MicroRNAs are highly investigated for their role in the pathogenesis of cardiovascular diseases. Nevertheless, evidence for clinical implementation is still lacking. In our systematic review, we evaluated the potential of microRNAs as pathophysiological and diagnostic biomarkers of heart failure. We identified 72 differentially expressed microRNA molecules among groups of heart failure patients and control groups by searching the PubMed database. We did not identify a substantial overlap of differentially expressed microRNAs among different studies; only five microRNAs (miR-1228, miR-122, miR-423-5p, miR-142-3p, and exosomal miR-92b-5p) were differentially expressed in more than one included study. Gene set enrichment analysis, based on the gene targets of microRNAs presented in the included studies, showed that gene targets of differentially expressed microRNAs were enriched in the MAPK, TGFβ, PI3K-Akt, and IL-2 signaling pathways, as well as apoptosis pathway, p53 activity regulation, and angiogenesis pathway. Results of our systematic review show that there is currently insufficient support for the use of any of the presented microRNAs as pathophysiological or prognostic biomarkers in the clinical setting.

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The distribution of the bcl-2, bax and caspase-3 proteins was investigated in the cells of developing human spinal ganglia. Paraffin sections of 10 human conceptuses between 5th and 9th gestational weeks were analysed morphologically, immunohistochemically and by TUNEL-method. Cells positive to caspase-3 had brown stained nuclei or nuclear fragmentations. At earliest stages, 6% of ganglion population were caspase-3 positive cells. Later on, a significant increase in number of caspase-3 positive cells appeared, particularly in the ventral part of ganglia (12%), and subsequently decreased to 6%. TUNEL-positive cells had the same distribution pattern as caspase-3 positive cells. Bax-positive cells followed the developmental pattern similar to caspase-3 cells, changing in range between 20% and 32%. There were 8% of bcl-2 positive cells at earliest stages. They increased significantly in dorsal part of the ganglion during the 7th week (28%), and than dropped to 15% by the end of the 8th week. These findings suggest a ventro-dorsal course of development in human spinal ganglia. Number of bcl-2, bax and caspase-3 positive cells changed in a temporally and spatially restricted manner, coincidently with ganglion differentiation. While apoptosis might control cell number, bcl-2 could act in suppression of apoptosis and enhancement of cell differentiation.

We demonstrated an association between the inflammatory marker hs-CRP and either CIMT or incidence of plaques/unstable plaques at the time of recruitment in Caucasians with T2DM. Moreover, we found the association between hs-CRP levels and either CIMT progression rate or a change in the number of sites with plaques in a 3.8-year follow-up in subjects with T2DM.

Most studies of long-term chondrocytes survival were for tissue banks. They showed a gradual reduction in the viable chondrocytes percentage as a function of time and ambient temperature, but the samples were harvested under optimal conditions. The aim of our study was to determine the most reliable combination of cartilage source and assay for the in vitro postmortem chondrocyte viability analysis in the conditions that imitate a dead body. Osteochondral cylinders were procured from femoral condyles and talar trochleas of three male donors and stored in the cell culture media at 4 ± 2°C and 23 ± 2°C. The samples were analyzed by a cell viability analyzer and a confocal laser scanning microscope (CLSM) initially 24-36 h after death and then in 4-week intervals. The results reconfirmed the significant influence of time (p = 0.0002), but not of the temperature (p = 0.237). The largest reproducibility was presented for the knee joint and the CLSM.

A genetic component of diabetes and its complications (including diabetic nephropathy (DN)) is obvious, but the causative genes and mechanisms have not yet been satisfactorily identified. Oxidative stress is a single mechanism relating all major pathways responsible for diabetic damage. Numerous oxidative stress-related genes are positional candidates (determined by GWAS) and candidate genes studies confirm the association of their polymorphisms with DN. We present here their overview and connection to the "new antioxidant" therapy principle.

Purpose: The aim of this study was to investigate the relationship between erythropoietin rs1617640 polymorphism and proliferative diabetic retinopathy (PDR) in Slovenian subjects with type 2 diabetes mellitus. The second aim was to find whether erythropoietin expression in fibrovascular membranes varies among individuals carrying different genotypes of the rs1617640. Methods: This was a retrospective cross-sectional study based on 797 unrelated Slovenian (Caucasian) participants with type 2 diabetes mellitus. The study group consisted of 217 cases with PDR and 580 controls without clinical signs of diabetic retinopathy. Each subject was genotyped for rs1617640 polymorphism. Fibrovascular membranes from 27 subjects who underwent vitreoretinal surgery were analysed with immunohistochemistry. We searched for expression of erythropoietin, its cognate receptor and for a pan-endothelial marker CD-34. Results: Our results show that subjects carrying a minor GG genotype had significantly higher risk for PDR in both unadjusted (p = 0.02) and adjusted (p = 0.04) recessive genetic models. Subjects with the GG genotype had a 1.6fold increased risk of developing PDR compared to subjects carrying the major T allele. In fibrovascular membranes from subjects with PDR, the mean number of cells expressing EPO was significantly higher in G allele carriers compared to the homozygotes for the common T allele. Conclusion: In Slovenian subjects with type 2 diabetes mellitus, a significant increased risk of PDR was found in GG carriers of the erythropoietin gene rs1617640 polymorphism.

The renin-angiotensin system is involved in the pathogenesis of coronary artery disease (CAD) and myocardial infarction (MI). The authors investigated the association of genetic variability in the renin-angiotensin system (RAS) with premature MI and interactive effects between gene polymorphisms and metabolic risk factors on MI risk. Their study compared 142 patients with MI younger than 55 years with 142 healthy subjects. Polymorphisms of angiotensin-I converting enzyme (ACE) gene (insertion/deletion), angiotensinogen gene (M235T), and angiotensin-II type-1 receptor (AGT1R) gene (A1166C) were tested. The ACE-DD (deletion/deletion) genotype conferred a twofold independent risk for MI (confidence interval [CI] = 1.1-3.7; p = 0.01) after adjustment for cardiovascular risk factors, whereas angiotensinogen-TT genotype and AGT1R-AA genotype were not independent risk factors for MI. An interactive effect on MI risk was found between ACE-DD and AGT1R-AA genotypes (odds ratio [OR]=2, 95% CI= 1-3.9), between ACE-DD and angiotensinogen-TT genotypes (OR = 2.7, 95% CI = 1-7.3), as well as among ACE-DD, angiotensinogen-TT, and AGT1R-AA genotypes (OR=4.8, 95% CI = 1-22.8). Similarly, metabolic risk factors interacted with angiotensinogen-TT genotype (OR= 2, 95% CI = 1.1-3.9) on MI risk. The ACE-DD genotype is an independent risk factor for MI in patients younger than 55 years. Additionally, the authors provide evidence of an interactive effect on MI risk between risk genotypes of RAS, as well as between the angiotensinogen-TT genotype and metabolic risk factors.