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1.
BMC Oral Health ; 24(1): 708, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38898439

RESUMO

BACKGROUND: Dental fluorosis (DF) is caused by excessive exposure to fluoride during odontogenesis and leads to various changes in the development of tooth enamel. Some regions in Mexico are considered endemic fluorosis zones due to the high fluoride content in drinking water. The objective of this study was to perform a systematic review and meta-analysis to identify the association between the concentration of fluoride in drinking water and the severity of dental fluorosis in northern and western Mexico. METHODS: This protocol was registered in the PROSPERO database (ID: CRD42023401519). The search for information was carried out in the PubMed/Medline, Scopus, SpringerLink, and Google Scholar databases between January 2015 and October 2023. The overall relative risk was calculated using the inverse of variance approach with the random effects method. The RoB 2.0 tool was used to construct risk plots. RESULTS: Eleven articles were analyzed qualitatively, and most of the included studies presented at least one level of DF severity; six articles were analyzed quantitatively, dividing them into two regions. In North region it was observed a higher prevalence of severe TF cases, corresponding to ≥ TF 5 category (4.78) [3.55, 6.42]. In the West region, most of the included studies presented a higher prevalence of less severe cases, corresponding to ≤ TF 4, in comparison with the North region (0.01) [0.00, 0.52], interpreted as a protective effect. CONCLUSION: The concentrations of fluorides in drinking water are reportedly high in these regions and are directly related to the severity of dental fluorosis experienced by the inhabitants. In the Northern region exists a major concentration of fluoride in drinking water compared with the Western region as well as a prevalence of higher severity cases of dental fluorosis.


Assuntos
Água Potável , Fluoretos , Fluorose Dentária , Fluorose Dentária/epidemiologia , Fluorose Dentária/etiologia , Humanos , México/epidemiologia , Fluoretos/análise , Fluoretos/efeitos adversos , Água Potável/química , Índice de Gravidade de Doença , Prevalência
3.
Artigo em Inglês | MEDLINE | ID: mdl-36925450

RESUMO

OBJECTIVE: The aim of this study was to investigate and compare the immunohistochemical expression of connexin 43 (Cx43) in tooth germs (TGs), ameloblastic fibromas (AFs), ameloblastic fibro-odontomas (AFOs), and conventional ameloblastomas (AMs). STUDY DESIGN: Nine TGs, 12 AFs, 12 AFOs, and 27 AMs were evaluated for Cx43 expression by immunohistochemistry. RESULTS: Most of the TGs expressed Cx43 in the mesenchyme (77.6%) and in the late stages of odontogenesis. Cx43 was more highly expressed (P < .05) in the mesenchymal layer of all groups than in the epithelial layer except for the AFOs. When comparing the expression of Cx43 in the different layers of the analyzed groups, statistically significant differences were observed between AFO vs AM (*P = .0158) in the epithelial layer and between AF vs AFO (P** = .0046) in the mesenchymal layer. CONCLUSIONS: The results obtained in this study showed that Cx43 is a protein with important expression in the mesenchymal layer of the embryonic and odontogenic tissues studied. It could be speculated that Cx43 participates in mineralization events based on the relationship of the expression of this protein between the epithelial and mesenchymal layers of odontogenic tissues.


Assuntos
Ameloblastoma , Tumores Odontogênicos , Odontoma , Humanos , Conexina 43/metabolismo , Tumores Odontogênicos/patologia , Ameloblastoma/metabolismo , Germe de Dente/metabolismo , Germe de Dente/patologia , Odontoma/metabolismo
4.
PLoS One ; 18(1): e0279681, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36701313

