Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 53
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Dig Liver Dis ; 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33257140

RESUMO

BACKGROUND: Diagnosis of malignant biliary obstruction is complicated and lacks accuracy. Exosomes may be secreted by malignant tumors; intact miRNAs from exosomes might serve as potential biomarkers for the disease. AIM: To identify exosomal microRNAs in human bile among benign and malignant biliary obstructions. METHODS: Bile samples were collected from patients undergoing therapeutic endoscopic retrograde cholangiopancreatography for biliary obstruction. Exosome microRNAs were determined by RNA-sequencing in the discovery cohort, which comprising benign (n = 5) cases and malignant biliary obstruction (n = 5) cases. Then, the diagnostic performance of the two up-regulated microRNAs (mir-483-5p and mir-126-3p) of bile exosomes was verified by analysis of 82 patients with a diagnosis of malignant (n=37) or nonmalignant (n=45) biliary obstruction. RESULTS: In both cohorts, the expressions of mir-483-5p and mir-126-3p were significantly higher in bile exosomes samples from patients with malignant biliary obstructions than controls. In the verification cohort, the two miRNAs can distinguished the benign and malignant groups with high diagnostic accuracy and specificity; the diagnostic values of the two microRNAs were better than serum carbohydrate antigen 19-9 (CA19-9), area under the curve (AUC) were 0.81 and 0.74. CONCLUSION: The expression of exosomal mir-483-5p and mir-126-3p in the bile samples discriminates between patients with malignant and nonmalignant biliary obstructions. CLINICAL TRIAL REGISTRATION NO: NCT03102268.

2.
FASEB J ; 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-33190300

RESUMO

Food withdrawal is usually used for accurate feed metabolizable energy (ME) assessment in poultry, but its effects on intestinal structure and the absorption of nutrients are unclear. In this study, broilers were fed ad libitum (CT) or withdrew food for 12 (FH12), 24 (FH24), 36 (FH36), or 48 hours (FH48). We showed that food withdrawal increased the energy assimilation when compared with the CT. Food withdrawal improved the digestibility of ether extract and the level of lipid substances and fatty acid-derived ß-hydroxybutyrate in serum. Compared to the CT, food withdrawal did not influence the digestibility of starch. Due to 12 hours or longer food withdrawal duration increased glutamate oxidation and uric acid excretion, the analyzed digestibility of crude protein was underestimated, although the upregulated amino acid transporter genes. In addition, histological analysis showed that short-term food withdrawal (12 hours) increased intestinal villus height, crypt depth, and proliferative cell, whereas prolonged food withdrawal (more than 24 hours) impaired villus structure due to the decreased cell proliferation. Moreover, proteomics analysis revealed upregulated pathways in birds withdrawn food for 36 hours involved in nutrient absorption and amino acid oxidation. In conclusion, food withdrawal changes nutrient absorption and utilization, especially for amino acid and ether extract, and results in increased ME. Both glutamate oxidation and fatty acid incomplete oxidation are involved in energy supply after refeeding. In contrast to short-term food withdrawal, prolonged food withdrawal impairs the intestinal structure and villus renewal. Our findings deserve attention from nutritionists who are analyzing food digestibility.

3.
Commun Biol ; 3(1): 611, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33097830

RESUMO

The renewal and repair of intestinal epithelium depend on the self-renewal of intestinal stem cells (ISCs) under physiological and pathological conditions. Although previous work has established that exogenous nutrients regulate adult stem cell activity, little is known about the regulatory effect of L-arginine on ISCs. In this study we utilize mice and small intestinal (SI) organoid models to clarify the role of L-arginine on epithelial differentiation of ISCs. We show that L-arginine increases expansion of ISCs in mice. Furthermore, CD90+ intestinal stromal cells augment stem-cell function in response to L-arginine in co-culture experiments. Mechanistically, we find that L-arginine stimulates Wnt2b secretion by CD90+ stromal cells through the mammalian target of rapamycin complex 1 (mTORC1) and that blocking Wnt2b production prevents L-arginine-induced ISC expansion. Finally, we show that L-arginine treatment protects the gut in response to injury. Our findings highlight an important role for CD90+ stromal cells in L-arginine-stimulated ISC expansion.

