RESUMEN
Asthma is a chronic allergic disease characterized by airway inflammation, airway hyper-responsiveness (AHR), and mucus hypersecretion. T-lymphocytes are involved in the pathogenesis of asthma, mediating airway inflammatory reactions by secreting cytokines. The phosphoinositide 3-kinase (PI3K) and Notch signaling pathways are associated with T cell signaling, proliferation, and differentiation, and are important in the progression of asthma. Thus, compounds that can modulate T cell proliferation and function may be of clinical value. Here, we assessed the effects of tangeretin, a plant-derived flavonoid, in experimental asthma. BALB/c mice at postnatal day (P) 12 were challenged with ovalbumin (OVA). Separate groups of mice (n=18/group) were administered tangeretin at 25 or 50 mg/kg body weight by oral gavage. Dexamethasone was used as a positive control. Tangeretin treatment reduced inflammatory cell infiltration in bronchoalveolar lavage fluid (BALF) and also restored the normal histology of lung tissues. OVA-specific IgE levels in serum and BALF were reduced. AHR, as determined by airway resistance and lung compliance, was normalized. Flow cytometry analyses revealed a reduced Th17 cell population. Tangeretin reduced the levels of Th2 and Th17 cytokines and raised IFN-γ levels. PI3K signaling was inhibited. The expressions of the Notch 1 receptor and its ligands Jagged 1 and 2 were downregulated by tangeretin. Our findings support the possible use of tangeretin for treating allergic asthma.
Asunto(s)
Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Flavonas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Animales , Animales Recién Nacidos , Asma/inmunología , Citocinas/efectos de los fármacos , Citocinas/inmunología , Modelos Animales de Enfermedad , Ratones , Ratones Endogámicos BALB C , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/inmunología , Células TH1/efectos de los fármacos , Células TH1/inmunología , Células Th17/efectos de los fármacos , Células Th17/inmunología , Células Th2/efectos de los fármacos , Células Th2/inmunologíaRESUMEN
Plant lectins are proteins that possess at least one non-catalytic domain, which could reversibly bind to specific monosaccharides or oligosaccharides. The important roles played by plant lectins in immune regulation, signaling pathways, and plant defense could be attributed to their specific binding activities with carbohydrates. In this study, a Pinellia integrifolia lectin gene, designated pia, was cloned using rapid amplification of cDNA ends. The open reading frame (ORF) of pia was constructed into the pET-28a vector, and a 33-kDa recombinant protein was induced in Escherichia coli BL21. The hemagglutination and anticancer properties of the purified recombinant protein were assayed in vitro. The results indicated that the full-length cDNA of pia was 1210 bp long, containing an 807-bp ORF encoding a 268-amino acid peptide. The putative P. integrifolia lectin protein (PIA) contained three mannose-binding sites. The agglutinating activity exhibited by PIA was inhibited by D-mannose. PIA was also shown to exert an anti-proliferative activity against nasopharyngeal carcinoma, human cervical carcinoma, and human breast cancer cell lines in vitro. These results could be applied to determine the function of PIA in the future.
Asunto(s)
Pinellia/genética , Lectinas de Plantas/genética , Secuencia de Aminoácidos , Antineoplásicos Fitogénicos/biosíntesis , Antineoplásicos Fitogénicos/farmacología , Proliferación Celular/efectos de los fármacos , Clonación Molecular , ADN Complementario/genética , Ensayos de Selección de Medicamentos Antitumorales , Escherichia coli , Células HeLa , Humanos , Lectinas de Plantas/biosíntesis , Lectinas de Plantas/farmacología , ARN de Planta/genéticaRESUMEN
The aim of this study was to elucidate the role of RUNX3 promoter methylation in the pathogenesis of hepatocellular carcinoma (HCC) among Asians. For this purpose, we performed a comprehensive search of Chinese and English language scientific literature databases using stringent selection criteria; ultimately, we identified relevant studies that specifically assessed the correlation between RUNX3 promoter methylation and HCC. All data was retrieved and analyzed by two independent investigators using the STATA software (version 12.0). Initially, 132 studies (103 in Chinese, 29 in English) were retrieved; 122 were eliminated through a stepwise filtering process. Finally, 10 studies conducted in Asian populations (5 Chinese, 4 Japanese, 1 Korean) fulfilled all the inclusion criteria of our meta-analysis. The studies included 588 HCC patients (641 cancer tissues; 593 adjacent normal tissues) and 184 healthy controls. We observed that RUNX3 promoter methylation was significantly higher in cancer tissues than in adjacent normal tissues (RR = 6.35, 95%CI = 3.62-11.14, P < 0.001) and normal control tissues (RR = 17.31, 95%CI = 7.08-42.34, P < 0.001). RUNX3 promoter methylation status did not differ significantly between patients with different TNM stages (RR = 0.88, 95%CI = 0.70-1.10, P = 0.269) and histological grades (RR = 0.86, 95%CI = 0.65-1.14, P = 0.304), suggesting that RUNX3 promoter methylation is linked to the origin of HCC but not to its progression from non-metastatic to metastatic stages. This in turn indicated that RUNX3 could be an early diagnostic marker distinguishing benign from malignant hepatocellular carcinoma.
