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1.
J Exp Clin Cancer Res ; 43(1): 33, 2024 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-38281027

RESUMO

BACKGROUND: Previous studies by our group have shown that oxidative phosphorylation (OXPHOS) is the main pathway by which pancreatic cancer stem cells (CSCs) meet their energetic requirements; therefore, OXPHOS represents an Achille's heel of these highly tumorigenic cells. Unfortunately, therapies that target OXPHOS in CSCs are lacking. METHODS: The safety and anti-CSC activity of a ruthenium complex featuring bipyridine and terpyridine ligands and one coordination labile position (Ru1) were evaluated across primary pancreatic cancer cultures and in vivo, using 8 patient-derived xenografts (PDXs). RNAseq analysis followed by mitochondria-specific molecular assays were used to determine the mechanism of action. RESULTS: We show that Ru1 is capable of inhibiting CSC OXPHOS function in vitro, and more importantly, it presents excellent anti-cancer activity, with low toxicity, across a large panel of human pancreatic PDXs, as well as in colorectal cancer and osteosarcoma PDXs. Mechanistic studies suggest that this activity stems from Ru1 binding to the D-loop region of the mitochondrial DNA of CSCs, inhibiting OXPHOS complex-associated transcription, leading to reduced mitochondrial oxygen consumption, membrane potential, and ATP production, all of which are necessary for CSCs, which heavily depend on mitochondrial respiration. CONCLUSIONS: Overall, the coordination complex Ru1 represents not only an exciting new anti-cancer agent, but also a molecular tool to dissect the role of OXPHOS in CSCs. Results indicating that the compound is safe, non-toxic and highly effective in vivo are extremely exciting, and have allowed us to uncover unprecedented mechanistic possibilities to fight different cancer types based on targeting CSC OXPHOS.


Assuntos
Neoplasias Pancreáticas , Rutênio , Humanos , Fosforilação Oxidativa , Rutênio/farmacologia , Mitocôndrias/metabolismo , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/metabolismo , Células-Tronco Neoplásicas/metabolismo
2.
J Biosoc Sci ; 56(2): 270-291, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38044837

RESUMO

Considered the epidemic of the 21st century by the WHO, obesity is a global problem that is on the rise and will continue to increase in the coming years. Spain and Andalusia, in particular, are no exception to this pathology, which has tripled since the 1970s, representing a public health challenge. The aim of this study is to analyse the socioeconomic determinants of this pathology, with special emphasis on answering the question of what has a greater influence on overweight, education level, or income. For this purpose, we have used the European Survey of Health in Spain (ESHS-2020), a microdata base, with a total of 22,072 valid individual observations (of which 2,820 belong to the Andalusian population). Results we obtain in our estimations of qualitative response models reveal that, although both income and educational attainment could be effective in the fight against overweight, the social gradient of this health problem is greater with respect to educational attainment. Additionally, there are many other variables and other factors related to the individual's overweight (mental health, subjective state of health, oral health, among others) which are much less explored and which must be considered in health policies to combat this disease.


Assuntos
Obesidade , Sobrepeso , Humanos , Sobrepeso/epidemiologia , Sobrepeso/prevenção & controle , Espanha/epidemiologia , Escolaridade , Obesidade/epidemiologia , Obesidade/prevenção & controle , Renda , Fatores Socioeconômicos
3.
IEEE Trans Image Process ; 32: 3465-3480, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37276104

RESUMO

Matching landmark patches from a real-time image captured by an on-vehicle camera with landmark patches in an image database plays an important role in various computer perception tasks for autonomous driving. Current methods focus on local matching for regions of interest and do not take into account spatial neighborhood relationships among the image patches, which typically correspond to objects in the environment. In this paper, we construct a spatial graph with the graph vertices corresponding to patches and edges capturing the spatial neighborhood information. We propose a joint feature and metric learning model with graph-based learning. We provide a theoretical basis for the graph-based loss by showing that the information distance between the distributions conditioned on matched and unmatched pairs is maximized under our framework. We evaluate our model using several street-scene datasets and demonstrate that our approach achieves state-of-the-art matching results.


