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by Souma Suzuki, Susumu Suzuki, Yuri Sato-Nagaoka, Chisaki Ito, Shinichiro Takahashi
Differentiation therapy using all-trans retinoic acid (ATRA) for acute promyelocytic leukemia (APL) is well established. However, because the narrow application and tolerance development of ATRA need to be improved, we searched for another efficient myeloid differentiation inducer. Kinase activation is involved in leukemia biology and differentiation block. To identify novel myeloid differentiation inducers, we used a Kinase Inhibitor Screening Library. Using a nitroblue tetrazolium dye reduction assay and real-time quantitative PCR using NB4 APL cells, we revealed that, PD169316, SB203580, SB202190 (p38 MAPK inhibitor), and triciribine (TCN) (Akt inhibitor) potently increased the expression of CD11b. We focused on TCN because it was reported to be well tolerated by patients with advanced hematological malignancies. Nuclear/cytoplasmic (N/C) ratio was significantly decreased, and myelomonocytic markers (CD11b and CD11c) were potently induced by TCN in both NB4 and acute myeloid leukemia (AML) M2 derived HL-60 cells. Western blot analysis using NB4 cells demonstrated that TCN promoted ERK1/2 phosphorylation, whereas p38 MAPK phosphorylation was not affected, suggesting that activation of the ERK pathway is involved in TCN-induced differentiation. We further examined that whether ATRA may affect phosphorylation of ERK and p38, and found that there was no obvious effect, suggesting that ATRA induced differentiation is different from TCN effect. To reveal the molecular mechanisms involved in TCN-induced differentiation, we performed microarray analysis. Pathway analysis using DAVID software indicated that “hematopoietic cell lineage” and “cytokine-cytokine receptor interaction” pathways were enriched with high significance. Real-time PCR analysis demonstrated that components of these pathways including IL1β, CD3D, IL5RA, ITGA6, CD44, ITGA2B, CD37, CD9, CSF2RA, and IL3RA, were upregulated by TCN-induced differentiation. Collectively, we identified TCN as a novel myeloid cell differentiation inducer, and trials of TCN for APL and non-APL leukemia are worthy of exploration in the future.In Tokyo 2020 Paralympic Games, there were the rule and goal size changes at the blind football competition. This study aimed to compare the scoring and head impact characteristics during blind football competition between the Rio 2016 and Tokyo 2020 Paralympic Games using the official videos.
Video-based observational study.
In total, 36 blind football (men’s football 5-a-side) game videos were obtained from the official International Paralympic Committee.
Head impact was defined as the sudden contact of any object with the head. Videos were analysed to assess the number of scores and head impacts along with their corresponding details (ie, round, playing phase, scoring situation, impact situation, occurrence area, impact object, head impact site, fall and foul).
The total number of goals scored at the Tokyo 2020 Paralympic Games was nearly double that at the Rio 2016 Paralympic Games. Regarding head impacts, a total of 2036 cases (Rio 2016, n=1105; Tokyo 2020, n=931) were evaluated. Significant differences were observed in head impact characteristics between the Rio 2016 and Tokyo 2020 Paralympic Games among seven outcomes (round, scoring situation, impact situation, occurrence area, impact object, site of head impact and fall).
Compared with the Rio 2016 Paralympic Games, the Tokyo 2020 Paralympic Games showed an increase in the number of points scored and different head impact characteristics.
by Sayaka Iizasa, Koji Nagao, Keisuke Tsuge, Yukio Nagano, Teruyoshi Yanagita
Hepatic steatosis is an early stage in the progression of non-alcoholic fatty liver disease (NAFLD) and can lead to the development of non-alcoholic steatohepatitis (NASH), a major cause of liver-related morbidity and mortality. Identification of dietary components that can alleviate hepatic steatosis is crucial for developing effective therapeutic strategies for NAFLD. Recently, we demonstrated the impact of lipids extracted from the marine red alga Susabinori (Pyropia yezoensis) in a murine model of type 2-diabete (db/db). We found that Susabinori lipids (SNL), abundant in eicosapentaenoic acid (EPA)-containing polar lipids, protected against obesity-induced hepatic steatosis in db/db mice. To understand the specific genes or biological pathways underlying the effects of SNL, we conducted RNA-Seq analysis of the hepatic transcriptome. By performing comparative analysis of differentially expressed genes between normal mice and db/db mice consuming a control diet, as well as SNL-fed db/db mice, we identified the 15 SNL-dependent up-regulated genes that were down-regulated in db/db mice but up-regulated by SNL feeding. Gene ontology and pathway analysis on these 15 genes demonstrated a significant association with the metabolisms of arachidonic acid (AA) and linoleic acid (LA). Furthermore, we observed alterations in the expression levels of monoacylglycerol lipase (Magl) and fatty acid-binding protein 4 (Fabp4) in the SNL-fed db/db mice, both of which are implicated in AA and LA metabolism. Additionally, the livers of SNL-fed db/db mice exhibited reduced levels of AA and LA, but a high accumulation of EPA. In conclusion, the SNL diet might affect the metabolisms of AA and LA, which contribute to the improvement of hepatic steatosis. Our findings provide insights into the molecular mechanisms underlying the beneficial effects of SNL.
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