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1.
Medicine (Baltimore) ; 98(34): e16957, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31441896

RESUMO

BACKGROUND: Atopic dermatitis (AD), also called eczema, is one of the most familiar chronic diseases in childhood. A possible pathological mechanism is immune dysfunction resulting in IgE sensitization to allergens. The recent studies demonstrated that the immune system can be affected by probiotics or prebiotics. However, the effectiveness and safety of probiotics or prebiotics on prevention of eczema are still unclear. To investigate this question, we conduct a systematic review and meta-analysis. METHODS: The protocol followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols. Four main databases (PubMed, Embase, the Cochrane Library, and the web of science) will be searched dating until 15 July 2019 for randomized controlled trials investigating the effects and safety of probiotics or prebiotics on prevention of eczema in children with no language restrictions. In addition, a manual search of the references of relevant published studies will also be considered.Studies selection, data extraction, and risk of bias assessment will be conducted by two independent reviewers. The primary outcome is the incidence of eczema. The second outcome is adverse events. The duration of intervention, the timing of intervention and intervention organism will be taken into consideration. RESULTS: The results will provide useful information about the effect and safety of probiotics or prebiotics on reducing the incidence of eczema in children. CONCLUSION: The findings of this study will be published in a peer-reviewed journal.PROSPERO registration number: CRD42019136528.


Assuntos
Dermatite Atópica/prevenção & controle , Eczema/prevenção & controle , Probióticos/administração & dosagem , Adulto , Criança , Feminino , Humanos , Masculino , Metanálise como Assunto , Gravidez , Ensaios Clínicos Controlados Aleatórios como Assunto , Revisão Sistemática como Assunto
2.
Brain Behav ; 9(6): e01290, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31007001

RESUMO

OBJECTIVES: Proinflammatory cytokines triggered by surgery and postoperative pain are major causes of postoperative delirium (POD). This study investigated the effects of flurbiprofen axetil on POD when used for postoperative analgesia after major noncardiac surgery in elderly patients. METHODS: Patients over 65 years old were randomly divided into two groups: the sufentanil group (S group), in which 150 µg of sufentanil was used in the patient-controlled analgesia (PCA) pump for 3 days; the sufentanil combined with flurbiprofen axetil group (SF group), in which 150 µg of sufentanil was combined with 300 mg of flurbiprofen axetil in the PCA pump for 3 days. The Confusion Assessment Method scale was used for POD evaluation. The pain intensity, side effects, and risk factors (age, gender, surgical position, and category of surgery) for POD were evaluated. RESULTS: Ultimately, 140 patients were included. The overall incidence of POD was not significantly different between the S and SF groups. The incidence of POD was significantly lower in the SF group than in the S group among patients over 70 years (5.1% vs. 20.7%, p = 0.045, odds ratio = 0.146, 95% confidence interval = 0.020-1.041). The incidence of POD was no difference in patients classified by the category of surgery, surgical position, or gender between groups. Sufentanil and flurbiprofen axetil in the PCA pump was completely used within 72 hr. The pain intensity, consumed sufentanil dosage of the PCA, and the side effects was not different between groups. CONCLUSIONS: Flurbiprofen axetil might reduce POD in patients over 70 years undergoing major noncardiac surgery.

3.
Fish Physiol Biochem ; 45(4): 1393-1407, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30989456

RESUMO

Probiotic is well known because of its health benefit on the host, including improve growth, treat disease, and enhance immunity. Currently, probiotic has been widely used in aquaculture. However, there is little information about the effect of probiotic on turbot. Therefore, an effort was made to explore the effect of a multi-strain probiotic on growth performance, non-specific immune response, and intestinal health of juvenile turbot, Scophthalmus maximus L. One hundred eighty juvenile turbot (20.04 ± 0.23 g) were randomly divided into three groups (T0, T1, T2), and fed diet were formulated to contain 0%, 1%, and 5% multi-strain probiotic, respectively. Sixty days after the feeding experiment, the growth performance, body composition, enzyme activities, and intestinal microorganism of turbot were analyzed. T2 and T1 showed better growth performance and significant higher (P < 0.05) enzyme activities than T0 (except lysozyme). Moreover, the IV (intestinal villus), IW (intestinal wall), and GC (goblet cell) were well modulated in probiotic treatments. Furthermore, Lactobacillus was found colonized in the intestine of the group fed with 5% multi-strain probiotic. These results suggested adding dietary multi-strain probiotic could positively affect for turbot aquaculture.

