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BACKGROUND: Dysregulation of long non-coding RNAs has been implied to connect with cancer progression. This research was to decipher the mechanism of long non-coding RNA SDCBP2-AS1 in ovarian cancer (OC) through regulation of microRNA (miR)-100-5p and ependymin-related protein 1 (EPDR1). METHODS: LncRNA SDCBP2-AS1 and EPDR1 levels in OC were assessed by Gene Expression Profiling Interactive Analysis. lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 levels in OC tissues and cells were determined. SKOV3 and A2780 cells were transfected with lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1-related plasmids or sequences, and then their functions in cell viability, apoptosis, migration, and invasion were evaluated. The interplay of lncRNA SDCBP2-AS1, miR-100-5p, and EPDR1 was clarified. RESULTS: LncRNA SDCBP2-AS1 and EPDR1 levels were suppressed whilst miR-100-5p level was elevated in OC. After upregulating lncRNA SDCBP2-AS1 or EPDR1, viability, migration, and invasion of OC cells were impaired, and apoptosis rate was increased. Downregulating EPDR1 or upregulating miR-100-5p partially mitigated upregulated lncRNA SDCBP2-AS1-induced impacts on the biological functions of OC cells. LncRNA SDCBP2-AS1 sponged miR-100-5p, and EPDR1 was targeted by miR-100-5p. CONCLUSION: It is illustrated that lncRNA SDCBP2-AS1 regulates EPDR1 by sponge adsorption of miR-100-5p to inhibit the progression of OC.
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MicroARNs , Neoplasias Ováricas , ARN Largo no Codificante , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Proteínas de Neoplasias , Proteínas del Tejido Nervioso , Neoplasias Ováricas/genética , PronósticoRESUMEN
In recent years, the development and application of plant proteins have drawn increasing scientific and industrial interests. Pea (Pisum sativum L.) is an important source of high-quality vegetable protein in the human diet. Its protein components are generally considered hypoallergenic, and many studies have highlighted the health benefits associated with the consumption of pea protein. Pea protein and its hydrolysates (pea protein hydrolysates [PPH]) possess health benefits such as antioxidant, antihypertensive, and modulating intestinal bacteria activities, as well as various functional properties, including solubility, water- and oil-holding capacities, and emulsifying, foaming, and gelling properties. However, the application of pea protein in the food system is limited due to its poor functional performances. Several frequently applied modification methods, including physical, chemical, enzymatic, and combined treatments, have been used for pea protein to improve its functional properties and expand its food applications. To date, different applications of pea protein in the food system have been extensively studied, for example, encapsulation for bioactive ingredients, edible films, extruded products and substitution for cereal flours, fats, and animal proteins. This article reviews the current status of the knowledge regarding pea protein, focusing on its health benefits, functional properties, and structural modifications, and comprehensively summarizes its potential applications in the food industry.
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Pisum sativum/química , Proteínas de Vegetales Comestibles/química , Manipulación de Alimentos/métodos , Proteínas de Vegetales Comestibles/farmacología , Hidrolisados de Proteína/químicaRESUMEN
Two Gram-stain-negative, rod-shaped bacterial strains, cai42T and b45, were isolated from oil-production water taken from Xinjiang Oilfield, China. Optimum growth was observed at 30 °C, at pH 8 and with 1-3% (w/v) NaCl. According to phylogenetic analyses, the two strains were members of the genus Defluviimonas, with 16S rRNA gene sequence similarities of 95.5-96.3 % with the type strains of species of the genus. The major cellular fatty acids of strains cai42T and b45 were C10 : 0 3-OH, C16 : 0 and summed feature 8 (C18 : 1ω7c/C18 : 1ω6c), and the predominant ubiquinone was Q-10, all of these data being typical for the genus Defluviimonas. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol, glycolipid, phosphatidylcholine, two unidentified aminolipids, an unidentified phospholipid and two unidentified lipids. The mean genomic DNA G+C contents of strains cai42T and b45 were 60.8±1.1 and 60.4±1.0 mol%, respectively. On the basis of phylogenetic, physiological and chemotaxonomic analyses, strains cai42T and b45 represent a novel species of the genus Defluviimonas, for which the name Defluviimonas alba sp. nov. is proposed. The type strain is cai42T (â= CGMCC 1.12518T = LMG 27406T).
