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Background and objectives: Arabinoxylans (AX) can gel and exhibit antioxidant capacity. Previous studies have demonstrated the potential application of AX microspheres as colon-targeted drug carriers. However, the cytotoxicity of AX gels has not been investigated so far. Therefore, the aim of the present study was to prepare AX-based particles (AXM) by coaxial electrospraying method and to investigate their antioxidant potential and cytotoxicity on human colon cells. Materials and Methods: The gelation of AX was studied by monitoring the storage (G') and loss (G'') moduli. The morphology of AXM was evaluated using optical and scanning electron microscopy (SEM). The in vitro antioxidant activity of AX before and after gelation was measured using the 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) methods. In addition, the effect of AX and AXM on the proliferation of human colon cells (CCD 841 CoN) was evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results: The final G' and G'' values for AX gels were 293 and 0.31 Pa, respectively. AXM presented spherical shape and rough surface with a three-dimensional and porous network. The swelling ratio and mesh size of AXM were 35 g water/g AX and 27 nm, respectively. Gelation decreased the antioxidant activity of AX by 61-64 %. AX and AXM did not affect proliferation or show any toxic effect on the normal human colon cell line CCD 841 CoN. Conclusion: The results indicate that AXM could be promising biocompatible materials with antioxidant activity.
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Linhagem Celular/efeitos dos fármacos , Xilanos/metabolismo , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Linhagem Celular/metabolismo , Colo/efeitos dos fármacos , Colo/fisiopatologia , Citotoxinas/farmacologia , Citotoxinas/uso terapêutico , Géis/metabolismo , Géis/uso terapêutico , Humanos , Extratos Vegetais/metabolismo , Extratos Vegetais/uso terapêutico , Xilanos/farmacologiaRESUMO
We previously reported age of onset (AOO) modifier genes in the world's largest pedigree segregating early-onset Alzheimer's disease (AD), caused by the p.Glu280Ala (E280A) mutation in the PSEN1 gene. Here we report the results of a targeted analysis of functional exonic variants in those AOO modifier genes in sixty individuals with PSEN1 E280A AD who were whole-exome genotyped for ~250,000 variants. Standard quality control, filtering, and annotation for functional variants were applied, and common functional variants located in those previously reported as AOO modifier loci were selected. Multiloci linear mixed-effects models were used to test the association between these variants and AOO. An exonic missense mutation in the G72 (DAOA) gene (rs2391191, P = 1.94 × 10(-4), P FDR = 9.34 × 10(-3)) was found to modify AOO in PSEN1 E280A AD. Nominal associations of missense mutations in the CLUAP1 (rs9790, P = 7.63 × 10(-3), P FDR = 0.1832) and EXOC2 (rs17136239, P = 0.0325, P FDR = 0.391) genes were also found. Previous studies have linked polymorphisms in the DAOA gene with the occurrence of neuropsychiatric symptoms such as depression, apathy, aggression, delusions, hallucinations, and psychosis in AD. Our findings strongly suggest that this new conspicuous functional AOO modifier within the G72 (DAOA) gene could be pivotal for understanding the genetic basis of AD.
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Doença de Alzheimer/genética , Proteínas de Transporte/genética , Mutação de Sentido Incorreto , Presenilina-1/genética , Idade de Início , Éxons , Feminino , Predisposição Genética para Doença , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , MasculinoRESUMO
The identification of mutations modifying the age of onset (AOO) in Alzheimer's disease (AD) is crucial for understanding the natural history of AD and, therefore, for early interventions. Patients with sporadic AD (sAD) from a genetic isolate in the extremes of the AOO distribution were whole-exome genotyped. Single- and multi-locus linear mixed-effects models were used to identify functional variants modifying AOO. A posteriori enrichment and bioinformatic analyses were applied to evaluate the non-random clustering of the associate variants to physiopathological pathways involved in AD. We identified more than 20 pathogenic, genome-wide statistically significant mutations of major modifier effect on the AOO. These variants are harbored in genes implicated in neuron apoptosis, neurogenesis, inflammatory processes linked to AD, oligodendrocyte differentiation, and memory processes. This set of new genes harboring these mutations could be of importance for prediction, follow-up and eventually as therapeutical targets of AD. © 2016 Wiley Periodicals, Inc.
