Periostin-expressing cell-specific transforming growth factor-β inhibition in pulmonary artery prevents pulmonary arterial hypertension

Transforming growth factor beta (TGF-β) has been shown to play a critical role in pathogenesis of pulmonary arterial hypertension (PAH) although the precise role of TGF-β signaling remains uncertain. A recent report has shown that periostin (Pn) is one of the most upregulated proteins in human PAH lung compared with healthy lungs. We established type I TGF-β receptor knockout mice specifically with Pn expressing cell (Pn-Cre/Tgfb1fl/fl mice). Increases in PA pressure and pulmonary artery muscularization were induced by hypoxia of 10% oxygen for 4 weeks. Lung Pn expression was markedly induced by 4 week-hypoxia. Pn-Cre/Tgfb1fl/fl mice showed lower right ventricular pressure elevation, inhibition of PA medial thickening. Fluorescent co-immunostaining showed that Smad3 activation in Pn expressing cell is attenuated. These results suggest that TGF-β signaling in Pn expressing cell may have an important role in the pathogenesis of PAH by controlling medial thickening

Mechanical Properties and Histological Evaluation of Bone Grafting Materials Containing Different Ratios of Calcium Phosphate Cement and Porous β-tricalcium Phosphate Granules

Article信州医学雑誌 66(2): 139-150(2018)journal articl

Bile Acids Induce Cdx2 Expression Through the Farnesoid X Receptor in Gastric Epithelial Cells

Clinical and experimental studies showed that the reflux of bile into the stomach contributes to the induction of intestinal metaplasia of the stomach and gastric carcinogenesis. Caudal-type homeobox 2 (Cdx2) plays a key role in the exhibition of intestinal phenotypes by regulating the expression of intestine-specific genes such as goblet-specific gene mucin 2 (MUC2). We investigated the involvement of the farnesoid X receptor (FXR), a nuclear receptor for bile acids, in the chenodeoxycholic acid (CDCA)-induced expression of Cdx2 and MUC2 in normal rat gastric epithelial cells (RGM-1 cells). RGM-1 cells were treated with CDCA or GW4064, an FXR agonist, in the presence or absence of guggulsterone, an FXR antagonist. CDCA induced dose-dependent expression of Cdx2 and MUC2 at both the mRNA and protein levels. The maximum stimulation of Cdx2 and MUC2 mRNA induced by CDCA was observed at 3 h and by 6 h, respectively. GW4064 also induced expression of these molecules. The effects of CDCA and GW4064 on expression of Cdx2 and MUC2 were abolished by guggulsterone. These findings suggest that bile acids may induce gastric intestinal metaplasia and carcinogenesis through the FXR

Lansoprazole, a Proton Pump Inhibitor, Suppresses Production of Tumor Necrosis Factor-α and Interleukin-1β Induced by Lipopolysaccharide and Helicobacter Pylori Bacterial Components in Human Monocytic Cells via Inhibition of Activation of Nuclear Factor-κB and Extracellular Signal-Regulated Kinase

Pathogenic bacterial components play critical roles in initiation of gastrointestinal inflammation via activation of intracellular signaling pathways which induce proinflammatory cytokines such as tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Lansoprazole (LANSO), a proton pump inhibitor, has been widely used for the treatment of peptic ulcers and reflux esophagitis due to its potent acid-suppressive effect. It has also been reported to have anti-inflammatory effects. In this study we investigated the effects of LANSO on the production of TNF-α and IL-1β induced by lipopolysaccharide (LPS) and Helicobacter pylori water-soluble extract (HpWE) in the human monocytic cell line (THP-1). LANSO (100 µM) significantly reduced mRNA expression and production of TNF-α and IL-1β by THP-1 cells stimulated by LPS and HpWE. LANSO inhibited phosphorylation and degradation of inhibitory factor κB-α (IκB-α) and phosphorylation of extracellular signal-regulated kinase (ERK) induced by LPS and HpWE in THP-1 cells. These findings suggest that LANSO exerts anti-inflammatory effects by suppressing induction of TNF-α and IL-1β via inhibition of nuclear factor (NF)-κB and ERK activation

Mitochondrial disorders in NSAIDs-induced small bowel injury

Recent studies using small bowel endoscopy revealed that non-steroidal anti-inflammatory drugs including low-dose aspirin, can often induce small bowel injury. Non-steroidal anti-inflammatory drugs-induced small bowel mucosal injury involves various factors such as enterobacteria, cytokines, and bile. Experimental studies demonstrate that both mitochondrial disorders and inhibition of cyclooxygenases are required for development of non-steroidal anti-inflammatory drugs-induced small bowel injury. Mitochondrion is an organelle playing a central role in energy production in organisms. Many non-steroidal anti-inflammatory drugs directly cause mitochondrial disorders, which are attributable to uncoupling of oxidative phosphorylation induced by opening of the mega channel called mitochondrial permeability transition pore on the mitochondrial membrane by non-steroidal anti-inflammatory drugs. Bile acids and tumor necrosis factor-α also can open the permeability transition pore. The permeability transition pore opening induces the release of cytochrome c from mitochondrial matrix into the cytosol, which triggers a cascade of events that will lead to cell death. Therefore these mitochondrial disorders may cause disturbance of the mucosal barrier function and elevation of the small bowel permeability, and play particularly important roles in early processes of non-steroidal anti-inflammatory drugs-induced small bowel injury. Although no valid means of preventing or treating non-steroidal anti-inflammatory drugs-induced small bowel injury has been established, advances in mitochondrial studies may bring about innovation in the prevention and treatment of this kind of injury

