RESUMEN
OBJECTIVE: The short-term benefits of brentuximab vedotin (BV) for classical Hodgkin lymphoma (cHL) are well established, but its long-term benefits for refractory/relapsing (r/r) cHL are unknown. A meta-analysis was undertaken to examine the overall survival (OS), and progression-free survival (PFS) from relevant studies with patients with r/r cHL post-autologous stem cell transplantation (ASCT) exposed to BV. MATERIALS AND METHODS: PubMed, Embase, and the Cochrane library were searched for available papers published up to January 2020. The main outcomes included 3-year OS/PFS and/or 5-year OS/PFS. Data were pooled using random-effects models. RESULTS: Four studies were included: one randomized controlled trial, one single-arm trial, and two retrospective studies. The four studies included a total of 383 patients (mean of 95.75/study). The proportion of females was 21%-89%. The median age was 26-33 years. The 3-year OS was available for one study and was 41% in patients with r/r cHL with BV after ASCT (OR=0.41, 95% CI: 0.16-0.67). The 5-year OS was available for two studies and was 34% in patients with r/r cHL with BV after ASCT (OR=0.34, 95% CI: 0.19-0.48; mixed-effects model). The 5-year PFS was available for three studies and was 31% in patients with r/r cHL with BV after ASCT (OR=0.31, 95% CI: 0.02-0.61; mixed-effects model). CONCLUSIONS: The 5-year OS in patients with r/r cHL treated with BV after ASCT is 34% (95 CI: 19%-48%). The 5-year PFS in patients with r/r cHL treated with BV after ASCT is 31% (95 CI: 2%-61%).
Asunto(s)
Antineoplásicos Inmunológicos/uso terapéutico , Brentuximab Vedotina/uso terapéutico , Enfermedad de Hodgkin/tratamiento farmacológico , Adulto , Femenino , Humanos , Masculino , Ensayos Clínicos Controlados Aleatorios como Asunto , Análisis de SupervivenciaRESUMEN
The blue-eggshell and dwarf traits have an important economic value in poultry production. Using a genetic aggregation-based strategy, the molecular marker-assisted selection technology was jointly used to provide a rapid breeding method for pure strain chickens simultaneously with hens exhibiting the blue-eggshell and dwarf traits. Overall, 80 male dwarf chickens and 1,000 hybrid blue-eggshell hens (F0) were used for the hybridization experiment. Subsequently, the crossing of F1 or F2 chicks was performed in succession. The F1 and F2 chicks were respectively detected by the joint molecular markers of the solute carrier organic anion transporter family, namely, 1B3 (SLCO1B3) and the growth hormone receptor (GHR) genes, which relate to blue-eggshell and dwarf traits. Meanwhile, the selection of blue-eggshell and dwarf phenotypes was used to validate the data obtained by the molecular markers. The results showed that F1 chicks included the heterozygous and wild-type of SLCO1B3, as well as the homozygous (hens) and heterozygous (roosters) of GHR. However, F2 chicks included 3 different genotypes of both SLCO1B3 and GHR. Ultimately, 196 F1 roosters (concurrently with heterozygous genotype of SLCO1B3 and GHR) and 1,073 F1 hens (concurrently with heterozygous genotype of SLCO1B3 and homozygous genotype of GHR) were obtained from the initial 10,040 F1 chicks. Further, 27 F2 roosters and 345 F2 hens, which simultaneously carried the homozygous genotype of SLCO1B3 and GHR, were screened from the initial 6,000 F2 chicks. Data obtained on the blue-eggshell and dwarf phenotypes were consistent with the results by molecular markers. Similarly, the purity verification of the strain obtained through 2 crossing experiments (F0â × F2â and F2â × F2â) revealed that all chickens had the blue-eggshell and dwarf traits, supporting that the obtained F2 strain was pure. In summary, for the first time, we successfully bred a pure strain chicken with blue-eggshell and dwarf traits by jointly using the molecular markers of the SLCO1B3 and GHR genes. Our study provides a new method for the rapid cultivation of new chicken strains.