4.
BMC Genomics ; 21(1): 412, 2020 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-32552672

RESUMO

BACKGROUND: In recent years, increased attention has been focused on breast muscle yield and meat quality in poultry production. Supplementation with nicotinamide and butyrate sodium can improve the meat quality of broilers. However, the potential molecular mechanism is not clear yet. This study was designed to investigate the effects of supplementation with a combination of nicotinamide and butyrate sodium on breast muscle transcriptome of broilers under high stocking density. A total of 300 21-d-old Cobb broilers were randomly allocated into 3 groups based on stocking density: low stocking density control group (L; 14 birds/m2), high stocking density control group (H; 18 birds/m2), and high stocking density group provided with a combination of 50 mg/kg nicotinamide and 500 mg/kg butyrate sodium (COMB; 18 birds/m2), raised to 42 days of age. RESULTS: The H group significantly increased cooking losses, pH decline and activity of lactate dehydrogenase in breast muscle when compared with the L group. COMB showed a significant decrease in these indices by comparison with the H group (P < 0.05). The transcriptome results showed that key genes involved in glycolysis, proteolysis and immune stress were up-regulated whereas those relating to muscle development, cell adhesion, cell matrix and collagen were down-regulated in the H group as compared to the L group. In contrast, genes related to muscle development, hyaluronic acid, mitochondrial function, and redox pathways were up-regulated while those associated with inflammatory response, acid metabolism, lipid metabolism, and glycolysis pathway were down-regulated in the COMB group when compared with the H group. CONCLUSIONS: The combination of nicotinamide and butyrate sodium may improve muscle quality by enhancing mitochondrial function and antioxidant capacity, inhibiting inflammatory response and glycolysis, and promoting muscle development and hyaluronic acid synthesis.

5.
Anim Sci J ; 91(1): e13409, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32524726

RESUMO

This study was aimed to explore the comparative acidifying properties of 2-hydroxy-4-(methylthio) butanoic acid (HMTBA) and a combination of DL-methionine (DLM) and acidifier in male broiler production. A total of 480 1-day-old broiler chicks were randomly divided into four treatments: A (low HMTBA, 0.057% HMTBA); B (low acidifier, 0.05% DLM + 0.057% acidifier); C (high HMTBA, 0.284% HMTBA); and D (high acidifier, 0.25% DLM + 0.284% acidifier). At 21 d, growth performance, chyme pH, digestive enzyme activities, and intestinal microflora were measured. The pH of crop, gizzard, and ileum contents was higher in the HMTBA treatment group than in DLM + acidifier treatment group. Furthermore, acidifier supplementation promoted growth of butyrate-producing bacteria such as Faecalibacterium, whereas high HMTBA (0.284%) inhibited the proliferation of acid-producing bacteria including Roseburia and Collinsella. The chymotrypsin activity was lower in the HMTBA group than in the DLM + acidifier group. In contrast, high-level HMTBA group showed higher average daily gain and average daily feed intake than the DLM + acidifier group. These results suggested that HMTBA work through different pathways with DLM plus acidifier.


Assuntos
Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Galinhas/crescimento & desenvolvimento , Galinhas/microbiologia , Galinhas/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Metionina/análogos & derivados , Metionina/farmacologia , Animais , Quimotripsina/metabolismo , Papo das Aves , Ingestão de Alimentos/efeitos dos fármacos , Conteúdo Gastrointestinal , Moela das Aves , Concentração de Íons de Hidrogênio , Íleo , Masculino , Ganho de Peso/efeitos dos fármacos
6.
Poult Sci ; 99(3): 1462-1470, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32115032

RESUMO

This study was conducted to investigate the effects of supplementation with nicotinamide (NAM) and sodium butyrate (BA) on meat quality and expression of muscle development genes in broilers reared at a high stocking density. A total of 567, 21-day-old AA broilers were randomly assigned to 5 treatment groups and 2 control groups, with 7 replicates of each group. The control groups included a low stocking density (LD; 12.9 birds/m2) and were fed a basal diet. The treatment groups were kept at a high stocking density (HD; 18.6 birds/m2) and received either a low dose of NAM (50 mg/kg; treatment LN), a high dose of NAM (100 mg/kg; treatment HN), a low dose of BA (500 mg/kg; treatment LB), a high dose of BA (1,000 mg/kg; treatment HB), or a compound supplement (50 mg/kg NAM+500 mg/kg BA; treatment COMB); broilers were reared till 42 D of age. The control groups were kept at HD or at LD (12.9 birds/m2) and were fed a basal diet. The heterophil-to-lymphocyte ratio was significantly higher in the HD control group than that in the LD group; this ratio was significantly lower in treatments LN, HN, HB, and COMB than that in the HD control group. The lightness of breast muscles at 45 min and 24 h after slaughter was significantly higher in the HD group than that in the LD group, and the HD group showed the highest drip loss at 24 h and 48 h. Lightness and drip loss were lower in the HN, LB, and COMB treatments than those in the HD group. HD rearing significantly reduced gene expression of myogenic regulatory factor 5 (MYF5) while significantly increased expression of the protein ubiquitin degradation genes FBXO9, FBXO22, and FBXO32. All treatments significantly reduced FBXO9 and FBXO32 expression. Our results suggest dietary supplementation with NAM and BA can improve meat quality of broilers under high stocking density by upregulating the expression of myogenic genes, and inhibiting protein ubiquitination.


