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991.
Endometriosis is a common gynecological disorder associated with infertility. However, treatment options remain limited at present. Since the pathogenesis involves immune responses, the immunomodulatory effect of macrolide on endometriosis has been the focus of much research. A previous study showed that clarithromycin decreased stromal proliferation and promoted apoptosis of fibroblasts in an endometriosis model in rats; however, the mechanism of the effect remains unknown. The aim of this study is to investigate the effect of clarithromycin, one of the major macrolides, and telithromycin, one of the antibiotics belonging to a macrolide group (ketolide), on IL6, IL10 and Ccl2 expression in a rat endometriosis model induced by the surgical transplantation of endometrium onto the peritoneum in 8-week-old female Sprague-Dawley rats. After autotransplantation, the rats were given daily administration of clarithromycin (16 mg/kg/day or telithromycin (12 mg/kg/day) for 3 days. The induced lesions were examined 4 days after autotransplantation. After treatment, IL10 expression in the lesions was increased in rats treated with clarithromycin (1.70-fold) and telithromycin (2.88-fold). The drugs attenuated proliferative stromal lesion of the endometriosis model. The results showed that in the endometriosis model, the drugs enhanced expression of IL10, which may play a role in inhibiting excess inflammatory reaction with its therapeutic effect on the lesion. Macrolide and ketolide therapy may have significant value for the treatment of human endometriosis. 相似文献
992.
Yamamoto K Kato M Takahashi M Haneda M Shinada K Nishida U Yoshida T Sonoda N Ono S Nakagawa M Mori Y Nakagawa S Mabe K Shimizu Y Moriya J Kubota K Matsuno Y Shimoda T Watanabe H Asaka M 《Helicobacter》2011,16(3):210-216
Background and Aims: The results of a randomized controlled study and meta‐analysis study have recently proved that Helicobacter pylori eradication has a preventive effect against the development of metachronous and primary gastric cancer. However, gastric cancer is sometimes detected after successful eradication. There is a lack of study about gastric cancers in eradicated patients. To clarify the characteristics of gastric cancers detected after H. pylori eradication, we analyzed the clinicopathological features of these cancers. Methods: The subjects were 18 early‐stage gastric cancer specimens resected from 17 patients who had received successful eradication of H. pylori from February 1995 to March 2009. The control group consisted of 36 specimens from noneradicated patients with persistent H. pylori infection who were matched with the subjects in age, sex, and depth of invasion. Clinicopathological features and mucin phenotypes of gastric cancer were clinically and immunohistologically evaluated. Results: The average diameter of gastric cancer was smaller and Ki‐67 index was lower in the eradication group. The morphological distribution of depression types was significantly lower in the control group. Immunohistochemical phenotyping revealed that 72.2% of the lesions in the eradicated group were complete gastric type or gastric predominant mixed type, whereas the percentages of gastric type and intestinal type in the control group were similar. Conclusion: Our findings indicate that the clinicopathological characteristics of gastric cancers detected after H. pylori eradication are different from those of gastric cancers in patients with persistent H. pylori infection. H. pylori eradication may suppress intestinalization during the development of gastric cancer. 相似文献
993.
994.
Burgett AW Poulsen TB Wangkanont K Anderson DR Kikuchi C Shimada K Okubo S Fortner KC Mimaki Y Kuroda M Murphy JP Schwalb DJ Petrella EC Cornella-Taracido I Schirle M Tallarico JA Shair MD 《Nature chemical biology》2011,7(9):639-647
Cephalostatin 1, OSW-1, ritterazine B and schweinfurthin A are natural products that potently, and in some cases selectively, inhibit the growth of cultured human cancer cell lines. The cellular targets of these small molecules have yet to be identified. We have discovered that these molecules target oxysterol binding protein (OSBP) and its closest paralog, OSBP-related protein 4L (ORP4L)--proteins not known to be involved in cancer cell survival. OSBP and the ORPs constitute an evolutionarily conserved protein superfamily, members of which have been implicated in signal transduction, lipid transport and lipid metabolism. The functions of OSBP and the ORPs, however, remain largely enigmatic. Based on our findings, we have named the aforementioned natural products ORPphilins. Here we used ORPphilins to reveal new cellular activities of OSBP. The ORPphilins are powerful probes of OSBP and ORP4L that will be useful in uncovering their cellular functions and their roles in human diseases. 相似文献
995.
996.
