Objective Recent data suggest that increased levels of the HOTAIR long non-coding RNA (lncRNA) are involved in the development of various types of malignancy, including breast cancer. The aim of present study was to investigate HOTAIR lncRNA expression profile in breast cancer (BC) patients and cell lines. Materials and Methods In this experimental study, expression level of HOTAIR lncRNA was evaluated in BC and normal tissues of 15 patients as well as MDA-MB-231, MCF-7 and MCF-10A cell lines, using quantitative reverse- transcription polymerase chain reaction (qRT-PCR). HOTAIR lncRNA expression levels were estimated using 2-ΔΔCt method. Further, receiver operating characteristic (ROC) curve analysis was done to evaluate the selected lncRNA diagnostic potential. The Cox’s proportional hazards regression model was performed to evaluate the predictive value of this lncRNA level in BC patients. Results The results of present study demonstrated no significant difference in the expression of HOTAIR lncRNA in MCF7 and MDA-MB-231 cancer cell lines compared to MCF-10A as normal cell line (P>0.05). However, we observed a significantly increase in the expression of HOTAIR in BC patients compared to normal tissues (P<0.001). Significant associations were found between gene expression and tumour size and margin. We found 91.1% sensitivity and 95.7% specificity of circulating HOTAIR with an area under the ROC curve of 0.969. The Kaplan-Meier analysis indicated significant correlation between HOTAIR expression and overall survival. Conclusion This study demonstrated that expression of HOTAIR is increased in BC and might be associated with its progression. According to these findings, HOTAIR expression could be proposed as biomarkers for BC early diagnosis and prognosis.

High blood pressure or hypertension is an outstanding public health problem affecting nearly 40% of the World’s adult population. Prevalence of hypertension has a strong socioeconomic impact and health burden. Recently, hypertension has reached epidemic proportions, and it is estimated that ≈25% of adult individuals will be hypertensive in the World by 2025. Untreated hypertension can result in various health complications, such as stroke, myocardial infarction, vascular disease, and chronic kidney diseases. Generally, hypertension is categorized as either primary or secondary according to its cause. However, there are several types of hypertension that are more or less common such as essential hypertension (EHT), pulmonary hypertension (PHT), pulmonary arterial hypertension (PAHT), white coat hypertension, and nocturnal hypertension. This article focuses on the 3 first types for which a significant amount of information on the role of noncoding RNAs (ncRNAs) is available. Essential, primary, or idiopathic hypertension refers to elevated blood pressure in which secondary causes such as renovascular disease, renal failure, pheochromocytoma, aldosteronism, or other causes of secondary hypertension, or Mendelian forms are not present. EHT is the most frequent type of hypertension, which accounts for 95% of all cases. PHT refers to an elevation of the pulmonary arterial pressure above 25 mm Hg at rest as assessed by right heart catheterization. This elevation can be caused by different underlying diseases, such as liver disease, thromboembolic disease, rheumatic disorders, lung conditions, including tumors, chronic obstructive pulmonary disease, pulmonary fibrosis, or cardiovascular diseases, including aortic valve disease, heart failure, and congenital heart disease. According to the latest World Health Organization classification, PHT is classified depending on its cause into 5 groups: PAHT, PHT caused by left heart disease, PHT caused by lung disease, PHT caused by chronic blood clots, and PHT associated with other unclear conditions. PAHT is defined as pulmonary vasculopathy and progressive pulmonary vasculature remodeling that cause the rise of pulmonary arterial pressure. Although PAHT is classified as a specific subgroup of PHT, in the literature, PHT is often used instead of PAHT. Thus, while PHT refers to an elevation of pressure in the lung arteries caused by a side disease, PAHT is caused by remodeling of pulmonary blood vessels. Owing to the fact that blood pressure is regulated by multiple physiological pathways, it is difficult to decipher a single causative agent of hypertension. Recent studies have shown that complex multifactorial cause of hypertension results from a dynamic interplay of genetic and environmental factors. Polygenic nature of hypertension involves many genes each with mild cumulative effects reacting to environmental factors that contribute to hypertension. Population-based studies have demonstrated that Mendelian forms of hypertension can be found in about 20% of families and reach 60% in twins. Integration of data from genome-wide linkage and association studies and system genetics approaches allowed the identification of >100 single nucleotide polymorphisms implicated in high blood pressure. Studies aiming to decipher the molecular pathways of high blood pressure have identified genes involved in the renin-angiotensin-aldosterone system (RAAS), signaling through G protein-coupled receptors, vascular inflammation, remodeling, and in the structure and regulation of vascular senescence and developmental programming. Although significant progress has been achieved in elucidating the molecular pathways involved in the pathophysiology of hypertension, the regulatory function of these pathways remains to be fully elucidated. Recent advances in epigenetics may provide at least some of the missing pieces of the hereditary puzzle that can explain the fact that a same genome can provide distinct phenotypes, without alterations in primary DNA structure. The key factor in figuring out the complex multifactorial nature of hypertension might well hence be the dark matter of the human genome. Indeed, while it used to be commonly accepted that each of human genes would encode proteins, it has more recently been discovered that the majority (>95%) of these genes are unable to produce proteins. These genes are transcribed into ncRNA molecules and they play multiple important roles in regulating protein-coding genes. The ubiquitous expression of ncRNAs allows them to regulate many physiological and pathological processes, in virtually all cell types. Because their discovery, ncRNAs have attracted an exponential interest by the biomedical research community, notably in the area of cardiovascular diseases and their major risk factor, hypertension. NcRNAs have been arbitrarily classified into short and long ncRNAs with a threshold of 200 nucleotides. In addition, ncRNAs have been classified according to their cellular localization (nuclear versus cytoplasmic), mechanism of action and