Assuntos
Proteínas Aviárias/genética , Ácido Butírico/metabolismo , Galinhas/fisiologia , Expressão Gênica , Carne/análise , Niacinamida/metabolismo , Ração Animal/análise , Animais , Proteínas Aviárias/metabolismo , Ácido Butírico/administração & dosagem , Galinhas/genética , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Niacinamida/administração & dosagem , Músculos Peitorais/fisiologia , Densidade Demográfica , Distribuição Aleatória , Estresse Fisiológico/genética , Ubiquitinação
7.
Anim Biotechnol ; 31(6): 520-531, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31253055

RESUMO

To study why flaxseed supplementation causes adverse effects on the performance of poultry, we investigated the gut microbiota of Peking ducks after consumption of a flaxseed diet. A total of 792, 12-day-old white Peking ducks were divided into four groups. In the control group, birds were provided with a basal diet. In the three experimental groups, the birds were fed flaxseed containing diet (10% flaxseed and 90% basal diet) for 30, 20 and 10 d, respectively. On day 42, ceca were collected to evaluate the bacterial diversity of the gut microbiota using microbial 16S rDNA gene profiling; serums were obtained to determine the levels of inflammatory mediators. The flaxseed diet decreased the alpha diversity and shifted the predominant genera of the gut microbiota. Flaxseed-fed groups had higher abundances of Escherichia/Shigella (p < 0.1) and Campylobacter (p < 0.05) than the control group. The abundance of pro-inflammatory bacteria such as Veillonellaceae increased (p < 0.05) at first and then decreased (p < 0.05) with prolonged flaxseed supplementation. The levels of prostaglandin E2 and Leukotriene B4 in serum showed the same pattern as that of the pro-inflammatory bacteria. In conclusion, flaxseed diets are associated with inflammation by altering the cecal microbiota dynamics.

8.
Ann Surg ; 271(3): 519-526, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-30148752

RESUMO

OBJECTIVE: The aim of the study was to evaluate the oncological outcomes of complete mesocolic excision (CME) in colon cancer patients. SUMMARY BACKGROUND DATA: CME is considered a standard procedure for colon cancer patients. However, previous evidence regarding the effect of CME on prognosis has fundamental limitations that prevent it from being fully accepted. METHODS: Patients who underwent radical resection for colon cancer were enrolled between November 2012 and March 2016. According to the principles of CME, patients were stratified into 2 groups based on intraoperative surgical fields and specimen photographs. The primary outcome was local recurrence-free survival (LRFS). The clinicopathological data and follow-up information were collected and recorded. The final follow-up date was April 2016. The trial was registered in ClinicalTrials.gov (identifier: NCT01724775). RESULTS: There were 220 patients in the CME group and 110 patients in the noncomplete mesocolic excision (NCME) group. Baseline characteristics were well balanced. Compared with NCME, CME was associated with a greater number of total lymph nodes (24 vs 20, P = 0.002). Postoperative complications did not differ between the 2 groups. CME had a positive effect on LRFS compared with NCME (100.0% vs 90.2%, log-rank P < 0.001). Mesocolic dissection (100.0% vs 87.9%, log-rank P < 0.001) and nontumor deposits (97.2% vs 91.6%, log-rank P < 0.022) were also associated with improved LRFS. CONCLUSIONS: Our findings demonstrate that, compared with NCME, CME improves 3-year LRFS without increasing surgical risks.


