Recent studies revealed that apoptotic cells are actively involved in immunosuppression and anti-inflammation. After being phagocytosed by macrophages, apoptotic cells can actively regulate cytokines secretion from li...Recent studies revealed that apoptotic cells are actively involved in immunosuppression and anti-inflammation. After being phagocytosed by macrophages, apoptotic cells can actively regulate cytokines secretion from lipopolysaccharide （LPS）-stimulated macrophages, in which the secretion of immunosuppressive cytokines such as interleukin-10 （1L-10） is increased while the pro-inflammatory cytokines such as tumor necrosis factor-alpha （TNFα）, interleukin-lbeta （IL-1β） and leukin-8 （IL-8） are suppressed. In this paper, we first present evidence that phagocytosed apoptotic cells regulate cytokine secretion of LPS-stimulated macrophages, but also inhibit the activation of T lymphocytes stimulated by ConA. These data suggest that apoptotic cells can alter the biological behavior of macrophages which gain immunosuppressive property.展开更多
Background: Floorball training offers a motivating and socially stimulating team activity for older adults, and 12 weeks of floorball training twice a week among men aged 65—76 years have been shown to have positive ...Background: Floorball training offers a motivating and socially stimulating team activity for older adults, and 12 weeks of floorball training twice a week among men aged 65—76 years have been shown to have positive effects on a number of physiological parameters important for health. However, the effect of long-term participation in floorball training among male elderly has not been investigated. The aim of the present study was to examine the effect of 26-month self-organized regular participation in floorball training on cardiovascular fitness, body composition, blood lipids, glucose control, and physical function among recreationally active men aged 66—78 years.Methods: After completing a 12-week randomized and controlled intervention with floorball and petanque training in the autumn 2014 or spring2015, 15 subjects chose to participate in floorball training(floorball group, FG), whereas 16 subjects resumed their usual lifestyle(control group,CG). FG took part in self-organized floorball training 1.7 sessions of 40 min/week, and CG continued their normal recreationally active lifestyle during a 26-month follow-up period. At baseline and after the follow-up period subjects were tested for cardiovascular fitness, glucose control(resting blood samples), body composition dual-energy X-ray absorptiometry(DXA-scanning), and functional capacity.Results: In FG, the decline in maximal oxygen uptake(VO_(2max)) during the follow-up period was lower(242 ± 379 mL/min, p = 0.01), blood glycosylated hemoglobin(HbA1c) increased less(—1.6 ± 2.9 mmol/L, p = 0.02), and leg bone mineral density increased more(0.03 ± 0.05 g/cm^2,p = 0.02) than those in CG. The effects on body mass, total lean body mass, fat mass, blood lipids, and physical function were similar in FG and CG.Conclusion: Approximately twice weekly floorball sessions with 40 min/session over 26-month appear to reduce age-related decline in cardiovascular fitness and glucose control and improve leg bone mineral density, suggesting that long-term participation in floorball training can be considered as a health-enhancing activity in recreationally active male elderly.展开更多
In this paper the self-regeneration process of the mixed resins consisting of cationand anion ion exchangers in the electrolialyser of the packed bed is analyzed and anelectric regeneration method is put forward to su...In this paper the self-regeneration process of the mixed resins consisting of cationand anion ion exchangers in the electrolialyser of the packed bed is analyzed and anelectric regeneration method is put forward to supply the desalinated water by mixedbed The electric regeneration technology is a new one used for regeneration of theexhausted ion exchangers in the mixed bed instead of the traditional regeneratingprocess by using acid and abc liquor Electric energy is consumed to regenerat theion exchangers loaded by salts from water treatment without any chemicals- acid alkali. The advantage of the electric regeneration process edibited convenientoperation, no discharge any waste, and therefore no Polluted to the recehang waterbode and the environmental ground展开更多
