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1.
Aging (Albany NY) ; 12(5): 4445-4462, 2020 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-32155132

RESUMO

Forest musk deer (Moschus berezovskii, FMD) is an endangered artiodactyl species, male FMD produce musk. We have sequenced the whole genome of FMD, completed the genomic assembly and annotation, and performed bioinformatic analyses. Our results showed that microsatellites (SSRs) displayed nonrandomly distribution in genomic regions, and SSR abundances were much higher in the intronic and intergenic regions compared to other genomic regions. Tri- and hexanucleotide perfect (P) SSRs predominated in coding regions (CDSs), whereas, tetra- and pentanucleotide P-SSRs were less abundant. Trifold P-SSRs had more GC-contents in the 5'-untranslated regions (5'UTRs) and CDSs than other genomic regions, whereas mononucleotide P-SSRs had the least GC-contents. The repeat copy numbers (RCN) of the same mono- to hexanucleotide P-SSRs had different distributions in different genomic regions. The RCN of trinucleotide P-SSRs had increased significantly in the CDSs compared to the transposable elements (TEs), intronic and intergenic regions. The analysis of coefficient of variability (CV) of P-SSRs showed that the RCN of mononucleotide P-SSRs had relative higher variation in different genomic regions, followed by the CV pattern of RCN: dinucleotide P-SSRs > trinucleotide P-SSRs > tetranucleotide P-SSRs > pentanucleotide P-SSRs > hexanucleotide P-SSRs. The CV variations of RCN of the same mono- to hexanucleotide P-SSRs were relative higher in the intron and intergenic regions, followed by that in the TEs, and the relative lower was in the 5'UTR, CDSs and 3'UTRs. 58 novel polymorphic SSR loci were detected based on genotyping DNA from 36 captive FMD and 22 SSR markers finally showed polymorphism, stability, and repetition.

2.
J Anim Sci ; 98(3)2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-32152634

RESUMO

Two experiments were conducted to investigate the effects of exogenous catalase (CAT) in the diet of weaned piglets on growth performance, oxidative capacity, and hepatic apoptosis after challenge with lipopolysaccharide (LPS). In experiment 1, 72 weaned piglets [Duroc × Landrace × Yorkshire, 6.90 ± 0.01 kg body weight (BW), 21 d of age] were randomly assigned to be fed either a basal diet (CON group) or a basal diet supplemented with 2,000 mg/kg CAT (CAT group; dietary CAT activity, 120 U/kg) for 35 d. Blood samples were collected on day 21 and day 35. At the end of this experiment, 12 pigs were selected from each of the CON and CAT groups, and six pigs were injected with LPS (50 µg/kg BW), while the remaining six pigs were injected with an equal amount of sterile saline, resulting in a 2 × 2 factorial arrangement of treatments (experiment 2). Blood samples and rectal temperature data were collected 0 and 4 h after challenge, and liver samples were obtained after evisceration. The gain-to-feed ratio was higher (P < 0.05) in piglets in the CAT group than in those in the CON group from day 1 to 35. Catalase and total superoxide dismutase (T-SOD) activities were higher (P < 0.05), whereas malondialdehyde (MDA) concentrations were lower (P < 0.05), in piglets in the CAT group than in those in the CON group at day 35. During challenge, rectal temperature and liver MDA and H2O2 concentrations increased significantly (P < 0.05), whereas plasma CAT and glutathione peroxidase (GSH-Px) activities and liver CAT activity decreased markedly (P < 0.05), in LPS-challenged piglets 4 h post-challenge. Increased CAT activity and decreased MDA concentration were observed in the plasma and liver of piglets in the CAT group 4 h post-challenge (P < 0.05). Dietary CAT supplementation markedly suppressed the LPS-induced decrease in plasma GSH-Px activity and liver CAT activity to levels observed in the CON group (P < 0.05) as well as significantly decreasing the concentration and mRNA expression of caspase-3 and caspase-9 (P < 0.05). LPS-induced liver injury was also attenuated by dietary CAT supplementation, as demonstrated by a decrease in liver caspase-3 mRNA expression (P < 0.05). Overall, dietary supplementation with 2,000 mg/kg exogenous CAT (dietary CAT activity, 120 U/kg) improves growth performance and has a beneficial effect on antioxidant capacity in weaned piglets; alleviates oxidative stress and reduces liver damage by suppressing hepatic apoptosis in LPS-challenged piglets.

3.
Aging (Albany NY) ; 12(3): 2373-2392, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32012120

RESUMO

Upregulated ubiquitin-conjugating enzyme E2M (UBE2M) is associated with poor prognosis in malignancies; However, the phenotype and mechanism of action of UBE2M in hepatocellular carcinoma (HCC) remain elusive. Here, we report that UBE2M is overexpressed and correlated with poor prognosis in HCC patients. The UBE2M level is an independent prognostic factor for HCC patients. UBE2M knockdown inhibits HCC cell proliferation, migration, and invasion, whereas its overexpression has an opposite effect. Mechanistically, upregulated UBE2M exerts oncogenic effects by translocation of accumulated ß-catenin from the cytoplasm to the nucleus, thus activating downstream ß-catenin/cyclin D1 signaling. In summary, our study demonstrates a notable role of UBE2M in promoting the growth of HCC, providing a novel strategy for HCC prevention and treatment.

