Integration of miRNA-lncRNA-mRNA profiles in liver tissue from EpCAM knockout mice

The epithelial cell adhesion molecule (EpCAM) is highly expressed in the liver during development and diseases. However, its role in the development and pathology of liver remains to be explored. The liver tissues of EpCAM-/- and wildtype (WT) mice at P0 stage were used for RNA sequencing. The differently expressed miRNAs, lncRNAs and mRNAs were selected and confirmed by qPCR. The expression of metabolism-related gene SET domain bifurcated 2 (Setdb2) was significantly increased in the liver of EpCAM-/- mice; the triglyceride (TG) and total cholesterol (TC) levels in the liver were also markedly decreased in EpCAM-/- mice. The microRNA (miRNA)-long noncoding RNA (lncRNA)-mRNA regulatory networks indicated that EpCAM may play important roles in glucose and lipid metabolism of the liver during development and in disease. The comprehensive miRNA, lncRNA and mRNA expression profiles in the developing liver of EpCAM-/- mice established here might help to elucidate functions and mechanisms of EpCAM during development and in diseases of the liver.

Association of rs780094 and rs1260326 glucokinase regulatory protein gene polymorphisms with dyslipidemia in a group of Serbian acute ischemic stroke patients

Although genetic variations rs780094 and rs1260326 of the glucokinase regulatory protein gene (GCKR) could be associated with lipid profile imbalance, their influence on acute ischemic stroke (AIS) risk has not yet been established. The aim of this study was to investigate the influence of GCKR single nucleotide polymorphisms (SNPs) rs780094 and rs1260326 on lipid profile parameters in patients with AIS, and to evaluate the association of these SNPs with the risk of AIS. In a casecontrol study, a total of 148 subjects were screened for GCKR rs780094 and rs1260326 SNPs using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. The lipid profile was determined based on serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triacylglycerol (TG) concentrations. The frequencies of the minor rs780094T allele and the minor rs1260326T allele were significantly lower in AIS patients compared to controls. The rs780094TT genotype and the rs1260326TT genotype were associated with decreased risk of AIS compared to wildtype carriers. In conclusion, this is the first study implying that decreased risk of AIS in rs780094 and rs1260326 homozygous minor allele carriers is not caused by dyslipidemia, but possibly by the lack of coagulation factor glycosylation.

Correlation between echocardiographic findings and biochemical markers in term newborns with moderate to severe perinatal asphyxia

Perinatal asphyxia (PA) is a condition characterized by a gas exchange disorder due to a lack of blood flow or gas exchange, with potential multiorgan dysfunction. Our study aimed to determine the correlation between biochemical markers and echocardiography findings in a group of asphyxiated newborns. The prospective cohort study included 120 neonates (52/120 with PA) treated at a tertial referral pediatric center, from 2012 to 2014. A moderate-strong positive correlation was recorded between the transtricuspid pressure gradient (TRPG) and serum lactate, and between TRPG and NT-proBNP in the PA group (P<0.001) on the 1st day of life. A moderate positive correlation was found between NT-proBNP, lactate and troponins on one side, and TRPG on the other in the PA group after the 2nd measurement. Multinomial regression analysis showed that the lactate level was an independent factor for survival on the 1st (odds ratio (OR) 41.3, 95%confidence interval (CI) 2.14-797.1) and 3rd (OR 136.4, 95% CI 2.27-8206.7) days. Our research confirmed a significant correlation between echocardiographic and biochemical parameters of the myocardial lesion and cardiac function. Due to their complementarity, the use of the biochemical and echocardiographic parameters may be conditioned by their availability.

