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| 1 | Protective action of glutamine in rats with severe acute liver failure显示文摘BACKGROUND Severe acute liver failure(SALF) is a rare, but high-mortality, rapidly evolving syndrome that leads to hepatocyte degeneration with impaired liver function.Thioacetamide(TAA) is a known xenobiotic, which promotes the increase of the formation of reactive oxygen species. Erythroid 2-related factor 2(Nrf2) activates the antioxidant protection of cells. Studies have evidenced the involvement of inflammatory mediators in conditions of oxidative stress.AIM To evaluate the antioxidant effects of glutamine on Nrf2 activation and NFκBmediated inflammation in rats with TAA-induced IHAG.METHODS Male Wistar rats(n = 28) were divided into four groups: control,control+glutamine, TAA, and TAA + glutamine. Two TAA doses(400 mg/kg)were administered intraperitoneally, 8 h apart. Glutamine(25 mg/kg) was administered at 30 min, 24 h, and 36 h. At 48 h, blood was collected for liver integrity analysis [aspartate aminotransferase(AST), alanine aminotransferase(ALT), and alkaline phosphatase(ALP)]. The liver was harvested for histology and assessment of oxidative stress [thiobarbituric acid-reactive substances(TBARS), catalase(CAT), glutathione peroxidase(GPx), glutathione S-transferase(GST), glutathione(GSH), Nrf2, Kelch-like ECH-associated protein 1(Keap1),NADPH quinone oxidoreductase1(NQO1), superoxide dismutase(SOD)] and inflammatory process.RESULTS TAA caused disruption of the hepatic parenchyma, with inflammatoryinfiltration, massive necrosis, and ballooning degeneration. Glutamine mitigated this tissue damage, with visible regeneration of hepatic parenchyma; decreased TBARS(P < 0.001), GSH(P < 0.01), IL-1β, IL6, and TNFα levels(P <0.01) in hepatic tissue; and decreased blood levels of AST, ALT, and ALP(P <0.05). In addition, CAT, GPx, and GST activities were restored in the glutamine group(P<0.01, P <0.01, and P <0.001, respectively vs TAA alone). Glutamine increased expression of Nrf2(P < 0.05), NQO1, and SOD(P < 0.01), as well as levels of IL-10(P <0.001), while decreasing expression of Keap1, TLR4, NFκB(P < 0.001), COX-2 and iNOS,(P < 0.01), and reducing NO_2 and NO_3 levels(P < 0.05).CONCLUSION In the TAA experimental model of IHAG, glutamine activated the Nrf2 pathway,thus promoting antioxidant protection, and blunted the NFκB-mediated pathway, reducing inflammation. | Elizangela G Schemitt Renata M Hartmann Josieli R Colares Francielli Licks Jéferson O Salvi Cláudio A Marroni Norma P Marroni | 2019 | World Journal of Hepatology2019，11，3： | 5 |
| 2 | Thiopurine-methyltransferase variants in inflammatory bowel disease:Prevalence and toxicity in Brazilian patients显示文摘AIM:To analyze the prevalence of thiopurine-methyltransferase(TPMT)genotypes and their associationwith drug toxicity in inflammatory bowel disease(IBD)patients from southeastern Brazil.METHODS:A total of 219 consecutive patients with IBD,of which 146 had Crohn’s disease and 73 had ulcerative colitis,regularly seen at the outpatient unit of the Division of Gastroenterology at the University Hospital Pedro Ernesto of the State University of Rio de Janeiro,a tertiary referral center,were enrolled in this study from February 2009 to January 2011.We analyzed the presence of major TPMT genetic variants(TPMT*2,*3A,*3C)in IBD patients by means of a specific allele and RFLP-PCR.Genomic DNA was isolated from