RESUMO
Following the publication of the original article the author listed as Antonio Herrera contacted the Publisher to state that his correct and full name is Antonio Herrera-Merchan. Antonio Herrera-Merchan has agreed to the publication of this erratum.
RESUMO
INTRODUCTION/PURPOSE: BRG1 is a key regulator of leukemia stem cells. Indeed, it has been observed that this type of cells is unable to divide, survive and develop new tumors when BRG1 is down-regulated. MATERIALS AND METHODS: We assessed BRG1 and miR-155 expression in 23 leukemia cell lines, and two no pathological lymphocyte samples using qPCR. MiR-155 transfection and western blot were used to analyze the relationship between miR-155 and its validated target, BRG1, by measuring protein expression levels. The effect of miR-155 on cell proliferation and prednisolone sensitivity were studied with resazurin assay. RESULTS: BRG1 expression levels could correlate negatively with miR-155 expression levels, at least in Burkitt's lymphoma and diffuse large B cell lymphoma (DLBCL) cell lines. To clarify the role of miR-155 in the regulation of BRG1 expression, we administrated miR-155 mimics in different leukemia/lymphoma cell lines. Our results suggest that miR-155 regulate negatively and significantly the BRG1 expression at least in the MOLT4 cell line. CONCLUSION: Our study revealed a previously unknown miR-155 heterogeneity that could result in differences in the treatment with miRNAs in our attempt to inhibit BRG1. However, the expression levels of BRG1 and miR-155, before prednisolone treatment were not statistically significantly associated prednisolone sensitive leukemia cells.
Assuntos
Proliferação de Células , DNA Helicases/metabolismo , Regulação Neoplásica da Expressão Gênica , Leucemia/patologia , Linfoma/patologia , MicroRNAs/genética , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , DNA Helicases/genética , Humanos , Leucemia/genética , Leucemia/metabolismo , Linfoma/genética , Linfoma/metabolismo , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Células Tumorais CultivadasRESUMO
DNA topoisomerases and DNA polymerases are enzymes that play a crucial role in DNA metabolism events such as replication, transcription, recombination, and chromosome segregation during mitosis. Thus, DNA topoisomerases and DNA polymerases inhibitors could be expected to have antitumor effects. Naturally occurring triterpenoids isolated from Junellia aspera (Gillies & Hook; Moldenke) (Verbenaceae) were assayed for human DNA topoisomerase I and Taq DNA polymerase inhibitory activities. Maslinic acid (2) and its diacetyl derivative (7) showed human DNA topoisomerase I inhibitory activity with IC50 values in the range of 76-80 microM and growth inhibition against various human solid tumour cell lines with GI50 values in the range of 5-18 microM. The triterpene frames could be used for screening new inhibitors of the enzyme, and computer-simulated drug design using the frame and pocket structure of enzyme may in theory be a possible approach to develop new inhibitors.
Assuntos
Antineoplásicos/farmacologia , Proliferação de Células/efeitos dos fármacos , Regulação Enzimológica da Expressão Gênica , Ácido Oleanólico/análogos & derivados , Taq Polimerase/antagonistas & inibidores , Inibidores da Topoisomerase I , Verbenaceae/química , Linhagem Celular Tumoral , Humanos , Concentração Inibidora 50 , Estrutura Molecular , Ácido Oleanólico/farmacologia , Análise EspectralRESUMO
PURPOSE: In this work, a novel descriptor of atoms in molecules is introduced. The Refractotopological State Index for atoms (R-state,R), rectifies the atomic refractivity values reported by Crippen et al with the atomic refractivity values of the topological environment of each skeletal atom in the molecule. METHOD: The R-state (R(i)), for atom i is an hybrid index that is defined as the intrinsic refractivity value of the atom i (AR(i)) plus a perturbation term Delta AR(i) in the non-hydrogen depleted graph. RESULTS: The variations of the R values in different molecules are showed. QSAR examples previously reported by other authors are given for benzimidazole inhibition of Lee strain flu virus and receptor binding affinity of beta-carbolines. CONCLUSIONS: The index does not only describe the representation of the atomic dispersive forces related to the molar refractivity but also the influence of bounded and unbounded atoms as a measure of the distance-effect of the other groups in the molecule. The R-state index has proved a good performance, either alone or combined with the electro topological (E)-state index. This implies that in those cases this representation of dispersive forces between the molecule and the active site is a valid approach to the biological problem
Assuntos
Química Farmacêutica , Modelos Químicos , Relação Quantitativa Estrutura-Atividade , Benzimidazóis/química , Benzimidazóis/farmacologia , Conformação Molecular , Orthomyxoviridae/efeitos dos fármacosRESUMO
PURPOSE: Development of a novel semi-empirical descriptor (MR(chi) for molecular modelling. METHOD: The index is based on a molar refractivity partition using Randictype graph-theoretical invariant. RESULTS: This hybrid index describes not only the London dispersive forces in a ligand fragment related to the molar refractivity but also structural features of the molecule It is also applicable in Quantitative Structure-Activity Relationship (QSAR) and Quantitative Structure-Property Relationship (QSPR) studies. CONCLUSIONS: The method is convenient and can discriminate between isomers.