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Yacimiento de Petróleo y Gas/microbiología , Filogenia , Rhodobacteraceae/clasificación , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/química , Datos de Secuencia Molecular , Fosfolípidos/química , ARN Ribosómico 16S/genética , Rhodobacteraceae/genética , Rhodobacteraceae/aislamiento & purificación , Análisis de Secuencia de ADN , Ubiquinona/análogos & derivados , Ubiquinona/químicaRESUMEN
OBJECTIVE: To explore the effects of resveratrol-induced apoptosis and autophagy in T-cell acute lymphoblastic leukemia (T-ALL) cells and potential molecular mechanisms. METHODS: The anti-proliferation effect of resveratrol-induced, apoptosis and autophagy on T-ALL cells were detected by using MTT test, immunofluorescence, electronic microscope, and flow cytometry, respectively. Western blotting was performed for detecting changes of apoptosis-associated proteins, cell cycle regulatory proteins and state of activation of Akt, mTOR, p70S6K, 4E-BP1, and p38-MAPK. RESULTS: Resveratrol inhibited the proliferation and induced apoptosis and autophagy in T-ALL cells in a dose and time-dependent manner. It also induced cell cycle arrest at G0/G1 phase via up regulating cyclin-dependent kinase (CDK) inhibitors p21 and p27 and down regulating cyclin A and cyclin D1. Western blotting revealed that resveratrol significantly decreased the expression of antiapoptotic proteins (Mcl-1 and Bcl-2) and increased the expression of proapoptotic proteins (Bax, Bim, and Bad), and induced cleaved-caspase-3 in a time-dependent manner. Significant increase in ratio of LC3-II/LC3-I and Beclin 1 was also detected. Furthermore, resveratrol induced significant dephosphorylation of Akt, mTOR, p70S6K, and 4E-BP1, but enhanced specific phosphorylation of p38-MAPK which could be blocked by SB203580. When autophagy was suppressed by 3-MA, apoptosis in T-ALL cells induced by resveratrol was enhanced. CONCLUSION: Our findings have suggested that resveratrol induces cell cycle arrest, apoptosis, and autophagy in T-ALL cells through inhibiting Akt/mTOR/p70S6K/4E-BP1 and activating p38-MAPK signaling pathways. Autophagy might play a role as a self-defense mechanism in T-ALL cells treated by resveratrol. Therefore, the reasonable inhibition of autophagy in T-ALL cells may serve as a promising strategy for resveratrol induced apoptosis and can be used as adjuvant chemotherapy for T-ALL.
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Antineoplásicos Fitogénicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/patología , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Estilbenos/farmacología , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Técnicas de Cultivo de Célula , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Citometría de Flujo , Humanos , Leucemia-Linfoma Linfoblástico de Células T Precursoras/enzimología , Resveratrol , Linfocitos T/efectos de los fármacos , Linfocitos T/enzimología , Linfocitos T/ultraestructuraRESUMEN
Recently, research interests are growing regarding the formation and mechanisms of amyloid fibrils from plant proteins. This study investigated the fibrillization kinetics and rheological behaviors of panda bean protein isolate (PBPI) at pH 2.0 and 90 °C for various heating times (0-24 h). Results showed that PBPI formed two distinct classes of fibrils after heating for 10 h, including flexible fibril with a contour length of â¼751 nm, and rigid fibril with periodicity of â¼40 nm. The secondary structural changes during fibril formation were monitored by circular dichroism spectroscopy and indicated that ß-sheet content increased first (0-12 h) and then decreased (>12 h), which coincided with similar changes in thioflavin T fluorescence. The gel electrophoresis revealed that the polypeptides of PBPI were progressively hydrolyzed upon heating, and the resulting short fragments were involved in fibril formation rather than PBPI monomer. PBPI-derived fibrils showed extremely high viscosity and storage modulus. A plausible molecular mechanism for PBPI fibrillation process was hypothesized, including protein unfolding, hydrolysis, assembly into matured fibrils, and dissociation of the fibrils. The findings provide useful information to manipulate the formation of legume proteins-based fibrils and will benefit future research to explore their potential applications.
