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

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

New insights on the cardiovascular effects of IGF-1

Cardiovascular (CV) disorders are steadily increasing, making them the world’s most prevalent health issue. New research highlights the importance of insulin-like growth factor 1 (IGF-1) for maintaining CV healthMethodsWe searched PubMed and MEDLINE for English and non-English articles with English abstracts published between 1957 (when the first report on IGF-1 identification was published) and 2022. The top search terms were: IGF-1, cardiovascular disease, IGF-1 receptors, IGF-1 and microRNAs, therapeutic interventions with IGF-1, IGF-1 and diabetes, IGF-1 and cardiovascular disease. The search retrieved original peer-reviewed articles, which were further analyzed, focusing on the role of IGF-1 in pathophysiological conditions. We specifically focused on including the most recent findings published in the past five years.ResultsIGF-1, an anabolic growth factor, regulates cell division, proliferation, and survival. In addition to its well-known growth-promoting and metabolic effects, there is mounting evidence that IGF-1 plays a specialized role in the complex activities that underpin CV function. IGF-1 promotes cardiac development and improves cardiac output, stroke volume, contractility, and ejection fraction. Furthermore, IGF-1 mediates many growth hormones (GH) actions. IGF-1 stimulates contractility and tissue remodeling in humans to improve heart function after myocardial infarction. IGF-1 also improves the lipid profile, lowers insulin levels, increases insulin sensitivity, and promotes glucose metabolism. These findings point to the intriguing medicinal potential of IGF-1. Human studies associate low serum levels of free or total IGF-1 with an increased risk of CV and cerebrovascular illness. Extensive human trials are being conducted to investigate the therapeutic efficacy and outcomes of IGF-1-related therapy.DiscussionWe anticipate the development of novel IGF-1-related therapy with minimal side effects. This review discusses recent findings on the role of IGF-1 in the cardiovascular (CVD) system, including both normal and pathological conditions. We also discuss progress in therapeutic interventions aimed at targeting the IGF axis and provide insights into the epigenetic regulation of IGF-1 mediated by microRNAs

Diabetic cardiomyopathy: The role of microRNAs and long non-coding RNAs

Diabetes mellitus (DM) is on the rise, necessitating the development of novel therapeutic and preventive strategies to mitigate the disease’s debilitating effects. Diabetic cardiomyopathy (DCMP) is among the leading causes of morbidity and mortality in diabetic patients globally. DCMP manifests as cardiomyocyte hypertrophy, apoptosis, and myocardial interstitial fibrosis before progressing to heart failure. Evidence suggests that non-coding RNAs, such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), regulate diabetic cardiomyopathy-related processes such as insulin resistance, cardiomyocyte apoptosis and inflammation, emphasizing their heart-protective effects. This paper reviewed the literature data from animal and human studies on the non-trivial roles of miRNAs and lncRNAs in the context of DCMP in diabetes and demonstrated their future potential in DCMP treatment in diabetic patients

Subacute thyroiditis following COVID-19 vaccination: Case presentation

Background:Subacute thyroiditis (SAT) is an organ-specific disease that various drugs, including COVID-19vaccines, can trigger. COVID-19 infection has been associated with thyroid gland damage and disease SARS-CoV-2direct action, euthyroid sick syndrome, and immune-mediated mechanisms are all potential mechanisms of thyroiddamage. It denotes thyroid gland inflammation, most commonly of viral origin, and belongs to the transitory, self-limiting thyroid gland diseases group, causing complications in approximately 15% of patients in the formof permanent hypothyroidism. Some authors say SAT is the most common thyroid disease associated withCOVID-19.Purpose:The occurrence of SAT many weeks after administering the second COVID-19 vaccine is rare and has limiteddocumentation in academic literature. This study aims to present the occurrence of SAT after administering the COVID-19vaccine. We present the case of a 37-year-old man who developed SAT 23 days after receiving the second dose of PfizerBioNTech’s COVID-19 mRNA vaccine.Research design and study sample:Due to neck pain and an elevated body temperature (up to 38.2°C), a 37-year-old male subject presented for examination 23 days after receiving the second Pfizer BioNTech mRNA vaccineagainst SARS-CoV-2 viral infection. The patient deniedever having an autoimmune disease or any other disease.Painful neck palpation and afirm, slightly enlarged thyroid gland with no surrounding lymphadenopathy wereidentified during the exam. The heart rate was 104 beatsper minute. All of the remaining physicalfindings werenormal.Data collection and/or Analysis:Data collected during the disease are integral to the medical record.Results:Hematology and biochemistry analyses at the initial and follow-up visits revealed minor leukocytosis, normocyticanaemia, and thrombocytosis, followed by a mild increase in lactate dehydrogenase and decreased iron levels. The patient’sthyroid function and morphology had recovered entirely from post-vaccine SAT.Conclusions: Results from this study emphasise the need for healthcare professionals to promptly report any case of SATrelated to COVID-19 vaccination. Further investigation is warranted to understand the immunopathogenesis of COVID-19-associated thyroiditis and the impact of COVID-19 immunization on this condition