Objective To reduce the toxicity and side effects of arsenic trioxide(ATO)and provide a new approach for the treatment of primary liver cancer,a folic acid-modified calcium arsenite liposomal“target-controlled”drug ...Objective To reduce the toxicity and side effects of arsenic trioxide(ATO)and provide a new approach for the treatment of primary liver cancer,a folic acid-modified calcium arsenite liposomal“target-controlled”drug delivery system(FA-LP-CaAs)was fabricated using the reverse microemulsion method.Methods A Malvern particle size analyzer and a transmission electron microscope were employed to determine the particle size,distribution,zeta potential and morphology of FA-LP-CaAs.Further,inductively coupled plasma emission spectrometry was employed to determine the drug loading capacity,entrapment efficiency,and in vitro release behavior of FA-LP-CaAs.To determine its toxicity in human hepatoma cells(HepG2)and human normal hepatocytes(LO2)and its effect on HepG2 cell cycle and apoptosis,the MTT method was used.Laser confocal and flow cytometry were also employed to determine the uptake of FA-LP-CaAs by cells.After establishing a mouse liver cancer model,the in vivo distribution of the drug included in the formulation was investigated using in vivo fluorescence.To evaluate the liver cancer targeting and anti-tumor effects of FALP-CaAs in vivo,the distribution of ATO in tissues and changes in tumor volume and body weight after liposomal administration were investigated using hematoxylin-eosin(HE)-stained tumor sections.Results The particle size,zeta potential and PDI of FA-LP-CaAs were(122.67±2.18)nm,(12.81±0.75)mV and 0.22±0.01,respectively,while its drug loading capacity was 18.49%±1.14%.In vitro experimental results revealed that FA-LP-CaAs had a strong killing effect on HepG2 cells.Further,the cell uptake capacity of this formulation was found to improve.Based on in vivo assessments,FA-LP-CaAs could significantly increase the distribution of ATO in tumor sites and inhibit tumor growth.Conclusions Herein,an FA-LP-CaAs formulation was successfully fabricated.This liposomal drug delivery system had a round appearance,uniform particle size,good polydispersity coefficient,evident“core-shell”structure,high drug loading capacity and pH response,tumor targeted drug delivery and sustained drug release.These findings support further research and the application of ATO as an anti-liver cancer prodrug and provide a new method for the treatment of liver cancer.展开更多
Objective： This study aimed to investigate, for the first time, the expression of circulating miRNAs （microRNAs） related to lipoprotein metabolism in patients with HF （heart failure）. Medlods： Twenty patients wi...Objective： This study aimed to investigate, for the first time, the expression of circulating miRNAs （microRNAs） related to lipoprotein metabolism in patients with HF （heart failure）. Medlods： Twenty patients with HF and 10 controls without HF were included. BNP （brain natxiuretic peptide）, a marker of HF severity, plasma lipid parameters and the expression of circulating miRNAs were determined. Key findings： Total, LDL-, non-HDL- and HDL-cholesterol, txiglycerides, and apo A-I did not differ between both groups, but apo B was lower in the HF group compared to controls （p = 0.007）. In respect to miRNAs, miR-33a, miR-144, miR-125, miR-30c, miR-122, miR-26a, miR-185, miR-758 and miR-106b were higher, from ten- to 25-fold, and miR-10b was lower about 4-fold, in HF group compared to controls. In HF patients a negative correlation between miR-26a and BNP, the marker of disease severity, was found （r = -0.552; p = 0.041）. Conclusions： Plasma levels of miRNAs involved in HDL and LDL metabolism regulation were strikingly changed in HF patients. The negative correlation between miR-26a and BNP values may suggest the possibility of the rise of a novel biomarker or therapeutic target in HF.展开更多
AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (10...AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy.RESULTSSitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 μg/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002.CONCLUSIONSitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.展开更多
SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-bin...SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-binding protein a （C/EBPa） during adipocyte differentiation. C/EBPa, but not C/EBPap30, activated SIRT1 promoter in both HeLa cells and 3T3-L1 preadipocytes. Furthermore, C/EBPa upregulated SIRT1 mRNA and protein levels in HeLa cells and increased SIRT1 expression in a p53-independent manner in Soas2 cells. In preadipocytes, ectopic expression of C/EBPa upregulated SIRT1 protein level and knockdown of C/EBPa led to the decrease of SIRTI pro- tein level. Moreover, by promoter deletion analysis, gel shift assay and chromatin immunoprecipitation, we found that C/EBPa bound to the SIRT1 promoter at a consensus C/EBPα binding site. These data demonstrate that C/ EBPα regulates SIRT1 expression during adipogenesis by directly binding to the SIRT1 promoter.展开更多
Fufang Zhenzhu Tiaozhi capsules （FTZc）, which is consisted of eight traditional Chinese herbal medicines and contains multiple bioactive ingredients, is a patented and clinically approved herbal formulation for the ...Fufang Zhenzhu Tiaozhi capsules （FTZc）, which is consisted of eight traditional Chinese herbal medicines and contains multiple bioactive ingredients, is a patented and clinically approved herbal formulation for the treatment of dyslipidemia. A feasible HPLC-DAD-ELSD method was developed to simultaneously determine 15 bioactive compounds （salidroside, specneuzhenide, magnoflorine, rosmarinic acid, salvianolic acid B, columbamine, jatrorrhizine, epiberberine, coptisine, palmatine, berberine, 5,7-dimethoxycoumarin, ginsenoside Rgl, ginsenoside Rbl and oleanic acid ） in FTZc for its quality control. The multiple wavelength detection mode of DAD was used. The chromatographic separation was performed on an Ultimate XB Cls column with gradient elution. The mobile phase A （acetonitrile） and B （0.25% glacial acetic acid and 0.13% triethylamine in water, v/v） were run at a flow rate of 0.8 mL/min. The developed method showed good precision and accuracy with overall intra- and inter-day variations of 0.7%-1.9% and 0.6%-3.0%, respectively. The recoveries measured at three concentration levels, varied from 95.5% to 103.8%. The validated method was successfully applied for the simultaneous determination of 15 bioactive compounds in three batches of FTZc. The results suggested that the developed method was convenient and reliable, particularly suitable for the routine quality control of FTZc.展开更多
Sinopodophylli Fructus is the commonly used traditional Tibetan medicinal herb. In the present study, we established a reversed-phase high performance liquid chromatography method to simultaneously determine three lig...Sinopodophylli Fructus is the commonly used traditional Tibetan medicinal herb. In the present study, we established a reversed-phase high performance liquid chromatography method to simultaneously determine three lignans and five flavonoid constituents, namely podophyllotoxin, desoxypodophyUotoxin, 4＇-demethyldesoxypodophyllotoxin, 8-prenylkaemferol, quercetin, kaempferol, 8,2＇-diprenylquercetin 3-methylether and 8-prenylquercetin, in Sinopodophylli Fructus. The chromatographic separation was achieved on a C_18 analytical column with a gradient mobile phase consisting of acetonitrile and 0.05% phosphoric acid at a flow rate of 1.0 mL/min. UV detection was set at 290 nm and 370 rim, and the column oven was set at 35℃. This method provided a good reproducibility, and its overall intra- and inter-day precision was less than 3% and 4%, respectively. The recovery of the method was 98.29%-101.60%, and a good linearity （R2≥0.9992） was obtained for all the analytes over a relatively wide range of concentration. A total of 17 samples ofS. hexandrum （12 fruits, 5 roots and rhizomes） were collected from different areas and then successfully quantified. The results indicated that the contents of eight compounds significantly varied （the sum content ranged from 16.90 to 55.68 mg/g）, and prenylated fiavonoids could be used as marker constituents in the identification and quality control of Sinopodophylli Fructus.展开更多
Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes,fatty liver and cardiovascular diseases.The lipid droplet(LD)is an important subcellular or...Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes,fatty liver and cardiovascular diseases.The lipid droplet(LD)is an important subcellular organelle responsible for lipid storage.We previously observed that Fsp27,a member of the CIDE family proteins,is localized to LD-contact sites and promotes atypical LD fusion and growth.Cidea,a close homolog of Fsp27,is expressed at high levels in brown adipose tissue.However,the exact role of Cidea in promoting LD fusion and lipid storage in adipose tissue remains unknown.Here,we expressed Cidea in Fsp27-knockdown adipocytes and observed that Cidea has similar activity to Fsp27 in promoting lipid storage and LD fusion and growth.Next,we generated Cidea and Fsp27 double-deficient mice and observed that these animals had drastically reduced adipose tissue mass and a strong lean phenotype.In addition,Cidea/Fsp27 double-deficient mice had improved insulin sensitivity and were intolerant to cold.Furthermore,we observed that the brown and white adipose tissues of Cidea/Fsp27double-deficient mice had significantly reduced lipid storage and contained smaller LDs compared to those of Cidea or Fsp27single deficient mice.Overall,these data reveal an important role of Cidea in controlling lipid droplet fusion,lipid storage in brown and white adipose tissue,and the development of obesity.展开更多
基金Project supported by the National Basic Research Program (973) of China (No. 2003CB515500) and the National Natural Science Foun-dation of China (No. 30371358)
文摘Recent studies revealed that apoptotic cells are actively involved in immunosuppression and anti-inflammation. After being phagocytosed by macrophages, apoptotic cells can actively regulate cytokines secretion from lipopolysaccharide （LPS）-stimulated macrophages, in which the secretion of immunosuppressive cytokines such as interleukin-10 （1L-10） is increased while the pro-inflammatory cytokines such as tumor necrosis factor-alpha （TNFα）, interleukin-lbeta （IL-1β） and leukin-8 （IL-8） are suppressed. In this paper, we first present evidence that phagocytosed apoptotic cells regulate cytokine secretion of LPS-stimulated macrophages, but also inhibit the activation of T lymphocytes stimulated by ConA. These data suggest that apoptotic cells can alter the biological behavior of macrophages which gain immunosuppressive property.
文摘Background: Floorball training offers a motivating and socially stimulating team activity for older adults, and 12 weeks of floorball training twice a week among men aged 65—76 years have been shown to have positive effects on a number of physiological parameters important for health. However, the effect of long-term participation in floorball training among male elderly has not been investigated. The aim of the present study was to examine the effect of 26-month self-organized regular participation in floorball training on cardiovascular fitness, body composition, blood lipids, glucose control, and physical function among recreationally active men aged 66—78 years.Methods: After completing a 12-week randomized and controlled intervention with floorball and petanque training in the autumn 2014 or spring2015, 15 subjects chose to participate in floorball training(floorball group, FG), whereas 16 subjects resumed their usual lifestyle(control group,CG). FG took part in self-organized floorball training 1.7 sessions of 40 min/week, and CG continued their normal recreationally active lifestyle during a 26-month follow-up period. At baseline and after the follow-up period subjects were tested for cardiovascular fitness, glucose control(resting blood samples), body composition dual-energy X-ray absorptiometry(DXA-scanning), and functional capacity.Results: In FG, the decline in maximal oxygen uptake(VO_(2max)) during the follow-up period was lower(242 ± 379 mL/min, p = 0.01), blood glycosylated hemoglobin(HbA1c) increased less(—1.6 ± 2.9 mmol/L, p = 0.02), and leg bone mineral density increased more(0.03 ± 0.05 g/cm^2,p = 0.02) than those in CG. The effects on body mass, total lean body mass, fat mass, blood lipids, and physical function were similar in FG and CG.Conclusion: Approximately twice weekly floorball sessions with 40 min/session over 26-month appear to reduce age-related decline in cardiovascular fitness and glucose control and improve leg bone mineral density, suggesting that long-term participation in floorball training can be considered as a health-enhancing activity in recreationally active male elderly.
