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2.
Mol Biol Rep ; 51(1): 458, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38551694

RESUMO

Arterial hypertension is characterized by systolic pressure ≥ 140 mmHg and/or diastolic pressure ≥ 90 mmHg and its treatment consists of the use of antihypertensive drugs, as losartan and hydrochlorothiazide. Blood pressure is regulated by angiotensin-converting enzyme (ACE) and polymorphisms in the ACE gene are associated to a greater predisposition to hypertension and response to treatment. The aim of this study was to evaluate the association of genetic polymorphisms of ACE rs4363, rs4291 and rs4335 and the response to antihypertensive drugs in hypertensive patients from Ouro Preto/MG, Brazil. A case-control study was carried out with 87 hypertensive patients being treated with losartan and 75 with hydrochlorothiazide, who answered a questionnaire and had blood samples collected. Biochemical analyzes were performed on serum using UV/Vis spectrophotometry and identification of ACE variants rs4363, rs4291 and rs4335 was performed by real-time PCR using the TaqMan® system. Univariate logistic regression test was performed to compare categorical data in STATA 13.0 software. The results showed that there was an influence of ACE polymorphisms on the response to losartan, demonstrating that AT or TT genotypes of rs4291 were more frequent in the group of controlled AH (54.9%), indicating that these individuals are 2.8 times more likely to of being controlled AH (95% CI 1.12-6.80, p. =0.026) compared to those with AA genotype. In contrast, no influence of ACE polymorphisms on the response to hydrochlorothiazide was observed. In conclusion, the presence of the T allele of the rs4291 variant was associated to controled blood pressure when losartan was used as an antihypertensive agent. These results show the importance of pharmacogenetic studies to detect genetic characteristics, enabling therapeutic individuality and reducing costs for the healthcare system.


Assuntos
Anti-Hipertensivos , Hipertensão , Losartan , Peptidil Dipeptidase A , Humanos , Anti-Hipertensivos/uso terapêutico , Anti-Hipertensivos/farmacologia , Pressão Sanguínea/genética , Estudos de Casos e Controles , Hidroclorotiazida/uso terapêutico , Hidroclorotiazida/farmacologia , Hipertensão/tratamento farmacológico , Hipertensão/genética , Losartan/uso terapêutico , Losartan/farmacologia , Polimorfismo de Nucleotídeo Único/genética , Peptidil Dipeptidase A/genética
3.
Environ Mol Mutagen ; 65(3-4): 143-152, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38523463

RESUMO

Cervical cancer is the fourth most commonly diagnosed cancer in women and is considered a preventable disease, as vaccination and screening programs effectively reduce its incidence and mortality rates. Disease physiopathology and malignant cell transformation is a complex process, but it is widely known that high-risk HPV (hrHPV) infection is a necessary risk factor for cancer development. Mitochondria, cell organelles with important bioenergetic and biosynthetic functions, are important for cell energy production, cell growth, and apoptosis. Mitochondrial DNA is a structure that is particularly susceptible to quantitative (mtDNA copy number variation) and qualitative (sequence variations) alterations that are associated with various types of cancer. Novel biomarkers with diagnostic and prognostic value in cervical cancer can be evaluated to provide higher specificity and complement hrHPV molecular testing, which is the most recommended method for primary screening. In accordance with this, this review aimed to assess mitochondrial alterations associated with cervical cancer in clinical cervicovaginal samples, in order to unravel their possible role as specific diagnostic and prognostic biomarkers for cervical malignancy, and also to guide the understanding of their involvement in carcinogenesis, HPV infection, and disease progression.


Assuntos
Variações do Número de Cópias de DNA , DNA Mitocondrial , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia , Neoplasias do Colo do Útero/patologia , DNA Mitocondrial/genética , Feminino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Infecções por Papillomavirus/virologia , Mitocôndrias/genética , Mitocôndrias/metabolismo , Biomarcadores Tumorais/genética , Prognóstico
4.
Toxicol Mech Methods ; 34(3): 237-244, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37982319

