The Diagnostic and Prognostic Potentials of Non-Coding RNA in Cholangiocarcinoma.

Cholangiocarcinoma (CCA) is a rare biliary tract tumor with high malignancy. CCA is the second most common primary hepatobiliary cancer after hepatocarcinoma. Despite its rarity, the incidence of CCA is steadily increasing globally. Most patients with CCA are asymptomatic in the early stages, resulting in a late-stage diagnosis and poor prognosis. Finding reliable biomarkers is essential to improve CCA's early diagnosis and survival rate. Non-coding RNAs (ncRNAs) are non-protein coding RNAs produced by genomic transcription. This includes microRNAs, long non-coding RNAs, and circular RNAs. ncRNAs have multiple functions in regulating gene expression and are crucial for maintaining normal cell function and developing diseases. Many studies have shown that aberrantly expressed ncRNAs can regulate the occurrence and development of CCA. ncRNAs can be easily extracted and detected through tumor tissue and liquid biopsies, representing a potential tool for diagnosing and prognosis CCA. This review will provide a detailed update on the diagnostic and prognostic potentials of lncRNAs and cirRNAs as biomarkers in CCA.

Comparative randomized trial study about the efficacy of photobiomodulation and curcumin antimicrobial photodynamic therapy as a coadjuvant treatment of oral mucositis in oncologic patients: antimicrobial, analgesic, and degree alteration effect.

INTRODUCTION: As conventional treatments currently available for mucositis are not considerably effective, there is a need to implement an adjuvant protocol for the treatment of oral mucositis in patients undergoing radiotherapy and chemotherapy. PURPOSE: To evaluate the effect of photobiomodulation (PBM) and antimicrobial photodynamic therapy (aPDT) mediated by curcumin and blue LED as an adjunct treatment of oral mucositis for oncology patients using chemotherapy and/or radiotherapy. METHODS: Clinical, randomized study, in a single location, in an oncology service of a general hospital, with a total of 30 patients (over 18 years old) with stable oral mucosa lesions in the process of chemotherapy and/or radiotherapy. The patients were divided into 3 groups: control group (treated with nystatin), PBM group (treated with low-level laser therapy), and the aPDT group (treated with 450-nm blue LED and curcumin photosensitizer). RESULTS: The results showed, by means of intra-group comparisons, that the two experimental treatments promoted yeast reduction of the genus Candida in the last two evaluations (21 days and 30 days), but not in the first two evaluations (7 days and 14 days). The intra-group comparisons showed that the control and aPDT group showed a significant difference in the degree of mucositis over the four evaluations performed, with the results pointing out that the mucositis worsened in the control group from the 14th day, while reduced in the aPDT group from the 21st day of treatment. CONCLUSION: A reduction in the degree of mucositis and pain score was observed in the PBM and aPDT groups, with the aPDT group standing out when presenting early clinical improvement in relation to the PBM group and the control group, thus emphasizing its effectiveness within the desired aspects. Regarding the antimicrobial effect, aPDT showed a greater reduction of yeasts of the genus Candida in the tested parameters.

Prediabetes blunts DPP4 genetic control of postprandial glycaemia and insulin secretion.

AIMS/HYPOTHESIS: Imbalances in glucose metabolism are hallmarks of clinically silent prediabetes (defined as impaired fasting glucose and/or impaired glucose tolerance) representing dysmetabolism trajectories leading to type 2 diabetes. CD26/dipeptidyl peptidase 4 (DPP4) is a clinically proven molecular target of diabetes-controlling drugs but the DPP4 gene control of dysglycaemia is not proven. METHODS: We dissected the genetic control of post-OGTT and insulin release responses by the DPP4 gene in a Portuguese population-based cohort of mainly European ancestry that comprised individuals with normoglycaemia and prediabetes, and in mouse experimental models of Dpp4 deficiency and hyperenergetic diet. RESULTS: In individuals with normoglycaemia, DPP4 single-nucleotide variants governed glycaemic excursions (rs4664446, p=1.63x10-7) and C-peptide release responses (rs2300757, p=6.86x10-5) upon OGTT. Association with blood glucose levels was stronger at 30 min OGTT, but a higher association with the genetic control of insulin secretion was detected in later phases of the post-OGTT response, suggesting that the DPP4 gene directly senses glucose challenges. Accordingly, in mice fed a normal chow diet but not a high-fat diet, we found that, under OGTT, expression of Dpp4 is strongly downregulated at 30 min in the mouse liver. Strikingly, no genetic association was found in prediabetic individuals, indicating that post-OGTT control by DPP4 is abrogated in prediabetes. Furthermore, Dpp4 KO mice provided concordant evidence that Dpp4 modulates post-OGTT C-peptide release in normoglycaemic but not dysmetabolic states. CONCLUSIONS/INTERPRETATION: These results showed the DPP4 gene as a strong determinant of post-OGTT levels via glucose-sensing mechanisms that are abrogated in prediabetes. We propose that impairments in DPP4 control of post-OGTT insulin responses are part of molecular mechanisms underlying early metabolic disturbances associated with type 2 diabetes.

