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Native breeds are a national asset in every country and their preservation is of great importance. The Busha cattle is one of the two native breeds in Serbia. Difficult calving is a major cause of loss for beef cattle producers. It results in an increased incidence of calf mortality at or near birth, increased cow mortality, and higher veterinary and labor costs. This study aimed to identify significant genetic variants and candidate genes associated with pelvic width (tuber ischii) using a genome-wide association study (GWAS). 36 young cows (2±0.1 years of age) were included in the analysis. The measurement of the pelvic width was carried out on the farm and corresponds to the distance between pin bones (tuber ischii). The blood samples were collected for DNA extraction and genotyped using the Illumina Bovine SNP50 BeadChip. Quality control and association analysis were conducted using PLINK 1.9 software. Several genetic variants have been detected with association significance of p<1x10-5. Based on the vicinity to the identified variants locations, candidate genes were identified, along with their previous associations with cattle traits: TATA-box binding protein Associated Factor 4 (skeletal development and growth), Cyclooxygenase-2 (body size and growth rate, inflammatory response), Utropin (muscle fiber integrity and function) and HHIPL2 (milk quality). The results of this study could be used for the preservation and sustainable use of Busha breed as an important genetic resource in Serbia.

Ferroptosis, a lipid peroxidation- and iron-mediated type of regulated cell death, relates to both neuroinflammation, which is common in relapsing-remitting multiple sclerosis (RRMS), and neurodegeneration, which is prevalent in progressive (P)MS. Currently, findings related to the molecular markers proposed in this paper in patients are scarce. We analyzed circulatory molecular indicators of the main ferroptosis-related processes, comprising lipid peroxidation (malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), and hexanoyl–lysine adduct (HEL)), glutathione-related antioxidant defense (total glutathione (reduced (GSH) and oxidized (GSSG)) and glutathione peroxidase 4 (GPX4)), and iron metabolism (iron, transferrin and ferritin) to estimate their contributions to the clinical manifestation of MS and differences between RRMS and PMS disease course. In 153 patients with RRMS and 69 with PMS, plasma/serum lipid peroxidation indicators and glutathione were quantified using ELISA and colorimetric reactions, respectively. Iron serum concentrations were determined using spectrophotometry, and transferrin and ferritin were determined using immunoturbidimetry. Compared to those with RRMS, patients with PMS had decreased 4-HNE (median, 1368.42 vs. 1580.17 pg/mL; p = 0.03). Interactive effects of MS course (RRMS/PMS) and disease-modifying therapy status on MDA (p = 0.009) and HEL (p = 0.02) levels were detected. In addition, the interaction of disease course and self-reported fatigue revealed significant impacts on 4-HNE levels (p = 0.01) and the GSH/GSSG ratio (p = 0.04). The results also show an association of MS course (p = 0.03) and EDSS (p = 0.04) with GSH levels. No significant changes were observed in the serum concentrations of iron metabolism indicators between the two patient groups (p > 0.05). We suggest circulatory 4-HNE as an important parameter related to differences between RRMS and PMS. Significant interactions of MS course and other clinically relevant parameter

The health-promoting benefits of walnut consumption are substantially ascribed to its fatty acid (FA) profile, which is rich in polyunsaturated FA with an exceptionally high n-3 to n-6 ratio. There are also phytonutrients in walnuts that are linked to health welfare. This review article integrates all studies on the effects of walnuts on the cardiovascular system performed on experimental animals, and thus is a source of data on the mechanisms underlying the observed effects. These studies, which are very diverse in experimental design, indicate that a diet enriched with walnuts or treating animals with walnut extract or chemical constituents of walnuts, has many favorable effects on heart and vascular system function. The cardiovascular effect of walnuts depends on the metabolic status of the organism. Among the cardiovascular effects of walnuts is that they improve the FA profile in the circulation and heart in favor of n-3 polyunsaturated FAs. In addition, a favorable effect on triglyceride and cholesterol status, which reduces cardiovascular disease risk, is observed. Intake of walnuts promotes FA catabolism and has anti-inflammatory, antioxidant, and antiarrhythmic effects. Walnuts also have a beneficial effect on vascular tone, accompanied by a decrease in blood pressure and reduced risk for atherosclerosis. In conclusion, studies on experimental animals encourage the consumption of walnuts as a simple, convenient approach to improve cardiovascular health.

