Circulating uncarboxylated matrix Gla protein in patients with atrial fibrillation or heart failure with preserved ejection fraction.

CONTEXT: Circulating uncarboxylated matrix Gla protein (ucMGP) is possibly related to coronary arterial calcification (CAC) in cardiovascular disease (CVD) patients. OBJECTIVE: We aimed to evaluate the relationships between circulating ucMGP, CVD pathology and CAC and its interplay with CVD risk factors. MATERIALS AND METHODS: ucMGP was measured in 99 CVD-patients. CAC score was determined by multislice computed tomography. Circulating ucMGP, uncarboxylated (ucOC) and carboxylated osteocalcin (cOC) were assayed by ELISA kits. Vitamin-K status was evaluated by ucOC/cOC ratio. RESULTS: A tendency for decreased ucMGP was observed for CAC ≥ 100 AU vs. CAC = 1-99 AU after exclusion of the patients on vitamin K-antagonist anticoagulants. Significant inverse correlations between ucMGP and vitamin-K status were indicated for the entire cohort and according to CAC score. Significant associations were found between ucMGP and risk factors for CVD. CONCLUSION: Circulating ucMGP may reflect certain stages of CVD and CAC. Future studies are needed to clarify its role as potential biomarker.

New Circulating Circular RNAs with Diagnostic and Prognostic Potential in Advanced Colorectal Cancer.

Circular RNAs (circRNAs) are a group of special endogenous long non-coding RNAs which are highly stable in the circulation, and, thus, more suitable as new biomarkers of colorectal cancer (CRC). The aim of our study was to explore the plasma expression levels of four circRNAs: has_circ_0001445, hsa_circ_0003028, hsa_circ_0007915 and hsa_circ_0008717 in patients with CRC and to evaluate their associations with clinicopathological characteristics and the clinical outcome of the patients. CircRNAs were extracted from patients' plasma obtained prior to chemotherapy. Their expression levels were measured by qPCR and calculated applying the 2-ΔΔCt method. The levels of all four circRNAs were significantly increased in the plasma of CRC patients. At the optimal cut-off values hsa_circ_0001445 and hsa_circ_0007915 in plasma could significantly distinguish between patients with or without metastatic CRC with 92.56% sensitivity and 42.86% specificity, and with 86.07% sensitivity and 57.14% specificity, respectively. The mean overall survival (OS) of patients with high/intermediate expression of hsa_circ_0001445 was 30 months, significantly higher in comparison with the mean OS of the patients with low expression-20 months (log-rank test, p = 0.034). In multivariate Cox regression analysis, the low levels of hsa_circ_0001445 were also associated with shorter survival (HR = 1.59, 95% CI: 1.02-2.47, p = 0.040). A prognostic significance of hsa_circ_0001445 for patients with metastatic CRC was established.

Oncogenic Functions and Clinical Significance of Circular RNAs in Colorectal Cancer.

Colorectal cancer (CRC) is ranked as the second most commonly diagnosed disease in females and the third in males worldwide. Therefore, the finding of new more reliable biomarkers for early diagnosis, for prediction of metastasis, and resistance to conventional therapies is an important challenge in overcoming the disease. The current review presents circular RNAs (circRNAs) with their unique features as potential prognostic and diagnostic biomarkers in CRC. The review highlights the mechanism of action and the role of circRNAs with oncogenic functions in the CRC as well as the association between their expression and clinicopathological characteristics of CRC patients. The comprehension of the role of oncogenic circRNAs in CRC pathogenesis is growing rapidly and the next step is using them as suitable new drug targets in the personalized treatment of CRC patients.

Vitamin D Status in Patients with Atrial Fibrillation and Heart Failure - Is there a Link?

BACKGROUND: The disturbed pleiotropic functions of vitamin D are related to numerous chronic non-skeletal diseases. The role of vitamin D insufficiency/deficiency in cardiovascular diseases (CVD) is controversial. Therefore, the aim was to study the vitamin D status in CVD patients and to reveal possible relationships with CVD risk factors. METHODS: This prospective study includes 93 individuals devided into two groups - patients with CVD (n = 49) and patients at risk for CVD (n = 44) served as controls. The CVD-patients were stratified into AF-group - with paroxysmal or persistent atrial fibrillation and HF-group - with heart failure with preserved ejection fraction, in sinus rhythm. Vitamin D status was assessed by measurement of serum 25-hydroxy-vitamin D (25OHD) using liquid chromatography with mass detection. Gene expression of the regulatory enzyme of vitamin D metabolism, 1-alfa-hydroxylase (CYP27B1), was evaluated by two-step real-time qPCR. Coronary artery calcium scans were performed and coronary artery calcium score (CACS) was calculated. Routine biochemical parameters were extracted from the medical documentation. Standard statistical methods (descriptive statistics, unpaired Student's t-test, one-way ANOVA, simple and multiple linear regression analyses) were applied. Statistical significance was considered at p < 0.05. RESULTS: Serum 25OHD levels of the controls were higher than those of the CVD-patients (37.36 ± 15.10 ng/mL vs. 27.70 ± 11.80 ng/mL, p = 0.008). The vitamin D status worsened with the severity of CVD pathology: significant decrease of 25OHD levels was found in the AF-group (29.56 ± 11.76 ng/mL, p = 0.044) and HF-group (24.47 ± 11.61 ng/mL, p = 0.003) vs. controls (37.36 ± 15.10 ng/mL). Significant reduction in circulating vitamin D levels with the increase of CACS (p = 0.007) was also observed. Linear regression analysis revealed significant negative association for serum 25OHD with CACS for both the entire studied group (p = 0.008) and for CVD patients (p = 0.049). The gene expression of CYP27B1 was down regulated with both the severity of CVD pathology (p = 0.05) and coronary calcium accumulation (p = 0.08). Moreover, we found a significant positive relationship (p = 0.041) between serum 25OHD levels and CYP27B1 gene expression. CONCLUSIONS: Vitamin D deficiency may be an independent cardiovascular risk factor associated with the severity of CVD pathology and increased coronary calcium deposition. The mechanism by which vitamin D itself can affect cardiovascular outcomes remains to be clarified.

