トチバニンジン (Panax) 属植物の摂取が運動に与える作用の臨床試験に基づく探索的研究

東京農業大学博士(農学)2022doctoral thesi

Activation of focal adhesion kinase via M1 muscarinic acetylcholine receptor is required in restitution of intestinal barrier function after epithelial injury

AbstractImpairment of epithelial barrier is observed in various intestinal disorders including inflammatory bowel diseases (IBD). Numerous factors may cause temporary damage of the intestinal epithelium. A complex network of highly divergent factors regulates healing of the epithelium to prevent inflammatory response. However, the exact repair mechanisms involved in maintaining homeostatic intestinal barrier integrity remain to be clarified.In this study, we demonstrate that activation of M1 muscarinic acetylcholine receptor (mAChR) augments the restitution of epithelial barrier function in T84 cell monolayers after ethanol-induced epithelial injury, via ERK-dependent phosphorylation of focal adhesion kinase (FAK). We have shown that ethanol injury decreased the transepithelial electrical resistance (TER) along with the reduction of ERK and FAK phosphorylation. Carbachol (CCh) increased ERK and FAK phosphorylation with enhanced TER recovery, which was completely blocked by either MT-7 (M1 antagonist) or atropine. The CCh-induced enhancement of TER recovery was also blocked by either U0126 (ERK pathway inhibitor) or PF-228 (FAK inhibitor). Treatment of T84 cell monolayers with interferon-γ (IFN-γ) impaired the barrier function with the reduction of FAK phosphorylation. The CCh-induced ERK and FAK phosphorylation were also attenuated by the IFN-γ treatment. Immunological and binding experiments exhibited a significant reduction of M1 mAChR after IFN-γ treatment. The reduction of M1 mAChR in inflammatory area was also observed in surgical specimens from IBD patients, using immunohistochemical analysis. These findings provide important clues regarding mechanisms by which M1 mAChR participates in the maintenance of intestinal barrier function under not only physiological but also pathological conditions

De Novo Formation of Left–Right Asymmetry by Posterior Tilt of Nodal Cilia

In the developing mouse embryo, leftward fluid flow on the ventral side of the node determines left–right (L-R) asymmetry. However, the mechanism by which the rotational movement of node cilia can generate a unidirectional flow remains hypothetical. Here we have addressed this question by motion and morphological analyses of the node cilia and by fluid dynamic model experiments. We found that the cilia stand, not perpendicular to the node surface, but tilted posteriorly. We further confirmed that such posterior tilt can produce leftward flow in model experiments. These results strongly suggest that L-R asymmetry is not the descendant of pre-existing L-R asymmetry within each cell but is generated de novo by combining three sources of spatial information: antero-posterior and dorso-ventral axes, and the chirality of ciliary movement

VLSI Implementation of a Scalable Pipeline MMSE MIMO Detector for a 4 x 4 MIMO-OFDM Receiver

MIMO-OFDM performs signal detection on a subcarrier basis which requires high speed computation in MIMO detection due to its large computational cost. Conventional designs in a MIMO detector increase processing time in proportion to the number of subcarriers and have difficulty in real-time processing for large numbers of subcarriers. A complete pipeline MMSE MIMO detector presented in our previous work can provide high speed computation. However, it tends to be excessive in a circuit scale for small numbers of subcarriers. We propose a new scalable architecture to reduce circuit scale by adjusting the number of iterative operations according to various types of OFDM system. The proposed detector has reduced circuit area to about 1/2 to 1/7 in the previous design with providing acceptable latency time

Exploratory Systematic Review and Meta-Analysis of Panax Genus Plant Ingestion Evaluation in Exercise Endurance

Background: Many studies that use food containing Panax genus plants (PGPs) have been conducted but most of them have not mentioned the effective compounds ginsenosides and their composition. Therefore, we conducted a systematic review and meta-analysis of time to exhaustion as an index of exercise endurance with ingestion of PGPs or ginsenosides to reveal their effects. Methods: We performed a systematic review with a comprehensive and structured literature search using seven literature databases, four clinical trial databases, and three general web search engines during 15–22 March 2021. A random-effects model was applied to calculate the standardized mean difference (SMD) and 95% confidence interval (CI) as the difference between the mean in the treatment and placebo groups. We evaluated the risk of bias of individual studies along with the risk of bias tool in the Cochrane handbook. This study was funded by Maruzen Pharmaceuticals Co., Ltd. (Hiroshima, Japan). The protocol for this study was registered with the UMIN-CTR (No. UMIN000043341). Results: Five studies met the inclusion criteria. The number of total participants was 90, with 59 in the ingestion-PGPs group and 64 in the control group, because three studies were crossover-design trials. We found that ingestion of PGPs or ginsenosides significantly improved exercise endurance (SMD [95% CI]: 0.58 [0.22–0.95], I2 = 0%). It was suggested that ginsenoside Rg1 (Rg1) and PGPs extract containing Rg1 were significantly effective in improving exercise endurance (SMD [95% CI]: 0.70 [0.14–1.27], I2 = 30%) by additional analysis. Conclusions: This systematic review suggests that the ingestion of PGPs or ginsenosides, especially Rg1, is effective in improving exercise endurance in healthy adults. However, further high-quality randomized controlled trials are required because imprecision and publication bias cannot be ignored in this systematic review

Experimental Fluid Dynamics Model of the Posterior Tilt Mechanism

<div><p>(A) Schematic representation of the model. Wires driven by stepper motors stir silicone fluid of 30,000 centipoise. Note that the fluid surface is in contact with the acrylic board. Resulting flow is visualized as movement of glitter particles inserted through holes on the board. Wires are connected to motor axles by elastomer connectors in order to smoothen the stepwise motion of the motors. The path of the wires is completely specified by the two angles θ and ψ, as shown in the diagram.</p> <p>(B) Photograph of the model. Corresponding directions are indicated.</p> <p>(C) Leftward flow. Flow generated by five rotating wires (visible as white lines in photo) drives glitter towards the left at the depth of 3 mm from the surface. Trajectory of the glitter becomes curved far from the wires (t = 3′) because the glitter has reached the chamber's wall. Scale = 1 cm.</p> <p>(D) Flow velocity (leftward component) as a function of tilt and bend angles. The flow velocity shown here represents the flow speed at the depth of 3 mm. The flow is most efficient when the path of the wire is tangential to the board surface during part of its rotation (i.e., ψ + θ = 90°).</p> <p>(E) Leftward flow near the surface. Glitter was injected on the right side at the surface of the fluid (no more than 1-mm depth). Only leftward flow was observed. Scale = 1 cm.</p></div

Trajectory of Node Cilia Movement

<div><p>(A) Trace of node cilia in enhanced DIC images after background subtraction. Positions of root are indicated in black, and tip in blue, green, and orange. Most cilia have a pattern consistent with the projection of a tilted cone (blue and green, see text) whereas some cilia move in a D-shape (orange). A, P, L, and R refer to anterior, posterior, left, and right sides of the node, respectively. The direction of cilia rotation was clockwise (arrows).</p> <p>(B) Relationship between essentially rotatory movement of cilia and their projected images at various tilt angles.</p></div

Flow Generation Mechanism

<p>Circular clockwise motion of a cilium can generate directional leftward flow if its axis is not perpendicular to the cell surface but tilted posteriorly. Due to distance from the cell surface, a cilium in the leftward phase (red arrow) drags surrounding water more efficiently than the rightward phase (blue arrow), resulting in leftward force in total (purple arrow). See text for details. The rotating cilium is drawn slightly bent due to viscous resistance, as seen in <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0030268#sv001" target="_blank">Video S1</a>.</p