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1.
Reprod Sci ; 31(6): 1601-1609, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38393627

RESUMO

Polycystic ovary syndrome (PCOS) is a multifactorial disorder and obesity occurs in 38% to 88% of these women. Although hyperandrogenism may contribute to telomere lengthening, increased body mass index (BMI) is associated with telomere erosion. We sought to compare leukocyte telomere length (LTL) in PCOS women with normal, overweight, and obese BMI. We evaluated the relationship between LTL and clinical variables of PCOS and inflammatory biomarkers independent of BMI. A total of 348 women (243 PCOS and 105 non-PCOS) were evaluated for anthropometric measures, total testosterone, androstenedione, estradiol (E2), follicle-stimulating hormone (FSH), luteinizing hormone (LH), sex hormone-binding globulin (SHBG), free androgen index (FAI), fasting insulin and glycemia, lipid profile, homocysteine, C-reactive protein (CRP) and homeostatic model of insulin resistance (HOMA-IR). LTL was measured by qPCR. The PCOS group presented higher weight, waist circumference, BMI, testosterone, LH, fasting insulin, FAI, and HOMA-IR, and lower E2, SHBG, and fasting glycemia measures compared with the non-PCOS. When stratified by BMI, LTL was increased in all subgroups in PCOS compared to non-PCOS. However, in the PCOS group, LTL was lower in overweight (P = 0.0187) and obese (P = 0.0018) compared to normal-weight women. The generalized linear model showed that BMI, androstenedione, homocysteine, and CRP were associated with telomere biology. Women with PCOS had longer LTL, however, overweight or obesity progressively contributes to telomere shortening and may affect reproductive outcomes of PCOS, while androstenedione may increase LTL.


Assuntos
Índice de Massa Corporal , Obesidade , Síndrome do Ovário Policístico , Encurtamento do Telômero , Humanos , Síndrome do Ovário Policístico/genética , Síndrome do Ovário Policístico/sangue , Síndrome do Ovário Policístico/metabolismo , Feminino , Obesidade/genética , Obesidade/sangue , Adulto , Adulto Jovem , Resistência à Insulina , Telômero/metabolismo , Leucócitos/metabolismo , Biomarcadores/sangue
2.
F S Sci ; 5(1): 2-15, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38070681

RESUMO

OBJECTIVE: To determine whether severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection affects male reproductive health, considering the many potential factors that contribute to declines in male fertility on a semiglobal scale. DESIGN: In total, 64 human semen samples-32 treatment and 32 control-were laboratory processed and bioinformatically analyzed to assess differences in DNA methylation patterns. Implementing multiple bioinformatic tools, the analyses conducted will elicit between-group differences with respect to epigenetic age, epigenetic instability, semiglobal, and regional methylation, in addition to methylation patterns as a function of time since infection. SETTING: University hospital. PATIENTS: The study cohort of 64 individuals was drawn from a larger population of 94 volunteer participants recruited at the Human Reproduction Center at the Clinical Hospital of the Ribeirao Preto Medical School-University of São Paulo between June 2021 and January 2022 as well as in accordance with the ethical guidelines established by the Declaration of Helsinki. INTERVENTION: Exposure to SARS-CoV-2. MAIN OUTCOME MEASURE(S): Effects on male reproductive health were reported as differences in DNA methylation measured using an array. Mean ß values at key regulatory loci for human spermatocytes were analyzed and compared between groups. Further analysis of ß values using epigenetic age, instability, semiglobal, and regional methylation tools provided an analysis with substantial breadth and depth. RESULTS: In all analyses, there were no differences between groups. Considering these results, it can be inferred that infection with SARS-CoV-2 does not alter the epigenome of human spermatocytes in significant and/or persistent ways. Tangentially, these data also suggest that human male reproductive health is minimally altered by the virus, or that it is altered in a way that is independent of epigenetic programming. CONCLUSION: Infection with SARS-CoV-2 has been reportedly associated with alterations in male fertility. This study asserts that such alterations do not have an epigenetic basis but are likely a result of concomitant symptomatology, i.e., fever and inflammation. Across the multiple bioinformatic analyses conducted, the results of this test did not detect any differences in DNA methylation patterns between coronavirus disease 2019 and noncoronavirus disease semen donor groups.


