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| 1.
論文 |
論文
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Higuchi, Akihiro ; Erina Oonishi ; Kawakita, Tetsuya ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />Purpose: 2-hydroxy estradiol (2-OHE2) is a catechol derivative of 17β -Estradiol (E2) and it is s
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ynthesized from E2 catalyzed by cytochrome P4501A1. Previous studies reported that 2-OHE2 is a physiologic antioxidant in lipoproteins, liver microsomes, and the brain. Catechol derivatives show an anti-inflammatory effect through the inhibition of prostaglandin endoperoxide synthase (PGS) activity. Corneal erosion caused by dry eye is related to an increase in oxidative stress and inflammation in ocular surface cells. We investigated the therapeutic effects of 2-OHE2 on corneal damage caused by dry eye. Methods: Steroidal radical scavenging activity was confirmed through the electron spin resonance (ESR) method. PGS activity was measured using the COX Fluorescent Activity Assay Kit. To evaluate the effect of 2-OHE2 on the treatment for dry eye, 2-OHE2 was applied as an eye drop experiment using dry eye model rats. Results: 2-OHE2 scavenged tyrosyl radical and possibly suppressed oxidative stress in corneal epithelial cells. In addition, 2-OHE2 inhibited PGS activity, and 2-OHE2 is probably a competitive inhibitor of PGS. Corneal PGS activity was upregulated in the dry eye group. Therefore, 2-OHE2 eye drops improved corneal erosion in dry eye model rats. Conclusions: 2-OHE2 is a candidate for the treatment of dry eye through the suppression of inflammation and oxidative stress in the cornea. © 2016 Molecular Vision.
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| 2.
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論文
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Echizen, Kanae ; Hirose, Osamu ; Maeda, Yusuke ; Oshima, Masanobu
概要:
Cyclooxygenase-2 (COX-2) and its downstream product prostaglandin E2 (PGE2) play a key role in generation of the inflamm
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atory microenvironment in tumor tissues. Gastric cancer is closely associated with Helicobacter pylori infection, which stimulates innate immune responses through Toll-like receptors (TLRs), inducing COX-2/PGE2 pathway through nuclear factor-κB activation. A pathway analysis of human gastric cancer shows that both the COX-2 pathway and Wnt/β-catenin signaling are significantly activated in tubular-type gastric cancer, and basal levels of these pathways are also increased in other types of gastric cancer. Expression of interleukin-11, chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and CXCL5, which play tumor-promoting roles through a variety of mechanisms, is induced in a COX-2/PGE2 pathway-dependent manner in both human and mouse gastric tumors. Moreover, the COX-2/PGE2 pathway plays an important role in the maintenance of stemness with expression of stem cell markers, including CD44, Prom1, and Sox9, which are induced in both gastritis and gastric tumors through a COX-2/PGE2-dependent mechanism. In contrast, disruption of Myd88 results in suppression of the inflammatory microenvironment in gastric tumors even when the COX-2/PGE2 pathway is activated, indicating that the interplay of the COX-2/PGE2 and TLR/MyD88 pathways is needed for inflammatory response in tumor tissues. Furthermore, TLR2/MyD88 signaling plays a role in maintenance of stemness in normal stem cells as well as gastric tumor cells. Accordingly, these results suggest that targeting the COX-2/PGE2 pathway together with TLR/MyD88 signaling, which would suppress the inflammatory microenvironment and maintenance of stemness, could be an effective preventive or therapeutic strategy for gastric cancer. © 2016 Japanese Cancer Association.
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| 3.
その他 |
その他
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| 4.
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論文
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Izumi, Kouji ; Mizokami, Atsushi ; Lin, Hsiu-Ping ; Ho, Hui-Min ; Iwamoto, Hiroaki ; Maolake, Aerken ; Natsagdorj, Ariunbold ; Kitagawa, Yasuhide ; Kadono, Yoshifumi ; Miyamoto, Hiroshi ; Huang, Chiung-Kuei ; Namiki, Mikio ; Lin, Wen-Jye
概要:
Prostate-specific antigen (PSA) is regarded as the most sensitive biomarker for prostate cancer. Although androgen/andro
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gen receptor (AR) signaling promotes prostate cancer progression, suppression of AR signaling induces chemokine (CC motif) ligand 2 (CCL2), which enables prostate cancer cells to gain metastatic potential. AR-controlled PSA alone may be an unreliable biomarker for patients receiving androgen deprivation therapy. Therefore, we investigated the validity of CCL2 as a complementary biomarker to PSA for prostate cancer. Our in vitro approach of enriching for prostate cancer cells with higher migration potential showed that CCL2 activated cellular migration. Importantly, we found that CCL2 levels were significantly different between men (n = 379) with and without prostate cancer. Patients with CCL2 ≥ 320 pg/mL had worse overall survival and prostate cancer -specific survival than those with CCL2 < 320 pg/mL. A novel risk classification was developed according to the risk factors CCL2 ≥ 320 pg/mL and PSA ≥ 100 ng/mL, and scores of 2, 1, and 0 were defined as poor, intermediate, and good risk, respectively, and clearly distinguished patient outcomes. CCL2 may serve as a novel biomarker for prostate cancer. The novel risk classification based on combining CCL2 and PSA is more reliable than using either alone.
