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1.
Mol Reprod Dev ; 87(2): 241-250, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32026564

RESUMO

Overweight and obese men face numerous health problems, including type 2 diabetes, subfertility, and even infertility. However, few studies have focused on the effects of nutritional status and obesity-related regulatory signals on fertility deficiency. Our previous observations have shown that the elevation of plasma 5'-adenosine monophosphate (5'-AMP) and the accumulation of adenosine in liver and muscle of obese diabetic db/db mice are related to insulin resistance. Here, we found that adenosine accumulation in testis is a common marker of both genetic obesity and high-fat-diet induced obese mice. An messenger RNA sequencing analysis indicated that 78 upregulated genes and 155 downregulated genes in the testis of 5'-AMP-treated mice overlapped with the same genes in the testis of ob/ob mice, and these genes belonged to the clusters of steroid metabolic process and regulation of hormone levels, respectively. Serum testosterone was reduced in ob/ob and 5'-AMP-treated mice. Metabolomic analysis based on 1 H nuclear magnetic resonance showed that the testicular metabolic profiles of ob/ob mice were similar to those of 5'-AMP treated mice. Exogenous 5'-AMP inhibited the phosphorylation of AKT and mammalian target of rapamycin signal transduction and reduced the proliferating cell nuclear antigen expressions in testes. Our results suggest that the accumulation of adenosine causes metabolic disorders in testes and associates lower testosterone level in obese mice.

2.
Int J Biol Macromol ; 150: 802-813, 2020 Feb 11.
Artigo em Inglês | MEDLINE | ID: mdl-32057883

RESUMO

Infectious diseases such as Listeria monocytogenes infection pose a great threat to the health of human beings and the development of livestock and poultry farming. Currently the treatment of Listeria infection mainly relies on antibiotics, which may result in excessive antibiotic residues in livestock and poultry products, as well as causing an increase in the occurrence of zoonotic diseases. Here, we demonstrate that Succinoglycan Riclin promoted the clearance of Listeria in the in vitro and in vivo infection model. The expression and secretion of inflammatory cytokines including IL-6 and IL-1ß were significantly increased after Riclin treatment upon infection. The protective effect of Riclin was mainly through activating MAPK/IL-6 axis. HO-1/IL-1ß signaling pathway was less important in this process. Moreover, Riclin caused significant metabolic changes including pathways involved in glycolysis, protein synthesis and oxidative stress during Listeria infection. These results suggest a potential use of Succinoglycan Riclin as non-antibiotic preventive and therapeutic anti-microbial agent in livestock and poultry farming and human diseases.

3.
Food Chem Toxicol ; 136: 111080, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31891755

RESUMO

Fumonisin B1 (FB1) is a mycotoxin, produced by Fusarium verticillioides and Fusarium proliferatum, and a common fungal contaminant of maize worldwide. Its potential health hazard as a natural toxin is well documented in human and domestic animals. However, the molecular mechanism and the key factors responsible for FB1-induced cytotoxicity have not been elucidated. In this study, we first examined the cytotoxicity induced by FB1 in human gastric epithelial cell line (GES-1). We found that FB1 notably decreased cell viability and induced apoptotic cell death. Furthermore, the levels of ER stress markers were significantly increased after FB1 exposure and the ER stress inhibitor 4-phenylbutyric acid strongly suppressed FB1-induced cytotoxicity. Interestingly, the inhibition of PERK activity by GSK2606414 or shPERK3 blocked FB1-induced apoptotic cell death and cell proliferation suppression, which indicated that the cytotoxicity induced by FB1 was dependent on this signalling pathway. Moreover, myriocin could relieve FB1-induced ER stress and prevent cell death, which implied that the disruption of sphingolipid metabolism is an apical event for FB1-induced cytotoxicity. In the present study, we demonstrated that the ER stress-related PERK-CHOP signalling pathway is a novel mechanism for FB1-induced cytotoxicity and the gastrointestinal injury caused by FB1 should be concerned in the future.

