RESUMEN
Recently, emerging evidence has shown that Stat3 controls tumor cell migration and invasion. However, the molecular mechanisms by which Stat3 controls the cell movement remain largely unknown. Embryonic gastrula progenitors display coordinated and orientated migration, called collective cell migration. Collective cell migration is the simultaneous movement of multiple cells and is universally involved in physiological and pathological programs. Stat3 activity is required for the migration of gastrula progenitors, but it does not affect cell specification, thus suggesting that gastrula movements are an excellent model to provide insight into Stat3 control of cell migration in vivo. In this study, we reveal a novel mechanism by which Stat3 modulates extracellular matrix (ECM) assembly to control the coherence of collective migration of prechordal plate progenitors during zebrafish embryonic gastrulation. We show that Stat3 regulates the expression of Efemp2a in the prechordal plate progenitors that migrate anteriorly during gastrulation. Alteration of Stat3-Efemp2a signaling activity disrupted the configuration of fibronectin (FN) and laminin (LM) matrices, resulting in defective coherence of prechordal plate progenitor movements in zebrafish embryos. We demonstrate that Efemp2a acts as a downstream effector of Stat3 to promote ECM configuration for coherent collective cell migrations in vivo.
Asunto(s)
Movimiento Celular/fisiología , Endodermo/citología , Proteínas de la Matriz Extracelular/metabolismo , Matriz Extracelular/fisiología , Gastrulación/fisiología , Factor de Transcripción STAT3/metabolismo , Células Madre/fisiología , Proteínas de Pez Cebra/metabolismo , Pez Cebra/embriología , Adenoviridae , Animales , Inmunoprecipitación de Cromatina , Clonación Molecular , Cartilla de ADN/genética , Perros , Proteínas de la Matriz Extracelular/genética , Técnica del Anticuerpo Fluorescente , Técnicas de Silenciamiento del Gen , Células HeLa , Células Endoteliales de la Vena Umbilical Humana , Humanos , Immunoblotting , Inmunoprecipitación , Hibridación in Situ , Células de Riñón Canino Madin Darby , Morfolinos/genética , Mutagénesis , Factor de Transcripción STAT3/genética , Imagen de Lapso de Tiempo , Pez Cebra/genética , Proteínas de Pez Cebra/genéticaRESUMEN
The left-right asymmetry is an essential feature shared by vertebrates. Cilia-driven counterclockwise flow in the mammalian node structure leads to the left-right asymmetric distribution of signals and subsequent asymmetric patterning. Although several signaling pathways have been identified in the specification of node ciliated cells, little is known about the direct downstream effectors of these signaling pathways. Here, we showed that zebrafish Ectoderm-Neural Cortex1-like (enc1l) is expressed in the Kupffer's Vesicle (KV), an equivalent structure of the mammalian node in zebrafish, and is necessary for KV ciliogenesis. Loss-of-function of enc1l increased the number and decreased the length of KV cilia. The enc1l expression in the KV region was specifically regulated by retinoic acid (RA), FGF, and Wnt signaling pathways. In addition, knocking down enc1l or ectopic enc1l expression was able to rescue the KV cilium defects caused by alteration of RA and FGF signaling, but not Wnt signaling. Taken together, these data indicate thatEnc1l is a direct downstream effector of RA and FGF signaling pathways and modulates KV ciliogenesis in the zebrafish embryo.
