Importance of Studying Non-Coding RNA in Children and Adolescents with Type 1 Diabetes.

Type 1 diabetes (T1D) mellitus is a chronic illness in children and teens, with rising global incidence rates. It stems from an autoimmune attack on pancreatic β cells, leading to insufficient insulin production. Genetic susceptibility and environmental triggers initiate this process.

A Dynamic Cellular Model as an Emerging Platform to Reproduce the Complexity of Human Vascular Calcification In Vitro.

Vascular calcification (VC) is a cardiovascular disease characterized by calcium salt deposition in vascular smooth muscle cells (VSMCs). Standard in vitro models used in VC investigations are based on VSMC monocultures under static conditions. Although these platforms are easy to use, the absence of interactions between different cell types and dynamic conditions makes these models insufficient to study key aspects of vascular pathophysiology.

Expression of miRNAs in Pre-Schoolers with Autism Spectrum Disorders Compared with Typically Developing Peers and Its Effects after Probiotic Supplementation.

Alteration of the microbiota-gut-brain axis has been recently recognized as a possible contributor to the physiopathology of autism spectrum disorder (ASD). In this context, microRNA (miRNAs) dysfunction, implicated both in several neuropathological conditions including ASD and in different gastrointestinal disorders (GIDs), could represent an important modulating factor. In this contextual framework, we studied the transcriptional profile of specific circulating miRNAs associated with both ASD (miR-197-5p, miR-424-5p, miR-500a-5p, miR-664a-5p) and GID (miR-21-5p, miR-320a-5p, miR-31-5p, miR-223-5p) in a group of pre-schoolers with ASD and in typically developing (TD) peers.

Circulating and Exosomal microRNA-33 in Childhood Obesity.

Background: MicroRNA-33 may control a wide range of different metabolic functions.

Methods: This study aims to assess the miR-33a circulating profile in normal-weight (N = 20) and obese (O = 30) adolescents and to correlate its expression levels to their metabolic parameters. In a subset of subjects, we compared circulating miR-33a with exosomal miR-33a.

Expression profile of adrenomedullin and its specific receptors in liver tissues from patients with hepatocellular carcinoma and in tumorigenic cell line-secreted extracellular vesicles.

The transcriptional profile of adrenomedullin (AM), a new metastasis-related factor involved in hepatocellular carcinoma (HCC), and its specific receptors (CLR, RAMP1, RAMP3) were evaluated in liver tissues of HCV-positive HCC subjects undergoing liver transplantation (LR) and in donors (LD). AM and its specific receptor expression were also assessed in extracellular vesicles (EVs) secreted by tumorigenic (HepG2) and non-tumorigenic (WRL68) cells by Real-Time PCR. AM expression resulted significantly elevated in LR concerning LD (p = 0.

Evaluation of Exosomal Coding and Non-Coding RNA Signature in Obese Adolescents.

Exosomes may contribute to the pathogenesis of obesity through their action as communication mediators. As we have previously demonstrated, in obese adolescents, some circulating miRNAs modified the C-type natriuretic peptide (CNP) expression and were associated with changes in metabolic functions. At present no data are available on miRNA transport by exosomes in this condition.

Connexin Expression in Human Minor Salivary Glands: An Immunohistochemical Microscopy Study.

Connexins (Cxs) are transmembrane proteins involved in the formation of hemichannels and gap junctions (GJs). GJs are involved in various physiological functions, including secretion in glandular tissue. It has been demonstrated that Cx26, Cx32, and Cx43 are mainly expressed in glands, but no data are available in human salivary glands to date.

Transcriptional level evaluation of osteopontin/miRNA-181a axis in hepatocellular carcinoma cell line-secreted extracellular vesicles.

Recent evidence suggested the role of secreted extracellular vesicles (EVs) in the intracellular signalling within the liver becoming a promising candidate as biomarker in hepatocellular carcinoma (HCC). Osteopontin (OPN) seems to play a relevant role both for early diagnosis of HCC than on the mechanisms that drive oncogenesis but, to date, information on the expression levels of OPN in EVs secreted by HCC tumor cell line are missing. The study aimed to verify, by transcriptional and proteomic study, the presence of OPN in EVs secreted by tumorigenic (HepG2) and non-tumorigenic hepatocyte cell line (WRL68), and to analyse the expression variations of OPN, its isoforms and miRNA-181a in both these EVs.

Bone morphogenetic protein-4 system expression in human coronary artery endothelial and smooth muscle cells under dynamic flow: effect of medicated bioresorbable vascular scaffolds at low and normal shear stress.

