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The dried leaves and rhizomes of Alpinia zerumbet have been traditionally used as food and medicine. Anti-inflammatory activity-guided phytochemical investigation into the rhizomes of A. zerumbet led to the isolation of 17 compounds including 10 neolignans (1-10, 1a, 1b, 2a, 2b, 3a, 3b, 4, and 5 are new compounds) and seven diarylheptanoids (11-17) in which 1-3 were three pairs of enantiomers. 4 was only one enantiomer and 5 was a racemic mixture. Compounds 1a, 1b, 2a, and 2b incorporated an 8',9'-dinorneolignan skeleton, which was rare in the lignan family. The planar structures of these compounds were elucidated by extensive analyses of spectroscopic data. The relative and absolute configurations were determined by the time-dependent density functional theory (TDDFT)-based electronic circular dichroism (ECD) calculation method. The 95% ethanol extract and ethyl acetate extract of A. zerumbet were found to show anti-inflammatory activity against croton oil-induced ear edema in mice with inhibition rates of 20.0 and 47.6% at a dose of 80 mg/kg, respectively. Bioassays showed that compounds 1a, 1b, 2a, 2b, and 12 moderately inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 cells with IC50 values of 3.62, 7.63, 6.51, 5.60, and 8.33 μM, respectively.

Histo-blood group antigens (HBGAs) have been found to be important host susceptibility factors or receptors for human rotavirus (RVs) with genotype-specific host ranges, impacting the disease patterns, epidemiology, and strategy development against RV diseases in humans. However, how the glycan factors contribute to RV diversity and host ranges to different animal species remains unclear. In this study using recombinant VP8* proteins as probes to perform glycan array analyses of RVs, we observed a wide range of glycan-binding profiles, including those binding to sialic acid-containing glycans, among group A (RVA) and group C (RVC) RVs that mainly infect different animal species. A tri-saccharide glycan Galα1-3Galβ1-4Glc containing a terminal α-Gal was recognised by multiple RVA/RVC genotypes, providing valuable information on RV evolution under selection of the step-wisely synthesised HBGAs in many animals before they were introduced to humans to be human pathogens. Saliva binding studies of VP8* also revealed strain-specific host ranges or species barriers between humans and these animal RV genotypes, further improved our understanding on RV host ranges, disease burdens, epidemiology, and vaccine strategy against RVs.

Rotaviruses cause severe gastroenteritis in infants, in which the viruses interact with human histo-blood group antigens (HBGAs) as attachment and host susceptibility factors. While gastroenteritis outbreaks caused by rotaviruses are uncommon in adolescents, we reported here one that occurred in a middle school in China. Rectal swabs and saliva samples were collected from symptomatic and asymptomatic students, and samples were also collected from the environment. Using PCR, followed by DNA sequencing, a single G9P[8] rotavirus strain was identified as the causative agent. The attack rate of the outbreak was 13.5% for boarders, which was significantly higher than that of day students (1.8%). Person-to-person transmission was the most plausible transmission mode. The HBGA phenotypes of the individuals in the study were determined by enzyme immunoassay, using saliva samples, while recombinant VP8* protein of the causative rotavirus strain was produced for HBGA binding assays to evaluate the host susceptibility. Our data showed that secretor individuals had a significantly higher risk of infection than nonsecretors. Accordingly, the VP8* protein bound nearly all secretor saliva samples, but not those of nonsecretors, explaining the observed infection of secretor individuals only. This is the first single-outbreak-based investigation showing that P[8] rotavirus infected only secretors. Our investigation also suggests that health education of school students is an important countermeasure against an outbreak of communicable disease.

The dried leaves and rhizomes of

Characterizing diversity and the antigenic relatedness of norovirus remains a primary focus in understanding its biological properties and vaccine designs. The precise antigenic and serological features of GI genotypes have not been studied. The study represented an investigation on a gastroenteritis outbreak related to GI.3 norovirus and the three most detected GI genotypes, GI.2 (belonging to immunotype B), GI.3 and GI.9 (belonging to immunotype C), were selected to characterize their phylogenetic relationship, HBGA binding profiles and antigenic relatedness within (intra-immunotype), and between (inter-immunotypes) genotypes using mouse sera and patient’s serum samples from the GI.3 related outbreak. Wide HBGA binding profiles and evolution of binding affinity were observed in the three GI genotypes studied. A low specific blockade antibody to GI.3 in the population generated the pool of susceptible individuals and supported virus spread in the outbreak. We found strong blockade immune response in homologous strains, moderate intra-immunotype blockade but weak inter-immunotypes blockade in humans following GI.3 norovirus infections. These findings further support the immunotypes grouping and will be valuable for optimizing the design of norovirus vaccine.

