Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1...Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and matrix metalloproteinase-13 （ MMP-13 ） in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone （25-800 mg · kg^-l · d^-1 ）, dexamethasone （3 mg/kg）, or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg · kg^-1 · d^-1 at 7 days or 14 daYs after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in luffg tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxypro- line. Expression of proteins of TGF-β1 TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg· kg^- 1 · d ^- 1, pirfenidone had significant anti-fibrotic effects for bleomy- cin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg · kg^-1 ·d^ -1（ HE： P 〈 0. 01, P 〈 0.01, and P = 0.064; sirius red： P 〈0.05, P 〈 0.01, and P 〈 0.05 ; hydroxyproline： P = 0.595, P 〈 0.01, and P = 0.976）. Pirfenidone at a dosage of 50 mg · kg^- l · d^-1 inhibited protein expression of TGF-131 and TIMP-1 in lung tissue in the early phase （0.79 and 0.75 times of control group）, but had no effect on ex- nr^eelnn nf MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg · kg^-1 · d^-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-131 and TIMP-β1 in lung tissue.展开更多
Hypoxia and transforming growth factor-β1 （TGF-β1） increase vascular endothelial growth factor A （VEGFA） expression in a number of malignancies. This effect of hypoxia and TGF-β1 might be responsible for tumor ...Hypoxia and transforming growth factor-β1 （TGF-β1） increase vascular endothelial growth factor A （VEGFA） expression in a number of malignancies. This effect of hypoxia and TGF-β1 might be responsible for tumor progression and metastasis of advanced prostate cancer. In the present study, TGF-β1 was shown to induce VEGFA165 secretion from both normal cell lines （HPV7 and RWPE1） and prostate cancer cell lines （DU 145 and PC3）. Conversely, hypoxia-stimulated VEGFA165 secretion was observed only in prostate cancer cell lines. Hypoxia induced TGF-β1 expression in PC3 prostate cancer cells, and the TGF-β1 type I receptor （ALK5） kinase inhibitor partially blocked hypoxia-mediated VEGFA16s secretion. This effect of hypoxia provides a novel mechanism to increase VEGFA expression in prostate cancer cells. Although autocrine signaling of VEGFA has been implicated in prostate cancer progression and metastasis, the associated mechanism is poorly characterized. VEGFA activity is mediated via VEGF receptor （VEGFR） 1 （Fit-l） and 2 （FIk-I/KDR）. Whereas VEGFR-1 mRNA was detected in normal prostate epithelial cells, VEGFR-2 mRNA and VEGFR protein were expressed only in PC3 cells. VEGFA165 treatment induced phosphorylation of extracellular signal-regulated kinase 1/2 （ERKI/2） in PC3 cells but not in HPV7 cells, suggesting that the autocrine function of VEGFA may be uniquely associated with prostate cancer. Activation of VEGFR-2 by VEGFA165 was shown to enhance migration of PC3 cells. A similar effect was also observed with endogenous VEGFA induced by TGF-β1 and hypoxia. These findings illustrate that an autocrine loop of VEGFA via VEGFR-2 is critical for the tumorigenic effects of TGF-β1 and hypoxia on metastatic prostate cancers.展开更多
Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （...Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.展开更多
New Zealand (NZ) young rabbits with the administration of insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) with and without mandibular anterior repositioning appliances are explored for th...New Zealand (NZ) young rabbits with the administration of insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) with and without mandibular anterior repositioning appliances are explored for the growth of the mandibular condylar cartilage (MCC). 32 growing NZ and rabbits were divided into 4 groups: the group with saline injection in TMJ, the group which received growth factor injection in TMJ, the group which received anterior positioning appliance and the group which received growth factors injection as well as mandibular repositioning appliance. Gene expression was studied by real-time RT-PCR and cartilage growth by histomorphometry. Administration of growth factors along with mandibular repositioning appliances has induced 1) 1.70-fold expression of Col-2Agene (p value < 0.0005) and 2) 1.47-fold expression of Col-10Agene (p value < 0.0005). In contrast, administration of only mandibular repositioning appliances induced 1) 1.28-fold expression of Col-2Agene (p value < 0.0005) and 2) merely 0.62-fold expression of Col-10Agene (p value < 0.0005), while administration of growth factors only induced 1) mere 0.56-fold expression of Col-2Agene (p value 10A gene (p value growth factors along with mandibular repositioning appliances causes an increase in genetic expressions which have been corroborated by histomorphometry and validated by statistical analysis, during an accelerated growth of mandibular condylar cartilage. Administration of growth factors in the TMJ could provide a synergistic role along with mandibular repositioning appliances for treatment of mandibular retrognathism as well as disorders on the MCC.展开更多
