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Objective To provide a basis for clinical diagnosis,a serum metabonomic dynamic study was carried out on the Tg2576 mouse model at different stages of Alzheimer's disease(AD) whose pathological progress is similar to that of human AD patients.Methods Serum samples of Tg2576 mice were collected at the early(6 months) and late(12 months) stages of Alzheimer's disease.The 1H NMR spectra of the serum samples were collected and the metabolic characteristics were analyzed by multivariate analysis.Results Significant differences in serum metabonomics were found in the transgenic Tg2576 mice and C57 mice at 6 and 12 months of age,and there were significant metabolic changes in Tg2576 mice at different stages of Alzheimer's disease.Compared with C57 mice,the Tg2576 mice at early stage of Alzheimer's disease showed higher levels of serum lactate,myo-inositol and amino acids(such as leucine,isoleucine,alanine),and lower levels of lipids,choline,phosphorylcholine,glycerol phosphorglcholine,betaine,glycine and glucose.At the late stage of Alzheimer's disease,the transgenic Tg2576 mice had higher levels of lactate,myo-inositol and alanine,while the serum levels of lipids,choline,phosphorylcholine,glycerophosphorylcholine,betaine,and glycine continued to drop.Meanwhile glutamine and creatine levels started to decline.By comparing the early and late serum metabolites of Alzheimer's disease,serum metabonomic profiles of the late stage of Alzheimer's disease indicated an up-regulation of lactate,myo-inositol and alanine,and a down-regulation of lipids,choline,phosphorylcholine and glycerophosphorylcholinelevels.Moreover,the levels of lactate,lipids,choline,phosphorylcholine and glycerophosphorylcholine showed statistical significance at the early stage of AD,and they were closely correlated with the severity of Alzheimer's disease.Conclusions The above results show that the changes of lactate,myo-inositol and alanine are positively-correlated with the development of AD,while the serum levels of lipids,choline,phosphorylcholine and glycerophosphorylcholine are inversely-proportional to the severity of AD.These metabolites are dynamically and progressively changed along with the disease progression,which hopefully may serve as early metabolic markers for the diagnosis of AD in clinical practice.
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Objective Shkbp is also called Shkbp1,can competitively inhibit binding CIN85 and c-Cbl,thereby blocking the epidermal growth factor receptor (EGFR) endocytosis and degradation,to play a role in tumor promotion.This study aims to explore the changes in blood cell classification and T cell subsets in blood,bone marrow,and spleen in Shkbp1-deletion (Shkbp-1-/-) mice.Methods Shkbp-1-/-transgenic mice were identified by PCR genotyping.Blood cell classification was performed using an automatic classification system.Flow cytometry was used to detect the T lymphocyte subsets in the blood,bone marrow,and spleen of Shkbp-1-/-and control mice.Results Routine blood examination showed that neutrophils and eosinophils tended to increase and showing significant differences,and there was no significant difference in lymphocytes.The flow cytometry results showed that there was a decrease of CD4+CD8+ double positive cells and increase of bone marrow CD3+ and CD4+ cells in the control group.However,there was a decreasing trend of CD3+,CD4+,CD8+,and CD4+CD8+ cells in the spleen tissues.Conclusions Shkbp1 is involved in the maturation and differentiation of blood cells,and affects the number of immune cells.This study lays a foundation for the study of how Shkbp1 is involved in the differentiation of blood cells.
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Objective To establish a mouse model of diethylnitrosamine(DEN)-induced hepatocellular carcinoma (HCC),and to explore the effects of two different diet formulas on the establishment of DEN-induced HCC model.Methods SPF C57BL/6 mice (8 males and 8 females) were injected intraperitoneally with 25 mg/kg DEN at day 14 to establish a HCC model.The mice were divided into two groups after weaning.One group was fed with the SPF class rodents cereal-based diet,another group was fed with AIN-93G formula diet.The mice were sacrificed at the age of 9 months.The livers were weighed and the growth of liver cancer was observed and recorded.Results All the mice in the cereal-based diet group developed HCC as expected.The body weight and liver mass of the mice in the AIN-93G diet group were significantly lower than that of the cereal-based diet group.The incidence of HCC,and the number and size of tumor nodules were also significantly lower in the AIN-93G diet group than that in the cereal-based diet group.Conclusions DEN-induced HCC model has been successfully established in mice fed with cereal-based diet,while mice fed with AIN93-G diet prevented the development of DEN-induced HCC,and their body weight was decreased significantly,suggesting that dietary factors play a key role in establishment of animal disease models.
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Objective PSGL-1 is specifically expressed in leucocytes.The aim of this study was to explore the changes of myeloid-derived suppressor cells (MDSCs) in the spleen and bone marrow in PSGL-1-deficient mice.Methods PSGL-1 -/-mice were used in the experiment.After identification of the offsprings, flow cytometry was used to test the expression of CD11b and Gr-1 in C57 and PSGL-1 -/-mice.Results Compared with the C57 mice, the expression of MDSCs was up-regulated in the PSGL-1-deficient mice ( P <0.001).Conclusion The expression of MDSCs is upregulated in PSGl-1-deficient mice.
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<p><b>OBJECTIVE</b>To investigate the role of type I collagen as an autocrine protein in promoting the growth lung cancer cells in a three-dimensional (3D) culture system.</p><p><b>METHODS</b>Immunohistochemistry and RT-PCR were used to detect the expression of type I collagen in lung cancer specimens and 5 lung cancer cell lines. The lung cancer cell lines in 3D cultures were treated with vectors harboring short hairpin RNA (shRNA) targeting type I collagen, and the cell growth suppression was evaluated using MTT assay and colony formation assay. The lung cancer cells stimulated with supernatant from lung cancer-derived fibroblasts were tested for the expression of type I collagen mRNA.</p><p><b>RESULTS</b>Type I collagen expressions were detected in both the lung cancer tissues and the cell lines. In the 3D culture system, the growth of the cancer cell lines was obviously suppressed by shRNA-mediated type I collagen knockdown evidenced by lowered cell growth rate and colony formation ability. Stimulation with fibroblast culture supernatant resulted in enhanced expressions of type I collagen in the cancer cell lines.</p><p><b>CONCLUSION</b>Autocrine of type I collagen I is required for maintaining lung cancer cell growth in 3D cultures, and its expression is regulated by fibroblasts. These findings provide new insights into the role of type I collagen I in the tumor microenvironment and point a new direction for targeted therapy of tumors.</p>