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Human papillomavirus (HPV)-positive Head and Neck Squamous Cell Carcinomas (HNSCC) comprise a particular cancer entity traditionally associated with better clinical outcomes. Around 25% of HNSCC are HPV positive, HPV16 being the most prevalent type. Nevertheless, close to 30% of the HPV-positive patients have an unfavorable prognosis, revealing that this type of tumor exhibits great heterogeneity leading to different clinical behaviors. Efforts have been made to identify RNA molecules with prognostic value associated with the clinical outcome of patients with HPV-positive HNSCC, with the aim of identifying patients at high risk of metastasis, disease recurrence, and poor survival, who would require closer clinical follow-up and timely intervention. Moreover, the molecular identification of those HPV-positive HNSCC patients with good prognosis will allow the implementation of de-escalating therapeutic strategies, aiming to reduce side effects, resulting in a better quality of life. This review compiles a series of recent studies addressing different methodological and conceptual approaches aimed at searching for potential gene expression-based biomarkers associated with the prognosis of patients with HPV-positive HNSCC.
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Biomarcadores Tumorais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Biomarcadores Tumorais/metabolismo , Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/virologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Prognóstico , Infecções por Papillomavirus/virologia , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/genética , Neoplasias de Cabeça e Pescoço/virologia , Neoplasias de Cabeça e Pescoço/genética , Papillomaviridae/genética , Regulação Neoplásica da Expressão GênicaRESUMO
INTRODUCTION AND AIM: Timely detection and diagnosis of hepatitis C virus (HCV) involves identifying the population that is predisposed to treatment and prevention, thus limiting complications and preventing infection. The aim of this study was to analyze and describe risk factors associated with anti-HCV antibody detection in a population with access to public healthcare that participated in a national screening program. MATERIAL AND METHODS: An analytic cross-sectional study was conducted that utilized data related to rapid tests carried out between September 2021 and October 2022 in 26 of the 32 states of Mexico. Anti-HCV reactive tests were selected, according to age and sex, for analyzing and comparing possible risk factors through descriptive and inferential statistics. The geographic distribution and density of the screening program at the state and municipal levels was analyzed. RESULTS: There were 75,185 anti-HCV antibody detections, 2,052 reactive tests, and mean participant age was 44.3 years (±15.1). Occupation: 32.3% were employees, 19% were housewives, and 18.2% were healthcare workers. Five out of every 10 cases had no indication of risk factors, but there was a 1.4 and 5-times greater likelihood of anti-HCV detection in men with a history of sharps injury or intravenous psychoactive substance use, compared with women. Regarding place of residence, 80% of the reactive tests were concentrated in the State of Mexico, Mexico City, and Guanajuato. CONCLUSIONS: The evidence herein helps determine the population and risk factors that should be focused on in carrying out the HCV microelimination strategy of continuous screening, diagnosis, medical treatment access, and epidemiologic surveillance.
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Acessibilidade aos Serviços de Saúde , Anticorpos Anti-Hepatite C , Hepatite C , Humanos , México/epidemiologia , Masculino , Feminino , Estudos Transversais , Fatores de Risco , Adulto , Pessoa de Meia-Idade , Hepatite C/diagnóstico , Hepatite C/epidemiologia , Anticorpos Anti-Hepatite C/sangue , Adulto Jovem , Idoso , Adolescente , Programas de RastreamentoRESUMO
Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized advanced cancer management. Nevertheless, the generalized use of these medications has led to an increase in the incidence of adverse immune-mediated events and the liver is one of the most frequently affected organs. Liver involvement associated with the administration of immunotherapy is known as immune-mediated hepatitis (IMH), whose incidence and clinical characteristics have been described by different authors. It often presents as mild elevations of amino transferase levels, seen in routine blood tests, that spontaneously return to normal, but it can also manifest as severe transaminitis, possibly leading to the permanent discontinuation of treatment. The aim of the following review was to describe the most up-to-date concepts regarding the epidemiology, diagnosis, risk factors, and progression of IMH, as well as its incidence in different types of common cancers, including hepatocellular carcinoma. Treatment recommendations according to the most current guidelines are also provided.