RESUMO

In a world with a rising use of pesticides, these chemicals, although designed to effectively control pests, pose potential threats to the environment and non-target organisms, including humans. Thus, this systematic review aims to investigate a possible association between genetic polymorphisms and susceptibility and genotoxicity in individuals occupationally exposed to pesticides. This review was conducted following the 2020 Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. A total of 14 carefully selected studies were thoroughly analyzed by two reviewers, who assigned scores based on previously set evaluation criteria. This study classified over half of the chosen studies as having moderate or strong quality, observing a correlation between certain genetic polymorphisms involved in xenobiotic metabolism and genotoxicity in workers exposed to pesticides. Results suggest that the genes associated with xenobiotic metabolism play a substantial role in determining individuals' susceptibility to genomic damage due to pesticide exposure, affecting both their peripheral blood and oral mucosa. This implies that individuals with specific genotypes may experience increased or decreased levels of DNA damage when exposed to these chemicals.


Assuntos
Exposição Ocupacional , Praguicidas , Humanos , Praguicidas/toxicidade , Exposição Ocupacional/efeitos adversos , Xenobióticos , Polimorfismo Genético , Dano ao DNA
5.
Mol Biol Rep, v. 51, n. 31, 2024.
Artigo em Inglês | Sec. Est. Saúde SP, SESSP-IBPROD, Sec. Est. Saúde SP | ID: bud-5214

RESUMO

Cardiovascular diseases are the leading cause of death worldwide. They are non-transmissible diseases that affect the cardiovascular system and have different etiologies such as smoking, lipid disorders, diabetes, stress, sedentary lifestyle and genetic factors. To date, lncRNAs have been associated with increased susceptibility to the development of cardiovascular diseases such as hypertension, acute myocardial infarction, stroke, angina and heart failure. In this way, lncRNAs are becoming a very promising point for the prevention and diagnosis of cardiovascular diseases. Therefore, this review highlights the most important and recent discoveries about the mechanisms of action of the lncRNAs ANRIL, H19 and TUG1 and their clinical relevance in these pathologies. This may contribute to early detection of cardiovascular diseases in order to prevent the pathological phenotype from becoming established.

6.
Biomarkers ; 28(8): 692-702, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38131287

RESUMO

BACKGROUND AND OBJECTIVES: In order to detect genetic damage, different methods have been developed, such as micronuclei and comet assay. The comet assay presents some advantages when compared to the other aforementioned methods, including wide versatility, as any eukaryotic cell can be evaluated at an individual cellular level. In this context, the aim of this systematic review was designed to help further elucidate the following question: is the comet assay a suitable biomarker of in vivo oral carcinogenesis? MATERIAL AND METHODS: The present systematic review was performed in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Full manuscripts from 18 studies were carefully selected in this setting. RESULTS: A total of 15 studies demonstrated positive findings for genotoxicity in peripheral blood or oral cells in patients with pre-malignant lesions or oral cancer. In the quality assessment of studies, 1 was classified as Strong, 5 were considered as Moderate, and 12 were classified as Weak. CONCLUSION: In summary, the comet assay can be a useful biomarker for oral carcinogenesis. However, further studies with more strict parameters are suggested (with less uncontrolled confounders) in order to increase findings reliability for diagnosis of oral potentially malignant lesions.


Assuntos
Dano ao DNA , Neoplasias Bucais , Humanos , Carcinogênese/genética , Ensaio Cometa/métodos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Reprodutibilidade dos Testes
7.
Mol Biol Rep ; 51(1): 31, 2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38155319

RESUMO

Cardiovascular diseases are the leading cause of death worldwide. They are non-transmissible diseases that affect the cardiovascular system and have different etiologies such as smoking, lipid disorders, diabetes, stress, sedentary lifestyle and genetic factors. To date, lncRNAs have been associated with increased susceptibility to the development of cardiovascular diseases such as hypertension, acute myocardial infarction, stroke, angina and heart failure. In this way, lncRNAs are becoming a very promising point for the prevention and diagnosis of cardiovascular diseases. Therefore, this review highlights the most important and recent discoveries about the mechanisms of action of the lncRNAs ANRIL, H19 and TUG1 and their clinical relevance in these pathologies. This may contribute to early detection of cardiovascular diseases in order to prevent the pathological phenotype from becoming established.


