[Alteration in the expression of platelet microRNAs in diseases with abnormal platelet activation]. / Vérlemezke-mikro-RNS-ek expressziójának változása thrombocytaaktivációval járó betegségekben.

MicroRNAs (miRNA) are short, non-coding RNAs consisting of 18-25 nucleotides that regulate posttranscriptionally the gene expression involved in the regulation of physiological processes of the cells. Their key role is to modulate the translation of target mRNAs via binding to complementary sequences within the 3' UTRs of mRNAs resulting in altered protein synthesis or even the degradation of mRNAs. miRNAs are carried not only by cells with nucleus, but also in platelets, red blood cells, and they are present in the circulation, in urine and in other body fluids as well. The fact about functional miRNAs in platelets without nucleus having a half-life of 8-12 days was questioned for a long time, thus it was also obscure whether platelets are able to produce proteins de novo when being exposed to different challenges. In the last few years, several publications have described the expression and function of certain platelet mRNAs with their regulatory miRNAs in terms of regulation of cell activation, especially in diseases in which platelet activation status is elevated, such as in type 2 diabetes mellitus or in sepsis. Apart from their pathophysiological role, miRNAs may be applied as potential new biomarkers in the investigation or differential diagnosis of these clinical conditions. This review article sought to summarize the recent findings about platelet miRNAs focusing on their altered expression in diabetes and sepsis. Orv Hetil. 2018; 159(47): 1962-1970.

[The role of miRNAs in the pathogenesis of pituitary adenomas]. / A mikro-RNS-ek szerepe az agyalapimirigy-daganatok tumorbiológiájában.

MicroRNAs (miRNAs) are short, single stranded RNA molecules which play regulatory roles through posttranscriptional regulation of their target genes. Based on our current knowledge, more than 30% of the human protein-coding genes are regulated by miRNAs, hence influencing basic cellular mechanisms including cell proliferation, differentiation and cell death. Differential miRNA expression pattern has been detected in many different types of tumors and, recently, several publications have referred to miRNAs as potential therapeutic targets. Through adjustment of miRNA levels by artificial miRNAs administration or miRNA inhibition, we can influence not only one target gene but also complex biological pathways. Pituitary adenoma is the second most frequent intracranial tumor. In spite of this, the molecular mechanism of the pituitary adenoma formation is not yet entirely revealed. Recently, more and more evidences have been found suggesting that miRNAs have an important role in pituitary adenoma pathogenesis. Here, we summarize the recent results related to this role and highlight the therapeutic potentials in pituitary adenomas. Orv Hetil. 2018; 159(7): 252-259.

[The pathogenetic role and expression profile of microRNAs in preeclampsia]. / A mikro-RNS-ek patogenetikai szerepe és expressziós mintázata praeeclampsiában.

Preeclampsia is the leading cause of maternal and fetal morbidity and mortality that affects 3-8% of pregnancies worldwide. Its main symptoms include new onset of high blood pressure and proteinuria after 20 weeks of pregnancy. The cause of the disease is still debated. microRNAs are short, non-coding RNA molecules that play a pivotal part in the posttranscriptional regulation of eukaryotic genes. They are involved in fine-tuning of vital physiological processes such as cell cycle, proliferation, differentiation and cell death. In genomic studies, hundreds of microRNAs were detected in the placenta, which are supposed to regulate placental development and contribute to uncomplicated pregnancy. Several studies have reported changes in the expression of microRNAs in pregnancy. Abnormal microRNA expression may have a role in the development of preeclampsia as it affects the proliferation, migration, and invasion of the trophoblast cells, spiral artery remodeling, and angiogenesis. Some placental microRNAs (e.g., the C19MC microRNA cluster) are able to reach the maternal circulation through their release via exosomes from the trophoblast layer. These 'circulating' microRNA molecules can be applied as biomarkers for the detection of various placental disorders owing to their stability and specificity. Orv Hetil. 2018; 159(14): 547-556.

[Pathogenic and diagnostic roles of microRNAs in adrenocortical tumours]. / A mikro-RNS-ek patogenetikai és diagnosztikai szerepe mellékvesekéreg-carcinomában.