4.
Ann Bot ; 123(7): 1179-1189, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-30916314

RESUMO

BACKGROUND AND AIMS: Differences in local abundance and ploidy level are predicted to impact the direction of introgression between species. Here, we tested these hypotheses on populations of Betula albosinensis (red birch) and Betula platyphylla (white birch) which were thought to differ in ploidy level, the former being tetraploid and the latter diploid. METHODS: We sampled 391 birch individuals from nine localities in China, and classified them into species based on leaf morphology. Twelve nuclear microsatellite markers were genotyped in each sample, and analysed using principal coordinates analysis and STRUCTURE software. We compared the effects of two different methods of scoring polyploid genotypes on population genetic analyses. We analysed the effect of ploidy, local species abundance and latitude on levels of introgression between the species. KEY RESULTS: Leaf morphology divided our samples into red and white birch, but genetic analyses unexpectedly revealed two groups within red birch, one of which was tetraploid, as expected, but the other of which appeared to have diploid microsatellite genotypes. Five individuals were identified as early-generation hybrids or backcrosses between white birch and red birch and five were identified between red birch and 'diploid' red birch. Cline analysis showed that levels of admixture were not significantly correlated with latitude. Estimated genetic differentiation among species was not significantly different between determined tetraploid and undetermined tetraploid genotypes. CONCLUSIONS: Limited hybridization and gene flow have occurred between red birch and white birch. Relative species abundance and ploidy level do not impact the direction of introgression between them, as genetic admixture is roughly symmetrical. We unexpectedly found populations of apparently diploid red birch and this taxon may be a progenitor of allotetraploid red birch populations. Incomplete lineage sorting may explain patterns of genetic admixture between apparently diploid and allotetraploid red birch.

5.
Exp Cell Res ; 379(1): 65-72, 2019 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-30898547

RESUMO

Olfactory ensheathing cells (OECs) are ideal candidates for cell-based therapies aimed at repairing spinal cord injury (SCI). Accurate targeting of OECs to the lesion site is critical to reconstructing the impaired nervous system. However, the key factors guiding the homing of transplanted OECs to the damaged area after SCI are still unclear. Here, we demonstrate that lysophosphatidic acid (LPA) can significantly facilitate the homing of OECs after SCI in rats. First, we found that OECs exhibited a robust chemotaxis response to LPA in vitro, with LPAR1 being predominant receptor expressed on OECs. We further found that ß-catenin signaling plays an important role in LPA-induced OEC migration. Moreover, silencing LPAR1 not only abolished the migration of OECs but also prevented ERK1/2 phosphorylation and ß-catenin activation, suggesting that LPAR1 ligation serves to activate the ERK1/2 and ß-catenin pathways in LPA-induced OEC chemotactic migration. Finally, cell transplantation experiments confirmed that endogenous LPA, which was observed to be produced at the lesion site after SCI in rat, is a key chemokine that facilitates OEC migration to the injury center. Collectively, our data provide a further description of the homing effects of LPA and a mechanism by which transplanted OECs migrate to the injured area after SCI in rats.

6.
PLoS One ; 14(3): e0212636, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30840647

RESUMO

The determination of the weights of decision makers (DMs) is an important problem in multi-attribute group decision making. Many approaches have been presented to determine DMs' weights. However, the computed weight vectors of DMs are usually assumed to be constant in existing studies, and this may cause irrationalities in the decision results. Therefore, this article proposes a novel method to determine DMs' weights based on variable weights theory in which the evaluation information is described as intuitionistic fuzzy sets (IFSs). First, DMs provide their assessment with IFSs, and the intuitionistic fuzzy weighted averaging (IFWA) operator is applied to obtain weighted decision matrix based on the prior given DMs' and attributes' weights. Second, the DMs' weights are obtained based on variable weights theory, and an alternative decision can be computed. Finally, the converted value of the achieved IFS of each alternative is calculated, and the best appropriate alternative is acquired. Two illustrative examples and the comparisons with exsiting approaches are also used to reflect the effectiveness of the proposed approach.

