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1.
Oral Dis ; 29(7): 2658-2666, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35796645

RESUMO

OBJECTIVE: Oral squamous cell carcinoma (OSCC) is one of the most common neoplasms worldwide. The current study aimed to identify potential biomarkers associated with OSCC survival. MATERIALS AND METHODS: Differentially expressed genes (DEGs) in atypical OSCC cases were identified using two public datasets: The Cancer Genome Atlas and the Gene Expression Omnibus database. Receiver operating characteristic (ROC) analysis was performed to identify the cutoff, and the candidate DEGs related to survival. Kaplan-Meier and Cox regression analysis using the categorized genes were employed to identify genes that impact the overall survival in OSCC. RESULTS: A total of 263 OSCC samples and 105 healthy tissues were used to identify 295 upregulated and 131 downregulated genes expressed only in non-smokers. ROC analyses identified 25 candidate genes associated with death. Survival analyses demonstrated that the following DEGs, namely CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5, are potential OSCC prognostic factors. CONCLUSION: We found that CSTA, FGFR2, MMP19, OLR1, PCSK1, RAMP2, and CGB5 are associated with a low survival rate in OSCC. However, further studies are needed to validate our findings and facilitate the development of these factors as potential biomarkers for OSCC survival.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas/patologia , Transcriptoma , Neoplasias Bucais/metabolismo , Regulação Neoplásica da Expressão Gênica , Análise de Sobrevida , Biomarcadores Tumorais/genética , Neoplasias de Cabeça e Pescoço/genética , Prognóstico
2.
Lasers Med Sci ; 37(5): 2509-2516, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35119554

RESUMO

The aim of this study is to investigate the antineoplastic potential of photodynamic therapy (PDT) mediated by an aluminum-phthalocyanine chloride nanoemulsion (AlPc-NE), against an oral squamous cell carcinoma (OSCC) cell line in vitro. Both OSCC (SCC9) and A431 cell lines were studied in vitro. Four study groups were used: Group 1 (phosphate-buffered saline [PBS]), Group 2 (PBS + 28.3 J/cm2 irradiation), Group 3 (AlPc-NE alone), and Group 4 (AlPc-NE + 28.3 J/cm2 irradiation). To test the effect of PDT with AlPc-NE, cell viability, migration, and cell death assays were performed. Moreover, the expressions of Ki-67 and TP53 were evaluated using immunoassays. The results showed that PDT mediated by all AlPc-NE concentrations evaluated (i.e., 0.7, 0.35, and 0.17 nM AlPc) significantly reduced the viability of SCC9 cells. Migration and cell death assays also revealed that PDT with AlPc-NE significantly reduced the rate of migration and increased cell death compared to the control groups. In addition, it was found that PDT with AlPc-NE reduced Ki-67 and mutated TP53 immunoexpression. PDT with AlPc-NE is effective in reducing the viability and migration of SCC9. Moreover, PDT with AlPc-NE nanoemulsions reduces the cell proliferation and expression of mutant TP53.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Nanopartículas , Compostos Organometálicos , Fotoquimioterapia , Alumínio , Carcinoma de Células Escamosas/tratamento farmacológico , Humanos , Isoindóis , Antígeno Ki-67 , Neoplasias Bucais/tratamento farmacológico , Compostos Organometálicos/farmacologia , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/farmacologia , Fármacos Fotossensibilizantes/uso terapêutico
3.
Pediatr Nephrol ; 36(8): 2327-2336, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33585978

