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A new series of compounds planned by molecular hybridization of the nucleobases uracil and thymine, or the xanthine theobromine, with coumarins, and linked through 1,2,3-triazole heterocycles were evaluated for their in vitro anticancer activity against the human tumor cell lines: colon carcinoma (HCT116), laryngeal tumor cells (Hep-2), and lung carcinoma cells (A549). The hybrid compound 9a exhibited better activity in the series, showing an IC50 of 24.19 ± 1.39 µM against the HCT116 cells, with a selectivity index (SI) of 6, when compared to the cytotoxicity against the non-tumor cell line HaCat. The in silico search for pharmacological targets was achieved through molecular docking studies on all active compounds, which suggested that the synthesized compounds possess a high affinity to the Topoisomerase 1-DNA complex, supporting their antitumor activity. The in silico toxicity prediction studies suggest that the compounds present a low risk of causing theoretical mutagenic and tumorigenic effects. These findings indicate that molecular hybridization from natural derivative molecules is an interesting approach to seek new antitumor candidates.
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Bacteria are an old concern to human health, as they are responsible for nosocomial infections, and the number of antibiotic-resistant microorganisms keeps growing. Copper is known for its intrinsic biocidal properties, and therefore, it is a promising material to combat infections when added to surfaces. However, its biocidal properties in the presence of light illumination have not been fully explored, especially regarding the use of microsized particles since nanoparticles have taken over all fields of research and subjugated microparticles despite them being abundant and less expensive. Thus, the present work studied the bactericidal properties of metallic copper particles, in microscale (CuMPs) and nanoscale (CuNPs), in the absence of light and under white LED light illumination. The minimum bactericidal concentration (MBC) of CuMPs against Staphylococcus aureus that achieved a 6-log reduction was 5.0 and 2.5 mg mL-1 for assays conducted in the absence of light and under light illumination, respectively. Similar behavior was observed against Escherichia coli. The bactericidal activity under illumination provided a percentage increase in log reduction values of 65.2% for S. aureus and 166.7% for E. coli when compared to the assays under dark. This assay reproduced the testing CuNPs, which showed superior bactericidal activity since the concentration of 2.5 mg mL-1 promoted a 6-log reduction of both bacteria even under dark. Its superior bactericidal activity, which overcame the effect of illumination, was expected once the nanoscale facilitated the interaction of copper within the surface of bacteria. The results from MBC were supported by fluorescence microscopy and atomic absorption spectroscopy. Therefore, CuMPs and CuNPs proved to have size- and dose-dependent biocidal activity. However, we have shown that CuMPs photoactivity is competitive compared to that of CuNPs, allowing their application as a self-cleaning material for disinfection processes assisted by conventional light sources without additives to contain the spread of pathogens.
Assuntos
Cobre , Staphylococcus aureus , Humanos , Cobre/farmacologia , Cobre/química , Escherichia coli , Iluminação , Antibacterianos/farmacologia , Antibacterianos/química , BactériasRESUMO
:Breast cancer is the object of thousands of studies worldwide. Nevertheless, few tools are available to corroborate prediction of response to neoadjuvant chemotherapy. Artificial intelligence is being researched for its potential utility in several fields of knowledge, including oncology. The development of a standardized Artificial intelligence-based predictive model for patients with breast cancer may help make clinical management more personalized and effective. We aimed to apply Artificial intelligence models to predict the response to neoadjuvant chemotherapy based solely on clinical and pathological data. Methods: Medical records of 130 patients treated with neoadjuvant chemotherapy were reviewed and divided into two groups: 90 samples to train the network and 40 samples to perform prospective testingand validate the results obtained by the Artificial intelligence method. Results: Using clinicopathologic data alone, the artificial neural network was able to correctly predict pathologic complete response in 83.3% of the cases. It also correctly predicted 95.6% of locoregional recurrence, as well as correctly determined whether patients were alive or dead at a given time point in 90% of the time. To date, no published research has used clinicopathologic data to predict the response to neoadjuvant chemotherapy in patients with breast cancer, thus highlighting the importance of the present study. Conclusions: Artificial neural network may become an interesting tool for predicting response to neoadjuvant chemotherapy, locoregional recurrence, systemic disease progression, and survival in patients with breast cancer (AU)
Assuntos
Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias da Mama/tratamento farmacológico , Inteligência Artificial , Terapia Neoadjuvante , Antineoplásicos/uso terapêutico , Progesterona/metabolismo , Estudos Retrospectivos , Redes Neurais de Computação , Receptor ErbB-2/metabolismo , Antígeno Ki-67/metabolismo , Estrogênios/metabolismo , Recidiva Local de NeoplasiaRESUMO
ABSTRACT Objective: To define histological scores for intervertebral disc degeneration that would enable the definition of morphological characteristics of disease, besides improving knowledge of the lumbar degenerative disc disease by means of immunohistochemical markers. Methods: Hematoxylin and Eosin, Alcian/PAS, Masson Trichrome and Safranin O/FCF staining was used on the intervertebral disc degeneration sections of patients with lumbar degenerative disc disease. The protein markers defined in immunohistochemistry were cell proliferation (Ki-67) and apoptosis (p53). Results: The study data enabled the determination of Safranin O/FCF stain as the most effective one for evaluating parameters such as area, diameter, and number of chondrocyte clusters. The importance of using stains in association, such as Safranin O/FCF, Masson Trichrome, Alcian/PAS and Hematoxylin and Eosin, was also determined, as they are complementary for the histopathological verification of intervertebral disc degeneration. By expressing proteins using the immunohistochemistry technique, it was possible to consider two stages of disc degeneration: cell proliferation with chondrocyte cluster formation, and induction of apoptosis. Conclusion: This study enabled the histological and immunohistochemical characterization to be determined for lumbar degenerative disc disease, and its degrees of evolution, by determining new disc degeneration scores.
