Effect of metformin and rosiglitazone in non-obese polycystic ovary syndrome women with insulin resistance / 中华妇产科杂志

Objective:To investigate effects of metformin and rosiglitazone in non-obese polycystic ovary syndrome (PCOS) women with insulin resistance.Methods:Totally 200 non-obese PCOS women with insulin resistance in West China Second Hospital of Sichuan University were enrolled into this study from Sep. 2013 to Jun. 2016, and were randomly divided into two treatment groups: metformin group (1 500 mg/d) and rosiglitazone group (4 mg/d). The treatment lasted for 6 months. Their clinical and biochemical parameters were collected and compared.Results:In both groups, menstrual cycles [metformin group (37±4) days, rosiglitazone group (35±4) days] were shorter after treatment for 6 months (both P<0.01). After treatment for 6 months, body mass index [metformin group (21.6±1.6) kg/m 2, rosiglitazone group (21.7±1.7) kg/m 2] decreased in both groups (both P<0.01); decreased LH/FSH ratio (metformin group 1.67±0.80, rosiglitazone group 1.70±0.83) was also observed (both P<0.05). After treatment for 6 months, fasting insulin level [metformin group (13.5±5.1) mU/L, rosiglitazone group (12.7±5.6) mU/L] and homeostasis model assessment-insulin resistance index (metformin group 3.0±1.2, rosiglitazone group 2.8±1.2) were decreased in both groups (all P<0.01). Conclusions:For non-obese PCOS insulin resistance patients, screening of anthropometric and metabolic parameters is necessary. For PCOS with insulin resistance, lifestyle plus insulin sensitizers such as metformin could improve their clinical symptoms, correct the biochemical and metabolic dysfunction.

Proliferation and migration of endothelial progenitor cells promoted by bone marrow mesenchymal stem cells conditioned medium with rosiglitazone / 中国组织工程研究

BACKGROUND: Studies have shown that mesenchymal stem cells can participate in the repair of wound injury caused by diabetes, but the high glucose environment obviously inhibits the function of mesenchymal stem cells and the effect of transplantation. OBJECTIVE: To observe the effect of conditioned medium of bone marrow mesenchymal stem cells intervened by rosiglitazone on the proliferation and migration of endothelial progenitor cells in high glucose environment. METHODS: (1) The bone marrow mesenchymal stem cells from the logarithmic growth period were cultured in three groups. The normal group was cultured with alpha-MEM medium containing 10% fetal bovine serum. The high glucose group was cultured with alpha-MEM medium containing 10% fetal bovine serum and 25 mmol/L glucose. The rosiglitazone group was cultured with alpha-MEM medium containing 10% fetal bovine serum, 25 mmol/L glucose and 10 μmol/L rosiglitazone. After 48 hours of culture, the culture supernatant was extracted as conditioned medium. The levels of vascular endothelial growth factor and matrix cell derived factor 1 in conditioned medium were detected by ELISA. (2) The endothelial progenitor cells from the logarithmic growth period were divided into three groups. The control group was cultured with the EGM-2 MV medium containing 10% fetal bovine serum. The model group was cultured with the EGM-2 MV medium containing 10% fetal bovine serum, 30 mmol/L glucose and conditioned medium of the high glucose group. The experimental group was cultured with EGM-2 MV medium containing 10% fetal bovine serum, 30 mmol/L glucose and conditioned medium of the rosiglitazone group. After 24 hours of culture, the ability of cell proliferation and migration was detected. RESULTS AND CONCLUSION: (1) The levels of vascular endothelial growth factor and matrix cell derived factor 1 in the conditioned medium of high glucose group were significantly lower than that of the normal group (P < 0.05). The levels of vascular endothelial growth factor and matrix cell derived factor 1 in the conditioned medium of the rosiglitazone group were significantly higher than in the high glucose group (P < 0.05). (2) The proliferation and migration ability of endothelial progenitor cells in the model group was lower than that in the control group (P < 0.05). The proliferation and migration ability of endothelial progenitor cells in the experimental group was higher than that in the model group (P < 0.05). (3) It is suggested that the conditioned medium of rosiglitazone intervened bone marrow mesenchymal stem cells can promote the proliferation and migration of endothelial progenitor cells.

Exercises regulate bone marrow adipocytes derived from mesenchymal stem cells: Roles and prospects / 中国组织工程研究