RESUMO

BACKGROUND: APOL1 high-risk genotypes (HRG) are associated with increased risk of kidney disease in individuals of African ancestry. We analyzed the effects of APOL1 risk variants on an ethnically diverse Brazilian pediatric nephrotic syndrome (NS) cohort. METHODS: Multicenter study including 318 NS patients, categorized as progressors to advanced CKD [estimated glomerular filtration rate (eGFR)] < 30 mL/min/1.73 m2] and slow/non-progressors (eGFR > 30 mL/min/1.73 m2 through the study). We employed Cox regression with progression time as the outcome and APOL1 genotype as the independent variable. We tested this association in the entire cohort and three subgroups; (1) focal segmental glomerulosclerosis (FSGS), (2) steroid-resistant NS (SRNS), and (3) those who underwent kidney biopsy. RESULTS: Nineteen patients (6%) had an HRG. Of these, 47% were self-reported White. Patients with HRG manifested NS at older ages and presented higher frequencies of FSGS and SRNS. HRG patients progressed to advanced CKD more often than low-risk-genotype (LRG) children in the whole NS cohort (p = 0.001) and the three subgroups. In SRNS and biopsied patients, a single risk variant was associated with trends of higher CKD progression risk. CONCLUSIONS: Novel discoveries include a substantial prevalence of HRG among patients self-reported White, worse kidney outcomes in HRG versus LRG children in the FSGS subgroup, and a trend of higher CKD progression risk associated with a single risk variant in the SRNS cohort. These findings suggest APOL1-associated NS extends beyond patients self-reported non-White, the HRG effect is independent of FSGS, and a single risk variant may have a detrimental impact in children with NS.


Assuntos
Glomerulosclerose Segmentar e Focal , Síndrome Nefrótica , Insuficiência Renal Crônica , Apolipoproteína L1/genética , Criança , Receptores ErbB , Glomerulosclerose Segmentar e Focal/diagnóstico , Glomerulosclerose Segmentar e Focal/genética , Humanos , Síndrome Nefrótica/genética
4.
J Vasc Bras ; 20: e20200123, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456983

RESUMO

We report a case of an asymptomatic, 77-year-old, male patient with arterial hypertension and no other comorbidities or risk factors for coronary disease. During a routine abdominal ultrasound examination, he was diagnosed with a hepatic vascular mass with an approximate diameter of 5 cm. Abdominal computed angiotomography was requested, showing an aneurysm of the hepatic artery, with maximum diameter of up to 5.2 cm, longest longitudinal axis of 7.2 cm, and a maximum true lumen caliber of 3.0 cm. We opted for endovascular aneurysm repair with implantation of three sequential Lifestream covered vascular stents (7x58mm, 8x58mm, and 8x37mm), successfully diverting the flow through the stents and excluding the aneurysm. The patient remains asymptomatic and free from clinical complications 2 years after the procedure. Control examinations with arterial duplex ultrasound 6 and 12 months after the procedure showed good flow through the stents with no leakage into the aneurysmal sac.

5.
Mol Genet Genomics ; 295(1): 135-142, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31520189

RESUMO

High-throughput techniques such as whole-exome sequencing (WES) show promise for the identification of candidate genes that underlie Mendelian diseases such as nephrotic syndrome (NS). These techniques have enabled the identification of a proportion of the approximately 54 genes associated with NS. However, the main pitfall of using WES in clinical and research practice is the identification of multiple variants, which hampers interpretation during downstream analysis. One useful strategy is to evaluate the co-inheritance of rare variants in affected family members. Here, we performed WES of a patient with steroid-resistant NS (SRNS) and intermittent microhematuria. Currently, 15 years after kidney transplantation, this patient presents normal kidney function. The patient was found to be homozygous for a rare MYO1E stop-gain variant, and was heterozygous for rare variants in NS-associated genes, COL4A4, KANK1, LAMB2, ANLN, E2F3, and APOL1. We evaluated the presence or absence of these variants in both parents and 11 siblings, three of whom exhibited a milder phenotype of the kidney disease. Analysis of variant segregation in the family, indicated the MYO1E stop-gain variant as the putative causal variant underlying the kidney disease in the patient and two of her affected sisters. Two secondary variants in COL4A4-identified in some other affected family members-require further functional studies to determine whether they play a role in the development of microhematuria in affected family members. Our data illustrate the difficulties in distinguishing the causal pathogenic variants from incidental findings after WES-based variant analysis, especially in heterogenous genetic conditions, such as NS.


