RESUMO
BACKGROUND: Oral squamous cell carcinoma has high recurrence and cisplatin resistance. As cancer stem cells, autophagy, and sphingolipids have been appointed as associated with chemotherapy resistance, we tested combined treatments targeting autophagy and/or sphingolipid metabolism with paclitaxel using cisplatin-resistant oral squamous cell carcinoma cells. METHODS: Cisplatin-resistant oral squamous cell carcinoma cells were maintained under exposition to FTY720 and chloroquine combined with paclitaxel and submitted to viability, clonogenicity, and spheres formation assays. The xenograft tumor model using cisplatin-resistant CAL27 cells was adopted to examine the drug combinations' potential antitumoral efficacy. Using an animal model, sphingolipids profiles from plasma and tissue samples were obtained by liquid chromatography coupled to mass spectrometry to identify potential lipids associated with drug response. RESULTS AND DISCUSSION: Our results showed higher autophagic flux in cisplatin-resistant Ooral squamous cell carcinoma (CAL27 and SCC9) cells than in parental cells. The combinations of an autophagy inhibitor (chloroquine) or an autophagy inducer/sphingosine kinase 1 antagonist (FTY720) with paclitaxel (PTX) had a synergistic antitumor effect. Treated CisR cells lost clonogenicity and tumor sphere abilities and reduced proteins associated with proliferation, survival, and cancer stem cells. FTY720 plus PTX had higher antitumor efficacy than PTX against CAL27 CisR xenograft tumor formation. Additionally, increases in glucosylceramide, dehydroglucosylceramide, and sphingomyelin were presented in responsive tumors. CONCLUSION: FTY720 sensitizes cisplatin-resistant oral squamous cell carcinoma cells for paclitaxel.
Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Humanos , Cisplatino/farmacologia , Paclitaxel/farmacologia , Cloridrato de Fingolimode/farmacologia , Cloridrato de Fingolimode/uso terapêutico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço , Apoptose , Neoplasias Bucais/tratamento farmacológico , Esfingolipídeos/farmacologia , Cloroquina/farmacologia , Linhagem Celular Tumoral , Resistencia a Medicamentos AntineoplásicosRESUMO
The dataset presented in this article was collected in a laboratory flow circuit, which was designed to investigate high-viscosity flows. The data set is composed of 1200 s (equivalent to 12,000 samples) of mass flow and pressure measurements taken at five points along the pipeline. The first 300 s were recorded when the flow in the loop was composed only of glycerol. The remaining data were acquired when the flow was composed of a water-glycerol mixture. During the data acquisition, two extractions were produced. The research reported in [1] uses 160 s of the data provided here. This article explains in detail the experimental set-up and the principal instruments used for obtaining the dataset. The dataset is in the form of seven columns: Time, Mass Flow, Pressure 1, Pressure 2, Pressure 3, Pressure 4, Pressure 5, in supplementary Excel and Matlab files.
RESUMO
Levels of urinary arsenic and levels of lead in blood were measured in children attending elementary schools located in an industrial zone in Salamanca, México. Its possible effects using telomere length and mitochondrial DNA copy number as biomarkers of genomic disequilibrium by oxidative stress were studied. Eighty-eight children (6-15 years old) were included and urine samples were collected for quantification of arsenic, while lead was measured in blood samples using inductively coupled plasma mass spectrometry (ICP-MS). DNA was isolated from peripheral blood and relative telomere length and the mitochondrial DNA copy number were determined by real-time PCR. The geometric mean of urinary arsenic was 54.16 µg/L (11.7-141.1 µg/L). Ninety-eight percent of the children were above 15 µg/L (biomonitoring equivalent value). With respect to the concentration of lead in blood, the mean was 3.78 µg/dL (LOD-22.61), where 24.5% of the participants had equal or above the reference value (5 µg/dL; Mexican Official Norm NOM-199-SSA1-2000, 2017). A positive association between urinary arsenic and telomere length was found (ß = 0.161; 95% CI: 0.12; 0.301; P = 0.034), while lead blood concentrations were negatively associated with mitochondrial DNA copy number (ß = - 0.198; 95% CI: - 2.81; - 0.17; P = 0.019), after adjusting by age, sex, and total white blood cell count. Differences in the mitochondrial DNA content were observed in children with lead blood levels from 2.5 µg/dL, (P ≤ 0.001), suggesting an effect at lead exposure levels considered acceptable (< 5 µg/dL). In conclusion, children living in an industrial area in Salamanca showed an exposure to arsenic and lead and an impact on telomere length and mitochondrial DNA content associated with arsenic and lead exposure, respectively.