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Idade de Início , Doença de Alzheimer/genética , Idoso , Exoma , Feminino , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , MutaçãoRESUMO
Pathogenic strains of Escherichia coli threaten public health due to their virulence factors and antibiotic resistance. Additionally, the virulence of this bacterium varies by region depending on environmental conditions, agricultural practices, and the use of antibiotics and disinfectants. However, there is limited research on the prevalence of antibiotic-resistant E. coli in agriculture. Therefore, this research aimed to determine the antibiotic resistance of E. coli isolated from the Honeydew melon production system in Hermosillo, Sonora, Mexico. Thirty-two E. coli strains were isolated from 445 samples obtained from irrigation water, harvested melons, the hands of packaging workers, boxes, and discarded melons. The resistance profile of the E. coli strains was carried out to 12 antibiotics used in antimicrobial therapeutics against this bacterium; a high level of resistance to ertapenem (100%) was detected, followed by meropenem (97%), and ampicillin (94%); 47% of the strains were classified as multidrug-resistant. It was possible to identify the prevalence of the extended-spectrum ß-lactamase (ESBLs) gene blaTEM (15.6%), as well as the non-ESBL genes qepA (3.1%) and aac(6')lb-cr (3.1%). The E. coli strains isolated from irrigation water were significantly associated with resistance to aztreonam, cefuroxime, amikacin, and sulfamethoxazole/trimethoprim. Irrigation water, packing workers' hands, and discarded melons showed a higher prevalence of antibiotic-resistant, ESBL, and non-ESBL genes of E. coli strains in a farm and packing facility of Honeydew melon in Hermosillo, Sonora.
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Escherichia coli is among the most prevalent food contaminant microorganisms that have evolved, generating variants based on their effects on the host; these include commensals or pathobiont strains. The last classifications of E. coli intestinal pathobionts found in this review are enteroinvasive, enterohemorrhagic, enteropathogenic, enterotoxigenic, diffusely adherent, and enteroaggregative strains. Meanwhile, the most ancestral are enteropathogenic and enteroaggregative, and the most contemporaries are the enterotoxigenic and enteroinvasive strains. These pathobionts have been proposed based on their infective mechanisms, including toxin production, adherence effects, and tissue damage. It is also evidenced that environmental stresses, including bacterial exposition to antibiotics and disinfectants, contribute to this evolution. Therefore, new antibacterial and antivirulence agents are being explored, mainly from natural sources. In this context, this review discusses the diversity of E. coli pathobionts, their participation in foodborne outbreaks, and strategies to survey and control their spread and virulence.
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Escherichia coli Enteropatogênica , Infecções por Escherichia coli , Proteínas de Escherichia coli , Antibacterianos , Diarreia/microbiologia , Escherichia coli/genética , Infecções por Escherichia coli/epidemiologia , Infecções por Escherichia coli/microbiologia , Inocuidade dos Alimentos , Humanos , VirulênciaRESUMO
Nonsyndromic orofacial clefts are a common complex birth defect caused by genetic and environmental factors and/or their interactions. A previous genome-wide linkage scan discovered a novel locus for cleft lip with or without cleft palate (CL/P) at 9q22-q33. To identify the etiologic gene, we undertook an iterative and complementary fine mapping strategy using family-based CL/P samples from Colombia, USA and the Philippines. Candidate genes within 9q22-q33 were sequenced, revealing 32 new variants. Concurrently, 397 SNPs spanning the 9q22-q33 2-LOD-unit interval were tested for association. Significant SNP and haplotype association signals (P = 1.45E - 08) narrowed the interval to a 200 kb region containing: FOXE1, C9ORF156 and HEMGN. Association results were replicated in CL/P families of European descent and when all populations were combined the two most associated SNPs, rs3758249 (P = 5.01E - 13) and rs4460498 (P = 6.51E - 12), were located inside a 70 kb high linkage disequilibrium block containing FOXE1. Association signals for Caucasians and Asians clustered 5' and 3' of FOXE1, respectively. Isolated cleft palate (CP) was also associated, indicating that FOXE1 plays a role in two phenotypes thought to be genetically distinct. Foxe1 expression was found in the epithelium undergoing fusion between the medial nasal and maxillary processes. Mutation screens of FOXE1 identified two family-specific missense mutations at highly conserved amino acids. These data indicate that FOXE1 is a major gene for CL/P and provides new insights for improved counseling and genetic interaction studies.