Assuntos
Colectomia/métodos , Neoplasias do Colo/cirurgia , Mesocolo/cirurgia , Adulto , Idoso , Neoplasias do Colo/mortalidade , Método Duplo-Cego , Feminino , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Fotografação , Complicações Pós-Operatórias , Estudos Prospectivos , Taxa de Sobrevida
9.
Food Funct ; 10(11): 7081-7090, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31670358

RESUMO

This study was conducted to investigate the effects of stocking density and dietary nicotinamide (NAM) and butyrate sodium (BA) supplementation on the growth performance, liver mitochondrial function and gut microbiota of broilers at high stocking density. A total of 342, 26-d-old Cobb500 broilers were divided into 5 groups with 6 replicates. Treatments were as follows: (a) Low stocking density (L, 9 birds per cage); (b) High stocking density (H, 12 birds per cage); (c) H + 50 ppm NAM; (d) H + 500 ppm BA; (e) H + 50 ppm NAM + 500 ppm BA (COMB). The results showed that high stocking density significantly reduced the feed intake and body weight gain of broilers, while COMB improved the growth performance at high stocking density. High stocking density significantly reduced the liver metallothionein content, liver mitochondrial membrane potential and the activities of Na+K+-ATPase and Ca2+Mg2+-ATPase. In contrast, the liver metallothionein contents in the NAM, BA and COMB fed group were higher than those in the H group. COMB increased the activity of ATPase as well, but it failed to enhance the mitochondrial membrane potential. Stocking density also affected gut microbiota of broilers. The high-density group increased the relative abundance of Blautia. Supplementation of BA and NAM increased the abundance of Lactobacillus and Bifidobacteria, respectively. In conclusion, a combination of NAM and BA can improve the performance, antioxidant capacity, mitochondrial function and intestinal microbiota of broilers at high stocking density.


Assuntos
Ácido Butírico/administração & dosagem , Galinhas/crescimento & desenvolvimento , Galinhas/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Fígado/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Niacinamida/análise , Ração Animal/análise , Animais , Galinhas/microbiologia , Suplementos Nutricionais/análise , Feminino , Fígado/metabolismo , Masculino , Mitocôndrias/metabolismo
10.
Anim Nutr ; 5(3): 241-247, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31528725

RESUMO

This study was designed to compare the effect of methionine (Met) sources (DL-methionine [DLM] and DL-2-hydroxy-4-methylthio-butanoic acid [HMTBa]) and their supplementation levels on broiler growth performance and redox state. A 2 × 2 factorial arrangement was used with 2 sources (DLM and HMTBa) and 2 supplementation levels (0.05% and 0.25%) of Met. A total of 480 one-day-old broiler chicks were randomly divided into 4 treatments with 8 replicates per treatment (15 birds per replicate). The experiment lasted for 21 d. Broiler growth performance, redox capacity, redox-related genes expression, and Met transporters in different tissues were tested. Broilers fed high Met supplementation levels had improved (P < 0.05) body weight (BW), average daily gain (ADG) and feed conversion ratio (FCR). Similarly, broilers fed high Met levels had better (P < 0.05) antioxidant abilities in the serum, small intestine, and liver. Whereas, interactive effects (P < 0.05) were also observed between Met sources and levels. Compared with DLM, birds fed HMTBa diets had decreased (P < 0.05) total glutathione (T-GSH) and oxidized glutathione (GSSG) contents in duodenum, ileum, and liver. Similarly, broilers fed HMTBa supplemented diets had increased (P < 0.05) thioredoxin (Trx) gene expression in the duodenum and ileum, but decreased (P < 0.05) glutaredoxin (Grx), glutathione reductase (GSR), and glutathione synthetase (GSS) genes expression. Furthermore, lower gene expression of Na+ and Cl- dependent neutral and cationic amino acid transporter (ATB 0, + ), and Na+ dependent neutral amino acid transporter (B 0 AT) in the duodenum brush border, but higher gene expression of diamine acetyltransferase 1 (SAT1) and Na+-independent branched-chain and aromatic amino acid transporter (LAT1) in the jejunum and ileum basement membrane along with higher expression of the proton dependent monocarboxylate transporter 1 (MCT1) gene in the ileum were detected in birds fed HMTBa diets. In conclusion, DLM can be effectively used in glutathione synthesis to exert antioxidant functions, whereas HMTBa favors S-adenosylmethionine (SAM) synthesis and thus stimulates antioxidant-related genes expression.

