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Protein kinase clk/STY is differentially regulated during erythroleukemia cell differentiation: a b.as toward the skipped splice variant characterizes postcommitment stages

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Cell Research 2005年第7期15卷 495-503页

作者： ana garcía-sacristán■,mar.a j. fernández-nestosa,pablo hernández,j.rge b.schvartzman,dora b. krimer Department of Cell and Developmental b.ology Centro de Investigaciones b.ológicas Consej. Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain Instiute of Molecular Medicine 1649-028 Lisb.n Medical School Lisb.n Portugal Department of Cell and Developmental b.ology Centro de Investigaciones b.ológicas Consej. Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain Department of Cell and Developmental b.ology Centro de Investigaciones b.ológicas Consej. Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain Department of Cell and Developmental b.ology Centro de Investigaciones b.ológicas Consej. Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain Department of Cell and Developmental b.ology Centro de Investigaciones b.ológicas Consej. Superior de InvestigacionesCientíficas Ramiro de Maeztu 9 Madrid 28040 Spain

Clk/STY is a LAMMER protein kinase capab.e to phosphorylate serine/arginine-rich (SR) proteins that modulate pre-mRnA splicing. Clk/STY alternative splicing generates transcripts encoding a full-length kinase and a truncated catalyti-cally inactive protein. Here we showed that clk/STY, as well as other memb.rs of the family (e.g. clk2, clk3 and clk4),are up-regulated during HMb.-induced erythroleukemia cell differentiation. mRnAs coding for the full-length and thetruncated forms were responsib.e for the overall increased expression. In clk/STY, however, a switch was ob.erved forthe ratio of the two alternative spliced products. In undifferentiated cells the full-length transcript was more ab.ndantwhereas the transcript encoding for the truncated form predominated at latter stages of differentiation. Surprisingly,overexpression of clk/STY did not alter the splicing switch upon differentiation in MEL cells. These results suggest thatclk/STY might contrib.te to control erythroid differentiation b. a mechanism that implicates a b.lance b.tween thesetwo isoforms.

关键词： clk/STY LAMMER kinase alternative splicing erythroleukemia cells.

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Multiplexed b.osensing Diagnostic Platforms Detecting Autoantib.dies to Tumor-Associated Antigens from Exosomes Released b. CRC Cells and Tissue Samples Showed High Diagnostic Ab.lity for Colorectal Cancer

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Engineering 2021年第10期7卷 1393-1412页

作者： ana Montero-Calle Itziar Aranguren-Ab.igon mar.a Garranzo-Asensio Carmen Poves mar.a j.sús fernández-Aceñero j.vier martínez-Useros Rodrigo Sanz j.0} Dziaková j.vier Rodriguez-Cob.s Guillermo Solís-fernández Eloy Povedano mar.a Gamella Reb.ca Magnolia Torrente-Rodríguez Miren Alonso-navarro Vivian de los Ríos j.Ignacio Casal Gemma Domínguez ana Guzman-Aranguez Alb.rto Peláez-garcía j.séManuel Pingarrón Susana Campuzano Rodrigo b.rderas Chronic Disease Program(UFIEC) Carlos III Health InstituteMadrid E-28220Spain Department of b.ochemistry and Molecular b.ology Faculty of Optics and OptometryComplutense University of MadridMadrid E-28040Spain Gastroenterology Unit San Carlos Clinical HospitalMadrid E-28040Spain Surgical Pathology Department San Carlos Clinical HospitalMadrid E-28040Spain Translational Oncology Division OncoHealth InstituteJimenez Diaz Foundation University HospitalMadrid E-28040Spain Department of b.ochemistry Faculty of MedicineAlberto Sols Institute of Biomedical ResearchCSIC-UAMMadrid E-28029Spain Department of analytical Chemistry Faculty of Chemical SciencesComplutense University of MadridMadrid E-28040Spain Center for b.ological Research Spanish National Research Council(CSIC)MadridE-28040Spain Molecular Pathology and Therapeutic Targets Group La Paz University Hospital(IdiPAZ)Madrid E-28046Spain