4.
Int J Biol Macromol ; 148: 1053-1060, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-31982527

RESUMO

Vulvovaginal candidiasis (VVC) is one of the most common infections in women. The purpose of this study was to evaluate the ability of a water-soluble ß-glucan salecan to protect against Candida albicans (C. albicans) vaginal infection. The model was reproduced with intravaginal inoculation of yeast blastoconidia in pseudoestrus mice. We found that mice that received salecan (0.5 mg per mouse) after infection had 85% fewer CFU than infected mice given saline. Compared with the C.albicans group, salecan reduced the migration of polymorphonuclear neutrophils (PMNs) in the vagina, decreased mRNA levels of cytokines IL23, IL22, IL17a, and IL17f, anti-candidal genes S100a8 and S100a9 and C.albicans pattern recognition receptor Dectin1. The analysis for vaginal microbial community composition at different taxa levels revealed that the bacterial flora composition in the vagina of the salecan-treated mice was similar to that of the uninfected mice, and distinguished from the infected mice. The vaginal lavages from the salecan treated group had more Enterococcus and its metabolite lactate. Our results suggest salecan might be a potential therapeutic agent for vaginal infection of C.albicans.

5.
Br J Nutr ; 123(6): 627-641, 2020 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-31813383

RESUMO

An oral starch administration trial was used to evaluate glucose homoeostasis in grass carp (Ctenopharyngodon idella) and Chinese longsnout catfish (Leiocassis longirostris Günther). Fish were administered with 3 g of a water and starch mixture (with 3:2 ratio) per 100 g body weight after fasting for 48 h. Fish were sampled at 0, 1, 3, 6, 12, 24 and 48 h after oral starch administration. In grass carp, plasma levels of glucose peaked at 3 h but returned to baseline at 6 h. However, in Chinese longsnout catfish, plasma glucose levels peaked at 6 h and returned to baseline at 48 h. The activity of intestinal amylase was increased in grass carp at 1 and 3 h, but no significant change in Chinese longsnout catfish was observed. The activity of hepatic glucose-6-phosphatase fell significantly in grass carp but change was not evident in Chinese longsnout catfish. The expression levels and enzymic activity of hepatic pyruvate kinase increased in grass carp, but no significant changes were observed in the Chinese longsnout catfish. Glycogen synthase (gys) and glycogen phosphorylase (gp) were induced in grass carp. However, there was no significant change in gys and a clear down-regulation of gp in Chinese longsnout catfish. In brief, compared with Chinese longsnout catfish, grass carp exhibited a rapid increase and faster clearance rate of plasma glucose. This effect was closely related to significantly enhanced levels of digestion, glycolysis, glycogen metabolism and glucose-induced lipogenesis in grass carp, as well as the inhibition of gluconeogenesis.

6.
Fish Shellfish Immunol ; 97: 351-358, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31874297

RESUMO

This study was conducted to investigate the effect of dietary Scenedesmus ovalternus on the growth and disease resistance of gibel carp (Carassius gibelio) during overwintering. Gibel carp (initial body weight: 90.39 ± 0.33 g) were fed with diets containing 0% or 4% Scenedesmus ovalternus (DS0 and DS4) for 4 weeks during the early overwintering period, and then all fish were left unfed during the late overwintering period. A bacterial challenge test using Aeromonas hydrophila was subsequently conducted. The 4% Scenedesmus ovalternus diet had no effect on the growth of gibel carp (P > 0.05), but did improve the survival rate after the challenge (P ≤ 0.05). In the DS0 group, the bacterial challenge decreased the contents of complement 3 (C3), immunoglobulin M (IgM), interleukin 2 (IL2) and tumor necrosis factor α (TNFα) in fish (P < 0.05); in the DS4 group, the challenge increased total antioxidant capacity (T-AOC) and myeloperoxidase (MPO) activity but decreased IL2 and TNFα contents (P < 0.05). The activities of MPO and contents of C3, IgM and TNFα were higher in the DS4 group than that fed the DS0 diet after bacterial challenge (P < 0.05). Compared to pre challenge, the expression levels of toll like receptor 2 (TLR2), toll like receptor 3 (TLR3), toll like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), Toll/IL-1 receptor domain-containing adaptor protein (TIRAP), TIR-domain-containing adapter-inducing interferon ß (TRIF), nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor α (IκBα), transforming growth factor ß (TGFß), interleukin 1ß (IL1ß), tumor necrosis factor α1 (TNFα1) and interleukin 10 (IL10) in the head kidney of gibel carp were induced after challenge (P < 0.05). Gibel carp fed the DS4 diet showed lower expression of TGFß in head kidney before the challenge and lower expression of TLR2, TLR3, TLR4, TIRAP, TRIF, IκBα, TNFα1, IL10 and TGFß after the challenge than that fed the DS0 diet (P < 0.05). Overall, Scenedesmus ovalternus supplement enhanced the resistances of gibel carp against A. hydrophila after overwintering via the TLR signaling pathway.