Asunto(s)
Factores de Crecimiento de Fibroblastos/metabolismo , Regulación del Desarrollo de la Expresión Génica , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/fisiología , Neuropéptidos/genética , Neuropéptidos/fisiología , Proteínas Nucleares/genética , Proteínas Nucleares/fisiología , Transducción de Señal , Tretinoina/metabolismo , Animales , Tipificación del Cuerpo , Cilios/metabolismo , Hibridación in Situ , Modelos Biológicos , ARN Mensajero/metabolismo , Factores de Tiempo , Distribución Tisular , Proteínas Wnt/metabolismo , Pez CebraRESUMEN
BACKGROUND & AIMS: The relationship between dietary fatty acids (FA) and clinical outcomes are relatively lacking in non-dialyzed and dialyzed chronic kidney disease (CKD) population, resulting in insufficient guide about the dietary FA intake in this population. In this study, we aimed to observe the association between the intake of total or different types of FA and all-cause and cardiovascular (CV) mortality in patients undergoing peritoneal dialysis (PD). METHODS: This is a prospective cohort study with data retrospectively analyzed in 881 patients undergoing PD. Dietary FA intake measured by 3-day dietary records. The outcomes were defined as all-cause and CV death. Baseline FA intake and time-averaged FA intake were categorized by tertiles based on the distribution among the study population. We used univariate and multivariate Cox proportional regression models to determine the association between amounts and types of FA and all-cause and CV mortality. RESULTS: During a median follow up of 45 months, 93 patients were still being maintained on PD, 467 had died, including 189 (40.5%) attributable to CV death. Compared to patients in the low tertile of total FA (TFA) intake at baseline group, the middle or/and high tertile groups were more likely to be male, younger, well-educated and better nutritional status (P < 0.05). At the baseline, no association was found between all-cause and CV death in either total or different types of FA after adjusting for nutritional variables. As for time-averaged analyses, the associations of TFA, saturated FA (SFA), monounsaturated FA (MUFA), ω-3 and ω-6 polyunsaturated FA (PUFA) and all-cause mortality were weakened after adjustment for laboratory and nutrients variables. However, PUFA independently reduced 5% of mortality even after adjustment for laboratory and nutrients variables [HR 0.95 (0.91, 0.99), P = 0.023], and the ratio of MUFA/PUFA was positively associated with the risk for all-cause mortality [HR 1.05 (1.01, 1.09), P = 0.008]. Furthermore, each 10% increase of the ratio of ω-6/ω-3 was only weakly associated with the risk for all-cause mortality [HR 1.02 (1.00, 1.04), P = 0.034]. As for CVD mortality, the impacts of total and each type of FA disappeared after adjustment for laboratory or nutrients variables. CONCLUSIONS: Time-averaged PUFA intake was independently associated with a lower risk for all-cause mortality in our PD cohort, while the higher ratio of MUFA/PUFA and ω-6/ω-3 increased all-cause mortality. More observational and interventional researches are needed to determine these associations.
Asunto(s)
Enfermedades Cardiovasculares , Ácidos Grasos Omega-3 , Diálisis Peritoneal , Humanos , Masculino , Femenino , Grasas de la Dieta/efectos adversos , Estudios Prospectivos , Enfermedades Cardiovasculares/epidemiología , Estudios Retrospectivos , Ácidos Grasos/efectos adversos , Diálisis Peritoneal/efectos adversosRESUMEN
OBJECTIVE: To investigate effects of exogenous 5'-nucleotides on acute alcohol intoxication in SD rats. METHODS: In our study, 24 male SD rats were randomly divided into 4 groups which included a control group treated with normal saline and three experimental groups treated with low, medium and high doses of exogenous 5'-nucleotides (0.2, 0.8, 3.2 g/kg body weight). All the rats were gavaged with 50% ethanol 30 minutes after treatment. Then rotarod test and open field test were taken to assess rats' neurobehavior changes; Tail blood samples were collected to test blood ethanol concentration; Then all the rats were anesthetized and killed to collect blood and liver samples. Contents of serum alanine amino transferase, aspartate amino transferase, triglyceride, total cholesterol, high density lipoprotein cholesterol, total protein and albumin were tested; Their serum superoxide dismutase activity, malondialdehyde content and liver alcohol dehydrogenase activity were measured. RESULTS: Compared with the controls, high dose nucleotides treated rats had lower serum ethanol concentration [(0.56±0.18 g/L)vs.(1.11±0.44 g/L), P<0.05]. However, exogenous 5'-nucleotides had no impact on neurobehavior and serum biochemical indicators; No difference was found in liver alcohol dehydrogenase activity, serum superoxide dismutase activity and malondialdehyde content were also found no different between the groups. CONCLUSION: Exogenous 5'-nucleotides have no protective properties for acute alcohol intoxication in rats.