Citrus limonoids are tetranortriterpenoids compounds mainly found in oranges, lemons, grapefruits, and other fruits of Citrus. They are proved to be the leading cause of bitterness in Citrus fruits and are mainly consumed for therapeutic purposes and as food. Numerous studies have focused on Citrus limonoids and intend to develop new chemotherapeutic or complementary medicine in recent years. Citrus limonoids showed various bioactivities such as anti-tumor, antioxidative, anti-inflammatory, anti-neurological diseases, immunomodulatory, anti -insect, anti-bacteria, antiviral activities, etc. This review summarized limonoids from Citrus to date, along with their chemical structures and biological activities with a particular focus on their anti-tumor potential.

Two novel nortriterpenoids together with 7 known compounds were isolated from the fruits of Evodia rutaecarpa. The structures of the new compounds were elucidated by spectroscopic analysis, X-ray, and electronic circular dichroism (ECD) calculations. Compound 1 is the first example of triterpenoid with a 27 (17 → 12)-abeo-five-ring skeleton. In turn, compound 2 possesses a unique C/D/E linear fused ring system and a methyl on C-21. Plausible biogenetic pathway for the new compounds 1 and 2 are also proposed. Compound 1 exhibited significantly antitumor activity against A549 and LoVo cells with IC50 values of 2.0 μM and 1.9 μM, respectively. Colony formation inhibition, cell cycle arrest and cell apoptosis of compound 1 were also evaluated. Compound 2, 6, 7 and 9 showed potent neuroprotective activities against serum-deprivation induced P12 cell damage.

Rotaviruses are known to recognize human histo-blood group antigens (HBGAs) as a host ligand that is believed to play an important role in rotavirus host susceptibility and host range. In this study, paired fecal and saliva samples collected from children with viral gastroenteritis, as well as paired serum and saliva samples collected from the general population in south China were studied to evaluate potential association between rotavirus infections and human HBGA phenotypes. Rotavirus was detected in 75 (28%) of 266 fecal samples and P[8] rotaviruses were found to be the predominant genotype. The HBGA phenotypes of the rotavirus-infected children were determined through their saliva samples. Secretor statuses were found to correlate with the risk of rotavirus infection and all P[8]/P[4] rotavirus infected children were secretors. Accordingly, recombinant VP8* proteins of the P[8]/P[4] rotaviruses bound saliva samples from secretor individuals. Furthermore, correlation between serum P[8]/P[4]-specific IgG and host Lewis and secretor phenotypes has been found among 206 studied serum samples. Our study supported the association between rotavirus infection and the host HBGA phenotypes, which would help further understanding of rotavirus host range and epidemiology.

Noroviruses (NoVs) are the leading cause of viral acute gastroenteritis affecting people of all ages worldwide. The disease is difficult to control due to its widespread nature and lack of an antiviral or vaccine. NoV infection relies on the interaction of the viruses with histo-blood group antigens (HBGAs) as host receptors. Here we investigated inhibition effects of Chinese medicinal herbs against NoVs binding to HBGAs for potential antivirals against NoVs. Blocking assays was performed using the NoV protrusion (P) protein as NoV surrogate and saliva as HBGAs. Among 50 clinically effective Chinese medicinal herbs against gastroenteritis diseases, two herbs were found highly effective. Chinese Gall blocked NoV P dimer binding to type A saliva at IC(50)=5.35 μg/ml and to B saliva at IC(50)=21.7 μg/ml. Similarly, Pomegranate blocked binding of NoV P dimer to type A saliva at IC(50)=15.59 μg/ml and B saliva at IC(50)=66.67 μg/ml. Literature data on preliminary biochemistry analysis showed that tannic acid is a common composition in the extracts of the two herbs, so we speculate that it might be the effective compound and further studies using commercially available, highly purified tannic acid confirmed the tannic acid as a strong inhibitor in the binding of NoV P protein to both A and B saliva (IC(50)≈0.1 μM). In addition, we tested different forms of hydrolysable tannins with different alkyl esters, including gallic acid, ethyl gallate, lauryl gallate, octyl gallate and propyl gallate. However, none of these tannins-derivatives revealed detectable inhibiting activities. Our data suggested that tannic acid is a promising candidate antiviral against NoVs.

