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Lipocalin 2 stimulates bone fibroblast growth factor 23 production in chronic kidney disease

Bone Research 2021年第3期9卷 385-395页

作者： Guillaume Courbon Connor Francis Claire Gerber Samantha Neuburg Xueyan Wang Emily Lynch Tamara Isakova Jodie LBabitt Myles Wolf aline martin Valentin David Division of Nephrology and Hypertension Department of Medicineand Center for Translational Metabolism and HealthInstitute for Public Health and MedicineNorthwestern University Feinberg School of MedicineChicagoILUSA Nephrology Division Program in Membrane BiologyMassachusetts General HospitalHarvard Medical SchoolBostonMAUSA Division of Nephrology Department of Medicineand Duke Clinical Research InstituteDuke University School of MedicineDurhamNCUSA

Bone-produced fibroblast growth factor 23(FGF23)increases in response to inflammation and iron deficiency and contributes to cardiovascular mortality in chronic kidney disease(CKD).Neutrophil gelatinase-associated lipocalin(NGAL or lipocalin 2;LCN2 the murine homolog)is a pro-inflammatory and iron-shuttling molecule that is secreted in response to kidney injury and may promote CKD *** investigated bone FGF23 regulation by circulating *** 23 weeks,Col4a3KO mice showed impaired kidney function,increased levels of kidney and serum LCN2,increased bone and serum FGF23,anemia,and left ventricular hypertrophy(LVH).Deletion of Lcn2 in CKD mice did not improve kidney function or anemia but prevented the development of LVH and improved survival in association with marked reductions in serum ***2 deletion specifically prevented FGF23 elevations in response to inflammation,but not iron deficiency or phosphate,and administration of LCN2 increased serum FGF23 in healthy and CKD mice by stimulating Fgf23 transcription via activation of cAMP-mediated signaling in bone *** results show that kidney-produced LCN2 is an important mediator of increased FGF23 production by bone in response to inflammation and in ***2 inhibition might represent a potential therapeutic approach to lower FGF23 and improve outcomes in CKD.

关键词： FGF23 kidney inflammation

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DMP1 prevents osteocyte alterations,FGF23 elevation and left ventricular hypertrophy in mice with chronic kidney disease

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Bone Research 2019年第2期7卷 171-182页

作者： Corey Dussold Claire Gerber Samantha White Xueyan Wang Lixin Qi Connor Francis Maralee Capella Guillaume Courbon Jingya Wang Chaoyuan Li Jian Q. Feng Tamara Isakova Myles Wolf Valentin David aline martin Division of Nephrology and Hypertension Center for Translational Metabolism and HealthFeinberg School of MedicineNorthwestern UniversityChicagoIL 60611USA Department of Biomedical Sciences Texas A&M College of DentistryDallasTX 75246USA Division of Nephrology Department of Medicineand Duke Clinical Research InstituteDuke University School of MedicineDurhamNC 27708USA

During chronic kidney disease (CKD),alterations in bone and mineral metabolism include increased production of the hormone fibroblast growth factor 23 (FGF23) that may contribute to cardiovascular *** osteocyte protein dentin matrix protein 1 (DMP1) reduces FGF23 and enhances bone mineralization,but its effects in CKD are *** tested the hypothesis that DMP1 supplementation in CKD would improve bone health,prevent FGF23 elevations and minimize consequent adverse cardiovascular *** investigated DMP1 regulation and effects in wild-type (WT) mice and the Col4a3^-/- mouse model of ***4a3^-/- mice demonstrated impaired kidney function,reduced bone DMP1 expression,reduced bone mass,altered osteocyte morphology and connectivity,increased osteocyte apoptosis,increased serum FGF23,hyperphosphatemia,left ventricular hypertrophy (LVH),and reduced *** or pharmacological supplementation of DMP1 in Col4a3^-/- mice prevented osteocyte apoptosis,preserved osteocyte networks,corrected bone mass,partially lowered FGF23 levels by attenuating NFAT-induced FGF23 transcription,and further increased serum *** impaired kidney function and worsened hyperphosphatemia,DMP1 prevented development of LVH and improved Col4a3^-/- *** data suggest that CKD reduces DMP1 expression,whereas its restoration represents a potential therapeutic approach to lower FGF23 and improve bone and cardiac health in CKD.

