IgA-enhancing effects of membrane vesicles derived from Lactobacillus sakei subsp. sakei NBRC15893

Immunoglobulin (Ig) A in the mucus of the intestinal tract plays an important role in preventing the invasion of pathogenic microorganisms and regulating the composition of the gut microbiota. Several strains of probiotic lactic acid bacteria (LAB) are known to promote intestinal IgA production. Bacteria are also known to naturally release spherical membrane vesicles (MVs) that are involved in various biological functions such as quorum sensing, pathogenesis, and host immunomodulation. However, the production of MVs by LAB and their effects on host immunity remain poorly understood. In this study, we investigated the MV production by Lactobacillus sakei subsp. sakei NBRC15893 isolated from kimoto, the traditional seed mash used for brewing sake. MVs were separated from the culture broth of L. sakei NBRC15893 through filtration and density gradient ultracentrifugation and were observed by transmission electron microscopy. The MVs showed a spherical morphology, with a diameter of 30–400 nm, and contained proteins and nucleic acids. In addition, both the LAB cells and purified MVs promoted IgA production by murine Peyer’s patch cells. This MV- and cell-induced IgA production was suppressed by neutralization of Toll-like receptor (TLR) 2, which recognizes cell wall components of gram-positive bacteria, using an anti-TLR2 antibody. Collectively, our results indicate that MVs released from L. sakei NBRC15893 enhance IgA production by activating host TLR2 signaling through its cell wall components. Thus, it is important to consider novel interactions between gut microbiota and hosts via MVs, and MVs derived from probiotic bacteria could have promising applications as safe adjuvants.Japan Society for the Promotion of Science (JSPS) KAKENHI grant (Nos. 16K18302 and 18K04857 [to S.Y.Y]; 15H05790, 16H01373, 17H04134, and 26293111 [to J.K.]

Enhancement of Catalytic Activity Associated with Carbon Deposits Formed on NiO/γ-Al2O3 Catalysts during Direct Dehydrogenation of Isobutane

The dehydrogenation of isobutane in the presence of CO2 over NiO supported on γ-Al2O3 was examined. For comparison, Cr2O3 supported on γ-Al2O3 was also used. It is generally accepted that a catalyst used for the dehydrogenation of various alkanes will suffer catalyst deactivation due to the formation of carbon deposits. In the present study, the yield of isobutene was significantly decreased with time-on-stream due to carbon deposition when using Cr2O3(x)/γ-Al2O3, in which x indicates the loading of a corresponding oxide by weight %. However, carbon deposits also were evident on NiO(x)/γ-Al2O3, but the yield of isobutene was enhanced with time-on-stream depending on the loading (x). This indicates that the contribution of the carbon deposition in the dehydrogenation on NiO(x)/γ-Al2O3 definitely differed from that on an ordinary catalyst system such as Cr2O3(x)/γ-Al2O3. In order to confirm the advantageous effect that carbon deposition exerted on the yield of isobutene, NiO(x)/γ-Al2O3 was first treated with isobutane and then the catalytic activity was examined. As expected, it became clear that the carbon deposits formed during the pretreatment contributed to the enhancement of the yield of isobutene. The presence of a Ni-carbide species together with the metallic Ni that was converted from NiO during dehydrogenation definitely enhanced of the yield of isobutene. Although carbon deposition is generally recognized as the main cause of catalyst deactivation, the results of the present study reveal that carbon deposition is not necessarily the cause of this phenomenon

Group cognitive behavioural therapy (GCBT) versus treatment as usual (TAU) in the treatment of irritable bowel syndrome (IBS): A study protocol for a randomized controlled trial