4.
Eur J Gastroenterol Hepatol ; 32(2): 265-275, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31789948

RESUMO

BACKGROUND: To explore the risk factors and prognostic factors related to the acute-on-chronic liver failure (ACLF) occurrence and adverse outcome after withdrawal of nucleos(t)ide analogs (NAs) in chronic hepatitis B (CHB) patients. METHODS: Hospitalized CHB patients with relapse after NAs withdrawal at our medical center were retrospectively included in the present study from January 2011 to May 2018. Logistic regression, Cox regression analysis, Kaplan-Meier log-rank test, and area under the receiver operating characteristic curves (AUROC) were used. RESULTS: A total of 389 CHB patients (including 46 ACLF patients) were included. Their median age was 48.0 years; 315 patients were male and 74 were female. The age ≥30 years and HBVDNA ≤1000 copies at admission in logistic regression were the independent risk factors for ACLF after NAs withdrawal in CHB patients. In patients who developed ACLF, only the model of end-stage liver disease combining serum natrium concentration (MELD-Na) score and relapse after Lamivudine (LAM) cessation in the Cox multivariate regression analysis were independent predictors for 12-week mortality. The artificial liver support system (ALSS) showed no improvement in the 12-week survival of ACLF patients. We further defined 22.35 as the optimal cutoff value of MELD-Na score to predict 12-week mortality for ACLF patients, with the AUROC of 0.817, a sensitivity of 76.5%, and a specificity of 75.9%. CONCLUSION: The age ≥30 years and HBVDNA ≤1000 copies at admission strongly correlate with occurrence of ACLF, and higher MELD-Na score and relapse after LAM withdrawal are closely related with 12-week mortality among patients with ACLF after NAs withdrawal.

5.
J Cell Biochem ; 121(4): 2938-2949, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31692072

RESUMO

BACKGROUND: Calcium-binding tyrosine phosphorylation-regulated protein (CABYR) is a group of isoforms produced by alternative splicing and is overexpressed in human malignancies including hepatocellular carcinoma (HCC). However, the prognostic value and biological functions of its major protein isoforms, named CABYR-a/b (combined CABYR-a and CABYR-b), in HCC remain to be established. METHODS: CABYR-a/b expression was detected in HCC tissues and cell lines by quantitative real-time polymerase chain reaction and Western blot analysis. The correlation of CABYR-a/b expression with clinical characteristics and its prognosis impact were determined by statistical analysis. Finally, the biological functions and molecular mechanism of CABYR-a/b were also investigated using molecular biology approaches. RESULTS: The present research found that CABYR-a/b was markedly elevated in HCC specimens and cell lines. Upregulated CABYR-a/b level had positive association with tumor size and differentiation in patients. Moreover, cases with elevated CABYR-a/b level had poorer overall survival (OS) and disease-free survival (DFS) than those with reduced CABYR-a/b level. Multivariate analysis and prognostic nomograms demonstrated that CABYR-a/b overexpression was an independent predictive indicator for OS and DFS. The calibration curve for the odds of OS and DFS demonstrated that the prediction by nomograms was in excellent accordance with actual situation. CABYR-a/b downregulation suppressed cell proliferation and induced G1-phase arrest via decreasing cyclin D1 and cyclin dependent kinase 4, while promoted apoptosis by reducing B-cell lymphoma 2 (Bcl-2) and increasing Bcl-2-associated death promoter. CONCLUSION: Our research indicates that CABYR-a/b exerts an oncogenic effect on HCC development and may become a new prognostic indicator for patients with HCC.

6.
Gut ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31767630

RESUMO

OBJECTIVE: Liver fibrosis and cirrhosis resulting from chronic liver injury represent a major healthcare burden worldwide. Growth differentiation factor (GDF) 11 has been recently investigated for its role in rejuvenation of ageing organs, but its role in chronic liver diseases has remained unknown. Here, we investigated the expression and function of GDF11 in liver fibrosis, a common feature of most chronic liver diseases. DESIGN: We analysed the expression of GDF11 in patients with liver fibrosis, in a mouse model of liver fibrosis and in hepatic stellate cells (HSCs) as well as in other liver cell types. The functional relevance of GDF11 in toxin-induced and cholestasis-induced mouse models of liver fibrosis was examined by in vivo modulation of Gdf11 expression using adeno-associated virus (AAV) vectors. The effect of GDF11 on leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5)+ liver progenitor cells was studied in mouse and human liver organoid culture. Furthermore, in vivo depletion of LGR5+ cells was induced by injecting AAV vectors expressing diptheria toxin A under the transcriptional control of Lgr5 promoter. RESULTS: We showed that the expression of GDF11 is upregulated in patients with liver fibrosis and in experimentally induced murine liver fibrosis models. Furthermore, we found that therapeutic application of GDF11 mounts a protective response against fibrosis by increasing the number of LGR5+ progenitor cells in the liver. CONCLUSION: Collectively, our findings uncover a protective role of GDF11 during liver fibrosis and suggest a potential application of GDF11 for the treatment of chronic liver disease.

