Acute Effects of Warm-up in Physical Activities : Effects of Conditioning Contraction on Subsequent Jump Performance

本研究は準備運動として行うコンディショニング収縮(即時的な筋力増強現象を引き起こす運動）が、その後に行うジャンプパフォーマンスに与える即時的効果を調査することを目的とした。本研究には19名の男性が参加した。対象者は、足関節のみで水平方向のジャンプ動作が行えるように設計されたレッグプレスマシン上で試技を行った。コンディショニング収縮としてカーフレイズ70%1RM10回を2セット行い、カーフレイズの前に3回、その後に6回(post-1min,3min,5min,7min,10min,12min)のジャンプを行った。加えて、ジャンプ動作中の運動学的、運動力学的データを記録し、関節トルクを算出した。カーフレイズ後、10分後にジャンプ高が有意な増加を示し(p<0.05)、足関節ピークトルクも10分後に有意な増加を示した(p<0.05)。これらから、コンディショニング収縮を行うことで、その後に行う単関節運動のジャンプパフォーマンスが向上することが示唆された

Induction of microRNA-214-5p in human and rodent liver fibrosis

BACKGROUND: miRNAs are non-coding RNAs that regulate gene expression in a wide range of biological contexts, including a variety of diseases. The present study clarified the role of miR-214-5p in hepatic fibrogenesis using human clinical tissue samples, livers from rodent models, and cultured hepatic stellate cells. METHODS: The expression of miR-214-5p and genes that are involved in liver fibrosis were analyzed in hepatitis C virus-infected human livers, rodent fibrotic livers, a human stellate cell line (LX-2), and the cells from intact mouse livers using real-time PCR. The effect of miR-214-5p overexpression in LX-2 cells on cell function was investigated. Twist-1 expression in the liver tissues of mouse models and primary-cultured stellate cells was also analyzed. RESULTS: miR-214-5p was upregulated in human and mouse livers in a fibrosis progression–dependent manner. miR-214-5p expression increased during the culture-dependent activation of mouse primary stellate cells and was significantly higher in stellate cells than in hepatocytes. The overexpression of miR-214-5p in LX-2 cells increased the expression of fibrosis-related genes, such as matrix metalloproteinase (MMP)-2, MMP-9, α-smooth muscle actin, and transforming growth factor (TGF)-β1. TGF-β stimulation induced miR-214-5p in LX-2 cells. Twist-1 was increased in fibrotic mouse livers and induced during mouse stellate cell activation. CONCLUSION: miR-214-5p may play crucial roles in the activation of stellate cells and the progression of liver fibrosis. Twist-1 may regulate miR-214-5p expression in the liver, particularly in stellate cells

A case of primary small cell carcinoma of the liver that was treated with chemotherapy

Primary small cell carcinoma (SSC) of the liver is very rare in Japan and only ten cases have been reported worldwide. We report herein the case of a 77-year-old man with primary SCC of the liver. He had a tumor over 10 cm in diameter which was localized in the right lobe of the liver and had invaded the right diaphragm. In laboratory tests, high serum levels of lactate dehydrase and neuron-specific enolase were observed. A biopsy specimen showed that the tumor cells were similar in cytology to a pulmonary SCC. The patient was first treated with carboplatin and etoposide according to the therapy protocol for pulmonary SCC and then with a regimen using etoposid and cisplatinum, resulting in an unfavorable outcome. We discuss the clinical course and therapy of extra-pulmonary SCC and review the literature of the cases previously reported

Pilot study of a basic individualized cognitive behavioral therapy program for chronic pain in Japan

Background: Chronic pain is a major health problem, and cognitive behavioral therapy (CBT) is its recommended treatment; however, efforts to develop CBT programs for chronic pain and assess their feasibility are remarkably delayed in Asia. Therefore, we conducted this pilot study to develop a basic individualized CBT for chronic pain (CBT-CP) and assessed its feasibility for use in Japan. Methods: Our study was an open-labeled before–after trial without a control group conducted cooperatively in five Japanese tertiary care hospitals. Of 24 outpatients, 15, age 20–80, who experienced chronic pain for at least three months were eligible. They underwent an eight-session CBT-CP consisting of relaxation via a breathing method and progressive muscle relaxation, behavioral modification via activity pacing, and cognitive modification via cognitive reconstruction. The EuroQol five-dimensional questionnaire five level (EQ5D-5 L) assessment as the primary outcome and quality of life (QOL), pain severity, disability, catastrophizing, self-efficacy, and depressive symptoms as secondary outcomes were measured using self-administered questionnaires at baseline, post-treatment, and 3-month follow-up. Intention-to-treat analyses were conducted. Results: Effect size for EQ5D-5 L score was medium from baseline to post-treatment (Hedge’s g = − 0.72, 90% confidence interval = − 1.38 to − 0.05) and up to the 3-month follow-up (g = − 0.60, CI = − 1.22 to 0.02). Effect sizes for mental and role/social QOL, disability, catastrophizing, self-efficacy, and depressive symptoms were medium to large, although those for pain severity and physical QOL were small. The dropout rate was acceptably low at 14%. No severe adverse events occurred. Conclusion: The findings suggest that CBT-CP warrants a randomized controlled trial in Japan

Histological and Nuclear Medical Comparison of Inflammation After Hemostasis with Non-Thermal Plasma and Thermal Coagulation

The objective of this study is to examine the invasiveness of hemostasis by non-thermal plasma (NTP) compared with hemostasis by thermal coagulation (TC). The inflammation recovery process after hemostasis by TC and NTP was compared by using histological methods and nuclear medical molecular imaging. The necrotic areas in the NTP group disappeared after 5 days, whereas they remained 15 days after hemostasis in the TC group. The accumulation of 2-deoxy-2-[F-18] fluoro-D-glucopyranose (F-18-FDG), which reflects the existence of inflammatory cells, was higher in the TC group than in the NTP group on day 15. Thus, this study indicates that hemostasis by NTP is less inflammatory than TC. This report is the first to evaluate inflammation that occurred after hemostasis with medical devices noninvasively

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

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