Adrenocortical tumours are quite prevalent. Most of these tumours are benign, hormonally inactive adrenocortical adenomas. Rare hormone-secreting adrenocortical adenomas are associated with severe clinical consequences, whereas the prognosis of the rare adrenocortical cancer is rather poor in its advanced stages. The pathogenesis of these tumours is only partly elucidated. MicroRNAs are small, non-coding RNA molecules that are pivotal in the regulation of several basic cell biological processes via the posttranscriptional regulation of gene expression. Their altered expression has been described in many tumours. Several tissue microRNAs, such as miR-483-5p, miR-503, miR-210, miR-335 and miR-195 were found to be differentially expressed among benign and malignant adrenocortical tumours, and these could also have pathogenic relevance. Due to their tissue specific and stable expression, microRNAs can be exploited in diagnostics as well. As the histological diagnosis of adrenocortical malignancy is difficult, microRNAs might be of help in the establishment of malignancy. Novel data show that microRNAs are secreted in various body fluids, projecting their applicability as biomarkers as part of liquid biopsy. In this review, we attempt to present a synopsis on the pathogenic relevance of microRNAs in adrenocortical tumours and their potential diagnostic applicability. Orv Hetil. 2018; 159(7): 245-251.

[The importance of "free" nucleic acids in the non-invasive diagnostics]. / A "szabad" nukleinsavak jelentosége a noninvazív diagnosztikában.

There is a great interest to determine the physiological role of "free" nucleic acids, and to use them in the clinical diagnostics. These could be DNA, mRNA, microRNA and long non-coding RNA molecules, they are in the body fluids, like serum, tear, saliva, etc. Their exact role in the normal and pathological physiological processes is still in the focus of the research, while their use in the diagnostics is becoming more and more important. The use of "free" DNA in the non-invasive prenatal diagnosis is the first clinical application of the new generation sequencers, these methods are able to reach 99.9% specificity and sensitivity for the detection of the most common trisomies. There are promising results in their use in the diagnosis and classification of heart and cardiovascular diseases. In oncology the possibility to use the "liquid biopsy" captured the attention of not only researchers and clinicians, but the whole community. There is not enough data until today for the clinical utility and applicability of these methods. Orv. Hetil., 2016, 157(48), 1900-1909.

[Non-alcoholic fatty liver disease and hepatocellular carcinoma - 2016]. / Nem alkoholos zsírmáj és hepatocellularis carcinoma - 2016.

In the past decade non-alcoholic liver disease became the most frequently diagnosed liver disease in developed countries. At the same time, the dramatic rise in the incidence of hepatocellular carcinoma is attributed to this common metabolic disorder, and mainly to its severe form, non-alcoholic steatohepatitis. The risk factors of these associated diseases are genetic predisposition, obesity and diabetes as well as chronic low grade necro-infammation, which often leads to liver fibrosis. Free fatty acids, cytokines, lipotoxicity, insulin resistance, microRNS dysregulation and alteration in intestinal microbiota play a pivotal role in the pathogenesis. Treatment of non-alcoholic fatty liver disease - weight reduction and physical exercise in obesity, metformin in diabetes, statins in dyslipidemia and, as a new option, obeticholic acid - may diminish the risk of the hepatocellular carcinoma related to this metabolic disease.

[Helicobacter pylori -- 2014]. / Helicobacter pylori -- 2014.

The author reviews the main achievements in Helicobacter pylori research in the past 2 years. Of the more than 1000 microRNAs described thus far, sets of over- and underexpressed samples were identified that are associated with either gastric cancer or precancerous lesions, and some of them could be either markers or therapeutic targets in the near future. Meta-analyses involved 95 new publications: the association between infection and oesophageal, colorectal, pancreatic and liver carcinomas is supported by the increased odds ratios, but the results do not reach the strength seen in gastric carcinoma. Epstein-Barr virus is an emerging pathogen: 10% of gastric cancers are virus-associated; the prevalence of the virus in normal mucosa, chronic gastritis and peptic ulcer are currently being studied. Current Helicobacter pylori eradication regimens frequently achieve suboptimal results: a few optimisation methods are presented, although not all are supported by the meta-analyses. In 2013, the European Helicobacter Study Group proposed the development of a pan-European registry; data from 5792 patients registered so far indicated that many therapeutic regimens resulted in a low eradication rate. In 2013, the Healthy Stomach Initiative was started with the aim of supporting and disseminating research performed in the field of healthy and diseased stomachs.