7.
Artigo em Inglês | MEDLINE | ID: mdl-30528703

RESUMO

A 30-days feeding trail was conducted to determine the sensitivity of Carassius auratus to the toxicological effects of elevated dietary Selenomethionine (Se-Met). C. auratus averaging 23.56 ±â€¯1.82 g were exposed to four Se-Met concentrations (mg Se/kg): 0 (Se-Met0), 5 (Se-Met5), 10 (Se-Met10) and 20 (Se-Met20) to estimate the effects on tissue selenium (Se) accumulation, blood biochemical profiles, transcript expression and intestinal microbiota. Se accumulated in the kidney, liver and muscle in a dose-dependent manner and followed this order: kidney > liver > muscle, the highest accumulation were obtained in kidney of Se-Met20 diet after 30 days of feeding. Serum contents of alanine transaminase (ALT), aspartate transaminase (AST) and alkaline phosphatase (ALP) in fish exposed to Se-Met20 group was significantly highest among Se-Met exposure groups. Hydrogen peroxide (H2O2) concentrations in liver were affected by dietary Se-Met exposures. Liver contents of total antioxidant capacity (TAC), catalase (CAT), glutathione peroxidase (GPx) and malondialdehyde (MDA) in fish exposure to Se-Met5 group was significantly highest among Se-Met exposure groups. Growth hormone receptor (GHR), insulin-like growth factor 1 (IGF-1) and antioxidant enzyme related genes including glutathione peroxidase (GPx), catalase (CAT) and glutathione S-transferase (GST) expression in liver were down-regulated with the concentration of Se-Met exposure groups. The results of high-throughput sequencing showed that gut microbial communities and hierarchy cluster heatmap analysis were significantly affected by Se-Met exposure. The abundances of Cetobacterium and Vibrio increased while fish exposed to Se-Met20 group. The abundance of Ralstonia increased when the Se-Met exposure dose reached 10 mg Se kg-1. The results suggested that the exposure to elevated dietary Se-Met may result toxic effects in C. auratus.


Assuntos
Microbioma Gastrointestinal/efeitos dos fármacos , Carpa Dourada/sangue , Selenometionina/farmacocinética , Ração Animal , Animais , Antioxidantes/metabolismo , Dieta/veterinária , Regulação da Expressão Gênica/efeitos dos fármacos , Carpa Dourada/metabolismo , Carpa Dourada/microbiologia , Peróxido de Hidrogênio , Fator de Crescimento Insulin-Like I/genética , Fator de Crescimento Insulin-Like I/metabolismo , Malondialdeído/metabolismo , Receptores da Somatotropina/genética , Receptores da Somatotropina/metabolismo , Selenometionina/farmacologia
8.
Biomed Pharmacother ; 110: 818-824, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30554120

RESUMO

INTRODUCTION: It has been demonstrated HOE-642 ameliorates ischemic contracture, prevents post-resuscitation diastolic dysfunction, and favors the earlier return of contractile function. This study is the first report to explore the optimal dose of HOE-642 in protecting the neuronal mitochondrial function after cardiac arrest. METHODS: Cardiac arrest was induced by 8 min asphyxia in rats. There were Sham (S), Normothermic (NORM), and Hypothermic (HYPO) groups. The NORM or HYPO groups consist of four subgroups: NORM/HYPO + HOE-642 0, 1, 3, and 5 mg/kg. Survival and NDS were evaluated after 24 h of resuscitation. ΔΨm, mitochondrial swelling, ROS production, and mitochondrial complex IIV activity of the hippocampus were detected. RESULTS: Survival in the HYPO + 1 mg group was the best and significantly higher than in the NORM + 0 mg and NORM + 1 mg groups. NDS in the HYPO + 0 mg, HYPO + 1 mg, and HYPO + 3 mg groups was significantly lower than in the NORM + 0 mg group. ΔΨm in the NORM + 1 mg (n = 5) group was significantly higher than in the NORM + 0 mg (n = 8), NORM + 3 mg (n = 5), and NORM + 5 mg (n = 5) groups. The ROS production in the NORM + 1 mg and NORM + 3 mg groups were significantly lower than in the NORM + 0 mg and NORM + 5 mg groups. Complex I and III activities in the HYPO + 1 mg (n = 5) group were significantly higher than in the HYPO + 3 mg (n = 5), and HYPO + 5 mg (n = 5) groups. Complex II and IV activities in the NORM + 3 mg and HYPO + 3 mg groups were significantly higher than in the NORM + 0 mg, NORM + 1 mg, and HYPO + 0 mg (n = 4)groups. CONCLUSIONS: HOE-642 1 or 3 mg/kg showed benefits compared to HOE-642 5 mg/kg used when initiating resuscitation. When combined with hypothermia after cardiac arrest, HOE-642 1 or 3 mg/kg improved survival and neurological function compared with hypothermia or HOE-642 alone, however, HOE-642 5 mg/kg plus hypothermia did not.


