Evolution in the indications for anti-viral therapy in chronic hepatitis B / 临床肝胆病杂志

In order to reduce the disease burden of chronic hepatitis B (CHB) and improve the treatment rate of CHB, the indications for anti-viral therapy have been gradually expanded and simplified in guidelines for the prevention and treatment of CHB released by Chinese Medical Association from 2005 to 2022. This article elaborates on the evolution in the indications for anti-viral therapy in CHB from the five aspects of converging indications of HBeAg-positive and HBeAg-negative CHB, reduction in the treatment threshold of HBV DNA, reduction in the treatment threshold of serum alanine aminotransferase, emphasis on the risk factors for disease progression, and gradual loosening of the requirements for virological indicators in patients with liver cirrhosis.

Tea tree oil, a vibrant source of neuroprotection via neuroinflammation inhibition: a critical insight into repurposing Melaleuca alternifolia by unfolding its characteristics / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Over the past few decades, complementary and alternative treatments have become increasingly popular worldwide. The purported therapeutic characteristics of natural products have come under increased scrutiny both in vitro and in vivo as part of efforts to legitimize their usage. One such product is tea tree oil (TTO), a volatile essential oil primarily obtained from the native Australian plant, Melaleuca alternifolia, which has diverse traditional and industrial applications such as topical preparations for the treatment of skin infections. Its anti-inflammatory-linked immunomodulatory actions have also been reported. This systematic review focuses on the anti-inflammatory effects of TTO and its main components that have shown strong immunomodulatory potential. An extensive literature search was performed electronically for data curation on worldwide accepted scientific databases, such as Web of Science, Google Scholar, PubMed, ScienceDirect, Scopus, and esteemed publishers such as Elsevier, Springer, Frontiers, and Taylor & Francis. Considering that the majority of pharmacological studies were conducted on crude oils only, the extracted data were critically analyzed to gain further insight into the prospects of TTO being used as a neuroprotective agent by drug formulation or dietary supplement. In addition, the active constituents contributing to the activity of TTO have not been well justified, and the core mechanisms need to be unveiled especially for anti-inflammatory and immunomodulatory effects leading to neuroprotection. Therefore, this review attempts to correlate the anti-inflammatory and immunomodulatory activity of TTO with its neuroprotective mechanisms.

Repurposing non-oncology small-molecule drugs to improve cancer therapy: Current situation and future directions

Drug repurposing or repositioning has been well-known to refer to the therapeutic applications of a drug for another indication other than it was originally approved for. Repurposing non-oncology small-molecule drugs has been increasingly becoming an attractive approach to improve cancer therapy, with potentially lower overall costs and shorter timelines. Several non-oncology drugs approved by FDA have been recently reported to treat different types of human cancers, with the aid of some new emerging technologies, such as omics sequencing and artificial intelligence to overcome the bottleneck of drug repurposing. Therefore, in this review, we focus on summarizing the therapeutic potential of non-oncology drugs, including cardiovascular drugs, microbiological drugs, small-molecule antibiotics, anti-viral drugs, anti-inflammatory drugs, anti-neurodegenerative drugs, antipsychotic drugs, antidepressants, and other drugs in human cancers. We also discuss their novel potential targets and relevant signaling pathways of these old non-oncology drugs in cancer therapies. Taken together, these inspiring findings will shed new light on repurposing more non-oncology small-molecule drugs with their intricate molecular mechanisms for future cancer drug discovery.

El consumo de un extracto de calafate (Berberis microphylla) modifica marcadores de respuesta inmune en ratones delgados y obesos

