The main goal of this research is to investigate the effect of copper on compressive strength of dental amalgam. For this purpose amalgam capsules with two different content of copper were used. Cylindrical samples wi...The main goal of this research is to investigate the effect of copper on compressive strength of dental amalgam. For this purpose amalgam capsules with two different content of copper were used. Cylindrical samples with diameter to height ratio 1 to 2, were prepared via molding method. To evaluate the role of copper element on compressive strength, com-pression test was done at different strain rates i.e. 0.02, 0.2, 0.4 and 2 min–1. The results and microscopic evaluations showed that an increase in copper content in amalgam caused to eliminate gamma2 phase and leaded to promote compressive strength.展开更多
Objective To study the effect of β3 adrenergic receptor （β3AR） Trp64Arg and peroxisome proliferator activated receptor gamma 2 （PPAR72） Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight...Objective To study the effect of β3 adrenergic receptor （β3AR） Trp64Arg and peroxisome proliferator activated receptor gamma 2 （PPAR72） Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment （HOMA）. PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state （IBS） was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio （WHR）, blood glucose （GLU）, and insulin （INS）, homeostasis model assessment insulin resistance index （HOMA-IR） of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index （BMI）, WHR, percent of body fat （PBF） and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR）,2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.展开更多
Recently, water treatment by ionizing radiation has gained increasing attention as a powerful technology for the destruction of refractory pollutants. 2-Mercaptobenzothiazole（MBT） is known as a widespread, toxic and...Recently, water treatment by ionizing radiation has gained increasing attention as a powerful technology for the destruction of refractory pollutants. 2-Mercaptobenzothiazole（MBT） is known as a widespread, toxic and poorly biodegradable pollutant. This paper studied the gamma irradiation of aqueous solutions of MBT. Moreover, the effect of the addition of persulfate（S2O82-） on the radiolytic destruction of MBT was investigated. The main transformation products of the studied compound were detected and the sequence of occurrence of the products was described. The change of biodegradability of MBT solution was also observed. The main results obtained in this study indicated that gamma radiation was effective for removing MBT in aqueous solution. Persulfate addition, which induced the formation of reactive sulfate radicals（SO4-U）, greatly enhanced the degradation of MBT. Benzothiazole was identified as the first radiation product, followed by 2-hydroxybenzothiazole. Decomposition of MBT started with the oxidation of –SH groups to sulfate ions. Possible pathways for MBT decomposition by gamma irradiation were proposed. The BOD/COD ratios of MBT samples were increased after radiation,indicating the improvement of biodegradability and reduction of toxicity.展开更多
BACKGROUND Multiple sites of metastasis and desmoplastic reactions in the stroma are key features of human pancreatic cancer(PC).There are currently no simple and reliable animal models that can mimic these features f...BACKGROUND Multiple sites of metastasis and desmoplastic reactions in the stroma are key features of human pancreatic cancer(PC).There are currently no simple and reliable animal models that can mimic these features for accurate disease modeling.AIM To create a new xenograft animal model that can faithfully recapitulate the features of human PC.METHODS Interleukin 2 receptor subunit gamma(IL2RG)gene knockout Syrian hamster was created and characterized.A panel of human PC cell lines were transplanted into IL2RG knockout Syrian hamsters and severe immune-deficient mice subcutaneously or orthotopically.Tumor growth,local invasion,remote organ metastasis,histopathology,and molecular alterations of tumor cells and stroma were compared over time.RESULTS The Syrian hamster with IL2RG gene knockout(named ZZU001)demonstrated an immune-deficient phenotype and function.ZZU001 hamsters faithfully recapitulated most features of human PC,in particular,they developed metastasis at multiple sites.PC tissues derived from ZZU001 hamsters displayed desmoplastic reactions in the stroma and epithelial to mesenchymal transition phenotypes,whereas PC tissues derived from immune-deficient mice did not present such features.CONCLUSION ZZU001 hamsters engrafted with human PC cells are a superior animal model compared to immune-deficient mice.ZZU001 hamsters can be a valuable animal model for better understanding the molecular mechanism of tumorigenesis and metastasis and the evaluation of new drugs targeting human PC.展开更多