BACKGROUND: Bone marrow adipocytes are derived from mesenchymal stem cells. It has been found that mesenchymal stem cells can also differentiate into osteoblasts, chondrocytes and myocytes. Current results show that marrow adipose tissue could negatively regulate the osteogenesis process because mesenchymal stem cells can differentiate into adipocytes in priority. Exercise promotes bone formation and plays an important role in preventing fractures. Exercise, diet, and rosiglitazone are shown to affect the generation of marrow adipose tissue, but the relationship between them is not clear. OBJECTIVE: To summarize the effects of exercise, diet and rosiglitazone on marrow adipose tissue and their relationship with bone mineral density. METHODS: Studies related to exercise regulating marrow adipose tissue published from January 1999 to June 2019 in CNKI, WanFang and PubMed databases were retrieved. The search terms were “marrow adipose tissue, exercise, rosiglitazone, high fat-diet, mesenchymal stem cell” in English and Chinese, respectively. Finally 66 eligible articles were enrolled for analysis. RESULTS AND CONCLUSION: Based on the current research results, exercise can affect the regulation of high-fat diet and rosiglitazone on the formation of bone marrow adipose tissue. Exercise intervention can inhibit the differentiation of mesenchymal stem cells into marrow adipose tissue. In the process of exercise intervention on marrow adipose tissue, there are many other ways participating in the regulation of fat synthesis, lipid absorption, bone metabolism, bone marrow hematopoietic function. Therefore, exercise intervention has an important part in regulating the above metabolic processes. In the future, the specific mechanism of exercise intervention in bone marrow adipose tissue should be further explored to make exercises become an important measure for regulating the above metabolic processes.

Pharmacoeconomic Evaluation of Rosiglitazone Sodium and Metformin in the Treatment of Type 2 Diabetes Mell i- tus / 中国药房

OBJECTIVE：To provid e reference for safe ，effective and economical medication scheme for type 2 diabetes mellitus（T2DM）. METHODS ：Markov model was established for rosiglitazone sodium and metformin in the treatment of T 2DM. According to the development characteristics of T 2DM，the development of T 2DM was simulated by the dynamic changes of event-free，complications and deaths of T 2DM. The long-term cost and effect of rosiglitazone sodium and metformin in the treatment of T 2DM were obtained by regression analysis and queue simulation analysis. QALYs was used as a health output indicator，and t he superiority and inferiority of different schemes were judged by the ICER value ，and in our study ICER value was WTP（12 000 yuan per year ）of diabetics. The sensitivity of cost ，utility and discount was analyzed to check the stability of the analysis results. RESULTS ：Cost-effectiveness analysis of Markov model showed that the cumulative cost and health effectiveness of rosiglitazone sodium therapy were 25 164.00 yuan and 7.50 QALYs，while 17 773.36 yuan and 7.36 QALYs for metformin ； ICER of rosiglitazone sodium relative to metformin was 50 983.08 yuan/QALYs，which was greater than WTP ，so the metformin treatment was an advantageous scheme. Sensitivity analysis showed that health utility value and discount rate of diabetes mellitus greatly influenced analysis results of the model ，but advantage plan had not changed within the sensiitivity analysis range seted in this study. CONCLUSIONS ：For T 2DM，metformin is more cost-effective than rosiglitazone sodium.

Rosiglitazone promotes phosphorylation of AMPK protein and improves insulin resistance in db/db mice / 上海预防医学

Objective To observe the effect of rosiglitazone on the protein expression of AMPK and GLUT4 in peripheral tissue (liver, skeletal muscle and fat) of type 2 diabetic db/db mice and to prove that rosiglitazone can regulate the glucose metabolism in db/db mice partly through the AMPK pathway. Methods db/db mice were randomly divided into model group and rosiglitazone group according to their blood glucose.The db/m mice were normal control group.After 4 weeks of administration, fasting blood glucose was detected in each group.Western blot was used to detect the contents of AMPK, p-AMPK and GLUT4 in liver, skeletal muscle and adipose tissue. Results (1) Rosiglitazone significantly reduced the fasting blood glucose of db/db mice; (2)Rosiglitazone increased the level of AMPK phosphorylation in the liver, skeletal muscle and adipose tissue of db/db mice, and increased the content of GLUT4 protein in skeletal muscle and adipose tissue. Conclusion Rosiglitazone can increase the phosphorylation of AMPK and the expression of GLUT4 protein in the liver, muscle and fat tissue of db/db mice, and promote the uptake and utilization of glucose in peripheral tissue, suggesting that it can regulate glucose metabolism in db/db mice partly through the AMPK pathway.

Rosiglitazone improves ovarian dysfunction of rats with chronic low-grade inflammation induced by lipopolysaccharide / 第二军医大学学报