Endothelial and smooth muscle cell dysfunction is an early event at the onset of atherosclerosis, a heterogeneous and multifactorial pathology of the vascular wall. Bone morphogenetic protein (BMP)-4, a mechanosensitive autocrine cytokine, and BMPR-1a, BMPR-1b, BMPR-2 specific receptors play a key role in atherosclerotic plaque formation and vascular calcification and BMP4 is regarded as a biomarker of endothelial cell activation. The study aimed to examine the BMP4 system expression by Real-Time PCR in Human Coronary Artery Endothelial (HCAECs) and Smooth Muscle Cells (HCASMCs) under different flow rates determining low or physiological shear stress in the presence/absence of medicated Bioresorbable Vascular Scaffold (BVS).

Data mining of key genes expression in hepatocellular carcinoma: novel potential biomarkers of diagnosis prognosis or progression.

Hepatocellular carcinoma (HCC) is one of the main cancer-related causes of death worldwide. The study aimed to perform a data mining analysis of the expression and regulatory role of key genes in HCC to reveal novel potential biomarkers of diagnosis prognosis, or progression since their availability is still almost lacking. Starting from data of our cohort of patients (HCV-positive HCC pts undergoing liver transplantation (LR, n = 10) and donors (LD, n = 14), deeply analyzed previously, in which apelin, osteopontin, osteoprotegerin, NOTCH-1, CASP-3, Bcl-2, BAX, PTX3, and NPTX2 were analyzed, we applied statistical analysis and in-silico tools (Gene Expression Profiling Interactive Analysis, HCCDB database and GeneMania, UALCAN) to screen and identify the key genes.

Screening and Identification of Putative Long Non-Coding RNA in Childhood Obesity: Evaluation of Their Transcriptional Levels.

Long non-coding RNAs (LncRNAs) and microRNAs are involved in the pathogenesis of obesity, a multifactorial disease that is characterized by inflammation, cardiometabolic complications, and increased cancer risk among other co-morbidities. The up/down regulation of LncRNAs and microRNAs may play an important role in this condition to identify new diagnostic/prognostic markers. The aim of the study was to identify circulating inflammatory LncRNAs in obese adolescents ( = 54) and to evaluate whether their expression behaved differently compared to normal-weight adolescents ( = 26).

Long Non-Coding RNAs and Obesity: New Potential Pathogenic Biomarkers.

Background: A portion of the human genome is characterized by long non-coding RNAs (lncRNAs), a class of non-coding RNA longer than 200 nucleotides. Recently, the development of new biomolecular methods made it possible to delineate the involvement of lncRNAs in the regulation of different biological processes, both physiological and pathological, by acting within the cell with different regulatory mechanisms based on their specific target. To date, obesity is one of the most important health problems spreading all over the world, including the children: the search for new potential early biomarkers could open the doors to novel therapeutic strategies useful to fight the disease early in life and to reduce the risk of obesity-related co-morbidities.

Epigenetic Regulation of Cardiac Troponin Genes in Pediatric Patients with Heart Failure Supported by Ventricular Assist Device.

Ventricular Assist Device (VAD) therapy is considered as a part of standard care for end-stage Heart Failure (HF) children unresponsive to medical management, but the potential role of miRNAs in response to VAD therapy on molecular pathways underlying LV remodeling and cardiac function in HF is unknown. The aims of this study were to evaluate the effects of VAD on miRNA expression profile in cardiac tissue obtained from HF children, to determine the putative miRNA targets by an in-silico analysis as well as to verify the changes of predicated miRNA target in the same cardiac samples. The regulatory role of selected miRNAs on predicted targets was evaluated by a dedicated in vitro study.

Leptin resistance before and after obesity: evidence that tissue glucose uptake underlies adipocyte enlargement and liver steatosis/steatohepatitis in Zucker rats from early-life stages.

Background: Leptin resistance occurs in obese patients, but its independent contribution to adiposity and the accompanying metabolic diseases, i.e., diabetes, liver steatosis, and steatohepatitis, remains to be established.

C-type natriuretic peptide in childhood obesity.

According to the World Health Organization obesity is the result of an energy imbalance between calories assumed and expended and over the past 30 years its incidence has dramatically increased. Recently, the problem of obesity has drastically increased also in childhood, assuming a social relevance. Childhood obesity, in fact, increases the possibility to be obese in adulthood, representing a risk for cardiovascular morbidity and mortality.

miRNA and long non-coding RNA transcriptional expression in hepatocellular carcinoma cell line-secreted extracellular vesicles.

