Thermosensory Transient Receptor Potential Ion Channels and Asthma.

Asthma is a widespread chronic disease of the bronchopulmonary system with a heterogeneous course due to the complex etiopathogenesis. Natural-climatic and anthropogenic factors play an important role in the development and progression of this pathology. The reception of physical and chemical environmental stimuli and the regulation of body temperature are mediated by thermosensory channels, members of a subfamily of transient receptor potential (TRP) ion channels. It has been found that genes encoding vanilloid, ankyrin, and melastatin TRP channels are involved in the development of some asthma phenotypes and in the formation of exacerbations of this pathology. The review summarizes modern views on the role of high and low temperatures in airway inflammation in asthma. The participation of thermosensory TRP channels (vanilloid, ankyrin, and melastatin TRP channels) in the reaction to high and low temperatures and air humidity as well as in the formation of bronchial hyperreactivity and respiratory symptoms accompanying asthma is described. The genetic aspects of the functioning of thermosensory TRP channels are discussed. It is shown that new methods of treatment of asthma exacerbations caused by the influence of temperature and humidity should be based on the regulation of channel activity.

Lipid-Induced Mechanisms of Metabolic Syndrome.

Metabolic syndrome (MetS) has a worldwide tendency to increase and depends on many components, which explains the complexity of diagnosis, approaches to the prevention, and treatment of this pathology. Insulin resistance (IR) is the crucial cause of the MetS pathogenesis, which develops against the background of abdominal obesity. In light of recent evidence, it has been shown that lipids, especially fatty acids (FAs), are important signaling molecules that regulate the signaling pathways of insulin and inflammatory mediators. On the one hand, the lack of n-3 polyunsaturated fatty acids (PUFAs) in the body leads to impaired molecular mechanisms of glucose transport, the formation of unresolved inflammation. On the other hand, excessive formation of free fatty acids (FFAs) underlies the development of oxidative stress and mitochondrial dysfunction in MetS. Understanding the molecular mechanisms of the participation of FAs and their metabolites in the pathogenesis of MetS will contribute to the development of new diagnostic methods and targeted therapy for this disease. The purpose of this review is to highlight recent advances in the study of the effect of fatty acids as modulators of insulin response and inflammatory process in the pathogenesis and treatment for MetS.

Peroxisome Proliferator-Activated Receptors as a Therapeutic Target in Asthma.

The complexity of the pathogenetic mechanisms of the development of chronic inflammation in asthma determines its heterogeneity and insufficient treatment effectiveness. Nuclear transcription factors, which include peroxisome proliferator-activated receptors, that is, PPARs, play an important role in the regulation of initiation and resolution of the inflammatory process. The ability of PPARs to modulate not only lipid homeostasis but also the activity of the inflammatory response makes them an important pathogenetic target in asthma therapy. At present, special attention is focused on natural (polyunsaturated fatty acids (PUFAs), endocannabinoids, and eicosanoids) and synthetic (fibrates, thiazolidinediones) PPAR ligands and the study of signaling mechanisms involved in the implementation of their anti-inflammatory effects in asthma. This review summarizes current views on the structure and function of PPARs, as well as their participation in the pathogenesis of chronic inflammation in asthma. The potential use of PPAR ligands as therapeutic agents for treating asthma is under discussion.