RESUMEN
The high mortality rate from ovarian cancer is due to the asymptomatic nature of the course of the disease, which leads to the diagnosis of ovarian cancer in later stages. The sodium-dependent phosphate transporter NaPi2b encoded by SLC34A2 gene is expressed in 80-90% of epithelial ovarian cancers and used as a target for therapeutic antibodies XMT-1536, and XMT-1592, which are derived from MX35 antibodies and used in clinical trials for the treatment of ovarian and lung cancers. In this work, we aimed to evaluate NaPi2b as a molecular marker for diagnostics and predicting the course and outcome of ovarian cancer disease. Quantitative analysis of SLC34A2 gene expression in ovarian tumor tissue was performed at the level of transcription and translation using real-time PCR, droplet digital PCR and Western blot analysis respectively. Statistical analysis was performed taking into account various clinicopathological characteristics of the ovarian cancer patients, including the stage of the disease, the tumor grade, the applying of neoadjuvant chemotherapy and the presence of ascites. In this work, we demonstrated that the expression of the human NaPi2b (hNaPi2b) transporter is downregulated in the tumors of patients receiving neoadjuvant therapy and during the development of disease. The data suggest that the level of expression of the SLC34A2 gene can serve as a potential marker for the monitoring and predicting responses to neoadjuvant and targeted therapy in patients with ovarian cancer.
RESUMEN
In the experiments on the isolated perfused rat heart the effects of liposomes, containing different concentrations (0.25 and 0.1 mg/mL) of emoxipine, on coronary flow restoration after total normothermic ischemia and reperfusion were studied. The coronary flow, levels of nitrates and nitrites in the outflowing perfusate from heart and level of free radical processes were assessed, The obtained results showed that 0.1 mg/mL liposomal emoxipine provide with stronger increase coronary flow during reperfusion mostly due to the increase concentration of endothelial nitric oxide compare with treatments at 0.25 mg/mL.
Asunto(s)
Antiarrítmicos/farmacología , Circulación Coronaria/efectos de los fármacos , Corazón/efectos de los fármacos , Daño por Reperfusión Miocárdica/prevención & control , Picolinas/farmacología , Animales , Velocidad del Flujo Sanguíneo/efectos de los fármacos , Corazón/fisiopatología , Técnicas In Vitro , Liposomas/química , Masculino , Malondialdehído/metabolismo , Daño por Reperfusión Miocárdica/metabolismo , Daño por Reperfusión Miocárdica/fisiopatología , Nitratos/metabolismo , Óxido Nítrico/metabolismo , Nitritos/metabolismo , Ratas , Ratas WistarRESUMEN
In this report we demonstrate that depletion of the major phospholipid phosphatidylethanolamine, a single non-bilayer forming phospholipid of Escherichia coli, significantly reduces the secretion efficiency of alkaline phosphatase in vivo. Secretion, however, is correlated with the content in membranes of cardiolipin, which in combination with selected divalent cations has a strong tendency to adopt a non-bilayer state indicating the possible involvement of lipid polymorphism in efficient protein secretion. Depletion of this zwitterionic phospholipid also inhibits expression of the protein controlled by the endogenous P(PHO) promoter but not the P(BAD) promoter, which is suggested to be due to the effect of unbalanced phospholipid composition on the orthophosphate signal transduction system (Pho regulon) through an effect on its membrane bound sensor.
Asunto(s)
Fosfatasa Alcalina/metabolismo , Escherichia coli/metabolismo , Fosfatidiletanolaminas/metabolismo , Fosfatasa Alcalina/genética , Secuencia de Bases , Transporte Biológico Activo , Cardiolipinas/metabolismo , Membrana Celular/metabolismo , Cartilla de ADN/genética , Escherichia coli/genética , Regulación Enzimológica de la Expresión Génica , Lípidos de la Membrana/metabolismo , Regiones Promotoras Genéticas , Transcripción GenéticaAsunto(s)
Residuos Industriales , Contaminación Química del Agua , Higiene , Residuos Industriales/análisis , Residuos Industriales/estadística & datos numéricos , Federación de Rusia , Contaminación Química del Agua/análisis , Contaminación Química del Agua/estadística & datos numéricos , Purificación del Agua/normas , Purificación del Agua/estadística & datos numéricos , Abastecimiento de Agua/análisis , Abastecimiento de Agua/normas , Abastecimiento de Agua/estadística & datos numéricosRESUMEN
The authors analyze the hygienic problems related to utilizing the recirculation water supply for washing freight cars. Hygienic standards for water quality in open systems of technical water supply to railway enterprises, first developed in 1994, are presented. Measures aimed at prevention of discharge of the remainder of freight into waste water are proposed, including the collection and realization thereof.
Asunto(s)
Higiene , Vías Férreas , Contaminación del Agua/prevención & control , Abastecimiento de Agua , Federación de RusiaAsunto(s)
Higiene , Vías Férreas , Abastecimiento de Agua , Microbiología del Agua , Contaminación del AguaRESUMEN
Hygienic criteria of treated sewage quality intended for the use in industry, municipal and agrarian enterprises were suggested.