Circulating miR-618 Has Prognostic Significance in Patients with Metastatic Colon Cancer.

The present study evaluated the prognostic role of circulating miRNA-618 in patients with metastatic colon cancer (mCC) and whether miR-618 gene rs2682818 single nucleotide polymorphisms (SNP) are associated with colon cancer susceptibility and expression levels of mature miR-618. In total, 104 patients with mCC before starting the chemotherapy were investigated. The expression status of circulating miR-618 in mCC was evaluated by quantitative PCR. TaqMan PCR assay was used for rs2682818 SNP genotyping. miR-618 was overexpressed in serum of mCC patients. Patients with high and intermediate expression of miR-618 had a significantly longer mean overall survival (OS) of 21 months than patients with low expression-16 months. In addition, multivariate Cox regression analysis confirmed the association between high/intermediate levels of miRNA-618 and longer OS, HR = 0.51, 95% CI: 0.30-0.86, p = 0.012. miR-618 rs2682818 SNP significantly decreased the risk of colon cancer susceptibility in both heterozygous codominant (AC vs. CC, OR = 0.39, 95% CI: 0.17-0.88, p = 0.024) and overdominant (AC vs. CC + AA, OR = 0.37, 95% CI: 0.16-0.85, p = 0.018) genetic models. Our data suggest that circulating miRNA-618 could be useful as a prognostic biomarker in mCC. Patients harboring AC rs2682818 genotype have a decreased risk for colon cancer in comparison with patients with CC and AA genotypes.

Statins, vascular calcification, and vitamin K-dependent proteins: Is there a relation?

The present cross-sectional clinical study aimed to examine the connection between statin exposure, coronary artery calcification (CAC), and vitamin K-dependent proteins (VKDPs) in patients with cardiovascular (CV) conditions. Two groups of patients were studied: patients with established CV disease (CVD) and healthy patients at moderate risk for CVD (a control group). The groups were also split into statin users and non-users. The following VKDPs were measured in plasma: uncarboxylated Matrix Gla-protein (ucMGP), undercarboxylated (ucOC), and carboxylated osteocalcin (cOC), Gla-rich protein (GRP). CAC score (CACS) was determined by multislice computed tomography. Among all the participants in the study, CACS was more pronounced in statin users compared to non-users; the same was found also among the CVD patients and among the controls. While the levels of ucMGP and GRP did not differ between statin users and non-users, ucOC and ucOC/cOC were significantly elevated in statin users, indicating vitamin K deficiency. There was a positive correlation between the levels of ucOC and CACS in the entire population and in the group of statin users, but not in statin non-users. No association was found between ucMGP or GRP and CACS. Statins had also an impact on the international normalized ratio and interacted with vitamin K antagonists (VKAs). Our results are in agreement with the existing evidence about positive association between statins and vascular calcification. They enlighten to a certain extent the possible mechanisms through which statins may enhance calcium accumulation in arterial wall, namely, by inhibition of vitamin K dependent proteins and functions involved in vascular protection.

Effects of sulphur-containing mineral water intake on oxidative status and markers for inflammation in healthy subjects.

CONTEXT: Sulphurous mineral waters (SMW) have a wide range of applications. Sulphur content of mineral waters is considered as possible determinant for their anti-inflammatory or pro-inflammatory effects. OBJECTIVE: To explore the healing properties of Varna basin mineral water by analysing possible antioxidative and anti-inflammatory effects. MATERIALS AND METHODS: An intervention with Varna SMW intake was performed with healthy volunteers. Total thiols, total glutathione and its fractions, reactive oxygen metabolites, malondialdehyde, intracellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) were measured. Expression of γ-gluthamyl-cysteinyl ligase (GCL) and sICAM-1 genes was also analysed. RESULTS: A significantly increased total glutathione and total thiols were observed at the end of the intervention. GCL and sICAM-1 gene expressions were increased after the intervention. CONCLUSION: SMW consumption improved redox status of the body. We suggested that these beneficial effects may be attributed to the established high levels of sulphur-containing compounds in Varna mineral water.

Metabolomic analysis in ophthalmology.

Modern science takes into account phenotype complexity and establishes approaches to track changes on every possible level. Many "omics" studies have been developed over the last decade. Metabolomic analysis enables dynamic measurement of the metabolic response of a living system to a variety of stimuli or genetic modifications. Important targets of metabolomics is biomarker development and translation to the clinic for personalized diagnosis and a greater understanding of disease pathogenesis. The current review highlights the major aspects of metabolomic analysis and its applications for the identification of relevant predictive, diagnostic and prognostic biomarkers for some ocular diseases including dry eye, keratoconus, retinal diseases, macular degeneration, and glaucoma. To date, possible biomarker candidates for dry eye disease are lipid metabolites and androgens, for keratoconus cytokeratins, urea, citrate cycle, and oxidative stress metabolites. Palmitoylcarnitine, sphingolipids, vitamin D related metabolites, and steroid precursors may be used for distinguishing glaucoma patients from healthy controls. Dysregulation of amino acid and carnitine metabolism is critical in the development and progression of diabetic retinopathy. Further work is needed to discover and validate metabolic biomarkers as a powerful tool for understanding the molecular mechanisms of ocular diseases, to provide knowledge on their etiology and pathophysiology and opportunities for personalized clinical intervention at an early stage.