关键词： alterations ventricular hypertrophy chronic kidney disease

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Desmarestia anceps Montagne (Phaeophyceae) against Colorectal Cancer Cells: Cytotoxic Activity and Proapoptotic Effects

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Advances in Biological Chemistry 2022年第6期12卷 228-245页

作者： Rafaele Frassini Daniela Steffens Sidnei Moura Cesar Aguzzoli aline Paternostro martins Pio Colepicolo Mutue Toyota Fujii Nair S. Yokoya Cláudio martin Pereira De Pereira Ana Cláudia Phillipus Miriam De Barcellos Falkenberg João Antonio Pêgas Henriques Mariana Roesch-Ely Laboratory of Applied Toxicology and Bioproducts University of Caxias do Sul RS Brazil Laboratory of Biosynthetic and Natural Products of Caxias do Sul RS Brazil Area of Exact Sciences and Engineering University of Caxias do Sul RS Brazil Laboratory of Biochemistry and Molecular Biology of Algae University of S&#227 o Paulo S&#227 o Paulo SP Brazil Nucleus Research Phycology Institute of Botany S&#227 o Paulo SP Brazil Laboratory of Lipidomics and Biorganic-LipidomicaBio Federal University of Pelotas Pelotas RS Brazil Study Group on Natural and Synthetic Products (GEPRONAS) Federal University of Santa Catarina SC Brazil

Impairment of apoptosis promotes abnormal cellular proliferation and accumulation of genetic alterations. Identifying bioactive compounds extracted from seaweeds that induce apoptosis in cancer cells may be explored as new agents for cancer chemoprevention and/or chemotherapy. The present study aimed to determine the chemical composition and biological activity of the chloroform crude extract and fractions from Antarctic seaweed Desmarestia anceps. The chloroform extract was obtained by three consecutive macerations and the fractionation by vacuum liquid chromatography. The chemical characterization of the extract and fractions was performed through Gas Chromatography. The cytotoxicity of the crude extract and fractions was evaluated by the MTT assay. Cell death and cell cycle evaluation after 24 hours of exposure to chloroform extract were performed by flow cytometry. A total of 48 compounds were identified. The results indicate that chloroform extract and its fractions presented cytotoxic activity against HCT 116 cell line in a dose dependent-manner. Proapoptotic events were observed after chloroform extract exposition, which promoted an increase of multinucleated cells and reduced cell viability. This study was the first to explore cytotoxic potential of seaweed D. anceps fractions against HCT colorectal cancer cell line, suggesting that these macroalgae may be a promising candidate against anticancer activity.

关键词： Antarctic Seaweeds Antitumor Activity Apoptosis Proapoptotic Effect Colorectal Cancer

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Chemical Characterization and Cytotoxic Activity of Antarctic Macroalgae Extracts against Colorectal Cancer

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Advances in Biological Chemistry 2019年第5期9卷 167-177页

作者： Rafaele Frassini Yeslei Paulino da Silva Sidnei Moura Leonardo Zambotti Villela aline Paternostro martins Pio Colepicolo Mutue Toyota Fujii Nair S.Yokoya Claudio martin Pereira de Pereira Vagner Reinaldo Zingalli Bueno Pereira Joao Antonio Pegas Henriques Mariana Roesch-Ely Laboratory of Genomics Proteomics and DNA RepairUniversity of Caxias do SulCaxias do SulRSBrazil Laboratory of Biosynthetic and Natural Products of Caxias do Sul Caxias do SulRSBrazil Laboratory of Biochemistry and Molecular Biology of Algae University of Sao PauloSao PauloSPBrazil Phycologycal Research Institute of BotanySao PauloSPBrazil Laboratory of Lipidomics and Biorganic—LLipidomicaBio Federal University of PelotasPelotasRSBrazil General Hospital University of Caxias do SulCaxias do SulRSBrazil