Assuntos
Exoma/genética , Síndrome Nefrótica/genética , Adulto , Feminino , Variação Genética/genética , Heterozigoto , Homozigoto , Humanos , Rim/patologia , Masculino , Linhagem , Fenótipo , Sequenciamento do Exoma/métodos , Adulto Jovem
6.
J Oral Pathol Med ; 48(10): 929-934, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31325182

RESUMO

OBJECTIVE: Malignant salivary gland tumors (MSGTs) present different phenotypic characteristics and various clinical outcomes, which proved to be a diagnostic challenge. Considering the heterogeneity of MSGT, this study aims to identify molecule related to the nature of MSGT. METHODS: For screening, proteomic analysis comparing MSGT with pleomorphic adenoma (PA) and salivary gland was performed. The MSGT-associated protein which presented in the higher number in the Gene Expression Omnibus (GEO) database was selected. To validate the data, immunohistochemistry (IHC) was performed in 14 patients with PA, 22 patients with MSGT, and 14 controls. RESULTS: 16 proteins were associated with MSGT. ANXA2 was the primary protein, according to GEO database analyses. ANXA2 was most expressed in the cell membrane. However, some ANXA2 staining was also observed in the cytoplasm and nucleus. ANXA2 was highly expressed in MSGT in comparison with control. Also, ANXA2 has a higher expression in adenocarcinoma not otherwise specified (ANOS) and myoepithelial carcinoma (MC) in comparison with PA. CONCLUSION: In conclusion, this study demonstrated that MSGT presented higher levels of ANXA2 in comparison with normal salivary glands. Also, ANXA2 might be interesting as a molecular marker of ANOS and MS.


Assuntos
Adenoma Pleomorfo/metabolismo , Anexina A2/metabolismo , Carcinoma Adenoide Cístico/metabolismo , Carcinoma Mucoepidermoide/metabolismo , Neoplasias das Glândulas Salivares/metabolismo , Adenoma Pleomorfo/patologia , Biomarcadores Tumorais/metabolismo , Carcinoma Adenoide Cístico/patologia , Carcinoma Mucoepidermoide/patologia , Estudos de Casos e Controles , Humanos , Proteoma , Proteômica , Neoplasias das Glândulas Salivares/patologia
7.
Mycopathologia ; 182(7-8): 625-632, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28324245

RESUMO

The performance of three molecular biology techniques, i.e., DNA microarray, loop-mediated isothermal amplification (LAMP), and real-time PCR were compared with DNA sequencing for properly identification of 20 isolates of Fusarium spp. obtained from blood stream as etiologic agent of invasive infections in patients with hematologic malignancies. DNA microarray, LAMP and real-time PCR identified 16 (80%) out of 20 samples as Fusarium solani species complex (FSSC) and four (20%) as Fusarium spp. The agreement among the techniques was 100%. LAMP exhibited 100% specificity, while DNA microarray, LAMP and real-time PCR showed 100% sensitivity. The three techniques had 100% agreement with DNA sequencing. Sixteen isolates were identified as FSSC by sequencing, being five Fusarium keratoplasticum, nine Fusarium petroliphilum and two Fusarium solani. On the other hand, sequencing identified four isolates as Fusarium non-solani species complex (FNSSC), being three isolates as Fusarium napiforme and one isolate as Fusarium oxysporum. Finally, LAMP proved to be faster and more accessible than DNA microarray and real-time PCR, since it does not require a thermocycler. Therefore, LAMP signalizes as emerging and promising methodology to be used in routine identification of Fusarium spp. among cases of invasive fungal infections.


Assuntos
Fusariose/diagnóstico , Fusarium/isolamento & purificação , Neoplasias Hematológicas/complicações , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Hibridização de Ácido Nucleico/métodos , Análise de Sequência de DNA/métodos , Fungemia/diagnóstico , Fungemia/microbiologia , Fusariose/microbiologia , Fusarium/classificação , Fusarium/genética , Humanos , Sensibilidade e Especificidade
8.
Tumour Biol ; 35(6): 6113-8, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24633888

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is considered a serious public health problem in many countries. Recently, genetic variations have been considered as important factors to cancer susceptibility and prognosis. More specifically, genetic polymorphisms have been associated with the development and prognosis of HNSCC. The purpose of the current study was to investigate an association among p16 (CDKN2A) gene polymorphism at rs11515, age, and HNSCC aggressiveness. PCR-RFLP analysis was used to investigate the p16 (CDKN2A) gene in 96 patients with HNSCC and in 100 individuals without HNSCC. A case group was categorized by age in younger (<60 years) and older (≥ 60 years) patients. Differences between the case and control groups were determined using Fisher and chi-squared tests. Time of survival was calculated from the date of diagnosis to the date of last follow-up visit or to the date of death using the Kaplan-Meier estimator and comparing this to the log-rank test. Statistical significance was set at p<0.05. In the present study, no association was established between HNSCC and rs11515 polymorphism, as indicated in a previous study. We found that HNSCC individuals with large-sized tumors and with metastatic disease presented worse overall survival, consistent with fundamental concepts that establish the effects of tumor size and lymph node metastasis to HNSCC outcomes. This study identified that there is no difference in the distribution of rs11515 between the control and HNSCC groups. In addition, no differences between rs11515 genotypes and clinicopathological parameters were observed.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Carcinoma de Células Escamosas/mortalidade , Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina , Feminino , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma de Células Escamosas de Cabeça e Pescoço
9.
Zygote ; 21(1): 59-63, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-21867598