Extracellular vesicles (EVs) are membrane-released vesicles acting as transporters of proteins, lipids and short/long non-coding RNA (miRNAs and lncRNAs). They are released by normal and pathological cells, including hepatocellular carcinoma (HCC). To date, studies focused on miRNAs and lncRNAs contained in EVs derived from HCC are limited.

Do pentraxin 3 and neural pentraxin 2 have different facet function in hepatocellular carcinoma?

The long pentraxin (PTX) 3 and the neuronal pentraxin (NPTX) 2 has been found to exert pleiotropic roles in cancers due to their action in inflammation. However, the accurate clinical significance of PTX3 and NPTX2 in hepatocellular carcinoma (HCC), one of the commonest cancers in the world has not been well-defined. The aim of the study was to analyze the expression profile of PTX3 and NPTX2 in liver biopsies of HCV-positive HCC patients (liver recipients, LR, n = 14, age 59.

Evaluation of Apelin/APJ system expression in hepatocellular carcinoma as a function of clinical severity.

Apelin, a peptide of 77 amino acids, and its endogenous ligand, angiotensin-like-receptor 1 (APJ), play a key role in the development of tumors by enhancing angiogenesis, metastasis, cell proliferation, development of cancer stem cells and drug resistance and inhibiting apoptosis of cancer cells. However, little is known about Apelin/APJ system involvement in hepatocellular carcinoma (HCC). The aim of this study was to evaluate Apelin and APJ expression in liver specimens, obtained from subjects with HCV-positive HCC who underwent liver transplantation, according to liver disease severity (liver recipients, LR, n = 14, age 59.

Heart and liver connexin expression related to the first stage of aging: A study on naturally aged animals.

Connexins are membrane-spanning proteins that form membrane channels and hemichannels. They are involved in the cellular communication and in the maintenance of tissue homeostasis. Recent studies in humans and animals have demonstrated that the expression and distribution of Cx43, the most studied connexin, can change during aging.

Circulating microRNAs associated with C-type natriuretic peptide in childhood obesity.

Circulating microRNAs (miRNAs) are potential biomarkers of metabolic disease implicated in the pathogenesis of obesity and at present, no data are available on a possible contribution of C-type natriuretic peptides (CNP)-linked miRNAs to childhood obesity. Our aims were to 1) perform an in silico-analysis to identify miRNAs targeting CNP gene; 2) recognize CNP-linked miRNAs associated with obesity; 3) characterize their circulating profiling in normal-weight (N) and obese adolescents (O). A clinical examination was performed in 25 N and 52 O adolescents.

Variations of circulating miRNA in paediatric patients with Heart Failure supported with Ventricular Assist Device: a pilot study.

Circulating miRNAs (c-miRNAs) are promising biomarkers for HF diagnosis and prognosis. There are no studies on HF pediatric patients undergoing VAD-implantation. Aims of this study were: to examine the c-miRNAs profile in HF children; to evaluate the effects of VAD on c-miRNAs levels; to in vitro validate putative c-miRNA targets.

Transcriptional evaluation of relaxin and endothelin-1 axis in heart failure patients: First evidence of its involvement during left ventricular assist device support.

Background: Left ventricular assist devices (LVAD) are implanted in patients with end-stage heart failure (ESHF) as a mechanical support for the failing myocardium, which is characterized by an activation of the neuro-hormonal system, with release of vasoactive mediators, such as endothelin (ET)-1 and relaxin (RLX)-2. The aim of this study was to evaluate whether LVAD is able to modulate the RLX-2 and ET-1 system expression in ESHF patients.

Methods: Cardiac tissue was collected from ESHF patients before LVAD implantation (pre-LVAD group, n = 22), at the time of cardiac transplantation with concomitant LVAD removal (post-LVAD group, n = 6), and from stable HF patients on medical therapy at the time of cardiac transplantation (HTx group, n = 7).

Aging and biomarkers: Transcriptional levels evaluation of Osteopontin/miRNA-181a axis in hepatic tissue of rats in different age ranges.

Osteopontin (OPN), a novel hepatic damage marker, as well as several non-coding RNA seem to be associated with liver aging, a little studied and not yet defined process. The aim of the study was to evaluate the expression variations of OPN and miRNA-181a, the transcriptional profiling of long non coding (lnc) RNA GAS-5/miRNA-222 axis and lncRNA NEAT-1 in liver tissue of rats. In addition, to monitor the senescence process, the telomere shortening and TERT/TERC gene expression were also measured.