BACKGROUND & AIMS: :Annexin A2 is a membrane scaffolding and binding protein, which mediated various cellular events. Its functions are generally affected by cellular localization. In the cytoplasm, they interacted with different phospholipid membranes in Ca2+ -dependent manner and play vital roles including actin binding, remodeling and dynamics, cytoskeletal rearrangement, and lipid-raft microdomain formation. However, upon cell exposure to certain stimuli, annexin A2 translocates to the external leaflets of the plasma membrane where annexin A2 was recently reported to serve as a virus receptor, play an important role in the formation of virus replication complex, or implicated in virus assembly and budding. Here, we review some of annexin A2 roles in virus infections and the potentiality of targeting annexin A2 in the design of novel and promising antivirus agent that may have a broader consequence in virus therapy.

背景与目标： : 膜联蛋白A2是一种膜支架和结合蛋白，介导各种细胞事件。其功能一般受细胞定位的影响。在细胞质中，它们以Ca2依赖性方式与不同的磷脂膜相互作用，并发挥重要作用，包括肌动蛋白结合，重塑和动力学，细胞骨架重排和脂质筏微区形成。然而，当细胞暴露于某些刺激时，膜联蛋白A2易位至质膜的外部小叶，最近据报道膜联蛋白A2充当病毒受体，在病毒复制复合物的形成中起重要作用，或与病毒组装和出芽有关。在这里，我们回顾了膜联蛋白A2在病毒感染中的一些作用，以及靶向膜联蛋白A2在设计新颖而有前途的抗病毒剂中的潜力，这些杀病毒可能在病毒治疗中产生更广泛的影响。

BACKGROUND & AIMS: BACKGROUND:Forsythoside A (FTA), one of the main active ingredients in Shuang-Huang-Lian (SHL), possesses strong antibacterial, antioxidant and antiviral effects, and its pharmacological effects was higher than that of other ingredients, but the absolute bioavailability orally was approximately 0.72%, which was significantly low, influencing clinical efficacies of its oral preparations seriously. MATERIALS AND METHODS:In vitro Caco-2 cell and in vivo pharmacokinetics study were simultaneously performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test and morphology observation, respectively. The pharmacological effects such as antivirus activity improvement by absorption enhancers were verified by MDCK damage inhibition rate after influenza virus propagation. RESULTS:The observations from in vitro Caco-2 cell showed that the absorption of FTA in SHL could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/mL was safe, but water-soluble chitosan at different concentrations was all safe for these cells. In pharmacokinetics study, water-soluble chitosan at dosage of 50 mg/kg improved the bioavailability of FTA in SHL to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with SHL with water-soluble chitosan at dosage of 50 mg/kg prevented MDCK damage after influenza virus propagation better significantly than that of control. CONCLUSION:Water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antivirus activity in vitro in SHL.

背景与目标：

BACKGROUND & AIMS: :This study is to investigate the synergistic effect of Anglica polysaccharide sulfate (APS-1) and Combivir, an anti-AIDS drug, on murine leukemia virus in vivo. As the results shown, the virus replication was significantly decreased by the combination of APS-1 and Combivir, which tended to be further decreased (58% inhibition) when compared with that of Combivir alone (51% inhibition). Furthermore, both the percentage of CD4(+) cells and CD4(+)/CD8(+) ratio in peripheral blood cells were significantly enhanced by this combined administration, while the CD4(+) cells was only slightly increased and CD4(+)/CD8(+) ratio was not affected by Combivir alone. Additionally, combination of APS-1 and Combivir also alleviated the toxicity of Combivir. APS-1 not only increased the survival rate of mice administered with LD(50) dose of Combivir, but also reduced the hematologic toxicity induced by Combivir, RBC, HGB and PLT were restored to normal level. These results suggest that APS-1 had synergistic effect with Combivir, which provided new insight into the potential clinical use of polysaccharide sulfate in anti-AIDS field.

背景与目标： : 本研究旨在研究langlica多糖硫酸盐 (APS-1) 和抗AIDS药物Combivir在体内对小鼠白血病病毒的协同作用。如结果所示，病毒复制通过APS-1和Combivir的组合而显著降低，与单独的Combivir (51% 抑制) 相比，其趋于进一步降低 (58% 抑制)。此外，通过联合给药，外周血细胞中CD4 () 细胞的百分比和CD4 ()/CD8 () 比率均显着提高。而CD4(+) 细胞仅略有增加，CD4(+)/CD8(+) 比值不受Combivir单独作用的影响。此外，APS-1和Combivir的组合也减轻了Combivir的毒性。APS-1不仅提高了LD(50) 剂量Combivir给药小鼠的存活率，而且降低了Combivir引起的血液学毒性，RBC，HGB和PLT恢复到正常水平。这些结果表明，APS-1与Combivir具有协同作用，这为硫酸多糖在抗艾滋病领域的潜在临床应用提供了新的见解。