Assuntos
Algoritmos , Aprendizagem
4.
Appl Res Qual Life ; : 1-27, 2023 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-37359221

RESUMO

The objective of this work is to deepen the analysis of the socioeconomic determinants of mental health, paying special attention to the impact of inequality, not only in income distribution but also in gender, racial, health and education inequality, social isolation, including new variables to measure loneliness, and healthy habits, on the mental health status. For this purpose, a cross-sectional model for a sample of 2735 counties in the United States is estimated using Ordinary Least Squares in its robust version to solve the detected heteroscedasticity problems. The results obtained show that inequality, social isolation and certain lifestyles, such as smoking or insomnia, are detrimental to mental health, while sexual activity prevents mental distress. On the other hand, poor counties suffer more cases of suicide, with food insecurity being the main problem for mental health. Finally, we found detrimental effects of pollution on mental health.

5.
J. oral res. (Impresa) ; 11(3): 1-10, jun. 30, 2022. tab
Artigo em Inglês | LILACS | ID: biblio-1427496

RESUMO

Introduction: Inadequate oral hygiene habits such as lack of tooth brushing, use of irrigators, fluoridated toothpastes, and dental floss, as well as the importance of worrying about going to the dentist in the event of any problem in the oral cavity and the continuity of treatment are factors that could increase the risk in patients. Objetive: To determine the association between the level of indifference to dental treatment and the oral hygiene habits of those surveyed adults. Material and Methods: An observational, analytical and cross-sectional study. The level of indifference to dental treatment was evaluated using a translated virtual questionnaire and subsequently internally validated (Cronbach's alpha: 0.91). There were a total of 249 participants, 150 males and 99 females, with a mean age of 30.69 years. For the association of the qualitative variables and the report of the crude and adjusted odds' ratio (OR), a logistic regression was used. We worked with a level of statistical significance of p<0.05 and a confidence interval of 95%. Results: A high level of indifference to dental treatment was obtained in 57.83% of the respondents. Likewise, a statistically significant association was found between indifference to dental treatment and education (p = 0.012). Regarding oral hygiene habits, a statistically significant association was found with flossing (OR = 2.22; 95% CI: 1.10-4.46) (p = 0.025) and brushing before sleeping (OR = 5.26; 95%: 2.26-12-22) (p<0.001). Conclusion: There is a statistically significant association between the level of indifference to dental treatment with oral hygiene habits, flossing and brushing before sleeping. It is advisable to carry out activities in the communities to promote oral health care to reduce levels of indifference to dental treatment.


Introducción: Los inadecuados hábitos de higiene bucal como la falta de cepillado dental, uso de irrigadores, pastas dentales fluoradas e hilo dental, así como la importancia de preocuparse por acudir al odontólogo ante cualquier problema en la cavidad oral y la continuidad del tratamiento son factores que podrían agravar el riesgo en los pacientes. Objetivo: Determinar la asociación entre el nivel de indiferencia al tratamiento dental y los hábitos de higiene bucal de los encuestados en adultos en edades comprendidas entre los 18 a 45 años de la urbanización Buenos Aires de Villa en Chorrillos, Perú. Material y Métodos: Se realizó un estudio observacional, analítico y transversal. El nivel de indiferencia al tratamiento dental fue evaluado mediante un cuestionario virtual traducido y posteriormente validado internamente (alpha de Cronbach: 0.91). Se tuvo un total de 249 participantes, entre ellos 150 hombres y 99 mujeres con una media edad de 30,69 años. Para la asociación de las variables cualitativas y el reporte de las Odds Ratio (OR) crudas y ajustadas, se empleó una regresión logística. Se trabajó con un nivel de significancia estadística de p<0.05 y un intervalo de confianza del 95%. Resultados: Se obtuvo un alto nivel de indiferencia al tratamiento dental en el 57.83% de los encuestados. Asimismo, se encontró una asociación estadísticamente significativa de la indiferencia al tratamiento dental con la educación (p= 0.012). Respecto a los hábitos de higiene bucal, se encontró asociación estadísticamente significativa con uso de hilo dental (OR=2.22; IC del 95%: 1.10-4.46) (p=0.025) y el cepillado antes de dormir (OR=5.26; IC del 95%: 2.26-12-22) (p<0.001). Conclusión: Se concluyó que existe una asociación estadísticamente significativa entre el nivel de indiferencia al tratamiento dental con los hábitos de higiene bucal uso de hilo dental y cepillado antes de dormir. Se aconseja realizar actividades en las comunidades para promover el cuidado de la salud bucal con la finalidad de reducir los niveles de indiferencia al tratamiento dental.


