PLASMA CELL INFILTRATION AND MUCOID DEGENERATION IN THE MEDIA OF ASCENDING AORTA IN PATIENT WITH CORONARY ARTERY DISEASE

Aims Atherosclerosis results in inflammatory changes in the aortic intima， but little is known regarding medial changes. Atherosclerosis of the ascending aorta coexists with coronary artery disease. The aim of this study was to investigate the atherosclerotic changes in 44 biopsy specimens of media of the ascending aorta associated with coronary artery disease. Plasma cells do not appear in non-inflammatory tissue. Methods We compared plasma cells，and matrix metalloproteinase (MMP)-2-，-9- and -12-positive cells immunohistochemically，and we also compared mucoid degeneration and fibrosis determined by staining using a point-counting method，for groups with a variable number of coronary stenotic (≧75%)lesions. Results In patients with one to three coronary stenotic lesions，plasma cells and mucoid degeneration were low in the aortic media. With four to five lesions，bo th plasma cells and mucoid degeneration increased significantly compared with those in the group with one to three lesions，and MMP-12-positive cells significantly decreased. In patients with six to nine lesions，the number of plasma cells was significantly lower than in patients with four or five lesions，whereas mucoid degeneration significantly increased. There was no change in fibrosis. Conclusions These findings may help us to better understand and treat atherosclerosis

Effect of herbal medicine daikenchuto on gastrointestinal symptoms following laparoscopic colectomy in patients with colon cancer: A prospective randomized study

We conducted a prospective randomized study to investigate the effect of daikenchuto (DKT) on abdominal symptoms following laparoscopic colectomy in patients with left-sided colon cancer. Patients who suffered from abdominal pain or distention on postoperative day 1 were randomized to either the DKT group or non-DKT group. The primary endpoints were the evaluation of abdominal pain, abdominal distention, and quality of life. The metabolome and gut microbiome analyses were conducted as secondary endpoints. A total of 17 patients were enrolled: 8 patients in the DKT group and 9 patients in the non-DKT group. There were no significant differences in the primary endpoints and postoperative adverse events between the two groups. The metabolome and gut microbiome analyses showed that the levels of plasma lipid mediators associated with the arachidonic acid cascade were lower in the DKT group than in the non-DKT group, and that the relative abundance of genera Serratia and Bilophila were lower in the DKT group than in the non-DKT group. DKT administration did not improve the abdominal symptoms following laparoscopic colectomy. The effects of DKT on metabolites and gut microbiome have to be further investigated

New Approach to Teaching Japanese Pronunciation in the Digital Era - Challenges and Practices

Pronunciation has been a black hole in the L2 Japanese classroom on account of a lack of class time, teacher\u2019s confidence, and consciousness of the need to teach pronunciation, among other reasons. The absence of pronunciation instruction is reported to result in fossilized pronunciation errors, communication problems, and learner frustration. With an intention of making a contribution to improve such circumstances, this paper aims at three goals. First, it discusses the importance, necessity, and e ectiveness of teaching prosodic aspects of Japanese pronunciation from an early stage in acquisition. Second, it shows that Japanese prosody is challenging because of its typological rareness, regardless of the L1 backgrounds of learners. Third and finally, it introduces a new approach to teaching L2 pronunciation with the goal of developing L2 comprehensibility by focusing on essential prosodic features, which is followed by discussions on key issues concerning how to implement the new approach both inside and outside the classroom in the digital era

DOCK2 is involved in the host genetics and biology of severe COVID-19

「コロナ制圧タスクフォース」COVID-19疾患感受性遺伝子DOCK2の重症化機序を解明 --アジア最大のバイオレポジトリーでCOVID-19の治療標的を発見--. 京都大学プレスリリース. 2022-08-10.Identifying the host genetic factors underlying severe COVID-19 is an emerging challenge. Here we conducted a genome-wide association study (GWAS) involving 2, 393 cases of COVID-19 in a cohort of Japanese individuals collected during the initial waves of the pandemic, with 3, 289 unaffected controls. We identified a variant on chromosome 5 at 5q35 (rs60200309-A), close to the dedicator of cytokinesis 2 gene (DOCK2), which was associated with severe COVID-19 in patients less than 65 years of age. This risk allele was prevalent in East Asian individuals but rare in Europeans, highlighting the value of genome-wide association studies in non-European populations. RNA-sequencing analysis of 473 bulk peripheral blood samples identified decreased expression of DOCK2 associated with the risk allele in these younger patients. DOCK2 expression was suppressed in patients with severe cases of COVID-19. Single-cell RNA-sequencing analysis (n = 61 individuals) identified cell-type-specific downregulation of DOCK2 and a COVID-19-specific decreasing effect of the risk allele on DOCK2 expression in non-classical monocytes. Immunohistochemistry of lung specimens from patients with severe COVID-19 pneumonia showed suppressed DOCK2 expression. Moreover, inhibition of DOCK2 function with CPYPP increased the severity of pneumonia in a Syrian hamster model of SARS-CoV-2 infection, characterized by weight loss, lung oedema, enhanced viral loads, impaired macrophage recruitment and dysregulated type I interferon responses. We conclude that DOCK2 has an important role in the host immune response to SARS-CoV-2 infection and the development of severe COVID-19, and could be further explored as a potential biomarker and/or therapeutic target

The whole blood transcriptional regulation landscape in 465 COVID-19 infected samples from Japan COVID-19 Task Force

「コロナ制圧タスクフォース」COVID-19患者由来の血液細胞における遺伝子発現の網羅的解析 --重症度に応じた遺伝子発現の変化には、ヒトゲノム配列の個人差が影響する--. 京都大学プレスリリース. 2022-08-23.Coronavirus disease 2019 (COVID-19) is a recently-emerged infectious disease that has caused millions of deaths, where comprehensive understanding of disease mechanisms is still unestablished. In particular, studies of gene expression dynamics and regulation landscape in COVID-19 infected individuals are limited. Here, we report on a thorough analysis of whole blood RNA-seq data from 465 genotyped samples from the Japan COVID-19 Task Force, including 359 severe and 106 non-severe COVID-19 cases. We discover 1169 putative causal expression quantitative trait loci (eQTLs) including 34 possible colocalizations with biobank fine-mapping results of hematopoietic traits in a Japanese population, 1549 putative causal splice QTLs (sQTLs; e.g. two independent sQTLs at TOR1AIP1), as well as biologically interpretable trans-eQTL examples (e.g., REST and STING1), all fine-mapped at single variant resolution. We perform differential gene expression analysis to elucidate 198 genes with increased expression in severe COVID-19 cases and enriched for innate immune-related functions. Finally, we evaluate the limited but non-zero effect of COVID-19 phenotype on eQTL discovery, and highlight the presence of COVID-19 severity-interaction eQTLs (ieQTLs; e.g., CLEC4C and MYBL2). Our study provides a comprehensive catalog of whole blood regulatory variants in Japanese, as well as a reference for transcriptional landscapes in response to COVID-19 infection