Objective: To detect the expression of peroxisome proliferator-activated receptor (PPAR) in ovarian tissues of rats with chronic low-grade inflammation, and to explore the effect of PPAR-γ agonist rosiglitazone on ovarian dysfunction induced by chronic low-grade inflammation. Methods: A chronic low-grade inflammation model of rats was established by intraperitoneal injection of lipopolysaccharide (LPS). Two hundred rats were randomly assigned to control group (NS group) and chronic low-grade inflammation group (LPS group), and the rats were intraperitoneally injected with normal saline and LPS, respectively. The ovarian function of rats was assessed by detecting the serum levels of estradiol (E2), follicle stimulating hormone (FSH), luteinizing hormone (LH), and anti-Müllerian hormone (AMH) during different stages of the estrus cycle (proestrus, estrus, metestrus and diestrus). The protein expression levels of PPAR-α, PPAR-γ and PPAR-γ in ovarian tissues were detected using Western blotting. Eighty rats of each group were randomly divided into two subgroups, which were administered intragastrically by normal saline and rosiglitazone, respectively. Fourteen days after intragastric administration, the levels of proinflammatory cytokines, including interleukin (IL)-1β, IL-6 and tumor necrosis factor α (TNF-α), in ovarian tissues and ovarian function of rats in each subgroup were observed during different stages of the estrus cycle. Results: Compared with the NS group, during different stages of the estrus cycle, the serum levels of E2 and AMH of rats in the LPS group were significantly decreased (all P < 0.05), while the serum levels of FSH and LH were significantly increased (all P < 0.05). During different stages of the estrus cycle, the expression levels of PPAR-γ in ovarian tissues were significantly decreased in the LPS group compared with the NS group (all P < 0.05), while the expression levels of PPAR-α and PPAR-δ were not significantly different between the two groups (all P < 0.05). Compared with the intraperitoneal injection of LPS intragastric administration of normal saline subgroup, during different stages of the estrus cycle, the expression levels IL-1β, IL-6 and TNF-α in ovarian tissues of rats were significantly decreased in the intraperitoneal injection of LPS intragastric administration of rosiglitazone subgroup (all P < 0.05), the serum levels of E2 and AMH were significantly increased (all P < 0.05), and the serum levels of FSH and LH were significantly decreased (all P < 0.05). Conclusion: PPAR-γ agonist rosiglitazone can attenuate LPS-induced chronic low-grade inflammatory and improve ovarian function in rats.

Changes in EGFR, FOXA2 and MUC5AC expression in respiratory syncytial virus-infected human bronchial epithelium cells and effects of rosiglitazone intervention / 中华微生物学和免疫学杂志

Objective To investigate the mechanism of epidermal growth factor receptor-forkhead transcription factor A2 (EGFR-FOXA2) pathway-involved high secretion of mucus in human bronchial epitheli-um (HBE) cells after respiratory syncytial virus (RSV) infection and to evaluate the effects of intervention using agonist ( rosiglitazone ) and antagonist ( GW9662 ) of peroxidase proliferation activated receptor γ( PPARγ) and EGFR inhibitor ( AG1478 ) . Methods HBE cells were randomly divided into six groups: A group ( AG1478+RSV) , B group ( rosiglitazone+RSV) , C group ( GW9662+RSV) , D group ( RSV) , E group (0. 1％ dimethyl sulfoxide DMSO) and F group (HBE cell control group). Two hours before RSV infection, A, B and C groups were respectively treated with 10 μmol/L of AG1478, rosiglitazone and GW9662. Expression of EGFR, PPARγ and FOXA2 at mRNA level in each group was detected by real-time fluorescence quantitative RT-PCR 12 h, 24 h and 48 h after HBE cells were infected with or without RSV. Expression of phosphorylated-EGFR ( p-EGFR) and EGFR at protein level was detected by Western blot. ELISA was performed to measure the expression of mucin-5AC (MUC5AC). Results Compared with F group, EGFR expression at mRNA lev-el, p-EGFR/EGFR protein ratio and MUC5AC expression at protein level were increased in a time-dependent manner in A, B, C and D groups at 12 h, 24 h and 48 h. Compared with group F, the expression of PPARγat mRNA level in A, B, and D groups increased at each time point. Moreover, PPARγ expression gradually in-creased over time in A and B groups, reaching the peaks at 48 h, but was in decline in D group. Expression of FOXA2 at mRNA level in RSV-infected HBE cells was declined at each time point compared with that in group F, especially in D group. Compared with group D, A and B groups showed significantly decreased EGFR ex-pression at mRNA level, p-EGFR/EGFR protein ratio and MUC5AC expression at protein level, but markedly increased FOXA2 expression at mRNA level. Conclusions RSV infection increased the expression of MUC5AC at protein level in HBE cells. PPARγand EGFR-FOXA2 signaling pathways were involved in the hypersecretion of airway mucus during RSV infection.

Effect of a novel PPARγ partial agonist CMHX008 on hyperglycemia-induced fibrogenesis in renal tubular epithelial HK-2 cells and its mechanism / 中国药理学通报

Aim To investigate the effect of CMHX008, a novel peroxisome proliferator-activated receptor γ (PPARγ) partial agonist, on fibrogenic pathways and its potential mechanism in renal tubular epithelial HK-2 cells in comparison with rosiglitazone. Methods HK-2 cells were cultured with 30 mmol . L 1 D-(+)-glucose, and then treated with rosiglitazone and CMHX008. Cell counting kit-8(CCK-8) was used to detect cell viability; immunoblotting was used to detect protein expression fibrogenic markers and p-PPARγ(ser273) in HK-2 cells; quantitative real time PCR (qRT-PCR) was used to detect fibrosis-related mRNA levels; wound healing assay and transwell assay were used to detect the migration and invasion ability of HK-2 cells. Results CCK-8 analysis showed that 3 (imol . L 1 rosiglitazone and 3 μmol . L 1 CMHX008 had no obvious cytotoxicity to HK-2 cells; immunoblotting revealed that rosiglitazone and CMHX008 could reverse the up-regulation of p-PPARγ(ser273), reduce transforming growth factor β1 (TGF-β1) and α-smooth muscle actin(α-SMA) protein levels, and up-regulate E-cadherin protein expression levels in HK-2 cells in high glucose conditions; wound healing assay and transwell assay showed that rosiglitazone and CMHX008 could inhibit the increase of migration and invasion ability of hyperglycemia-cultured HK-2 cells. Conclusions The novel PPAR7 agonist CMHX008 can improve hyperglycemia-induced renal tubular fibrosis, which may be possibly related to the inhibition of p-PPARγ(Ser273) phosphorylation.

