RESUMEN
This study is aimed at investigating the effects of dietary supplementation with Artemisia ordosica crude polysaccharides (AOCP) on lactation performance, antioxidant status, and immune status of lactating donkeys and analyzing rectal microbiomes and serum metabolomes. Fourteen lactating Dezhou donkeys with similar age (6.16 ± 0.67 yr of BW ± SD), weight (250.06 ± 25.18 kg), DIM (39.11 ± 7.42 d), and average parity of 3 were randomly allocated into 2 treatments: a control group (CON, basal diet) and an AOCP group (AOCP, basal diet with 1.0 g/kg DM AOCP). Ten weeks were allotted for the experiment, 2 wk for adaptation, and 8 wk for collecting data and samples. The results showed that supplementation of donkey diets with AOCP increased lactation performance, including DMI, milking yield, estimated milk yield, solids-corrected milk, ECM, milk fat yield, milk protein yield, milk lactose yield, milk TS yield, and milk SNF yield. The digestibility of DM, CP, ADF, and NDF was increased in the AOCP group compared with the CON group. The AOCP group increased the concentrations of IgA, IgG, and IgM, the activities of the superoxide dismutase, catalase, and total antioxidant capacity in the serum. Artemisia ordosica crude polysaccharides decreased the concentrations of tumor necrosis factor-α, nitric oxide, reactive oxygen species, and malondialdehyde in the serum. Compared with the CON group, AOCP increased propionate, butyrate, isovalerate, and total VFA concentrations in rectal feces (P < 0.05). The addition of AOCP to increased diversity (Shannon index) and altered structure of the rectal microflora. As a result of AOCP supplementation, there has been a significant improvement in the colonization of beneficial bacteria, including Lactobacillus, Unclassified_f_Prevotellacea, Ruminococcus, and Fibrobacter genera. In contrast, a decrease in the colonization of the Clostridium_sensu_stricto_1 bacterial genus and other pathogenic bacteria was observed. Meanwhile, metabolomics analysis found that AOCP supplementation upregulated metabolites l-tyrosine content while downregulating 9(S)-HODE, choline, sucrose, lysophosphatidylcholine (LysoPC) (18:0), LysoPC (18:1(9Z)), and LysoPC (20:2(11Z,14Z)) concentrations. These altered metabolites were involved in the PPAR signaling pathway, prolactin signaling pathway, glycerophospholipid metabolism, carbohydrate digestion and absorption, and tyrosine metabolism pathways, which were mainly related to antioxidant capacity, immune responses, and protein metabolism in the lactating donkeys. As a consequence of feeding AOCP diets, beneficial bacteria were abundant, and antioxidant and protein metabolism-related pathways were enriched, which may enhance lactation performance in donkeys. Therefore, supplementing AOCP diets is a desirable dietary strategy to improve donkey health and lactation performance.
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Antioxidantes , Artemisia , Dieta , Equidae , Lactancia , Leche , Polisacáridos , Animales , Femenino , Lactancia/efectos de los fármacos , Polisacáridos/farmacología , Antioxidantes/metabolismo , Leche/química , Dieta/veterinaria , Artemisia/química , Alimentación Animal/análisis , Suplementos Dietéticos , Microbiota/efectos de los fármacos , Microbioma Gastrointestinal/efectos de los fármacosRESUMEN
Artemisia ordosica is one of the main shrubby perennials belonging to Artemisia species of Asteraceae and could be used in folk Chinese/Mongolian medicine to treat symptoms of various inflammatory ailments. The present study was conducted to investigate the protective effects of dietary Artemisia ordosica polysaccharide (AOP) against lipopolysaccharide (LPS) induced oxidative stress in broilers via Nrf2/Keap1 and TLR4/NF-κB pathway. A total of 192 1-day-old Arbor Acres male broilers were randomly allotted to four treatments with 6 replicates (n = 8): (1) CON group, non-challenged broilers fed basal diet; (2) LPS group, LPS-challenged broilers fed basal diet; (3) AOP group, non-challenged broilers fed basal diet supplemented with 750 mg/kg AOP; (4) LPS+AOP group, LPS-challenged broilers fed basal diet supplemented with 750 mg/kg AOP. The trial included starter phase (d 1-14), stress period â (d 15-21), convalescence â (d 22-28), stress period â ¡ (d 29-35) and convalescence â ¡ (d 36-42). During stress period â (on d 15, 17, 19 and 21) and stress period â ¡ (on d 29, 31, 33 and 35), broilers were injected intra-abdominally either with LPS solution or with an equal amount of sterile saline. The results showed that dietary AOP supplementation alleviated LPS-induced reduction in antioxidant enzyme activity and excessive production of ROS, 8-OHdG and PC in serum of broilers challenged with LPS. Moreover, dietary AOP supplementation alleviated the decrease of T-AOC and activities of SOD, CAT and GPx in liver of broilers challenged with LPS by increasing expression of Nrf2, and inhibiting over-expression of Keap1 both at gene and protein level. Additionally, dietary AOP supplementation decreased the over-production of IL-1ß and IL-6 in liver of broilers challenged by LPS through decreasing mRNA expression of TLR4, MyD88, NF-κB P65, IL-1ß and IL-6, and alleviating the increase of protein expression of TLR4, IKKß, NF-κB P65, IL-1ß, IL-6, and the decrease of protein expression of IkBα. In conclusion, dietary AOP supplementation could alleviate LPS-induced oxidative stress through Nrf2/Keap1 and TLR4/NF-κB pathway.
