Репозиторий Университета

© 2020 Cellulose nanocrystals (CNC), also known as nanowhiskers, have recently gained much attention due to their biodegradable nature, advantageous chemical and mechanical properties, economic value and renewability thus making them attractive for a wide range of applications. However, before these materials can be considered for potential uses, investigation of their toxicity is prudent. Although CNC exposures are associated with pulmonary inflammation and damage as well as oxidative stress responses and genotoxicity in vivo, studies evaluating cell transformation or tumorigenic potential of CNC's were not previously conducted. In this study, we aimed to assess the neoplastic-like transformation potential of two forms of CNC derived from wood (powder and gel) in human pulmonary epithelial cells (BEAS-2B) in comparison to fibrous tremolite (TF), known to induce lung cancer. Short-term exposure to CNC or TF induced intracellular ROS increase and DNA damage while long-term exposure resulted in neoplastic-like transformation demonstrated by increased cell proliferation, anchorage-independent growth, migration and invasion. The increased proliferative responses were also in-agreement with observed levels of pro-inflammatory cytokines. Based on the hierarchical clustering analysis (HCA) of the inflammatory cytokine responses, CNC powder was segregated from the control and CNC-gel samples. This suggests that CNC may have the ability to influence neoplastic-like transformation events in pulmonary epithelial cells and that such effects are dependent on the type/form of CNC. Further studies focusing on determining and understanding molecular mechanisms underlying potential CNC cell transformation events and their likelihood to induce tumorigenic effects in vivo are highly warranted.

© 2020 Cellulose nanocrystals (CNC), also known as nanowhiskers, have recently gained much attention due to their biodegradable nature, advantageous chemical and mechanical properties, economic value and renewability thus making them attractive for a wide range of applications. However, before these materials can be considered for potential uses, investigation of their toxicity is prudent. Although CNC exposures are associated with pulmonary inflammation and damage as well as oxidative stress responses and genotoxicity in vivo, studies evaluating cell transformation or tumorigenic potential of CNC's were not previously conducted. In this study, we aimed to assess the neoplastic-like transformation potential of two forms of CNC derived from wood (powder and gel) in human pulmonary epithelial cells (BEAS-2B) in comparison to fibrous tremolite (TF), known to induce lung cancer. Short-term exposure to CNC or TF induced intracellular ROS increase and DNA damage while long-term exposure resulted in neoplastic-like transformation demonstrated by increased cell proliferation, anchorage-independent growth, migration and invasion. The increased proliferative responses were also in-agreement with observed levels of pro-inflammatory cytokines. Based on the hierarchical clustering analysis (HCA) of the inflammatory cytokine responses, CNC powder was segregated from the control and CNC-gel samples. This suggests that CNC may have the ability to influence neoplastic-like transformation events in pulmonary epithelial cells and that such effects are dependent on the type/form of CNC. Further studies focusing on determining and understanding molecular mechanisms underlying potential CNC cell transformation events and their likelihood to induce tumorigenic effects in vivo are highly warranted.

© 2020 Elsevier Inc. Chronic obstructive pulmonary disease (COPD) is a common term for alveolar septal wall destruction resulting in emphysema, and chronic bronchitis accompanied by conductive airway remodelling. In general, this disease is characterized by a disbalance of proteolytic/anti-proteolytic activity, augmented inflammatory response, increased oxidative/nitrosative stress, rise in number of apoptotic cells and decreased proliferation. As the first responder to the various environmental stimuli, epithelium occupies an important position in different lung pathologies, including COPD. Epithelium sequentially transitions from the upper airways in the direction of the gas exchange surface in the alveoli, and every cell type possesses a distinct role in the maintenance of the homeostasis. Basically, a thick ciliated structure of the airway epithelium has a major function in mucus secretion, whereas, alveolar epithelium which forms a thin barrier covered by surfactant has a function in gas exchange. Following this line, we will try to reveal whether or not the chronic bronchitis and emphysema, being two pathological phenotypes in COPD, could originate in two different types of epithelium. In addition, this review focuses on the role of lung epithelium in COPD pathology, and summarises underlying mechanisms and potential therapeutics.

Recently, organ-on-a-chip models, which are microfluidic devices that mimic the cellular architecture and physiological environment of an organ, have been developed and extensively investigated. The chips can be tailored to accommodate the disease conditions pertaining to many organs; and in the case of this review, the lung. Lung-on-a-chip models result in a more accurate reflection compared to conventional in vitro models. Pharmaceutical drug testing methods traditionally use animal models in order to evaluate pharmacological and toxicological responses to a new agent. However, these responses do not directly reflect human physiological responses. In this review, current and future applications of the lung-on-a-chip in the respiratory system will be discussed. Furthermore, the limitations of current conventional in vitro models used for respiratory disease modeling and drug development will be addressed. Highlights of additional translational aspects of the lung-on-a-chip will be discussed in order to demonstrate the importance of this subject for medical research.