Effect of rosiglitazone on motor function recovery of hind limbs in rats with spinal cord injury / 中华创伤杂志

Objective To investigate the effect of the peroxide proliferator-activated receptorgamma (PPAR-γ) agonist rosiglitazone on the motor function recovery of hind limbs in rats with spinal cord injury.Methods Sixty-eight female SD rats were used to establish spinal cord injury model by modified Allen method.(1) Eight rats were randomly divided into negative control group and rosiglitazone group with four rats in each group.The expression of aspartate proteolytic enzyme-1 (caspase-1) in spinal cord of rats 7 days after injury was detected by immunohistochemical staining.(2) Forty-eight rats were randomly divided into negative control group,rosiglitazone group,rosiglitazone + Clostridium chitosans group [nuclear factor kappa B (NF-kappa B) activator],rosiglitazone + monosodium urate group [oligomerization domain-like receptor protein 3 (NLRP3) antagonist],with 12 rats in each group.BBB scores of hindlimb motor function were assessed at 1,3,14,21 and 28 days after injury in each group.The expression of interleukin-1 β (IL-1 β) and tumor necrosis factor-α (TNF-α) in each group was detected by ELISA at 28 days after injury.Microglia were isolated from the spinal cord of 12 rats and cultured for 7 days.They were randomly divided into the following five groups:(1) negative control group:no drug treatment;(2) rosiglitazone group:1 micromol/L rosiglitazone treatment;(3) rosiglitazone + Clostridium chitin group:1 micromol/L rosiglitazone + 20 micromol/L Clostridium chitosporin treatment;(4) Clostridium chitosan treatment Mycoplasma group:20 μ mol/L shell Clostridium treatment;(5) Clostridium chitosanin + MCC950 group [(NLRP3) antagonist]:20 μmol/L Clostridium chitosanin + 100 nmol/L MCC950;Western blot was used to detect the expressions of caspase-1,NF-kappa B and NLRP3 in microglia cells;ELISA was used to detect the expressions of IL-1β and TNF-α in the supernatant of microglia culture.Results Compared with negative control group,caspase-1 expression was decreased in rosiglitazone group in spinal cord injury area [gray matter area:5.1 ± 0.8∶6.9 ± 1.1;white matter area:5.6 ± 0.9 ∶ 7.5 ± 1.1] (P ＜ 0.05).At 28 days after operation,the rosiglitazone group had the highest BBB score [(14.7 ± 1.6) points],and the BBB score of rosiglitazone + Clostridium chitosans group (10.5 ± 2.1) points was superior to that of rosiglitazone + monosodium urate group [(7.2 ± 1.3)points,P ＜ 0.05].The expressions of IL-1β and TNF-α in rosiglitazone + monosodium uric acid group were lower than those in other groups at 28 days after injury (P ＜ 0.05).In vitro,the expressions of caspase-1,NF-kappa B,IL-1β and TNF-α in rosiglitazone group were lower than those in negative control group (P ＜ O.05).The expressions of caspase-1,NLRP3,IL-1β and TNF-α in rosiglitazone + Clostridium chitosani group were higher than those in rosiglitazone group,(P ＜ 0.05).The expressions of caspase-1 and IL-1β were higher than those in Clostridium chitosani + MCC950 group (P ＜0.05),but there was no significant difference in the expression of TNF-α between the two groups (P ＞0.05).Conclusion Rosiglitazone can promote the recovery of hind limb motor function in rats with spinal cord injury by inhibiting the expression of NF-kappa B,thereby reducing the activation of NLRP3 inflammatory bodies in microglia and ultimately inhibiting the occurrence of inflammation.

