BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have ...BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.展开更多
Objective: In women with pelvic organ prolapse (POP), decreased expression of transforming growth factor-beta 1 (TGF-β1) has been shown in POP tissues. However, no studies have evaluated plasma TGF-β1 levels in pati...Objective: In women with pelvic organ prolapse (POP), decreased expression of transforming growth factor-beta 1 (TGF-β1) has been shown in POP tissues. However, no studies have evaluated plasma TGF-β1 levels in patients with POP, so it is unknown whether they are also changed or not. Therefore, we compared plasma TGF-β1 levels in women with and without POP. Methods: Participants were 49 women with POP and 23 healthy control women. All participants were postmenopausal. We measured plasma TGF-β1 and compared data between patients with POP and controls, and between patients with uterine prolapse (UP, n = 19) and those with a cystocele (CC, n = 30). In addition, in patients, we assessed the POP quantification system (POP-Q) stage. Results: Plasma TGF-β1 levels were significantly lower in patients than in healthy controls. POP-Q stage was not significantly different between the UP and CC subgroups, but POP-Q stage IV was diagnosed in 63% of patients with UP and 7% of those with CC. Plasma TGF-β1 levels were significantly lower in the CC subgroup than in the UP subgroup. Conclusion: Plasma TGF-β1 is decreased in POP. It remains unclear whether the lower levels indicate a reduction in systemic TGF-β1 activity, but they can be assumed to reflect reduced TGF-β1 expression in POP tissues.展开更多
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
The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basi...The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF β 1 gene at different doses was transduced into the rat bone marrow derived MSCs to examine the effects of TGF β 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 μl lipofectamine mediated 1 μg TGF β 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine=1μg/3μl), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3 H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF β 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.展开更多
To study the osteogenic potential of cultured bone marrow stromal cells transfected with transforming growth factor β 1 gene in vitro , cultured BMSCs were transfected with the complexes of pcDNA 3 TGF β ...To study the osteogenic potential of cultured bone marrow stromal cells transfected with transforming growth factor β 1 gene in vitro , cultured BMSCs were transfected with the complexes of pcDNA 3 TGF β 1 and Lipofectamine Reagent in vitro . The cell proliferation was detected by MTT method and the morphological features of transfected BMSCs was observed. ALP stains and PNP method were used to measure ALP activity. In addition, the collagen type Ⅰ propeptides and mineralized matrixes were examined by immunohistochemical staining and tetracycline fluorescence labeling respectively. The morphological and biological characters of the transfected BMSCs were similar to those of osteoblasts and the cell proliferation was promoted. The cell layer displayed strong positive reaction for ALP stains and immunohistochemical staining. ALP activity and collagen type Ⅰ expression increased remarkably after transfection. Mineralized matrixes formed earlier and more in transfected BMSCs as compared with control group. It is concluded that transfecting with TGF β 1 gene could promote the osteogenic potential of cultured BMSCs.展开更多
The effects of heparin on the expression of transforming growth factor-β 1 (TGF-β 1) and two extracellular matrix components laminin (LN) and fibronectin (FN) in diabetic rat glomeruli were investigated. Twent...The effects of heparin on the expression of transforming growth factor-β 1 (TGF-β 1) and two extracellular matrix components laminin (LN) and fibronectin (FN) in diabetic rat glomeruli were investigated. Twenty-six rats were randomly divided into control group (C, n=8), diabetic group (D, n=9), and diabetes+heparin group (DH, n=9). After 8-week therapy of heparin (200 U once daily by abdominal injection), TGF-β 1, LN and FN expression in glomeruli was detected by immunohistochemical method. The results showed that the expression levels of TGF-β 1, LN and FN were higher in group D than in group C. It was found that heparin could reduce 24-h urinary albumin excretion and inhibit overexpression of TGF-β 1, LN and FN in glomeruli of diabetic rats. It suggested that the inhibitory effect of heparin on diabetic glomerular sclerosis was at least partly related with the inhibition of TGF-β 1 expression.展开更多
Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium ...Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium sulfate(DSS)-induced experimental colitis model.This study aimed to explore the effects of TL1A on human colonic fibroblasts.Methods A trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic(Tg)or wild-type(WT)mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis.The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell(PBMC)supernatant.The proliferation and activation of CCD-18Co cells were detected by BrdU assays,flow cytometry,immunocytochemistry and Western blotting.Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction(RT-qPCR).Results The level of collagen metabolism in the TNBS+ethyl alcohol(EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group.Transforming growth factor-β1(TGF-β1)and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group.The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A,and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4%at 24 h.TL1A promoted cell activation and increased the levels of COL1A2,COL3A1,and TIMP-1 in CCD-18Co cells.Treatment of CCD-18Co cells with TL1A increased the expression of TGF-β1 and p-Smad3.Conclusion TL1A promotes TGF-β1-mediated intestinal fibroblast activation,proliferation,and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway.展开更多
基金the Ethic Committee of Suzhou Hospital of Anhui Medical University(Approval No.C2024003).