RESUMO

The pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected millions of people worldwide. Public health strategies to reduce viral transmission are based on widespread diagnostic testing to detect and isolate contagious patients. Several reverse transcription (RT)-PCR tests, along with other SARS-CoV-2 diagnostic assays, are available to attempt to cover the global demand. Loop-mediated isothermal amplification (LAMP) based methods have been established as rapid, accurate, point of care diagnostic tests for viral infections; hence, they represent an excellent alternative for SARS-CoV-2 detection. The aim of this study was to develop and describe molecular detection systems for SARS-CoV-2 based on RT-LAMP. Recombinant DNA polymerase from Bacillus stearothermophilus and thermostable engineered reverse transcriptase from Moloney Murine Leukemia Virus were expressed using a prokaryotic system and purified by fast protein liquid chromatography. These enzymes were used to set up fluorometric real time and colorimetric end-point RT-LAMP assays. Several reaction conditions were optimized such as reaction temperature, Tris-HCl concentration, and pH of the diagnostic tests. The key enzymes for RT-LAMP were purified and their enzymatic activity was determined. Standardized reaction conditions for both RT-LAMP assays were 65°C and a Tris-HCl-free buffer at pH 8.8. Colorimetric end-point RT-LAMP assay was successfully used for viral detection from clinical saliva samples with 100% sensitivity and 100% specificity compared to the results obtained by RT-qPCR based diagnostic protocols with Ct values until 30. The developed RT-LAMP diagnostic tests based on purified recombinant enzymes allowed a sensitive and specific detection of the nucleocapsid gene of SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Animais , Camundongos , Humanos , SARS-CoV-2/genética , COVID-19/diagnóstico , Sensibilidade e Especificidade , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Reação em Cadeia da Polimerase em Tempo Real , Testes Diagnósticos de Rotina , RNA Viral/genética , Teste para COVID-19
5.
Biol Trace Elem Res ; 201(3): 1051-1062, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35397104

RESUMO

The intake of high concentrations of fluoride, mainly through drinking water, diet and fluoridated dentifrices, produces fluorosis, which in its early stages is manifested as dental fluorosis (DF). To recognize exposure to fluoride in endemic areas and to evaluate the risk of developing health impairment, the WHO has established several biomarkers that are used to determine systemic fluorine (F-) exposure. Thus, the aim of this study was to conduct a systematic review and meta-analysis of the relationship between the severity of DF and fluoride biomarkers in endemic areas. The protocol of this study was previously registered as CRD42021244974. A digital search was carried out in PubMed/Medline, SpringerLink, Scopus, Cochrane and Google Scholar by employing the keywords "urine", "nails", "hair", "plasma", "saliva" and "dental fluorosis" for the original studies with content associated with F- for the biomarkers and DF. The mean difference was established as the effect measure for the meta-analysis. Seven studies fulfilled the eligibility criteria, among which five assessed urine and two employed nails as fluoride biomarkers. A positive significant difference was found between the biomarkers and the severity of DF (0.27, p < 0.001) and individually for each biomarker (urine: 0.14, p = 0.001; nails: 0.88, p < 0.05). The F- concentration in urine and nails is correlated with the severity of DF, with the most evident differences between healthy individuals and those with mild severity. Both biomarkers are adequate to assess this relationship in endemic areas of fluoride and DF.


Assuntos
Água Potável , Fluorose Dentária , Humanos , Fluoretos/análise , Fluorose Dentária/epidemiologia , Água Potável/análise , Dieta , Biomarcadores/análise , Prevalência
6.
Dent J (Basel) ; 10(12)2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36547041

RESUMO

Periodontal disease (PD) and obesity are characterized by a dysregulated inflammatory state. Both conditions trigger inflammatory and immune responses with an increase in proinflammatory cytokines such as Interleukin 6 (IL-6) and the release of inflammatory mediators such as C-reactive protein (CRP). Individuals with a high body mass index (BMI) present a chronic inflammatory state. The aim of the present study was to perform a systematic review of inflammatory markers (IL-6 and CRP) in obese patients with PD and their possible relationship by analyzing the levels of these markers. A digital literature search was performed in three databases-PubMed, SciElo and Medigraphic-through an advanced search for original articles, employing IL-6 and CRP in obese patients with PD, within a publication period from 2010 to 2021. PRISMA guidelines, the JADAD scale and a qualitative analysis of scientific evidence were performed using the Cochrane collaboration method and the RoB 2 assessment tool. Ten articles were included in this analysis with the variables recorded and associated with subjects with obesity and PD. Of the ten articles included, three analyzed IL-6 and CRP, four analyzed IL-6 and three analyzed CRP. In conclusion, and based on the available evidence, the aforementioned markers of inflammation demonstrate that there is a relationship between PD and obesity.

