Parenteral nutrition-associated liver disease (PNALD) is a severe
complication in patients completely dependent on parenteral
nutrition (PN). The gold diagnostic standard, liver biopsy, is
associated with significant health risk and therefore its use is
limited. MicroRNAs (miRNAs) are small non-coding regulatory
RNA molecules with highly tissue-specific expression and the
secreted miRNAs may serve as non-invasive diagnostic
biomarkers. The aim of this study was to evaluate the expression
of a panel of specific miRNAs associated with liver diseases of
different origin in PN-dependent adult patients in order to design
miRNA panel enabling to precise monitoring of PNALD
progression. Twelve PN-dependent patients with short bowel
syndrome (SBS) were monitored on three/four-month basis for
up to 24 months. Forty-five age- and sex-matched subjects
without any known liver pathology served as controls. Specific
miRNAs expression was determined by RT-qPCR using TaqMan
probes (Thermofisher). Liver function test parameters were
determined in certified clinical laboratories. Six of the tested
miRNAs exhibited significantly altered expression compared with
healthy controls, three of them (MIR122, MIR1273g, and
MIR500a) were upregulated while three were down-regulated
(MIR505, MIR199a, MIR139). MIR122 positively correlated with
serum AST and ALT activities while MIR1273g positively
correlated with serum CRP concentration and GGT activity.
MIR505, MIR199a, and MIR139 negatively correlated with serum
GGT activity. Fluctuation of these parameters well paralleled
serum miRNA concentrations in all patients throughout the whole
observation period. We identified six miRNAs whose serum
concentrations are significantly altered in PN-dependent patients
with PNALD and correlate with markers of inflammation,
cholestasis or hepatic injury. Their reliability as markers of PNALD
progression needs to be further evaluated.
MicroRNAs (miRNAs) are a class of short non-coding regulatory RNA molecules which play an important role in intracellular communication and cell signaling and which influence cellular processes such as proliferation, differentiation, and cellular death. Over the past two decades, the crucial role of m icroRNAs in controlling tissue homeostasis and disease in cardiovascular systems has become widely recogni zed. By controlling the expression levels of their targets, several miRNAs have been shown to modulate the function of endothelial cells (miR-221/222 and -126), vascular smooth muscle cells (miR-143/145) and macrophages (miR-33, -758, and -26), thereby regulating the development and progression of atherosclerosis. The stability of miRNAs within the blood suggests that circulating miRNAs may function as important biomarkers of disease development and progression. Numerous circulating miRNAs have been found to be dysregulated in a wide variety of different disease states, including diabetes, cancer, and cardiovascular disease., D. Dlouhá, J. A. Hubáček., and Obsahuje bibliografii
Rhabdomyosarcoma (RMS) is a malignant tumour of soft tissues, occurring mainly in children and young adults. RMS cells derive from muscle cells, which due to mutations and epigenetic
modifications have lost their ability to differentiate. Epigenetic modifications regulate expression of genes responsible for cell proliferation, maturation, differentiation and apoptosis. HDAC inhibitors suppress histone acetylation; therefore, they are a promising tool used in cancer therapy. Trichostatin A (TsA) is a
pan-inhibitor of HDAC. In our study, we investigated the effect of TsA on RMS cell biology. Our findings strongly suggest that TsA inhibits RMS cell proliferation, induces cell apoptosis, and reactivates tumour cell differentiation. TsA up-regulates miR-27b expression, which is involved in the process of myogenesis. Moreover, TsA increases susceptibility of RMS cells to routinely used chemotherapeutics. In conclusion, TsA exhibits anti-cancer properties, triggers differentiation, and thereby can complement an existing spectrum of chemotherapeutics used in RMS therapy. and Corresponding author: Maciej Tarnowski