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AIM: To explore whether necroptosis contributes to the high glucose (HG)-induced damage in hu-man umbilical vein endothelial cells (HUVECs).METHODS: The protein levels of receptor-interacting protein 3 (RIP3) and cleaved caspase-3 were detected by Western blot.The intracellular levels of reactive oxygen species (ROS) were deter-mined by DCFH-DA staining followed by photofluorography.Mitochondrial membrane potential (MMP) was measured by rhodamine 123 staining followed by photofluorography.RESULTS: Treatment of HUVECs with HG at different concentra-tions (10, 20 and 40 mmol/L glucose) for 24 h gradually enhanced the expression levels of RIP3.Treatment of HUVECs with HG (40 mmol/L glucose) for different time (3 h, 6 h, 9 h, 12 h and 24 h) also up-regulated the expression levels of RIP3, peaking at 9 h.Pretreatment of HUVECs with 20 μmol/L Z-VAD-FMK (an inhibitor of caspase) for 30 min before exposure to HG enhanced the expression level of RIP3.Pretreatment of HUVECs with 100 μmol/L necrostatin-1 (an inhi-bitor of necroptosis) for 1 h before exposure to HG alleviated the HG-induced injuries, such as a decrease in cell viability, an increase in ROS generation and dissipation of MMP, but up-regulated the protein level of cleaved caspase-3.CON- CLUSION: Necroptosis mediates HG-induced injury in HUVECs.There is a negative interacting between necroptosis and apoptosis.
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AIM: To investigate whether Janus kinase/signal transducer and activator of transcription ( JAK/STAT) signaling pathway mediates high glucose-induced damage in human umbilical vein endothelial cells ( HUVECs ) . METHODS:The cell viability was examined by CCK-8 assay.The expression levels of JAK2, STAT3, caspase-9 and en-dothelial nitric oxide synthase ( eNOS) were detected by Western blot .The intracellular levels of reactive oxygen species ( ROS) were tested by DCFH-DA staining followed by photofluorography .Mitochondrial membrane potential ( MMP) was measured by rhodamine 123 staining followed by photofluorography .RESULTS:Treatment of HUVECs with high glucose (40 mmol/L glucose) for 6~12 h enhanced the protein level of phosphorylated JAK 2, peaking at 9 h.Treatment of the cells with high glucose for 6~12 h also increased the protein level of p-STAT3 with the peak value at 12 h.Pretreatment with the inhibitor of JAK/STAT pathway AG490 for 1 h before exposure of the HUVECs to high glucose significantly inhibi-ted the high glucose -induced injury , as evidenced by an increase in the cell viability , decreases in the expression of caspase-9 and the intracellular ROS production , and increases in MMP and the expression of eNOS .CONCLUSION:JAK/STAT signaling pathway is involved in the high glucose-induced damage in HUVECs .
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AIM: To explore whether strontium ranelate ( Sr ) promotes osteogenic differentiation of rat bone mesenchymal stem cells (BMSCs) through the Hedgehog/Gli1 signaling pathway.METHODS:BMSCs were isolated from 4-week-old rats by adherent culture and induced to differentiate into osteoblasts .According to the experimental purposes , the cells were exposed to different concentrations of Sr , cyclopamine ( Cy, an inhibitor of Hedgehog receptor ) or Gli1-siR-NA.The expression of Gli1 and Runx2 in the cells was detected by Western blotting .The activity of alkaline phosphatase ( ALP) was measured by the method of colorimetry , and the mineralized nodules were observed under microscope with aliz-arin red staining .RESULTS:Exposure to Sr at concentrations of 0.1 to 5 mmol/L for 7 d markedly increased the expres-sion of Gli1 in the BMSCs , and the increase in Gli1 expression was the most obvious following Sr exposure at concentration of 3 mmol/L.Cy at concentration of 10 μmol/L inhibited Sr-induced up-regulation of Gli1 expression.Transfection of the BMSCs with Gli1-siRNA not only obviously inhibited Sr-induced up-regulation of Gli1 and Runx2 ( a downstream protein of Gli1) expression, but also antagonized Sr-induced enhancement of ALP activity and the formation of mineralized nodules . CONCLUSION:The Hedgehog/Gli1 pathway is involved in Sr-induced osteogenic differentiation of rat BMSCs .