7.
Artigo em Inglês | MEDLINE | ID: mdl-36011941

RESUMO

Introduction: Knowledge of the oral manifestations associated with SARS-CoV-2 infection, the new coronavirus causing the COVID-19 pandemic, was hindered due to the restrictions issued to avoid proximity between people and to stop the rapid spread of the disease, which ultimately results in a hyperinflammatory cytokine storm that can cause death. Because periodontal disease is one of the most frequent inflammatory diseases of the oral cavity, various theories have emerged postulating periodontal disease as a risk factor for developing severe complications associated with COVID-19. This motivated various studies to integrate questions related to periodontal status. For the present work, we used a previously validated self-report, which is a useful tool for facilitating epidemiological studies of periodontal disease on a large scale. Methodology: A blinded case-control study with participants matched 1:1 by mean age (37.7 years), sex, tobacco habits and diseases was conducted. After the diagnostic samples for SARS-CoV-2 detection were taken in an ad hoc location at Guadalajara University, the subjects were interviewed using structured questionnaires to gather demographic, epidemiological and COVID-19 symptom information. The self-reported periodontal disease (Self-RPD) questionnaire included six questions, and subjects who met the criteria with a score ≥ 2 were considered to have periodontal disease. Results: In total, 369 participants were recruited, with 117 participants included in each group. After indicating the subjects who had self-reported periodontal disease, a statistically significant difference (p value ≤ 0.001) was observed, showing that self-reported periodontal disease (n = 95, 85.1%) was higher in SARS-CoV-2-positive individuals than in controls (n = 66, 56.4%), with an OR of 3.3 (1.8-6.0) for SARS-CoV-2 infection in people with self-reported periodontal disease. Cases reported a statistically higher median of symptoms (median = 7.0, Q1= 5.5, Q3 = 10.0) than controls (p value ≤ 0.01), and cases with positive self-RPD had a significantly (p value ≤ 0.05) higher number of symptoms (median = 8.0, Q1 = 6.0, Q3 = 10.0) in comparison with those who did negative self-RPD (median = 6.0, Q1 = 5.0, Q3 = 8.0). Conclusions: According to this study, self-reported periodontal disease could be considered a risk factor for SARS-CoV-2 infection, and these individuals present more symptoms.


Assuntos
COVID-19 , Doenças Periodontais , Adulto , COVID-19/epidemiologia , Estudos de Casos e Controles , Humanos , Pandemias , Doenças Periodontais/epidemiologia , SARS-CoV-2 , Autorrelato
8.
Front Immunol ; 13: 848054, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35432364