Objective:To observe the influence of the the transforming growth factorβ1(TGF-β1)eve drops on rabbit aqueous humor TGF-β1 concentration,and to analyze the best drug concentration.Methods:A total of 30 New Zealand ...Objective:To observe the influence of the the transforming growth factorβ1(TGF-β1)eve drops on rabbit aqueous humor TGF-β1 concentration,and to analyze the best drug concentration.Methods:A total of 30 New Zealand white rabbits were randomly divided into5 groups with 6 in each.Habits in control group had PBS eye drops,group A,B.C,D adopted TGF-β1 eye drops at 0.5,1.0.2.0.4.0 mg/L,respectively.4 times a day.Aqueous humor of right eye was extracted 1 week after administration lo delect concentration changes of TGF-β1 by ELISA;rabbits in fpur hroups adopted 2.0 mg/L eye drops to left eyes 4 times a day,0.2 mL aqueous humor was extracted left eye at the scheduled time point 0,30 min,2 h,4 h,24 h for testing,the slit lamp was used to observe the cornea,chamber and lens.Results:No obvious pathological changes in conjunctiva,cornea,rabbit conjunctival,anterior chamber,and the lens was found.Concentration of TGF-β1 in rabbit aqueous humor in C.D group was significantly higher than the control group(P<0.05).Conclusions:TGF-β1 eye drops at 2.0 mg/L.4.0 mg/L can significantly increase concentration of TGF-β1 in rabbit aqueous humor,withe good ocular surfac permeability.展开更多
AIM: To estimate the levels of serum cytokines in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC) patients in order to evaluate their usefulness as possible biomarkers.METHODS: The study included 1...AIM: To estimate the levels of serum cytokines in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC) patients in order to evaluate their usefulness as possible biomarkers.METHODS: The study included 167 Caucasian patients: 74 with PDAC(28 men and 42 women, aged 30-88 years), 78 with CP(50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor(TGF)-β1, HA and s-Fr were measured in patients with CP(n = 78), PDAC(n = 74) and healthy controls(n = 15) using ELISA(Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification.RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level(1066 ± 582and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr(2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA(199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course(2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group(986 vs 839, P = 0.043). CONCLUSION: Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.展开更多
AIM： To investigate the anti-fibrosis effect of rosmarinic acid（RA） in pterygium epithelial cells（PECs） to determine if RA is a potent agent for treating pterygium.METHODS： The PECs（1×10-4 cells/mL） were ...AIM： To investigate the anti-fibrosis effect of rosmarinic acid（RA） in pterygium epithelial cells（PECs） to determine if RA is a potent agent for treating pterygium.METHODS： The PECs（1×10-4 cells/mL） were treated with 100 μmol/L of RA for 1, 3 and 6h. After RA treatment, the cell viability was determined by staining with acridine orange/DAPI and analysis via a NucleoC ounter NC-3000. The protein expression levels of type I collagen, transforming growth factor beta-1（TGF-β1）, TGF-β type Ⅱ receptor（TGF-βRⅡ）, p-Smad1/5, p-Smad2, p-Smad3, and Smad4 of the cell lysates were measured by Western blot analysis.RESULTS： The cell viability of PECs was significantly decreased after RA treatment（P〈0.01）. As the result, RA reduced the protein expression of typeⅠcollagen and TGF-β1 of PECs. Additionally, RA also inhibited TGF-β1/Smad signaling by decreasing the protein expressions of TGF-βRII, p-Smad1/5, p-Smad2, p-Smad3, and Smad4.CONCLUSION： This study demonstrate that RA could inhibit fibrosis of PECs by down-regulating type I collagen expression and TGF-β1/Smad signaling. Therefore, RA is a potent therapeutic agent for the treatment of pterygium.展开更多
