MicroRNA: key gene expression regulators Moreno-Moya, Juan Manuel; Vilella, Felipe; Simón, Carlos
Fertility and sterility,
06/2014, Volume:
101, Issue:
6
Journal Article
Peer reviewed
Open access
MicroRNAs, also called miRNAs, are small 19-22 nucleotide (nt) sequences of noncoding RNA that work as endogenous epigenetic gene expression regulators. They are transcribed as large primary miRNAs ...or pre-miRNAs by RNA polymerase II and III, and are subsequently processed by the ribonucleases Drosha and Dicer to give rise to their mature forms. These mature miRNAs are then incorporated into the RISC complex (RNA-induced silencing complex) where they bind to the 3'-UTR mRNA complementary region, which induces their degradation or inhibits their translation, resulting in gene silencing. MicroRNAs are essential for embryo, cell, and tissue development, regulating cell differentiation, proliferation, and apoptosis, hence their importance in human reproduction. Currently, methods of detecting these molecules include real-time polymerase chain reaction, microarrays, in situ hybridization, and deep sequencing as well as novel approaches such as Nanostring nCounter. However, functional characterization is still required to confirm their biologic roles. Furthermore, miRNAs are not only found in cells but also have been identified in most biologic fluids, including serum, plasma, and saliva. Once miRNAs are secreted by cells, they are either incorporated into microvesicles or become associated with proteins, which protect them from RNase degradation so that they may remain intact for long periods of time. This suggests that they might also mediate paracrine signaling via different pathways and could therefore represent potential new biomarkers. Indeed, many pharmaceutic companies have recently started to investigate these molecules as possible routes to develop new human disease treatments.
Investigations into the sensitivity of heart rate‐(HR) derived indices for tracking parasympathetic nervous system (PNS) changes in functionally overreached (F‐OR) endurance‐trained athletes have ...produced equivocal findings. Lack of clarity may be a result of methodological inconsistencies. Therefore, the aims of this systematic review and meta‐analysis were (a) to determine the sensitivity of resting and post‐exercise vagal‐related HR variability (HRV) and HR recovery (HRR) indices to detect PNS modulation in F‐OR and non‐overreached (non‐OR) athletes, and (b) to investigate the influence of methodological factors on the sensitivity of HR‐based indices to detect PNS hyperactivity in F‐OR athletes. We searched CENTRAL, Scopus, PubMed, Embase, and Web of Science up to May 2020 for the following terms: male and female endurance‐trained athletes, controlled and uncontrolled studies that carried out an overload training period, and PNS modulation measured in resting and post‐exercise, pre‐ and post‐overload training period. A random‐effects model of standardized mean difference (SMD) was estimated for each outcome measure based on the training‐induced fatigue status (F‐OR vs non‐OR athletes), and the influence of methodological issues to detect PNS hyperactivity in F‐OR was assessed by subgroup analyses. Pooled analysis showed that resting vagal‐related HRV indices did not detect PNS hyperactivity in F‐OR athletes (SMD+ = −0.01; 95% confidence interval CI = −0.51, 0.50), and no statistical difference (P = .600) was found with non‐OR athletes (SMD+ = 0.15; 95% CI = −0.14, 0.45). However, subgroup analysis based on HRV parameter showed a moderate statistical increase in weekly averaged HRV in F‐OR athletes (SMD+ = 0.81; 95% CI = 0.35, 1.26), while isolated HRV values did not reach statistical significance (SMD+ = −0.45; 95% CI = −0.96, 0.06). We observed a moderate and statistically significant increase in HRR indices among F‐OR athletes (SMD+ = 0.65; 95% CI = 0.44, 0.87), no changes for non‐OR athletes (SMD+ = 0.10; 95% CI = −0.15, 0.34), and statistically significant differences between F‐OR and non‐OR athletes (P < .001). Insufficient data prevented meta‐analysis for post‐exercise vagal‐related HRV indices. Our findings show that when methodological factors are considered, HR‐based indices are sensitive to increased PNS modulation in F‐OR.