peripheral blood leukocytes by proteinase-K/Sodium Dodecyl Sulfate digestion and phenol-chloroform extraction.TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes were detected by real-time polymerase chain reaction followed by direct sequencing with specific primers.Clinical data were systematically recorded,and correlated with the genotype results.RESULTS:The distribution of the selected TPMT gene polymorphism TPMT*2(C238G),TPMT*3A(G460A/A719G),and TPMT*3C(A719G)genotypes was 3.6%,5.4%,and 7.7%of the patients,respectively.Among the side effects recorded from patients taking azathioprine,14 patients presented with pancreatitis and/or an elevation of pancreatic enzymes,while 6 patients had liver toxicity,and 2 patients exhibited myelosuppression/neutropenia.TPMT polymorphisms were detected in 37/219 patients(8 heterozygous for*2,11 heterozygous for*3A,and 18 heterozygous for*3C).No homozygotic polymorphisms were found.Despite the prevalence of the TPMT*3C genotype,no differences among the genotype frequencies were significant.Although no association was detected regarding myelotoxicity or hepatotoxicity,a trend towards the elevation of pancreatic enzymes was observed for TPMT*2 and TPMT*3C genotypes.CONCLUSION:The prevalence of TPMT genotypes was high among Brazilian patients.Variants genes*2and*3C may be associated with azathioprine pancreatic toxicity in a IBD southeastern Brazilian population. | Ana Teresa P Carvalho Barbara C Esberard Renata S B Fróes Davy C M Rapozo Ana B Grinman Tatiana A Simo Juliana C V C Santos Antonio José V Carneiro Luis Felipe Ribeiro-Pinto Heitor S P de Souza | 2014 | World Journal of Gastroenterology2014，20，12： | 3 |
| 3 | Therapeutic targets associated to E-cadherin dysfunction in gastric cancer显示文摘 | Patrí cia Carneiro Joana Figueiredo Renata Bordeira-Carriç o Maria Sofia Fernandes Joana Carvalho Carla Oliveira Raquel Seruca | 2013 | Expert Opinion on Therapeutic Targets2013，，10： | 2 |
| 4 | NT157 has antineoplastic effects and inhibits IRS1/2 and STAT3/5 in JAK2^(V617F)-positive myeloproliferative neoplasm cells显示文摘Recent data indicate that IGF1R/IRS signaling is a potential therapeutic target in BCR-ABL1-negative myeloproliferative neoplasms(MPN);in this pathway,IRS2 is involved in the malignant transformation induced by JAK2^(V617F),and upregulation of IGF1R signaling induces the MPN phenotype.NT157,a synthetic compound designed as an IGF1R-IRS1/2 inhibitor,has been shown to induce antineoplastic effects in solid tumors.Herein,we aimed to characterize the molecular and cellular effects of NT157 in JAK2^(V617F)positive MPN cell lines(HEL and SET2)and primary patient hematopoietic cells.In JAK2^(V617F)cell lines,NT157 decreased cell viability,clonogenicity,and cell proliferation,resulting in increases in apoptosis and cell cycle arrest in the G2/M phase(p<0.05).NT157 treatment inhibited IRS1/2,JAK2/STAT,and NFκB signaling,and it activated the AP-1 complex,downregulated four oncogenes(CCND1,MYB,WT1,and NFKB1),and upregulated three apoptotic-related genes(CDKN1A,FOS,and JUN)(p<0.05).NT157 induced genotoxic stress in a JAK2/STAT-independent manner.NT157 inhibited erythropoietin-independent colony formation in cells from polycythemia vera patients(p<0.05).These findings further elucidate the mechanism of NT157 action in a MPN context and suggest that targeting IRS1/2 proteins may represent a promising therapeutic strategy for MPN. | Bruna Alves Fenerich Jaqueline Cristina Fernandes Ana Paula Nunes Rodrigues Alves Juan Luiz Coelho-Silva Renata Scopim-Ribeiro Priscila Santos Scheucher Christopher A.Eide Cristina E.Tognon Brian J.Druker Eduardo Magalhães Rego João Agostinho Machado-Neto Fabiola Traina | 2020 | Signal Transduction and Targeted Therapy2020，5，1： | 2 |