[Potential relevance of microRNAs in the diagnostics of inflammatory bowel diseases]. / A mikro-RNS-ek szerepe a gyulladásos bélbetegségek diagnosztikájában.

Inflammatory bowel diseases are chronic inflammatory disorders characterized by relapses and remissions. Several factors have been suggested to participate in their development, although their detailed pathogenesis still remains largely unknown. MicroRNAs are single strained, non-coding RNAs, consisting of 18-25 nucleotides that regulate gene expression at the posttranscriptional level. Aberrant expression of microRNAs has been found in several malignant tumors. Recently the role of microRNAs in the pathogenesis of inflammatory-autoimmune disorders (such as inflammatory bowel disease) is being intensively investigated. Beside their pathogenic roles, microRNAs can also be exploited as diagnostic markers, especially in cases where the interpretation of histological data is difficult. In this review the authors discuss recent findings in the field of microRNAs in the diagnosis and pathogenesis of inflammatory bowel diseases.

[Epigenetic mechanisms in physiologic and pathologic pregnancies]. / Epigenetikai mechanizmusok élettani és kóros terhességben.

Epigenetic factors are nowadays in the focus of scientific interest in medicine including obstetrics. The environment in utero and early neonatal life may induce a permanent response in the fetus and the newborn leading to enhanced susceptibility to later diseases. There is now growing evidence that the effects of developmental programming may also manifest themselves in the next generations without further suboptimal exposure. The so-called fetal programming may also highlight a tight connection between pathological conditions in pregnancy, environmental factors and the development of chronic diseases in adulthood. Investigation of epigenetic factors may yield new possibilities for the prevention of chronic diseases affecting a significant part of the population.

[Significance of microRNA expression in body fluids in the diagnosis of gastrointestinal tumors]. / A testváladékok mikro-RNS-kifejezodésének jelentosége a gyomor-bél rendszeri tumorok diagnosztikájában.

MicroRNAs are small, non-coding, single strained RNAs that regulate gene expression at the posttranscriptional level. They are involved in all major aspects of cellular functions, such as cell cycle, differentiation, migration, apoptosis etc. The role of microRNAs as potential biomarkers of several malignant diseases is being intensively investigated, since they can be found in the body fluids, too, besides their usual intracellular localisation. MicroRNAs have been detected in blood, saliva, stool, breast milk, urine, bile etc. In this review the authors discuss recent findings in the field of microRNAs in stool, bile and saliva, underlying their potential significance in the diagnosis of gastrointestinal tumors.

[Genetic and epigenetic aspects of celiac disease]. / A coeliakia genetikai és epigenetikai vonatkozásai.

Genetic background of coeliac disease has been subjects to intensive research since decades. However, only results of HLA phenotyping have been taken over to routine clinical practice. Meanwhile, data on the role of epigenetical factors in the manifestation of diseases have been emerging. In coeliac disease, there are several questions both in the fields of genetics and epigenetics yet to be answered. In this review, a cross section of current knowledge on these issues is presented with special interest regarding the future clinical applications.

[MicroRNA expression profiles in squamous cell carcinomas of the meso- and hypopharynx]. / Mikro-RNS-expressziós mintázatok mesopharynx-hypopharynx laphámcarcinomákban.

