Effect of Keishi-bukuryo-gan on autonomic nervous activity

桂枝茯苓丸の自律神経活動に対する効果を明らかとするために,レーザードプラ血流計,R-R間隔および収縮期血圧のスペクトル解析を用いて検討した。健常者8名を対象とし,自律神経活動の変化を桂枝茯苓丸料と微温湯において統計学的に解析した。桂枝茯苓丸により,皮膚血流量(SBF)は前値に比較して一旦15分後に減少し,90分後に有意に増加した。収縮期血圧低周波成分(SBP-LF)・収縮期血圧成分比(SBP-L/H)は前値に比較して一旦15分後に増加し,60及び90分後に有意に減少した。微温湯では有意な変化はみられなかった。SBFは交感神経活動にともない変化し,SBP-LF及びSBP-L/Hは交感神経活動と関連するとされている。今回の結果は,桂枝茯苓丸が交感神経活動に対する作用を有していることを示唆するものである。 In order to confirm any effects of Keishi-bukuryo-gan (KBG) on the autonomic nervous system, 8 healthy volunteers were evaluated with laser Doppler flowmetry and spectral analysis of the R-R intervals (RR) and systolic blood pressure (SBP). After evaluation of the "oketsu" score and measurement of the electrophysiological parameters (PRE), each subject was administered KBG or hot water. The same parameters were re-measured at 15, 30, 45, 60 and 90 minutes after their administration to each subject. Changes in the parameters after the administration of KBG or hot water were investigated compared with PRE. In the experiment with KBG, skin blood flow (SBF) was increased at 90 min, although it had been significantly decreased at 15 min. By spectral analysis, SBP-low frequency (LF) and SBP-low to high frequency ratio (L/H) were initially increased at 15 min, and then were significantly decreased at 60 and 90 min. As for hot water, there were no significant changes in any of the parameters. It is known that SBF changes with sympathetic nervous activity, and SBP-LF and SBP-L/H reflect sympathetic nervous activity. These results suggest that KBG has certain effects on sympathetic nervous activity

Enhanced O-GlcNAcylation Mediates Cytoprotection under Proteasome Impairment by Promoting Proteasome Turnover in Cancer Cells

The proteasome is a therapeutic target in cancer, but resistance to proteasome inhibitors often develops owing to the induction of compensatory pathways. Through a genome-wide siRNA screen combined with RNA sequencing analysis, we identified hexokinase and downstream O-GlcNAcylation as cell survival factors under proteasome impairment. The inhibition of O-GlcNAcylation synergistically induced massive cell death in combination with proteasome inhibition. We further demonstrated that O-GlcNAcylation was indispensable for maintaining proteasome activity by enhancing biogenesis as well as proteasome degradation in a manner independent of Nrf1, a well-known compensatory transcription factor that upregulates proteasome gene expression. Our results identify a pathway that maintains proteasome function under proteasome impairment, providing potential targets for cancer therapy

Anomalous negative excursion of carbon isotope in organic carbon after the last Paleoproterozoic glaciation in North America

Early Paleoproterozoic time (2.5–2.0 Ga) spanned a critical phase in Earth's history, characterized by repeated glaciations and an increase in atmospheric oxygen (the Great Oxidation Event (GOE)). Following the last and most intense glaciation of this period, marine carbonates record a large positive excursion of δ^(13)C value (termed the “Lomagundi event”) between about 2.2 and 2.1 Ga coinciding with the global appearances of red beds and sulfates, which suggest an accumulation of high levels of atmospheric oxygen. Here we report the discovery of large negative excursions of δ^(13)C in organic matter (down to −55‰) from quartzose sandstones (of the Marquette Range and the Huronian Supergroups, North America) intermediate in age between the last Paleoproterozoic glaciation and the possible onset of the Lomagundi event. The negative excursion is concomitant with the appearance of intensely weathered quartzose sandstones, which may represent hot and humid conditions. There are some interpretations that potentially explain the negative excursions: (1) redeposition of older ^(13)C-depleted kerogen, (2) later post-depositional infiltration of oil, (3) active methane productions by methanogens in shallow-marine environments, or (4) dissociation of methane hydrate. If the latter two were the case, they would provide clues for understanding the environmental change connecting the intense glaciation and an increase in oxygen

Full-Length Sequence of Mouse Acupuncture-Induced 1-L (Aig1l) Gene Including Its Transcriptional Start Site