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Carcinoma Hepatocelular , Hepatite A , Hepatite , Neoplasias Hepáticas , Humanos , Hepatite/epidemiologia , Hepatite/etiologia , Hepatite/terapia , Carcinoma Hepatocelular/etiologia , Imunoterapia/efeitos adversos , Neoplasias Hepáticas/complicaçõesRESUMO
In Mexico occurs 25% of all worldwide cases of scorpion sting envenomation (SSE). An outbreak of SSE was identified in Villa Unión, Sinaloa, Mexico. The objective of this study is to describe the outbreak, and prevention and control strategies implemented. The design was a cross-sectional study. Eligibility criteria included confirmed cases (n = 425) identified from the date the outbreak was recognized (from November 08, 2023 to July 10, 2023). The cases from Villa Unión (n = 231) were included for the analysis of epidemiological and clinical findings. The research followed the recommendations of the Initiative Reporting of studies Conducted Using Observational Routinely collected Data (RECORD). Of the total cases (n = 425), 398 (93.6%) were from the municipality of Mazatlán, and 231 (58%) were from Villa Unión. The incidence rate was 13.64 per 1000 persons. The average cases per week was 51.5(SD ± 12). The male-to-female ratio was 3:4, the average age was 30.7(SD ± 19) years. Most of cases occurred in the 25-44 age group. The sting occurred mostly inside houses (n = 200, 86.5%). The predominant symptoms were local pain (95.2%), and local paresthesia (75.8%). The Case fatality rate was 0%. Implementation of prevention and control strategies based on field epidemiological research and scientific evidence are necessary to reduce the incidence and prevent fatal complications.
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Picadas de Escorpião , Venenos de Escorpião , Animais , Masculino , Humanos , Feminino , Adulto , Picadas de Escorpião/epidemiologia , Picadas de Escorpião/prevenção & controle , México/epidemiologia , Estudos Transversais , Escorpiões , Surtos de Doenças/prevenção & controleRESUMO
OBJECTIVE: To examine the association between the level of marginalization and tooth loss in adults aged ≥50 years in Mexico. METHODS: A retrospective crosssectional study was conducted on 2098 adults selected from communities presenting both high and medium levels of marginalization, with data obtained from the annual reports of the Epidemiological Surveillance System of Oral Pathologies 2019-2022. Analysis considered sociodemographic characteristics such as sex, age, and years of education. The prevalence of tooth loss was determined using the Decayed, Missing and Filled teeth (DMFT) index. Negative binomial regression was used to estimate rate ratio (RR) and 95% confidence intervals (CIs), using the presence of lost teeth as an outcome. RESULTS: Most (62.4%) participants had lost at least one tooth, of whom 60.3% had a medium level of marginalization, 28.8% a high level, and 10.9% a very high level. More adults who lived in high or very high marginalization communities had lost teeth [RR=1.19 (95% CI 1.08 - 1.30)] than those living in communities with a medium level of marginalization. More males [RR=1.19 (95% CI 1.09 - 1.31)], adults ≥70 years [RR=1.77 (95% CI 1.57 - 1.99)], people who were illiterate [RR=1.60 (95% CI 1.35 - 1.88)] or who had poor oral hygiene [RR=1.26 (95% CI 1.15 - 1.38)] had also lost teeth. CONCLUSION: High and very high marginalization was associated with tooth loss in adults ≥50 years in Mexico. Effective oral health strategies are required to prevent tooth loss, as are interventions to improve access to and quality of dental services for marginalized communities.