During the past norovirus (NoV) epidemic season, a new GII.17 variant emerged as a predominant NoV strain, surpassed the GII.4 NoVs, causing outbreaks of acute gastroenteritis (AGE) in China. Here we report a study of an AGE outbreak in an elementary school in December 2014 caused by the new GII.17 NoV to explore the potential mechanism behind the sudden epidemics of the GII.17 NoV. A total of 276 individuals were sick with typical NoV infection symptoms of vomiting (93.4%), abdominal pain (90.4%), nausea (60.0%) and diarrhea (10.4%) at an attack rate of 5.7–16.9%. Genotyping of the symptomatic patients showed that individuals with a secretor positive status, including those with A, B and O secretors and Lewis positive blood types, were sensitive to the virus, while the non-secretors and the Lewis negative individual were not. Accordingly, the recombinant capsid P protein of the GII.17 isolate showed a wide binding spectrum to saliva samples of all A, B and O secretors. Thus, the broad binding spectrum of the new GII.17 variant could explain its widely spread nature in China and surrounding areas in the past two years.

Noroviruses (NVs) are important causes of nonbacterial gastroenteritis in humans, but the role of NVs as a cause of diseases in the Chinese people, particularly in Chinese military personnel, remains unclear. This study investigated antibody prevalence and factors that associate with the prevalence of antibody to NVs among students attending a military medical university. Serum specimens were tested by an enzyme-linked immunosorbent assay for immunoglobulin G antibody to recombinant capsid antigens of three NVs (rNorwalk, rMxV, and rVA387). Of 588 serum samples tested, the antibody prevalence was 88.9, 54.1, or 90.0% for the three antigens, respectively. There were significant differences in the prevalence of antibody to rMxV between blood types ( P < 0.05); the prevalence for type O was the highest (62.5%), and the prevalence for type B was the lowest (49.1%). The average optical density values for antibody to rNorwalk and rMxV were lowest among students with type B. The number of students who did not have antibody to any of the three antigens was the highest for blood type B (6.9%) compared to other blood types (0.8 to 3.4% [ P < 0.006]). The antibody prevalence also varied with the hometown residencies of the students before joining the military, with the highest rates for students from rural areas, lower rates for students from small towns or villages, and the lowest rates for students from large cities. The numbers of students who did not have antibody to any of the three antigens were highest for students from the large cities, lower for students from small towns or villages, and lowest for students from rural areas. The distribution of ABO blood types did not differ among the three groups. These data suggest that NVs are prevalent in China and that both genetic and environmental factors play a role in NV infection.

Rotavirus (RV) and norovirus (NoV) are the two most important causes of viral gastroenteritis. While vaccine remains an effective prophylactic strategy, development of other approaches, such as passive immunization to control and treat clinical infection and illness of these two pathogens, is necessary. Previously we demonstrated that high titers of NoV-specific IgY were readily developed by immunization of chickens with the NoV P particles. In this study, we developed a dual IgY against both RV and NoV through immunization of chickens with a divalent vaccine comprising neutralizing antigens of both RV and NoV. This divalent vaccine, named P-VP8(∗) particle, is made of the NoV P particle as a carrier with the RV spike protein VP8(∗) as a surface insertion. Approximately 45mg of IgY were readily obtained from each yolk with high titers of anti-P particle and anti-VP8(∗) antibodies detected by ELISA, Western blot, HBGA blocking (NoV and RV) and neutralization (RV) assays. Reductions of RV replication were observed with viruses treated with the IgY before and after inoculation into cells, suggesting an application of the IgY as both prophylactic and therapeutic treatment. Collectively, our data suggested that the P-VP8(∗) based IgY could serve as a practical approach against both NoV and RV.

