Effect of Keishibukuryogan, a Japanese Traditional Kampo Prescription, on Improvement of Microcirculation and Oketsu and Induction of Endothelial Nitric Oxide: A Live Imaging Study

Oketsu is a characteristic condition that plays an important role in Kampo, Japanese traditional medicine, and includes multiple aspects of hemodynamic disorders. This study aims to clarify the microcirculation of Oketsu and the pharmacological effect of Keishibukuryogan, an anti-Oketsu Kampo prescription, using live imaging techniques. Oral administration of Keishibukuryogan induced significant vasodilation of murine subcutaneous arterioles compared to the preadministration level. This vasodilatation peaked 60 min after administration and persisted for 90 min. The blood velocity in the subcutaneous capillary was also increased by Keishibukuryogan in generally the same manner. In rat mesenteric arterioles, Keishibukuryogan administration improved microhemodynamic parameters, including the resolution of erythrocyte congestion and the cell-free layer, which are representative of Oketsu pathology. Live imaging revealed an increase of diaminofluorescein-2 diacetate fluorescence, a nitric oxide (NO) specific reagent, in the arterial endothelium following Keishibukuryogan administration. This fluorescence was most remarkable at vascular bifurcations but was present throughout the mesenteric arterioles. This study demonstrates the successful imaging of Oketsu pathology with respect to microcirculation and the anti-Oketsu effects of Keishibukuryogan, namely, vasodilation of arterioles, increased blood velocity, and resolution of erythrocyte congestion. The anti-Oketsu effect of Keishibukuryogan is related to endothelial NO production

High Efficacy of Preoperative Low-Dose Radiotherapy with Sanazole (AK-2123) for Extraskeletal Ewing's Sarcoma: A Case Report

Extraskeletal Ewing's sarcoma is a rare soft tissue tumor that is morphologically indistinguishable from Ewing's sarcoma of bone. We report a case of extraskeletal Ewing's sarcoma with several systemic problems. A 69-year-old man presented with a 5-month history of a rapidly enlarging mass in the right thigh. Because preoperative radiotherapy with sanazole (AK-2123) contributed the tumor mass reduction down to 40% in size, the tumor was successfully resected with clear surgical margins and repaired with a musculocutaneous flap. The high efficacy of pre-operative low-dose radiotherapy with sanazole was histologically confirmed that the resected tumor specimen involved no viable tumor cells and showed 100% necrosis. Based on clinical outcomes in this case, the combined modality of pre-operative low-dose radiotherapy with hypoxic cell radiosensitizer and adequate surgical resection might provide for the useful clinical application of extraskeletal Ewing's sarcoma treatment

Effect of Keishibukuryogan, a Japanese Traditional Kampo Prescription, on Improvement of Microcirculation and Oketsu and Induction of Endothelial Nitric Oxide: A Live Imaging Study

Oketsu is a characteristic condition that plays an important role in Kampo, Japanese traditional medicine, and includes multiple aspects of hemodynamic disorders. This study aims to clarify the microcirculation of Oketsu and the pharmacological effect of Keishibukuryogan, an anti-Oketsu Kampo prescription, using live imaging techniques. Oral administration of Keishibukuryogan induced significant vasodilation of murine subcutaneous arterioles compared to the preadministration level. This vasodilatation peaked 60 min after administration and persisted for 90 min. The blood velocity in the subcutaneous capillary was also increased by Keishibukuryogan in generally the same manner. In rat mesenteric arterioles, Keishibukuryogan administration improved microhemodynamic parameters, including the resolution of erythrocyte congestion and the cell-free layer, which are representative of Oketsu pathology. Live imaging revealed an increase of diaminofluorescein-2 diacetate fluorescence, a nitric oxide (NO) specific reagent, in the arterial endothelium following Keishibukuryogan administration. This fluorescence was most remarkable at vascular bifurcations but was present throughout the mesenteric arterioles. This study demonstrates the successful imaging of Oketsu pathology with respect to microcirculation and the anti-Oketsu effects of Keishibukuryogan, namely, vasodilation of arterioles, increased blood velocity, and resolution of erythrocyte congestion. The anti-Oketsu effect of Keishibukuryogan is related to endothelial NO production

CO Multi-line Imaging of Nearby Galaxies (COMING). IX. 12^{12}CO(JJ=2-1)/12^{12}CO(JJ=1-0) line ratio on kiloparsec scales