© 2019, Pediatria Ltd. All rights reserved. Brain–lung–thyroid syndrome (BLTS) is a rare genetic disease associated with mutations in the NKX2.1 gene encoding thyroid transcription factor 1. The most common manifestations of this syndrome are benign hereditary chorea, hypothyroidism and respiratory distress syndrome, however, mutations in the NKX2.1 gene can also cause other pathologies of nervous, respiratory systems and thyroid gland. The article describes 4 patients with mutations in the NKX2.1 gene observed by authors. Based on the analysis of the observations of 168 patients with BLTS presented in the world literature from 1998 to 2019, current information on the genetics, pathogenesis, clinical X-ray manifestations, outcomes and treatment of the syndrome are summarized.

© 2018 Medknow Publications. All rights reserved. 2-Amino-4H-chromene derivatives possess anticancer property proved on different in vivo and in vitro models of malignancies such breast, nasopharyngeal, bladder, ovary carcinomas, astrocytoma, and osteosarcoma. We assumed it might be effective to apply one of the derivatives as promising approach to lung carcinoma treatment.To evaluate how novel 4-Aryl substituted 2-Amino-4H-chromene derivative AX-554 impacts tumor growth and progression, as well as possible mechanisms for anticancer effect development on in vivo patient-derived heterotopic xenograft model of lung carcinoma in mice. This was an experimental in vivo study. 40 nu/nu BALB/c female mice were randomly allocated into four equal groups: Intact, control, reference, and main group. Animals of three latter groups were ingrafted with human-derived lung adenocarcinoma. Antitumor and antimetastatic action of AX-554 novel aminochromone derivative as a substance were studied. Mice survival was registered. Kinase of anaplastic lymphoma (ALK), tubulin Beta-3 (TUBB3), and c-mesenchymal-epithelial transition (MET) concentrations in the prime tumor nodes homogenates were determined by quantitative enzyme-linked immunosorbent assay. Dannet's parametric criterion and the nonparametric exact Fisher test were used. The normality of the distribution was determined using ANOVA. The survival curve was analyzed using Gehan's criterion with the Yates's correction. Aminochromone derivative possesses an inhibitory effect on human lung adenocarcinoma transplanted into nu/nu BALB/c female mice, as well as significant antimetastatic activity. About 50 mg/kg/day AX-554 intragastric course increases animals' life expectancy of more than 3.3 times when compared with the control and induces remission in 60% of cases. The anticancer effect of the derivative is due to anti-ALK-mediated activation of tumor cells apoptosis and suppression TUBB3-dependent cell proliferation.

© 2018 Kapeleris, Kulasinghe, Warkiani, Vela, Kenny, O'Byrne and Punyadeera. Lung cancer affects over 1. 8 million people worldwide and is the leading cause of cancer related mortality globally. Currently, diagnosis of lung cancer involves a combination of imaging and invasive biopsies to confirm histopathology. Non-invasive diagnostic techniques under investigation include "liquid biopsies" through a simple blood draw to develop predictive and prognostic biomarkers. A better understanding of circulating tumor cell (CTC) dissemination mechanisms offers promising potential for the development of techniques to assist in the diagnosis of lung cancer. Enumeration and characterization of CTCs has the potential to act as a prognostic biomarker and to identify novel drug targets for a precision medicine approach to lung cancer care. This review will focus on the current status of CTCs and their potential diagnostic and prognostic utility in this setting.

© 2018, Pediatria Ltd. All rights reserved. Materials and methods: the study assessed safety and clinical efficacy of combined use of vaccine preparations against S. pneumoniae and H. influenzae type b, leading pathogens in bronchopulmonary diseases exacerbations development, in previously unvaccinated 38 children aged 2–17 years with chronic bronchopulmonary diseases: 19 with malformations of the bronchi and lungs (MBL); 10 with malformations of bronchi and lungs in combination with bronchial asthma (MBL+BA); 9 with bronchial asthma (BA). The control group consisted of 19 unvaccinated children of the same age with a similar pathology. Combined vaccination against these infections, as well as their separate administration, did not cause adverse effects. Results: a year after the introduction of Pneumo-23 vaccine, the incidence of acute respiratory infections (ARI) and exacerbations of the main disease decreased by 2,3 times; Act-HIB by 2,3 and 2,1 times respectively; by 1,7 and 1,5 times respectively with simultaneous administration of these preparations. In children with BA the duration of one exacerbation decreased by 3,4 times, the average duration of temperature reaction by 1,9 times and the systemic antibiotic therapy of one exacerbation episode by 2,4 times. In the group of children with MBL+BA these indicators decreased by 2,1, 1,8 and 1,6 times, respectively, and in patients with MBL by 1,6, 1,5 and 1,4 times, respectively. Conclusion: vaccination against pneumococcal and hemophilic type b infections using one or both vaccines in patients with MBL and with MBL+BA is safe and positively affects the clinical course of the main disease.