文摘BACKGROUND Acute myeloid leukemia(AML)is a disease in which immature hematopoietic cells accumulate in the bone marrow and continuously expand,inhibiting hematopoiesis.The treatment and prognosis of this disease have always been unsatisfactory.AIM To investigate the correlation between vascular endothelial growth factor(VEGF)and transforming growth factor-β1(TGFβ1)expression and prognosis in older adults with AML.METHODS This study enrolled 80 patients with AML(AML group),including 36 with complete response(AML-CR),23 with partial response(AML-PR),and 21 with no response(AML-NR).The expression levels of VEGF and TGFβ1 were detected by reverse transcription polymerase chain reaction in bone marrow mononuclear cells isolated from 56 healthy controls.Kaplan-Meier analysis was performed to assess overall survival(OS)and progression-or disease-free survival(DFS).Prognostic risk factors were analyzed using a Cox proportional hazards model.RESULTS The AML group showed a VEGF level of 2.68±0.16.VEGF expression was lower in patients with AML-CR than those with AML-PR or AML-NR(P<0.05).TGFβ1 expression in the AML group was 0.33±0.05.Patients with AML-CR showed a higher TGFβ1 expression than those with AML-PR or AML-NR(P<0.05).VEGF and TGFβ1 expression in patients with AML was significantly correlated with the counts of leukocytes,platelets,hemoglobin,and peripheral blood immature cells(P<0.05);Kaplan-Meier survival analysis revealed that patients with high TGFβ1 expression had better OS and DFS than those with low TGFβ1 expression(P<0.05),whereas patients with low VEGF levels showed better OS and DFS than those with high VEGF levels(P<0.05).VEGF,TGFβ1,and platelet count were identified by the Cox proportional hazards model as independent risk factors for OS(P<0.05),while VEGF,TGFβ1,and white blood cell count were independent risk factors for DFS(P<0.05).CONCLUSION Decreased VEGF expression and increased TGFβ1 expression in patients with AML provide valuable references for determining and individualizing clinical treatment strategies.
文摘Objective: In women with pelvic organ prolapse (POP), decreased expression of transforming growth factor-beta 1 (TGF-β1) has been shown in POP tissues. However, no studies have evaluated plasma TGF-β1 levels in patients with POP, so it is unknown whether they are also changed or not. Therefore, we compared plasma TGF-β1 levels in women with and without POP. Methods: Participants were 49 women with POP and 23 healthy control women. All participants were postmenopausal. We measured plasma TGF-β1 and compared data between patients with POP and controls, and between patients with uterine prolapse (UP, n = 19) and those with a cystocele (CC, n = 30). In addition, in patients, we assessed the POP quantification system (POP-Q) stage. Results: Plasma TGF-β1 levels were significantly lower in patients than in healthy controls. POP-Q stage was not significantly different between the UP and CC subgroups, but POP-Q stage IV was diagnosed in 63% of patients with UP and 7% of those with CC. Plasma TGF-β1 levels were significantly lower in the CC subgroup than in the UP subgroup. Conclusion: Plasma TGF-β1 is decreased in POP. It remains unclear whether the lower levels indicate a reduction in systemic TGF-β1 activity, but they can be assumed to reflect reduced TGF-β1 expression in POP tissues.
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.
