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1.
Oral Dis ; 2024 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-38488212

RESUMO

OBJECTIVE: This study evaluated the effectiveness of face-to-face (F2F) and online OralDETECT training programme in enhancing early detection skills for oral cancer. METHODS: A total of 328 final-year dental students were trained across six cohorts. Three cohorts (175 students) received F2F training from the academic years 2016/2017 to 2018/2019, and the remaining three (153 students) underwent online training during the Covid-19 pandemic from 2019/2020 to 2021/2022. Participant scores were analysed using the Wilcoxon signed rank test, the Mann-Whitney test, Cohen's d effect size, and multiple linear regression. RESULTS: Both F2F and online training showed increases in mean scores from pre-test to post-test 3: from 67.66 ± 11.81 to 92.06 ± 5.27 and 75.89 ± 11.03 to 90.95 ± 5.22, respectively. Comparison between F2F and online methods revealed significant differences in mean scores with large effect sizes at the pre-test stage (p < 0.001), while significant differences with small effect sizes were noted for post-test 1 (p = 0.002) and post-test 3 (p = 0.041). Regression analysis indicated that the delivery method is associated with the participants' final scores. CONCLUSION: F2F and online versions of the OralDETECT training programme significantly enhance participants' knowledge and skills in oral cancer detection. Although F2F appeared to be more effective, the difference was not substantial enough to be considered educationally meaningful.

2.
Clin Oral Investig ; 28(1): 98, 2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38225483

RESUMO

OBJECTIVES: The aim of this systematic review and meta-analysis is to assess the diagnostic potential of salivary metabolomics in the detection of oral potentially malignant disorders (OPMDs) and oral cancer (OC). MATERIALS AND METHODS: A systematic review was performed in accordance with the 3rd edition of the Centre for Reviews and Dissemination (CRD) and Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. Electronic searches for articles were carried out in the PubMed, Web of Science, and Scopus databases. The quality assessment of the included studies was evaluated using the Newcastle-Ottawa Quality Assessment Scale (NOS) and the new version of the QUADOMICS tool. Meta-analysis was conducted whenever possible. The effect size was presented using the Forest plot, whereas the presence of publication bias was examined through Begg's funnel plot. RESULTS: A total of nine studies were included in the systematic review. The metabolite profiling was heterogeneous across all the studies. The expression of several salivary metabolites was found to be significantly altered in OPMDs and OCs as compared to healthy controls. Meta-analysis was able to be conducted only for N-acetylglucosamine. There was no significant difference (SMD = 0.15; 95% CI - 0.25-0.56) in the level of N-acetylglucosamine between OPMDs, OC, and the control group. CONCLUSION: Evidence for N-acetylglucosamine as a salivary biomarker for oral cancer is lacking. Although several salivary metabolites show changes between healthy, OPMDs, and OC, their diagnostic potential cannot be assessed in this review due to a lack of data. Therefore, further high-quality studies with detailed analysis and reporting are required to establish the diagnostic potential of the salivary metabolites in OPMDs and OC. CLINICAL RELEVANCE: While some salivary metabolites exhibit significant changes in oral potentially malignant disorders (OPMDs) and oral cancer (OC) compared to healthy controls, the current evidence, especially for N-acetylglucosamine, is inadequate to confirm their reliability as diagnostic biomarkers. Additional high-quality studies are needed for a more conclusive assessment of salivary metabolites in oral disease diagnosis.


Assuntos
Doenças da Boca , Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Acetilglucosamina , Reprodutibilidade dos Testes , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/patologia
3.
Oral Dis ; 29(2): 380-389, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33914993

RESUMO

OBJECTIVE: To evaluate the accuracy of MeMoSA®, a mobile phone application to review images of oral lesions in identifying oral cancers and oral potentially malignant disorders requiring referral. SUBJECTS AND METHODS: A prospective study of 355 participants, including 280 with oral lesions/variants was conducted. Adults aged ≥18 treated at tertiary referral centres were included. Images of the oral cavity were taken using MeMoSA®. The identification of the presence of lesion/variant and referral decision made using MeMoSA® were compared to clinical oral examination, using kappa statistics for intra-rater agreement. Sensitivity, specificity, concordance and F1 score were computed. Images were reviewed by an off-site specialist and inter-rater agreement was evaluated. Images from sequential clinical visits were compared to evaluate observable changes in the lesions. RESULTS: Kappa values comparing MeMoSA® with clinical oral examination in detecting a lesion and referral decision was 0.604 and 0.892, respectively. Sensitivity and specificity for referral decision were 94.0% and 95.5%. Concordance and F1 score were 94.9% and 93.3%, respectively. Inter-rater agreement for a referral decision was 0.825. Progression or regression of lesions were systematically documented using MeMoSA®. CONCLUSION: Referral decisions made through MeMoSA® is highly comparable to clinical examination demonstrating it is a reliable telemedicine tool to facilitate the identification of high-risk lesions for early management.