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Perda de Dente , Masculino , Adulto , Humanos , Idoso , Perda de Dente/epidemiologia , México/epidemiologia , Estudos Transversais , Estudos Retrospectivos , Saúde BucalAssuntos
Síndrome Antifosfolipídica , Hipoprotrombinemias , Lúpus Eritematoso Sistêmico , Humanos , Síndrome Antifosfolipídica/complicações , Síndrome Antifosfolipídica/diagnóstico , Inibidor de Coagulação do Lúpus , Hipoprotrombinemias/diagnóstico , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnósticoRESUMO
Mitochondria participate in multiple functions in eukaryotic cells. Although disruption of mitochondrial function has been associated with energetic deregulation in cancer, the chronological changes in mitochondria during cancer development remain unclear. With the aim to assess the role of mitochondria throughout cancer development, we analyzed samples chronologically obtained from induced hepatocellular carcinoma (HCC) in rats. In our analyses, we integrated mitochondrial proteomic data, mitochondrial metabolomic data and nuclear genome transcriptomic data. We used pathway over-representation and weighted gene co-expression network analysis (WGCNA) to integrate expression profiles of genes, miRNAs, proteins and metabolite levels throughout HCC development. Our results show that mitochondria are dynamic organelles presenting specific modifications in different stages of HCC development. We also found that mitochondrial proteomic profiles from tissues adjacent to nodules or tumor are determined more by the stage of HCC development than by tissue type, and we evaluated two models to predict HCC stage of the samples using proteomic profiles. Finally, we propose an omics integration pipeline to massively identify molecular features that could be further evaluated as key regulators, biomarkers or therapeutic targets. As an example, we show a group of miRNAs and transcription factors as candidates, responsible for mitochondrial metabolic modification in HCC.
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Carcinoma Hepatocelular/patologia , Dietilaminas/toxicidade , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Metaboloma , Mitocôndrias/metabolismo , Proteoma/metabolismo , Transcriptoma , Animais , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Perfilação da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Mitocôndrias/efeitos dos fármacos , Proteoma/análise , Ratos , Ratos Endogâmicos F344RESUMO
Experimental evidence in mice models has demonstrated that a high regulator of G-protein signaling 2 (RSG2) protein levels precede an insulin resistance state. In the same context, a diet rich in saturated fatty acids induces an increase in RGS2 protein expression, which has been associated with decreased basal metabolism in mice; however, the above has not yet been analyzed in humans. For this reason, in the present study, we examined the association between RGS2 expression and insulin resistance state. The incubation with palmitic acid (PA), which inhibits insulin-mediated Akt Ser473 phosphorylation, resulted in the increased RGS2 expression in human umbilical vein endothelial-CS (HUVEC-CS) cells. The RGS2 overexpression without PA was enough to inhibit insulin-mediated Akt Ser473 phosphorylation in HUVEC-CS cells. Remarkably, the platelet RGS2 expression levels were higher in type 2 diabetes mellitus (T2DM) patients than in healthy donors. Moreover, an unbiased principal component analysis (PCA) revealed that RGS2 expression level positively correlated with glycated hemoglobin (HbA1c) and negatively with age and high-density lipoprotein cholesterol (HDL) in T2DM patients. Furthermore, PCA showed that healthy subjects segregated from T2DM patients by having lower levels of HbA1c and RGS2. These results demonstrate that RGS2 overexpression leads to decreased insulin signaling in a human endothelial cell line and is associated with poorly controlled diabetes.
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INTRODUCTION: Reconstruction of the anterior cruciate ligament attempts to reproduce the native ligament; make independent tunnels optimize the entry points and effectiveness the anatomy. Perform radiographic measurements of the knee, identify position of femoral and tibial tunnels in patients operated for reconstruction of anterior cruciate ligament with anatomical technique. MATERIAL AND METHODS: Patients were identified in the period January 2018 to December 2019. 98 patients were retrospectively evaluated. Radiographic measurements in the femur, the inclination angle of the tunnel, the insertion site with respect to the Blumensaat line and the transosseous distance were determined. In tibia, the location in percentage of the tibial plateau location in anteroposterior and lateral view, tibial tunnel angle. RESULTS: Postoperative patients were 98. (75.5%) male, female (24.5%). Postoperative in 2018 (57.15%) and 2019 (42.85%) Age range: affected group was 21-25 years, right side affected in 57.15%; Radiographic measurements in femur, the angle of inclination of the tunnel was 45o, percentage in the Blumensaat line was 20%, and the transosseous distance was 3.43 cm. In tibia the percentage distance in anteroposterior projection was 44%, and lateral 28%, The angle in tibial tunnel anteroposterior projection of 73 degrees, and lateral 114. CONCLUSION: The anatomical technique is a good option to perform tunnels with an optimal anatomical position. By making independent tunnels it allows to improve coverage of normal antomic footprint. Increases degrees and inclination of tunnels, causes added injuries.
