Aim: To investigate the transforming growth factor β_1 (TGF-β_1) and basic fibroblast growth factor (bFGF) expressions in benign prostatic hyperplasia (BPH) and the effect of β-radiation. Methods: TGF-β_1 and bFGF...Aim: To investigate the transforming growth factor β_1 (TGF-β_1) and basic fibroblast growth factor (bFGF) expressions in benign prostatic hyperplasia (BPH) and the effect of β-radiation. Methods: TGF-β_1 and bFGF expression was studied by means of an immunohistochemical method in nine normal prostatic (NP) tissues, 15 hyperplastic prostatic tissues and 35 hyperplastic prostatic tissues treated with ^(90)Sr/^(90)Y. Results: The TGF-β_1 expression in the epithelium and stroma of normal prostatic tissues was 68.2 % ± 10.5 % and 29.7 % ± 4.6 %, respectively, while it was 64.8 % ± 9.3 % and 28.6 % ± 4.1%, respectively, in hyperplastic prostatic tissues. Compared with the controls, TGF-β_1 expression in the epithelia and stroma of BPH treated with ^(90)Sr/^(90)Y increased significantly (P < 0.01). The bFGF expression in epithelia and stroma of normal prostatic tissues was 17.4 % ± 3.7 % and 42.5 % ± 6.8 %, respectively, and was 46.3 % ± 8.2 % and 73.2 % ± 12.1%, respectivley, in hyperplastic prostatic tissues. Compared with the controls, expressions of bFGFin the epithelia and stroma of BPH treated with a ^(90)Sr/^(90)Y prostatic hyperplasia applicator decreased significantly (P < 0.01). Conclusion: Exposure of β-rays had noticeable effects on BPH tissues, enhancing TGF-β_1 expression and inhibiting bFGF expression.展开更多
Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined wit...Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined with differential adherence to isolate and culture Sprague-Dawley(SD)suckling mouse Cardiac fibroblasys(CFB)in vitro.Divided into:blank group,blank rat serum group,model group,and LGZGD medicated serum group(5%、10%、20%).Except for blank group and blank rat serum group,they were stimulated with 5 ng/ml TGF-β1 for 12 hours,and then then intervene with LGZGD medicated serum(5%、10%、20%)and continue to culture for 24 hours.Use immunofluorescence and Western blot(WB)to detect the expression ofα-smooth muscle actin(α-SMA),Enzyme-linked immunosorbent assay(ELISA)and WB to detect type Ⅰ collagen(Collagen Ⅰ),type Ⅰ collagen(Collagen Ⅲ)and fibronectin(FN)expression.Results:Compared with the blank group,the expressions of Collagen Ⅰ,Collagen Ⅲ,α-SMA and FN in the model group were significantly increased(P<0.01);Compared with the model group,the expressions of Collagen Ⅰ and Collagen Ⅲ in each concentration group of the experiment were significantly reduced(P<0.01);the expression ofα-SMA and FN were significantly reduced(P<0.01).Conclusions:LGZGD has an inhibitory effect on collagen synthesis and the expression ofα-SMA and FN,indicating that the anti-fibrosis effect of LGZGD is related to it.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: MicroRNAs (miRNAs) are important regulators that play a key role in tumorigenesis and rumor progression. Transforming growth factor-β1 (TGF-β1) is involved in invasion and metastasis in many tumors. ...Objective: MicroRNAs (miRNAs) are important regulators that play a key role in tumorigenesis and rumor progression. Transforming growth factor-β1 (TGF-β1) is involved in invasion and metastasis in many tumors. In this study, we investigated the microRNAs (miRNA) profiles altered by TGF-β1 in gastric cancer (GC) cells. Methods: We detected the expression profiles of miRNA by miRNA microarray and quantitative real- time polymerase chain reaction. Migration and invasion, wound-healing assay, prediction of miRNA targets, Western blot and qRT-PCR analysis were carried out to determine the role of one selected miRNA, namely miR-193b, in affecting the biological behaviors of GC BGC823 cells. Results: Among 847 human miRNAs in the microarray, three miRNAs (miR-27a, miR-29b-1 and miR-194) were up-regulated and three (miR-574-3p, miR-193b and miR-130b) were down-regulated in BGC823 cells treated with TGF-β1 compared with control, miR-193b suppressed the invasion and metastasis of GC cells in vivo and in vitro, and down-regulated urokinase-type plasminogen activator (uPA) protein in GC cells. Conclusions: TGF-β1 altered miRNA expression profile in BGC823 cells. Among the altered miRNAs, TGF-β1 induced the down-regulation of miR-193b, which inhibited cell invasion and metastasis in vivo and in vitro, and down-regulated uPA protein in GC cells.展开更多