Assuntos
Neoplasias Bucais , Telemedicina , Adulto , Humanos , Estudos Prospectivos , Neoplasias Bucais/diagnóstico , Sensibilidade e Especificidade , Encaminhamento e Consulta , Telemedicina/métodos
4.
Eur J Dent Educ ; 27(1): 78-86, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35100466

RESUMO

INTRODUCTION: Dental education involves performing clinical procedures on patients under expert supervision. The COVID-19 pandemic has disrupted routine face-to-face teaching-learning-assessment dynamics world over. This study assessed the self-perceived preparedness of dental undergraduate students for practice, whose clinical training was interrupted by the COVID-19 pandemic from dental schools across Malaysia. MATERIALS AND METHODS: This cross-sectional web-based questionnaire survey was done among new dental graduates of the academic year 2019-2020 and the final year undergraduate students (academic year 2020-2021) from dental schools in Malaysia, using the Dental Undergraduates Preparedness Assessment Scale (DU-PAS), from 6th to 26th April 2021. The questionnaire addressed clinical skill competence, and cognitive and behavioral attributes. The number of respondents needed to achieve a confidence level of 95% with margin of error of 5% was 306. RESULTS: A total of 453 (243 final year students and 210 new graduates) responded from dental schools nationwide, with a response rate of 30.6%. The overall mean score for preparedness for dental practice was 76.3±14.7, for clinical skills 39.7±7.3, and behavioral and cognitive attributes 36.5±9.1. New graduates had significantly higher mean preparedness score (78.6±14.4) as compared to students in their final year (74.2±14.7). Performing endodontic treatment on multi-rooted teeth had the lowest perceived competency (29.8%), followed by assessing treatment needs of patients requiring orthodontics (37.1%), prescribing drugs (46.6%) and providing crowns using principles of tooth preservation (48.1%). CONCLUSIONS: Satisfactory scores were obtained for most attributes. The final-year cohort was significantly less prepared for dental practice compared to the newly graduated cohort.


Assuntos
COVID-19 , Humanos , Estudantes de Odontologia/psicologia , Estudos Transversais , Pandemias , Educação em Odontologia/métodos , Inquéritos e Questionários , Competência Clínica
5.
J Cancer Educ ; 37(2): 319-327, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-32821988

RESUMO

Early diagnosis of oral cancer results in less aggressive treatment and improves the quality of life and overall 5-year survival rate. Well-trained dental professionals can play a crucial role in the early detection of oral cancers. The present study aims to determine the effectiveness of the training program "OralDETECT", a spaced repetitive, test-enhanced learning tool with a corrective feedback mechanism for early detection of oral cancer. Thirty-two dentists and 259 dental students from three Malaysian dental schools were involved in this study. All participants were trained and calibrated to recognize oral potentially malignant disorders (OPMD) and oral cancer using "OralDETECT", which is comprised of a series of pre-test, lecture, post-tests and review sessions. The percentage of correct answers (scores) for each test given by the participants was calculated and analysed using a paired t test. It was found that the overall percentage of diagnostic accuracy for both dental professionals and student groups increased to above 80% from the pre-tests to the final post-tests. There was a significant improvement in overall scores between the pre-tests and all three post-tests for the dental professional groups and the student groups. The diagnostic accuracy for individual OPMD and lesions suspicious of oral cancer also increased to above 80% for both groups. The results of our study demonstrate that the "OralDETECT" is an efficient and effective competency tool which can be used to train dental professionals and students for the early detection of OPMD and oral cancer.