基金This project was supported by a grant from NationalNatural Science Foundation of China (No. 30 170 2 70 )
文摘The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF β 1 gene at different doses was transduced into the rat bone marrow derived MSCs to examine the effects of TGF β 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 μl lipofectamine mediated 1 μg TGF β 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine=1μg/3μl), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3 H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF β 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.
文摘To study the osteogenic potential of cultured bone marrow stromal cells transfected with transforming growth factor β 1 gene in vitro , cultured BMSCs were transfected with the complexes of pcDNA 3 TGF β 1 and Lipofectamine Reagent in vitro . The cell proliferation was detected by MTT method and the morphological features of transfected BMSCs was observed. ALP stains and PNP method were used to measure ALP activity. In addition, the collagen type Ⅰ propeptides and mineralized matrixes were examined by immunohistochemical staining and tetracycline fluorescence labeling respectively. The morphological and biological characters of the transfected BMSCs were similar to those of osteoblasts and the cell proliferation was promoted. The cell layer displayed strong positive reaction for ALP stains and immunohistochemical staining. ALP activity and collagen type Ⅰ expression increased remarkably after transfection. Mineralized matrixes formed earlier and more in transfected BMSCs as compared with control group. It is concluded that transfecting with TGF β 1 gene could promote the osteogenic potential of cultured BMSCs.
文摘The effects of heparin on the expression of transforming growth factor-β 1 (TGF-β 1) and two extracellular matrix components laminin (LN) and fibronectin (FN) in diabetic rat glomeruli were investigated. Twenty-six rats were randomly divided into control group (C, n=8), diabetic group (D, n=9), and diabetes+heparin group (DH, n=9). After 8-week therapy of heparin (200 U once daily by abdominal injection), TGF-β 1, LN and FN expression in glomeruli was detected by immunohistochemical method. The results showed that the expression levels of TGF-β 1, LN and FN were higher in group D than in group C. It was found that heparin could reduce 24-h urinary albumin excretion and inhibit overexpression of TGF-β 1, LN and FN in glomeruli of diabetic rats. It suggested that the inhibitory effect of heparin on diabetic glomerular sclerosis was at least partly related with the inhibition of TGF-β 1 expression.
基金supported by grants from the National Natural Science Foundation of China(No.82270545 and No.81870381)Natural Science Foundation of Hebei Province(No.H2014206446)。
文摘Objective Intestinal fibrosis is a refractory complication of inflammatory bowel disease(IBD).Tumor necrosis factor ligand-related molecule-1A(TL1A)is important for IBD-related intestinal fibrosis in a dextran sodium sulfate(DSS)-induced experimental colitis model.This study aimed to explore the effects of TL1A on human colonic fibroblasts.Methods A trinitrobenzene sulfonic acid(TNBS)-induced experimental colitis model of LCK-CD2-TL1A-GFP transgenic(Tg)or wild-type(WT)mice was established to determine the effect and mechanism of TL1A on intestinal fibrosis.The human colonic fibroblast CCD-18Co cell line was treated concurrently with TL1A and human peripheral blood mononuclear cell(PBMC)supernatant.The proliferation and activation of CCD-18Co cells were detected by BrdU assays,flow cytometry,immunocytochemistry and Western blotting.Collagen metabolism was tested by Western blotting and real-time quantitative polymerase chain reaction(RT-qPCR).Results The level of collagen metabolism in the TNBS+ethyl alcohol(EtOH)/Tg group was greater than that in the TNBS+EtOH/WT group.Transforming growth factor-β1(TGF-β1)and p-Smad3 in the TNBS+EtOH/Tg group were upregulated as compared with those in the TNBS+EtOH/WT group.The proliferation of CCD-18Co cells was promoted by the addition of human PBMC supernatant supplemented with 20 ng/mL TL1A,and the addition of human PBMC supernatant and TL1A increased CCD-18Co proliferation by 24.4%at 24 h.TL1A promoted cell activation and increased the levels of COL1A2,COL3A1,and TIMP-1 in CCD-18Co cells.Treatment of CCD-18Co cells with TL1A increased the expression of TGF-β1 and p-Smad3.Conclusion TL1A promotes TGF-β1-mediated intestinal fibroblast activation,proliferation,and collagen deposition and is likely related to an increase in the TGF-β1/Smad3 signaling pathway.