Assuntos
Doenças Cardiovasculares , RNA Longo não Codificante , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/fisiopatologia , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Humanos , Predisposição Genética para Doença
8.
Nat Prod Res ; : 1-7, 2023 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-38126137

RESUMO

Quinones are chemical compounds produced from the oxidation of phenols. Among the quinones, naphthoquinones stand out as potential antitumor agents. Bladder tumour is the tenth most diagnosed in the world. Based on this, using a urothelial carcinoma cell line (T24), two naphthoquinones had their cytotoxicity tested by the MTT colorimetric method and were submitted to assays of clonogenic survival, morphology, cell cycle, cell migration and species reactive oxygen. The results showed 8-methoxy-α-lapachone and lausone presented selectivity indexes (19.5 and 28.0, respectively) for T24 cells. Moreover, the two naphthoquinones reduced the cell viability, interfered with the process of cell migration, changed the cell cycle kinectics and induced the production of species reactive oxygen (ROS). Additionaly, 8-methoxy-α-lapachone altered the morphology of the cells. In conclusion, the studied naphthoquinones showed potential antiproliferative effects in bladder cancer cells, interfering in cellular processes, possibly through oxidative stress.

9.
Arq. bras. cardiol ; 120(12): e20230396, dez. 2023. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1527796

RESUMO

Resumo Fundamento Genes e suas variantes associadas a fatores ambientais contribuem para o desenvolvimento do fenótipo hipertenso. O gene da subunidade beta 3 da proteína G ( GNB3 ) está envolvido no processo de sinalização intracelular e suas variantes têm sido relacionadas à suscetibilidade à hipertensão arterial. Objetivo Determinar a associação da variante GNB3 (rs5443:C>T) com a hipertensão arterial, parâmetros bioquímicos, idade e obesidade em indivíduos hipertensos e normotensos de Ouro Preto, Minas Gerais. Método A identificação das variantes foi realizada por PCR em tempo real, utilizando o sistema TaqMan®, em amostras de 310 pacientes (155 hipertensos e 155 normotensos). Análises bioquímicas (função renal, perfil lipídico e glicemia) foram realizadas a partir do soro por meio de espectrofotometria UV/Vis e eletrodo íon-seletivo. Foi utilizado um modelo de regressão logística múltipla para identificar fatores associados à hipertensão arterial. A análise das variáveis contínuas com distribuição normal foi realizada usando o teste t de Student não pareado; dados não normais foram analisados usando o teste de Mann-Whitney. Valores de p < 0,05 foram considerados significativos. Resultados A variante rs5443:C>T não esteve associada à hipertensão arterial na população avaliada (p = 0,88). Em relação às medidas bioquímicas, o alelo T esteve associado a níveis elevados de triglicerídeos, glicose e ácido úrico em indivíduos hipertensos (p < 0,05). Conclusão Os presentes resultados mostram a importância do diagnóstico genético para prevenir as causas e consequências de doenças e sugerem que a variante GNB3 rs5443:C>T pode estar associada a alterações no perfil bioquímico em indivíduos hipertensos.


Abstract Background Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. Objective To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. Method The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. Results The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). Conclusion These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.

10.
Arq Bras Cardiol ; 120(12): e20230396, 2023 Dec.
Artigo em Português, Inglês | MEDLINE | ID: mdl-38126445

RESUMO

BACKGROUND: Central Illustration : G Protein Subunit Beta 3 (GNB3) Variant Is Associated with Biochemical Changes in Brazilian Patients with Hypertension. BACKGROUND: Genes and their variants associated with environmental factors contribute to the development of the hypertensive phenotype. The G protein beta 3 subunit gene (GNB3) is involved in the intracellular signaling process, and its variants have been related to susceptibility to arterial hypertension. OBJECTIVE: To determine the association of the GNB3 variant (rs5443:C>T) with arterial hypertension, biochemical parameters, age, and obesity in hypertensive and normotensive individuals from Ouro Preto, Minas Gerais, Brazil. METHOD: The identification of variants was performed by real-time PCR, using the TaqMan® system, in 310 samples (155 hypertensive and 155 normotensive). Biochemical analyses (renal function, lipid profile and glycemia) were performed from the serum using UV/Vis spectrophotometry and ion-selective electrode. A multiple logistic regression model was used to identify factors associated with arterial hypertension. The analysis of continuous variables with normal distribution was performed using the unpaired Student's t test; non-normal data were analyzed using Mann-Whitney. P < 0.05 was considered significant. RESULTS: The rs5443:C>T variant was not associated with arterial hypertension in the evaluated population (p = 0.88). Regarding biochemical measures, the T allele was associated with high levels of triglycerides, glucose and uric acid in hypertensive individuals (p < 0.05). CONCLUSION: These results show the importance of genetic diagnosis to prevent the causes and consequences of diseases and imply that the GNB3 rs5443:C>T variant may be associated with changes in the biochemical profile in hypertensive individuals.