Assuntos
Doenças da Boca , Neoplasias Bucais , Detecção Precoce de Câncer/métodos , Retroalimentação , Humanos , Neoplasias Bucais/diagnóstico , Qualidade de Vida
6.
Medicina (Kaunas) ; 58(9)2022 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-36143906

RESUMO

Background and Objectives: Oral squamous cell carcinoma (OSCC) is the sixth most common malignancy in the world. Transient receptor potential vanilloid 4 (TRPV4) channel has been shown to be involved in angiogenesis in multiple types of tumors. However, not much is known about TRPV4's involvement in OSCC. Thus, in this study, we investigate the effect of administering a TRPV4 agonist on angiogenesis in OSCC. Materials and Methods: Thirty-six Sprague Dawley (SD) rats were used in this study. 4-nitroquinoline 1-oxide (4NQO) was used to induce OSCC. Cisplatin (an anticancer drug), and GSK1016790A (an agonist for TRPV4) was used in this study. Immunohistochemistry was employed to examine the TRPV4 expression. An RT2 Profiler PCR Array was performed for gene expression analysis of TRPV4, vascular growth factors that correspond directly with angiogenesis, such as angiopoietin (Ang-1 and Ang-2), and tyrosine kinase (Tie-1 and Tie-2) receptors. Tumor vessel maturity was assessed by microvessel density and microvessel-pericyte-coverage index. Results: RT2 profiler PCR array showed significant elevated levels of Ang-1 (2.1-fold change; p < 0.05) and Tie-2 (4.5-fold change; p < 0.05) in OSCC following the administration of a combination of GSK1016790A and cisplatin. Additionally, the combination treatment significantly reduced the microvessel density (p < 0.01) and significantly increased the percentage of microvessels covered with pericytes (p < 0.01) in OSCC. Furthermore, tumor size was significantly reduced (p < 0.05) in rats that received cisplatin alone. The combination treatment also greatly reduced the tumor size; however, the data were not statistically significant. Conclusions: The findings suggest that combining a TRPV4 agonist with cisplatin for treatment of OSCC promote vessels normalization via modulation of Ang-1/Tie-2 pathway.


Assuntos
Antineoplásicos , Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Nitroquinolinas , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Cisplatino/farmacologia , Cisplatino/uso terapêutico , Modelos Animais de Doenças , Leucina/análogos & derivados , Neoplasias Bucais/tratamento farmacológico , Neovascularização Patológica/tratamento farmacológico , Neovascularização Patológica/metabolismo , Óxidos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor TIE-2/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Sulfonamidas , Canais de Cátion TRPV
7.
Medicina (Kaunas) ; 58(10)2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-36295584

RESUMO

Background and Objectives: Studies examining the importance of inflammatory markers before treatment as prognosticators of OSCC are available, but information on post-therapy inflammatory markers and their prognostic significance is limited. This study aimed to evaluate the prognostic abilities of pre- and post-treatment inflammatory markers in patients with OSCC. Materials and Methods: In this retrospective analysis, information on 151 OSCC patients' socio-demographic, clinico-pathological, recurrence, metastasis, and survival data were gathered from clinical records. A multivariable Cox proportional hazards regression (stepwise model) was conducted to identify the prognostic predictors of OS and DFS. The multivariable models' performances were evaluated using Harrell's concordance statistics. Results: For OS, high pre-treatment LMR (HR 3.06, 95%CI 1.56, 5.99), and high post-treatment PLC (HR 3.35, 95%CI 1.71, 6.54) and PLR (HR 5.26, 95%CI 2.62, 10.58) were indicative of a poor prognosis. For DFS, high pre-treatment SII (HR 2.59, 95%CI 1.50, 4.48) and high post-treatment PLC (HR 1.92, 95%CI 1.11, 3.32) and PLR (HR 3.44, 95%CI 1.98, 5.07) were associated with increased mortality. The fitness of the OS and DFS stepwise Cox regression models were proven with a time-dependent AUC of 0.8787 and 0.8502, respectively. Conclusions: High pre-treatment levels of LMR and SII and high post-treatment levels of PLC and PLR are independent predictors of a poor prognosis for patients with OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Humanos , Prognóstico , Neoplasias Bucais/terapia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço , Estudos Retrospectivos , Biomarcadores Tumorais
8.
Clin Oral Investig ; 25(9): 5411-5419, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33629155