RESUMO Objetivo: Definir escores histológicos de degeneração do disco intervertebral que permitam a identificação de características morfológicas da doença, além de melhorar o conhecimento sobre a discopatia degenerativa lombar por meio de marcadores imuno-histoquímicos. Métodos: As colorações histológicas de hematoxilina e eosina, azul de alcian/PAS, tricrômica de Masson e safranina O/FCF foram utilizadas em cortes de disco intervertebral degenerado de pacientes com discopatia degenerativa lombar. Os marcadores proteicos definidos na imuno-histoquímica permitiram a avaliação da proliferação celular (Ki-67) e da apoptose (p53). Resultados: Os dados do estudo permitiram a determinação da coloração de safranina O/FCF como a mais eficaz para avaliar os parâmetros tais como a área, o diâmetro e o número de agrupamentos de condrócitos. Também se determinou a importância do uso das colorações histológicas de forma associada, como safranina O/FCF, tricrômica de Masson, azul de alcian/PAS e hematoxilina e eosina, uma vez que elas são complementares para a verificação histopatológica da degeneração do disco intervertebral. Pela técnica da expressão de proteínas com técnica imuno-histoquímica, foi possível considerar dois estágios de degeneração do disco: proliferação de células com a formação de agrupamentos de condrócitos, seguida pela indução de apoptose. Conclusão: Este estudo permitiu definir a caracterização histológica e imuno-histoquímica em discopatia degenerativa lombar e seus graus de evolução, determinando novos escores de degeneração discal.
RESUMEN Objetivo: Definir valores histológicos de degeneración del disco intervertebral que permitan la definición de las características morfológicas de la enfermedad y mejorar el conocimiento de la enfermedad degenerativa del disco lumbar mediante marcadores inmunohistoquímicos. Métodos: Las coloraciones histológicas con hematoxilina y eosina, azul alcián/PAS, tricrómico de Masson y safranina O/FCF se utilizaron en secciones de los discos intervertebrales degenerados de pacientes con enfermedad degenerativa del disco lumbar. Los marcadores de proteínas definidos por inmunohistoquímica permitieron la evaluación de la proliferación celular (Ki-67), y la apoptosis (p53) . Resultados: Los datos de la determinación permitieron establecer la tinción con safranina O/FCF como la más eficaz para evaluar parámetros tales como el área, diámetro y número de agrupaciones de condrocitos. Se determinó también la importancia del uso asociado de diversas tinciones, como safranina O/FCF, tricrómico de Masson, azul de alcián/PAS y hematoxilina y eosina, ya que son complementarias para la verificación histopatológica de la degeneración del disco intervertebral. Por la técnica de la expresión de proteína con análisis inmunohistoquímica, fue posible establecer dos etapas de la degeneración del disco: la proliferación de células con la formación de agrupaciones de condrocitos y la inducción de la apoptosis. Conclusión: Este estudio permitió definir la caracterización histológica e inmunohistoquímica en la enfermedad degenerativa del disco lumbar y sus grados de evolución, mediante la determinación de nuevas puntuaciones de degeneración del disco.