RESUMEN La obesidad ha sido identificada como factor de riesgo de severidad de infecciones respiratorias. Apoyar la respuesta inmune en sujetos obesos es de interés. El presente trabajo evaluó el efecto del consumo de un extracto de calafate sobre marcadores de respuesta inmune en ratones delgados y obesos. Ratones C57BL/6J machos fueron expuestos por 82 días a dieta estándar (DE) y alta en grasas (DAG). A un subgrupo de ambos grupos, se les administró 50 y 100 mg [polifenoles totales]/kg peso de animal/día, de extracto, en las últimas dos semanas. Se evaluó expresión génica y secreción de marcadores de respuesta inmune, en tejido pulmonar y plasma. Se observó un efecto del tratamiento con extracto en la expresión de IFN-ϓ. Se observaron efectos inducidos por la DAG y el tratamiento con extracto de manera independiente, en la expresión de IL-12. Se observó un efecto global de la DAG sobre IFN-ϓ plasmático, específicamente una disminución en animales alimentados con DAG. Se observó una interacción entre la dieta y el tratamiento con extracto sobre IL-12 plasmática. El tratamiento utilizado modula marcadores que activan la respuesta inmune ante infecciones respiratorias principalmente de origen viral, en animales delgados y obesos.

ABSTRACT Obesity has been identified as a risk factor for severity of respiratory infections. Thus, the support of the immune response in obese subjects is of interest. The present work evaluated the effect of the consumption of a calafate extract on markers of the immune response in lean and obese mice. Male C57BL/6J mice were exposed for 82 days to a standard or a high-fat diet (HFD). A subgroup of both groups was given 50 and 100 mg [total polyphenols]/kg body weight/day of extract in the last two weeks. Gene expression and secretion of immune response markers were evaluated in lung tissue and plasma. An effect of extract treatment on IFN-ϓ expression was observed. Effects induced by the HFD and treatment with extract were observed independent of the expression of IL-12. An overall effect of the HF diet on plasma IFN-ϓ was observed, specifically a decrease in animals fed the HFD. An interaction between diet and extract treatment was observed over plasma IL-12. The treatment used modulates markers that activate the immune response to respiratory infections, mainly of viral origin, in lean and obese animals.

A Computational Approach On Understanding Structural Interactions Of Envelope Protein Of Dengue Virus Bound With Squalene, A Prototype Anti-Viral Compound

Objective: The objective of the work was to validate the structural binding affinity of Squalene with the envelope protein of Dengue virus by means of molecular simulations. Methods: Three-dimensional (3D) structure of dengue 2 virus envelope protein was retrieved from Protein Data Bank PDB and Squalene compound from the ZINC database. Molecular docking between the E protein and Squalene were carried out by means of Auto Dock 4.2. Results: Based on the study, it was observed that the binding/docking energy for the complex structure was calculated to be-5.55 kcal/mol. Critical residues to interact with E protein were scrutinized by analyzing the interface of the complex within 4 Å proximity. Residues such as Thr 48, Glu49, Ala 50, Val 130, Leu 135, Ser 186, Pro 187, Thr 189, Gly 190, Leu 191, Phe 193, Leu 198, Leu 207, Thr 268, Phe 279, Thr 280, Gly 281, His 282 and Leu 283 were found to be non-covalently located around the squalene. Conclusion: Scopes to design de novo anti-viral compounds to the dengue viruses by using squalene as a new class of template structure have also been concisely brought into fore.

Antiviral and antifibrotic therapies reduce occurrence of hepatocellular carcinoma in patients with chronic hepatitis B and liver fibrosis: a 144-week prospective cohort study / 南方医科大学学报

