Importance of the gut microbiota in the gut-liver axis in normal and liver disease.

The gut microbiota is of growing interest to clinicians and researchers. This is because there is a growing understanding that the gut microbiota performs many different functions, including involvement in metabolic and immune processes that are systemic in nature. The liver, with its important role in detoxifying and metabolizing products from the gut, is at the forefront of interactions with the gut microbiota. Many details of these interactions are not yet known to clinicians and researchers, but there is growing evidence that normal gut microbiota function is important for liver health. At the same time, factors affecting the gut microbiota, including nutrition or medications, may also have an effect through the gut-liver axis.

Early Detection of Atrial Fibrillation in Chronic Obstructive Pulmonary Disease Patients.

Atrial fibrillation (AF) is an important medical problem, as it significantly affects patients' quality of life and prognosis. AF often complicates the course of chronic obstructive pulmonary disease (COPD), a widespread disease with heavy economic and social burdens. A growing body of evidence suggests multiple links between COPD and AF. This review considers the common pathogenetic mechanisms (chronic hypoxia, persistent inflammation, endothelial dysfunction, and myocardial remodeling) of these diseases and describes the main risk factors for the development of AF in patients with COPD. The most effective models based on clinical, laboratory, and functional indices are also described, which enable the identification of patients suffering from COPD with a high risk of AF development. Thus, AF in COPD patients is a frequent problem, and the search for new tools to identify patients at a high risk of AF among COPD patients remains an urgent medical problem.

Involvement of Lipids and Lipid Mediators in Inflammation and Atherogenesis.

Atherosclerosis is the pathophysiological basis for major diseases, such as coronary heart disease, cerebral stroke, and peripheral arterial disease, which have become epidemic in modern Western society. Atherosclerosis has a complex nature that involves mutually related immune and metabolic mechanisms. Many cells of the vascular wall and peripheral bloodstream, including endothelial cells, monocytes and macrophages, platelets, and others, are involved in the development and progression of atherosclerosis. These cells perform a number of innate immune functions, disorders of which are associated with atherosclerosis. Furthermore, lipids are not only a morphological substrate but also important participants in the development of atherosclerosis. They are involved in the development and resolution of inflammation and mediate vascular cell function.

Identification of Important Genes Associated with the Development of Atherosclerosis.

Atherosclerosis is one of the most important medical problems due to its prevalence and significant contribution to the structure of temporary and permanent disability and mortality. Atherosclerosis is a complex chain of events occurring in the vascular wall over many years. Disorders of lipid metabolism, inflammation, and impaired hemodynamics are important mechanisms of atherogenesis. A growing body of evidence strengthens the understanding of the role of genetic and epigenetic factors in individual predisposition and development of atherosclerosis and its clinical outcomes. In addition, hemodynamic changes, lipid metabolism abnormalities, and inflammation are closely related and have many overlapping links in regulation. A better study of these mechanisms may improve the quality of diagnosis and management of such patients.

Analysis of the Comorbid Course of Chronic Obstructive Pulmonary Disease.

(1) Background. Chronic obstructive pulmonary disease (COPD) has a heterogeneous natural history, manifested both in the variability of clinical features and in association with various comorbid pathologies. Atherosclerotic cardiovascular disease (ASCVD) is of great clinical importance and contributes significantly to the natural history and prognosis of COPD. The present study aimed to evaluate the nature of the comorbid course of COPD during a 15-year follow-up. (2) Methods: A total of 170 male COPD patients were included in this study. Spirometry values, symptom severity, presence of risk factors, and comorbidities were considered. Prognostic factors were evaluated using the Kaplan-Meier method. (3) Results: ASCVD was the most common comorbidity and the main cause of death in patients with COPD. Patients with comorbid COPD and ASCVD had more severe dyspnea, higher frequency of COPD exacerbations, and worse survival than patients without ASCVD (p < 0.01). Among patients with COPD, the risk of death from ASCVD was higher in those older than 60 years (OR 3.23, 95% CI [1.72, 6.07]), those with rapidly declining FEV1 (OR 4.35, 95% CI [2.28, 8.30]), those with more than two exacerbations per year (OR 3.21, 95% CI [1.71, 6.11]), and those with a pack year index greater than 30 (OR 2.75, 95% CI [1.38, 5.51]. High Charlson comorbidity index scores in patients with COPD were associated with a more severe disease course, including severity of dyspnea, frequency of exacerbations, and multivariate index scores. A high Charlson comorbidity index score was an adverse prognostic factor. (4) Conclusions: ASCVD influences the course of the disease and is a major cause of mortality in COPD patients.