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Higiene Bucal/estatística & dados numéricos , Atitude Frente a Saúde , Saúde Bucal/estatística & dados numéricos , Peru/epidemiologia , Inquéritos e Questionários , Assistência Odontológica/estatística & dados numéricos , Hábitos
6.
Cancers (Basel) ; 14(6)2022 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-35326669

RESUMO

Pancreatic ductal adenocarcinoma (PDA) is characterized by an extremely poor prognosis due to its late diagnosis and strong chemoresistance to the current treatments. Therefore, finding new therapeutic targets is an urgent need nowadays. In this study, we report the role of the chromatin remodeler BPTF (Bromodomain PHD Finger Transcription Factor) as a therapeutic target in PDA. BPTF-silencing dramatically reduced cell proliferation and migration in vitro and in vivo in human and mouse PDA cell lines. Moreover, BPTF-silencing reduces the IC50 of gemcitabine in vitro and enhanced its therapeutic effect in vivo. Mechanistically, BPTF is required for c-MYC recruitment to the promoter of ABC-transporters and its downregulation facilitates gemcitabine accumulation in tumour cells, increases DNA damage, and a generates a strong synergistic effect in vivo. We show that BPTF is a therapeutic target in pancreatic ductal adenocarcinoma due to its strong effect on proliferation and in response to gemcitabine.

7.
Proc Natl Acad Sci U S A ; 119(9)2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35193983

RESUMO

Researchers have long debated the degree to which Native American land use altered landscapes in the Americas prior to European colonization. Human-environment interactions in southern South America are inferred from new pollen and charcoal data from Laguna El Sosneado and their comparison with high-resolution paleoenvironmental records and archaeological/ethnohistorical information at other sites along the eastern Andes of southern Argentina and Chile (34-52°S). The records indicate that humans, by altering ignition frequency and the availability of fuels, variously muted or amplified the effects of climate on fire regimes. For example, fire activity at the northern and southern sites was low at times when the climate and vegetation were suitable for burning but lacked an ignition source. Conversely, abundant fires set by humans and infrequent lightning ignitions occurred during periods when warm, dry climate conditions coincided with ample vegetation (i.e., fuel) at midlatitude sites. Prior to European arrival, changes in Native American demography and land use influenced vegetation and fire regimes locally, but human influences were not widely evident until the 16th century, with the introduction of nonnative species (e.g., horses), and then in the late 19th century, as Euro-Americans targeted specific resources to support local and national economies. The complex interactions between past climate variability, human activities, and ecosystem dynamics at the local scale are overlooked by approaches that infer levels of land use simply from population size or that rely on regionally composited data to detect drivers of past environmental change.


Assuntos
Efeitos Antropogênicos , Ecossistema , Mudança Climática , Humanos , América do Sul
8.
Mol Phylogenet Evol ; 162: 107184, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-33932615

RESUMO

African amphibian diversity remains underestimated with many cryptic lineages awaiting formal description. An important hotspot of amphibian diversification is the Guineo-Congolian rainforest in Central Africa, its richness attributable to present day and ancestral range fragmentation through geological barriers, habitat expansion and contraction, and the presence of steep ecological gradients. The charismatic Nectophryne tree toads present an interesting case study for diversification in this region. The two formally described species comprising this genus show nearly identical geographic distributions extending across most of the Guineo-Congolian rainforest, but show little morphological disparity. Both species harbour extensive genetic diversity warranting taxonomic revisions, and interestingly, when comparing the subclades within each, the two species show remarkably parallel diversification histories, both in terms of timing of phylogenetic splits and their geographic distributions. This indicates that common processes may have shaped the evolutionary history of these lineages.


