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1.
Sci Rep ; 9(1): 10589, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31332232

RESUMO

Women on average live longer than men, which seems to suggest that women also age slower than men. However, the potential difference in the pace of aging between the sexes is a relatively controversial topic, and both positions, i.e. "men age faster" and "men and women age at the same pace", have found some support. We therefore employ parametric models previously established in model organisms as well as two nonparametric approaches to compare the pace of aging between the sexes using freely available mortality data from 13 high-income countries. Our results support the hypothesis that men age faster than women while also suggesting that the difference is small and that from a practical standpoint male mortality rates behave similarly to the mortality rates of women approximately eight years their senior.

2.
Pharmacol Rep ; 71(4): 669-675, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31195344

RESUMO

BACKGROUND: Neurotrophins, especially brain-derived neurotrophic factor (BDNF) have gained significant therapeutic interest particularly in neurologic and psychiatric disorders and they have been found in human breast milk of mothers who suffered from adverse outcomes in pregnancy. This study tested the hypothesis that oral administration of BDNF/GDNF (glial cell line-derived neurotrophic factor) can exert a biological effect in a rat model of severe neuropathology induced by olfactory bulbectomy (OBX), which exhibits dysregulation of BDNF signaling and impaired blood-brain barrier. METHODS: Adult male albino Sprague-Dawley rats underwent the OBX surgery and separate groups of OBX and sham-operated controls received one oral dose of vehicle, BDNF (0.005 mg/kg), GDNF (0.03 mg/kg) or their combination. One week after neurotrophin dosing the rats were sacrificed and BDNF level was assessed by ELISA in the blood serum and cerebrospinal fluid. RESULTS: A significant decrease of serum BDNF level was found in the OBX model. This alteration was normalized by all types of treatment BDNF, GDNF, or their combination. No influence of sham surgery or treatment was observed in the control rats. BDNF levels in cerebrospinal fluid were below detection limit. CONCLUSION: This study indicates that oral administration of neurotrophins is able to exert a biological effect in the OBX model. There is a number of potential mechanisms, which remain to be elucidated.

3.
PLoS One ; 14(6): e0218323, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31211819

RESUMO

BACKGROUND: Great progress has been made in the understanding of inflammatory processes in psoriasis. However, clarifying the role of genetic variability in processes regulating inflammation, including post-transcriptional regulation by microRNA (miRNA), remains a challenge. OBJECTIVES: We therefore investigated single nucleotide polymorphisms (SNPs) with a predicted change in the miRNA/mRNA interaction of genes involved in the psoriasis inflammatory processes. METHODS: Studied SNPs rs2910164 C/G-miR-146a, rs4597342 T/C-ITGAM, rs1368439 G/T-IL12B, rs1468488 C/T-IL17RA were selected using a bioinformatics analysis of psoriasis inflammation-associated genes. These SNPs were then genotyped using a large cohort of women with psoriasis (n = 241) and healthy controls (n = 516). RESULTS: No significant association with psoriasis was observed for rs2910164, rs1368439, and rs1468488 genotypes. However, the major allele T of rs4597342 -ITGAM was associated with approximately 28% higher risk for psoriasis in comparison to the patients with the C allele (OR = 1.28, 95% CI 1.01-1.61, p = 0.037). In case of genotypes, the effect of the T allele indicates the dominant model of disease penetrance as the CT and TT genotypes increase the chance of psoriasis up to 42% in comparison to CC homozygotes of rs4597342 (OR = 1.42, 95% CI = 1.05-1.94, p = 0.025). CONCLUSION: SNP rs4597342 in 3'UTR of ITGAM influencing miR-21 binding may be considered a risk factor for psoriasis development. Upregulated miR-21 in psoriasis is likely to inhibit CD11b production in the case of the rs4597342 T allele which may lead to Mac-1 dysfunction, resulting in an aberrant function of innate immune cells and leading to the production of cytokines involved in psoriasis pathogenesis.