RESUMO

OBJECTIVE: This study aims to examine the ability of optical coherence tomography (OCT) to differentiate ex vivo epithelial structure of benign disorders, dysplastic, and oral squamous cell carcinoma (OSCC) in comparison with the structure of normal marginal mucosa of oral biopsies. As a secondary objective, we examined the inter- and intra-observer variations of OCT measurements of two calibrated assessors. MATERIALS AND METHODS: Oral biopsies (n = 44) were scanned using the swept source OCT (SSOCT) and grouped by pathology diagnosis to benign, dysplasia or carcinoma. Two trained and calibrated assessors scored on the five OCT variables: thickness of keratin layer (KL), epithelial layer (EL), homogeneity of lamina propria (LP), basement membrane integrity (BMI), and the degree of reflection of the epithelial layer (Ep Re). Chi-square tests and Fischer's exact method were used to compare the data. RESULTS: The OCT images showed breached BM status in all the OSCC samples (100%). Epithelial reflection was noted to be hyper-reflective in all the OSCC and oral dysplasia samples (100%). An increase in KL in 66.67% of the OSCC and 100% of the oral dysplasia samples was found. EL was increased in all the OSCC samples (100%) and 85.72% of the oral dysplasias. Kappa values showed that there was very good agreement (over 0.7) when scoring individual parameters between the two assessors. CONCLUSION: The study showed that the BM status was a key parameter in the detection of SCC and for differentiating SCC from oral dysplasia or benign disorders. CLINICAL RELEVANCE: OCT is a non-invasive and non-radioactive adjunct diagnostic tool that can provide immediate results on the structure of oral mucosa. The BM status measured ex vivo was a key parameter in the detection of SCC and for differentiating SCC from oral dysplasia or benign disorders.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Biópsia , Carcinoma de Células Escamosas/diagnóstico por imagem , Humanos , Mucosa Bucal/diagnóstico por imagem , Neoplasias Bucais/diagnóstico por imagem , Tomografia de Coerência Óptica
9.
J Contemp Dent Pract ; 22(10): 1079-1081, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35197372

RESUMO

Autophagy, first described by the Belgian biochemist Christian De Duve in 1963, is derived from the Greek word "autóphagos," which means "self-devouring." It is a cellular homeostatic process in which the body rids itself of flawed or damaged cells and other defective cellular organelles.1 The implication of defective autophagy in various human diseases has been well documented. The vital importance of autophagy is underscored by the fact that robust cellular health and function are intricately linked with it.


Assuntos
Autofagia , Humanos
10.
Sensors (Basel) ; 20(20)2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33053886

RESUMO

Oral mucosal lesions (OML) and oral potentially malignant disorders (OPMDs) have been identified as having the potential to transform into oral squamous cell carcinoma (OSCC). This research focuses on the human-in-the-loop-system named Healthcare Professionals in the Loop (HPIL) to support diagnosis through an advanced machine learning procedure. HPIL is a novel system approach based on the textural pattern of OML and OPMDs (anomalous regions) to differentiate them from standard regions of the oral cavity by using autofluorescence imaging. An innovative method based on pre-processing, e.g., the Deriche-Canny edge detector and circular Hough transform (CHT); a post-processing textural analysis approach using the gray-level co-occurrence matrix (GLCM); and a feature selection algorithm (linear discriminant analysis (LDA)), followed by k-nearest neighbor (KNN) to classify OPMDs and the standard region, is proposed in this paper. The accuracy, sensitivity, and specificity in differentiating between standard and anomalous regions of the oral cavity are 83%, 85%, and 84%, respectively. The performance evaluation was plotted through the receiver operating characteristics of periodontist diagnosis with the HPIL system and without the system. This method of classifying OML and OPMD areas may help the dental specialist to identify anomalous regions for performing their biopsies more efficiently to predict the histological diagnosis of epithelial dysplasia.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Imagem Óptica , Carcinoma de Células Escamosas/diagnóstico por imagem , Atenção à Saúde , Humanos , Neoplasias Bucais/diagnóstico por imagem , Padrões de Referência
11.
Telemed J E Health ; 26(3): 278-285, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31081720