Fine powders of γ-Fe_2O_3,doped with Y_2O_3,CeO_2,Eu_2O_3 or Tb_2O_3 have been prepared by the chemical co-precipitation method.The sensitivity of gas sensation has been measured with respect to the relative resist- ...Fine powders of γ-Fe_2O_3,doped with Y_2O_3,CeO_2,Eu_2O_3 or Tb_2O_3 have been prepared by the chemical co-precipitation method.The sensitivity of gas sensation has been measured with respect to the relative resist- ance change in the ceramic matrix upon introduction of inflammable gases.The structure of the materials has been studied with X-ray diffraction spectroscopy(XRD),electron diffraction spectroscopy( ED) and transmis- sion electron microscopy(TEM).The addition of rare earth oxides,which improves ceramic microstructure of γ-Fe_2O_3,improves gas sensitivity of γ-Fe_2O_3.The stability can be increased because of the increase of phase transition temperature.In addition,the selectivity of gas sensation of γ-Fe_2O_3 can be improved because of the variation of rare earth oxides.展开更多
Mitofusin2 （Mfn2） plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells （VSMCs）. The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracell...Mitofusin2 （Mfn2） plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells （VSMCs）. The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracellular cholesterol in the foam ceils derived from rat VSMCs （rVSMCs） and also to investigate the effects of Mfn2 on the expression of adenosine triphosphate-binding cassette subfamily A member 1 （ABCA1）, adenosine triphosphate-binding cassette subfamily G member 1 （ABCG1） and peroxisome proliferator-activated receptor gamma （PPARy）. The rVSMCs were co-cultured with oxi- dized low density lipoprotein （LDL, 80 ~tg/mL） to produce foam cells and cholesterol accumulation in cells. Before oxidized LDL treatment, different titers （20, 40 and 60 pfu/cell） of recombinant adenovirus containing Mfn2 gene （Adv-Mfn2） were added into the culture medium for 24 h to transfect the Mfn2 gene into the rVSMCs. Then the cells were harvested for analyses. The protein expression of Mfn2 was significantly higher in Adv-Mfn2-transfected group than in untransfected group （P〈0.05）, and the ex- pression levels significantly increased when the titer of Adv-Mfn2 increased （P〈0.05）. At 24 or 48 h af- ter oxidized LDL treatment, rVSMCs became irregular and their nuclei became larger, and their plasma abounded with red lipid droplets. However, the number of red lipid droplets was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group. At 48 h after oxidized LDL treatment, the intracellular cholesterol in rVSMCs was significantly increased （P〈0.05）, but it was sig- nificantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）, and it also significantly decreased when the titer of Adv-Mfn2 increased （P〈0.05）. The mRNA and pro- tein expression levels of ABCA1 and ABCG1 were significantly increased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. Though the mRNA and protein expression levels of PPARy was not significantly increased （P〉0.05）, the phosporylation levels of PPARy were signifi- cantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. These results suggest that the transfection of Adv-Mfn2 can significantly reduce intracellular cholesterol in oxidized LDL-induced rVSMCs possibly by decreasing PPAR＇/phosporylation and then increasing pro- tein expression levels of ABCAI and ABCG1, which may be helpful to suppress the formation of foam cells.展开更多
Objective To investigate the kinetics and the magnitude of intragraft gene expression of interleukin-2(IL-2), interferon-gamma (IFN-y), perforin and granzyme B, and intragraft expression of interieukin-2receptor (IL-...Objective To investigate the kinetics and the magnitude of intragraft gene expression of interleukin-2(IL-2), interferon-gamma (IFN-y), perforin and granzyme B, and intragraft expression of interieukin-2receptor (IL-2R) and intercellular adhesion molecule-1 ( ICAM-1 ) during acute rejection episodes, and to analyze the changes in apoptosis in small intestinal allograft rejection.Methods Heterotopic small intestine transplantation was performed with inbred rats F344/N (RT11) and Wistar/A (RT1-Ak, RT1-Ed). All recipients were divided into four groups: group 1 : Wistar, native control;group 2: Wistar→Wistar; group 3: F344→Wistar and group 4: F344→Wistar + cyclosporine A (6 mg·kg-1 ·d-1 I.M. ). The grafts were harvested on postoperative days (PODs) 3, 5 and 7. All samples were examined pathologically. Intragraft mRNA expression of IL-2, IFN-γ, perforin and granzyme B were detected with reverse transcriptase polymerase chain reaction (RT-PCR) and intragraft expression of IL-2R and ICAM-1 were stained using immunohistochemistry. We also analyzed the change in apoptosis rejection with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL).Results Mild acute rejection occurred on POD 3 in the ailograft group, moderate acute rejection on POD 5, and severe acute rejection on POD 7, while none of the