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Artemisia , Lipopolisacáridos , Alimentación Animal/análisis , Animales , Artemisia/metabolismo , Pollos/metabolismo , Dieta , Suplementos Dietéticos , Proteína 1 Asociada A ECH Tipo Kelch/genética , Lipopolisacáridos/toxicidad , Masculino , Factor 2 Relacionado con NF-E2/genética , FN-kappa B/genética , FN-kappa B/metabolismo , Estrés Oxidativo , Polisacáridos , Receptor Toll-Like 4/genéticaRESUMEN
Objective: To explore the relationship between daily tea intake and cardiovascular disease (CVD) mortality. Methods: PubMed, EMbase, The Cochrane, Chinese Biomedical Literature Database, CNKI, and Wanfang Database were searched to collect research on tea intake and CVD mortality. The search period was from the establishment of the database to June 2020. Two researchers independently screened and extracted literature. The risk of bias was evaluated in the included studies, a dose-response meta-analysis was conducted, sensitivity analysis and publication bias analysis of the research results, and quality evaluation of the included literature and GRADE classification of the evidence body were performed. Results: A total of 21 cohort or case-control studies were included, including 1 304 978 subjects. Among them, 38 222 deaths from CVD were reported. The quality scores of the included studies were all ≥ 6 points. The dose-response meta-analysis showed that for every additional cup of tea intake per day, the mortality rate of CVD decreased by about 3% (95%CI 0.95-0.98, P<0.05), and there was a non-linear dose-response relationship (P<0.05). Compared with people who do not drink tea, people who drink 1 to 8 cups of tea a day have 8% lower CVD mortality (RR=0.92, 95%CI 0.89-0.95), 13% (RR=0.87, 95 %CI 0.84-0.91), 15% (RR=0.85, 95%CI 0.82-0.89), 15% (RR=0.85, 95%CI 0.81-0.89), 16% (RR=0.84, 95%CI 0.80-0.89), 16% (RR=0.84, 95%CI 0.81-0.88), 16% (RR=0.84, 95%CI 0.81-0.87), 16% (RR=0.84, 95%CI 0.80-0.88), respectively. The results of traditional meta-analysis showed that compared with people who do not drink tea, people who drink more than 1 cup of tea a day are associated with 14% lower CVD mortality rate (RR=0.86, 95%CI 0.81-0.91, I2=73.2%, P<0.05). The results of subgroup analysis showed that compared with the corresponding people who did not drink tea, men who drank more than 1 cup of tea a day reduced the CVD mortality rate by 24%, women by 14%, European and American populations by 12%, and Asian populations by 15%. The population who consumed green tea decreased CVD mortality by 15%, and the population of non-smokers decreased CVD mortality by 20% (all P<0.05). The population who consumed black tea decreased CVD mortality by 8%, and the smoking population who consumed black tea decreased CVD mortality by 3%, and the difference was not statistically significant (all P>0.05). The results of the bias analysis showed that Begg=0.42 and Egger=0.62, indicating that the distribution on both sides of the funnel chart is symmetrical, suggesting that there is no publication bias. The results of sensitivity analysis showed that the effect size of the outcome index did not change significantly after excluding any article, indicating that the results are robust and credible. The GRADE evaluation showed that the evidence grades of the outcome indicators were all low grade. Conclusions: Daily tea consumption is related to reduced CVD mortality. It is therefore recommended to drink an appropriate amount of tea daily.
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Enfermedades Cardiovasculares , Estudios de Casos y Controles , Causas de Muerte , Estudios de Cohortes , Femenino , Humanos , Masculino , TéRESUMEN
A study was conducted to evaluate the effects of forage-to-concentrate (F:C) ratio and forage particle length (FPL) on intake, duodenal flow, and digestibility of individual AA in the intestine of lactating dairy cows. The experiment was designed as a 4 × 4 Latin square with a 2 × 2 factorial arrangement of treatments using 4 lactating dairy cows (parity 2) with ruminal and duodenal cannulas. Low (35:65) and high (60:40) F:C ratios (dry matter basis) were combined with 2 FPL of alfalfa silage (short vs. long; 7.9 vs. 19.1 mm). Few interactions between F:C and FPL for duodenal flow and intestinal digestibility of AA occurred, but interactions were detected for intakes of several AA. Intake of essential AA and nonessential AA decreased with increasing F:C, and the intake of several individual AA increased or decreased with increasing FPL. Increasing F:C decreased duodenal flows of essential AA, nonessential AA, and microbial AA due to consistent decreased flows of most individual AA (except Glu). Degradability of most individual AA in the rumen was not affected by F:C ratio or FPL except that the degradability of His was greater with high than low F:C diets, and the degradability of Ser was greater with long versus short FPL diets. However, the degradability of individual AA within diet varied considerably. Overall, F:C ratio and FPL did not affect intestinal digestibility of AA and rumen undegradable protein AA, whereas the digestibility of individual AA in the intestine varied considerably regardless of dietary treatment. These results indicate that increasing F:C ratio decreased AA supply due to decreased flow of AA to the duodenum but altering FPL did not affect AA supply. The results also revealed the necessity to consider both the flows and digestibility of individual AA when optimizing ration formulation to meet AA requirements of dairy cows.
