Diabetes and associated cardiovascular complications: The role of microRNAs

Diabetes mellitus (DM) refers to a complex cluster of metabolic disorders characterized by hyperglycemia caused by inadequate insulin secretion, insulin resistance, or excessive glucagon secretion. If not correctly treated, the prolonged effects of DM-associated metabolic perturbations lead to systemic vascular complications and cardiovascular disease (CVD), the principal cause of mortality among patients with DM. Given the increase in the global prevalence of diabetes, novel diagnostic and therapeutic procedures are necessary for its effective identification and treatment. Recent findings point to an important role of microRNA (miRNAs) in DM initiation and progression, as well as the occurrence of associated cardiovascular complications. miRNAs are short, highly conserved, single-stranded, non-coding RNAs that contribute to the maintenance of physiological homeostasis through the regulation of crucial processes such as metabolism, cell proliferation, and apoptosis. The increased availability of high-throughput methodologies for identifying and characterizing non-coding RNAs has led to considerable interest in miRNAs as potential biomarkers and therapeutic agents for DM. In this review, we first comprehensively detail the regulatory miRNAs involved in the pathophysiology of DM and diabetic cardiomyopathy (DCMP). Subsequently, we summarize findings regarding the utility of several of these miRNAs as potential prognostic and diagnostic biomarkers for DM and DM-associated CVD. Finally, we evaluate the potential of miRNA-based therapeutic approaches for treating DM and DCMP in the clinical setting

Editorial: Oxidative stress and inflammation in cardiometabolic disorders

Editorial on the Research Topic: Oxidative stress and inflammation in cardiometabolic disorder

Insulin-like growth factor-1 reduces cardiac autosis through decreasing AMPK/FOXO1 signaling and Na+/K+-ATPase-Beclin-1 interaction

Introduction: Insulin-like growth factor-1 (IGF-1) promotes survival and inhibits cardiac autophagy disruption. Methods: Male Wistar rats were treated with IGF-1 (50 μg/kg), and 24 h after injection hearts were excised. The level of interaction between Beclin-1 and the α1 subunit of sodium/potassium-adenosine triphosphates (Na+/K+-ATPase), and phosphorylated forms of IGF-1 receptor/insulin receptor (IGF-1R/IR), forkhead box protein O1 (FOXO1) and AMP-activated protein kinase (AMPK) were measured. Results: The results indicate that IGF-1 decreased Beclin-1’s association with Na+/K+-ATPase (p < 0.05), increased IGF-1R/IR and FOXO1 phosphorylation (p < 0.05), and decreased AMPK phosphorylation (p < 0.01) in rats’ hearts. Conclusions: The new IGF-1 therapy may control autosis and minimize cardiomyocyte mortality

Novel insights regarding the role of noncoding RNAs in diabetes

Diabetes mellitus (DM) is a group of metabolic disorders defined by hyperglycemia induced by insulin resistance, inadequate insulin secretion, or excessive glucagon secretion. In 2021, the global prevalence of diabetes is anticipated to be 10.7% (537 million people). Noncoding RNAs (ncRNAs) appear to have an important role in the initiation and progression of DM, according to a growing body of research. The two major groups of ncRNAs implicated in diabetic disorders are miRNAs and long noncoding RNAs. miRNAs are singlestranded, short (17–25 nucleotides), ncRNAs that influence gene expression at the post-transcriptional level. Because DM has reached epidemic proportions worldwide, it appears that novel diagnostic and therapeutic strategies are required to identify and treat complications associated with these diseases efficiently. miRNAs are gaining attention as biomarkers for DM diagnosis and potential treatment due to their function in maintaining physiological homeostasis via gene expression regulation. In this review, we address the issue of the gradually expanding global prevalence of DM by presenting a complete and upto-date synopsis of various regulatory miRNAs involved in these disorders. We hope this review will spark discussion about ncRNAs as prognostic biomarkers and therapeutic tools for DM. We examine and synthesize recent research that used novel, high-throughput technologies to uncover ncRNAs involved in DM, necessitating a systematic approach to examining and summarizing their roles and possible diagnostic and therapeutic uses

Treatment of Barrett's Esophagus with radiofrequency ablation

Introduction: Barrett’s esophagus (BE) represents the distal esophageal epithelium changes that carry a high risk of developing esophageal adenocarcinoma. One of the most challenging aspects of diagnosing BE by endoscopy is precisely discerning between normal epithelium and BE changes, which is essential for therapy success. The objectives of this study were to compare the success of radio-frequency ablation (RFA) therapy to conservative treatment with proton pump inhibitor (PPI) drugs between the clinical presentation and endoscopy findings of BE at 2, 6, 12, and 24 months after administered therapy. Material and methods: Seventy-five subjects were divided into two groups (RFA and PPI) based on the BE treatment regimen in this case-control study to compare the quality of treatments applied over a 24-month follow-up. Subjects who received RFA therapy were further divided into groups: those who received focal HALO 90 and those who received circumferential HALO 360, based primarily on EGDS findings or endoscopist experience. Results: The results show that using the RFA therapeutic modality in the treatment of BE is more effective (by 94.2% in the second month of follow-up, i.e., by 99% at the final visit after 24 months) than using PPI therapy alone. Re-RFA therapy was given to 15% of the subjects, mostly applied in the same therapeutic modality (HALO 90). Conclusions: Our findings show that RFA and re-RFA therapy have a high efficacy and safety profile, with no registered worsening of histology findings, the occurrence of esophageal adenocarcinoma, or adverse effects of the therapy