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Pollos/genética , Enanismo/genética , Cáscara de Huevo , Hibridación Genética , Animales , Cruzamiento/métodos , Color , Femenino , Masculino , Receptores de Somatotropina/genética , Miembro 1B3 de la Familia de los Transportadores de Solutos de Aniones Orgánicos/genéticaRESUMEN
Intramuscular fat is important in improving meat quality; however, the lack of high-purity intramuscular preadipocyte (IMP) in vitro has severely limited the in-depth research on the mutual regulation of myocytes and adipocytes in chicken. In this study, we establish a new method by combining the mature adipocyte ceiling method and the transwell co-culture system. Mature intramuscular adipocyte (MIA) and muscle satellite cell (MSC) were obtained from digested pectoralis major, and MIAs were transformed into IMPs by dedifferentiation with ceiling culture. MSCs were then purified by differential adhesion for 2 h. The results by inverted-microscope observation, MTT assay, Oil Red O staining, and q-PCR revealed that the de-differentiated cells from MIA were identified as the IMPs, and had the same the cellular morphology, the capacity on differentiation, proliferation and passage with the abdominal fat preadipocytes (P > 0.05). The applicability of the obtained IMPs in co-cultured experiment with the MSC revealed that it could meet the requirements of the experimental study. Finally, a co-culture system of IMPs and MSCs was established using a transwell chamber. The co-cultured results indicated that MSCs in the proliferative stage tend to accelerate the differentiation of IMPs to induce more fat content in co-cultured IMPs than in single-culture IMPs (P < 0.05), in the non-proliferative stage, the results tend to show the opposite (P < 0.05). The mRNA levels of related genes significantly changed in accordance with the fat content in cells. The results strongly supported the view that the established co-culture system was effective and feasible. In summary, we successfully found a new method to explore the interaction between myocytes and adipocytes of chicken. Our findings can deepen research on the regulation of chicken myocytes and adipocytes.
Asunto(s)
Adipocitos/citología , Técnicas de Cultivo de Célula/veterinaria , Pollos , Técnicas de Cocultivo/veterinaria , Músculos Pectorales/fisiología , Células Satélite del Músculo Esquelético/citología , Animales , Técnicas de Cultivo de Célula/métodos , Técnicas de Cocultivo/métodos , Células Musculares/citologíaRESUMEN
1. Lipid metabolism is an indispensable process in an organism, though little is known about the regulatory mechanisms of fat deposition in different types of adipose tissues. 2. The differentially expressed genes related to triglyceride (TG) metabolism between abdominal and intramuscular fat (IMF) of Beijing-You chickens were investigated in this study. 3. TG content in abdominal fat (AF) (349.7 mg/g) was significantly higher (P < 0.01) than in the breast and thigh (12.3 mg/g and 24.8 mg/g, respectively). 4. Using Agilent chicken gene-expression profiling in adipose tissues between AF and muscle (breast and thigh), certain representative genes related to fatty acid metabolism, lipoprotein catabolism and esterification reactions were significantly upregulated (P < 0.05 or P < 0.01). 5. Genes involved in fatty acid oxidation or carbohydrate utilisation were significantly up- or downregulated (P < 0.05 or P < 0.01), including those involved with highly enriched pathways of lipid metabolism (PPAR, Wnt pathway and inositol phosphate metabolism), cell junctions (focal adhesion and regulation of actin cytoskeleton) and muscle contraction. 6. Overall, higher TG levels were observed in AF tissue than in adipose tissues of breast and thigh, which could be regulated through gene expression of pathways related to lipid metabolism (PPAR, Wnt pathway and inositol phosphate metabolism), cell junctions (focal adhesion and regulation of actin cytoskeleton) and muscle contraction. These results provide clues to understanding the molecular mechanisms of TG metabolism between abdominal and IMF.
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Grasa Abdominal/metabolismo , Tejido Adiposo/metabolismo , Pollos/metabolismo , Perfilación de la Expresión Génica , Metabolismo de los Lípidos/genética , Triglicéridos/metabolismo , Animales , Pollos/genética , Regulación de la Expresión Génica , Redes y Vías Metabólicas/genética , Músculo Esquelético/metabolismo , Muslo/fisiologíaRESUMEN
Calpain 9 (CAPN9) is expressed in the stomach and small intestine. CAPN9 has regulatory roles in hypertension, heart disease, gastric mucosal defense, and kidney disease. The involvement of CAPN9 has not been reported in the development of chickens. CAPN9 mRNA was found in adipose and muscle tissue in this study. Two linkage single nucleotide polymorphisms (SNP; G7518A and C7542G) in intron 4 were screened from 160 birds of the D2 chicken line. The 2 mutation sites were associated with carcass weight, evisceration weight, abdominal fat weight (AFW), abdominal fat percentage (AFP), and breast muscle percentage (all P < 0.05). Intramuscular fat (IMF) content was not significantly different in the 3 genotypes. But, the AA(7518)/GG(7542) genotype had the highest IMF content, highest breast muscle weight, and lower AFW and AFP. Moreover, the mRNA level of CAPN9 in abdominal fat tissue was significantly different (P < 0.05 or P < 0.01) between any 2 genotypes, consistent with AFW and AFP. In summary, the expression of CAPN9 in adipose and breast muscle tissue is reported for the first time. CAPN9 affected production performance of chickens. As a marker, the linkage G7518A and C7542G polymorphisms in intron 4 of CAPN9 could affect the production traits by regulating mRNA expression. The findings concerning the marker enrich the theoretical foundation for molecular breeding of high-quality broilers.