7.
J Anim Sci Biotechnol ; 10: 72, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31452881

RESUMO

Background: This study aimed to investigate the effects of oral administration of Enterococcus faecium NCIMB 10415 (E. faecium) on intestinal development, immunological parameters and gut microbiota of neonatal piglets challenged with enterotoxigenic Escherichia coli K88 (ETEC). A total of 96 1-day-old sow-reared piglets were randomly assigned to 2 groups, with 48 piglets in each group. The piglets were from 16 litters (6 piglets each litter), and 3 piglets each litter were allocated to the E. faecium-supplemented (PRO) group, while the other 3 piglets were allocated to the control (CON) group. After colostrum intake, piglets in the PRO group were orally administrated with 3 × 109 CFU E. faecium per day for a period of one week. On day 8, one piglet per litter from each group was challenged (CON+ETEC, PRO+ETEC) or not (CON-ETEC, PRO-ETEC) with ETEC in a 2 × 2 factorial arrangement of treatments. On day 10 (2 days after challenge), blood and tissue samples were obtained from piglets. Results: Before ETEC challenge, there were no significant differences for the average daily gain (ADG) and fecal score between the two groups of piglets. After ETEC challenge, the challenged piglets had greater fecal score compared to the non-challenged piglets, whereas E. faecium administration was able to decrease the fecal score. Piglets challenged with ETEC had shorter villous height, deeper crypt depth, and reduced number of goblet cells in the jejunum and decreased mRNA abundance of claudin-1 in the ileum, whereas increased the percentage of lymphocytes, concentrations of IL-1ß in the plasma and TNF-α in the ileal mucosa, as well as increased the mRNA abundances of innate immunity-related genes in the ileum tissue. These deleterious effects caused by ETEC were partly alleviated by feeding E. faecium. In addition, piglets in PRO-ETEC group had decreased the percentage of CD8+ T cells of the peripheral blood when compared to those in CON-ETEC group. Moreover, E. faecium administration increased Verrucomicrobia at phylum level and decreased Bilophila at genus level. Conclusions: These results suggest that oral administration of E. faecium alleviated the intestinal injury and diarrhea severity of neonatal piglets challenged by ETEC, partly through improving the intestinal microbiota and immune response. This offers a potential strategy of dietary intervention against intestinal impairment by ETEC in neonatal piglets.

8.
Animals (Basel) ; 9(7)2019 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-31284518

RESUMO

To investigate the effects of the ratio of insoluble fiber to soluble fiber (ISF:SF) on sow performance and piglet intestinal development, we randomly assigned 64 gilts to four treatments comprising diets with the same level of dietary fiber, but different ISF:SF values of 3.89 (T1), 5.59 (T2), 9.12 (T3), and 12.81 (T4). At birth and weaning, six piglets per treatment at each phase were slaughtered for sampling. As ISF:SF increased, the mean piglet body weight (BW) at weaning and piglet BW gain, which were all significantly higher in T1 and T2 compared with T3 and T4 (p < 0.05), showed a linear decrease (p < 0.05); the crypt depth of the jejunum in weaned piglets linearly increased, whereas the duodenal weight, jejunal villus height, and villus height/crypt depth in newborn piglets and enzymatic activity of lactase, sucrase, and maltase linearly decreased (p < 0.05). No differences were observed in the yield and composition of milk (p > 0.05). Moreover, when the ISF:SF was 3.89 in gestation diets, higher piglet BW at weaning occurred, possibly because the ISF:SF affected development and enzymatic activity in the small intestine-effects related to digestion and absorption of nutrients-and consequently enhanced piglet BW gain.