RESUMO

Background: Up to 86% of oral cancer (OC) patients present at the late stage where survival is dismal. Limited access to specialist diagnosis is a significant factor for late presentation. The increasing use of smartphones presents an opportunity to use digital technology to facilitate early detection of OC. Aim: To evaluate the feasibility of using Mobile Mouth Screening Anywhere (MeMoSA®) to facilitate early detection of OC. Methods: A mobile phone app named MeMoSA was developed and the feasibility of integrating this for documentation of oral lesions, and communication between dentists and specialists for management decisions were evaluated. The experience of dentists and specialists in using MeMoSA was determined using qualitative questionnaires. Results: Communication between specialist and dentists using MeMoSA stratified cases and streamlined referral of patients. Twelve of 48 patients were found to have oral lesions or signs suspicious of cancer and 3 required referrals. The patient's compliance for referral was tracked with MeMoSA. All dentists agreed that MeMoSA could facilitate early detection of OC and believed that MeMoSA could assist in the identification of oral mucosal lesions through direct communication with specialists and continuous learning in the recognition of high-risk lesions. Conclusions: MeMoSA has the potential to be used to promote equitable health care and streamline patient management that could result in early detection of OC.


Assuntos
Telefone Celular , Detecção Precoce de Câncer/instrumentação , Aplicativos Móveis , Neoplasias Bucais , Telemedicina , Odontólogos , Países em Desenvolvimento , Humanos , Neoplasias Bucais/diagnóstico
12.
Cancer Invest ; 37(7): 275-287, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31307249

RESUMO

Previous studies found that ethnicity influences oral cancer patients' survival; however, most studies were limited to certain ethnic groups particularly from the West, thus of limited relevance to Asians where the disease is most prevalent. We investigated the relationship between ethnicity and patient survival in multi-racial Malaysia. 5-year survival rate was 40.9%. No statistically significant difference was observed in survival between Malays, Chinese, Indians and Indigenous peoples (45.7%, 44.0%, 41.3%, 27.7% respectively). Increased tumor size, lymph node involvement and advanced tumor were predictive of poor survival. We conclude that ethnicity has no effect on survival or its prognostic indicators.


Assuntos
Neoplasias Bucais/etnologia , Neoplasias Bucais/mortalidade , Adulto , Idoso , Estudos de Coortes , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Malásia/etnologia , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/patologia , Prognóstico , Taxa de Sobrevida , Carga Tumoral
13.
Proc Natl Acad Sci U S A ; 113(3): 596-601, 2016 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-26733676

RESUMO

RNAs with 5'-triphosphate (ppp) are detected in the cytoplasm principally by the innate immune receptor Retinoic Acid Inducible Gene-I (RIG-I), whose activation triggers a Type I IFN response. It is thought that self RNAs like mRNAs are not recognized by RIG-I because 5'ppp is capped by the addition of a 7-methyl guanosine (m7G) (Cap-0) and a 2'-O-methyl (2'-OMe) group to the 5'-end nucleotide ribose (Cap-1). Here we provide structural and mechanistic basis for exact roles of capping and 2'-O-methylation in evading RIG-I recognition. Surprisingly, Cap-0 and 5'ppp double-stranded (ds) RNAs bind to RIG-I with nearly identical Kd values and activate RIG-I's ATPase and cellular signaling response to similar extents. On the other hand, Cap-0 and 5'ppp single-stranded RNAs did not bind RIG-I and are signaling inactive. Three crystal structures of RIG-I complexes with dsRNAs bearing 5'OH, 5'ppp, and Cap-0 show that RIG-I can accommodate the m7G cap in a cavity created through conformational changes in the helicase-motif IVa without perturbing the ppp interactions. In contrast, Cap-1 modifications abrogate RIG-I signaling through a mechanism involving the H830 residue, which we show is crucial for discriminating between Cap-0 and Cap-1 RNAs. Furthermore, m7G capping works synergistically with 2'-O-methylation to weaken RNA affinity by 200-fold and lower ATPase activity. Interestingly, a single H830A mutation restores both high-affinity binding and signaling activity with 2'-O-methylated dsRNAs. Our work provides new structural insights into the mechanisms of host and viral immune evasion from RIG-I, explaining the complexity of cap structures over evolution.