OBJECTIVE@#To compare the efficacy and safety of different antiviral and antifibrotic regimens in patients with chronic hepatitis B (CHB) and hepatic fibrosis and the incidence of hepatocellular carcinoma (HCC) associated with these therapies.@*METHODS@#A total of 840 patients with CHB and concurrent hepatic fibrosis, who received antiviral therapy in Nanfang Hospital between June, 2010 and June, 2018, were enrolled in this follow-up cohort study. The patients were assigned to 3 cohorts matched for gender, age (difference≤5 years), HBeAg status and liver stiffness measurement (LSM) for treatment with one of the 3 antiviral drugs, namely entecavir, tenofovir dipivoxil and adefovir dipivoxil; each cohort was divided into 2 groups, with one of the groups having a combined treatment with Fufang Biejiaruangan tablet. The cumulative negative conversion rate of HBV DNA, normalization rate of ALT, hepatic fibrosis regression and the incidence of HCC were compared among the 3 cohorts and across the 6 groups at 144 weeks.@*RESULTS@#A total of 749 patients were available to follow-up at 144 weeks. Compared with the baseline data, the cumulative negative conversion rate of HBV DNA increased gradually and the abnormal rate of ALT decreased significantly over time during the treatment in all the 6 groups (all < 0.001). Compared with the any of the antiviral drugs used alone, the combined treatments all resulted in significantly better antifibrotic effects (χ=11.345, χ=10.160, χ=6.358; all < 0.05). At 144 weeks, the incidence of HCC were 2.2%, 1.7%, 1.7% and 3.3% in enecavir group, enecavir with Biejiaruangan tablet group, adefovir group, and adefovir with Biejiaruangan tablet group, respectively, showing no significant difference between the two cohorts (4 groups; χ=6.813, =0.138). None of the patients in the 2 groups with tenofovir treatment had HCC by the end of the observation.@*CONCLUSIONS@#Antiviral therapy combined with antifibrotic therapy can effectively reverse hepatic fibrosis and reduce the incidence of HCC in patients with CHB; among the 3 antiviral drugs, tenofovir dipivoxil can be a better option for reducing the incidence of HCC in these patients.

Enterovirus D68 protease 2A affects anti-viral interferon type Ⅰ pathway / 中华微生物学和免疫学杂志

Objective To analyze how enterovirus D68 (EV-D68) protease 2A affects the anti-vi-ral interferon typeⅠ(IFN-Ⅰ) pathway in 293T cells following infection. Methods Western blot was used to detect the expression of recombinant protease 2A, IFN-α and signal transducers and activators of tran-scription 1 (STAT1) at protein level. Expression of EV-D68 viral protein (VP1) and protease 2A was ana-lyzed by immunofluorescence at different time points. Cytopathic effects were recorded to calculate 50％ cell culture infective dose ( CCID50 ) . Expression of the genes involved in the anti-viral IFN-Ⅰ pathway was measured by real-time PCR (RT-PCR). Results The recombinant plasmid pCLIPf-2A was successfully constructed and the expression of recombinant protease 2A could be detected by Western blot 24 h after transfection. The recombinant protease 2A promoted the proliferation of EV-D68 at the late stage of infection and induced the production of IFN-α. Expression of the genes involved in the anti-viral IFN-Ⅰ pathway at mRNA level was up- or down-regulated to different degrees with various trends in different groups following infection. Expression of STAT1 was enhanced in all groups. Conclusions EV-D68 protease 2A promoted the activation of anti-viral IFN-Ⅰpathway in response to viral infection and enhanced the proliferation of virus at the late stage of infection.

Knowledge, attitude and practices of general practitioners about use of antiviral drugs in viral infections other than HIV

Background: Antiviral drugs for viral infections other than HIV are effective only for hepatitis, herpes and influenza. It has been observed that general practitioners (GPs) treat viral infections with antibiotics. The use of antibiotics in viral infections is not rational. Hence, authors conducted this study to assess the Knowledge, Attitude and Practices of General Practitioners (GPs) about treatment of viral infections other than HIV.Methods: It was a descriptive, observational, cross- sectional study among 100 GPs in Southern Pune. A pretested questionnaire was used to assess their knowledge, attitude and practices about treatment of viral infections other than HIV. Prior informed written consent was taken from the GPs who were grouped under MBBS, BHMS and BAMS categories according to their qualifications. Correct answers among these groups were analysed using chi-square test, Spearman’s coefficient test and ANOVA.Results: The percentages of correct answers in the groups were comparable.56% GPs have poor knowledge of Influenza treatment.30-36% do not treat Herpes genitalis and zoster with antiviral drugs. Authors found that 44%, 30% and 28% of total GPs don’t have proper knowledge, attitude and practice respectively about common viral infections other than HIV and antiviral drugs.Conclusions: GPs are significantly unaware about rational use of antiviral drugs. They have poor knowledge about management of influenza.