9.
J Anim Sci ; 97(8): 3426-3439, 2019 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-31233597

RESUMO

This study was conducted to investigate the effects of Clostridium butyricum addition to diets in late gestation and lactation on the reproductive performance and gut microbiota for sows. A total of 180 healthy Landrace × Yorkshire sows at 90 d of gestation were randomly assigned to one of four groups, with 45 replicates per group, receiving a basal commercial diet (Control, 0% C. butyricum) or diet added with 0.1% C. butyricum (1 × 108 CFU/kg of feed), 0.2% C. butyricum (2 × 108 CFU/kg of feed), 0.4% C. butyricum (4 × 108 CFU/kg of feed), respectively. The experiment was conducted from 90 d of gestation to weaning at 21 d of lactation. The results showed that the interval between piglet born was linearly (P < 0.05) decreased, and the duration of farrowing was significantly (quadratic, P < 0.05) shortened as C. butyricum addition increased. There was a linear (P < 0.05) increase in litter weight at weaning and litter weight gain. The concentrations of IgG and IgM in colostrum, and IgM in milk were linearly increased (P < 0.05) as C. butyricum addition. Serum MDA concentrations of sows at parturition and 14 d in lactation, and piglets at 14 and 21 d of age were linearly (P < 0.05) decreased, respectively. The serum total antioxidant capacity concentrations of sows at parturition and 14 and 21 d in lactation, and piglets at 14 and 21 d of age were linearly (P < 0.05) increased as C. butyricum addition, respectively. There was a linear decrease in the serum endotoxin concentration of sows on 21 d in lactation (P < 0.05). The serum cortisol concentrations of piglets at 14 and 21 d of age were both significantly (quadratic, P < 0.05) decreased. The 0.2% C. butyricum increased the relative abundance of Bacteroidetes (P = 0.016) at phylum level, Prevotellaceae_NK3B31_group, Prevotella_1, Prevotellaceae_UCG-003, Prevotella_9, Alloprevotella (P < 0.05) at genus level, and decreased the relative abundance of Proteobacteria, Gemmatimonadetes, Actinobacteria (P < 0.001) at phylum level, and Clostridium_sensu_stricto_1, Streptococcus, Escheruchia-Shigella, Sphingomonas, Succinivibrio (P < 0.05) at genus level and Firmicutes/Bacteroidetes ratio (P = 0.020). In conclusion, the present research indicated that dietary addition with C. butyricum could shorten the duration of farrowing and enhance the growth performance of suckling piglets. Moreover, 0.2% C. butyricum administration to sows changed the composition of intestinal microbiota, especially increased the relative abundance of Prevotella.


Assuntos
Ração Animal/análise , Clostridium butyricum/fisiologia , Microbioma Gastrointestinal , Reprodução , Suínos/microbiologia , Animais , Antioxidantes/análise , Colostro/imunologia , Dieta/veterinária , Feminino , Imunoglobulina G/imunologia , Imunoglobulina M/imunologia , Intestinos/microbiologia , Lactação , Leite/imunologia , Parto , Gravidez , Suínos/imunologia , Desmame , Ganho de Peso/efeitos dos fármacos
10.
Arch Med Res ; 50(1): 10-17, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31101236

RESUMO

BACKGROUND AND AIMS: Cyclin B2 (CCNB2) has been reported to be highly expressed in a few malignancies. However, the biological function of CCNB2 in hepatocellular carcinoma (HCC) is largely unknown. We aimed to investigate the effect of CCNB2 in HCC. METHODS: The expression of CCNB2 in HCC and normal liver tissues and connection of its expression with prognosis and clinical parameters were studied. The effect of knocking down CCNB2 on cell proliferation, migration, cell cycle distribution, and apoptosis were estimated in BEL-7404 cells. RESULTS: Compared to normal liver tissues, the level of CCNB2 was higher in HCC tissues from the Gene Expression Profiling Interactive Analysis (GEPIA). The 5 year overall survival and disease-free survival of HCC patients with high CCNB2 levels were shorter than that of those with low CCNB2 levels. Immunohistochemistry analysis also discovered the expression differences of CCNB2 in HCC and normal liver tissues and showed that CCNB2 expression was significantly associated with tumor number, tumor size, tumor thrombus, and alanine aminotransferase level. CCNB2 expression was higher in HCC cell lines (BEL-7404, Hep3B, BEL-7402, and SMMC-7721) than that in the normal hepatic cell line (HL-7702). Knockdown of CCNB2 inhibited cell proliferation and migration, promoted cell apoptosis, and caused S phase arrest in BEL-7404 cells. Finally, CCNB2 was associated with Polo Like Kinase 1 (PLK1) in the GEPIA database and BEL-7404 cells. CONCLUSIONS: CCNB2 may serve as a prognostic factor and participated in the development and progression and promote cell proliferation and migration through CCNB2/PLK1 pathway in HCC.


Assuntos
Carcinoma Hepatocelular/patologia , Proteínas de Ciclo Celular/metabolismo , Ciclina B2/metabolismo , Neoplasias Hepáticas/patologia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Apoptose/genética , Proteínas Reguladoras de Apoptose , Carcinoma Hepatocelular/mortalidade , Ciclo Celular/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ciclina B2/genética , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Neoplasias Hepáticas/mortalidade , Masculino , Prognóstico
11.
Cancer Med ; 8(8): 4043-4054, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31134761

RESUMO

BACKGROUND: Most mammary Paget disease (MPD) is associated with underlying in situ or invasive breast cancer. The objective of this study was to compare the clinicopathological characteristics and survival outcomes between breast cancer with Paget disease (PD) and breast cancer alone. METHODS: From the Surveillance, Epidemiology, and End Results (SEER) database, 2000-2015, of the US National Cancer Institute, we identified 1569 women who had PD with invasive ductal carcinoma (PD-IDC) and 1489 women who had PD with ductal carcinoma in situ (PD-DCIS). Independent demographic and clinicopathological variables as well as survival outcomes of these patients were compared to patients with the corresponding breast cancer without concomitant PD. RESULTS: PD-IDC and PD-DCIS both had worse survival outcomes and poorer tumor characteristics than the corresponding disease without PD. Contrary to in the breast cancer alone groups, in the breast cancer with PD groups, the HR status (P = 0.182 in PD-IDC and P = 0.371 in PD-DCIS), HER2 status (P = 0.788 in PD-IDC and P = 0.643 in PD-DCIS), and combined molecular subtype (P = 0.196 in PD-IDC and P = 0.853 in PD-DCIS) were not found to affect disease prognosis. After matching tumor characteristics and treatment approaches, PD-IDC as well as PD-DCIS exhibited no significant difference in disease prognosis with corresponding IDC and DCIS. Finally, by comparative analysis, a kind of PD-DCIS (ICD-O-3 code 8543/3) showed many invasive behaviors (31.8% of 8543/3 patients had stage I-III cancer) and was associated with worse survival outcomes than the other type of PD-DCIS. CONCLUSIONS: Breast cancer with concomitant PD was associated with more aggressive tumor characteristics and worse survival outcomes. The HR status, HER2 status, and combined molecular subtype could not affect the prognosis of breast cancer with PD. Moreover, a portion of the PD-DCIS cases were invasive breast cancer cases that required special treatment.

