Co-culturing of follicles with interstitial cells in collagen gel reproduce follicular development accompanied with theca cell layer formation

<p>Abstract</p> <p>Background</p> <p>The mechanism of theca cell layer formation in mammalian ovaries has not been elucidated; one reason is that there is no follicle culture system that can reproduce theca cell layer formation in vitro. Therefore, a three-dimensional follicle culture system that can reproduce theca cell layer formation is required.</p> <p>Methods</p> <p>A collagen gel was used in the follicle culture system. To determine the optimum conditions for follicle culture that can reproduce theca cell layer formation, the effects of hormonal treatment and cell types co-cultured with follicles were examined. In addition, immunohistochemistry was used to examine the properties of the cell layers formed in the outermost part of follicles.</p> <p>Results</p> <p>Follicles maintained a three-dimensional shape and grew in collagen gel. By adding follicle-stimulating hormone (FSH) and co-culturing with interstitial cells, the follicles grew well, and cell layers were formed in the outermost part of follicles. Immunohistochemistry confirmed that the cells forming the outermost layers of the follicles were theca cells.</p> <p>Conclusion</p> <p>In this study, follicle culture system that can reproduce theca cell layer formation <it>in vitro </it>was established. In our opinion, this system is suitable for the analysis of theca cell layer formation and contributes to our understanding of the mechanisms of folliculogenesis.</p

Root canal treatment with high-frequency waves in rats

The purpose of this study was to develop a high-frequency wave therapy model in rats and to investigate the influence of high-frequency waves on root canal treatment, which may provide a novel strategy for treating apical periodontitis. Root canal treatments with and without high-frequency wave irradiation were performed on the mandibular first molars of 10-week-old male Wistar rats. The mesial roots were evaluated radiologically, bacteriologically, and immunohistochemically. At 3 weeks after root canal treatment, lesion volume had decreased significantly more in the irradiated group than in the non-irradiated group, indicating successful development of the high-frequency therapy model. The use of high-frequency waves provided no additional bactericidal effect after root canal treatment. However, high-frequency wave irradiation was found to promote healing of periapical lesions on the host side through increased expression of fibroblast growth factor 2 and transforming growth factor-β1 and could therefore be useful as an adjuvant nonsurgical treatment for apical periodontitis

Assessment of the functional efficacy of root canal treatment with high-frequency waves in rats

The purpose of this study was to develop a high-frequency wave therapy model in rats and to investigate the influence of high-frequency waves on root canal treatment, which may provide a novel strategy for treating apical periodontitis. Root canal treatments with and without high-frequency wave irradiation were performed on the mandibular first molars of 10-week-old male Wistar rats. The mesial roots were evaluated radiologically, bacteriologically, and immunohistochemically. At 3 weeks after root canal treatment, lesion volume had decreased significantly more in the irradiated group than in the non-irradiated group, indicating successful development of the high-frequency therapy model. The use of high-frequency waves provided no additional bactericidal effect after root canal treatment. However, high-frequency wave irradiation was found to promote healing of periapical lesions on the host side through increased expression of fibroblast growth factor 2 and transforming growth factor-β1 and could therefore be useful as an adjuvant nonsurgical treatment for apical periodontitis.Assessment of the functional efficacy of root canal treatment with high-frequency waves in rats. Saori Matsui, et al. PLOS ONE. 2020.9(29) doi.org/10.1371/journal.pone.023966

看護学部における新入生セミナーの活動

報告Reports　本学看護学部では、新入生が抱く入学時の不安や緊張を和らげる目的で学生スタッフ参画による「新入生セミナー」が実施されている。この新入生セミナーは150 名前後の在学生スタッフが主体となって、１年間にわたり企画、運営を行う組織的活動である。この自主的な活動は新入生に対する効果だけでなく、在学生スタッフに対しても、主体的活動による達成感やリーダーシップの獲得、縦と横のつながりの形成などの効果があると考えられる。在学生スタッフの意欲的な活動は、新入生のモデルとなり、スタッフへの自主的な参加へとつながる形で10 年以上継続されている。今回、本学部の新入生セミナーの活動についての概要を報告する