Assuntos
COVID-19 , Humanos , Masculino , COVID-19/genética , COVID-19/metabolismo , Sêmen , SARS-CoV-2/genética , Espermatozoides/metabolismo , Metilação de DNA/genética
3.
Toxicon ; 238: 107591, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38160738

RESUMO

Bufadienolides are digitalis-like aglycones mainly found in skin secretions of toads. Among their biological properties, the mechanisms of antiproliferative action on tumor cells remain unclear for many compounds, including against leukemia cells. Herein, it was evaluated the mechanisms involved in the antiproliferative and genotoxic actions of hellebrigenin on tumor cell lines and in silico capacity to inhibit the human topoisomerase IIa enzyme. Firstly, its cytotoxic action was investigated by colorimetric assays in human tumor and peripheral blood mononuclear cells (PBMC). Next, biochemical and morphological studies were detailed by light microscopy (trypan blue dye exclusion), immunocytochemistry (BrdU uptake), flow cytometry and DNA/chromosomal damages (Cometa and aberrations). Finally, computational modelling was used to search for topoisomerase inhibition. Hellebrigenin reduced proliferation, BrdU incorporation, viability, and membrane integrity of HL-60 leukemia cells. Additionally, it increased G2/M arrest, internucleosomal DNA fragmentation, mitochondrial depolarization, and phosphatidylserine externalization in a concentration-dependent manner. In contrast to doxorubicin, hellebrigenin did not cause DNA strand breaks in HL-60 cell line and lymphocytes, and it interacts with ATPase domain residues of human topoisomerase IIa, generating a complex of hydrophobic and van der Waals interactions and hydrogen bonds. So, hellebrigenin presented potent anti-leukemic activity at concentrations as low as 0.06 µM, a value comparable to the clinical anticancer agent doxorubicin, and caused biochemical changes suggestive of apoptosis without genotoxic/clastogenic-related action, but it probably triggers catalytic inhibition of topoisomerase II. These findings also emphasize toad steroid toxins as promising lead antineoplasic compounds with relatively low cytotoxic action on human normal cells.


Assuntos
Antineoplásicos , Bufanolídeos , Leucemia , Humanos , Leucócitos Mononucleares , Bromodesoxiuridina/farmacologia , Dano ao DNA , Antineoplásicos/farmacologia , Bufanolídeos/química , Células HL-60 , Apoptose , DNA/farmacologia , Doxorrubicina/farmacologia
4.
Adv Exp Med Biol ; 1429: 41-58, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37486515

RESUMO

Long non-coding RNAs (lncRNAs) are one of the most abundant and heterogeneous transcripts with key roles in chromatin remodeling and gene regulation at the transcriptional and post-transcriptional levels. Due to their role in cell growth and differentiation, lncRNAs have emerged as an important biomarker in cancer diagnosis, prognosis, and targeted treatment. Recent studies have focused on elucidating lncRNA function during malignant transformation, tumor progression and drug resistance. The advent of the CRISPR system has made it possible to precisely edit complex genomic loci such as lncRNAs. Thus, we summarized the advances in CRISPR-Cas approaches for functional studies of lncRNAs including gene knockout, knockdown, overexpression and RNA targeting in tumorigenesis and drug resistance. Additionally, we highlighted the perspectives and potential applications of CRISPR approaches to treat cancer, as an emerging and promising target therapy.


Assuntos
Neoplasias , RNA Longo não Codificante , Humanos , RNA Longo não Codificante/genética , Sistemas CRISPR-Cas/genética , Neoplasias/genética , Neoplasias/terapia , Regulação da Expressão Gênica , Transformação Celular Neoplásica/genética
5.
Arch Endocrinol Metab ; 67(5): e000627, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37249458

RESUMO

Objective: This study aimed to determine the differences in body fat distribution and central obesity indicators using dual-energy X-ray absorptiometry (DXA), adiposity indices, and anthropometric indices between women with and without polycystic ovary syndrome (PCOS). Materials and methods: Clinical and laboratory examination history, including transvaginal ultrasound, fasting blood samples, anthropometric measurements, and DXA scans were conducted in 179 women with PCOS (PCOS group) and 100 without PCOS (non-PCOS group). The volunteers were grouped by body mass index (BMI): normal (18-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (>30 kg/m2). The visceral adiposity index (VAI) and lipid accumulation product (LAP) were calculated, regions of interest (ROIs) were determined, and the fat mass index (FMI) was calculated using DXA. Results: VAI, LAP, ROIs, FMI, and adiposity indices by DXA were higher in women with PCOS and normal BMI. In both PCOS and non-PCOS groups, the ROIs progressively increased from normal BMI to overweight and obese, and from overweight to obese. Obese women with PCOS showed high trunk fat mass. However, obesity was not able to modify these trunk/periphery fat ratios in PCOS from overweight to higher BMI. These variables were associated with the incidence of PCOS. Conclusion: In women with PCOS and normal BMI, both DXA and the adiposity indices, VAI and LAP, are more sensitive methods to evaluate total body fat and fat accumulation in the central abdominal region. It was also observed that as BMI increased, the differences in measurements between women with and without PCOS decreased.


Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico , Feminino , Humanos , Adiposidade , Índice de Massa Corporal , Absorciometria de Fóton , Sobrepeso , Obesidade/complicações , Obesidade Abdominal/diagnóstico por imagem , Obesidade Abdominal/complicações
6.
Front Cell Dev Biol ; 11: 1116805, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36866275

RESUMO

Disruption of the epigenetic program of gene expression is a hallmark of cancer that initiates and propagates tumorigenesis. Altered DNA methylation, histone modifications and ncRNAs expression are a feature of cancer cells. The dynamic epigenetic changes during oncogenic transformation are related to tumor heterogeneity, unlimited self-renewal and multi-lineage differentiation. This stem cell-like state or the aberrant reprogramming of cancer stem cells is the major challenge in treatment and drug resistance. Given the reversible nature of epigenetic modifications, the ability to restore the cancer epigenome through the inhibition of the epigenetic modifiers is a promising therapy for cancer treatment, either as a monotherapy or in combination with other anticancer therapies, including immunotherapies. Herein, we highlighted the main epigenetic alterations, their potential as a biomarker for early diagnosis and the epigenetic therapies approved for cancer treatment.

7.
Am J Lifestyle Med ; 17(1): 140-151, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36636404

RESUMO

The purpose of this study to assess the effects of different protocols of physical exercise on the domains of the quality of life (QoL), sexual function, anxiety, and depression scores in women with polycystic ovary syndrome (PCOS). Data of 112 women with PCOS were extracted from 2 trials with different protocols of physical exercise: continuous aerobic training (ContinuousAT, n = 23), intermittent aerobic training (IntermittentAT, n = 22), and progressive resistance training (ResistanceT, n = 43) alongside a control group (CG, n = 24). Volunteers who completed self-report questionnaires-Female Sexual Function Index (FSFI), the Hospital Anxiety and Depression Scale (HADS), and the MOS 36-Item Short-Form Health Survey (SF-36) for QoL-preprotocol and postprotocol of physical exercise were included. Within groups, from baseline to week 16, all ContinuousAT, IntermittentAT, and ResistanceT protocols promoted improvements in multiple FSFI domains and HADS scores. However, ResistanceT did not improve the QoL aspects. Between groups, from other physical training protocols, the IntermittentAT was most effective for QoL and FSFI domains as well as HADS scores. It is concluded that all interventions were effective and improved indicators of sexual function, anxiety, and depression. When comparing protocols, interval training with high-intensity stimuli and active recovery was more effective.

8.
Arch. endocrinol. metab. (Online) ; 67(5): e000627, Mar.-Apr. 2023. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1439246

RESUMO

ABSTRACT Objective: This study aimed to determine the differences in body fat distribution and central obesity indicators using dual-energy X-ray absorptiometry (DXA), adiposity indices, and anthropometric indices between women with and without polycystic ovary syndrome (PCOS). Materials and methods: Clinical and laboratory examination history, including transvaginal ultrasound, fasting blood samples, anthropometric measurements, and DXA scans were conducted in 179 women with PCOS (PCOS group) and 100 without PCOS (non-PCOS group). The volunteers were grouped by body mass index (BMI): normal (18-24.9 kg/m2), overweight (25-29.9 kg/m2), or obese (>30 kg/m2). The visceral adiposity index (VAI) and lipid accumulation product (LAP) were calculated, regions of interest (ROIs) were determined, and the fat mass index (FMI) was calculated using DXA. Results: VAI, LAP, ROIs, FMI, and adiposity indices by DXA were higher in women with PCOS and normal BMI. In both PCOS and non-PCOS groups, the ROIs progressively increased from normal BMI to overweight and obese, and from overweight to obese. Obese women with PCOS showed high trunk fat mass. However, obesity was not able to modify these trunk/periphery fat ratios in PCOS from overweight to higher BMI. These variables were associated with the incidence of PCOS. Conclusion: In women with PCOS and normal BMI, both DXA and the adiposity indices, VAI and LAP, are more sensitive methods to evaluate total body fat and fat accumulation in the central abdominal region. It was also observed that as BMI increased, the differences in measurements between women with and without PCOS decreased.

