Biofabricated Structures Reconstruct Functional Urinary Bladders in Radiation-Injured Rat Bladders

The ability to repair damaged urinary bladders through the application of bone marrow-derived cells is in the earliest stages of development. We investigated the application of bone marrow-derived cells to repair radiation-injured bladders. We used a three-dimensional bioprinting robot system to biofabricate bone marrow-derived cell structures. We then determined if the biofabricated structures could restore the tissues and functions of radiation-injured bladders. The bladders of female 10-week-old Sprague-Dawley (SD) rats were irradiated with 2-Gy once a week for 5 weeks. Adherent and proliferating bone marrow-derived cells harvested from the femurs of male 17-week-old green fluorescence protein-transfected Tg-SD rats were cultured in collagen-coated flasks. Bone marrow-derived cell spheroids were formed in 96-well plates. Three layers of spheroids were assembled by the bioprinter onto a 9x9 microneedle array. The assembled spheroids were perfusion cultured for 7 days, and then the microneedle array was removed. Two weeks after the last radiation treatment, the biofabricated structures were transplanted into an incision on the anterior wall of the bladders (n=10). Control rats received the same surgery but without the biofabricated structures (sham-structure, n=12). At 2 and 4 weeks after surgery, the sham-structure control bladder tissues exhibited disorganized smooth muscle layers, decreased nerve cells, and significant fibrosis with increased presence of fibrosis-marker P4HB-positive cells and hypoxia-marker hypoxia-induced factor 1 (HIF1)-positive cells. The transplanted structures survived within the recipient tissues, and blood vessels extended within them from the recipient tissues. The bone marrow-derived cells in the structures differentiated into smooth muscle cells and formed smooth muscle clusters. The recipient tissues near the transplanted structures had distinct smooth muscle layers and reconstructed nerve cells, and only minimal fibrosis with decreased presence of P4HB- and HIF1-positive cells. At 4 weeks after surgery, the sham-structure control rats exhibited significant urinary frequency symptoms with irregular and short voiding intervals, and low micturition volumes. In contrast, the structure-transplanted rats had regular micturition with longer voiding intervals and higher micturition volumes compared with the control rats. Furthermore, the residual volume of the structure-transplanted rats was lower than for the controls. Therefore, transplantation of biofabricated bone marrow-derived cell structures reconstructed functional bladders.ArticleTISSUE ENGINEERING PART A.24(21-22):1574-1587(2018)journal articl

Combined treatment with β3-adrenergic receptor agonist and a muscarinic receptor antagonist inhibits detrusor overactivity induced by cold stress in spontaneously hypertensive rats

AimsThis study determined if combined treatment with the muscarinic receptor (MR) antagonist solifenacin and the (3)-adrenergic receptor (AR) agonist mirabegron could inhibit detrusor overactivity induced by cold stress in spontaneously hypertensive rats (SHRs). MethodsThirty-two female 10-week-old SHRs were fed an 8% NaCl-supplemented diet for 4 weeks. Cystometric measurements of the unanesthetized, unrestricted rats were performed at room temperature (RT, 272 degrees C) for 20min. The rats were then intravenously administered vehicle, 0.1mg/kg solifenacin alone, 0.1mg/kg mirabegron alone, or the combination of 0.1mg/kg mirabegron and 0.1mg/kg solifenacin (n=8 each group). Five minutes later, the treated rats were exposed to low temperature (LT, 42 degrees C) for 40min. Finally, the rats were returned to RT. After the cystometric investigations, the (3)-ARs and M-3-MRs expressed within the urinary bladders were analyzed. ResultsJust after transfer from RT to LT, vehicle-, solifenacin-, and mirabegron-treated SHRs exhibited detrusor overactivity that significantly decreased voiding interval and bladder capacity. However, treatment with the combination of solifenacin and mirabegron partially inhibited the cold stress-induced detrusor overactivity patterns. The decreases of voiding interval and bladder capacity in the combination-treated rats were significantly inhibited compared to other groups. Within the urinary bladders, there were no differences between expression levels of M-3-MR and (3)-AR mRNA. The tissue distribution of M-3-MRs was similar to that of the (3)-ARs. ConclusionsThis study suggested that the combination of solifenacin and mirabegron act synergistically to inhibit the cold stress-induced detrusor overactivity in SHRs. Neurourol. Urodynam. 36:1026-1033, 2017. (c) 2016 The Authors. Neurourology and Urodynamics Published by Wiley Periodicals, Inc.ArticleNEUROUROLOGY AND URODYNAMICS.36(4):1026-1033(2016)journal articl