Asunto(s)
Carcinoma Hepatocelular/genética , Subunidad alfa 3 del Factor de Unión al Sitio Principal/genética , Metilación de ADN , Neoplasias Hepáticas/genética , Regiones Promotoras Genéticas , Adulto , Anciano , Anciano de 80 o más Años , Pueblo Asiatico , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Metástasis de la NeoplasiaRESUMEN
The central task of this study was to mine the gene-to-medium relationship. Adequate knowledge of this relationship could potentially improve the accuracy of differentially expressed gene mining. One of the approaches to differentially expressed gene mining uses conventional clustering algorithms to identify the gene-to-medium relationship. Compared to conventional clustering algorithms, self-organization maps (SOMs) identify the nonlinear aspects of the gene-to-medium relationships by mapping the input space into another higher dimensional feature space. However, SOMs are not suitable for huge datasets consisting of millions of samples. Therefore, a new computational model, the Function Clustering Self-Organization Maps (FCSOMs), was developed. FCSOMs take advantage of the theory of granular computing as well as advanced statistical learning methodologies, and are built specifically for each information granule (a function cluster of genes), which are intelligently partitioned by the clustering algorithm provided by the DAVID_6.7 software platform. However, only the gene functions, and not their expression values, are considered in the fuzzy clustering algorithm of DAVID. Compared to the clustering algorithm of DAVID, these experimental results show a marked improvement in the accuracy of classification with the application of FCSOMs. FCSOMs can handle huge datasets and their complex classification problems, as each FCSOM (modeled for each function cluster) can be easily parallelized.
Asunto(s)
Algoritmos , Medios de Cultivo/farmacología , Minería de Datos , Drosophila melanogaster/genética , Perfilación de la Expresión Génica , Genes de Insecto , Animales , Análisis por Conglomerados , Etanol , Modelos Genéticos , Estándares de ReferenciaRESUMEN
This study aimed to investigate the correlation between the expression of Ki67 and FasL and prognosis of cervical carcinoma and to explore the biological processes and signal pathways related to cervical carcinoma. Cervical carcinoma tissue specimens from 200 patients and normal tissue specimens adjacent to lesions from 30 cases were collected in this study. Ki67 and FasL proteins in these specimens were detected by immunohistochemical methods. A series of statistical methods were carried out to investigate the correlation between the expression of Ki67 and FasL and prognosis of cervical carcinoma. The expression of Ki67 and FasL in cervical carcinoma tissues was significantly higher than that in normal cervical tissue. The positive rate of Ki67 and FasL increased with the increase in the degree of cervical lesions. There was a positive correlation between the expression of Ki67 and FasL in cervical lesions. The expression of Ki67 and FasL affected the five-year survival rate of postoperative patients. Ki67 and FasL were independent factors for the prognosis of patients with cervical cancer. The expression of Ki67 and FasL is closely related to the occurrence and development of cervical carcinoma. There is a positive correlation between Ki67 and FasL, and they may be biomarkers of cervical cancer.