Asunto(s)
Intoxicación Alcohólica/tratamiento farmacológico , Nucleótidos/uso terapéutico , Enfermedad Aguda , Animales , Masculino , Distribución Aleatoria , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: This study evaluated the effectiveness of the multidisciplinary team (including a specialist, a dietitian, a physical exercise trainer, a surgeon for bariatric surgery, an acupuncturist, and several health educators) for obesity management and the body composition change and improvements in metabolic biomarkers during a 2-year follow-up. MATERIALS AND METHODS: A total of 119 patients participated in the multidisciplinary team for obesity. Patients were followed up at 3 months, 6 months, 1 year, 18 months, and 2 years after their first visit. Individuals were divided into the high-protein diet (HPD) and standard-protein diet (SPD) group according to their results on a diet questionnaire that they filled out during follow-up. RESULTS: After 1.2 years, the mean body weight of the participants dropped from 89.7 kg to 80.9 kg (p < 0.001). The body adiposity index was reduced from 33.9 to 32.0 (p < 0.001), while the fat-free mass index from 17.0 to 15.2 (p = 0.043). Fasting glucose and HbA1c were also lower after treatment (p = 0.002 and 0.038 for FPG and HbA1c, respectively). Fasting insulin and HOMA-IR were reduced (p = 0.002 and <0.001 for fasting insulin and HOMA-IR, respectively). HDL-c increased along with weight loss (1.06 mmol/L vs. 1.19 mmol/L, p < 0.001), and transaminase levels significantly dropped (p = 0.001 and 0.021 for ALT and AST, respectively). During treatment, mean protein intake was 29.9% in the HPD group and 19.5% in the SPD group (p < 0.001). Weight loss, reduction of visceral fat area, maintenance of lean body mass, body adiposity index, and fat-free mass index showed no statistical significance between the HPD and SPD groups, as well as glucose metabolic variables. CONCLUSIONS: A multidisciplinary team for obesity management could significantly reduce body weight and improve metabolic indicators, including HDL-c, transaminase, and insulin resistance. A high-protein diet does not produce better weight control or body composition compared with a standard calorie-restricted diet.
Asunto(s)
Composición Corporal , Obesidad/terapia , Grupo de Atención al Paciente , Adiposidad , Adulto , Peso Corporal , Restricción Calórica , HDL-Colesterol/sangre , Dieta Rica en Proteínas , Femenino , Estudios de Seguimiento , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Obesidad/metabolismoRESUMEN
To investigate the knowledge-attitude-practice (KAP) score in diabetes patients living in urban China regarding Medical Nutrition Therapy (MNT) and explore the influencing factors, this national survey recruited diabetes and prediabetes patients in 40 hospitals across 26 provinces in China. A self-designed questionnaire was used to collect the data and assess the knowledge, attitude, and practice regarding MNT. Logistic regression was used to explore the factor influencing KAP scores. A total of 6441 diabetes patients (mean age: 60.02 ± 13.14 years) completed this survey. The mean glycosylated hemoglobin (HbA1c) level was 8.12 ± 2.12%, and the control rate of HbA1c (HbA1c < 7.0%) was 38.92%. Of the total, 53.56% had received MNT education. Over half of the patients had a poor total KAP score as well as poor K, A, and P scores. Patients with higher KAP scores had higher control rate of HbA1c (P < 0.05) but lower levels of fasting plasma glucose (FPG) and 2-hour postprandial blood glucose (2h-PG). Gender, occupation, residence, education level, and MNT education could influence the KAP scores (P < 0.05). This study showed that diabetes patients in urban China generally had poor understandings and practices related to MNT. Patients with higher KAP scores exhibited better control of blood glucose.