9.
Clin Epigenetics ; 14(1): 133, 2022 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-36284309

RESUMO

BACKGROUND: Penile cancer is one of the most aggressive male tumors. Although it is preventable, the main etiologic causes are lifestyle behaviors and viral infection, such as human papillomavirus (HPV). Long-term epigenetic changes due to environmental factors change cell fate and promote carcinogenesis, being an important marker of prognosis. We evaluated epidemiological aspects of penile squamous cell carcinoma (SCC) and the prevalence of HPV infection using high-risk HPV (hrHPV) and p16INK4A expression of 224 participants. Global DNA methylation was evaluated through 5-methylcytosine (5mC) and 5-hydroxymethylcytosine (5hmC). RESULTS: The incidence of HPV was 53.2% for hrHPV and 22.32% for p16INK4a. hrHPV was not related to systemic or lymph node metastasis and locoregional recurrence, nor influenced the survival rate. P16INK4a seems to be a protective factor for death, which does not affect metastasis or tumor recurrence. Lymph node and systemic metastases and locoregional recurrence increase the risk of death. An increased 5mC mark was observed in penile SCC regardless of HPV infection. However, there is a reduction of the 5hmC mark for p16INK4a + (P = 0.024). Increased 5mC/5hmC ratio (> 1) was observed in 94.2% of penile SCC, irrespective of HPV infection. Despite the increase in 5mC, it seems not to affect the survival rate (HR = 1.06; 95% CI 0.33-3.38). CONCLUSIONS: P16INK4a seems to be a good prognosis marker for penile SCC and the increase in 5mC, an epigenetic mark of genomic stability, may support tumor progression leading to poor prognosis.


Assuntos
Alphapapillomavirus , Carcinoma de Células Escamosas , Infecções por Papillomavirus , Neoplasias Penianas , Masculino , Humanos , Neoplasias Penianas/genética , Neoplasias Penianas/epidemiologia , Neoplasias Penianas/patologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/epidemiologia , Inibidor p16 de Quinase Dependente de Ciclina/genética , Prognóstico , 5-Metilcitosina , Metilação de DNA , Recidiva Local de Neoplasia/genética , Papillomaviridae/genética , Carcinoma de Células Escamosas/metabolismo , Alphapapillomavirus/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Epigênese Genética , DNA Viral
10.
J Assist Reprod Genet ; 39(8): 1873-1886, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35689735

RESUMO

PURPOSE: To evaluate the genetic variants related to polycystic ovary syndrome (PCOS) and its metabolic complications in girls born small for gestational age (SGA). DESIGN: Retrospective birth cohort study. MATERIALS AND METHODS: We evaluated 66 women of reproductive age born at term (37-42 weeks of gestational age) according to the birth weight in relation to gestational age: 26 SGA and 40 AGA (Adequate for gestational age). Anthropometric and biochemical characteristics were measured, as well as the PCOS prevalence. We analyzed 48 single nucleotide polymorphisms (SNPs) previously associated with PCOS and its comorbidities using TaqMan Low-Density Array (TLDA). miRNet and STRING databases were used to predict target and disease networks. RESULTS: Anthropometric and biochemical characteristics did not differ between the SGA and AGA groups, as well as insulin resistance and PCOS prevalence. Two SNPs were not in Hardy-Weinberg equilibrium, the rs2910164 (MIR146A C > G) and rs182052 (ADIPOQ G > A). The rs2910164 minor allele frequency (MAF) was increased in SGA (OR, 2.77; 95%; CI, 1.22-6.29), while the rs182052 was increased AGA (OR, 0.34; 95%; CI, 0.13 - 0.88). The alleles related to reduced miRNA-146a (C) and ADIPOQ (A) activity showed increased frequency in SGA. The mature miR-146a targets 319 genes, been the CXCR4, TMEM167A and IF144L common targets and contributes to PCOS. The ADIPOQ main protein interactions were ERP44, PPARGCIA and CDH13. CONCLUSIONS: The miR-146a (rs2910164) and ADIPOQ (rs182052) allelic variants are related to birth weight in SGA and may predict health-related outcomes, such as PCOS and obesity risk.


Assuntos
MicroRNAs , Síndrome do Ovário Policístico , Adiponectina/genética , Adulto , Peso ao Nascer/genética , Estudos de Coortes , Feminino , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Recém-Nascido Pequeno para a Idade Gestacional , MicroRNAs/genética , Síndrome do Ovário Policístico/epidemiologia , Síndrome do Ovário Policístico/genética , Estudos Retrospectivos
11.
J Clin Pathol ; 75(2): 85-93, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33234697

RESUMO

AIMS: DNA methylation has its distribution influenced by DNA demethylation processes with the catalytic conversion of 5-methylcytosine (5mC) into 5-hydroxymethylcytosine (5hmC). Myelodysplastic syndrome (MDS) has been associated with epigenetic dysregulation of genes related to DNA repair system, chronic immune response and cell cycle. METHODS: We evaluated the tissue DNA methylation/hydroxymethylation in bone marrow trephine biopsies of 73 patients with MDS, trying to correlate with the mRNA expression of 21 genes (POLH, POLL, REV3L, POLN, POLQ, POLI, POLK, IRF-1, IRF-2, IRF-3, IRF-4, IRF-5, IRF6, IRF-7, IRF-8,IRF-9, MAD2, CDC20, AURKA, AURKB and TPX2). RESULTS: The M-score (5mC) was significantly higher in patients with chromosomal abnormalities than patients with normal karyotype (95% CI -27.127779 to -2.368020; p=0.022). We observed a higher 5mC/5hmC ratio in patients classified as high-risk subtypes compared with low-risk subtypes (95% CI -72.922115 to -1.855662; p=0.040) as well as patients with hypercellular bone marrow compared with patients with normocellular/hypocellular bone marrow (95% CI -69.189259 to -0.511828; p=0.047) and with the presence of dyserythropoiesis (95% CI 17.077703 to 51.331388; p=0.001). DNA pols with translesion activity are significantly influenced by methylation. As 5mC immunoexpression increases, the expressions of POLH (r=-0.816; r2 =0.665; p=0.000), POLQ (r=-0.790; r2=0.624; p=0.001), PCNA (r=-0.635; r2=0.403; p=0.020), POLK (r=-0.633; r2=0.400; p=0.036 and REV1 (r=-0.578; r2=0.334; p=0.049) decrease. CONCLUSIONS: Our results confirm that there is an imbalance in the DNA methylation in MDS, influencing the development of chromosomal abnormalities which may be associated with the low expression of DNA polymerases with translesion synthesis polymerases activity.