Assuntos
Arsênio/metabolismo , Exposição Ambiental/estatística & dados numéricos , Poluentes Ambientais/metabolismo , Chumbo/metabolismo , Adolescente , Criança , DNA Mitocondrial , Feminino , Humanos , Masculino , MéxicoRESUMO
The effect of management (ecological and conventional) on functional groups of microorganisms of soil in agroecosystems with different resilience scores reported to climate variability in Anolaima, Colombia was evaluated. Were found clustering associated with management and cellulolytic bacteria and fungi abundances. No differences found in diversity of phosphate solubilizing or nitrogen-fixing microorganisms, related to management. The diversity of microbial functional groups was affected by the climatic condition of sampling season. Management was relevant in relationships between resilience scores to climate variability and cellulolytic microorganisms; in ecological agroecosystems, biodiversity knowledge, agroecological main structure, and the participation of farmers in organizations were important.(AU)
Assuntos
Microbiologia do Solo , Análise do Solo , Biologia do Solo/análise , Fosfatos , Fixação de NitrogênioRESUMO
The effect of management (ecological and conventional) on functional groups of microorganisms of soil in agroecosystems with different resilience scores reported to climate variability in Anolaima, Colombia was evaluated. Were found clustering associated with management and cellulolytic bacteria and fungi abundances. No differences found in diversity of phosphate solubilizing or nitrogen-fixing microorganisms, related to management. The diversity of microbial functional groups was affected by the climatic condition of sampling season. Management was relevant in relationships between resilience scores to climate variability and cellulolytic microorganisms; in ecological agroecosystems, biodiversity knowledge, agroecological main structure, and the participation of farmers in organizations were important.
Assuntos
Análise do Solo , Biologia do Solo/análise , Fosfatos , Microbiologia do Solo , Fixação de NitrogênioRESUMO
The Andean Páramos are high mountain ecosystems whose soils are essential for the management of South American water resources, but research on anthropic impacts to these soils is currently minimal and insufficient. The objective of this study was to evaluate the impacts of potato (Solanum tuberosum) cultivation and livestock on the physicochemical parameters and enzymatic activities that determine the soil quality of the Neotropical high Andean Páramo ecosystem in the Nevados National Natural Park (Nevados NNP) in Colombia. It was hypothesised that sites with potato crops and livestock farming would exhibit significant changes in soil physicochemical parameters and enzymatic activities compared with Páramo sites that have been conserved without agriculture. Samples were collected from soils under potato cultivation, livestock and Páramo (subject to the lowest degree of human intervention possible), on three farms in the El Bosque District at three different altitudes (Buenos Aires, El Edén and La Secreta) during two seasons (dry and rainy). The results showed that none of the physical parameters under study presented statistically significant differences due to the type of use (livestock, potato crop or Páramo), season of sampling (dry or rainy season) or altitude (different farms). The chemical parameters that statistically significantly differed due to land use were organic carbon, cation exchange capacity, calcium, potassium, and ammonium and those that showed statistically significant differences associated with the sampling timing were organic carbon, nitrogen, cation exchange capacity, total carbon, C/N and nitrate. Additionally, there were differences in organic carbon due to the altitude of the farms. With respect to enzymatic activities, those of ß-glucosidase, phosphodiesterase and urease significantly decreased in soils under potato cultivation and livestock relative to those of Páramo, but those of acid phosphatase and protease increased significantly under potato cropping and livestock. The activities of ß-glucosidase, acid phosphatase, alkaline phosphatase, phosphodiesterase and protease were higher during the dry season than the rainy season, and the activities of ß-glucosidase, acid phosphatase and urease decreased statistically in the lower-altitude farm (La Secreta). These decreases in enzymatic activities are attributable to changes in the organic carbon of the soil. This study provides a novel insight on the relationships between land use and the physicochemical parameters and enzymatic activities of Páramo soils (which have been minimally studied to date) at different altitudes and during different seasons. The results suggest that changes in agricultural practices should be implemented to maintain the organic carbon of soil and, therefore, its enzymatic activities.
Assuntos
Agricultura/métodos , Criação de Animais Domésticos , Ecossistema , Microbiologia do Solo , Solanum tuberosum/crescimento & desenvolvimento , Animais , Bovinos , Colômbia , Produtos Agrícolas , Monitoramento Ambiental , Fazendas , Nitrogênio , Solo/químicaRESUMO
AIM: The purpose of this study was to determine if there is a correlation between telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) in children. METHODS: Leukocyte TL and mtDNAcn were measured by real-time PCR in 98 Mexican children 6-12 years of age from Salamanca, México. RESULTS: A positive association was found between TL and mtDNAcn after a natural log transformation (Pearson correlation r = 0.72; p < 0.0001). No correlation between age and body mass index (BMI) biomarkers was found, and no differences according to sex were observed. After adjustment for these variables, a linear regression model showed an association between TL and mtDNAcn (ß = 0.739, 95% confidence interval 0.594; 0.885, p < 0.0001). CONCLUSIONS: A strong positive correlation between TL and mtDNAcn was found in the study population; age, sex, and BMI seemed to have no effect on this correlation.