RESUMO

Trichostatin A (TSA) is a histone deacetylase inhibitor that induces histone hyperacetylation and increases gene expression levels. The aim of the present study was to establish a suitable condition for the use of TSA in in vitro cultures of bovine embryos, and to determine whether TSA would increase blastocyst rates by improvement of chromatin remodelling during embryonic genome activation and by increasing the expression of crucial genes during early development. To test this hypothesis, 8-cell embryos were exposed to four concentrations of TSA for different periods of time to establish adequate protocols. In a second experiment, three experimental groups were selected for the evaluation of embryo quality based on the following parameters: apoptosis, total cell number and blastocyst hatching. TSA promoted embryonic arrest and degeneration at concentrations of 15, 25 and 50 nM. All treated groups presented lower blastocyst rates. Exposure of embryos to 5 nM for 144 h and to 15 nM for 48 h decreased blastocyst hatching. However, the terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling assay (TUNEL) assay revealed similar apoptosis rates and total cell numbers in all groups studied. Although, in the present study, TSA treatment did not improve the parameters studied, the results provided background information on TSA supplementation during in vitro culture of bovine embryos and showed that embryo quality was apparently not affected, despite a decrease in blastocyst rate after exposure to TSA.


Assuntos
Blastocisto/efeitos dos fármacos , Bovinos/embriologia , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Animais , Apoptose/efeitos dos fármacos , Blastocisto/citologia , Blastocisto/fisiologia , Montagem e Desmontagem da Cromatina/efeitos dos fármacos , Relação Dose-Resposta a Droga , Técnicas de Cultura Embrionária , Embrião de Mamíferos/citologia , Feminino , Fertilização in vitro , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Masculino
10.
Monash Bioeth Rev ; 41(2): 181-197, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37156990

RESUMO

Due to the rapid advance of the pandemic caused by COVID-19, several countries perceived that human and material resources would be insufficient to meet the demand of infected patients. The aim of this study is to analyze the knowledge of health professionals working in the pandemic about the application of ethical criteria in decision-making in situations of resource scarcity. This is a cross-sectional, descriptive, and quantitative survey study, conducted from June to December 2020, with health professionals working in the COVID-19 pandemic in Brazil. We applied a questionnaire to assess the professionals' knowledge about ethical criteria in decision-making in the allocation of scarce resources during the pandemic, containing 14 questions and possible score from 0 to 70, which was developed by researchers from documents and protocols validated by organizations from various countries, available in the first months of the pandemic, a sociodemographic characterization questionnaire and a self-assessment questionnaire regarding knowledge about bioethics. A total of 197 health professionals participated in the study, 37.6% of whom were nurses and 22.8% of whom were physicians, working in the Family Health Unit (28.4%) with a degree at the level of specialization (46.2%). Moreover, (9.5%) of nurses, (18.2%) of dental surgeons and (24.4%) of physicians reported that they have no prior knowledge about bioethics. Physicians and hospital workers scored higher on the knowledge assessment questionnaire. The mean score of the participants was 45.4 (SD = 7.2). Investments in training and professional education in the field of health focused on Bioethics are necessary, considering models and ethical theories that help professionals, managers and society to better position themselves in the face of pandemic contexts.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Pandemias , Estudos Transversais , Pessoal de Saúde , Alocação de Recursos
11.
Gene ; 851: 147041, 2023 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-36375658