Assuntos
Modelos Químicos , Estrutura Molecular , Química Farmacêutica , Simulação por Computador , Ligantes , Modelos Estatísticos , Preparações Farmacêuticas/química , Relação Quantitativa Estrutura-Atividade , Relação Estrutura-Atividade , TermodinâmicaRESUMO
From the aerial parts of Laennecia sophiifolia (Kunth) G.L. Nesom, a neo-clerodane and an acyclic furano diterpene were isolated, along with four known compounds, 2beta-hydroxyhardwickiic acid, hawtriwaic acid, apigenin, and beta-sitosterol. Their structures were established as 12-epi-bacchotricuneatin A and (2E,6E)-9-(3-furyl)-6-methyl-2-(4-methylpent-3-enyl)-nona-2,6-dienoic acid, by analysis of spectral evidence. The absolute structure of 12-epi-bacchotricuneatin A was determined by a circular dichroism spectral comparison with that of bacchotricuneatin A.
Assuntos
Asteraceae/química , Diterpenos/isolamento & purificação , Diterpenos/química , Estrutura Molecular , Análise EspectralRESUMO
The present report explores the role of nitric oxide into the immune response against Neisseria meningitidis serogroup B. Here we show that NO mediates the alphaTNF increase induced by N. meningitidis derived lipopolysaccharides (LPS), at the same time that participates in the bactericidal activity of resting or gammaIFN activated macrophages and plays a role in the specific DTH and IgG response induced by a commercial anti-meningococcal vaccine. Our findings suggest a positive role for NO at the final effector mechanisms and in the early events driving the immunity against N. meningitidis, suggesting also an insight into its role in endotoxic shock.
Assuntos
Neisseria meningitidis/imunologia , Óxido Nítrico/imunologia , Animais , Cápsulas Bacterianas , Vacinas Bacterianas/biossíntese , Inibidores Enzimáticos , Humanos , Hipersensibilidade Tardia/imunologia , Interferon gama/biossíntese , Camundongos , Polissacarídeos Bacterianos/imunologia , Fator de Necrose Tumoral alfa/biossíntese , ômega-N-MetilargininaRESUMO
We studied the role of advanced glycosylation end products on the induction of nitric oxide synthase in peritoneal mouse macrophages previously exposed to modified BSA. A dose-dependent increment in the nitric oxide production induced by LPS and IFN-gamma was observed when cell cultures were pretreated with modified BSA for 48 hours. In addition, the up regulation of nitric oxide production was also time-dependent, being maximal at 24-48 hours. Experiments carried out in the presence of neutralizing antibodies to IL-1 and TNF-alpha, suggested that up regulation was not due to the capacity of modified BSA to induce both proinflammatory signals. The up regulation of nitric oxide production was paralleled with an increase in iNOS mRNA.
Assuntos
Produtos Finais de Glicação Avançada/farmacologia , Macrófagos Peritoneais/efeitos dos fármacos , Óxido Nítrico Sintase/biossíntese , Animais , Indução Enzimática , Interferon gama/farmacologia , Lipopolissacarídeos/farmacologia , Macrófagos Peritoneais/enzimologia , Macrófagos Peritoneais/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
The effects of chlorpromazine on either the activity of mouse brain nitric oxide synthase or the induction of lung nitric oxide synthase in mice and rats were studied. Chlorpromazine inhibited the nitric oxide synthase activity in mouse brain cytosol. This effect could be reversed by adding an excess of calmodulin. In addition, chlorpromazine was able to inhibit the induction of lung nitric oxide synthase, in both species, after LPS administration. Furthermore, chlorpromazine also inhibited arginase activity in mouse lung cytosol.