Asunto(s)
Proteínas Aviares/genética , Calpaína/genética , Pollos/genética , Regulación de la Expresión Génica , Polimorfismo de Nucleótido Simple , Grasa Abdominal/metabolismo , Animales , Proteínas Aviares/metabolismo , Secuencia de Bases , Peso Corporal/genética , Calpaína/metabolismo , Pollos/metabolismo , Músculos Pectorales/crecimiento & desarrollo , Músculos Pectorales/metabolismoRESUMEN
Intramuscular fat (IMF) content contributes to meat flavor and improves meat quality. Excessive abdominal fat, however, leads to a waste of feed resources. Here, an independent up-selection for IMF was used as a control (Line C), and a balanced selection program, with up-selection for IMF and down-selection AFP (Line B), was studied in JingXing yellow chickens. The mean of IMF and AFP within a family was the phenotypic value upon which selection was based. The selective pressures of IMF in line B and line C were the same in each generation. At G5, the IMF was significantly higher (P < 0.05) than that at G0 in both lines. For AFP, Line C was significantly higher at G5 (P < 0.05) than at G0, but the difference in Line B was not significant (P > 0.05). IMF increased by 11.4% and AFP decreased by 1.5% in Line B compared with the G0 generation. In contrast, the IMF increased by 17.6%, but was accompanied by an 18.7% increase in AFP, in control Line C. Of 10 other traits measured, body weight at 56 d age (BW56) and the percentages of eviscerated weight (EWP) showed a significant difference between the 2 lines (P < 0.05). The heritabilities for IMF and AFP, estimated by the DMU package, were 0.16 and 0.32, respectively. A moderate positive correlation existed between IMF and AFP (0.35). A balanced selection program for increasing IMF while controlling AFP (Line B) is shown here to be effective in practical chicken breeding.
Asunto(s)
Grasa Abdominal/metabolismo , Tejido Adiposo/metabolismo , Pollos/genética , Herencia , Selección Genética , Animales , Pollos/metabolismo , Femenino , Masculino , Músculo Esquelético/metabolismoRESUMEN
Hepatocellular carcinoma (HCC) is a major cause of cancer-related deaths worldwide. MicroRNA-34 (miR-34) gene plays a key role in altering the apoptotic cycle and pathways of downstream cells, and therefore influences carcinogenesis. In this case-control study, we assessed the role of the pri-miR-34b/c rs4938723 polymorphism in HCC risk. The pri-miR-34b/c polymorphic genotype was determined in 286 patients with HCC and 572 controls using polymerase chain reaction-restriction fragment length polymorphism. The male gender (X2 = 12.95, P < 0.001), regular alcohol consumption (X2 = 16.81, P < 0.001), and a family history of cancer (X2 = 11.88, P = 0.001) were associated with HCC risk. However, the age (t = 1.19, P = 0.12) and tobacco smoking habit (X2 = 0.64, P = 0.42) of HCC patients were comparable to those of the controls. The TC (adjusted OR = 1.46, 95%CI = 1.06-2.01) and CC (adjusted OR = 3.07, 95%CI = 1.77-5.34) genotypes of pri-miR-34b/c rs4938723 were correlated with a higher risk of HCC compared to the TT genotype. Moreover, the TC+CC genotype was correlated with an increased risk of HCC compared to the TT genotype (adjusted OR = 1.64, 95%CI = 1.21-2.22). In the recessive model, the CC genotype of pri-miR-34b/c rs4938723 was significantly correlated with an elevated risk of HCC compared to the TT+TC genotype (adjusted OR = 2.50, 95%CI = 1.49-4.22). Further large-scale and multi-center studies are required to confirm these results.