Background/Aim: Antarctic seaweeds are considered a promising source of compounds with anticancer activity. Colorectal cancer (CRC) is one of the most incident cancers with high mortality rates worldwide. This work aimed to characterize chemically extracts of the Antarctic macroalgae Iridaea cordata, Cystosphaera jacquinotii and Desmarestia anceps and to evaluate the cytotoxic effects against human colon cancer HCT 116 cell line. Materials and Methods: The extracts were obtained by depletion using an ultrasound probe and were identified by High-Performance Liquid Chromatography (HPLC) and Gas Chromatography coupled with Mass Spectrometry (GC-MS). Cell viability was determined by MTT assay. Results: Hexanic and chloroform extracts of the I. cordata and the hexanic, chloroform and methanolic extracts of D. anceps were able to inhibit growth of colorectal cancer cells in the three different incubation times (24, 48 and 72 h). Through GC analysis, 01 compounds were identified in the hexane extract and 02 compounds in the chloroform extract of the algae I. cordata. The hexane extract of D. anceps macroalgae presented 5 compounds, chloroform extract 10 and methanolic extract 3 respectively, with special highlight to fucosterol. Carotenoid analysis by HPLC identified β-carotene in all species, while zeaxanthin was present in the spectrum of I. cordata and C. jacquinotii. Fucoxanthin and violaxanthin were confirmed in the brown seaweeds C. jacquinotii and D. anceps. Conclusion: Extracts of macroalgae I. Cordata and D. anceps may be a source of therapeutic agents against CRC.

关键词： Antarctic Seaweeds Antitumor Activity Colorectal Cancer

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Interaction between muscarinic and β-adrenergic receptors

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中国药理通讯 2012年第3期29卷 16-17页

作者： martin C. Michel Dept. of Pharmacology University of Mainz Mainz Germany

In many tissues the parasympathetic and sympathetic nervous system regulate smooth musc tone via their transmitters aeetylcholine and noradrenaline, respectively. Direct smooth musc e e effects of acetylcholine via muscarinic receptors always promote contraction, but non-neuronal sources can importantly contribute to such stimulation. Direct smooth muscle effects of noradren- aline can promote contraction via al- and sometimes also α2-adrenoceptors but can promote re- laxation and inhibit contraction via β-adrenoceptors. I will focus on the interaction between sub- types of muscarinic and β-adrenergic receptors, largely using the urinary bladder as an exam- ple.

关键词： via can tone also but

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音乐屋——奥尔堡创意中心

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城市环境设计 2020年第4期126卷 174-185页

作者：沃尔夫·狄·普瑞克斯 Marcelo Bernardi Jesper Bork Bo Stjerne Hansen Roberta Jiraschek Daniel Krüger Carsten Laursen martin Oberascher Florian Pfeifer Robert Pippan Marita Schnepper Sigrid Svensson Eva Wolf Carola B?ker Moa Carlson Isak Foged Annina G?hwiler Patricia Gola Robin Heather Per Kruse Win Man Ruth Mandl aline Müller Tenna Olsen Anke Pasolt Annemarie Pedersen Eva Ravnborg Carolin Schmitz-Remberg Tim Seidl Guro Sollid Michele Zanella Jan-Ruben Fischer Markus Pillhofer Markus Baumann Robin Heather Anja Sorger Bo Stjerne Thomsen Anna Wasserthal Philip Wilck Blaine Lepp Talya Kozminsky Hannes Walzl Morten Grau Jensen Stephanie Neufeld Tyler Bornstein Laura Githa Julia G?rtner Jenny Draxlbauer Duccio Malagamba martin Schubert

项目大事记/CHRONOLOGY竞赛（第一名）/Competition （1st Place）:2003一期规划设计/Layout Planning Ho M I:2003—2005项目延期/Postponement of the Project:2006—2007二期规划设计/Start of Layout Planning Ho M II:2008二期动工/Start of Construction Ho M II:2010二期竣工/Completion Ho M II:2014项目参数/PROJECT DATA建筑净面积/Net Floor Area:17 637m2建筑毛面积/Gross Floor Area:20 257m2音乐厅/Concert Hall:1 298座/1 289 Seats

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