Assuntos
Aminoácido Oxirredutases/biossíntese , Encéfalo/efeitos dos fármacos , Clorpromazina/farmacologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Animais , Arginase/biossíntese , Citrulina/biossíntese , Citosol/metabolismo , Indução Enzimática/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Pulmão/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico/biossíntese , Óxido Nítrico Sintase , Ratos , Ratos Sprague-Dawley , Choque Séptico/etiologiaRESUMO
Survival after lipopolysaccharide challenge (LD80, 20 mg.kg-1, i.p.) was significantly enhanced by previous treatment with a microdose of LPS (50 micrograms.kg-1, i.v.). When NG-monomethyl-L-arginine, a specific inhibitor of the formation of nitric oxide from L-arginine, was given 30 minutes before microdose, survival was significantly reduced. When we monitored the serum Tumor Necrosis Factor (TNF) levels in both groups a significant reduction of TNF level after the microdose was observed in mice previously treated with L-NMMA. The ability of L-NNMA to reduce TNF release was dose dependent.
Assuntos
Lipopolissacarídeos/uso terapêutico , Óxido Nítrico/metabolismo , Sepse/prevenção & controle , Animais , Arginina/análogos & derivados , Arginina/metabolismo , Arginina/farmacologia , Relação Dose-Resposta a Droga , Lipopolissacarídeos/administração & dosagem , Lipopolissacarídeos/toxicidade , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Sepse/etiologia , Sepse/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , ômega-N-MetilargininaRESUMO
The concentration of the anti-oxidant enzymes catalase (CAT), peroxidases (POD) and superoxide dismutases (SOD) in different blood fractions, and the chromosomal sensitivity of lymphocytes to bleomycin-induced free radicals (expressed as frequency of dicentrics per bleomycin dose) were analyzed in 10 normal human donors. Our results demonstrate that the physiological concentration of the enzymes as well as the chromosomal sensitivity exhibited a wide interindividual variability. An inverse correlation between chromosomal sensitivity to bleomycin and SOD concentration in whole blood, plasma and red cells was found. On the other hand, no correlation between the yield of bleomycin-induced dicentrics and the concentration of CAT or POD was detected in any of the blood fractions analyzed. These findings suggest that the concentration of SOD may play an important role in the cellular susceptibility to DNA damage by free radicals.
Assuntos
Bleomicina/toxicidade , Aberrações Cromossômicas , Adulto , Catalase/sangue , Dano ao DNA , Humanos , Linfócitos/efeitos dos fármacos , Masculino , Oxirredução , Peroxidases/sangue , Superóxido Dismutase/sangueRESUMO
The DNA composition and the in situ hybridization of satellite fractions were analysed in the New World camelids llama, alpaca, guanaco and vicuña. In the four camelid forms, it was possible to identify a similar main band DNA and five satellite fractions (I-V) with G + C base contents ranging from 32% to 66%. Satellites II-V from llama were in situ reannealed on chromosomes from the four camelid forms. The results obtained were: (a) the four satellites hybridized with regions of C-banding (centromeric regions of all chromosomes and short arms of some autosomes); (b) in general, homologous hybridizations (llama DNA versus llama chromosomes) were more efficient than heterologous reassociations; there were however three exceptions to this rule (vicuña and alpaca satellite fraction II, chromosome group B; vicuña fraction V, chromosome groups A and B); (c) X chromosomes from the four camelids had satellites III-V but lacked satellite II, (d) no satellite fraction was detected on chromosome Y. The analysis of the in situ hybridization patterns allowed to conclude that most or all C-banded chromosome regions comprise several satellite DNA fractions. It is, moreover, proposed that there is an ample interspecies variation in the number of chromosomes that cross-react with a given satellite fraction. Our data give further support to the close genomic kinship of New World camelids.
Assuntos
Artiodáctilos/genética , Camelídeos Americanos/genética , DNA Satélite/isolamento & purificação , Animais , Composição de Bases , Camelídeos Americanos/classificação , Feminino , Temperatura Alta , Masculino , Desnaturação de Ácido Nucleico , Hibridização de Ácido Nucleico , FilogeniaAssuntos
Neoplasias da Mama/epidemiologia , Tumor Filoide/epidemiologia , Adolescente , Adulto , Idoso , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Criança , Feminino , Humanos , Pessoa de Meia-Idade , Panamá , Tumor Filoide/patologia , Tumor Filoide/cirurgia , Terminologia como AssuntoAssuntos
Criança , Adolescente , Adulto , Pessoa de Meia-Idade , Humanos , Feminino , Neoplasias da Mama , Adenofibroma , Tumor FiloideRESUMO
PIP: The article discusses the case of a young patient with ruptured benign adenoma of the liver, possibly related to previous treatment with oral contraceptives. The patient, whose adenoma was bleeding into the peritoneal cavity, underwent right hepatectomy by the Lin technique. There were no complications. Complete resection is the only known adequate treatment for these benign tumors, and Lin's technique and surgical instruments have proven to be very helpful.^ieng