4.
Biol Lett ; 15(6): 20190091, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31164060

RESUMO

Many studies during the past 50 years have found an association between father absence and earlier menarche. In connection with these findings, several evolutionary theories assume that father absence is a causal factor accelerating reproductive development. However, a recent study analysing data from the Avon Longitudinal Study of Parents and Children (ALSPAC) found that father absence does not predict age at menarche when adjusted for sibling relatedness. In this study, we have replicated these results in the Czech section of the European Longitudinal Study of Pregnancy and Childhood (ELSPAC), which used the same questionnaires as ALSPAC to study a geographically distinct population. Our results support the conclusion that sibling relatedness rather than father absence predicts age at menarche. Furthermore, our results show that age at menarche in 1990s UK and Czech cohorts is very similar despite socioeconomic differences between the two countries.

5.
Bioessays ; 41(6): e1900014, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31087675

RESUMO

Most contemporary models of disease development consider the interaction between genotype and environment as static. The authors argue that because time is a key factor in genotype-environment interaction, this approach oversimplifies the pathology analysis and may lead to wrong conclusions. In reviewing the field, the authors suggest that the history of genotype-environment interactions plays an important role in the development of diseases and that this history may be analyzed using the phenotype as a proxy. Furthermore, a theoretical and experimental framework is proposed based on the assumption that phenotypes do not change from one to another randomly but are interconnected and follow certain phenotype trajectories. It then follows that analysis of such phenotype trajectories might be useful to predict the future phenotypes including the onset of disease. In addition, an analysis of phenotype trajectories can be subsequently used to choose better control subjects in comparative studies reducing noise and bias in studies investigating disease mechanisms.

6.
Cent Eur J Public Health ; 27(1): 83, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30927404

RESUMO

We would like to submit the following correction to our recently published paper due to an error in the Table 2. The corrected table is given below.

7.
J Am Heart Assoc ; 8(2): e008968, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30638108

RESUMO

Background Myocarditis is an important cause of acute and chronic heart failure. Men with myocarditis have worse recovery and an increased need for transplantation compared with women, but the reason for the sex difference remains unclear. Elevated sera soluble (s) ST2 predicts mortality from acute and chronic heart failure, but has not been studied in myocarditis patients. Methods and Results Adults with a diagnosis of clinically suspected myocarditis (n=303, 78% male) were identified according to the 2013 European Society of Cardiology position statement. Sera sST2 levels were examined by ELISA in humans and mice and correlated with heart function according to sex and age. Sera sST2 levels were higher in healthy men ( P=8×10-6) and men with myocarditis ( P=0.004) compared with women. sST2 levels were elevated in patients with myocarditis and New York Heart Association class III - IV heart failure ( P=0.002), predominantly in men ( P=0.0003). Sera sST2 levels were associated with New York Heart Association class in men with myocarditis who were ≤50 years old ( r=0.231, P=0.0006), but not in women ( r=0.172, P=0.57). Sera sST2 levels were also significantly higher in male mice with myocarditis ( P=0.005) where levels were associated with cardiac inflammation. Gonadectomy with hormone replacement showed that testosterone ( P<0.001), but not estradiol ( P=0.32), increased sera sST2 levels in male mice with myocarditis. Conclusions We show in a well-characterized subset of heart failure patients with clinically suspected and biopsy-confirmed myocarditis that elevated sera sST2 is associated with an increased risk of heart failure based on New York Heart Association class in men ≤50 years old.

8.
JCI Insight ; 3(23)2018 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-30518699

RESUMO

In this study, the circulating miRNome from diagnostic neuroblastoma serum was assessed for identification of noninvasive biomarkers with potential in monitoring metastatic disease. After determining the circulating neuroblastoma miRNome, 743 miRNAs were screened in 2 independent cohorts of 131 and 54 patients. Evaluation of serum miRNA variance in a model testing for tumor stage, MYCN status, age at diagnosis, and overall survival revealed tumor stage as the most significant factor impacting miRNA abundance in neuroblastoma serum. Differential abundance analysis between patients with metastatic and localized disease revealed 9 miRNAs strongly associated with metastatic stage 4 disease in both patient cohorts. Increasing levels of these miRNAs were also observed in serum from xenografted mice bearing human neuroblastoma tumors. Moreover, murine serum miRNA levels were strongly associated with tumor volume. These findings were validated in longitudinal serum samples from metastatic neuroblastoma patients, where the 9 miRNAs were associated with disease burden and treatment response.