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Aminoácidos/metabolismo , Alimentación Animal/análisis , Bovinos/fisiología , Dieta/veterinaria , Digestión , Intestinos/fisiología , Animales , Bovinos/microbiología , Duodeno/fisiología , FemeninoRESUMEN
In this study, a novel polysaccharide was isolated from Artemisia ordosica by water-extraction-ethanol-precipitation method. The optimal extraction conditions of Artemisia ordosica polysaccharide (AOP) were determined by single factor investigation and response surface methodology optimization, and were shown as follows: a liquid-solid ratio of 15.4 : 1 mL g-1, extraction time of 4.3 h, extraction temperature of 60 °C. Under the optimal conditions, the extraction yield and the sugar content of the AOP were 5.56% and 52.65%. Gel permeation chromatography coupled to multi-angle laser light scattering, a refractive index detection system and ion-exchange chromatography were used to determine the characterization of AOP. These results indicated that AOP, with a molecular weight of 2.1 kDa (62.6%) and 1.5 kDa (37.4%), had narrow polydispersity and rod conformations, and was composed of arabinose, galactose, glucose, xylose, mannose, galacturonic acid and glucuronic acid with molar ratio of 6.87 : 10.67 : 54.13 : 2.49 : 18.37 : 4.83 : 2.64 : 2.64. In addition, AOP exerted antioxidant ability in vitro and in vivo (rats). Moreover, AOP significantly modulated the composition of cecal microbiota population. Therefore, AOP is expected to be a functional ingredient for health improvement through improving antioxidant ability and modulating gut health.
RESUMEN
It is known that physiological overproduction of nitric oxide (NO) contributes to oxidative stress and inflammation. Our published studies indicated that vitamin A (VA) reduces NO-induced oxidative stress in bovine mammary epithelial cells (BMECs) by increasing antioxidant enzyme activities. However, the precise mechanism is unclear. The present study was conducted to examine the protective effects of VA on NO-induced damage to BMECs in vitro using diethylenetriamine nitric oxide (DETA-NO) as the NO donor and to explore the intracellular signaling mechanisms of VA that involve nuclear factor erythroid 2-related factor (Nrf2) and nuclear factor kappa-B (NF-κB). Subconfluent BMECs were divided into 10 treatment groups with 6 replicates per treatment and were cultured with dimethyl sulfoxide (DMSO, vehicle negative control) or 0, 0.05, 0.1, 0.2, 0.5, 1, 2, 3, or 4 µg/mL of VA for 24 h and then incubated in the absence or presence of DETA-NO (1,000 µmol/liter) and VA for an additional 6 h. The results showed that exposure to DETA alone decreased cell proliferation compared with the negative control. Pretreatment with VA promoted the proliferation of BMECs, increased the activities of antioxidative enzymes including selenoprotein glutathione peroxidase (GPx) and thioredoxin reductase (TrxR) and their gene and protein expression but decreased NO and interleukin 1 (IL-1) contents in a quadratic manner (P < 0.05). In addition, the expression of mRNA and protein of factors that are related to NF-κB or Nrf2 signaling pathways in BMECs were regulated by VA in a quadratic dose-dependent manner; VA at a concentration of 1 µg/mL exhibited the strongest effect. Together, these results suggest that VA promotes antioxidant functions of BMECs by regulating the synthesis of selenoproteins including GPx and TrxR and by reducing concentrations of IL-1 and NO in vitro by modulating Nrf2 and NF-κB signaling pathways.
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Antioxidantes/metabolismo , Óxido Nítrico/efectos adversos , Transducción de Señal/efectos de los fármacos , Vitamina A/farmacología , Animales , Bovinos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Células Epiteliales/fisiología , Femenino , Inflamación/tratamiento farmacológico , Inflamación/veterinaria , Glándulas Mamarias Animales/fisiología , Factor 2 Relacionado con NF-E2/efectos de los fármacos , FN-kappa B/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacosRESUMEN
The protective effects of chitosan (CS) supplementations on oxidative stress induced by diquat in weaned piglets were investigated. A total of 36 crossbreed piglets with an average live body weight (BW) of 8.80 ± 0.53 kg were weaned at 28 ± 2 days and randomly divided into six dietary treatments (n = 6): control (basal diet), negative control (10 mg diquat/kg BW injected to piglets fed with basal diet), and basal diet treatments containing either 250, 500, 1000, or 2000 mg/kg of CS administered to piglets injected with 10 mg diquat/kg BW. The experiment conducted for 21 days which consisted of pre-starter period (14 days) and starter period (7 days). BW, feed intake, and fecal consistency were monitored. Blood samples were collected to determine antioxidative and immune parameters. CS supplementation improved the growth performance and decreased fecal score of piglets from days 1 to 14. Diquat also induced oxidative stress and inflammatory responses by decreasing the activities of antioxidant and regulating cytokines. But dietary CS alleviated these negative effects induced by diquat that showed decreasing serum concentrations of pro-inflammatory cytokines but increasing activities of antioxidant enzymes and anti-inflammatory cytokines. Results indicated that CS attenuated the oxidative stress of piglets caused by diquat injection.