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Cromossomos Humanos Par 9/genética , Fenda Labial/genética , Fissura Palatina/genética , Fatores de Transcrição Forkhead/genética , Mapeamento Cromossômico , Haplótipos , Humanos , Escore LodRESUMO
Arabinoxylans (AX) are polysaccharides with antioxidant activity and emulsifying properties, which make them an attractive alternative for its potential application as a natural antioxidant in oils. Therefore, this work aimed to investigate the effect of ultrasonic treatment of AX on their antioxidant capacity and its ability to improve the oxidative stability of soybean oil. For this purpose, AX were exposed to ultrasonic treatment at 25% (100 W, AX-1) and 50% (200 W, AX-2) power and an operating frequency of 20 KHz during 15 min, and their macromolecular properties (weight average molecular weight (Mw), polydispersity index and intrinsic viscosity) were evaluated. The antioxidant capacity of AX was determined by the DPPH assay and Rancimat test. Results showed that ultrasonic treatment did not affect the molecular identity of the polysaccharide but modified its Mw distribution. AX-1 showed the highest antioxidant activity (75% inhibition) at 533 µg/mL by the DPPH method compared to AX and AX-2. AX at 0.25% (w/v) and AX-1 at 0.01% (w/v) exerted the highest protective effects on oxidative stability of soybean oil with induction periods of 7.69 and 5.54 h, respectively. The results indicate that AX could be a good alternative for the potential application as a natural antioxidant in oils.
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In the last years, biomedical research has focused its efforts in the development of new oral delivery systems for the treatment of different diseases. Ferulated arabinoxylans are polysaccharides from cereals that have been gaining attention in the pharmaceutical field due to their prebiotic, antioxidant, and anticancer properties. The antioxidant and anticancer properties of these polysaccharides make them attractive compounds for the treatment of cancer, particularly colon cancer. In addition, ferulated arabinoxylans can form covalent gels through the cross-linking of their ferulic acids. Due to their particular characteristics, ferulated arabinoxylan gels represent an excellent alternative as colon-targeted drug delivery systems. The aim of the present work is to review the physicochemical and functional properties of ferulated arabinoxylans and their gels and to present the future perspectives for potential application as antioxidant and anticancer agents.
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Antineoplásicos/uso terapêutico , Antioxidantes/uso terapêutico , Géis/uso terapêutico , Xilanos/uso terapêutico , Antineoplásicos/farmacologia , Antioxidantes/farmacologia , Xilanos/farmacologiaRESUMO
Abstract: Objective: To evaluate the effect of the ingestion of a fibrous extract of Stevia rebaudiana Bertoni stems on postprandial glycemia levels in healthy subjects. Materials and Methods: Cross-sectional, experimental research, carried out with ethical conditions of consent and reliability, in the Laboratory for the Evaluation of Nutritional Status of the Autonomous University of Carmen. For the clinical and anthropometric assessment of the participants, a medical history and body composition scan were used, respectively. The study population consisted of 16 healthy women with normal body mass indices (20-25 kg/m2). Instruments: a) Clinical-dietetic record and b) Biochemical data obtained from blood sampling obtained at different times. The data analysis was carried out with descriptive statistics. Results: The results shown in the group of participants in this study, it was observed that the mean value of the area under the curve (AUC) of glucose was 709.18 ± 23.60, while that of the fibrous extract of stevia stems was 556.59 ± 50.47. Conclusions: Stevia rebaudiana stems, due to their dietary fiber content, can be an alternative for the use and revaluation of sustained waste in the circular economy in the development of functional products, giving it an added value that contributes in some way to reducing overweight and obesity, with a hypoglycemic effect in patients with type 2 diabetes mellitus (DM).