Simultaneous Determination of Carbamazepine, Venlafaxine, Rosiglitazone and Nifedipine in Human Plasma by UPLC-MS/MS / 中国药房

OBJECTIVE:To develop a method for simultaneous determination of carbamazepine,venlafaxine,rosiglitazone and nifedipine in human plasma.METHODS:UPLC-MS/MS method was adopted to determine plasma sample after precipitated with methanol (containing 0.1％ formic acid) using pioglitazone hydrochloride as internal standard.The determination was performed on Waters ACQUITY UPLC HSS C18 column with mobile phase consisted of aqueous solution containing 0.01％ formic acid-methanol containing 0.01％ formic acid (gradient elution) at the flow rate of 0.3 mL/min.The column temperature was 50 ℃,and sample size was 5 μL.ESI was used for positive ion scanning by multi reaction monitoring mode.The ion pairs for quantitative analysis were m/z 237.00 to 194.05 (carbamazepine),m/z 278.20 to 58.10 (venlafaxine),m/z 358.08 to 135.04 (rosiglitazone),m/z 347.15 to 315.17 (nifedipine),m/z 357.09 to 134.06 (internal standard).RESULTS:The liner ranges of carbamazepine,venlafaxine hydrochloride,rosiglitazone hydrochloride and nifedipine were 2.00-2 000.00 (r=0.995 9,n=5),2.12-2 120.00(r=0.990 5,n=5),2.00-2 000.00(r=0.991 5,n=5) and 2.04-1 020.00(r=0.991 0,n=5) ng/mL;the minimum detection limits were 0.200,0.106,0.100,1.020 ng/mL,respectively.RSDs of inter-day and intra-day were less than 15％.The absolute values of RE were less than 15％.The extraction recoveries were 65.66％-96.36％ (RSD％ ＜15％,n=5),and matrix effects ranged 80.99％-114.33％.The plasma concentrations of carbamazepine in 2 epileptic patients were (1 500.41 ± 169.11),(1 159.01 ±59.24) ng/mL(RSD were 11.27％,5.60％,n=3).The plasma concentrations of nifedipine in 2 hypertensive patients were (14.68 ±1.92),(21.18 ± 3.59)ng/mL (RSD were 16.98％,13.10％,n=3).CONCLUSIONS:The method is simple,specific,sensitive,accurate and suitable for the monitoring of plasma concentration and pharmacodynamic study of above drugs.

The Regulatory Effect of PPARγ in the Apoptosis against Renal Cell Carcinoma / 昆明医科大学学报

Objective To explore the effects of PPARγ agonist rosiglitazone and inhibitor T0070907 on apoptosis and anti-tumor in renal carcinoma A498 cells.Methods A498 cells were divided into three groups and PBS, rosiglitazone (50 μmol/L) and T0070907 50 (μmol/L) were added respectively of 24 h incubation completely. each group of cell proliferation was determined by MTT method and Western Blot analysis and RT-qPCR were applied to detect the expression level of BAX, Caspase 3, Cyt C and Bcl-2. A498 cell morphological changes were observed under light microscope and fluorescence microscope. Results MTT experiment results showed that rosiglitazone and T0070907 could significantly inhibit A498 cell proliferation rate (P＜0.05), increased the protein and mRNA expression levels of Caspase 3, Cyt C and Bax in A498 cell, and decreased the protein and mRNA expression levels of Bcl-2 (P＜0.05); Microscopic observation and Hochest staining also found that rosiglitazone and T0070907 could promote apoptosis of A498 cells. Conclusion Rosiglitazone and T0070907 can inhibit the proliferation of renal cell carcinoma A498 cells and induce apoptosis. The anti-tumor mechanism may be related to PPARγ mediation.

Structure-based design, synthesis, and biological evaluation of novel pyrimidinone derivatives as PDE9 inhibitors

The pathological processes of Alzheimer's disease and type 2 diabetes mellitus have been demonstrated to be linked together. Both PDE9 inhibitors and PPAR agonists such as rosiglitazone exhibited remarkable preclinical and clinical treatment effects for these two diseases. In this study, a series of PDE9 inhibitors combining the pharmacophore of rosiglitazone were discovered. All the compounds possessed remarkable affinities towards PDE9 and four of them have the IC values <5 nmol/L. In addition, these four compounds showed low cell toxicity in human SH-SY5Y neuroblastoma cells. Compound , the most effective one, gave the IC of 1.1 nmol/L towards PDE9, which is significantly better than the reference compounds PF-04447943 and BAY 73-6691. The analysis of putative binding patterns and binding free energy of the designed compounds with PDE9 may explain the structure-activity relationships and provide evidence for further structural modifications.

Rosiglitazone role in the expression of KLF6 caco-2 colon cancer cells / Rol de rosiglitazona en la expresión de KLF6 en células caco-2 de cáncer de colon

Kruppel-like factor 6 (KLF6) is a member of the family of Kruppel transcription factors, this plays an important role in the regulation of cell growth, differentiation and angiogenesis. Rosiglitazone is a PPARy agonist drug, its antitumor effect has been described in models of breast and colon cancer. The aim of this study is to evaluate the level of expression of KLF6 in Caco2 cells treated with Avandia. For this a Immunofluorescence was performed, the Caco2 cells were cultured and treated with Rosiglitazone, another group was treated with Rosiglitazone and GW-9662, inhibitor for Immunofluorescence an anti-KLF6 antibody and a secondary antibody coupled to Alexa-488 was used . Cells were observed in a fluorescence microscope and images were processed. The results show that KLF6 is expressed in the cytoplasm of cells Caco2. Compared to treatment with Avandia, KLF6 increases its expression in the cytoplasm. When cells were treated with GW-9662 inhibitor, an expression of KLF6 in the nucleus was observed. KLF6 expression in the cytoplasm of cells Caco2, could be explained by the knowledge of splicing variants SV1 and SV2, these abnormally accumulate in the cytoplasm and promotes cell growth. It is concluded that in untreated Caco 2 cells, KLF6 is expressed in the cytoplasm. Compared to treatment with Rosiglitazone, KLF6 upregulated in the cytoplasm and compared to treatment with the inhibitor, KLF6 is expressed in the nucleus of Caco 2 cells.