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Quitosano/farmacología , Suplementos Dietéticos , Diquat/toxicidad , Estrés Oxidativo/efectos de los fármacos , Sustancias Protectoras/farmacología , Porcinos/metabolismo , Destete , Animales , Antioxidantes/metabolismo , Biomarcadores/sangre , Diarrea/sangre , Diarrea/patología , Heces , Femenino , Inmunoglobulinas/sangre , Masculino , Malondialdehído/sangre , Porcinos/sangre , Porcinos/crecimiento & desarrolloRESUMEN
This experiment aimed to investigate the relieving action of Artemisia argyi aqueous extract (AAE) on immune stress in broiler chickens. A 2 × 2 factorial design was used to test the effect of 2 dietary treatments (adding 0 or 1000 mg/kg AAE) and 2 immune stress treatments (injecting saline or lipopolysaccharide (LPS)). A total of 96 one-day-old Arbor Acres (AA) broilers were randomly divided into four treatment groups with six replicates, four birds in each replicate. Broilers in Treatment groups 1 and 2 were fed with the basal diet, and those in Treatment groups 3 and 4 were fed with the experimental diet supplemented with 1000 mg/kg AAE. On days 14, 16, 18 and 20, broilers in both Treatments 1 and 3 were injected intra-abdominally with LPS solution at the dose of 500 µg LPS per kg BW with the LPS dissolved in sterile saline at a concentration of 100 µg/ml, and those in Treatments 2 and 4 were injected intra-abdominally with equal amount of sterile 0.9% saline. Blood samples were collected on days 21 and 28. The results showed that dietary supplementation of AAE prevented reductions in average daily gain (ADG) and average daily feed intake (ADFI) of broilers caused by LPS on d 15-21. On day 21, the injection of LPS increased serum adrenocorticotropic hormone (ACTH) and corticosterone (CORT); meanwhile, feeding AAE reduced the rise of CORT caused by LPS. Immune parameters such as interleukin-1 (IL-1), interleukin-2 (IL-2), interleukin-6 (IL-6), immunoglobulin G (IgG) and immunoglobulin A (IgA) were also improved by LPS, but the content of IL-2 and IgG in broilers fed with AAE diet was significantly lower than that of broilers fed with control diet. All the data suggested that diets supplemented with AAE could relieve the immune stress response of broilers.
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Artemisia/química , Pollos/fisiología , Extractos Vegetales/farmacología , Estrés Fisiológico/efectos de los fármacos , Alimentación Animal/análisis , Fenómenos Fisiológicos Nutricionales de los Animales , Animales , Dieta/veterinaria , Extractos Vegetales/química , Estrés Fisiológico/inmunologíaRESUMEN
Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor with tremendous invasion and metastasis capacities, and it has a high incidence in southeast Asia and southern China. Previous studies identified that far upstream element-binding protein 1 (FBP1), a transcriptional regulator of c-Myc that is one of the most frequently aberrantly expressed oncogenes in various human cancers, including NPC, is an important biomarker for many cancers. Our study aimed to investigate the expression and function of FBP1 in human NPC. Quantitative real-time RT-PCR (qRT-PCR), western blot and immunohistochemical staining (IHC) were performed in NPC cells and biopsies. Furthermore, the effect of FBP1 knockdown on cell proliferation, colony formation, side population tests and tumorigenesis in nude mice were measured by MTT, clonogenicity analysis, flow cytometry and a xenograft model, respectively. The results showed that the mRNA and protein levels of FBP1, which are positively correlated with c-Myc expression, were substantially higher in NPC than that in nasopharyngeal epithelial cells. IHC revealed that the patients with high FBP1 expression had a significantly poorer prognosis compared with the patients with low expression (P=0.020). In univariate analysis, high FBP1 and c-Myc expression predicted poorer overall survival (OS) and poorer progression-free survival. Multivariate analysis indicated that high FBP1 and c-Myc expression were independent prognostic markers. Knockdown of FBP1 reduced cell proliferation, clonogenicity and the ratio of side populations, as well as tumorigenesis in nude mice. These data indicate that FBP1 expression, which is closely correlated with c-Myc expression, is an independent prognostic factor and promotes NPC progression. Our results suggest that FBP1 can not only serve as a useful prognostic biomarker for NPC but also as a potential therapeutic target for NPC patients.