Background: Irritable bowel syndrome (IBS) is a common disease that affects the quality of life (QOL) and social functioning of sufferers. Visceral anxiety is currently considered a key factor in the onset and exacerbation of IBS, and cognitive-behavioural therapy (CBT) targeting visceral anxiety is thought to be effective. However, access to CBT is limited due to the lack of trained therapists, the substantial time required for therapy and the associated costs. Group CBT (GCBT) may solve some of these problems. We have therefore planned this trial to examine the efficacy of GCBT for IBS. Methods: The trial is a two-armed, parallel group, open label, stratified block randomized superiority trial. The study group will consist of 112 participants (aged 18–75 years) with IBS (Rome-III or IV criteria). Participants will be randomly allocated 1:1 to (i) the intervention group: ten-week GCBT plus treatment as usual (TAU) or (ii) the control group: waiting list (WL) plus TAU. The co-primary outcomes are the change in IBS severity or disease-specific quality of life from baseline to week 13 which is 1 month after the end of treatment. The efficacy of GCBT for IBS will be examined through mixed-effects repeated-measures analysis. Discussion: GCBT, if found effective, can address the issues of the shortage of therapists as well as the time required and the costs associated with individual CBT. Clinically, the findings will help make effective CBT programmes accessible to a large number of distressed IBS patients at lower costs. Theoretically, the results will clarify the relationship between IBS and psychological stress and will help elucidate the underlying mechanisms of IBS. Trial registration: UMIN, CTR-UMIN000031710. Registered on March 13, 2018

A phospho-switch controls RNF43-mediated degradation of Wnt receptors to suppress tumorigenesis.

Funder: Japan Foundation for Applied Enzymology; doi: https://doi.org/10.13039/100008695Funder: Pancreas Research Foundation of Japan Collaborative Research Project Program of the Medical Institute of Bioregulation, Kyushu University, Japan Joint Research Program of the Institute for Molecular and Cellular Regulation, Gunma University, Japan Grant for Joint Research Project of the Research Institute for Microbial Diseases Osaka UniversityFunder: European Research Council (ERC (639050) and the Interpark Bio-Convergence Center Grant Program.Frequent mutation of the tumour suppressor RNF43 is observed in many cancers, particularly colon malignancies. RNF43, an E3 ubiquitin ligase, negatively regulates Wnt signalling by inducing degradation of the Wnt receptor Frizzled. In this study, we discover that RNF43 activity requires phosphorylation at a triplet of conserved serines. This phospho-regulation of RNF43 is required for zebrafish development and growth of mouse intestinal organoids. Cancer-associated mutations that abrogate RNF43 phosphorylation cooperate with active Ras to promote tumorigenesis by abolishing the inhibitory function of RNF43 in Wnt signalling while maintaining its inhibitory function in p53 signalling. Our data suggest that RNF43 mutations cooperate with KRAS mutations to promote multi-step tumorigenesis via the Wnt-Ras-p53 axis in human colon cancers. Lastly, phosphomimetic substitutions of the serine trio restored the tumour suppressive activity of extracellular oncogenic mutants. Therefore, harnessing phospho-regulation of RNF43 might be a potential therapeutic strategy for tumours with RNF43 mutations

重傷外傷の認識が遅れ救急外来で緊急開腹術を行った１例

An８１-year-old man fell down and bruised his left abdomen. After a while the back pain got worse, and he admitted to the Emergency Department. At hospitals admission, several signs of shock were observed, and contrast-enhanced CT revealed a splenic injury. However, it took an hour and a half to diagnose and convene the trauma team because of the lack of information shared among medical staffs and the delay of the recognition as a severe traumatic injury. Since there was no available operation room at the time, nor there wasn’t time to transfer to another hospital, he was forced to undergo emergency open splenectomy at the Emergency Department. That decision saved his life as a result. In ２００２, it revealed that the deaths of about ４０％ of expired trauma patients who arrived at emergency centers were probably preventable. Since then, much progress has been made in establishing and generalizing the trauma care and evaluation guidelines. Our hospital is also making progress in organizing a trauma team and the massive transfusion protocol. However, even if they are well maintained, we won’t be able to decrease the number of preventable trauma deaths（PTD）unless we diagnose it. Improving clinical management as well as making efforts on teamwork, leads to a rapid definitive care in trauma patients

ビタミン E摂取量が母体の健康状態と胎児の発育に及ぼす影響について ―実験動物を用いての検討―

This study is focused on overdose of vitamin E. In particular，we examined its influence on pregnancy using a laboratory animal. It showed no change of hemoglobin level and triglyceride level in blood by the difference of vitamin E dose. However，it showed that antioxygenation of the vitamin E was shown because the fall of TBARS value in the brain that was taken have much vitamin E intakes. The cause was not clear，the vitamin E intake of inappropriate quantity may cause pregnancy abnormality. Because, pregnancy abnormal ratios increased that growth insufficiency of the fetus was observed low group and high group in vitamin E. It suggested that the surplus intake of the vitamin E have possibilities to cause bad influence to pregnancy