isografts had histological evidence of acute rejection. Cyclosporine A could effectively control rejection. Gene expression was virtually negative in the native control. Only on POD 5 was IL-2 mRNA expression of ailografts significantly higher than that of isografts ( P ＜ 0.05). IFN-γ mRNA expression was significantly higher than that of the control groups ( P ＜0.01 ) on PODs 3, 5 and 7, and the level of perforin and granzyme B mRNA expression reached significantly higher levels than in the other two control groups on POD 5 and POD 7. Intragraft IL-2Rexpression of the allograft was significantly higher than that of the other three control groups. Only on POD 3 was intragraft ICAM-1 expression of allografts significantly higher than isografts. The number of apoptotic cells per crypt of allografts was significantly higher than that of the other three control groups on POD 3 and POD 5 ( P ＜ 0.01 ).Conclusion Transcription of IL-2, IFN-γ, perforin and granzyme B, and expression of IL-2R and ICAM-1as well as apoptosis of epithelial cells of the grafts play an important role in small intestine allograft rejection.Intragraft gene expression of IFN-γ and intragraft expression of IL-2R as well as apoptotic epithelial cells may become a specific and sensitive diagnostic method of clinical value. Furthermore, therapeutic strategies to alter these molecules in small intestine transplantation may improve the outcome of current antirejection therapy.展开更多
Background Pioglitazone is effective in nonalcoholic steatohepatitis （NASH）, but the mechanisms of action are not completely understood. This study was designed to investigate the effects of pioglitazone on hepatic ...Background Pioglitazone is effective in nonalcoholic steatohepatitis （NASH）, but the mechanisms of action are not completely understood. This study was designed to investigate the effects of pioglitazone on hepatic nuclear factor-kappa B （NF-KB） and cyclooxygenases-2 （COX-2） expression in NASH rats. Methods Thirty Sprague-Dawley male rats were randomly assigned to a control group （n=10）, NASH group （n=10）, and pioglitazone treatment group （n=10）. Liver tissues were processed for histology by hematoxylin ＆ eosin and Masson stained. Serum alanine aminotransferase （ALT）, cholesterol, triglyceride, fasting blood glucose （FBG）, fasting insulin （FINS） levels and biochemical parameters of antioxidant enzyme activities, tumor necrosis factor alpha （TNF-a）, prostaglandin E2 （PGE2） levels in serum and liver were measured. The mRNA and protein expression of peroxisome proliferator-activated receptor gamma （PPARy）, NF-KB and COX-2 were determined by real-time polymerase chain reaction, Western blotting and immunohistochemistry. One-way analysis of variance （ANOVA） and Wilcoxon＇s signed-rank test was used for the statistical analysis. Results There were severe steatosis, moderate inflammatory cellular infiltration and fibrosis in NASH rats. After pioglitazone treatment, steatosis, inflammation and fibrosis were significantly improved compared with the NASH group （X2=20.40, P 〈0.001; X2=20.17, P 〈0.001; X2=13.98, P=0.002）. Serum ALT, cholesterol, triglyceride, FBG, FINS levels were significantly elevated in the NASH group （P 〈0.05）. In the NASH group, total anti-oxidation competence （T-AOC）, superoxide dismutase （SOD）, catalase （CAT）, glutathione peroxidase （GSH-PX） and malondialdehyde （MDA） levels in serum and liver were conspicuous disordered than those parameters in the control group. Meanwhile, TNF-a and PGE2 levels in serum and liver were significantly increased compared with the control group. Immunohistochemistry showed NF-KB and COX-2 expression in liver was significantly elevated. However, PPARy level was decreased in the NASH group. Real-time PCR and Western blotting revealed mRNA and protein expression of COX-2 were increased in the NASH group compared with the control group （0.57±0.08 vs. 2.83±0.24; 0.38±0.03 vs. 1.00±0.03, P 〈0.001 and P=-0.004, respectively）. After pioglitazone intervention, all of those parameters markedly improved （P 〈0.05 or P 〈0.01）. Conclusion Down-regulating hepatic NF-KB and COX-2 expression, at least in part, is one of the possible therapeutic mechanisms of pioglitazone in NASH rats.展开更多
Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows...Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.展开更多
文摘The main goal of this research is to investigate the effect of copper on compressive strength of dental amalgam. For this purpose amalgam capsules with two different content of copper were used. Cylindrical samples with diameter to height ratio 1 to 2, were prepared via molding method. To evaluate the role of copper element on compressive strength, com-pression test was done at different strain rates i.e. 0.02, 0.2, 0.4 and 2 min–1. The results and microscopic evaluations showed that an increase in copper content in amalgam caused to eliminate gamma2 phase and leaded to promote compressive strength.