Effect of acute adrenalectomy on rat liver glucocorticoid receptor

In order to improve current clinical treatment of human hypocortisolism, it is necessary to understand molecular aspects of this pathophysiology. In this study liver tissues from male Wistar rats were used as an experimental model to study structural and functional properties of glucocorticoid receptor (GR) in the absence of glucocorticoid hormones (GC). Results show that acute adrenalectomy (ADX) significantly increases the number of GR binding sites and GR protein content. In addition, acute ADX stimulates increase in stability of the GR, decrease in stability of the glucocorticoid- receptor complex (G-R), and changes in accumulation of the G-R complex in nuclei and its cellular distribution.

Nitric Oxide and its Role in Cardiovascular Diseases

Nitric oxide synthases (NOS) are the enzymes responsible for nitric oxide (NO) generation. NO is a free radical which reacts with various molecules to cause multiple biological effects. It is clear that the generation and actions of NO under physiological and pathophysiological conditions are exquisitely regulated and extend to almost every cell type and function within the circulation. While the molecule mediates many physiological functions, an excessive presence of NO is toxic to cells. The enzyme NOS, constitutively or inductively, catalyses the production of NO in several biological systems. NO is derived not only from NOS isoforms but also from NOS-independent sources. In mammals, to date, three distinct NOS isoforms have been identified: neuronal NOS (nNOS), inducible NOS (iNOS), and endothelial NOS (eNOS). The molecular structure, enzymology and pharmacology of these enzymes have been well defined, and reveal critical roles for the NOS system in a variety of important physiological processes. This review focuses on recent advances in the understanding of the interactions between NOS enzymes and pathophysiology of cardiovascular diseases (CVD) and the role of NO agonists as potential therapeutic agents in treatment of CVD.The Open Nitric oxide Journal has been discontinued

Non-alcoholic fatty liver disease: a multidisciplinary clinical practice approach—the institutional adaptation to existing Clinical Practice Guidelines

Non-alcoholic fatty liver disease (NAFLD) is among the most frequently encountered chronic liver diseases in everyday clinical practice. It is considered the hepatic manifestation of metabolic syndrome. Today, liver biopsy is still the gold standard for NAFLD confirmation and assessing NAFLD's possible progression to non-alcoholic steatohepatitis, fibrosis, cirrhosis, and hepatocellular carcinoma. Because of the high prevalence of NAFLD and potential associated risks of invasive diagnostic procedures, it is of great interest to recruit the patients for liver biopsy. However, as the presence of liver fibrosis determines the further clinical course, liver biopsy is expectedly reserved for those with increased fibrosis risk. The quality of liver biopsy recruitment and patient monitoring could be significantly improved by using non-invasive tools to assess liver fibrosis presence and interactive collaboration between general practitioners, gastroenterologists, and endocrinologists. As a result, the quality of liver biopsy recruitment and patients monitoring could be significantly improved. Here, we proposed clinical practice guidelines that could be implemented for everyday clinical practice in NAFLD patients

The role of G protein coupled receptor kinases in neurocardiovascular pathophysiology

In coronary artery disease the G protein related kinases (GRKs) play a role in desensitization of beta-adrenoreceptors (AR) after coronary occlusion. Targeted deletion and lowering of cardiac myocyte GRK-2 decreases the risk of post-ischemic heart failure (HF). Studies carried out in humans confirm the role of GRK-2 as a marker for the progression of HF after myocardial infarction (MI). The level of GRK-2 could be an indicator of beta-AR blocker efficacy in patients with acute coronary syndrome. Elevated levels of GRK-2 are an early ubiquitous consequence of myocardial injury. In hypertension an increased level of GRK-2 was reported in both animal models and human studies. The role of GRKs in vagally mediated disorders such as vasovagal syncope and atrial fibrillation remains controversial. The role of GRKs in the pathogenesis of neurocardiological diseases provides an insight into the molecular pathogenesis process, opens potential therapeutic options and suggests new directions for scientific research

The relationship between vitamin D and obesity

Currently, vitamin D deficiency and obesity are pandemic diseases and they are associated with cardiovascular (CV) disease, metabolic syndrome and type 2 diabetes mellitus (T2DM) and other diseases. Concentrations of 25-hydroxyvitamin D (25(OH) D) (25D) are considered as the best indicator of total body vitamin D stores. An association between reduced circulating 25D concentrations and obesity is well known, but the mechanisms are not totally clear. The role of vitamin D supplementation is still uncertain and prospective interventions will establish its influence, if any, in the treatment of obesity. Vitamin D deficiency is associated with the presence of a cardiometabolic risk profile in the obese. Future trials may establish a role for Vitamin D supplementation in individuals at increased CV risk