Asunto(s)
Diabetes Mellitus Tipo 1/dietoterapia , Diabetes Mellitus Tipo 2/dietoterapia , Conocimientos, Actitudes y Práctica en Salud , Terapia Nutricional , Estado Prediabético/dietoterapia , Salud Urbana , Adulto , Anciano , Anciano de 80 o más Años , China , Estudios Transversales , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/prevención & control , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/prevención & control , Femenino , Hemoglobina Glucada/análisis , Hospitales Urbanos , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Necesidades , Encuestas Nutricionales , Cooperación del Paciente , Educación del Paciente como Asunto , Estado Prediabético/sangre , Estudios Retrospectivos , Adulto JovenRESUMEN
Glycemic control and weight reduction are primary goals for the management of overweight and obese type 2 diabetes mellitus (T2DM). Effective management cannot be achieved without an appropriate diet. Our study aimed to evaluate the short- and long-term effects of oat intake and develop a reasonable dietary plan for overweight T2DM patients. A randomized control trial, registered under ClinicalTrials.gov (Identification code: NCT01495052), was carried out among adult T2DM patients. A subgroup of 298 overweight subjects was selected and received a 30-day centralized intervention and 1-year free-living follow-up. Participants were randomly allocated to one of the following four groups. The usual care group (n = 60) received no intervention; the healthy diet group (n = 79) received a low-fat and high-fiber diet ("healthy diet"); the 50 g-oats group (n = 80) and 100 g-oats group (n = 79) received the "healthy diet" with the same amount of cereals replaced by 50 g and 100 g oats respectively. Anthropometric, blood glycemic and lipid variables were measured. For the 30-day intervention, significant differences in the changes of FPG (fasting plasma glucose), PPG (postprandial plasma glucose), HbA1c (glycosylated hemoglobin), HOMA-IR (homeostasis model assessment of insulin resistance), TC (total cholesterol), TG (total triglycerides), and LDL-c (low-density lipoprotein cholesterol) were observed among the four groups. Compared to the healthy diet group, the 50 g-oats group had a bigger reduction in PPG (mean difference (MD): -1.04 mmol/L; 95% CI: -2.03, -0.05) and TC (MD: -0.24 mmol/L; 95% CI: -0.47, -0.01); the 100 g-oats group had a bigger reduction in PPG (MD: -1.48 mmol/L; 95% CI: -2.57, -0.39), HOMA-IR (MD: -1.77 mU·mol/L²; 95% CI: -3.49, -0.05), TC (MD: -0.33 mmol/L; 95% CI: -0.56, -0.10) and LDL-c (MD: -0.22 mmol/L; 95% CI: -0.41, -0.03). In the 1-year follow-up, greater effects in reducing weight (MD: -0.89 kg; 95% CI: -1.56, -0.22), HbA1c (MD: -0.64%; 95% CI: -1.19, -0.09) and TG (MD: -0.70 mmol/L; 95% CI: -1.11, -0.29) were observed in the 100 g-oats group. In conclusion, short- and long-term oat intake had significant effects on controlling hyperglycemia, lowering blood lipid and reducing weight. Our study provided some supportive evidence for recommending oat as a good whole grain selection for overweight diabetics.
Asunto(s)
Avena , Diabetes Mellitus Tipo 2/dietoterapia , Dieta Saludable , Sobrepeso/dietoterapia , Factores de Tiempo , Granos Enteros , Glucemia/metabolismo , HDL-Colesterol/sangre , LDL-Colesterol/sangre , Diabetes Mellitus Tipo 2/sangre , Dieta con Restricción de Grasas , Fibras de la Dieta/administración & dosificación , Femenino , Estudios de Seguimiento , Hemoglobina Glucada/metabolismo , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Obesidad/sangre , Obesidad/dietoterapia , Sobrepeso/sangre , Periodo Posprandial , Triglicéridos/sangreRESUMEN
The present study aimed to explore the metabolic response of oat bran consumption in dyslipidemic rats by a high-throughput metabolomics approach. Four groups of Sprague-Dawley rats were used: N group (normal chow diet), M group (dyslipidemia induced by 4-week high-fat feeding, then normal chow diet), OL group and OH group (dyslipidemia induced, then normal chow diet supplemented with 10.8% or 43.4% naked oat bran). Intervention lasted for 12weeks. Gas chromatography quadrupole time-of-flight mass spectrometry was used to identify serum metabolite profiles. Results confirmed the effects of oat bran on improving lipidemic variables and showed distinct metabolomic profiles associated with diet intervention. A number of endogenous molecules were changed by high-fat diet and normalized following supplementation of naked oat bran. Elevated levels of serum unsaturated fatty acids including arachidonic acid (Log2Fold of change=0.70, P=.02 OH vs. M group), palmitoleic acid (Log2Fold of change=1.24, P=.02 OH vs. M group) and oleic acid (Log2Fold of change=0.66, P=.04 OH vs. M group) were detected after oat bran consumption. Furthermore, consumption of oat bran was also characterized by higher levels of methionine and S-adenosylmethionine. Pathway exploration found that most of the discriminant metabolites were involved in fatty acid biosynthesis, biosynthesis and metabolism of amino acids, microbial metabolism in diverse environments and biosynthesis of plant secondary metabolites. These results point to potential biomarkers and underlying benefit of naked oat bran in the context of diet-induced dyslipidemia and offer some insights into the mechanism exploration.