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Vigna , Vigna/metabolismo , Cinética , Proteínas de Plantas/química , Amiloide/química , Concentración de Iones de Hidrógeno , Dicroismo CircularRESUMEN
This study aimed to investigate the rheological and textural properties of heat-induced gels from twelve legume protein isolates at pH 3.0 and 7.0, including black kidney bean (BKPI), speckled kidney bean (SKPI), panda bean (PDPI), cowpea (CPPI), mung bean (MPI), adzuki bean (API), rice bean (RPI), black soybean (BPI), soybean (SPI), chickpea (CPI), broad bean (BRPI) and pea (PPI). SDS-PAGE revealed that 7S globulin was prominent protein in BKPI, SKPI, PDPI, CPPI, MPI, API and RPI, the main protein fraction of CPI was 11S globulin, and BPI, SPI, BRPI and PPI contained both 7S and 11S globulins as major components. Based on the gel's Power Law constant (K') and hardness, twelve legume proteins were divided into three categories with high, medium and low gel strength. BKPI, SKPI and PDPI with Phaseolin being the major protein fraction showed high gel strength regardless of pH. Electrostatic interactions, hydrophobic interactions and hydrogen bonds were the most important intermolecular forces in the formation of legume protein gel networks, of which gel strength at pH 3.0 and pH 7.0 was significantly affected by electrostatic interactions and hydrogen bonds, respectively. Moreover, gel strength was also remarkably negatively influenced by the non-network proteins. SEM observation indicated that the microstructure of gels at pH 7.0 was denser and more homogeneous than that at pH 3.0, leading to better water holding capacity. These findings would be of great importance for understanding the differences in legume protein gels, and also laid the scientific support for expanding applications of legume proteins in gel-based foods.
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Globulinas , Phaseolus , Calor , Proteínas de Plantas/química , Globulinas/química , Verduras , Geles/químicaRESUMEN
BACKGROUND: Immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by the destruction of the platelets resulting from autoimmune recognition and subsequent attack. Heat shock proteins (HSPs) are directly associated with progression and pathogenesis in some specific autoimmune diseases. The aim of this study was to investigate the serum expression of HSP-70 in ITP children and healthy controls. MATERIALS AND METHODS: A total of 86 children aged 1-6 years were enrolled in the study. The participants were divided into 20 newly diagnosed ITP (ndITP), 34 chronic ITP (cITP) patients and 32 healthy children. The white blood cells and platelet counts were determined and compared between the groups. HSP-70 serum levels were analyzed by sandwich ELISA. Data analysis was done using SPSS and the data variables assessment was done through histogram, probability plots and Shapiro-Wilk tests to determine normal distribution. RESULTS: The white blood cell counts were 8.9 (4.2-10.4) for new diagnosis ITP, 7.1(3.9-11.9) for the chronic ITP group and 7.0 (4.3-9.5) for the healthy controls. The platelet counts were significantly increased in the chronic ITP group, 83.5(31.7-297) compared to the ndITP group 27.4 (3.7-63.7), but significantly lower compared to the healthy controls 271(172-462) (P = 0.0009). There were significantly increased HSP-70 serum levels in cITP patients compared to the ndITP and the healthy group. In addition, there was a positive correlation between the serum HSP-70 level and the thrombocyte counts among the ITP children. CONCLUSIONS: HSP-70 has a role in the progression of childhood ITP. Increased HSP-70 level is associated with the severity of childhood primary ITP.