RESUMO

New vaccine design approaches, platforms, and immunization strategies might foster antiviral mucosal effector and memory responses to reduce asymptomatic infection and transmission in vaccinated individuals. Here, we investigated a combined parenteral and mucosal immunization scheme to induce local and serum antibody responses, employing the epitope-based antigens 3BT and NG19m. These antigens target the important emerging and re-emerging viruses PRRSV-2 and SARS-CoV-2, respectively. We assessed two versions of the 3BT protein, which contains conserved epitopes from the GP5 envelope protein of PRRSV-2: soluble and expressed by the recombinant baculovirus BacDual-3BT. On the other hand, NG19m, comprising the receptor-binding motif of the S protein of SARS-CoV-2, was evaluated as a soluble recombinant protein only. Vietnamese mini-pigs were immunized employing different inoculation routes: subcutaneous, intranasal, or a combination of both (s.c.-i.n.). Animals produced antigen-binding and neut1ralizing antibodies in serum and mucosal fluids, with varying patterns of concentration and activity, depending on the antigen and the immunization schedule. Soluble 3BT was a potent immunogen to elicit binding and neutralizing antibodies in serum, nasal mucus, and vaginal swabs. The vectored immunogen BacDual-3BT induced binding antibodies in serum and mucosae, but PRRSV-2 neutralizing activity was found in nasal mucus exclusively when administered intranasally. NG19m promoted serum and mucosal binding antibodies, which showed differing neutralizing activity. Only serum samples from subcutaneously immunized animals inhibited RBD-ACE2 interaction, while mini-pigs inoculated intranasally or via the combined s.c.-i.n. scheme produced subtle neutralizing humoral responses in the upper and lower respiratory mucosae. Our results show that intranasal immunization, alone or combined with subcutaneous delivery of epitope-based antigens, generates local and systemic binding and neutralizing antibodies. Further investigation is needed to evaluate the capability of the induced responses to prevent infection and reduce transmission.


Assuntos
COVID-19 , Vírus da Síndrome Respiratória e Reprodutiva Suína , Vacinas Virais , Animais , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , COVID-19/prevenção & controle , Epitopos , Feminino , Imunização , SARS-CoV-2 , Suínos , Porco Miniatura
10.
Rev. ADM ; 79(2)2022.
Artigo em Espanhol | LILACS, BNUY-Odon, BNUY | ID: biblio-1370287

RESUMO

Introducción: Los principales factores de riesgo con los que se asocia el carcinoma oral de células escamosas son el hábito de tabaco y alcohol. La inflamación también es un factor de riesgo importante en el desarrollo del cáncer, ésta posiblemente inducida por el acúmulo de bacterias que se refleja en la placa bacteriana (biofilm microbiano) y posterior cálculo dental debido a una higiene oral deficiente. Objetivo: Asociar la higiene oral deficiente como factor de riesgo del carcinoma oral de células escamosas. Material y métodos: Estudio de casos y controles en el que se utilizó el índice de higiene oral simplificado para biofilm y cálculo como instrumento de medida. Se registraron los hábitos de tabaco y alcohol. El riesgo fue estimado obteniendo Odds Ratio y la significancia estadística fue tomada con base a χ2. Resultados: La higiene oral deficiente con altos niveles de placa bacteriana fue identificada como factor de riesgo de carcinoma oral de células escamosas, los factores de riesgo conocidos (tabaco y alcohol) fueron también identificados en nuestra población; sin embargo, el riesgo fue menor en contraste con la higiene oral deficiente. Conclusión: La higiene oral deficiente es un factor de riesgo significativo que contribuye a la presencia de cáncer oral y puede ser mayor en comparación con el consumo de tabaco y alcohol.


Assuntos
Higiene Bucal , Neoplasias Bucais , Placa Dentária , Biofilmes
11.
J Oral Maxillofac Pathol ; 25(2): 368, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34703136

RESUMO

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most common malignancy in this region, and thus, further elucidation of its tumoral mechanisms is important. One of the main roles of the acute-phase protein orosomucoid-1 (ORM1) is the promotion of angiogenesis, which is key for tumor nutrition and growth. AIM: Our aim was to evaluate the immunohistochemical expression of ORM1 and the angiogenic activity indicated by microvascular density (MVD) in OSCC samples according to histological grade. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded sections from 45 OSCC cases were submitted to immunohistochemistry: 25 were well-differentiated OSCC, 18 were moderately differentiated OSCC and 2 were poorly differentiated OSCC. ORM1 staining was evaluated by a semiquantitative method, and CD34-positive blood vessels were quantified to calculate the MVD. The results were statically analyzed. RESULTS: All cases exhibited immunoexpression of ORM1 and CD34. However, no significant differences were found between the expression of both markers among the histological grades. In addition, the presence of ORM1 in inflammatory cells and in the extracellular matrix was detected in most cases. CONCLUSION: These results suggest that the induction of angiogenesis is not the main role of ORM1 in OSCC and may be associated with the regulation of the immune/inflammatory response or the transport of protumoral molecules, such as sialyl-Lewis X or phorbol esters, which requires confirmation in future studies.