Assuntos
Bufonidae/genética , Filogenia , Filogeografia , Floresta Úmida , Animais , Feminino , Masculino
9.
Gastroenterology ; 161(1): 318-332.e9, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33819482

RESUMO

BACKGROUND & AIMS: The existence of different subtypes of pancreatic ductal adenocarcinoma (PDAC) and their correlation with patient outcome have shifted the emphasis on patient classification for better decision-making algorithms and personalized therapy. The contribution of mechanisms regulating the cancer stem cell (CSC) population in different subtypes remains unknown. METHODS: Using RNA-seq, we identified B-cell CLL/lymphoma 3 (BCL3), an atypical nf-κb signaling member, as differing in pancreatic CSCs. To determine the biological consequences of BCL3 silencing in vivo and in vitro, we generated bcl3-deficient preclinical mouse models as well as murine cell lines and correlated our findings with human cell lines, PDX models, and 2 independent patient cohorts. We assessed the correlation of bcl3 expression pattern with clinical parameters and subtypes. RESULTS: Bcl3 was significantly down-regulated in human CSCs. Recapitulating this phenotype in preclinical mouse models of PDAC via BCL3 genetic knockout enhanced tumor burden, metastasis, epithelial to mesenchymal transition, and reduced overall survival. Fluorescence-activated cell sorting analyses, together with oxygen consumption, sphere formation, and tumorigenicity assays, all indicated that BCL3 loss resulted in CSC compartment expansion promoting cellular dedifferentiation. Overexpression of BCL3 in human PDXs diminished tumor growth by significantly reducing the CSC population and promoting differentiation. Human PDACs with low BCL3 expression correlated with increased metastasis, and BCL3-negative tumors correlated with lower survival and nonclassical subtypes. CONCLUSIONS: We demonstrate that bcl3 impacts pancreatic carcinogenesis by restraining CSC expansion and by curtailing an aggressive and metastatic tumor burden in PDAC across species. Levels of BCL3 expression are a useful stratification marker for predicting subtype characterization in PDAC, thereby allowing for personalized therapeutic approaches.


Assuntos
Proteína 3 do Linfoma de Células B/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Células-Tronco Neoplásicas/metabolismo , Neoplasias Pancreáticas/metabolismo , Animais , Proteína 3 do Linfoma de Células B/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/secundário , Diferenciação Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Metabolismo Energético , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Nus , Invasividade Neoplásica , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Transdução de Sinais , Carga Tumoral , Células Tumorais Cultivadas
10.
Food Chem ; 356: 129627, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33839531

RESUMO

Homopolysaccharides (HoPS) produced by lactic acid bacteria (LAB) are highly versatile, biocompatible and safe compounds. In this work, six HoPS from different species of Weisella and Leuconostoc were identified as thermally stable dextrans, with endothermic crystalline deformations between 214 and 239 °C. These dextrans proved to have greater solubility and capacities to retain water and oil than similar polymers in other reports. Furthermore, a surface morphology study presented cubic grumps, stratify mesh with irregular grumps, and highly compact filaments. Assays in vitro revealed moderate antioxidant, browning and foaming activities as well as technological properties, such as anti-syneresis, emulsifying and flocculating activities, even at low concentrations. Taking into account bipolymers' microstructure, functionalities and performance in both, aqueous and hydrophobic matrixes, plus their capacity to maintain themselves at elevated temperatures, we consider these HoPS beneficial and natural food additives.


Assuntos
Aditivos Alimentares/química , Lactobacillales/química , Polissacarídeos/química , Emulsões , Aditivos Alimentares/metabolismo , Interações Hidrofóbicas e Hidrofílicas , Lactobacillales/metabolismo , Solubilidade , Água/química
11.
Anim Biosci ; 34(10): 1632-1642, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33677908

RESUMO

OBJECTIVE: The hypothesis was that apparent ileal digestibility (AID), basal endogenous losses, and standardized ileal digestibility (SID) of amino acids (AA) are not affected by adding acid to collection containers or bags used to collect ileal digesta from pigs. METHODS: Twenty-four growing barrows (initial body weight: 77.8±4.5 kg) that were fitted with a T-cannula in the distal ileum were fed diets for three 7-d periods. An N-free diet and 3 diets containing corn, soybean meal, or wheat middlings as the sole source of AA were used. Within each period, each of the 4 diets were fed to 6 pigs. Among the 6 pigs, digesta from 3 pigs were collected in bags containing no HCl, whereas 40 mL of 3 N HCl was included in the bags used to collect digesta from the remaining 3 pigs. Every other bag collected from each pig was emptied into a container without adding HCl, whereas the remaining bags were added to a container along with 40 mL of 3 N HCl for each bag. All digesta were stored at -20°C immediately after collection. Data were analyzed using a model that included feed ingredient, HCl in bags, HCl in containers, and all 2-way and 3-way interactions as fixed effects. No 3-way interactions were significant, and data were, therefore, reanalyzed independently for each diet as a 2×2 factorial. RESULTS: There were no interactions between adding HCl to collection bags and to containers, and no effects of adding HCl to collection bags or containers for AID, basal endogenous losses, or SID of most AA were observed. CONCLUSION: It is not necessary to add acid to digesta collection bags or collection containers if ileal digesta are stored at -20°C immediately after collection.

