MicroRNAs in Prion Diseases-From Molecular Mechanisms to Insights in Translational Medicine.

MicroRNAs (miRNAs) are small non-coding RNA molecules able to post-transcriptionally regulate gene expression via base-pairing with partially complementary sequences of target transcripts. Prion diseases comprise a singular group of neurodegenerative conditions caused by endogenous, misfolded pathogenic (prion) proteins, associated with molecular aggregates. In humans, classical prion diseases include Creutzfeldt-Jakob disease, fatal familial insomnia, Gerstmann-Sträussler-Scheinker syndrome, and kuru. The aim of this review is to present the connections between miRNAs and prions, exploring how the interaction of both molecular actors may help understand the susceptibility, onset, progression, and pathological findings typical of such disorders, as well as the interface with some prion-like disorders, such as Alzheimer's. Additionally, due to the inter-regulation of prions and miRNAs in health and disease, potential biomarkers for non-invasive miRNA-based diagnostics, as well as possible miRNA-based therapies to restore the levels of deregulated miRNAs on prion diseases, are also discussed. Since a cure or effective treatment for prion disorders still pose challenges, miRNA-based therapies emerge as an interesting alternative strategy to tackle such defying medical conditions.

NOS3 Polymorphisms Can Influence the Effect of Multicomponent Training on Blood Pressure, Nitrite Concentration and Physical Fitness in Prehypertensive and Hypertensive Older Adult Women.

Associations of endothelial nitric oxide synthase (NOS3) polymorphisms with hypertension and response to exercise training in prehypertensive and hypertensive older adult women remain unclear. This study used a multicomponent program (various capacities and motor skills) in the physical training intervention. It analyzed the influence of NOS3 polymorphisms [-786T > C, 894G > T (Glu298Asp), and intron 4b/a] on the response of blood pressure (BP), nitrite concentration, and physical fitness in older adult women. Fifty-two participants aged between 50 and 80 underwent body mass index, BP, 6-min walk, elbow flexion, and sit and stand-up tests to assess physical fitness. The intervention duration was 12 weeks, twice a week, on non-consecutive days. Each session lasted 90 min, maintaining an intensity between 13 (moderate) and 15 (intense), controlled by the Subjective Effort Perception Scale. Plasma/blood samples were collected to assess nitrite concentration and genotyping. The statistical analysis included Fisher's exact test and linear mixed-effects models. The multicomponent training's positive effect was observed with a similar response in both prehypertensive and hypertensive groups. However, carriers of different genotypes demonstrated different responses to training: the decreases in systolic and diastolic BP and increases in nitrite expected from the physical training were smaller in variant genotype than ancestral genotype carriers, especially in the hypertensive group. At positions -786T > C and Glu298Asp, only the ancestral genotypes showed a decrease in diastolic BP (Δ% = -8.1, and Δ% = -6.5, respectively) and an increase on nitrite (Δ% = 19.1, and Δ% = 24.1, respectively) in the hypertensive group. Our results show that the benefits of a multicomponent training intervention seem to be genotype-dependent. It should be possible to consider genetic variants when selecting an exercise treatment intervention.

Panagrolaimus superbus tolerates hypoxia within Gallium metal cage: implications for the understanding of the phenomenon of anhydrobiosis.

Panagrolaimus superbus nematodes are able to tolerate desiccation by entering into a peculiar state of suspended animation known as anhydrobiosis. When desiccated, anhydrobiotic organisms are also able to tolerate other physical stresses, as high and low levels of temperature and pressure. Here, we decided to investigate the tolerance of desiccated P. superbus to an unprecedented double stress - hypoxia within 99.99% Gallium (Ga) metal cage. The authors observed that regardless of the external relative humidity, desiccated P. superbus tolerated 7 d confined within the metal cage, displaying no negative effects on its survival and population growth rates over 40 d. The results evidence that anhydrobiosis also renders nematodes tolerant to otherwise lethal concentrations of Ga, in an oxygen-poor environment; thus, expanding its polyextremotolerance profile.Panagrolaimus superbus nematodes are able to tolerate desiccation by entering into a peculiar state of suspended animation known as anhydrobiosis. When desiccated, anhydrobiotic organisms are also able to tolerate other physical stresses, as high and low levels of temperature and pressure. Here, we decided to investigate the tolerance of desiccated P. superbus to an unprecedented double stress ­ hypoxia within 99.99% Gallium (Ga) metal cage. The authors observed that regardless of the external relative humidity, desiccated P. superbus tolerated 7 d confined within the metal cage, displaying no negative effects on its survival and population growth rates over 40 d. The results evidence that anhydrobiosis also renders nematodes tolerant to otherwise lethal concentrations of Ga, in an oxygen-poor environment; thus, expanding its polyextremotolerance profile.

ß2 adrenergic interaction and cardiac autonomic function: effects of aerobic training in overweight/obese individuals.

PURPOSE: To verify the influence of different volumes and intensities of aerobic exercise on cardiac autonomic function (CAF) through heart rate variability (HRV) analysis as well the influence of ß2 adrenergic receptor (ADRB2) variants in overweight/obese individuals. METHODS: 70 physically inactive adults were randomly allocated into the following 16-week training: 1-high-intensity interval training (HIIT) (n = 25, 1 × 4 min bout at 85-95%HR peak, 3×/week), 4-HIIT (n = 26, 4 × 4 min bouts at 85-95%HR peak, interspersed with 3 min of recovery at 50-70%HR peak, 3×/week), and moderate continuous training (MCT) (n = 19, 30 min at 60-70%HR peak, 5×/week). Before and after the exercise training, anthropometric, BP, cardiorespiratory fitness, and HRV measures were evaluated. R-R intervals recorded for 10 min in a supine position at pre- and post-intervention were used to analyze HRV in the plot-Poincare indexes (SD1, SD2), and frequency-domain (LF, HF, LF/HF). Full blood samples were used for genotyping. RESULTS: 4-HIIT and MCT showed positive outcomes for almost all variables while 1-HIIT had a positive influence only on SBP and SD2 index. No associations were observed between isolated ADRB2 variants and changes in HRV. In the analysis of the interaction genotypes, all groups responded positively for the SD1 index of HRV and only the H1 (GG and CC) and H2 (GG and CG + GG) groups presented increases in the RMSSD index. Furthermore, there was an increase in the LF index only in the H3 (CC and AA + AG) and H4 (AA + AG and CG + GG) groups. CONCLUSIONS: ADRB2 variants and aerobic exercise training are important interacting variables to improve autonomic function and other health variables outcomes in overweight or obese individuals.