Anti-influenza Virus Activity of Coix-seed Reactive Derivatives / 日本補完代替医療学会誌

Objective: We examined anti-influenza virus (anti-IFV) activity of Coix-seed Reactive Derivatives (CRD) extract.Methods: H1N1 A/Puerto Rico/8/34 (PR8) strain was infected to Malin Darby Canine Kidney (MDCK) cells. The infected cells were cultured by medium supplemented CRD extract for 24 h, and the supernatants were harvested to analyze virus titer by focus-forming reduction assay. Polyphenols were removed by PVPP treatment, and anti-influenza virus activity was compared with normal CRD extract. Results: CRD extract showed anti-IFV activity. In addition, CRD extract inhibited viral adsorption and replication. The study of CRD extract by PVPP treatment suggested that polyphenols are the main active component. Conclusion: This study revealed that CRD extract has anti-IFV activity against PR8 strain. The mechanism of action was inhibited viral adsorption and replication. It was also suggested that anti-IFV activity of CRD extract is due to polyphenols.

Qualitative pathological assessment of liver fibrosis regression after antiviral therapy in patients with chronic hepatitis B / 中华肝脏病杂志

Objective@#To investigate the methods for qualitative pathological assessment of dynamic changes in liver fibrosis/cirrhosis after antiviral therapy in patients with chronic hepatitis B (CHB), since antiviral therapy can partially reverse liver fibrosis and cirrhosis caused by hepatitis B and semi-quantitative, rather than qualitative, pathological assessment is often used for the research on liver fibrosis regression.@*Methods@#Previously untreated CHB patients with liver fibrosis and cirrhosis were enrolled, and liver biopsy was performed before treatment and at 78 weeks after the antiviral therapy based on entecavir. The follow-up assessment was performed once every half a year. Based on the proportion of different types of fibrous septum, we put forward the new qualitative criteria called P-I-R classification (predominantly progressive, predominantly regressive, and indeterminate) for evaluating dynamic changes in liver fibrosis. This classification or Ishak fibrosis stage was used to evaluate the change in liver fibrosis after treatment and Ishak liver inflammation score was used to evaluate the change in liver inflammation after treatment.@*Results@#A total of 112 CHB patients who underwent liver biopsy before and after treatment were enrolled, and among these patients, 71 with an Ishak stage of ≥3 and qualified results of live biopsy were included in the final analysis. Based on the P-I-R classification, 58% (41/71) were classified as predominantly progressive, 29% (21/71) were classified as indeterminate, and 13% (9/71) were classified as predominantly regressive; there were no significant differences between the three groups in alanine aminotransferase, aspartate aminotransferase, albumin, HBeAg positive rate, HBV DNA, and liver stiffness (P < 0.05). After treatment, the proportion of predominantly progressive, indeterminate, or predominantly regressive patients changed to 11% (8/71), 11% (8/71), and 78% (55/71), respectively. Among the 35 patients who had no change in Ishak stage after treatment, 72% (25/35) were classified as predominantly regressive and had certain reductions in the Laennec score, percentage of collagen area, and liver stiffness.@*Conclusion@#This new P-I-R classification can be used to assess the dynamic changes in liver fibrosis after antiviral therapy in CHB patients.

Emerging Novel Anti HIV biomolecules from marine Algae: An overview.

Over the past 3 decades, despite enormous scientific advancements and developments in the field of vaccine development and drugs, HIV-1 is still posing a major challenge to human health. While development of vaccines is still clearly many years ahead, administration of FDA approved drugs leads to severe side effects and toxicity. Marine algae due to its biodiversity has been a rich source of biologically active compounds with varying degree of actions such as anti-viral, anti-cancer, anti-amyloid, anti-inflammatory and anti-oxidant properties. The primary and secondary metabolites obtained from the marine algae have shown potent anti-viral activities in vitro and in animal model. This review focus on the bioactive compounds from marine algae that have been recently identified and studied.

