C2C12筋管細胞においてモリンはデキサメタゾン誘導性の酸化ストレスと筋萎縮を抑制する

Glucocorticoids are the drugs most commonly used to manage inflammatory diseases. However, they are prone to inducing muscle atrophy by increasing muscle proteolysis and decreasing protein synthesis. Various studies have demonstrated that antioxidants can mitigate glucocorticoid-induced skeletal muscle atrophy. Here, we investigated the effect of a potent antioxidative natural flavonoid, morin, on the muscle atrophy and oxidative stress induced by dexamethasone (Dex) using mouse C2C12 skeletal myotubes. Dex (10 μM) enhanced the production of reactive oxygen species (ROS) in C2C12 myotubes via glucocorticoid receptor. Moreover, Dex administration reduced the diameter and expression levels of the myosin heavy chain protein in C2C12 myotubes, together with the upregulation of muscle atrophy-associated ubiquitin ligases, such as muscle atrophy F-box protein 1/atrogin-1, muscle ring finger protein-1, and casitas B-lineage lymphoma proto-oncogene-b. Dex also significantly decreased phosphorylated Foxo3a and increased total Foxo3a expression. Interestingly, Dex-induced ROS accumulation and Foxo3a expression were inhibited by morin (10 μM) pretreatment. Morin also prevented the Dex-induced reduction of myotube thickness, together with muscle protein degradation and suppression of the upregulation of atrophy-associated ubiquitin ligases. In conclusion, our results suggest that morin effectively prevents glucocorticoid-induced muscle atrophy by reducing oxidative stress

Ycf12 is a core subunit in the photosystem II complex

AbstractThe latest crystallographic model of the cyanobacterial photosystem II (PS II) core complex added one transmembrane low molecular weight (LMW) component to the previous model, suggesting the presence of an unknown transmembrane LMW component in PS II. We have investigated the polypeptide composition in highly purified intact PS II core complexes from Thermosynechococcus elongatus, the species which yielded the PS II crystallographic models described above, to identify the unknown component. Using an electrophoresis system specialized for separation of LMW hydrophobic proteins, a novel protein of ∼5 kDa was identified as a PS II component. Its N-terminal amino acid sequence was identical to that of Ycf12. The corresponding gene is known as one of the ycf (hypothetical chloroplast reading frame) genes, ycf12, and is widely conserved in chloroplast and cyanobacterial genomes. Nonetheless, the localization and function of the gene product have never been assigned. Our finding shows, for the first time, that ycf12 is actually expressed as a component of the PS II complex in the cell, revealing that a previously unidentified transmembrane protein exists in the PS II core complex

Prevention of contrast-induced nephropathy by chronic pravastatin treatment in patients with cardiovascular disease and renal insufficiency

SummaryBackgroundContrast-induced nephropathy (CIN) is known to increase morbidity and mortality of cardiovascular disease. Recent studies have shown statins prevented CIN after contrast media exposure, but optimal statin type and dosage are still unknown.PurposeThe aims of the present study were to evaluate whether chronic pravastatin treatment before scheduled coronary angiography or percutaneous coronary intervention could reduce the incidence of CIN and to elucidate the factors related to CIN in patients with renal insufficiency.MethodsWe studied 431 consecutive patients with renal insufficiency. One hundred ninety-four patients were receiving pravastatin treatment as standard chronic treatment of hypercholesterolemia. Serum creatinine levels were measured at baseline (pre-procedure) and within 48h after contrast media exposure (peak post-procedure). CIN was defined as an increase in the serum creatinine values of ≥25% or ≥0.5mg/dl after contrast media exposure. Logistic regression analysis was performed to evaluate the important factors related to CIN using four variables: age, pravastatin, pre-procedure serum creatinine, and contrast volume.ResultsCIN was observed in 36 patients (8.4%). Patients without pravastatin (p<0.01), high level pre-procedure serum creatinine (p<0.01), and high contrast volume (p=0.034) had a significantly higher incidence of CIN. Logistic regression analysis revealed that pravastatin treatment (χ2=6.549, p=0.011, odds ratio=0.34), pre-procedure serum creatinine (χ2=6.294, p=0.009, odds ratio=2.78), and contrast volume (χ2=4.484, p=0.034, odds ratio=1.01) were independently related to the decreased risk of CIN.ConclusionsChronic pravastatin treatment before contrast media exposure was important for preventing CIN in patients with renal insufficiency. Also, reducing the dose of contrast media was important for preventing CIN in patients with high-baseline serum creatinine levels