Assuntos
Proteínas Heterotriméricas de Ligação ao GTP , Hipertensão , Humanos , Alelos , Pressão Sanguínea/genética , Brasil , Genótipo , Hipertensão/genética , Subunidades Proteicas/genética , Proteínas Heterotriméricas de Ligação ao GTP/genética
11.
Bioorg Med Chem ; 96: 117516, 2023 12 15.
Artigo em Inglês | MEDLINE | ID: mdl-37944413

RESUMO

Cancer still represents a serious public health problem and one of the main problems related to the worsening of this disease is the ability of some tumors to develop metastasis. In this work, we synthesized a new series of chalcones and isoxazoles derived from eugenol and analogues as molecular hybrids and these compounds were evaluated against different tumor cell lines. This structural pattern was designed considering the cytotoxic potential already known for eugenol, chalcones and isoxazoles. Notably, chalcones 7, 9, 10, and 11 displayed significant activity (4.2-14.5 µM) against two cancer cell lines, surpassing the potency of the control drug doxorubicin. The reaction of chalcones with hydroxylamine hydrochloride provided the corresponding isoxazoles that were inactive against these cancer cells. The dihydroeugenol chalcone 7 showed the most promising results, demonstrating higher potency against HepG2 (CC50: 4.2 µM) and TOV-21G (CC50: 7.2 µM). Chalcone 7 was also three times less toxic than doxorubicin considering HepG2 cells, with a selectivity index greater than 11. Further investigations including clonogenic survival, cell cycle progression and cell migration assays confirmed the compelling antitumoral potential of chalcone 7, as it reduced long-term survival due to DNA fragmentation, inducing cell death and inhibiting HepG2 cells migration. Moreover, in silico studies involving docking and molecular dynamics revealed a consistent binding mode of chalcone 7 with metalloproteinases, particularly MMP-9, shedding light on its potential mechanism of action related to anti-migratory effects. These significant findings suggest the inclusion of compound 7 as a promising candidate for future studies in the field of cancer therapeutics.


Assuntos
Antineoplásicos , Chalcona , Chalconas , Neoplasias , Chalcona/farmacologia , Chalcona/química , Chalconas/farmacologia , Chalconas/química , Eugenol/farmacologia , Antineoplásicos/química , Linhagem Celular Tumoral , Doxorrubicina/farmacologia , Isoxazóis/farmacologia , Proliferação de Células , Estrutura Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Simulação de Acoplamento Molecular , Relação Estrutura-Atividade
12.
Eur J Med Chem ; 258: 115622, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37441850

RESUMO

Chagas disease (CD) is a neglected tropical disease endemic in 21 countries and affects about 8 million people around the world. The pharmacotherapy for this disease is limited to two drugs (Benznidazole and Nifurtimox) and both are associated with important limitations, as low cure rate in the chronic phase of the disease, high toxicity and increasing resistance by Trypanosoma cruzi. Recently, we reported a bioactive 1,2,3-triazole (compound 35) active in vitro (IC50 42.8 µM) and in vivo (100 mg/kg) against T. cruzi Y strains and preliminary in silico studies suggested the cysteine protease cruzain as a possible target. Considering these initial findings, we describe here the design and synthesis of new 1,2,3-triazoles derivatives of our hit compound (35). The triazoles were initially evaluated against healthy cells derived from neonatal rat cardiomyoblasts (H9c2 cells) to determine their cytotoxicity and against epimastigotes forms of T. cruzi Y strain. The most active triazoles were compounds 26 (IC50 19.7 µM) and 27 (IC50 7.3 µM), while benznidazole was active at 21.6 µM. Derivative 27 showed an interesting selectivity index considering healthy H9c2 cells (>77). Promising activities against trypomastigotes forms of the parasite were also observed for triazoles 26 (IC50 20.74 µM) and 27 (IC50 8.41 µM), mainly 27 which showed activity once again higher than that observed for benznidazole (IC50 12.72 µM). While docking results suggested cruzain as a potential target for these compounds, no significant enzyme inhibition was observed in vitro, indicating that their trypanocidal activity is related to another mode of action. Considering the promising in vitro results of triazoles 26 and 27, the in vivo toxicity was initially verified based on the evaluation of behavioral and physiological parameters, mortality, effect in body weight gain, and through the measurement of AST/ALT enzymes, which are markers of liver toxicity. All these evaluations pointed to a good tolerability of the animals, especially considering triazole 27. A reduction in parasitemia was observed among animals treated with triazole 27, but not among those treated with derivative 26. Regarding the dosage, derivative 27 (100 mg/kg) was the most active sample against T. cruzi infection, showing a 99.4% reduction in parasitemia peak. Triazole 27 at a dosage of 100 mg/kg influenced the humoral immune response and reduced myocarditis in the animals, bringing antibody levels closer to those observed among healthy mice. Altogether, our results indicate compound 27 as a new lead for the development of drug candidates to treat Chagas disease.


