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Toll-like receptor 9 polymorphisms and Helicobacter pylori influence gene expression and risk of gastric carcinogenesis in the Brazilian population

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World Journal of Gastrointestinal Oncology 2019年第11期11卷 998-1010页

作者： Manoela Dias Susi de Matos Lourenco Caroline Lucas Trevizani Rasmussen Spencer Luis Marques Payao Ana Flavia Teixeira Rossi Ana Elizabete Silva juliana garcia de oliveira-Cucolo department of Graduate-Level Research USCSacred Heart UniversityBauru 17011-970SPBrazil department of Genetics and Molecular Biology FAMEMA-Marilia Medical SchoolMarília 17519-030SPBrazil department of Biology Sao Paulo State University-UNESPSao Jose do Rio Preto 15054-000SPBrazil department of Molecular Biological and Genetics and Molecular Biology Research Unit-UPGEMFaculty of Medicine of Sao Jose do Rio Preto-FAMERPSao Jose do Rio Preto 15090-000SPBrazil

BACKGROUND Toll-like receptors(TLRs)are the first line of host defense,and are involved in Helicobacter pylori(***)recognition and activation of both inflammatory and carcinogenic *** presence of single nucleotide polymorphisms(SNPs)in genes that activate the immune response may modulate the risk of precancerous lesions and gastric cancer(GC).Among them,Toll-like receptor 9(TLR9)polymorphisms have emerged with a risk factor of infectious diseases and cancer,however the studies are still *** To evaluate whether TLR9 rs5743836 and rs187084 SNPs contribute to the risk of gastric carcinogenesis,and its influence on mRNA *** A case-control study was conducted to evaluate two TLR9 SNPs(TLR9-1237 TCrs5743836 and TLR9-1486 CT-rs187084)in chronic gastritis(CG)and GC patients.A total of 609 DNA samples of peripheral blood[248 CG,161 GC,and 200 samples from healthy individuals(C)]were genotyped by polymerase chain reaction-restriction fragment length *** samples were tested for the *** infection using Hpx1 and Hpx2 *** polymerase chain reaction by TaqMan?assay was used to quantify TLR9 mRNA from fresh gastric tissues(48 GC,26 CG,and 14 C).RESULTS For TLR9-1237,the TC+CC or CC genotypes were associated with a higher risk of GC than C[recessive model odds ratio(OR)=5.01,95%confidence interval(CI):2.52-9.94,Pdel OR=4.63;95%CI:2.44-8.79,Pdel OR=2.72,95%CI:1.57-4.72,Pdel OR=1.79,95%CI:1.15-2.79,P=0.0094)was observed when compared to the C ***,the presence of TLR9-1237 TC/CC+TLR9-1486 CC genotypes potentiate the risk for this neoplasm(OR=18.57;95%CI:5.06-68.15,P<0.0001).The TLR9 mRNA level was significantly higher in the GC group(RQ=9.24,P<0.0001)in relation to the CG group(RQ=1.55,P=0.0010)and normal mucosa(RQ=1.0).When the sa

关键词： Toll-like receptor 9 Helicobacter pylori Gastric cancer Chronic gastritis Polymorphisms Gene expression

Characterization and strong risk association of TLR2 del-196 to-174 polymorphism and Helicobacter pylori and their influence on mRNA expression in gastric cancer

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World Journal of Gastrointestinal Oncology 2020年第5期12卷 535-548页

作者： Caroline de Matos Lourenco Manoela Dias Susi Mariah Cristina Antunes do Nascimento Vilson Serafim Junior Ana Paula Simedan Vila Gabriela Helena Rodrigues-Flemming Eny Maria Goloni-Bertollo Ana Elizabete Silva juliana garcia de oliveira-Cucolo department of Graduate-Level Research Sacred Heart UniversityBauruSao Paulo 17011-970Brazil department of Molecular Biology Sao Josédo Rio Preto School of MedicineSao Josédo Rio PretoSao Paulo 15090-000Brazil department of Biology Sao Paulo State UniversitySao Josédo Rio PretoSao Paulo 15054-000Brazil