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Púrpura Trombocitopénica Idiopática , Trombocitopenia , Niño , Humanos , Púrpura Trombocitopénica Idiopática/diagnóstico , Proteínas HSP70 de Choque Térmico , Recuento de Plaquetas , Plaquetas/patologíaRESUMEN
Panda bean protein isolate (PDPI), a legume-protein with Chinese characteristics, was investigated as an alternative potential food protein source. The physicochemical characteristics, functional properties and amino-acid composition of PDPI were determined and compared with soybean (SPI) and pea protein isolate (PPI). Results showed that PDPI was rich in phaseolin (mainly 7S vicilin), and its molecular weight was lower than that of SPI and PPI which were rich in legumin and vicilin. In comparison to SPI and PPI, PDPI showed the lowest solubility, surface-charge and surface-tension at pH 3.0, 7.0 and 9.0, but it exhibited comparable or even superior functionalities, especially in emulsifying and foaming abilities, gelling behaviour, rheological and textural properties. Moreover, the amino-acid composition and protein efficiency ratio of PDPI were excellent. The knowledge gained in the study is expected to provide reliable scientific science data for the potential application of PDPI in the food industry.
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Fabaceae , Proteínas de Guisantes , Vigna , Aminoácidos , Fabaceae/química , Solubilidad , Tensión Superficial , VerdurasRESUMEN
The roles of panda bean protein amyloid fibrils (PDPF) in modifying the textural and rheological properties of heat-induced pea protein isolate (PPI) gels were investigated. It was found that the incorporation of PDPF significantly enhanced (p < 0.05) the strength of PPI gel. This effect was PDPF concentration-dependent and was predominantly attributable to the enhanced intermolecular interactions between PDPF and PPI through hydrogen bonds and hydrophobic interactions. Synchronously, the non-network proteins content in PPI-PDPF gels decreased from 23.6 % to 6.6 % when PDPF concentration increased from 0 to 1.50 % (w/w). Cryo-scanning electron microscopy proved that PDPF was filled in the PPI gel network leading to more compact and interconnected gel structure. However, the water holding capacity and secondary structures of PPI gel were not significantly affected. The findings of this study showed that PDPF was effective in improving the PPI gel functional quality, which provided scientific support for PDPF as a promising gel ingredient in food industrial applications.
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Amiloide , Proteínas de Guisantes , Calor , Coloides , GelesRESUMEN
Congenital heart disease (CHD) is a common cardiac disorder in humans. Despite many advances in the understanding of CHD and the identification of many associated genes, the fundamental etiology for the majority of cases remains unclear. The planar cell polarity (PCP) signaling pathway, responsible for tissue polarity in Drosophila and gastrulation movements and cardiogenesis in vertebrates, has been shown to play multiple roles during cardiac differentiation and development. The disrupted function of PCP signaling is connected to some CHDs. Here, we summarize our current understanding of how PCP factors affect the pathogenesis of CHD.
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Polaridad Celular/genética , Gastrulación/genética , Cardiopatías Congénitas/genética , Corazón/crecimiento & desarrollo , Vía de Señalización Wnt , Animales , Drosophila melanogaster/citología , Drosophila melanogaster/embriología , Drosophila melanogaster/genética , Humanos , Morfogénesis/genéticaRESUMEN
UNLABELLED: Hyper IgE syndrome (HIES) is a rare primary immunodeficiency disorder, characterized by eczema, recurrent skin and lung infections, and significantly elevated serum IgE level. It was previously diagnosed based on clinical manifestations and laboratory markers that were not specific to the disease. Recent studies have demonstrated that mutations in signal transducer and activator of transcription 3 (STAT3) cause the autosomal dominant or sporadic HIES, which make the disease definitively characterized at molecular level. Here, we reported a 3-year old Chinese boy with neonatal-onset rash and multiple serious Staphylococcus aureus infections including recurrent skin abscesses, liver abscess, sepsis, and destructive pulmonary infection (pneumonia, multiple pulmonary abscesses, pyopneumothorax, and finally, pneumatocele). Genetic study revealed a heterozygous mutation in exon 21 of STAT3 gene (g.66583 A > C, c.1970A > C) in the boy, which resulted in a substitution of tyrosine at the amino acid position 657 to serine (p.Y657S) in the Src homology 2 (SH2) domain of STAT3. Functional prediction with bioinformatics programs of the Sorting Intolerant from Tolerant (SIFT) and the Polymorphism Phenotyping (PolyPhen) reported "deleterious (SIFT score 0.02)" and "probably damaging (PSIC score difference 2.94)" values, respectively. Further study of family members revealed that neither his parents, nor his twin brother carried the mutation, indicating the mutation was likely to occur de novo in our patient. CONCLUSION: The mutation,p.Y657S,in SH2 domain of STAT3 is a disease-causing mutation in the boy with HIES.
