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MEK阻害剤PD0325901はERKリン酸化阻害を介して 内皮細胞におけるCD34発現を上昇させる
Full text linkCD34-positive endothelial progenitor cells (EPCs) promote angiogenesis and are a promising
tool for regenerative cell therapy of ischemic diseases. However, the number and quality of CD34-positive cells decrease owing to various external and internal factors; thus, an efficient method is needed to establish CD34-positive EPCs. The generation of functional cells by reprogramming, that is, manipulating
cell fate via gene transfer and/or treatment with chemical compounds, has recently been reported.
Therefore, we aimed to generate CD34-positive cells by the reprogramming of endothelial cells (ECs).
Methods: Based on previous reports, seven candidate chemical compounds were selected to reprogram human umbilical vein ECs (HUVECs) to CD34-positive cells. Following stimulation with the chemical compounds, the expression of CD34 was evaluated using quantitative PCR, flow cytometry, and immunocytochemistry.
Results: HUVECs treated with the compounds exhibited increased CD34 expression. We cultured cells in alternate media lacking one of the seven compounds and found no CD34 expression in cells treated with PD0325901-free media, suggesting that PD0325901da MEK inhibitordmainly contributed to the increase
in CD34 expression. We found that 98% of cells were CD34-positive after PD0325901 treatment
alone for 7 d. Western blotting revealed that the phosphorylation of ERK was suppressed in PD0325901- treated cells. No upregulation of CD34 was observed in fibroblast cell lines, even after PD0325901 treatment. These results suggested that PD0325901 induces CD34-positive cells by inhibiting ERK phosphorylation in ECs.
Conclusions: CD34 expression was strongly induced in ECs by treatment with the MEK inhibitor PD0325901 in vitro. Our study provides a useful reference for the establishment of CD34-positive EPCs and will contribute to the development of regenerative therapies, especially for ischemic diseases.© 2024 The Author(s). Published by Elsevier BV on behalf of The Japanese Society for Regenerative
Medicine. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/
licenses/by-nc-nd/4.0/)
Consideration of the use of Generative AI by Local Government Pubilc Health Nurses
Full text link近年、人口減少に伴う問題を解決する方策として、生成的人工知能Generative Artificial
Intelligence（以下、生成AI)を導入する自治体が増えている。本稿では、自治体における生成AI
導入状況、自治体保健師による生成AI活用事例を概観し、自治体保健師が行う公衆衛生に適
した業務継続の方策について生成AIを用いて導くことを試行した。その試行プロセスから自治
体保健師による生成AI活用方法を考察した。自治体保健師による生成AI活用方法は、生成AI
に専門知識や自治体情報を深層学習させないことで多様なアイディアや原点回帰を得る方法と、
深層学習させることで自治体の正確な姿や現実的な将来像を得る方法があげられた。このことか
ら、自治体保健師が生成AIの深層学習の有無をうまく使い分けることで、「想像力」と「創造力」を
補完し、多様で新たな施策を構築できる可能性が示唆された
CPAPアドヒアランスの多次元的予測
Full text linkObjective: Continuous positive airway pressure (CPAP) is the standard treatment for obstructive sleep apnea (OSA). Unsatisfactory adherence to CPAP is an important clinical issue to resolve. Cluster analysis is a powerful tool to distinguish subgroups in a multidimensional fashion. This study aimed to investigate the use of cluster analysis for predicting CPAP adherence using clinical polysomnographic (PSG) parameters and patient
characteristics.
Patients/methods: Participants of this multicenter observational study were 1133 patients with OSA who were newly diagnosed and implemented CPAP. Ward’s method of cluster analysis was applied to in-laboratory
diagnostic PSG parameters and patient characteristics. CPAP adherence was assessed during 90- and 365-day periods after CPAP initiation in each cluster. We adopted the Centers for Medicare and Medicaid Services criterion for CPAP adherence, i.e., CPAP use ≥4 h per night for 70 % or more of the observation period. Logistic regression analysis was performed to stratify clusters according to CPAP adherence.
Results: Five clusters were identified through cluster analysis. Clustering was significantly associated with CPAP adherence at 90- and 365-day periods after CPAP initiation. Logistic regression revealed that the cluster with
features including apnea predominant sleep-disordered breathing, high apnea-hypopnea index, and relatively older age demonstrated the highest CPAP adherence.