Astragalus mongholicus （AM） derived from the dry root ofAstragalus membranaceus Bge. var. mongolicus （Bge.） Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of...Astragalus mongholicus （AM） derived from the dry root ofAstragalus membranaceus Bge. var. mongolicus （Bge.） Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction （UUO）. We divided 48 Sprague-Dawley rats randomly into 4 groups： sham-operated group （Sham）, untreated UUO group, AM-treated （10 g/（kg.d）） UUO group, and losartan-treated （20 mg/（kg.d）） UUO group as positive control. Haematoxylin ＆ eosin （HE） and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin （FN）, type I collagen （coil）, hepatocyte growth factor （HGF）, transforming growth factor-β1 （TGF-β1）, and eL-smooth muscle actin （α-SMA） were analyzed by real-time polymerase chain reaction （PCR）, immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and coil from UUO by reducing the expressions of TGF-β1 and α-SMA （P〈0.05）, whereas HGF increased greatly with AM treatment （P〈0.05）. Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition ofmyofibroblast activation, inducing of HGF and reducing of TGF-β1 expression.展开更多
Objective: To evaluate the antioxidation of dihydrobiopterin reductase and to explore the effect of A278C mutation of the quinoid dihydropteridine reductase(QDPR) gene on its antioxidant activity. Methods: First, plas...Objective: To evaluate the antioxidation of dihydrobiopterin reductase and to explore the effect of A278C mutation of the quinoid dihydropteridine reductase(QDPR) gene on its antioxidant activity. Methods: First, plasmids with different genes(wild and mutant QDPR) were constructed. After gene sequencing, they were transfected into human kidney cells(HEK293T). Then, the intracellular production of reactive oxygen species(ROS) and tetrahydrobiopterin(BH4) was detected after cells were harvested. Activations of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4), glutathione peroxidase 3(GPX3), and superoxide dismutase 1(SOD1) were analyzed to observe the oxidative stress after transfection. The expression of the neuronal nitric oxide synthase(n NOS) gene was analyzed by semiquantitative reverse-transcription polymerase chain reaction(RT-PCR). We also detected the activation of transforming growth factor β1(TGF-β1) by enzyme-linked immunosorbent assay(ELISA) to observe the connection of TGF-β1 and oxidative stress. Results: The exogenous wild-type QDPR significantly decreased the expression of n NOS, NOX4, and TGF-β1 and induced the expression of SOD1 and GPX3, but the mutated QDPR lost this function and resulted in excessive ROS production. Our data also suggested that the influence on the level of BH4 had no significant difference between mutated and the wild-type QDPR transfection. Conclusions: Wild-type QDPR played an important role in protecting against oxidative stress, but mutant QDPR failed to have these beneficial effects.展开更多
基金Supported by National Ministry of Education Doctor Foundation of China(20020023045)
文摘Objective To investigate the optimal dosage of pirfenidone for the treatment of pulmonary fibrosis induced by bleomycin in Wistar rats, and the alteration of expressions of transforming growth factor beta-1 （ TGF-β1 ）, tissue inhibitor of metalloproteinase-1 （ TIMP-1 ）, and matrix metalloproteinase-13 （ MMP-13 ） in lung tissue. Methods Male Wistar rats were endotracheally instilled with bleomycin or normal saline. Pirfenidone （25-800 mg · kg^-l · d^-1 ）, dexamethasone （3 mg/kg）, or 1% carboxymethylcellulose sodium were given daily by feed 2 days before instillation of bleomycin. Groups T7 and T14 were fed pirfenidone 50 mg · kg^-1 · d^-1 at 7 days or 14 daYs after bleomycin instillation. Lungs were harvested at 28 days after bleomycin instillation. Patholological changes in luffg tissues were evaluated with HE staining. Lung collagen was stained by sirius red and measured by content of hydroxypro- line. Expression of proteins of TGF-β1 TIMP-1, and MMP-13 were detected by Western blotting. Results At doses of 25, 50, and 100 mg· kg^- 1 · d ^- 1, pirfenidone had significant anti-fibrotic effects for bleomy- cin-induced rat pulmonary fibrosis, and these effects were most significantly attenuated at the dosage of 50 mg · kg^-1 ·d^ -1（ HE： P 〈 0. 01, P 〈 0.01, and P = 0.064; sirius red： P 〈0.05, P 〈 0.01, and P 〈 0.05 ; hydroxyproline： P = 0.595, P 〈 0.01, and P = 0.976）. Pirfenidone at a dosage of 50 mg · kg^- l · d^-1 inhibited protein expression of TGF-131 and TIMP-1 in lung tissue in the early phase （0.79 and 0.75 times of control group）, but had no effect on ex- nr^eelnn nf MMP-13. Conclusion Low dose pirfenidone, especially at dosage of 50 mg · kg^-1 · d^-1, has significant anti-fibrotic effects on bleomycin-induced rat pulmonary fibrosis. Pirfenidone partially inhibits the enhancement of the expression of TGF-131 and TIMP-β1 in lung tissue.