Nanomaterials have become increasingly important over time as research technology has enabled the progressively precise study of materials at the nanoscale. Developing an understanding of how nanomaterials are produced and tuned allows scientists to utilise their unique properties for a variety of applications, many of which are already incorporated into commercial products. Fullerenol nanoparticles C60(OH)n, 2 ≤ n ≤ 44 are fullerene derivatives and are produced synthetically. They have good biocompatibility, low toxicity and no immunological reactivity. In addition, their nanometre size, large surface area to volume ratio, ability to penetrate cell membranes, adaptable surface that can be easily modified with different functional groups, drug release, high physical stability in biological media, ability to remove free radicals, magnetic and optical properties make them desirable candidates for various applications. This review comprehensively summarises the various applications of fullerenol nanoparticles in different scientific fields such as nanobiomedicine, including antibacterial and antiviral agents, and provides an overview of their use in agriculture and biosensor technology. Recommendations are also made for future research that would further elucidate the mechanisms of fullerenols actions.

Multiple sclerosis (MS) and glioblastoma (GBM) are CNS diseases in whose development and progression immune privilege is intimately important, but in a relatively opposite manner. Maintenance and strengthening of immune privilege have been shown to be an important mechanism in glioblastoma immune evasion, while the breakdown of immune privilege leads to MS initiation and exacerbation. We hypothesize that molecular signaling pathways can be oppositely regulated in peripheral blood CD8+ T cells of MS and glioblastoma patients at a transcriptional level. We analyzed publicly available data of the peripheral blood CD8+ T cell MS vs. control (MSvsCTRL) and GBM vs. control (GBMvsCTRL) differentially expressed gene (DEG) contrasts with Qiagen’s Ingenuity pathway analysis software (IPA). We have identified sphingolipid signaling pathway which was significantly downregulated in the GBMvsCTRL and upregulated in the MSvsCTRL. As the pathway is important for the CD8+ T lymphocytes CNS infiltration, this result is in line with our previously stated hypothesis. Comparing publicly available lists of differentially expressed serum exosomal miRNAs from MSvsCTRL and GBMvsCTRL contrasts, we have identified that hsa-miR182-5p has the greatest potential effect on sphingolipid signaling regarding the number of regulated DEGs in the GBMvsCTRL contrast, while not being able to find any relevant potential sphingolipid signaling target transcripts in the MSvsCTRL contrast. We conclude that the sphingolipid signaling pathway is a top oppositely regulated pathway in peripheral blood CD8+ T cells from GBM and MS, and might be crucial for the differences in CNS immune privilege maintenance of investigated diseases, but further experimental research is necessary.

Background The majority of CAKUT-associated CNVs overlap at least one miRNA gene, thus affecting the cellular levels of the corresponding miRNA. We aimed to investigate the potency of restitution of CNV-affected miRNA levels to remediate the dysregulated expression of target genes involved in kidney physiology and development in vitro. Methods Heterozygous MIR484 knockout HEK293 and homozygous MIR185 knockout HEK293 cell lines were used as models depicting the deletion of the frequently affected miRNA genes by CAKUT-associated CNVs. After treatment with the corresponding miRNA mimics, the levels of the target genes have been compared to the non-targeting control treatment. For both investigated miRNAs, MDM2 and PKD1 were evaluated as common targets, while additional 3 genes were investigated as targets of each individual miRNA (NOTCH3, FIS1 and APAF1 as hsa-miR-484 targets and RHOA, ATF6 and CDC42 as hsa-miR-185-5p targets). Results Restitution of the corresponding miRNA levels in both knockout cell lines has induced a change in the mRNA levels of certain candidate target genes, thus confirming the potential to alleviate the CNV effect on miRNA expression. Intriguingly, HEK293 WT treatment with investigated miRNA mimics has triggered a more pronounced effect, thus suggesting the importance of miRNA interplay in different genomic contexts. Conclusions Dysregulation of multiple mRNA targets mediated by CNV-affected miRNAs could represent the underlying mechanism behind the unresolved CAKUT occurrence and phenotypic variability observed in CAKUT patients. Characterizing miRNAs located in CNVs and their potential to become molecular targets could eventually help in understanding and improving the management of CAKUT.