文摘In this paper the self-regeneration process of the mixed resins consisting of cationand anion ion exchangers in the electrolialyser of the packed bed is analyzed and anelectric regeneration method is put forward to supply the desalinated water by mixedbed The electric regeneration technology is a new one used for regeneration of theexhausted ion exchangers in the mixed bed instead of the traditional regeneratingprocess by using acid and abc liquor Electric energy is consumed to regenerat theion exchangers loaded by salts from water treatment without any chemicals- acid alkali. The advantage of the electric regeneration process edibited convenientoperation, no discharge any waste, and therefore no Polluted to the recehang waterbode and the environmental ground
基金funding support from the National Natural Science Foundation of China (No. 81873014)。
文摘Objective To reduce the toxicity and side effects of arsenic trioxide(ATO)and provide a new approach for the treatment of primary liver cancer,a folic acid-modified calcium arsenite liposomal“target-controlled”drug delivery system(FA-LP-CaAs)was fabricated using the reverse microemulsion method.Methods A Malvern particle size analyzer and a transmission electron microscope were employed to determine the particle size,distribution,zeta potential and morphology of FA-LP-CaAs.Further,inductively coupled plasma emission spectrometry was employed to determine the drug loading capacity,entrapment efficiency,and in vitro release behavior of FA-LP-CaAs.To determine its toxicity in human hepatoma cells(HepG2)and human normal hepatocytes(LO2)and its effect on HepG2 cell cycle and apoptosis,the MTT method was used.Laser confocal and flow cytometry were also employed to determine the uptake of FA-LP-CaAs by cells.After establishing a mouse liver cancer model,the in vivo distribution of the drug included in the formulation was investigated using in vivo fluorescence.To evaluate the liver cancer targeting and anti-tumor effects of FALP-CaAs in vivo,the distribution of ATO in tissues and changes in tumor volume and body weight after liposomal administration were investigated using hematoxylin-eosin(HE)-stained tumor sections.Results The particle size,zeta potential and PDI of FA-LP-CaAs were(122.67±2.18)nm,(12.81±0.75)mV and 0.22±0.01,respectively,while its drug loading capacity was 18.49%±1.14%.In vitro experimental results revealed that FA-LP-CaAs had a strong killing effect on HepG2 cells.Further,the cell uptake capacity of this formulation was found to improve.Based on in vivo assessments,FA-LP-CaAs could significantly increase the distribution of ATO in tumor sites and inhibit tumor growth.Conclusions Herein,an FA-LP-CaAs formulation was successfully fabricated.This liposomal drug delivery system had a round appearance,uniform particle size,good polydispersity coefficient,evident“core-shell”structure,high drug loading capacity and pH response,tumor targeted drug delivery and sustained drug release.These findings support further research and the application of ATO as an anti-liver cancer prodrug and provide a new method for the treatment of liver cancer.
文摘Objective： This study aimed to investigate, for the first time, the expression of circulating miRNAs （microRNAs） related to lipoprotein metabolism in patients with HF （heart failure）. Medlods： Twenty patients with HF and 10 controls without HF were included. BNP （brain natxiuretic peptide）, a marker of HF severity, plasma lipid parameters and the expression of circulating miRNAs were determined. Key findings： Total, LDL-, non-HDL- and HDL-cholesterol, txiglycerides, and apo A-I did not differ between both groups, but apo B was lower in the HF group compared to controls （p = 0.007）. In respect to miRNAs, miR-33a, miR-144, miR-125, miR-30c, miR-122, miR-26a, miR-185, miR-758 and miR-106b were higher, from ten- to 25-fold, and miR-10b was lower about 4-fold, in HF group compared to controls. In HF patients a negative correlation between miR-26a and BNP, the marker of disease severity, was found （r = -0.552; p = 0.041）. Conclusions： Plasma levels of miRNAs involved in HDL and LDL metabolism regulation were strikingly changed in HF patients. The negative correlation between miR-26a and BNP values may suggest the possibility of the rise of a novel biomarker or therapeutic target in HF.