Strength training is crucial for soccer players' long-term development at early ages and the biological maturation may influence specific strength-training adaptations. The aim of this study was to ...propose a strength-training programme for the strength development of pre-pubertal players and to analyse the adaptations to this training programme in players with different maturity status. One hundred and thirty young male soccer players participated in an 8-week strength-training programme consisting of two sessions per week (20-minutes of a combination of plyometric and resistance exercises) which was conducted prior to their normal soccer training. Three maturity groups were defined according to the years from/to their peak height velocity (PHV) as Pre-, Mid- and Post-PHV. Initial differences between the maturity groups were found in anthropometrical (weight and height) and physical performance variables (One Repetition Maximum (RM), Peak Power output (PP), 30-m sprint and T-test). The strength-training programme was beneficial for the three maturity groups (p< 0.05) with general greater improvements for the Pre- and Mid-PHV groups, with large effects in RM, PP and T-test, than for the Post-PHV group (moderate effects). The strength-training programme proposed in the present study seems to be positive for the strength-related development in young soccer players especially for Pre- and Mid-PHV players. The differences in the training adaptations for players with different maturity status suggest the individualization of the training stimulus for the correct long-term development of the players.
Exercise intensity distribution is crucial for exercise individualization, prescription, and monitoring. As traditional methods to determine intensity thresholds present limitations, heart rate ...variability (HRV) using DFA a1 has been proposed as a biomarker for exercise intensity distribution. This index has been associated with ventilatory and lactate thresholds in previous literature. This study aims to assess DFA a1's reliability and validity in determining intensity thresholds during an incremental cycling test in untrained healthy adults. Sixteen volunteers (13 males and 3 females) performed two identical incremental cycling stage tests at least 1 week apart. First and second ventilatory thresholds, lactate thresholds, and HRV thresholds (DFA a1 values of 0.75 and 0.5 for HRVT1 and HRVT2, respectively) were determined in heart rate (HR), relative oxygen uptake (VO
rel), and power output (PO) values for both tests. We used intraclass correlation coefficient (ICC), change in mean, and typical error for the reliability analysis, and paired t-tests, correlation coefficients, ICC, and Bland-Altman analysis to assess the agreement between methods. Regarding reliability, HRV thresholds showed the best ICCs when measured in PO (HRVT1: ICC = .87; HRVT2: ICC = .97), comparable to ventilatory and lactate methods. HRVT1 showed the strongest agreement with LA 2.5 in PO (
= 0.09,
= .93, ICC = .93, bias = 9.9 ± 21.1), while HRVT2 reported it with VT2 in PO (
= 0.367,
= .92, ICC = .92, bias = 5.3 ± 21.9). DFA a1 method using 0.75 and 0.5 values is reliable and valid to determine HRV thresholds in this population, especially in PO values.
Second-generation bioethanol is considered a suitable option for replacing fossil fuels. Agricultural residues are being studied as feedstocks for sugar generation, which are in turn converted into ...ethanol. Among them, barley straw (BS) is a promising raw material, due to its high abundance, lignocellulosic composition and lack of other practical applications. Under these assumptions, the central aim of this study is to suggest an efficient bioethanol production scheme from BS at different levels of integration in co-fermentation with Escherichia coli SL100, including separate hydrolysis and co-fermentation (SHCF), simultaneous saccharification and co-fermentation (SSCF), and presaccharification and simultaneous saccharification and co-fermentation (PSSCF), using the water-insoluble solid (WIS) and slurry fractions obtained after steam explosion (SE) pretreatment. The best results in terms of ethanol yield were achieved following the SHCF process, using the WIS and the slurry as substrates, with yields of 89.1% and 78.8% of the theoretical maximum, respectively. Considering all of the above points, the following scheme is proposed for the conversion of BS into ethanol: SE pretreatment (160 °C, 30 min) of BS previously soaked overnight in 2.88% w/v phosphoric acid solution, filtration of the slurry, followed by enzymatic hydrolysis and co-fermentation of the two fractions obtained separately, with previous detoxification of the prehydrolysate with ammonium hydroxide (5 N). Under these conditions, 19.43 g of bioethanol was produced from 100 g of BS.
