AIM:To test whether colchicine would be an effective antif ibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon.METHODS:Seventy-four patients(46 males,28 female...AIM:To test whether colchicine would be an effective antif ibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon.METHODS:Seventy-four patients(46 males,28 females) aged 40-66 years(mean 53±13 years) participated in the study.The patients were affected by chronic liver diseases with cirrhosis which was proven histologically(n=58);by chronic active hepatitis C(n=4),chronic active hepatitis B(n=2),and chronic persistent hepatitis C(n=6).In the four patients lacking histology,cirrhosis was diagnosed from anamnesis,serum laboratory tests,esophageal varices and ascites.Patients were assigned to colchicine(1 mg/d) or standard treatment as control in a randomized,double-blind trial,and followed for 4.4 years with clinical and laboratory evaluation.RESULTS:Survival at the end of the study was 94.6% in the colchicine group and 78.4% in the control group(P=0.001).Serum N-terminal peptide of type Ⅲ procollagen levels fell from 34.0 to 18.3 ng/mL(P=0.0001),and pseudocholinesterase levels rose from 4.900 to 5.610 mU/mL(P=0.0001) in the colchicine group,while no signif icant change was seen in controls.Best results were obtained in patients with chronic hepatitis C and in alcoholic cirrhotics.CONCLUSION:Colchicine is an effective and safe antifibrotic drug for long-term treatment of chronic liver disease in which fi brosis progresses towards cirrhosis.展开更多
OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, C...OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.展开更多
Objective To explore the role of serum fibrotic indices including hyaluronic acid （HA）, procollagen type Ⅲ NH2-terminal peptide （PCIIIP）, and laminin （LN） in assessing the severity of myocardial fibrosis in chr...Objective To explore the role of serum fibrotic indices including hyaluronic acid （HA）, procollagen type Ⅲ NH2-terminal peptide （PCIIIP）, and laminin （LN） in assessing the severity of myocardial fibrosis in chronic congestive heart failure （CHF）. Methods Serum levels of HA, PCIIIP, and LN in 39 patients with CHF E [14 with New York Heart Association （NYHA） functional class II, 21 with class Ⅲ, 4 with class Ⅳ] and in 46 patients with NYHA functional class I were assessed by radioimmunoassay. Results The serum concentrations of HA, PCMP, and LN were 359.75 ± 84.59 μg/L, 77.88 ± 24. 67 μg/L, 86. 73 ± 23.90 μg/L in CHF group, and 211.60 ±54. 80 μg/L, 64.82 ±23.99 μg/L, 82. 26 ±23.98 μg/L in NYHA functional class Ⅰ group, respectively. The HA level was significantly higher in CHF patients as compared with NYHA functional class Ⅰ group （ P 〈 0.05 ）. However, no difference was found in the levels of PCIIIP and LN between CHF group and NYHA functional class Ⅰ group. The serum HA concentration was negatively correlated with left ventricular ejection fraction （ r = - 0.71, P 〈 0.05 ）. Conclusion Serum HA level may act as an indicator for myocardial fibrosis.展开更多
AIM:To investigate the role of procollagen C-proteinase enhancer 1(PCPE1)in retinal angiogenesis and relevant mechanisms.METHODS:The Pcolce1-knockout(KO)mice were used to explore the effect of PCPE1 on retinal angioge...AIM:To investigate the role of procollagen C-proteinase enhancer 1(PCPE1)in retinal angiogenesis and relevant mechanisms.METHODS:The Pcolce1-knockout(KO)mice were used to explore the effect of PCPE1 on retinal angiogenesis in vivo.Pcolce1 si RNA were designed,cell count kit 8(CCK8)assays and tube formation assays were performed to investigate the cell proliferation and tube formation abilities of retinal microvascular endothelial cells(h RMECs)in vitro.Mouse embryo fibroblasts(MEF)cells were isolated and cultured to analyze the effect of PCPE1 on enhancing procollagen cleavage.RESULTS:In vivo studies showed that the retinal vascular density of Pcolce1-/-mice was significantly lower than that of the control group.Furthermore,silencing of Pcolce1 inhibited cell proliferation and tube formation abilities of h RMECs in vitro.Additionally,much more procollagen was found in Pcolce1-/-MEF cells,compared to wild type MEF cells.CONCLUSION:PCPE1 may promote physiological retinal angiogenesis by regulating the processing of collagen,which may provide a potential therapeutic target of retinal vascular disease.展开更多