The Role of Smoking in the Mechanisms of Development of Chronic Obstructive Pulmonary Disease and Atherosclerosis.

Tobacco smoking is a major cause of chronic obstructive pulmonary disease (COPD) and atherosclerotic cardiovascular disease (ASCVD). These diseases share common pathogenesis and significantly influence each other's clinical presentation and prognosis. There is increasing evidence that the mechanisms underlying the comorbidity of COPD and ASCVD are complex and multifactorial. Smoking-induced systemic inflammation, impaired endothelial function and oxidative stress may contribute to the development and progression of both diseases. The components present in tobacco smoke can have adverse effects on various cellular functions, including macrophages and endothelial cells. Smoking may also affect the innate immune system, impair apoptosis, and promote oxidative stress in the respiratory and vascular systems. The purpose of this review is to discuss the importance of smoking in the mechanisms underlying the comorbid course of COPD and ASCVD.

Effects of Atherogenic Factors on Endothelial Cells: Bioinformatics Analysis of Differentially Expressed Genes and Signaling Pathways.

(1) Background: Atherosclerosis is a serious medical condition associated with high morbidity and mortality rates. It develops over many years as a complex chain of events in the vascular wall involving various cells and is influenced by many factors of clinical interest. (2) Methods: In this study, we performed a bioinformatic analysis of Gene Expression Omnibus (GEO) datasets to investigate the gene ontology of differentially expressed genes (DEGs) in endothelial cells exposed to atherogenic factors such as tobacco smoking, oscillatory shear, and oxidized low-density lipoproteins (oxLDL). DEGs were identified using the limma R package, and gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and protein-protein interaction (PPI) network analysis were performed. (3) Results: We studied biological processes and signaling pathways involving DEGs in endothelial cells under the influence of atherogenic factors. GO enrichment analysis demonstrated that the DEGs were mainly involved in cytokine-mediated signaling pathway, innate immune response, lipid biosynthetic process, 5-lipoxygenase activity, and nitric-oxide synthase activity. KEGG pathway enrichment analysis showed that common pathways included tumor necrosis factor signaling pathway, NF-κB signaling pathway, NOD-like receptor signaling pathway, lipid and atherosclerosis, lipoprotein particle binding, and apoptosis. (4) Conclusions: Atherogenic factors such as smoking, impaired flow, and oxLDL contribute to impaired innate immune response, metabolism, and apoptosis in endothelial cells, potentially leading to the development of atherosclerosis.

The Role of Multidimensional Indices for Mortality Prediction in Chronic Obstructive Pulmonary Disease.