12.
Kinesiologia ; 40(1): 68-74, 20210301.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1352704

RESUMO

Introducción: La prevalencia anual de dolor cervical oscila entre un 16,7% y un 75,1%, durando alrededor de 6 meses o más en el 14% de los casos, desencadenando en restricción del movimiento y dolor principalmente. Esto podría deberse a la relación entre la cabeza, columna cervical y estructuras relacionadas a la articulación temporomandibular (ATM). El objetivo de esta investigación es describir a través de la evidencia científica el efecto de las técnicas manuales orales en la disminución del dolor cervical. Métodos: Se incluyeron ensayos clínicos aleatorizados y revisiones sistemáticas encontrados en las bases de datos PubMed, Cochrane y PEDro. Realizando la extracción de datos a través de una tabla estructurada para cada tipo de estudio. Resultados: De 10 estudios seleccionados, 3 corresponden a revisiones sistemáticas y 7 a ensayos clínicos, donde la disminución del dolor cervical fue significativa al aplicar la terapia manual con ejercicios por sobre la terapia manual por sí sola. Por otro lado, las técnicas orofaciales fueron beneficiosas al combinarlas con terapia manual en comparación con un tratamiento habitual. No se encontraron diferencias significativas al aplicar ejercicios de Maitland y movilizaciones en comparación con ejercicios de flexibilidad, fortalecimiento, ejercicios de Mulligan y movilizaciones. Conclusión: Los resultados son debatibles, ya que la terapia manual por sí sola o combinada con ejercicios es la técnica más efectiva no solo en la disminución del dolor cervical, también en la mejoría de la calidad de vida.


Introduction: The annual prevalence of cervical pain ranges from 16.7% to 75.1%, lasting about 6 months or more in 14% of cases, triggering mainly movement restriction and pain. This could be due to the relationship between the head, cervical spine and structures related to the temporomandibular joint (TMJ). The objective of this research is to describe through scientific evidence the effect of oral techniques in reducing cervical pain. Methods: Randomized clinical trials and systematic reviews found in the PubMed, Cochrane and PEDro databases were included. Data extraction was done through a structured table for each type of study. Results: Out of 10 selected studies, 3 correspond to systematic reviews and 7 to clinical trials, where the decrease in neck pain was significant when applying manual therapy with exercises over manual therapy alone. On the other hand, orofacial techniques were beneficial when combined with manual therapy compared to an usual treatment. No significant differences were found when applying Maitland exercises and mobilizations compared to flexibility, strengthening, Mulligan exercises, and mobilizations (p<0.05). Conclusion: The results are debatable, as manual therapy alone or combined with exercises is the most effective technique not only in reducing neck pain, but also in improving quality of life.

13.
Food Chem ; 350: 128659, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33342609

RESUMO

Salicornia neei halophyte extends in Argentina seashores. To envisage potential applications, cell wall sequential extraction performed on dry plant yielded 1.1, 2.4, 0.3 and 0.9% of pectin fractions respectively extracted by room temperature water, 90 °C-water, CDTA and Na2CO3. They contained 21-33% uronic acids (UA) with low degree of methylation and 0.5-1.2 M ratios of neutral sugars to UA. High arabinose level suggests that long arabinan side-chains maintain cell wall flexibility in water deficit. Fractions also contained 10-36% of proteins. The KOH-soluble fractions (4.3%) were mainly arabinoxylans. At 2.0% w/v, pectin fractions developed "weak gel"-type networks with Ca2+, while arabinoxylans generated "dilute solutions". Cellulose (28%) and lignin (45.1%) were the main biopolymers in the final residue, which showed low water swelling capacity (3.6 mL/g) due to lignin, increasing when arabinoxylans were also present. Phenolics (9.8%) were mainly water-extractable. Salicornia is a source of biopolymers and antioxidants potentially useful for food applications.