Conclusion: Cluster analysis revealed hidden connections using patient characteristics and PSG parameters to successfully identify patients more likely to adhere to CPAP for 90 days and up to 365 days. When prescribing
CPAP, it is possible to identify patients with OSA who are more likely to be non-adherent.権利情報：© 2024 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies
β-ヒドロキシ酪酸はラットにおける血液暴露に起因する関節障害の病理学的変化を抑制する
Full text linkArthropathy is a common complication in haemophilia and decreases quality of life. It has been known that concentrations of β-hydroxybutyrate (BHB) in blood are increased by a ketogenic diet, and elevated levels of circulating BHB restricts the progression of inflammation-mediated joint pathological changes. We hypothesized that elevation of blood BHB concentrations could be effective for reducing the progression of bleeding-induced arthropathy by moderating the inflammatory responses of macrophages. In this study, we investigated whether BHB alleviates the arthropathy caused by repeated intra-articular blood injection in rats. To increase blood BHB levels, rats were fed with ketogenic diet. Repeated intra-articular blood injection induced significant joint swelling, whereas ketogenic diet intake significantly increased blood BHB concentrations and ameliorated the joint swelling. The periarticular tissue-fibrosis observed in the control diet intake group appeared to be significantly alleviated in the ketogenic diet intake group. In addition, the IL-1β, which is involved in the progression of arthropathy, levels in the supernatants of blood-exposed macrophages derived from THP-1 cell line were significantly suppressed by BHB supplementation. In summary, BHB moderated the pathological joint changes caused by intra-articular blood exposure.権利情報：© The Author(s) 2024. This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in
any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you modified the licensed material. You do not have
permission under this licence to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated
otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to
obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc-nd/4.0/
トホグリフロジンは肝硬変ラットにおける類洞毛細血管化を抑制することで門脈圧亢進症を抑制する
Full text linkBackground: Liver cirrhosis leads to portal hypertension (PH) with capillarization of
liver sinusoidal endothelial cells (LSECs), although drug treatment options for PH are currently limited. Sodium glucose transporter 2 inhibitors, which are antidiabetic agents, have been shown to improve endothelial dysfunction. We aimed to elucidate the effect of tofogliflozin on PH and liver fibrosis in a rat cirrhosis model. Methods: Male-F344/NSlc rats repeatedly received carbon tetrachloride (CCl4
) intraperitoneally to induce PH and liver cirrhosis alongside tofogliflozin (10 or 20 mg/kg). Portal hemodynamics and hepatic phenotypes were assessed after 14 weeks. An in vitro study investigated the effects of tofogliflozin on the crosstalk between LSEC and activated hepatic stellate cells (Ac-HSC), which are relevant to PH development. Results: Tofogliflozin prevented PH with attenuated intrahepatic vasoconstriction, sinusoidal capillarization, and remodeling independent of glycemic status in CCl4-treated rats. Hepatic macrophage infiltration, proinflammatory
response, and fibrogenesis were suppressed by treatment with tofogliflozin. In vitro assays showed that tofogliflozin suppressed Ac-HSC-stimulated capillarization and vasoconstriction in LSECs by enhancing the antioxidant capacity, as well as inhibited the capilliarized LSEC-stimulated contractive, profibrogenic, and proliferative activities of Ac-HSCs. Conclusions: Our study provides strong
support for tofogliflozin in the prevention of liver cirrhosis-related PH.権利情報：© 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
EOB造影MRIの肝細胞相を用いた切除不能肝細胞癌に対するアテゾリズマブ＋ベバシズマ ブ併用療法の治療効果予測
Full text linkBackground: This study aimed to examine whether the coefficient of variation (CV) in the hepatobiliary-phase (HBP) of Gd-EOB-DTPA-MRI could be an independent predictive factor
for tumor progression. Methods: Patients who underwent Gd-EOB-DTPA-MRI before Atezolizumab/
bevacizumab therapy at six affiliated institutions between 2018 and 2022 were included. CV for each patient was calculated as the mean value for up to five tumors larger than 10 mm, and CV of the whole tumor was calculated using LIFEx software. The tumor response was evaluated within 6–10 weeks. The primary endpoint was to investigate the predictive factors, including CV, related to tumor progression using logistic regression analysis. The secondary endpoints were tumor
response rate and progression-free survival (PFS) based on CV. Results: Of the 46 enrolled patients, 13 (28.3%) underwent early progressive disease. Multivariate analysis revealed that a high CV (≥0.22) was an independent predictive factor for tumor progression (p = 0.043). Patients with a high CV had significantly frequent PD than those with a low CV (43.5 vs. 13.0%, p = 0.047). Patients with a high CV tended to have shorter PFS than those with a low CV (3.5 vs. 6.7 months, p = 0.071). Conclusion: Quantitative analysis using CV in the HBP of Gd-EOB-DTPA-MRI may be useful for predicting tumor progression for atezolizumab/bevacizumab therapy.権利情報：© 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/)
ミトコンドリア品質管理と骨格筋成熟に対する 3 種類の中鎖脂肪酸の作用の差異
Full text linkNutritional interventions are one focus of sarcopenia treatment. As medium-chain fatty
acids (MCFAs) are oxidized in the mitochondria and produce energy through oxidative phospho rylation (OXPHOS), they are key parts of nutritional interventions. We investigated the in vitro
effects of three types of MCFA, caprylic acid (C8), capric acid (C10), and lauric acid (C12), in skeletal muscle cells. Compared with C10 and C12, C8 promoted mitophagy through the phosphatase and tensin homolog (PTEN)-induced kinase 1-Parkin pathway and increased the expression of peroxisome proliferator-activated receptor gamma coactivator 1-α and dynamin-related protein 1 to reduce mitochondrial oxidative stress and promote OXPHOS. Furthermore, the expression of myogenic
differentiation 1 and myosin heavy chain increased in myotubes, thus promoting muscle differentia tion and maturation. These results suggest that C8 improves mitochondrial quality and promotes skeletal muscle maturation; in contrast, C10 and C12 poorly promoted mitochondrial quality control and oxidative stress and suppressed energy production. Future animal experiments are required to establish the usefulness of C8 for nutritional interventions for sarcopenia.権利情報：© 2024 by the authors.