We have been investigating the molecular efficacy of electroacupuncture (EA), which is one type of acupuncture therapy. In our previous molecular biological study of acupuncture, we found an EA-induced gene, named acupuncture-induced 1-L (Aig1l), in mouse skeletal muscle. The aims of this study consisted of identification of the full-length cDNA sequence of Aig1l including the transcriptional start site, determination of the tissue distribution of Aig1l and analysis of the effect of EA on Aig1l gene expression. We determined the complete cDNA sequence including the transcriptional start site via cDNA cloning with the cap site hunting method. We then analyzed the tissue distribution of Aig1l by means of northern blot analysis and real-time quantitative polymerase chain reaction. We used the semiquantitative reverse transcriptase-polymerase chain reaction to examine the effect of EA on Aig1l gene expression. Our results showed that the complete cDNA sequence of Aig1l was 6073 bp long, and the putative protein consisted of 962 amino acids. All seven tissues that we analyzed expressed the Aig1l gene. In skeletal muscle, EA induced expression of the Aig1l gene, with high expression observed after 3 hours of EA. Our findings thus suggest that the Aig1l gene may play a key role in the molecular mechanisms of EA efficacy

HbA1c and telemedicine during COVID-19

Aims/Introduction: To investigate whether the COVID-19 pandemic affected behavioral changes and glycemic control in patients with diabetes and to conduct a survey of telemedicine during the pandemic. Materials and Methods: In this retrospective study, a total of 2,348 patients were included from 15 medical facilities. Patients were surveyed about their lifestyle changes and attitudes toward telemedicine. Hemoglobin A1c (HbA1c) levels were compared among before (from June 1 to August 31, 2019) and in the first (from June 1 to August 31, 2020) and in the second (from June 1 to August 31, 2021) year of the pandemic. A survey of physician attitudes toward telemedicine was also conducted. Results: The HbA1c levels were comparable between 2019 (7.27 ± 0.97%), 2020 (7.28 ± 0.92%), and 2021 (7.25 ± 0.94%) without statistical difference between each of those 3 years. Prescriptions for diabetes medications increased during the period. The frequency of eating out was drastically reduced (51.7% in 2019; 30.1% in 2020), and physical activity decreased during the pandemic (48.1% in 2019; 41.4% in 2020; 43.3% in 2021). Both patients and physicians cited increased convenience and reduced risk of infection as their expectations for telemedicine, while the lack of physician–patient interaction and the impossibility of consultation and examination were cited as sources of concern. Conclusions: Our data suggest that glycemic control did not deteriorate during the COVID-19 pandemic with appropriate intensification of diabetes treatment in patients with diabetes who continued to attend specialized diabetes care facilities, and that patients and physicians shared the same expectations and concerns about telemedicine

SILVERRUSH. VII. Subaru/HSC Identifications of 42 Protocluster Candidates at z~6-7 with the Spectroscopic Redshifts up to z=6.574: Implications for Cosmic Reionization

We report fourteen and twenty-eight protocluster candidates at z=5.7 and 6.6 over 14 and 19 deg^2 areas, respectively, selected from 2,230 (259) Lya emitters (LAEs) photometrically (spectroscopically) identified with Subaru/Hyper Suprime-Cam (HSC) deep images (Keck, Subaru, and Magellan spectra and the literature data). Six out of the 42 protocluster candidates include 1-12 spectroscopically confirmed LAEs at redshifts up to z=6.574. By the comparisons with the cosmological Lya radiative transfer (RT) model reproducing LAEs with the reionization effects, we find that more than a half of these protocluster candidates are progenitors of the present-day clusters with a mass of > 10^14 M_sun. We then investigate the correlation between LAE overdensity delta and Lya rest-frame equivalent width EW_Lya^rest, because the cosmological Lya RT model suggests that a slope of EW_Lya^rest-delta relation is steepened towards the epoch of cosmic reionization (EoR), due to the existence of the ionized bubbles around galaxy overdensities easing the escape of Lya emission from the partly neutral intergalactic medium (IGM). The available HSC data suggest that the slope of the EW_Lya^rest-delta correlation does not evolve from the post-reionization epoch z=5.7 to the EoR z=6.6 beyond the moderately large statistical errors. There is a possibility that we would detect the evolution of the EW_Lya^rest - delta relation from z=5.7 to 7.3 by the upcoming HSC observations providing large samples of LAEs at z=6.6-7.3

Differentiation of murine B cells induced by chondroitin sulfate B

A two-step culture system was used to investigate the role of chondroitin sulfate (CS) B, which is mitogenic to B cells, in differentiation of B cells. Mouse spleen B cells were incubated for 3 days with CSB in the presence of interleukin (IL)-4 and IL-5. After washing, the cells were replated at 10(5) viable cells/well and recultured without CSB in the presence of IL-4 and IL-5. CSB dose-dependently increased IgM production, the greatest enhancement being 450%. Dextran sulfate had a similar effect, whereas other glycosaminoglycans, CSA, CSC, heparin and hyaluronic acid, were marginally effective. Treatment of B cells with CSB resulted in increases in the number of IgM-secreting cells and numbers of CD138-positive cells and CD45R/B220-negative cells. CSB-induced IgM production was inhibited by the protein kinase C (PKC) inhibitor GF109203X but not by the phosphatidylinositol 3-kinase (P13K) inhibitor wortmannin. These results demonstrated that CSB promoted differentiation of B cells in the presence of IL-4 and IL-5 and suggested that PKC but not P13K is crucial for CSB-induced IgM production.</p