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Biomarcadores de Tumor/metabolismo , ADN Helicasas/metabolismo , Proteínas de Unión al ADN/metabolismo , Neoplasias Nasofaríngeas/enzimología , Adulto , Anciano , Animales , Antineoplásicos/farmacología , Carcinoma , Línea Celular Tumoral , Proliferación Celular , Progresión de la Enfermedad , Resistencia a Antineoplásicos , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Estimación de Kaplan-Meier , Masculino , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , Análisis Multivariante , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Trasplante de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Proteínas Proto-Oncogénicas c-myc/metabolismo , Proteínas de Unión al ARN , Tolerancia a Radiación , Células de Población Lateral/metabolismo , Adulto JovenRESUMEN
The objective of this study was to evaluate the effects of the different ratios of unsaturated fatty acids (UFAs) (oleic acid, linoleic acid, and linolenic acid) on the cell viability and triacylglycerol (TAG) content, as well as the mRNA expression of the genes related to lipid and protein synthesis in bovine mammary epithelial cells (BMECs). Primary cells were isolated from the mammary glands of Holstein dairy cows and were passaged twice. Afterward, the cells were randomly allocated to six treatments, five UFA-treated groups, and one control group. For all of the treatments, the the fetal bovine serum in the culture solution was replaced with fatty acid-free BSA (1 g/L), and the cells were treated with different ratios of oleic, linoleic, and linolenic acids (0.75:4:1, 1.5:10:1, 2:13.3:1, 3:20:1, and 4:26.7:1) for 48 h, which were group 1 to group 5. The control culture solution contained only fatty acid-free BSA without UFAs (0 µM). The results indicated that the cell viability was not affected by adding different ratios of UFAs, but the accumulation of TAG was significantly influenced by supplementing with different ratios of UFAs. Adding different ratios of UFAs suppressed the expression of ACACA and FASN but had the opposite effect on the abundances of FABP3 and CD36 mRNA. The expression levels of PPARG, SPEBF1, CSN1S1, and CSN3 mRNA in the BMECs were affected significantly after adding different ratios of UFAs. Our results suggested that groups 1, 2, and 3 (0.75:4:1, 1.5:10:1, and 2:13.3:1) had stronger auxo-action on fat synthesis in the BMECs, where group 3 (2:13.3:1) was the best, followed by group 4 (3:20:1). However, group 5 (4:26.7:1) was the worst. Genes related to protein synthesis in the BMECs were better promoted in groups 2 and 3, and group 3 had the strongest auxo-action, whereas the present study only partly examined the regulation of protein synthesis at the transcriptional level; more studies on translation level are needed in the future. Therefore, when combining fat and protein synthesis, group 3 could be obviously fat and protein synthesis in the BMECs concurrently. However, further studies are necessary to elucidate the mechanism for regulating fat and protein synthesis in the BMECs.
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Ácidos Grasos Insaturados/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Glándulas Mamarias Animales/citología , Acetil-CoA Carboxilasa/genética , Animales , Antígenos CD36/genética , Bovinos , Células Cultivadas , Células Epiteliales/efectos de los fármacos , Acido Graso Sintasa Tipo I/genética , Proteínas de Unión a Ácidos Grasos/genética , Ácidos Grasos Insaturados/química , Femenino , Metabolismo de los Lípidos/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , Glándulas Mamarias Animales/efectos de los fármacos , Glándulas Mamarias Animales/fisiología , Fragmentos de Péptidos , Triglicéridos/metabolismoRESUMEN
BACKGROUND: The impact of combining plasma fibrinogen levels with Epstein-Barr Virus DNA (EBV DNA) levels on the prognosis for patients with nasopharyngeal carcinoma (NPC) was evaluated. METHODS: In this observational study, 2563 patients with non-metastatic NPC were evaluated for the effects of circulating plasma fibrinogen and EBV DNA levels on disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). RESULTS: Compared with the bottom biomarker tertiles, TNM stage-adjusted hazard ratios (HR, 95% confidence intervals (CIs)) for predicting DFS in fibrinogen tertiles 2 to 3 were 1.26 (1.00 to 1.60) and 1.81 (1.45 to 2.26), respectively; HR for EBV DNA tertiles 2 to 3 were 1.49 (1.12 to 1.98) and 4.24 (3.27 to 5.49), respectively. After additional adjustment for established risk factors, both biomarkers were still associated (P for trend <0.001) with reduced DFS (HR: 1.79, 95% CI, 1.43 to 2.25 for top fibrinogen tertiles; HR: 4.04, 95% CI: 3.10 to 5.27 for top EBV DNA tertiles compared with the bottom tertiles). For patients with advanced-stage disease, those with high fibrinogen levels (3.34 g l(-1)) presented with worse DFS, regardless of EBV DNA 4000 or <4000 copies ml(-1) subgroup. Similar findings were observed for DMFS and OS. CONCLUSIONS: Circulating fibrinogen and EBV DNA significantly correlate with NPC patients survival. Combined fibrinogen and EBV DNA data lead to improved prognostic prediction in advanced-stage disease.
