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Objective To investigate the effects of different doses of artemether on glycolipid metabolism in C57BL/KsJ-db/db mice. Methods Eight-week-old male C57BL/KsJ-db/db mice were divided into model group (ig given 1% methylcellulose) and artemether 400, 200, 100, 50 groups (ig given 400, 200, 100, 50 mg/kg artemether respectively + 1% methylcellulose), with six mice in each group. Another six male C57BL/KsJ-db/+ mice were selected as the control group. All groups were administered for 4 weeks. The quality of the mice was measured every 2 d; The food intake of the mice was measured every 3 d and the average daily food intake and body mass changes were evaluated; The amount of water in mice was measured every 2 d; The urine volume of the mice was measured every 3 d; After 8 h of fasting, blood was collected from the tail vein, and the fasting blood glucose of the mice was measured by Roche blood glucose meter and matching test paper every 7 d. Mice were assessed for glucose tolerance and sensitivity to insulin by ip glucose tolerance test (IPGTT) and ip insulin tolerance test (IPITT). The serum total cholesterol (TC), triglyceride (TG), and free fatty acid (FFA) levels of the mice were determined by a biochemical kit. The whole liver of mice was weighed and the morphological changes of the pancreas and liver in mice were observed by HE staining. The expression of AMP-activated protein kinase (AMPK), glucose transporter 4 (GLUT-4), and insulin receptor β (IRβ) protein in liver of mice was analyzed by Western blotting. Results Compared with the control group, the food intake, water intake, and urine volume of the model group were significantly increased (P < 0.001). Compared with the model group, each dose of artemether significantly reduced the water intake and urine volume of the mice (P < 0.01, 0.001); Artemether 400, 200, 100 mg/kg can significantly reduce the body weight and food intake in a dose-dependent manner (P < 0.05, 0.01); Artemether 400, 200, 100 mg/kg significantly reduced fasting blood glucose levels in mice, reduced the area under the curve of IPGTT (AUCs), and improved insulin resistance in mice (P < 0.01, 0.001). Compared with the control group, the TC, TG, and FFA levels of mice in the model group were significantly increased (P < 0.05). Compared with the model group, artemether significantly decreased the levels of TC, TG, and FFA in the serum of mice in a dose-dependent manner (P < 0.05), and significantly improved islet vacuolar degeneration and hepatic steatosis in db/db mice; The protein expression of AMPK, GLUT-4, and IRβ in the liver of mice was increased (P < 0.05). With the prolongation of the intervention time, the higher the dose of artemether, the higher the mortality rate and the incidence of adverse reactions in mice. Conclusion Artemether can significantly improve the high-fat state and insulin resistance of diabetic mice. It can treat fatty liver and may up-regulate the expression of GLUT-4 and IRβ protein through the AMPK pathway to exert its effects. It is expected to be used in the treatment of type 2 diabetes mellitus, which is mainly caused by metabolic syndrome. However, higher doses of artemether and longer-term application may lead to more adverse events.
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Studies concerning the association between arsenic exposure and hepatitis B virus (HBV) infection have been lacking.The present study aimed to examine the association between total urinary arsenic (TUA) and infection of HBV.A total of 5186 participants from National Health and Nutrition Examination Survey (NHANES) 2003-2014 were included in the analysis.We used logistic regression to evaluate the association.We defined two measures of TUA.TUA1 was the sum of arsenous acid,arsenicacid,monomethylarsonic acid and dimethylarsenic acid.TUA2 was defined as TUA minus arsenobetaine and arsenocholine.The results showed that the weighted overall prevalence of HBV infection was 6.08%.For NHANES 2003-2014,the medians (interquartile range) of TUA1 and TUA2 were 5.60 μg/L (3.97-8.09 μg/L) and 4.91 μg/L (2.36-9.11 μg/L),respectively.Comparing the highest quartile to the lowest quartile after multivariable adjustment showed that the odds ratios (ORs) and 95% confidence intervals (CIs) for TUA1 and TUA2 were 2.44 (1.40-4.27) and 2.84 (1.60-5.05),respectively.In conclusion,elevated urinary arsenic was associated with the risk of HBV infection.Further studies,especially prospective studies,are needed to confirm the causal relationship between arsenic exposure and HBV infection.