(1) Background: Chronic obstructive pulmonary disease (COPD) is one of the most important respiratory diseases. It is characterised by a progressive course with individual differences in clinical presentation and prognosis. The use of multidimensional indices such as the BODE, eBODE, BODEX, CODEX, ADO, and Charlson Comorbidity Index has been proposed to predict the survival rate of COPD patients. However, there is limited research on the prognostic significance of these indices in predicting long-term survival rates in patients with COPD. The aim of this prospective cohort study was to investigate the prognostic value of the BODE, eBODE, BODEX, CODEX, ADO, COTE and Charlson Comorbidity Index in predicting 5- and 10-year survival in patients with COPD. (2) Methods: A total of 170 patients were included in the study and their clinical and functional characteristics of COPD progression, such as dyspnoea, body mass index and spirometry data, were evaluated. A Kaplan-Meier survival analysis was used to calculate 5- and 10-year survival rates. The predictive value of each index was assessed using Cox proportional hazards regression models. (3) Results: The 5-year survival rate was 62.35% and the 10-year survival rate was 34.70%. The BODE, eBODE, BODEX, CODEX, ADO, COTE and Charlson Comorbidity Index were all significantly associated with the 10-year survival rate of COPD patients (p < 0.05). The hazard ratios (HRs) for these indices were as follows: BODE (HR = 1.30, 95% confidence interval [CI] 1.21-1.39); eBODE (HR = 1.29, 95% CI 1.21-1.37); BODEX (HR = 1.48, 95% CI 1.35-1.63); CODEX (HR = 1.42, 95% CI 1.31-1.54); COTE (HR = 1.55, 95% CI 1.36-1.75); ADO (HR = 1.41, 95% CI 1.29-1.54); and Charlson Comorbidity Index (HR = 1.35, 95% CI 1.22-1.48). (4) Conclusions: The multidimensional indices are a useful clinical tool for assessing the course and prognosis of COPD. These indices can be used to identify patients at a high risk of mortality and guide the management of COPD patients.

Participation of Krüppel-like Factors in Atherogenesis.

Atherosclerosis is an important problem in modern medicine, the keys to understanding many aspects of which are still not available to clinicians. Atherosclerosis develops as a result of a complex chain of events in which many cells of the vascular wall and peripheral blood flow are involved. Endothelial cells, which line the vascular wall in a monolayer, play an important role in vascular biology. A growing body of evidence strengthens the understanding of the multifaceted functions of endothelial cells, which not only organize the barrier between blood flow and tissues but also act as regulators of hemodynamics and play an important role in regulating the function of other cells in the vascular wall. Krüppel-like factors (KLFs) perform several biological functions in various cells of the vascular wall. The large family of KLFs in humans includes 18 members, among which KLF2 and KLF4 are at the crossroads between endothelial cell mechanobiology and immunometabolism, which play important roles in both the normal vascular wall and atherosclerosis.

Immune and metabolic cross-links in the pathogenesis of comorbid non-alcoholic fatty liver disease.

In recent years, there has been a steady growth of interest in non-alcoholic fatty liver disease (NAFLD), which is associated with negative epidemiological data on the prevalence of the disease and its clinical significance. NAFLD is closely related to the metabolic syndrome and these relationships are the subject of active research. A growing body of evidence shows cross-linkages between metabolic abnormalities and the innate immune system in the development and progression of NAFLD. These links are bidirectional and largely still unclear, but a better understanding of them will improve the quality of diagnosis and management of patients. In addition, lipid metabolic disorders and the innate immune system link NAFLD with other diseases, such as atherosclerosis, which is of great clinical importance.

The Importance of the Plasma Membrane in Atherogenesis.

Atherosclerotic cardiovascular diseases are an important medical problem due to their high prevalence, impact on quality of life and prognosis. The pathogenesis of atherosclerosis is an urgent medical and social problem, the solution of which may improve the quality of diagnosis and treatment of patients. Atherosclerosis is a complex chain of events, which proceeds over many years and in which many cells in the bloodstream and the vascular wall are involved. A growing body of evidence suggests that there are complex, closely linked molecular mechanisms that occur in the plasma membranes of cells involved in atherogenesis. Lipid transport, innate immune system receptor function, and hemodynamic regulation are linked to plasma membranes and their biophysical properties. A better understanding of these interrelationships will improve diagnostic quality and treatment efficacy.

Clinical Significance of Lipid Transport Function of ABC Transporters in the Innate Immune System.