10.
PLoS One ; 13(10): e0205812, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30335807

RESUMO

While stress is a widely utilized concept, no direct methods facilitating its measurement are currently available. In our previous work we proposed stress entropic load (SEL) as a potential new marker of stress response in the human body. However, at that time no method for SEL measurement existed. In this pilot study we devised and then tested methodology for SEL measurement. Healthy male participants were monitored by indirect calorimetry and thermography while resting and subsequently while under prolonged mental effort. The acquired data was then used to calculate the temporal development of SEL for each participant. Our results show that SEL production increased significantly in participants subjected to prolonged mental effort. Furthermore, we observed that the calculated development of SEL over time may be used to accurately determine the time point at which participants started performing stressful tasks.

11.
Obesity (Silver Spring) ; 26(12): 1870-1878, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30369078

RESUMO

OBJECTIVE: Interest in metabolites produced by adipose tissue has increased substantially in the past several decades. Previously regarded as an inert energy storage depot, adipose tissue is now viewed as a complex metabolically active organ with considerable impact on human health. The emerging field of mass spectrometry-based metabolomics presents a powerful tool for the study of processes in complex biological matrices including adipose tissue. RESULTS: A large number of structurally distinct metabolites can be analyzed to facilitate the investigation of differences between physiological and pathophysiological metabolic profiles associated with adipose tissue. Understanding the molecular basis of adipose tissue regulation can thereby provide insight into the monitoring of obesity-related metabolic disorders and lead to the development of novel diagnostic and prognostic biomarkers. CONCLUSIONS: This review provides the current state of knowledge, recent progress, and critical evaluation of metabolomics approaches in the context of white adipose tissue and obesity. An overview of basic principles and resources describing individual groups of metabolites analyzed in white adipose tissue and biological fluids is given. The focus is on metabolites that can serve as reliable biomarkers indicative of metabolic alterations associated with obesity.

12.
Sci Rep ; 8(1): 16072, 2018 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-30375446

RESUMO

Since aging seems omnipresent, many authors regard it as an inevitable consequence of the laws of physics. However, recent research has conclusively shown that some organisms do not age, or at least do not age on a scale comparable with other aging organisms. This begets the question why aging evolved in some organisms yet not in others. Here we present a simulation model of competition between aging and non-aging individuals in a sexually reproducing population. We find that the aging individuals may outcompete the non-aging ones if they have a sufficiently but not excessively higher initial fecundity or if individuals mate assortatively with respect to their own phenotype. Furthermore, the aging phenotype outcompetes the non-aging one or resists dominance of the latter for a longer period in populations composed of genuine males and females compared to populations of simultaneous hermaphrodites. Finally, whereas sterilizing parasites promote non-aging, the effect of mortality-enhancing parasites is to enable longer persistence of the aging phenotype relative to when parasites are absent. Since the aging individuals replace the non-aging ones in diverse scenarios commonly found in nature, our study provides important insights into why aging has evolved in most, but not all organisms.

