物治疗相关性研究

目的:探讨亚临床型生殖器疱疹患者的排毒与血清抗体检测及与药物治疗的相关性。方法:收集亚临床型生殖器疱疹患者,用分子生物学方法测定排毒质粒情况,及用酶联免疫法(ELISA)测定患者血清抗体(IgG和IgM)情况,以及和用药治疗后排毒情况。结果:入选病例300例中,排毒阳性160例,占53.3%;其中男性190例中,排毒阳性90例,占47.4%:女性110例中,排毒阳性70例,占63.6%。总的排毒质粒数最高值4.41×103Copies/ml,最低值80,平均910。血清学抗体HSV-l及HSV-2IgG和IgM检测,入选300例中,阳性201例,占67.0%。排毒阳性160例中,血清学阳性71例,占44.4%,排毒阴性140例中,阳性110例,占78.6%,二者阳性率有极显著性差异(χ2=36.48,P<0.01)。排毒阳性160例中,用药治疗后二组(伐昔洛韦片组和阿昔洛韦咀嚼片组)第5天、第10天及第4个月抑制排毒情况与对照组相比,均有显著性差异。结论:排毒阳性患者用药治疗后能明显抑制患者排毒率。

阴离子交换树脂对玉米秸秆蒸汽爆破预处理液的选择性脱毒

分别以糖-酸-醛模拟液和玉米秸秆蒸汽爆破预处理液为实验材料,比较了4种典型的阴离子交换树脂的选择性交换吸附脱毒性能,从中筛选出大孔型苯乙烯系阴离子交换树脂D301。D301树脂可以选择性地吸附脱除模拟液大部分酸类和呋喃醛类抑制物,但几乎不吸附糖类。其中,酸类的交换吸附符合Freundlich多分子层等温吸附特征,而糖类和呋喃醛类符合Langmuir单分子层吸附特征。在玉米秸秆蒸汽爆破预处理液中,D301树脂仍然保持对酸和呋喃醛类抑制物的选择性交换吸附性能,但是受未知成分杂质的复杂交换作用的影响和干扰,它对酸类和糠醛类抑制物的总脱除率由70.2%显著下降至44.5%,降幅达36.6%;而对单糖类的吸附率由1.2%大幅急剧提高至25.5%～37.9%,增幅达20～31倍;低聚木糖和低聚葡萄糖的吸附率分别达到13.7%和10.6%。采用减压蒸发浓缩与树脂吸附相结合联合脱毒方法可脱除69.1%和94.4%的酸类和醛类,脱除75.4%色素类和33.9%木质素分解物质,同时造成糖类损失16.3%。联合脱毒方法可以有效提高玉米秸秆蒸汽爆破预处理液的发酵生产性能,但是距离工业化发酵生产水平的差距仍然较大,仍需要针对木质纤维原料预处理体系的脱毒技术开展更加广泛和深入的研究工作。

替比夫定治疗恶性肿瘤并发慢性乙型肝炎30例疗效观察

慢性乙型肝炎系HBV持续感染引起的肝脏慢性炎症坏死性疾病。在恶性肿瘤和慢乙肝并存时，患者应用细胞毒性药物化疗或肾上腺皮质激素，以及放射治疗可使机体免疫防御、自稳功能失调，耐受状态被打破，HBV大量复制，诱发一系列级联反应，在促炎分子的作用下，导致机体损伤，使得肝炎急性加剧、甚至发生肝衰竭。本组根据中华医学会《慢性乙型肝炎防治指南》，对恶性肿瘤合并乙型肝炎的患者接受放化疗前给予替比夫定600mg／d治疗，并观察疗效。

Future prospectives for the management of chronic hepatitis B

Chronic hepatitis B virus infection affects about 400 million people around the globe and causes approximately a million deaths a year. Since the discovery of interferon-α as a therapeutic option the treatment of hepatitis B has evolved fast and management has become increasingly complicated. The amount of viral replication reflected in the viral load （HBV-DNA） plays an important role in the development of cirrhosis and hepatocellular carcinoma. The current treatment modalities for chronic hepatitis B are immunomodulatory （interferons） and antiviral suppressants （nucleoside and nucleotide analogues） all with their own advantages and limitations. An overview of the treatment efficacy for both immunomodulatory as antiviral compounds is provided in order to provide the clinician insight into the factors influencing treatment outcome. With nucleoside or nucleotide analogues suppression of viral replication by 5-7 log10 is feasible, but not all patients respond to therapy. Known factors influencing treatment outcome are viral load, ALT levels and compliance. Many other factors which might influence treatment are scarcely investigated. Identifying the factors associated with response might result in stopping rules, so treatment could be adapted in an early stage to provide adequate treatment and avoid the development of resistance. The efficacy of compounds for the treatment of mutant virus and the cross-resistance is largely unknown. However, genotypic and phenotypic testing as well as small clinical trials provided some data on efficacy in this population. Discontinuation of nucleoside or nucleotide analogues frequently results in viral relapse; however, some patients have a sustained response. Data on the risk factors for relapse are necessary in order to determine when treatment can be discontinued safely. In conclusion： chronic hepatitis B has become a treatable disease; however, much research is needed to tailor therapy to an individual patient, to predict the sustainability of response and determine the best treatment for those failing treatment.