Kruppel-like factor 6 (KLF6) is a member of the family of Kruppel transcription factors, this plays an important role in the regulation of cell growth, differentiation and angiogenesis. Rosiglitazone is a PPARy agonist drug, its antitumor effect has been described in models of breast and colon cancer. The aim of this study is to evaluate the level of expression of KLF6 in Caco2 cells treated with Avandia. For this a Immunofluorescence was performed, the Caco2 cells were cultured and treated with Rosiglitazone, another group was treated with Rosiglitazone and GW-9662, inhibitor for Immunofluorescence an anti-KLF6 antibody and a secondary antibody coupled to Alexa-488 was used . Cells were observed in a fluorescence microscope and images were processed. The results show that KLF6 is expressed in the cytoplasm of cells Caco2. Compared to treatment with Avandia, KLF6 increases its expression in the cytoplasm. When cells were treated with GW-9662 inhibitor, an expression of KLF6 in the nucleus was observed. KLF6 expression in the cytoplasm of cells Caco2, could be explained by the knowledge of splicing variants SV1 and SV2, these abnormally accumulate in the cytoplasm and promotes cell growth. It is concluded that in untreated Caco 2 cells, KLF6 is expressed in the cytoplasm. Compared to treatment with Rosiglitazone, KLF6 upregulated in the cytoplasm and compared to treatment with the inhibitor, KLF6 is expressed in the nucleus of Caco 2 cells.

Rosiglitazone alleviates vascular endothelial dysfunction in type 2 diabetic rats / 基础医学与临床

To observe metabolic abnormalities, histology changes and eNOS expression of aorta in type 2 diabetes rat.And to observe intervention effect of rosiglitazone.Methods 80 male Wistar rats were randomized to control group, high diet group, diabetes group, and rosiglitazone treatment group (diabetes plus rosiglitazone treatment).Type 2 diabetes models were developed and rosiglization group was treated with rosiglitazone .Six weeks and twelve weeks after treatment with rosiglitazone, blood glucose, endothlin and nitric oxide were tested.Histology changes of aorta in different groups were observed under microscopy .Meanwhile the protein and mRNA expression of eNOS in aorta were examined.Results 1)Compared with control group, ET in high fat diet group, diabetes group and rosiglitazone group increased significantly , and the level of NO decreased significantly at 6 week and 12 week.At 12 week, ET in diabetes group increased, and NO decreased significantly than that of high fat diet group and rosiglitazone group.2)Histology changes were observed in high fat diet group , diabetes group and rosiglitazone group at 12 week.3)Compared with control group, protein and mRNA expression in high fat diet group , diabetes group and rosiglitazone group were down regulated at 6 week and 12 week.And protein expression in diabetes group was down regulated than that in rosiglitazone group .Conclusions Rosiglization can ease the endothelial dysfunction in type 2 diabetes rat.

Clinical Observation of Insulin Glargine for Type 2 Diabetes Mellitus Patients with Poor Control by Rosigli-tazone and Metformin / 中国药房

OBJECTIVE:To observe the effects of insulin glargine in type 2 diabetes mellitus patients with poor glucose con-trol by rosiglitazone and metformin. METHODS:A total of 90 patients with type 2 diabetes mellitus with poor glucose control by rosiglitazone and metformin admitted to our hospital from Aug. 2013 to Dec. 2015 were divided into control group and observation group according to random number table,with 45 cases in each group. Control group was given Acarbose tablets 50 mg orally be-fore meal,tid,with maximal dose of 300 mg/d. Observation group was given Insulin glargine injection subcutaneously,qd,with initial dose of 0.15 u/kg,adjusted according to blood glucose monitoring,with maximal dose of 40 u/d. Both group were treated for 24 weeks. The levels of fasting blood glucose,2 h postprandial blood glucose,HbA1c,fasting C peptide and 2 h postprandial C peptide were compared between 2 groups before and after treatment. The time of blood glucose reaching target and the occur-rence of adverse events were recorded,and the incidence of adverse events was calculated. RESULTS:Before treatment,there was no statistical significance in above indexes between 2 groups(P>0.05). After treatment,The levels of fasting blood glucose and 2 h postprandial blood glucose in 2 groups were significantly lower than before treatment,and the levels of fasting C peptide,2 h postprandial C peptide and HbA1c were significantly higher than before treatment;except for fasting blood glucose,above indexes of observation group were significantly better than those of control group,with statistical significance (P<0.05). The time of blood glucose reaching target in observation group was significantly shorter than control group,the incidence of nocturnal hypogly-cemia,severe hypoglycemia,edema and gastrointestinal reactions and total adverse events in observation group were significantly lower than control group,with statistical significance(P<0.05). CONCLUSIONS:The application of insulin glargine in type 2 di-abetes mellitus patients with poor glucose control by rosiglitazone and metformin can effectively reduce the levels of blood glucose and HbA1c,and improve islet function with good safety.