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| 5.
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論文
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Juanjuan, Zhao ; Okamoto, Yasuo ; Takuwa, Yoh
概要:
The lysophospholipid mediator sphingosine-1-phosphate (S1P) exerts diverse biological activities including the regulatio
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n of leukocyte migration and vascular barrier integrity, suggesting that S1P signaling could be involved in inflammatory fibrotic diseases. Pulmonary fibrosis is a devastating disease characterized by fibroblast accumulation and extracellular matrix deposition in lungs, and bleomycin–induced pulmonary fibrosis is the most widely used experimental model. We studied the effects of the S1P–specific receptor S1P2 on the phenotypes of lung fibroblasts isolated from bleomycin- and saline-administered wild-type and S1P2–null (S1pr2-/-) mice. The lung fibroblasts from bleomycin-administered wild-type and S1pr2-/- mice failed to proliferate in the presence of serum, unlike fibroblasts from saline-administered mice. The fibroblasts from bleomycin-administered mice also showed the enlarged and flattened morphology compared with fibroblasts from control mice. Bleomycin administration increased the protein expression of the cell cycle inhibitor p16INK4a in fibroblasts and the number of senescence–associated β-galactosidase (SA-β-gal)-positive fibroblasts. In S1pr2-/- fibroblasts, bleomycin administration-induced increases in p16INK4a protein expression and SA–β-gal–positive cells were augmented. Furthermore, bleomycin increased mRNA expression of interleukin-6 and matrix metalloproteinases in S1pr2-/- fibroblasts compared with wild-type fibroblasts. In addition, the activation of Akt in response to platelet–derived growth factor and S1P was enhanced in S1pr2-/- fibroblasts compared with wild-type fibroblasts. These results indicate that S1P2 deletion enhances bleomycin administration–induced cellular senescence of lung fibroblasts, which may lead to inhibition of lung fibrosis through the mechanisms involving increased matrix metalloproteinases expression. Thus, S1P2 may be a novel therapeutic target for lung fibrosis.
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| 6.
論文 |
論文
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Higashida, Haruhiro
概要:
子どものこころの発達研究センター<br />Oxytocin (OT) is released into the brain from the cell soma, axons, and dendrites of neurosecretor
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y cells in the hypothalamus. Locally released OT can activate OT receptors, form inositol-1,4,5-trisphosphate and elevate intracellular free calcium (Ca2+) concentrations [(Ca2+)i] in self and neighboring neurons in the hypothalamus, resulting in further OT release: i.e., autocrine or paracrine systems of OT-induced OT release. CD38-dependent cyclic ADP-ribose (cADPR) is also involved in this autoregulation by elevating [Ca2+]i via Ca2+ mobilization through ryanodine receptors on intracellular Ca2+ pools that are sensitive to both Ca2+ and cADPR. In addition, it has recently been reported that heat stimulation and hyperthermia enhance [Ca2+]i increases by Ca2+ influx, probably through TRPM2 cation channels, suggesting that cADPR and TRPM2 molecules act as Ca2+ signal amplifiers. Thus, OT release is not simply due to depolarization–secretion coupling. Both of these molecules play critical roles not only during labor and milk ejection in reproductive females, but also during social behavior in daily life in both genders. This was clearly demonstrated in CD38 knockout mice in that social behavior was impaired by reduction of [Ca2+]i elevation and subsequent OT secretion. Evidence for the associations of CD38 with social behavior and psychiatric disorder is discussed, especially in subjects with autism spectrum disorder. © 2015 The Author(s)<br />Embargo Period 12 months
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| 7.
図書 |
図書
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岡口基一著
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| 8.
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論文
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Yasuda, Shigeo ; Yokosawa, Haruna ; Mukai, Chisato
概要:
Treatment of the allenylazetidine–alkynes with a catalytic amount of [RhCl(CO)dppp]2 (dppp: 1,3-bis(diphenylphosphino)pr
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opane) effected the intramolecular hetero-[6+2]-type ring-closing reaction via the C–C bond cleavage of the azetidine ring to produce azabicyclo[6.4.0]dodecatriene derivatives in good to excellent yields. The formation of the oxa analogue could also be achieved.
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| 9.
論文 |
論文
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Yasuda, Shigeo ; Yokosawa, Haruna ; Mukai, Chisato
概要:
Treatment of the allenylazetidine–alkynes with a catalytic amount of [RhCl(CO)dppp]2 (dppp: 1,3-bis(diphenylphosphino)pr
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opane) effected the intramolecular hetero-[6+2]-type ring-closing reaction via the C–C bond cleavage of the azetidine ring to produce azabicyclo[6.4.0]dodecatriene derivatives in good to excellent yields. The formation of the oxa analogue could also be achieved.
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| 10.
図書 |
図書
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Tao Le ... [et al.]
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