Roles of FoxP3-positive Regulatory T Cells in Lymphoid Follicle Formation Associated with Lung Squamous Cell Carcinoma

Background：We previously reported that lymphoid follicle formation by tumor infiltrating lymphocytes（TILs）is a negative predictor of prognosis in patients with lung squamous cell carcinoma（SCC）following surgery. However, the roles of FoxP3⁺/CD4⁺/CD25⁺-regulatory T cells（Tregs）in formation of lymphoid follicles as well as survival remain unclear.Methods：Specimens obtained from patients during resection of lung SCC were examined for lymphoid follicle formation and subjected to immunohistochemistry analysis for the presence of TILs.Results：The appearance of Tregs was correlated with lymphoid follicle formation（p＝0.001）. Univariate analysis also showed that Tregs tended to be correlated with overall survival（p＝0.097）, whereas multivariate analysis revealed that lymphoid follicle formation（p＝0.042）and pleural invasion（p＝0.031）were independent prognostic factors related to overall survival, while the appearance of Tregs was not.Conclusion：Treg appearance was correlated with lymphoid follicle formation. That lymphoid follicle formation, rather than appearance of Tregs, is a predictor of patients survival following surgery for lung SCC

ニホンゴ ガクシュウ サイト 「マルゴト + (マルゴトプラス)」 ノ カイハツ -カダイ スイコウ ト イブンカ リカイ ヲ タスケル ウェブサイト-

JF 日本語教育スタンダード準拠の海外の成人向け教科書『まるごと日本のことばと文化』の開発に合わせ、関西国際センターでは、この教科書を使って学ぶ学習者のためのサポートサイト「まるごと+(まるごとプラス)」を開発した。「『日本語を使ってできること』が増やせる」、「『リアリティ』のある練習ができる」、「大人が『楽しく使える』」の3つをキーコンセプトとして定め、課題遂行を意識した練習、異文化理解のための情報やきっかけを提供するサイトを目指すこととした。「まるごと+」は教科書の「入門A1」、「初級1 A2」の2つのレベルに対応した種々のコンテンツを提供しており、動画を使った会話練習や異文化理解のためのコンテンツを中心に、学習者や教師から好評を得ている。本稿では、「まるごと+」の開発方針とそれをどのように具現化したか、また、サイトの反響を報告する。MARUGOTO Plus is a support website for Japanese language learners developed by The Japan Foundation Japanese-Language Institute, Kansai. It was created in conjunction with the "Marugoto :Japanese Language and Culture" textbook, which is based on the JF Standard for Japanese-Language Education and aimed at adults overseas. "MARUGOTO Plus" was developed with three key concepts inmind, "Increasing the `Things able to be accomplished using Japanese\u27", "Ability to practice with `Practical\u27settings", and "`Fun to use\u27 for adults". It aims to assist with the practice of task performance and the creation of opportunities to gather information for intercultural understanding. "MARUGOTO Plus"is compatible with two levels of the textbook, "Starter A1" and "Elementary 1 A2", and offers a variety of content. This paper will report about the concept of "MARUGOTO Plus" and how the site was realized according to the concept and, in addition, the reactions to the site

Anti-myeloma Activity by Thiazolidine-2,4-dione compounds

Proviral Integrations of Moloney virus 2 (PIM2) kinase is overexpressed in multiple myeloma (MM) cells, and regarded as an important therapeutic target. Here, we aimed to validate the therapeutic efficacy of different types of PIM inhibitors against MM cells for their possible clinical application. Intriguingly, the thiazolidine 2,4 dione family compounds SMI 16a and SMI 4a reduced PIM2 protein levels and impaired MM cell survival preferentially in acidic conditions, in contrast to other types of PIM inhibitors, including AZD1208, CX 6258 and PIM447. SMI 16a also suppressed the drug efflux function of breast cancer resistance protein, minimized the sizes of side populations, and reduced in vitro colony forming capacity and in vivo tumorigenic activity in MM cells, suggesting impairment of their clonogenic capacity. PIM2 is known to be subject to ubiquitination-independent proteasomal degradation. Consistently, the proteasome inhibitors bortezomib and carfilzomib increased PIM2 protein levels in MM cells without affecting its mRNA levels. However, SMI 16a mitigated the PIM2 protein increase and cooperatively enhanced anti MM effects in combination with carfilzomib. Collectively, the thiazolidine 2,4 dione family compounds SMI 16a and SMI 4a uniquely reduce PIM2 protein in MM cells, which may contribute to their profound efficacy in addition to their immediate kinase inhibition. Their combination with proteasome inhibitors is envisioned