Amelioration of neuropilin-1 and rage/matrix metalloproteinase-2 pathway-induced renal injury in diabetic rats by rosuvastatin

Advanced glycation end-products (AGEs) induce the production of reactive oxygen species (ROS) and extra cellular matrix (ECM) degradation via suppression of neuropilin-1 (NRP-1) and interaction with AGE-receptors (RAGE). This study aimed to reveal whether modulation of NRP-1 by rosuvastatin (RT) prevents AGE-induced renal injury via targeting RAGE/matrix metalloproteinase-2 (MMP-2) signaling in diabetic rats. Treatment with RT ameliorated the altered level of markers of glycemic control, renal injury, cholesterol, triglyceride (TG) and hepatic HMG-CoA reductase activity; the level of circulatory carboxymethyl-lysine (CML) and the accumulation of fluorogenic-AGEs in renal tissue was reduced; the expression of renal NRP-1, a checkpoint target, was stimulated; the transcription of RAGE, NF?B-2, TGF-?1 and MMP-2 was suppressed; the circulatory carbonyl content (CC) and paraoxonase-1 (PON-1) activity was ameliorated, and renal histopathological features were attenuated as evidenced by improved glomerular appearance, Bowman?s space and abundant podocytes in kidneys. In conclusion, RT exhibited the potential to counteract diabetes and AGE-induced renal pathologies via stimulation of NRP-1, suppression of RAGE, and of genes responsible for ECM disintegration (MMP-2) and the inflammatory response (NF?B-2).

Immunohistochemical analysis of the arterial supply and mast cells of the trigeminal ganglion

The aim of this study was to quantify the distribution of microvessels and mast cells in all three parts of the trigeminal ganglion (TG). Statistical analyses were applied to investigate possible micromorphological regional differences in their density. Five serially sectioned human TGs were prepared for CD34 and mast cell tryptase immunostaining. The following quantifications were performed in microscopic fields of three parts of the TG: microvessel density (MVD), mast cell density (MCD) and ganglionic cell count. The density of CD34-positive microvessels was not significantly different in any of the three observed parts of the TG. The distribution of neurons showed no significant statistical difference in three parts of the TG. There was no difference in the density of tryptase-positive mast cells within the TG, but there was an abundant presence of mast cells in the periganglionic dural and subdural tissues, a finding hitherto not reported. We can say that there is a homogenous vascular pattern within the TG which excludes local predominance in pathogenesis of trigeminal neuralgia. Second, and more important, the finding of peri-trigeminal mast cells indicates their important role in migraine pain and confirms their degranulation as the main therapeutic goal for this condition.

Two long non-coding RNAs, CAT179 and CAT 1796, differentiate between benign prostate hyperplasia and prostate cancer

Several long non-coding RNAs (lncRNAs) have recently emerged as potential biomarkers in cancer biology. In the present study, we examined the expression of four lncRNAs (CAT179, CAT1796, PRCAT47, and CAT1066) to evaluate their ability to discriminate prostate tumors from benign prostate hyperplasia (BPH). Expression of these four lncRNAs was examined in 20 prostate cancer and 20 benign prostate hyperplasia (BPH) samples, as well as in urine samples (11 BPH, and 11 cancer). Total RNA was extracted for cDNA syntheses. The expression of the candidate lncRNAs was evaluated by quantitative real-time PCR (qRT-PCR). The lncRNAs CAT1796 and CAT179 were both upregulated in prostate cancer compared to BPH clinical samples (P<0.05). ROC curve analysis showed that CAT1796 had high sensitivity and specificity for diagnosis of prostate cancer (AUC=0.8151[95%CI 0.65-0.97]), suggesting that CAT1796 lncRNA could be a prostate cancer biomarker.

Morphometric analysis of the human endoneurial extracellular matrix components during aging

The aim of this study was to analyze the expression of extracellular matrix (ECM) proteins in human endoneurium during aging. We harvested 15 cadaveric sural nerves, distributed in 3 age groups (I: 25-44, II: 45-64, III: 65-86 years old). Histological sections were stained immunohistochemically for the presence of collagen type I, type IV and laminin, and the ImageJ processing program was used in morphometrical analysis to determine the percentages of these endoneurial proteins. In two younger groups, the endoneurial matrix of the sural nerve was composed from about equal proportions of these proteins, which may be considered a favorable microenvironment for the regeneration of nerve fibers. Linear regression analysis showed a significant increase in endoneurial collagen type IV with age, while collagen type I and laminin significantly decreased during the aging process. In cases older than 65 years, remodeling of the endoneurial matrix was observed to be significantly higher for the presence of collagen type IV, and lower for the expression of collagen type I and laminin. This age-related imbalance of ECM proteins could represent a disadvantageous microenvironment for nerve fiber regeneration in older adults. Our findings contribute to the development of therapeutic approaches for peripheral nerve regeneration.