Asunto(s)
Carcinoma Hepatocelular/genética , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , MicroARNs/genética , Polimorfismo de Nucleótido Simple/genética , Regiones Promotoras Genéticas , Estudios de Casos y Controles , Demografía , Femenino , Humanos , Neoplasias Hepáticas/genética , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Factores de RiesgoRESUMEN
The positron emission tomography (PET) radioligand (-)-[(18)F]flubatine is specific to α4ß2(â) nicotinic acetylcholine receptors (nAChRs) and has promise for future investigation of the acetylcholine system in neuropathologies such as Alzheimer's disease, schizophrenia, and substance use disorders. The two goals of this work were to develop a simplified method for α4ß2(â) nAChR quantification with bolus plus constant infusion (B/I) (-)-[(18)F]flubatine administration, and to assess the radioligand's sensitivity to acetylcholine fluctuations in humans. Healthy human subjects were imaged following either bolus injection (n=8) or B/I (n=4) administration of (-)-[(18)F]flubatine. The metabolite-corrected input function in arterial blood was measured. Free-fraction corrected distribution volumes (VT/fP) were estimated with modeling and graphical analysis techniques. Next, sensitivity to acetylcholine was assessed in two ways: 1. A bolus injection paradigm with two scans (n=6), baseline (scan 1) and physostigmine challenge (scan 2; 1.5mg over 60min beginning 5min prior to radiotracer injection); 2. A single scan B/I paradigm (n=7) lasting up to 240min with 1.5mg physostigmine administered over 60min beginning at 125min of radiotracer infusion. Changes in VT/fP were measured. Baseline VT/fP values were 33.8±3.3mL/cm(3) in thalamus, 12.9±1.6mL/cm(3) in cerebellum, and ranged from 9.8 to 12.5mL/cm(3) in other gray matter regions. The B/I paradigm with equilibrium analysis at 120min yielded comparable VT/fP values with compartment modeling analysis of bolus data in extrathalamic gray matter regions (regional means <4% different). Changes in VT/fP following physostigmine administration were small and most pronounced in cortical regions, ranging from 0.8 to 4.6% in the two-scan paradigm and 2.8 to 6.5% with the B/I paradigm. These results demonstrate the use of B/I administration for accurate quantification of (-)-[(18)F]flubatine VT/fP in 120min, and suggest possible sensitivity of (-)-[(18)F]flubatine binding to physostigmine-induced changes in acetylcholine levels.
Asunto(s)
Acetilcolina/metabolismo , Benzamidas/farmacocinética , Encéfalo/metabolismo , Compuestos Bicíclicos Heterocíclicos con Puentes/farmacocinética , Imagen Molecular/métodos , Tomografía de Emisión de Positrones/métodos , Receptores Nicotínicos/metabolismo , Adulto , Benzamidas/administración & dosificación , Encéfalo/diagnóstico por imagen , Compuestos Bicíclicos Heterocíclicos con Puentes/administración & dosificación , Simulación por Computador , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Infusiones Intraventriculares , Tasa de Depuración Metabólica , Persona de Mediana Edad , Modelos Neurológicos , Neurotransmisores/metabolismo , Radiofármacos/administración & dosificación , Radiofármacos/farmacocinética , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Distribución Tisular , Adulto JovenAsunto(s)
Pollos/genética , Resistencia a la Enfermedad/genética , Salmonelosis Animal/genética , Receptor Toll-Like 4/genética , Alelos , Animales , Carga Bacteriana , Cruzamiento , Ciego/microbiología , Análisis Mutacional de ADN , Genotipo , Interleucina-1/sangre , Interleucina-6/sangre , Factor 88 de Diferenciación Mieloide/metabolismo , Polimorfismo de Nucleótido Simple , Salmonella enteritidis , Análisis de Secuencia de ADN , Receptor Toll-Like 4/metabolismoRESUMEN
Excessive fat accretion is a crucial problem during broiler production. Abdominal fat weight (AbFW) and abdominal fat percentage (AbFP) are major phenotypic indices of fat traits. The present study used F2 females derived from a cross between Beijing-You and Cobb-Vantress chickens. Cohorts with extreme AbFP and AbFW phenotypes were chosen to construct high- and low-abdominal fat libraries (HAbF and LAbF, respectively) to investigate the expression profiles by RNA-sequencing and microRNA (miRNA)-sequencing. Compared with the LAbF library, 62 differentially expressed miRNAs (DEMs) and 303 differentially expressed genes (DEGs) were identified in the HAbF birds. Integrated analysis of DEMs and DEGs showed that a total of 106 DEGs were identified as target genes for the 62 DEMs. These genes were designated as intersection genes, and 11 of these genes are involved in lipid metabolism pathways. The miRNA gga-miR-19b-3p accelerated the proliferation of preadipocytes, as well as adipocyte differentiation, by down- regulating ACSL1. These findings suggest that some strong candidate miRNAs and genes, important in relation to abdominal adipose deposition, were identified by the integrated analysis of DEMs and DEGs. These findings add to our current understanding of the molecular genetic controls underlying abdominal adipose accumulation in chickens.