INTRODUCCIÓN: En la reconstrucción de ligamento cruzado anterior se intenta reproducir ligamento nativo, realizar túneles independientes, optimizar los puntos de entrada y la efectividad de la anatomía; hacer mediciones radiográficas de rodilla, identificar la posición del túnel femoral y tibial en pacientes operados de reconstrucción de ligamento cruzado anterior con técnica anatómica. MATERIAL Y MÉTODOS: Se identificaron pacientes en el período de Enero de 2018 a Diciembre de 2019. Se evaluaron de manera retrospectiva 98 pacientes. Mediciones radiográficas en fémur: se determinó el ángulo de inclinación del túnel, el sitio de inserción con respecto a la línea de Blumensaat y la distancia transósea. En tibia: la ubicación en porcentaje de la localización de platillo tibial en proyección anteroposterior y lateral, ángulo de túnel tibial. RESULTADOS: Los pacientes postoperados fueron 98, masculinos (75.5%) y femeninos (24.5%). Postoperados en el año 2018 (57.15%) y en 2019 (42.85%). Rango de edad: el grupo afectado fue de 21-25 años, lado afectado: derecho en 57.15%. Mediciones radiográficas en fémur: el ángulo de inclinación del túnel fue de 45o, el porcentaje en la línea de Blumensaat fue de 20% y la distancia transósea fue 3.43 cm. En tibia la distancia porcentual en proyección anteroposterior fue de 44% y lateral de 28%. El ángulo en túnel tibial en proyección anteroposterior fue de 73º y lateral de 114º. CONCLUSIÓN: La técnica anatómica es una buena opción para efectuar túneles con posición anatómica óptima. Realizar túneles independientes permite mejorar la cobertura de la huella anatómica normal, aumenta los grados y la inclinación de túneles y provoca lesiones agregadas.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Adulto , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/cirurgia , Feminino , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Humanos , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Masculino , Estudos Retrospectivos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Adulto JovemRESUMO
Trypanosoma cruzi, a flagellate protozoan parasite, is responsible for Chagas disease. The parasite major cysteine protease, cruzain (Cz), plays a vital role at every stage of its life cycle and the active-site region of the enzyme, similar to those of other members of the papain superfamily, is well characterized. Taking advantage of structural information available in public databases about Cz bound to known covalent inhibitors, along with their corresponding activity annotations, in this work, we performed a deep analysis of the molecular interactions at the Cz binding cleft, in order to investigate the enzyme inhibition mechanism. Our toolbox for performing this study consisted of the charge density topological analysis of the complexes to extract the molecular interactions and machine learning classification models to relate the interactions with biological activity. More precisely, such a combination was useful for the classification of molecular interactions as "active-like" or "inactive-like" according to whether they are prevalent in the most active or less active complexes, respectively. Further analysis of interactions with the help of unsupervised learning tools also allowed the understanding of how these interactions come into play together to trigger the enzyme into a particular conformational state. Most active inhibitors induce some conformational changes within the enzyme that lead to an overall better fit of the inhibitor into the binding cleft. Curiously, some of these conformational changes can be considered as a hallmark of the substrate recognition event, which means that most active inhibitors are likely recognized by the enzyme as if they were its own substrate so that the catalytic machinery is arranged as if it is about to break the substrate scissile bond. Overall, these results contribute to a better understanding of the enzyme inhibition mechanism. Moreover, the information about main interactions extracted through this work is already being used in our lab to guide docking solutions in ongoing prospective virtual screening campaigns to search for novel noncovalent cruzain inhibitors.