Rosiglitazone promotes apoptosis in colon cancer HT29 and HCT116cells through AKT/GSK3βsignalling pathway / 中国比较医学杂志

Objective To investigate the effect of rosiglitazone on the proliferation and apoptosis of colon cancer cells and the changes in the AKT/GSK3β signaling pathway. Methods Different concentrations of rosiglitazone ( 20. 0μmol/L, 40. 0 μmol/L, 80. 0 μmol/L) were used to treat colon cancer HT29 cells and HCT116 cells. Cell proliferation was detected by MTT assay. Annexin V FITC/PI cell death detection kit was used to test the cell apoptosis rate. The expression of apoptotic protein Bcl-2, Bax and Akt, GSK3β were detected by Western blot. Results Different concentrations of rosiglitazone had different effect on the proliferation of colon cancer cells compared with the blank control group, and showed a dose dependence (P< 0. 01). With the increase of rosiglitazone dose, the apoptosis-inducing effect @was increased dose-dependently (P< 0. 01). When the cells were treated with rosiglitazone for 48 h, the expressions of Bcl-2/Bax, p-GSK3β, and p-Akt were significantly decreased compared with the blank control group (P< 0. 01), but the expression level of Akt and GSK3β was not significantly different compared with the blank control group ( P > 0. 05 ) . Conclusions Rosiglitazone significantly induces apoptosis and inhibits the proliferation of HT29 cells. It may be via inhibiting Akt/GSK3β signaling pathway and change the ratio of Bcl-2/Bax.

Effects of perfusion of rosiglitazone in lesion areas on the expression levels of perihematomal occludin and zonula occluden-1 mRNA and the permeability of blood-brain-barrier in a rabbit with cerebral hemorrhage / 中国脑血管病杂志

Objective To observe the effects of perfusion of rosiglitazone (RSG) in lesion areas on the expression levels of the perihematomal tight junction-associated proteins occludin and zonula occluden-1 (ZO-1) mRNA,the permeability of blood-brain-barrier (BBB),and neurological function score in a rabbit model of cerebral hemorrhage (ICH).Methods A total of 45 healthy male rabbits were selected (a body mass of 2.0 to 2.5 kg).They were divided into 3 groups,a control group,a ICH model group,and a RSG treatment group (n =15,5 of them for BBB determination) according to the random number table.The control group was use to simulate the process of making intracranial hematoma.After successful puncture,the target was iujected with isotonic saline 0.3 ml and isotonic saline 0.1 ml was injected again after 6 h;after successful puncture,the ICH model group was injected with 0.3 ml of autologous non-anticoagulant arterial blood,and the target was injected into isotonic saline 0.1 ml after 6 h;RSG 0.5 mg was infused into the hematoma area (dissolved in 0.1 ml isotonic saline) in the RSG treatment group at 6 h after the ICH model was successfully induced.All rabbits in each group were sacrificed on day 7 after the neurological deficit scale score (Purdy score).Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression levels of perihematomal oecludin and ZO-1 mRNA.The formamide method was used to measure the Evans blue (EB) content in the perihematomal tissue in order to evaluate the permeability of BBB.Results (1) Neurological function scores:Purdy scores of the control group,ICH model group,and RSG treatment group were 2.53 ± 0.05,8.13 ± 0.06),and 6.67 ± 0.08,respectively.There were significant differences among the groups (F =459.116,P ＜ 0.01).Compared with the control group,Purdy scores of the ICH model group and RSG treatment group were increased significantly (all P ＜ 0.01).Compared with the ICH model group,Purdy scores of the RSG treatment group were decreased (P ＜ 0.05).(2) The expression levels of occludin and ZO-1 mRNA:The differences were statistically significant in occludin and ZO-1 mRNA in the control group,ICH model group,and RSG treatment group (1.013 ±0.051,1.001 ± 0.045;0.221 ± 0.017,0.247 ± 0.019;0.498 ± 0.041,and 0.613 ± 0.045,respectively in each group;F =443.924 and 381.929 respectively,all P ＜ 0.01).Compared with the control group,the expression levels of occludin and ZO-1 mRNA were significantly decreased in the ICH model group and RSG treatment group (all P ＜ 0.01).Compared with the ICH model group,the expression levels of occludin and ZO-1 mRNA were increased in the RSG treatment group (all P ＜ 0.05).(3) The permeability of BBB:The EB content in the control group,ICH model group,and RSG treatment group were 12.0 ± 1.0,51.6 ± 0.9,and 36.4 ± 1.0 μg/g,respectively.The differences were statistically significant among the groups (F =223.516,P ＜ 0.01).Compared with the control group,the EB content was significantly increased in the ICH model group and RSG treatment group (all P ＜ 0.01).Compared with the model group,the EB content was significantly decreased in the RSG treatment group (P ＜ 0.01).Conclusion The perfusion of RSG in the lesion area can significantly improve the neurological function of rabbits after ICH,increase the expression levels of occludin and ZO-1 mRNA in the perihematomal tissue,and decrease the permeability of BBB.

