The long noncoding RNA landscape in cardiovascular disease: a brief update.

Purpose Of Review: In this review, we summarize new knowledge on long noncoding RNAs (lncRNAs) linked to cardiovascular disease, in particular to heart failure.

Recent Findings: LncRNAs are dysregulated in specific developmental and pathological conditions and regulate critical responses to stress. LncRNAs are being recognized as molecules regulating myocardial remodeling during disease, participating for instance in the regulation of cardiomyocyte hypertrophy and function and fibroblast proliferation.

Proprotein Convertase Subtilisin-Kexin type-9 (PCSK9) and triglyceride-rich lipoprotein metabolism: Facts and gaps.

After more than a decade of intense investigation, Pro-protein Convertase Subtilisin-Kexin type 9 (PCSK9) remains a hot topic of research both at experimental and clinical level. Interestingly PCSK9 is expressed in different tissues suggesting the existence of additional function(s) beyond the modulation of the Low-Density Lipoprotein (LDL) receptor in the liver. Emerging data suggest that PCSK9 might play a role in the modulation of triglyceride-rich lipoprotein (TGRL) metabolism, mainly Very Low-Density Lipoproteins (VLDL) and their remnants.

Sex differences in the daily rhythmicity of morphine consumption after major abdominal surgery.

Objective: The sex of the patients has been shown to affect postoperative pain and morphine consumption; still a clear understanding able to explain the reasons behind this difference struggles to emerge. Our research aimed to investigate one specific aspect of the variability in morphine consumption between sexes. Previous studies have shown that circadian rhythm can influence opioid consumption.

Epigenetic and transcriptional modulation of WDR5, a chromatin remodeling protein, in Huntington's disease human induced pluripotent stem cell (hiPSC) model.

DNA methylation (DNAm) changes are of increasing relevance to neurodegenerative disorders, including Huntington's disease (HD). We performed genome-wide screening of possible DNAm changes occurring during striatal differentiation in human induced pluripotent stem cells derived from a HD patient (HD-hiPSCs) as cellular model. We identified 240 differentially methylated regions (DMRs) at promoters in fully differentiated HD-hiPSCs.

Changes in total plasma and serum N-glycome composition and patient-controlled analgesia after major abdominal surgery.

Systemic inflammation participates to the complex healing process occurring after major surgery, thus directly affecting the surgical outcome and patient recovery. Total plasma N-glycome might be an indicator of inflammation after major surgery, as well as an anti-inflammatory therapy response marker, since protein glycosylation plays an essential role in the inflammatory cascade. Therefore, we assessed the effects of surgery on the total plasma N-glycome and the association with self-administration of postoperative morphine in two cohorts of patients that underwent major abdominal surgery.

Effect of Preoperative Inflammatory Status and Comorbidities on Pain Resolution and Persistent Postsurgical Pain after Inguinal Hernia Repair.

Poor acute pain control and inflammation are important risk factors for Persistent Postsurgical Pain (PPSP). The aim of the study is to investigate, in the context of a prospective cohort of patients undergoing hernia repair, potential risk factors for PPSP. Data about BMI, anxious-depressive disorders, neutrophil-tolymphocyte ratio (NLR), proinflammatory medical comorbidities were collected.

Pegylated Trastuzumab Fragments Acquire an Increased in Vivo Stability but Show a Largely Reduced Affinity for the Target Antigen.

PEGylation of biomolecules is a major approach to increase blood stream half-life, stability and solubility of biotherapeutics and to reduce their immunogenicity, aggregation potential and unspecific interactions with other proteins and tissues. Antibodies have generally long half-lives due to high molecular mass and stability toward proteases, however their size lowers to some extent their potential because of a reduced ability to penetrate tissues, especially those of tumor origin. Fab or otherwise engineered smaller fragments are an alternative but are less stable and are much less well retained in circulation.

High-level expression of a recombinant active microbial transglutaminase in Escherichia coli.

Background: Bacterial transglutaminases are increasingly required as industrial reagents for in vitro modification of proteins in different fields such as in food processing as well as for enzymatic site-specific covalent conjugation of therapeutic proteins to polyethylene glycol to get derivatives with improved clinical performances. In this work we studied the production in Escherichia coli of a recombinant transglutaminase from Streptomyces mobaraensis (microbial transglutaminase or MTGase) as enzymatically active chimeric forms using different expression systems under the control of both lac promoter or thermoinducible phage lambda promoter.

