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Interplay between post-translational cyclooxygenase-2 modifications and the metabolic and proteomic profile in a colorectal cancer cohort

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World Journal of Gastroenterology 2019年第4期25卷 433-446页

作者： Patricia Prieto Rafael I Jaén Daniel Calle María Gómez-Serrano Estefanía Nú?ez María Fernández-Velasco Paloma Martín-Sanz Sergio Alonso Jesús Vázquez Sebastián Cerdán Miguel ángel Peinado Lisardo Boscá Department of Metabolism and Physiopathology of Inflammatory Diseases Instituto de Investigaciones Biomédicas Alberto Sols (CSIC-UAM) Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (Ciber-CV) Instituto de Salud Carlos III (ISCIII) Laboratorio de Imagen Médica Hospital Universitario Gregorio Mara?ón Laboratorio de Proteómica Cardiovascular Centro Nacional de Investigaciones Cardiovasculares (CNIC) Instituto de Investigación Sanitaria del Hospital Universitario la Paz(IdiPaz) Programa de Medicina Predictiva y Personalizada del Cáncer (PMPPC) Fundación Instituto de investigación en ciencias de la salud Germans Trias i PujolCtra Can Ruti

BACKGROUND Colorectal cancer(CRC) is the second most common cause of cancer death worldwide. It is broadly described that cyclooxygenase-2(COX-2) is mainly overexpressed in CRC but less is known regarding post-translational modifications of this enzyme that may regulate its activity, intracellular localization and stability. Since metabolic and proteomic profile analysis is essential for cancer prognosis and diagnosis, our hypothesis is that the analysis of correlations between these specific parameters and COX-2 state in tumors of a high number of CRC patients could be useful for the understanding of the basis of this cancer in *** To analyze COX-2 regulation in colorectal cancer and to perform a detailed analysis of their metabolic and proteomic *** Biopsies from both healthy and pathological colorectal tissues were taken under informed consent from patients during standard colonoscopy procedure in the University Hospital of Bellvitge(Barcelona, Spain) and Germans Trias i Pujol University Hospital(Campus Can Ruti)(Barcelona, Spain). Western blot analysis was used to determine COX-2 levels. Deglycosylation assays were performed in both cells and tumor samples incubating each sample with peptide N-glycosidase F(PNGase F). prostaglandin E2(PGE2) levels were determined using a specific ELISA. 1 H high resolution magic angle spinning(HRMAS) analysis was performed using a Bruker AVIII 500 MHz spectrometer and proteomic analysis was performed in a nano-liquid chromatography-tandem mass spectrometer(nano LC-MS/MS) using a QExactive HF orbitrap *** Our data show that COX-2 has a differential expression profile in tumor tissue of CRC patients vs the adjacent non-tumor area, which correspond to a glycosylated and less active state of the protein. This fact was associated to a lesser PGE2 production in tumors. These results were corroborated in vitro performing deglycosylation assays in HT29 cell line where COX-2 protein profile was modified after PN

关键词： Colon Carcinoma Cyclooxygenase prostaglandin Proteomics High resolution magic angle spinning

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Bimatoprost/timolol fixed combination(BTFC) in patients with primary open angle glaucoma or ocular hypertension in Greece

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International Journal of Ophthalmology(English edition) 2016年第1期9卷 69-75页

作者： Tryfon G.Rotsos Vasso G.Kliafa Kevin J.Asher Dimitrios Papaconstantinou 1st Department of Ophthalmology University of Athens Department of Regulatory Affairs Nexus Medicals S.A. Department of Regional Scientific Services Allergan Holdings Limited

AIM：To evaluate the efficacy and tolerability of the fixed combination of bimatoprost 0.03%and timolol 0.5%（BTFC）in patients in Greece with primary open angle glaucoma（POAG）or ocular hypertension（OHT）whose previous therapy provided insufficient lowering of intraocular pressure（IOP）.·METHODS：A multicenter,prospective,open-label,non-interventional,observational study of the use of BTFC in clinical practice was conducted at 41 sites in *** primary endpoint was the reduction in IOP from baseline at study end,approximately 12wk after initiation of BTFC therapy.·RESULTS：A total of 785 eligible patients were enrolled in the study and 97.6%completed the *** mean±SD IOP reduction from baseline at 12wk after initiation of BTFC was 6.3±2.8 mm Hg（=764;〈0.001）.In patients（=680）who replaced their previous IOP-lowering monotherapy（a single drug,or a fixed combination of 2drugs in a single ophthalmic drop）with once-daily BTFC,the mean±SD IOP reduction from baseline at 12wk was 6.2±2.8 mm Hg（〈0.001）.IOP was reduced from baseline in 99.2%of patients,and 58.0%of patients reached or exceeded their target *** mean IOP reductions were observed regardless of the previous *** was well tolerated,with 96.0%of patients who completed the study rating the tolerability of BTFC as＂good＂or＂very good.＂Adverse events were reported in 8.3%of patients;only 0.6%of patients discontinued the study due to adverse events.·C ONCLUSION：In clinical practice in Greece,BTFC is well tolerated and effectively lower the IOP in patients with POAG or OHT who requires additional IOP lowering on their previous therapy.

