21 research outputs found
Integrative network analysis identified key genes and pathways in the progression of hepatitis C virus induced hepatocellular carcinoma
Background: Incidence of hepatitis C virus (HCV) induced hepatocellular carcinoma (HCC) has been increasing in the United States and Europe during recent years. Although HCV-associated HCC shares many pathological characteristics with other types of HCC, its molecular mechanisms of progression remain elusive. Methods: To investigate the underlying pathology, we developed a systematic approach to identify deregulated biological networks in HCC by integrating gene expression profiles with high-throughput protein-protein interaction data. We examined five stages including normal (control) liver, cirrhotic liver, dysplasia, early HCC and advanced HCC. Results: Among the five consecutive pathological stages, we identified four networks including precancerous networks (Normal-Cirrhosis and Cirrhosis-Dysplasia) and cancerous networks (Dysplasia-Early HCC, Early-Advanced HCC). We found little overlap between precancerous and cancerous networks, opposite to a substantial overlap within precancerous or cancerous networks. We further found that the hub proteins interacted with HCV proteins, suggesting direct interventions of these networks by the virus. The functional annotation of each network demonstrates a high degree of consistency with current knowledge in HCC. By assembling these functions into a module map, we could depict the stepwise biological functions that are deregulated in HCV-induced hepatocarcinogenesis. Additionally, these networks enable us to identify important genes and pathways by developmental stage, such as LCK signalling pathways in cirrhosis, MMP genes and TIMP genes in dysplastic liver, and CDC2-mediated cell cycle signalling in early and advanced HCC. CDC2 (alternative symbol CDK1), a cell cycle regulatory gene, is particularly interesting due to its topological position in temporally deregulated networks. Conclusions: Our study uncovers a temporal spectrum of functional deregulation and prioritizes key genes and pathways in the progression of HCV induced HCC. These findings present a wealth of information for further investigation
Особенности воспалительных паттернов бронхов и клинико-функциональная характеристика тяжелой неконтролируемой астмы у больных с холодовой гиперреактивностью дыхательных путей
The aim of this study was to investigate airway inflammation patterns and clinical and functional features of severe uncontrolled asthma.Methods. The study involved 25 patients aged 45 to 55 years with severe uncontrolled asthma. Medical history was analyzed. Lung function tests, cytological and cytochemical investigation of induced sputum were performed in all patients. Asthma control was assessed using the Asthma Control Test questionnaire.Results. The patients were divided into groups: with eosinophilic (> 2% of eosinophils; n = 11) or mixed (≥ 2% of eosinophils and ≥ 61% of neutrophils; n = 14) airway inflammation patterns according to induced sputum cytology. Oxidative function of leucocytes according to myeloper oxidase level in the cells and the degree of cytolysis were increased in the mixed inflammation group. More severe symptoms, more frequent asthma exacerbations, a tendency to worse asthma control and lower FEF50 and MEF25–75 were found in the mixed inflammation group. Coldinduced air way hyperresponsiveness was diagnosed in 12 patients of the mixed inflammation group and in 3 patients of the eosinophilic inflammation group. Severity of the disease, lung function abnormalities and coldinduced airway hyperresponsiveness in patients with severe uncontrolled asthma were related to the airway inflammation pattern.Conclusion. The mixed inflammation pattern was associated to more severe asthma course and worse control of the disease.Персистенция воспаления дыхательных путей у больных бронхиальной астмой (БА) способствует развитию тяжелого неконтролируемого течения болезни.Цель. Изучение особенностей воспалительных паттернов и клиникофункциональных параметров тяжелой неконтролируемой БА.Материалы и методы. В холодный период года (ноябрь – март) проведено обследование больных (n = 25) в возрасте от 45 до 55 лет с установленным диагнозом тяжелой неконтролируемой БА при помощи определения реактивности дыхательных путей на холодовой стимул по данным анамнестического тестирования, исследования функции внешнего дыхания по стандартной методике, цитологического и цитохимического исследования индуцированной мокроты (ИМ).Результаты. По данным анализа цитограмм ИМ больные были разделены на 2 группы: 1я (n = 11) – с эозинофильным (> 2 % эозинофилов), 2я (n = 14) – со смешанным (≥ 2 % эозинофилов + ≥ 61 % нейтрофилов) паттернами воспаления. Оксидативная функция лейкоцитов, оцениваемая по уровню миелопероксидазы в клетках, степени деструкции и интенсивности цитолиза, доминировала во 2й группе. У пациентов этой группы выявлены более выраженные симптомы и большее число случаев обострения БА, тенденция к снижению уровня контроля над болезнью по вопроснику Asthma Control Test, более значимое снижение максимальной объемной скорости в момент выдоха 25, 50 и 75 % форсированной жизненной емкости легких соответственно. Холодовая гиперреактивность дыхательных путей (ХГДП) по клинически значимым признакам установлена у больных 2й (n = 12) и 1й (n = 3) групп. Показано, что проявления тяжести течения болезни, нарушения вентиляционной функции легких и частота развития ХГДП у больных тяжелой неконтролируемой БА сопряжены с паттерном воспаления бронхов.Заключение. Смешанный воспалительный паттерн связан с утяжелением течения БА и более сложной проблемой контроля над болезнью