Chronic obstructive pulmonary disease (COPD) is one of the main causes of disease and death incidences worldwide. Different organs and systems are involved in COPD activating tissue hypoxia. It affects especially tissue functioning with the high level of intensity of metabolic processes, and the nervous system suffers first. Neuroimaging studies show white and grey matter damage and cerebral atrophy, which may clinically manifest themselves in different neurological symptoms depended on vascular system lesions, and cognitive and affective impairments. Despite of its potential importance, encephalopathy in COPD remains a little-studied concomitant pathology. Application of cytoprotective drugs is pathogenetically justified in this case and must be included in COPD complex therapy. In particular, the inclusion of mexicor in the treatment of patients with chronic pulmonary heart increases the efficacy of treatment of the main and associated diseases (chronic cerebral ischemia, cardiac insufficiency and arrhythmia).

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. In this article we present a clinical case of a quick recovery and restoration of pulmonary function after withdrawal of amiodarone in a patient with drug-associated acute lung injury induced by intake of amiodarone for two months.

© 2018 Medical Education. All rights reserved. Clinical signs and course of pulmonary disease of Fedor M. Dostoevskiy (1821 - 1881) has been analyzed in the article on the basis of memoirs of contemporaries and physicians who followed the writer up to the end of his life. Diagnostic hypotheses of the disease and the cause of death have been discussed.

© 2018 Copyright O. Zolnikova et al. We have reviewed the currently published results on a role of the gut microflora in a prevention of acute respiratory infections. The main biological properties of probiotic bacteria are presented in a context of their modulating activity on an inflammatory immune response. Available data on the reduction of a possible risk, duration, and severity of respiratory infection symptoms during a probiotic medication intake were analyzed. Potential antiviral probiotic mechanisms have been reviewed and discussed.

© 2018 Medical Education. All Rights Reserved. Chest computed tomography (CT) helps better understanding clinical and pathological features of respiratory diseases. However, interpretation of CT images is difficult without information on clinical course of the disease in the given patient. Therefore, the definite diagnosis could be reached through cooperation of a clinician and a radiologist. This publication presents a lecture aimed at improving a physician's knowledge on interpretation of lung computed tomography (CT) patterns including imaging, structure and extension of abnormal signs. This information is believed to help the clinician to diagnose and differentiate pulmonary diseases based both on CT syndromes and clinical signs. A particular attention is paid on lung tissue attenuation pattern as the most common chest CT abnormality that includes five key entities, such as ground glass opacity, mosaic attenuation, consolidation, atelectasis, and soft-tissue mass.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. Purpose: to elucidate predictors of development of chronic thromboembolic pulmonary hypertension (CTEPH) after acute pulmonary artery thromboembolism (PTE). Material and methods. We included in this study 210 patients hospitalized with diagnosis of submassive and massive PTE from 2013 to 2017. In 1 to 3 years after initial hospitalization these patients were invited for control examination. According to results of this examination patients were divided into two groups: with (group 1, n=45) and without (group 2, n=165) signs of CTEPH. Severity of pulmonary artery vascular bed involvement was assessed by multislice computed tomography (MSCT) angiography and lung scintigraphy. For detection of thrombosis in the inferior vena cava system we used ultrasound angioscanning. Examination also included echocardiography. Results. In the process of mathematical analysis, the following risk factors for the development of CTEPH embolism were determined: duration of thrombotic history (group 1 - 13.70±2.05 days, group 2- 16.16±1.13 days, p=0.015), localization of venous thrombosis in the lower extremities (the most favorable - shin veins, popliteal, and common femoral veins, unfavorable - superficial femoral vein). The choice of the drug for thrombolytic and anticoagulant therapy: streptokinase and urokinase were significantly more effective than alteplase, rivaroxaban was superior to the combination of unfractionated or low molecular weight heparins with warfarin. Also, risk factors for the development of CTEPH were the initial degree of pulmonary hypertension and tricuspid insufficiency, as well as the positive dynamics of these indicators at the background of thrombolytic or anticoagulant therapy. Of concomitant diseases, significant risk factors for development of CTEPH were grade 3 hypertensive disease, diabetes mellitus, postinfarction cardiosclerosis. On the other hand, age, gender, degree of severity at the time of admission, presence of infarction pneumonia, surgical prevention of recurrent pulmonary embolism, number of pregnancies and deliveries, history of trauma and malignancies, cardiac arrhythmias produced no significant impact on the development of CTEPH.