看護学部学生の学業とアルバイトに関する実態調査

報告Reports　本調査は、東海地方にあるＡ看護系大学に在籍する623 名を対象に、アルバイト実施の実態と学業への影響を把握し、学生指導の方向性を検討することを目的に実施した。　本論では、アルバイトが原因と思われる眠気や体調不良について学業への影響の有無とアルバイトの職種、実施時期、週の回数などの実施状況から、学業に影響を及ぼす要因を探ると共に、学生のアルバイト経験から得られたことの自由記載内容を社会人基礎力（箕浦，2014）を参考に分析し、社会性の発達効果について検討した。　本調査の結果、学業に影響を及ぼす要因として、複数のアルバイトに従事している、従事日数が週4 日以上、就労時間が６時間以上、終了時刻が夜10 時以降の４項目に関与が認められた。また学生が個人的努力として、アルバイトと学業を両立するために、課題やレポート提出の期限に対し「アルバイトの入れ方の調整」や「終了時刻の調整」をしていても、学業に影響が出ている実態が明らかになった。　しかしアルバイトの経験は、学生の社会性の発達向上を促しており、アルバイトで得た収入を学費に充てる必要がある学生もいることから、全てを制限するのではなく、アルバイトと学業を両立させていくための実施の目安となる基準を学生指導の方針に盛り込んでいく必要性が示唆された

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

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The examination of welfare community from the view point of barrier-free in child-rearing

The "barrier-free in child-rearing" has been used as an expression that showed the maintenance of the environment of living that supported the child-rearing. There is an aim promoting barrierfree in child-rearing, such as the public buildings, the public transport facilities, and the city park, etc. The barrier-free in child-rearing needs not only material maintenances but also consciousness of people against the barrier-free in child-rearing. This research will show the information that the parents who are in child-rearing tend to miss out at the facilities concerning the barrier-free in child-rearing. As a result, to improve the convenience with utilization of facilities from the parents in child-rearing of view, as well as the wheelchair marks, the mark that is available for the parents in child-rearing. In addition there is effort that provides some information with publicity. Furthermore, user will feel mental barrier from the building structures. Therefore there are some cases that they will hesitate to use the facilities even staff recommend it

Lenvatinib Suppresses Angiogenesis through the Inhibition of both the VEGFR and FGFR Signaling Pathways

Lenvatinib mesilate (lenvatinib) is an oral multiple-receptor tyrosine kinase inhibitor that selectively inhibits the kinase activities of Vascular Endothelial Growth Factor Receptor (VEGFR) 1-3, Fibroblast Growth Factor Receptor (FGFR) 1-4, Platelet-Derived Growth Factor Receptor (PDGFR) α, KIT, and RET. The VEGFR and FGFR signaling pathways are the master regulators of normal and tumor angiogenesis. Lenvatinib showed significant activity in patients with radioiodine-refractory thyroid cancer in a Phase III study and is used in the United States, the European Union, and Japan. Moreover, based on Phase II study, lenvatinib has been approved in the United States for the treatment of patients with advanced renal cell carcinoma in combination with everolimus. In addition, the efficacy of lenvatinib is being evaluated in other cancers, including hepatocellular carcinoma and endometrial cancer. The purpose of this study was to elucidate the mechanism underlying the clinical activities of lenvatinib by using in vitro and in vivo angiogenesis models.&nbsp;First, we established an in vitro tube formation system, in which capillary-like structures formed on basement membrane extract in response to pro-angiogenic factors. Lenvatinib suppressed tube formation induced by bFGF alone and by bFGF plus VEGF. Furthermore, plasma levels of VEGF and FGF23, pharmacodynamic biomarkers of inhibition of the VEGFR and FGFR signaling pathways, respectively, were up-regulated after the administration of lenvatinib to mice. By contrast, the administration of another VEGFR inhibitor, sorafenib tosylate (sorafenib), up-regulated plasma levels of VEGF but not FGF23. Finally, lenvatinib suppressed bFGF-driven angiogenesis in Matrigel plug assays at low dosage (3 mg/kg), whereas sorafenib did so only at a higher dose (30 mg/kg). These results indicate that lenvatinib inhibits both VEGFR and FGFR in vitro and in vivo. This combined inhibition of both VEGFR and FGFR may lead significant clinical activities.</p