ABC transporters are a large family of proteins that transport a variety of substrates across cell plasma membranes. Because of this, they are involved in many physiological processes. It is of interest to note that many ABC transporters are involved in the transport of various lipids. In addition, this function may be related to the innate immune system. The evidence that ABC transporters are involved in the regulation of the innate immune system through the transport of various substances greatly enhances the understanding of their clinical significance. ABC transporters are involved in the cellular homeostasis of cholesterol as well as in the regulation of its content in lipid rafts. Through these mechanisms, they can regulate the function of membrane proteins, including receptors of the innate immune system. By regulating lipid transport, some members of ABC transporters are involved in phagocytosis. In addition, ABC transporters are involved in the transport of lipopolysaccharide, lipid mediators of inflammation, and perform other functions in the innate immune system.

Clinical significance of polyunsaturated fatty acids in the prevention of cardiovascular diseases.

Cardiovascular diseases are one of the most important problems of modern medicine. They are associated with a large number of health care visits, hospitalizations and mortality. Prevention of atherosclerosis is one of the most effective strategies and should start as early as possible. Correction of lipid metabolism disorders is associated with definite clinical successes, both in primary prevention and in the prevention of complications of many cardiovascular diseases. A growing body of evidence suggests a multifaceted role for polyunsaturated fatty acids. They demonstrate a variety of functions in inflammation, both participating directly in a number of cellular processes and acting as a precursor for subsequent biosynthesis of lipid mediators. Extensive clinical data also support the importance of polyunsaturated fatty acids, but all questions have not been answered to date, indicating the need for further research.

Immune Function of Endothelial Cells: Evolutionary Aspects, Molecular Biology and Role in Atherogenesis.

Atherosclerosis is one of the key problems of modern medicine, which is due to the high prevalence of atherosclerotic cardiovascular diseases and their significant share in the structure of morbidity and mortality in many countries. Atherogenesis is a complex chain of events that proceeds over many years in the vascular wall with the participation of various cells. Endothelial cells are key participants in vascular function. They demonstrate involvement in the regulation of vascular hemodynamics, metabolism, and innate immunity, which act as leading links in the pathogenesis of atherosclerosis. These endothelial functions have close connections and deep evolutionary roots, a better understanding of which will improve the prospects of early diagnosis and effective treatment.

Genetic and Epigenetic Regulation of Lipoxygenase Pathways and Reverse Cholesterol Transport in Atherogenesis.

Atherosclerosis is one of the most important medical and social problems of modern society. Atherosclerosis causes a large number of hospitalizations, disability, and mortality. A considerable amount of evidence suggests that inflammation is one of the key links in the pathogenesis of atherosclerosis. Inflammation in the vascular wall has extensive cross-linkages with lipid metabolism, and lipid mediators act as a central link in the regulation of inflammation in the vascular wall. Data on the role of genetics and epigenetic factors in the development of atherosclerosis are of great interest. A growing body of evidence is strengthening the understanding of the significance of gene polymorphism, as well as gene expression dysregulation involved in cross-links between lipid metabolism and the innate immune system. A better understanding of the genetic basis and molecular mechanisms of disease pathogenesis is an important step towards solving the problems of its early diagnosis and treatment.

High-Density Lipoproteins: A Role in Inflammation in COPD.

Chronic obstructive pulmonary disease (COPD) is a widespread disease associated with high rates of disability and mortality. COPD is characterized by chronic inflammation in the bronchi as well as systemic inflammation, which contributes significantly to the clinically heterogeneous course of the disease. Lipid metabolism disorders are common in COPD, being a part of its pathogenesis. High-density lipoproteins (HDLs) are not only involved in lipid metabolism, but are also part of the organism's immune and antioxidant defense. In addition, HDL is a versatile transport system for endogenous regulatory agents and is also involved in the removal of exogenous substances such as lipopolysaccharide. These functions, as well as information about lipoprotein metabolism disorders in COPD, allow a broader assessment of their role in the pathogenesis of heterogeneous and comorbid course of the disease.

Role of Short-Chain Fatty Acids Produced by Gut Microbiota in Innate Lung Immunity and Pathogenesis of the Heterogeneous Course of Chronic Obstructive Pulmonary Disease.