Altitude training is a common strategy to improve performance in endurance athletes. In this context, the monitoring of training and the athletes’ response is essential to ensure positive ...adaptations. Heart rate variability (HRV) has been proposed as a tool to evaluate stress and the response to training. In this regard, many smartphone applications have emerged allowing a wide access to recording HRV easily. The purpose of this study was to describe the changes of HRV using a validated smartphone application before (Pre-TC), during (TC), and after (Post-TC) an altitude training camp in female professional cyclists. Training load (TL) and vagal markers of heart rate variability (LnRMSSD, LnRMSSDcv) of seven professional female cyclists before, during, and after and altitude training camp were monitored. Training volume (SMD = 0.80), LnRMSSD (SMD = 1.06), and LnRMSSDcv (SMD = −0.98) showed moderate changes from Pre-TC to TC. Training volume (SMD = 0.74), TL (SMD = 0.75), LnRMSSD (SMD = −1.11) and LnRMSSDcv (SMD = 0.83) showed moderate changes from TC to Post-TC. Individual analysis showed that heart rate variability responded differently among subjects. The use of a smartphone application to measure HRV is a useful tool to evaluate the individual response to training in female cyclists.
Background The fat mass estimators waist-to-height ratio (WHtR) and relative fat mass--pediatric (RFMp) complement the widely accepted body mass index (BMI) in obesity evaluation. Aims of the Study: ...Conduct an easy appraisal of trunk fat and the cardiometabolic risk associated with pediatric obesity. Methods A total of 472 children (39% boys in the total sample) were classified as underweight, normal weight, overweight or obese (nutritional groups, NGs) according to BMI Z-score after initial anthropometric data were obtained and ad hoc exclusion criteria were applied. WHtR and RFMp (% of total fat) were calculated for each group, associations were assessed through multiple linear regression (MLR), and differences between sexes were evaluated (medians, IQR). Results The mean age (mean (95% CI)) was 10.8 y (10.1-11.1). The values in the total sample were as follows: WHtR, 0.5 (0.49-0.51) and RFMp%, 32.3 (31.7-33.0). In the overweight group, the values were as follows: WHtR, 0.51 (0.50-0.52) and RFMp(%), 34.2 (33.3-35.1). In the obese group, the values were as follows: WHtR, 0.56 (0.55-0.57) and RFMp(%), 37.8 (36.9-38.6). The associations were as follows (NG; independent variables): In the NG, adjusted R.sup.2 values were between 0.74 and 0.78. In the total sample, the beta coefficient was 3.36 (P < 0.001) for RFMp for girls; for waist circumference (WC), the beta coefficient was 2.97 (P < 0.001), and for WHtR the beta coefficients were - 0.01 (p < 0.001) and 0.03 (p < 0.001),for girls and for WC respectively. The sex differences were as follows: BMI exhibited no differences in the NG (Mann-Whitney U). WHtR (median (IQR)) differed (M vs. F) in the total sample (0.49 (0.45-0.54) vs. 0.52 (0.45-0.56), p < 0.004); in the overweight group (0.51 (0.48-0.53) vs. 0.54 (0.51-0.55), p < 0.001); and in the obese group (0.55 (0.52-0.57) vs. 0.57 (0.54-0.60), p < 0.004). RFMp (%) differed in the total group (29.21 (24.27-32.92) vs. 36.63 (30.2-39.51), p < 0.001); in the overweight group (31.24 (28.35-32.35) vs. 37.95 (35.75-38.82), p < 0.001) and in the obese group (35.89 (32.05-36.15) vs. 40.63 (38.27-42.42), p < 0.001). Conclusions WHtR and RFMp are simple and reliable indices that do not require centile charts. Their values, including waist circumference, can be used to estimate the different trunk fat components in boys and girls better than BMI, especially if individuals are overweight or obese. RFMp proved to be more reliable as it considers sex. Both should be included in routine anthropometric readings. Keywords: Abdominal fat, Easy anthropometry, Pediatric obesity, Sex distribution
Objective
Cancer patients are at increased risk for psychological difficulties and COVID-19. We sought to analyze anxiety and depression levels during the COVID-19 pandemic and the association ...between sociodemographic, clinical, and psychological factors in patients with advanced cancer.