Role of Th17 and Treg during the Chronic Infection of Hepatitis C Virus

Hepatitis C virus (HCV) is one of the main causes of liver disease. 1~2% of the Korean people has been reported to be infected by HCV. Although HCV is less infectious than hepatitis B virus (HBV), it is more prone to develop chronic infection (~ 80%) which may link to cirrhosis and hepatocellular carcinogenesis. In addition, prevalence of hepatitis caused by HCV infection is gradually increased every year in Korea. Recently, a large number of clinical trials using direct-acting antiviral (DAA) drugs have been shown efficient therapeutic results for chronic HCV infections and some of them are on the market. However, there is still a concern on viral evasion to the DAAs and the effective mechanisms of immunological clearance of HCV remains to be elucidated. Here, we introduce the recent findings on the role of Th17-Treg axis which may play a critical role of the viral pathogenesis and/or immunological defense against HCV infection. The underlying regulatory mechanisms of Th17-Treg axis might be a potential candidate for the better control of HCV chronic infections.

Antiviral effects of pudilan xiaoyan oral liquid on respiratory syncytial virus and adenovirus in vitro / 实用医学杂志

Objective To study the antiviral effects of Pudilan xiaoyan oral liquid on Hep-2 cell models infected with respiratory syncytial virus (RSV), adenoviruses serotype 3 strains (ADV3) in vitro. Methods The cell cytotoxic and inhibition effect of Pudilan xiaoyan oral liquid on RSV or ADV3 were investigated by MTT assay and the inhibitory assay for cytopathic effect (CPE) in Hep-2 cell cultures to detect its antiviral effects. Results The median toxic concentration (TC50) of Pudilan xiaoyan oral liquid on Hep-2 cells was 776.97 mg/L. The median effective concentration (EC50) of inhibiting RSV and ADV3 were 28.08, 28.10 mg/L,whose therapeutic index (TI) were 27.67 and 27.65 respectively. The safety coefficient of Pudilan xiaoyan oral liquid is higher than that of control, ribavirin. Compared with the virus control group, Pudilan xiaoyan oral liquid can obviously produce actions of a dose-dependent relationship to inhibit CPE in Hep-2 cells infected with RSV or ADV3 virus. Conclusions Pudilan xiaoyan oral liquid significantly improves the protection against RSV and ADV3 virus infection in Hep-2 cells. And the inhibition of CPE induced by viruses infection increased with the elevation of higher drug concentration for its antiviral effect augmented in vitro.

Clinical analysis of the first patient with imported Middle East respiratory syndrome in China / 中华危重病急救医学