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Enfermedades en Gemelos/genética , Síndrome de Job/genética , Mutación Puntual , Factor de Transcripción STAT3/genética , Preescolar , Análisis Mutacional de ADN , Heterocigoto , Humanos , Síndrome de Job/complicaciones , Síndrome de Job/diagnóstico , Enfermedades Pulmonares/etiología , Masculino , Infecciones Estafilocócicas/etiología , Gemelos DicigóticosRESUMEN
Naturally-sourced oligoguluronate (GB) has Ca-binding ability and can be employed to modulate Ca-dependent gels. Here soy protein isolate (SPI) gel was used as a model to investigate the influence of GB on the microstructure and properties of Ca-dependent food gels. The results showed that GB significantly decreased the storage modulus (G'), mechanical strength, elasticity, hardness and chewiness of SPI gels. Among all samples, the gel containing 30 mM GB showed the most compact network structure and thus the highest water holding capacity of 77.5 %. It should be noted that Ca-GB dimers were beneficial to the gel formation and can modify the gel properties but have no impact on the gelation kinetics. The findings gained in this study confirmed the great potential of GB in modulating the structure and properties of Ca-dependent gels, thereby obtaining food products with desired characteristics (e.g., soft and brittle tofu).
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Calcio/química , Geles/química , Ácido Glucurónico/química , Proteínas de Soja/química , Agua/química , ReologíaRESUMEN
BACKGROUND: Limited research has been conducted to address stroke etiology in young patients in developing countries. We aimed to analyze risk factors and etiology of ischemic stroke (IS) in young patients of northeast China. METHODS: We retrospectively analyzed ischemic stroke patients aged 15-49 years in a single-center study from January 2013 to December 2017. Demographics and clinical information, including imaging studies, were retrieved for all patients. Patients were first compared according to sex and age. They were then divided into the first-ever and recurrent stroke groups; risk factors and stroke etiology between the two groups were compared. RESULTS: Of the 956 patients (median age 45 years) included, 78.9% were males. The most frequent risk factors were hypertension (60.0%), dyslipidemia (55.3%), smoking (54.1%), and alcohol consumption (49.6%). The most common etiology of stroke was large-artery atherosclerosis (LAA, 43.7%). In total, 789 patients experienced first-ever stroke and 167 patients experienced recurrent stroke. Recurrent stroke patients more often suffered from hypertension (70.7% versus 57.8%, P=0.002), diabetes (35.3% versus 24.8%, P=0.005), and coronary heart disease (10.2% versus 5.1%, P=0.011), and were less likely to be smokers (44.3% versus 56.1%, P=0.005) and consume alcohol (38.3% versus 52.0%, P=0.001). Recurrent strokes were more frequently caused by LAA (42.1% versus 52.5%, P=0.026) and less often by small-vessel disease (40.9% versus 29.9%, P=0.008). CONCLUSIONS: LAA is the most common etiology in Chinese young stroke patients, especially in those with recurrent stroke. Our data highlight the need of screening of LAA and prevention and management of conventional stroke risk factors in young people of China.