[Objectives]To study the effect of total flavonoids extracted from Polygonum perfoliatum L.(TFP)on immune-mediated liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide(BCG+LPS)in mice,and to explor...[Objectives]To study the effect of total flavonoids extracted from Polygonum perfoliatum L.(TFP)on immune-mediated liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide(BCG+LPS)in mice,and to explore its action mechanism.[Methods]60 Kunming mice were divided into normal group,model group,control group(bifendate)and TFP low,medium and high dose groups according to random number table method,with 10 mice in each group.On the first day of modeling,mice were injected with 0.2 mL of BCG solution(12.5 mg/mL)through the tail vein,and on the eleventh day,0.2 mL of LPS(37.5μg/mL)were injected into the tail vein to prepare a mouse model of immune-mediated liver injury;from the first day of modeling,the normal group and the model group were administered intragastrically with the corresponding volume of distilled water,and the bifendate group and the TFP high,medium,and low dose groups were administered intragastrically with the corresponding doses once a day for 11 d.After the last time administration,fasting but giving water for 16 h,took blood from eyes,then collected the liver tissue.The levels of alanine transaminase(ALT)and aspartate transaminase(AST)in serum were detected by biochemical method;transforming growth factor-β1(TGF-β1),intercellular adhesion molecule-1(ICAM-1),interleukin-6(IL-6)and interleukin-1β(IL-1β)expression levels in liver tissue were detected by enzyme-linked immunosorbent assay(ELISA);phosphorylated protein tyrosine kinase JAK-2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)protein expression levels were detected by Western Blot method;the degree of liver tissue lesions was detected by HE staining.[Results]Compared with the model group,the levels of ALT and AST in the serum of mice in each dose group of TFP(high dose 600 mg/kg,medium dose 400 mg/kg,and low dose 200 mg/kg)were reduced,and the activities of T-SOD and GSH-Px were increased;the content or expression ofβ1,ICAM-1,IL-6,IL-1βdecreased,and the expression of p-JAK2 and p-STAT3 protein decreased;pathological sections showed that the degree of inflammatory necrosis and the degree of lesions in the liver tissues of each dose group of TFP were reduced by varying degrees.[Conclusions]TFP has a protective effect on BCG+LPS-induced immune-mediated liver injury in mice.The mechanism may be related to regulating the phosphorylation level of JAK2 and inhibiting the inflammatory reaction,thereby regulating the TGF-β1/STAT3 signaling pathway and improving the immune-mediated liver injury.展开更多
Objective:To study the correlation between the expression of transforming growth factor-β1(TGF-β1),Rho A,SOX9 and renal interstitial fibrosis in rats with chronic kidney disease.Methods:Forty specific pathogen-free(...Objective:To study the correlation between the expression of transforming growth factor-β1(TGF-β1),Rho A,SOX9 and renal interstitial fibrosis in rats with chronic kidney disease.Methods:Forty specific pathogen-free(SPF)male SD rats were randomly divided into study group and control group,with 20 cases in each group.The study group was given adenine suspension by gavage,while the control group was given the same amount of saline by gavage.Blood,urine and renal tissue specimens were collected from all rats at 3rd and 6th weeks after modeling.The kidney weight,kidney weight/body weight,renal function indexes,the expression of TGF-β1,Rho A and SOX9 m RNA in renal tissues,Masson staining and renal interstitial fibrosis score were compared between the two groups.Pearson correlation was used to analyze the relationship between the renal interstitial fibrosis score and the expression of TGF-β1,Rho A and SOX9 m RNA in renal tissues of rats with chronic kidney disease.Results:The kidney weight and kidney weight/body weight of rats in the study group were higher than those in the control group at 3rd and 6th weeks after modeling(P<0.05).The quantitative levels of creatinine,urea nitrogen and 24-hour urinary protein in the study group were higher than those in the control group at 3rd and 6th weeks after modeling(P<0.05).The expression levels