Search

The purpose of this study was to determine whether the mitochondrial DNA (mitDNA) copy number in blood samples of patients with thyroiditis, benign nodules or malignant nodules is different from that in healthy individuals, and to examine whether mtDNAcn has the ability to distinguish between different thyroid diseases.This study consists of principal groups as thyroid patients and control group. The thyroid patient group comprised 30 patients with malignant nodules, 33 with benign nodules and 31 with thyroiditis, whereas the control group was composed of 21 healthy individuals. Blood samples were collected from the patients before treatment. Results were evaluated between groups.We could not find an adequate number of participants for inclusion to match the groups. Similarly, since there is a gender difference in terms of disease prevalence, it was not possible to pair the populations in terms of gender. Instead, the results were analyzed with an adjusted model, including man characteristics as cofounders. We found that the mtDNAcn of the thyroid patients was significantly lower than that measured for the control group (p = 0.01). Furthermore the mtDNAcn of the benign group was significantly lower than that measured in the control group (p = 0.0001). A similar significant difference was found between the thyroiditis group and the control group (p = 0.005).It was observed that mtDNAcn in the malignant group was significantly higher than that measured in the benign group (p = 0.004), which would indicate that it may be used as a diagnostic and therapeutic marker in thyroid diseases.

The guanine nucleotide exchange factor cytohesin-2 (ARNO) is a major activator of the small GTPase ARF6, and has been shown to play an important role(s) in cell adhesion, migration and cytoskeleton reorganization in various cell types and models of disease. Interestingly, dysregulated cell migration, in tandem with hyper-inflammatory responses, is one of the hallmarks associated with activated synovial fibroblasts (SFs) during chronic inflammatory joint diseases, like rheumatoid arthritis. The role of ARNO in this process was unknown but we hypothesized that the pro-inflammatory milieu of inflamed joints induces local activation of ARNO-mediated pathways in SFs, promoting an invasive cell phenotype that ultimately leads to bone and cartilage damage. Thus, we used small interference RNA to investigate the impact of ARNO on the pathological migration and inflammatory responses of murine SFs, revealing a fully functional ARNO-ARF6 pathway in SFs, which can be rapidly activated by IL-1β. Such activation promotes cell migration and formation of focal adhesions. Unexpectedly, ARNO was also shown to modulate SF-inflammatory responses, dictating the precise cytokine and chemokine expression profile. Our results uncover a novel role for ARNO in SF-dependent inflammation, that potentially links pathogenic migration with initiation of local joint inflammation, offering new approaches for targeting the fibroblast compartment in chronic arthritis and joint disease.

Aims Actin-binding protein filamin A (FLNA) regulates signal transduction important for cell locomotion, but the role of FLNA after myocardial infarction (MI) has not been explored. The main purpose of this study was to determine the impact of endothelial deletion of FLNA on post-MI remodelling of the left ventricle (LV). Methods and results We found that FLNA is expressed in human and mouse endothelial cells (ECs) during MI. To determine the biological significance of endothelial expression of FLNA, we used mice that are deficient for endothelial FLNA by cross-breeding adult mice expressing floxed Flna ( Flna o/fl) with mice expressing Cre under the vascular endothelial-specific cadherin promoter ( VECadCre+ ). Male Flna o/fl and Flna o/fl /VECadCre+ mice were subjected to permanent coronary artery ligation to induce MI. Flna o/fl /VECadCre+ mice that were deficient for endothelial FLNA exhibited larger and thinner LV with impaired cardiac function as well as elevated plasma levels of NT-proBNP and decreased secretion of VEGF-A. The number of capillary structures within the infarcted areas was reduced in Flna o/fl /VECadCre+ hearts. ECs silenced for Flna mRNA expression exhibited impaired tubular formation and migration, secreted less VEGF-A, and produced lower levels of phosphorylated AKT and ERK1/2 as well as active RAC1. Conclusion Deletion of FLNA in ECs aggravated MI-induced LV dysfunction and cardiac failure as a result of defective endothelial response and increased scar formation by impaired endothelial function and signalling.