Type 2 Diabetes Mellitus and its comorbidity, Alzheimer’s disease: Identifying critical microRNA using machine learning

MicroRNAs (miRNAs) are critical regulators of gene expression in healthy and diseased states, and numerous studies have established their tremendous potential as a tool for improving the diagnosis of Type 2 Diabetes Mellitus (T2D) and its comorbidities. In this regard, we computationally identify novel top-ranked hub miRNAs that might be involved in T2D. We accomplish this via two strategies: 1) by ranking miRNAs based on the number of T2D differentially expressed genes (DEGs) they target, and 2) using only the common DEGs between T2D and its comorbidity, Alzheimer’s disease (AD) to predict and rank miRNA. Then classifier models are built using the DEGs targeted by each miRNA as features. Here, we show the T2D DEGs targeted by hsa-mir-1-3p, hsa-mir-16-5p, hsa-mir-124-3p, hsa-mir-34a-5p, hsa-let-7b-5p, hsa-mir-155-5p, hsa-mir-107, hsa-mir-27a-3p, hsa-mir-129-2-3p, and hsa-mir-146a-5p are capable of distinguishing T2D samples from the controls, which serves as a measure of confidence in the miRNAs’ potential role in T2D progression. Moreover, for the second strategy, we show other critical miRNAs can be made apparent through the disease’s comorbidities, and in this case, overall, the hsa-mir-103a-3p models work well for all the datasets, especially in T2D, while the hsa-mir-124-3p models achieved the best scores for the AD datasets. To the best of our knowledge, this is the first study that used predicted miRNAs to determine the features that can separate the diseased samples (T2D or AD) from the normal ones, instead of using conventional non-biology-based feature selection methods

New biomarkers: prospect for diagnosis and monitoring of thyroid disease

After the metabolic syndrome and its components, thyroid disorders represent the most common endocrine disorders, with increasing prevalence in the last two decades. Thyroid dysfunctions are distinguished by hyperthyroidism, hypothyroidism, or inflammation (thyroiditis) of the thyroid gland, in addition to the presence of thyroid nodules that can be benign or malignant. Thyroid cancer is typically detected via an ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) and cytological examination of the specimen. This approach has significant limitations due to the small sample size and inability to characterize follicular lesions adequately. Due to the rapid advancement of high-throughput molecular biology techniques, it is now possible to identify new biomarkers for thyroid neoplasms that can supplement traditional imaging modalities in postoperative surveillance and aid in the preoperative cytology examination of indeterminate or follicular lesions. Here, we review current knowledge regarding biomarkers that have been reliable in detecting thyroid neoplasms, making them valuable tools for assessing the efficacy of surgical procedures or adjunctive treatment after surgery. We are particularly interested in providing an up-to-date and systematic review of emerging biomarkers, such as mRNA and non-coding RNAs, that can potentially detect thyroid neoplasms in clinical settings. We discuss evidence for miRNA, lncRNA and circRNA dysregulation in several thyroid neoplasms and assess their potential for use as diagnostic and prognostic biomarkers