RESUMO

Differences in the features of aggressiveness of non-melanoma skin cancer (NMSC) subtypes, between basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are relevant characteristics. Comparing the characteristics between NMSC subtypes might help identify molecules associated with cancer metastasis and invasion. Considering these facts, the current study aimed to identify a molecular target for inhibiting skin cancer metastasis and invasion. Proteomic analysis suggested that heat shock protein 90 kDa, alpha, class B member 1 (HSP90AB1), pentaxin (PTX3), caspase-14 (CASP14), S100, actin-1, and profilin were the primary targets related to metastasis and invasion. However, after a differential expression comparison between BCC and SCC, HSP90AB1 was identified as the best target to repress metastasis and invasion. Based on molecular docking results, gallic acid (GA) was selected to inhibit HSP90AB1. A specific Hsp90ab1 siRNA targeting was designed and compared to GA. Interestingly, GA was more efficient in silencing HSP90AB1 than siRNAhsp90ab1. Hence, our data suggest that HSP90AB1 is a crucial biomarker for identifying invasion and metastasis and that its inhibition may be a viable strategy for treating skin cancer.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Neoplasias Cutâneas , Humanos , Proteínas de Choque Térmico , Ácido Gálico/farmacologia , Proteômica , Simulação de Acoplamento Molecular , Carcinoma Basocelular/metabolismo , Carcinoma de Células Escamosas/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Proteínas de Choque Térmico HSP90/genética
12.
Epigenetics Chromatin ; 15(1): 15, 2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35562812

RESUMO

BACKGROUND: Beef tenderness is a complex trait of economic importance for the beef industry. Understanding the epigenetic mechanisms underlying this trait may help improve the accuracy of breeding programs. However, little is known about epigenetic effects on Bos taurus muscle and their implications in tenderness, and no studies have been conducted in Bos indicus. RESULTS: Comparing methylation profile of Bos indicus skeletal muscle with contrasting beef tenderness at 14 days after slaughter, we identified differentially methylated cytosines and regions associated with this trait. Interestingly, muscle that became tender beef had higher levels of hypermethylation compared to the tough group. Enrichment analysis of predicted target genes suggested that differences in methylation between tender and tough beef may affect signal transduction pathways, among which G protein signaling was a key pathway. In addition, different methylation levels were found associated with expression levels of GNAS, PDE4B, EPCAM and EBF3 genes. The differentially methylated elements correlated with EBF3 and GNAS genes overlapped CpG islands and regulatory elements. GNAS, a complex imprinted gene, has a key role on G protein signaling pathways. Moreover, both G protein signaling pathway and the EBF3 gene regulate muscle homeostasis, relaxation, and muscle cell-specificity. CONCLUSIONS: We present differentially methylated loci that may be of interest to decipher the epigenetic mechanisms affecting tenderness. Supported by the previous knowledge about regulatory elements and gene function, the methylation data suggests EBF3 and GNAS as potential candidate genes and G protein signaling as potential candidate pathway associated with beef tenderness via methylation.


Assuntos
Metilação de DNA , Carne , Animais , Bovinos , Ilhas de CpG , Carne/análise , Músculo Esquelético/metabolismo , Transdução de Sinais
13.
Biochim Biophys Acta Gene Regul Mech ; 1865(8): 194886, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36265837

RESUMO

Single nucleotide polymorphisms showing allele-specific expression (ASE SNPs) are useful for cis-regulatory variants discovery. Despite this potential, there are expensive costs involved in genome-level ASE analysis for large sample sizes. If different data resolutions are available, genotype imputation can be used to mitigate this limitation. Aiming to increase the power to detect regulatory variants, we used a large dataset (>4 million) of imputed SNP genotypes and RNA-Seq data from 190 Nelore steers. Differences between major and minor allele expressions in muscle were tested with a Binomial Test. We identified 38,177 ASE SNPs (FDR ≤ 0.05) within 7304 linkage disequilibrium blocks. After that, we searched for aseQTLs (i.e., neighboring SNPs potentially regulating the ASE SNPs' allelic expression) by comparing the ASE of heterozygous to homozygous sample groups under a Wilcoxon Rank Sum test. We identified 21,543 aseQTLs potentially regulating 430 ASE SNPs (FDR ≤ 0.05). A total of 3333 cis-eQTLs (being 2098 ASE SNPs and 1075 aseQTLs) were associated with the expression of 758 transcripts (FDR ≤ 0.05), demonstrating the cis-regulatory effect of these ASE SNPs and aseQTLs. Data integration showed reproducibility with previous studies in bovine ASE and genomic imprinting. Furthermore, we identified 36,756 novel ASE regions due to the imputation approach. Comparisons with epigenetics data from Functional Annotation of Animal Genomes (FAANG) suggest a regulatory potential of the ASE-related SNPs. The affected genes were enriched in metabolic pathways essential for muscle homeostasis. These findings reinforce the potential of using ASE for discovering cis-regulatory SNPs that may affect muscle-related traits.