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Biomarcadores de Tumor/sangre , Carcinoma/sangre , ADN Viral/sangre , Fibrinógeno/metabolismo , Herpesvirus Humano 4/genética , Neoplasias Nasofaríngeas/sangre , Recurrencia Local de Neoplasia/sangre , Adulto , Carcinoma/patología , Carcinoma/virología , Supervivencia sin Enfermedad , Femenino , Estudios de Seguimiento , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/virología , Recurrencia Local de Neoplasia/virología , Estadificación de Neoplasias , Tasa de SupervivenciaRESUMEN
Extracellular cysteine (Cys)/cystine (CySS) redox potential (Eh) plays a crucial role in maintaining redox homeostasis and an alteration of redox state occurs in various physiological conditions, including diabetes, cancer, and aging. This study was designed to determine whether a variation in extracellular redox state would alter the function of insulin-resistant PC12 cells. Various redox states were established by providing different extracellular Cys/CySS Eh to insulin-resistant PC12 cells. We intensively investigated the relationship between redox state and catecholamine biosynthesis in PC12 cells, and evaluated the changes in cellular reactive oxygen species (ROS), catecholamine (CA) synthesis, tyrosine hydroxylase (TH) expressions, and the activity of rate-limiting enzyme in CA synthesis by using DCF-fluorescence, HPLC, and the real-time PCR, respectively. We also determined the protein levels of NF-E2-related factor 2 (Nrf2), a redox sensitive transcription factor, using an ELISA assay. We found that the oxidized Cys/CySS Eh (0 mV) pretreatment decreased CA, TH, and Nrf2 levels, but induced ROS overproduction. Insulin induced a significant increase in CA synthesis and ROS production, blocked by more reducing redox conditions. The paradox of CA and TH alterations between insulin and 0 mV groups may be attributed to degree of redox imbalance as evidenced by different ROS levels in 2 groups, which is further confirmed by CA alterations in different concentrations of hydrogen peroxide. Additionally, dithiole-3-thione (D3T, an inducer of Nrf2) corrected 0 mV-induced TH inhibition. In conclusion, CA biosynthesis in insulin-resistant PC12 cells could be influenced by extracellular Cys/CySS redox effects on cellular redox sensitive transcription factors.
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Catecolaminas/biosíntesis , Espacio Extracelular/metabolismo , Resistencia a la Insulina , Animales , Antioxidantes/metabolismo , Supervivencia Celular/efectos de los fármacos , Cisteína/metabolismo , Cistina/metabolismo , Espacio Extracelular/efectos de los fármacos , Factor 2 Relacionado con NF-E2/metabolismo , Oxidación-Reducción/efectos de los fármacos , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismo , Tionas/farmacología , Tiofenos/farmacologíaRESUMEN
Insulin resistance has been proposed to play a pivotal role in vasoconstriction due to increased oxidative stress. Hyperthyroidism would amplify cardiovascular disease risk in diabetic patients, though thyroid hormone advance vascular relaxation and reduce vascular contraction by virtue of NO production in vascular smooth muscle cells (VSMCs). Thus, we aimed to investigate the vascular tone and its underlying mechanism in insulin resistance accompanied by hyperthyroidism. Vascular reactivity studies showed that endothelium-denuded thoracic aortic rings from rats fed with high-fat high-sucrose (HFHS) diet and L-T4 (HFHS+L-T4) exhibited a stronger contractile response to noradrenaline than HFHS rats, which was reversed by L-NAME and GSH. Furthermore, rat thoracic aortic smooth muscle cells (A10) simultaneously stimulated with high glucose insulin (high Glc/Ins) and T3 demonstrated lower NO, superoxide anion ( [Formula: see text] ) levels, and higher iNOS, nitrite ( [Formula: see text] ), peroxynitrite (ONOO(-)) levels than that treated with T3 only. Excessive ONOO(-) markedly aggravated oxidative stress. Thus, we hypothesized that the elevated concentration of ONOO(-) which is generated by NO and [Formula: see text] could be critically instrumental in the progression of vasoconstriction by increasing oxidative stress.
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Resistencia a la Insulina/fisiología , Ácido Peroxinitroso/metabolismo , Hormonas Tiroideas/farmacología , Vasoconstricción/efectos de los fármacos , Animales , Glucemia/metabolismo , Línea Celular , Hipertiroidismo/metabolismo , Hipertiroidismo/fisiopatología , Técnicas In Vitro , Masculino , Óxido Nítrico/biosíntesis , Óxido Nítrico/metabolismo , Ácido Peroxinitroso/biosíntesis , Ratas , Ratas Sprague-Dawley , Triyodotironina/farmacologíaRESUMEN
Several lines of evidence indicate that reactive oxygen species (ROS) overproduction under the metabolic syndrome condition is the leading cause of cardiovascular events. Calcium is an important stimulus for vasoconstriction and plays a pivotal role in the development of hypertension. Here, we investigate whether a relationship exists between metabolic syndrome-induced mitochondrial ROS overproduction and Ang II-mediated Ca2+ release in vascular smooth muscle cells (VSMC). The effect of mitochondrial ROS on AT1 expression, and Ca2+ and IP3 generation was studied in 2 VSMC models of metabolic syndrome using fura-2/AM probes and ELISA-based assay. Ang II-mediated aortic ring contraction in SD rats fed with high-fat diet (HFD) was measured using a force transducer connected to chart recorder. In the metabolic syndrome, almost 2-fold increased mitochondrial O2 - significantly upregulated AT1 expressions by ~60%, companied by elevated Ca2+ and IP3 levels in VSMC and enhanced aortic rings contraction. All these increments were blocked by rotenone (inhibitor of mitochondrial respiratory chain complex I), ruthenium red (inhibitor of calcium uniporter), cyclosporin A (inhibitor of mitochondrial permeability pore), and N-acetylcysteine. Therefore, in the states of metabolic syndrome, ROS overproduction in mitochondrial complex I enhances Ang II-mediated vascular contraction via an AT1-dependent pathway. In addition, the import of Ca2+ from endoplasmic reticulum to mitochondria via calcium uniporter and mitochondrial permeability pore seems to serve as a mechanism to further aggravate mitochondrial damage and vascular dysfunction that may contribute to the occurrence of hypertension.