Assuntos
Antiarrítmicos/uso terapêutico , Cardiotônicos/uso terapêutico , Guanidinas/uso terapêutico , Parada Cardíaca/prevenção & controle , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Sulfonas/uso terapêutico , Animais , Antiarrítmicos/farmacologia , Cardiotônicos/farmacologia , Relação Dose-Resposta a Droga , Guanidinas/farmacologia , Parada Cardíaca/metabolismo , Parada Cardíaca/patologia , Masculino , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Neurônios/metabolismo , Neurônios/patologia , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/antagonistas & inibidores , Espécies Reativas de Oxigênio/metabolismo , Sulfonas/farmacologia
9.
PLoS Genet ; 14(9): e1007640, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30248107

RESUMO

Hair plays an important role in primates and is clearly subject to adaptive selection. While humans have lost most facial hair, eyebrows are a notable exception. Eyebrow thickness is heritable and widely believed to be subject to sexual selection. Nevertheless, few genomic studies have explored its genetic basis. Here, we performed a genome-wide scan for eyebrow thickness in 2961 Han Chinese. We identified two new loci of genome-wide significance, at 3q26.33 near SOX2 (rs1345417: P = 6.51×10-10) and at 5q13.2 near FOXD1 (rs12651896: P = 1.73×10-8). We further replicated our findings in the Uyghurs, a population from China characterized by East Asian-European admixture (N = 721), the CANDELA cohort from five Latin American countries (N = 2301), and the Rotterdam Study cohort of Dutch Europeans (N = 4411). A meta-analysis combining the full GWAS results from the three cohorts of full or partial Asian descent (Han Chinese, Uyghur and Latin Americans, N = 5983) highlighted a third signal of genome-wide significance at 2q12.3 (rs1866188: P = 5.81×10-11) near EDAR. We performed fine-mapping and prioritized four variants for further experimental verification. CRISPR/Cas9-mediated gene editing provided evidence that rs1345417 and rs12651896 affect the transcriptional activity of the nearby SOX2 and FOXD1 genes, which are both involved in hair development. Finally, suitable statistical analyses revealed that none of the associated variants showed clear signals of selection in any of the populations tested. Contrary to popular speculation, we found no evidence that eyebrow thickness is subject to strong selective pressure.

10.
J Ophthalmol ; 2018: 7397610, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29850212

RESUMO

Purpose: To examine the difference in the vitreal protein profiles of patients with proliferative diabetic retinopathy (PDR) with and without preoperative intravitreal conbercept (IVC) treatment. Methods: Liquid chromatography-tandem mass spectrometry- (LC-MS/MS-) based proteomic methods were used to determine the protein profiles of the vitreous humor in patients with PDR treated with (IVC group; n = 9) and without (PDR group; n = 8) preoperative IVC. Gene ontology (GO) annotation and REACTOME pathway analysis were obtained to overview differentially expressed proteins between each group. Intravitreal levels of apolipoprotein A-II (APOA2) and ceruloplasmin (CP) were measured using enzyme-linked immunosorbent assays. Results: 307 proteins were expressed differentially between PDR and IVC groups, including 218 proteins downregulated in response to IVC. The most notable GO annotations in level 3 and REACTOME pathways describing the differentially expressed proteins were "innate immune response" and "platelet degranulation." The intravitreal levels of APOA2 and CP were lower in the IVC group than in the PDR group (p < 0.01). Conclusions: In addition to decreasing the intravitreal vascular endothelial growth factor level, IVC may alter the vitreal protein profile in patients with PDR, with the differentially regulated proteins involved in the immune response, platelet degranulation, complement activation, and inflammation.