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INTRODUCTION: Non-cardiac chest pain is defined as a clinical syndrome characterized by retrosternal pain similar to that of angina pectoris, but of non-cardiac origin and produced by esophageal, musculoskeletal, pulmonary, or psychiatric diseases. AIM: To present a consensus review based on evidence regarding the definition, epidemiology, pathophysiology, and diagnosis of non-cardiac chest pain, as well as the therapeutic options for those patients. METHODS: Three general coordinators carried out a literature review of all articles published in English and Spanish on the theme and formulated 38 initial statements, dividing them into 3 main categories: (i)definitions, epidemiology, and pathophysiology; (ii)diagnosis, and (iii)treatment. The statements underwent 3rounds of voting, utilizing the Delphi system. The final statements were those that reached >75% agreement, and they were rated utilizing the GRADE system. RESULTS AND CONCLUSIONS: The final consensus included 29 statements. All patients presenting with chest pain should initially be evaluated by a cardiologist. The most common cause of non-cardiac chest pain is gastroesophageal reflux disease. If there are no alarm symptoms, the initial approach should be a therapeutic trial with a proton pump inhibitor for 2-4weeks. If dysphagia or alarm symptoms are present, endoscopy is recommended. High-resolution manometry is the best method for ruling out spastic motor disorders and achalasia and pH monitoring aids in demonstrating abnormal esophageal acid exposure. Treatment should be directed at the pathophysiologic mechanism. It can include proton pump inhibitors, neuromodulators and/or smooth muscle relaxants, psychologic intervention and/or cognitive therapy, and occasionally surgery or endoscopic therapy.
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Dor no Peito/terapia , Dor no Peito/diagnóstico , Consenso , Humanos , MéxicoRESUMO
Resumen OBJETIVO Analizar el efecto en México de la mortalidad producida por la enfermedad renal crónica secundaria a la diabetes mellitus. MATERIAL Y MÉTODO Estudio observacional efectuado de 1998 a 2014, en el que se tomó como base un registro nacional correspondiente a un lapso relativamente prolongado de 17 años, reconociendo a esta enfermedad en tanto entidad nosológica diferenciada, utilizando como metodología de análisis la minería de datos, y evitando en lo posible las ambigüedades o limitaciones detectadas en los estudios previamente publicados. RESULTADOS En las dos últimas décadas se han duplicado la prevalencia y las tasas de mortalidad por enfermedad renal crónica en la República Mexicana, lo que supone un elevado costo humano y financiero, además de que esta enfermedad reduce significativamente la calidad y la esperanza de vida de la población adulta mexicana. CONCLUSIONES Es necesario optimizar las estrategias de atención del paciente con enfermedad renal crónica sin descartar el uso de estrategias de prevención eficaces, dirigidas a la población general.
Abstract OBJECTIVE To analyze the impact in Mexico of the mortality produced by chronic renal failure secondary to diabetes mellitus. MATERIAL AND METHOD An observational study was done from 1998 to 2014 on the basis of a national registry corresponding to a relatively long period of 17 years, recognizing this pathology as a differentiated nosological entity, using the data mining as methodology of analysis, and avoiding as far as possible the ambiguities or limitations detected in previously published studies. RESULTS In the last two decades, the prevalence and mortality rates for chronic renal failure has doubled in Mexico, which means a high human and financial cost, in addition to the fact that this disease significantly reduces the quality of life and the life expectancy of the Mexican adult population. CONCLUSION It is necessary to optimize the care strategies for patients with chronic renal failure, without ruling out the use of effective prevention strategies focused on the general population.