Assuntos
Guanosina/análogos & derivados , Imunidade Inata , Capuzes de RNA/metabolismo , RNA Helicases/metabolismo , Trifosfato de Adenosina/metabolismo , Motivos de Aminoácidos , Proteínas de Transporte/metabolismo , Cristalografia por Raios X , Guanosina/química , Guanosina/metabolismo , Células HEK293 , Humanos , Hidrólise , Metilação , Conformação de Ácido Nucleico , Estrutura Terciária de Proteína , RNA/química , RNA de Cadeia Dupla , Transdução de Sinais
14.
Clin Oral Investig ; 23(5): 2287-2301, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30291495

RESUMO

OBJECTIVES: In vivo study was performed to determine the chemopreventive efficacy of the DC resin methanol extract on a 4-nitroquinoline-1-oxide (4NQO) oral cancer animal model. MATERIALS AND METHODS: This study involves administration of 4NQO solution for 8 weeks alone (cancer induction) or with Dracaena cinnabari (DC) extract at 100, 500, and 1000 mg/kg. DC extract administration started 1 week before exposure until 1 week after the carcinogen exposure was stopped. All rats were sacrificed after 22 weeks, and histological analysis was performed to assess any incidence of pathological changes. Immunohistochemical expressions of selected tumor marker antibodies were analyzed using an image analyzer computer system, and the expression of selected genes involved in apoptosis and proliferative mechanism related to oral cancer were evaluated using RT2-PCR. RESULTS: The incidence of OSCC decreased with the administration of DC extract at 100, 500, and 1000 mg/kg compared to the induced cancer group. The developed tumor was also observed to be smaller when compared to the induced cancer group. The DC 1000 mg/kg group inhibits the expression of Cyclin D1, Ki-67, Bcl-2, and p53 proteins. It was observed that DC 1000 mg/kg induced apoptosis by upregulation of Bax and Casp3 genes and downregulation of Tp53, Bcl-2, Cox-2, Cyclin D1, and EGFR genes when compared to the induced cancer group. CONCLUSIONS: The data indicated that systemic administration of the DC resin methanol extract has anticarcinogenic potency on oral carcinogenesis. CLINICAL RELEVANCE: Chemoprevention with DC resin methanol extract may significantly reduce morbidity and possibly mortality from OSCC.


Assuntos
Dracaena/química , Neoplasias Bucais/prevenção & controle , Extratos Vegetais/uso terapêutico , 4-Nitroquinolina-1-Óxido , Animais , Carcinogênese , Feminino , Masculino , Neoplasias Bucais/induzido quimicamente , Ratos , Ratos Sprague-Dawley
15.
Am J Pathol ; 187(8): 1893-1906, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28609645

RESUMO

Sweet syndrome (SS) is a prototypical neutrophilic dermatosis, a class of inflammatory diseases marked by elevated levels of tumor necrosis factor (TNF)-α and IL-17A, pathologic neutrophil recruitment, and microvascular remodeling. Histologic analyses of four matrix proteins-collagen I and IV, laminin, and fibronectin-in skin biopsies of patients with SS reveal that the basement membrane of dermal postcapillary venules undergoes changes in structure and composition. Increased neutrophil recruitment in vivo was associated with increases in collagen IV, decreases in laminin, and varied changes in fibronectin. In vitro studies using TNF-α and IL-17A were conducted to dissect basement membrane remodeling. Prolonged dual activation of cultured human pericytes with TNF-α and IL-17A augmented collagen IV production, similar to in vivo remodeling. Co-activation of pericytes with TNF-α and IL-17A also elevated fibronectin levels with little direct effect on laminin. However, the expression of fibronectin- and laminin-specific matrix metalloproteinases (MMPs), particularly MMP-3, was significantly up-regulated. Interactions between pericytes and neutrophils in culture yielded even higher levels of active MMPs, facilitating fibronectin and laminin degradation, and likely contributing to the varied levels of detectable fibronectin and the decreases in laminin observed in vivo. These data indicate that pericyte-neutrophil interactions play a role in mediating microvascular changes in SS and suggest that targeting MMP-3 may be effective in protecting vascular wall integrity.


Assuntos
Membrana Basal/efeitos dos fármacos , Interleucina-17/farmacologia , Neutrófilos/metabolismo , Pericitos/efeitos dos fármacos , Síndrome de Sweet/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Idoso , Membrana Basal/metabolismo , Membrana Basal/patologia , Células Cultivadas , Colágeno Tipo IV/metabolismo , Feminino , Fibronectinas/metabolismo , Humanos , Laminina/metabolismo , Masculino , Metaloproteinase 3 da Matriz/metabolismo , Pessoa de Meia-Idade , Neutrófilos/patologia , Pericitos/metabolismo , Pericitos/patologia , Síndrome de Sweet/patologia
16.
Nucleic Acids Res ; 44(16): 7511-26, 2016 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-27317694

