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961.
Sato-Hashimoto M Saito Y Ohnishi H Iwamura H Kanazawa Y Kaneko T Kusakari S Kotani T Mori M Murata Y Okazawa H Ware CF Oldenborg PA Nojima Y Matozaki T 《Journal of immunology (Baltimore, Md. : 1950)》2011,187(1):291-297
The molecular basis for formation of lymphoid follicle and its homeostasis in the secondary lymphoid organs remains unclear. Signal regulatory protein α (SIRPα), an Ig superfamily protein that is predominantly expressed in dendritic cells or macrophages, mediates cell-cell signaling by interacting with CD47, another Ig superfamily protein. In this study, we show that the size of the T cell zone as well as the number of CD4(+) T cells were markedly reduced in the spleen of mice bearing a mutant (MT) SIRPα that lacks the cytoplasmic region compared with those of wild-type mice. In addition, the expression of CCL19 and CCL21, as well as of IL-7, which are thought to be important for development or homeostasis of the T cell zone, was markedly decreased in the spleen of SIRPα MT mice. By the use of bone marrow chimera, we found that hematopoietic SIRPα is important for development of the T cell zone as well as the expression of CCL19 and CCL21 in the spleen. The expression of lymphotoxin and its receptor, lymphotoxin β receptor, as well as the in vivo response to lymphotoxin β receptor stimulation were also decreased in the spleen of SIRPα MT mice. CD47-deficient mice also manifested phenotypes similar to SIRPα MT mice. These data suggest that SIRPα as well as its ligand CD47 are thus essential for steady-state homeostasis of T cells in the spleen. 相似文献
962.
Okamoto M Kushiro T Jikumaru Y Abrams SR Kamiya Y Seki M Nambara E 《Phytochemistry》2011,72(8):717-722
Abscisic acid (ABA) catabolism is important for regulating endogenous ABA levels. To date, most effort has focused on catabolism of ABA to phaseic acid (PA), which is generated spontaneously after 8′-hydroxylation of ABA by cytochrome P450s in the CYP707A subfamily. Neophaseic acid (neoPA) is another well-documented ABA catabolite that is produced via ABA 9′-hydroxylation, but the 9′-hydroxylase has not yet been defined. Here, we show that endogenous neoPA levels are reduced in loss-of-function mutants defective in CYP707A genes. In addition, in planta levels of both neoPA and PA are reduced after treatment of plants with uniconazole-P, a P450 inhibitor. These lines of evidence suggest that CYP707A genes also encode the 9′-hydroxylase required for neoPA synthesis. To test this, in vitro enzyme assays using microsomal fractions from CYP707A-expressing yeast strains were conducted and these showed that all four Arabidopsis CYP707As are 9′-hydroxylases, although this activity is minor. Collectively, our results demonstrate that ABA 9′-hydroxylation is catalyzed by CYP707As as a side reaction. 相似文献
963.
964.
Kaku T Hitaka T Ojida A Matsunaga N Adachi M Tanaka T Hara T Yamaoka M Kusaka M Okuda T Asahi S Furuya S Tasaka A 《Bioorganic & medicinal chemistry》2011,19(21):6383-6399
A novel naphthylmethylimidazole derivative 1 and its related compounds were identified as 17,20-lyase inhibitors. Based on the structure-activity relationship around the naphthalene scaffold and the results of a docking study of 1a in the homology model of 17,20-lyase, the 6,7-dihydro-5H-pyrrolo[1,2-c]imidazole derivative (+)-3c was synthesized and identified as a potent and highly selective 17,20-lyase inhibitor. Biological evaluation of (+)-3c at a dose of 1mg/kg in a male monkey model revealed marked reductions in both serum testosterone and dehydroepiandrosterone concentrations. Therefore, (+)-3c (termed orteronel [TAK-700]) was selected as a candidate for clinical evaluation and is currently in phase III clinical trials for the treatment of castration-resistant prostate cancer. 相似文献
965.
Satoru Inoguchi Naohiko Seki Takeshi Chiyomaru Tomoaki Ishihara Ryosuke Matsushita Hiroko Mataki Toshihiko Itesako Shuichi Tatarano Hirofumi Yoshino Yusuke Goto Rika Nishikawa Masayuki Nakagawa Hideki Enokida 《FEBS letters》2014
Here, we found that microRNA-24-1 (miR-24-1) is significantly reduced in bladder cancer (BC) tissues, suggesting that it functions as a tumour suppressor. Restoration of mature miR-24-1 inhibits cancer cell proliferation and induces apoptosis. Forkhead box protein M1 (FOXM1) is a direct target gene of miR-24-1, as shown by genome-wide gene expression analysis and luciferase reporter assay. Overexpressed FOXM1 is confirmed in BC clinical specimens, and silencing of FOXM1 induces apoptosis in cancer cell lines. Our data demonstrate that the miR-24-1–FOXM1 axis contributes to cancer cell proliferation in BC, and elucidation of downstream signalling will provide new insights into the molecular mechanisms of BC oncogenesis. 相似文献
966.
967.