Role of Chemerin in Cardiovascular Diseases

(1) Background: Obesity is closely connected to the pathophysiology of cardiovascular diseases (CVDs). Excess fat accumulation is associated with metabolic malfunctions that disrupt cardiovascular homeostasis by activating inflammatory processes that recruit immune cells to the site of injury and reduce nitric oxide levels, resulting in increased blood pressure, endothelial cell migration, proliferation, and apoptosis. Adipose tissue produces adipokines, such as chemerin, that may alter immune responses, lipid metabolism, vascular homeostasis, and angiogenesis. (2) Methods: We performed PubMed and MEDLINE searches for articles with English abstracts published between 1997 (when the first report on chemerin identification was published) and 2022. The search retrieved original peer-reviewed articles analyzed in the context of the role of chemerin in CVDs, explicitly focusing on the most recent findings published in the past five years. (3) Results: This review summarizes up-to-date findings related to mechanisms of chemerin action, its role in the development and progression of CVDs, and novel strategies for developing chemerin-targeting therapeutic agents for treating CVDs. (4) Conclusions: Extensive evidence points to chemerin’s role in vascular inflammation, angiogenesis, and blood pressure modulation, which opens up exciting perspectives for developing chemerin-targeting therapeutic agents for the treatment of CVDs

Supplementary data for the article: Uzelac, T. N.; Nikolić-Kokić, A. L.; Spasić, S. D.; Mačvanin, M. T.; Nikolić, M. R.; Mandić, L. M.; Jovanović, V. B. Opposite Clozapine and Ziprasidone Effects on the Reactivity of Plasma Albumin SH-Group Are the Consequence of Their Different Binding Properties Dependent on Protein Fatty Acids Content. Chemico-Biological Interactions 2019, 311. https://doi.org/10.1016/j.cbi.2019.108787

Supplementary material for: [https://www.sciencedirect.com/science/article/pii/S0009279719310257?via%3Dihub]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/3333]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/3865

Perikardni izliv kao inicijalna prezentacija novodijagnostikovane primarne hipotiroze – prikaz slučaja

Uvod i cilj. Hipotiroza je često endokrinološko oboljenje, sa širokim spektrom kliničke prezentacije: od asimptomatske do multiorganske, koja prognostički može biti ozbiljna. Atipične prezentacije hipotiroze retko mogu biti i inicijalne, poput perikardnog izliva (PI). Prikazujemo bolesnika sa novodijagnostikovanom primarnom hipotirozom, prezentovanom simptomima i znacima srčane insuficijencije, sa ehokardiografski detektovanim PI. Metode. Bolesnik je obrađen klinički, elektrokardiografski, laboratorijski i ultrasonografski (štitasta žlezda i srce). Rezultati. Muškarac star 47 godina se javlja u hitnu internističku ambulantu zbog otoka nogu, lica i zamaranja, trajanja oko godinu dana. Anamnestički bez poznatih komorbiditeta. Objektivno se kod hipometaboličnog bolesnika sa JVP 1+, bez prisustva Bekove trijade, detektuju pretibijalni edemi, bez drugog patološkog nalaza po sistemima. TA 110/70 mmHg, P 56/min. EKG: sinusni ritam, frekvence oko 55/min, niže voltaže, bez ST i T promena. U laboratorijskim analizama beleže se blaga normocitna anemija, HLP 2b i povišene vrednosti CK i transaminaza. TFT ukazuju na autoimunsku primarnu hipotirozu (TSH 35, FT4 <1.93, Anti TPO 234). Ehokardiografski nalaz ukazuje na cirkularni PI, bez znakova preteće tamponade, dok ultrazvuk štitaste žlezde odgovara hroničnom tiroiditisu. Vrednosti tumorskih i sistemskih autoimunskih markera su bez odstupanja. Započinje se postepenom supstitucijom levotiroksinom. Kontrolna ehokardiografska studija (pet nedelja nakon inicijalne) ukazuje na smanjenje PI, dok se laboratorijski registruje pad nivoa TSH (6.35). Zaključak. PI je retka inicijalna prezentacija hipotiroze, koja ako se prepozna blagovremeno, sprečava razvoj ozbiljnog kardiovaskularnog morbiditeta. Potrebno je, posebno kod mlađih bolesnika, razmotriti postojanje pridruženih uzroka PI (SBVT, maligne i infektivne bolesti), koji se klinički mogu prezentovati mitigirano.KES2022 : 8. Kongres endokrinologa Srbije sa međunarodnim učešćem, Nov 30 - Dec 3, 2022, Beogra