12.
Cells ; 10(9)2021 09 18.
Artigo em Inglês | MEDLINE | ID: mdl-34572115

RESUMO

OBJECTIVES: Tissue architecture and cell morphology suffer profound alterations during oral cancer and are important markers for its progression and outcome. For precise visualization of tissue architecture in oral cancer, we used confocal microscopy to examine the staining pattern of wheat germ agglutinin, a lectin that binds membrane glycoproteins, and the staining patterns of structural proteins. MATERIALS AND METHODS: Paraffin sections of oral squamous cell carcinoma were stained with fluorescently labeled wheat germ agglutinin and with antibodies against structural proteins, which were revealed by immunohistochemistry with tyramide signal amplification. RESULTS: Membrane localization of wheat germ agglutinin was markedly decreased in the basal layers and in regions of tumor invasion, accompanied by cytoplasmic redistribution of E-cadherin, ß-actin and syndecan-1. Wheat germ agglutinin staining clearly identified tumor clusters within the surrounding stroma, and tumor cells with elongated morphology. CONCLUSIONS: Our results suggest that the wheat germ agglutinin staining pattern is indicative of the degree of cell cohesion in oral squamous cell carcinoma, which decreases in basal layers and invasive tumor clusters with more migratory morphologies. Wheat germ agglutinin staining in combination with confocal microscopy could constitute, therefore, a valuable tool for the study of tissue architecture in oral cancer.


Assuntos
Carcinoma de Células Escamosas/patologia , Glicoproteínas de Membrana/metabolismo , Neoplasias Bucais/patologia , Aglutininas do Germe de Trigo/metabolismo , Carcinoma de Células Escamosas/metabolismo , Humanos , Imuno-Histoquímica , Microscopia Confocal , Neoplasias Bucais/metabolismo , Inclusão em Parafina , Coloração e Rotulagem
13.
Cancers (Basel) ; 13(12)2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34204259

RESUMO

Head and neck squamous cell carcinomas (HNSCCs) are aggressive, recurrent, and metastatic neoplasms with a high occurrence around the world and can lead to death when not treated appropriately. Several molecules and signaling pathways are involved in the malignant conversion process. Epithelial-mesenchymal transition (EMT) has been described in HNSCCs, a major type of aggressive carcinoma. EMT describes the development of epithelial cells into mesenchymal cells, which depends on several molecular interactions and signaling pathways that facilitate mesenchymal conversion. This is related to interactions with the microenvironment of the tumor, hypoxia, growth factors, matrix metalloproteinases, and the presence of viral infections. In this review, we focus on the main molecules related to EMT, their interactions with the tumor microenvironment, plasticity phenomena, epigenetic regulation, hypoxia, inflammation, their relationship with immune cells, and the inhibition of EMT in the context of HNSCCs.

