Interleukins: Pathogenesis in Non-Alcoholic Fatty Liver Disease.

Inflammatory cytokines have been implicated as crucial contributors to the onset and progression of non-alcoholic fatty liver disease (NAFLD). The exact mechanisms by which interleukins (ILs) contribute to NAFLD may vary, and ongoing research is aimed at understanding the specific roles of different ILs in the pathogenesis of this condition. In addition, variations in environmental factors and genetics in each individual can influence the onset and/or progression of NAFLD. The lack of clinical studies related to the potential therapeutic properties of IL-1 inhibitors currently does not allow us to conclude their validity as a therapeutic option, although preclinical studies show promising results. Further studies are needed to elucidate their beneficial properties in NAFLD treatment.

Vascular complications and outcomes following transcatheter aortic valve replacement in patients on chronic steroid therapy: a meta-analysis.

BACKGROUND: Chronic steroid (CS) therapy was reportedly linked to increased vascular complications following percutaneous coronary intervention. However, its association with vascular complications after transcatheter aortic valve replacement (TAVR) remained uncertain, with conflicting results being reported. OBJECTIVE: The authors aimed to compare the rate of vascular complications and outcomes between patients with and without CS use after TAVR. METHODS: The authors conducted a comprehensive literature search in PubMed, Embase, and Cochrane databases from their inception until 18th April 2022 for relevant studies. Endpoints were described according to Valve Academic Research Consortium-2 definitions. Effect sizes were pooled using DerSimonian and Laird random-effects model as risk ratio (RR) with 95% CI. RESULTS: Five studies with 6136 patients undergoing TAVR were included in the analysis. The included studies were published between 2015 and 2022. The mean ages of patients in both study groups were similar, with the CS group averaging 80 years and the nonsteroid group averaging 82 years. Notably, a higher proportion of patients in the CS group were female (56%) compared to the nonsteroid group (54%). CS use was associated with a significantly higher risk of major vascular complications (12.5 vs. 6.7%, RR 2.32, 95% CI: 1.73-3.11, P <0.001), major bleeding (16.8 vs. 13.1%, RR 1.61, 95% CI: 1.27-2.05, P <0.001), and aortic annulus rupture (2.3 vs. 0.6%, RR 4.66, 95% CI: 1.67-13.01, P <0.001). There was no significant difference in terms of minor vascular complications (RR 1.43, 95% CI: 1.00-2.04, P =0.05), in-hospital mortality (2.3 vs. 1.4%, RR 1.86, 95% CI: 0.74-4.70, P =0.19), and 30-day mortality (2.9 vs. 3.1%, RR 1.14, 95% CI: 0.53-2.46, P =0.74) between both groups. CONCLUSION: Our study showed that CS therapy is associated with increased major vascular complications, major bleeding, and annulus rupture following TAVR. Further large multicenter studies or randomized controlled trials are warranted to validate these findings.

Interleukins: pathophysiological role in acute pancreatitis.

Acute pancreatitis (AP) is a common inflammatory state characterized by a clinical course that can lead to serious local and extrapancreatic organ malfunction and failure. Interleukins (ILs) are biologically active glycoproteins primarily produced by macrophages and lymphocytes. According to the literature, there are many ILs. However, this article represents a summary of the role of ILs in AP, such as IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7, IL-8, IL-9, IL-10, IL-11, IL-12, IL-13, IL-14, IL-15, IL-16, IL-17, IL-18, IL-19, and IL-20. The ways to modulate IL activity to reduce inflammation and improve outcomes in individuals with this condition are under investigation. Drugs that target specific ILs might be developed to mitigate the effects of AP.

The Association between Coagulation and Atrial Fibrillation.

The existing literature highlights the presence of numerous coagulation factors and markers. Elevated levels of coagulation factors are associated with both existing and newly diagnosed cases of atrial fibrillation (AF). However, this article summarizes the role of coagulation in the pathogenesis of AF, which includes fibrinogen and fibrin, prothrombin, thrombomodulin, soluble urokinase plasminogen activator receptor, von Willebrand factor, P-selectin, D-dimer, plasminogen activator inhibitor-1, and platelet activation. Coagulation irregularities play a significant role in the pathogenesis of AF.

Role of Cardiac Biomarkers in Hepatic Disorders: A Literature Review.

Various studies have reported the association between cardiac markers and hepatic disorders. The main objective of this review article was to elucidate the significance of important cardiac indicators such as ischemia-modified albumin, cardiac troponin, cardiac natriuretic peptides, creatine kinase, creatine kinase-MB, lactate dehydrogenase, heart-type fatty acid-binding protein, osteopontin, soluble suppression of tumorigenicity 2, C-reactive protein, and lipoprotein(a) in the development of hepatic disorders. In addition, it highlighted recent notable discoveries and accomplishments in this field and identified areas requiring further investigation, ongoing discussions, and potential avenues for future research. Early identification and control of these cardiac markers might be helpful to control the prevalence of hepatic disorders associated with cardiovascular diseases.