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BACKGROUND: HER2 over-expression is related with a poor prognosis in patients with invasive breast cancer tumors. Clinical associations have reported that somatic mutations of p53 more frequently detected in cases of sporadic breast cancer of the HER2 subtypes, besides a high percentage of HER2-amplifying tumors carry germline mutations of p53. The mechanisms responsible for the acquisition of oncogenic functions of p53 mutant proteins (mtp53), known as Gain of Function (GOF), over HER2 expression have not been reported. The objective of this study was to evaluate a possible relationship between p53 mutants and HER2 regulation. METHODS: HER2 expression (transcription and protein), as well as HER2 protein stabilization have been evaluated after inducing or silencing of p53 mutants' expression in cell lines. Finally, we evaluated the interaction of the p53 mutants over the HER2 receptor promoter. RESULTS: Higher HER2 expression in cell lines harboring endogenous mtp53 compared with wt or null expression of p53 cell lines. Transfection of p53 mutants (R248Q and R273C) in cell lines increased the expression of HER2. Silencing of p53 mutants, decrease HER2 expression. The p53 mutants R248Q and R273C significantly increase the luciferase activity on the HER2 promoter, and both mutants also promote acetylation of H3 and H4 histones binding in it. CONCLUSIONS: These findings show for the first time that p53 mutants induce over-expression of HER2 at transcriptional level of the HER2 protein. Our results could have clinical implications in breast cancer and other types of cancer where HER2 is over-expressed and used as a therapy target.
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Mutação com Ganho de Função , Receptor ErbB-2/genética , Proteína Supressora de Tumor p53/genética , Acetilação , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Histonas/metabolismo , Humanos , Regiões Promotoras GenéticasRESUMO
Pig farming is an important activity in the economic development of Mexico with millions of tons of meat produced annually. Antibiotics are used in therapeutic dose to prevent diseases, and sometimes as growth promoters. These compounds are not completely metabolized; they are carried into the environment in its active form at concentrations that could induce antibiotic resistance in bacteria, which could be transferred to human pathogens by horizontal gene transfer. The objective of this work was to develop methods of analysis for simultaneous quantification of the antibiotics Oxytetracycline (OXT), Chlortetracycline (CLT), Enrofloxacin (ENRO) and Ciprofloxacin (CIPRO) by field-amplified sampling injection in capillary zone electrophoresis (FASI-CZE). The method was validated by parameters of (1) linearity, obtaining a lineal range of 0.05 at 1⯵gâ¯mL-1 for ENRO and CIPRO, and from 0.1 to 1⯵gâ¯mL-1 for OXT and CLT; (2) precision, obtaining values <5% of standard deviation for CIPRO and ENRO and <10% of standard deviation for OXT and CLT; (3) accuracy, with recovery values from 93 to 115%; (4) selectivity, with values of resolution >2 for the all antibiotics tested. To prove the method, a sample of wastewater from a local pig farm was analyzed, detecting a concentration of 0.140⯱â¯0.009 for OXT. This concentration was higher than the minimal selective concentration, indicating the point in which resistance to a determined antibiotic could develop. The methods were validated with precision and sensitivity comparable to chromatographic methods, which can be used to analyze wastewater from pig farms directly.