Asunto(s)
Exposición a Riesgos Ambientales , Filtración , Aguas del Alcantarillado , Microbiología del Agua , Abastecimiento de Agua/análisis , Abastecimiento de Agua/normas , Animales , Enfermedades Gastrointestinales/epidemiología , Humanos , Higiene , Kazajstán/epidemiología , Morbilidad , Ratas , Salud UrbanaRESUMEN
Maximum allowable concentrations of 9 half-products of drug synthesis were substantiated. Threshold concentrations influencing organoleptic properties of substances, selfpurification of water and toxicological effects were determined.
Asunto(s)
Industria Farmacéutica , Contaminantes Químicos del Agua/normas , Animales , Dosificación Letal Mediana , Concentración Máxima Admisible , RatasRESUMEN
Stereochemical analysis of signal peptide interaction with E. coli membrane phospholipids revealed the structural complementarity of N-terminus of signal peptide alpha-helix and acid phospholipids. The formation of their complex leads to neutralization of charges and decrease in hydrophilicity of both components, and promotes insertion of peptide and phospholipid into the membrane, not separately but as a complex. Interaction of acid phospholipids with the E. coli alkaline phosphatase (AP) signal peptide was thoroughly analyzed, and it was shown that in this case a complex of signal peptide alpha-helix with phosphatidylglycerol is inserted into the membrane with the lowest energy expense. On the basis of the results of stereochemical analysis and the available experimental data, a molecular mechanism of protein translocation initiation across the membrane has been proposed, in which the key events are the formation of the complex "signal peptide alpha-helix-acid phospholipid", the coupled insertion of hydrophobic peptide-lipid complex into a nonpolar membrane interior and translocation across the membranes.
Asunto(s)
Iniciación de la Cadena Peptídica Traduccional , Fosfolípidos/metabolismo , Señales de Clasificación de Proteína/metabolismo , Fosfatasa Alcalina/metabolismo , Secuencia de Aminoácidos , Transporte Biológico , Membrana Celular/metabolismo , Electroquímica , Escherichia coli/metabolismo , Datos de Secuencia Molecular , Conformación Proteica , Señales de Clasificación de Proteína/químicaRESUMEN
Recent observations confirm the participation of acid phospholipids in protein translocation. The hypothesis proposed coupled protein translocation with transmembrane movement of acid phospholipids, their metabolism as a precursor of cell envelope components and recycling. These factors ensure the unidirectional vector value of the secretion, restoration of the membrane site competent for protein translocation and its self-organization.
Asunto(s)
Proteínas Bacterianas/metabolismo , Membrana Celular/metabolismo , Lípidos de la Membrana/fisiología , Fosfolípidos/fisiología , Bacterias/metabolismo , Transporte Biológico Activo , Potenciales de la Membrana , Procesamiento Proteico-PostraduccionalAsunto(s)
Proteínas Bacterianas/metabolismo , Metabolismo Energético , Escherichia coli/metabolismo , Proteínas de la Membrana/metabolismo , Fosfatasa Alcalina/biosíntesis , Fosfatasa Alcalina/metabolismo , Transporte Biológico , Escherichia coli/enzimología , Bacterias Gramnegativas/enzimología , Bacterias Gramnegativas/metabolismo , Potenciales de la MembranaRESUMEN
The study of ozone inactivation of enteroviruses in sewage showed the presence in sewage of suspensions of organic origin and bacterial flora to influence the rate of inactivation. The inactivation rate of poliomyelitis virus in sewage free from organic suspension and bacterial flora was significantly higher than that in sewage containing such suspension and bacterial flora. The inactivation rate of enteroviruses was found not to depend upon the protein and salt composition and pH of sewage or strain appurtenance of viruses. The inactivation rate of enteroviruses directly depended upon the dose of ozone and time of contact with it. Differences in the resistance of different types of poliomyelitis virus, ECHO and Coxsackie viruses to the effect of ozone are likely exist. These differences are manifested within the range of relatively small doses of ozone. E. coli is more resistant to ozone than entero-viruses. The results of laboratory studies were used to choose the regimen of sanitation of urban sewage to be used in technological cycles of industrial enterprises.
Asunto(s)
Enterovirus/efectos de los fármacos , Ozono/farmacología , Aguas del Alcantarillado , Microbiología del Agua , Relación Dosis-Respuesta a Droga , Escherichia coli/efectos de los fármacos , Concentración de Iones de Hidrógeno , Poliovirus/efectos de los fármacos , Factores de TiempoRESUMEN
The synthesis of alkaline phosphatase, an enzyme secreted by E. coli, is decreased in the cells pretreated with the lipotropic antibiotic polymixin prior to derepression. The decrease of the enzyme synthesis in the cell is correlated with the changes in the intracellular and intramembrane ratios of acid phospholipids, presumably at the level of the cytoplasmic membrane. The interaction between alkaline phosphatase and artificial lipid membranes has been shown to be a function of pH and ionic strength and is increased in the liposomes rich in acid phospholipids and decreased in the polymixin-treated liposomes.