Adipokines and Their Role in Heart Failure: A Literature Review.

Obesity is a major risk factor for heart failure (HF). The relationship between adipokines and HF has been implicated in many previous studies and reviews. However, this review article summarizes the basic role of major adipokines, such as apelin, adiponectin, chemerin, resistin, retinol-binding protein 4 (RBP4), vaspin, visfatin, plasminogen activator inhibitor-1, monocyte chemotactic protein-1, nesfatin-1, progranulin, leptin, omentin-1, lipocalin-2, and follistatin-like 1 (FSTL1), in the pathogenesis of HF. Apelin is reduced in patients with HF and upregulated following favorable left ventricular (LV) remodeling. Higher levels of adiponectin have been found in patients with HF compared to in control patients. Also, high plasma chemerin levels are linked to a higher risk of HF. Serum resistin is related to the severity of HF and associated with a high risk for adverse cardiac events. Evidence indicates that RBP4 can contribute to inflammation and damage heart muscle cells, potentially leading to HF. Vaspin might stop the progression of cardiac degeneration, fibrosis, and HF according to experiments on rats with experimental isoproterenol-induced chronic HF. The serum concentrations of visfatin are significantly lower in patients with systolic HF. Leptin levels were found to be correlated with low LV mass and myocardial stiffness, both of which are significant risk factors for the development of HF with preserved ejection fraction (HFpEF). Measuring serum omentin-1 levels appears to be a novel prognostic indicator for risk stratification in HF patients. Increased expression of neutrophil gelatinase-associated lipocalin in both systemic circulation and myocardium in clinical and experimental HF suggests that innate immune responses may contribute to the development of HF. FSTL1 was elevated in patients with HF with reduced ejection fraction and associated with an increase in the size of the left ventricle of the heart. However, other adipokines, such as plasminogen activator inhibitor-1, monocyte chemotactic protein-1, nesfatin-1, and progranulin, have not yet been studied for HF.

Association of adiponectin gene expression with atrial fibrillation in a Pakistani populace.

Adiponectin, an adipocytokine produced and secreted by adipose tissue, has anti-diabetic, anti-atherogenic, and anti-inflammatory properties. This case-control study was aimed to assess the expression and serum levels of adiponectin in subject suffereing from atrial fibrillation (AF). The study's subjects (n = 690) were enrolled from the Punjab Institute of Cardiology, Lahore and were grouped into control, AF without Metabolic syndrome (MetS), and AF with MetS groups. Along with the collection of demographic data, an analysis of adiponectin and biochemical parameters were performed. A highly significant difference in serum levels of adiponectin was observed among the control, AF without MetS, and AF with MetS groups (61.61 ± 45.30 ng/ml, 37.20 ± 19.46 ng/ml, 63.78 ± 61.69 ng/ml). The expression analysis of adiponectin was decreased (n-fold = Ì´ 0.30) in AF without MetS group as compared to control group (n-fold = ~ 1.16) but increased in AF with MetS group (n-fold = Ì´ 6.26). The correlation analysis revealed a highly significant positive relationship between the expression of the adiponectin gene with waist-to-hip ratio (WHR) in AF without MetS group. Whereas, serum adiponectin was negatively related to serum triglycerides (TG) in AF with MetS group. In multiple regression analysis using adiponectin expression as the dependent variable, WHR was a determinant in AF without MetS. Whereas, when serum adiponectin was used as the dependent variable, serum TG was the determinant in group AF with MetS. The present study implicates that decreased expression and serum levels of adiponectin were associated with the development of AF in which WHR and serum TG also contributed towards the onset of atrial fibrillation.

The Role of Biochemical Cardiac Markers in Atrial Fibrillation.