Assuntos
DNA Mitocondrial/genética , Leucócitos/ultraestrutura , Telômero/metabolismo , Biomarcadores/metabolismo , Criança , Variações do Número de Cópias de DNA , DNA Mitocondrial/metabolismo , Feminino , Dosagem de Genes , Humanos , Leucócitos/citologia , Leucócitos/metabolismo , Masculino , México , Mitocôndrias/genética , Reação em Cadeia da Polimerase em Tempo Real , Telômero/genética , Encurtamento do Telômero/genéticaRESUMO
A systematized survey was conducted to find soil-borne microbes that degrade cellulose in soils from unique ecosystems, such as the Superpáramo, Páramo, and the High Andean Forest in the Nevados National Natural Park (NNNP), Colombia. These high mountain ecosystems represent extreme environments, such as high levels of solar radiation, low atmospheric pressure, and extreme daily changes in temperature. Cellulolytic activity of the microorganisms was evaluated using qualitative tests, such as growth in selective media followed by staining with congo red and iodine, and quantitative tests to determine the activity of endoglucanase, β-glucosidase, exoglucanase, and total cellulase. Microorganisms were identified using molecular markers, such as the 16S rRNA gene for bacteria and the internal transcribed spacer region (ITS) of ribosomal DNA for fungi. Multivariate statistical analysis (MVA) was used to select microorganisms with high cellulolytic capacity. A total of 108 microorganisms were isolated from the soils and, in general, the enzymatic activities of fungi were higher than those of bacteria. Our results also found that none of the organisms studied were able to degrade all the components of the cellulose and it is therefore suggested that a combination of bacteria and/or fungi with various enzymatic activities be used to obtain high total cellulolytic activity. This study gives an overview of the potential microorganism that could be used for cellulose degradation in various biotechnological applications and for sustainable agricultural waste treatment.
Assuntos
Bactérias/isolamento & purificação , Bactérias/metabolismo , Celulose/metabolismo , Fungos/isolamento & purificação , Fungos/metabolismo , Microbiologia do Solo , Bactérias/classificação , Colômbia , Celulase/análise , DNA Bacteriano/química , DNA Fúngico/química , DNA de Helmintos/química , DNA Espaçador Ribossômico/química , DNA Ribossômico/química , Fungos/classificação , HidróliseRESUMO
A systematized survey was conducted to find soil-borne microbes that degrade cellulose in soils from unique ecosystems, such as the Superpáramo, Páramo, and the High Andean Forest in the Nevados National Natural Park (NNNP), Colombia. These high mountain ecosystems represent extreme environments, such as high levels of solar radiation, low atmospheric pressure, and extreme daily changes in temperature. Cellulolytic activity of the microorganisms was evaluated using qualitative tests, such as growth in selective media followed by staining with congo red and iodine, and quantitative tests to determine the activity of endoglucanase, β-glucosidase, exoglucanase, and total cellulase. Microorganisms were identified using molecular markers, such as the 16S rRNA gene for bacteria and the internal transcribed spacer region (ITS) of ribosomal DNA for fungi. Multivariate statistical analysis (MVA) was used to select microorganisms with high cellulolytic capacity. A total of 108 microorganisms were isolated from the soils and, in general, the enzymatic activities of fungi were higher than those of bacteria. Our results also found that none of the organisms studied were able to degrade all the components of the cellulose and it is therefore suggested that a combination of bacteria and/or fungi with various enzymatic activities be used to obtain high total cellulolytic activity. This study gives an overview of the potential microorganism that could be used for cellulose degradation in various biotechnological applications and for sustainable agricultural waste treatment.
Assuntos
Bactérias/isolamento & purificação , Bactérias/metabolismo , Celulose/metabolismo , Fungos/isolamento & purificação , Fungos/metabolismo , Microbiologia do Solo , Bactérias/classificação , Bactérias/genética , Colômbia , Celulase/análise , DNA Bacteriano/química , DNA Bacteriano/genética , DNA Fúngico/química , DNA Fúngico/genética , DNA de Helmintos/química , DNA de Helmintos/genética , DNA Espaçador Ribossômico/química , DNA Espaçador Ribossômico/genética , DNA Ribossômico/química , DNA Ribossômico/genética , Fungos/classificação , Fungos/genética , Hidrólise , /genética , Análise de Sequência de DNARESUMO
A systematized survey was conducted to find soil-borne microbes that degrade cellulose in soils from unique ecosystems, such as the Superpáramo, Páramo, and the High Andean Forest in the Nevados National Natural Park (NNNP), Colombia. These high mountain ecosystems represent extreme environments, such as high levels of solar radiation, low atmospheric pressure, and extreme daily changes in temperature. Cellulolytic activity of the microorganisms was evaluated using qualitative tests, such as growth in selective media followed by staining with congo red and iodine, and quantitative tests to determine the activity of endoglucanase, ß-glucosidase, exoglucanase, and total cellulase. Microorganisms were identified using molecular markers, such as the 16S rRNA gene for bacteria and the internal transcribed spacer region (ITS) of ribosomal DNA for fungi. Multivariate statistical analysis (MVA) was used to select microorganisms with high cellulolytic capacity. A total of 108 microorganisms were isolated from the soils and, in general, the enzymatic activities of fungi were higher than those of bacteria. Our results also found that none of the organisms studied were able to degrade all the components of the cellulose and it is therefore suggested that a combination of bacteria and/or fungi with various enzymatic activities be used to obtain high total cellulolytic activity. This study gives an overview of the potential microorganism that could be used for cellulose degradation in various biotechnological applications and for sustainable agricultural waste treatment.