基金This study was supported by the National Natural Science Foundation of China (30371223)the Major State Basic Research Development Program of China (2001CB510310).
文摘Objective To study the effect of β3 adrenergic receptor （β3AR） Trp64Arg and peroxisome proliferator activated receptor gamma 2 （PPAR72） Prol2Ala polymorphisms on insulin resistance. Methods One hundred and eight dizygotic twin pairs were enrolled in this study. Microsatellite polymorphism was used to diagnose zygosity of twins. Insulin sensitivity was estimated with logarithm transformed homeostasis model assessment （HOMA）. PCR-RFLP analysis was performed to detect the variants. As a supplement to the sib-pair method, identity by state （IBS） was used to analyze the association of polymorphisms with insulin sensitivity. Results The genotype frequencies of Trp64Trg, Trp64Arg, and Arg64Arg were 72.3%, 23.8%, and 3.9%, respectively, while the genotype frequencies of Pro12Pro, Pro12Ala, and Ala12Ala were 89.9%, 9.6%, and 0.5%, respectively. For β3AR Trp64Arg the interclass co-twin correlations of Waist-to-hip ratio （WHR）, blood glucose （GLU）, and insulin （INS）, homeostasis model assessment insulin resistance index （HOMA-IR） of the twin pairs sharing 2 alleles of IBS were greater than those sharing 0-1 allele of IBS, and HOMA4R had statistic significance. For PPAR3t2 Prol2Ala most traits of twin pairs sharing 2 alleles of IBS had greater correlations and statistic significance in body mass index （BMI）, WHR, percent of body fat （PBF） and GLU, but there were low correlations of either insulin or HOMA-IR of twin pairs sharing 1 or 2 alleles of IBS. The combined effects of the two variations showed less squared significant twin-pair differences of INS and HOMA-IR among twins sharing 4 alleles of IBS. Condusions β3AR Trp64Arg and PPAR）,2 Pro 12Ala polymorphisms might be associated with insulin resistance and obesity, and there might be slight synergistic effects between this two gene loci, and further studies are necessary to confirm this finding.
基金the National Hi-Tech Research and Development Program(863)of China(No.2009AA063905)supported by the Chinese Ministry of Science and Technology and the Independent Research Project(No.20101081929)supported by Tsinghua University
文摘Recently, water treatment by ionizing radiation has gained increasing attention as a powerful technology for the destruction of refractory pollutants. 2-Mercaptobenzothiazole（MBT） is known as a widespread, toxic and poorly biodegradable pollutant. This paper studied the gamma irradiation of aqueous solutions of MBT. Moreover, the effect of the addition of persulfate（S2O82-） on the radiolytic destruction of MBT was investigated. The main transformation products of the studied compound were detected and the sequence of occurrence of the products was described. The change of biodegradability of MBT solution was also observed. The main results obtained in this study indicated that gamma radiation was effective for removing MBT in aqueous solution. Persulfate addition, which induced the formation of reactive sulfate radicals（SO4-U）, greatly enhanced the degradation of MBT. Benzothiazole was identified as the first radiation product, followed by 2-hydroxybenzothiazole. Decomposition of MBT started with the oxidation of –SH groups to sulfate ions. Possible pathways for MBT decomposition by gamma irradiation were proposed. The BOD/COD ratios of MBT samples were increased after radiation,indicating the improvement of biodegradability and reduction of toxicity.
基金Supported by the National Key R and D Program of China,No.2016YFE0200800Nature Sciences Foundation of China,No.81771776+1 种基金Nature Sciences Foundation of China,No.U1704282Medical Research of Council,No.MR/M015696/1.