12.
Gene ; 696: 219-224, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30802535

RESUMO

BACKGROUND AND AIMS: The extracellular calcium-binding protein family member thrombospondin-4 (THBS4) regulates cell migration, proliferation, attachment, adhesion, angiogenesis, neural development, tissue structure, organ development, pain signal transduction, and tumor growth. The aim of this study was to study THBS4 expression in hepatocellular carcinoma (HCC) and determine if it was a prognostic marker for this malignancy. METHODS: We used immunohistochemistry and tissue microarrays to evaluate THBS4 expression in 84 HCC and matched para-cancerous tissues. Then, we assessed relationships between THBS4 expression and clinicopathological parameters. RESULTS: THBS4 expression was higher in HCCs than in matched para-cancerous tissues (P < 0.001). There was a significant correlation between high THBS4 levels and preoperative serum alanine aminotransferase (P < 0.04). In HCC patients, high THBS4 expression was associated with shorter overall and disease-free survival compared with low THBS4 expression. Additionally, subgroup analysis showed that high THBS4 levels were only associated with poor overall survival for alpha-fetoprotein >40 ng/mL (P = 0.028) and cirrhosis (P = 0.002). Multivariate analysis showed that high THBS4 expression was an independent prognostic factor for both overall and disease-free survival. CONCLUSIONS: Our data suggest that THBS4 may play a role in HCC development, and thus may be an independent prognostic marker and/or potential therapeutic target for HCC patients.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinogênese/patologia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Trombospondinas/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/mortalidade , Intervalo Livre de Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Fígado/patologia , Neoplasias Hepáticas/mortalidade , Masculino , Pessoa de Meia-Idade , Prognóstico , Análise Serial de Tecidos , Regulação para Cima
13.
EBioMedicine ; 41: 623-635, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30772303

RESUMO

BACKGROUND: Global consumption of protein per capita is rising, while rates of infertility are increasing. However, a clear relationship between protein intake and reproductive health has not been demonstrated. The activation of the quiescent primordial follicles is the first step of folliculogenesis, and their activation must be tightly controlled to prevent premature exhaustion of the ovarian follicular reserve. METHODS: The primordial follicle reserve of wild-type or liver-specific ablation of fibroblast growth factor 21 (FGF21) in mice, subjected to limited or excessive protein diets or oral gavage test, were detected in vivo. Mouse ovary organ cultures were used to examine the direct role of metabolites or metabolic hormones on primordial follicle activation. FINDINGS: Mouse primordial follicle activation, was reduced by restricted protein intake and was accelerated by excessive protein intake, in an ovarian mTORC1 signaling-dependent manner. Furthermore, restricted or excessive protein intake resulted in an augmentation or decline of oocyte number and fertility at older age, respectively. Liver-specific ablation of FGF21, which resulted in a reduction of 87% in circulating FGF21, abrogated the preserving effect of low-protein intake on primordial follicle pool. Interestingly, FGF21 had no direct effect on the activation of primordial follicles, but instead required an adipokine adiponectin. Moreover, AdipoRon, an oral adiponectin receptor agonist, prevented the over-activation effect of excessive protein intake on primordial follicle activation. INTERPRETATION: Dietary protein consumption controlled ovarian primordial follicle reserve and fertility, which required coordination between FGF21 and adiponectin. FUND: Natural Science Foundation of China (Grant 31772616).


Assuntos
Adiponectina/metabolismo , Dieta com Restrição de Proteínas , Fatores de Crescimento de Fibroblastos/genética , Adiponectina/sangue , Administração Oral , Animais , Feminino , Fatores de Crescimento de Fibroblastos/sangue , Fatores de Crescimento de Fibroblastos/metabolismo , Técnicas In Vitro , Fígado/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Oócitos/citologia , Técnicas de Cultura de Órgãos , Folículo Ovariano/efeitos dos fármacos , Folículo Ovariano/crescimento & desenvolvimento , Folículo Ovariano/metabolismo , Ovário/metabolismo , Ovário/patologia , Piperidinas/farmacologia , RNA Mensageiro/metabolismo , Transdução de Sinais
14.
J Sci Food Agric ; 99(5): 2096-2107, 2019 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-30298675

