Duration of viral shedding of Influenza A (H1N1) virus infection treated with oseltamivir and/or Traditional Chinese Medicine in China: A retrospective analysis

AbstractObjectiveH1N1 was a new and potentially serious infectious disease, in human, the severity of influenza can vary from mild to severe, thus to find an effective and safety way to control the influenza pandemic is of crucial importance. This retrospective study describes the duration of viral shedding in H1N1 patients that were hospitalized and treated in China.MethodsClinical data were collected from May to July, 2009 in China for 963 patients with influenza A (H1N1) virus infection. Patients were treated based on the guidelines issued by the Chinese Ministry of Health. The primary outcome was duration of viral shedding and statistical comparisons were performed.ResultsIn the patients with body temperature greater than 38.0°C, there were no differences in virus shedding duration among the patients taking oseltamivir within two days, patients undergoing Traditional Chinese Medicine (TCM) therapy or those receiving no drug therapy. In patients with body temperature ≥38.1°C, TCM therapy reduced the viral shedding duration (P<0.05, vs. oseltamivir therapy). Furthermore, taking oseltamivir two days after onset of symptoms might prolong the virus shedding duration (P<0.05, vs. taking oseltamivir less than 2 days of onset).ConclusionTCM therapy is effective for reducing the length of virus shedding in patients with body temperature ≥38.0°C. Oseltamivir used for reducing virus shedding duration should be taken within two days of onset

Paclitaxel Enhances the Innate Immunity by Promoting NLRP3 Inflammasome Activation in Macrophages

Microtubules play critical roles in regulating the activation of NLRP3 inflammasome and microtubule-destabilizing agents such as colchicine have been shown to suppress the activation of this inflammasome. However, it remains largely unknown whether paclitaxel, a microtubule-stabilizing agent being used in cancer therapy, has any influences on NLRP3 inflammasome activation. Here we showed that paclitaxel pre-treatment greatly enhanced ATP- or nigericin-induced NLRP3 inflammasome activation as indicated by increased release of cleaved caspase-1 and mature IL-1β, enhanced formation of ASC speck, and increased gasdermin D cleavage and pyroptosis. Paclitaxel time- and dose-dependently induced α-tubulin acetylation in LPS-primed murine and human macrophages and further increased ATP- or nigericin-induced α-tubulin acetylation. Such increased α-tubulin acetylation was significantly suppressed either by resveratrol or NAD+ (coenzyme required for deacetylase activity of SIRT2), or by genetic knockdown of MEC-17 (gene encoding α-tubulin acetyltransferase 1). Concurrently, the paclitaxel-mediated enhancement of NLRP3 inflammasome activation was significantly suppressed by resveratrol, NAD+, or MEC-17 knockdown, indicating the involvement of paclitaxel-induced α-tubulin acetylation in the augmentation of NLRP3 inflammasome activation. Similar to paclitaxel, epothilone B that is another microtubule-stabilizing agent also induced α-tubulin acetylation and increased NLRP3 inflammasome activation in macrophages in response to ATP treatment. Consistent with the in vitro results, intraperitoneal administration of paclitaxel significantly increased serum IL-1β levels, reduced bacterial burden, dampened infiltration of inflammatory cells in the liver, and improved animal survival in a mouse model of bacterial infection. Collectively, our data indicate that paclitaxel potentiated NLRP3 inflammasome activation by inducing α-tubulin acetylation and thereby conferred enhanced antibacterial innate responses, suggesting its potential application against pathogenic infections beyond its use as a chemotherapeutic agent

An Updated Search of Steady TeV γ−\gamma-Ray Point Sources in Northern Hemisphere Using the Tibet Air Shower Array

Using the data taken from Tibet II High Density (HD) Array (1997 February-1999 September) and Tibet-III array (1999 November-2005 November), our previous northern sky survey for TeV $\gamma-$ray point sources has now been updated by a factor of 2.8 improved statistics. From $0.0^{\circ}$ to $60.0^{\circ}$ in declination (Dec) range, no new TeV $\gamma-$ray point sources with sufficiently high significance were identified while the well-known Crab Nebula and Mrk421 remain to be the brightest TeV $\gamma-$ray sources within the field of view of the Tibet air shower array. Based on the currently available data and at the 90% confidence level (C.L.), the flux upper limits for different power law index assumption are re-derived, which are approximately improved by 1.7 times as compared with our previous reported limits.Comment: This paper has been accepted by hepn

