Many different cells produce and release membraneous microvesicles (MV) or exosomes into their microenvironment. Exosomes represent a specific subtype of secreted derived vesicles which are defined as homogenous vesicles of 30-100 nm lined by a lipid bilayer, which contain a specific set of proteins, lipids, and nucleic acids. There are clear evidences that they serve as important biological signals messengers and carriers in physiological as well as in pathological processes. Those derived from tumours (tumour-derived exosomes, TDexosomes) function as protumourigenic factors that can mediate intercellular communication in the tumour microenvironment and also contribute to cancer progression. The main functions of exosomes in the cancer microenvironment include the following: promotion of primary cancer growth, stimulation of angiogenesis, activation of stromal fibroblasts, sculpting the cancer ECM, generation of a premetastatic niche and suppression of host immune response. Exosomes have recently emerged as potentially promising diagnostic and prognostic biomarkers in cancer and other diseases. This article is a summary of information about the structure and origin of exosomes and also indicates the importance of exosomes and microRNAs in lung cancer. The role of exosomes in NSCLC is little known, and its explanation requires thorough research.
Myeloid-derived suppressor cells (MDSCs) are present in the human lung microenvironment, and they may be involved in the local inflammatory process in chronic obstructive pulmonary disease (COPD). Chronic inflammation in COPD may induce immunogenic cell death of structural airway cells, causing the release of damage-associated molecular patterns (DAMPs). DAMPs may activate the innate and adaptive immune system. The relationship between MDSCs and DAMPs in COPD is poorly described in the available literature. Objectives. (1) Assessment of MDSC percentage and DAMP concentration in bronchoalveolar lavage fluid (BALF) and peripheral blood. (2) Analysis of the relationship between MDSC percentage and chosen DAMPs. Patients and Methods. 30 COPD patients were included. Using monoclonal antibodies directly conjugated with fluorochromes in flow cytometry, MDSCs were assessed in BALF and peripheral blood. The concentration of DAMPs was estimated using sandwich ELISA. Using the Bradford method, the total protein concentrations were evaluated. Results. The percentage of MDSCs among MC in BALF correlated well with the concentration of defensin and heat shock protein 27. Assessing the percentage of MDSCs among all leukocytes in BALF, we revealed a significant correlation with the concentration of defensin, hyaluronic acid, and surfactant protein A. No dependencies occurred between DAMPs and MDSCs in peripheral blood. Conclusion. MDSCs and DAMPs occur in the COPD patient lung microenvironment. Significant correlations between them found in BALF may indicate their influence on the local inflammatory process in COPD. These relationships allow better understanding of the inflammatory process in COPD.
Key Clinical MessageThe relevance of this case lies in the extensive diagnostic workup that can be avoided with proper laboratory evaluation of relatively unsophisticated tests.
Degenerative aortic valve stenosis is the most common valvular heart disease seen in developed countries. Since the implementation of transcatheter aortic valve replacement, there has been a surge of efforts to improve procedural technique as well as reduce mortality. Until recently, the mainstay method of assessment of valve implantation as well as paravalvular regurgitation has relied heavily on imaging techniques including transesophageal echocardiography and aortic root angiography. There has been a lot of scientific inquiry to identify biomarkers in the management of patients with aortic stenosis. von Willebrand factor activity and high molecular weight multimer level assessment has emerged as an excellent biomarker with intraoperative, point of care potential. These implications can both supplement imaging modalities as well as potentially serve as a more accurate assessment TAVR complications.
Chronic exposure to detrimental environmental factors may induce immunogenic cell death of structural airway cells in chronic obstructive pulmonary disease (COPD). Damage-associated molecular patterns (DAMPs) is a family of heterogeneous molecules released from injured or dead cells, which activate innate and adaptive immune responses on binding to the pattern recognition receptors on cells. This study seeks to define the content of DAMPs in the bronchoalveolar lavage fluid (BALF) and serum of COPD patients, and the possible association of these molecules with clinical disease features. Thirty COPD in advanced disease stages were enrolled into the study. Pulmonary function tests, arterial blood gas content, 6-minute walk test, and BODE index were assessed. The content of DAMPs was estimated using the commercial sandwich-ELISA kits. We found differential alterations in the content of various DAMP molecules. In the main, BALF DAMPs positively associated with age, forced expiratory volume in one second (FEV1), and residual volume (RV); and inversely with PaO, residual volume/total lung capacity (RV/TLC) ratio, and the disease severity staging. In serum, DAMPS positively associated with the intensity of smoking and inversely with age, PaO, and TLC. In conclusion, DAMPs are present in both BALF and serum of COPD patients, which points to enhanced both local in the lung environment as well as systemic pro-inflammatory vein in this disease. These molecules appear involved with the lung damage and clinical variables featuring COPD. However, since the involvement of various DAMPs in COPD is variable, the exact role they play is by far unsettled and is open to further exploration.
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