Resumen: Objetivo: Evaluar el efecto de la ingesta de un extracto fibroso de tallos de Stevia rebaudiana Bertoni sobre los niveles de glicemia postprandial en sujetos sanos. Materiales y Métodos: Investigación transversal, experimental, realizada con condiciones éticas de consentimiento y confiabilidad, en el laboratorio de Evaluación del Estado Nutricional de la Universidad Autónoma del Carmen. Para la valoración clínica y antropométrica de los participantes se utilizó una historia clínica y escáner de composición corporal, respectivamente. La población de estudio fue conformada por 16 mujeres sanas con índices de masa corporal normales (20-25 kg/m2). Instrumentos: a) Expediente clínico-dietético y b) Datos bioquímicos obtenidos de la toma sanguínea obtenidos en los diferentes tiempos. Se realizó el análisis de los datos con estadística descriptiva. Resultados: Los resultados mostrados en el grupo de participantes en este estudio, se observó que el valor medio del área bajo la curva (AUC) de la glucosa fue de 709.18 ± 23.60, mientras que el del extracto fibroso de tallos de stevia fue de 556.59 ± 50.47. Conclusiones: Los tallos de Stevia rebaudiana Bertoni. por su contenido en fibra dietética, pueden ser una alternativa para el uso y revalorización de residuos sostenidos en la economía circular en el desarrollo de productos funcionales, otorgándole un valor agregado que contribuye de alguna manera a reducir el sobrepeso y la obesidad, con efecto hipoglucemiante en pacientes con diabetes mellitus (DM) tipo 2.
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We have applied a GWAS to 40 consanguineous families segregating cases of non-syndromic cleft lip with or without cleft palate (NS CL/P) (a total of 160 affected and unaffected individuals) in order to trace potential recessive loci that confer susceptibility to this common facial malformation. Pedigree-based association test (PBAT) analyses reported nominal evidence of association and linkage over SNP markers located at 11q25 (rs4937877, P = 2.7 × 10(-6)), 19p12 (rs4324267, P = 1.6 × 10(-5)), 5q14.1 (rs4588572, P-value = 3.36 × 10(-5)), and 15q21.1 (rs4774497, P = 1.08 × 10(-4)). Using the Versatile Gene-Based Association Study to complement the PBAT results, we found clusters of markers located at chromosomes 19p12, 11q25, and 8p23.2 overcome the threshold for GWAS significance (P < 1 × 10(-7)). From this study, new recessive loci implicated in NS CL/P include: B3GAT1, GLB1L2, ZNF431, ZNF714, and CSMD1, even though the functional association with the genesis of NS CL/P remains to be elucidated. These results emphasize the importance of using homogeneous populations, phenotypes, and family structures for GWAS combined with gene-based association analyses, and should encourage. other researchers to evaluate these genes on independent patient samples affected by NS CL/P.
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Fenda Labial/genética , Fissura Palatina/genética , Genes Recessivos , Encéfalo/anormalidades , Estudos de Casos e Controles , Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Proteínas de Ligação a DNA/genética , Feminino , Marcadores Genéticos , Predisposição Genética para Doença/genética , Estudo de Associação Genômica Ampla , Glucuronosiltransferase/genética , Glicosídeo Hidrolases/genética , Humanos , Masculino , Proteínas de Membrana/genética , Linhagem , Fatores de Transcrição/genética , Proteínas Supressoras de TumorRESUMO
OBJECTIVE: To examine genetic variations in the region surrounding loci of the major histocompatibility complex, and to investigate the probable location of a new candidate region on the short arm of chromosome 6 predisposing to primary Sjögren's syndrome (SS). METHODS: We conducted an association study and positional candidate gene approach by microsatellite analysis. Five polymorphic microsatellite markers, D6S273, D6S439, D6S1645, D6S291, and DS61019, spanning the region 6p21.3, and establishing particular landmarks to discriminate between the human leukocyte antigen class II and tumor necrosis factor-a loci, were genotyped by polymerase chain reaction technique. RESULTS: A total of 64 patients with primary SS and 120 matched controls were examined. There was no genetic stratification among cases and controls. Genotype distribution analysis disclosed a significantly higher number of homozygotes for D6S439 locus in patients than in controls [odds ratio (OR): 3, 95% confidence interval (CI): 1.46-6.14, p = 0.004]. Confirmation of this homozygosity was established by the gene correlation intra-locus test (Fis value = +0.233, p = 0.0007). Allele D6S439*274 was associated to disease (OR: 3, 95% CI: 1.35-6.65, p = 0.006, pc = 0.04). Among patients, no significant linkage disequilibrium (LD) value was found between the studied microsatellites and TAP, HLA-DRB1, or HLA-DQB1 loci. In controls, there was LD between D6S1645 and D6S291 loci. CONCLUSION: Our results indicate that D6S439 microsatellite defines a new susceptibility region for primary SS, independent of LD with TAP and HLA DQ/DR. These findings might imply that a gene surrounding this location is causally related to the disease.