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Calcio/metabolismo , Hipertensión/etiología , Síndrome Metabólico/fisiopatología , Músculo Liso Vascular/fisiopatología , Estrés Oxidativo/fisiología , Angiotensina II/fisiología , Animales , Aorta/fisiopatología , Línea Celular , Dieta Alta en Grasa/efectos adversos , Masculino , Síndrome Metabólico/complicaciones , Mitocondrias Musculares/química , Mitocondrias Musculares/metabolismo , Contracción Muscular/fisiología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Superóxido Dismutasa/metabolismo , Superóxidos/metabolismo , Vasoconstricción/fisiologíaRESUMEN
1. Two experiments were conducted to investigate the effects of dietary chitosan on growth performance, energy availability and protein retention in broilers. 2. Experiment 1 was a 42-d growth assay, in which 294 1-d-old male broilers were given one of 7 dietary treatments. A control feed was supplemented with 5 levels of chitosan (0.2, 0.5, 1.0, 3.0 and 5.0 g/kg) or 50 mg/kg chlortetracycline (CTC). 3. Increasing chitosan inclusion gave a nonlinear increase (P< 0.001) in feed conversion efficiency (FCE). Optimal growth and feed conversion were obtained with 0.5-1.0 g/kg chitosan. 4. In experiment 2, 42 1-d-old male broilers (6/treatment) were individually housed but fed on the same diets as in experiment 1. Excreta were collected from d 19-21 and d 40-42. 5. The addition of 0.5-1.0 g/kg chitosan increased nitrogen retention compared with the control group (P< 0.01), while apparent metabolisable energy in the diets was not altered.
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Pollos/crecimiento & desarrollo , Pollos/metabolismo , Quitosano/farmacología , Proteínas en la Dieta/metabolismo , Metabolismo Energético/efectos de los fármacos , Alimentación Animal , Animales , Antibacterianos/farmacología , Quitosano/administración & dosificación , Clortetraciclina/farmacología , Dieta , Suplementos Dietéticos , Relación Dosis-Respuesta a Droga , Masculino , Aumento de Peso/efectos de los fármacosRESUMEN
BACKGROUND: The scarring of the heart that results from myocardial infarction has been interpreted as evidence that the heart is composed of myocytes that are unable to divide. However, recent observations have provided evidence of proliferation of myocytes in the adult heart. Therefore, we studied the extent of mitosis among myocytes after myocardial infarction in humans. METHODS: Samples from the border of the infarct and from areas of the myocardium distant from the infarct were obtained from 13 patients who had died 4 to 12 days after infarction. Ten normal hearts were used as controls. Myocytes that had entered the cell cycle in preparation for cell division were measured by labeling of the nuclear antigen Ki-67, which is associated with cell division. The fraction of myocyte nuclei that were undergoing mitosis was determined, and the mitotic index (the ratio of the number of nuclei undergoing mitosis to the number not undergoing mitosis) was calculated. The presence of mitotic spindles, contractile rings, karyokinesis, and cytokinesis was also recorded. RESULTS: In the infarcted hearts, Ki-67 expression was detected in 4 percent of myocyte nuclei in the regions adjacent to the infarcts and in 1 percent of those in regions distant from the infarcts. The reentry of myocytes into the cell cycle resulted in mitotic indexes of 0.08 percent and 0.03 percent, respectively, in the zones adjacent to and distant from the infarcts. Events characteristic of cell division--the formation of the mitotic spindles, the formation of contractile rings, karyokinesis, and cytokinesis--were identified; these features demonstrated that there was myocyte proliferation after myocardial infarction. CONCLUSIONS: Our results challenge the dogma that the adult heart is a postmitotic organ and indicate that the regeneration of myocytes may be a critical component of the increase in muscle mass of the myocardium.
Asunto(s)
Mitosis , Infarto del Miocardio/patología , Miocardio/citología , Regeneración , Anticuerpos Monoclonales , Estudios de Casos y Controles , División Celular , Corazón/fisiología , Humanos , Antígeno Ki-67/análisis , Antígeno Ki-67/inmunología , Microscopía Confocal , Índice Mitótico , Infarto del Miocardio/fisiopatología , Miocardio/químicaRESUMEN
Different cyclosporine concentration zones can exist in plasma due to the temperature dependency in distribution and association, therefore cyclosporine therapeutic and toxic effects may partially be related to these concentration zones.