Destruxin E Decreases Beta-Amyloid Generation by Reducing Colocalization of Beta-Amyloid-Cleaving Enzyme 1 and Beta-Amyloid Protein Precursor

Alzheimer-disease-associated beta-amyloid (A beta) is produced by sequential endoproteolysis of beta-amyloid protein precursor (beta APP): the extracellular portion is shed by cleavage in the juxtamembrane region by beta-amyloid-cleaving enzyme (BACE)/beta-secretase, after which it is cleaved by presenilin (PS)/gamma-secretase near the middle of the transmembrane domain. Thus, inhibition of either of the secretases reduces A beta generation and is a fundamental strategy for the development of drugs to prevent Alzheimer disease. However, it is not clear how small compounds reduce A beta production without inhibition of the secretases. Such compounds are expected to avoid some of the side effects of secretase inhibitors. Here, we report that destruxin E (Dx-E), a natural cyclic hexadepsipeptide, reduces A beta generation without affecting BACE or PS/gamma-secretase activity. In agreement with this, Dx-E did not inhibit Notch signaling. We found that Dx-E decreases colocalization of BACE1 and beta APP, which reduces beta-cleavage of beta APP. Therefore, the data demonstrate that Dx-E represents a novel A beta-reducing process which could have fewer side effects than secretase inhibitors. Copyright (C) 2009 S. Karger AG, Base

Comparison of Count Normalization Methods for Statistical Parametric Mapping Analysis Using a Digital Brain Phantom Obtained from Fluorodeoxyglucose-positron Emission Tomography

Objective(s): Alternative normalization methods were proposed to solve the biased information of SPM in the study of neurodegenerative disease. The objective of this study was to determine the most suitable count normalization method for SPM analysis of a neurodegenerative disease based on the results of different count normalization methods applied on a prepared digital phantom similar to one obtained using fluorodeoxyglucose-positron emission tomography (FDG-PET) data of a brain with a known neurodegenerative condition.Methods: Digital brain phantoms, mimicking mild and intermediate neurodegenerative disease conditions, were prepared from the FDG-PET data of 11 healthy subjects. SPM analysis was performed on these simulations using different count normalization methods. Results: In the slight-decrease phantom simulation, the Yakushev method correctly visualized wider areas of slightly decreased metabolism with the smallest artifacts of increased metabolism. Other count normalization methods were unable to identify this slightly decreases and produced more artifacts. The intermediate-decreased areas were well visualized by all methods. The areas surrounding the grey matter with the slight decreases were not visualized withthe GM and VOI count normalization methods but with the Andersson. The Yakushev method well visualized these areas. Artifacts were present in all methods. When the number of reference area extraction was increased, the Andersson method better-captured the areas with decreased metabolism and reduced the artifacts of increased metabolism. In the Yakushev method, increasing the threshold for the reference area extraction reduced such artifacts.Conclusion: The Yakushev method is the most suitable count normalization method for the SPM analysis of neurodegenerative disease

歩き遍路を主体とした鳴門教育大学「阿波学」における教科横断型授業の展開

Naruto University of Education offers an undergraduate class called "Awa (Tokushima) Studies", which is taught by twelve instructors whose specialties span history, geography, psychology, art, physical education, and linguistics. In this class, after studying the background and history of Ohenro, a pilgrimage route in Shikoku, in classroom lectures, the students and the instructors walk a part of the pilgrimage route on a one-night-two-day trip, in which interdisciplinary studies are practiced. This class is an ideal opportunity for teacher training and therefore can serve to strategically promote Naruto University of Education as a unique university in offering such a class

Text Data Mining of English Interviews

Part 8: ICBAKE 2015 WorkshopInternational audienceAn “interview” is the technique to gain the particular data effectively which the interviewers want to know through the conversation. In this paper, we metrically analyzed some English interviews: Larry King Live on CNN, and compared these with English news (CNN Live Today) and the inaugural addresses of the three U.S. Presidents. In short, frequency characteristics of character- and word-appearance were investigated using a program written in C++. These characteristics were approximated by an exponential function. Furthermore, we calculated the percentage of American basic vocabulary to obtain the difficulty-level as well as the K-characteristic of each material