14.
J Oral Pathol Med ; 50(7): 708-715, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33733498

RESUMO

BACKGROUND: Increased lipogenesis and lipid droplet accumulation are observed in diverse tumors, and these processes are associated with poor prognosis in several tumors, representing potential therapeutic targets. The presence of lipid droplets in odontogenic tissues and/or tumors is unknown. METHODS: Immunohistochemistry for perilipin 1 and adipophilin was performed in 12 human tooth germs (TG), 27 conventional ameloblastoma (AM), and 8 ameloblastic carcinoma (AC) samples. Cytoplasmic staining was analyzed using an immunoreactive score (IRS), and the results were compared for the TG, AM, and AC samples by Kruskal-Wallis test followed by Dunn's post-test and confirmed by Mann-Whitney U test. RESULTS: Perilipin 1 was negative in 91.7% of the TG samples, positive in 48.2% of the AM samples, and positive in 87.5% of the AC samples. Adipophilin was positive in 100% of the TG samples, 92.6% of the AM samples, and 100% of the AC samples. The perilipin 1 and adipophilin IRS revealed statistically significant differences between the TG, AM, and AC samples (p = .007 and p = .018, respectively). The perilipin 1 levels among the TG and AC samples were statically significant (**p = .0085), as well as the adipophilin levels when TG and AM samples were compared (**p < .0029). CONCLUSIONS: Adipophilin exhibits significant activity in human tooth development. The immunoexpression of perilipin 1 and adipophilin in the AM and AC samples suggests the presence of lipid droplets, providing further evidence of metabolic alterations in these tumors. Additional studies with larger samples and alternative techniques are necessary to confirm these findings.


Assuntos
Ameloblastoma , Carcinoma , Perilipina-1 , Perilipina-2 , Proteínas de Transporte , Humanos , Gotículas Lipídicas/metabolismo , Proteínas de Membrana/metabolismo , Perilipina-1/metabolismo , Perilipina-2/metabolismo , Germe de Dente/metabolismo
15.
Artigo em Inglês | MEDLINE | ID: mdl-33406716

RESUMO

Fluorides are compounds that can be found in the minerals of soil with volcanic rocks. Different populations are exposed to high levels of fluorides through drinking water that, due to their chronic intake, cause several types of damage to health. Nails and hair, denominated as recent biomarkers, have been employed for monitoring systemic fluoride from long-term exposure to fluorides. The aim of this study was to perform a systematic review of the use of recent biomarkers for monitoring systemic fluoride levels in exposed populations and verify their validity in the measurement of the fluorine (F-) concentration within the body. A digital search was performed in the databases PubMed/Medline, Springer Link, Cochrane, and Scopus of original articles that employed recent biomarkers for monitoring systemic F-. Seventeen articles were included in this analysis; the recorded variables were the F- amount in each assessed biomarker, source of exposure, and total daily fluoride intake (TDFI). TDFI was associated with F- in nails and hair, as well as the exposure through drinking water. In conclusion, recent biomarkers are adequate for monitoring the systemic fluoride levels by evaluating the chronic/subchronic exposure through different sources, mainly drinking water, considering nails better than hair for this purpose.


Assuntos
Biomarcadores/análise , Água Potável , Fluoretos/análise , Estudos Transversais , Água Potável/análise , Exposição Ambiental/análise , Cabelo/química , Humanos , Unhas/química
16.
Artigo em Inglês | MEDLINE | ID: mdl-32178265

RESUMO

The ENAM gene is important in the formation of tooth enamel; an alteration can affect the lengthening of the crystals, and the thickness in enamel. The objective was to determine the presence of the single nucleotide variant (SNV) rs12640848 of the ENAM gene in students exposed to different concentrations of fluoride. METHODS: A cross-sectional study was conducted on students exposed to high concentrations of fluoride in the city of Durango which were divided according to the severity of fluorosis and dental caries. Genotype determination was performed by DNA sequencing. The relationship between the severity of dental fluorosis and the allele distribution was determined by the Fisher's exact and Kruskal-Wallis tests. RESULTS: Seventy-one students were included for the sequencing. In the different allelic variations, for the normal genotype AA/TT, the control group presented 75%, for the AG/TC variation, 70.8% in the TF ≤ 4 group, 65% in TF ≥ 5, and 16.7% in TF = 0; with respect to GG/CC variation, 12.5% in TF ≤ 4, 22% in TF ≥ 5, and 8.3% in TF = 0 group (p = 0.000). CONCLUSION: The ENAM gene showed an association in the population exposed to different concentrations of fluoride.