| 5 | Electromagnetic Stimulation Combined with Aloe vera Increases Collagen Reorganization in Burn Repair显示文摘 | Sofia Poletti Leticia D. Lucke Fernanda O Bortolazzo Renata M. Acunha Marcos G. Mattos Femanda OG. Gaspi Thiago A. M. Andrade Maria Esmeria C. Amaral Andrea A .Aro Edson R Pimentel Marcelo AM. Esquisatto Fernanda A. S. Mendonga Glaucia M. T. Santos | 2018 | Journal of Pharmacy and Pharmacology2018，6，7： | 1 |
| 6 | Multidrug-resistant Pseudomounas qeruginosa andAcinetobacter baumanni:resistance mechanisms and implica-tion for theraphy显示文摘 | Alexandre P Zavascki Celilia G Carvalhaes Renata C Pica′o | 2010 | Expert Rev Anti Infet Ther2010，8，1： | 1 |
| 7 | Antioxidant activity and phenolic compounds in 32 selected herbs 显示文摘 | Aneta W Jan O Renata C | 2007 | Food Chemisry2007，105，： | 1 |
| 8 | Ultrasound-Guided Lung Recruitment in a 3-Month-Old Infant With Acute Respiratory Distress Syndrome显示文摘 | Yoshino Tamaki Sameshima Jo?o Fernando Louren?o de Almeida Murilo Marques Almeida Silva Renata Remondini Luciana Branco Haddad Miguel José Francisco Neto Marcelo Buarque de Gusm?o Funari | 2014 | Ultrasound Quarterly2014，，4： | 1 |
| 9 | Decreased anti-Müllerian hormone and altered ovarian follicular cohort in infertile patients with mild/minimal endometriosis显示文摘 | Nadiane Albuquerque Lemos Elisangela Arbo Renata Scalco Eduardo Weiler Virginia Rosa Jo?o Sabino Cunha-Filho | 2008 | Fertility and Sterility2008，，5： | 1 |
| 10 | ANTIBACTERIAL EFFECT (in vitro) OF Moringa oleifera AND Annona muricata AGAINST GRAM POSITIVE AND GRAM NEGATIVE BACTERIA显示文摘 | Vieira Gustavo Hitzschky Fernandes Mour?o Jozeanne Alves ?ngelo ?ngela Maria Costa Renata Albuquerque Vieira Regine Helena Silva dos Fernandes | 2010 | Revista do Instituto de Medicina Tropical de S茫o Paulo2010，，3： | 1 |
| 11 | Co-nanoencapsulated meloxicam and curcumin improves cognitive impairment induced by amyloid-beta through modulation of cyclooxygenase-2 in mice显示文摘Alzheimer’s disease is a progressive brain disorder and complex mechanisms are involved in the physiopathology of Alzheimer’s disease.However,there is data suggesting that inflammation plays a role in its development and progression.Indeed,some non-steroidal antiinflammatory drugs,such as meloxicam,which act by inhibiting cyclooxygenase-2 have been used as neuroprotective agents in different neurodegenerative disease models.The purpose of this study was to investigate the effects of co-nanoencapsulated curcumin and meloxicam in lipid core nanocapsules(LCN)on cognitive impairment induced by amyloid-beta peptide injection in mice.LCN were prepared by the nanoprecipitation method.Male Swiss mice received a single intracerebroventricular injection of amyloid-beta peptide aggregates(fragment 25–35,3 nmol/3μL)or vehicle and were subsequently treated with curcumin-loaded LCN(10 mg/kg)or meloxicam-loaded LCN(5 mg/kg)or meloxicam+curcumin-co-loaded LCN(5 and 10 mg/kg,respectively).Treatments were given on alternate days for 12 days(i.e.,six doses,once every 48 hours,by intragastric gavage).Our data showed that amyloid-beta peptide infusion caused long-term memory deficits in the inhibitory