Asunto(s)
Grasa Abdominal/metabolismo , Pollos/genética , MicroARNs/metabolismo , ARN Mensajero/metabolismo , Regiones no Traducidas 3' , Grasa Abdominal/citología , Animales , Secuencia de Bases , Aves/genética , Aves/metabolismo , Diferenciación Celular , Proliferación Celular , Pollos/metabolismo , Coenzima A Ligasas/antagonistas & inhibidores , Coenzima A Ligasas/genética , Coenzima A Ligasas/metabolismo , Bases de Datos Genéticas , Femenino , Perfilación de la Expresión Génica , Biblioteca de Genes , Redes Reguladoras de Genes , Metabolismo de los Lípidos/genética , MicroARNs/química , Fenotipo , ARN Mensajero/química , Alineación de Secuencia , Análisis de Secuencia de ARN , TranscriptomaRESUMEN
Brain natriuretic peptide (BNP) is related to lipid metabolism in mammals, but its effect and the molecular mechanisms underlying it in chickens are incompletely understood. We found that the level of natriuretic peptide precursor B (NPPB, which encodes BNP) mRNA expression in high-abdominal-fat chicken groups was significantly higher than that of low-abdominal-fat groups. Partial correlations indicated that changes in the weight of abdominal fat were positively correlated with NPPB mRNA expression level. In vitro, compared with the control group, preadipocytes with NPPB interference showed reduced levels of proliferation, differentiation, and glycerin in media. Treatments of cells with BNP led to enhanced proliferation and differentiation of cells and glycerin concentration, and mRNA expression of its receptor natriuretic peptide receptor 1 (NPR1) was upregulated significantly. In cells exposed to BNP, 482 differentially expressed genes were identified compared with controls without BNP. Four genes known to be related to lipid metabolism (diacylglycerol kinase; lipase, endothelial; 1-acylglycerol-3-phosphate O-acyltransferase 1; and 1-acylglycerol-3-phosphate O-acyltransferase 2) were enriched in the glycerolipid metabolism pathway and expressed differentially. In conclusion, BNP stimulates the proliferation, differentiation, and lipolysis of preadipocytes through upregulation of the levels of expression of its receptor NPR1 and key genes enriched in the glycerolipid metabolic pathway.
Asunto(s)
Adipocitos/metabolismo , Proteínas Aviares/metabolismo , Metabolismo de los Lípidos , Péptido Natriurético Encefálico/metabolismo , Receptores del Factor Natriurético Atrial/metabolismo , Adipocitos/citología , Animales , Proteínas Aviares/genética , Diferenciación Celular , Proliferación Celular , Células Cultivadas , Pollos , Glucolípidos/metabolismo , Metabolismo de los Lípidos/genética , Lipólisis , Redes y Vías Metabólicas , Péptido Natriurético Encefálico/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores del Factor Natriurético Atrial/genética , Regulación hacia ArribaRESUMEN
Myocardial infarction (MI) is currently a leading cause of death worldwide, and is caused by various environmental and genetic factors. We therefore conducted a case-control study to investigate the association between polymorphisms in interleukins IL-1ß, IL-8, and IL-10 and MI risk. This study recruited 260 MI patients and 285 control subjects. Genotyping of IL-1ß +3954C/T, IL-8 -251T/A, IL-10 -1082A/G, and IL-10 -819C/T were assessed using the polymerase chain reaction-restriction fragment length polymorphism method. By comparing the risk factors of MI between the case and control groups, we discovered that MI patients were more likely to have smoking and drinking habits, have a history of hypertension and diabetes, have higher triglycerides and low-density lipoprotein cholesterol levels, and a lower high-density lipoprotein cholesterol level (P < 0.05). Unconditional regression analyses showed that subjects carrying the GG genotype of the IL-10 -1082A/G polymorphism were associated with increased risk of MI, and the OR (95%CI) was 2.04 (1.15-3.65). Our study found that the IL-10 -1082A/G polymorphism plays an important role in influencing the development of MI.