BACKGROUND Toll-like receptor-2(TLR2) is responsible for recognizing Helicobacter pylori(***) and activating the immune response. Polymorphisms in TLR2 may modulate gastric *** To evaluate whether the TLR2 19216 T/C(rs3804099) and TLR2-196 to-174 ins/del(rs111200466) polymorphisms contribute to gastric carcinogenesis in the Brazilian population, and to determine the influence of both polymorphisms and H. pylori infection on TLR2 mRNA *** DNA was extracted from 854 peripheral blood leukocyte or gastric tissue samples[202 gastric cancer(GC), 269 chronic gastritis(CG), and 383 control/healthy(C)]and genotyped by allele-specific PCR or restriction fragment length polymorphism(RFLP)-PCR. Quantitative polymerase chain reaction by Taq Man■ assay was used to quantify TLR2 mRNA levels in fresh gastric tissues(48 GC, 36 CG, and 14 C).RESULTS Regarding the TLR2-196 to -174 polymorphism, the ins/del and del/del genotypes were associated with a higher risk of GC by comparison with the C in all of the analyzed inheritance models(codominant, dominant, recessive, overdominant and log-additive;P del polymorphism had an increased risk of gastric carcinogenesis [codominant(P =0.0120), dominant(P = 0.0051), overdominant(P = 0.0240) and log-additive(P =0.0030)], while TLR2 19216 T/C was associated with a protective effect[codominant(P = 0.0039), dominant(P < 0.0001), overdominant(P = 0.0097) and log-additive(P = 0.0021)]. TLR2 mRNA levels were sig

关键词： Toll-like receptor 2 Helicobacter pylori Gastric cancer Chronic gastritis Polymorphisms Gene expression

Artemisia vulgaris Induces Tumor-Selective Ferroptosis and Necroptosis via Lysosomal Ca^(2+) Signaling

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Chinese Journal of Integrative Medicine 2024年第6期30卷 525-533页

作者： Lucas dos Santos Zamarioli Michele Rosana Maia Santos Adolfo garcia Erustes Vanessa Marques Meccatti Thais Cristine Pereira Soraya S Smaili Maria Cristina Marcucci Carlos Rocha oliveira Gustavo JS Pereira Claudia Bincoletto department of Pharmacology Paulista School of MedicineFederal University of São PauloSão PauloSP04044-020Brazil Research Group on Phytocomplexes and Cell Signaling School of Health SciencesAnhembi Morumbi UniversitySão PauloSP03164-000Brazil department of Biosciences and Oral Diagnosis Institute of Science and TechnologySão Paulo State University(ICT-UNESP)São PauloSP12231-280Brazil

Objective To evaluate the chemical composition and effects of Artemisia vulgaris(AV)hydroalcoholic extract(HEAV)on breast cancer cells(MCF-7 and SKBR-3),chronic myeloid leukemia(K562)and NIH/3T3 *** Phytochemical analysis of HEAV was done by high-performance liquid chromatography-mass(HPLC)*** and cell death studies were performed using trypan blue and Annexin/FITC-7AAD,***-1(Fer-1)and necrostatin-1(Nec-1)were used to assess the mode of HEAV-induced cell death and acetoxymethylester(BAPTA-AM)was used to verify the involvement of cytosolic calcium in this *** calcium measurements were made using *** HEAV decreased the viability of MCF-7,SKBR-3 and K562 cells(Pdeath primarily by late apoptosis and necrosis in assays using annexin V-FITC/7-AAD(Pdecreased the number of non-viable cells treated with HEAV(Pdeath,which are partially dependent on lysosomal release of Ca^(2+).These effects may be related to artemisinin and caffeoylquinic acids,the main compounds identified in HEAV.

关键词： Artemisia vulgaris necroptosis ferroptosis late apoptosis Ca^(2+)signaling

TLR2 and TLR4 polymorphisms influence m RNA and protein expression in colorectal cancer

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World Journal of Gastroenterology 2015年第25期21卷 7730-7741页

作者： Marcela Alcantara Proenca juliana garcia de oliveira Aline Cristina Targa Cadamuro Maysa Succi Joao Gomes Netinho Eny Maria Goloni-Bertolo érika Cristina Pavarino Ana Elizabete Silva department of Biology UNESPSao Paulo State University USC-Sacred Heart University PróReitoria de Pesquisa e Pós Graduacao department of Surgery School of MedicineFAMERPSao Josédo Rio Preto 15090-000SPBrazil UPGEM School of MedicineFAMERPSao Josédo Rio Preto 15090-000SPBrazil