BACKGROUND & AIMS: :At the start of the 21st century, respiratory syncytial virus (RSV) remains a serious global health concern. Although RSV has traditionally been acknowledged as a leading cause of morbidity and mortality in the paediatric population, the elderly and people with suppressed immune systems are now also recognised as being at risk from serious RSV infection. This problem is currently exacerbated by the lack of an effective vaccine to prevent RSV infection. Although the virus proteins play a variety of roles during the virus replication cycle, in many cases these tasks are performed via specific interactions with host-cell factors, including proteins, carbohydrates and lipids. The way in which RSV interacts with the host cell is currently being examined using a battery of different techniques, which encompass several scientific disciplines. This is providing new and interesting insights into how RSV interacts with the host cell at the molecular level, which in turn is offering the hope of new strategies to prevent RSV infection.

背景与目标： : 在21世纪开始时，呼吸道合胞病毒 (RSV) 仍然是一个严重的全球健康问题。尽管传统上认为RSV是儿科人群发病率和死亡率的主要原因，但老年人和免疫系统受到抑制的人现在也被认为有严重RSV感染的风险。目前，由于缺乏有效的疫苗来预防RSV感染，这一问题更加严重。尽管病毒蛋白在病毒复制周期中起着多种作用，但在许多情况下，这些任务是通过与宿主细胞因子 (包括蛋白质，碳水化合物和脂质) 的特定相互作用来执行的。RSV与宿主细胞相互作用的方式目前正在使用一系列不同的技术进行检查，该技术涵盖了多个科学学科。这为RSV如何在分子水平上与宿主细胞相互作用提供了新的有趣的见解，这反过来又为预防RSV感染的新策略提供了希望。

BACKGROUND & AIMS: :As an essential lipid, cholesterol is of great value in keeping cell homeostasis, being the precursor of bile acid and steroid hormones, and stabilizing membrane lipid rafts. As a kind of cholesterol metabolite produced by enzymatic or radical process, oxysterols have drawn much attention in the last decades. Among which, the role of 25-hydroxycholesterol (25-HC) in cholesterol and bile acid metabolism, antivirus process, and inflammatory response has been largely disclosed. This review is aimed at revealing these functions and underlying mechanisms of 25-HC.

背景与目标： : 作为一种必需的脂质，胆固醇在保持细胞稳态，胆汁酸和类固醇激素的前体以及稳定膜脂筏方面具有重要价值。作为一种通过酶促或自由基过程产生的胆固醇代谢产物，氧化甾醇在过去的几十年中引起了广泛的关注。其中，25-羟基胆固醇 (25-HC) 在胆固醇和胆汁酸代谢，抗病毒过程和炎症反应中的作用已被广泛公开。这篇综述旨在揭示25-hc的这些功能和潜在机制。

BACKGROUND & AIMS: :Ion channels are membrane proteins that are found in a number of viruses and which are of crucial physiological importance in the viral life cycle. They have one common feature in that their action mode involves a change of electrochemical or proton gradient across the bilayer lipid membrane which modulates viral or cellular activity. We will discuss a group of viral channel proteins that belong to the viroproin family, and which participate in a number of viral functions including promoting the release of viral particles from cells. Blocking these channel-forming proteins may be "lethal", which can be a suitable and potential therapeutic strategy. In this review we discuss seven ion channels of viruses which can lead serious infections in human beings: M2 of influenza A, NB and BM2 of influenza B, CM2 of influenza C, Vpu of HIV-1, p7 of HCV and 2B of picornaviruses.

背景与目标： 离子通道是在许多病毒中发现的膜蛋白，在病毒生命周期中具有至关重要的生理意义。它们有一个共同的特征，即它们的作用模式涉及跨双层脂质膜的电化学或质子梯度的变化，从而调节病毒或细胞活性。我们将讨论一组属于病毒体蛋白家族的病毒通道蛋白，它们参与许多病毒功能，包括促进病毒颗粒从细胞中释放。阻断这些通道形成蛋白可能是 “致命的”，这可能是一种合适且潜在的治疗策略。在这篇综述中，我们讨论了可导致人类严重感染的病毒的七个离子通道: 甲型流感的M2，乙型流感的NB和BM2，丙型流感的CM2，HIV-1的Vpu，HCV的p7和小核糖核酸病毒的2B。