INTRODUCTION: MicroRNAs play a role in carcinogenesis through their genome regulatory function. AIM: The aim of the authors was to identify and compare microRNA expression signatures of meso- and hypopharynx squamous cell cancers on the basis of the cancer field hypothesis. METHOD: Using standard mapping biopsy (tumour tissue and macroscopically normal tissues obtained 1, 2 and 3 cm from margin) 13 snap frozen sample series were analysed for microRNA expression with quantitative real-time polymerase chain reaction. RESULTS: MiR-221 was significantly overexpressed in mesopharynx cancers, whole miR-21, miR-143 and miR-155 showed significant overexpression in hypopharynx cancers. CONCLUSIONS: Using microRNA expression profiles the authors were able to distinguish peritumoural tissues according to distance from the primary tumour site. Future application of the method may prove to be useful in early detection of the altered epigenetic regulation in tissue fields representing normal phenotype. This may be helpful in cancer risk assessment and prevention.

New aspects of the development of liver diseases ­ with special regard to the role of autophagy and microRNA / A májbetegségek kialakulásának új szempontjai - különös tekintettel az autophagiára és a mikro-RNS szerepére.

Autophagy plays an important role in the homeostasis of the cells and it may be upregulated in response to several types of stresses. Deregulation of autophagy is a key mechanism in the pathogenesis and progression of several liver diseases. Deficient autophagy can contribute to liver steatosis, to endoplasmic reticulum stress and to the progression of non-alcoholic fatty liver disease. Chronic alcohol consumption inhibits autophagy. The accumulated mutant protein in the endoplasmic reticulum can be degraded by autophagy in alpha-1-antitrypsin deficiency. Hepatitis C and B viruses may exploit the autophagy pathway to promote the own replication. Hepatitis C virus non-structural protein 5A and 5B have roles in the induction of autophagosomes. MicroRNAs regulate multiple physiological, pathological functions and autophagy through the modulation of gene expression. MicroRNA-122 is involved in HCV replication. In HBV-infected livers, the microRNA pathways related to cell death, DNA damage, recombination and signal transduction were activated. MicroRNA-122 effects multiple important factors which regulate the lipid and carbohydrate metabolisms in human non-alcoholic fatty liver disease. Oxidative stress and free oxygen radicals generation involved in alcoholic liver diseases development are regulated by microRNAs through different pathways. MicroRNAs control autophagy process and autophagy regulates the expression of microRNA-s. The exploration of their interactions contributes to understanding the development of liver diseases. Orv Hetil. 2020; 161(35): 1499-1455.

[Circular ribonucleic acid and its tumor-biological relevance]. / A cirkuláris ribonukleinsav és tumorbiológiai jelentosége.

One of the most remarkable chapters in recent years' research of molecular biology is the quest for non-coding ribonucleic acids (RNAs). Circular RNAs form a distinct group within non-coding RNAs and their significance is being discovered only now. These uncommonly stable molecules take part in the regulation of gene expression by various mechanisms, e.g., by decoying microRNAs or by acting upon the translational machinery. The altered expression of circular RNAs was described in different types of cancers, and considering their stability, circular RNAs could be exploited as future biomarkers and even as molecular targets. In this synopsis, the authors present the biological characteristics and the tumor-biological relevance of circular RNAs. Orv Hetil. 2020; 161(11): 403-412.

[The importance of microRNAs in the development of systemic autoimmune disorders]. / A mikro-RNS-ek jelentosége szisztémás autoimmun betegségek kialakulásában.

MicroRNAs (miRNAs) are 18-25 nucleotide long, single stranded, endogenous, non-coding small RNAs playing an important role in regulating gene expression at posttranscriptional level. miRNAs control approximately 90% of protein-coding genes, and play a central role in various biological processes including immune cell lineage commitment, differentiation, proliferation, apoptosis and maintenance of immune homeostasis. Changes in the expression of certain miRNAs may lead to the development of many diseases, including systemic autoimmune diseases. In this study, we summarize the biogenesis of miRNAs, their role in regulation of the immune system, and review the latest research findings in systemic lupus erythematosus, primary Sjögren's syndrome, rheumatoid arthritis and systemic sclerosis. In the future, miRNAs may help not only in establishing diagnosis and prognosis but potentially serve as targets for modern therapeutic approaches in autoimmune diseases. Orv Hetil. 2019; 160(15): 563-572.