Background/Aim. The renin-angiotensin system (RAS) is linked to the development of atherosclerosis (As), including its initiation and progression. Besides the well-known angio-tensin-converting enzyme (ACE), two newer RAS family members are related to vascular remodeling - ACE2 as a homolog of ACE and collectrin [transmembrane protein 27 (TMEM27)] as a homolog of ACE2. Up to now, a limited number of studies have examined the expression of these RAS components in advanced carotid plaque (CP) tissue based on the sex of the patients and plaque phenotypes (PPs). There are two ultrasonographically defined PPs - the hypoechogenic plaque (HoP) and the hyperechogenic plaque (HerP) phenotype. The aim of the study was to investigate whether there was a correlation between the expression of RAS components in the CP and the sex and PPs of patients. Methods. We examined 74 patients with advanced CP who underwent carotid endarterectomy. The intraplaque expression of RAS components was determined with the real-time polymerase chain reaction, using the TaqMan® gene expression assays and Western blot. A two-way ANOVA followed by a post-hoc Tukey test was performed for the statistical analysis of results. Results. No interaction was recorded between the sex of the patients and PPs in influencing the relative expression of ACE and TMEM27 messenger RNA (mRNA) (p > 0.05). In 56.06% of plaque samples, no expression of ACE2 mRNA was detected. Among the plaques where ACE2 mRNA expression was detected, its expression level was higher in females with the HoP phenotype compared to females with the HerP phenotype (p < 0.001). In patients with the HoP phenotype, females had higher expression of ACE2 mRNA than males (p < 0.05). In the male study group, ACE protein levels were significantly lower in the HoP phenotype compared to the HerP phenotype (p < 0.001). Fe-males with the HoP phenotype had significantly higher ACE protein levels than males with the HoP phenotype (p < 0.0001). Conclusion. Ou, Renin-angiotenzin sistem (RAS) povezan je sa razvojem ateroskleroze (As), uključujući njen nastanak i progresiju. Pored dobro poznatog angiotenzinkonvertujućeg enzima (angiotensin-converting enzyme – ACE), dva nova člana RAS familije povezana su sa remodelovanjem zidova krvnih sudova – ACE2 kao homolog ACE i kolektrin [transmembrane protein 27 (TMEM27)] kao homolog ACE2. Do sada je mali broj studija ispitivao ekspresiju komponenti RAS sistema u tkivu uznapredovalog karotidnog plaka (KP) u odnosu na pol bolesnika i fenotip plaka (FP). Postoje dva tipa KP definisana primenom ultrazvuka – fenotip hipoehogenog plaka (HoP) i fenotip hiperehogenog plaka (HerP). Cilj rada bio je da se ispita da li postoji korelacija između ekspresije komponenti RAS u KP i pola i FP bolesnika. Metode. Ispitano je 74 bolesnika sa uznapredovalim KP koji su bili podvrgnuti operativnoj proceduri karotidne endarterektomije. Ekspresija komponenti RAS sistema u tkivu plaka utvrđena je lančanom reakcijom polimeraze u realnom vremenu (real-time polymerase chain reaction)primenom eseja TaqMan® tehnologije i metode Western blota. Dvosmerna analiza varijanse i Tukey post-hoc test korišćen su za statističku obradu rezultata. Rezultati. Nije utvrđena interakcija FP i pola bolesnika u uticaju na relativnu ekspresiju informacione RNK (iRNK) za ACE i TMEM27 (p > 0,05). U 56,06% uzoraka plaka nije detektovana ekspresija iRNK za ACE2. U plakovima u kojima je detektovana ekspresija iRNK za ACE2, njen nivo bio je viši kod žena sa HoP u poređenju sa ženama sa HerP (p < 0,001). U grupi bolesnika sa fenotipom HoP, žene su imale viši nivo iRNK za ACE2 nego muškarci (p < 0,05). U grupi muškaraca, nivoi ekspresije ACE proteina bili suznačajno niži u fenotipu HoP u poređenju sa HerP (p < 0,001). Žene sa fenotipom HoP imale su značajno viši nivo ACE proteina u poređenju sa muškarcima sa HoP (p < 0,0001). Zaključak. Naši rezultati pokazali su da postoje promene nivoa ekspresije ACE i ACE2, na nivou proteina i iRNK u uzn