Assuntos
Aberrações Cromossômicas , Metilação de DNA , DNA Polimerase Dirigida por DNA/genética , Epigênese Genética , Síndromes Mielodisplásicas/genética , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , DNA Polimerase Dirigida por DNA/metabolismo , Feminino , Humanos , Imuno-Histoquímica , Cariotipagem , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/enzimologia , Reação em Cadeia da Polimerase em Tempo Real , Adulto Jovem
12.
Reprod Sci ; 29(3): 680-694, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-33826098

RESUMO

Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders, affecting approximately 5-20% of women of reproductive age. PCOS is a multifactorial, complex, and heterogeneous disease, characterized by hyperandrogenism, ovulatory dysfunction, and polycystic ovaries, which may lead to impaired fertility. Besides the reproductive outcomes, multiple comorbidities, such as metabolic disturbances, insulin resistance, obesity, diabetes, and cardiovascular disease, are associated with PCOS. In addition to the clear genetic basis, epigenetic alterations may also play a central role in PCOS outcomes, as environmental and hormonal alterations directly affect clinical manifestations and PCOS development. Here, we highlighted the epigenetic modifications in the multiplicity of clinical manifestations, as well as environmental epigenetic disruptors, as intrauterine hormonal and metabolic alterations affecting embryo development and the adulthood lifestyle, which may contribute to PCOS development. Additionally, we also discussed the new approaches for future studies and potential epigenetic biomarkers for the treatment of associated comorbidities and improvement in quality of life of women with PCOS.


Assuntos
Epigênese Genética , Síndrome do Ovário Policístico/genética , Adulto , Feminino , Humanos
13.
Artigo em Inglês | MEDLINE | ID: mdl-34769797

RESUMO

Metabolic and hormonal outcomes of polycystic ovary syndrome (PCOS) have implications on telomere biology and physical activity may prevent telomere erosion. We sought to observe the effects of continuous (CAT) and intermittent (IAT) aerobic training on telomere length, inflammatory biomarkers, and its correlation with metabolic, hormonal, and anthropometric parameters of PCOS. This randomized controlled clinical trial study included 87 PCOS randomly stratified according to body mass index (BMI) in CAT (n = 28), IAT (n = 29) and non-training control group (CG, n = 30). The exercises were carried out on a treadmill, three times per week for 16 weeks. The participants' anthropometric characteristics and biochemical and hormonal concentrations were measured before and after aerobic training or observation period, as the telomere length that was evaluated using quantitative real-time PCR. Four months of aerobic exercises (CAT or IAT) did not alter telomere length and inflammatory biomarkers in PCOS women. Obesity index as BMI and waist circumference (WC), and inflammatory biomarkers negatively affect telomeres. The hyper-andro-genism measured by testosterone levels was reduced after both exercises (CAT, p ≤ 0.001; IAT, p = 0.019). In particular, the CAT reduced WC (p = 0.045), hip circumference (p = 0.032), serum cholesterol (p ≤ 0.001), and low-density lipoprotein (p = 0.030). Whereas, the IAT decreased WC (p = 0.014), waist-to-hip ratio (p = 0.012), free androgen index (FAI) (p = 0.037). WC (p = 0.049) and body fat (p = 0.015) increased in the non-training group while total cholesterol was reduced (p = 0.010). Booth exercises reduced obesity indices and hyperandrogenism on PCOS women without changes in telomere length or inflammatory biomarkers.