of TGF-β1,Rho A and SOX9 m RNA in renal tissues of rats in the study group were higher than those in the control group at 3rd and 6th weeks after modeling(P<0.05).The renal interstitial fibrosis score in the study group was higher than that in the control group at 3rd and 6th weeks after modeling(P<0.05).Pearson correlation analysis confirmed that the renal interstitial fibrosis score in rats with chronic kidney disease was positively correlated with the expression of TGF-β1,Rho A and SOX9 m RNA in renal tissues(P<0.05).Conclusion:The expression of TGF-β1,Rho A and SOX9 was abnormally high in rats with chronic kidney disease and was closely related to renal interstitial fibrosis,which may play a promoting role in the process of renal interstitial fibrosis.展开更多
Diabetic nephropathy is a major cause of end-stage renal disease (ESRD) in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; theref...Diabetic nephropathy is a major cause of end-stage renal disease (ESRD) in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin (90 mg/kg) in neonatal rats and then these rats were treated with rosiglitazone (1.0 mg/kg) in combination with glimepiride (0.5 mg/kg) or with pioglitazone (2.5 mg/kg) in combination with glimepiride (0.5 mg/kg). Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepiride is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-α signaling during the development of streptozotocin induced type 2 diabetic nephropathy.展开更多
Ivermectin is a US Food and Drug Administration(FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties.Although recent studies reported the possible anti-inflammatory activity of ivermectin ...Ivermectin is a US Food and Drug Administration(FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties.Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries,its potential therapeutic effect on pulmonary fibrosis(PF)has not been investigated.This study aimed to explore the ability of ivermectin(0.6 mg/kg)to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model.This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF.The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury,as manifested by the reduced infiltration of inflammatory cells,as well as decreased the inflammation and fibrosis scores.Intriguingly,ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-β1(TGF-β1)and fibronectin protein expression,highlighting its anti-fibrotic activity.This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome,as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),with a subsequent decline in the interleukin-1β(IL-1β)level.In addition,ivermectin inhibited the expression of intracellular nuclear factor-κB(NF-κB)and hypoxia‑inducible factor‑1α(HIF-1α)proteins along with lowering the oxidative stress and apoptotic markers.Altogether,this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin.These beneficial effects were mediated,at least partly,via the downregulation of TGF-β1 and fibronectin,as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1αand NF-κB.展开更多
文摘Aim: To investigate the transforming growth factor β_1 (TGF-β_1) and basic fibroblast growth factor (bFGF) expressions in benign prostatic hyperplasia (BPH) and the effect of β-radiation. Methods: TGF-β_1 and bFGF expression was studied by means of an immunohistochemical method in nine normal prostatic (NP) tissues, 15 hyperplastic prostatic tissues and 35 hyperplastic prostatic tissues treated with ^(90)Sr/^(90)Y. Results: The TGF-β_1 expression in the epithelium and stroma of normal prostatic tissues was 68.2 % ± 10.5 % and 29.7 % ± 4.6 %, respectively, while it was 64.8 % ± 9.3 % and 28.6 % ± 4.1%, respectively, in hyperplastic prostatic tissues. Compared with the controls, TGF-β_1 expression in the epithelia and stroma of BPH treated with ^(90)Sr/^(90)Y increased significantly (P < 0.01). The bFGF expression in epithelia and stroma of normal prostatic tissues was 17.4 % ± 3.7 % and 42.5 % ± 6.8 %, respectively, and was 46.3 % ± 8.2 % and 73.2 % ± 12.1%, respectivley, in hyperplastic prostatic tissues. Compared with the controls, expressions of bFGFin the epithelia and stroma of BPH treated with a ^(90)Sr/^(90)Y prostatic hyperplasia applicator decreased significantly (P < 0.01). Conclusion: Exposure of β-rays had noticeable effects on BPH tissues, enhancing TGF-β_1 expression and inhibiting bFGF expression.