© 2018 Tomsk National Research Medical Center of the Russian Academy of Sciences. All Rights Reserved. The differential diagnosis of pulmonary diseases is extremely difficult and requires high qualifications of the radiologist and clinician. The differential diagnosis is used to distinguish different lung diseases: nonspecific inflammatory lung diseases (empyema, abscess, pneumonia), tuberculosis, sarcoidosis, benign tumors, lung cancer, lymphogranulomatosis, metastatic changes, and inflammatory changes in lung tissue. We present a clinical case, in which the differential diagnosis between tumor and inflammatory changes in lung tissue allowed the choice of optimal treatment tactics.

© 2018, Media Sphera Publishing Group. All rights reserved. The review of the literature deals with the participation of Clara cells now called club cells (CCs) of the epithelium in the respiratory and terminal bronchioles in the pathogenesis and morphogenesis of chronic inflammatory diseases, precancer, and cancer of the lung, which develop in the respiratory segments. The review summarizes data on the histophysiology of CCs and their participation in the pathogenesis and morphogenesis of chronic interstitial lung diseases, pneumoconiosis, chronic obstructive diseases, adenomatosis, and adenocarcinoma of the lung. In this area, there is a bronchioloalveolar junction area (BAJA), one of the most important stem cell niches. CCs are located in the BAJA; they are progenitor tissue stem cells and play an important role in the regeneration of the epithelium of the respiratory bronchioles and alveoli. Pathology of CCs in the BAJA leads to the maintenance of chronic inflammation, to the destruction of the lung elastic frame, and to impaired epithelial regeneration, interstitial fibrosis, and adenomatosis. In this case, decompensated inflammation, pathological regeneration, and fibrosis develop, which, along with the action of carcinogenic agents, can contribute to the accumulation of mutations and epigenetic rearrangements in the CCs, which subsequently results in atypical adenomatous hyperplasia and adenocarcinoma of the lung.

© 2018 Media Sphera Publishing Group. All rights reserved. The results of a clinical study showing the importance of surfactant proteins A and D in assessing the activity and progression of idiopathic pulmonary fibrosis and chronic lung sarcoidosis are presented. Aim. To study the clinical significance of SP-A, SP-D in assessing the activity of idiopathic pulmonary fibrosis and sarcoidosis. We examined 81 patients with morphologically confirmed diagnoses of idiopathic pulmonary fibrosis (ILF) and sarcoidosis, a control group of 20 healthy individuals. The MSCT of the thoracic organs of the chest was performed, the diffusivity of the lungs was examined, oxygen saturation was determined. In the serum, the surfactant proteins SP-A and SP-D were determined by the enzyme-linked immunosorbent assay. Results. A significant increase in SP-A and SP-D (p<0.05) was observed in patients compared with patients in the control group, a direct correlation was found with signs of activity: SP-A with alveolitis (p<0.05), SP- D with progressive fibrosis (p<0.05), inverse correlation of surfactant proteins with respiratory function indices (p<0.05). Conclusion. Serological parameters of SP-A and SP-D reflect the activity of alveolitis and the progression of pulmonary fibrosis in patients with ILF and sarcoidosis.

© 2018 Medical Education. All rights reserved.  Long-acting bronchodilators (long-acting β 2 -agonists (LABA), long-acting anticholinergics (LAMA) and their combinations) are the basic drugs for treatment of stable chronic obstructive pulmonary disease (COPD). Indacaterol/glycopyrronium (IND/GLY) is the first fixed LABA/LAMA combination acquired significant evidence of its efficacy for improvement lung function, symptoms, and quality of life, and decrease in the rate of acute exacerbations of COPD. The aim of this review was to reassess clinical efficacy of IND/GLY in treatment of COPD with regard to recent data and to outline the further role of this combination in therapy of COPD.

© 2018 Media Sphera Publishing Group. All rights reserved. The primary autoimmune liver diseases conventionally include primary biliary cholangitis, primary sclerosing cholangitis and autoimmune hepatitis. Despite of primary autoimmune affection of different parts of the hepatobiliary system, in the recent decades, a lot of data has emerged indicating the presence of extrahepatic manifestations of these diseases, in particular, lung lesions, such as nodular and interstitial changes with possible progression and development of fibrosis and respiratory failure. In case of lungs disease, both pulmonary parenchyma and lung vessels, pleura, and intrathoracic lymph nodes can be involved. The most sensitive and specific procedure to assess the extent of the lung lesions and their evolution is high-resolution computed tomography. Due to the possibility of long-term asymptomatic course of the pulmonary disease with development of irreversible changes in patients with autoimmune liver diseases, it seems reasonable to conduct screening studies aimed at early detection and treatment of lung lesions in this population.