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BACKGROUND: Resveratrol is a polyphenol that is found in plants and has been proposed to have a potential therapeutic effect through the activation of SIRT1, which is a crucial member of the mammalian NAD+-dependent deacetylases. However, how its activity is enhanced toward specific substrates by resveratrol derivatives has not been studied. This study aimed to evaluate the types of interaction of resveratrol and its derivatives with SIRT1 as the target protein, as well as to find out the best ligand with the strangest interaction with SIRT1. METHODS: In this study, we employed the extensive molecular docking analysis using AutoDock Vina to comparatively evaluate the interactions of resveratrol derivatives (22 molecules from the ZINC database) as ligands with SIRT1 (PDB ID: 5BTR) as a receptor. The ChemDraw and Chem3D tools were used to prepare 3D structures of all ligands and energetically minimize them by the MM2 force field. RESULTS: The molecular docking and visualizations showed that conformational change in resveratrol derivatives significantly influenced the parameter for docking results. Several types of interactions, including conventional hydrogen bonds, carbon-hydrogen bonds, Pi-donor hydrogen bonds, and Pi-Alkyl, were found via docking analysis of resveratrol derivatives and SIRT1 receptors. The possible activation effect of resveratrol 4'-(6-Galloylglucoside) with ZINC ID: ZINC230079516 with higher binding energy score (-46.8608 kJ/mol) to the catalytic domain (CD) of SIRT1 was achieved at the maximum value for SIRT1, as compared to resveratrol and its other derivatives. CONCLUSION: Finally, resveratrol 4'-(6-Galloylglucoside), as a derivative for resveratrol, has stably interacted with the CD of SIRT1 and might be a potential effective activator for SIRT1.
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BACKGROUND: Natural treatment of cancer has received a lot of attention recently due to its advantages including low cost, and fewer side effects. In this study, we aimed to investigate the antimetastatic properties of Cyrtopodion scabrum, a common home gecko, through Epithelial-Mesenchymal Transition (EMT) process. METHODS: Human colon cancer HCT116 cell line was selected and allocated into the following experimental groups: untreated control, vehicle control (DMSO), Retinoic acid (RA), and two treatment groups including aqueous C.scabrum Whole Extract (CWE) and C.scabrum Cell Extract (CCE) groups. The effects of the two different extracts on the viability, migration, and morphology of HCT116 cells were investigated using MTT, colony formation, and wound healing assay as well as microscopic evaluation. We also investigated the gene expression of E-cad, N-cad, and Snail genes using Real-Time PCR analysis. RESULTS: Our findings revealed that CWE and CCE were toxic to the HCT116 cell line with IC50 values of 590 and 680 µg/mL, respectively. Colony formation and migration ability of cancer cells were also inhibited by the two extracts, and the morphology of the cells were determined as epithelial phenotype. Moreover, the expression of N-cad and Snail were remarkably decreased in CWE and CCE, and RA groups, while E-cad didn't change significantly as compared to the control. CONCLUSION: The results suggest that C. scabrum extract (CsE) may induce its anti-cancer activity through the inhibition of cancer cell growth and the EMT process. CCE, as a valuable natural source, could be also suggested, to be used as an alternative/complementary medicine for the treatment of cancer, in clinical trials.
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Neoplasias do Colo , Lagartos , Humanos , Animais , Transição Epitelial-Mesenquimal , Projetos de Pesquisa , Células HCT116RESUMO
BACKGROUND: UBE2Q1-dependent ubiquitination of key proteins including ß 1,4- galactosyltransferase (GalT1), and P53 might play a pivotal role in cancer development. OBJECTIVE: The present study aimed to evaluate the molecular analysis of possible interactions between UBE2Q1 with B4GALT1 and P53 proteins. METHODS: We established SW1116 colorectal cancer cell line stably transfected with UBE2Q1. To verify the overexpression of UBE2Q1, we performed western blot and fluorescent microscopy analysis. Using the immunoprecipitation (IP) product of the over-expressed protein on the silver staining gel, we observed the potential interacting partners of UBE2Q1. The Molecular Operating Environment (MOE) software was also used to perform the molecular docking of the UBC domain of UBE2Q1 (2QGX) with B4GALT1 (2AGD), and P53 (tetramerization (1AIE) and DNA binding domains (1GZH)) proteins. RESULTS: Western blot and IP analysis detected a UBE2Q1-GFP band in transfected cells, while no band was detected for mock-transfected cells. Moreover, the overexpression of UBE2Q1 tagged with GFP was observed under fluorescent microscopy as well with about 60-70% shining. Silver staining of IP gel revealed several bands in colorectal cancer (CRC) with UBE2Q1 overexpression. Protein- Protein interaction (PPI) analysis also depicted a high affinity of the UBC domain of UBE2Q1 to the B4GALT1 and P53 (tetramerization and DNA binding domains). Molecular docking also revealed hot-spot regions for all poses. CONCLUSION: Our data suggest that UBE2Q1 as an E2 enzyme of ubiquitination system can interact with B4GALT1 and P53, and may contribute to the accumulation of misfolded important proteins and colorectal tumor development.