Background Congenital anomalies of the kidney and urinary tract (CAKUT) represent a frequent cause of pediatric kidney failure. CNVs, as a major class of genomic variations, can also affect miRNA regions. Common CNV corresponding miRNAs (cCNV-miRNAs) are functional variants regulating crucial processes which could affect urinary system development. Thus, we hypothesize that cCNV-miRNAs are associated with CAKUT occurrence and its expressivity. Methods The extraction and filtering of common CNVs, identified in control samples deposited in publicly available databases gnomAD v2.1 and dbVar, were coupled with mapping of miRNA sequences using UCSC Genome Browser. After verification of the mapped miRNAs using referent miRBase V22.1, prioritization of cCNV-miRNA candidates has been performed using bioinformatic annotation and literature research. Genotyping of miRNA gene copy numbers for MIR9-3, MIR511, and MIR1299, was conducted on 221 CAKUT patients and 192 controls using TaqMan™ technology. Results We observed significantly different MIR9-3 and MIR1299 gene copy number distribution between CAKUT patients and controls (Chi-square, P = 0.006 and P = 0.0002, respectively), while difference of MIR511 copy number distribution showed nominal significance (Chi-square, P = 0.027). The counts of less and more than two of MIR1299 copy numbers were more frequent within CAKUT patients compared to controls (P = 0.01 and P = 0.008, respectively) and also in cohort of patients with anomalies of the urinary tract compared to controls (P = 0.016 and P = 0.003, respectively). Conclusions Copy number variations of miRNA genes represent a novel avenue in clarification of the inheritance complexity in CAKUT and provide potential evidence about the association of common genetic variation with CAKUT phenotypes.

Background The MMP-9 is a known player in atherosclerosis, yet associations of the MMP-9 -1562 C/T variant (rs3918242) with various atherosclerotic phenotypes and tissue mRNA expression are still contradictory. This study aimed to investigate the MMP-9 -1562 C/T variant, its mRNA and protein expression in carotid plaque (CP) tissue, as a risk factor for CP presence and as a marker of different plaque phenotypes (hyperechoic and hypoechoic) in patients undergoing carotid endarterectomy. The MnSOD as an MMP-9 negative regulator was also studied in relation to CP phenotypes. Methods and results Genotyping of 770 participants (285 controls/485 patients) was done by tetra-primer ARMS PCR. The MMP-9 mRNA expression in 88 human CP tissues was detected by TaqMan® technology. The protein levels of MMP-9 and MnSOD were assessed by Western blot analysis. The MMP-9 -1562 C/T variant was not recognized as a risk factor for plaque presence or in predisposing MMP-9 mRNA and protein levels in plaque tissue. Patients with hypoechoic plaques had significantly lower MMP-9 mRNA and protein levels than those with hyperechoic plaque (p = 0.008, p = 0.003, respectively). MnSOD protein level was significantly higher in hypoechoic plaque compared to hyperechoic (p = 0.039). MMP-9 protein expression in CP tissue was significantly affected by sex and plaque type interaction (p = 0.009). Conclusions Considering the differences of MMP-9 mRNA and protein expression in CP tissue regarding different plaque phenotypes and the observed sex-specific effect, the role of MMP-9 in human atherosclerotic plaques should be further elucidated.

