RESUMEN
PM2.5 is one of the most harmful components of airborne pollution and includes particles with diameters of less than 2.5 µm. Almost 90% of the world's population lives in areas with poor air quality exceeding the norms established by the WHO. PM2.5 exposure affects various organs and systems of the human body including the upper respiratory tract which is one of the most prone to its adverse effects. PM2.5 can disrupt nasal epithelial cell metabolism, decrease the integrity of the epithelial barrier, affect mucociliary clearance, and alter the inflammatory process in the nasal mucosa. Those effects may increase the chance of developing upper respiratory tract diseases in areas with high PM2.5 pollution. PM2.5's contribution to allergic rhinitis (AR) and rhinosinusitis was recently thoroughly investigated. Numerous studies demonstrated various mechanisms that occur when subjects with AR or rhinosinusitis are exposed to PM2.5. Various immunological changes and alterations in the nasal and sinonasal epithelia were reported. These changes may contribute to the observations that exposure to higher PM2.5 concentrations may increase AR and rhinosinusitis symptoms in patients and the number of clinical visits. Thus, studying novel strategies against PM2.5 has recently become the focus of researchers' attention. In this review, we summarize the current knowledge on the effects of PM2.5 on healthy upper respiratory tract mucosa and PM2.5's contribution to AR and rhinosinusitis. Finally, we summarize the current advances in developing strategies against PM2.5 particles' effects on the upper respiratory tract.
RESUMEN
The recent classification of chronic rhinosinusitis (CRS) focusses on investigating underlying immunopathophysiological mechanisms. Primary CRS is subdivided based on endotype dominance into type 2 (that relates mostly to the Th2 immune response with high levels of IL-5, IL-13, and IgE), or non-type 2 (that corresponds to the mix of type 1 and type 3). The treatment selection of CRS is dependent on endotype dominance. Currently, the majority of patients receive standardized care-traditional pharmacological methods including local or systemic corticosteroids, nasal irrigations or antibiotics (for a selected group of patients). If well-conducted drug therapy fails, endoscopic sinus surgery is conducted. Aspirin treatment after aspirin desensitization (ATAD) with oral aspirin is an option for the treatment in nonsteroidal anti-inflammatory drug (NSAID)-exacerbated respiratory disease (N-ERD) patients. However, in this review the focus is on the role of biological treatment-monoclonal antibodies directed through the specific type 2 immune response targets. In addition, potential targets to immunotherapy in CRS are presented. Hopefully, effective diagnostic and therapeutic solutions, tailored to the individual patient, will be widely available very soon.
RESUMEN
Chronic rhinosinusitis (CRS) is related to persistent inflammation with a dysfunctional relationship between environmental agents and the host immune system. Disturbances in the functioning of the sinus mucosa lead to common clinical symptoms. The major processes involved in the pathogenesis of CRS include airway epithelial dysfunctions that are influenced by external and host-derived factors which activate multiple immunological mechanisms. The molecular bases for CRS remain unclear, although some factors commonly correspond to the disease: bacterial, fungal and viral infections, comorbidity diseases, genetic dysfunctions, and immunodeficiency. Additionally, air pollution leads increased severity of symptoms. CRS is a heterogeneous group of sinus diseases with different clinical courses and response to treatment. Immunological pathways vary depending on the endotype or genotype of the patient. The recent knowledge expansion into mechanisms underlying the pathogenesis of CRS is leading to a steadily increasing significance of precision medicine in the treatment of CRS. The purpose of this review is to summarize the current state of knowledge regarding the immunological aspects of CRS, which are essential for ensuring more effective treatment strategies.
RESUMEN
Extracellular vesicles (EVs) are produced and released by all cells and are present in all body fluids. They exist in a variety of sizes, however, small extracellular vesicles (sEVs), the EV subset with a size range from 30 to 150 nm, are of current interest. By transporting a complex cargo that includes genetic material, proteins, lipids, and signaling molecules, sEVs can alter the state of recipient cells. The role of sEVs in mediating inflammatory processes and responses of the immune system is well-documented, and adds another layer of complexity to our understanding of frequent diseases, including chronic rhinosinusitis (CRS), asthma, chronic obstructive pulmonary disease (COPD), and upper airway infections. In these diseases, two aspects of sEV biology are of particular interest: (1) sEVs might be involved in the etiopathogenesis of inflammatory airway diseases, and might emerge as attractive therapeutic targets, and (2) sEVs might be of diagnostic or prognostic relevance. The purpose of this review is to outline the biological functions of sEVs and their capacity to both augment and attenuate inflammation and immune response in the context of pathogen invasion, CRS, asthma, and COPD.
RESUMEN
NADPH oxidases (NOX) are commonly expressed ROS-producing enzymes that participate in the regulation of many signaling pathways, which influence cell metabolism, survival, and proliferation. Due to their high expression in several different types of cancer it was postulated that NOX promote tumor progression, growth, and survival. Thus, the inhibition of NOX activity was considered to have therapeutic potential. One of the possible outcomes of anticancer therapy, which has recently gained much interest, is cancer cell senescence. The induction of senescence leads to prolonged inhibition of proliferation and contributes to tumor growth restriction. The aim of our studies was to investigate the influence of low, non-toxic doses of diphenyleneiodonium chloride (DPI), a potent inhibitor of flavoenzymes including NADPH oxidases, on p53-proficient and p53-deficient HCT116 human colon cancer cells and MCF-7 breast cancer cells. We demonstrated that the temporal treatment of HCT116 and MCF-7 cancer cells (both p53 wild-type) with DPI caused induction of senescence, that was correlated with decreased level of ROS and upregulation of p53/p21 proteins. On the contrary, in the case of p53-/- HCT116 cells, apoptosis was shown to be the prevailing effect of DPI treatment. Thus, our studies provided a proof that inhibiting ROS production, and by this means influencing ROS sensitive pathways, remains an alternative strategy to facilitate so called therapy-induced senescence in cancers.