Assuntos
Resistência à Insulina , Síndrome do Ovário Policístico , Índice de Massa Corporal , Exercício Físico , Feminino , Humanos , Obesidade , Telômero , Testosterona
14.
Sci Rep ; 11(1): 18380, 2021 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-34526543

RESUMO

The imprinted H19 long non-coding RNA, a knowing oncofetal gene, presents a controversial role during the carcinogenesis process since its tumor suppressor or oncogenic activity is not completely elucidated. Since H19 lncRNA is involved in many biological pathways related to tumorigenesis, we sought to develop a non-cancer lineage with CRISPR-Cas9-mediated H19 knockdown (H19-) and observe the changes in a cellular context. To edit the promoter region of H19, two RNA guides were designed, and the murine C2C12 myoblast cells were transfected. H19 deletion was determined by DNA sequencing and gene expression by qPCR. We observed a small deletion (~ 60 bp) in the promoter region that presented four predicted transcription binding sites. The deletion reduced H19 expression (30%) and resulted in increased proliferative activity, altered morphological patterns including cell size and intracellular granularity, without changes in viability. The increased proliferation rate in the H19- cell seems to facilitate chromosomal abnormalities. The H19- myoblast presented characteristics similar to cancer cells, therefore the H19 lncRNA may be an important gene during the initiation of the tumorigenic process. Due to CRISPR/Cas9 permanent edition, the C2C12 H19- knockdown cells allows functional studies of H19 roles in tumorigenesis, prognosis, metastases, as well as drug resistance and targeted therapy.


Assuntos
Sistemas CRISPR-Cas , Neoplasias/genética , Neoplasias/patologia , Regiões Promotoras Genéticas , RNA Longo não Codificante/genética , Deleção de Sequência , Animais , Sequência de Bases , Biomarcadores Tumorais , Carcinogênese/genética , Ciclo Celular/genética , Proliferação de Células/genética , Análise Citogenética , Edição de Genes , Técnicas de Silenciamento de Genes , Humanos , Camundongos , RNA Longo não Codificante/química
15.
Arch Endocrinol Metab ; 64(3): 257-268, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555992

RESUMO

OBJECTIVE: To assess the utility of bioimpedance (BIA) and skinfolds thickness (SF) in body fat percentage measuring (%BF) compared to the reference method dual-energy x-ray absorptiometry (DXA) in Brazilian reproductive age women, as well as to estimate of inter- and intra-observer precision for SF. SUBJECTS AND METHODS: 170 women aged 18-37 years with BMI between 18 and 39.9 kg/m2 were selected for this cross-sectional study. Body density was evaluated through equations proposed by Jackson, Pollock and Ward (1980) (EqJPW) and Petroski (1995) (EqPET), and %BF was estimated by BIA, DXA and Siri's formula (1961). The SF were measured by two separate observers: A and B (to determine inter-observer variability), who measured the folds at three times with 10-minute interval between them (to determine intra-observer variability - we used only observer A). RESULTS: The %BF by DXA was higher than those measured by SF and BIA (p<0.01, for all) of 90 volunteers. The Lin coefficient of agreement was considered satisfactory for %BF values obtained by EqJPW and BIA (0.55) and moderate (0.76) for sum of SF (ΣSF) values obtained by EqJPW and EqPET. No agreement was observed for the values obtained by SF (EqJPW and EqPET), BIA and DXA. Analysis of inter- and intra-observer of 59 volunteers showed that different measures of SF thickness met acceptability standards, as well as the % BF. CONCLUSION: BIA and SF measurements may underestimate %BF compared with DXA. In addition, BIA and SF measurements are not interchangeable with DXA. However, our results suggest the equation proposed by Jackson, Pollock and Ward (three skinfolds) compared to BIA are interchangeable to quantify the %BF in Brazilian women in reproductive age. Furthermore, our results show acceptable accuracy for intra- and inter-observer skinfold measurements. Arch Endocrinol Metab. 2020;64(3):257-68.


Assuntos
Absorciometria de Fóton , Tecido Adiposo/anatomia & histologia , Antropometria/métodos , Composição Corporal , Impedância Elétrica , Dobras Cutâneas , Adolescente , Adulto , Análise de Variância , Estudos Transversais , Feminino , Humanos , Masculino , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Adulto Jovem
16.
Gynecol Endocrinol ; 36(12): 1119-1123, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32496827

RESUMO

BACKGROUND: Idiopathic central precocious puberty (iCPP) presents a disproportionate advancement of bone age and maturation, as well as metabolic and endocrinological changes that may be related to effects on telomere biology. OBJECTIVE: To investigate the telomere length in iCPP girls treated with GnRHa. STUDY DESIGN: Observational case-control study with 85 girls, including 45 iCPP treated with GnRHa and 40 controls. It was analyzed age, height, weight and body mass index (BMI), insulin, triglycerides, testosterone, insulin resistance by HOMA, and telomere length by real-time PCR. Statistical analyses were determined by Wilcoxon test and Spearman correlation was carried out. RESULTS: Weight, BMI, insulin level and HOMA index were higher in the iCPP than in the control group (p < .01); without difference between mean ages. The telomere length did not differ between iCPP and control group. However, a negative correlation was observed between the telomere length and age in iCPP (p = .0009) and control group (p = .014), and weight in the iCPP (p = .017). CONCLUSIONS: We did not observe any difference in the telomere length in the iCPP and control group. Even though, some characteristics of the disease, such as increased weight and body fat, negatively influence the telomere biology.