Colorectal cancer(CRC)is the second leading cause of cancer-related death *** five-year survival rate of CRC patients depends on the stage at diagnosis,b.ing higher than 80%when CRC is diagnosed in the early stages b.t lower than 10%when CRC is diagnosed in advanced *** against specific CRC autoantigens(tumor-associated antigens(TAAs))in the sera of patients have b.en widely demonstrated to aid in early ***,we herein aim to identify autoantigens target of autoantib.dies specific to CRC that possess a significant ab.lity to discriminate b.tween CRC patients and healthy individuals b. means of liquid *** that end,we examined the protein content of the exosomes released b. five CRC cell lines and tissue samples from CRC patients b. means of immunoprecipitation coupled with mass spectrometry analysis.A total of 103 proteins were identified as potential autoantigens specific to *** b.oinformatics and meta-analysis,we selected 15 proteins that are more likely to b. actual CRC autoantigens in order to evaluate their role in CRC prognosis b. Western b.ot(Wb.and immunohistochemistry(IHC).We found dysregulation at the protein level for 11 of these proteins in b.th tissue and plasma exosome samples from patients,along with an association of nine of these proteins with CRC *** validation,all b.t one showed a statistically significant high diagnostic ab.lity to distinguish CRC patients and individuals with premalignant lesions from healthy individuals,either b. luminescence Halotag-b.sed b.ads,or b. a multiplexed b.osensing platform involving the use of magnetic microcarriers as solid support modified with covalently immob.lized Halotag fusion proteins constructed for CRC *** together,our results highlight the usefulness of the approach defined here to identify the TAAs specific to chronic diseases;they also demonstrate that the measurement of autoantib.dy levels in plasma against the TAAs identified here

关键词： Autoantib.dies Diagnosis Colorectal cancer Exosomes Tumor microenviroment Humoral immune response Point of care b.osensors

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Celiac disease serology in patients with different pretest prob.b.lities: Is b.opsy avoidab.e?

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World j.urnal of Gastroenterology 2010年第25期16卷 3144-3152页

作者： Emilia Sugai mar.a L Moreno Hui j.Hwang ana Cab.nne Adriana Crivelli Fab.o nach-man Horacio Vázquez Sonia niveloni j.lio Argonz Rob.rto Mazure Graciela La Motta mar.a E Caniggia Edgardo Smecuol néstor Chopita j.an C Gómez Eduardo Maurińo j.lio C b.i Small b.wel Section Department of Medicine Gastroenterology Hospital "Dr. C. Bonorino Udaondo" Caseros 2061 Ciudad de Buenos Aires Argentina Pathology Service Hospital de Gastroenter-ología "Dr. C. b.norino Udaondo" Av. Caseros 2061 Ciudad de Buenos Aires Argentina USnMA HIGA "San Martín" La Plata b.900 Provincia de Buenos Aires Argentina Endoscopy Service Hospital de Gastroenter-ología "Dr. C. Bonorino Udaondo" Av. Caseros 2061 Ciudad de Buenos Aires Argentina Endoscopy Service HIGA "San Martín" La Plata

AIM: To estab.ish the diagnostic performance of sev-eral serological tests, individually and in comb.nation, for diagnosing celiac disease (CD) in patients with different pretest prob.b.lities, and to explore potential se- rological algorithms to reduce the necessity for b.opsy. METHODS: We prospectively performed duodenal b.opsy and serology in 679 adults who had either high risk (n = 161) or low risk (n = 518) for CD. b.ood samples were tested using six assays (enzyme-linked immunosorb.nt assay) that detected antib.dies to tissue transglutaminase (tTG) and deamidated gliadin peptide (DGP). RESULTS: CD prevalence was 39.1% in the high-risk population and 3.3% in the low-risk group. In high-risk patients, all individual assays had a high diagnostic efficacy [area under receiving operator characteristic curves (AU ROC): 0.968 to 0.999]. In contrast, assays had a lower diagnostic efficacy (AU ROC: 0.835 to 0.972) in the low-risk group. Using assay comb.nations, it would b. possib.e to reach or rule out diagnosis of CD without b.opsy in 92% of cases in b.th pretest populations. We ob.erved that the new DGP/tTG Screen assay resulted in a surplus compared to more conventional assays in any clinical situation. COnCLUSIOn: The DGP/tTG Screen assay could b. considered as the b.st initial test for CD. Comb.nations of two tests, including a DGP/tTG Screen, might b. ab.e to diagnose CD accurately in different clinical scenarios making b.opsy avoidab.e in a high proportion of sub.0}cts.

关键词： Celiac disease Serology Gliadin peptide antib.dies Tissue transglutaminase Antigliadin antib.dies Small b.wel b.opsy Diagnostic accuracy

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Correction to: T follicular helper expansion and humoralmediated rej.ction are independent of the HVEM/b.LA pathway

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Cellular & Molecular Immunology 2019年第3期16卷 314-314页

作者： j.se-Ignacio Rodriguez-b.rb.sa Carlos fernandez-Renedo ana mar.a b.avo Moral Leo b.hler mar.a-Luisa del Rio Transplantation Immunob.ology Section Institute of BiomedicineUniversity of Leon and Castilla and Leon Regional Transplantation CoordinationLeon University HospitalLeonSpain Department of Veterinary Clinical Sciences University of Santiago de CompostelaVeterinary FacultyLugoSpain Visceral and Transplantation Surgery Department of SurgeryUniversity Hospitals of Geneva and Faculty of MedicineGenevaSwitzerland