Background: Right ventricular (RV) dysfunction is recognized as a cardinal prognostic marker in heart failure (HF) patients. Myocardial infarction (MI) is often followed by unrecognized RV dysfunction, which can be associated with worse outcome. It is recently shown that the ratio between TAPSE and PASP (RV/PA) may depict cardiopulmonary hemodynamics better than the two parameters alone. Aim: To evaluate the interactions between left ventricular (LV) and RV function in early phase of MI and to assess the prognostic significance of RV/PA coupling in patients with first MI during 5 years follow up. Methods: The prospective study included 144 patients with the first MI treated with the primary percutaneous coronary intervention (p PCI) who underwent Doppler echocardiography within 2±1 days of MI. LV function analysis included: LV ejection fraction (EF), ratio between early diastolic velocity and tissue annular velocity (E/e) and global longitudinal strain (GLS). RV function and RV-PA interaction was expressed as ratio between TAPSE and PASP. During the five-year follow-up, major cardiovascular events and especially hospitalization for HF were analyzed. Results: Progressive RV/PA uncoupling was associated with higher degree of LV impairment and dysfunction (EF p<0.001, E/e p=0.002, GLS p<0.001) and severity of mitral regurgitation (p=0.013). Lower baseline RV/PA coupling significantly reflects the frequency of hospitalizations for HF in the population of patients with first MI during five-year follow-up (0.62 v.s.0.51, p=0.021). After multivariate adjustment RV/PA remained an independent predictor of all major cardiac events (MACE) after five years (OR 14.0 [1.5–130.8], p=0.019). Conclusion: A lower baseline RV-PA coupling, reflecting a higher degree of LV-induced pulmonary hypertension and secondary RV-dysfunction, is associated with decline of LV function in early phase of MI, and is independently associated with worse prognosis after five years. The value of RV-PA ra

Last decade provided multiple evidence that link disturbances in metabolic processes and energy metabolism with diseases of central nervous system and neurodegeneration. Initial phases of insulin resistance (IR) are present in natural course of multiple sclerosis (MS) and leptin was recognized as a player in MS pathophysiology and moreover cognitive decline. We aimed to investigate association of genetic variants in leptin (LEP) rs7799039, its receptor LEPR rs1137101 and proliferator-activated receptor gamma co-activator 1-alpha (PGCA1A) rs8192678 with IR parameters (HOMA-IR index, area under the curve for insulin and glucose, Cederholm insulin sensitivity index (ISIced), the insulinogenic index in the first 30 min of oral glucose tolerance test (OGTT) in patients with MS. Seventy eight relapsing-remitting patients in clinical remission, free of corticosteroids for at least three months, were included in the study. None of the 3 variants’ genotypes were associated with HOMA-IR index, area under the curve for insulin and glucose and the insulinogenic index in the first 30 min of OGTT. PGC1A variant was significantly associated with ISIced (Kruskal-Wallis ANOVA, p = 0.04). Leptin gene variant was significantly associated with impaired GT (p=0.029 adjusted for gender and other two variants). None of the variant showed association with IR. In conclusion, we found that genetic variants in leptin signalling pathway affect glucose tolerance and insulin sensitivity in patients with MS. As both, leptin and PGC1A have role in preventing neuronal death and reducing oxidative stress neuronal damage current results favour further investigation toward preserving cognitive status and neuroprotection in MS.

