Osteosarcoma is a malignant tumor that histologi- cally forms a tumor-like osteoid or bone. Plasmino- gen activator inhibitor 1 (PAI-1) is highly expressed in the blood of patients with various malignant tumors or in the tumors themselves, and its expres- sion is positively correlated with tumor grade. Therefore, PAI-1 is a potential target for cancer therapy. In this study, a small-molecule PAI-1 inhib- itor, TM5614, was tested on U2OS cells, which are osteosarcoma cell-like cells, to examine its effect on cell metabolism. The MTT assays and cell count analysis showed that TM5614 inhibited U2OS cell proliferation. We also tested the apoptotic activity of U2OS cells by multiple assays, and no induction of apoptosis by TM5614 was observed. In contrast, cell cycle analysis revealed that TM5614 induced U2OS cells in G2-M arrest. This study revealed that TM5614 treatment increased p53 and p21 Waf1/Cip1 expression in U2OS cells. In conclusion, we showed that the PAI-1 inhibitor TM5614 induced G2-M arrest in U2OS cells.

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A number of dominantly inherited neurodegen- erative disorders have been attributed to abnor- mal expansions of microsatellites. The mutation causing spinocerebellar ataxia type 37 (SCA37) has recently been identified as an insertion of an expanded ATTTC repeat into a polymorphic locus where a short repeat of ATTTT is usually observed. To clarify variations at the SCA37 locus in the Jap- anese population, genomic DNA samples of a cohort of 167 patients with degenerative ataxic disorders were analyzed. Repeat length was evaluated with polymerase chain reaction and resequencing at the SCA37 locus. We found that the majority (96.4%) of alleles were within the range between 8 and 17 ATTTT repeats. Short expansions consisting of fewer than 40 repeats of ATTTT were identified in 12 alleles (3.6%), but neither long ATTTT repeat expansions nor ATTTC repeat were observed. The most commonly observed alleles were 12 and 13 repeats of ATTTT, with frequencies of 38.3% and 40.1%, respectively. The present study clarified allele frequencies of the polymorphic SCA37 locus in Japanese patients with ataxic disorders. Long expansions of ATTTT repeats appeared to be extremely rare, which may be one of the reasons for the observed scarcity of SCA37 in Japan.

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¹⁸F-fluorodeoxyglucose positron emission tomogra- phy/computed tomography (¹⁸F-FDG PET/CT) is a widely used imaging modality for the detection of liver metastases. Recently, deep neural networks (DNNs) have demonstrated excellent performance in image denoising. This study aimed to assess the performance of a deep learning-based denois- ing algorithm, the Advanced Intelligent Clear-IQ Engine, for ¹⁸F-FDG PET/CT images in the detection of liver metastases. A total of 14 histopathologi- cally proven cancer patients with liver metastases who underwent ¹⁸F-FDG PET/CT between May 2020 and August 2022 were included in the study. The number and size of liver metastases were recorded to compare the lesion detectability between deep learning-based (DL) images and conventional Gaussian-filtered (GF) images. Quantitative anal- ysis was performed using metrics including the contrast-to-noise ratio (CNR) of the lesion and the signal-to-noise ratio (SNR) of the liver. DL images detected 113 out of 168 lesions. The respective number for GF images was 99. Fourteen lesions that were missed in GF images were detected in DL images. All of these 14 lesions were with a diameter ≤ 10mm. In quantitative analysis, DL images showed significantly higher CNR and SNR than GF images. DL images improved lesion detectability, particu- larly for cases with small lesions.

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Studies on the pathogenesis of asthma attacks are limited, and the mechanism underlying asthma attacks remains obscure. This study aimed to clarify the characteristic cytokine profiles in asthma exacerbation. [Materials and Methods] Serum cytokine levels were measured in patients who visited the hospital for asthma attacks and compared with cytokine lev- els in patients with stable asthma and in normal par- ticipants. Serum interleukin (IL)-4, IL-5, IL-10, IL-13, IL-17, IL-33, periostin, and thymic stromal lymph- opoietin (TSLP) concentrations were measured in 16 patients with asthma attacks, 49 patients with stable asthma, and 26 normal participants. [Results] IL-10, IL-13, and TSLP levels were signifi- cantly higher in patients with asthma attacks than in patients with stable asthma, whereas IL-5 and IL-17 levels were significantly lower. [Discussion] Asthma is a heterogeneous disease, and the pathology of an asthma attack will also vary from person to person. In some asthma endtypes, IL-13 production, which induces mucus secre- tion and bronchoconstriction, would contribute to develop asthma attacks. This IL-13 production is not prevented by the enhanced IL-10 production or step-up treatment (i.e., increased steroid inhalation etc.), although IL-10 can suppress IL-5 and IL-17 production.

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