关键词： fixed combination glaucoma intraocularpressure ocular hypertension primary open angle glaucoma prostaglandin prostamide timolol

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Effect of Fructus Psoraleae on motility of gallbladder isolated smooth muscle strips from guinea pigs

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World Journal of Gastroenterology 2006年第32期12卷 5214-5218页

作者： Shan Jin Mei Li Mei-Ling Lin Yong-Hui Ding Song-Yi Qu Wei Li Tian-Zhen Zheng Department of Physiology School Of Basic Medical ~clences Lanzhou University Lanzhou 730000 Gansu ProvinceChina Gansu Food and Drug Administration Lanzhou 730000 Gansu Province China

AIM： To observe the effect of Fructus Psoraleae on motility of isolated gallbladder muscle strips of guinea pigs and its mechanism. METHODS： Guinea pigs were hit to lose consciousness and the whole gallbladder was removed quickly. Two or three smooth muscle strips （8 mm×3mm） were cut along a longitudinal direction. The mucosa was gently removed. Every longitudinal muscle strip was suspended in a tissue chamber which was continuously perfused with 5 mL Krebs solution （37℃）, pH 7.4, and aerated with 950 mL/L 02 and 50 mL/L CO2. The isometric response was recorded with an ink-writing recorder. After 2 h equilibration under i g-load, 50 μL Fructus Psoraleae （10, 20, 70, 200, 700, 1000 g/L） was added cumulatively into the tissue chamber in turn every 2 rain to observe their effects on gallbladder muscle strips （cumulating final concentration of Fructus Psoraleae was 0.1, 0.3, 1.0, 3.0, 10.0, 20.0 g/L）. The antagonists, including 4-DAMP, benzhydramine, hexamethonium, phentolamine, verapamil and idomethine were given 2 min before Fructus Psoraleae respectively to investigate the mechanisms involved. RESULTS： Fructus Psoraleae dose-dependently increased the resting tension （r=0.992, P〈0.001）, decreased the mean contractile amplitude （r=0.970, P〈0.001） and meanwhile increased the contractile frequency of the gallbladder muscle strip in vitro （r=0.965, P〈0.001）. The exciting action of Fructus Psoraleae on the resting tension could be partially blocked by 4-DAMP （the resting tension decreased from 1.37 ± 0.41 to 0.70 ± 0.35, P〈0.001）, benzhydramine （from 1.37 ±0.41 to 0.45±0.38, P〈0.001）, hexamethonium （from 1.37 ± 0.41 to 0.94 ± 0.23, P〈0.05）, phentolamine （ from 1.37±0.41 to 0.89±0.22, P〈0.01） and verapamil （from 1.37±0.41 to 0.94±0.26, P〈0.05）. But the above antagonists had no significant effect on the action of Fructus Psoraleae-induced mean contractile amplitude （P〉0.05）. Moreover, the increase of the contractile frequency due to Fructus Psoraleae was inhibited by 4-DAMP

关键词： Fructus Psoraleae Gallbladder smooth muscle strips M3, N, α, H1 receptors Ca^2+ channel prostaglandin

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Ginger extract enhances antioxidant ability and immunity of layers

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Animal Nutrition 2019年第4期5卷 407-409页

作者： Shengying An Guanzhong Liu Xin Guo Yahui An Renyu Wang College of Animal Science and Technology Hebei Agricultural UniversityBaoding071000China

This experiment was to investigate ginger extract on production performance,antioxidant ability and immunity of laying hens.A total of 600 Hy-Line brown laying hens aged at 25 wk old were randomly divided into 2 treatments,4 replicates per treatment,75 layers each *** control group hens were fed a basal diet;the experimental group hens were fed basal diets with 0.1%ginger *** results were shown as follows:1)ginger extract significantly enhanced laying rates(Pprostaglandin E2(PGE2)content(P<0.05).This study shows that ginger extract not only can improve the birds’antioxidant capacity,enhance immune function,but also has a potential of reducing inflammatory response.