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Interleucinas/genética , Infarto del Miocardio/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de RestricciónRESUMEN
This study aimed to screen single nucleotide polymorphisms (SNPs) in the chicken gap junction protein alpha 1 (GJA1) gene, and to investigate their association with five growth traits measured in 269 chickens encompassing Chinese indigenous Beijing-You (BJY) and commercial Cobb broiler (CB) populations. Four variants were detected in the chicken GJA1 gene, in which one synonymous mutation was located in an exon (C61223231T or c.-1110 C>T), two in an intron (A61229799C or c.5460 A>C, T61229928A or c.5589 T>A) and one in the promoter (A61230599C or c. 6260 A>C) regions. Genotyping was performed by high-resolution melting analysis (SNP in an exon) and DNA sequencing (SNP in the introns and promoter). Association analysis revealed that each SNP had a significant effect on growth traits in chicken. A higher level of genetic diversity was observed in the indigenous BJY breed than in the commercial CB breed. Strong linkage disequilibrium was observed between the C61223231T and A61229799C polymorphisms, and four previously undiscovered haplotypes (CA, TC, CC, TA) were constructed from those two mutations. Association analysis between haplotype combinations (diplotypes) and growth traits was highly significant where diplotype CC + CC was dominant for all traits. We speculated that GJA1 either is a major gene, or is associated with a major gene, affecting chicken growth traits. Therefore, further studies are needed in large populations to evaluate polymorphisms located in different regions of this gene, as well as its functional study, to better understand its role in muscle development in chicken.
Asunto(s)
Peso Corporal/genética , Pollos/genética , Conexina 43/genética , Músculo Esquelético/metabolismo , Polimorfismo de Nucleótido Simple , Carácter Cuantitativo Heredable , Animales , Cruzamiento , Pollos/crecimiento & desarrollo , Pollos/metabolismo , Exones , Femenino , Expresión Génica , Estudios de Asociación Genética , Técnicas de Genotipaje , Haplotipos , Intrones , Desequilibrio de Ligamiento , Masculino , Músculo Esquelético/crecimiento & desarrollo , Fenotipo , Regiones Promotoras Genéticas , Análisis de Secuencia de ADNRESUMEN
This study aimed to evaluate the influence of supplemental dietary nicotinic acid (NA) on lipid metabolism and hepatic expression of related genes in female chickens of two distinct broiler strains [Arbor Acres (AA) and Beijing-You (BJY)]. The treatments were arranged in a 2 × 4 factorial in a completely randomized design. Day-old females (n = 384) were allocated to four treatments with six cages per treatment and fed diets (basal contained approximately 25 mg NA/kg) supplemented with 0, 30, 60 and 120 mg NA/kg. A sample of 72 birds from each breed was slaughtered and sampled at their different market times (8 week for AA and 16 week for BJY). Arbor Acres broilers had thickness of subcutaneous fat plus the skin (SFS), and plasma concentration of low-density lipoprotein cholesterol (LDLC) and lower percentage of abdominal fat (PAF), plasma concentrations of TG, NEFA and adiponectin than the BJY line. The hepatic transcription of apolipoprotein A-I (ApoA-I), apolipoproteinB (ApoB), and adiponectin was significantly higher in AA broilers than in BJY broilers. In both breeds, BW, PAF, SFS, NEFA and TG were increased with increasing supplementation from 0 to 60 mg NA/kg, but then decreased slightly with 120 mg added NA/kg. With increasing supplementation, hepatic expression and plasma concentrations of adiponectin decreased from 0 to 60 mg added NA/kg and then increased with 120 mg added NA/kg. The expression of ApoA-I and ApoB mRNA showed linear response to dietary supplementation with NA. These findings indicate that: (i) supplementation of NA influenced the lipid metabolism and related gene expression; (ii) when supplemented with 120 mg NA/kg, some pharmacologic actions on lipid metabolism appeared; and (iii) changes in BW and fat deposition appeared to be associated with hepatic expression of adiponectin.
