Functional characterization of UBXN-6, a C-terminal cofactor of CDC-48, in C. elegans.

CDC-48 is a AAA (ATPases associated with diverse cellular activities) chaperone and participates in a wide range of cellular activities. Its functional diversity is determined by differential binding of a variety of cofactors. In this study, we analyzed the physiological role of a CDC-48 cofactor UBXN-6 in Caenorhabditis elegans.

Daidzein reductase of Eggerthella sp. YY7918, its octameric subunit structure containing FMN/FAD/4Fe-4S, and its enantioselective production of R-dihydroisoflavones.

S-Equol is a metabolite of daidzein, a type of soy isoflavone, and three reductases are involved in the conversion of daidzein by specific intestinal bacteria. S-Equol is thought to prevent hormone-dependent diseases. We previously identified the equol producing gene cluster (eqlABC) of Eggerthella sp.

DNA methylation analyses of the candidate genes identified by a methylome-wide association study revealed common epigenetic alterations in schizophrenia and bipolar disorder.

Aim: Schizophrenia (SZ) and bipolar disorder (BD) have been known to share genetic and environmental risk factors, and complex gene-environmental interactions may contribute to their pathophysiology. In contrast to high genetic overlap between SZ and BD, as revealed by genome-wide association studies, the extent of epigenetic overlap remains largely unknown. In the present study, we explored whether SZ and BD share epigenetic risk factors in the same manner as they share genetic components.

Generation of biallelic F0 mutants in medaka using the CRISPR/Cas9 system.

Several animal models generated by genome editing methods develop somatic mosaic mutations including wild-type genome sequence in F0 generation because it is difficult to use editing tools at the one-cell stage. Producing complete knockout animals quickly is a great advantage in determining the function of target genes. This study investigated the generation of F0 knockout medaka using the CRISPR/Cas9 system.

A conserved α helix of Bcs1, a mitochondrial AAA chaperone, is required for the Respiratory Complex III maturation.

Bcs1 is a transmembrane chaperone in the mitochondrial inner membrane, and is required for the mitochondrial Respiratory Chain Complex III assembly. It has been shown that the highly-conserved C-terminal region of Bcs1 including the AAA ATPase domain in the matrix side is essential for the chaperone function. Here we describe the importance of the N-terminal short segment located in the intermembrane space in the Bcs1 function.

Antiviral activity of diarylheptanoid stereoisomers against respiratory syncytial virus in vitro and in vivo.

We previously showed that (5S)-5-hydroxy-7-(4-hydroxyphenyl)-1-phenylhept-3-one (AO-0011) and (5S)-5-methoxy-1,7-diphenylhept-3-one (AO-0016) isolated from Alpinia officinarum exhibited stronger anti-influenza virus activity and anti-respiratory syncytial virus (RSV) activity, respectively, than the other isolated diarylheptanoids. In this study, we synthesized an enantiomer (AO-0503) and racemate (AO-0504) of AO-0011 and an enantiomer (AO-0514) of AO-0016. The anti-RSV activities of the three stereoisomers (AO-0503, AO-0504, and AO-0514) and AO-0011 were examined in vitro and in vivo to evaluate the stereoisomeric effect on anti-RSV activity.

Antiviral activities of diarylheptanoids isolated from Alpinia officinarum against respiratory syncytial virus, poliovirus, measles virus, and herpes simplex virus type 1 in vitro.

Alpinia officinarum has been used as a folk medicine and contains diarylheptanoids that have various biological activities. However, their antiviral activities are less elucidated. We examined the antiviral activities of nine diarylheptanoids isolated from A.

Efficacy of Brazilian Propolis against Herpes Simplex Virus Type 1 Infection in Mice and Their Modes of Antiherpetic Efficacies.