文摘BACKGROUND Multiple sites of metastasis and desmoplastic reactions in the stroma are key features of human pancreatic cancer(PC).There are currently no simple and reliable animal models that can mimic these features for accurate disease modeling.AIM To create a new xenograft animal model that can faithfully recapitulate the features of human PC.METHODS Interleukin 2 receptor subunit gamma(IL2RG)gene knockout Syrian hamster was created and characterized.A panel of human PC cell lines were transplanted into IL2RG knockout Syrian hamsters and severe immune-deficient mice subcutaneously or orthotopically.Tumor growth,local invasion,remote organ metastasis,histopathology,and molecular alterations of tumor cells and stroma were compared over time.RESULTS The Syrian hamster with IL2RG gene knockout(named ZZU001)demonstrated an immune-deficient phenotype and function.ZZU001 hamsters faithfully recapitulated most features of human PC,in particular,they developed metastasis at multiple sites.PC tissues derived from ZZU001 hamsters displayed desmoplastic reactions in the stroma and epithelial to mesenchymal transition phenotypes,whereas PC tissues derived from immune-deficient mice did not present such features.CONCLUSION ZZU001 hamsters engrafted with human PC cells are a superior animal model compared to immune-deficient mice.ZZU001 hamsters can be a valuable animal model for better understanding the molecular mechanism of tumorigenesis and metastasis and the evaluation of new drugs targeting human PC.
基金The project supported by the National Natural Science Foundation of China
文摘Fine powders of γ-Fe_2O_3,doped with Y_2O_3,CeO_2,Eu_2O_3 or Tb_2O_3 have been prepared by the chemical co-precipitation method.The sensitivity of gas sensation has been measured with respect to the relative resist- ance change in the ceramic matrix upon introduction of inflammable gases.The structure of the materials has been studied with X-ray diffraction spectroscopy(XRD),electron diffraction spectroscopy( ED) and transmis- sion electron microscopy(TEM).The addition of rare earth oxides,which improves ceramic microstructure of γ-Fe_2O_3,improves gas sensitivity of γ-Fe_2O_3.The stability can be increased because of the increase of phase transition temperature.In addition,the selectivity of gas sensation of γ-Fe_2O_3 can be improved because of the variation of rare earth oxides.
基金supported by the National Natural Science Foundation of China(No.30971244)
文摘Mitofusin2 （Mfn2） plays a pivotal role in the proliferation and apoptosis of vascular smooth muscle cells （VSMCs）. The purpose of this study was to investigate the effects of Mfn2 on the traffick- ing of intracellular cholesterol in the foam ceils derived from rat VSMCs （rVSMCs） and also to investigate the effects of Mfn2 on the expression of adenosine triphosphate-binding cassette subfamily A member 1 （ABCA1）, adenosine triphosphate-binding cassette subfamily G member 1 （ABCG1） and peroxisome proliferator-activated receptor gamma （PPARy）. The rVSMCs were co-cultured with oxi- dized low density lipoprotein （LDL, 80 ~tg/mL） to produce foam cells and cholesterol accumulation in cells. Before oxidized LDL treatment, different titers （20, 40 and 60 pfu/cell） of recombinant adenovirus containing Mfn2 gene （Adv-Mfn2） were added into the culture medium for 24 h to transfect the Mfn2 gene into the rVSMCs. Then the cells were harvested for analyses. The protein expression of Mfn2 was significantly higher in Adv-Mfn2-transfected group than in untransfected group （P〈0.05）, and the ex- pression levels significantly increased when the titer of Adv-Mfn2 increased （P〈0.05）. At 24 or 48 h af- ter oxidized LDL treatment, rVSMCs became irregular and their nuclei became larger, and their plasma abounded with red lipid droplets. However, the number of red lipid droplets was significantly decreased in Adv-Mfn2-transfected group as compared with untransfected group. At 48 h after oxidized LDL treatment, the intracellular cholesterol in rVSMCs was significantly increased （P〈0.05）, but it was sig- nificantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）, and it also significantly decreased when the titer of Adv-Mfn2 increased （P〈0.05）. The mRNA and pro- tein expression levels of ABCA1 and ABCG1 were significantly increased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. Though the mRNA and protein expression levels of PPARy was not significantly increased （P〉0.05）, the phosporylation levels of PPARy were signifi- cantly decreased in Adv-Mfn2-transfected group as compared with untransfected group （P〈0.05）. These results suggest that the transfection of Adv-Mfn2 can significantly reduce intracellular cholesterol in oxidized LDL-induced rVSMCs possibly by decreasing PPAR＇/phosporylation and then increasing pro- tein expression levels of ABCAI and ABCG1, which may be helpful to suppress the formation of foam cells.