Cardiovascular disease (CVD) remains the leading cause of death worldwide and, despite continuous advances, better diagnostic and prognostic tools, as well as therapy, are needed. The human transcriptome, which is the set of all RNA produced in a cell, is much more complex than previously thought and the lack of dialogue between researchers and industrials and consensus on guidelines to generate data make it harder to compare and reproduce results. This European Cooperation in Science and Technology (COST) Action aims to accelerate the understanding of transcriptomics in CVD and further the translation of experimental data into usable applications to improve personalized medicine in this field by creating an interdisciplinary network. It aims to provide opportunities for collaboration between stakeholders from complementary backgrounds, allowing the functions of different RNAs and their interactions to be more rapidly deciphered in the cardiovascular context for translation into the clinic, thus fostering personalized medicine and meeting a current public health challenge. Thus, this Action will advance studies on cardiovascular transcriptomics, generate innovative projects, and consolidate the leadership of European research groups in the field. COST (European Cooperation in Science and Technology) is a funding organization for research and innovation networks (www.cost.eu).

As the knowledge base and importance of mitochondrial physiology to human health expands, the necessity for harmonizing the terminologyconcerning mitochondrial respiratory states and rates has become increasingly apparent. Thechemiosmotic theoryestablishes the mechanism of energy transformationandcoupling in oxidative phosphorylation. Theunifying concept of the protonmotive force providestheframeworkfordeveloping a consistent theoretical foundation ofmitochondrial physiology and bioenergetics.We followguidelines of the International Union of Pure and Applied Chemistry(IUPAC)onterminology inphysical chemistry, extended by considerationsofopen systems and thermodynamicsof irreversible processes.Theconcept-driven constructive terminology incorporates the meaning of each quantity and alignsconcepts and symbols withthe nomenclature of classicalbioenergetics. We endeavour to provide a balanced view ofmitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes.Uniform standards for evaluation of respiratory states and rates will ultimatelycontribute to reproducibility between laboratories and thussupport the development of databases of mitochondrial respiratory function in species, tissues, and cells.Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery.

The 677 C>T (rs1799986) polymorphism is located at position 677 in exon 3 of the LRP1 gene. The aim of this study was to determine the allele and genotype frequencies of the polymorphism in Bosnian population. The study included 100 unrelated healthy individuals. Genotyping of 677 C>T polymorphism of the LRP1 gene was performed with PCR-RFLP method. The most frequent allele was the C allele (91%), while the T allele was represented by 9%. These results suggested that presence of the 677 C>T polymorphism of the LRP1 gene in our population should be a base for further case-control association or population genetics studies.

Aim To investigate association of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms with recurrent pregnancy loss in Bosnian women. Methods A total of 60 women with two or more consecutive miscarriages before 20 weeks of gestation with the same partners and without history of known causes or recurrent pregnancy loss were included. A control group included 80 healthy women who had one or more successful pregnancies without history of any complication which could be associated with miscarriages. Genotyping of factor V Leiden, prothrombin G20210A, MTHFR C677T and PAI-1 4G/5G polymorphisms were performed by polymerase chain reaction/restriction fragments length polymorphism method (PCR/RFLP). Results Both factor V Leiden and MTHFR C677T polymorphisms were significantly associated with recurrent pregnancy loss (RPL) in Bosnian women while prothrombin G20210A and PAI-1 4G/5G polymorphisms did not show strongly significant association. Conclusion The presence of thrombophilic polymorphisms may predispose women to recurrent pregnancy loss. Future investigation should be addressed in order to find when carriers of those mutations, polymorphisms should be treated with anticoagulant therapy.

One of the genes considered as a risk factor for coronary artery disease (CAD) is the angiotensin-converting enzyme (ACE) gene. Many studies have been published regarding the relation between the ACE gene insertion/deletion (I/D) polymorphism and CAD. However, studies have provided controversial results. To explore this further in the population of Bosnia and Herzegovina, we compared the ACE I/D genotypes and alleles distribution between two groups: 100 CAD patients and 100 healthy control subjects. The higher distribution of DD genotype (47.0%) and D allele (65.5%) were found in CAD patients compared to controls (DD 34.0%; D allele 51.0%). Genotype odds ratio, (DD + ID) on the II, was 2.471 (1.252 – 4.876; 95% CI; p < 0.05). This leads to the conclusion that the DD genotype of the ACE I/D polymorphism affects the risk for development of coronary artery disease in Bosnian population.