Introduction: Congenital anomalies of the kidney and urinary tracts(CAKUT) are a diverse spectrum of defects with complex etiology and not fully explained genetic background. miRNA-containing copy number variants (CNVs) are described as genetic risk factor for the disease development. We aimed to identify miRNAs with the maximum regulatory coverage of previously reported differentially expressed genes in CAKUT tissue compared to controls and bioinformatically characterize a set of these miRNAs which are located in common CNVs. Methods: Differentially expressed genes were identified from ureter tissue transcriptome open data GSE83946 from 15 CAKUT patients and 7 healthy controls, generated in house previously. miRPathDB v2.0 was used for identification of miRNAs with maximum coverage of DEGs(miRNAs which complimentarily regulate all DEGs). Mapping of maximum coverage miRNAs onto common CNVs (frequency >0.2) was performed using UCSC genome browser and gnomAD database. miRNA mapping common CNVs were further bioinformatically analyzed using miRPathDB v2.0. Results: In a maximum coverage set of 50 miRNAs interacting with DEGs in CAKUT, we have identified 3 miRNA geneslocated in the common CNVs(hsa-miR-663b, hsa-miR-3180-3p and hsa-miR-1302). Using Reactome database we identified all three miRNAsto be significantly enriched in the pathway Neuronal System: -log(p-value)>2.326 for hsa-miR-1302; -log(p-value)>1.556 for hsa-miR-3180-3p; and -log(pvalue)>1.703 for hsa-miR-663b. Conclusion: CAKUT is characterized with variable penetrability and expressivity and often followed with other comorbiditiessuch as neurodevelopmental disorders. miRNAsinvolved in DEG networks and prone to CNV effects could present modulating factors of the disease phenotype. Further studies should provide additional evidence about hsa-miR-1302, hsa-miR-3180-3p and hsa-miR-663b involvements in CAKUT etiology

Molecular background and biomarkers of highly heterogenous and hardly predictable disease progression among relapse-onset MS patients are of high research interest. In the current pilot study, we aimed to employ next-generation sequencing to investigate the expression of whole small non-coding microRNAs (miRNome) in two groups of MS patients with highly distinctive progression phenotype: one with fast progressing, severely disabling course vs. mild course of MS, longitudinally followed 10 years. Peripheral blood mononuclear cells (PBMC) miRNome data was obtained from mild phenotype MS (n=4 patients) and progressive phenotype MS (n=5 patients), using TakaraBio SMARTer smRNA-Seq Kit on iSeq100 (Illumina). Pre-processing of raw sequencing data, quality control and miRNA differential expression analysis was performed using sRNAtoolbox pipeline. Functional interpretation of differentially expressed miRNA target genes was done in DIANA-miRPathv3.0. Tarbase v8.0 served as a resource of miRNA:gene interactions. Achieved read depth was approximately 1 million raw reads/sample, allowing detection of up to 92 mature miRNAs after genome alignment and miRbase v22 annotation. Differential expression analysis identified the significant upregulation of hsa-miR-23c (log2FC=4.29, Padj= 0.03) in progressive phenotype. Top significantly enriched KEGG pathways in hsa-miR-23c targets suggested regulation of molecular pathways involved in autoimmunity (antigen presentation, Epstein-Barr virus infection) and cancer. In conclusion, this pilot study indicates phenotype-related differences in expression of miRNAs, molecules with high regulatory and biomarker properties. Although detected in PBMC, has-miR-23c is highly expressed in the brain and target MS relevant genes such as, HLA (A, B, C), transferrin receptor, Nrf2, recently proposed to play important role in neurodegeneration.

The significance of CD8+ T cell central nervous system migration and activation in the progression of glioblastoma is well documented. However, molecular signaling pathways regulation related to migration and activation in CD8+ cells in glioblastoma is scarce. Therefore we have analyzed the molecular pathway regulation in differentially expressed mRNAs of tumor infiltrating vs. peripheral blood CD8+ T cells from glioblastoma patients. Tumor-infiltrating vs. peripheral blood differentially expressed mRNAs were obtained by analyzing the FASTAQ files on the Galaxy platform using the LimmaVoom tool with filtering low count mRNAs (CPM > 2). We used publically avaliable FASTAQ files with CD8+ T cells mRNA sequencing data deposited at NCBI’s GEO database (accession number GSE171197). The differentially expressed mRNA were analyzed with Qiagen’s Ingenuity pathway analysis (p adj. cutoff 0.05). Protein-protein interaction network was constructed on the NetworkAnalyst platform using the IMeX database with minimal order parameters. The top rated disease canonical pathway was the multiple sclerosis (MS) signaling pathway, with 18 differentially expressed mRNA hits (out of possible 222), p adj. = 0.0009 and Z score = 2.828, implying significant upregulation of this pathway in tumor-infiltrating CD8+ T cells. The MS signaling pathway describes the molecular cascade which leads to the autoimmune phenotype in lymphocytes, including activation and central nervous tissue infiltration. To further specify the aspects of the canonical MS signaling pathway which might influence tumor infiltrating phenotype we have constructed a minimal order protein-protein interaction network. Results showed a number of lymphocyte migration and activation KEGG terms within the network, such as: TNF signaling pathway (p adj. = 0.0000115), IL-17 signaling pathway (p adj. = 0.00000427), sphingolipid signaling pathway (p adj. = 0.00171), NF-kappa B signaling pathway (p adj. = 0.0000694) and TCR signaling pa

