RESUMO
Identifying biomarker genes and characterizing interaction pathways with high-dimensional and low-sample size microarray data is a major challenge in computational biology. In this field, the construction of protein-protein interaction (PPI) networks using disease-related selected genes has garnered much attention. Support vector machines (SVMs) are commonly used to classify patients, and a number of useful tools such as lasso, elastic net, SCAD, or other regularization methods can be combined with SVM models to select genes that are related to a disease. In the current study, we propose a new Net-SVM model that is different from other SVM models as it is combined with L1/2-norm regularization, which has good performance with high-dimensional and low-sample size microarray data for cancer classification, gene selection, and PPI network construction. Both simulation studies and real data experiments demonstrated that our proposed method outperformed other regularization methods such as lasso, SCAD, and elastic net. In conclusion, our model may help to select fewer but more relevant genes, and can be used to construct simple and informative PPI networks that are highly relevant to cancer.
Assuntos
Modelos Biológicos , Neoplasias/metabolismo , Domínios e Motivos de Interação entre Proteínas , Máquina de Vetores de Suporte , Algoritmos , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Redes Reguladoras de Genes , Marcadores Genéticos , Humanos , Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Mapas de Interação de ProteínasRESUMO
Hemagglutinin (HA) protein plays an important role in binding the influenza virus to infected cells and therefore mediates infection. Deposited HA sequences of 86 Asian strains of influenza A (H1N1) viruses during the first outbreak were obtained from the NCBI database and compared. Interaction of the HA protein of influenza A (H1N1) virus with the human sialic acid receptor was also studied using bioinformatics. Overall, not more than three single-point amino acid variants/changes were observed in the HA protein region of influenza A (H1N1) virus from Asian countries when a selected group sequence comparison was made. The bioinformatics study showed that the HA protein of influenza A (H1N1) binds to the sialic acid receptor in human airway receptors, possibly key to air-borne infection in humans.
Assuntos
Glicoproteínas de Hemaglutininação de Vírus da Influenza/metabolismo , Vírus da Influenza A Subtipo H1N1/metabolismo , Ácido N-Acetilneuramínico/metabolismo , Receptores Virais/metabolismo , Substituição de Aminoácidos , Ásia , Sítios de Ligação , Glicoproteínas de Hemaglutininação de Vírus da Influenza/química , Glicoproteínas de Hemaglutininação de Vírus da Influenza/genética , Humanos , Ligação de Hidrogênio , Vírus da Influenza A Subtipo H1N1/genética , Modelos Moleculares , Mutação , Ácido N-Acetilneuramínico/química , Ligação ProteicaRESUMO
The EtOAc extract of the whole plant of the Argentinian species Nierembergia aristata showed significant cytotoxicity against eleven different cancer cell lines. In addition to several known compounds, bioassay-guided fractionation led to the isolation of three new cardenolides, 17-epi-11 alpha-hydroxy-6, 7-dehydrostrophanthidin-3-O-beta-boivinopyranoside[1],6, 7-dehydrostrophanthidin-3-O-beta-boivinopyranoside [2], and 6,7-dehydrostrophanthidin-3-O-beta-oleandropyranoside[3], of which the latter demonstrated activity against all the cell lines tested. To our knowledge, this is the first report of the isolation of cardiac glycosides from a species in the Solanaceae.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Cardenolídeos/química , Plantas Medicinais/química , Antineoplásicos Fitogênicos/farmacologia , Argentina , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas de Bombardeamento Rápido de Átomos , Espectrofotometria Infravermelho , Células Tumorais CultivadasRESUMO