Assuntos
Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Bovinos/genética , Animais , Alelos , Reprodutibilidade dos Testes , Músculos
14.
Genes (Basel) ; 13(12)2022 12 11.
Artigo em Inglês | MEDLINE | ID: mdl-36553605

RESUMO

Traditional transcriptomics approaches have been used to identify candidate genes affecting economically important livestock traits. Regulatory variants affecting these traits, however, remain under covered. Genomic regions showing allele-specific expression (ASE) are under the effect of cis-regulatory variants, being useful for improving the accuracy of genomic selection models. Taking advantage of the better of these two methods, we investigated single nucleotide polymorphisms (SNPs) in regions showing differential ASE (DASE SNPs) between contrasting groups for beef quality traits. For these analyses, we used RNA sequencing data, imputed genotypes and genomic estimated breeding values of muscle-related traits from 190 Nelore (Bos indicus) steers. We selected 40 contrasting unrelated samples for the analysis (N = 20 animals per contrasting group) and used a beta-binomial model to identify ASE SNPs in only one group (i.e., DASE SNPs). We found 1479 DASE SNPs (FDR ≤ 0.05) associated with 55 beef-quality traits. Most DASE genes were involved with tenderness and muscle homeostasis, presenting a co-expression module enriched for the protein ubiquitination process. The results overlapped with epigenetics and phenotype-associated data, suggesting that DASE SNPs are potentially linked to cis-regulatory variants affecting simultaneously the transcription and phenotype through chromatin state modulation.


Assuntos
Carne , Músculo Esquelético , Bovinos/genética , Animais , Alelos , Fenótipo , Genótipo , Músculo Esquelético/metabolismo
15.
Front Genet ; 12: 709937, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646299

RESUMO

Animals with muscle hypertrophy phenotype are targeted by the broiler industry to increase the meat production and the quality of the final product. Studies characterizing the molecular machinery involved with these processes, such as quantitative trait loci studies, have been carried out identifying several candidate genes related to this trait; however, validation studies of these candidate genes in cell culture is scarce. The aim of this study was to evaluate SAP30 as a candidate gene for muscle development and to validate its function in cell culture in vitro. The SAP30 gene was downregulated in C2C12 muscle cell culture using siRNA technology to evaluate its impact on morphometric traits and gene expression by RNA-seq analysis. Modulation of SAP30 expression increased C2C12 myotube area, indicating a role in muscle hypertrophy. RNA-seq analysis identified several upregulated genes annotated in muscle development in treated cells (SAP30-knockdown), corroborating the role of SAP30 gene in muscle development regulation. Here, we provide experimental evidence of the involvement of SAP30 gene as a regulator of muscle cell hypertrophy.

16.
J Infect Dev Ctries ; 15(10): 1551-1554, 2021 10 31.
Artigo em Inglês | MEDLINE | ID: mdl-34780380

RESUMO

INTRODUCTION: Human T-lymphotropic virus (HTLV) 1 and 2 infections can lead to neurological diseases, mainly in HIV/HTLV 1 coinfected. Furthermore, HTLV 1 infection in HIV/AIDS patients has also been associated with AIDS progression. Despite this, HTLV 1/2 infections are not of mandatory notification in Brazil. Here, we describe the prevalence of HTLV 1/2 in HIV/AIDS patients from Paraíba state, Brazil, as well as the sociodemographic characteristics of the coinfected individuals. METHODOLOGY: Information about HIV viral load and TCD4 lymphocyte count were obtained from patients' records. Data on the patients' sociodemographic characteristics were obtained by interview conducted after signing the informed consent form. The serological diagnosis for HTLV 1/2 was performed by Enzyme-Linked Immunosorbent Assay (ELISA) and Western Blot (WB). RESULTS: A total of 401 HIV/AIDS patients participated in the study, of whom about 1.5% (6/401) were positive for antibodies against HTLV, specifically for HTLV 1, evaluated by both ELISA and WB. No risk factors were found associated with HIV/HTLV 1/2 coinfection. CONCLUSIONS: We report a 1.5% prevalence of HTLV 1 infection in HIV/AIDS patients from Paraíba state. Although we have not identified risk factors associated with HTLV 1, we describe the most observed sociodemographic characteristics in HIV/HTLV 1 coinfection.