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Antibacterianos/análise , Eletroforese Capilar/métodos , Fazendas , Águas Residuárias/química , Poluentes Químicos da Água/análise , Animais , Limite de Detecção , Modelos Lineares , Reprodutibilidade dos Testes , SuínosRESUMO
Resveratrol (RES), a polyphenol compound with antiproliferative properties, has been previously evaluated for its beneficial effects against a variety of tumour cells. The current study elucidated the means by which RES enhances the antiproliferative effects of cisplatin (CIS) on MCF7 cells, focusing on the inhibitory effects on DNA repair of doublestrand breaks (DSBs). Chemoresistant MCF7 cells (MCF7R) were generated by continuous exposure to low concentrations of CIS (10 µM CISIC40) during 5 passages, with the IC50 value increasing ~3fold. Using an MTT assay, we estimated the changes in IC50 for CIS in MCF7, T47D, MDAMB231 and MCF7R cells in the presence of RES. The relative transcript level of Nbs1, Mre11 and Rad50 genes was assessed using RTqPCR analysis. Rad51 and H2AX [pSer139] protein expression was determined by western blot analysis. RES at 50 and 100 µM significantly enhanced the antiproliferative effects of CIS in both MCF7 and MCF7R cells, decreasing the IC50 values for CIS to onetenth and onesixth, respectively. A total of 100 µM RES decreased the relative transcript levels of homologous recombination (HR) initiation complex components and the Rad51 protein level in MCF7 and MCF7R cells. After 48 h of CIS DNA damage, the levels of Rad51 protein increased, but this effect was inhibited by 100 µM RES. RES also maintained serine 139 phosphorylation of histone H2AX, suggesting that RES prevents the repair of DSBs. It was observed that RES exerts an antagonistic effect over CIS on the activation of Rad51 and sustained phosphorylation of H2AX. The results suggest that RES in combination with DNA damagebased therapy has potential as a strategy to overcome resistance and provide much safer and more effective treatment for breast cancer.
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Neoplasias da Mama/genética , Cisplatino/farmacologia , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Rad51 Recombinase/genética , Estilbenos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/metabolismo , Linhagem Celular Tumoral , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Histonas/metabolismo , Humanos , Células MCF-7 , Fosforilação/efeitos dos fármacos , Rad51 Recombinase/metabolismo , ResveratrolRESUMO
INTRODUCTION AND AIMS: Double-balloon enteroscopy has been improving the visualization of the entire intestine for more than a decade. It is a complementary method in the study of intestinal diseases that enables biopsies to be taken and treatments to be administered. Our aim was to describe its main indications, insertion routes, diagnostic/therapeutic yield, and complications. MATERIALS AND METHODS: All patients referred to our unit with suspected small bowel pathology were included. The insertion route (oral/anal) was determined through diagnostic suspicion. The variables measured were: insertion route, small bowel examination extent, endoscopic diagnosis/treatment, biopsy/histopathology report, complications, and surgical findings. RESULTS: The study included 28 double-balloon enteroscopies performed on 23 patients, of which 10 were women and 13 were men (mean age of 52.95 years). The oral approach was the most widely used (n=21), the main indication was overt small bowel bleeding (n=16), and the general diagnostic yield was 65.21%. The therapeutic intervention rate was 39.1% and the procedure was effective in all the cases. The most widely used treatment was argon plasma therapy (n=7). The complication rate was 8.6%; one patient presented with low blood pressure due to active bleeding and another had deep mucosal laceration caused by the argon plasma. CONCLUSIONS: Double-balloon enteroscopy is a safe and efficacious method for the study and management of small bowel diseases, with an elevated diagnostic and therapeutic yield.
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Enteroscopia de Duplo Balão , Enteropatias/diagnóstico por imagem , Enteropatias/terapia , Intestino Delgado/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Enteroscopia de Duplo Balão/efeitos adversos , Enteroscopia de Duplo Balão/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
BACKGROUND: The entomopathogenic nematode Steinernema carpocapsae has been used worldwide as a biocontrol agent for insect pests, making it an interesting model for understanding parasite-host interactions. Two models propose that these interactions are co-evolutionary processes in such a way that equilibrium is never reached. In one model, known as "arms race", new alleles in relevant genes are fixed in both host and pathogens by directional positive selection, producing recurrent and alternating selective sweeps. In the other model, known as"trench warfare", persistent dynamic fluctuations in allele frequencies are sustained by balancing selection. There are some examples of genes evolving according to both models, however, it is not clear to what extent these interactions might alter genome-level evolutionary patterns and intraspecific diversity. Here we investigate some of these aspects by studying genomic variation in S. carpocapsae and other pathogenic and free-living nematodes from phylogenetic clades IV and V. RESULTS: To look for signatures of an arms-race dynamic, we conducted massive scans to detect directional positive selection in interspecific data. In free-living nematodes, we detected a significantly higher proportion of genes with sites under positive selection than in parasitic nematodes. However, in these genes, we found more enriched Gene Ontology terms in parasites. To detect possible effects of dynamic polymorphisms interactions we looked for signatures of balancing selection in intraspecific genomic data. The observed distribution of Tajima's D values in S. carpocapsae was more skewed to positive values and significantly different from the observed distribution in the free-living Caenorhabditis briggsae. Also, the proportion of significant positive values of Tajima's D was elevated in genes that were differentially expressed after induction with insect tissues as compared to both non-differentially expressed genes and the global scan. CONCLUSIONS: Our study provides a first portrait of the effects that lifestyle might have in shaping the patterns of selection at the genomic level. An arms-race between hosts and pathogens seems to be affecting specific genetic functions but not necessarily increasing the number of positively selected genes. Trench warfare dynamics seem to be acting more generally in the genome, likely focusing on genes responding to the interaction, rather than targeting specific genetic functions.