基金the Physicians’Services Incorporated Foundation 10q2083(Joy TR and Beaton MD)Academic Medical Organization of Southwestern Ontario,No.F10-002(Beaton MD)+1 种基金partly funded through academic research funds from the Program of Experimental Medicine(Joy TR)Department of Medicine Academic Funds(Joy TR)from Western University,London,Ontario,Canada
文摘AIMTo evaluate the effect of sitagliptin vs placebo on histologic and non-histologic parameters of non-alcoholic steatohepatitis (NASH).METHODSTwelve patients with biopsy-proven NASH were randomized to sitagliptin (100 mg daily) (n = 6) or placebo (n = 6) for 24 wk. The primary outcome was improvement in liver fibrosis after 24 wk. Secondary outcomes included evaluation of changes in NAFLD activity score (NAS), individual components of NAS (hepatocyte ballooning, lobular inflammation, and steatosis), glycemic control and insulin resistance [including measurements of glycated hemoglobin (HbA1C) and adipocytokines], lipid profile including free fatty acids, adipose distribution measured using magnetic resonance imaging (MRI), and thrombosis markers (platelet aggregation and plasminogen activator inhibitor 1 levels). We also sought to determine the correlation between changes in hepatic fat fraction (%) [as measured using the Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL) MRI technique] and changes in hepatic steatosis on liver biopsy.RESULTSSitagliptin was not significantly better than placebo at reducing liver fibrosis score as measured on liver biopsy (mean difference between sitagliptin and placebo arms, 0.40, P = 0.82). There were no significant improvements evident with the use of sitagliptin vs placebo for the secondary histologic outcomes of NAS total score as well as for the individual components of NAS. Compared to baseline, those patients who received sitagliptin demonstrated improved HbA1C (6.7% ± 0.4% vs 7.9% ± 1.0%, P = 0.02), and trended towards improved adiponectin levels (4.7 ± 3.5 μg/mL vs 3.9 ± 2.7 μg/mL, P = 0.06) and triglyceride levels (1.26 ± 0.43 mmol/L vs 2.80 ± 1.64 mmol/L, P = 0.08). However, when compared with placebo, sitagliptin did not cause a statistically significant improvement in HbA1C (mean difference, -0.7%, P = 0.19) nor triglyceride levels (mean difference -1.10 mmol/L, P = 0.19) but did trend towards improved adiponectin levels only (mean difference, 0.60 μg/mL, P = 0.095). No significant changes in anthropometrics, liver enzymes, other adipocytokines, lipid profile, thrombosis parameters, or adipose distribution were demonstrated. The MRI IDEAL procedure correlated well with steatosis scores obtained on liver biopsy in both groups at baseline and post-treatment, and the Spearman correlation coefficients ranged from r = 0.819 (baseline) to r = 0.878 (post-treatment), P = 0.002.CONCLUSIONSitagliptin does not improve fibrosis score or NAS after 24 wk of therapy. The MRI IDEAL technique may be useful for non-invasive measurement of hepatic steatosis.
文摘SIRT1 plays an important role in adipogenesis, but how SIRT1 is regulated in adipogenesis is largely unknown. In this study, we show that both SIRT1 protein and mRNA levels were increased along with CCAAT/enhancer-binding protein a （C/EBPa） during adipocyte differentiation. C/EBPa, but not C/EBPap30, activated SIRT1 promoter in both HeLa cells and 3T3-L1 preadipocytes. Furthermore, C/EBPa upregulated SIRT1 mRNA and protein levels in HeLa cells and increased SIRT1 expression in a p53-independent manner in Soas2 cells. In preadipocytes, ectopic expression of C/EBPa upregulated SIRT1 protein level and knockdown of C/EBPa led to the decrease of SIRTI pro- tein level. Moreover, by promoter deletion analysis, gel shift assay and chromatin immunoprecipitation, we found that C/EBPa bound to the SIRT1 promoter at a consensus C/EBPα binding site. These data demonstrate that C/ EBPα regulates SIRT1 expression during adipogenesis by directly binding to the SIRT1 promoter.