Assuntos
Infecções por HIV/epidemiologia , Infecções por HTLV-I/epidemiologia , Brasil/epidemiologia , Coinfecção , Estudos Transversais , Feminino , Infecções por HIV/transmissão , Infecções por HTLV-I/transmissão , Humanos , Masculino , Prevalência , Fatores de Risco
17.
Protein Pept Lett ; 28(7): 735-749, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33302827

RESUMO

BACKGROUND: Oral cancer is a significant health problem worldwide. Oral squamous cell carcinoma (OSCC) is a malignant neoplasm of epithelial cells that mostly affects different anatomical sites in the head and neck and derives from the squamous epithelium or displays similar morphological characteristics. Generally, OSCC is often the end stage of several changes in the stratified squamous epithelium, which begin as epithelial dysplasia and progress by breaking the basement membrane and invading adjacent tissues. Several plant-based drugs with potent anti-cancer effects are considered inexpensive treatments with limited side effects for cancer and other diseases. OBJECTIVE: The aim of this review is to explore whether some Brazilian plant extracts or constituents exhibit anti-tumorigenic activity or have a cytotoxic effect on human oral carcinoma cells. METHODS: Briefly, OSCC and several metabolites derived from Brazilian plants (i.e., flavonoids, vinblastine, irinotecan, etoposide and paclitaxel) were used as keywords to search the literature on PubMed, GenBank and GeneCards. RESULTS: The results showed that these five chemical compounds found in Cerrado Biome plants exhibit anti-neoplastic effects. Evaluating the compounds revealed that they play a main role in the regulation of cell proliferation. CONCLUSION: Preserving and utilising the biodiversity of our planet, especially in unique ecosystems, such as the Cerrado Biome, may prove essential to preserving and promoting human health in modern contexts.


Assuntos
Anticarcinógenos/farmacologia , Antineoplásicos Fitogênicos/farmacologia , Carcinogênese/efeitos dos fármacos , Carcinoma de Células Escamosas/tratamento farmacológico , Neoplasias Bucais/tratamento farmacológico , Proteínas de Neoplasias/genética , Anticarcinógenos/química , Anticarcinógenos/isolamento & purificação , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Brasil , Carcinogênese/genética , Carcinogênese/metabolismo , Carcinogênese/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Proliferação de Células/efeitos dos fármacos , Biologia Computacional/métodos , Etoposídeo/química , Etoposídeo/isolamento & purificação , Etoposídeo/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica , Humanos , Irinotecano/química , Irinotecano/isolamento & purificação , Irinotecano/farmacologia , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Proteínas de Neoplasias/antagonistas & inibidores , Proteínas de Neoplasias/metabolismo , Paclitaxel/química , Paclitaxel/isolamento & purificação , Paclitaxel/farmacologia , Extratos Vegetais/química , Plantas Medicinais , Vimblastina/química , Vimblastina/isolamento & purificação , Vimblastina/farmacologia
18.
Sci Rep ; 11(1): 7321, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33795794