Congenital anomalies of the kidney and urinary tract (CAKUT) represent structural and functional urinary system malformations and take place as one of the most common congenital malformations with an incidence of 1:500. Ureteral obstruction-induced hydronephrosis is associated with renal fibrosis and chronic kidney diseases in the pediatric CAKUT. We aimed to construct interaction network of previously bioinformatically associated miRNAs with CAKUT differentially expressed genes in order to prioritize those associated with fibrotic process and to experimentally validate the expression of selected miRNAs in CAKUT patients compared to control group. We constructed interaction network of hsa-miR-101-3p, hsa-miR-101-5p and hsa-miR-29c-3p that showed significant association with fibrosis. The top enriched molecular pathway was extracellular matrix-receptor interaction (adjusted p = .0000263). We experimentally confirmed expression of three miRNAs (hsa-miR-29c-3p, hsa-miR-101-3p and hsa-miR-101-5p) in obstructed ureters (ureteropelvic junction obstruction and primary obstructive megaureter) and vesicoureteral reflux. The hsa-miR-29c-3p was shown to have lower expression in both patient groups compared to controls. Relative levels of hsa-miR-101-5p and hsa-miR-101-3p showed significant positive correlations in both groups of patients. Statistically significant correlation was observed between hsa-miR-101 (-3p and -5p) and hsa-miR-29c-3p only in the obstructed group. The significant downregulation of anti-fibrotic hsa-miR-29c-3p in obstructive CAKUT could explain activation of genes involved in fibrotic processes. As miRNAs are promising candidates in therapeutic approaches our results need further measurement of fibrotic markers or assessment of extent of fibrosis and functional evaluation of hsa-miR-29c.

Galectin-3 is encoded by LGALS-3, located in a unique haplotype block in Caucasians. According to the Tagger server, rs4040064, rs11628437, and rs7159490 cover 82% (r2 > 0.8) of the genetic variance of this HapBlock. Our aims were to examine the association of their haplotypes with first myocardial infarction (MI), changes in left ventricular echocardiographic parameters over time, and impact on plasma galectin-3 and LGALS-3 mRNA in peripheral blood mononuclear cells, both 6 months post-MI. The study group consisted of 546 MI patients and 323 controls. Gene expression was assessed in 92 patients and plasma galectin-3 in 189 patients. Rs4040064, rs11628437, rs7159490, and LGALS-3 mRNA expression were detected using TaqMan® technology. Plasma galectin-3 concentrations were determined by the ELISA method. We found that the TGC haplotype could have a protective effect against MI (adjusted OR 0.19 [0.05–0.72], p = 0.015) and that the GAC haplotype had significantly higher galectin-3 concentrations (48.3 [37.3–59.4] ng/mL vs. 18.9 [14.5–23.4] ng/mL, p < 0.0001), both in males and compared to the referent haplotype GGC. Higher plasma Gal-3 was also associated with higher NYHA class and systolic dysfunction. Our results suggest that variants tagging LGALS-3 HapBlock could reflect plasma Gal-3 levels 6 months post-MI and may have a potential protective effect against MI in men. Further replication, validation, and functional studies are needed.