11.
Bull Environ Contam Toxicol ; 100(5): 683-689, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29541817

RESUMO

Triplicate groups of sea cucumbers (4.83 ± 0.15 g) were exposed to one of the four nominal concentrations of dietary mercury [0 (control), 67.6, 338, and 676 mg/kg dry weight, and actually total mercury were 17.55, 87.00, 275.50, 468.50 mg/kg, respectively; Table 3] for 21 days. Mercury accumulation in the intestine showed the greatest mercury burden (77.96 ± 1.20 mg Hg/kg tissue wet weight basis). However, survival rate (SR) was not affected. Body weight gain after the 676 mg Hg/kg treatment was significantly lower than the control group. The feed conversion rate of the 676 mg Hg/kg treatment group was significantly higher than the control group. Additionally, the superoxide dismutase (SOD) and total antioxidant capacity (T-AOC) of sea cucumbers decreased as the mercury dose increased. SOD, T-AOC and alkaline phosphatase of the 676 mg Hg/kg treatment group were significantly lower than the control group. However, there were no significant differences between the four groups in acid phosphatase and catalase (CAT) activity.


Assuntos
Mercúrio/toxicidade , Stichopus/fisiologia , Poluentes Químicos da Água/toxicidade , Fosfatase Alcalina/metabolismo , Animais , Antioxidantes/metabolismo , Dieta , Exposição Dietética , Imunidade Inata , Intestinos , Mercúrio/metabolismo , Pepinos-do-Mar , Stichopus/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Poluentes Químicos da Água/metabolismo
12.
Plant Physiol ; 176(3): 2292-2304, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-29431631

RESUMO

Through natural or human selection, many fleshy fruits have evolved vivid external or internal coloration, which often develops during ripening. Such developmental changes in color are associated with the biosynthesis of pigments as well as with degreening through chlorophyll degradation. Here, we demonstrated that natural variation in the coding region of the gene ETHYLENE RESPONSE FACTOR17 (ERF17) contributes to apple (Malus domestica) fruit peel degreening. Specifically, ERF17 mutant alleles with different serine (Ser) repeat insertions in the coding region exhibited enhanced transcriptional regulation activity in a dual-luciferase reporter assay when more Ser repeats were present. Notably, surface plasmon resonance analysis showed that the number of Ser repeats affected the binding activity of ERF17 to the promoter sequences of chlorophyll degradation-related genes. In addition, overexpression of ERF17 in evergreen apples altered the accumulation of chlorophyll. Furthermore, we demonstrated that ERF17 has been under selection since the origin of apple tree cultivation. Taken together, these results reveal allelic variation underlying an important fruit quality trait and a molecular genetic mechanism associated with apple domestication.

13.
Molecules ; 24(1)2018 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-30597911

RESUMO

Berberine has many pharmacological effects, such as antidiabetic, antimicrobial, anti-inflammatory, and antioxidant, but the question remains on how its low oral bioavailability has greatly limited its clinical application. As a safer hypoglycemic agent, we must evaluate the bioavailability of berberine organic acid salts (BOAs) to ensure that the bioavailability of berberine is not negatively affected. It has been proven that the bioavailability of BOAs is higher than that of BH (berberine hydrochloride); especially BF (berberine fumarate) and BS (berberine succinate), which are improved by 1.278-fold and 1.313-fold, respectively. After 1 h of oral administration, berberine mainly acted on the stomach of mice, it also influenced the liver, kidney, lungs, and intestines after 4 h. The accumulation of BF in the lung is more evident than BH. Our analysis shows that these results are closely related to the regulation of organic acids and berberine in the intestinal tract, they also indicate the influence of intestinal flora on berberine metabolism.