11.
Transplant Proc ; 51(6): 2124-2131, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31399188

RESUMO

BACKGROUND: Acute rejection of a kidney allograft results from adaptive immune responses and marked inflammation. The eicosanoid prostaglandin E2 (PGE2) modulates the inflammatory response, is generated by cyclooxygenase 2 (COX-2), and binds to 1 of the 4 G protein-coupled E prostanoid cell surface receptors (EP1-4). Receptor activation results in in proinflammatory (EP1 and EP3) or anti-inflammatory (EP2 and EP4) responses. We theorized that expression of the components of the COX-PGE2-EP signaling pathway correlates with acute rejection in a porcine model of allogeneic renal transplantation. METHOD: COX-2 enzyme and EP receptor protein expression were quantitated with western blotting and immunohistochemistry from allotransplants (n = 18) and autotransplants (n = 5). Linear regression analysis was used to correlate EP receptor expression with the Banff category of rejection. RESULTS: Pigs with advanced rejection demonstrated significant increases in serum PGE2 metabolites, while pigs with less rejection demonstrated higher tissue concentrations of PGE2 metabolites. A significant negative correlation between COX-2 expression and Banff category of rejection (R = -0.877) was shown. Rejection decreased expression of EP2 and EP4. For both receptors, there was a significant negative correlation with the extent of rejection (R = -0.760 and R = -0.891 for EP2 and EP4, respectively). Rejection had no effect on the proinflammatory receptors EP1 and EP3. CONCLUSION: Downregulation of COX-2 and the anti-inflammatory EP2 and EP4 receptors is associated with acute rejection in unmatched pig kidney transplants, suggesting that the COX-2-PGE2-EP pathway may modulate inflammation in this model. Enhancing EP2 and/or EP4 activity may offer novel therapeutic approaches to controlling the inflammation of acute allograft rejection.


Assuntos
Dinoprostona/biossíntese , Rejeição de Enxerto/metabolismo , Transplante de Rim , Receptores de Prostaglandina/biossíntese , Animais , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo , Transdução de Sinais/fisiologia , Suínos
12.
Spectrochim Acta A Mol Biomol Spectrosc ; 223: 117347, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31325843

RESUMO

Enteromorpha prolifera, the marine algae frequently causing green tide in the littoral areas in recent years, was investigated as a feasible biosorbent to remove azo dye Direct Fast Scarlet 4BS (DFS-4BS) from aqueous solution. The FTIR spectra of the acid-treated Enteromorpha prolifera (ATEP) biomass before and after dye sorption were used to identify the main functionalities involved in the biosorption process. Results of batch experiments showed that the adsorption capacity of ATEP was dependent on solution pH, ATEP dosage and temperature. The adsorption kinetics followed the pseudo-second order rate equation, while the adsorption isotherm could be well described by the Langmuir model with maximum sorption capacity of 318.87mg·g-1, demonstrating the excellent performance of ATEP as a biosorbent to remove DFS-4BS from aqueous solution. The negative values of free energy change (ΔG°) and positive value of enthalpy change (ΔH°) confirmed that the sorption of DFS-4BS onto ATEP was spontaneous and endothermic in the temperature range of 303-333K. The isosteric heat of adsorption increased with the increase of surface loading, suggesting that the ATEP biomass had heterogeneous surface and lateral interactions might exist among adsorbed molecules. According to the sorption results and the FTIR spectra, it was deduced that the adsorption mechanism involved hydrogen bonding, electrostatic attraction and bonding, and hydrophobic and van der Waals interaction.


Assuntos
Compostos Azo/isolamento & purificação , Clorófitas/metabolismo , Poluentes Químicos da Água/análise , Água/química , Adsorção , Compostos Azo/química , Biodegradação Ambiental , Concentração de Íons de Hidrogênio , Cinética , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Temperatura
13.
J Biochem ; 166(3): 271-279, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31157375

RESUMO

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death worldwide. miR-484 is previously reported to be a crucial modulator during the process from precancerous lesion to cancer. Tumour suppressor candidate 5 (TUSC5) is a potential tumour suppressor, but its expression and function in HCC are obscure. In this study, we aimed to explore the roles of miR-484 and TUSC5 in HCC, and clarify the relationship between them. We demonstrated that miR-484 was significantly up-regulated in HCC, while TUSC5 was down-regulated. TUSC5 was validated as the target gene of miR-484 and both of them were associated with the prognosis of HCC patients. miR-484 mimics markedly promoted the malignant phenotypes while TUSC5 plasmid had the opposite effect. In conclusion, miR-484/TUSC5 is potential diagnostic biomarkers and therapy targets for HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , MicroRNAs/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/diagnóstico , Linhagem Celular Tumoral , Feminino , Humanos , Neoplasias Hepáticas/diagnóstico , Masculino , Proteínas de Membrana/análise , Proteínas de Membrana/genética , MicroRNAs/análise , MicroRNAs/genética , Pessoa de Meia-Idade , Proteínas Supressoras de Tumor/análise , Proteínas Supressoras de Tumor/genética
14.
Front Immunol ; 10: 838, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31057556