RESUMO

The 5' m7G cap is an evolutionarily conserved modification of eukaryotic mRNA. Decades of research have established that the m7G cap serves as a unique molecular module that recruits cellular proteins and mediates cap-related biological functions such as pre-mRNA processing, nuclear export and cap-dependent protein synthesis. Only recently has the role of the cap 2'O methylation as an identifier of self RNA in the innate immune system against foreign RNA has become clear. The discovery of the cytoplasmic capping machinery suggests a novel level of control network. These new findings underscore the importance of a proper cap structure in the synthesis of functional messenger RNA. In this review, we will summarize the current knowledge of the biological roles of mRNA caps in eukaryotic cells. We will also discuss different means that viruses and their host cells use to cap their RNA and the application of these capping machineries to synthesize functional mRNA. Novel applications of RNA capping enzymes in the discovery of new RNA species and sequencing the microbiome transcriptome will also be discussed. We will end with a summary of novel findings in RNA capping and the questions these findings pose.


Assuntos
Capuzes de RNA/metabolismo , Animais , Células Eucarióticas/metabolismo , Humanos , Modelos Moleculares , Nucleotidiltransferases/metabolismo , Capuzes de RNA/química , RNA Viral/metabolismo
17.
Nucleic Acids Res ; 44(2): 896-909, 2016 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-26612866

RESUMO

RIG-I (Retinoic Acid Inducible Gene-I) is a cytosolic innate immune receptor that detects atypical features in viral RNAs as foreign to initiate a Type I interferon signaling response. RIG-I is present in an autoinhibited state in the cytoplasm and activated by blunt-ended double-stranded (ds)RNAs carrying a 5' triphosphate (ppp) moiety. These features found in many pathogenic RNAs are absent in cellular RNAs due to post-transcriptional modifications of RNA ends. Although RIG-I is structurally well characterized, the mechanistic basis for RIG-I's remarkable ability to discriminate between cellular and pathogenic RNAs is not completely understood. We show that RIG-I's selectivity for blunt-ended 5'-ppp dsRNAs is ≈3000 times higher than non-blunt ended dsRNAs commonly found in cellular RNAs. Discrimination occurs at multiple stages and signaling RNAs have high affinity and ATPase turnover rate and thus a high katpase/Kd. We show that RIG-I uses its autoinhibitory CARD2-Hel2i (second CARD-helicase insertion domain) interface as a barrier to select against non-blunt ended dsRNAs. Accordingly, deletion of CARDs or point mutations in the CARD2-Hel2i interface decreases the selectivity from ≈3000 to 150 and 750, respectively. We propose that the CARD2-Hel2i interface is a 'gate' that prevents cellular RNAs from generating productive complexes that can signal.


Assuntos
RNA Helicases DEAD-box/metabolismo , RNA/metabolismo , Adenosina Trifosfatases/metabolismo , Sequência de Bases , Sítios de Ligação , Proteína DEAD-box 58 , RNA Helicases DEAD-box/genética , Polarização de Fluorescência , Células HEK293 , Humanos , Interferon beta/genética , Interferon beta/metabolismo , Dados de Sequência Molecular , Estrutura Terciária de Proteína , RNA/química , RNA de Cadeia Dupla/metabolismo , Receptores Imunológicos
18.
Ethn Health ; 23(1): 1-15, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-27781495

RESUMO

OBJECTIVES: To obtain data on the prevalence of oral mucosal lesions (OMLs) among Cambodians, and to assess the relationship between known risk habits of oral diseases with prevalence of oral potentially malignant disorders (OPMDs). DESIGN: This was a population-based, cross-sectional study whereby subjects were adults aged 18 years old and above. A workshop on the identification of OML was held to train and calibrate dental officers prior to data collection in the field. Sociodemographic and risk habits data were collected via face-to-face interview, whilst presence of OML and clinical details of lesions such as type and site were collected following clinical oral examination by the examiners. Data analysis was carried out using the Statistical Package for Social Science (SPSS) version 12.0. The association between risk habits and risk of OPMD was explored using logistic regression analysis. RESULTS: A total of 1634 subjects were recruited. Prevalence of OML for this population was 54.1%. Linea alba was the most common lesion seen (28.7%). This study showed an overall OPMD prevalence of 5.6%. The most common type of OPMD was leukoplakia (64.8%), followed by lichen planus (30.8%). Subjects who only smoked were found to have an increased risk for OPMD of almost four-fold (RR 3.74, 95%CI 1.89-7.41). The highest risk was found for betel quid chewers, where the increased risk observed was more than six times (RR 6.75, 95%CI 3.32-13.72). Alcohol consumption on its own did not seem to confer an increased risk for OPMD, however when practiced concurrently with smoking, a significant risk of more than five times was noted (RR 5.69 95%CI 3.14-10.29). CONCLUSION: The prevalence of OML was 54.1%, with linea alba being the most commonly occurring lesion. Smoking, alcohol consumption and betel quid chewing were found to be associated with the prevalence of OPMD, which was 5.6%.