Assuntos
Doença de Chagas , Tripanossomicidas , Trypanosoma cruzi , Camundongos , Ratos , Animais , Eugenol/farmacologia , Triazóis/farmacologia , Triazóis/uso terapêutico , Parasitemia/tratamento farmacológico , Tripanossomicidas/toxicidade , Doença de Chagas/tratamento farmacológico
13.
Sci Rep ; 13(1): 8475, 2023 05 25.
Artigo em Inglês | MEDLINE | ID: mdl-37231003

RESUMO

Climacteric women often experience unfavorable metabolic changes. Consequently, identifying markers that may contribute to such undesirable changes is imperative. This study aimed to evaluate serum uric acid (UA) concentration and its association with metabolic and clinical parameters in climacteric women. We selected 672 women between 40 and 65 years and performed interviews, biochemical analyses, blood pressure, and anthropometric measurements. UA levels were determined using the enzymatic-colorimetric method. We compared variables according to the quartiles of UA using the Kruskal-Wallis test. The mean UA level was 4.9 ± 1.5 mg/dl, ranging from 2.0 to 11.6 mg/dl. We found that UA levels greater than 4.8 mg/dl were associated with adverse metabolic parameters in climacteric women. For all anthropometric and biochemical variables, we observed significantly better results in women who had lower UA levels (p < 0.05). Similarly, we observed a significant increase in blood pressure, frequency of metabolic syndrome, and cardiovascular risk as UA levels increased (p < 0.05). Our findings showed that climacteric women with high levels of UA were more likely to have adverse metabolic and clinical parameters than those with lower UA levels. Further studies may determine the causal relationship between UA and metabolic changes in climacteric women.


Assuntos
Síndrome Metabólica , Ácido Úrico , Humanos , Feminino , Antropometria , Menopausa , Pressão Sanguínea
14.
Molecules ; 28(5)2023 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-36903656

RESUMO

Long non-coding RNAs are frequently found to be dysregulated and are linked to carcinogenesis, aggressiveness, and chemoresistance in a variety of tumors. As expression levels of the JHDM1D gene and lncRNA JHDM1D-AS1 are altered in bladder tumors, we sought to use their combined expression to distinguish between low-and high-grade bladder tumors by RTq-PCR. In addition, we evaluated the functional role of JHDM1D-AS1 and its association with the modulation of gemcitabine sensitivity in high-grade bladder-tumor cells. J82 and UM-UC-3 cells were treated with siRNA-JHDM1D-AS1 and/or three concentrations of gemcitabine (0.39, 0.78, and 1.56 µM), and then submitted to cytotoxicity testing (XTT), clonogenic survival, cell cycle progression, cell morphology, and cell migration assays. When JHDM1D and JHDM1D-AS1 expression levels were used in combination, our findings indicated favorable prognostic value. Furthermore, the combined treatment resulted in greater cytotoxicity, a decrease in clone formation, G0/G1 cell cycle arrest, morphological alterations, and a reduction in cell migration capacity in both lineages compared to the treatments alone. Thus, silencing of JHDM1D-AS1 reduced the growth and proliferation of high-grade bladder-tumor cells and increased their sensitivity to gemcitabine treatment. In addition, the expression of JHDM1D/JHDM1D-AS1 indicated potential prognostic value in the progression of bladder tumors.