Assuntos
Humanos , Disco Intervertebral , Técnicas Histológicas , Imuno-Histoquímica , Degeneração do Disco IntervertebralRESUMO
Objective: Triple negative breast cancer (TNBC) is a subset of tumors with an aggressive intrinsic biology, resulting in poor prognosis. Androgen receptor (AR) is currently one of the most studied biomarkers in TNBC, playing a role in the genesis and development of breast cancer. Methods: In this cross-sectional study, we retrospectively reviewed the medical records of all patients with TNBC who received care from 2012 to 2014 at a single health center in southern Brazil. Histological material from breast tumors was analyzed by immunohistochemistry for AR expression and related to age, histological grade, tumor-infiltrating lymphocytes (TILs), and Ki-67. Results: Of 34 TNBC cases identified, 23 (67.6%) were AR negative and 11 (32.4%) were AR positive. The average age of the patients was 51.9 years (range: 3082 years). Among positive cases, AR was weakly expressed in 6 and strongly expressed in 5 cases. Most patients (n=28; 82.0%) had poorly differentiated tumors. Mean Ki-67 expression was 65.0% in AR-negative and 43.6% in AR-positive cases (p<0.05). There was a significant association between age and AR expression (p<0.005), which was associated with mean age 70.8 years in the strongly AR-positive group and 42.3 years in the weakly AR-positive group. The mean percentage of TILs was 38.6% in AR-positive and 39.1% in AR-negative cases (p=0.391). Conclusion: There was no significant association between AR expression and histological grade or TILs. AR positivity in TNBC was associated with older age and tumors with lower Ki-67 expression, indicating two subgroups with distinct phenotypes in patients with TNBC.
Objetivo: O câncer de mama negativo triplo (triple negative breast cancer TNBC) é um subtipo de tumores com biologia intrínseca agressiva, resultando em pior prognóstico. O receptor de andrógeno (androgen receptor AR) é atualmente um dos biomarcadores mais estudados em TNBC, desempenhando papel na gênese e no desenvolvimento do câncer de mama. Métodos: Neste estudo transversal, revisamos retrospectivamente os registros médicos de todos os pacientes com TNBC que receberam atendimento de 2012 a 2014 em um único centro no sul do Brasil. O material histológico dos tumores de mama foi analisado por imuno-histoquímica para a expressão de AR e relacionado a idade, grau histológico, linfócitos infiltrantes de tumores (TILs) e Ki-67. Resultados: Dos 34 casos identificados de TNBC, 23 (67,6%) eram AR negativos e 11 (32,4%), AR positivos. A idade média foi de 51,9 anos (3082 anos). Entre os casos positivos, AR foi fracamente expresso em 6 e fortemente expresso em 5 casos. A maioria dos pacientes (n=28, 82,0%) apresentou tumores pouco diferenciados. A expressão média de Ki-67 foi de 65,0% em AR-negativo e 43,6% em AR-positivo (p<0,05). Houve associação significativa entre a idade e a expressão de AR (p<0,005), associada à idade média de 70,8 anos no grupo com AR fortemente positivo e de 42,3 anos no grupo com AR fracamente positivo. A porcentagem média de TILs foi de 38,6% em AR-positivo e de 39,1% em AR-negativo (p=0,391). Não houve associação significativa entre expressão AR e grau histológico ou TILs. Conclusão: A positividade de AR em TNBC foi associada com idade mais avançada e tumores com menor expressão de Ki-67, indicando dois subgrupos com fenótipos distintos em pacientes com TNBC.
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Aims: Rotavirus (RV) and norovirus (NoV) are the most common cause of diarrhea in children aged less than five years throughout the world. However, RV and NoV have frequently been overlooked as pathogens in elderly individuals. This study examined the frequency of RV and NoV among elderly patients with complaints of diarrhea in the city of Caxias do Sul, southern Brazil.Methods: Between 2010 and 2012, stool samples from patients aged 60 years or older with acute gastroenteritis treated at a private healthcare center were analyzed, seeking to identify RV and NoV. RV detection was performed by latex agglutination (LA) methods and polyacrylamide gel electrophoresis (PAGE). One third of the samples were further tested for NoV by reverse transcription polymerase chain reaction (RT-PCR).Results: A total of 145 stool samples from patients aged 60 to 105 years were analyzed. RV was detected in 6/145 (4.14%) and 5/125 (4.00%) of the samples by LA and PAGE, respectively. NoV was detected in 6/51 (11.76%). Mixed infection (RV and NoV) was detected in a single sample: 1/51 (1.96%).Conclusions: This study adds further evidence that viral agents are involved in the etiology of gastroenteritis in the elderly, contributing significantly to the understanding of RV and NoV infections in the mature population.