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BACKGROUND & AIMS: LESSONS LEARNED:Novaferon showed moderate efficacy and was well-tolerated in patients with metastatic colorectal cancer (mCRC), especially with the 20 μg injected 3 times a week strategy.Although Novaferon did not provide a survival benefit for mCRC patients who have failed standard treatment, it may play a role in improvement of immune function. BACKGROUND:To observe the efficacy, safety, and optimal dosage of recombinant antitumor and antivirus protein (Novaferon) in treating patients with metastatic colorectal cancer (mCRC) who failed at least two prior palliative regimens. METHODS:We enrolled 108 patients from May 2011 to December 2012. According to different treatment modalities and therapeutic dosages, the participants were randomly divided into four cohorts at a 2:2:2:1 ratio: (a) 20 μg Novaferon (Genova Biotech, Beijing, People's Republic of China, http://www.genovabiotech.net) injected twice per week, (b) 20 μg Novaferon injected 3 times per week, (c) 40 μg Novaferon injected 3 times per week, or (d) saline injected 3 times per week. The primary endpoint was overall survival. RESULTS:There was no significant difference in overall survival among the four cohorts. The 20-μg dose of Novaferon injected 3 times per week had the highest disease control rate (44.0%) at 6 weeks but without significant differences when compared with placebo (p = .159). Major adverse events with Novaferon were influenza-like symptoms, bone marrow suppression, liver dysfunction, and gastrointestinal discomfort. The level of natural killer cells increased and regulatory T cells decreased significantly after treatment with Novaferon, whereas levels in the placebo group remained the same. CONCLUSION:Novaferon showed moderate efficacy and was well tolerated in patients with mCRC, especially with the 20-μg dose injected 3 times per week. Furthermore, Novaferon might improve immune function of these patients.

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BACKGROUND & AIMS: :Phytochemical investigation of the methanol extract of Vitex limonifolia leaves led to the isolation of three new labdane-type diterpenoids, vitexlimolides A-C (1-3) and eight known compounds, 5,4'-dihydroxy-3,7-dimethoxyflavone (4), vitecetin (5), 5,4'-dihydroxy-7,3'-dimethoxyflavone (6), verrucosin (7), 2α, 3α-dihydroxy-urs-12-en-28-oic acid (8), euscaphlic acid (9), 18,19-seco, 2α, 3α-dihydroxy-19-oxo-urs-11,13(18)-dien-28-oic acid (10), and maslinic acid (11). Their chemical structures were elucidated by physical and chemical methods. All compounds were evaluated for antiviral activities against CVB3, HRV1B, and EV71 viruses. As a result, compounds 4 and 6 showed potent antiviral activity against CVB3 infection with IC50 values of 0.12 ± 0.06 and 1.86 ± 0.18 (µM), respectively.

背景与目标： : 对牡荆叶片甲醇提取物的植物化学研究导致隔离出三种新的labdane型二萜类化合物，牡荆内酯A-C (1-3) 和八种已知化合物，5,4 '-dihydroxy-3，7-二甲氧基黄酮 (4)，vitecetin (5)，5,4'-dihydroxy-7，3 '-二甲氧基黄酮 (6)，verrucosin (7)，2α，3α-二羟基-urs-12-en-28-oic酸 (8)，白沙糖酸 (9)，18,19-seco，2α，3α-二羟基-19-oxo-urs-11,13(18)-dien-28-oic (10) 和山糖油酸 (11)。通过物理和化学方法阐明了它们的化学结构。评估了所有化合物对CVB3，HRV1B和EV71病毒的抗病毒活性。结果，化合物4和6显示出针对CVB3感染的有效抗病毒活性，IC50值分别为0.12 ± 0.06和1.86 ± 0.18 (µ m)。

BACKGROUND & AIMS: :A novel bovine interferon-ω (BoIFN-ω) gene, which encodes a protein of 195 amino acids with a 23-amino acid signal peptide, was amplified from bovine liver genomic DNA through PCR and named BoIFN-ω24 according to its position in the bovine genome. In this study, the recombinant protein was expressed in Escherichia coli and antiviral or antiproliferation activity was determined in vitro. Results showed that BoIFN-ω24 exhibits high antiviral activity, which can be abrogated using PAb against BoIFN-ω24, and inhibits cell proliferation. BoIFN-ω24 also presents high sensitivity to trypsin and stability at pH 2.0 or 65°C, which are typical characteristics of type I IFN. This study revealed that BoIFN-ω24 is a potential novel effective therapeutic agent and provided a basis for further research on the BoIFN-ω multigene family.