While molecular gas mass is usually derived from $^{12}$CO($J$=1-0) - the most fundamental line to explore molecular gas - it is often derived from $^{12}$CO($J$=2-1) assuming a constant $^{12}$CO($J$=2-1)/$^{12}$CO($J$=1-0) line ratio ($R_{2/1}$). We present variations of $R_{2/1}$ and effects of the assumption that $R_{2/1}$ is a constant in 24 nearby galaxies using $^{12}$CO data obtained with the Nobeyama 45-m radio telescope and IRAM 30-m telescope. The median of $R_{2/1}$ for all galaxies is 0.61, and the weighted mean of $R_{2/1}$ by $^{12}$CO($J$=1-0) integrated-intensity is 0.66 with a standard deviation of 0.19. The radial variation of $R_{2/1}$ shows that it is high (~0.8) in the inner ~1 kpc while its median in disks is nearly constant at 0.60 when all galaxies are compiled. In the case that the constant $R_{2/1}$ of 0.7 is adopted, we found that the total molecular gas mass derived from $^{12}$CO($J$=2-1) is underestimated/overestimated by ~20%, and at most by 35%. The scatter of a molecular gas surface density within each galaxy becomes larger by ~30%, and at most by 120%. Indices of the spatially resolved Kennicutt-Schmidt relation by $^{12}$CO($J$=2-1) are underestimated by 10-20%, at most 39% in 17 out of 24 galaxies. $R_{2/1}$ has good positive correlations with star-formation rate and infrared color, and a negative correlation with molecular gas depletion time. There is a clear tendency of increasing $R_{2/1}$ with increasing kinetic temperature ($T_{\rm kin}$). Further, we found that not only $T_{\rm kin}$ but also pressure of molecular gas is important to understand variations of $R_{2/1}$. Special considerations should be made when discussing molecular gas mass and molecular gas properties inferred from $^{12}$CO($J$=2-1) instead of $^{12}$CO($J$=1-0).Comment: 29 pages, 18 figures, 5 tables. Accepted for publication in PASJ. The original resolution version is available here (https://astro3.sci.hokudai.ac.jp/~radio/coming/publications/COMING_IX_org_res.pdf

Social skills and loneliness in junior high school students

The purposes of this study were to examine the relationship between social skills and loneliness, and to contribute to prevention and intervention of loneliness in junior high school students. Questionnaires were administered to 83 students (45 males and 38 females). Correlation analysis showed that loneliness score was negatively related to the scores of peer reinforcement, social initiation, conflict resolution and assertion skills, and also positively related to the score of withdrawal behaviors. In addition, this study found gender differences in the role of social skills and problem behaviors on loneliness. Boys' loneliness was negatively related to peer reinforcement, social initiation, and assertion skills, and girls' loneliness was negatively related to conflict resolution skills, whereas both boys' and girls' loneliness were associated with withdrawal behaviors. These findings were discussed in terms of the context of social skills training

Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1

Osteoclasts have a unique bone-destroying capacity, playing key roles in steady-state bone remodeling and arthritic bone erosion. Whether the osteoclasts in these different tissue settings arise from the same precursor states of monocytoid cells is presently unknown. Here, we show that osteoclasts in pannus originate exclusively from circulating bone marrow-derived cells and not from locally resident macrophages. We identify murine CX3CR1hiLy6CintF4/80+I-A+/I-E+ macrophages (termed here arthritis-associated osteoclastogenic macrophages (AtoMs)) as the osteoclast precursor-containing population in the inflamed synovium, comprising a subset distinct from conventional osteoclast precursors in homeostatic bone remodeling. Tamoxifen-inducible Foxm1 deletion suppressed the capacity of AtoMs to differentiate into osteoclasts in vitro and in vivo. Furthermore, synovial samples from human patients with rheumatoid arthritis contained CX3CR1+HLA-DRhiCD11c+CD80−CD86+ cells that corresponded to mouse AtoMs, and human osteoclastogenesis was inhibited by the FoxM1 inhibitor thiostrepton, constituting a potential target for rheumatoid arthritis treatment.Hasegawa T., Kikuta J., Sudo T., et al. Identification of a novel arthritis-associated osteoclast precursor macrophage regulated by FoxM1. Nature Immunology 20, 1631 (2019); https://doi.org/10.1038/s41590-019-0526-7