Methods
A prospective, multicenter cohort of 401 consecutive patients with newly diagnosed, advanced cancer completed the Brief Symptom Inventory, Michel Uncertainty in Illness Scale, Herth Hope Index, and Cancer Worry Scale between February 2020 and May 2021. Linear regression analyses explored the effects of uncertainty, hopelessness, and cancer worry on anxiety and depression, adjusting for sociodemographic and clinical variables.
Results
The incidence of anxiety and depression was 36% and 35%, respectively. Emotional distress was greater among women, patients < 65 years of age, and those with an estimated survival of > 18 months. Linear regression analysis revealed that being female, preoccupation about cancer, and hopelessness were associated with increased levels of anxiety (
p
< 0.001) and depression (
p
< 0.001) and younger age was associated with a higher risk of anxiety. No differences in anxiety or depression levels were found in relation to marital status, children, educational level, cancer type, histology, stage, or type of treatment.
Conclusions
Patients with advanced cancer who initiated treatment during the pandemic experienced high levels of depression and anxiety. Early diagnosis and the development of intervention strategies are necessary, especially for specific patient subgroups, such as young women with long survival times.
Using non-reducing Western blotting to assess protein thiol redox state is challenging because most reduced and oxidised forms migrate at the same molecular weight and are, therefore, ...indistinguishable. While copper catalysed Click chemistry can be used to ligate a polyethylene glycol (PEG) moiety termed Click PEGylation to mass shift the reduced or oxidised form as desired, the potential for copper catalysed auto-oxidation is problematic. Here we define a catalyst-free trans-cyclooctene-methyltetrazine (TCO-Tz) inverse electron demand Diels Alder chemistry approach that affords rapid (k ~2000 M
s
), selective and bio-orthogonal Click PEGylation. We used TCO-Tz Click PEGylation to investigate how fertilisation impacts reversible mitochondrial ATP synthase F
-F
sub-unit alpha (ATP-α-F
) oxidation-an established molecular correlate of impaired enzyme activity-in Xenopus laevis. TCO-Tz Click PEGylation studies reveal substantial (~65%) reversible ATP-α-F
oxidation at evolutionary conserved cysteine residues (i.e., C
and C
) before and after fertilisation. A single thiol is, however, preferentially oxidised likely due to greater solvent exposure during the catalytic cycle. Selective reduction experiments show that: S-glutathionylation accounts for ~50-60% of the reversible oxidation observed, making it the dominant oxidative modification type. Intermolecular disulphide bonds may also contribute due to their relative stability. Substantial reversible ATP-α-F
oxidation before and after fertilisation is biologically meaningful because it implies low mitochondrial F
-F
ATP synthase activity. Catalyst-free TCO-Tz Click PEGylation is a valuable new tool to interrogate protein thiol redox state in health and disease.
•Olive leaves constitute a biomass source rich in sugars and natural antioxidants.•First report on steam explosion to recover interesting products olive leaves.•Conditions for simultaneous ...maximization of sugars and antioxidants were assessed.•Response surface methodology showed that temperature is the most influential factor.•18.39g sugars and 1950mg antioxidants were obtained from 100g dry olive leaves.
In this work, steam-explosion treatment was evaluated as a procedure to recover sugars and natural antioxidants from olive tree leaves. The treatment was carried out following a Box-Behnken experimental design, with three factors, temperature (180–220°C), process time (2–10min) and milling time (0–15s). Response surface methodology showed that temperature was the most influential factor, followed by process time, while the best results were achieved with whole leaves. The operational conditions for simultaneously maximizing the sugars and natural antioxidants recoveries resulted to be 180°C, 8.3min and whole leaf; under these conditions 18.39g and 1950mg were obtained from 100g dry olive leaves, respectively. This is equivalent to 70% recovery of the initial sugars present in olive leaves, with a very low formation of inhibitory compounds and an important amount of natural products with antioxidant capacity such as oleuropein, hydroxytyrosol and flavonoids.
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