13.
Ginekol Pol ; 89(8): 424-31, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30215461

RESUMO

OBJECTIVES: To evaluate risk factors associated with the local recurrence of invasive squamous cell vulvar cancer in patient group with tumor-free pathological margins. MATERIAL AND METHODS: This is a retrospective analysis of 47 patients who underwent surgical treatment at University Hospital Brno, the Czech Republic between 2007 and 2014. 24 patients were classified as IB stage and three as II stage. A further 20 patients representing stage III showed the metastatic involvement of regional lymph nodes. Seven prognostic factors were analyzed in relation to local tumour recurrence: tumour size, margin distance, depth of invasion, lymphovascular space involvement (LVSI), midline involvement, metastatic lymph nodes and FIGO stage. RESULTS: All prognostic factors were found to be statistically significant with respect to the risk of local recurrence. The highest risk of local recurrence was observed for the depth of invasion > 5 mm (HR, 12.42 [95% CI; 3.44-44.84]) and for the presence of LVSI (HR, 10.83 [95% CI; 3.87-30.28]). The study also established a clear difference in the risk of local recurrence between patient groups with resection margin < 8 vs. ≥ 8 mm (HR, 4.91 [95% CI; 1.73-13.93; p = 0.003]. CONCLUSIONS: Tumour-free pathological margin of ≥ 8 mm is a major prognostic factor of local recurrence which can be influenced by the surgeon. A perfect knowledge of the extent of the disease prior to surgery supports adequately radical surgical trends. The emphasis is given on adequate radicality as well as on the reduction of overtreatment without worse-ning prognosis by simultaneously preserving the quality of life.

14.
Acta Neurol Belg ; 118(3): 493-501, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30069682

RESUMO

Pro-inflammatory and anti-inflammatory cytokines have been shown to play a crucial role in the pathophysiology of multiple sclerosis (MS). We investigated the association between interleukin (IL) IL6-174 G/C (rs1800795), IL7RA C/T (rs6897932), and IL-12B A1188C (rs3212227) gene polymorphisms (SNPs) and MS. The study consisted of 297 unrelated MS patients and 135 healthy individuals. In IL6-174G/C (rs1800795), a significant association between the C allele and MS risk [OR 1.41, 95% CI (1.05-1.92); P = 0.025] was found. Carriage of genotypes CC and CG were more common in MS patients [OR 1.58, 95% CI (1.04-2.39); P = 0.031] and also in female MS patients [OR 1.68, 95% CI (1.02-2.79); P = 0.043]. However, after applying Bonferroni's correction the differences did not remain significant. No significant association between the IL7RA C/T (rs6897932) and IL12B A1188C (rs3212227) gene polymorphisms and MS susceptibility was observed. Regarding IL-12B A1188C (rs3212227), a significant association between the CC genotype and MS progression, expressed as MSSS, was demonstrated in the female MS group. Our results indicate that the distribution of IL6-174G/C (rs1800795) SNP was marginally associated with MS susceptibility. We also showed that IL-12B A1188C (rs3212227) can contribute to the progression of the disease in the Czech population.

15.
J Epidemiol Community Health ; 72(12): 1141-1146, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30061097

RESUMO

BACKGROUND: Little is known about the effects of physical activity and fitness on sleep timing parameters in adolescence. METHODS: We investigated the development of sleep timing between age 8 and 15 and its association with physical fitness at age 15 in 787 adolescents (408 males, 379 females). Physical fitness was measured using the physical work capacity (PWC) protocol. Information on sport activity was collected at ages 11 and 15. Finally, the contribution of other covariates (sex, body mass index (BMI), parental education and occupational skill level) to the association between sleep parameters and physical fitness was evaluated. The correlation of BMI and physical fitness was assessed separately. RESULTS: Mild correlation of sleep duration at ages 8 and 15 was observed (r=0.08-0.16). Higher sport activity participation and physical fitness were found to be mildly associated with delayed bedtime and reduced sleep duration; the association with bedtime was significant after adjustment for all covariates. Sport activity at age 11 was not associated with sleep timing at age 15. Interestingly, higher BMI was linked to delayed bedtime and higher physical fitness. CONCLUSION: Our findings do not support existing hypotheses suggesting the association of low physical activity and fitness with shorter sleep duration and high BMI in a generally non-obese adolescent population without severe sleep restriction.