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Pollos/genética , Pollos/metabolismo , Suplementos Dietéticos , Regulación de la Expresión Génica/efectos de los fármacos , Metabolismo de los Lípidos/efectos de los fármacos , Niacina/farmacología , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Femenino , Metabolismo de los Lípidos/genética , Metabolismo de los Lípidos/fisiología , Niacina/administración & dosificaciónRESUMEN
Several lines of evidence suggest that schizophrenia is associated with deficits in glutamatergic transmission at the N-methyl-d-aspartate (NMDA) receptors. Glycine is a NMDA receptor co-agonist, and extracellular levels of glycine are regulated in the forebrain by the glycine type-1 transporters (GlyT-1). GlyT-1 inhibitors elevate extracellular glycine and thus potentiate NMDA transmission. This mechanism represents a promising new avenue for the treatment of schizophrenia. Here, the recently introduced positron emission tomography radiotracer [11C]GSK931145 was used to quantify the relationship between occupancy of GlyT-1 by a GlyT-1 inhibitor, Org 25935, and its impact on spatial working memory performances in rhesus monkeys. The effect of Org 25935 on working memory was assessed both in control conditions and during a state of relative NMDA hypofunction induced by ketamine administration, at a dose selected for each animal to reduce task performance by about 50%. Under control conditions, Org 25935 had no effect on working memory at GlyT-1 occupancies lower than 75% and significantly impaired working memory at occupancies higher than 75%. Under ketamine conditions, Org 25935 reversed the deficit in working memory induced by ketamine and did so optimally in the 40-70% GlyT-1 occupancy range. The results confirm the efficacy of this mechanism to correct working memory deficits associated with NMDA hypofunction. These data also suggest the existence of an inverted-U dose-response curve in the potential therapeutic effect of this class of compounds.
Asunto(s)
Encéfalo/fisiología , Proteínas de Transporte de Glicina en la Membrana Plasmática/antagonistas & inhibidores , Memoria a Corto Plazo/fisiología , Memoria Espacial/fisiología , Animales , Benzamidas , Encéfalo/diagnóstico por imagen , Radioisótopos de Carbono , Fármacos del Sistema Nervioso Central/farmacocinética , Fármacos del Sistema Nervioso Central/farmacología , Antagonistas de Aminoácidos Excitadores/farmacología , Femenino , Proteínas de Transporte de Glicina en la Membrana Plasmática/metabolismo , Ketamina/farmacología , Macaca mulatta , Masculino , Memoria a Corto Plazo/efectos de los fármacos , N-Metilaspartato/metabolismo , Pruebas Neuropsicológicas , Tomografía de Emisión de Positrones , Radiofármacos , Memoria Espacial/efectos de los fármacos , Tetrahidronaftalenos/farmacocinética , Tetrahidronaftalenos/farmacologíaRESUMEN
Intramuscular fat (IMF) is a crucial factor for the meat quality of chickens. With the aim of studying the molecular mechanisms underlying IMF deposition in chickens, the expression profiles of five candidate transcription factors involved in lipid metabolism in several tissues were examined in Beijing-You (BJY) chickens at five ages (0, 4, 8, 14 and 20 wk). Results showed that accumulation of IMF in breast (IMFbr), thigh (IMFth) and abdominal fat weight increased significantly (P<0.01) after 8 wk. Accumulation of both IMFbr and IMFth from 8 to 14 wk exceeded that from 14 to 20 wk; IMFth was 4-7 times of IMFbr. As for the expression profiles of key transcription factors: 1) expression of C/EBPα and PPARγ in abdominal fat was significantly higher than that in breast and thigh muscles at all ages. The expression of C/EBPα was positively correlated with PPARγ in both breast and thigh muscles, which indicated that both C/EBPα and PPARγ promoted fat deposition and might act through a unified pathway; 2) the expression of SREBP-1 in 0, 4, and 8 wk in thigh muscle was significantly higher than that in breast; 3) expression of C/EBPß at 4 and 8 wk was significantly higher than that at 14 and 20 wk; and it was positively correlated with IMFth and IMFbr from 0 to 8 wk; 4) expression of PPARα in breast and thigh muscles was significantly higher than that in abdominal fat. Taken together, all five transcription factors studied play roles in lipid metabolism in chickens with C/EBPα and PPARγ being important effectors.