7.
J Agric Food Chem ; 67(48): 13307-13317, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31679333

RESUMO

Epidemiological studies have demonstrated that hypercholesterolemia is associated with an elevated risk of atherosclerosis and cardiovascular diseases. In addition to the available cholesterol-lowering drugs, nutritionally balanced diets containing functional foods have attracted much interest as potential candidates to improve hypercholesterolemia. In the study, we demonstrated that dietary succinoglycan riclin effectively alleviated diet-induced hypercholesterolemia. Compared with the high-cholesterol-diet (HCD) group, the high-riclin group significantly decreased levels of the serum total cholesterol, low-density lipoprotein cholesterol (LDL-C), and hepatic cholesterol (34, 40, and 51%, respectively), consequently improving hepatic steatosis and reducing proinflammatory cytokine expressions. 1H nuclear magnetic resonance (NMR)-based lipidomics and metabolomics analyses revealed that the riclin group partially reversed metabolic profile changes induced by the HCD, approaching that of the normal diet (ND) group. Riclin has no direct effects on cholesterol metabolism-related gene expression among the three HCD model groups. Basically, riclin increased the solution viscosity and interfered in the process of bile acid-cholesterol emulsification, decreasing cholesterol digestion and promoting cholesterol and bile acid excretion in the feces. These results suggested potential therapeutic utility of succinoglycan riclin as a food additive for people suffering from hypercholesterolemia and related diseases.


Assuntos
Anticolesterolemiantes/metabolismo , Hipercolesterolemia/dietoterapia , Polissacarídeos Bacterianos/metabolismo , Animais , Ácidos e Sais Biliares/metabolismo , LDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Hipercolesterolemia/etiologia , Hipercolesterolemia/metabolismo , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL
8.
Nanoscale ; 11(46): 22343-22350, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31728477

RESUMO

The design of pH-sensitive supramolecular drug delivery systems for efficient antineoplastic drug delivery remains a huge challenge. Herein, we describe the development of pH-responsive core-shell tecto dendrimers (CSTDs) formed using benzimidazole (BM)-modified generation 3 (G3) poly(amidoamine) (PAMAM) dendrimers (G3.NHAc-BM) as a shell and ß-cyclodextrin (CD)-modified G5 PAMAM dendrimers (G5.NHAc-CD) as a core. By virtue of the host-guest recognition and pH-responsiveness of BM/ß-CD assembly, the pH-sensitive supramolecular CSTDs of G5.NHAc-CD/BM-G3.NHAc were formed and adopted to encapsulate the anticancer drug doxorubicin (DOX) via hydrophobic interactions for pH-responsive drug delivery applications. The synthesis of dendrimer derivatives and the loading of the DOX were well characterized via different methods. We show that the encapsulated DOX can be released in a sustained manner with a rapid release speed under a slightly acidic pH condition (pH < 6), which is similar to acidic tumor microenvironment. The enhanced intracellular release of DOX and improved anticancer activity of the drug-loaded pH-responsive CSTDs were demonstrated and compared with the control CSTDs formed without pH-responsiveness through flow cytometry and viability assays of cancer cells. Furthermore, the pH-sensitive CSTDs also showed efficient drug penetration and growth inhibition of three-dimensional tumor spheroids owing to the faster DOX release in an acidic pH environment. The pH-sensitive G5.NHAc-CD/BM-G3.NHAc CSTDs may be employed as a valuable intelligent delivery system for various anticancer drugs.

9.
BMC Geriatr ; 19(1): 292, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664918

RESUMO

BACKGROUND: Person-centered care is widely recognized as a gold standard and is based on a supportive psychosocial climate for both residents and staff in nursing homes. Residents and staff may have different perspectives as to whether the climate in which they interact is person-centered, perhaps due to their different expectations of the nursing home environment and the provision of care services. The aim of this study was to explore and compare resident and staff perspectives of person-centered climate in aged care nursing homes. METHODS: This is a descriptive cross-sectional study using a cluster random sampling method. The study collected data in 2016 from residents (n = 251) and nursing staff (n = 249) in 23 nursing homes using a Person-centered Climate Questionnaire-Patient version and Person-centered Climate-Staff version. T-tests for independent-samples were used to compare scores ranked by nursing staff and residents. RESULTS: The mean scores of 'A climate of safety' subscale and 'A climate of everydayness' subscale rated by residents were significantly lower than those rated by nursing staff. The mean scores of 'A climate of hospitality' rated by residents were very low among the three subscales, an indicator of the need to improve a more home-like environment for residents. Residents in larger size nursing homes showed a higher score of person-centered climate compared with their counterparts in small size nursing homes. CONCLUSIONS: This study reveals that the perspectives and perceptions of person-centered climate differ between residents and nursing staff. Therefore, both resident and staff perspectives should be taken into account in attempting to improve person-centered climate for better care outcomes.