RESUMO

BACKGROUND: Limited studies have examined links between maternal methyl donor (MET) supplementation and the growth-development characteristics of offspring, and possible underlying mechanisms for such links. This study investigated the effect of maternal or post-weaning MET-supplementation on growth performance, carcass characteristics, and meat quality of the finishing (d 180) offspring. Twenty-four sows were placed on a control (C) or MET-supplemented diet during pregnancy and lactation. Forty-eight female offspring were fed the control or MET-supplemented diet from weaning to 6 months of age, resulting in four study groups (six litters per group): C/C, C/MET, MET/C, and MET/MET. RESULTS: Maternal MET-supplementation increased average daily gain (ADG), body weight (BW), lean percentage and longissimus dorsi (LD) of the offspring at day 180 (P < 0.05), and upregulated the myosin heavy chain IIx, myogenic differentiation and muscle regulatory factor 4 mRNA levels in the LD muscle (P < 0.05). Meanwhile, offspring from maternal MET-supplementation exhibited a higher pH24h post mortem and superoxide dismutase activity, a lower L* 45min , glycolytic potential, malonaldehyde content in the LD muscle, and plasma homocysteine concentration (P < 0.05). CONCLUSION: Maternal MET-supplementation has a remarkable effect on growth performance, carcass traits, and meat quality of the offspring, which is associated with increased expression levels of myogenic genes and anti-oxidant capacity. © 2018 Society of Chemical Industry.


Assuntos
Suplementos Nutricionais/análise , Carne/análise , Suínos/crescimento & desenvolvimento , Ração Animal/análise , Animais , Betaína/metabolismo , Peso Corporal , Feminino , Ácido Fólico/metabolismo , Humanos , Masculino , Fenômenos Fisiológicos da Nutrição Materna , Metionina/metabolismo , Gravidez , Suínos/genética , Suínos/metabolismo , Desmame
15.
Perfusion ; 34(3): 211-216, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30370815

RESUMO

INTRODUCTION: Extracellular histones have been recently identified as damage-associated molecular-pattern (DAMP) molecules involved with the pathogenesis of various inflammatory diseases. This study intended to investigate whether extracellular histones can indicate the prognosis in critically ill patients supported by extracorporeal membrane oxygenation (ECMO) therapy. METHODS: A total of 56 patients undergoing ECMO were analysed retrospectively. Median concentrations of extracellular histones in patients before ECMO were assessed and used to divide the patients into two groups (Group 1 <48 µg/ml and Group 2 ⩾48 µg/ml). Mortality rate, Sequential Organ Failure Assessment (SOFA) scores and systemic inflammation were compared between the groups. RESULTS: There were relatively higher concentrations of extracellular histones in Group 2 patients (57.78 µg/ml [48.4, 71.3]) than in Group 1 patients (36.76 µg/ml [28.5, 39.3], p<0.0001). The hospital mortality rate was 55.4% for the entire study subjects, with significantly worsened mortality in Group 2 in contrast to Group 1 (58.8% vs. 50%, p=0.031). Moreover, Group 2 patients had significantly higher SOFA scores and more pronounced systemic inflammation than Group 1 patients prior to ECMO initialization. CONCLUSIONS: Extracellular histones are known contributors to cell damage and organ injury. Our study showed that extracellular histones have a predictive value in the assessment of outcome of patients undergoing ECMO therapy and may be helpful for risk stratification in clinical settings.


Assuntos
Oxigenação por Membrana Extracorpórea , Histonas/sangue , Inflamação/sangue , Adulto , Idoso , Estado Terminal , Citocinas/sangue , Oxigenação por Membrana Extracorpórea/efeitos adversos , Oxigenação por Membrana Extracorpórea/mortalidade , Feminino , Humanos , Inflamação/diagnóstico , Masculino , Pessoa de Meia-Idade , Escores de Disfunção Orgânica , Prognóstico , Estudos Retrospectivos
16.
Nanotechnology ; 30(6): 065502, 2019 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-30523802

RESUMO

Fatty acids (FAs) are important dietary sources of fuel for animals and structural components for cells. The number, position and configuration of olefins in the alkyl chains play important roles in the impacts of FAs on human health. Currently, structural profiling of FAs in edible oils and fats is an important issue in nutrition industries and food safety. Due to the lack of distinct functional groups, it is extremely difficult to discriminate FAs with structural differences by facile and in situ sensing methods. A few chemosensors have been developed for shape selective sensing of FAs, but their capability and performance were still limited. Herein, for the first time, we proposed a multichannel Au nanosensor for visual and pattern-generating inspection of FAs based on the highly selective binding ability of Ag+ to olefinic bonds and Ag+ regulable color variation of Au nanoparticles. As a result, the nanosensor showed good selectivity for five FAs with subtle structural difference as low as 5 nM. By further deriving three channel signals in respect of color and color depth, a signature-like signal pattern could be generated by principal component analysis for each FA and even different FA mixtures such as edible oils. Hence, structural variation of FAs in edible hot pot oils with heat treatment was successfully monitored by this Au nanosensor over time. This sensor holds great promise in point-of-care inspection of edible oils and fats.