Asunto(s)
Avena , Dieta Alta en Grasa , Fibras de la Dieta/administración & dosificación , Dislipidemias/metabolismo , Metabolómica , Animales , Ácido Araquidónico/química , Biomarcadores/sangre , Biopsia , Dieta , Dislipidemias/dietoterapia , Ácidos Grasos Monoinsaturados/química , Ácidos Grasos Insaturados/sangre , Ácidos Grasos Insaturados/química , Cromatografía de Gases y Espectrometría de Masas , Hiperlipidemias/metabolismo , Hígado/patología , Masculino , Metionina/química , Análisis Multivariante , Ácido Oléico/química , Ratas , Ratas Sprague-Dawley , S-Adenosilmetionina/químicaRESUMEN
The Snail family member snail encodes a zinc finger-containing transcriptional factor that is involved in heart formation. Yet, little is known about how Snail regulates heart development. Here, we identified that one of the duplicated snail genes, snai1b, was expressed in the heart region of zebrafish embryos. Depletion of Snai1b function dramatically reduced expression of α5 integrin, disrupted Fibronectin layer in the heart region, especially at the midline, and prevented migration of cardiac precursors, resulting in defects in cardiac morphology and function in zebrafish embryos. Injection of α5ß1 protein rescued the Fibronectin layer and then the myocardial precursor migration in snai1b knockdown embryos. The results provide the molecular mechanism how Snail controls the morphogenesis of heart during embryonic development.
Asunto(s)
Desarrollo Embrionario , Fibronectinas/metabolismo , Integrina alfa5/metabolismo , Factores de Transcripción/genética , Proteínas de Pez Cebra/genética , Animales , Movimiento Celular/genética , Embrión no Mamífero , Fibronectinas/genética , Corazón/crecimiento & desarrollo , Integrina alfa5/genética , Morfogénesis/genética , Miocardio/citología , Factores de Transcripción de la Familia Snail , Factores de Transcripción/antagonistas & inhibidores , Pez Cebra , Proteínas de Pez Cebra/antagonistas & inhibidoresRESUMEN
Although ER stress in pancreas, liver, and adipose tissue was reported to be a novel event linked to the pathogenesis of type 2 diabetes mellitus, there is much less information on this event in skeletal muscle. Some studies indicated that treatment with antioxidants had beneficial effects on ER stress and diabetes. This study focuses on the effects of a strong antioxidant, grape seed proanthocyanidin extracts (GSPE), on skeletal muscle in diabetic rats induced with low dose streptozotocin- and a high-carbohydrate/high-fat diet. After 16 wk of GSPE treatment, diabetic rats showed decreased plasma glucose levels and insulin resistance. The efficacious effect of GSPE was manifested by the amelioration of muscular damage and dysfunction, as observed by histological examination and periodic acid Schiff staining. Concurrently, calcium overload and the abnormal activities of antioxidant enzymes and ATPases in diabetic muscles were partially reversed by GSPE treatment. GSPE also increased the activity of protein kinase B (a mediator of insulin's metabolic action) and partially alleviated severe ER stress. These findings suggest that GSPE may have auxiliary therapeutic potential for type 2 diabetes mellitus by decreasing oxidative stress and ER stress in skeletal muscle.