10.
Fish Shellfish Immunol ; 94: 548-557, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31539573

RESUMO

A 56-day growth trial was conducted to investigate the effects of dietary yeast hydrolysate on the growth performance, antioxidation, immune response and resistance against Aeromonas hydrophila in largemouth bass. Four experimental diets were prepared with yeast hydrolysate levels of 0% (Y0), 1.5% (Y1.5), 3.0% (Y3.0) and 4.5% (Y4.5). Each diet was randomly assigned to triplicate 150-L tanks and each tank was stocked with 30 largemouth bass (initial body weight, IBW = 7.71 ±â€¯0.02 g). A challenge test was carried out after the feeding trial by injecting A. hydrophila intraperitoneally for 4-day observation. The results showed that the FBW and WGR in Y1.5 group were significantly higher than those in Y0 group (P < 0.05) and the feed conversion ratio (FCR) got the lowest value in Y1.5 group. And the hydrolysate supplement significantly increased the 4-day cumulative survival rate after the bacterial challenge (P < 0.05). The plasma malondialdehyde was lower in the yeast hydrolysate supplement groups in both pre- and post-challenge test (P < 0.05), while the plasma C3 increased (P < 0.05). In post-challenge test, the plasma superoxide dismutase (SOD) and catalase (CAT) activities increased in the Y1.5 and Y3.0 groups respectively (P < 0.05), and plasma lysozyme in Y1.5 group and the plasma IgM in Y3.0 group were higher than those in others respectively (P < 0.05). For the q-PCR results, in post-challenge test, the hepatic hep2 expression level in Y1.5 and Y4.5 groups were both significantly higher than those in others (P < 0.05), as well as il-8 in Y3.0 group. The spleen hif-1alpha and tgf-beta1 expression levels in Y4.5 group were all significantly lower than those in others (P < 0.05), while the gilt was significantly higher (P < 0.05) in the post-challenge test. And the expression levels of spleen tnf-alpah1 in Y1.5 and Y3.0 groups and il-8 in Y3.0 group were all significantly higher than those in other groups (P < 0.05) in the post-challenge test. The head kidney gilt expression level was significantly higher in the yeast hydrolysate supplement groups compared with the Y0 group (P < 0.05), and the head kidney il-8 expression level in Y1.5 group was significant higher than those in other groups in post-challenge test (P < 0.05). The present results indicated dietary yeast hydrolysate improved the antioxidant ability and enhanced the immune response of largemouth bass without negative effect on growth. And 1.5% or 3.0% of dietary yeast hydrolysate was recommended for largemouth bass based on the present results.


Assuntos
Bass , Resistência à Doença/efeitos dos fármacos , Doenças dos Peixes/imunologia , Expressão Gênica/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Fermento Seco/metabolismo , Aeromonas hydrophila/fisiologia , Ração Animal/análise , Animais , Bass/crescimento & desenvolvimento , Dieta/veterinária , Suplementos Nutricionais/análise , Doenças dos Peixes/genética , Doenças dos Peixes/metabolismo , Infecções por Bactérias Gram-Negativas/genética , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/metabolismo , Fermento Seco/administração & dosagem
11.
J Photochem Photobiol B ; 198: 111552, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31382089

RESUMO

A 58-day cultivation experiment was carried out to investigate the effects of photoperiods on growth, lipid metabolism and oxidative stress of juvenile gibel carp. Juveniles (5.41 ±â€¯0.01 g) were cultured under seven light photoperiods (0 h of light (L):24 h of darkness (D), 4L:20D (12:00-16:00 light), 8L:16D (10:00-18:00 light), 12L:12D (8:00-20:00 light), 16L:8D (6:00-22:00 light), 20L:4D (4:00-24:00 light) and 24L:0D) in an indoor recirculating aquaculture system. The light intensity was 1.02 µmol·m-2·s-1 (at the tank bottom in a 0.5-m water depth). The fish were fed to satiety three times daily (8:30, 14:30 and 18:30). At the end of the experiment, final body weight, specific growth rate, feed efficiency and feed intake were significantly higher in 16L:8D, 20L:4D and 24L:0D groups than those in other groups (P < 0.05). Long-day photoperiods (16L:8D, 20L:4D and 24L:0D) simultaneously promoted lipogenesis, lipolysis and fatty acid oxidation. The increases in lipid retention efficiency, whole body lipid concentration and liver lipid content (P < 0.05) indicated that lipogenesis exceeded fatty acid oxidation. Liver oxidative stress was induced in juvenile gibel carp by short day lengths. The hepatic total antioxidant capacity, superoxide dismutase, glutathione peroxidase and the contents of metabolite glutathione were the highest in the short-day-length groups (0L:24D, 4L:20D and 8L:16D) (P < 0.05). Based on the growth performance and health status in the long-term cultivation experiment, the optimal photoperiods were 16L:8D, 20L:4D and 24L:0D in juvenile gibel carp.