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Distribución de la Grasa Corporal , Pollos/genética , Pollos/metabolismo , Metabolismo de los Lípidos/genética , Factores de Transcripción/genética , Grasa Abdominal , Animales , Proteína alfa Potenciadora de Unión a CCAAT/genética , Proteína beta Potenciadora de Unión a CCAAT/genética , Regulación de la Expresión Génica , Masculino , Músculo Esquelético/fisiología , PPAR alfa/genética , PPAR gamma/genética , Proteína 1 de Unión a los Elementos Reguladores de Esteroles/genética , Factores de Transcripción/metabolismoRESUMEN
By estimating the genetic parameters of various semen quality traits in Beijing-You chickens, this study aims to elucidate the inheritance patterns of these traits and the correlations between them to facilitate setting up appropriate breeding strategies for enhanced semen quality. Semen samples were collected from 518 Beijing-You roosters at 43 wk of age from 3 selection lines related to meat flavor traits. Seven semen quality traits, consisting of semen volume, pH, and color, and sperm viability, motility, percent deformity, and concentration, were determined. Sizeable variations (18-24% CV) were observed for all traits, except for semen pH. The effects of semen collection time and origin of the chickens (line) were analyzed to optimize the proper models for estimating genetic parameters for each trait. The multiple-trait derivative-free restricted maximum likelihood method was used for estimating variance components. The results revealed that sperm viability, motility, and percent deformity exhibited high heritabilities (h(2) = 0.52, 0.85, and 0.60, respectively). Semen volume, semen color, and sperm concentration had moderate heritabilities (h(2) = 0.28, 0.19, and 0.12, respectively). Semen pH showed low heritability (h(2) = 0.03). Genetic and phenotypic correlations between sperm motility and viability were positive and high (rA = 0.88 and rP = 0.59). In addition, these 2 traits were genetically negatively correlated with percent deformity. This implied the possibility of reducing sperm deformity, which is difficult to measure, by indirect selection. It is concluded from this study that semen quality can be improved by selection. The traits with high variations and heritabilities such as semen volume are promising traits for selection to improve semen quality and likely reproductive performance of native chicken breeds.
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Cruzamiento , Pollos/fisiología , Variación Genética , Semen/fisiología , Crianza de Animales Domésticos , Animales , Pollos/genética , Masculino , Reproducción , Análisis de Semen/veterinariaRESUMEN
1. Changes resulting from divergent selection after 5 generations for intramuscular fat (IMF) content in breast muscle in a population of purebred Beijing-You chickens were investigated. Female chickens from lines selected-up (UL) and selected-down (DL) for 5 generations and random-bred controls (CL) were studied at 120 d of age. 2. In the UL, IMF in breast muscle (4.65%) was 1.38 times that in the DL (3.36%). The IMF content in leg muscle was also higher in UL compared to DL. 3. There were significant differences in growth, carcase traits and meat quality between the two selected lines. However, ultimate pH (pHu) was lower and lightness (L*) and yellowness (b*) were higher in breast muscles of UL birds compared to DL birds. Similar trends for pHu and L* value between UL and DL were observed in leg muscle. 4. Significant mRNA expression differences of the heart fatty acid-binding protein (H-FABP) gene between UL and DL were observed in breast muscle, and a negative correlation between expression of mRNA and IMF% in breast and leg muscles pointed to H-FABP as a potential selection candidate gene.
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Tejido Adiposo/metabolismo , Proteínas Aviares/genética , Pollos/fisiología , Regulación de la Expresión Génica , Selección Genética , Animales , Proteínas Aviares/metabolismo , Pollos/genética , Pollos/crecimiento & desarrollo , Femenino , Carne/análisis , Músculo Esquelético/crecimiento & desarrollo , Músculo Esquelético/metabolismo , ARN Ribosómico 18S/genética , ARN Ribosómico 18S/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinariaRESUMEN
Endocannabinoids and their attending cannabinoid type 1 (CB1) receptor have been implicated in animal models of post-traumatic stress disorder (PTSD). However, their specific role has not been studied in people with PTSD. Herein, we present an in vivo imaging study using positron emission tomography (PET) and the CB1-selective radioligand [(11)C]OMAR in individuals with PTSD, and healthy controls with lifetime histories of trauma (trauma-exposed controls (TC)) and those without such histories (healthy controls (HC)). Untreated individuals with PTSD (N=25) with non-combat trauma histories, and TC (N=12) and HC (N=23) participated in a magnetic resonance imaging scan and a resting PET scan with the CB1 receptor antagonist radiotracer [(11)C]OMAR, which measures the volume of distribution (VT) linearly related to CB1 receptor availability. Peripheral levels of anandamide, 2-arachidonoylglycerol, oleoylethanolamide, palmitoylethanolamide and cortisol were also assessed. In the PTSD group, relative to the HC and TC groups, we found elevated brain-wide [(11)C]OMAR VT values (F(2,53)=7.96, P=0.001; 19.5% and 14.5% higher, respectively), which were most pronounced in women (F(1,53)=5.52, P=0.023). Anandamide concentrations were reduced in the PTSD relative to the TC (53.1% lower) and HC (58.2% lower) groups. Cortisol levels were lower in the PTSD and TC groups relative to the HC group. Three biomarkers examined collectively--OMAR VT, anandamide and cortisol--correctly classified nearly 85% of PTSD cases. These results suggest that abnormal CB1 receptor-mediated anandamide signaling is implicated in the etiology of PTSD, and provide a promising neurobiological model to develop novel, evidence-based pharmacotherapies for this disorder.