文摘Hypoxia and transforming growth factor-β1 （TGF-β1） increase vascular endothelial growth factor A （VEGFA） expression in a number of malignancies. This effect of hypoxia and TGF-β1 might be responsible for tumor progression and metastasis of advanced prostate cancer. In the present study, TGF-β1 was shown to induce VEGFA165 secretion from both normal cell lines （HPV7 and RWPE1） and prostate cancer cell lines （DU 145 and PC3）. Conversely, hypoxia-stimulated VEGFA165 secretion was observed only in prostate cancer cell lines. Hypoxia induced TGF-β1 expression in PC3 prostate cancer cells, and the TGF-β1 type I receptor （ALK5） kinase inhibitor partially blocked hypoxia-mediated VEGFA16s secretion. This effect of hypoxia provides a novel mechanism to increase VEGFA expression in prostate cancer cells. Although autocrine signaling of VEGFA has been implicated in prostate cancer progression and metastasis, the associated mechanism is poorly characterized. VEGFA activity is mediated via VEGF receptor （VEGFR） 1 （Fit-l） and 2 （FIk-I/KDR）. Whereas VEGFR-1 mRNA was detected in normal prostate epithelial cells, VEGFR-2 mRNA and VEGFR protein were expressed only in PC3 cells. VEGFA165 treatment induced phosphorylation of extracellular signal-regulated kinase 1/2 （ERKI/2） in PC3 cells but not in HPV7 cells, suggesting that the autocrine function of VEGFA may be uniquely associated with prostate cancer. Activation of VEGFR-2 by VEGFA165 was shown to enhance migration of PC3 cells. A similar effect was also observed with endogenous VEGFA induced by TGF-β1 and hypoxia. These findings illustrate that an autocrine loop of VEGFA via VEGFR-2 is critical for the tumorigenic effects of TGF-β1 and hypoxia on metastatic prostate cancers.
基金supported by grants from the National Nature Science foundation of China(Grant Nos.30872912 and 30830108)
文摘Aim To determine the effect of local simvastatin application on the mRNA expression level of transforming growth factor-β1 （TGF-β1）, bone morphogenetic protein-2 （BMP-2） and vascular endothelial growth factor （VEGF） in the tooth sockets of rat. Methodology Forty-eight male Wistar rats were randomly divided into experimental and control groups （n=24）. Polylactic acid/polyglycolic acid copolymer carriers, with or without simvastatin, were implanted into extraction sockets of right mandibular incisors. The expression of TGF-β1, BMP-2 and VEGF mRNA was determined by in situ hybridization in the tooth extraction socket at five days, one week, two weeks and four weeks after implantation. Results The fusiform stroma cells in the tooth extraction socket began to express TGF-β1, BMP-2 and VEGF mRNA in both experimental and control groups from one week after tooth extraction until the end of experiment. The expression of TGF-131 and BMP-2 mRNA in the experimental group was significantly up-regulated after one, two and four weeks, and expression of VEGF mRNA was significantly increased after one and two weeks compared with that in the control group. Conclusion The findings indicate that local administration of simvastatin can influence alveolar bone remodeling by regulating the expression of a school of growth factors which are crucial to osteogenesis in the tooth extraction socket.
文摘New Zealand (NZ) young rabbits with the administration of insulin-like growth factor (IGF-1) and transforming growth factor-β (TGF-β) with and without mandibular anterior repositioning appliances are explored for the growth of the mandibular condylar cartilage (MCC). 32 growing NZ and rabbits were divided into 4 groups: the group with saline injection in TMJ, the group which received growth factor injection in TMJ, the group which received anterior positioning appliance and the group which received growth factors injection as well as mandibular repositioning appliance. Gene expression was studied by real-time RT-PCR and cartilage growth by histomorphometry. Administration of growth factors along with mandibular repositioning appliances has induced 1) 1.70-fold expression of Col-2Agene (p value < 0.0005) and 2) 1.47-fold expression of Col-10Agene (p value < 0.0005). In contrast, administration of only mandibular repositioning appliances induced 1) 1.28-fold expression of Col-2Agene (p value < 0.0005) and 2) merely 0.62-fold expression of Col-10Agene (p value < 0.0005), while administration of growth factors only induced 1) mere 0.56-fold expression of Col-2Agene (p value 10A gene (p value growth factors along with mandibular repositioning appliances causes an increase in genetic expressions which have been corroborated by histomorphometry and validated by statistical analysis, during an accelerated growth of mandibular condylar cartilage. Administration of growth factors in the TMJ could provide a synergistic role along with mandibular repositioning appliances for treatment of mandibular retrognathism as well as disorders on the MCC.