基金Thisstudywassupportedbythe" 9. 5"MilitaryMedicalResearchFoundationofChina (No 96M0 2 1)
文摘Objective To investigate the kinetics and the magnitude of intragraft gene expression of interleukin-2(IL-2), interferon-gamma (IFN-y), perforin and granzyme B, and intragraft expression of interieukin-2receptor (IL-2R) and intercellular adhesion molecule-1 ( ICAM-1 ) during acute rejection episodes, and to analyze the changes in apoptosis in small intestinal allograft rejection.Methods Heterotopic small intestine transplantation was performed with inbred rats F344/N (RT11) and Wistar/A (RT1-Ak, RT1-Ed). All recipients were divided into four groups: group 1 : Wistar, native control;group 2: Wistar→Wistar; group 3: F344→Wistar and group 4: F344→Wistar + cyclosporine A (6 mg·kg-1 ·d-1 I.M. ). The grafts were harvested on postoperative days (PODs) 3, 5 and 7. All samples were examined pathologically. Intragraft mRNA expression of IL-2, IFN-γ, perforin and granzyme B were detected with reverse transcriptase polymerase chain reaction (RT-PCR) and intragraft expression of IL-2R and ICAM-1 were stained using immunohistochemistry. We also analyzed the change in apoptosis rejection with terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL).Results Mild acute rejection occurred on POD 3 in the ailograft group, moderate acute rejection on POD 5, and severe acute rejection on POD 7, while none of the isografts had histological evidence of acute rejection. Cyclosporine A could effectively control rejection. Gene expression was virtually negative in the native control. Only on POD 5 was IL-2 mRNA expression of ailografts significantly higher than that of isografts ( P ＜ 0.05). IFN-γ mRNA expression was significantly higher than that of the control groups ( P ＜0.01 ) on PODs 3, 5 and 7, and the level of perforin and granzyme B mRNA expression reached significantly higher levels than in the other two control groups on POD 5 and POD 7. Intragraft IL-2Rexpression of the allograft was significantly higher than that of the other three control groups. Only on POD 3 was intragraft ICAM-1 expression of allografts significantly higher than isografts. The number of apoptotic cells per crypt of allografts was significantly higher than that of the other three control groups on POD 3 and POD 5 ( P ＜ 0.01 ).Conclusion Transcription of IL-2, IFN-γ, perforin and granzyme B, and expression of IL-2R and ICAM-1as well as apoptosis of epithelial cells of the grafts play an important role in small intestine allograft rejection.Intragraft gene expression of IFN-γ and intragraft expression of IL-2R as well as apoptotic epithelial cells may become a specific and sensitive diagnostic method of clinical value. Furthermore, therapeutic strategies to alter these molecules in small intestine transplantation may improve the outcome of current antirejection therapy.
基金This study was supported by-a gran-t of the Natural Science Foundation of Shanghai （No. 05ZR14156）. The authors have no conflict of interest.