Assuntos
Biopolímeros/metabolismo , Parede Celular/química , Chenopodiaceae/química , Plantas Tolerantes a Sal/química , Antioxidantes/análise , Celulose/análise , Chenopodiaceae/metabolismo , Lignina/análise , Pectinas/análise , Proteínas de Plantas/análise
14.
Nat Commun ; 11(1): 5265, 2020 10 16.
Artigo em Inglês | MEDLINE | ID: mdl-33067432

RESUMO

Pancreatic ductal adenocarcinoma (PDAC), the fourth leading cause of cancer death, has a 5-year survival rate of approximately 7-9%. The ineffectiveness of anti-PDAC therapies is believed to be due to the existence of a subpopulation of tumor cells known as cancer stem cells (CSCs), which are functionally plastic, and have exclusive tumorigenic, chemoresistant and metastatic capacities. Herein, we describe a 2D in vitro system for long-term enrichment of pancreatic CSCs that is amenable to biological and CSC-specific studies. By changing the carbon source from glucose to galactose in vitro, we force PDAC cells to utilize OXPHOS, resulting in enrichment of CSCs defined by increased CSC biomarker and pluripotency gene expression, greater tumorigenic potential, induced but reversible quiescence, increased OXPHOS activity, enhanced invasiveness, and upregulated immune evasion properties. This CSC enrichment method can facilitate the discovery of new CSC-specific hallmarks for future development into targets for PDAC-based therapies.


Assuntos
Carcinoma Ductal Pancreático/imunologia , Evasão da Resposta Imune , Células-Tronco Neoplásicas/imunologia , Neoplasias Pancreáticas/imunologia , Animais , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Feminino , Humanos , Camundongos , Camundongos Nus , Invasividade Neoplásica , Células-Tronco Neoplásicas/metabolismo , Fosforilação Oxidativa , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia
15.
Nat Commun ; 11(1): 2682, 2020 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-32472071

RESUMO

Pancreatic cancer stem cells (PaCSCs) drive pancreatic cancer tumorigenesis, chemoresistance and metastasis. While eliminating this subpopulation of cells would theoretically result in tumor eradication, PaCSCs are extremely plastic and can successfully adapt to targeted therapies. In this study, we demonstrate that PaCSCs increase expression of interferon-stimulated gene 15 (ISG15) and protein ISGylation, which are essential for maintaining their metabolic plasticity. CRISPR-mediated ISG15 genomic editing reduces overall ISGylation, impairing PaCSCs self-renewal and their in vivo tumorigenic capacity. At the molecular level, ISG15 loss results in decreased mitochondrial ISGylation concomitant with increased accumulation of dysfunctional mitochondria, reduced oxidative phosphorylation (OXPHOS) and impaired mitophagy. Importantly, disruption in mitochondrial metabolism affects PaCSC metabolic plasticity, making them susceptible to prolonged inhibition with metformin in vivo. Thus, ISGylation is critical for optimal and efficient OXPHOS by ensuring the recycling of dysfunctional mitochondria, and when absent, a dysregulation in mitophagy occurs that negatively impacts PaCSC stemness.


Assuntos
Carcinoma Ductal Pancreático/patologia , Transformação Celular Neoplásica/genética , Citocinas/metabolismo , Mitofagia/genética , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/patologia , Ubiquitinas/metabolismo , Linhagem Celular , Plasticidade Celular/fisiologia , Transformação Celular Neoplásica/patologia , Citocinas/genética , Humanos , Metformina/farmacologia , Mitocôndrias/genética , Mitocôndrias/metabolismo , Fosforilação Oxidativa , Neoplasias Pancreáticas/mortalidade , Edição de RNA/genética , Ubiquitinas/genética
16.
Carbohydr Polym ; 230: 115653, 2020 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-31887934