Rebamipide, a mucoprotective drug, inhibits NSAIDs-induced gastric mucosal injury: possible involvement of the downregulation of 15-hydroxyprostaglandin dehydrogenase

Prostaglandin E2 plays an important role in the maintenance of gastric mucosal integrity. The level of biologically active prostaglandin E2 in the tissue is regulated by the balanced expression of its synthetic enzymes, such as cyclooxygenase, and its catabolic enzyme, 15-hydroxyprostaglandin dehydrogenase. We examined the effect of rebamipide, a mucoprotective drug, on prostaglandin E2 production and metabolism in the gastric tissue and its effect on indomethacin-induced gastric mucosal injury in mice. Rebamipide suppressed indomethacin-induced gastric mucosal injury. Suppressive effect of rebamipide on indomethacin-induced gastric mucosal injury was also observed in cyclooxygenase-2-knockout mice. The mice that were treated with rebamipide showed a 2-fold increase in cyclooxygenase-2 mRNA expression in the gastric tissue, whereas 15-hydroxyprostaglandin dehydrogenase mRNA expression markedly decreased as compared to vehicle-treated control mice. Rebamipide did not affect the expression of cyclooxygenase-1 in the gastric tissue. Rebamipide did not increase prostaglandin E2 production in the gastric tissue; however, it induced a 1.4-fold increase in the concentration of prostaglandin E2 in the gastric tissue as compared to vehicle-treated control mice. These results suggest that the suppressive effect of rebamipide on non-steroidal anti-inflammatory drugs-induced gastric mucosal injury can be attributed to reduced 15-hydroxyprostaglandin dehydrogenase expression, which increases the prostaglandin E2 concentration in the gastric tissue

"Matkalla jo jutellaan, mitähän mielenkiintoista taas saa kuulla" : Äänikirjalukupiiri Vaasan kaupunginkirjastossa

Tutkimuksen tavoitteena oli selvittää kvalitatiivisten menetelmien avulla lukupiiriläisten kokemuksellisuutta. Opinnäytetyössäni painotettiin äänikirjojen lukemisen kokemuksellisuutta. Vertailututkimuksessa käytettiin perinteisempää, painettuja teoksia lukevaa kirjallisuuspiiriä. Tutkimusongelmaan pyrittiin hakemaan vastauksia seuraavien kysymysten kautta: miksi halutaan kuulua lukupiirin, mitä luetaan, millaisista aiheista keskustellaan, kuinka lukupiirissä lukeminen eroaa yksinlukemisesta, mikä merkitys lukupiirin kuulumisella ja siihen liittyvällä kanssakäymisellä on, ja miten äänikirjalukeminen koetaan. Lisäksi selvitettiin, kuinka äänikirjalukupiirissä lukeminen eroaa niin sanotussa perinteisessä lukupiirissä lukemisesta. Kvalitatiivisina tutkimusmetodeina käytettiin havainnointia ja haastatteluja. Äänikirjalukupiirissä havainnointitapaamisia oli kaksi ja vertailulukupiirissä yksi kerta. Molemmista lukupiireistä haastattelin kuutta piiriläistä, eli yhteensä 12 jäsentä. Lukupiiriin kuulumisen perusteluja käsiteltiin seuraavien ulottuvuuksien kautta: lukemisen merkitys, kokemus lukijana, keskustelut lukukokemuksista ja muiden aiheiden merkitys, lukupiirin jäsenten välinen sosiaalinen kanssakäyminen sekä lukija yhteisöllisen lukupiirin jäsenenä. Tutkimustulosten mukaan lukupiireihin hakeuduttiin laajemman kirjallisuudentuntemuksen saamiseksi, yhteisen keskustelun ja lukukokemusten jakamisen vuoksi. Äänikirjalukupiiriin kuulumisessa korostettiin laajemman mahdollisuuden saamista kirjallisuuden harrastamiseen, aineiston tärkeää ja helppoa saamista kerhon kautta. Celian rinkiin pääsy kerhon kautta oli osa koettua merkitystä. Lukupiirien sosiaalisissa kontakteissa pyrittiin ” helppouteen perustuvaan ystävyyteen”, jossa ryhmään hakeudutaan viihtymään ja nauttimaan yhdessäolosta. Lukupiirien sosiaaliset suhteet koettiin työelämän suhteiden korvaajina. Koettiin oppimisen iloa, itsetuntemuksen lisääntymistä, antamisen ja auttamisen iloa. Muutostoiveet liitettiin keskustelun parantamiseen, tietoisuuden lisääntymiseen ja omaan oppimiseen.The aim of the study was to examine, through qualitative methods, experience among the literature circle. The thesis study emphasized experience during the reading of audio books. In addition, differences between an audio book circle and a traditional literature circle were studied. The research questions were the following: why the members want to participate in literature circles; what books are read; what kinds of issues are discussed; how reading in a literature circle differs from reading alone; what participating in a literature circle means to the participants, and what the participants thought about the listening of audio books. In addition, it was examined how the reading of audio books differs from reading in a traditional literature circle. I used qualitative methods, observation and interviews. I interviewed six members of an audio books circle and six members of the literature circle. Arguments for membership in a reading circle were analysed thought the following dimensions: the significance of reading, experience as a reader, discussions about reading experiences others methods meaning of the reading, experience as reader, discussions from read experiences and the significance of others topics, interaction between the members of the literature circles, and the reader as a member in a communal reading circle. According to the results, the interviewees joined the literature circles in order to improve their knowledge of literature, to have common discussions, and to share reading experiences. The members of the audio book circle emphasized the opportunity to take an interest in literature and easy access to materials through the club. Becoming a customer of Celia through the circle was part of its perceived significance. In the social contacts in the reading circles, “friendship based on easiness” was sought. The social relationships within the group were perceived as a substitute to relationships in working life