关键词： Antioxidant ability Immunity Ginger extract Layers prostaglandin E2

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Possible role of PGD_2 in malaria infections

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Asian Pacific Journal of Tropical Medicine 2016年第9期9卷 834-837页

作者： Pimwan Thongdee Jiraporn Kuesap Raewadee Wisedpanichkij Kesara Na-Bangchang Graduate Program in Bioclinical Sciences Chulabhorn International College of MedicineThammasat University Graduate Program in Biomedical Sciences Faculty of Allied Health SciencesThammasat University Department of Hematology Rama College of MedicineMahidol University Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma Thammasat University

Objective:To preliminarily investigate the possible role of prostaglandin D_2(PGD_2) in malaria ***:Blood and urinary samples(n=120 each) were collected from Thai patients with Plasmodium falciparum(***) with moderate(n=26) and high(n=4) parasitemia,patients with Plasmodium vivax(***)(n=30),patients with fever associated with other infections(n=30),and healthy subjects(n=30).PGD_2 concentrations in plasma and urinary samples of healthy subjects,patients with fever associated with other infections and patients with malaria were determined using prostaglandin D2-MOX express EIA kit(Cayman Chemical,USA).Results:The possible association between PGD_2 and malaria infections is clearly demonstrated with PGD_2 concentration in *** urinary PGD_2 concentrations were relatively high(about 5-fold) in patients with *** with moderate parasitemia and *** infections compared with other ***,the concentration in patients with *** with moderate parasitemia and *** infection were significantly higher than that in healthy subjects and patients with fever associated with other ***:Urinary PGD_2 concentrations may offer a more dependable and useful tool for predicting malaria *** is this preliminary finding is required with a larger sample size.

关键词： Malaria Plasmodium vivax Plasmodium falciparum prostaglandin D2(PGD2) Malaria severity

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Clinical Study on Treatment of Primary Dysmenorrhea with Qihuang Herbal Warm Bag

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Journal of Acupuncture and Tuina Science 2007年第5期5卷 304-306页

作者：姚敏李沛肖元春(翻译) Fujian College of Traditional Chinese Medicine Fuzhou 350003 P. R. China 不详

To investigate the effect of Qihuang herbal warm bag on primary dysmenorrhea. Methods： Thirty-two patients with primary dysmenorrhea were selected as subjects and treated by compression with the herbal warm bag for two months. The curative effect was evaluated, and prostaglandin F2a（PGF2a） and 13-endorphin（13-EP） were measured before and after treatment. Results： The herbal warm bag had positive effects on dysmenorrhea at different degrees and could decrease the contents of blood PGF2a and β-EP. Conclusion： The herbal warm bag is quite effective for primary dysmenorrhea possibly by decreasing serum PGF2a and increasing serum β-EP.

关键词： Acupoint Sticking Therapy Point, Guanyuan Point, Shenque Dysmenorrhea prostaglandin

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The role of latanoprost in an inflammatory bowel disease flare

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Gastroenterology Report 2014年第3期2卷 232-234页

作者： Sonali Paul Martin Wand Geoffrey T.Emerick James M.Richter Department of Gastroenterology and Hepatology Tufts Medical CenterBostonMAUSA Department of Ophthalmology University of Connecticut School of Medicine and Consulting OphthalmologistsFarmingtonCTUSA Department of Gastroenterology Massachusetts General HospitalBostonMAUSA

Ulcerative colitis and Crohn’s disease(CD)are characterized by inflammation of the intestinal mucosa and symptoms of abdominal pain and *** studies have shown an association between elevated levels of prostaglandins and mucosal damage in inflammatory bowel *** report a 50-year-old woman with a history of CD and open-angle *** glaucoma was treated with latanoprost,a prostaglandin analog,which was associated with an exacerbation of her *** discontinuation of latanoprost,her CD symptoms disappeared *** case suggests that in a patient with CD,topical administration of latanoprost may result in sufficient systemic absorption and circulation to promote a relapse of *** finding has important implications,not only for patients with inflammatory bowel disease and glaucoma,but also for both ophthalmologists and gastroenterologists.

关键词： lantanoprost Crohn’s disease prostaglandin glaucoma

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冠心病微血栓患者血浆前列腺素与血小板功能的变化

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中国血液流变学杂志 1995年第2期5卷 9-10页

作者：郭渝成曾祖荫张志高葛萍菊贵州贵阳解放军四十四医院 550009

Changes of plasma prostaglandin and platelet abnormal function play an important role in the occurrence and development of coronary diseases. The present study indicates: patients with cornary diseases have an increase in platelet aggregation and release function and 70- 80% cases of myocardiac infarction have blood stasis in their coronary vessels. In our eight year microcirculation study, we found that 23. 8 % of the patients with coronary diseases had microstasis in bullar conjuncti- val micorcirculation. Reports from abroad rated 27%. Microstassis is the mark of the obstruction in Microcirculation. We detected plasma TXA2, 6-k-pgf {12} and platelet aggregation rate of the pa- tients relation between plasma prostaaglandin, platelet function and microstasis.