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Neoplasias Colorretais , Proteína Supressora de Tumor p53 , Humanos , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Simulação de Acoplamento Molecular , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , DNA , Enzimas de Conjugação de Ubiquitina/genética , Enzimas de Conjugação de Ubiquitina/metabolismoRESUMO
Bladder cancer as one of the main comorbid diseases might be more susceptible to develop COVID-19 infection with a higher mortality risk during the COVID-19 pandemic. The European Association of Urology (EAU) recommended a comprehensive panel for bladder cancer diagnosis and treatment during this global health problem. The urgent need for treatments of COVID-19 during the pandemic has persuaded researchers to evaluate the different medications, which may lead to drug shortages. Therefore, in this review paper, we have focused on the least recommendations of EAU about bladder cancer during of COVID-19 pandemic to provide a comprehensive panel for high-risk patients.
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COVID-19 , Neoplasias da Bexiga Urinária , Humanos , Atenção à Saúde , Invasividade Neoplásica , Pandemias , Neoplasias da Bexiga Urinária/diagnóstico , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/terapiaRESUMO
PURPOSE: Sonic hedgehog (SHH) signaling pathway in oxidative stress condition has been acknowledged as a key trigger for angiogenesis and collateral vessel growth in the ischemic brain, and it exerts a protective effect on neuronal cells during oxidative stress. METHODS: A total of sixty patients (n = 30 good collateral profile and n = 30 poor collateral profile) diagnosed with acute cerebral ischemia were enrolled in this study. qRT-PCR was performed to analyze the expression levels of SHH, Gli1, and superoxide dismutase (SOD), genes. Also, the serum levels of oxidative stress markers were determined in experimental groups. RESULTS: The expression levels of SHH and Gli1 genes were significantly (p < 0.05) higher in stroke patients with good collateral circulation compared with those with poor collateral circulation, while SOD gene expression was similar between two groups (p > 0.05). A significantly positive correlation was found between the gene expression of SHH and Gli1 (r = 0.604, p < 0.001), SOD and Gli1 (r = 0.372, p < 0.003) genes. Our findings showed that the serum level of total antioxidant capacity (TAC) and Glutathione (GSH) and SOD enzyme activity was significantly (p < 0.05) increased, while serum total oxidant status (TOS) and malondialdehyde (MDA) levels were significantly (p < 0.05) decreased in patients with good collateral circulation as compared with those with poor collateral circulation. CONCLUSION: Our observations shed light on the association of the SHH/Gli1 signaling pathway with cerebral collateral vessel development following ischemia. Oxidative stress in stroke patients with poor collateral circulation may result in the overexpression of SHH/Gli1 signaling pathway which possibly contribute to oxidative stress attenuation, as well as modulate angiogenesis and collateral vessels development.
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Proteínas Hedgehog , Estresse Oxidativo , Acidente Vascular Cerebral , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/genética , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Proteína GLI1 em Dedos de Zinco/genética , Proteína GLI1 em Dedos de Zinco/metabolismoRESUMO
This study was aimed to investigate the effect of microalgae Chlorella vulgaris (C. vulgaris) on nonalcoholic fatty liver disease (NAFLD)-related complications induced by high-fat diet (HFD). Fifty adult male rats were divided into six groups. Control group and HFD group treated with or without C. vulgaris 5% and 10%. Biochemical parameters in serum were measured by spectrophotometric and enzyme-linked immunosorbent assay (ELISA) methods. The relative gene expression levels of Tumor Necrosis Factor-alpha (TNF-α), NF-kappa B (NF-ÆB), and p38 Mitogen-Activated Protein Kinases (p38 MAPK) in the liver were assessed by using quantitative real-time PCR, while the protein levels of NF-ÆB and TNF-α in the liver homogenate were determined by ELISA. The effects of HFD significantly were reversed by C. vulgaris, especially at a 10% dose. Therefore, it can be concluded that C. vulgaris therapeutically could be useful to improve NAFLD and its complications. PRACTICAL APPLICATIONS: It is established that NAFLD is associated with the resistance to insulin, dyslipidemia, and inflammation. Accordingly, modulating of these conditions may be useful in the management of NAFLD. Our results showed the effectiveness of C. vulgaris against NAFLD-related complication through the alleviating insulin resistance, dyslipidemia and also down-regulation of inflammatory genes in p38 MAPK/TNF-α/NF-ÆB pathway. The results of our study may be useful for scientist to prepare an effective supplement from C. vulgaris to overcoming NAFLD-related complications.