Assuntos
Ácidos Graxos/análise , Ouro/química , Nanopartículas/química , Reconhecimento Automatizado de Padrão , Colorimetria , Oxirredução , Óleos Vegetais/análise , Prata
17.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 31(11): 1357-1362, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31898565

RESUMO

OBJECTIVE: To explore whether extracellular histones aggravate acute respiratory distress syndrome (ARDS) by inducing peripheral blood mononuclear cell (PBMC) pyroptosis. METHODS: Twenty patients with ARDS admitted to Shanghai Pulmonary Hospital, Tongji University School of Medicine from April to September in 2019 were enrolled, and 20 healthy volunteers were enrolled as controls. In vivo experiment: peripheral blood samples of patients with ARDS within 24 hours after diagnosis and healthy volunteers were collected, and the levels of plasma extracellular histone, interleukins (IL-1ß and IL-18) and lactic dehydrogenase (LDH) were determined by enzyme-linked immunosorbent assay (ELISA). PBMC were harvested, the expression levels of the pyroptosis associated N terminal-gasdermin-D (GSDMD-N) protein were determined by Western Blot. In vitro experiment: PBMC isolated from healthy volunteers were divided into four groups. Blank control group without any treatment; lipopolysaccharide (LPS) group was treated with 1 mg/L LPS for 4 hours; LPS+histones group was treated with 100 mg/L exogenous histones for 24 hours after LPS treatment; LPS+histone+heparin group was treated with 200 U heparin for 24 hours after LPS and exogenous histones treatment. The GSDMD-N protein expression was determined by Western Blot, and the levels of IL-1ß, IL-18 and LDH in cell supernatant were determined by ELISA. Spearman test was used to test the correlation among the parameters. RESULTS: In vivo experiment results: compared with healthy control group, the GSDMD-N protein expression in PBMC of patients with ARDS was significantly increased [GSDMD-N/GAPDH: 0.136 (0.062, 0.246) vs. 0.026 (0.018, 0.036), P < 0.01], as well as the plasma levels of IL-1ß, IL-18, LDH and extracellular histones [IL-1ß (ng/L): 120.0 (94.2, 213.0) vs. 88.5 (82.3, 105.3), IL-18 (ng/L): 164.5 (70.8, 236.3) vs. 60.5 (52.0, 89.0), LDH (U/L): 30.9 (24.7, 39.5) vs. 19.8 (17.2, 21.5), extracellular histones (mg/L): 73.0 (42.8, 112.9) vs. 12.2 (9.6, 16.9), all P < 0.01], indicating that the PBMC of ARDS patients had significant pyroptosis and release of a large number of inflammatory factors. The oxygenation index (PaO2/FiO2) of ARDS patients was 135.5 (94.5, 196.0) mmHg (1 mmHg = 0.133 kPa). Correlation analysis showed that the expression of GSDMD-N protein in patients with ARDS was negatively correlated with PaO2/FiO2 (r = -0.935, P < 0.01) and positively correlated with IL-1ß, IL-18, LDH and extracellular histones (r value was 0.844, 0.843, 0.887, 0.899, respectively, all P < 0.01). In vitro experiment results: compared with blank control group, the expression of GSDMD-N protein in PBMC and the levels of inflammatory mediators in the supernatant of the LPS group were significantly increased [GSDMD-N/GAPDH: 0.035±0.006 vs. 0.028±0.006, IL-1ß (ng/L): 39.8±5.5 vs. 22.6±4.7, IL-18 (ng/L): 31.2±4.4 vs. 20.0±2.2, LDH (U/L): 51.2±7.3 vs. 36.6±7.6, all P < 0.05], indicating that LPS stimulation could increase PBMC pyroptosis and the release of inflammatory mediators. Compared with LPS group, the expression of GSDMD-N protein and the levels of inflammatory mediators of the LPS+histones group were further increased [GSDMD-N/GAPDH: 0.114±0.009 vs. 0.035±0.006, IL-1ß (ng/L): 119.0±18.7 vs. 39.8±5.5, IL-18 (ng/L): 49.2±8.5 vs. 31.2±4.4, LDH (U/L): 127.8±19.8 vs. 51.2±7.3, all P < 0.01], indicating that the stimulation of LPS on PBMC could be significantly amplified by exogenous histone treatment, GSDMD-N protein expression could be up-regulated and inflammatory factor release could be promoted to further induce PBMC pyroptosis. These adverse effects of exogenous histones on PBMC could be abrogated by heparin, the expression of GSDMD-N protein and the levels of inflammatory mediators were significantly lower than those of LPS+histones group [GSDMD-N/GAPDH: 0.063±0.004 vs. 0.114±0.009, IL-1ß (ng/L): 46.8±8.6 vs. 119.0±18.7, IL-18 (ng/L): 33.0±5.1 vs. 49.2±8.5, LDH (U/L): 65.4±11.0 vs. 127.8±19.8, all P < 0.05]. CONCLUSIONS: Extracellular histones in plasma may aggravate ARDS by mediating PBMC pyroptosis.