Assuntos
Berberina/química , Berberina/farmacologia , Hipoglicemiantes/química , Hipoglicemiantes/farmacologia , Sais , Administração Oral , Animais , Berberina/administração & dosagem , Berberina/farmacocinética , Disponibilidade Biológica , Cromatografia Líquida de Alta Pressão , Diabetes Mellitus Experimental , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/administração & dosagem , Hipoglicemiantes/farmacocinética , Absorção Intestinal , Masculino , Camundongos , Ratos , Distribuição Tecidual
14.
Oxid Med Cell Longev ; 2018: 8930374, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30662584

RESUMO

Both alterations to the intestinal microflora and chronic systemic inflammation predispose towards type 2 diabetes (T2D). Changes in the composition of the intestinal microflora are associated with glucose metabolism changes in rats with T2D. Here, we demonstrate that a berberine fumarate (BF) has a hypoglycemic effect by regulating the intestinal microflora and metabolism of diabetic rats. The T2D rats had disorders of glucose and lipid metabolism, an abnormal intestinal microflora, fewer butyrate-producing and probiotic-type bacteria, larger numbers of potentially pathogenic and sulfate-reducing bacteria, and tissue inflammation. Administration of berberine fumarate significantly ameliorated the metabolic disorder; increased the populations of Bacteroidetes, Clostridia, Lactobacillales, Prevotellaceae, and Alloprevotella; and reduced those of Bacteroidales, Lachnospiraceae, Rikenellaceae, and Desulfovibrio. In addition, it reduced inflammation, inhibiting the overexpression of TLR4 and p-JNK and increasing the expression of PI3K, GLUT2, and other proteins, which are closely related to oxidative stress, thereby promoting the metabolism of glucose.


Assuntos
Berberina/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Estresse Oxidativo/efeitos dos fármacos , Animais , Bacteroidetes/efeitos dos fármacos , Berberina/uso terapêutico , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Fezes/microbiologia , Glucose/metabolismo , Hipoglicemiantes/uso terapêutico , Proteínas Quinases JNK Ativadas por Mitógeno/genética , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Fígado/patologia , Masculino , Fosfatidilinositol 3-Quinases/genética , Fosfatidilinositol 3-Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo
15.
Elife ; 62017 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-29027902

RESUMO

Histone tail modifications can greatly influence chromatin-associated processes. Asymmetrically modified nucleosomes exist in multiple cell types, but whether modifications on both sister histones contribute equally to chromatin dynamics remains elusive. Here, we devised a bivalent nucleosome system that allowed for the constitutive assembly of asymmetrically modified sister histone H3s in nucleosomes in Saccharomyces cerevisiae. The sister H3K36 methylations independently affected cryptic transcription in gene coding regions, whereas sister H3K79 methylation had cooperative effects on gene silencing near telomeres. H3K4 methylation on sister histones played an independent role in suppressing the recruitment of Gal4 activator to the GAL1 promoter and in inhibiting GAL1 transcription. Under starvation stress, sister H3K4 methylations acted cooperatively, independently or redundantly to regulate transcription. Thus, we provide a unique tool for comparing symmetrical and asymmetrical modifications of sister histone H3s in vivo.


Assuntos
Histonas/metabolismo , Nucleossomos/metabolismo , Processamento de Proteína Pós-Traducional , Saccharomyces cerevisiae/genética , Transcrição Genética , Regulação Fúngica da Expressão Gênica , Metilação
16.
Sci Rep ; 7(1): 10013, 2017 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-28855566