Assuntos
Hormônio Liberador de Gonadotropina/análogos & derivados , Leuprolida/uso terapêutico , Puberdade Precoce/metabolismo , Telômero/metabolismo , Adolescente , Fatores Etários , Composição Corporal , Índice de Massa Corporal , Peso Corporal , Estudos de Casos e Controles , Criança , Impedância Elétrica , Feminino , Humanos , Insulina/sangue , Resistência à Insulina , Puberdade Precoce/tratamento farmacológico , Homeostase do Telômero , Adulto Jovem
17.
J Affect Disord ; 262: 350-358, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31735408

RESUMO

BACKGROUND: Both physical and mental health care for women with polycystic ovary syndrome (PCOS) require a multidisciplinary approach. We evaluated the effects of continuous (CAT) and intermittent (IAT) aerobic training in different protocols that measure body image, anxiety, depression and sexual dysfunction in women with PCOS. METHODS: In this controlled clinical trial, women with PCOS were randomly allocated for 16 weeks to 1 out of 3 groups: CAT (n = 28), IAT (n = 29), or control group (CG, n = 30). For data collection, we used the Body Shape Questionnaire (BSQ), Figure Rating Scale (FRS), Female Sexual Function Index (FSFI), Hospital Anxiety and Depression Measurement Scales (HADS). RESULTS: No effects of CAT, IAT or CG groups were identified in the perceptual dimension of body image. The dis(satisfaction) grade improved after exercise in the CAT group (p ≤ 0.01) compared to the CG, as well as improved within CAT and IAT groups. Total FSFI, and HADS-A and HADS-D scores improved after exercise in the both groups. At baseline and after the study period, there were positive correlations between scores for dis(satisfaction), HADS-A and HADS-D scores. HADS-A and HADS-D scores had a negative correlation with FSFI total in the IAT (p = =0.02) group compared to the CG, as well as within CAT and IAT groups. LIMITATIONS: The participants were not matched for body mass index (normal, overweight and obese) which may interfere on body image dimensions. CONCLUSION: Aerobic exercise improves sexual function and indices related to anxiety and depression. Likewise, it interferes in cognitive-affective dimension of the body image.


Assuntos
Imagem Corporal/psicologia , Terapia por Exercício/métodos , Exercício Físico/psicologia , Síndrome do Ovário Policístico/psicologia , Síndrome do Ovário Policístico/terapia , Adulto , Ansiedade/etiologia , Ansiedade/terapia , Índice de Massa Corporal , Depressão/etiologia , Depressão/terapia , Feminino , Humanos , Obesidade/complicações , Obesidade/psicologia , Sobrepeso/complicações , Sobrepeso/psicologia , Satisfação Pessoal , Síndrome do Ovário Policístico/complicações , Disfunções Sexuais Psicogênicas/etiologia , Disfunções Sexuais Psicogênicas/terapia , Resultado do Tratamento
18.
Arch Endocrinol Metab ; 63(4): 417-426, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31365630

RESUMO

OBJECTIVE: To investigate the associations among visceral adiposity index (VAI), lipid accumulation product (LAP), body fat percentage (%), and android/gynoid ratio (A/G ratio) in women with polycystic ovary syndrome (PCOS) and verify if the parameters representative of visceral obesity correlate with and exhibit the same frequency as body composition variables; anthropometric indices; and metabolic, hormonal, and inflammatory parameters. SUBJECTS AND METHODS: This was a cross-sectional study that included 94 women with PCOS. Hormonal, metabolic, and inflammatory parameters were analyzed in all women. Free androgen index (FAI) and homeostasis model assessment (HOMA-IR), as well as LAP, VAI, and anthropometric indices, were calculated. The regions of interest (ROIs) in body composition and body composition indices were evaluated using a dual X-ray absorptiometry (DXA). Overall, 32 variables were selected as markers of body fat distribution. RESULTS: Among the 32 markers evaluated, 29 correlated with LAP, whereas 25 correlated with VAI, 19 with body fat (%), and 30 with A/G ratio. Additionally, some markers correlated with the four adiposity indices evaluated: ROIs, except for total mass and leg fat (%); body composition (body mass index, waist circumference, and hip circumference) indices; fasting insulin; and C-reactive protein. CONCLUSION: LAP and VAI may be sensitive measures for screening and preventing metabolic syndrome and insulin resistance in PCOS, with LAP being more sensitive than VAI, and the A/G ratio may be more sensitive than body fat percentage.