Combined effect of interventions with pure or enriched mixtures of (poly)phenols and anti-diabetic medication in type 2 diabetes management: a meta-analysis of randomized controlled human trials.

PURPOSE: (Poly)phenols have been reported to confer protective effects against type 2 diabetes but the precise association remains elusive. This meta-analysis aimed to assess the effects of (poly)phenol intake on well-established biomarkers in people with type 2 diabetes or at risk of developing diabetes. METHODS: A systematic search was conducted using the following selection criteria: (1) human randomized controlled trials involving individuals with prediabetes and type 2 diabetes; (2) one or more of the following biomarkers: glucose, glycated haemoglobin (HbA1c), insulin, pro-insulin, homeostatic model assessment of insulin resistance (HOMA-IR), islet amyloid polypeptide (IAPP)/amylin, pro-IAPP/pro-amylin, glucagon, C-peptide; (3) chronic intervention with pure or enriched mixtures of (poly)phenols. From 488 references, 88 were assessed for eligibility; data were extracted from 27 studies and 20 were used for meta-analysis. The groups included in the meta-analysis were: (poly)phenol mixtures, isoflavones, flavanols, anthocyanins and resveratrol. RESULTS: Estimated intervention/control mean differences evidenced that, overall, the consumption of (poly)phenols contributed to reduced fasting glucose levels (- 3.32 mg/dL; 95% CI - 5.86, - 0.77; P = 0.011). Hb1Ac was only slightly reduced (- 0.24%; 95% CI - 0.43, - 0.044; P = 0.016) whereas the levels of insulin and HOMA-IR were not altered. Subgroup comparative analyses indicated a stronger effect on blood glucose in individuals with diabetes (- 5.86 mg/dL, 95% CI - 11.34, - 0.39; P = 0.036) and this effect was even stronger in individuals taking anti-diabetic medication (- 10.17 mg/dL, 95% CI - 16.59, - 3.75; P = 0.002). CONCLUSIONS: Our results support that the consumption of (poly)phenols may contribute to lower glucose levels in individuals with type 2 diabetes or at risk of diabetes and that these compounds may also act in combination with anti-diabetic drugs.

Evaluation of dentistry students' knowledge on hematologic disorders / Avaliação do conhecimento de estudantes de Odontologia acerca dos distúrbios hematológicos

ABSTRACT Objective: To determine the knowledge level of undergraduate dentistry students of UESB on hematological disorders and their implications in the treatment of the patient. Methods: This is a descriptive, quantitative and cross-sectional study in which a questionnaire with 16 questions was used as a data collection instrument. The study subjects were 192 students enrolled at UESB Dentistry Course. For data analysis, SPSS statistical software (version 16.0) was used. Results: The response rate was 87.5%. Only 54.2% of respondents reported having information about blood disorders and 78% considered themselves not enough informed, fact observed through the low percentage of right answers in a knowledge test. Conclusion: The level of knowledge of UESB Dentistry academics on hematological disorders is insufficient and there isn't a gradual increment of this knowledge throughout the semesters, polarized mainly in the 6th and 10th semester.

RESUMO Objetivo: Verificar o nível de conhecimento de graduandos do curso de Odontologia da UESB sobre os distúrbios hematológicos e suas implicações para o tratamento do paciente em âmbito odontológico. Métodos: Trata-se de um estudo descritivo, quantitativo e de corte transversal, onde adotou-se como instrumento de coleta de dados um questionário, composto por 16 perguntas. Os sujeitos da pesquisa foram os 192 estudantes regularmente matriculados no curso de Odontologia da UESB. Para análise dos dados foi utilizado o software estatístico SPSS (versão 16.0). Resultados: A taxa de resposta foi de 87,5%. Apenas 54,2% dos entrevistados relataram ter informações acerca dos distúrbios hematológicos e 78% consideraram-se insuficientemente informados, fato corroborado pelas baixas porcentagens de acertos nos testes de conhecimento. Conclusão: O nível de conhecimento dos acadêmicos de Odontologia da UESB sobre os distúrbios hematológicos mostrou-se insuficiente e não houve um crescimento gradual deste conhecimento ao longo dos semestres, estando o mesmo polarizado principalmente nos 6º e 10º semestres.

