RESUMEN

Although the type and amount of salivary components are influenced by many factors, due to easy, quick, cheap, and noninvasive sampling method alongside with the existence of the vast majority of the substances found in peripheral blood and urine in it, in recent years saliva has been considered as an ideal biofluid for disease research. Salivary circular RNA (circRNA), as an endogenous RNA molecule with a great variety of regulatory potency, is becoming a novel focus for detecting wide range of local or systemic diseases. Expectantly, with characterization of many more circRNAs in saliva, their motifs, and target sites, they can be used routinely in personalized medicine.

Asunto(s)

RESUMEN

BACKGROUND/AIMS: MiRNAs transpire as promising elements in molecular medicine for the identification of new diagnostic, prognostic and targeting therapeutic biomarkers. This study consisted of four steps: First, to investigate one or a group of specific diagnostic miRNAs for Systemic Lupus Erythematosus (SLE) disease in patients with and without renal involvement, second, to identify cytokines genes' expression profiling, third, comparing the profiles with related amounts in the serum and finally, to study target-gene-mediated functional roles of miRNAs, which have been correlated to disease development and progression. METHODS: In order to use in microarray assays total RNA and miRNAs were isolated from blood and serum samples that were obtained from 16 SLE patients (9 with renal involvement and 7 without renal involvement). Taking coexistence of factors such as hypocomplementemia, positive ANA and anti-DNA into account, obtained data were processed. For each differentially expressed miRNA, potential target genes were predicted by microRNAorg, TargetScan and PITA prediction tools. Obtained mRNA profiling data were interrogated for the target genes. MiRNA and mRNA microarray results were confirmed by QRT-PCR. Finally, the amounts of cytokines were measured by multiplex ELISA method. RESULTS: The results of study showed that among differentially expressed miRNAs in SLE patients with renal involvement compared to those without renal involvement, hsa-miR-766-3p, may play pivotal roles in PI3K-AKT-mTOR pathway. In addition according to the obtained data it is suggested that blood-borne proinflammatory cytokines such as IL-4, IL-6 and TNF-α alongside with disease stage and severity may contribute to this differential expression of these miRNA which may be leading to insulin resistance. Finally, hsa-miR-621, which was differentially expressed in hypertensive SLE patients without renal involvement and a positive ANA test with its predicted target gene "Kallikrein-related peptidase 9" may play a role in the pathophysiology of hypertension in SLE. CONCLUSIONS: We reported some human miRNAs which were differentially expressed in SLE patients according to disease activity and renal involvement. Larger studies are necessary to confirm our findings and detect further biomarkers.

Asunto(s)

RESUMEN

BACKGROUND: Glucose is the preferred carbon and energy source in most organisms and plays an active role in the regulation of many biological processes. However, an excess of glucose leads to such undesirable conditions as diabetes and age-related diseases. Since Schizosaccharomyces pombe homologous of many human genes, it offers several advantages for the investigation of the molecular mechanisms underlying human disease and aging studies. We have identified two glucose-repression-resistant mutants (ird5 and ird11) of S. pombe. OBJECTIVES: We aimed to investigate the possible relationship between lifespan extension and oxidative stress response induced by exposure to hydrogen peroxide alongside the trehalose accumulation level by using the two S. pombe mutants (i.e. ird5 and ird11), which are repressed by glucose and are resistant to oxidative stress. MATERIALS AND METHODS: We employed trehalose accumulation measurement and colony-forming unit (CFU) counting using the ird mutants in exponential and stationary phases and compared them to the wild type grown in repressed, de-repressed, and stressed conditions to clarify the possible relationship between glucose signaling, oxidative stress response, and lifespan in S. pombe. RESULTS: The lifespan of the ird5 mutant was significantly longer that of either the ird11 mutant or the wild type cells. Under repressed condition, the trehalose content was increased remarkably on the 3rd day of the study in the ird11 mutant and the wild type. Under de-repressed condition, the level of intracellular trehalose was notably increased on the 3rd day in ird11. Under stressed condition, the trehalose level in ird11 was increased on the 3rd day as a pattern similar to that observed in the wild type. CONCLUSIONS: Our results demonstrated no significant correlation between the ird5 lifespan and the trehalose concentration. Likewise, the correlation between lifespan extension, trehalose accumulation, and cellular resistance to hydrogen peroxide was not significant.