Shuhei Tanida Kaoru Akita Akiko Ishida Yugo Mori Munetoyo Toda Mizue Inoue Mariko Ohta Masakazu Yashiro Tetsuji Sawada Kosei Hirakawa Hiroshi Nakada 《The Journal of biological chemistry》2013,288(44):31842-31852
Because MUC1 carries a variety of sialoglycans that are possibly recognized by the siglec family, we examined MUC1-binding siglecs and found that Siglec-9 prominently bound to MUC1. An immunochemical study showed that Siglec-9-positive immune cells were associated with MUC1-positive cells in human colon, pancreas, and breast tumor tissues. We investigated whether or not this interaction has any functional implications for MUC1-expressing cells. When mouse 3T3 fibroblast cells and a human colon cancer cell line, HCT116, stably transfected with MUC1cDNA were ligated with recombinant soluble Siglec-9, β-catenin was recruited to the MUC1 C-terminal domain, which was enhanced on stimulation with soluble Siglec-9 in dose- and time-dependent manners. A co-culture model of MUC1-expressing cells and Siglec-9-expressing cells mimicking the interaction between MUC1-expressing malignant cells, and Siglec-9-expressing immune cells in a tumor microenvironment was designed. Brief co-incubation of Siglec-9-expressing HEK293 cells, but not mock HEK293 cells, with MUC1-expressing cells similarly enhanced the recruitment of β-catenin to the MUC1 C-terminal domain. In addition, treatment of MUC1-expressing cells with neuraminidase almost completely abolished the effect of Siglec-9 on MUC1-mediated signaling. The recruited β-catenin was thereafter transported to the nucleus, leading to cell growth. These findings suggest that Siglec-9 expressed on immune cells may play a role as a potential counterreceptor for MUC1 and that this signaling may be another MUC1-mediated pathway and function in parallel with a growth factor-dependent pathway. 相似文献
997.
Tamio Ohno Masakazu Okamoto Toru Hara Naozumi Hashimoto Kazuyoshi Imaizumi Miyoko Matsushima Masahiko Nishimura Kaoru Shimokata Yoshinori Hasegawa Tsutomu Kawabe 《Immunogenetics》2013,65(1):17-24
Asthma is regarded as a multifactorial inflammatory disorder arising as a result of inappropriate immune responses in genetically susceptible individuals to common environmental antigens. However, the precise molecular basis is unknown. To identify genes for susceptibility to three asthma-related traits, airway hyperresponsiveness (AHR), eosinophil infiltration, and allergen-specific serum IgE levels, we conducted a genetic analysis using SMXA recombinant inbred (RI) strains of mice. Quantitative trait locus analysis detected a significant locus for AHR on chromosome 17. For eosinophil infiltration, significant loci were detected on chromosomes 9 and 16. Although we could not detect any significant loci for allergen-specific serum IgE, analysis of consomic strains showed that chromosomes 17 and 19 carried genes that affected this trait. We detected genetic susceptibility loci that separately regulated the three asthma-related phenotypes. Our results suggested that different genetic mechanisms regulate these asthma-related phenotypes. Genetic analyses using murine RI and consomic strains enhance understanding of the molecular mechanisms of asthma in human. 相似文献
998.
Although it has been documented that plants generate isothiocyanates (ITCs) through the glucosinolate-myrosinase system to defend against biotic stresses, the roles of ITCs in defending against abiotic stresses have scarcely been studied. Here, we report that exogenously applied ITCs enhance the heat tolerance of Arabidopsis thaliana. Pre-administration of phenethyl ITC to Arabidopsis plants mitigated growth inhibition after heat stress at 55?°C for 1?h. Although methyl ITC and allyl ITC also tended to reduce the growth inhibition that the same heat treatment caused, the reduction effects were weaker. The expression levels of heat shock protein 70 genes in Arabidopsis were elevated after phenethyl ITC treatment. These results suggest that ITCs may act as heat-tolerance enhancers in plants. 相似文献
999.
Masakazu Atobe Naomi Maekawara Masashi Kawanishi Hiroko Suzuki Eiichi Tanaka Shiro Miyoshi 《Bioorganic & medicinal chemistry letters》2013,23(7):2111-2116
A series of 1,1-dioxothieno[2,3-d]isothiazole (thienosultam) derivatives were designed and synthesized as novel ADAMTS-5 inhibitors for an investigation into a side chain of thienosultam for the S1′ pocket. The resulting compounds (19 and 24) show high ADAMTS-5 inhibition and other MMP selectivity, and these compounds show good oral bioavailability. 相似文献
1000.
Masakazu Atobe Naomi Maekawara Noriko Ishiguro Shinya Sogame Yoshihito Suenaga Masashi Kawanishi Hiroko Suzuki Norimasa Jinno Eiichi Tanaka Shiro Miyoshi 《Bioorganic & medicinal chemistry letters》2013,23(7):2106-2110
A series of thiazole bearing thiazolidin-4-one was discovered via high-throughput screening as non-competitive inhibitors of ADAMTS-5. Compound 31 appeared to give the best ADAMTS-5 inhibition and good selectivity over other metalloproteases. 相似文献