RESUMO
An 8-week growth trial was conducted to study enterohepatic recirculation of bile acid metabolism and the intestinal microbiota of Amur sturgeon (Acipenser schrenckii) fed with three diets, including 540 g/kg, 270 g/kg or 0 g/kg fishmeal, which was correspondingly replaced by a plant protein blend (named P0, P50 and P100, respectively). The diets were designed to be isonitrogenous, isoenergetic and essential nutrients balanced. With rising levels of dietary plant protein, disruption of the spiral valve intestinal microbiota and more morbidity with liver disease were observed in the P100 group, although there were no haematological abnormalities observed. An obvious bile acids enterohepatic circulation disorder was found with phenotypes of increased liver bile acids compensatory synthesis, and reduced expression of bile acid receptors (FXR and TGR5), which induced BA accumulative toxicity. Accompanied by increased oxidative stress, it further induced hepatic lesions and hypoimmunity, which were non-negligible reasons for the high mortality and low utilization ability of plant protein by Amur sturgeon.
Assuntos
Ácidos e Sais Biliares/metabolismo , Circulação Êntero-Hepática , Peixes/imunologia , Microbioma Gastrointestinal/efeitos dos fármacos , Proteínas de Vegetais Comestíveis/metabolismo , Ração Animal/análise , Animais , Dieta/veterinária , Suplementos Nutricionais/análise , Relação Dose-Resposta a Droga , Intestinos/microbiologia , Proteínas de Vegetais Comestíveis/administração & dosagem , Distribuição AleatóriaRESUMO
OBJECTIVE: To explore whether micro ribonucleic acid (miR)-7 affects the resistance of breast cancer cells to adriamycin (ADR) through regulating the epidermal growth factor receptor (EGFR)/phosphatidylinositol 3-hydroxy kinase (PI3K) signaling pathway. MATERIALS AND METHODS: MiR-7 expression was compared among MCF-10A, MCF-7 and MCF-7/ADR cells. The MCF-7/ADR cells were divided into three groups, namely miR-7 control group (MCF-7/ADR drug-resistant strains), miR-7 inhibition group (miR-7-inhibited MCF-7/ADR drug-resistant strains) and miR-7 promotion group (MCF-7/ADR drug-resistant strains transfected with miR-7), and the messenger RNA (mRNA) and protein expression levels of MCF-7/ADR were evaluated via Western blotting. RESULTS: The expression level of miR-7 was substantially decreased in MCF-7 and MCF-7/ADR cells (p<0.05), and it was lowered more obviously in MCF-7/ADR cells than that in MCF-7 cells (p<0.05). Compared with that in miR-7 control group, miR-7 expression in miR-7 promotion group was notably raised (p<0.05), proving that the sensitivity of MCF-7/ADR cells to ADR was enhanced, while that in miR-7 inhibition group was significantly lowered (p<0.05). Compared with those in miR-7 control group, the mRNA and protein expression levels of EGFR and PI3K were elevated in miR-7 inhibition group (p<0.05), while they were lowered in miR-7 promotion group (p<0.05). Additionally, compared with those in miR-7 control group, the proliferation and apoptosis abilities of cells in miR-7 inhibition group were markedly enhanced (p<0.05) and weakened (p<0.05), respectively, while they were weakened (p<0.05) and significantly strengthened (p<0.05), respectively in miR-7 inhibition group. CONCLUSIONS: MiR-7 plays an important role in the resistance of breast cancer cells to ADR, and its over-expression can inhibit the EGFR/PI3K signaling pathway to raise their sensitivity to the chemotherapy drug ADR.
Assuntos
Antibióticos Antineoplásicos/farmacologia , Neoplasias da Mama/tratamento farmacológico , Doxorrubicina/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/metabolismo , Transdução de Sinais/genética , Antibióticos Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/genética , Regulação para Baixo , Doxorrubicina/uso terapêutico , Receptores ErbB/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Células MCF-7 , MicroRNAs/antagonistas & inibidores , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
Objective: To evaluate the feasibility of susceptibility weighted imaging (SWI) to reflect the progression of renal fibrosis (RF) induced by unilateral ureteral obstruction (UUO) in rabbits. Methods: Total of 32 New Zealand white rabbits (aged 4-5 months) were used to establish the UUO model (RF group) and were divided into 4 subgroups (including RF-2W group, RF-4W group , RF-6W group and RF-8W group) according to the duration of obstruction(2, 4, 6 and 8 weeks). Another 8 rabbits, underwent sham operation, were used as the control group (Sham group). T2 weighted imaging (T(2)WI) and SWI sequences were performed on the rabbits at 2, 4, 6 and 8 weeks after UUO, respectively. Rabbits were sacrificed and specimens were obtained after MR examination, then hematoxylin&eosin staining and Masson staining were performed to explore the renal tubular injury and interstitial fibrosis. The relationship between the relative signal-to-noise ratio(rSNR)measured on the SWI fusion maps and the degree of renal fibrosis was analyzed. Analysis of variance was used to compare the difference of rSNRs among 5 groups. Results: The rSNRs of the inner medulla gradually decreased over time, the rSNRs of Sham group, RF-2W group, RF-4W group, RF-6W group and RF-8W group was 2.29±0.18, 1.73±0.30, 1.67±0.08, 1.42±0.28, 1.12±0.15, respectively (F=25.876, P<0.01). In RF-2W group, the rSNRs of the outer medulla and cortex increased when compared with those in the Sham group, then they decreased gradually over time in the other groups (F=5.230, 7.621, both P<0.05). The pathological results demonstrated that the morphology of renal tubules in Sham group was normal and no apoptosis or necrosis was seen in the tubular epithelial cells. In the RF-2W group, the main pathological manifestations included renal tubules dilatation, tubular epithelial cell degeneration or necrosis and the infiltration of inflammatory cell. In Masson staining, lots of blue areas were present in the interstitial. As the obstruction time prolonged, the renal tubular collapse, inflammatory cells and fibroblasts increased significantly. Meanwhile blue area also increased significantly in Masson staining. Conclusion: SWI can be used as a noninvasive method to evaluate the pathological progression of fibrosis in the rabbit UUO model.