Objective:To determine the effect of Lentinula edodes extract on ultraviolet(UV)A and UVB-induced changes in matrix metalloproteinase(MMP)and type I procollagen expression using human immortalized HaCaT keratinocytes....Objective:To determine the effect of Lentinula edodes extract on ultraviolet(UV)A and UVB-induced changes in matrix metalloproteinase(MMP)and type I procollagen expression using human immortalized HaCaT keratinocytes.Methods:Lentinula edodes ethanol extract(LEE)was obtained by extraction with 80%ethanol for 4 h at 80℃.Effect of LEE on UVinduced alteration on the expression and production of MMPs and type I procollagen in keratinocytes was investigated using ELISA,RT-PCR,and Western blotting assay.To determine the underlying mechanism of LEE-mediated effects,mitogen-activated protein kinase(MAPK)and activator protein 1 signaling pathways were analysed by Western blotting assay.Results:LEE significantly inhibited the expression of MMP-1 and MMP-9 and increased the expression of type I procollagen in UVA and UVB-irradiated HaCaT keratinocytes.The phosphorylation levels of p38 were significantly inhibited by LEE whereas it did not affect c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation.Suppression of p38 phosphorylation was also accompanied by downregulation of UVA and UVB-induced increase in c-Fos.Conclusions:LEE effectively inhibits the expression of MMP-1 and MMP-9 and increases type I procollagen production through the p38 MAPK/c-Fos signaling pathway in UVA and UVB-irradiated HaCaT keratinocytes.This findings suggest that Lentinula edodes may be developed as a cosmetic material to suppress UV exposuremediated skin aging.展开更多
Objective:To investigate the effect of TGFβ, IFNs and TNFα on promoter activities in mouse α2(I )procollagen gene. Methods: Recombinant constructions PCOL 0. 4, pCOL0. 8, pAZ1009 containing CAT reportergene fused r...Objective:To investigate the effect of TGFβ, IFNs and TNFα on promoter activities in mouse α2(I )procollagen gene. Methods: Recombinant constructions PCOL 0. 4, pCOL0. 8, pAZ1009 containing CAT reportergene fused respectively with 400, 800 and 2 000 hp length of the 5'--flanking region in mouse α2(Ⅰ) procollagengene were used for transfection. Promoter activities were determined by CAT reporter gene assay(CAT--ELISA) intransfected cells treated with different cytokines. Results: TGFβ(2 ng/ml ) increased the activities of -- 2kb-- +54hp, -- 780~ + 54hp and -- 348~ +54 hp fragments as promoter respectively, with the increase of activity of 2kb -- + 54hp being most evident. TNFα (100 u/ml ) decreased the activity of -- 2kb ~ + 54hp sequence aspromoter. A slight increase, but not decrease of CAT activities was found in cells treated with IFNα(1000 u/ml)or IFNγ(1 000 u/ml) when pAZ1009 was trans feeted. But CAT expression was decreased more greatly if IFNα orIFNγ was used in combination with TNFα compared with TNFα treatment alone. The same change was seen ifPCOLO. 4 or PCOLO. 8 was used for transfection. Conclusion: Positive TGFβ--responsive elements exist within Zkbflanking region in mouse α2 (Ⅰ ) procollagen gene mediating the fibrogenic effect, while some negative elementsmediate the antifibrotic effect of TNFα. The target antifibrotic effect of IFNs might lie outside this 2kb-- +54bpregion or posttranscriptionally.展开更多
Progressive inflammation and fibrosis are the central processes in the pathogenesis of pulmonary fibrosis. It is believed that macrophages in areas of chronically inflamed lung play a key role in fibrotic response. Th...Progressive inflammation and fibrosis are the central processes in the pathogenesis of pulmonary fibrosis. It is believed that macrophages in areas of chronically inflamed lung play a key role in fibrotic response. Therefore, we investigated the effects of alveolar macrophage (AmΦ) conditioned media from interstitial lung disease (ILD) patients on lung fibroblast proliferation and procollagen mRNA expression. After stimulating with AmΦ conditioned media from ILD patients, the fibroblast proliferation increased 71. 4 % compared with the control, but for media from bronchial carcinoma (BC) patients, it just increased 14. 3%. There is a significant difference between the two groups (P<0. 05). The procollagen a1 (Ⅰ) mRNA in fibroblasts stimulated with AmΦ conditioned media from ILD patients was increased 21. 3 %, and a1 ( Ⅲ) was 37. 2% higher than control (P<0.05). It increased 6. 8% and 12. 8% for media from BC patients respectively, but there was no difference when compared to the control. We considered that AmΦ from ILD patients might be in an activated state and could release some growth factors to stimulate fibroblast proliferation and promote collagen DNA expression.展开更多