Ethanol extracts (AF-06, 07, and 08, 10 mg/kg) of Brazilian propolis were administered orally to cutaneously herpes simplex virus type 1 (HSV-1)-infected mice three times daily on days 0 to 6 after infection to evaluate their efficacies against HSV-1 infection and significantly limited development of herpetic skin lesions. AF-07 and 08 significantly reduced virus titers in brain and/or skin on day 4 without toxicity, but AF-08 had no anti-HSV-1 activity in vitro. AF-06 and 08 significantly enhanced delayed-type hypersensitivity (DTH) to inactivated HSV-1 antigen in infected mice.

In vitro and in vivo anti-influenza virus activity of diarylheptanoids isolated from Alpinia officinarum.

Background: Diarylheptanoids (AO-0002 [7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-4E-hepten-3-one] and AO-0011 [(5S)-5-hydroxy-7-(4''-hydroxyphenyl)-1-phenyl-3-heptanone]) isolated from Alpinia officinarum have been reported to exhibit anti-influenza virus activity in vitro. Hence, efficacies against influenza virus infection and the mode of antiviral action were evaluated in vivo and in vitro, respectively.

Methods: In a murine influenza virus infection model, diarylheptanoids were orally administered three times daily to mice infected with influenza A/PR/8/34 virus for 6 days after infection.

Functional disorder of primary immunity responding to respiratory syncytial virus infection in offspring mice exposed to a flame retardant, decabrominated diphenyl ether, perinatally.

Perinatal exposure to a representative flame retardant, decabrominated diphenyl ether (DBDE), was shown previously to increase viral titers in the lungs of respiratory syncytial virus (RSV)-infected offspring on day 5 post-infection, resulting in exacerbation of pneumonia. In this study, the significant increase of pulmonary viral titers was confirmed even on day 1 post-infection and the effect on the primary immune response to RSV infection were examined to assess a mode of DBDE action on developmental immunotoxicity. On day 1 after infection, the secretion of both TNF-alpha and IL-6 decreased significantly in the bronchoalveolar lavage fluid prepared from RSV-infected offspring exposed to DBDE perinatally, but IL-1beta increased.

Antiviral activities of diarylheptanoids against influenza virus in vitro.

The anti-influenza A/PR/8/34 (H1N1) virus activities of ten diarylheptanoids isolated from Alpinia officinarum were examined using the MTT method. The 50% inhibitory concentration of each diarylheptanoid examined was clearly lower than its 50% cytotoxic concentration determined by the MTT assay and/or maximum non-cytotoxic concentration (MNCC) determined by the morphological change of cells. In particular, the influenza virus was more susceptible to 7-(4''-hydroxy-3''-methoxyphenyl)-1-phenyl-4E-hepten-3-one (3) and (5S)-5-hydroxy-7-(4''-hydroxyphenyl)-1-phenyl-3-heptanone (8) than the other diarylheptanoids.

Effects of tetrabromobisphenol A, a brominated flame retardant, on the immune response to respiratory syncytial virus infection in mice.

Effects of the brominated flame retardants (BFRs), decabrominated diphenyl ether (DBDE), hexabromocyclododecane (HBCD), and tetrabromobisphenol A (TBBPA), on host immunity of mice were evaluated using respiratory syncytial virus (RSV) infection. Five-week-old female mice were fed a diet containing 1% BFRs for 28days, and subsequently infected with RSV. No toxicological sign was observed in BFR-treated mice before infection.

Modulation of cytokine production by 7-hydroxycoumarin in vitro and its efficacy against influenza infection in mice.

We previously demonstrated that 7-hydroxycoumarin (7HC) was effective in reducing proinflammatory cytokine production in lipopolysaccharide-exposed macrophage-like P388D1 cells and fever production by suppressing the increase in interleukin (IL)-1alpha production in an influenza virus-intranasal infection model in mice. In this study, we assessed the effects of modulation of cytokine production by 7HC on influenza virus infection in relation to its efficacy in influenza virus-infected mice. 7HC was confirmed to suppress proinflammatory cytokine levels in P388D1 cells due to influenza virus infection.