👤 Andrew Mazurek

With the aim of identifying key proteins that play a role in the disorder tinnitus, interactions between proteins involved in thalamo-amygdala signaling under conditions of normal hearing (NH), acoustic stimulation (AS), and tinnitus (Tin) were studied. Three gene lists compiled from the GeneCards database using keywords were characterized by analyses of overlap, protein-protein interaction (PPI) networks, and by protein-enrichment analysis. Key proteins were selected on the basis of the degree and combined score value of the corresponding PPI network. In the NH process, BDNF, CASP3, and PVALB were identified as high-degree proteins (HDPs). In the AS process, BDNF, PVALB, and DLG4 are the top three HDPs; in the Tin process, these are BDNF, APP, and TNF. In the Tin process, key proteins appear that differ pre- and postsynaptically from those detectable in NH or AS. The glucocorticoid receptor NR3C1 and its interaction with FKBP5, a glucocorticoid receptor-induced co-chaperone, appear to be of particular importance for the emotional aspects of tinnitus. In tinnitus, the HDPs, together with their high-score interaction proteins, indicate processes of chronic neurodegeneration and of changes in transcription, intercellular communication, and in the survival and growth of neurons. Show less

Intrauterine development is a key period in human life. The foetal progress largely depends on the function of the placenta, whose responsibility is transportation and biosynthesis of fatty acids. Desaturation enzymes play a key role in placental fatty acid metabolism. Expression of genes coding for desaturases may be associated with pregnancy abnormalities. The objective of this study was to determine the transcriptional activity of the placental genes Fatty Acid Desaturases 1, 2 and 3 (FADS 1, 2 and 3) in women who gave birth to the infants appropriate for gestational age, large for gestational age, small for gestational age, with intrauterine growth restriction and born preterm. 34 pregnant women aged 21-37 years old participated in the study. The placental samples were taken from a site located 2-3 cm away from the umbilical cord attachment. The collected tissue sections were stored in RNAlater according to the manufacturer's protocol, until required for molecular analysis. The expression profiles of FADS1, FADS2 and FADS3 were determined with RT-qPCR. There was no difference in FADS1 and FADS2 expression between the groups. However, the differences in the expression of the FADS3 were found. Analysis of the FADS1, FADS2 and FADS3 transcription showed significant differences between most of the examined groups. Our findings suggest that the transcriptional activity of FADS genes changes with the severity of intrauterine disorders and is associated with foetal lipid disorders linked to a greater accumulation of fat in the foetal tissues. Show less

Coronary artery disease (CAD), which is the manifestation of atherosclerosis in coronary arteries, is the most common single cause of death and is responsible for disabilities of millions of people worldwide. Despite numerous dedicated clinical studies and an enormous effort to develop diagnostic and therapeutic methods, coronary atherosclerosis remains one of the most serious medical problems of the modern world. Hence, new markers are still being sought to identify and manage CAD optimally. Trying to face this problem, we have raised the question of the most predominant gastrointestinal hormones; glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), mainly involved in carbohydrates disorders, could be also used as new markers of incidence, clinical course, and recurrence of CAD and are related to extent and severity of atherosclerosis and myocardial ischemia. We describe GIP and GLP-1 as expressed in many animal and human tissues, known to be connected to inflammation and related to enormous noncardiac and cardiovascular (CV) diseases. In animals, GIP and GLP-1 improve endothelial function and lead to reduced atherosclerotic plaque macrophage infiltration and stabilize atherosclerotic lesions by directly blocking monocyte migration. Moreover, in humans, GIPR activation induces the pro-atherosclerotic factors ET-1 (endothelin-1) and OPN (osteopontin) but also has anti-atherosclerotic effects through secretion of NO (nitric oxide). Furthermore, four large clinical trials showed a significant reduction in composite of CV death, MI, and stroke in long-term follow-up using GLP-1 analogs for DM 2 patients: liraglutide in LEADER, semaglutide in SUSTAIN-6, dulaglutide in REWIND and albiglutide in HARMONY. However, very little is known about GIP metabolism in the acute phase of myocardial ischemia or for stable patients with CAD, which constitutes a direction for future research. This review aims to comprehensively discuss the impact of GIP and GLP-1 on atherosclerosis and CAD and its potential therapeutic implications. Show less

We carried out an admixture mapping study of lipid traits in two samples from Mexico City. Native American locus ancestry was significantly associated with triglyceride levels in a broad region of chromosome 11 overlapping the BUD13, ZNF259 and APOA5 genes. In our fine-mapping analysis of this region using dense genome-wide data, rs964184 is the only marker included in the 99% credible set of SNPs, providing strong support for rs964184 as the causal variant within this region. The frequency of the allele associated with increased triglyceride concentrations (rs964184-G) is between 30-40% higher in Native American populations from Mexico than in European populations. The evidence currently available for this variant indicates that it may be exerting its effect through three potential mechanisms: 1) modification of enhancer activity, 2) regulation of the expression of several genes in cis and/or trans, or 3) modification of the methylation patterns of the promoter of the APOA5 gene. Show less