Noroviruses (NoVs) are a leading cause of epidemic acute gastroenteritis affecting millions of people worldwide. Understanding of NoV remains limited due to the lack of a cell culture system and small animal models. Currently, there are no available vaccines or antivirals against NoVs. In this study, an approach for large-scale production of anti-NoV antibodies for use as a potential treatment for NoV disease using passive immunization was evaluated. NoV-specific immunoglobulins (IgY) were produced by immunizing chickens with NoV P particles. The birds continuously produced high titers of antibodies in their eggs for at least 3 months, in which NoV-specific antibody levels reached 4.7-9.2 mg/egg yolk. The egg yolk antibodies strongly reacted with NoV P particles by both ELISA and Western blot and blocked NoV virus-like particle (VLP) and P particle binding to the histo-blood group antigen (HBGA) receptors with a BT50 of about 1:800. The blocking activity of the chicken IgY remained after an incubation at 70°C for 30 min or treatment at pH 4 to 9 for 3 h. These data suggested that chicken IgY could be a practical strategy for large-scale production of anti-NoV antibodies for potential use as passive immunization against NoV infection, as well as for diagnostic purposes.

Human noroviruses (NoVs) are an important cause of epidemic acute gastroenteritis. Their role in sporadic cases, however, is less clear. In this study, we performed a two-year surveillance (September 2005 to August 2007) of NoV gastroenteritis in outpatient clinics in a southern city of China, Jiangmen City. NoVs were detected in 115 patients (115/881, 13.1%) with 30 (26.1%) co-infections with rotaviruses. Sequence analysis showed that all 115 NoVs belonged to genogroup II, with GII.4 being the most predominant (87.8%). NoV-associated infection can be seen year-around, with autumn and winter peaks. This study provides basic information on sporadic cases of major NoV gastroenteritis in children in different seasons, which is valuable for future disease control and prevention.

To observe the changes in the hemodynamics of rats with immunological liver fibrosis and explore the pathogenesis of "blood stasis" in liver fibrosis.Rat models of liver fibrosis were established by multiple intraperitoneal injections of pig serum. The hematocrit, blood viscosity at the shear rate of 150/s, 30/s, 5/s, and 1/s, serum markers for liver fibrosis, and serum transaminase levels were measured in the control and model rats.The hematocrit, blood viscosity at different shear rates, hyaluronic acid (HA), laminin (LN), procollagen type III (PCIII), type IV collagen (CIV), glutamic-pyruvic transaminase (ALT) and glutamic-oxaloacetic transaminase (AST) increased significantly in the rats with experimental liver fibrosis appeared as compared with those in the control rats. Positive correlations were noted between blood viscosity at different shear rates and serum concentrations of the fibrosis markers (HA, LN, PCIII, and CIV) in the model rats.The changes in the hemodynamics in rats with immunological liver fibrosis suggests the role of "blood stasis" in the pathogenesis of liver fibrosis and provide experimental evidence for therapies to "activate the blood circulation and dissipate blood stasis" for treatment of liver fibrosis.

To analyze the proteomic characteristics of Gan (肝)-stagnancy syndrome (GSS) by seeking the differential protein in blood and tissues of GSS model rats. GSS model rats were established by chronic restraint stress, keeping rats in restrain chamber for 6 h every day for 21 successive days. Their blood and liver samples were collected at the end of experiment for differential protein detection with methods of isoelectrofocusing and polyacrylamide SDS-PAGE, silver staining, and scanning. The gel images were analyzed with Imagemaster 2D Elite software, and the excavated differential protein spots were identified with matrix assistant laser resolving TOF mass spectrometry, Western blot, ELISA, and RT-PCR, respectively. A method for isolating the protein in blood serum and tissues by two-dimensional gel electrophoresis was established and optimized. Six serum proteins and three liver proteins that differentially expressed were identified. The down-regulated differential proteins in serum of GSS model rats were serum albumin precursor, beta 1 globin, antibody against muscle acetylcholine receptor, Ig lambda-2 C region, and transthyretin (TTR), and those in liver tissue were aryl sulfotransferase, enoyl-CoA hydratase, and TTR. TTR down-regulation was found in both serum and liver. Preliminary biological information analysis showed that these differential proteins involved in immune, neuroendocrine, nutrition, and substance metabolism. Proteomic analysis of differential proteins showed that TTR, aryl sulfotransferase, and enoyl-CoA hydratase expressions are downregulated in the GSS model rats, suggesting that the susceptibility of cancer could be enhanced by chronic stress.