Results: Thermoinducible and constitutive expression vectors were constructed expressing Met-MTGase with chimeric LacZ1-8PNP1-20 or LacZ1-8 fusion protein under different promoters.

Effect of postoperative analgesia on acute and persistent postherniotomy pain: a randomized study.

Study Objective: The study objective is to identify differences in postoperative pain management according to different analgesic treatments, targeting 2 main pathways involved in pain perception.

Design: The design is a randomized, parallel groups, open-label study.

Setting: The setting is in an operating room, postoperative recovery area, and surgical ward.

Continuous wound infusion of local anesthetic and steroid after major abdominal surgery: study protocol for a randomized controlled trial.

Background: Inflammatory response is one of the key components of pain perception. Continuous infusion (CWI) of local anesthetics has been shown to be effective in controlling pain and reducing postoperative morphine consumption, but the effect of adding a potent anti-inflammatory drug (such as a steroid) has never been addressed. In our study, we want to investigate the effect of CWI with local anesthetic + methylprednisolone on acute and persistent pain, correlating clinical data with biomarkers of inflammation and genetic background.

Preclinical and clinical phase I studies of a new recombinant Filgrastim (BK0023) in comparison with Neupogen®.

Background: Filgrastim or methionyl-granulocyte colony-stimulating factor (Met-G-CSF), is a recombinant therapeutic protein widely used to treat severe neutropenia caused by myelosuppressive drugs in patients with nonmyeloid malignancies. In addition to its role in the regulation of granulopoiesis, treatment with G-CSF is considered the standard approach to mobilize CD34 positive (CD34+) mononuclear cells for reconstituting hemopoietic ability for bone marrow transplantation. An intended biosimilar filgrastim (coded BK0023) was produced in GMP conditions by E.

Involvement of caspase 8 and c-FLIPL in the proangiogenic effects of the tumour necrosis factor-related apoptosis-inducing ligand (TRAIL).

Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), a cytokine of the tumour necrosis factor superfamily, is a potent cell-apoptosis inducer, although its effects vary as a function of concentration. In fact, low concentrations of TRAIL are associated with non-apoptotic effects, such as cell proliferation. Here, the effects of TRAIL at different concentrations have been evaluated on mitogenesis and migration on human umbilical vein endothelial cells (HUVEC) in vitro, as well as in the chick embryo chorioallantoic membrane (CAM) angiogenesis model in vivo.

Circulating miR-29a, among other up-regulated microRNAs, is the only biomarker for both hypertrophy and fibrosis in patients with hypertrophic cardiomyopathy.

Objectives: The purpose of this paper was to determine whether microRNAs (miRNAs) involved in myocardial remodeling were differentially expressed in the blood of hypertrophic cardiomyopathy (HCM) patients, and whether circulating miRNAs correlated with the degree of left ventricular hypertrophy and fibrosis.

Background: miRNAs-small, noncoding ribonucleic acids (RNAs) that regulate gene expression by inhibiting RNA translation-modulate cellular function. Myocardial miRNAs modulate processes such as cardiomyocyte (CM) hypertrophy, excitation-contraction coupling, and apoptosis; non-CM-specific miRNAs regulate myocardial vascularization and fibrosis.

The circulating level of FABP3 is an indirect biomarker of microRNA-1.

Objectives: This study sought to identify proteins from the cardiomyocyte (CM) secretome that are directly targeted by the muscle-specific microRNA-1 (miR-1), and thus reflect the pathophysiological state of the CM.

Background: MicroRNAs play critical regulatory roles during myocardial remodeling and progression to heart failure. However, it remains unknown whether secreted microRNA-targeted proteins can be used as indicators of myocardial microRNA expression and function.

Endothelial dysfunction and high cardiovascular risk profile in severe alcoholics improve only partially following a medium-term alcohol withdrawal.

Background: Little is known about brachial artery flow-mediated vasodilatation (FMD) in active and medium-term withdrawing heavy alcoholics (HA).

Methods: FMD and some parameters of cardiovascular (CV) risk were measured in 29 HA (average alcohol intake 135, range 86 to 215 g per day) at baseline and after a 9 ± 7 months withdrawal and in 35 teetotalers.

Results: HA showed baseline impaired maximal % FMD (8.

The antimitogenic effect of the cannabinoid receptor agonist WIN55212-2 on human melanoma cells is mediated by the membrane lipid raft.

Here are reported the antiproliferative effects of the cannabinoid agonist WIN upon human melanoma cells expressing mRNA and protein for both CB1 and CB2 receptors. While WIN exerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce such effects and selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death. Cells treated with WIN, preincubated with the lipid raft disruptor methylcyclodestrin, were rescued from death.