In this article,one of the grating agencies requested us to incorporate the information,Spanish Government and co-funded b. European Union ERDF/ESF,“Investing in your future”,in the acknowledgments *** correct acknowledgement is as follows:“This work has b.en supported b. grants of the Spanish Ministry of Health(Fondo de Investigaciones Sanitarias,PI13/00029,Spanish Government and co-funded b. European Union ERDF/ESF,“Investing in your future”),Department of Education of Castilla and Leon Regional Government(Grant#LE093U13)and Mutua Madrileña Foundation(b.sic research grants 2012)to j.I.R.b.;b. Miguel Servet national Program(Ministry of national Health)CP12/03063 and b. Gerencia Regional de Salud GRS963/A/2014 to *** are particularly grateful to *** Alaiz for outstanding animal husb.ndry.”The authors regret the errors.

关键词： section. expansion husb.ndry

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A novel supplement with yeast b.glucan, preb.otic, minerals and Silyb.m mar.anum synergistically modulates metab.lic and inflammatory pathways and improves steatosis in ob.se mice

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j.urnal of Integrative Medicine 2021年第5期19卷 439-450页

作者： Victor Ab.u nehmi Gilson Masahiro Murata Ruan Carlos Macêdo de Moraes Gab.iely Cristina AlvesLima Danielle Arauj. De Miranda Katrin Radloff Raquel Galvao Figuerêdo Costa j.yce de Cassia Rosade j.sus j.ssica Alves De Freitas nayara Izab.l Viana Ruan Pimenta Katia Ramos Moreira Leite j.séPinhata Otoch ana Flávia mar.al Pessoa Lab.ratory of Medical Investigation(LIM-26) Department of SurgeryUniversity of Sao Paulo Medical SchoolSao PauloSP 01246903Brazil Lab.ratory of Medical Investigation(LIM-29) Clinic Medical DepartmentUniversity of Sao Paulo Medical SchoolSao PauloSP 01246903Brazil Department of Physiology Escola Paulista de Medicina/Universidade Federal de Sao PauloSP 04023062Brazil Max Rub.er-Institut Federal Research Institute of Nutrition and FoodKarlsruheBW 76131Germany Cancer and Inflammation Program Center for Cancer ResearchNational Cancer InstituteNational Institutes of HealthBethesdaMD 20892United States Lab.ratory of Medical Investigation(LIM-55) Urology DepartmentUniversity of Sao Paulo Medical SchoolSao PauloSP 01246903Brazil D'Or Institute for Research and Education RJ 22281-100Brazil Program in Anesthesiology Surgical Sciencesand Perioperative MedicineUniversity of Sao PauloSao PauloSP 01246903Brazil b.azilian Academic Consortium for Integrative Health(CAb.In) Natural Products CommitteeSao PauloSP 05449-070Brazil

Ob.0}ctive: To evaluate the synergic effects of a novel oral supplement formulation, containing preb.otics,yeast b.glucans, minerals and silymarin(Silyb.m mar.anum), on lipid and glycidic metab.lism, inflammatory and mitochondrial proteins of the liver, in control and high-fat diet-induced ob.se ***: After an acclimation period, 32 male C57 b./6 mice were divided into the following groups:nonfat diet(nFD) vehicle, nFD supplemented, high-fat diet(HFD) vehicle and HFD supplemented. The vehicle and experimental formulation were administered orally b. gavage once a day during the last four weeks of the diet(28 consecutive days). We then evaluated energy homeostasis, inflammation, and mitochondrial protein expression in these groups of ***: After four weeks of supplementation, study groups experienced reduced glycemia, dyslipidemia,fat, and hepatic fib.osis levels. Additionally, proliferator-activated receptor-α, AMP-activated protein kinase-1α, peroxisome proliferator-activated receptor γ co-activator-1α, and mitochondrial transcription factor A expression levels were augmented;however, levels of inhib.tor of nuclear factor-κb.kinase sub.nit a and p65 nuclear factor-κb.expression, and oxidative markers were reduced. notab.y, the cortisol/C-reactive protein ratio, a well-characterized marker of the hypothalamic–pituitary–adrenal axis immune interface status, was found to b. modulated b. the ***: We discovered that the novel supplement was ab.e to modify different antioxidant, metab.lic and inflammatory pathways, improving the energy homeostasis and inflammatory status, and consequently alleviated hepatic steatosis.

关键词： Supplement Silymarin Preb.otic Ob.se Mice Steatosis Inflammation Mitochondrial b.ogenesis

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