Licensee MDPI, Basel, Switzerland.
This article is an open access article
distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/
4.0/)
加齢がマウスの耳石器の形態と機能に与える影響について
Full text linkBackground: Increased fall risk caused by vestibular system impairment is a significant problem associated with aging. A vestibule is composed of linear acceleration-sensing otoliths and rotation-sensing semicircular canals. Otoliths, composed of utricle and saccule, detect linear accelerations. Otolithic organs partially play a role in falls due to aging. Aging possibly changes the morphology
and functions of otoliths. However, the specific associations between aging and otolith changes remain unknown. Therefore, this study aimed to clarify these associations in mice.
Methods: Young C56BL/6 N (8 week old) and old (108–117 weeks old) mice were used in a micro-computed tomography (μCT) experiment for morphological analysis and a linear acceleration experiment for functional analysis. Young C56BL/6 N (8 week old) and middle-aged (50 week old) mice were used in
electron microscopy experiments for morphological analysis.
Results: μCT revealed no significant differences in the otolith volume (p = 0.11)
but significant differences in the otolith density (p = 0.001) between young and old mice. μCT and electron microscopy revealed significant differences
in the structure of striola at the center of the otolith (μCT; p = 0.029, electron
microscopy; p = 0.017). Significant differences were also observed in the
amplitude of the eye movement during the vestibulo-ocular reflex induced
by linear acceleration (maximum amplitude of stimulation = 1.3G [p = 0.014];
maximum amplitude of stimulation = 0.7G [p = 0.015]), indicating that the otolith
function was worse in old mice than in young mice.
Discussion: This study demonstrated the decline in otolith function with age
caused by age-related morphological changes. Specifically, when otolith
density decreased, inertial force acting on the hair cells decreased, and when the
structure of striola collapsed, the function of cross-striolar inhibition decreased,
thereby causing a decline in the overall otolith function.権利情報：© 2024 Ueda, Imai, Ito, Okayasu, Harada,
Kamakura, Ono, Katsuno, Tanaka, Tatsumi,
Hibino, Wanaka and Kitahara. This is an
open-access article distributed under the
terms of the Creative Commons Attribution
License (CC BY). The use, distribution or
reproduction in other forums is permitted,
provided the original author(s) and the
copyright owner(s) are credited and that the
original publication in this journal is cited, in accordance with accepted academic
practice. No use, distribution or reproduction
is permitted which does not comply with
these terms
The Progress and Future Directions in Support for Persons with Mental Disorder
Full text link精神に障害がある人への支援の動向として、精神医療政策の転換により、地域生活支
援が重視され、看護師の役割は病院内のケアから訪問看護やデイケアなど地域支援へと拡
大した。支援の中心となる概念のリカバリー志向が日本でも活用されるようになり、患者
の自己決定や社会的役割の再構築が目指されている。また、多職種連携による包括的支援
が進んできた。COVID-19の影響により患者の治療やケアにおいてテクノロジーが進展
し、新たな治療やケア手法が導入されている。一方、精神に障害がある人への支援者の人
材確保や精神看護教育では人材育成の課題が指摘される。国際的には、地域ケアやデジタ
ル技術を活用した支援が進展しているが、日本では患者の長期入院の問題や支援者の倫理
的問題の課題が指摘されている。今後日本において、地域ケアやテクノロジー活用がさら
に進み、精神看護の実践は新たなステージに入ると予測される。その中で看護師は、柔軟
な思考と高い専門性を発揮し続ける必要がある