RESUMO

Agarose and κ-carrageenan were oxidized using (2,2,6,6-tetramethylpiperidinyl)oxy (TEMPO) in the presence of NaOCl and NaBr. Products with several degrees of oxidation were structurally characterized. The mechanical spectra were determined: derivatives with a medium to high degree of oxidation give rise to polysaccharides that behave like dilute solutions in water, whereas those with a degree of oxidation close to 20 % keep the gelling properties with a different thermo-rheological response towards pH (6.5 or 4.0) and counterions (K+ or Ca2+) in comparison with the native polysaccharides. For instance, they showed a marked dependence on the presence of calcium ions, observed in the increase of thermal stability and dynamic elastic component (G') value, due to the known interaction of this divalent cation with the carboxylate groups. In this sense, these derivatives with low oxidation degrees have proven to be not only thermosensitive, like the native polysaccharide, but also pH- and calcium-sensitive.


Assuntos
Carragenina/química , Géis/química , Reologia , Sefarose/química , Óxidos N-Cíclicos/química , Concentração de Íons de Hidrogênio , Íons/química , Oxirredução , Rodófitas/metabolismo , Alga Marinha/metabolismo , Viscosidade
17.
Carbohydr Polym ; 228: 115388, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31635746

RESUMO

The structure of the arabinoglucuronoxylans from brea gum was elucidated through an chemical and NMR spectroscopical analysis. They are composed of xylose, arabinose, glucuronic acid and 4-O-methylglucuronic acid in a molar ratio 1:0.44:0.16:0.22. The structure consists of a central chain of (1→4)-ß-d-xylopyranose of which ca.70% are susbstituted in C2 with single stubs of others sugars (ß-d-Xylp, α-d-GlcpA and 4-O-Me-α-d-GlcpA), with disaccharides (α-l-Arap-(1→2)-4-O-Me-α-d-GlcpA-(1→, α-l-Arap-(1→2)-α-d-GlcpA-(1→, ß-l-Araf-(1→3)-α-l-Araf-(1→ and α-l-Araf-(1→3)-α-l-Araf-(1→5), and possibly with trisaccharides of xylose. The determination of the location of the acetyl groups and their quantification in these arabinoglucuronoxylans has been achieved for the first time. Brea gum presents a higher thickening effect than gum arabic in 5% aqueous solution, demonstrating its potential usefulness for food and pharmaceutical applications.


Assuntos
Fabaceae/metabolismo , Gomas Vegetais/química , Xilanos/química , Conformação Molecular , Reologia , Viscosidade
18.
J Anim Sci ; 97(9): 3972-3983, 2019 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-31300813

RESUMO

The primary objective of this experiment was to test the hypothesis that concentrations of soluble (SDF), insoluble (IDF), and total dietary fiber (TDF) in feed ingredients used in diets for pigs and poultry analyzed using Method AOAC 2011.25 are greater than values determined using Method AOAC 991.43. A second objective was to determine the variation that may exist among 3 laboratories using the 2 methods with the AnkomTDF Dietary Fiber Analyzer (Ankom Technology, Macedon, NY). The 3 laboratories were the Ministry of Agriculture Feed Industry Center (MAFIC) at China Agricultural University, Trouw Nutrition, and Hans H. Stein Monogastric Nutrition Laboratory at University of Illinois at Urbana-Champaign (UIUC). All laboratories analyzed SDF and IDF in feed ingredients in duplicate or triplicate using both methods AOAC 991.43 and 2011.25 with the AnkomTDF Dietary Fiber Analyzer. The 9 test ingredients were wheat, soybean meal, rapeseed meal, sugar beet pulp, peas, horse beans, native pea starch, and 2 samples of corn; 1 from Europe and 1 from China. All ingredient samples, with the exception of Chinese corn, were procured by Trouw Nutrition, ground to pass through a 0.5 mm screen, subsampled, and sent to MAFIC and UIUC. Data were analyzed using SDF, IDF, and TDF as response variables, replication as random effect, and method and location as fixed effects over all ingredients and within each ingredient. When averaged among 9 different ingredients, results indicated that SDF, IDF, and TDF values were not different with either method or at any laboratory. However, the concentration of IDF in corn, wheat, peas, and sugar beet pulp determined using Method AOAC 991.43 was greater (P < 0.05) compared with 2011.25. Soluble dietary fiber determined using Method AOAC 2011.25 was greater (P < 0.05) in corn, rapeseed meal, soybean meal, and sugar beet pulp compared with 991.43. There was no difference in TDF determined with either method, except for wheat having greater (P < 0.05) TDF when determined using Method AOAC 991.43. Interlaboratory variation for SDF, IDF, and TDF was 0.38, 0.87, 1.20, respectively, with Method AOAC 991.43 and 0.40, 0.93, and 1.27, respectively, with 2011.25. Therefore, values determined with the AnkomTDF Analyzer are repeatable among laboratories and can be used in feed formulation worldwide. In conclusion, it is recommended that Method AOAC 991.43 be used to determine SDF, IDF, and TDF in feed ingredients and diets for pigs and poultry.