The role of ccr5 polymorphism in colorectal cancer and liver metastasis in the Tunisian population

Chemokines and their receptors are involved in cancer initiation and progression, including colorectal cancer (CRC) and liver metastasis formation. Our aim was to elucidate C-C chemokine receptor type 5 (CCR5) gene polymorphism (CCR5?32) impact on CRC and colorectal cancer liver metastases (CRLM) occurrence risk. We analyzed the CCR5 gene mutational status in 108 primary CRC cases, 35 CRLM and 248 healthy individuals, and evaluated CCR5 expression in healthy tissue and tumors. Rare allele ??32? was more frequent in controls (7.2% vs 2.8% in CRC). All 35 metastases had wild-type CCR5. Our analysis showed that CCR5 wild type has a significant risk of 2.73-fold (95% CI=1.22-7.31) to cause CRC while ?32 reduced the risks 0.36-fold (95% CI=0.13-0.82). For CRC, CCR5 correlated with left-sided tumors and liver metastases (P=0.040 and P= 0.039 respectively). As for CRLM, no correlation was found. Immunohistochemical profile analysis of CCR5 revealed a significant association with the male gender (P=0.049) and non-mucinous carcinomas (P< 0.001) in primary CRC. CCR5 expression revealed an association with the degree of tumor differentiation for both CRC and CRLM (P < 0.001). CCR5?32 might be a protective factor against CRC development and dissemination.

Thyroid fibrous band and levator glandulae thyroideae muscle: Two different structures associated with the pyramidal lobe of the thyroid gland

We investigated two structures that are in close association with the pyramidal lobe of the thyroid gland. Our investigation was performed using microdissection and histological examination in 106 human postmortem specimens. The first investigated structure was identified as the thyroid fibrous band that was present in 28.3% of cases. This band was always associated with the pyramidal lobe (which was significantly longer and thicker when associated with this band) and it had a constant hyo-pyramidal extension; it was located close to the midsagittal plane and predominantly composed of dense irregular connective tissue. The second investigated structure was the levator glandulae thyroideae muscle, which was associated with the pyramidal lobe in only 13.6% of cases. This muscle had a double extension, hyo-pyramidal and laryngo-pyramidal, located farther from the midsagittal plane, it was longer and thinner than the thyroid fibrous band and predominantly composed of striated muscle fibers. We confirmed our hypothesis that the thyroid fibrous band, which may be considered as the partial fibrous remnant of the thyroglossal duct and levator glandulae thyroideae, and which may be considered as infrahyoid or laryngeal muscle, are two different structures of the thyroid gland.

Neural pathways underlying the interplay between emotional experience and behavior, from old theories to modern insight

Emotions are specific psychological states brought about by neurophysiological changes associated with feelings, thoughts and behavioral responses. Emotions were considered as irrational experiences beyond the domain of logical perception because of their intertwinement with mood, temperament, creativity, motivation and personality. Through the centuries, emotions have been the focus of research among great classical philosophers, doctors, neuropsychologists, neuroscientists, neurologists and psychiatrists. The neurophysiological basis of behavior, such as emotional facial expression, and autonomic events in the physiological theory of William James and James-Lange and modified by Cannon-Bard, was followed by the two-factor theory of emotions of Schachter-Singer and Lazarus? higher-order cognitive evaluation. Four components that influence each other represent the concept of emotions and complete the overall emotional experience, and these are: autonomous (increase in heart rate, blood pressure); somatic (body language, facial expressions); cognitive (control, management), and subjective feeling (emotion, individual experience). The interplay between emotions and cognition has been the subject of research. Emotions can be evoked reflexively by simple physical stimuli (bottom-up), but can also be complex reactions involving cognitive, physiological and behavioral reactions (top-down). The amygdala, the ?alert" or ?neural alarm? structure, is responsible for conditioning fear, while the medial prefrontal cortex participates in emotion self-regulation and decision making.