Assuntos
Carpa Dourada/metabolismo , Metabolismo dos Lipídeos , Estresse Oxidativo , Animais , Peso Corporal , Ingestão de Alimentos , Glutationa , Glutationa Peroxidase , Carpa Dourada/crescimento & desenvolvimento , Fígado/metabolismo , Fotoperíodo , Superóxido Dismutase/metabolismo
12.
Diabetologia ; 62(11): 2106-2117, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31410531

RESUMO

AIMS/HYPOTHESIS: Plasma 5'-AMP (pAMP) is elevated in mouse models of type 2 diabetes. However, the metabolic regulatory role of adenine nucleotides in type 2 diabetes remains unclear. METHODS: Adenine nucleotides and their metabolites in plasma and liver were examined by HPLC. 1H NMR-based metabolomics analysis was performed to explore the changes of metabolites in mouse models of type 2 diabetes. Na+/K+ ATPase and Na+/H+ exchanger activity were measured in response to adenine nucleotide metabolites. Human recombinant protein tyrosine phosphatase 1B (PTP1B) was used for enzyme kinetic assays. Protein binding assays were performed with microscale thermophoresis. The intracellular pH of hepatocyte AML12 cell lines was measured using the BCECF-AM method. We also analysed pAMP levels in participants with type 2 diabetes. RESULTS: Elevation of pAMP was a universal phenomenon in all mouse models of type 2 diabetes including db/db vs lean mice (13.9 ± 2.3 µmol/l vs 3.7 ± 0.9 µmol/l; p < 0.01), ob/ob vs lean mice (9.1 ± 2.0 µmol/l vs 3.9 ± 1.2 µmol/l; p < 0.01) and high-fat diet/streptozotocin-induced vs wild-type mice (6.6 ± 1.5 µmol/l vs 4.1 ± 0.9 µmol/l; p < 0.05); this elevation was required for the occurrence of hyperglycaemia in obese mice. 1H NMR-based metabolomics study following HPLC analysis revealed that the metabolite profile in wild-type mice treated with 5'-AMP was similar to that in db/db diabetic mice, especially the accumulation of a large quantity of ATP and its metabolites. The glucose-lowering drug metformin reduced the severity of hyperglycaemia both in 5'-AMP-induced wild-type mice and db/db mice. Metformin decreased the accumulation of liver ATP but not its metabolites in these hyperglycaemic mice. ATP and metformin reciprocally change cellular pH homeostasis in liver, causing opposite shifts in liver activity of PTP1B, a key negative regulator of insulin signalling. Furthermore, pAMP levels were also elevated in individuals with type 2 diabetes (45.2 ± 22.7 nmol/l vs 3.1 ± 1.9 nmol/l; p < 0.01). CONCLUSIONS/INTERPRETATION: These results reveal an emerging role for adenine nucleotide in the regulation of hyperglycaemia and provide a potential therapeutic target in obesity and type 2 diabetes.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31447776

RESUMO

Increased plasma free fatty acids (FFA) level plays a central role in the development of type 2 diabetes. Our previous studies have shown that plasma 5'-adenosine monophosphate (5'-AMP) elevates and acts as a potential upstream regulator of hyperglycemia in diabetic db/db mice. The relationship between FFA and plasma adenosine nucleotides in type 2 diabetes remains unclear. Here we found that plasma 5'-AMP level was also increased in diabetic mice induced by a high-fat diet and streptozotocin (HFD-STZ), as observed in diabetic db/db mice. The metabolites of adenosine nucleotides in plasma were increased in obese mice compared to lean mice. An acute oil gavage to lean mice increased both FFA and plasma purine metabolites, accompanying with glucose intolerance. 5'-AMP administration resulted in an increase in dose-dependent purine metabolites and different levels of glucose intolerance. FFA induced a release of adenine nucleotides from cultural human umbilical vein endothelial cells (HUVECs) prior to induction of their apoptosis. FFA also reduced red blood cells (RBCs) resistance to reactive oxygen species (ROS), leading to hemolysis, thereby increasing plasma nucleotides. Our results suggest that plasma adenine nucleotides play an intermediary role in FFA-induced glucose intolerance and hyperglycemia in obese mice.

