Changes in MicroRNA Expression during Rabbit Hemorrhagic Disease Virus (RHDV) Infection.

Current knowledge on the role of microRNAs (miRNAs) in rabbit hemorrhagic disease virus (RHDV) infection and the pathogenesis of rabbit hemorrhagic disease (RHD) is still limited. RHDV replicates in the liver, causing hepatic necrosis and liver failure. MiRNAs are a class of short RNA molecules, and their expression profiles vary over the course of diseases, both in the tissue environment and in the bloodstream. This paper evaluates the expression of miRNAs in the liver tissue (ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p) and serum (ocu-miR-122-5p) of rabbits experimentally infected with RHDV. The expression levels of ocu-miR-122-5p, ocu-miR-155-5p, and ocu-miR-16b-5p in liver tissue were determined using reverse transcription quantitative real-time PCR (RT-qPCR), and the expression level of circulating ocu-miR-122-5p was established using droplet digital PCR (ddPCR). The expression levels of ocu-miR-155-5p and ocu-miR-16b-5p were significantly higher in the infected rabbits compared to the healthy rabbits (a fold-change of 5.8 and 2.5, respectively). The expression of ocu-miR-122-5p was not significantly di�erent in the liver tissue from the infected rabbits compared to the healthy rabbits (p = 0.990), while the absolute expression level of the circulating ocu-miR-122-5p was significantly higher in the infected rabbits than in the healthy rabbits (p < 0.0001). Furthermore, a functional analysis showed that ocu-miR-155-5p, ocu-miR-16b-5p, and ocu-miR-122-5p can regulate the expression of genes involved in processes correlated with acute liver failure (ALF) in rabbits. Search tool for the retrieval of interacting genes/proteins (STRING) analysis showed that the potential target genes of the three selected miRNAs may interact with each other in di�erent pathways. The results indicate the roles of these miRNAs in RHDV infection and over the course of RHD and may reflect hepatic inflammation and impairment/dysfunction in RHD

A Review of the Molecular Mechanisms Underlying Cardiac Fibrosis and Atrial Fibrillation

The cellular and molecular mechanism involved in the pathogenesis of atrial fibrosis are highly complex. We have reviewed the literature that covers the effectors, signal transduction and physiopathogenesis concerning extracellular matrix (ECM) dysregulation and atrial fibrosis in atrial fibrillation (AF). At the molecular level: angiotensin II, transforming growth factor-β1, inflammation, and oxidative stress are particularly important for ECM dysregulation and atrial fibrotic remodelling in AF. We conclude that the Ang-II-MAPK and TGF-β1-Smad signalling pathways play a major, central role in regulating atrial fibrotic remodelling in AF. The above signalling pathways induce the expression of genes encoding profibrotic molecules (MMP, CTGF, TGF-β1). An important mechanism is also the generation of reactive oxygen species. This pathway induced by the interaction of Ang II with the AT2R receptor and the activation of NADPH oxidase. Additionally, the interplay between cardiac MMPs and their endogenous tissue inhibitors of MMPs, is thought to be critical in atrial ECM metabolism and fibrosis. We also review recent evidence about the role of changes in the miRNAs expression in AF pathophysiology and their potential as therapeutic targets. Furthermore, keeping the balance between miRNA molecules exerting anti-/profibrotic effects is of key importance for the control of atrial fibrosis in AF

The Diagnostic and Therapeutic Potential of Galectin-3 in Cardiovascular Diseases

Galectin-3 plays a prominent role in chronic inflammation and has been implicated in the development of many disease conditions, including heart disease. Galectin-3, a regulatory protein, is elevated in both acute and chronic heart failure and is involved in the inflammatory pathway after injury leading to myocardial tissue remodelling. We discussed the potential utility of galectin-3 as a diagnostic and disease severity/prognostic biomarker in different cardio/cerebrovascular diseases, such as acute ischemic stroke, acute coronary syndromes, heart failure and arrhythmogenic cardiomyopathy. Over the last decade there has been a marked increase in the understanding the role of galectin-3 in myocardial fibrosis and inflammation and as a therapeutic target for the treatment of heart failure and myocardial infarction

Application of Priming Strategy for Enhanced Paclitaxel Biosynthesis in <i>Taxus</i> × <i>Media</i> Hairy Root Cultures

Despite huge progress in biotechnological approaches to paclitaxel production, Taxus spp. in vitro culture productivity still remains a challenge. This could be solved by developing a new strategy engaging mechanisms of the primed defence response joined with subsequent elicitation treatment to circumvent limitations in paclitaxel biosynthesis. The hairy roots were primed by preincubation with β-aminobutyric acid (BABA) for 24 h or 1 week, and then elicited with methyl jasmonate (MeJA) or a mixture of MeJA, sodium nitroprusside and L-phenylalanine (MIX). The effect of priming was evaluated on a molecular level by examination of the expression profiles of the four genes involved in paclitaxel biosynthesis, i.e., TXS (taxadiene synthase), BAPT (baccatin III: 3-amino, 3-phenylpropanoyltransferase), DBTNBT (3′-N-debenzoyl-2-deoxytaxol-N-benzoyltransferase) and PAM (phenylalanine aminomutase), as well as rolC (cytokinin-β-glucosidase), originated from the T-DNA of Agrobacterium rhizogenes. The maximum paclitaxel yield was achieved in cultures primed with BABA for 1 week and elicited with MIX (3179.9 ± 212 µg/g dry weight), which corresponded to the highest expression levels of TXS and BAPT genes. Although BABA itself induced the investigated gene expression over control level, it was not translated into paclitaxel production. Nevertheless, preincubation with BABA essentially affected paclitaxel yield, and the duration of BABA pretreatment seemed to have the most pronounced impact on its productivity