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To improve sustained-release property, stability and bioavailability of anthocyanins (ACNs) in vitro, we fabricated the nanocomplexes with chitosan hydrochloride (CHC), carboxymethyl chitosan (CMC) and ß-Lactoglobulin (ß-Lg). Response surface methodology (RSM) combined with desirability function was employed to optimize ACNs-loaded chitosan/ß-Lg (CHC/CMC expressed with chitosan) nanocomplexes with maximum anthocyanins retention rate, preferred particle size and high encapsulation efficiency. The result suggested that the optimized conditions were 5.16â¯mg/mL of ß-Lg, 1.45â¯mg/mL of CMC and 6.09 of pH CMC solution. Based on optimized conditions, anthocyanins retention rate, particle size and encapsulation efficiency of ACNs-loaded chitosan/ß-Lg nanocomplexes were 68.9%, 91.71â¯nm and 69.33%, respectively. ACNs-loaded chitosan/ß-Lg nanocomplexes was more stable in simulated gastric fluid (SGF, pHâ¯1.2) and simulated intestinal fluid (SIF, pHâ¯6.8) by showing less ACNs release (%) than that ACNs solution and ACNs-loaded CHC/CMC nanocomplexes. Further, stability and bioavailability of ACNs in simulated gastrointestinal (GI) tract were significantly improved by nanocomplexes encapsulation. Compared with ACNs-loaded CHC/CMC nanocomplexes, ACNs-loaded chitosan/ß-Lg nanocomplexes displayed better sustained ACNs release, stability and bioavailability.
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Antocianinas/química , Quitosano/química , Estabilidad de Medicamentos , Lactoglobulinas/química , Antocianinas/farmacología , Disponibilidad Biológica , Quitosano/análogos & derivados , Portadores de Fármacos/química , Tracto Gastrointestinal/metabolismo , Técnicas In Vitro , Nanopartículas/química , Tamaño de la PartículaRESUMEN
BACKGROUND: This study aimed to explore the physiological functions that were significantly affected by the exercise training. METHODS: Microarray dataset of GSE53598 was downloaded and preprocessed to identify the differentially expressed genes (DEGs) between pre- and post-exercise muscle biopsies. Then hierarchical clustering, protein-protein interaction (PPI) network construction and functional enrichment analysis were conducted. Finally, the significant physiological functions were identified using logistic regression algorithm. RESULTS: Total 420 up- and 420 down-regulated DEGs were identified. DEGs including E2F transcription factor 6, hypocretin (Orexin) neuropeptide precursor, caveolin 1, platelet-derived growth factor beta polypeptide, and transforming growth factor, beta 1 had higher degree in the PPI network. Functions related to blood vessel development, regulation of cell migration, negative regulation of gene expression, and negative regulation of metabolic process changed significantly after exercise. CONCLUSIONS: Functions related to blood vessel development, regulation of cell migration, negative regulation of gene expression and negative regulation of metabolic process may be closely associated with exercising.
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Biología Computacional/métodos , Ejercicio Físico/fisiología , Músculo Esquelético/fisiología , Regulación hacia Abajo , Expresión Génica , HumanosRESUMEN
MicroRNAs (miRNAs) are a class of small endogenous RNAs that play important regulatory roles in cells by negatively affecting gene expression at both transcriptional and post-transcriptional levels. There have been extensive studies aiming to identify miRNAs and to elucidate their functions in various plant species. In the present study, we employed the high-throughput sequencing technology to profile miRNAs in blueberry fruits. A total of 9,992,446 small RNA tags with sizes ranged from 18 to 30 nt were obtained, indicating that blueberry fruits have a large and diverse small RNA population. Bioinformatic analysis identified 412 conserved miRNAs belonging to 29 families, and 35 predicted novel miRNAs that are likely to be unique to blueberries. Among them, expression profiles of five conserved miRNAs were validated by stem loop qRT-PCR. Furthermore, the potential target genes of conserved and novel miRNAs were predicted and subjected to Gene Ontology (GO) annotation. Enrichment analysis of the GO-represented biological processes and molecular functions revealed that these target genes were potentially involved in a wide range of metabolic pathways and developmental processes. Particularly, anthocyanin biosynthesis has been predicted to be directly or indirectly regulated by diverse miRNA families. This study is the first report on genome-wide miRNA profile analysis in blueberry and it provides a useful resource for further elucidation of the functional roles of miRNAs during fruit development and ripening.