Assuntos
Ração Animal/análise , Fibras na Dieta/análise , Análise de Alimentos/métodos , Suínos/fisiologia , Animais , China , Dieta/veterinária , Europa (Continente) , Fabaceae , Análise de Alimentos/instrumentação , Sensibilidade e Especificidade , Solubilidade , Triticum , Zea mays
19.
J Anim Sci Biotechnol ; 10: 39, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31049199

RESUMO

The current paper reviews the content and variation of fiber fractions in feed ingredients commonly used in swine diets. Carbohydrates serve as the main source of energy in diets fed to pigs. Carbohydrates may be classified according to their degree of polymerization: monosaccharides, disaccharides, oligosaccharides, and polysaccharides. Digestible carbohydrates include sugars, digestible starch, and glycogen that may be digested by enzymes secreted in the gastrointestinal tract of the pig. Non-digestible carbohydrates, also known as fiber, may be fermented by microbial populations along the gastrointestinal tract to synthesize short-chain fatty acids that may be absorbed and metabolized by the pig. These non-digestible carbohydrates include two disaccharides, oligosaccharides, resistant starch, and non-starch polysaccharides. The concentration and structure of non-digestible carbohydrates in diets fed to pigs depend on the type of feed ingredients that are included in the mixed diet. Cellulose, arabinoxylans, and mixed linked ß-(1,3) (1,4)-d-glucans are the main cell wall polysaccharides in cereal grains, but vary in proportion and structure depending on the grain and tissue within the grain. Cell walls of oilseeds, oilseed meals, and pulse crops contain cellulose, pectic polysaccharides, lignin, and xyloglucans. Pulse crops and legumes also contain significant quantities of galacto-oligosaccharides including raffinose, stachyose, and verbascose. Overall, understanding the structure, characteristics and measurable chemical properties of fiber in feed ingredients may result in more accurate diet formulations, resulting in an improvement in the utilization of energy from less expensive high-fiber ingredients and a reduction in reliance on energy from more costly cereal grains.

20.
Carbohydr Res ; 478: 18-24, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-31048118

RESUMO

The brown seaweed Scytosiphon lomentaria produces moderate amounts of fucoidans. By cetrimide fractionation, typical heavily sulfated galactofucans are obtained, with no major signs of chemical heterogeneity, together with fractions with higher proportions of xylose, mannose and uronic acids. Anyway, fucose is the most important monosaccharide in most of the subfractions of the subsequent extracts. The fucan moieties appear to be mostly as 3-linked α-l-fucopyranosyl units, with several patterns of sulfate and branching. Galactose is mostly 6-linked, whereas mannose appears to be 2-linked, and xylose appears mostly as terminal stubs. Small amounts of 2-O-acetylated fucose units appear. A high and selective antiviral activity against HSV-1 and HSV-2 was determined for the galactofucan fractions whereas the uronofucoidans were inactive.


Assuntos
Antivirais/farmacologia , Fucose/farmacologia , Galactose/farmacologia , Herpesvirus Humano 1/efeitos dos fármacos , Herpesvirus Humano 2/efeitos dos fármacos , Polissacarídeos/farmacologia , Antivirais/química , Antivirais/isolamento & purificação , Configuração de Carboidratos , Fucose/química , Fucose/isolamento & purificação , Galactose/química , Galactose/isolamento & purificação , Testes de Sensibilidade Microbiana , Polissacarídeos/química , Polissacarídeos/isolamento & purificação
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