Análise radiográfica para estimativa de idade utilizando o método demirjian em uma população do nordeste do brasil / Radiographic analysis to age estimation using demirjian method in a population of Northeast Brazil

A estimativa da idade é um elemento importante na investigação odontolegal, sendo o método Demirjianet al. (1973) um dos mais difundidos para estimar a idade dental. Diversos estudos foram realizados comeste método, entretanto, poucos são os estudos de impacto realizados na população brasileira até o presente momento. Neste sentido, este trabalho objetivou estimar a idade dental aplicando o métodoDemirjian et al. (1973) em uma cidade no nordeste do Brasil. Para isso, foram analisadas 300 radiografiaspanorâmicas de pacientes com idade entre 3 e 18 anos, obtidas a partir do arquivo digital de um institutode radiologia. Os resultados indicam uma forte correlação entre a idade cronológica - IC - (11, 683 anos) ea idade dental - ID - (11,667 anos) quando da aplicação do método Demirjian et al. (1973). A exatidãomédia (EM) comparou ID e IC de acordo com os gêneros, mostrando que, em ambos os sexos, as IC e IDsão compatíveis. Para o gênero feminino, nas idades de 5, 7, 8, 13 e 14 anos houve um maior percentualde coincidência entre a ID e a IC. Para o gênero masculino, nas idades de 3, 7, 8, 9 e 12 anos obteve-seo maior percentual de coincidência entre a ID e a IC. Assim, observa-se que é viável a utilização dométodo para estimar a idade na população desta região amostrada. Contudo, por ser o Brasil um paísmiscigenado, novos estudos devem ser realizados.

Estimating dental age is an important asset on forensic dentistry, and Demirjian et al. method (1973) havebeen one of the most recurrent mechanisms to reach this finality. A variety of studies regarding Demirjianet al. (1973) method have taken place so far, however very few of them were precise to determine thesubject in Brazilian populations. To this end, the purpose of the present study was estimating dental ageby applying Demirjian et al. method (1973) in a northeastern population of Brazil. To fulfil this goal,panoramic radiographs of 300 people, between the age of 3 and 18 were obtained from a digital archive ofa radiology institute and analysed. The results indicate a strong correlation between chronological age CA(11, 683 years) and dental age DA (11,667 years), when applying Demirjian et al. method (1973). Theaverage accuracy compared CA and DA according to gender, revealing both male and female to becompatible between these rates.The highest compatibility rate between CA and DA was found amongmales aged from 3, 7, 8, 9 and 12, as well as among females aged from 5, 7, 8, 13 and 14. In brief,Demirjian et al. (1973) method has proved to be a viable technique to estimate dental age in theaforementioned population. However, since Brazil is well-know for its miscegenation, new studies shall beencouraged.

Analysis of the effect of soil saprophytic fungi on the eggs of Baylisascaris procyonis.

Baylisascaris procyonis is a soil-transmitted helminth mainly found in raccoons (Procyon lotor) which can also affect other domestic and sylvatic animals, as well as humans, when the eggs released in the feces of parasitized raccoons are accidentally ingested. Three assays have been conducted to assess the effect of three saprophytic fungi, Mucor circinelloides, Paecilomyces lilacinus, and Verticillium sp., on the eggs of B. procyonis. Firstly, their ovicidal effect was in vitro ascertained by placing 1 mL with 2 × 10(6) spores of each fungus in Petri plates with water-agar (2 %) and simultaneously adding 200 eggs of Baylisascaris/plate. Two in vivo probes were carried out, by spraying the fungal spores (3 mL containing about 2 × 10(6) spores/mL) on the feces of raccoons and coatis (Nasua narica) passing eggs of B. procyonis in a zoological park; the other assay consisted of evaluating the activity of the fungi after adding sand to fecal samples from raccoons. An ovicidal type 3 activity characterized by morphological damage of the eggshell with hyphal penetration, internal egg colonization, and embryo alteration was observed for all the tested fungi. In the plate assays, viability of Baylisascaris eggs reduced significantly by 53-69 % with Mucor, 45-62 % with Paecilomyces, and 52-67 % with Verticillium. A similar ovicidal effect was detected in the feces with sand. These results demonstrate the usefulness of spraying spores of M. circinelloides, Pa. lilacinus, or Verticillium sp. on the feces of animals infected by Baylisascaris to decrease the numbers of viable eggs and, thus, the risk of infection.