RESUMO

Directed migration of the transplanted mesenchymal stem cells (MSCs) to the lesion sites plays a pivotal role in the efficacy of cell-based therapy. Our previous study demonstrates that MSCs under varying neural differentiation states possess different migratory capacities in response to chemoattractants. However, the underlying mechanism has not been fully addressed. Herein, we show that the assembly and turnover of focal adhesions, the phosphorylation of FAK and paxillin, and the reorganisation of F-actin in MSCs are closely related to their differentiation states in response to SDF-1α. Upon SDF-1α stimulation, FAs turnover more rapidly with the most obvious reduction in the existing time of FAs in MSCs of 24-h preinduction that exhibit the most effective migration towards SDF-1α. Further, we confirm that PI3K/Akt and MAPK pathways participate in the regulation of SDF-1α-induced cell migration and FA assembly, and moreover, that the regulatory effects vary greatly depending on the differentiation states. Collectively, these results demonstrate that FA assembly and turnover, which is accompanied with F-actin reorganisation in response to SDF-1α, correlates closely with the differentiation states of MSCs, which might contribute to the different chemotactic responses of these cells, and thus help develop new strategy to improve the efficacy of MSCs-based therapy.

17.
Small ; 12(44): 6098-6105, 2016 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-27600373

RESUMO

The swimming locomotion of fish involves a complex interplay between a deformable body and induced flow in the surrounding fluid. While innovative robotic devices, inspired by physicomechanical designs evolved in fish, have been created for underwater propulsion of large swimmers, scaling such powerful locomotion into micro-/nanoscale propulsion remains challenging. Here, a magnetically propelled fish-like artificial nanoswimmer is demonstrated that emulates the body and caudal fin propulsion swimming mechanism displayed by fish. To mimic the deformable fish body for periodic shape changes, template-electrosynthesized multisegment nanowire swimmers are used to construct the artificial nanofishes (diameter 200 nm; length 4.8 µm). The resulting nanofish consists a gold segment as the head, two nickel segments as the body, and one gold segment as the caudal fin, with three flexible porous silver hinges linking each segment. Under an oscillating magnetic field, the propulsive nickel elements bend the body and caudal fin periodically to generate travelling-wave motions with speeds exceeding 30 µm s-1 . The propulsion dynamics is studied theoretically using the immersed boundary method. Such body-deformable nanofishes exhibit a high swimming efficiency and can serve as promising biomimetic nanorobotic devices for nanoscale biomedical applications.


Assuntos
Biomimética/instrumentação , Peixes/fisiologia , Fenômenos Magnéticos , Nanopartículas/química , Natação/fisiologia , Animais , Simulação por Computador , Locomoção , Nanotecnologia
18.
Eur J Cell Biol ; 95(9): 342-53, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-27377850

RESUMO

Mesenchymal stem cells (MSCs) exhibit the potential to repair a wide variety of injured adult tissues. The migration capability of MSCs is an important determinant of the efficiency of MSC transplant therapy. MicroRNAs (miRNAs) are increasingly implicated in regulating the migration of MSCs. Herein, we show that the expression of miR-124 was downregulated in rat MSCs (rMSCs) treated with hepatocyte growth factor (HGF). Overexpression of miR-124 significantly reduced the chemotactic migration of rMSCs toward HGF, while inhibition of endogenous miR-124 promoted the chemotactic migration. A further study revealed that miR-124 directly targeted FZD4 and LRP6, which encode a receptor and co-receptor of the Wnt/ß-catenin signaling pathway, respectively, thus reducing the activity of this signaling. Consistently, activation of the Wnt/ß-catenin signaling pathway by LiCl and ΔN89ß-catenin rescued the inhibitory effect of miR-124 on the chemotactic migration of rMSCs toward HGF, while inhibition of Wnt/ß-catenin signaling by FH535 abrogated the enhanced chemotactic response achieved by the miR-124 inhibitor. Collectively, our study demonstrates that miR-124 downregulates Wnt/ß-catenin signaling via targeting FZD4 and LRP6 and thus suppresses the chemotactic migration of rMSCs toward HGF.