Assuntos
Mucosa Bucal/fisiopatologia , Neoplasias Bucais/epidemiologia , Lesões Pré-Cancerosas/classificação , Adulto , Consumo de Bebidas Alcoólicas , Areca/efeitos adversos , Camboja/epidemiologia , Estudos Transversais , Feminino , Humanos , Leucoplasia Oral , Líquen Plano Bucal , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Fatores Sexuais , Fumar/epidemiologia , Inquéritos e Questionários
19.
BMC Complement Altern Med ; 18(1): 50, 2018 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-29402248

RESUMO

BACKGROUND: Dracaena cinnabari (DC) is a perennial tree that located on the Southern coast of Yemen native to the Socotra Island. This tree produces a deep red resin known as the Dragon's blood, the Twobrother's Blood or Damm Alakhwain. The current study performed to evaluate the safety of the DC resin methanol extract after a single or 28 consecutive daily oral administrations. METHODS: In assessing the safety of DC resin methanol extract, acute and sub-acute oral toxicity tests performed following OECD guidelines 423 and 407, respectively, with slight modifications. In acute oral toxicity test, DC resin methanol extract administered to female Sprague Dawley rats by oral gavage at a single dose of 300 and 2000 mg/kg body weight. Rats observed for toxic signs for 14 days. In sub-acute oral toxicity test, DC resin methanol extract administered to the rats by oral gavage at 500, 1000, and 1500 mg/kg body weight daily up to 28 days to male and female Spradgue Dawley rats. The control and high dose in satellite groups were also maintained and handled as the previous groups to determine the late onset toxicity of DC resin methanol extract. At the end of each test, hematological and biochemical analysis of the collected blood were performed as well as gross and microscopic pathology. RESULTS: In acute oral toxicity, no treatment-related death or toxic signs were observed. It revealed that the DC resin methanol extract could be well tolerated up to the dose 2000 mg/kg body weight and could be classified as Category 5. The sub-acute test observations indicated that there are no treatment-related changes up to the high dose level compared to the control. Food consumption, body weight, organ weight, hematological parameters, biochemical parameters and histopathological examination (liver, kidney, heart, spleen and lung) revealed no abnormalities. Water intake was significantly higher in the DC resin methanol extract treated groups compared to the control. CONCLUSION: This study demonstrates tolerability of DC resin methanol extract administered daily for 28 days up to 1500 mg/kg dose.


Assuntos
Dracaena/química , Resinas Vegetais/toxicidade , Administração Oral , Animais , Peso Corporal/efeitos dos fármacos , Ingestão de Líquidos/efeitos dos fármacos , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Coração/efeitos dos fármacos , Rim/efeitos dos fármacos , Masculino , Metanol , Tamanho do Órgão/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Resinas Vegetais/administração & dosagem , Testes de Toxicidade Aguda , Testes de Toxicidade Subcrônica
20.
Molecules ; 23(2)2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29382121

RESUMO

A relatively new class of three-dimensional ordered mesoporous silicates, KIT-6, incorporated with Earth-abundant metals such as Zr, Nb, and W (termed as M-KIT-6), show remarkable tunability of acidity and metal dispersion depending on the metal content, type, and synthetic method. The metal-incorporation is carried out using one-pot synthesis procedures that are amenable to easy scale-up. By such tuning, M-KIT-6 catalysts are shown to provide remarkable activity and selectivity in industrially-significant reactions, such as alcohol dehydration, ethylene epoxidation, and metathesis of 2-butene and ethylene. We review how the catalytic properties of M-KIT-6 materials may be tailored depending on the application to optimize performance.


Assuntos
Metais Pesados/química , Dióxido de Silício/química , Catálise , Desidratação , Porosidade
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