Three new labdane diterpenes, gaudichaudols A-C [1-3], a new clerodane diterpenoid, gaudichaudone [4], and the known clerodane, articulin acetate [5] have been isolated from the aerial parts of Baccharis gaudichaudiana, together with the known compounds, apigenin, hispidulin, spathulenol, and ursolic acid. Through the application of 1D- and 2D nmr spectroscopy, the structures of the new diterpenoids [1-4] were, in turn; elucidated as 15,16,18,19-tetrahydroxylabd-5-ene, 15-O-acetyl-16,18,19-trihydroxylabd-5-ene, 16-O-p-trans-coumaroyl-15,18,19-trihydroxylabd-5-ene, and 2 beta-hydroxy-15,16-epoxycleroda-1(10),15,16-trien-18,19-olide++ +. The isolated compounds were evaluated in P-388 lymphocytic leukemia cells as well as a battery of human cancer cell lines. Among the diterpenoids, gaudichaudol C [3], gaudichaudone [4], and articulin acetate [5] exhibited significant cytotoxic activity against certain cancer cells.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Diterpenos/isolamento & purificação , Plantas Medicinais/química , Animais , Antineoplásicos Fitogênicos/farmacologia , Diterpenos/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Camundongos , América do Sul , Células Tumorais CultivadasRESUMO
A new cytotoxic (P-388 ED50 4 microgm/ml) arylnaphthalene lignan has been isolated from the Mexican medicinal plant Hyptis verticillata (Lamiaceae) and characterized as 5-methoxydehydropodophyllotoxin [1]. Eight additional lignans were also obtained by bioactivity-directed fractionation using the brine shrimp lethality test. Of these, the dehydro-beta-peltatin methyl ether 2 (P-388 ED50 1.8 microgm/ml) is reported for the first time as a natural product isolate. The other bioactive compounds were identified as dehydropodophyllotoxin [3], deoxydehydropodophyllotoxin [4]. (--)-yatein [5], 4'-demethyldeoxypodophyllotixin [6], isodeoxypodophyllotoxin [7], deoxypicropodophyllin [8], and beta-apopicropodophyllin [9]. Each of these compounds was evaluated against a panel of cell lines comprising a number of human cancer cell types [breast, colon, fibrosarcoma, lung, prostate, KB, and KB-VI (a multi-drug resistant cell line derived from KB)] and murine lymphocytic leukemia (P-388). Lignans 1-4 showed marginal cytotoxic activity against the human cell lines tested. In contrast, compounds 5-9 demonstrated a general nonspecific activity comparable to that of podophyllotoxin [12] (ED50 < 10-2 microgm/ml). In addition, the antimitotic potential of these compounds was determined in the astrocytoma (ASK) assay. Finally, the plant was also shown to contain the flavonoid sideritoflavone (KB ED50 1.6 microgm/ml) and the known pentacyclic triterpenoids ursolic, maslinic, 2 alpha-hydroxyursolic and oleanolic acids.
Assuntos
Antineoplásicos Fitogênicos/isolamento & purificação , Plantas Medicinais/química , Podofilotoxina/análogos & derivados , Animais , Antineoplásicos Fitogênicos/farmacologia , Artemia/fisiologia , Candida albicans/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Leucemia P388/tratamento farmacológico , México , Camundongos , Testes de Sensibilidade Microbiana , Podofilotoxina/isolamento & purificação , Podofilotoxina/farmacologia , Podofilotoxina/toxicidade , RatosRESUMO
Fifteen asthmatic children (mean age = 14.5 years) who required daily theophylline therapy were studied for effect of erythromycin ethyl-succinate on theophylline clearance. After a one week course of EES, there was 25.8 +/- 18.4% reduction in theophylline clearance rate (P less than 0.001), and a concomitant elevation in steady-state serum theophylline concentration of 40.0 +/- 35.3% (P less than 0.01). Three subjects reached serum theophylline concentrations greater than 20 micrograms/ml. Patients receiving therapeutic doses of theophylline are at considerable risk of theophylline toxicity if EES is co-administered.
Assuntos
Asma/tratamento farmacológico , Eritromicina/farmacologia , Teofilina/metabolismo , Adolescente , Eritromicina/metabolismo , Feminino , Humanos , Masculino , Taxa de Depuração Metabólica , Teofilina/sangue , Teofilina/uso terapêuticoRESUMO
Three generic aminophylline products were examined and found to have equivalent bioavailability. Plasma theophylline levels were found to be reproducible in most patients (intraclass r = 0.7). There were some patients who showed wide swings in plasma theophylline levels without signs of toxicity or clinical deterioration.