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<p><b>OBJECTIVE</b>To observe the therapeutic effect and safety of vildagliptin combined with insulin aspart injection in elderly patients with type 2 diabetes.</p><p><b>METHODS</b>Sixty-six elderly patients with type 2 diabetes who had poor blood glucose control with insulin aspart injection were divided into two groups to have additional Vildagliptin (50 mg, twice daily, n=36, observation group) or Acarbose (50 mg, three times a day, n=30, control group). Blood glucose (including FBG and 2hPG), HbA1C, fasting c-peptide, postprandial c-peptide, BMI and GFR were observed after 12 weeks.</p><p><b>RESULTS</b>In the observation group, FBG, 2hPG and HbA1C decreased significantly (P<0.05), fasting and postprandial c-peptide increased (P<0.05), and BMI and GFR showed no obvious changes (P>0.05). In the control group, 2hPG and HbA1C were significant lowered (P<0.05) but FBG, fasting and postprandial c-peptide, BMI or GFR showed no changes (P>0.05). Compared with those in the control group, FBG in the observation group showed a significant reduction (P<0.05), but no significant differences were found in 2hPG, HbA1C, BMI or GFR (P>0.05). No hypoglycemia occurred in the two groups during the treatment.</p><p><b>CONCLUSION</b>Vildagliptin with insulin aapart injection has equivalent effect with Acarbose combined with insulin aspart injection in decreasing 2hPG and HbA1C without increasing the body weight or the risk to hypoglycemia or causing lowered GFR. Vildagliptin has better effect in decreasing FBG and improving the function of the islet cells.</p>
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Idoso , Humanos , Adamantano , Usos Terapêuticos , Glicemia , Diabetes Mellitus Tipo 2 , Tratamento Farmacológico , Hemoglobinas Glicadas , Metabolismo , Hipoglicemiantes , Usos Terapêuticos , Injeções , Insulina Aspart , Usos Terapêuticos , Nitrilas , Usos Terapêuticos , Pirrolidinas , Usos TerapêuticosRESUMO
<p><b>OBJECTIVE</b>To observe the effect of zoledronic acid on bone mineral density (BMD) and bone metabolic markers in elderly patients with primary osteoporosis.</p><p><b>METHODS</b>Forty-eight elderly patients with osteoporosis were randomly assigned to zoledronic acid group (n=23) to receive treatment with 5 mg zoledronic acid once a year and the control group (n=25). In both groups, the patients were given Vitamin D3 and caltrate on a daily basis for a year. The bone mineral density (BMD) and bone metabolic markers were observed after the treatment.</p><p><b>RESULTS</b>Compared with the control group, zoledronic acid group had significantly higher L1-4, neck, Inter and Ward's BMD (P<0.05) with reduced B-NTX (P<0.05). The N-MID and CT showed no significant differences between the two groups (P<0.05).</p><p><b>CONCLUSION</b>Zoledronic acid administration once a year can increase BMD and lower the serum bone turnover metabolism, and can be used in the treatment of primary osteoporosis in elderly patients.</p>
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Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Densidade Óssea , Conservadores da Densidade Óssea , Usos Terapêuticos , Difosfonatos , Usos Terapêuticos , Imidazóis , Usos Terapêuticos , Osteoporose , Tratamento Farmacológico , Metabolismo , Resultado do TratamentoRESUMO
0.05); while in the 12th month, BMD markedly increased in group A and decreased in group B (P 0.05) but ?-CTX level increased after treatment (P
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Objective To investigate the relationship between Homocysteine (Hcy) and incipient diabetic nephropathy in type 2 diabetes mellitus (DM).Methods The plasma Hcy level was measured by high performance liquid chromatography with fluorescence detection in 67 patients with type 2 DM and 47 control persons,the plasma thrombomodulin(sTM),folate and vitamin B 12 were determined simultaneously.Results The plasma Hcy level was higher in type 2 DM patients than that in control subjects (15.27?6.04?mol/L vs 12.10?1.86?mol/L, P
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0.05). CONCLUSION: Genotype of VDR is related to BMD, but there is no enough evidence to support genotype of VDR as a genetic marker in predicting the risk of developing osteoporosis in Guangzhou postmenopausal women.