ObjectiveTo report the treatment of the first imported Middle East respiratory syndrome (MERS) in China, and to investigate the clinical features and treatment of the patient.Methods On May 28th, 2015, the first patient of imported MERS to China was admitted to Department of Critical Care Medicine of Huizhou Municipal Central Hospital. The clinical features and treatments of this patient were analyzed.Results①A 43 years old male of South Korean nationality was admitted with the complaint of back ache for 7 days and fever 2 days with the following characteristics: back ache 7 days ago, without fever or cough or expectoration. He had been suspected to suffer from infection of Middle East respiratory syndrome coronavirus (MERS-CoV) by the Disease Control Department of South Korea, but no specific treatment was given. He had fever for 2 days with maximum body temperature of 39.7℃. He had no chills, cough, expectoration, short of breath, abdominal pain, diarrhea, frequent micturition, or urgency or pain of urination, and no sore throat. The patient had a history of exposure to MERS-CoV patient. He was considered to be a patient of the second batch of South Korean epidemic.② Auxiliary examination: 3 copies of throat swab specimens for virus nucleic acid detection were performed by the Disease Prevention Control Center of China (China CDC), and they were positive on May 29th, 2015, and also for serum, sputum and stool. Based on the results of whole genome sequence analysis, the virus strains were implicated to be derived from Riyahh and Jeddah regions of Saudi Arabia. On admission, the patient's blood test showed that the white blood cell count was low (3.22×109/L), the proportion of the neutrophils was high (0.73), and that of the platelet was low (81×109/L). On admission, the patient's chest X-ray showed that a small amount of infiltration in the lung.③ Treatment: a high-flow nasal cannula (HFNC) with oxygen concentration of 0.50-0.80 was given, with a flow rate was set at 60 L/min if tolerated. It was changed to a low flow oxygen inhalation nasal cannula on the 20th day, and oxygen treatment was stopped on the 24th day. Ribavirin 2.0 g was given as the first dose, and was switched to 600 mg every 8 h (q8h), and it was reduced to 600 mg q12h after 10 days, and extenuated since the 13th day. Ceftriaxone was added on the 4th day with 2.0 g a day , and it was changed to meropenem 2.0 g, q8h on the 7th day for 2 weeks. Gamma globulin was given for 7 days (20 g, qd). Thymosin-α1 was given on the 8th day for 2 weeks. Interferon was given once a week, but only one dose was used. At the same time symptomatic treatment such as methimazole and liver protection therapy were given.④ Patient began to cough at admission, and it disappeared on the 18th day. There was no sputum at first, then a small amount of sputum with a little blood appeared after the admission. Then there was cough without sputum. Mild shortness of breath and diarrhea after exertion were noticed. He had no chest pain, difficulty in breathing or other symptoms. There was dullness on percussion in both sides of chest, and it disappeared gradually. Fine moist rales were detectable in scapular area and interscapular area on the 5th day, and they disappeared after 3 days. Breath sounds on both sides was weak, and it became more obvious in the right lung after 5 days, and returned to normal after 18 days. He had a sustaining fever for 1 week with the maximum temperature of 39.5℃, then the body temperature returned to normal. The viral nucleic acid test as performed by the Center for Disease Control of Guangdong (CDC, Guangdong) showed that the pharyngeal swab cultured turned negative on the 3rd day, that of serum specimens turned negative on the 8th day, that of stool specimen after 2 weeks, and it was persistently positive for sputum culture until 5 days before discharge. The oxygenation index gradually increased, and it was over 300 mmHg (1 mmHg = 0.133 kPa) after 15 days. Pleural effusion was rapidly increased during the first week as shown by chest X-ray films, and it began to be absorbed gradually in the second week, but it was not completely absorbed until discharge.Conclusions The disease course of the reported patient was short, with an acute onset, with fever as the chief complaint, but there were no respiratory symptoms, though there were high fever, cough, shortness of breath, diarrhea and other clinical symptoms after admission. Virus in sputum disappeared after treatment, but pleural effusion was not completely absorbed. Negative test for virus in sputum was late, indicating that clearance of virus was slow from the lungs. It is the first case of MERS in China, therefore, the clinical manifestations and the treatment strategy need to be further explored.

Efficacy of Hubei Wingnut(Malus hapehensis) Leaf Decoction on Viral Conjunctivitis Infected with HSV-1 / 医药导报

Objective To investigate the therapeutic effect of the Hubei Wingnut ( Malus hapehensis ) leaf decoction (MHD) against conjunctivitis infected with human simplex virus type I (HSV-1). Methods Malus hupehcnsis decoction was used as the active treatment and ribavirin ( RBV) eye drop was used as the positive control. Both of the Vero cells and rabbit eye conjunctiva were infected with HSV-1. The effect and mechanism of the MHD on viral replication was determined by observing the cytopathic effect ( CPE) . The efficacy of MHD at different doses on the rabbit viral conjunctivitis was examined by pathological changes of eye conjunctiva tissues. Results MHD did not inhibit the proliferation of HSV-1 in vitro. The inflammatory reactions of rabbit viral conjunctivitis caused by HSV-1 were obviously attenuated or disappeared after treatment with MHD at 6 kg·L-1 and 3 kg·L-1 for 7 consecutive days,compared with the negative control of 0. 9% NaCl. The curative rate of MHD at the middle and high doses was 83. 3% and 100. 0%, respectively. Conclusion MHD has the potential for treating eye conjunctivitis caused by HSV-1 by relieving inflammation.