Assuntos
RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , RNA Longo não Codificante/genética , Gencitabina , Bexiga Urinária/metabolismo , Linhagem Celular Tumoral , Neoplasias da Bexiga Urinária/patologia , Biomarcadores , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
15.
Cancer Invest ; 41(2): 164-172, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36373675

RESUMO

Bladder cancer is the 10th most common cancer worldwide. It is a heterogeneous disease, comprising several tumor subtypes with differences in histology, genomic aberrations, prognosis and sensitivity to anti-cancer treatments. Although the treatment of bladder cancer is based tumor classifications and gradings, patients have different clinical response. In recent years, long non-coding RNAs (lncRNAs) were associated with bladder cancer chemoresistance. Thus, lncRNAs seem to be promising targets in treatment of bladder cancer. This review highlights the recent findings concerning lncRNAs and their relevance to the chemoresistance of bladder cancer. This may provide a basis for exploiting more robust therapeutic approaches in the future.


Assuntos
RNA Longo não Codificante , Neoplasias da Bexiga Urinária , Humanos , RNA Longo não Codificante/genética , Resistencia a Medicamentos Antineoplásicos/genética , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Prognóstico
16.
Nat Prod Res ; 37(13): 2285-2292, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35133203

RESUMO

Naphthoquinones are natural plants products or synthesized compounds. They have α, ß-cyclic aromatic dienones structure with a naphthalene skeleton. Little is known about naphthoquinone and nothing about naphtho [2,3-b] thiophen-4,9-quinone effects on bladder cancer. In this study, a naphthoquinone containing a hetero sulfur atom was synthesized using classical synthetic method. The molecular structure was elucidated by NMR techniques and the antitumor effects were evaluated on bladder tumor cell lines with different TP53 status using tripan blue and MTT cytotoxic method, quantification of reactive oxygen species (ROS), wound healing, cell morphology and cell cycle progression assays. The results showed selective cytotoxicity, colonies reduction, morphological change, inhibition of the cell migration process, induction of ROS production and cell cycle arrest. Naphtho [2,3-b] thiophen-4,9-quinone presents antiproliferative activity regardless TP53 status and may be a promising agent in the treatment of bladder cancer, as they have an oxidizing effect and interfere with cell cycle.


Assuntos
Antineoplásicos , Naftoquinonas , Neoplasias da Bexiga Urinária , Humanos , Bexiga Urinária/metabolismo , Tiofenos , Espécies Reativas de Oxigênio/metabolismo , Proliferação de Células , Antineoplásicos/química , Linhagem Celular Tumoral , Neoplasias da Bexiga Urinária/tratamento farmacológico , Naftoquinonas/farmacologia , Naftoquinonas/química , Apoptose , Ensaios de Seleção de Medicamentos Antitumorais
17.
Mol Biol Rep ; 50(2): 1487-1497, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36507965

RESUMO

INTRODUCTION: The genetic component, including genes and their variants, plays a significant role in the pathophysiology of arterial hypertension (AH). Thus, clinical, epidemiological and genetic studies have been carried out to improve the understanding of disease mechanisms, improve diagnostic quality and contribute to prevention. OBJECTIVE: To determine the association of risk factors, biochemical parameters and different ACE gene polymorphisms with AH. METHOD: The case-control study was carried out in the population of Ouro Preto, Brazil. The subjects answered a questionnaire containing clinical and sociodemographic data. The ACE gene polymorphisms rs4291, rs4363 and rs4335 were evaluated by real time-polymerase chain reaction (real-time PCR) in 310 people (155 hypertensive and 155 normotensive patients), in addition to biochemical parameters. A multivariate logistic regression model was used to identify factors associated with AH. Analysis of continuous variables was performed using the Kruskal-Wallis test to assess significance between groups and Dunn's post-test for multiple comparisons. RESULTS: The results showed that AH was associated with age, education, smoking, obesity and high levels of triglycerides, sodium, glucose and uric acid. Regarding the biochemical parameters, in hypertensive patients, the rs4363 and rs4335 polymorphisms were associated with high levels of triglycerides, urea and glucose; the rs4291 polymorphism was associated with elevated urea and glucose levels. No association was detected between SNPs and HA. CONCLUSION: AH was associated with socioeconomic status, lifestyle habits and biochemical parameters. ACE polymorphisms may have influenced the levels of triglycerides, urea and glucose in hypertensive patients.