avoidance and object recognition tests in mice.In the inhibitory avoidance test,both meloxicam and curcumin formulations(oil or co-loaded LCN)improved amyloid-beta-induced memory impairment in mice.However,only meloxicam and curcumin-co-loaded LCN attenuated non-aversive memory impairment in the object recognition test.Moreover,the beneficial effects of meloxicam and curcuminco-loaded LCN could be explained by the anti-inflammatory properties of these drugs through cortical cyclooxygenase-2 downregulation.Our study suggests that the neuroprotective potential of meloxicam and curcumin co-nanoencapsulation is associated with cortical cyclooxygenase-2 modulation.This study was approved by the Committee on Care and Use of Experimental Animal Resources,the Federal University of Pampa,Brazil(approval No.02-2015)on April 16,2015. | Maria Eduarda Ziani Gutierrez Anne Suély Pinto Savall Edina da Luz Abreu Kelly Ayumi Nakama Renata Bem Dos Santos Marina Costa Monteiro Guedes Daiana SilvaÁvila Cristiane Luchese Sandra Elisa Haas Caroline Brandão Quines Simone Pinton | 2021 | Neural Regeneration Research2021，16，4： | 1 |
| 12 | CardiacPI3K-Akt impairs insulin-stimulated glucose uptake independ-ent of mTORCl and GLUT4 translocation显示文摘 | Zhu Yi Pereira Renata O O'Neill Brian T | 2012 | Mol Endocri-nol2012，27，1： | 1 |
| 13 | Molecular Targets Related to Inflammation and Insulin Resistance and Potential Interventions显示文摘 | Sandro M. Hirabara Renata Gorj?o Marco A. Vinolo Alice C. Rodrigues Renato T. Nachbar Rui Curi Hartmut Jaeschke | 2012 | <journal-title>Journal of Biomedicine and Biotechnology2012，，： | 1 |
| 14 | Gene expression reprogramming protects macrophage from septic-induced cell death显示文摘 | Edielle Sant’Anna Melo Denise F. Barbeiro Renata Gorj?o Ester Correia Sarmento Rios Dewton Vasconcelos Irineu T. Velasco Csaba Szabo Rui Curi Thais Martins de Lima-Salgado Francisco Garcia Soriano | 2010 | Molecular Immunology2010，，16： | 1 |
| 15 | Discrepancies among three laboratory methods for C lostridium difficile detection and a proposal for their optimal use显示文摘 | Alexandre A. Monteiro Renata N. Pires Ludmila F. Baethgen Lilian C. Carneiro Rejane G. Tavares Juliana Caier?o Steven Park David S. Perlin Edison M. Rodrigues Filho Alessandro C. Pasqualotto | 2014 | FEMS Microbiol Lett2014，，2： | 1 |
| 16 | Effect of antiretroviral drugs on the DNA damage in mice显示文摘 | Hugo Martins de Oliveira Adriani Paganini Damiani Renata de Oliveira Dias Pedro R.T. Rom?o Vanessa M. Andrade | 2014 | Environmental Toxicology and Pharmacology2014，，： | 1 |
| 17 | The influence of UV-irradiation on poly(vinyl chloride) modified by poly(vinyl acetate)显示文摘 | Halina Kaczmarek Renata Drag Ma?gorzata ?wi?tek Dagmara O?dak | 2002 | Surface Science2002，，： | 1 |
| 18 | T-helper cell type 17/regulatory T-cell immunoregulatory balance in human radicular cysts and periapical granulomas 显示文摘 | Juliana RB Marcal MSC Renata O | 2010 | Journal of Endodontics2010，36，6： | 1 |
| 19 | Anovel trypsin Kazal-type inhibitor from Aedes aegypti with thrombin coagulantin hibitory activity显示文摘 | Renata M O Watanabe Tatiane S Soares Karen Morais-Zani | 2010 | Biochimie2010，92，： | 1 |
| 20 | Influence of temperature on the kinetics of adsorption and desorption of clavulanic acid by ionic exchange显示文摘 | Marlei Barboza Renata M R G Almeida Carlos O Hokka | 2003 | Biochemical Engineering Journal2003，14，： | 1 |
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