基金supported by National Natural Science Foundation Project(No.81371067)
文摘Objective:To observe the influence of the the transforming growth factorβ1(TGF-β1)eve drops on rabbit aqueous humor TGF-β1 concentration,and to analyze the best drug concentration.Methods:A total of 30 New Zealand white rabbits were randomly divided into5 groups with 6 in each.Habits in control group had PBS eye drops,group A,B.C,D adopted TGF-β1 eye drops at 0.5,1.0.2.0.4.0 mg/L,respectively.4 times a day.Aqueous humor of right eye was extracted 1 week after administration lo delect concentration changes of TGF-β1 by ELISA;rabbits in fpur hroups adopted 2.0 mg/L eye drops to left eyes 4 times a day,0.2 mL aqueous humor was extracted left eye at the scheduled time point 0,30 min,2 h,4 h,24 h for testing,the slit lamp was used to observe the cornea,chamber and lens.Results:No obvious pathological changes in conjunctiva,cornea,rabbit conjunctival,anterior chamber,and the lens was found.Concentration of TGF-β1 in rabbit aqueous humor in C.D group was significantly higher than the control group(P<0.05).Conclusions:TGF-β1 eye drops at 2.0 mg/L.4.0 mg/L can significantly increase concentration of TGF-β1 in rabbit aqueous humor,withe good ocular surfac permeability.
文摘AIM: To estimate the levels of serum cytokines in chronic pancreatitis(CP) and pancreatic ductal adenocarcinoma(PDAC) patients in order to evaluate their usefulness as possible biomarkers.METHODS: The study included 167 Caucasian patients: 74 with PDAC(28 men and 42 women, aged 30-88 years), 78 with CP(50 men and 21 women, aged 20-79 years) and 15 age-matched healthy controls hospitalized in the Department of Digestive Tract Diseases, Medical University of Lodz, Poland between 2006 and 2013. Serum MCP-1, transforming growth factor(TGF)-β1, HA and s-Fr were measured in patients with CP(n = 78), PDAC(n = 74) and healthy controls(n = 15) using ELISA(Corgenix United Kingdom Ltd R and D Systems). The severity of CP was assessed according to the Cambridge classification.RESULTS: Both patients with CP and PDAC had a significantly higher mean TGF-β1 serum level(1066 ± 582and 888 ± 356 vs 264 ± 93, P < 0.0001), mean s-Fr(2.42 ± 1.385 and 2.41 ± 1.275 vs 0.6 ± 0.370, P < 0.0001) and mean HA(199 ± 254 and 270 ± 358 vs 40 ± 26, P < 0.0001) compared to controls. There was no difference in mean MCP-1 between all the groups. There were no significant differences in any cytokine levels between the PC and PDAC groups. No significant differences between serum cytokines depending on age, gender or smoking status were found in CP patients. Mean s-Fr concentration was significantly higher in CP, lasting longer than 5 years compared to those with a shorter disease clinical course(2.639 ± 1.125 vs 1.870 ± 0.970, P < 0.03). There was no correlation between tumor size, localization or TNM classification and serum TGF-β1, MCP-1, s-Fr and HA levels in patients with PDAC. No significant differences between cytokines depending on diabetes presence in CP were found. Nevertheless, mean serum TGF-β1 concentration in PDAC patients was higher in those with diabetes compared to the remaining group(986 vs 839, P = 0.043). CONCLUSION: Serum TGF-β1, s-Fr and HA may be considered additional diagnostic markers of CP and PDAC. TGF-β1 may be useful to predict endocrine insufficiency in PDAC.