Assuntos
Histonas/metabolismo , Síndrome do Desconforto Respiratório do Adulto , China , Humanos , Interleucina-1beta , Peptídeos e Proteínas de Sinalização Intracelular , Leucócitos Mononucleares , Proteínas de Ligação a Fosfato , Piroptose
18.
Sci Rep ; 8(1): 18068, 2018 12 24.
Artigo em Inglês | MEDLINE | ID: mdl-30584255

RESUMO

Weaned piglets are vulnerable to nutritional, physiological, and psychological stressors, leading to abrupt taxonomic and functional shifts in the intestinal microbiome. In this study, an integrated approach combination of 16S rDNA gene sequencing and the mass spectrometry-based metabolomics techniques was used to investigate the effects of weaning stress on intestinal microbial composition and its metabolic profiles of piglets. Three litters of suckling piglets with same parity were chosen. The samples of colonic contents were collected from each selected piglets (weaned day, 3 days after weaned) for microbial and metabolomics analysis. The results showed that Lachnospiraceae, Negativicutes, Selenomonadales, Campylobacterales and other 15 species increased after weaning, while Porphyromonadaceace, Alloprevotella, Barnesiella and Oscillibacter decreased. Based on the function profiles prediction and metabolomic analysis, five key metabolic pathways including Phenylalanine metabolism, Citrate cycle (TCA cycle), Glycolysis or Gluconeogenesis, Propanoate metabolism, Nicotinate and nicotinamide metabolism might be the relevant pathways involved in weaning stress-induced gut microbiota dysbiosis. Taken together, these results indicated that weaning stress not only changed microbial composition and function but altered the microbial metabolic profiles in the intestine, which might provide a new insight in alleviating weaning stress and facilitating disease prevention during the period of weaning in piglets.


Assuntos
Microbioma Gastrointestinal , Estresse Psicológico/microbiologia , Desmame , Animais , Metaboloma , Metagenoma , Suínos
19.
Thorac Cardiovasc Surg Rep ; 7(1): e39-e42, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30473989

RESUMO

Stents have been widely used to restore the patency of the iliac vein in the treatment of its obstruction. However, various complications related to those stents have been reported. This case report covers a 67-year-old male who was diagnosed with left iliofemoral venous post-thrombotic syndrome with recurrent acute deep venous thrombosis. Thrombosis of the inferior vena cava was induced by pronounced extension of left iliac vein stents. Extending stents in this way covers the outlet of the contralateral common iliac vein and may induce thrombosis in the inferior vena cava.

20.
mSystems ; 3(5)2018.
Artigo em Inglês | MEDLINE | ID: mdl-30320222

RESUMO

Fecal microbiota transplantation (FMT) is one of the most effective ways to regulate the gut microbiota. Here, we investigated the effect of exogenous fecal microbiota on gut function from the perspective of analysis of the mucosal proteomes in a piglet model. A total of 289 differentially expressed proteins were annotated with 4,068 gene ontology (GO) function entries in the intestinal mucosa, and the levels of autophagy-related proteins in the forkhead box O (FoxO) signaling pathway were increased whereas the levels of proteins related to inflammation response were decreased in the recipient. Then, to assess the alleviation of epithelial injury in the Escherichia coli K88-infected piglets following FMT, intestinal microbiome-metabolome responses were determined. 16S rRNA gene sequencing showed that the abundances of beneficial bacteria, such as Lactobacillus and Succinivibrio, were increased whereas those of Enterobacteriaceae and Proteobacteria bacteria were decreased in the infected piglets following FMT. Metabolomic analysis revealed that levels of 58 metabolites, such as lactic acid and succinic acid, were enhanced in the intestinal lumen and that seven metabolic pathways, such as branched-chain amino acid metabolism pathways, were upregulated in the infected piglets following FMT. In concordance with the metabolome data, results of metagenomics prediction analysis also demonstrated that FMT modulated the metabolic functions of gut microbiota associated with linoleic acid metabolism. In addition, intestinal morphology was improved, a result that coincided with the decrease of intestinal permeability and the enhancement of mucins and mucosal expression of tight junction proteins in the recipient. Taken together, the results showed that FMT triggered intestinal mucosal protective autophagy and alleviated gut barrier injury through alteration of the gut microbial structure. IMPORTANCE The gut microbiota plays a crucial role in human and animal health, and its disorder causes multiple diseases. Over the past decade, FMT has gained increasing attention due to the success in treating Clostridium difficile infection (CDI) and inflammatory bowel disease (IBD). Although FMT appears to be effective, how FMT functions in the recipient remains unknown. Whether FMT exerts this beneficial effect through a series of changes in the host organism caused by alteration of gut microbial structure is also not known. In the present study, newborn piglets and E. coli K88-infected piglets were selected as models to explore the interplay between host and gut microbiota following FMT. Our results showed that FMT triggered intestinal mucosal autophagy and alleviated gut barrier injury caused by E. coli K88. This report provides a theoretical basis for the use of FMT as a viable therapeutic method for gut microbial regulation.

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