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Chlorella vulgaris , Dislipidemias , Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Animais , Dislipidemias/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , RatosRESUMO
Cells translate the mechanosensing of extracellular matrix component dysregulation and stiffness into the signal transduction including Osteopontin (OPN) through the Hippo pathway. But how extracellular matrix (ECM) component dysregulation and stiffness are ultimately linked to transitional cell carcinoma (TCC) development remains poorly understood. This study was aimed to evaluate the possible links between ECM component alteration after cancer surgery and OPN and Yes-associated protein (YAP) expression in TCC and adjacent tissues. In this study, we used 50 TCC (25 newly diagnosed and 25 recurrent) and 50 adjacent tissues to determine the tissue stiffness using atomic force microscopy. The mRNA expression of SPP1, Indian hedgehog (IHH), and YAP was also determined using qRT-PCR. Western blotting and ELISA were performed to assess the tissue and serum levels of OPN, respectively. To assess the glycoproteins and elastic fibers content, Periodic Acid Schiff, and Verhoeff-Van Gieson Staining were performed, respectively. Matrix stiffness was markedly higher in TCCs than adjacent tissues (p < 0.05). Gene expression analysis showed that YAP, SPP1, and IHH genes were upregulated in TCC tissues (p < 0.05). Additionally, the OPN protein overexpression was observed in the tissue and the serum of TCC patients (p < 0.05). We also found that glycoproteins, elastic fibers content of recurrent TCC tissues was remarkably higher as compared to adjacent tissues (p < 0.05). Our results suggest that glycoproteins and elastic fibers content modulation and ECM stiffness may upregulates the expression of YAP, SPP1 and IHH genes, and possibly contribute to the TCC development and relapse.
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Carcinoma de Células de Transição/genética , Matriz Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Recidiva Local de Neoplasia/genética , Osteopontina/genética , Neoplasias da Bexiga Urinária/genética , Proteínas de Sinalização YAP/genética , Idoso , Carcinoma de Células de Transição/sangue , Estudos de Casos e Controles , Elastina/metabolismo , Feminino , Expressão Gênica , Proteínas Hedgehog/genética , Via de Sinalização Hippo/genética , Humanos , Masculino , Recidiva Local de Neoplasia/sangue , Osteopontina/sangue , Proteoglicanas/metabolismo , Regulação para Cima/genética , Neoplasias da Bexiga Urinária/sangueRESUMO
Reactive Oxygen Species Modulator 1 (ROMO1) plays a pivotal role in the regulation of mitochondrial structure integrity, and the production of reactive oxygen species (ROS). Increased ROMO1 expression was reported in various cancer cell lines; however, the possible association between ROMO1 expression and bladder cancer was not well studied. The present study aimed to investigate the rate of ROMO1 expression and the correlation of oxidative stress with the development of bladder cancer. In this study, a total of 35 cancerous and healthy adjacent tissues were examined using quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the gene expression of ROMO1. Also, we evaluated the serum level of ROMO1 and Total Antioxidant Capacity (TAC), as well as Total Oxidant Status (TOS) in patients with bladder cancer along with age- and sex-matched healthy individuals. The ROMO1 gene was significantly higher in cancerous tissues than that of adjacent healthy tissues. Also, the serum levels of ROMO1, TAC, TOS, and Oxidative Stress Index (OSI) were increased in patients with bladder cancer compared with healthy subjects. It can be concluded that the overexpression of the ROMO1 gene is associated with advanced grades of bladder cancer as well as an increase in oxidative stress conditions. Our findings also suggest that the serum level of ROMO1 might be a promising tumor marker for bladder cancer.