Asunto(s)
Proteína Ligando Fas/metabolismo , Antígeno Ki-67/metabolismo , Neoplasias del Cuello Uterino/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Proteína Ligando Fas/genética , Femenino , Expresión Génica , Humanos , Estimación de Kaplan-Meier , Antígeno Ki-67/genética , Metástasis Linfática , Persona de Mediana Edad , Pronóstico , Neoplasias del Cuello Uterino/mortalidad , Neoplasias del Cuello Uterino/patologíaRESUMEN
The purpose of this study was to observe the hemodynamic changes of unexplained syncope patients in the head-up tilt test and their correlations with age and gender. Eighty-six patients with unexplained syncope were administered the basic head-up test and nitroglycerin provocation test with continuous monitoring and recording of electrocardiogram and blood pressure changes. Basic characteristics of the patients and their hemodynamic responses throughout the tests were analyzed. All 86 patients tolerated and completed the head-up test. Forty-nine (56.98%) of the patients displayed a positive reaction, 37 (43.02%) patients displayed a negative reaction. Patients were divided into groups as follows: Group A, age ≤ 35 years; Group B, age 36-45 years; and Group C, age ≥ 46 years. Older patients were more prone to chronotropic incompetence, and younger patients were more prone to an excessive increase in heart rate. Older age correlated with the occurrence of autonomic nerve reaction disorder and mixed vasovagal syncope, whereas younger age was related to the occurrence of vasodepressor type vasovagal syncope (P < 0.01). Gender did not significantly correlate with negative or positive head-up test results (P = 0.184). During the head-up test, younger patients mainly manifested an excessive heart rate increase, whereas older patients did not have significant heart rate changes. Analyzing the hemodynamic changes in the head-up test and studying the relationships between age, gender, and hemodynamic responses are crucial to determine etiologies of syncope and select appropriate treatment.
Asunto(s)
Hemodinámica/fisiología , Síncope/fisiopatología , Pruebas de Mesa Inclinada , Adulto , Factores de Edad , Anciano , Femenino , Frecuencia Cardíaca , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Black disease is an acute disease of sheep and cattle. The pathogen is the obligate anaerobe, Clostridium novyi. Due to difficulties of anaerobic culturing in the country or disaster sites, a simple, rapid, and sensitive method is required. In this study, an electrochemical method, the cyclic voltammetry method, basing on loop-mediated isothermal amplification (LAMP), electrochemical ion bonding (positive dye, methylene blue), was introduced. DNA extracted from C. novyi specimens was amplified through the LAMP reaction. Then the products combined were with methylene blue, which lead to a reduction in the oxidation peak current (ipA) and the reduction peak current (ipC) of the cyclic voltammetry. The changes of ipA/ipC were real-time measured by special designed electrode, so the DNA was quantitatively detected. The results displayed that this electrochemical detection of C. novyi could be completed in 1-2 h with the lowest bacterial concentration of 10(2) colony forming units/mL, and high accuracy (96.5%), sensitivity (96%), and specificity (97%) compared to polymerase chain reation. The cyclic voltammetry method was a simple and fast method, with high sensitivity and high specificity, and has great potential to be a usable molecular tool for fast diagnosis of Black disease.
Asunto(s)
Enfermedades de los Animales/genética , Clostridium/genética , ADN Bacteriano/genética , Oveja Doméstica/microbiología , Enfermedades de los Animales/microbiología , Animales , Bovinos , Clostridium/patogenicidad , Técnicas de Amplificación de Ácido Nucleico/métodos , Reacción en Cadena de la Polimerasa/métodosRESUMEN
We used a newly developed electrochemical method, real-time resistance measurement, based on loop-mediated isothermal amplification (LAMP), with real-time resistance monitoring and derivative analysis. DNA extracted from specimens was amplified through LAMP reaction. The 2 products of LAMP, DNA and pyrophosphate, both are negative ions; they combine with positive dye (crystal violet) and positive ions (Mg(2+)), which leads to an increase in the resistivity of the reaction liquid. The changes of resistivity were measured in real-time with a specially designed resistance electrode, to detect Clostridium difficile DNA. We found that electrochemical detection of C. difficile could be completed in 0.5-1 h, with a detection limit of 10(2) CFU/mL, with high accuracy (95.0%), sensitivity (91.1%), and specificity (97.3%) compared to PCR methods. C. difficile is commonly associated with antibiotic-induced diarrhea. Due to the difficulty in performing anaerobic culture and cytotoxicity neutralization assays, a simple, rapid, sensitive, and accurate method is preferred. We conclude that real-time resistance measurement is a rapid, sensitive, and stable method for the diagnosis of C. difficile infection that could be applied to gene chips and pocket instruments.