Assuntos
Distribuição da Gordura Corporal , Gordura Intra-Abdominal , Síndrome do Ovário Policístico/sangue , Adolescente , Adulto , Biomarcadores/sangue , Glicemia/análise , Composição Corporal , Proteína C-Reativa/análise , Estudos Transversais , Feminino , Humanos , Mediadores da Inflamação/sangue , Insulina/sangue , Produto da Acumulação Lipídica , Sobrepeso/sangue , Sensibilidade e Especificidade , Globulina de Ligação a Hormônio Sexual/análise , Testosterona/sangue , Adulto Jovem
19.
Arch. endocrinol. metab. (Online) ; 63(4): 417-426, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS | ID: biblio-1019352

RESUMO

ABSTRACT Objective To investigate the associations among visceral adiposity index (VAI), lipid accumulation product (LAP), body fat percentage (%), and android/gynoid ratio (A/G ratio) in women with polycystic ovary syndrome (PCOS) and verify if the parameters representative of visceral obesity correlate with and exhibit the same frequency as body composition variables; anthropometric indices; and metabolic, hormonal, and inflammatory parameters. Subjects and methods This was a cross-sectional study that included 94 women with PCOS. Hormonal, metabolic, and inflammatory parameters were analyzed in all women. Free androgen index (FAI) and homeostasis model assessment (HOMA-IR), as well as LAP, VAI, and anthropometric indices, were calculated. The regions of interest (ROIs) in body composition and body composition indices were evaluated using a dual X-ray absorptiometry (DXA). Overall, 32 variables were selected as markers of body fat distribution. Results Among the 32 markers evaluated, 29 correlated with LAP, whereas 25 correlated with VAI, 19 with body fat (%), and 30 with A/G ratio. Additionally, some markers correlated with the four adiposity indices evaluated: ROIs, except for total mass and leg fat (%); body composition (body mass index, waist circumference, and hip circumference) indices; fasting insulin; and C-reactive protein. Conclusion LAP and VAI may be sensitive measures for screening and preventing metabolic syndrome and insulin resistance in PCOS, with LAP being more sensitive than VAI, and the A/G ratio may be more sensitive than body fat percentage.


Assuntos
Humanos , Feminino , Adolescente , Adulto , Adulto Jovem , Síndrome do Ovário Policístico/sangue , Gordura Intra-Abdominal , Distribuição da Gordura Corporal , Testosterona/sangue , Glicemia/análise , Composição Corporal , Proteína C-Reativa/análise , Globulina de Ligação a Hormônio Sexual/análise , Biomarcadores/sangue , Estudos Transversais , Sensibilidade e Especificidade , Mediadores da Inflamação/sangue , Sobrepeso/sangue , Produto da Acumulação Lipídica , Insulina/sangue
20.
J Affect Disord ; 253: 385-393, 2019 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-31082731

RESUMO

BACKGROUND: Polycystic ovary syndrome (PCOS) is associated with lower levels of satisfaction with body image, which can affect sexuality and social well-being. Thus, we evaluated body image in women with PCOS and its association with body dis(satisfaction), anthropometric indices, sexual function, anxiety, and depression. METHODS: In this cross-sectional study, 94 women of reproductive age were grouped by body mass index (BMI) and sexual function. The Female Sexual Function Index (FSFI), Body Shape Questionnaire (BSQ), Figure Rating Scale (FRS), hospital anxiety (HADS-A) and depression (HADS-D) measurement scales, and anthropometric indices were used for data collection. RESULTS: Women with PCOS presented with perceptual distortions of self-image independent of sexual function and BMI. There were negative correlations between HADS-A and HADS-D scores and the FSFI total score, and HADS-D scores had positive correlations with weight, anthropometric indices, and BSQ total score. The degree of dis(satisfaction) was a predictor of FSFI total score, depression, and anxiety, and the FSFI total score was predicted by HADS-D. Desired and ideal-gender BMIs were risk factors for sexual dysfunction, and overweight and obesity were risk factors for the degree of dis(satisfaction). LIMITATIONS: This study had the limitations of using a cross-sectional design and it investigated a restricted number of clinical/biochemical parameters, as well as lacked objective measures of acne and hirsutism, and a control group. CONCLUSIONS: Perception and cognitive-affective dimensions appear to play important roles in body image dysfunction in women with PCOS, and impact sexual dysfunction and depression associated the syndrome. Furthermore, these results provide additional treatment considerations for women with PCOS.


Assuntos
Ansiedade/etiologia , Imagem Corporal/psicologia , Depressão/etiologia , Satisfação Pessoal , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/psicologia , Disfunções Sexuais Fisiológicas/psicologia , Adulto , Índice de Massa Corporal , Estudos Transversais , Feminino , Humanos , Obesidade/psicologia , Sobrepeso/complicações , Fatores de Risco , Autoimagem , Comportamento Sexual/psicologia
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