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Proteínas de Membrana/metabolismo , Proteínas Mitocondriais/metabolismo , Neoplasias da Bexiga Urinária/sangue , Idoso , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Proteínas de Membrana/sangue , Proteínas de Membrana/genética , Proteínas Mitocondriais/sangue , Proteínas Mitocondriais/genética , Gradação de Tumores , Estresse Oxidativo/genética , Espécies Reativas de Oxigênio/metabolismo , Regulação para Cima , Neoplasias da Bexiga Urinária/genéticaRESUMO
Changes in the cellular microenvironment play a critical role in the development of bladder cancer (BC). Yes-associated protein (YAP), a central mediator of the Hippo pathway, functions as a nuclear sensor of mechanotransduction that can be induced by stiffness of the extracellular matrix (ECM), including stiffness resulting from surgical manipulations. We aimed to clarify the possible association between surgically-related ECM stiffness and YAP activation in BC patients. We compared 30 bladder cancer tissues with grade II (n = 15 recurrent and n = 15 newly diagnosed) with 30 adjacent healthy tissues. Atomic force microscopy showed that patients with recurrent BC had stiffer ECM than newly diagnosed patients (P < 0.05). Gene expression profiles showed that ß1 integrin (ITGB1), focal adhesion kinase (FAK), CDC42, and YAP were upregulated in cancerous tissues (P < 0.05); additionally, ß1 integrin activation was confirmed using a specific antibody. Nuclear localization of YAP was higher in recurrent cancerous tissues compared with newly diagnosed and it was positively associated with higher stiffness (P < 0.05). Our results suggest that postsurgery-induced ECM stiffness can influence integrin-FAK-YAP activity and thereby YAP trafficking to the nucleus where it contributes to BC progression and relapse.
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Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Biomarcadores Tumorais/metabolismo , Mecanotransdução Celular/fisiologia , Fatores de Transcrição/metabolismo , Microambiente Tumoral/fisiologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/cirurgia , Proteínas Adaptadoras de Transdução de Sinal/química , Idoso , Biomarcadores Tumorais/química , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Fatores de Transcrição/química , Neoplasias da Bexiga Urinária/patologia , Proteínas de Sinalização YAPRESUMO
Gas hydrate formation is a high-risk and common flow assurance problem in subsea oil production plants. The modern strategies to mitigate hydrate formation have switched from thermodynamic inhibition to risk management. In this new mitigation strategy, hydrate formation is allowed as long as it does not lead to plugging of pipelines. Thus, understanding the growth kinetics of gas hydrates plays a critical role in risk management strategies. Here, we report a new accurate and in situ approach to probe the kinetics of gas hydrate formation. This approach is based on the hot-wire method, which probes the thermal properties of the medium surrounding the hot-wire. As the thermal properties of gas hydrate and its initial constituents are different, variation in these properties is used to probe kinetics of hydrate growth front. Through this in situ method, we determine kinetics of cyclopentane hydrate formation in both mixing and flow conditions. The findings show that at ambient pressure and a temperature of 1-2 °C, the hydrate formation rate under mixing condition varies between 1.9 × 10-5 and 3.9 × 10-5 kg m-2 s-1, while in flow condition, this growth rate drops to 4.5 × 10-6 kg m-2 s-1. To our knowledge, this is the first reported growth rate of cyclopentane hydrate. This in situ approach allows us to probe kinetics of hydrate formation where there is no optical access and provides a tool to rationally design risk management strategies for subsea infrastructures.
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OBJECTIVES: Smoking may impact oral self-care (OSC). This study aimed to analyze the role of smoking in OSC among Iranian dental health professionals. MATERIALS AND METHODS: The cross-sectional data were collected at two annual dental meetings and seven randomly selected dental schools in Iran. A total of 1,459 respondents composed of 967 general dental practitioners (GDPs), 229 dental educators (DE), and 263 senior dental students (DS) anonymously completed a self-administered questionnaire inquiring about smoking status and OSC. RESULTS: Thirty percent of the male and 12% of the female dental health professionals reported smoking tobacco. There was no difference between their professional status. Women reported better OSC than did men, but only 26% of the women and 17% of the men followed the three most important recommendations for OSC. Smoking was associated with infrequent tooth brushing and flossing, irregular use of fluoride containing toothpaste, consumption of sugary snacks and weak adherence to the recommended OSC guidelines. CONCLUSION: Dental health education should place more emphasis on smoking counseling and cessation among dental health professionals.