Assuntos
Cárie Dentária , Proteínas da Matriz Extracelular , Fluoretos , Fluorose Dentária , Alelos , Estudos Transversais , Cárie Dentária/genética , Proteínas da Matriz Extracelular/genética , Fluorose Dentária/genética , Humanos , Estudantes
17.
World J Clin Oncol ; 11(1): 31-42, 2020 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-31976308

RESUMO

BACKGROUND: Ameloblastomas are common benign epithelial odontogenic neoplasms that present an aggressive and unpredictable behavior that may modify treatment strategies. Different signaling pathways that participate in the progression of these tumors have been identified. B-raf proto-oncogene serine/threonine kinase (BRAF) is a protein involved in the behavior of ameloblastomas, and it is related to many cell mechanisms. BRAF gene mutations have been identified in ameloblastomas, of which the BRAF V600E (valine substituted by glutamic acid at amino acid 600) mutation has been the most common and can be present concomitantly with other mutations that may be involved in its behavior. Targeted therapies have been used as an alternative in the case of resistance or contraindications to conventional treatments. AIM: To document the presence of BRAF V600E and additional mutations, their behavior, and targeted therapies in these tumors. METHODS: An electronic literature search was conducted according to PRISMA guidelines in PubMed/MEDLINE, Cochrane, EMBASE, and SpringerLink using the terms "ameloblastomas", "BRAF V600E", "additional mutations", and "targeted therapies". Ameloblastomas were classified according to WHO guidelines. Inclusion criteria were articles in English, published not more than 10 years ago, and studies with laboratory works related to BRAF V600E. Articles were evaluated by two independent reviewers and retrieved for full-text evaluation. The EBLIP Critical Appraisal Checklist was used to evaluate the quality of the eligible studies. Descriptive statistical analysis was performed. RESULTS: Two independent reviewers, with a substantial concordance indicated by a kappa coefficient of k = 0.76, evaluated a total of 19 articles that were included in this study. The analysis registered 521 conventional ameloblastomas (AM), 81 unicystic ameloblastomas (UA), 13 ameloblastic carcinomas (AC), three metastatic ameloblastomas (MA), and six peripheral ameloblastomas (PA), of which the histopathological type, anatomic location, laboratory tests, expression of BRAF mutation, and additional mutations were registered. The BRAF V600E mutation was found in 297 AM (57%), 63 UA (77.7%), 3 AC (23%), 1 MA (50%), and 5 PA (83.3%). Follicular type predominated with a total of 116 cases (40%), followed by plexiform type with 63 cases (22.1%). Furthermore, both types presented additional mutations, in which alterations in JAK3 P132T, SMARCB1, PIK3CA, CTNNB1, SMO, and BRAF G606E genes were found. Four case reports were found with targeted therapy to BRAF V600E. CONCLUSION: The identification of BRAF V600E and additional mutations as an aid in targeted therapies has been a breakthrough in alternative treatments of ameloblastomas where surgical treatments are contraindicated.

18.
PLoS Negl Trop Dis ; 14(1): e0007815, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31923219

RESUMO

Triosephosphate isomerases (TPIs) from Taenia solium (TsTPI) and Schistosoma mansoni (SmTPI) are potential vaccine and drug targets against cysticercosis and schistosomiasis, respectively. This is due to the dependence of parasitic helminths on glycolysis and because those proteins elicit an immune response, presumably due to their surface localization. Here we report the crystal structures of TsTPI and SmTPI in complex with 2-phosphoglyceric acid (2-PGA). Both TPIs fold into a dimeric (ß-α)8 barrel in which the dimer interface consists of α-helices 2, 3, and 4, and swapping of loop 3. TPIs from parasitic helminths harbor a region of three amino acids knows as the SXD/E insert (S155 to E157 and S157 to D159 in TsTPI and SmTPI, respectively). This insert is located between α5 and ß6 and is proposed to be the main TPI epitope. This region is part of a solvent-exposed 310-helix that folds into a hook-like structure. The crystal structures of TsTPI and SmTPI predicted conformational epitopes that could be used for vaccine design. Surprisingly, the epitopes corresponding to the SXD/E inserts are not the ones with the greatest immunological potential. SmTPI, but not TsTPI, habors a sole solvent exposed cysteine (SmTPI-S230) and alterations in this residue decrease catalysis. The latter suggests that thiol-conjugating agents could be used to target SmTPI. In sum, the crystal structures of SmTPI and TsTPI are a blueprint for targeted schistosomiasis and cysticercosis drug and vaccine development.