ABSTRACT
Studies concerning the association between arsenic exposure and hepatitis B virus (HBV) infection have been lacking.The present study aimed to examine the association between total urinary arsenic (TUA) and infection of HBV.A total of 5186 participants from National Health and Nutrition Examination Survey (NHANES) 2003-2014 were included in the analysis.We used logistic regression to evaluate the association.We defined two measures of TUA.TUA1 was the sum of arsenous acid,arsenicacid,monomethylarsonic acid and dimethylarsenic acid.TUA2 was defined as TUA minus arsenobetaine and arsenocholine.The results showed that the weighted overall prevalence of HBV infection was 6.08%.For NHANES 2003-2014,the medians (interquartile range) of TUA1 and TUA2 were 5.60 μg/L (3.97-8.09 μg/L) and 4.91 μg/L (2.36-9.11 μg/L),respectively.Comparing the highest quartile to the lowest quartile after multivariable adjustment showed that the odds ratios (ORs) and 95% confidence intervals (CIs) for TUA1 and TUA2 were 2.44 (1.40-4.27) and 2.84 (1.60-5.05),respectively.In conclusion,elevated urinary arsenic was associated with the risk of HBV infection.Further studies,especially prospective studies,are needed to confirm the causal relationship between arsenic exposure and HBV infection.
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<p><b>BACKGROUND</b>Glucolipotoxicity might play an important role in the β cell decompensation stage during the development of obesity-associated type 2 diabetes. Tissue inhibitor of metalloproteinase-1 (TIMP-1) inhibits matrix metalloproteinase (MMP) activity and regulates proliferation and apoptosis of a variety of cell types, including pancreatic β-cells. In the present study, we investigated whether TIMP-1 counteracts glucolipotoxicity in the pancreatic β-cell line INS-1.</p><p><b>METHODS</b>INS-1 cells were incubated in normal or high glucose, with or without palmitate (0.4 mmol/L), in the presence of TIMP-1 or MMP inhibitor GM60001. In some experiments, cells were pretreated with phosphatidylinositol-3 (PI-3) kinase inhibitor, LY294002 or wortmannin. The amount of dead INS-1 cells was determined by HO342 and propidium iodide staining. Akt phosphorylation was evaluated by Western blotting analysis to investigate a possible mechanism of TIMP-1's action.</p><p><b>RESULTS</b>TIMP-1 protected INS-1 cells from glucolipotoxicity independent of MMP inhibition. TIMP-1 stimulated Akt phosphorylation. Inhibition of the PI-3 kinase pathway abolished the survival effect of TIMP-1.</p><p><b>CONCLUSION</b>TIMP-1 may counteract glucolipotoxicity induced β-cell death via a PI-3 kinase pathway.</p>
Subject(s)
Animals , Rats , Cell Line , Glucose , Pharmacology , Insulin-Secreting Cells , Metabolism , Palmitates , Pharmacology , Phosphatidylinositol 3-Kinases , Phosphorylation , Proto-Oncogene Proteins c-akt , Metabolism , Signal Transduction , Tissue Inhibitor of Metalloproteinase-1 , PharmacologyABSTRACT
Objective To observe the therapeutic effect of microencapsulated human retinal pigment epithelial (RPE) cell transplantation into the striatum in a rat model of Parkinson' disease (PD). Methods Cultured RPE cells were microencapsulated by alginate-polylysine-alginate (APA) using a high voltage electrostatic system. The Parkinsonian rats were divided into 4 groups, namely the model group, RPE group, APA group and RPE-APA group, and in the latter 3 groups, RPE cells, empty APA microcapsules and APA-capsulated RPE cells, respectively, were transplanted into the right striatum of the rats via stereotactic surgery. After the transplantation, the changes in apomorphine-induced rotation of the rats were investigated and the striatum DA contents were measured with high-performance liquid chromatography with electrochemical detection. Results TThe rotation of the rats in RPE-APA group was reduced by 51.48%, showing significant difference from that in the model control group 4 weeks after the transplantation (P<0.05). At 8 weeks after the transplantation, apomorphine-induced rotation in the RPE-APA group showed further significant reduction by 54.43% (P<0.05). The changes of DA contents in the striatum after transplantation were consistent with the changes in the rotation behavior of the rats. Conclusions Microencapsulated human RPE cell transplantation is a promising approach for the treatment of PD.