16.
Dis Markers ; 2018: 7628957, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29997715

RESUMO

Irisin, an adipomyokine identified in 2012, has been investigated in association with common pregnancy complications, including gestational diabetes mellitus, preeclampsia, and intrauterine growth restriction. The objective of this study is to examine the potential role of irisin in preterm birth (PTB) by comparing its level between mothers with term and preterm labor. Maternal peripheral blood and cord blood samples were collected from 30 mothers who delivered prematurely and from 35 mothers who delivered at term. Irisin concentrations were measured in all samples using ELISA, and four common single nucleotide polymorphisms in the irisin gene were determined (rs16835198, rs726344, rs3480, and rs1746661). Univariable and multivariable regression modeling was applied to evaluate maternal and cord blood irisin concentrations in relation to preterm/term labor. Irisin concentration in umbilical cord blood was found to be associated with PTB in the univariable model (p = 0.046). On the other hand, no differences in maternal blood irisin levels between mothers with preterm and term deliveries were established. To the best of our knowledge, this is the first study determining irisin levels in term and preterm deliveries in maternal peripheral blood and umbilical cord blood. Our study shows a possible association between cord blood irisin concentration and PTB occurrence.


Assuntos
Sangue Fetal/metabolismo , Fibronectinas/metabolismo , Trabalho de Parto Prematuro/etiologia , Regulação para Cima , Adulto , Estudos de Casos e Controles , Feminino , Fibronectinas/sangue , Fibronectinas/genética , Estudos de Associação Genética , Idade Gestacional , Humanos , Mães , Trabalho de Parto Prematuro/metabolismo , Polimorfismo de Nucleotídeo Único , Gravidez , Adulto Jovem
17.
Eur J Obstet Gynecol Reprod Biol ; 228: 154-160, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29957400

RESUMO

OBJECTIVE: This study aimed to evaluate the impact of the secondary cytoreductive surgery on survival parameters in women with platinum-sensitive recurrent ovarian cancer who undergone secondary cytoreduction following chemotherapy compared to women who recieved chemotherapy alone. STUDY DESIGN: In a retrospective study, data were rewieved from women who were diagnosed and treated with ovarian cancer and its primary platinum-sensitive recurrence at the University Hospital Brno in the Czech Republic between November 2009 and March 2016. Out of the total number of 62 patients with recurrence, 30 women underwent cytoreductive surgery plus chemotherapy and 32 were treated with chemotherapy alone. The good performance status expressed by ECOG score 0-1, the single site of recurrence regardless of platinum-free interval or multiple sites of recurrence but no carcinomatosis and platinum-free interval >12 months, and no or small-volume ascites (<500 ml) were considered inclusion criteria for cytoreductive surgery. Women not meeting these criteria were treated by chemotherapy alone. Descriptive statistics, Kaplan-Meier survival curves and Log-Rank test were used for statistical estimations. RESULTS: The analysis confirmed more favorable prognosis in patient group treated with a combination secondary cytoreduction and chemotherapy. Mean disease-free survival (DFS) was 49.8 months (95% CI; 33.2-66.3) and mean overall survival (OS) stood at 54.0 months (95% CI; 39.4-68.6) in this patient cohort, while in patient group treated with chemotherapy alone it was found that mean DFS was 16.6 months (95% CI; 7.4-25.8) and mean OS stood at 26.2 months (95% CI; 16.6-35.8). When testing the difference between survival curves, statistically significant differences were observed in both DFS (p = 0.010) and OS (p = 0.007) rates between two treatment groups. Age < 60 years at the time of recurrence and zero macroscopic residual disease after secondary cytoreduction were identified as favorable prognostic factors for both DFS and OS in a multivariate analysis. CONCLUSION: Secondary cytoreductive surgery is acceptable as a viable treatment option for highly selected women with ovarian cancer recurrence. Complete resection is considered ultimate goal of secondary cytoreduction on condition that the balance between maximal survival gain and minimal operative morbidity will be kept.

18.
Neurol Sci ; 39(6): 989-998, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-29627943

RESUMO

Traumatic brain injury is one of the most common causes for intervention in neurosurgery. Apart from its acute consequence, it can represent a further burden on individuals as well as society by being associated with significant comorbidity-mainly early-onset dementia. Oxidative stress is one of the crucial mechanisms conferring the damage to nervous tissue, and it is believed it could be, to some extent, influenced by dietary composition, largely by antioxidants contained in the diet. Under stressful conditions, cell-derived reactive oxygen species in the brain can induce the formation of lipid peroxides and the shifting of redox homeostasis. This review discusses the potential of vitamin E as a potent antioxidant and its derived molecules, including vitamin E-based lazaroids, in traumatic brain injury, summarizing the current state of knowledge of its role in TBI-associated dementia.