Endocannabinoids inhibit release of nerve growth factor by inflammation-activated mast cells.

Nerve growth factor (NGF) is a pleiotropic member of the neurotrophin family. Beside its neuronal effects, NGF plays a role in various processes, including angiogenesis. Mast cells release NGF and are among elements contributing to angiogenesis, a process regulated by arrays of factors, including the inhibitory cannabinoids.

Increased arginine-vasopressin response to hypertonic stimulation and upright posture in idiopathic hyperprolactinemia.

To evaluate the possible influence of idiopathic hyperprolactinemia on the arginine-vasopressin (AVP) response to osmotic and pressure-volumetric stimuli, 14 idiopathic hyperprolactinemic women and 13 normoprolactinemic women were studied during a hypertonic saline infusion test (0.51M NaCl infusion for 2h) and an orthostatic test (standing upright and maintaining an orthostatic position for 20min). In both experimental conditions, the AVP response was significantly higher in women with idiopathic hyperprolactinemia than in normal normoprolactinemic women.

Unexpectedly low mutation rates in beta-myosin heavy chain and cardiac myosin binding protein genes in Italian patients with hypertrophic cardiomyopathy.

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease. Fourteen sarcomeric and sarcomere-related genes have been implicated in HCM etiology, those encoding β-myosin heavy chain (MYH7) and cardiac myosin binding protein C (MYBPC3) reported as the most frequently mutated: in fact, these account for around 50% of all cases related to sarcomeric gene mutations, which are collectively responsible for approximately 70% of all HCM cases. Here, we used denaturing high-performance liquid chromatography followed by bidirectional sequencing to screen the coding regions of MYH7 and MYBPC3 in a cohort (n = 125) of Italian patients presenting with HCM.

Effects of pomegranate juice and extract polyphenols on platelet function.

Several studies have shown that polyphenols reduce cardiovascular accidents in high-risk patients; in particular, the inhibition of platelet function may be responsible for part of this benefit. This research studied the antiplatelet effect of Wonderful variety pomegranate (Punica granatum) products, which contain primarily hydrolyzed tannins such as ellagitannins. We have investigated in vitro the effects of treatment with either pomegranate juice (PJ) or the polyphenol-rich extract from pomegranate fruit (POMx) on platelet aggregation, calcium mobilization, thromboxane A(2) production, and hydrogen peroxide formation, induced by collagen and arachidonic acid.

Oxytocin inhibits the stimulatory effect of ghrelin on circulating neuropeptide Y levels in humans.

Unlabelled: Oxytocin (OT) effect on ghrelin-stimulated neuropeptide Y (NPY) secretion was evaluated in 12 normal men.

Tests: ghrelin (1 microg/kg B.W.

Effects of moderate ethanol drinking on the GH and cortisol responses to physical exercise.

Objective: To evaluate the effects of moderate amounts of ethanol on the GH and cortisol responses to physical exercise.

Methods: Ten normal men underwent three bicycle ergometer tests. Test were carried out in basal conditions (control test) or after drinking 0.

Adrenocorticotropic hormone/cortisol response to physical exercise in abstinent alcoholic patients.

Background: Alterations in the hypothalamic-pituitary-adrenal (HPA) axis in alcoholic patients have been reported in various experimental conditions.

Methods: To establish whether alcoholism affects the HPA axis activation during physical exercise, 10 recent abstinent alcoholic patients (age range: 33-45 years; duration of alcohol dependence: range 4-6 years) were tested by exercising on a bicycle ergometer. Ten age-matched healthy nonalcoholic men participated as controls.

Detrimental effects of anabolic steroids on human endothelial cells.

The aim of this study is to investigate the effects in vitro induced by androgenic anabolic steroids (AAS) (testosterone, nandrolone, androstenedione, norandrostenedione, and norandrostenediol) used illicitly in sport competitions, on the proliferation ability, apoptosis and the intracellular calcium concentration ([Ca2+]i) in human umbilical vein endothelial cells (HUVECs), selected as a prototype of a biological target system whose structure and function can be affected by steroids. For this purpose, we evaluated the proliferation inhibition by cytotoxic assay expressed as the concentration of drug inducing a 50% decrease in growth (IC50). The IC50 was reached for testosterone at 100 microM, androstenedione at 375 microM, nandrolone at 9 microM, norandrostenedione at 500 microM.