RESUMO

Single nucleotide polymorphisms (SNPs) located in transcript sequences showing allele-specific expression (ASE SNPs) were previously identified in the Longissimus thoracis muscle of a Nelore (Bos indicus) population consisting of 190 steers. Given that the allele-specific expression pattern may result from cis-regulatory SNPs, called allele-specific expression quantitative trait loci (aseQTLs), in this study, we searched for aseQTLs in a window of 1 Mb upstream and downstream from each ASE SNP. After this initial analysis, aiming to investigate variants with a potential regulatory role, we further screened our aseQTL data for sequence similarity with transcription factor binding sites and microRNA (miRNA) binding sites. These aseQTLs were overlapped with methylation data from reduced representation bisulfite sequencing (RRBS) obtained from 12 animals of the same population. We identified 1134 aseQTLs associated with 126 different ASE SNPs. For 215 aseQTLs, one allele potentially affected the affinity of a muscle-expressed transcription factor to its binding site. 162 aseQTLs were predicted to affect 149 miRNA binding sites, from which 114 miRNAs were expressed in muscle. Also, 16 aseQTLs were methylated in our population. Integration of aseQTL with GWAS data revealed enrichment for traits such as meat tenderness, ribeye area, and intramuscular fat . To our knowledge, this is the first report of aseQTLs identification in bovine muscle. Our findings indicate that various cis-regulatory and epigenetic mechanisms can affect multiple variants to modulate the allelic expression. Some of the potential regulatory variants described here were associated with the expression pattern of genes related to interesting phenotypes for livestock. Thus, these variants might be useful for the comprehension of the genetic control of these phenotypes.


Assuntos
Alelos , Carne , Músculo Esquelético/metabolismo , Animais , Sítios de Ligação , Biotecnologia/métodos , Bovinos , Metilação de DNA , Expressão Gênica , Regulação da Expressão Gênica , Marcadores Genéticos , Genoma , Estudo de Associação Genômica Ampla , Genótipo , Heterozigoto , Desequilíbrio de Ligação , Metilação , MicroRNAs/metabolismo , Fenótipo , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
19.
Reprod Fertil Dev ; 22(6): 1041-8, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20591338

RESUMO

Trichostatin A (TSA) induces histone hyperacetylation by inhibiting histone deacetylases and consequently increasing gene expression. The hypothesis was that TSA supplementation during the in vitro culture (IVC) of bovine embryos would increase the blastocyst rate, particularly in low-quality and female embryos. Oocytes were fertilised separately with X and Y spermatozoa and, 70 h after IVF, the IVC medium was supplemented with 5 nM and 15 nM TSA for 48 or 144 h. Incubation of female embryos with 5 nM and 15 nM TSA resulted in similar increases in acetylated histone H3K9 levels. However, to see comparable effects on acetylated histone H3K9 levels in male embryos, the culture medium needed to be supplemented with 15 nM TSA (as opposed to 5 nM TSA for female embryos). Treatment of male and female embryos with 5 nM TSA for 48 h or female embryos with 5 nM for 144 h had no effect on blastocyst rates, although 15 nM TSA compromised embryonic development. The terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labelling (TUNEL) assay revealed increased apoptosis in female embryos treated with 5 nM TSA for 144 h, as well as in male and female embryos treated with 15 nM TSA for 48 h, but this increase in apoptosis was not observed in low-quality embryos. The results of the present study suggest that TSA treatment promotes histone hyperacetylation, but has no beneficial effects on the in vitro production of male and female bovine embryos during preimplantation development.


Assuntos
Blastocisto/metabolismo , Desenvolvimento Embrionário/fisiologia , Histonas/metabolismo , Acetilação/efeitos dos fármacos , Análise de Variância , Animais , Apoptose/efeitos dos fármacos , Apoptose/fisiologia , Blastocisto/efeitos dos fármacos , Bovinos , Técnicas de Cultura Embrionária , Desenvolvimento Embrionário/efeitos dos fármacos , Feminino , Inibidores de Histona Desacetilases/farmacologia , Ácidos Hidroxâmicos/farmacologia , Imuno-Histoquímica , Marcação In Situ das Extremidades Cortadas , Masculino , Fatores Sexuais
20.
IBRO Rep ; 9: 9-13, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33336100

RESUMO

Cancer patients present a higher risk of experiencing anxiety disorders (AD). However, it is not clear if AD might be associated with cancer development. Thus, our study aimed to evaluate if AD might be related to head and neck squamous cell carcinoma (HNSCC) development. The combination of an applied animal basic study and a retrospective diagnostic case and control study in patients was performed. As a result, we obtained that stress reduced the locomotor activity of the animals in the group stress and stress + 4NqO (p < 0.0001). The stress showed no influence on the progression of neoplasia in mice. In the same way, the case group did not present differences in anxiety scores in comparison to control. Moreover, no association between HNSCC staging and anxiety scores was observed. In conclusion, our in vivo findings in humans and animals have shown that there is no relationship between AD and oral squamous cell carcinoma.

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