Clinical observation of metformin combined with rosiglitazone in the treatment of newly diagnosed type / 中国生化药物杂志

Objective To explore the primary treatment of type 2 diabetes, clinical effect of rosiglitazone combined with metformin treatment.Methods In 40 patients with type 2 diabetes mellitus patients implementation of routine treatment for metformin, and 40 patients in the control group based on the use of rosiglitazone intervention treatment, two groups of patients in our hospital from January 2015 to December 2016 were compared between the two groups.Results Treatment efficiency, obvious effective rate of observation group were higher in the observation group was 95%, while only 82.5% of the control group,comparison between groups showed significant differences(P<0.05);the two groups of patients with fasting blood glucose levels, 2 hour postprandial blood glucose level There were no significant difference before treatment, after treatment group observation group significantly improved, comparison between groups showed significant differences(P<0.05).Conclusion Rosiglitazone Combined with metformin in newly diagnosed type 2 diabetes clinical observation, which can help to improve the clinical symptoms of patients, reduce blood glucose, compared with pure medication.To improve the treatment effect, it is worthy of reference.

Effects of myocardial PPAR-gamma expression change on reperfusion arrhythmias in ischemia/reperfusion rats / 重庆医学

Objective To investigate the effects of PPAR-gamma expression on reperfusion arrhythmias in different precon ditioning myocardial ischemia/reperfusion(I/R) animal model.Methods Thirty-two SD rats were randomly divided into 4 groups(n =8):rosiglitazone+ I/R group (ROS group),GW9662 + I/R group(GW group),I/R group and sham group (Sham group).The I/ R animal model was constructed by ligation of the left anterior descending coronary artery,with ischemia for 30 min and reperfusion for 120 min.The dynamic limb Ⅱ lead electrocardiogram monitoring was performed;PPAR-gamma mRNA was detected by fluorescent quantitative PCR and the change of PPAR-gamma protein expression was detected by Western blot.Results The increasing range of QRS wave width detected before operation,at 30 min of ischemia,at 1,2 h of reperfusion from large to small were in turn the ROS group,I/R group,GW group and Sham group;the reperfusion arrhythmia score in the ROS group was significantly higher than that in the other groups(P＜0.05),while the GW group was relatively reduced.The expression level of PPAR-gamma mRNA in the ROS group detected by fluorescent quantitative PCR was significantly up-regulated(P＜0.05),while which in the GW group was down-regulated compared with the I/R group and ROS group(P＜0.05).The expression of PPAR-gamma protein was similar to that of PPAR-gamma mRNA.Conclusion Up-regulation of myocardial PPAR-gamma expression may increase the occurrence of reperfusion arrhythmias in myocardial I/R animal model.

The effects of rosiglitazone on the expression of adiponectin receptor in gingival tissue of rats with experimental periodontitis / 实用口腔医学杂志

Objective:To evaluate the effects of rosiglitazone (ROS) on the expression of adiponectin receptors (AdipoR1 and AdipoR2) mRNA in gingival tissue and inflammatory factors,and on the potential of bone loss in the rats with experimental periodontitis.Methods:10 male Sprague-Dawley rats without treatment were used as the controls;40 were used for the creation of periodontis models and then treated by rosiglitazone at 0(periodontitis control),1,3,10 mg/kg(low,median and high dose groups) respectively 1/d for 4 weeks.RT-PCR was used to examine the expression of AdipoR1 and AdipoR2 mRNA in gingiva tissue.Levels of gingival TNF-α,MMP-9 and plasma adiponectin was measured by ELISA.CEJ-A was measured for the evaluation of alveolar bone loss by standard digital photographs.Results:The expression levels of gingival AdipoRl and AdipoR2 mRNA in periodontitis group is lower than that in the control group(P ＜ 0.01).The concentration of plasma adiponectin had no significant difference between control group and periodontitis group(P ＞ 0.05).The concentration of gingival TNF-α,MMP-9 in periodontitis group was significantly higher than that in control group (P ＜ 0.01).Compared with periodontitis group,ROS treatment increased the expression levels of AdipoR1 mRNA(P ＜ 0.05)and decreased the concentration of TNF-α in gingival tissue.Median and high dose treatment increased the expression levels of AdipoR2 (P ＜ 0.01) and the concentration of plasma adiponectin(P ＜ 0.05),decreased the concentration of MMP-9 in gingival tissue (P ＜ 0.01)and the alveolar bone loss(P ＜ 0.01).Conclusion:Rosiglitazone treatment may reduce inflammatory response and suppress the bone resorption probably through up-regulation of the expression of adiponectin receptors and decrease of the concentration of TNF-α,MMP-9 in gingival tissue.