Assuntos
Schistosoma mansoni/enzimologia , Taenia solium/enzimologia , Triose-Fosfato Isomerase/química , Sequência de Aminoácidos , Animais , Cristalografia por Raios X , Desenho de Fármacos , Epitopos/química , Proteínas de Helminto/química , Vacinas
19.
Arch Oral Biol ; 110: 104626, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31838295

RESUMO

OBJECTIVE: Dental fluorosis (DF) is a dental development disorder caused by chronic fluoride overconsumption. There are differences in the susceptibility to and severity of DF in studied populations. The objective of the present study was to determine if single-nucleotide variations (SNVs) in the genes Amelogenin (AMELX), Odontogenic Ameloblast Associated (ODAM) and Matrix Metalloproteinase 20 (MMP20) are associated with DF by evaluating the relationship between variations in these genes and the degree of DF severity. SUBJECTS AND METHODS: Schoolchildren from two regions of Durango State and Mexico City, Mexico, were studied. The DF phenotype was determined using the Thylstrup and Fejerskov (TF) index. DNA was obtained from the buccal mucosa of each participant, and the presence of the variations rs946252 in AMELX, rs1514392 in ODAM and rs1784418 in MMP20 was determined by bidirectional DNA sequencing. RESULTS: A total of 180 DNA samples from 30 schoolchildren from 2 areas of Durango State were sequenced and analyzed. Differences in the severity of DF were found between the study areas (p = 0.006). SNVs in theMMP20 gene were present in 76.9 % of the participants in the high fluoride concentration and lower DF severity area. CONCLUSION: AMELX and ODAM variations was not different between the two populations with respect to DF severity; however, the presence of rs1784418 differed between phenotypes with regard to susceptibility to DF. Therefore, MMP20 might be related to the various phenotypes of DF and may serve as a protective marker.


Assuntos
Amelogenina , Fluorose Dentária , Peptídeos e Proteínas de Sinalização Intracelular , Metaloproteinase 20 da Matriz , Amelogenina/genética , Amiloide , Proteínas de Transporte , Criança , Fluoretos , Fluorose Dentária/genética , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Metaloproteinase 20 da Matriz/genética , México , Proteínas de Neoplasias , Fenótipo , Análise de Sequência de DNA
20.
Front Immunol ; 10: 1734, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31404149

RESUMO

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous cell population with potent immunosuppressive functions. They play major roles in cancer and many of the pathologic conditions associated with inflammation. Long non-coding RNAs (lncRNAs) are untranslated functional RNA molecules. The lncRNAs are involved in the control of a wide variety of cellular processes and are dysregulated in different diseases. They can participate in the modulation of immune function and activity of inflammatory cells, including MDSCs. This mini review focuses on the emerging role of lncRNAs in MDSC activity. We summarize how lncRNAs modulate the generation, recruitment, and immunosuppressive functions of MDSCs and the underlying mechanisms.


Assuntos
Inflamação/imunologia , Células Supressoras Mieloides/imunologia , Neoplasias/imunologia , RNA Longo não Codificante/fisiologia , Animais , Proteína beta Intensificadora de Ligação a CCAAT/fisiologia , Linhagem da Célula , Epigênese Genética , Previsões , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoterapia , Camundongos , Células Supressoras Mieloides/classificação , Neoplasias/genética , Neoplasias/terapia , Óxido Nítrico/metabolismo , Pseudogenes , RNA Longo não Codificante/genética , RNA Longo não Codificante/imunologia , RNA Neoplásico/imunologia , RNA Neoplásico/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Evasão Tumoral , Microambiente Tumoral
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