基金Supported by Ministry of Science and Technology,Taiwan(No.NSC 106-2314-B-212-004)
文摘AIM： To investigate the anti-fibrosis effect of rosmarinic acid（RA） in pterygium epithelial cells（PECs） to determine if RA is a potent agent for treating pterygium.METHODS： The PECs（1×10-4 cells/mL） were treated with 100 μmol/L of RA for 1, 3 and 6h. After RA treatment, the cell viability was determined by staining with acridine orange/DAPI and analysis via a NucleoC ounter NC-3000. The protein expression levels of type I collagen, transforming growth factor beta-1（TGF-β1）, TGF-β type Ⅱ receptor（TGF-βRⅡ）, p-Smad1/5, p-Smad2, p-Smad3, and Smad4 of the cell lysates were measured by Western blot analysis.RESULTS： The cell viability of PECs was significantly decreased after RA treatment（P〈0.01）. As the result, RA reduced the protein expression of typeⅠcollagen and TGF-β1 of PECs. Additionally, RA also inhibited TGF-β1/Smad signaling by decreasing the protein expressions of TGF-βRII, p-Smad1/5, p-Smad2, p-Smad3, and Smad4.CONCLUSION： This study demonstrate that RA could inhibit fibrosis of PECs by down-regulating type I collagen expression and TGF-β1/Smad signaling. Therefore, RA is a potent therapeutic agent for the treatment of pterygium.
基金(No.30170437) supported by the National Natural Science Foundation of China
文摘Astragalus mongholicus （AM） derived from the dry root ofAstragalus membranaceus Bge. var. mongolicus （Bge.） Hsiao is a widely used traditional Chinese medicine. The present study investigated the potential role of AM on renal fibrosis on a rat model of unilateral ureteral obstruction （UUO）. We divided 48 Sprague-Dawley rats randomly into 4 groups： sham-operated group （Sham）, untreated UUO group, AM-treated （10 g/（kg.d）） UUO group, and losartan-treated （20 mg/（kg.d）） UUO group as positive control. Haematoxylin ＆ eosin （HE） and Masson staining were used to study the dynamic histological changes of the kidneys 7 and 14 d after operation. The expressions of fibronectin （FN）, type I collagen （coil）, hepatocyte growth factor （HGF）, transforming growth factor-β1 （TGF-β1）, and eL-smooth muscle actin （α-SMA） were analyzed by real-time polymerase chain reaction （PCR）, immunohistochemistry staining, and Western blot. Results show that, similar to losartan, AM alleviated the renal damage and decreased the deposition of FN and coil from UUO by reducing the expressions of TGF-β1 and α-SMA （P〈0.05）, whereas HGF increased greatly with AM treatment （P〈0.05）. Our findings reveal that AM could retard the progression of renal fibrosis. The renoprotective effect of AM might be related to inhibition ofmyofibroblast activation, inducing of HGF and reducing of TGF-β1 expression.
基金supported by the National Natural Science Foundation of China(No.81130066)the International Cooperation and Exchanges of the National Natural Science Foundation of China(No.81620108031)
文摘Objective: To evaluate the antioxidation of dihydrobiopterin reductase and to explore the effect of A278C mutation of the quinoid dihydropteridine reductase(QDPR) gene on its antioxidant activity. Methods: First, plasmids with different genes(wild and mutant QDPR) were constructed. After gene sequencing, they were transfected into human kidney cells(HEK293T). Then, the intracellular production of reactive oxygen species(ROS) and tetrahydrobiopterin(BH4) was detected after cells were harvested. Activations of nicotinamide adenine dinucleotide phosphate oxidase 4(NOX4), glutathione peroxidase 3(GPX3), and superoxide dismutase 1(SOD1) were analyzed to observe the oxidative stress after transfection. The expression of the neuronal nitric oxide synthase(n NOS) gene was analyzed by semiquantitative reverse-transcription polymerase chain reaction(RT-PCR). We also detected the activation of transforming growth factor β1(TGF-β1) by enzyme-linked immunosorbent assay(ELISA) to observe the connection of TGF-β1 and oxidative stress. Results: The exogenous wild-type QDPR significantly decreased the expression of n NOS, NOX4, and TGF-β1 and induced the expression of SOD1 and GPX3, but the mutated QDPR lost this function and resulted in excessive ROS production. Our data also suggested that the influence on the level of BH4 had no significant difference between mutated and the wild-type QDPR transfection. Conclusions: Wild-type QDPR played an important role in protecting against oxidative stress, but mutant QDPR failed to have these beneficial effects.