14.
Front Vet Sci ; 6: 165, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31192238

RESUMO

To test the hypothesis that effects of dietary carbohydrate and lipid concentrations on growth performance, feeding utilization, glucose and lipid metabolism in gibel carp A strain may be differ from F strain, these two strain of gibel carp were fed with one of three different isonitrogenous diets: HCLL (45% carbohydrate, 2% lipid), MCML (30% carbohydrate, 8% lipid), or LCHL (15% carbohydrate, 14% lipid). After 8 weeks, the HCLL-fed fish had the highest hepatosomatic index, hepatic crude lipid levels, and triglyceride levels and lipid retention efficiency. Enhanced lipogenesis and lipid uptake potential were observed in fish fed HCLL and MCML diets. Moreover, increases in glucose transport (glut2, P = 0.003) and glycolysis (gk, P = 0.012; 6pfk, P = 0.005) in livers of both strains were induced by the high-carbohydrate diet. Genotype-specific effect was identified on plasma lipid content. Plasma triglyceride levels were also greater in the F strain than in the A strain. Furthermore, the F strain had higher levels of fatty acid ß-oxidation and glycolysis compared with the A strain. Nutrient retention was affected (P < 0.05) by the interaction between genotype and diet, implied dietary carbohydrate played a vital role in lipid accumulation in gibel carp. As dietary lipids increased, the F strain exhibited better feed utilization and a higher PRE than the A strain. However, the A strain had better growth performance. Overall, the F strain had better glucose uptake, glycolysis potential, and lipid utilization ability than the A strain.

15.
FEBS J ; 286(21): 4232-4244, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31199585

RESUMO

The formation and hydrolysis of hepatic retinyl esters (RE) is a key process in maintaining serum retinol homeostasis. During vitamin A deficiency, the activity of RE hydrolases (REH) in liver increases to cope with the reduced dietary vitamin A intake. However, it remains unclear which REH is the main enzyme responsible for RE hydrolysis in the liver under physiological conditions. Our previous studies have shown that pancreatic lipase-related protein 2 (PLRP2) is conditionally expressed in the liver and may be involved in the hydrolysis of hepatic RE. In the current study, we generated Plrp2-/- mice using transcription activator-like effector nuclease technology to investigate the role of PLRP2 in the metabolism of hepatic RE. Compared with the mice fed normal diet, the hepatic REH activity of wild-type (WT) mice fed vitamin A-deficient diet (VAD) increased significantly, while this activity did not increase in Plrp2-/- mice fed VAD. Plrp2-/- mice showed higher residual RE content in liver and lower serum retinol level, compared with WT mice fed VAD. Hepatic metabolic profiling from 1 H NMR-based metabolomics suggested that Plrp2-/- mice were more sensitive to VAD. Docking analysis and enzyme activity assay revealed that retinyl palmitate was the substrate with higher affinity for PLRP2. Our results indicate that Plrp2 can be activated in the liver and is responsible for the increased REH activity in the liver of mice fed VAD.

16.
Cancer Chemother Pharmacol ; 84(1): 105-116, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31069451

RESUMO

PURPOSE: Methotrexate (MTX) is a widely used cancer chemotherapy agent. The efficacy of MTX is often limited by serious side effects, such as intestinal mucositis. The aim of this study was to evaluate the protective effect of water-soluble ß-glucan salecan on MTX-induced intestinal toxicity in mice. METHODS: Intestinal mucositis was induced in C57BL/6 mice by intraperitoneal injection of MTX for two consecutive days. Mice were orally administrated with saline or salecan for 6 days before MTX injection and continued to the end of the study. Several histological and biochemical parameters were measured in the jejunum. RESULTS: Orally administration of salecan improved the severity of intestinal mucositis in a dose-dependent manner, as evidenced by the well-maintained mucosal architecture and body weight in salecan-treated groups. Salecan treatment inhibited MTX-induced oxidative stress and effectively scavenged free radicals both in vitro and in vivo. Metabolomics analysis revealed that salecan treatment reversed the intestinal metabolic profiling changes in mice with MTX-induced mucositis. Salecan treatment modulated the innate immunity through the regulation of TLR and Dectin1 expression in the jejunum, thus protecting mice from MTX-induced intestinal damage. CONCLUSIONS: Salecan has potential advantages in the treatment of MTX-induced intestinal mucositis, and its protective effect is mainly attributed to its antioxidant and immunomodulatory properties.