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The optimal preparation parameters to create anthocyanin-loaded chitosan nanoparticles was predicted using response surface methodology (RSM). A Box-Behnken design was used to determine the preparation parameters that would achieve the preferred particle size and high encapsulation efficiency. The result suggested that the optimized conditions were 2.86mg/mL carboxymethyl chitosan (CMC), 0.98mg/mL chitosan hydrochloride (CHC) and 5.97mg anthocyanins. Using the predicted amounts, the experimentally prepared particles averaged 219.53nm with 63.15% encapsulation efficiency. The result was less than 5% different than the predicted result of 214.83nm particle size and 61.80% encapsulation efficiency. Compared with the free anthocyanin solution, the anthocyanin-loaded chitosan nanoparticles showed a slowed degradation in simulated gastrointestinal fluid. Compared with the free anthocyanin solutions in a model beverage system, the stability of the anthocyanins was increased in the anthocyanin-loaded chitosan nanoparticles.
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Antocianinas/metabolismo , Quitosano/análogos & derivados , Quitosano/química , Portadores de Fármacos/química , Nanopartículas , Bebidas , Líquidos Corporales , Tracto Gastrointestinal , Humanos , Tamaño de la PartículaRESUMEN
Glucocorticoid (GC) resistance in children with acute lymphoblastic leukemia (ALL) usually resulted in the failure of treatment. Exploring new agents to overcome GC resistance is important. Here we reported for the first time that low-dose anisomycin has the potential to sensitize GC-resistant T-ALL CEM-C1 cells to dexamethasone (DEX). Compared with the use of DEX or low-dose anisomycin alone, co-treatment with them resulted in a significant increase of growth inhibition, apoptosis and cell cycle arrest in CEM-C1 cells through induction of activated caspase-3 and up-regulation of Bim, p21and p27, and down-regulation of Mcl-1, Bcl-2, c-myc, cyclin A and cyclin D1. Furthermore, co-treatment remarkably activated glucocorticoid receptor (GR), p38-MAPK and JNK, and all of them were canceled only by the GR inhibitor RU486, indicating GR might be an at the upstream of GR-p38-MAPK/JNK pathway. We conclude that low-dose anisomycin sensitizes GC-resistant CEM-C1 cells to DEX and this effect is mediated, at least in part, by activation of the GR-p38-MAPK/JNK signaling pathway.
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Anisomicina/farmacología , Apoptosis/efectos de los fármacos , Dexametasona/farmacología , Resistencia a Antineoplásicos , Glucocorticoides/farmacología , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Leucemia-Linfoma Linfoblástico de Células T Precursoras/metabolismo , Receptores de Glucocorticoides/agonistas , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Anisomicina/administración & dosificación , Puntos de Control del Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Humanos , Transducción de Señal/efectos de los fármacosRESUMEN
Although glucocorticoids (GCs) have been used to treat acute lymphoblast leukemia (ALL) for decades, the mechanisms of GC sensitivity and resistance in ALL cells are poorly understood. This study investigated the role and mechanisms of pro-apoptotic protein BIM in apoptosis of GC-sensitive and- resistant ALL cells. The dramatic apoptosis was observed in GC-sensitive CEM-C7 cells after incubated with DEX for 48 h, while not in GC-resistant CEM-C1 cells. The significant up-regulation of BIM in CEM-C7 cells induced by DEX was also observed, but no up-regulation of BIM was detected in DEX-induced CEM-C1 cells. When treated with DEX plus RU486, a glucocorticoid receptor blocker, the apoptosis and BIM expression of CEM-C7 cells were canceled. P38MAPK-blocking pharmacon SB203580 also significantly inhibited the up-regulation of BIM in CEM-C7 cells. These suggested that the absence of BIM up-regulation is one of the important mechanisms of GC resistance, GC-GR conjugation is indispensible in both GC-induced apoptosis and up-regulation of BIM, and p38 MAPK signal pathway is also involved in this process.