基金Guangdong Administration of Traditional Chinese Medicine Research Projects China (Grant No. 2010200)a cooperation Project in Industry, Education and Research of Guangdong Province and Ministry of Education of China (Grant No. 2009B090300349)+1 种基金a cooperation project of National Science Foundation of Guangdong Province (Grant No. 10351022401000000)a Guangzhou City Science and Technology Support Program (Grant No. 2009Z1-E361)
文摘Fufang Zhenzhu Tiaozhi capsules （FTZc）, which is consisted of eight traditional Chinese herbal medicines and contains multiple bioactive ingredients, is a patented and clinically approved herbal formulation for the treatment of dyslipidemia. A feasible HPLC-DAD-ELSD method was developed to simultaneously determine 15 bioactive compounds （salidroside, specneuzhenide, magnoflorine, rosmarinic acid, salvianolic acid B, columbamine, jatrorrhizine, epiberberine, coptisine, palmatine, berberine, 5,7-dimethoxycoumarin, ginsenoside Rgl, ginsenoside Rbl and oleanic acid ） in FTZc for its quality control. The multiple wavelength detection mode of DAD was used. The chromatographic separation was performed on an Ultimate XB Cls column with gradient elution. The mobile phase A （acetonitrile） and B （0.25% glacial acetic acid and 0.13% triethylamine in water, v/v） were run at a flow rate of 0.8 mL/min. The developed method showed good precision and accuracy with overall intra- and inter-day variations of 0.7%-1.9% and 0.6%-3.0%, respectively. The recoveries measured at three concentration levels, varied from 95.5% to 103.8%. The validated method was successfully applied for the simultaneous determination of 15 bioactive compounds in three batches of FTZc. The results suggested that the developed method was convenient and reliable, particularly suitable for the routine quality control of FTZc.
基金National Key Technology R&D Program"New Drug Innovation"of China(Grant No.2009ZX09308-004,2013ZX09103002-006)
文摘Sinopodophylli Fructus is the commonly used traditional Tibetan medicinal herb. In the present study, we established a reversed-phase high performance liquid chromatography method to simultaneously determine three lignans and five flavonoid constituents, namely podophyllotoxin, desoxypodophyUotoxin, 4＇-demethyldesoxypodophyllotoxin, 8-prenylkaemferol, quercetin, kaempferol, 8,2＇-diprenylquercetin 3-methylether and 8-prenylquercetin, in Sinopodophylli Fructus. The chromatographic separation was achieved on a C_18 analytical column with a gradient mobile phase consisting of acetonitrile and 0.05% phosphoric acid at a flow rate of 1.0 mL/min. UV detection was set at 290 nm and 370 rim, and the column oven was set at 35℃. This method provided a good reproducibility, and its overall intra- and inter-day precision was less than 3% and 4%, respectively. The recovery of the method was 98.29%-101.60%, and a good linearity （R2≥0.9992） was obtained for all the analytes over a relatively wide range of concentration. A total of 17 samples ofS. hexandrum （12 fruits, 5 roots and rhizomes） were collected from different areas and then successfully quantified. The results indicated that the contents of eight compounds significantly varied （the sum content ranged from 16.90 to 55.68 mg/g）, and prenylated fiavonoids could be used as marker constituents in the identification and quality control of Sinopodophylli Fructus.
基金supported by grants from the National Basic Research Program(2013CB530602 and 2011CB910801 to Li Peng)the National Natural Science Foundation of China(30925017,31030038 and 90913024)the China Postdoctoral Science Foundation(2012M520249 and 2013T60103 to Zhou LinKang)
文摘Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes,fatty liver and cardiovascular diseases.The lipid droplet(LD)is an important subcellular organelle responsible for lipid storage.We previously observed that Fsp27,a member of the CIDE family proteins,is localized to LD-contact sites and promotes atypical LD fusion and growth.Cidea,a close homolog of Fsp27,is expressed at high levels in brown adipose tissue.However,the exact role of Cidea in promoting LD fusion and lipid storage in adipose tissue remains unknown.Here,we expressed Cidea in Fsp27-knockdown adipocytes and observed that Cidea has similar activity to Fsp27 in promoting lipid storage and LD fusion and growth.Next,we generated Cidea and Fsp27 double-deficient mice and observed that these animals had drastically reduced adipose tissue mass and a strong lean phenotype.In addition,Cidea/Fsp27 double-deficient mice had improved insulin sensitivity and were intolerant to cold.Furthermore,we observed that the brown and white adipose tissues of Cidea/Fsp27double-deficient mice had significantly reduced lipid storage and contained smaller LDs compared to those of Cidea or Fsp27single deficient mice.Overall,these data reveal an important role of Cidea in controlling lipid droplet fusion,lipid storage in brown and white adipose tissue,and the development of obesity.