17.
Fish Physiol Biochem ; 45(1): 267-286, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30167883

RESUMO

The present study investigated differences in the utilization of fishmeal (FM) and rapeseed meal (RM) by gibel carp (Carassius gibelio) and explored the effects of protein sources on the responses of different genotypes. Gibel carp strains A (4.12 ± 0.03 g) and F (3.47 ± 0.00 g) were fed FM diet or RM diet for 56 days, and after which, growth performance, body composition, hematologic indices, and hepatic transcriptomes were measured. The effects of strain and diet on growth performance, body composition, and hematologic indices were analyzed by two-way analysis of covariance (ANCOVA). The results revealed that total replacement of FM with RM caused poor growth and feed utilization in both strains as well as the existence of genotype-diet interactions. Strain A showed better growth performance than strain F in the FM group, while the strain F grew better than strain A in the RM group. Transcriptomic analysis showed that the three main biological processes affected by the RM diet were amino acid metabolism, lipid metabolism, and digestive system. The different responses to the RM diet between strains were involved in amino acid metabolism, immune responses, and lipid metabolism. Identifying the underlying mechanisms by which different strains differently respond to meal sources might be the basis to develop a selective breeding program towards strains accepting alternative meal sources.


Assuntos
Ração Animal/análise , Brassica rapa , Carpas/crescimento & desenvolvimento , Dieta/veterinária , Produtos Pesqueiros , Fenômenos Fisiológicos da Nutrição Animal , Animais , Carpas/metabolismo , Distribuição Aleatória , Transcriptoma
18.
Fish Shellfish Immunol ; 86: 913-921, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30550991

RESUMO

The present study was conducted to evaluate dietary inosine 5'-monophosphate (5'-IMP) on growth, immune genes expression and disease resistance against Aeromonas hydrophila in juvenile gibel carp (Carassius auratus gibelio var. CAS Ⅲ) (initial body weight: 7.48 g). Six diets were formulated containing exogenous 5'-IMP at three gradient levels (0, 0.1% and 0.2%) in the high dietary fishmeal group (15% fishmeal: D1, D2, D3) and in the high dietary soybean meal group (33% soybean meal: D4, D5, D6). Each diet was randomly allotted to triplicate tanks in a recirculating system. After the feeding trial, fish were exposed to Aeromonas hydrophila challenge. Hematological and immunological responses were analyzed before and after challenge. The results indicated that feeding rate in all 5'-IMP supplemented treatments (D2, D3, D5 and D6) and daily growth coefficient in D5 and D6 were reduced compared with those of respective control treatments (D1 and D4) without 5'-IMP addition (P < 0.05). The cumulative survival rates were numerically improved by dietary 5'-IMP supplementation (P > 0.05). Compared with the respective control treatment, in the high fishmeal group, plasma SOD and MPO were significantly elevated in D3 at the end of feeding trial (P < 0.05), plasma SOD and lysozyme were significantly increased in D3 after bacterial challenge (P < 0.05); in high soybean meal group, plasma lysozyme activity was significantly elevated in D5 post bacterial challenge (P < 0.05). Most of the expression of immune related genes (intelectin, major histocompatibility complex class II ß (MHC II ß), Complement 3 (C3), Complement component C7-1 (ccC7), lysozyme C, Interleukin 1ß (IL-1ß), Tumor necrosis factor α1 (TNF-α1), Transforming growth factor-beta (TGF-ß) and Interleukin 8 (IL-8)) in spleen, kidney and liver of the fish were significantly affected by supplementation of 5'-IMP at the end of feeding trial and post bacterial challenge. Additionally, adding 5'-IMP in high soybean meal diets exerted further effects of promoting immunity than counterparts in high fishmeal diets. Considering enhanced disease resistance, the immunopotentiation of 5'-IMP was manifested when the addition level was 0.1% in high soybean meal diets and 0.2% in high fishmeal diets.