RESUMO

Long non-coding RNAs (lncRNAs) have recently emerged as new regulatory molecules with diverse functions in regulating gene expression and significant roles in the immune response. However, the function of many unknown lncRNAs is still unclear. By studying the regulatory effect of daidzein (DA) on immunity, we identified a novel lncRNA with an immune regulatory function: lncRNA- XLOC_098131. In vivo, DA treatment upregulated the expression of lncRNA- XLOC_098131, FOS, and JUN in chickens and affected the expression of activator protein 1 (AP-1) to regulate MAPK signaling, Toll-like receptor signaling, and related mRNA expression. It also enhanced macrophage activity and increased the numbers of blood neutrophils and mononuclear cells, which can improve the body's ability to respond to stress and bacterial and viral infections. Furthermore, DA treatment also reduced B lymphocyte apoptosis and promoted the differentiation of B lymphocytes into plasma cells, which in turn resulted in the production of more immunoglobulins and the promotion of antigen presentation. In vitro, using HEK293FT cells, we demonstrated that mir-548s could bind to and decrease the expression of both FOS and lncRNA- XLOC_098131. LncRNA- XLOC_098131 served as a competitive endogenous RNA to stabilize FOS by competitively binding to miR-548s and thereby reducing its inhibitory effect of FOS expression. Therefore, we concluded that the novel lncRNA XLOC_098131 acts as a key regulatory molecule that can regulate the Toll-like receptor signaling pathway and related immune function by serving as a competitive endogenous RNA to stabilize FOS mRNA expression.


Assuntos
Proteínas Aviárias/imunologia , Galinhas/imunologia , Proteínas Proto-Oncogênicas c-fos/imunologia , Estabilidade de RNA/imunologia , RNA Longo não Codificante/imunologia , RNA Mensageiro/imunologia , Transdução de Sinais/imunologia , Receptores Toll-Like/imunologia , Animais , Células HEK293 , Humanos
15.
J Anim Sci Biotechnol ; 10: 26, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30988947

RESUMO

Background: There is growing interest in carbohydrate and protein nutrition to enhance the efficiency of animal production. Reduced-crude protein diets depress environmental pollution and feeding cost, but the challenge to their adoption is maintaining digestive function and growth performance of birds. The present study was conducted to evaluate the influence of different dietary starch sources and protein levels on intestinal functionality and mucosal amino acid catabolism. Methods: Six dietary treatments, based on maize and soybean meal, were offered to 360 AA+ male chicks from 6 to 35 d post-hatch as a 3 × 2 factorial array. Either waxy rice or amylose was added to a conventional maize-soy diet to provide three sources of starch with different digestion rates and relatively high and low dietary protein levels. Growth performance, parameters of intestinal functionality and concentrations of free amino acid in the portal circulation were determined. Results: In the grower phase, starch source influenced (P < 0.02) weight gain as diets containing amylose supported significantly higher weight gains than waxy rice. Significant increase of ileal ATP concentrations and Na+/K+-ATPase activity were found in amylose treatment. Also, amylose decreased BrdU positive cell numbers and down-regulated mRNA expression for CASP-3. GOT activity in the ileum was higher (P < 0.01) in birds offered low protein diets and there was a trend (P = 0.057) for waxy rice as a starch source to increase ileal GOT activities. There was a significant influence on the concentration of seventeen amino acids in the portal circulation with tryptophan the one exception. Waxy rice as a starch source generated 13.6% and 22.4% numerically higher concentrations of non-essential amino acids than maize and amylose, respectively. Conclusions: Amino acid catabolism in the gut mucosa is subject to nutritional regulation. Given that amino acids can be spared from catabolism in the gut mucosa by supplementation of amylose, it follows their post-enteral availability would be improved and intestinal energy would be derived more efficiently from glucose.