Hepatitis B virus-3p-siRNA inhibits hepatitis B virus replication and activates interferon-βexpression in mice / 中华传染病杂志

Objective To observe the activation of anti-viral innate immune response of type Ⅰinterferon and inhibition of hepatitis B virus (HBV)genome replication in mice by HBV-3p-siRNA. Methods HBV-3p-siRNA was designed by targeting specific sequence of HBV S/P mRNA and was generated by in vitro transcription.Negative control siRNA (NC-siRNA)and non-modified HBV-siRNA were used as control groups.Blood samples were collected from tail vein of mice and the model of HBV-infected mice were established by hydrodynamic injection.Forty mice were divided into 4 groups with 10 in each group.The model group was only injected with pGL3.0-HBV1 .2 copy plasmid.The negative control group received peritoneal injection of NC-siRNA.HBV-siRNA group received peritoneal injection of HBV-siRNA and HBV-3p-siRNA group received peritoneal injection of HBV-3p-siRNA.The interferon-β(IFN-β)and hepatitis B surface antigen (HBsAg)in serum were detected by enzyme linked immunosorbent assay (ELISA).The copies of HBV DNA were assessed by fluore scence quantitative polymerase chain reaction (PCR ).The statistical difference between groups was determined using One way-ANOVA analysis by LSD or Dunnett T3.Results Serum level of IFN-β was (12.37±5 .32)pg/mL in model group,(22.61 ±6.29 )pg/mL in negative control group,(26.40±5 .39)pg/mL in HBV-siRNA group and (68.37± 21 .00 ) pg/mL in HBV-3p-siRNA group.The secretions of IFN-β into serum were significantly enhanced by HBV-siRNA and HBV-3p-siRNA compared with model group (F =23.988 and 46.523,respectively,both P <0.01).Serum level of HBsAg was (2 864.86±907.11 )ng/mL in model group,(2 198.86±456.89 )ng/mL in negative control group,(1 049.71 ± 396.28 )ng/mL in HBV-siRNA group and (640.86±383.08)ng/mL in HBV-3p-siRNA group.The expressions of HBsAg were inhibited by HBV-3p-siRNA and HBV-siRNA compared with model group (F = 23.537 and 39.144, respectively;P =0.025 and 0.010,respectively).Serum level of HBV DNA was (2.54 ×104 ±1 .46 × 104 )copy/mL in model group,(2.22×104 ±2.62×103 )copy/mL in negative control group,(3.59×103 ±2.88×103 )copy/mL in HBV-siRNA group and (2.65 ×103 ±1 .46×103 )copy/mL in HBV-3p-siRNA group.Serum level of HBV DNA were inhibited by HBV-3p-siRNA and HBV-siRNA compared with model group (F =15 .013 and 16.741 ,respectively,both P <0.05 ).All of the indicated siRNA used in the experiments showed no apparent effects on the body mass index of the mice models.Conclusion HBV-3p-siRNA,which induces the production of IFN-β and inhibits HBV replication through gene silencing in vivo ,may be a powerful bifunctional antiviral molecule.

Research progress of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) / 中国人兽共患病学报

Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) is a novel coronavirus which can cause severe acute respiratory illness with a high mortality rate .There is no proven medication or vaccine for MERS-CoV .Currently MERS-CoV has spread from the main epidemic area ,the Middle East area ,to many other countries including United States of America and has the potential of global endemic .It has raised global public health concerns regarding the current situation and its future evolution .This review will mainly focus on the research progress of MERS-CoV about the animal reservoir and transmission , infection mechanisms and development of anti-viral drugs or vaccine .The goal is to provide with useful references to the devel-opment of specific drug and vaccine and an effective control and prevention of M ERS-CoV infection .