Assuntos
Fator de Crescimento de Hepatócito/farmacologia , Células-Tronco Mesenquimais/citologia , MicroRNAs/biossíntese , Via de Sinalização Wnt/genética , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Quimiotaxia/genética , Regulação para Baixo , Células HEK293 , Humanos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/administração & dosagem , MicroRNAs/antagonistas & inibidores , MicroRNAs/genética , Ratos , Ratos Sprague-Dawley , Transfecção , Via de Sinalização Wnt/efeitos dos fármacos
19.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 47(2): 159-63, 2016 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-27263286

RESUMO

OBJECTIVE: To explore whether aspirin could sensitize arsenic trioxide on human hepatocelluar carcinoma cell line and understanding the combination mechanisms underlying co-treatment. METHODS: Cell viability was detected by MTT assay, cell apoptosis rate and reactive oxygen species (ROS) level were measured by flow cytometry, and Western blot assay was used to estimated the protein expression of heme oxygenase-1 (HO-1) in total protein and NF-E2-related factor 2 (Nrf2) in nuclear protein. RESULTS: 10 µmol/L arsenic trioxide can decreased the cell viability, while cell apoptosis rate, ROS level, HO-1 and Nrf2 protein expression was increased (P < 0.05). When compared with arsenic trioxide alone, co-treatment of arsenic trioxide with aspirin in different concentration (0, 0.1, 1.0, 2.5, 5.0 mmol/L) exhibited dual effects in intracellular ROS level, HO-1 and Nrf2 expression. Specifically, with the increasing of aspirin concentrations, the level of ROS induced by arsenic trioxide showed a rising trend after the first reduction, whereas, HO-1 and Nrf2 protein expression were decreased at first and then increased. CONCLUSION: Low concentration, less than 2.5 mmol/L, of aspirin may reduce the ROS accumulation through activating of Nrf2-HO-1 pathway, therefore decreasing the apoptotic cell death induced by arsenic trioxide. On the contrary, 5 mmol/L aspirin could increase the sensitivity of HepG2 to arsenic trioxide through enhancing the arsenic trioxide-induced apoptosis by ROS accumulation resulting in inhibiting the Nrf2-HO-1 pathway.


Assuntos
Aspirina/farmacologia , Carcinoma Hepatocelular/patologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Hepáticas/patologia , Óxidos/toxicidade , Apoptose , Trióxido de Arsênio , Arsenicais , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral/efeitos dos fármacos , Sobrevivência Celular , Citometria de Fluxo , Heme Oxigenase-1/metabolismo , Humanos , Neoplasias Hepáticas/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo
20.
FASEB J ; 30(9): 3133-45, 2016 09.
Artigo em Inglês | MEDLINE | ID: mdl-27251173

RESUMO

It has been reported that some small noncoding RNAs are involved in the regulation of insulin sensitivity. However, whether long noncoding RNAs also participate in the regulation of insulin sensitivity is still largely unknown. We identified and characterized a long noncoding RNA, regulator of insulin sensitivity and autophagy (Risa), which is a poly(A)(+) cytoplasmic RNA. Overexpression of Risa in mouse primary hepatocytes or C2C12 myotubes attenuated insulin-stimulated phosphorylation of insulin receptor, Akt, and Gsk3ß, and knockdown of Risa alleviated insulin resistance. Further studies showed that overexpression of Risa in hepatocytes or myotubes decreased autophagy, and knockdown of Risa up-regulated autophagy. Moreover, knockdown of Atg7 or -5 significantly inhibited the effect of knockdown of Risa on insulin resistance, suggesting that knockdown of Risa alleviated insulin resistance via enhancing autophagy. In addition, tail vein injection of adenovirus to knock down Risa enhanced insulin sensitivity and hepatic autophagy in both C57BL/6 and ob/ob mice. Taken together, the data demonstrate that Risa regulates insulin sensitivity by affecting autophagy and suggest that Risa is a potential target for treating insulin-resistance-related diseases.-Wang, Y., Hu, Y., Sun, C., Zhuo, S., He, Z., Wang, H., Yan, M., Liu, J., Luan, Y., Dai, C., Yang, Y., Huang, R., Zhou, B., Zhang, F., Zhai, Q. Down-regulation of Risa improves insulin sensitivity by enhancing autophagy.


Assuntos
Autofagia/fisiologia , Regulação para Baixo/fisiologia , Regulação da Expressão Gênica/fisiologia , Resistência à Insulina/fisiologia , RNA Longo não Codificante/metabolismo , Animais , Técnicas de Silenciamento de Genes , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Obesos , RNA Longo não Codificante/genética
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