Blowing snow experiments for modeling of sublimation process using a large cold wind-tunnel

第3回極域科学シンポジウム/第35回極域気水圏シンポジウム 11月29日（木） 国立国語研究所 ２階ロビ

Effect Of Isometric Exercises Using an Active Therapeutic Movement Device for Patients with Acute Low Back Pain

Background: This study aimed to investigate the effects of isometric exercise using ATM®2 for acute low back pain (LBP) patients as a flexion or extension type. Methods: The subjects were twenty individuals (age 39.7±8.0ys, 12 males / 8 females) with acute LBP of less than four weeks duration who volunteered to participate in the study. The participants were allocated into four groups. First, the participants were classified by the direction of the movement causing pain in flexion and extension types. Secondly, both types were allocated randomly into two groups which were given exercises using the ATM®2 group and the usual care group. Finally, both groups were treated three times weekly for two weeks, totaling six sessions. Results: In terms of the extension type of LBP, the effect of the extension pain in the ATM®2-group significantly decreased pain (p=0.04) immediately. And in both groups significantly decreased (p=0.01, 0.001) for two weeks of intervention. Furthermore, in the flexion type of LBP, the effect of the flexion pain in the ATM®2-group and usual care group significantly decreased (p=0.001, p=0.03) during the two weeks intervention. However, neither group had an immediate effect. Conclusion: Isometric exercise using ATM®2 may have an immediate and short-term effect on acute LBP, which is greater in patients with an extension-type pattern. The ATM®2 exercise may reduce the pain of the acute LBP. Furthermore, it will be a problem in the future to analyze if the influence of pain is reduced in the immediate natural period that gives to chronic LBP

Effect of Cblin and celastrol on muscle atrophy

Two novel reagents, N-myristoylated Cbl-b inhibitory peptide (C14-Cblin) and celastrol, a quinone methide triterpene, are reported to be effective in preventing myotube atrophy. The combined effects of C14-Cblin and celastrol on rat L6 myotubes atrophy induced by 3D-clinorotation, a simulated microgravity model, was investigated in the present study. We first examined their effects on expression in atrogenes. Increase in MAFbx1/atrogin-1 and MuRF-1 by 3D-clinorotation was significantly suppressed by treatment with C14-Cblin or celastrol, but there was no additive effect of simultaneous treatment. However, celastrol significantly suppressed the upregulation of Cbl-b and HSP70 by 3D-clinorotation. Whereas 3D-clinorotation decreased the protein level of IRS-1 in L6 myotubes, C14-Cblin and celastrol inhibited the degradation of IRS-1. C14-Cblin and celastrol promoted the phosphorylation of FOXO3a even in microgravity condition. Simultaneous administration of C14-Cblin and celastrol had shown little additive effect in reversing the impairment of IGF-1 signaling by 3D-clinorotation. While 3D-clinorotation-induced marked oxidative stress in L6 myotubes, celastrol suppressed 3D-clinorotation-induced ROS production. Finally, the C14-Cblin and celastrol-treated groups were inhibited decrease in L6 myotube diameter and increased the protein content of slow-twitch MyHC cultured under 3D-clinorotation. The simultaneous treatment of C14-Cblin and celastrol additively prevented 3D-clinorotation-induced myotube atrophy than single treatment

Development and application of a simple LC-MS method for the determination of plasma rilpivirine (TMC-278) concentrations

Rilpivirine (TMC-278) is a second-generation non-nucleoside reverse transcriptase inhibitor that is high potent against both wild-type and drug-resistant HIV-1 strains. Therefore, rilpivirine is expected to treat therapy-experienced patients who failed to use current drugs due to the emergence of drug-resistant HIV mutants. The quantification of rilpivirine in human plasma is important to support clinical studies and determine pharmacokinetic parameters of rilpivirine in HIV-1 infected patients. Consequently, simple and easy system to determine plasma rilpivirine concentrations has been required. In this study, we developed a conventional LC-MS method to quantify plasma rilpivirine. Subsequently the method was validated by estimating the precision and accuracy for inter- and intraday analysis in the concentration range of 18-715 ng/ml. The calibration curve was linear in this range. Average accuracy ranged from 100.0 to 100.6%. Relative standard deviations of both inter- and intraday assays were less than 3.3%. Recovery of rilpivirine was more than 82.0%. These results demonstrate that our LC-MS method provides a conventional, accurate and precise way to determine rilpivirine in human plasma. This method can be used in routine clinical application for HIV-1 infected patients, and permits management of drug interactions and toxicity for rilpivirine