Objetivos: Rotavírus (RV) e norovírus (NoV) são a causa mais comum de diarreia em crianças menores de cinco anos em todo o mundo; entretanto, como patógenos em idosos, esses vírus têm sido pouco investigados. Este estudo examinou a frequência de RV e NoV entre idosos com queixas de diarreia na cidade de Caxias do Sul, no sul do Brasil. Métodos: Entre 2010 e 2012 foram analisadas amostras de fezes de pacientes de umCentro de Atenção à Saúde privado, com idade de 60 anos ou mais, com gastroenterite aguda,buscando-se identificar RV e NoV. A detecção de RV foi realizada pelos métodos Aglutinação em Látex (LA) e Eletroforese em Gel de Poliacrilamida (PAGE). Uma terceira parte das amostras foi ainda testada quanto a NoV por Transcrição Reversa e Reação em Cadeia da Polimerase (RTPCR).Resultados: Ao todo foram analisadas 145 amostras de fezes de pacientes com idade entre 60 e 105 anos. RV foi detectado em 6/145 (4,14%) e 5/125 (4,00%) das amostras por LA e PAGE, respectivamente. NoV foi detectado em 6/51 (11,76%). Infecção mista (RV e NoV) foi detectada em uma única amostra: 1/51 (1,96%). Conclusões: Este estudo acrescenta mais evidências de que agentes virais estão envolvidos na etiologia da gastroenterite em idosos, e contribui para a compreensão das infecções por RV e NoV na população idosa.
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To review the potential role of stem cells in treating degenerative disc disease of the intervertebral disc (IVD). A review was performed of articles from the Medline database concerning stem cells and degenerative disc disease (DDD). To discuss the data, the papers were classified as: review, in vitro, experimental, and clinical. The currently available treatments were basically for symptom reduction, not to revert the IVD degenerative process. The use of mesenchymal stem cells (MSC) is being proposed as an option of treatment for DDD. In vitro studies have shown that the MSC are able to differentiate into NP cells and that the MSC also reduce the inflammatory levels of the degenerated IVD. Besides, experimental studies demonstrated that the MSC remained viable when injected into the IVD, and that they were able to regenerate partially from the degenerated IVD and its structure. The few clinical studies found in the literature presented diverging results. The use of MSC is being widely studied and shows promising results for the treatment of DDD. Although many advances are being achieved in studies in vitro and experimental, there is a lack of clinical studies to prove the role of MSC in DDD management.
Revisar o potencial papel das células-tronco para o tratamento de doença degenerativa do disco intervertebral (IVD). Foi realizada uma revisão dos trabalhos da base de dados Medline em relação a células-tronco e doença degenerativa discal (DDD). Para fins de discussão dos dados, os trabalhos foram divididos em: revisão, in vitro, experimentais e clínicos. Os tratamentos disponíveis atualmente focam basicamente na redução dos sintomas, e não na reversão do processo degenerativo do DIV. O uso de células-tronco mesenquimais (CTM) vem sendo proposto como uma opção de tratamento para DDD. Estudos in vitro demonstraram que as CTM são capazes de se diferenciarem em células do NP e que as CTM também diminuem os níveis inflamatórios do DIV degenerado. Além disso, estudos experimentais demonstraram que as CTM permaneciam viáveis quando injetadas no DIV e que eram capazes de regenerar parcialmente do DIV degenerado e sua estrutura. Os poucos estudos clínicos presentes na literatura apresentam resultados divergentes. O uso de CTM esta sendo amplamente estudado e mostra resultados promissores para o tratamento da DDD. Embora muitos avanços venham sendo alcançados em estudos in vitro e experimentais, ainda faltam estudos clínicos para comprovar o papel das CTM no manejo da DDD.
Revisar el papel potencial de las células madre en el tratamiento de la enfermedad degenerativa del disco intervertebral (IVD). Se realizó una revisión de los artículos de la base de datos Medline sobre células madre y la enfermedad degenerativa del disco (DDD). Para fines de discusión de los datos, los trabajos se dividieron en: revisión, in vitro, experimentales y clínicos. Los tratamientos disponibles actualmente enfocan básicamente la reducción de los síntomas, y no la reversión del proceso degenerativo del IVD. El uso de células madre mesenquimales (MSC) se propone como una opción de tratamiento para DDD. Estudios in vitro demostraron que las MSC son capaces de diferenciarse en células NP y que las MSC también reducen los niveles inflamatorios de la IVD degenerado. Además, estudios experimentales demostraron que las MSC se mantuvieron viables cuando inyectadas en el IVD y que eran capaces de regenerarse parcialmente del IVD degenerado y su estructura. Los pocos estudios clínicos presentes en la literatura presentan resultados divergentes. El uso de MSC se está estudiando ampliamente y muestra resultados prometedores en el tratamiento de la DDD. Aunque se hayan logrado muchos avances en estudios in vitro y experimentales, aún faltan estudios clínicos para comprobar el papel de las MSC en el manejo de la DDD.