文摘Background Pioglitazone is effective in nonalcoholic steatohepatitis （NASH）, but the mechanisms of action are not completely understood. This study was designed to investigate the effects of pioglitazone on hepatic nuclear factor-kappa B （NF-KB） and cyclooxygenases-2 （COX-2） expression in NASH rats. Methods Thirty Sprague-Dawley male rats were randomly assigned to a control group （n=10）, NASH group （n=10）, and pioglitazone treatment group （n=10）. Liver tissues were processed for histology by hematoxylin ＆ eosin and Masson stained. Serum alanine aminotransferase （ALT）, cholesterol, triglyceride, fasting blood glucose （FBG）, fasting insulin （FINS） levels and biochemical parameters of antioxidant enzyme activities, tumor necrosis factor alpha （TNF-a）, prostaglandin E2 （PGE2） levels in serum and liver were measured. The mRNA and protein expression of peroxisome proliferator-activated receptor gamma （PPARy）, NF-KB and COX-2 were determined by real-time polymerase chain reaction, Western blotting and immunohistochemistry. One-way analysis of variance （ANOVA） and Wilcoxon＇s signed-rank test was used for the statistical analysis. Results There were severe steatosis, moderate inflammatory cellular infiltration and fibrosis in NASH rats. After pioglitazone treatment, steatosis, inflammation and fibrosis were significantly improved compared with the NASH group （X2=20.40, P 〈0.001; X2=20.17, P 〈0.001; X2=13.98, P=0.002）. Serum ALT, cholesterol, triglyceride, FBG, FINS levels were significantly elevated in the NASH group （P 〈0.05）. In the NASH group, total anti-oxidation competence （T-AOC）, superoxide dismutase （SOD）, catalase （CAT）, glutathione peroxidase （GSH-PX） and malondialdehyde （MDA） levels in serum and liver were conspicuous disordered than those parameters in the control group. Meanwhile, TNF-a and PGE2 levels in serum and liver were significantly increased compared with the control group. Immunohistochemistry showed NF-KB and COX-2 expression in liver was significantly elevated. However, PPARy level was decreased in the NASH group. Real-time PCR and Western blotting revealed mRNA and protein expression of COX-2 were increased in the NASH group compared with the control group （0.57±0.08 vs. 2.83±0.24; 0.38±0.03 vs. 1.00±0.03, P 〈0.001 and P=-0.004, respectively）. After pioglitazone intervention, all of those parameters markedly improved （P 〈0.05 or P 〈0.01）. Conclusion Down-regulating hepatic NF-KB and COX-2 expression, at least in part, is one of the possible therapeutic mechanisms of pioglitazone in NASH rats.
基金supported by the Shanghai Science&Technology Commission(18140902502)the National Key Research and Development Program of China(2016YFC1303100)+2 种基金the National Natural Science Foundation of China(81472423)the Shanghai Clinical and Medical Center of Key Program(2017ZZ01016)the Shanghai Science and Technology Innovation Project of Traditional Chinese Medicine(ZYKC201701020).
文摘Background:The aim of this study is to assess the effect of baicalein on chronic stress-mediated ovarian dysfunction in a mouse model.Methods:Forty female C57BL/6 mice were randomly divided into four groups as follows:the normal saline group(control,n=10),the daily stress group(daily stress,n=10),the baicalein group(baicalein,n=10),and the daily stress+baicalein group(daily stress+baicalein,n=10).For the daily stress model,we used a restricted stress model.Baicalein(10 mg/kg)was administered by gavage every day,and control mice received normal saline equivalently.Biopsy specimens were harvested after 4 weeks.Measurement of norepinephrine(NE)in serum was performed to assess the psychological stress level of the mice.In addition,histological changes of the uterus and ovaries and the levels of anti-Müllerian hormone(AMH)in serum were assessed to evaluate changes in ovarian function.To detect the underlying mechanisms of the amelioration of baicalein in chronic stress-mediated ovarian dysfunction,immunohistochemical methods,and quantitative real-time polymerase chain reaction were applied to determine the expression of gamma-aminobutyric acid(GABA)receptors.Results:Compared with values in the control group,serum NE concentrations were significantly increased(P<0.001),AMH concentrations were markedly decreased(P<0.01),the thickness of the endometrium was clearly reduced,and the percentage of atretic follicles was significantly increased in the daily stress group(P<0.001),indicating that the chronic stress model was successfully established.In contrast,compared with values in the daily stress group,serum NE concentrations were significantly reduced(P<0.001),AMH concentrations were significantly enhanced(P<0.05),the thickness of the endometrium was clearly increased,and the percentage of atretic follicles was significantly reduced(P<0.001)in the daily stress+baicalein group,indicating that baicalein clearly attenuated the ovarian dysfunction mediated by chronic stress.Moreover,the expression of the GABAB2 receptor in the daily stress group was significantly reduced(P<0.01).In contrast,treatment with baicalein resulted in increased expression of the GABAB2 receptor(P<0.01).Conclusions:Treatment with baicalein ameliorates the enhancing effect of chronic stress on ovarian dysfunction,and the mechanism can be attributed,in part,to the increased expression of the GABAB2 receptor.