Satoru Sawai Kiyoshi Ohyama Shuhei Yasumoto Hikaru Seki Tetsushi Sakuma Takashi Yamamoto Yumiko Takebayashi Mikiko Kojima Hitoshi Sakakibara Toshio Aoki Toshiya Muranaka Kazuki Saito Naoyuki Umemoto 《The Plant cell》2014,26(9):3763-3774
Potatoes (Solanum tuberosum) contain α-solanine and α-chaconine, two well-known toxic steroidal glycoalkaloids (SGAs). Sprouts and green tubers accumulate especially high levels of SGAs. Although SGAs were proposed to be biosynthesized from cholesterol, the biosynthetic pathway for plant cholesterol is poorly understood. Here, we identify sterol side chain reductase 2 (SSR2) from potato as a key enzyme in the biosynthesis of cholesterol and related SGAs. Using in vitro enzyme activity assays, we determined that potato SSR2 (St SSR2) reduces desmosterol and cycloartenol to cholesterol and cycloartanol, respectively. These reduction steps are branch points in the biosynthetic pathways between C-24 alkylsterols and cholesterol in potato. Similar enzymatic results were also obtained from tomato SSR2. St SSR2-silenced potatoes or St SSR2-disrupted potato generated by targeted genome editing had significantly lower levels of cholesterol and SGAs without affecting plant growth. Our results suggest that St SSR2 is a promising target gene for breeding potatoes with low SGA levels. 相似文献
968.
Petra I. Baeumler Johannes Fleckenstein Shin Takayama Michael Simang Takashi Seki Dominik Irnich 《PloS one》2014,9(12)
Background
The effect of acupuncture on sensory perception has never been systematically reviewed; although, studies on acupuncture mechanisms are frequently based on the idea that changes in sensory thresholds reflect its effect on the nervous system.Methods
Pubmed, EMBASE and Scopus were screened for studies investigating the effect of acupuncture on thermal or mechanical detection or pain thresholds in humans published in English or German. A meta-analysis of high quality studies was performed.Results
Out of 3007 identified articles 85 were included. Sixty five studies showed that acupuncture affects at least one sensory threshold. Most studies assessed the pressure pain threshold of which 80% reported an increase after acupuncture. Significant short- and long-term effects on the pressure pain threshold in pain patients were revealed by two meta-analyses including four and two high quality studies, respectively. In over 60% of studies, acupuncture reduced sensitivity to noxious thermal stimuli, but measuring methods might influence results. Few but consistent data indicate that acupuncture reduces pin-prick like pain but not mechanical detection. Results on thermal detection are heterogeneous. Sensory threshold changes were equally frequent reported after manual acupuncture as after electroacupuncture. Among 48 sham-controlled studies, 25 showed stronger effects on sensory thresholds through verum than through sham acupuncture, but in 9 studies significant threshold changes were also observed after sham acupuncture. Overall, there is a lack of high quality acupuncture studies applying comprehensive assessments of sensory perception.Conclusions
Our findings indicate that acupuncture affects sensory perception. Results are most compelling for the pressure pain threshold, especially in pain conditions associated with tenderness. Sham acupuncture can also cause such effects. Future studies should incorporate comprehensive, standardized assessments of sensory profiles in order to fully characterize its effect on sensory perception and to explore the predictive value of sensory profiles for the effectiveness of acupuncture. 相似文献969.
Nicola J. Robertson Takenori Kato Alan Bainbridge Manigandan Chandrasekaran Osuke Iwata Andrew Kapetanakis Stuart Faulkner Jeanie Cheong Sachiko Iwata Mariya Hristova Ernest Cady Gennadij Raivich 《Journal of neurochemistry》2013,124(5):645-657
Na+/H+ exchanger (NHE) blockade attenuates the detrimental consequences of ischaemia and reperfusion in myocardium and brain in adult and neonatal animal studies. Our aim was to use magnetic resonance spectroscopy (MRS) biomarkers and immunohistochemistry to investigate the cerebral effects of the NHE inhibitor, methyl isobutyl amiloride (MIA) given after severe perinatal asphyxia in the piglet. Eighteen male piglets (aged < 24 h) underwent transient global cerebral hypoxia‐ischaemia and were randomized to (i) saline placebo; or (ii) 3 mg/kg intravenous MIA administered 10 min post‐insult and 8 hourly thereafter. Serial phosphorus‐31 (31P) and proton (1H) MRS data were acquired before, during and up to 48 h after hypoxia‐ischaemia and metabolite‐ratio time‐series Area under the Curve (AUC) calculated. At 48 h, histological and immunohistochemical assessments quantified regional tissue injury. MIA decreased thalamic lactate/N‐acetylaspartate and lactate/creatine AUCs (both p < 0.05) compared with placebo. Correlating with improved cerebral energy metabolism, transferase mediated biotinylated d‐UTP nick end‐labelling (TUNEL) positive cell density was reduced in the MIA group in cerebral cortex, thalamus and white matter (all p < 0.05) and caspase 3 immunoreactive cells were reduced in pyriform cortex and caudate nucleus (both p < 0.05). Microglial activation was reduced in pyriform and midtemporal cortex (both p < 0.05). Treatment with MIA starting 10 min after hypoxia‐ischaemia was neuroprotective in this perinatal asphyxia model. 相似文献
970.
Kenji Tagai Maiko Ono Manabu Kubota Soichiro Kitamura Keisuke Takahata Chie Seki Yuhei Takado Hitoshi Shinotoh Yasunori Sano Yasuharu Yamamoto Kiwamu Matsuoka Hiroyuki Takuwa Masafumi Shimojo Manami Takahashi Kazunori Kawamura Tatsuya Kikuchi Maki Okada Haruhiko Akiyama Hitoshi Shimada 《Neuron》2021,109(1):42-58.e8