Animals ; Birds ; Communicable Disease Control ; methods ; Disease Outbreaks ; prevention & control ; statistics & numerical data ; Health Planning ; Humans ; Influenza A Virus, H5N1 Subtype ; Influenza in Birds ; epidemiology ; virology ; Risk Factors ; Singapore ; epidemiology

Adolescent ; Adult ; Aged ; Blood Glucose ; analysis ; Cross-Over Studies ; Diabetes Mellitus ; blood ; drug therapy ; Female ; Glycated Hemoglobin A ; analysis ; Humans ; Insulin ; analogs & derivatives ; therapeutic use ; Insulin Lispro ; Male ; Middle Aged

Objective: To evaluate the in vitro activities of the ethyl acetate (EA) fraction of Houttuynia cordata (H. cordata) Thunb. (Saururaceae) and three of its constituent flavonoids (quercetin, quercitrin and rutin) against murine coronavirus and dengue virus (DENV). Methods: The antiviral activities of various concentrations of the EA fraction of H. cordata and flavonoids were assessed using virus neutralization tests against mouse hepatitis virus (MHV) and DENV type 2 (DENV-2). Cinanserin hydrochloride was also tested against MHV. The EA fraction of H. cordata was tested for acute oral toxicity in C57BL/6 mice. Results: The EA fraction of H. cordata inhibited viral infectivity up to 6 d. Cinanserin hydrochloride was able to inhibit MHV for only 2 d. The 50% inhibitory concentrations (IC

Objective: To investigate the inhibitory effects against dengue virus serotype 2 (DENV-2) by five different fractions (extracted by methanol, ethanol, benzene, chloroform and n-hexane) of Rumex dentatus, Commelina benghalensis, Ajuga bracteosa and Ziziphus mauritiana, as well as their constituents (gallic acid, emodin, and isovanillic acid). Methods: All the samples were tested for cytotoxicity on baby hamster kidney cells by MTT assay and for anti-DENV-2 activity by plaque reduction neutralization assay using two DENV-2 doses (45 and 90 plaque- forming units or PFU). Results: All the samples except isovanillic acid exhibited significant prophylactic effects against DENV-2 infectivity (without cytotoxicity) when administered to cells before infection, but were not effective when given 6 h post-infection. The methanol extract of Rumex dentatus demonstrated the highest antiviral efficacy by inhibiting DENV-2 replication, with IC

The respiratory tract is primary contact site of the body and environment,and it is ventilated by 10-20 thousand liters of air per day.Inevitably,the respiratory system comes into contact with airborne microbes,which contain the disease-causing pathogens.Airway epithelial cells (AECs) are known to have innate sensor functions,which are similar to the "professional" immune cells,such as alveolar macrophage and sub-or intra-epithelial dendritic cells (DCs).Thus AECs are able to detect invading microbial danger including different types of respiratory viruses,and mount a potent host response,for example,activating type Ⅰ interferon signaling pathway genes.To avoid chronic inflammation and maintain the immunological homeostasis,the pulmonary system has developed intrinsic mechanisms to control local immune responses.Most recently,the role of AECs in control of local immunity has gained much attention,as 1) AECs express the pattern recognition receptors (PRRs),such as Toll-like receptors,retinoic acid inducible gene Ⅰ (RIG-Ⅰ)-like receptor,and so on,thus AECs are equipped to Participate in innate detection of microbial encounter;2) To keep immunological homeostasis in the respiratory tract,AECs behave not only as innate immune sensors but also as immune modulators in parallel,through modulating the sensitivity of innate immune sensing of both AECs per se and sub-or intra-epithelial immune cells;3) Loss of modularity capacity of AECs might be involved in the development of chronic airway diseases.In present review,how the AECs act will be intensively discussed in response to respiratory viruses and modulate the local immunity through cis-and trans-factors (direct and indirect factors),as well as the consequence of impairment of this control of local immunity,in the development and exacerbation of airway diseases,such as acute and chronic rhinosinusitis.

Positive-sense RNA viruses modify intracellular calcium stores, endoplasmic reticulum and Golgi apparatus (Golgi) to generate membranous replication organelles known as viral factories. Viral factories provide a conducive and substantial enclave for essential virus replication via concentrating necessary cellular factors and viral proteins in proximity. Here, we identified the vital role of a broad-spectrum antiviral, peruvoside in limiting the formation of viral factories. Mechanistically, we revealed the pleiotropic cellular effect of Src and PLC kinase signaling via cyclin-dependent kinase 1 signaling leads to Golgi-specific brefeldin A-resistance guanine nucleotide exchange factor 1 (GBF1) phosphorylation and Golgi vesiculation by peruvoside treatment. The ramification of GBF1 phosphorylation fosters GBF1 deprivation consequentially activating downstream antiviral signaling by dampening viral factories formation. Further investigation showed signaling of ERK1/2 pathway via cyclin-dependent kinase 1 activation leading to GBF1 phosphorylation at Threonine 1337 (T1337). We also showed 100% of protection in peruvoside-treated mouse model with a significant reduction in viral titre and without measurable cytotoxicity in serum. These findings highlight the importance of dissecting the broad-spectrum antiviral therapeutics mechanism and pave the way for consideration of peruvoside, host-directed antivirals for positive-sense RNA virus-mediated disease, in the interim where no vaccine is available.