Effect of particle size on the physicochemical and antioxidant properties of Forsythia suspensa (Thunb.)Vahl leaf powders

Four powders of Forsythia suspensa leaf were prepared by coarse grinding and subsequent ball milling. The effects of particle size on the physicochemical and antioxidant properties of the powders were evaluated. The results showed that the particle size of the powder decreased from 107.99 to 29.20 mu m by ball milling for 5 h. In addition, the ball-milled powders had substantial advantages in water holding, solubility and swelling capacities. Thus, the ball-milled powders had a better dissolution of phenolic, flavonoid, and polysaccharide components (25.45, 1.99 and 44.19 mg/g of powder for 5 h of ball milling), ultimately resulting in a superior antioxidant activity (maximum reductions of 14.96% and 19.20% for DPPH and ABTS radicals, respectively). The FTIR analysis showed that the structure of the active ingredients remained intact after ball milling. In conclusion, ball milling is a promising technique for preparing Forsythia suspensa leaf powder with improved physicochemical and biological properties

Effect of particle size on the physicochemical and antioxidant properties of Forsythia suspensa (Thunb.)Vahl leaf powders

Four powders of Forsythia suspensa leaf were prepared by coarse grinding and subsequent ball milling. The effects of particle size on the physicochemical and antioxidant properties of the powders were evaluated. The results showed that the particle size of the powder decreased from 107.99 to 29.20 mu m by ball milling for 5 h. In addition, the ball-milled powders had substantial advantages in water holding, solubility and swelling capacities. Thus, the ball-milled powders had a better dissolution of phenolic, flavonoid, and polysaccharide components (25.45, 1.99 and 44.19 mg/g of powder for 5 h of ball milling), ultimately resulting in a superior antioxidant activity (maximum reductions of 14.96% and 19.20% for DPPH and ABTS radicals, respectively). The FTIR analysis showed that the structure of the active ingredients remained intact after ball milling. In conclusion, ball milling is a promising technique for preparing Forsythia suspensa leaf powder with improved physicochemical and biological properties

Green Extraction of Forsythoside A, Phillyrin and Phillygenol from Forsythia suspensa Leaves Using a beta-Cyclodextrin-Assisted Method

In this study, a green process of beta-cyclodextrin (beta-CD)-assisted extraction of active ingredients from Forsythia suspensa leaves was developed. Firstly, the optimal process of extraction was as follows: the ratio between Forsythia suspensa leaves and beta-CD was 3.61:5, the solid-liquid ratio was 1:36.3, the temperature was 75.25 degrees C and the pH was 3.94. The yields of forsythoside A, phillyrin and phillygenol were 11.80 +/- 0.141%, 5.49 +/- 0.078% and 0.319 +/- 0.004%, respectively. Then, the structure characteristics of the beta-CD-assisted extract of Forsythia suspensa leaves (FSE-beta-CD) were analyzed using powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and molecular docking to demonstrate that the natural active products from Forsythia suspensa leaves had significant interactions with the beta-CD. Additionally, the loss of forsythoside A from aqueous FSE-CD at 80 degrees C was only 12%, compared with Forsythia suspensa leaf extract (FSE) which decreased by 13%. In addition, the aqueous solubility of FSE-CD was significantly increased to 70.2 g/L. The EC50 for scavenging DPPH and ABTS radicals decreased to 28.98 ug/mL and 25.54 ug/mL, respectively. The results showed that the beta-CD-assisted extraction process would be a promising technology for bioactive compounds extracted from plants

Green Extraction of Forsythoside A, Phillyrin and Phillygenol from Forsythia suspensa Leaves Using a beta-Cyclodextrin-Assisted Method

In this study, a green process of beta-cyclodextrin (beta-CD)-assisted extraction of active ingredients from Forsythia suspensa leaves was developed. Firstly, the optimal process of extraction was as follows: the ratio between Forsythia suspensa leaves and beta-CD was 3.61:5, the solid-liquid ratio was 1:36.3, the temperature was 75.25 degrees C and the pH was 3.94. The yields of forsythoside A, phillyrin and phillygenol were 11.80 +/- 0.141%, 5.49 +/- 0.078% and 0.319 +/- 0.004%, respectively. Then, the structure characteristics of the beta-CD-assisted extract of Forsythia suspensa leaves (FSE-beta-CD) were analyzed using powder X-ray diffraction (PXRD), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC), scanning electron microscopy (SEM) and molecular docking to demonstrate that the natural active products from Forsythia suspensa leaves had significant interactions with the beta-CD. Additionally, the loss of forsythoside A from aqueous FSE-CD at 80 degrees C was only 12%, compared with Forsythia suspensa leaf extract (FSE) which decreased by 13%. In addition, the aqueous solubility of FSE-CD was significantly increased to 70.2 g/L. The EC50 for scavenging DPPH and ABTS radicals decreased to 28.98 ug/mL and 25.54 ug/mL, respectively. The results showed that the beta-CD-assisted extraction process would be a promising technology for bioactive compounds extracted from plants

Polymer Membranes with Vertically Oriented Pores Constructed by 2D Freezing at Ambient Temperature

Polymer membranes with well-controlled and vertically oriented pores are of great importance in the applications for water treatment and tissue engineering. On the basis of two-dimensional solvent freezing, we report environmentally friendly facile fabrication of such membranes from a broad spectrum of polymer resources including poly­(vinylidene fluoride), poly­(l-lactic acid), polyacrylonitrile, polystyrene, polysulfone and polypropylene. Dimethyl sulfone, diphenyl sulfone, and arachidic acid are selected as green solvents crystallized in the polymer matrices under two-dimensional temperature gradients induced by water at ambient temperature. Parallel Monte Carlo simulations of the lattice polymers demonstrate that the directional process is feasible for each polymer holding suitable interaction with a corresponding solvent. As a typical example of this approach, poly­(vinylidene fluoride) membranes exhibit excellent tensile strength, high optical transparence, and outstanding separation performance for the mixtures of yeasts and lactobacilli

Baicalin Inhibits NOD-Like Receptor Family, Pyrin Containing Domain 3 Inflammasome Activation in Murine Macrophages by Augmenting Protein Kinase A Signaling

The flavonoid baicalin has been reported to possess potent anti-inflammatory activities by suppressing inflammatory signaling pathways. However, whether baicalin can suppress the activation of NOD-like receptor (NLR) family, pyrin containing domain 3 (NLRP3) inflammasome in macrophages is largely unknown. Here, we showed that baicalin treatment dose-dependently inhibited adenosine triphosphate (ATP) or nigericin-induced NLRP3 inflammasome activation, as revealed by the decreased release of mature interleukin (IL)-1β, active caspase-1p10, and high-mobility group box-1 protein from lipopolysaccharide (LPS)-primed bone marrow-derived macrophages. The formation of ASC specks, a critical marker of NLRP3 inflammasome assembly, was robustly inhibited by baicalin in the macrophages upon ATP or nigericin stimulation. All these inhibitory effects of baicalin could be partly reversed by MDL12330A or H89, both of which are inhibitors of the protein kinase A (PKA) signaling pathway. Consistent with this, baicalin strongly enhanced PKA-mediated phosphorylation of NLRP3, which has been suggested to prevent ASC recruitment into the inflammasome. Of note, the PKA inhibitor H89 could block baicalin-induced NLRP3 phosphorylation on PKA-specific sites, further supporting PKA’s role in this process. In addition, we showed that when administered pre and post exposure to Escherichia coli infection baicalin treatment significantly improved mouse survival in bacterial sepsis. Baicalin administration also significantly reduced IL-1β levels in the sera of bacterial infected mice. Altogether, our results revealed that baicalin inhibited NLRP3 inflammasome activation at least partly through augmenting PKA signaling, highlighting its therapeutic potential for the treatment of NLRP3-related inflammatory diseases