Effective impairment of myeloma cells and their progenitors by hyperthermia

Multiple myeloma (MM) remains incurable, and MM-initiating cells or MM progenitors are considered to contribute to disease relapse through their drug-resistant nature. In order to improve the therapeutic efficacy for MM, we recently developed novel superparamagnetic nanoparticles which selectively accumulate in MM tumors and extirpate them by heat generated with magnetic resonance. We here aimed to clarify the therapeutic effects on MM cells and their progenitors by hyperthermia. Heat treatment at 43°C time-dependently induced MM cell death. The treatment upregulated endoplasmic reticulum (ER) stress mediators, ATF4 and CHOP, while reducing the protein levels of Pim-2, IRF4, c-Myc and Mcl-1. Combination with the proteasome inhibitor bortezomib further enhanced ER stress to potentiate MM cell death. The Pim inhibitor SMI-16a also enhanced the reduction of the Pim-2-driven survival factors, IRF4 and c-Myc, in combination with the heat treatment. The heat treatment almost completely eradicated “side population” fractions in RPMI8226 and KMS-11 cells and suppressed their clonogenic capacity as determined by in vitro colony formation and tumorigenic capacity in SCID mice. These results collectively demonstrated that hyperthermia is able to impair clonogenic drug-resistant fractions of MM cells and enhance their susceptibility to chemotherapeutic drugs

無散瞳眼底カメラによる高齢者の眼底検査に関する研究

Many countries are experiencing an increase in the average age of the adult population. This has serious implications for the health of the people and it is important to consider the physiological changes and diseases associated with age. A majour disease related to age is hypertension, a disease connected to lifestyles, which has steadily increased. In order to check whether the circulatory organs were functioning properly.a measurement of blood pressure was usually used. In this study we substituted the funduscopy for blood pressure. Funduscopy using a non mydriasis retinal camera is easy and useful to check the function of circulatory organs. The subjects were residents of Yoshimi, Saitama prefecture, who visited Arakawa-so, and who were aged from 60 to 80 years old. Twenty-nine healthy subjects, 6 were in their 60\u27s, with the remaining 23 being in their 70\u27s do some work on their own farms. In the subjects, approximately 45% showed signs of abnormal retina. Compared with retina measured in the health examinations of aging subjects working in a factory, the residents showed signs of abnormality in greater proportion. This abnormality enabled us to infer the disorder in circulatory organs of aging workers in Yoshimi

Analysis of Expressed Sequence Tags from the Fungus Aspergillus oryzae Cultured Under Different Conditions

We performed random sequencing of cDNAs from nine biologically or industrially important cultures of the industrially valuable fungus Aspergillus oryzae to obtain expressed sequence tags (ESTs). Consequently, 21 446 raw ESTs were accumulated and subsequently assembled to 7589 non-redundant consensus sequences (contigs). Among all contigs, 5491 (72.4%) were derived from only a particular culture. These included 4735 (62.4%) singletons, i.e. lone ESTs overlapping with no others. These data showed that consideration of culture grown under various conditions as cDNA sources enabled efficient collection of ESTs. BLAST searches against the public databases showed that 2953 (38.9%) of the EST contigs showed significant similarities to deposited sequences with known functions, 793 (10.5%) were similar to hypothetical proteins, and the remaining 3843 (50.6%) showed no significant similarity to sequences in the databases. Culture-specific contigs were extracted on the basis of the EST frequency normalized by the total number for each culture condition. In addition, contig sequences were compared with sequence sets in eukaryotic orthologous groups (KOGs), and classified into the KOG functional categories

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