Assuntos
Antioxidantes/administração & dosagem , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/dietoterapia , Demência/prevenção & controle , Vitamina E/análogos & derivados , Vitamina E/administração & dosagem , Animais , Lesões Encefálicas Traumáticas/psicologia , Demência/etiologia , Suplementos Nutricionais , Humanos
19.
J Mol Neurosci ; 64(4): 559-566, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29589202

RESUMO

Vitamin D receptor polymorphisms have been the target of many studies focusing on multiple sclerosis. However, previously reported results have been inconclusive. The objective of this study was to investigate the association between five vitamin D receptor polymorphisms (EcoRV, FokI, ApaI, TaqI, and BsmI) and multiple sclerosis susceptibility and its course. The study was carried out as a case-control and genotype-phenotype study, consisted of 296 Czech multiple sclerosis patients and 135 healthy controls. Genotyping was carried out using polymerase chain reaction and restriction analysis. In multiple sclerosis men, allele and/or genotype distributions differed in EcoRV, TaqI, BsmI, and ApaI polymorphisms as compared to controls (EcoRV, pa = 0.02; Taq, pg = 0.02, pa = 0.02; BsmI, pg = 0.02, pa = 0.04; ApaI, pg = 0.008, pa = 0.005). In multiple sclerosis women, differences in the frequency of alleles and genotypes were found to be significant in ApaI (controls vs multiple sclerosis women: pg = 0.01, pa = 0.05). Conclusive results were observed between multiple sclerosis women in the case of EcoRV [differences in Expanded Disability Status Scale (p = 0.05); CT genotype was found to increase the risk of primary progressive multiple sclerosis 5.5 times (CT vs CC+TT pcorr = 0.01, sensitivity 0.833, specificity 0.525, power test 0.823)] and FokI [borderline difference in Multiple Sclerosis Severity Score (p = 0.05)]. Our results indicate that the distribution of investigated vitamin D receptor polymorphisms is a risk factor for multiple sclerosis susceptibility and progression in the Czech population. The association between disease risk and polymorphisms was found to be stronger in men. The association of disease progression with polymorphisms was observed only in women.


Assuntos
Esclerose Múltipla/genética , Polimorfismo de Nucleotídeo Único , Receptores de Calcitriol/genética , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/patologia , Fatores Sexuais
20.
Mech Ageing Dev ; 173: 29-38, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29580825

RESUMO

Transposable elements (TEs) are powerful drivers of genome evolutionary dynamics but are principally deleterious to the host organism by compromising the integrity and function of the genome. The transposition of TEs may result in mutations and DNA damage. DNA double-strand breaks (DSBs), which may be caused by the transposition, are one of the processes directly linked to aging. TEs may thus be considered to constitute an internal source of aging and the frequency of transposition may, in turn, be considered to affect the pace of aging. The PIWI-piRNA pathway is a widespread strategy used by most animals to effectively suppress transposition. Interestingly, the PIWI-piRNA pathway is expressed predominantly in the animal germline, a more or less continuous immortal lineage set aside after the first few cell divisions of a developing embryo. Recent findings further imply that the PIWI-piRNA pathway and TE suppression constitute an important mechanism regulating aging. This article discusses the proposed role of the PIWI-piRNA pathway in setting the pace of aging as well as the possible mechanisms underlying this process.


Assuntos
Envelhecimento , Proteínas Argonauta , Divisão Celular/genética , Dano ao DNA , RNA Interferente Pequeno , Envelhecimento/genética , Envelhecimento/metabolismo , Animais , Proteínas Argonauta/genética , Proteínas Argonauta/metabolismo , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
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