Assuntos
Hipertensão , Peptidil Dipeptidase A , Humanos , Angiotensinas , Estudos de Casos e Controles , Genótipo , Hipertensão/genética , Hipertensão/tratamento farmacológico , Peptidil Dipeptidase A/genética , Polimorfismo de Nucleotídeo Único/genética , Triglicerídeos
18.
Nat Prod Res ; 37(22): 3838-3843, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36441214

RESUMO

Resveratrol is a polyphenolic compound whose antitumor activity has been demonstrated in several types of cancer. However, there are few studies on its molecular mechanisms of action in bladder cancer. Therefore, we aimed to evaluate resveratrol activity in bladder tumour cells with different TP53 gene status. Cytotoxicity, cell proliferation, reactive oxygen species (ROS) production, cell migration, mutagenicity, and CDH1, CTNNBIP1, HAT1, HDAC1, MYC, and SMAD4 gene expression were evaluated. An increase in ROS after resveratrol treatment was accompanied by reduced cell viability and proliferation in all cell lines. In TP53 wild-type cells, the inhibition of cell migration was accompanied by CDH1 and SMAD4 modulation. In TP53 mutated cells, cell migration inhibition with CDH1 and CTNNB1P1 upregulation was observed. In conclusion, resveratrol has antiproliferative effect in bladder tumour cells and its mechanism of action occurred through ROS production, interference with cell cycle, and inhibition of cell migration, independent of TP53 status.

19.
Nat Prod Res ; 37(11): 1877-1881, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36093567

RESUMO

This study was conducted with the aim of exploring the molecular and cellular mechanisms of action of the chrysin (natural flavonoid compound) on bladder tumour cell lines with different status of TP53 (RT4, 5637 and T24). The cells were treated with different concentrations of chrysin (20, 40, 60, 80 and 100 µM) to analyze the cell viability, nuclear division index, mutagenicity, apoptosis rates and expression of genes related to epigenetic events (DNMT1, HAT1 and HDAC1). Results showed that the treatment with chrysin reduced the cell viability and caused apoptosis, regardless TP53. Moreover, in the TP53-mutated cell lines, chrysin modulated the expression of the DNMT1, HAT1 and HDAC1 epigenetic genes, which might be a plus to the death observed in the cells with p53 mutation.


Assuntos
Neoplasias da Bexiga Urinária , Bexiga Urinária , Humanos , Bexiga Urinária/metabolismo , Bexiga Urinária/patologia , Sobrevivência Celular , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/genética , Flavonoides/farmacologia , Apoptose/genética , Epigênese Genética , Linhagem Celular Tumoral
20.
Psychol Health Med ; 28(6): 1450-1459, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36334097

RESUMO

Due to the COVID-19 pandemic, the Higher Education Institutions had to suspend their on-site activities and adapt to the new scenario. Therefore, the objective of the research was to investigate the effects of the COVID-19 pandemic on the mental health of the academic community of a Brazilian public university. This is a cross-sectional study, at a Brazilian public university, that used the baseline data from a longitudinal study carried out with employees and students. Participants answered a self-administered and confidential questionnaire in online platform, composed of sociodemographic, economic, lifestyles and mental health issues. 1,353 students and 372 employees participated. The prevalence of anxiety disorder symptoms among students and employees was 46.12% and 17.47%, depression 54.62% and 22.85% and stress 47.45% and 22.58%, respectively. The co-occurrence of symptoms was 33.56% among university students and 10.75% among employees. Falling family income, having stopped smoking and negative self-rated health, during the COVID-19 pandemic, may be the reasons for the high prevalence of co-occurrence of anxiety, depression and stress disorders among the academic community.


Assuntos
COVID-19 , Saúde Mental , Humanos , COVID-19/epidemiologia , Estudos Transversais , Estudos Longitudinais , Pandemias , Ansiedade/epidemiologia , Universidades , Depressão/epidemiologia
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