チタン鋳造における鋳型温度の影響

The purpose of this study was to evaluate the titanium castability with a vacuum pressured type casting machine. We tested ethyl-silicate bonded investment "TITAVESTPS" of metal frame work. Four different mold temperatures (room temperature, 300℃, 600℃, and 900℃) were prepared for the present study, and casting was done in five times in each condition. When the mold temperature increased, high percentage of castability was gained. Mold temperature showed a highly significant (p<0.001) correlation on the castability. These results indicate that high performance of castability on the titanium was achieved when the mold temperature increased by using vacuum pressured type casting machine

Effects of pectin liquid on gastroesophageal reflux disease in children with cerebral palsy

<p>Abstract</p> <p>Background</p> <p>The use of thickeners is a standard therapy for decreasing episodes of regurgitation or vomiting in infants. However, it remains to be investigated whether thickener is effective for vomiting and/or chronic respiratory symptoms in children with cerebral palsy.</p> <p>Methods</p> <p>We enrolled 18 neurologically impaired children caused by cerebral palsy, with gastroesophageal reflux disease. In the first part of this study (pH monitoring), subjects were randomly allocated to two groups: fed with a high-pectin diet [enteral formula: pectin liquid = 2:1 (v/v)], or a low-pectin diet [enteral formula: pectin liquid = 3:1 (v/v)]. Two-channel esophageal pH monitoring was performed over 48 h. In the second part (clinical trial), subjects were fed a high- or low-pectin diet and non-pectin diet for 4 weeks in a crossover manner. Nurses recorded the feeding volume, number of episodes of vomiting, volume of gastric residue, episodes of cough and wheeze, frequency of using oxygen for dyspnea, and the day when the child could return to school. Cough and wheeze were recorded as a cough-score.</p> <p>Results</p> <p>The median value for the % time pH < 4 at the lower and upper esophagus was significantly decreased with a high-pectin diet [9.2% (6.2–22.6) vs. 5.0% (3.1–13.1); P < 0.01, 3.8% (2.9–11.2) vs. 1.6% (0.9–8.9); P < 0.01 (interquartile range), non-pectin and high-pectin, respectively]. The number of reflux episodes per day and duration of longest reflux were decreased significantly with a high-pectin, but not with a low-pectin diet. The median number of episodes of vomiting decreased significantly with a high-pectin diet [2.5/week (1.0–5.0) vs. 1.0 (1.0–1.5), P < 0.05]. The median cough-score was significantly decreased by both concentrations of pectin [8.5/week (1.0–11.5) vs. 2.0/week (0.0–3.0), fed with a high-pectin diet; 7.0/week (1.0–14.5) vs. 1.0/w (0.0–5.0), fed with a low-pectin diet, P < 0.05].</p> <p>Conclusion</p> <p>Pectin liquid partially decreased gastroesophageal reflux as measured by eshophageal pH monitoring, and might improve vomiting and respiratory symptoms in children with cerebral palsy.</p> <p>Trial registration</p> <p>ISRCTN19787793</p

BioHackathon series in 2011 and 2012: penetration of ontology and linked data in life science domains

The application of semantic technologies to the integration of biological data and the interoperability of bioinformatics analysis and visualization tools has been the common theme of a series of annual BioHackathons hosted in Japan for the past five years. Here we provide a review of the activities and outcomes from the BioHackathons held in 2011 in Kyoto and 2012 in Toyama. In order to efficiently implement semantic technologies in the life sciences, participants formed various sub-groups and worked on the following topics: Resource Description Framework (RDF) models for specific domains, text mining of the literature, ontology development, essential metadata for biological databases, platforms to enable efficient Semantic Web technology development and interoperability, and the development of applications for Semantic Web data. In this review, we briefly introduce the themes covered by these sub-groups. The observations made, conclusions drawn, and software development projects that emerged from these activities are discussed