基金National natural science foundation of China(No.81973844)。
文摘Objective:To explore the protective effect of Linggui Zhugan Decoction(LGZGD)medicated serum on myocardial fibrosis induced by transforming growth factor-β1(TGF-β1).Methods:Using enzyme digestion method,combined with differential adherence to isolate and culture Sprague-Dawley(SD)suckling mouse Cardiac fibroblasys(CFB)in vitro.Divided into:blank group,blank rat serum group,model group,and LGZGD medicated serum group(5%、10%、20%).Except for blank group and blank rat serum group,they were stimulated with 5 ng/ml TGF-β1 for 12 hours,and then then intervene with LGZGD medicated serum(5%、10%、20%)and continue to culture for 24 hours.Use immunofluorescence and Western blot(WB)to detect the expression ofα-smooth muscle actin(α-SMA),Enzyme-linked immunosorbent assay(ELISA)and WB to detect type Ⅰ collagen(Collagen Ⅰ),type Ⅰ collagen(Collagen Ⅲ)and fibronectin(FN)expression.Results:Compared with the blank group,the expressions of Collagen Ⅰ,Collagen Ⅲ,α-SMA and FN in the model group were significantly increased(P<0.01);Compared with the model group,the expressions of Collagen Ⅰ and Collagen Ⅲ in each concentration group of the experiment were significantly reduced(P<0.01);the expression ofα-SMA and FN were significantly reduced(P<0.01).Conclusions:LGZGD has an inhibitory effect on collagen synthesis and the expression ofα-SMA and FN,indicating that the anti-fibrosis effect of LGZGD is related to it.
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 Natural Science Foundation of China(No.81001080)Natural Science Foundation of China(No.30901452)
文摘Objective: MicroRNAs (miRNAs) are important regulators that play a key role in tumorigenesis and rumor progression. Transforming growth factor-β1 (TGF-β1) is involved in invasion and metastasis in many tumors. In this study, we investigated the microRNAs (miRNA) profiles altered by TGF-β1 in gastric cancer (GC) cells. Methods: We detected the expression profiles of miRNA by miRNA microarray and quantitative real- time polymerase chain reaction. Migration and invasion, wound-healing assay, prediction of miRNA targets, Western blot and qRT-PCR analysis were carried out to determine the role of one selected miRNA, namely miR-193b, in affecting the biological behaviors of GC BGC823 cells. Results: Among 847 human miRNAs in the microarray, three miRNAs (miR-27a, miR-29b-1 and miR-194) were up-regulated and three (miR-574-3p, miR-193b and miR-130b) were down-regulated in BGC823 cells treated with TGF-β1 compared with control, miR-193b suppressed the invasion and metastasis of GC cells in vivo and in vitro, and down-regulated urokinase-type plasminogen activator (uPA) protein in GC cells. Conclusions: TGF-β1 altered miRNA expression profile in BGC823 cells. Among the altered miRNAs, TGF-β1 induced the down-regulation of miR-193b, which inhibited cell invasion and metastasis in vivo and in vitro, and down-regulated uPA protein in GC cells.