16.
J Investig Med ; 66(8): 1109-1117, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30006478

RESUMO

In kidney transplantation acute allograft rejection is the most common cause of late allograft loss. Changes in indoleamine 2,3 dioxygenase (IDO) activity, which catabolizes the degradation of tryptophan to kynurenine, may predict rejection. However, exogenous IDO is immunosuppressive in rodent kidney transplantation. Thus, the increase in IDO activity observed in acute allograft rejection is insufficient to prevent rejection. To address this question, we assessed the regulation of IDO and its role in acute rejection in a porcine model of kidney transplant. In tissue samples from rejecting kidney allografts, we showed a 13-fold increase in IDO gene transcription and 20-fold increase in IDO enzyme activity when compared with autotransplanted kidneys. Allografts also demonstrated an over fourfold increase in tissue interferon (IFN)-γ, with marked increases in tumor necrosis factor (TNF)-α, TNF-ß and interleukin 1ß. Gene transcription and protein levels of kynurenine 3-monooxygenase (KMO) were decreased. KMO generates the immunosuppressive kynurenine, 3-hydroxykynurenine. The results of these studies demonstrate a clear association between rejection and increased allograft IDO expression, likely driven in part by IFN-γ and facilitated by other cytokines of the allogeneic response. Moreover, the loss of downstream enzymatic activity in the IDO metabolic pathway may suggest novel mechanisms for the perpetuation of rejection.


Assuntos
Aloenxertos/transplante , Rejeição de Enxerto/enzimologia , Indolamina-Pirrol 2,3,-Dioxigenase/metabolismo , Transplante de Rim/efeitos adversos , Animais , Creatinina/sangue , Citocinas/genética , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Regulação Enzimológica da Expressão Gênica , Rejeição de Enxerto/sangue , Indolamina-Pirrol 2,3,-Dioxigenase/genética , Rim/patologia , Cinurenina/metabolismo , Suínos , Transcrição Genética , Transplante Homólogo
17.
FASEB J ; 32(7): 3803-3815, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29475397

RESUMO

Evidence is provided that the fibroproliferative actions of TGF-ß are dependent on a metabolic adaptation that sustains pathologic growth. Specifically, profibrotic TGF-ß signaling is shown to require fatty acid synthase (FASN), an essential anabolic enzyme responsible for the de novo synthesis of fatty acids. With the use of pharmacologic and genetic approaches, we show that TGF-ß-stimulated FASN expression is independent of Smad2/3 and is mediated via mammalian target of rapamycin complex 1. In the absence of FASN activity or protein, TGF-ß-driven fibrogenic processes are reduced with no apparent toxicity. Furthermore, as increased FASN expression was also observed to correlate with the degree of lung fibrosis in bleomycin-treated mice, inhibition of FASN was examined in a murine-treatment model of pulmonary fibrosis. Remarkably, inhibition of FASN not only decreased expression of profibrotic targets, but lung function was also stabilized/improved, as assessed by peripheral blood oxygenation.-Jung, M.-Y., Kang, J.-H., Hernandez, D. M., Yin, X., Andrianifahanana, M., Wang, Y., Gonzalez-Guerrico, A., Limper, A. H., Lupu, R., Leof, E. B. Fatty acid synthase is required for profibrotic TGF-ß signaling.


Assuntos
Ácido Graxo Sintase Tipo I/metabolismo , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Animais , Bleomicina/toxicidade , Linhagem Celular , Ácido Graxo Sintase Tipo I/genética , Camundongos , Camundongos Endogâmicos C57BL , Fibrose Pulmonar/etiologia , Transdução de Sinais , Proteínas Smad/metabolismo
18.
Oncotarget ; 8(41): 69995-70005, 2017 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-29050258

RESUMO

Cholangiocarcinoma (CCA) is an aggressive malignancy associated with unfavorable prognosis, and it's difficult to diagnose and no effective treatments are available. Long non-coding RNAs (lncRNAs) play important roles in tumorigenesis and metastasis. Intact lncRNAs from exosomes have sparked much interest as potential biomarker for the non-invasive analysis of disease. Here, via exosome sequencing on lncRNAs, GO analysis, KEGG pathway and co-expression analysis, receiver operating characteristic curve and survival analyses, we found that, compared with control group, lncRNAs of ENST00000588480.1 and ENST00000517758.1 showed significantly increased expressions in CCA group. Moreover, area under the curve (AUC) was increased to 0.709 when combined the two lncRNAs, they had a sensitivity and specificity of 82.9% and 58.9% respectively. Further, the higher levels of the two lncRNAs showed a significantly increasing trend with the advancement of cancer TNM stages, and prognosticated a poor survival. In addition, KEGG pathway analysis showed that the most significant difference term was "p53 signaling pathway" (KEGG ID: hsa04115, p: 0.001). The altered lncRNAs and their target genes were included to reconstruct a co-expression network. These altered lncRNAs were mainly related to cellular processes, environmental information processing and organismal systems, etc. Collectively, our findings provided the potential roles of lncRNAs of ENST00000588480.1 and ENST00000517758.1 in CCA, and implicated these lncRNAs as potential diagnostic and therapeutic targets for CCA.