AIM: To evaluate the effect of promoter region polymorphisms of toll-like receptor(TLR)2-196 to-174 del and TLR4-1607T/C(rs10759932) on m RNA and protein expression in tumor tissue and of TLR4+896A/G(rs4986790) on colorectal cancer(CRC) ***: The TLR2-196 to-174 del polymorphism was investigated using allele-specific polymerase chain reaction(PCR) and the TLR4-1607T/C and TLR4+896A/G by PCR-restriction fragment length p o l y m o r p h i s m( R F L P). W e g e n o t y p e d 4 3 4 D N A samples from 194 CRC patients and 240 healthy individuals. The m RNA relative quantification(RQ) was performed in 40 tumor tissue samples by quantitative PCR Taq Man assay, using specific probes for TLR2 and TLR4 genes, and ACTB and GAPDH reference geneswere used as endogenous controls. Protein expression was analyzed by immunohistochemistry with specific primary ***: No association was found for TLR4-1607T/C and TLR4+896A/G by three statistical models(logadditive, dominant and recessive). However, based on dominant and log-additive models, the polymorphic variant TLR2-196 to-174 del was associated with increased CRC risk [dominant: odds ratio(OR) = 1.72, 95%CI: 1.03-2.89; P = 0.038 and log-additive: OR =1.59, 95%CI: 1.02-2.48; P = 0.039]. TLR2 m RNA expression was increased in tumor tissue(RQ = 2.36) when compared to adjacent normal tissue(RQ = 1; P del variant carriers showed m RNA relative expression 2.19 times higher than wild-genotype carriers. The TLR2 protein expression was also higher for the TLR2-196 to-174 del variant carriers [117 ± 10 arbitrary unit(a.u.) vs 95 ± 4 a.u., P = 0.03]. However, for the TLR4-1607T/C polymorphism no significant difference was found for both m RNA(P = 0.56) and protein expression(P

关键词： Toll-like receptor 2 Toll-like receptor 4 Colorectal cancer Protein expression Gene expression Genetic polymorphisms

development of a Ready-to-Use PSMA-11 Kit Formulation and Biological Evaluation of Binding Affinity

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Advances in Molecular Imaging 2024年第2期13卷 7-22页

作者： Maria Renata Valente Brandão Freire Natália Marchesan Bexiga Marco Antonio Stephano João Ezequiel oliveira Carlos Roberto Jorge Soares Ana Cláudia Camargo Miranda Anna Carolina de Alcântara Barbosa Marycel Figols de Barboza Laura Fernanda garcia Luiz Felipe S. Teixeira Maria Helena Marumo Bellini Natanael Gomes da Silva Luiza Mascarenhas Balieiro Joel Mendes Elaine Bortoleti de Araújo Centro de Radiofarmcia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil departamento de Tecnologia Farmacutica Faculdade de Cincias Farmacuticas (USP) Cidade Universitria So Paulo Brasil Centro de Biotecnologia Instituto de Pesquisas Energticas e Nucleares (IPEN) Cidade Universitria So Paulo Brasil departamento de Medicina Nuclear do Hospital Israelita Albert Einstein So Paulo/SP Brasil

Introduction: 68Ga-PSMA-11 is considered the gold standard in detection of micro and oligometastases in advanced prostate cancer, being used for therapeutic planning, as well as, potentially, for evaluating response to treatment. The development of ready-to-use lyophilized kit of PSMA-11 adds quality and safety to the routine use of this radiopharmaceutical and represents a pharmacotechnical challenge as it must preserve the integrity and specificity of the ligand. Methods: PSMA-11 kit formulation was proposed, considering radiolabeling parameters and the preservation of the peptide during the lyophilization process, using mannitol as an excipient. Critical temperature characterization studies were carried out using DSC equipment and the freeze-drying process was developed. The direct radiolabeling conditions were evaluated and standardized using 68Ge/68Ga generator eluate from two different manufacturers (ITG and Eckert & Ziegler). The radiochemical purity was evaluated by TLC and HPLC. Biological evaluation was carried out with lyophilized PSMA-11 to demonstrate the integrity of the peptide and preservation of biological activity after the lyophilization process. Results: Based on critical temperature characterization studies, the freeze-drying cycle was designed to reach a freezing temperature of around −40˚C and primary drying at 2˚C. Using 20 mg of mannitol, an intact and elegant lyophilized cake was obtained. PSMA-11 lyophilized kit was directly labeled with 68Ga eluate from 68Ge/68Ga GMP generators (ITG and Eckert & Ziegler) resulting in % RP > 95% at pH 4.0 to 4.5. The results obtained from in vitro and in vivo biological competition studies confirmed the preservation of PSMA-11 affinity for the receptor after lyophilization. Conclusion: A lyophilized formulation (Kit) of PSMA-11 was successfully obtained, which preserved the integrity and biological activity of the peptide and guaranteed radiolabeling efficiency.

关键词： 68Ga-PSMA-11 Prostate-Specific Membrane Antigen (PSMA) Ready-to-Use Kit GMP-Grade Generators Metastatic Prostate Cancer PET Imaging

High-throughput phenotyping of two plant-size traits of Eucalyptus species using neural networks

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Journal of Forestry Research 2022年第2期33卷 591-599页

作者： Marcus Vinicius Vieira Borges Janielle de oliveira garcia Tays Silva Batista Alexsandra Nogueira Martins Silva Fabio Henrique Rojo Baio Carlos Antônio da Silva Junior Gileno Brito de Azevedo Glauce Taís de oliveira Sousa Azevedo Larissa Pereira Ribeiro Teodoro Paulo Eduardo Teodoro Federal University of Mato Grosso Do Sul(UFMS) Chapadão Do SulMato Grosso Do Sul 79560000Brazil department of Geography State University of Mato Grosso(UNEMAT)SinopMato Grosso 78555000Brazil

In forest modeling to estimate the volume of wood,artificial intelligence has been shown to be quite effi-cient,especially using artificial neural networks(ANNs).Here we tested whether diameter at breast height(DBH)and the total plant height(Ht)of eucalyptus can be pre-dicted at the stand level using spectral bands measured by an unmanned aerial vehicle(UAV)multispectral sensor and vegetation *** do so,using the data obtained by the UAV as input variables,we tested different configurations(number of hidden layers and number of neurons in each layer)of ANNs for predicting DBH and Ht at stand level for different Eucalyptus *** experimental design was randomized blocks with four replicates,with 20 trees in each experimental *** treatments comprised five Eucalyptus species(***,***,***,***-dis,and ***)and Corymbria *** and Ht for each plot at the stand level were measured seven times in separate overflights by the UAV,so that the multispectral sensor could obtain spectral bands to calculate vegetation indices(VIs).ANNs were then constructed using spectral bands and VIs as input layers,in addition to the categorical variable (species), to predict DBH and Ht at the stand level simultaneously. This report represents one of the first appli-cations of high-throughput phenotyping for plant size traits in Eucalyptus species. In general, ANNs containing three hidden layers gave better statistical performance (higher esti-mated r, lower estimated root mean squared error-RMSE) due to their greater capacity for self-learning. Among these ANNs, the best contained eight neurons in the first layer, seven in the second, and five in the third (8 − 7 − 5). The results reported here reveal the potential of using the gener-ated models to perform accurate forest inventories based on spectral bands and VIs obtained with a UAV multispectral sensor and ANNs, reducing labor and time.

关键词： Computational intelligence Diameter at breast height Forest inventory Remote sensing Vegetation indices

Brazilian payment for environmental services programs emphasize water-related services

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International Soil and Water Conservation Research 2023年第2期11卷 276-289页

作者： Ingrid Mamedes Angélica Guerra Dulce B.B.Rodrigues Letícia Couto garcia Raquel de Faria Godoi Paulo Tarso S.oliveira Faculty of Engineering Architecture and Urbanism and GeographyFederal University of Mato Grosso do SulMS79070-900Brazil Programa de Pós-Graduaçāo em Ecologia e Conservaaçāo Universidade Federal de Mato Grosso do SulCampo GrandeBrazil Laboratorio de Ecologia da Intervenaçāo-LEl Instituto de BiociênciasUniversidade Federal de Mato Grosso do SulCampo GrandeBrazil department of Hydraulics and Sanitary Engineering Sao Carlos School of EngineeringUniversity of Sao PauloSao CarlosSPBrazil

Based on"user pays"and"provider gets"principles,the Payment for Environmental Services(PES)consists of providing economic incentives or compensation for land users who adopt activities that promote ecosystem *** PES initiatives have grown rapidly in Brazil over the last few decades,however,studies that address the panorama of these programs in the country are still scarce,regional,or ***,we investigate the PES overview in Brazil through interviews and an extensive literature *** found in total 80 PES programs implemented in Brazil,of which 14 were *** pro-grams are poorly distributed across the country,mostly concentrated in the Atlantic Forest(56.25%)and Savanna(36.25%)biomes,in Southeastern *** majority of programs primarily prioritize improving water quality and ***,reforestation,protection of native vegetation,and soil and water conservation are their main proposed *** positive impacts of Brazil's PES experi-ences are evident;while the lack of transparency and monitoring,and poor spatial and financial dis-tribution are still major *** conclude that if correctly implemented,PES schemes offer a path to reconcile environmental conservation with agricultural production in Brazil.