基金Natural Science Foundation Project of Guangxi(2017GXNSFAA 198326)。
文摘[Objectives]To study the effect of total flavonoids extracted from Polygonum perfoliatum L.(TFP)on immune-mediated liver injury induced by bacillus Calmette-Guerin plus lipopolysaccharide(BCG+LPS)in mice,and to explore its action mechanism.[Methods]60 Kunming mice were divided into normal group,model group,control group(bifendate)and TFP low,medium and high dose groups according to random number table method,with 10 mice in each group.On the first day of modeling,mice were injected with 0.2 mL of BCG solution(12.5 mg/mL)through the tail vein,and on the eleventh day,0.2 mL of LPS(37.5μg/mL)were injected into the tail vein to prepare a mouse model of immune-mediated liver injury;from the first day of modeling,the normal group and the model group were administered intragastrically with the corresponding volume of distilled water,and the bifendate group and the TFP high,medium,and low dose groups were administered intragastrically with the corresponding doses once a day for 11 d.After the last time administration,fasting but giving water for 16 h,took blood from eyes,then collected the liver tissue.The levels of alanine transaminase(ALT)and aspartate transaminase(AST)in serum were detected by biochemical method;transforming growth factor-β1(TGF-β1),intercellular adhesion molecule-1(ICAM-1),interleukin-6(IL-6)and interleukin-1β(IL-1β)expression levels in liver tissue were detected by enzyme-linked immunosorbent assay(ELISA);phosphorylated protein tyrosine kinase JAK-2(p-JAK2),phosphorylated signal transducer and activator of transcription 3(p-STAT3)protein expression levels were detected by Western Blot method;the degree of liver tissue lesions was detected by HE staining.[Results]Compared with the model group,the levels of ALT and AST in the serum of mice in each dose group of TFP(high dose 600 mg/kg,medium dose 400 mg/kg,and low dose 200 mg/kg)were reduced,and the activities of T-SOD and GSH-Px were increased;the content or expression ofβ1,ICAM-1,IL-6,IL-1βdecreased,and the expression of p-JAK2 and p-STAT3 protein decreased;pathological sections showed that the degree of inflammatory necrosis and the degree of lesions in the liver tissues of each dose group of TFP were reduced by varying degrees.[Conclusions]TFP has a protective effect on BCG+LPS-induced immune-mediated liver injury in mice.The mechanism may be related to regulating the phosphorylation level of JAK2 and inhibiting the inflammatory reaction,thereby regulating the TGF-β1/STAT3 signaling pathway and improving the immune-mediated liver injury.
文摘Objective:To study the correlation between the expression of transforming growth factor-β1(TGF-β1),Rho A,SOX9 and renal interstitial fibrosis in rats with chronic kidney disease.Methods:Forty specific pathogen-free(SPF)male SD rats were randomly divided into study group and control group,with 20 cases in each group.The study group was given adenine suspension by gavage,while the control group was given the same amount of saline by gavage.Blood,urine and renal tissue specimens were collected from all rats at 3rd and 6th weeks after modeling.The kidney weight,kidney weight/body weight,renal function indexes,the expression of TGF-β1,Rho A and SOX9 m RNA in renal tissues,Masson staining and renal interstitial fibrosis score were compared between the two groups.Pearson correlation was used to analyze the relationship between the renal interstitial fibrosis score and the expression of TGF-β1,Rho A and SOX9 m RNA in renal tissues of rats with chronic kidney disease.Results:The kidney weight and kidney weight/body weight of rats in the study group were higher than those in the control group at 3rd and 6th weeks after modeling(P<0.05).The quantitative levels of creatinine,urea nitrogen and 24-hour urinary protein in the study group were higher than those in the control group at 3rd and 6th weeks after modeling(P<0.05).The expression levels of TGF-β1,Rho A and SOX9 m RNA in renal tissues of rats in the study group were higher than those in the control group at 3rd and 6th weeks after modeling(P<0.05).The renal interstitial fibrosis score in the study group was higher than that in the control group at 3rd and 6th weeks after modeling(P<0.05).Pearson correlation analysis confirmed that the renal interstitial fibrosis score in rats with chronic kidney disease was positively correlated with the expression of TGF-β1,Rho A and SOX9 m RNA in renal tissues(P<0.05).Conclusion:The expression of TGF-β1,Rho A and SOX9 was abnormally high in rats with chronic kidney disease and was closely related to renal interstitial fibrosis,which may play a promoting role in the process of renal interstitial fibrosis.