Avaliação in vitro da citotoxicidade do enxaguatório Periogard© em diferentes períodos de tempo / In vitro assessment of the cytotoxicity of Periogard© mouthwash at different periods

O estudo teve como objetivo avaliar a citotoxicidade do enxaguatório a base de clorexidina Periogard® em diferentes períodos de tempo, 0, 15, 30, 45, 60 e 120 segundos, quanto ao seu efeito citotóxico em fibroblastos gengivais L929. Utilizou-se 3 grupos controle: positivo (C+) detergente celular Tween 80, negativo (C-) PBS e controle de célula (CC), onde as mesmas não foram expostas a nenhum material. O ensaio de citotoxicidade foi realizado utilizando cultura celular de fibroblasto de camundongo (L929). Após contato do enxaguatório com as células, as mesmas foram colocadas em contato com o corante vital vermelho neutro utilizando-se a técnica “dye up take”. Os valores da quantidade de células viáveis foram submetidos à análise da variância (ANOVA) para determinar se havia diferença estatística entre os grupos e, posteriormente, ao teste de Tukey (p<0.05). Os resultados demonstraram citotoxicidade do enxaguatório Periogard® em todos os períodos avaliados. Foram encontradas diferenças estatísticas entre os grupos experimentais com todos os demais controles (p>0.05). Pode-se concluir com a realização deste trabalho que o Periogard® é citotóxico aos fibroblastos no período de 0 a 120 segundos.

This study aimed to evaluate the cytotoxicity of chlorhexidine-based mouthwash (Periogard©) in different periods, 0, 15, 30, 45, 60 and 120 seconds, for its cytotoxic effect on gingival fibroblasts L929. Three control groups were used: positive (C +) cell detergent Tween 80, negative (C -) PBS, and control of cell (CC) with cells that were not exposed to any material. The cytotoxicity test was performed using fibroblast cell culture of mouse (L929). After the the cells were in contact with the mouthwash, they were placed in contact with Neutral red using the dye up take technique. The values of the quantity of viable cells were submitted to analysis of variance (ANOVA) to determine whether there were statistical differences between groups, and then submitted toTukey test (p <0.05). The results demonstrated cytotoxicity of mouthwash Periogard© in all periods. Differences were observed between the experimental groups with all other controls (p> 0.05). It is possible to conclude that Periogard© is cytotoxic to fibroblasts in the periodsfrom 0 to 120 seconds

Histology, bioenergetics and oxidative stress in mouse liver exposed to N-diethylnitrosamine.

BACKGROUND: A mouse model in which N-diethylnitrosamine (DEN) induces Hepatocellular carcinoma (HCC) has histological and genetic resemblance to human tumours. MATERIAL AND METHODS: Male ICR mice were divided into control (n=10) and DEN-treated (n=10) groups. DEN was administered via intraperitoneal injection, once a week, for eight consecutive weeks. Animals were euthanized seven weeks after the last administration of DEN and their livers were collected. Plasma albumin, total bilirubin, alanine transaminase and aspartate aminotransferase activity were all measured and liver mitochondrial bioenergetics and oxidative stress were also evaluated. RESULTS: Histologically, pre-neoplastic lesions were identified in the livers of mice from the DEN group. Total plasma bilirubin increased significantly in the group exposed to DEN and mitochondrial complex I and IV were significantly inhibited (p=0.0403 and p=0.0053, respectively). CONCLUSION: DEN induced changes in liver bioenergetics and antioxidant capacity towards reactive oxygen species, seven weeks after administration. At this stage, liver tissues in mice exposed to DEN still had the ability to counteract the oxidative effects of DEN by increasing the activity of antioxidant enzymes.

Organochlorine pesticides and polychlorinated biphenyls in soil and water samples in the Northeastern part of São Paulo State, Brazil.

Detailed analyses of persistent organic pollutants (POPs) such as organochlorine pesticides (OCPs), hexachlorocyclohexane (HCH) isomers (HCHs), dichlorodiphenyltrichloro ethane (DDT) and its metabolites (DDTs) and congeners of polychlorinated biphenyls (PCBs) in soil and surface water from the northeastern São Paulo, Brazil allowed the evaluation of the contamination status, distribution and possible pollution sources. The pesticides and PCBs demonstrated markedly different distributions, reflecting different agricultural, domestic and industrial usage in each region studied. The ranges of HCH, DDT, and PCBs concentrations in the soil samples were 0.05-0.92, 0.12-11.01, 0.02-0.25 ng g(-1) dry wt, respectively, and in the surface water samples were 0.02-0.6, 0.02-0.58 and 0.02-0.5 ng l(-1), respectively. Overall elevated levels of DDT and PCB were recorded in region 2, a site very close to melting, automotive batteries industries, and agricultural practice regions. High ratios of metabolites of DDT to DDT isomers revealed the recent use of DDT in this environment. The sources of contamination are closely related to human activities, such as domestic and industrial discharge, street runoff, agricultural pesticides and soil erosion, due to deforestation as well as atmospheric transport.