Atrial fibrillation (AF) is the most common type of cardiac arrhythmia. Proteins are a component of cardiac biomarkers containing cell structures that are released into the circulation when a myocardial injury occurs. They are essential in the diagnosis, risk assessment, and treatment of patients who have chest pain, are thought to have acute coronary syndrome, or are experiencing acute heart failure exacerbations. There are numerous biochemical cardiac markers, but this article summarizes the basic role of major biochemical cardiac markers, including cardiac natriuretic peptides, cardiac troponins, C-reactive protein (CRP), creatine kinase-MB, heart-type fatty acid-binding protein, ischemia-modified albumin, lipoprotein (a), osteopontin (OPN), and soluble suppression of tumorigenicity 2 (sST2), in AF. Atrial natriuretic peptide may serve as an indicator of atrial integrity, which may help to select appropriate treatment approaches for AF. Higher levels of N-terminal pro-B-type natriuretic peptide and brain natriuretic peptide are predictive of incidental AF. Increased troponin T release may indicate better clinical results following AF ablation. Similarly, CRP increases the risk of the AF-increasing calcium (Ca) influx in atrial myocytes, but not because of atrial fibrosis. Patients with postoperative AF have lower FABP3 gene expression in the atrium. Lipoprotein (a) (Lp[a]) may play a causative role in the onset of AF and impact various cardiac tissues. Clinical trials for Lp(a)-lowering drugs should assess their impact on preventing AF. Also, OPN was highly expressed in the circulation of AF patients and further increased with the progression of AF. sST2 was a reliable predictor of new-onset AF and can improve the accuracy of the AF risk model. There is a greater chance that these cardiac biomarkers might be employed to enhance clinical risk stratification in AF.

Role of liver parameters in diabetes mellitus - a narrative review.

Diabetes mellitus is characterized by hyperglycemia and abnormalities in insulin secretion and function. This review article focuses on various liver parameters, including albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), alpha fetoprotein (AFP), alpha 1 antitrypsin (AAT), ammonia, bilirubin, bile acid, gamma-glutamyl transferase (GGT), immunoglobulin, lactate dehydrogenase (LDH), and total protein. These parameters play significant roles in the development of different types of diabetes such as type 1 diabetes (T1DM), type 2 diabetes (T2DM) and gestational diabetes (GDM). The article highlights that low albumin levels may indicate inflammation, while increased ALT and AST levels are associated with liver inflammation or injury, particularly in non-alcoholic fatty liver disease (NAFLD). Elevated ALP levels can be influenced by liver inflammation, biliary dysfunction, or bone metabolism changes. High bilirubin levels are independently linked to albuminuria in T1DM and an increased risk of T2DM. Elevated GGT levels are proposed as markers of oxidative stress and liver dysfunction in T2DM. In GDM, decreased serum AFP levels may indicate impaired embryo growth. Decreased AFP levels in T2DM can hinder the detection of hepatocellular carcinoma. Hyperammonemia can cause encephalopathy in diabetic ketoacidosis, and children with T1DM and attention deficit hyperactivity disorder often exhibit higher ammonia levels. T2DM disrupts the regulation of nitrogen-related metabolites, leading to increased blood ammonia levels. Bile acids affect glucose regulation by activating receptors on cell surfaces and nuclei, and changes in bile acid metabolism are observed in T2DM. Increased LDH activity reflects metabolic disturbances in glucose utilization and lactate production, contributing to diabetic complications. Poor glycemic management may be associated with elevated levels of IgA and IgG serum antibodies, and increased immunoglobulin levels are also associated with T2DM.

Irregularities of Coagulation in Hypertension.

PURPOSE OF REVIEW: This review article summarizes the role of coagulation in the pathogenesis of hypertension. It specifically focuses on significant factors and markers associated with coagulation, including D-dimer, fibrinogen and fibrin, prothrombin, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, tissue factor, tissue plasminogen activator, von Willebrand factor, ß-thromboglobulin, and Stuart-Prower factor. RECENT FINDINGS: D-dimer levels were elevated in hypertensive individuals compared to healthy controls, and the levels increased with the severity of hypertension. These findings indicate that increased coagulation activity of fibrin plays a role in the development of thromboembolic complications in hypertensive patients. Additionally, both fibrinogen levels and D-dimer levels displayed a positive correlation with the duration of hypertension, suggesting that these biomarkers were positively associated with the length of time an individual had been hypertensive. Increased systolic and diastolic blood pressures have been linked to higher levels of prothrombin time and activated partial thromboplastin time in individuals with hypertension as well as those with normal blood pressure. Also, the presence of P-selectin, produced by activated platelets and endothelial cells during angiotensin II stimulation, played a role in the development of cardiac inflammation and fibrosis associated with hypertension. Moreover, the change in systolic blood pressure was associated with baseline soluble urokinase plasminogen activator receptor (suPAR) in hypertensive participants, and the change in suPAR levels was associated with the development of hypertension. Moreover, it was observed a decrease in thrombomodulin expression in the placenta of preeclamptic patients, suggesting its potential involvement in placental dysfunction, possibly driven by an imbalance in angiogenic factors. Tissue factors and autophagy might have significant implications in the pathogenesis of chronic thromboembolic pulmonary hypertension, particularly in the context of vascular remodelling. Likewise, ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) might be a promising biomarker for the early detection of pulmonary arterial hypertension and the von Willebrand factor is a candidate prognostic biomarker. The arterial ß-thromboglobulin levels were significantly lower than venous levels. This article concludes that D-dimer, fibrinogen and fibrin, prothrombin, P-selectin, soluble urokinase plasminogen activator receptor, thrombomodulin, tissue factor, tissue plasminogen activator, von Willebrand factor, and ß-thromboglobulin are important factors involved in the pathogenesis of hypertension.

