Diurnal variation of clock genes expression and other sleep-wake rhythm biomarkers among acute ischemic stroke patients.

There is accumulating evidence about sleep-wake rhythm disturbances as potential modifiable risk factors of both incident and recurrent stroke and less favorable outcomes after stroke. To our best knowledge this is the first study designed to investigate clock genes expression profiles in ischemic stroke patients and their relations to other biological and behavioral sleep-wake rhythm biomarkers, sleep structural and clinical stroke features. Altogether, 27 ischemic stroke patients (20 males) with the median age of 56 years and 25 gender and age matched controls were investigated with neurological and objective examination, scales, polysomnography, actigraphy and 24-h blood sampling for melatonin and clock genes profiles. Median melatonin plasma concentrations at four time points at 7, 11 p.m., 3 a.m. and 12 p.m. did not differ significantly between patients and controls, only early morning melatonin concentration at 7 a.m. was significantly lower and cortisol plasma concentration - significantly higher among stroke patients. All four clock genes (ARNTL (BMAL1), NR1D1 (Rev-erbα/ß), PER1, and PER3) showed significant time-of-day variation in both patients' and controls' groups, except expression of NR1D1 (Rev-erbα/ß) at 7 a.m. and PER1 at 12 p.m. differed significantly. In conclusion, acute ischemic stroke patients tended to preserve most of diurnal variation of sleep-wake rhythm molecular patterns. Nevertheless, early morning time point showing higher cortisol and lower melatonin concentrations and lower NR1D1 (Rev-erbα/ß) expression, as well as lower PER1 midday expression reflect specific circadian desynchrony features in different loops of the molecular circadian clock system.

miRNome Profiling and Functional Analysis Reveal Involvement of hsa-miR-1246 in Colon Adenoma-Carcinoma Transition by Targeting AXIN2 and CFTR.

Regulatory changes occurring early in colorectal cancer development remain poorly investigated. Since the majority of cases develop from polyps in the adenoma-carcinoma transition, a search of early molecular features, such as aberrations in miRNA expression occurring prior to cancer development, would enable identification of potentially causal, rather than consequential, candidates in the progression of polyp to cancer. In the current study, by employing small RNA-seq profiling of colon biopsy samples, we described differentially expressed miRNAs and their isoforms in the adenoma-carcinoma transition. Analysis of healthy-adenoma-carcinoma sequence in an independent validation group enabled us to identify early deregulated miRNAs including hsa-miR-1246 and hsa-miR-215-5p, the expressions of which are, respectively, gradually increasing and decreasing. Loss-of-function experiments revealed that inhibition of hsa-miR-1246 lead to reduced cell viability, colony formation, and migration rate, thereby indicating an oncogenic effect of this miRNA in vitro. Subsequent western blot and luciferase reporter assay provided evidence of hsa-miR-1246 being involved in the regulation of target AXIN2 and CFTR genes' expression. To conclude, the present study revealed possible involvement of hsa-miR-1246 in early colorectal cancer development and regulation of tumor suppressors AXIN2 and CFTR.

Time Evolution of Sublingual Microcirculatory Changes in Recreational Marathon Runners.

We aimed to evaluate changes in sublingual microcirculation induced by a marathon race. Thirteen healthy male controls and 13 male marathon runners volunteered for the study. We performed sublingual microcirculation, using a Cytocam-IDF device (Braedius Medical, Huizen, Netherlands), and systemic hemodynamic measurements four times: 24 hours prior to their participation in the Kaunas Marathon (distance: 41.2 km), directly after finishing the marathon, 24 hours after the marathon, and one week after the marathon. The marathon runners exhibited a higher functional capillary density (FCD) and total vascular density of small vessels at the first visit compared with the controls. Overall, we did not find any changes in sublingual microcirculation of the marathon runners at any of the other visits. However, in a subgroup of marathon runners with a decreased FCD compared to the subgroup with increased FCD, the subgroup with decreased FCD had shorter running time (190.37 ± 30.2 versus 221.80 ± 23.4 min, p = 0.045), ingested less fluids (907 ± 615 versus 1950 ± 488 mL, p = 0.007) during the race, and lost much more weight (-2.4 ± 1.3 versus -1.0 ± 0.8 kg, p = 0.041). Recreational marathon running is not associated with an alteration of sublingual microcirculation. However, faster running and dehydration may be crucial for further impairing microcirculation.