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Evolução Biológica , Interações Hospedeiro-Parasita , Insetos/genética , Insetos/parasitologia , Nematoides/genética , Nematoides/fisiologia , Animais , Caenorhabditis/genética , Frequência do Gene , Genoma , Nematoides/classificação , FilogeniaRESUMO
The aim of this study was to evaluate the fermentation of dietary fiber from green bean (Phaseolus vulgaris) and prickly pear shell (Opuntia ficus-indica) by Lactobacillus acidophilus LA-5 and Bifidobacterium bifidum 450B growing as mono-culture and co-culture, the fermentation products, and proteins expressed during this process. The analysis of the fermentation profile showed a major growth of bacteria in the culture media of each dietary fiber supplemented with glucose, and particularly B. bifidum 450B at 48 h showed the highest growth. In the case of the co-culture, the growth was lower indicating the possible negative interaction between L. acidophilus LA-5 and B. bifidum 450B and may be due to the less amount of carbohydrates and the high content of non-soluble fiber that affected the nutrients availability for the bacterial strains. The pH changes indicated the presence of short-chain fatty acids (SCFAs), being acetate (46-100%) the main SCFA. Changes in the proteome concerned proteins that are involved in carbohydrate and other carbohydrate pathways. The characterization of the bacteria according to the growth, metabolites, and proteins expressed allows understanding the response to the change of environmental conditions and could be useful to understand L. acidophilus LA-5 and B. bifidum 450B strains' adaptation to specific applications.
Assuntos
Bifidobacterium bifidum/metabolismo , Fibras na Dieta/metabolismo , Lactobacillus acidophilus/metabolismo , Opuntia/metabolismo , Phaseolus/metabolismo , Microbiologia Ambiental , Ácidos Graxos Voláteis/metabolismo , Fermentação/fisiologiaRESUMO
The acaricidal effects of 55 strains of Metarhizium anisopliae (Metschnikoff) Sorokin, 1883 (Hypocreales: Clavicipitaceae) isolated from paddocks of cattle farms were evaluated in two Rhipicephalus microplus (Canestrini 1887) (Ixodida: Ixodidae) populations, of which one was multi-resistant and one was susceptible to chemical acaricides. Percentage mortality and reproductive efficiency indices in R. microplus were evaluated by adult immersion tests at a dose of 1 × 108 conidia/mL for each fungal strain. Some strains were selected to calculate lethal concentrations to kill 50% (LC50 ) and 99% (LC99 ) of engorged ticks. Strains MaV22, MaV26 and MaV55 induced 100% mortality in R. microplus on day 14. Strains MaV05, MaV09 and MaV22 caused mortality of >90% from day 12 onward in both tick populations. The most effective acaricidal fungal strain, MaV55, inhibited egg laying by 54.86 and 55.86% in acaricide-resistant and -susceptible R. microplus populations, respectively. None of the fungal strains had statistically significant effects on larval hatching. In conclusion, nine strains of M. anisopliae demonstrated high acaricidal effects against R. microplus and reduced its egg laying. No differences in acaricidal effects were observed between the two populations of ticks tested.