19.
Sci Rep ; 7(1): 7334, 2017 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-28779076

RESUMO

Necrotic enteritis (NE) caused by Clostridium perfringens is one of the most detrimental infectious diseases in poultry. This study examined the effect of blends of essential oils (BEOs) (25% thymol and 25% carvacrol) on NE and bacterial dynamics and functions in chicks challenged with C. perfringens. Chicks were assigned to a Control diet and BEOs diet (Control diet + 120 mg/kg BEOs), were challenged with C. perfringens from days 14 to 20 and were killed on day 21 for assessment. Supplementation with BEOs decreased the mortality, alleviated gut lesions, and decreased the virulence factors of pathogenic bacteria (VF 0073-ClpE, VF0124-LPS, and VF0350-BSH). Lack of supplementation also changed the nutrient and immunological dynamics of host microbiota in responding to C. perfringens infection. Adding BEOs changed the host ileum microbial population by increasing the numbers of Lactobacillus crispatus and Lactobacillus agilis, and decreasing Lactobacillus salivarius and Lactobacillus johnsonii. The functional roles of these changing host bacterial populations coupled with the putative reduced pathogenicity of C. perfringens by BEOs contributed to the reduction in gut lesions and mortality in infected chickens. It suggests that dietary supplementation with BEOs could significantly reduce the impact of NE caused by C. perfringens on broilers.


Assuntos
Infecções por Clostridium/veterinária , Clostridium perfringens/efeitos dos fármacos , Enterocolite Necrosante/veterinária , Lactobacillus/efeitos dos fármacos , Monoterpenos/farmacologia , Doenças das Aves Domésticas/tratamento farmacológico , Doenças das Aves Domésticas/microbiologia , Timol/farmacologia , Animais , Galinhas , Cimenos , Suplementos Nutricionais , Microbioma Gastrointestinal , Íleo/microbiologia , Lactobacillus/genética , Masculino , Metagenoma , Metagenômica/métodos , Doenças das Aves Domésticas/mortalidade , Doenças das Aves Domésticas/patologia
20.
Mol Biol Cell ; 28(20): 2701-2711, 2017 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-28768825

RESUMO

Delivery of biomolecules to the correct subcellular locales is critical for proper physiological function. To that end, we have previously determined that type I and II transforming growth factor beta (TGF-ß) receptors (TßRI and TßRII, respectively) localize to the basolateral domain in polarized epithelia. While TßRII targeting was shown to be regulated by sequences between amino acids 529 and 538, the analogous region(s) within TßRI is unknown. To address that question, sequential cytoplasmic TßRI truncations and point mutations identified a targeting motif between residues 158 and 163 (VxxEED) required for basolateral TßRI expression. Further studies documented that receptor internalization, down-regulation, direct recycling, or Smad signaling were unaffected by motif mutations that caused TßRI mislocalization. However, inclusion of amino acids 148-217 containing the targeting motif was able to direct basolateral expression of the apically sorted nerve growth factor receptor (NGFR, p75; extracellular and transmembrane regions) in a dominant manner. Finally, coexpression of apically targeted type I and type II TGF-ß receptors mediated Smad3 signaling from the apical membrane of polarized epithelial cells. These findings demonstrate that the absence of apical TGF-ß signaling in normal epithelia is primarily a reflection of domain-specific receptor expression and not an inability to couple with the signaling machinery.


Assuntos
Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Fatores de Crescimento Transformadores beta/genética , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Motivos de Aminoácidos , Animais , Membrana Celular/metabolismo , Polaridade Celular/fisiologia , Citoplasma/metabolismo , Cães , Expressão Gênica , Humanos , Células Madin Darby de Rim Canino , Ligação Proteica , Transporte Proteico , Receptor do Fator de Crescimento Transformador beta Tipo II , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA