Influenza A Virus Nucleoprotein Exploits Hsp40 to Inhibit PKR Activation

BACKGROUND: Double-stranded RNA dependent protein kinase (PKR) is a key regulator of the anti-viral innate immune response in mammalian cells. PKR activity is regulated by a 58 kilo Dalton cellular inhibitor (P58(IPK)), which is present in inactive state as a complex with Hsp40 under normal conditions. In case of influenza A virus (IAV) infection, P58(IPK) is known to dissociate from Hsp40 and inhibit PKR activation. However the influenza virus component responsible for PKR inhibition through P58(IPK) activation was hitherto unknown. PRINCIPAL FINDINGS: Human heat shock 40 protein (Hsp40) was identified as an interacting partner of Influenza A virus nucleoprotein (IAV NP) using a yeast two-hybrid screen. This interaction was confirmed by co-immunoprecipitation studies from mammalian cells transfected with IAV NP expressing plasmid. Further, the IAV NP-Hsp40 interaction was validated in mammalian cells infected with various seasonal and pandemic strains of influenza viruses. Cellular localization studies showed that NP and Hsp40 co-localize primarily in the nucleus. During IAV infection in mammalian cells, expression of NP coincided with the dissociation of P58(IPK) from Hsp40 and decrease PKR phosphorylation. We observed that, plasmid based expression of NP in mammalian cells leads to decrease in PKR phosphorylation. Furthermore, inhibition of NP expression during influenza virus replication led to PKR activation and concomitant increase in eIF2α phosphorylation. Inhibition of NP expression also led to reduced IRF3 phosphorylation, enhanced IFN β production and concomitant reduction of virus replication. Taken together our data suggest that NP is the viral factor responsible for P58(IPK) activation and subsequent inhibition of PKR-mediated host response during IAV infection. SIGNIFICANCE: Our findings demonstrate a novel role of IAV NP in inhibiting PKR-mediated anti-viral host response and help us understand P58(IPK) mediated inhibition of PKR activity during IAV infection

Decomposition-Assembly of Tetraphenylethylene Nanoparticles With Uniform Size and Aggregation-Induced Emission property

Tetraphenylethylene (TPE)-substituted poly(allylamine hydrochloride) (PAH-g-TPE) is synthesized by a Schiff base reaction between PAH and TPE-CHO. The PAH-g-TPE forms micelles in water at pH 6, which are further transformed into pure TPE-CHO nanoparticles (NPs) with a diameter of approximate to 300 nm after incubation in a solution of low pH value. In contrast, only amorphous precipitates are obtained when TPE-CHO methanol solution is incubated in water. The aggregation-induced emission feature of the TPE molecule is completely retained in the TPE NPs, which can be internalized into cells and show blue fluorescence. Formation mechanism of the TPE NPs is proposed by taking into account the guidance effect of linear and charged PAH molecules, and the propeller-stacking manner between the TPE-CHO molecules

Effectiveness and safety of traditional Chinese medical bath therapy combined with ultraviolet irradiation in the treatment of psoriasis: A systematic review and meta-analysis of randomized controlled trials

<div><p>Background and objective</p><p>To systematically evaluate the clinical effects and safety of traditional Chinese medical bath therapy (TCMBT) combined with ultraviolet irradiation in the treatment of psoriasis.</p><p>Methods</p><p>Electronic database retrieval was utilized. The foreign retrieval databases consulted included those of the Cochrane Library, PubMed and EMBASE; the domestic retrieval databases included the Chinese Biomedical Literature Database (Sino-Med), the China National Knowledge Infrastructure (CNKI), VIP and the WangFang Database. Clinical randomized controlled trials were conducted to evaluate the effects of TCMBT combined with ultraviolet irradiation in the treatment of psoriasis; the language of the retrieved articles was Chinese or English. Each database was searched from its inception to August 1, 2015. Two researchers independently collected the data and analyzed the methodology of the documented literature. The researchers conducted a meta-analysis with RevMan 5.2.3 software.</p><p>Results</p><p>According to the available literature, 25 RCTs (randomized controlled trials) of low research quality were conducted. According to the meta-analysis, the total effective rate of TCMBT combined with ultraviolet irradiation was relatively higher than that of ultraviolet irradiation alone. The recurrence rate, incidence of adverse reactions and Psoriasis Area and Severity Index (PASI) for the combined therapy was lower than that of ultraviolet irradiation (<i>P<0</i>.<i>05</i>).</p><p>Conclusion</p><p>For the treatment of psoriasis, the clinical effects and safety of TCMBT combined with ultraviolet irradiation are generally better than those of ultraviolet irradiation alone. However, the original literature was written in Chinese, and the quality of the studies was not high. Thus, it is difficult to confirm the clinical effects and safety of TCMBT combined with ultraviolet irradiation. It is necessary to conduct a scientific, normalized and high-quality RCT with multiple large samples and centers.</p></div

A New Ursane-Type Nor-Triterpenoid from the Leaves of Eucommia ulmoides Oliv.

A new ursane-type nortriterpenoid, (11S,12S)-4-methyl-11,12-epoxy-2-hydroxy-3-oxoursa-1,4-dine-28-oic acid &amp;#947;-lactone (1), named ulmoidol A, together with ten known compounds: ulmoidol (2), corosolic acid (3), 2&amp;#945;,3&amp;#945;-dihydroxy-24-nor-4(23),12-oleanadien-28-oic acid (4), oleanolic acid (5), ursolic acid (6), cycloart-3&amp;#946;, 25-diol (7), foliasalacioside B1 (8), (6R,7E,9R)-9-hydroxy-4,7-megastigmadien-3-one-9-O-&amp;#945;-L-arabinopyranosyl-(1&amp;#8594;6)-&amp;#946;-D-glucopyranoside (9), (6R,7E,9R)-9-hydroxy-4,7-megastigma-dien-3-one-9-O-&amp;#946;-D-xylopyranosyl-(1&amp;#8594;6)-&amp;#946;-D-glucopyranoside (10), and quercetin 3-O-sambubioside (11) were isolated from the leaves of Eucommia ulmoides Oliv. The structure of compound 1 was determined by extensive spectroscopic analysis, and its absolute configuration was determined by CD experiments and a computational method. Compounds 3, 4, 7&amp;#8211;10 were isolated from this plant for the first time. Compounds 3 and 4 showed inhibition to PTPIB activities, with IC50 values of 0.69 and 3.98 &amp;#956;M, respectively

Comparison of recurrence rate between TCMBT plus ultraviolet irradiation versus ultraviolet irradiation treatment.

<p>Comparison of recurrence rate between TCMBT plus ultraviolet irradiation versus ultraviolet irradiation treatment.</p

Comparison of the total effective rate of TCMBT plus ultraviolet irradiation treatment compared to ultraviolet irradiation treatment.

<p>Comparison of the total effective rate of TCMBT plus ultraviolet irradiation treatment compared to ultraviolet irradiation treatment.</p

The incidence of adverse reactions in TCMBT plus ultraviolet irradiation compared to ultraviolet irradiation treatment.

<p>The incidence of adverse reactions in TCMBT plus ultraviolet irradiation compared to ultraviolet irradiation treatment.</p

Study selection flow chart.

<p>Study selection flow chart.</p