Assuntos
Dieta/veterinária , Regulação da Expressão Gênica/imunologia , Carpa Dourada/genética , Carpa Dourada/imunologia , Inosina Monofosfato/metabolismo , Aeromonas hydrophila/fisiologia , Ração Animal/análise , Animais , Dieta/classificação , Suplementos Nutricionais/análise , Resistência à Doença/efeitos dos fármacos , Doenças dos Peixes/imunologia , Proteínas de Peixes/genética , Proteínas de Peixes/imunologia , Carpa Dourada/crescimento & desenvolvimento , Infecções por Bactérias Gram-Negativas/imunologia , Infecções por Bactérias Gram-Negativas/veterinária , Inosina Monofosfato/administração & dosagem
19.
BMC Health Serv Res ; 18(1): 816, 2018 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-30359243

RESUMO

BACKGROUND: Residents living in nursing homes usually have complex healthcare needs and require a comprehensive care approach to identifying and meeting their care needs. Suboptimal quality of care is reported in nursing homes and is associated with the poor health and well-being of the residents, the burden on acute care hospitals and the high costs of healthcare for the government. The aim of this study is to test the hypothesis that an Aged Care Clinical Mentoring Model will create and sustain evidence-based quality improvement in priority areas and will be cost-effective in nursing homes in Hunan Province, China. METHODS: A cluster randomized controlled trial will be applied to the study. Fourteen nursing homes will be randomly allocated to either the intervention group (n = 7) or the control group (n = 7). Forty staff will be recruited from each nursing home and the estimated sample size will be 280 staff in each group. The intervention includes a structured, evidence-based quality improvement education program for staff to facilitate knowledge translation in evidence-based quality improvement targeting urinary incontinence, pressure injury and falls prevention. The primary outcomes are nursing homes' capacity to create and sustain quality improvement, staff perceptions of person-centered care, self-reported quality of care by residents and selected quality indicators at 12 months follow-up adjusted for baseline value. Secondary outcomes are residents' quality of life, residents' unplanned admissions to acute care hospitals, quality of care reported by staff, staff job satisfaction and staff intention to leave adjusted for baseline value. A mixed linear regression model will be adopted to compare the significant differences between groups over a 12-month period. DISCUSSION: Although the Aged Care Clinical Mentoring Model has been tested as an effective model to bring positive changes in nursing homes in a high-income country, factors affecting the adaptation of the model in nursing homes in low- and middle-income countries are unknown. The carefully planned intervention protocol enables the project team to consider enablers and barriers when adapting the Model. Therefore, strategies and resources will be in place to manage challenges while demonstrating best practice in this study. TRIAL REGISTRATION: Prospectively registered via Chinese Clinical Trial Registry (ChiCTR), ChiCTR-IOC-17013109 , Registered on 25 October 2017.


Assuntos
Instituição de Longa Permanência para Idosos/normas , Tutoria/normas , Casas de Saúde/normas , Melhoria de Qualidade/normas , Acidentes por Quedas/prevenção & controle , Idoso , China , Análise por Conglomerados , Análise Custo-Benefício , Assistência à Saúde/economia , Assistência à Saúde/normas , Feminino , Humanos , Satisfação no Emprego , Masculino , Tutoria/economia , Mentores , Casas de Saúde/economia , Melhoria de Qualidade/economia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra
20.
Int Immunopharmacol ; 64: 131-139, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30173053

RESUMO

Piceatannol, a natural derivative of resveratrol, has been shown to exert similar anti-oxidant and anti-inflammatory effects as resveratrol. However, it remains unknown whether piceatannol has hepatoprotective effect against acute liver injury. In this study, we investigated the in vivo effect of piceatannol on D-GalN/LPS-induced fulminant hepatic failure (FHF), and its in vitro effect on ER stress-inducing drug thapsigargin (TG)-induced proinflammatory cytokines production and ROS release. Our results indicated that piceatannol markedly decreased the mortality rate, reduced the serum levels of alanine transaminase and aspartic aminotransferase, ameliorated the liver damage induced by D-GalN/LPS in mice. In addition, piceatannol reduced the expression of proinflammatory cytokines, including TNF-α, IL-1ß and IL-6, the expression of ER stress markers CHOP and phosphorylated-IRE1α, and the generation of oxidative stress in D-GalN/LPS-treated mouse liver. In vitro results were consistent with in vivo observations, demonstrating that piceatannol suppressed the secretion of proinflammatory cytokines, inflammasome activation and the production of ROS induced by TG with or without LPS priming in J774A.1 macrophages. Our study proposes piceatannol as a promising medication for preventing acute liver failure and the mechanisms may be related to its inhibitory effects on ER stress, inflammation and oxidative stress.


Assuntos
Anti-Inflamatórios/farmacologia , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Galactosamina/toxicidade , Lipopolissacarídeos/toxicidade , Falência Hepática Aguda/prevenção & controle , Fígado/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Estilbenos/farmacologia , Animais , Células Cultivadas , Citocinas/biossíntese , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Espécies Reativas de Oxigênio/metabolismo
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