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Cromossomos Humanos Par 6 , Predisposição Genética para Doença , Repetições de Microssatélites/genética , Polimorfismo Genético , Síndrome de Sjogren/genética , DNA/análise , Primers do DNA/química , Feminino , Antígenos HLA-DQ/genética , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Homozigoto , Humanos , Desequilíbrio de Ligação/genética , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
Familial clustering and linkage disequilibrium studies suggest that genetic factors predispose to vitiligo, although a clear transmission pattern and cosegregation of vitiligo with specific mutations have not been demonstrated. We collected pedigree data on vitiligo from a set of 56 multigeneration families belonging to the Paisa community from Antioquia, Colombia, with the goal of applying the unified model of complex segregation and linkage disequilibrium analyses to test the hypotheses of the existence of a major gene predisposing to vitiligo and that allelic or haplotype polymorphisms of microsatellite loci at 6p21.3-21.4 spanning HLA (D6S276, D6S265, D6S273, and D6S291) are associated with this predisposition. Minimum sibship sample size to discriminate dominant and recessive inheritance models was largely accomplished. Between the 15 models of complex segregation used, the one that best fitted the data was that of a major dominant gene and the existence of strong environmental effects acting on the recessive genotype. The penetrance and risk estimations discriminated two sets of vitiligo patients: those with early onset of vitiligo cosegregating with a dominant mode of inheritance without environmental effects, and those with late onset of vitiligo cosegregating with the recessive genotype and being influenced by environmental effects. After establishing the normal distribution of allelic frequencies and performing multiple comparisons correction, the linkage disequilibrium analysis suggested that a major genetic factor could be located at 6p21.3-21.4, because we detected significant case-control differences for allele 122 at D6S265 ( Pc=0.0264) and significant linkage disequilibrium between loci D6S276 and D6S273 in the cases but not in the controls. We cannot explain these results as a consequence of evolutionary forces or as genetic stratification acting differentially on cases and controls, because there was neither deviation from the Hardy-Weinberg expectations nor genetic subdivision between cases and controls, as theta; (non-biased F(ST)) was not significantly different from 0.
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Antígenos HLA/genética , Desequilíbrio de Ligação , Repetições de Microssatélites/genética , Vitiligo/genética , Feminino , Genótipo , Humanos , MasculinoRESUMO
Con la finalidad de examinar el espectro de la edad de inicio de la epilepsia idiopática en familias extendidas multigeneracionales y determinar si existe real anticipación genética o si dicho fenómeno puede ser explicado en términos de sesgo de búsqueda o reclutamiento, se diseñó un experimento de comparación de la edad media de inicio de la enfermedad entre pares de relacionados biológicos (padres-hijos, abuelos-nietos, tios y sobrinos) mediante el uso de la prueba no paramétrica apareada de Wilcoxon para determinar si existen diferencias significativas mayores de 0, lo que refuta la hipótesis nula de no anticipación. Un total de 84 pares de relacionados biológicos se construyeron a partir de 72 genealogías extendidas multigeneracionales. Las edades de inicio del cuadro epiléptico de los pares mostraron una diferencia significativamente >0 confirmando la existencia de diferencia intergeneracional con una tendencia al inicio más temprano en la medida que transcurren las generaciones. Esto ocurrió en todos los pares relacionados biológicos lo que está en contra de sesgos de reclutamiento. Estos resultado plantean la existencia de mutaciones inestables o producidas por un número variable de repeticiones nucleotídicas en salvas como una probable explicación de la susceptibilidad para desarrollar algunas de las formas de epilepsia idiopática