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<p><b>OBJECTIVE</b>To investigated the effect of Escherichia coli (Ec) LPS on alkaline phosphatase (ALP) activity and expression of dentin sialophosphoprotein (DSPP) and osteocalcin (OCN) genes in vitro differentiation human dental pulp cell.</p><p><b>METHODS</b>Odontoblast-like cells were cultured, cells exposed to Ec LPS for 12 h, total RNA was isolated and DSPP, OCN transcripts were examined by real-time RT-PCR. ALP kit were used to assessed the changes of ALP activity.</p><p><b>RESULTS</b>Real-time RT-PCR analysis indicated that Ec LPS induced about a 3.6-fold decrease for DSPP gene and a 1.6-fold decrease for OCN gene in odontoblast-like cells as compared with controls. At the same time, cells treated with LPS could depress ALP activity from (1156.10 +/- 100.60) pmol x h(-1) x ng(-1) down to (884.80 +/- 26.72) pmol x h(-1) x ng(-1).</p><p><b>CONCLUSIONS</b>These results indicate that exposure of odontoblast-like cells to LPS can alter cells function by downregulating cell markers of odontoblastic activity.</p>
Subject(s)
Humans , Alkaline Phosphatase , Metabolism , Cell Differentiation , Cells, Cultured , Dental Pulp , Cell Biology , Escherichia coli , Lipopolysaccharides , Pharmacology , Minerals , Metabolism , Odontoblasts , Osteocalcin , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To investigate the expression of CXCR4 in cultured human dental pulp cells (HDPC) in vitro and the corresponding ligand SDF-1alpha level of HDPC supernatants stimulated by lipopolysaccharide (LPS) and tumor necrosis factor-alpha (TNF-alpha), and to explore the role of SDF-1alpha on the proliferation and the migration of HDPC.</p><p><b>METHODS</b>The expression of CXCR4 in HDPC was detected by immunocytochemistry technique and indirect immunofluorescence technique. The culture supernatants of HDPC were collected after HDPC had been simulated by LPS and TNF-alpha of different concentrations for 48h and then the SDF-1alpha level was assayed by quantitative sandwich ELISA. Meanwhile, the effects of recombinant human SDF-1alpha (rhSDF-1alpha) on the proliferation and the migration of HDPC at different concentrations were observed by MTT and Boyden Chamber Assay.</p><p><b>RESULTS</b>CXCR4 was expressed in cytomembrane of HDPC and SDF-1alpha was secreted into their normal cell supernatants with a concentration of (4513.55 +/- 962.92) ng/L. The secretion of SDF-1alpha was both significantly decreased by stimulation with LPS and TNF-alpha (P < 0.05). In addition, rhSDF-1alpha stimulated the HDPC proliferation at the concentrations of 50, 100, 200 microg/L (P < 0.01) and increased the chemotactic migration of HDPC significantly after 9h's incubation with the concentrations of 50, 100 microg/L (P < 0.05).</p><p><b>CONCLUSIONS</b>SDF-1alpha accelerated the proliferation and the migration of HDPC which expressed CXCR4. SDF-1-CXCR4 axis may play a role in repair of pulp injury.</p>
Subject(s)
Humans , Cell Movement , Cell Proliferation , Cells, Cultured , Chemokine CXCL12 , Metabolism , Dental Pulp , Cell Biology , Metabolism , Receptors, CXCR4 , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To isolate Nanobacteria from dental pulp stone and perform culturing and the identification of Nanobacteria.</p><p><b>METHODS</b>Freshly collected 27 dental pulp stones were divided into nine samples. Each sample contained three dental pulp stones. All samples were used for the isolation and culture of Nanobacteria. The shape and the growth characteristics of the cultured bacteria were observed. Nanobacteria were identified by von Kossa staining, immunohistochemical staining and indirect immunofluorescence staining, double staining including Hoechst staining and von Kossa staining.</p><p><b>RESULTS</b>The characteristics growth and morphology of the bacteria detected in seven samples were similar to Nanobacteria. von Kossa staining, immunohistochemical staining, indirect immunofluorescent staining were positive for Nanobacteria. In double staining method, Hoechst staining of the samples was negative for Nanobacteria, but von Kossa staining was positive. Hoechst staining of the dental pulp cells was positive. No Nanobacteria was found in the other two samples.</p><p><b>CONCLUSIONS</b>The bacteria isolated from dental pulp stone in this study was similar to Nanobacteria in terms of growth rate, morphology and staining properties. These unusual properties of the bacteria may play an important role in the formation of pulp stone.</p>