文摘Diabetic nephropathy is a major cause of end-stage renal disease (ESRD) in the general population. It is estimated that diabetic nephropathy will eventually develop in about 40% of all patients with diabetes; therefore, prevention is critical for delaying the development and progression of diabetic kidney disease. Despite extensive efforts, medical advances are still not successful enough to prevent the progression of the disease. In the present study, we focused on the comparison of combination therapies and whether they offered additional renoprotection. Type 2 diabetes mellitus was induced by intraperitoneally administering streptozotocin (90 mg/kg) in neonatal rats and then these rats were treated with rosiglitazone (1.0 mg/kg) in combination with glimepiride (0.5 mg/kg) or with pioglitazone (2.5 mg/kg) in combination with glimepiride (0.5 mg/kg). Diabetic nephropathy markers were evaluated by biochemical and ELISA kits and renal structural changes were examined by light microscopy and transmission electron microscopy. Results show that the combination of pioglitazone with glimepiride is more effective in amelioration of diabetic nephropathy than rosiglitazone with glimepiride drug therapy due to glycemic control, suppressing albumin excretion rate, total protein excretion rate and augmented TNF-α signaling during the development of streptozotocin induced type 2 diabetic nephropathy.
基金supported by Open access funding provided by the Science,Technology&Innovation Funding Authority(STDF)in cooperation with the Egyptian Knowledge Bank(EKB).
文摘Ivermectin is a US Food and Drug Administration(FDA)-approved antiparasitic agent with antiviral and anti-inflammatory properties.Although recent studies reported the possible anti-inflammatory activity of ivermectin in respiratory injuries,its potential therapeutic effect on pulmonary fibrosis(PF)has not been investigated.This study aimed to explore the ability of ivermectin(0.6 mg/kg)to alleviate bleomycin-induced biochemical derangements and histological changes in an experimental PF rat model.This can provide the means to validate the clinical utility of ivermectin as a treatment option for idiopathic PF.The results showed that ivermectin mitigated the bleomycin-evoked pulmonary injury,as manifested by the reduced infiltration of inflammatory cells,as well as decreased the inflammation and fibrosis scores.Intriguingly,ivermectin decreased collagen fiber deposition and suppressed transforming growth factor-β1(TGF-β1)and fibronectin protein expression,highlighting its anti-fibrotic activity.This study revealed for the first time that ivermectin can suppress the nucleotide-binding oligomerization domain(NOD)-like receptor family pyrin domain-containing protein 3(NLRP3)inflammasome,as manifested by the reduced gene expression of NLRP3 and the apoptosis-associated speck-like protein containing a caspase recruitment domain(ASC),with a subsequent decline in the interleukin-1β(IL-1β)level.In addition,ivermectin inhibited the expression of intracellular nuclear factor-κB(NF-κB)and hypoxia‑inducible factor‑1α(HIF-1α)proteins along with lowering the oxidative stress and apoptotic markers.Altogether,this study revealed that ivermectin could ameliorate pulmonary inflammation and fibrosis induced by bleomycin.These beneficial effects were mediated,at least partly,via the downregulation of TGF-β1 and fibronectin,as well as the suppression of NLRP3 inflammasome through modulating the expression of HIF‑1αand NF-κB.