Chronic obstructive pulmonary disease (COPD) is a widespread socially significant disease. The development of COPD involves the innate immune system. Interestingly, the regulation of the innate lung immune system is related to the gut microbiota. This connection is due to the production by gut microorganisms of short-chain fatty acids (SCFAs) such as acetate, propionate, and butyrate. Nutritional disturbances and changes in the structure of the intestinal microbiota lead to a decrease in SCFAs production and their effect on pulmonary immunity. The presence of a metabolic and immune axis linking the lungs and gut plays an important role in the pathogenesis of COPD. In addition, the nature of nutrition and SCFAs may participate in the development of the clinically heterogeneous course of COPD.

Molecular Pharmacology of Inflammation Resolution in Atherosclerosis.

Atherosclerosis is one of the most important problems of modern medicine as it is the leading cause of hospitalizations, disability, and mortality. The key role in the development and progression of atherosclerosis is the imbalance between the activation of inflammation in the vascular wall and the mechanisms of its control. The resolution of inflammation is the most important physiological mechanism that is impaired in atherosclerosis. The resolution of inflammation has complex, not fully known mechanisms, in which lipid mediators derived from polyunsaturated fatty acids (PUFAs) play an important role. Specialized pro-resolving mediators (SPMs) represent a group of substances that carry out inflammation resolution and may play an important role in the pathogenesis of atherosclerosis. SPMs include lipoxins, resolvins, maresins, and protectins, which are formed from PUFAs and regulate many processes related to the active resolution of inflammation. Given the physiological importance of these substances, studies examining the possibility of pharmacological effects on inflammation resolution are of interest.

Analysis of differentially expressed genes and signaling pathways involved in atherosclerosis and chronic obstructive pulmonary disease.

Atherosclerosis is an important medical and social problem, and the keys to solving this problem are still largely unknown. A common situation in real clinical practice is the comorbid course of atherosclerosis with chronic obstructive pulmonary disease (COPD). Diseases share some common risk factors and may be closely linked pathogenetically. METHODS: Bioinformatics analysis of datasets from Gene Expression Omnibus (GEO) was performed to examine the gene ontology (GO) of common differentially expressed genes (DEGs) in COPD and peripheral arterial atherosclerosis. DEGs were identified using the limma R package with the settings p < 0.05, corrected using the Benjamini & Hochberg algorithm and ǀlog 2FCǀ > 1.0. The GO, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment, and the protein-protein interaction (PPI) network analysis were performed with the detected DEGs. RESULTS: The biological processes and signaling pathways involving common DEGs from airway epithelial datasets in COPD and tissue in peripheral atherosclerosis were identified. A total of 15 DEGs were identified, comprising 12 upregulated and 3 downregulated DEGs. The GO enrichment analysis demonstrated that the upregulated hub genes were mainly involved in the inflammatory response, reactive oxygen species metabolic process, cell adhesion, lipid metabolic process, regulation of angiogenesis, icosanoid biosynthetic process, and cellular response to a chemical stimulus. The KEGG pathway enrichment analysis demonstrated that the common pathways were Toll-like receptor signaling pathway, NF-kappa B signaling pathway, lipid and atherosclerosis, and cytokine-cytokine receptor interaction. CONCLUSIONS: Biological processes and signaling pathways associated with the immune response may link the development and progression of COPD and atherosclerosis.

Involvement of Fatty Acids and Their Metabolites in the Development of Inflammation in Atherosclerosis.

Despite all the advances of modern medicine, atherosclerosis continues to be one of the most important medical and social problems. Atherosclerosis is the cause of several cardiovascular diseases, which are associated with high rates of disability and mortality. The development of atherosclerosis is associated with the accumulation of lipids in the arterial intima and the disruption of mechanisms that maintain the balance between the development and resolution of inflammation. Fatty acids are involved in many mechanisms of inflammation development and maintenance. Endothelial cells demonstrate multiple cross-linkages between lipid metabolism and innate immunity. In addition, these processes are linked to hemodynamics and the function of other cells in the vascular wall, highlighting the central role of the endothelium in vascular biology.