The Role of Major Biomarkers of Stress in Atrial Fibrillation: A Literature Review.

Numerous studies have reported that physical or emotional stress can provoke atrial fibrillation (AF) or vice versa, which suggests a potential link between exposure to external stressors and AF. This review article sought to describe in detail the relationship between major stress biomarkers and the pathogenesis of AF and presents up-to-date knowledge on the role of physiological and psychological stress in AF patients. For this purpose, this review article contends that plasma cortisol is linked to a greater risk of AF. A previous study has investigated the association between increased copeptin levels and paroxysmal AF (PAF) in rheumatic mitral stenosis and reported that copeptin concentration was not independently associated with AF duration. Reduced levels of chromogranin were measured in patients with AF. Furthermore, the dynamic activity of antioxidant enzymes, including catalase as well as superoxide dismutase, was examined in PAF patients during a period of <48 h. Malondialdehyde activity, serum high-sensitivity C-reactive protein, and high mobility group box 1 protein concentrations were significantly greater in patients with persistent AF or PAF compared to controls. Pooled data from 13 studies confirmed a significant reduction in the risk of AF related to the administration of vasopressin. Other studies have revealed the mechanism of action of heat shock proteins (HSPs) in preventing AF and also discussed the therapeutic potential of HSP-inducing compounds in clinical AF. More research is required to detect other biomarkers of stress, which have not been reported in the pathogenesis of AF. Further studies are required to identify their mechanism of action and drugs to manage these biomarkers of stress in AF patients, which might help to reduce the prevalence of AF globally.

The Role of Major Inflammatory Biomarkers in the Pathogenesis of Atrial Fibrillation.

Many studies have reported a relationship between inflammation and atrial fibrillation (AF). According to the literature, inflammation is the key component in pathophysiological processes during the development of AF; the amplification of inflammatory pathways triggers AF, and, at the same time, AF increases the inflammatory state. The plasma levels of several inflammatory biomarkers are elevated in patients with AF; therefore, inflammation might contribute to both the maintenance and occurrence of AF and its thromboembolic complications. Numerous inflammatory markers have been linked to AF, including CD40 ligand, fibrinogen, matrix metalloproteinase (MMP)-9, monocyte chemoattractant protein-1, myeloperoxidase, plasminogen activator inhibitor-1, and serum amyloid A. There are many pathophysiological aspects of AF that are linked to these inflammatory biomarkers, including atrial structural remodeling and atrial dilatation, increased atrial myocyte expression, fluctuations in calcium cycling, cardiac remodeling promotion, increased cardiac myocyte proliferation and terminal differentiation, production of several MMPs, the pathogenesis of atherosclerosis and cardiomyocyte apoptosis, an increased degree of fibrosis in atrial myocardium, and the progression and development of atherogenesis and atherothrombosis. The present review article aims to provide an updated overview and focus on the basic role of different biomarkers of inflammation in the pathophysiological aspects of the pathogenesis of AF.

Biomarkers of Metabolic Syndrome: Role in Pathogenesis and Pathophysiology Of Atrial Fibrillation.

The relationship between Metabolic syndrome and Atrial Fibrillation is confirmed by many studies. The components of Metabolic syndrome cause remodeling of the atrial. Metabolic syndrome and metabolic derangements of the syndrome could be the cause of the pathogenesis of AF. This review article discusses the major biomarkers of Metabolic syndrome and their role in the pathogenesis of AF. The biomarkers are adiponectin, leptin, Leptin/ Adiponectin ratio, TNF-α, Interleukin-6, Interleukin-10, PTX3, ghrelin, uric acid, and OxLDL.The elevated plasma levels of adiponectin were linked to the presence of persistent AF. Leptin signaling contributes to angiotensin-II evoked AF and atrial fibrosis. Tumor necrosis factor-alpha involvement has been shown in the pathogenesis of chronic AF. Similarly, Valvular AF patients showed high levels of TNF-α. Increased left atrial size was associated with the interleukin-6 because it is a well-known risk factor for AF. Interleukin-10 as well as TNF-α were linked to AF recurrence after catheter ablation. PTX3 could be superior to other inflammatory markers that were reported to be elevated in AF. The serum ghrelin concentration in AF patients was reduced and significantly increased after treatment. Elevated levels of uric acid could be related to the burden of AF. Increased OxLDL was found in AF as compared to sinus rhythm control.