背景与目标： : 通过PCR从牛肝基因组DNA中扩增出一个新的牛干扰素-ω (BoIFN-ω) 基因，该基因编码具有23个氨基酸信号肽的195个氨基酸的蛋白质，并根据其在牛基因组中的位置将其命名为BoIFN-ω24。在这项研究中，重组蛋白在大肠杆菌中表达，并在体外确定了抗病毒或抗增殖活性。结果表明，BoIFN-ω24具有很高的抗病毒活性，可以使用PAb消除BoIFN-ω24，并抑制细胞增殖。BoIFN-ω24还表现出对胰蛋白酶的高灵敏度和在pH 2.0或65 °C下的稳定性，这是I型IFN的典型特征。这项研究表明，BoIFN-ω24是一种潜在的新型有效治疗剂，并为进一步研究BoIFN-ω 多基因家族提供了基础。

BACKGROUND & AIMS: OBJECTIVE:The objective of this study was to determine whether reactivation of Epstein-Barr (EBV) or activation of the anti-EBV immune response correlates with MS disease activity on MR imaging. METHODS:Subjects with early, active relapsing-remitting MS were studied for 16 weeks with blood and saliva samples collected every 2 weeks and brain MRI performed every 4 weeks. We isolated peripheral blood mononuclear cells from each blood sample and tested the immune response to EBV, autologous EBV-infected lymphoblastoid cell lines (LCL), human herpesvirus 6 (HHV6), varicella zoster virus (VZV), tetanus, and mitogens. We measured the proliferative response and the number of interferon-γ secreting cells with ELISPOT. We measured the amounts of EBV, HHV6, and VZV DNA in blood and saliva with quantitative PCR. On MRI, we measured number and volume of contrast enhancing and T2 lesions. We tested for correlation between the immunologic assays and the MRI results, assessing different time intervals between the MRI and immunologic assays. RESULTS:We studied 20 subjects. Ten had enhancing lesions on one or more MRI scans and one had new T2 lesions without enhancement. The most significant correlation was between proliferation to autologous LCL and the number of combined unique active lesions on MRI 4 weeks later. Both proliferation and number of cells secreting interferon-γ in response to LCL correlated with the number of enhancing lesions 8 weeks later. CONCLUSIONS:We find evidence for correlation of antiviral immune responses in the blood with subsequent disease activity on MRI scans.

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BACKGROUND & AIMS: :The uptake and transepithelial transport of the three main constituents macrocarpal A (M-A), macrocarpal B (M-B), and cypellocarpa C (Cy-C) from the fruits of Eucalyptus globulus Labill. were investigated. Monolayers of the human intestinal epithelial cancer cell line Caco-2 were incubated with M-A, M-B, and Cy-C to model its intestinal absorption and transport, respectively. The determination of compounds was performed by HPLC. The apparent permeability coefficients (P(app)) for M-A, M-B, and Cy-C in the apical-to-basolateral direction of a Caco-2 monolayer were (1.70+/-0.06)x10(-6), (1.99+/-0.10)x10(-6), and (6.08+/-0.41)x10(-6)cm/s, respectively. In the presence of iodoacetamide, the P(app) of Cy-C were both reducted in apical-to-basolateral and basolateral-to-apical directions. M-A and M-B appear to accumulate in the epithelial cells. The intestinal absorption of M-A, M-B, and Cy-C was passive diffusion as the dominating process and Cy-C was partly ATP-dependent.

背景与目标： : 桉树果实中三种主要成分大腕A (m-a)，大腕B (m-b) 和cypellocarpa C (cy-c) 的吸收和跨上皮运输。被调查。将人肠上皮癌细胞系Caco-2的单层分别与m-a，m-b和cy-c孵育，以模拟其肠吸收和转运。化合物的测定通过HPLC进行。M-A、M-B和Cy-C在Caco-2单层的顶端至基底外侧方向的表观渗透系数 (P(app)) 为 (1.70 +/-0.06)x10(-6)，(1.99 +/-0.10)x10(-6) 和 (6.08 +/-0.41)x10(-6)cm/s。在存在碘乙酰胺的情况下，Cy-C的P(app) 均在顶端至基底外侧和基底外侧至顶端方向上还原。M-a和m-b似乎积聚在上皮细胞中。M-A，M-B和Cy-C的肠道吸收是被动扩散的主要过程，而Cy-C部分依赖于ATP。

BACKGROUND & AIMS: :The antiviral extract from Rhodopseudomonas capsulata was purified and the predominant active component was defined as cis-vaccenic acid (Cl-8:1 delta 11) by gas-liquid chromatography and gas chromatography-mass spectrometry analyses. Antiviral activities of unsaturated fatty acids and related alcohols against T5 phage were also tested. Among them, linoelaidic acid, oleic acid, and petroselenyl alcohol inactivated 98%, 53%, 67% of T5 phage at the concentration of 50 micrograms/ml, respectively.

背景与目标： : 通过气相色谱和气相色谱-质谱分析，纯化了荚膜红假单胞菌的抗病毒提取物，并将主要活性成分定义为顺式疫苗酸 (Cl-8:1 delta 11)。还测试了不饱和脂肪酸和相关醇对T5噬菌体的抗病毒活性。其中，亚麻酸，油酸和石油硒醇分别以50微克/毫升的浓度灭活T5噬菌体的98%，53%，67%。

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