Vitamin C Is an Essential Factor on the Anti-viral Immune Responses through the Production of Interferon-alpha/beta at the Initial Stage of Influenza A Virus (H3N2) Infection

L-ascorbic acid (vitamin C) is one of the well-known anti-viral agents, especially to influenza virus. Since the in vivo anti-viral effect is still controversial, we investigated whether vitamin C could regulate influenza virus infection in vivo by using Gulo (-/-) mice, which cannot synthesize vitamin C like humans. First, we found that vitamin C-insufficient Gulo (-/-) mice expired within 1 week after intranasal inoculation of influenza virus (H3N2/Hongkong). Viral titers in the lung of vitamin C-insufficient Gulo (-/-) mice were definitely increased but production of anti-viral cytokine, interferon (IFN)-alpha/beta, was decreased. On the contrary, the infiltration of inflammatory cells into the lung and production of pro-inflammatory cytokines, tumor necrosis factor (TNF)-alpha and interleukin (IL)-alpha/beta, were increased in the lung. Taken together, vitamin C shows in vivo anti-viral immune responses at the early time of infection, especially against influenza virus, through increased production of IFN-alpha/beta.

YMDD motif mutations in chronic hepatitis B antiviral treatment naïve patients: a multi-center study

OBJECTIVE: This study aimed to determine the natural prevalence of variants of tyrosine-methionine-aspartic acid-aspartic acid (YMDD) motif in patients with chronic hepatitis B (CHB), and to explore its relation with demographic and clinical features, hepatitis B virus (HBV) genotypes, and HBV DNA levels. METHODS: A total of 1,042 antiviral treatment naïve CHB patients (including with lamivudine [LAM]) in the past year were recruited from outpatient and inpatient departments of six centers from December 2008 to June 2010. YMDD variants were analyzed using the HBV drug resistance line probe assay (Inno-Lipa HBV-DR). HBV genotypes were detected with polymerase chain reaction (PCR) microcosmic nucleic acid cross-ELISA, and HBV deoxyribonucleic acid (DNA) was quantitated with real-time PCR. All serum samples underwent tests for HBV, HCV, and HDV with ELISA. RESULTS: YMDD variants were detected in 23.3% (243/1042) of CHB patients. YMDD mutation was accompanied by L180M mutation in 154 (76.9%) patients. Both wild-type HBV and YMDD variant HBV were present in 231 of 243 patients. Interestingly, 12 patients had only YIDD and/or YVDD variants without wild YMDD motif. In addition, 27.2% (98/359) of HbeAg-positive patients had YMDD mutations, which was higher than that in HbeAg-negative patients (21.2%, 145/683). The incidence of YMDD varied among patients with different HBV genotypes, but the difference was not significant. Moreover, the incidence of YMDD in patients with high HBV DNA level was significantly higher than that in those with low HBV DNA level. CONCLUSION: Mutation of YMDD motif was detectable at a high rate in CHB patients in this study. The incidence of YMDD may be correlated with HBeAg and HBV DNA level.

Benzimidazole: A short review of their antimicrobial activities.

Benzimidazole is the heterocyclic compound formed from benzene and imidazole ring containing nitrogen, oxygen sulphor and its derivatives are of wide interest because of their diverse biological activity and clinical applications, they are remarkably effective compounds both with respect to their inhibitory activity and their favourable selectivity ratio. Reported nucleus is a constituent of vitamin-B12. Benzimidazoles are regarded as a promising class of bioactive heterocyclic compounds that exhibit a range of biological activities like anti-microbial, anti-viral, anti-diabetic, anti-cancer activity, numerous anti-oxidant, anti-parasitic, anti-helmintics, anti-proliferative, anti-HIV, anti-convulsant, anti-inflammatory, anti-hypertensive, anti-neoplastic, proton pump inhibitor and anti-trichinellosis. Benzimidazoles exhibit significant activity as potential antitumor agents, smooth muscle cell proliferation inhibitors, a treatment for intestinal cystitis, and in diverse area of chemistry. Some of the important benzimidazole derivatives have been reported as thyroid receptor agonist gonadotropin releasing hormone receptor antagonists, non-nucleoside HIV-1 reverse transcriptase inhibitors and interestingly alkynylbenzimidazoles as modulators of metabotropic glutamate receptors. The imidazole core is a common moiety in a large number of natural products and pharmacologically active compounds. The synthesis of novel benzimidazole derivatives remains a main focus of medicinal research. This comprehensive overview summarizes the chemistry of different derivative of substituted benzimidazole along with their anti-microbial activity containing anti-malarial anti-fungal, anti-bacterial, anti-viral activities.