Asunto(s)
Ciclosporina/efectos adversos , Ciclosporina/uso terapéutico , Ciclosporina/sangre , Ciclosporina/farmacocinética , HumanosAsunto(s)
Adyuvantes Inmunológicos/administración & dosificación , Antivirales/administración & dosificación , Hepatitis B Crónica/tratamiento farmacológico , Interferón-alfa/administración & dosificación , Timosina/análogos & derivados , Timosina/administración & dosificación , Adolescente , Adulto , Antivirales/efectos adversos , Humanos , Interferón-alfa/efectos adversos , Persona de Mediana Edad , Timalfasina , Resultado del TratamientoRESUMEN
The repeated amino-acid sequences in Citrobacter Freundii beta-lactamase may be indispensable for its function, because such repetitions cannot be simply attributed to a chance. In order to fully explore the functional units in Citrobacter Freundii beta-lactamase, it may need to analyse all the amino acid pairs, triplets, etc. along Citrobacter Freundii beta-lactamase from one terminal to the other terminal, to count their frequencies and calculate their probabilities. The amino-acid sequence of Citrobacter Freundii beta-lactamase was counted according to two-, three- and four-amino-acid sequences. The counted frequency and probability were compared with the predicted frequency and probability. The amino acid sequences, which appear in Citrobacter Freundii beta-lactamase and can be predicted from its amino acid composition according to a purely random mechanism, should not be deliberately evolved and conserved. By contrast, the amino acid sequences, which appear in Citrobacter Freundii beta-lactamase but cannot be predicted from its amino acid composition according to a purely random mechanism, should be deliberately evolved and conversed. Accordingly 99 (26.053%) and 33 (8.684%) of 380 two-amino-acid sequences can be predicted by the frequency and probability according to a purely random mechanism. Some kinds of amino acid sequences, which absent in Citrobacter Freundii beta-lactamase and can be predicted from its amino acid composition according to a purely random mechanism, should not be deliberately excluded from Citrobacter Freundii beta-lactamase. By contrast, some kinds of amino acid sequences, which absent in Citrobacter Freundii beta-lactamase and cannot be predicted from its amino acid composition according to a purely random mechanism, should be deliberately excluded from Citrobacter Freundii beta-lactamase. Accordingly 89 (48.370%) and 41 (22.283%) of 184 kinds of absent two-amino-acid sequences can be predicted by the frequency and probability according to a purely random mechanism, and 7236 (99.848%) of 7247 kinds of absent three-amino-acid sequences can be predicted by the frequency according to a purely random mechanism. The amino acids, whose probabilities in following certain preceding amino acids can be predicted from Citrobacter Freundii beta-lactamase amino acid composition according to a purely random mechanism, should not be deliberately evolved and conversed, accordingly 2 (0.526%) of 380 counted first order Markov transition probabilities for the second amino acid in two-amino-acid sequences match the predicted conditional probabilities.
Asunto(s)
Citrobacter/enzimología , Secuencias Repetitivas de Aminoácido , beta-Lactamasas/química , Cadenas de Markov , ProbabilidadRESUMEN
OBJECTIVE: To determine the alteration of nuclear size in myocardial cells and the relationship between nuclear size and DNA ploidy classes in normal and cardiomyopathic human hearts. STUDY DESIGN: The study group consisted of 46 hearts obtained at biopsy. These patients had undergone cardiac transplantation for intractable congestive heart failure (18 cases with ischemic cardiomyopathy and 28 cases with idiopathic dilated cardiomyopathy). Another 10 hearts were collected at autopsy and used as control hearts according to preautopsy, autopsy and histology criteria. One hundred fibroblasts and 200 myocytes were evaluated in each ventricle. The nuclear area and DNA content were estimated using image cytometry. RESULTS: End-stage ischemic and dilated cardiomyopathies were characterized by an increase in nuclear size of both the myocyte and nonmyocyte population. The nuclear area of interstitial cells increased about 30% in cardiomyopathic hearts. Augmentation of average nuclear area of myocytes was 1.2-fold in the ischemic group and about 1.5-fold in the dilated group as compared with the control group. Also, a tendency was found for the coefficient of variation of average nuclear area to decrease in the interstitial cell population and increased in the myocyte population in cardiomyopathic situations. Furthermore, the nuclear area of myocytes enlarged as augmentation of nuclear DNA content. The relative nuclear areas of myocytes can be presented as: 2c:4c:8c:16c :32c:64c = 1:1.65:2.75:4.60:7.25:9.18. CONCLUSION: The increase in nuclear size follows either one of two different processes: the first does not involve an increase in DNA content, whereas the second is concomitant with an incremental increase in DNA content. In the first instance, the enlargement of nuclear size is limited. In the second, augmentation of nuclear size can become very impressive. In end-stage ischemic and dilated cardiomyopathies, the nuclear growth of myocytes and interstitial cells may be due to different mechanisms. Enlargement of the nuclear area of myocytes represents a complex process, including simple nuclear hypertrophy, polyploidization and multinucleation. The main pattern of nuclear growth of interstitial cells is nuclear hypertrophy without an increase in DNA content.