关键词： Conservation funding Ecological restoration Environmental compliance Public policy Soil and water conservation

Genetic Identification of Quantitative Trait Loci for Contents of Mineral Nutrients in Rice Grain

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Journal of Integrative Plant Biology 2009年第1期51卷 84-92页

作者： Ana Luisa garcia-oliveira department of Plant Genetics and Breeding and State Key Laboratory of Plant Physiology and Biochemistry China Agricultural University National Centre for Evaluation of Agricultural Wild Plant Rice Beijing Key Laboratory of Crop Genetic Improvement and Genome of Ministry of Agriculture

In present study, Fe, Zn, Mn, Cu, Ca, Mg, P and K contents of 85 introgression lines （ILs） derived from a cross between an elite indica cultivar Teqing and the wild rice （Oryza rufipogon） were measured by inductively coupled argon plasma （ICAP） spectrometry. Substantial variation was observed for all traits and most of the mineral elements were significantly positive correlated or independent except for Fe with Cu. A total of 31 putative quantitative trait loci （QTLs） were detected for these eight mineral elements by single point analysis. Wild rice （O. rufipogon） contributed favorable alleles for most of the QTLs （26 QTLs）, and chromosomes 1,9 and 12 exhibited 14 QTLs （45%） for these traits. One major effect of QTL for zinc content accounted for the largest proportion of phenotypic variation （11%-19%） was detected near the simple sequence repeats marker RM152 on chromosome 8. The co-locations of QTLs for some mineral elements observed in this mapping population suggested the relationship was at a molecular level among these traits and could be helpful for simultaneous improvement of these traits in rice grain by marker assisted selection.

关键词： introgression lines mineral elements Oryza sativa Oryza rufipogon quantitative trait loci.

Magnetic lipid nanovehicles synergize the controlled thermal release of chemotherapeutics with magnetic ablation while enabling non-invasive monitoring by MRI for melanoma theranostics

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Bioactive Materials 2022年第2期7卷 153-164页

作者： Lorena garcia-Hevia Inigo Casafont Jessica oliveira Nuria Teran Monica L.Fanarraga Juan Gallo Manuel Banobre-Lopez Advanced(Magnetic)Theranostic Nanostructures Lab.International Iberian Nanotechnology Laboratory Avda.Mestre Jose Veiga s/n4715-330BragaPortugal Grupo de Nanomedicina.Universidad de Cantabria-IDIVAL Herrera Oria s/n39011SantanderSpain

Nowadays,a number of promising strategies are being developed that aim at combining diagnostic and therapeutic capabilities into clinically effective ***,the combination of a modified release provided by an organic encapsulation and the intrinsic physico-chemical properties from an inorganic counterpart opens new perspectives in biomedical ***,a biocompatible magnetic lipid nanocomposite vehicle was developed through an efficient,green and simple method to simultaneously incorporate magnetic nanoparticles and an anticancer drug(doxorubicin)into a natural *** theranostic performance of the final magnetic formulation was validated in vitro and in vivo,in melanoma *** systemic administration of the proposed magnetic hybrid nanocomposite carrier enhanced anti-tumoral activity through a synergistic combination of magnetic hyperthermia effects and antimitotic therapy,together with MRI reporting *** application of an alternating magnetic field was found to play a dual role,(i)acting as an extra layer of control(remote,on-demand)over the chemotherapy release and(ii)inducing a local thermal ablation of tumor *** combination of chemotherapy with thermotherapy establishes a synergistic platform for the treatment of solid malignant tumors under lower drug dosing schemes,which may realize the dual goal of reduced systemic toxicity and enhanced anti-tumoral efficacy.

关键词： Drug delivery systems Theranosis Magnetic hyperthermia Magnetic resonance imaging Melanoma