关键词： plasma prostaglandin microthrombsis microstasis platelet function

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慢性阻塞性肺疾病急性加重合并呼吸衰竭患者血清环氧化酶2和前列腺素E2及磷脂酶A2水平的变化及其临床意义

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中国医药 2014年第3期9卷 328-330页

作者：张杰根戴富林武凡河北省涿州市医院呼吸科 072750

目的观察慢性阻塞性肺疾病急性加重合并呼吸衰竭患者血清环氧化酶2、前列腺素E2和磷脂酶A2水平变化及意义.方法选取河北省涿州市医院2011年12月至2012年12月100例慢性阻塞性肺疾病急性加重患者,完全随机分为无呼吸衰竭组（50例）和呼... 详细信息

目的观察慢性阻塞性肺疾病急性加重合并呼吸衰竭患者血清环氧化酶2、前列腺素E2和磷脂酶A2水平变化及意义.方法选取河北省涿州市医院2011年12月至2012年12月100例慢性阻塞性肺疾病急性加重患者,完全随机分为无呼吸衰竭组（50例）和呼吸衰竭组（50例）,另选择20例健康查体者作为健康对照组.观察3组患者血清环氧化酶2、前列腺素E2和磷脂酶A2的变化.结果呼吸衰竭组和无呼吸衰竭组血清环氧化酶2、前列腺素E2和磷脂酶A2浓度明显高于健康对照组[（158±45）、（132±12）μg/L比（57±12）μg/L,（317±213）、（207±30）ng/L比（103±18）ng/L,（28.2±1.5）、（20.2±1.4）μg/L比（7.0±2.4）μg/L],差异均有统计学意义（均P＜0.05）.呼吸衰竭组血清环氧化酶2、前列腺素E2和磷脂酶A2浓度与无呼吸衰竭组比较,差异有统计学意义（P＜0.05）.呼吸衰竭组血清环氧化酶2、前列腺素E2水平与磷脂酶A2水平呈正相关（r分别为0.406、0.356,P＜0.05）;血清环氧化酶2水平与前列腺素E2水平呈正相关（r为0.848,P＜0.01）.结论慢性阻塞性肺疾病急性加重合并呼吸衰竭患者血清环氧化酶2、前列腺素E2和磷脂酶A2的浓度明显升高,血清环氧化酶2、前列腺素E2和磷脂酶A2三者之间相互关联并相互作用,共同导致呼吸衰竭的发生和发展.

关键词：肺疾病,慢性阻塞性呼吸衰竭环氧化酶2 前列腺素E2 磷脂酶A2 Cyclooxygenase-2 prostaglandin E2 Phospholipases A2

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前列腺素E1在慢性肾功能衰竭治疗中的应用

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中国基层医药 2014年第2期21卷 214-216页

作者：范德墉徐云芬湖州市中心医院肾内科浙江省湖州313000

目的观察前列腺素E1（PGE1）在慢性肾衰竭（CKD 2 ～4期）治疗中的临床应用效果.方法选取CKD 2 ～4期患者128例,以随机数字表法分为观察组与对照组,每组各64例.对照组给予常规药物治疗,观察组在对照组的基础上增加PGE1,两组均治疗3个... 详细信息

目的观察前列腺素E1（PGE1）在慢性肾衰竭（CKD 2 ～4期）治疗中的临床应用效果.方法选取CKD 2 ～4期患者128例,以随机数字表法分为观察组与对照组,每组各64例.对照组给予常规药物治疗,观察组在对照组的基础上增加PGE1,两组均治疗3个月.比较治疗前后的肾功能指标、治疗后临床疗效以及不良反应.结果治疗前两组患者肾功能指标比较,差异均无统计学意义（t=0.27～0.95,P＞0.05）；治疗后,观察组与对照组24h尿蛋白定量（t=3.41,P＜0.05）、内生肌酐清除率（t=4.04,P＜0.05）、血清肌酐值（t =4.15,P＜0.05）、血清尿素氮（t=3.92,P＜0.05）指标比较,差异均具有统计学意义.观察组与对照组总有效率分别为84.37％、57.81％,差异有统计学意义（x2=5.63,P＜0.05）.观察组未见不良反应.结论在目前尚缺乏特别有效治疗方法的情况下,前列腺素E1的应用可能在改善患者尿蛋白及肾功能方面起到一定的积极作用.

关键词：前列腺素E1 慢性肾功能衰竭尿蛋白 prostaglandin E1 (PGE1)

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