Inhibitory Effects of Aromatic Compounds on Soil Nitrification

Aromatic compounds (ACs) in soil can induce competitive inhibition for soil NH3 oxidation, and nitrification inhibitors can be used to this end. A laboratory incubation experiment was performed with 12 nitroaromatic compounds (NACs), 15 amidoaromatic compounds (AACs) and 20 hydroxyaromatic compounds (HACs) to assess the inhibitory effects of ACs on soil nitrification. Based on these results, the critical and optimal concentrations of ACs were determined for better inhibitory effects. Most of the test ACs were able to inhibit soil nitrification; the effectiveness differed with soil type. Among the ACs, the NACs with m-nitryl, amino or hydroxyl and the AACs with a nitro group or a chlorine atom on aromatic ring or with a p-hydroxyl were more effective. 3-nitroaniline, 4-aminophenol and 3-nitrophenol showed the greatest potential as nitrification inhibitors. The critical concentration of these compounds in brown soil and cinnamon soil was found to be 0.5 mg kg-1 soil. Due to the toxicity, carcinogenicity and mutagenicity of ACs, further toxicological and ecotoxicological research is necessary before ACs are used as nitrification inhibitors in agricultural and horticultural practices.

Viral suppression of RNA silencing

Gene silencing (RNA silencing) plays a fundamental role in antiviral defense in plants, fungi and invertebrates. Viruses encode proteins that suppress gene silencing to counter host defense. Viral suppressors of RNA silencing (VSRs) have been identified from almost all plant virus genera and some viruses of insects and mammals. Recent studies have revealed that VSRs counter host defense and interfere with host gene regulation by interacting with RNA or important components of the RNA silencing pathway. Here, we review the current understanding of the complex mechanisms of VSRs that have been revealed by recent studies.

A perspective on picornavirus inhibitors and concrete evolution of WIN compounds

The family Picornaviridae is one of the largest families of human viral pathogens,causing an extensive range of clinical manifestations from mild fever,common cold to serious paralytic poliomyelitis,COPD,etc.,some of which can even be life-threatening.Picornaviruses also cause zoonotic epidemics that result in dramatic social and economical losses.Although no efficient antivirus agent for prophylaxis or treatment of picornarivus infections has been officially approved yet,a large number of anti-picornavirus compounds with potent activity have been developed and investigated,through which further information about picornavirus has been revealed as well.Viral mRNA translation,viral mRNA replication and especially the viral capsid are the three main targets of these compounds having been extensively studied.The typical one is the WIN series of compounds that bind to the viral capsid and inhibit rival attachment or uncoating.Herein,a perspective on picornavirus inhibitors and a concrete evolution of WIN compounds will be presented in this paper.

In vitro inhibitory and pro-apoptotic effect of Stellera Chamaejasme LExtract on human lung cancer cell line NCI-H157

OBJECTIVE:To investigate the inhibitory and pro-apoptotic effect of Stellera Chamaejasme L extract(ESC) in vitro.METHODS:ESC was first extracted with ethanol,and then washed using a polyamide column with 60% ethanol.ESC was then decompressively recycled and vacuum dried at room temperature to obtain active fractions.Subsequently,the cytotoxic and apoptotic effects of ESC on NCI-H157 human lung cancer cells were determined.RESULTS:The results showed that ESC was rich in isomers of Chamaejasminor,neochamaejasmine and Sikokianin.ESC had significant cytotoxicity against NCI-H157 cells,with an IC 50 of approximately 18.50 μg.mL-1.ESC caused significant increase in total apoptotic rate,the activity of caspase 3 and 8,and Fas protein expression(P<0.05).CONCLUSION:The inhibitory effect of ESC on NCI-H157 tumor cells might partly be attributed to its apoptotic induction through activation of the Fas death receptor pathway.

Insights from investigating the interactions of natural product inhibitors with neuraminidase of the 2009 H1N1 influenza virus

Neuraminidase(NA) plays a biologically vital role in the replication of influenza virus, and NA inhibitors(NAIs) are most widely used in the clinical anti-flu therapy. NA of 2009 H1 N1 influenza virus(09 N1) possesses a different substrate-binding cavity compared with other NA subtypes, making 09 N1 a more appropriate starting point for the discovery of potent 09 N1 inhibitors. As natural products are of great structural diversity, research on the interaction between natural NAIs and 09 N1 can throw light on the design of new structural NAIs. In this study, we, for the first time, conducted molecular docking procedure with GOLD on 10 natural inhibitors to 09 N1, and acquired their binding modes with 09 N1. The docking results showed that the active site S1 was important in the binding of NAIs to 09 N1. Then five scaffolds were extracted from these NAIs with interactions to site S1, and these could be used in the structural modification of NAIs. Besides, we found that the addition of H-bonding interaction with the active site could improve the NA inhibitory activity of NAIs, and it might be the reason why the approved NAIs showed high efficiency. Two terminal hydrophobic sites(Terminal 1 and Terminal 2) with no interactions to the approved NAI zanamivir were found in the 09 N1 active cavity, and four NAIs were first found to bind with the terminals. Till now, there are few studies on the meaning of Terminal 2 in the binding of NAI to NA, which could be a new direction for the rational design of NAIs.

Antiviral drug design based on structural insights into the N-terminal domain and C-terminal domain of the SARS-CoV-2 nucleocapsid protein

Nucleocapsid(N) protein plays crucial roles in the life cycle of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2), including the formation of ribonucleoprotein(RNP) complex with the viral RNA.Here we reported the crystal structures of the N-terminal domain(NTD) and C-terminal domain(CTD) of the N protein and an NTD-RNA complex. Our structures reveal a unique tetramer organization of NTD and identify a distinct RNA binding mode in the NTD-RNA complex, which could contribute to the formation of the RNP complex. We also screened small molecule inhibitors of N-NTD and N-CTD and discovered that ceftriaxone sodium, an antibiotic, can block the binding of RNA to NTD and inhibit the formation of the RNP complex. These results together could facilitate the further research of antiviral drug design targeting N protein.