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OBJECTIVES: Health education in schools is one of the most effective ways of promoting health in a society. Studies have shown the effectiveness of health interventions aimed at improving students' knowledge, attitude, and behaviors about health issues. The aim of this study was to evaluate health issues in primary school textbooks in Iran. MATERIALS AND METHODS: In school year 2010-2011, the contents of all primary school textbooks in Iran were assessed in accordance to their health-related teachings. Health lessons of these 27 textbooks in the form of picture and text were retrieved and analyzed using content analysis method. RESULTS: In total, 502 health-related lessons were found. The textbooks of the third grade contained the highest (144) and those of the fourth grade had the lowest (26) number of health lessons. Among health-related issues, the largest number (87) of lessons were about personal hygiene, while prevention of high risk behaviors comprised the least number (8). Some important health issues such as nutrition, oral health, and prevention of high-risk behaviors were not adequately discussed in the textbooks. CONCLUSION: The potential of primary school textbooks in delivering health messages has been neglected in Iran. Taking the critical importance of school ages into account, incorporating health issues in textbooks should be more strongly emphasized.
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PURPOSE: To study risk-based preventive practice among Iranian dentists. MATERIALS AND METHODS: A questionnaire survey was conducted at two annual dental meetings in 2004 and 2005 in Tehran. Using a five-point Likert scale, respondents indicated their level of agreement with taking preventive measures including oral hygiene, use of fluoride, diet and dental check-up for a high- and a low-risk (HR and LR, respectively) hypothetical patient case. Respondent's smoking and activity in smoking cessation were enquired about as well. Of 1033 responding dentists, 980 (64% men) were eligible for this study. Statistical evaluation was by the chi-square test and logistic regression. RESULTS: The top four of the eight measures were instructions on tooth brushing and flossing, advice related to fluoridated toothpaste, and regular dental check-ups, with the choice 'fully agree' being more prevalent for the HR (74%-58%) than for the LR case (59%-41%). For the HR case, 45% of the respondents fully agreed with applying chair-side tooth cleaning, 41% with advice on diet modification, and 38% with advice on home-use of sodium fluoride mouthwash. Of all respondents, 76% were nonsmokers and 56% reported that they always recommend their smoking patients to quit. Female gender and activity in professional reading were associated with higher levels of agreement for applying preventive measures to the HR case. Non-smoking was the strongest explanatory factor (OR = 3.6, 95% CI = 2.6-5.1) of dentist's higher involvement in smoking cessation. CONCLUSION: Risk-based preventive dental care should be emphasised and applied in order to maximise efficient use of resources.
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Padrões de Prática Odontológica/estatística & dados numéricos , Odontologia Preventiva , Adulto , Distribuição de Qui-Quadrado , Educação Continuada em Odontologia , Feminino , Educação em Saúde Bucal , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Abandono do Hábito de Fumar , Inquéritos e QuestionáriosRESUMO
AIM: To study the oral health behaviour of Iranian dentists. DESIGN: A cross-sectional study. SETTING: Two annual dental meetings in Tehran, Iran. PARTICIPANTS: 1,033 dentists responded, 980 were eligible for this study. METHOD: Data were collected using a self-administered questionnaire which covered dentists' oral self-care, dental attendance, and smoking. Recommended oral self-care (ROSC) included tooth brushing > 1/day, eating sugary snacks < daily, and regularly using fluoride toothpaste. Knowledge of preventive dental care was assessed by nine Likert-scale statements. Dentist's gender, age, and professional reading were recorded. Statistical evaluation was by the Chi-square test and logistic regression. RESULTS: In total, 59% of respondents reported brushing their teeth at least 2/day, 59% consumed sugary snacks < daily, 74% used fluoride toothpaste regularly, and 76% were non-smokers. Of all, 27% followed ROSC. Women reported desirable behaviours more frequently than did the men (p < 0.01). Female gender (OR 1.4-2.3), being a non-smoker (OR 1.3-1.5), and wider professional reading (OR = 1.2) were the major factors that contributed to dentists' desirable oral health behaviour. CONCLUSIONS: That only a small number of Iranian dentists follow the ROSC calls for more attention to behavioural contributions to oral diseases and its consequences with general and oral health, regarding both dental curriculum and continuing education.