The current study revealed that increased synthesis and secretion of collagen types I and III play major roles in arterial wall remodeling, aneurysm formation, and atherosclerotic cap stability. The aim is to investig...The current study revealed that increased synthesis and secretion of collagen types I and III play major roles in arterial wall remodeling, aneurysm formation, and atherosclerotic cap stability. The aim is to investigate the age-related changes of the procollagen alpha polypeptide gene mRNA and protein expression in the vascular smooth muscle cells (VSMCs) in rats, as well as the possible underlying mechanisms. We tested in vitro culture of VSMC from the thoracoabdominal aorta in neonate and 9-month-old healthy male Wistar rats;procollagen alpha polypeptide mRNA and procollagen alpha polypeptide protein expression were detected, using RT-PCR, VG staining, Western blot and ELISA methods. Semi-quantitative analysis displayed that, in the real-time reverse transcription polymerase chain reaction (RT-PCR), the type I collagen α polypeptide chain mRNA increased in the adult group, but not significantly (<em>P</em> = 0.05). Further, there was no significant difference between the two groups of type III collagen α polypeptide chain mRNA (<em>P</em> > 0.05). Both the type I and type III procollagen alpha polypeptide protein expression were increased significantly in the older group as compared with the young group (<em>P</em> < 0.05). This phenomenon mainly lies in the fact that the regulatory pathway on age-related changes of procollagen alpha polypeptides may be one of the molecular mechanisms in vascular remodeling during aging.展开更多
Objectives To evaluate the changes of serum intact terminal peptide of procollagen in patients with chronic Keshan disease (KD) and investigate their clinical significance. Methods The concentrations of serum intact N...Objectives To evaluate the changes of serum intact terminal peptide of procollagen in patients with chronic Keshan disease (KD) and investigate their clinical significance. Methods The concentrations of serum intact N-terminal peptide of type procollagen (P NP) and intact N-terminal peptide of type procollagen were measured by radioimmunoassay in 35 patients with chronic KD and 31 normal control. Doppler ultrasounds was used to determine several parameters of left ventricular systole and diastole functions. Results The concentration of serum P NP (74.07±16.74)μg/L and the ratio of P NP/ P NP (18.02 ±4.60) in chronic KD were significantly increased as compared to the control (39.63±12.07 μg/L, 12.12±4.24; P< 0.001). Serum P NP (4.19±0.64)μg/L in chronic KD was higher than that in the control (3.36±0.65 μg/L,P < 0.001) too. The higher of serum concentration of P NP and the ratio of P NP/ P NP, the worse of cardiac function in patients with chronic KD. A negative correlation was found between serum P NP/ P NP, P NP and VE/VA, LVEF (γ=-0.4502, -0.4608, P< 0.01 and γ=-0.3936, -0.3904, respectively; P<0.05). Conclusions These findings suggested that tissue synthesis of collagen type and type was abnormally increased in chronic KD. On the other hand, our results indicated that P NP and P NP were related to several functional alterations of the left ventricle. Serum procollagen peptide measurements might therefore provide indirectly diagnostic information on myocardial fibrosis associated with chronic KD.展开更多
目的:探讨急性髓系白血病(AML)患者采用DCAG方案化疗后血清同源盒基因A9(HOXA9)、可溶性E钙黏蛋白(SE-CAD)及Ⅲ型前胶原蛋白(PCⅢ)水平的变化及其与预后的关系。方法:回顾性分析2018年3月至2021年12月经本院确诊并收治的80例复发难治性...目的:探讨急性髓系白血病(AML)患者采用DCAG方案化疗后血清同源盒基因A9(HOXA9)、可溶性E钙黏蛋白(SE-CAD)及Ⅲ型前胶原蛋白(PCⅢ)水平的变化及其与预后的关系。方法:回顾性分析2018年3月至2021年12月经本院确诊并收治的80例复发难治性AML患者的资料,按照治疗方案不同将其分为DCAG组(n=40)与CAG组(n=40),对比治疗前后各组的临床疗效及HOXA9、SE-CAD、PCⅢ水平的变化;另按照临床疗效将所有患者分为缓解组(n=58)与未缓解组(n=22),通过单因素和多因素分析影响AML患者预后的危险因素;采用ROC曲线分析HOXA9、SE-CAD、PCⅢ三项单一指标及三者联合对预后的预测效能。结果:相比于治疗前,DCAG组与CAG组患者在治疗后的HOXA9、SE-CAD、PCⅢ水平均有所下降,但DCAG组患者各指标的改善效果明显优于CAG组,且DCAG组患者在治疗后的临床疗效显著优于CAG组(均P<0.05);多因素分析结果显示,骨髓原始细胞比率、HOXA9 m RNA、SE-CAD及PCⅢ水平升高是影响AML患者化疗疗效的独立危险因素(均P<0.05);ROC曲线分析显示,HOXA9 m RNA、SE-CAD及PCⅢ联合能够有效预测AML预后情况,其敏感度为84.80%、特异度为88.20%。结论:应用DCAG的化疗方案能够显著改善AML患者的HOXA9 m RNA、SE-CAD及PCⅢ水平;且这三项指标作为影响AML患者预后的危险因素,通过联合检测能够对AML患者的预后情况进行有效预测。展开更多
文摘AIM:To test whether colchicine would be an effective antif ibrotic agent for treatment of chronic liver diseases in patients who could not be treated with α-interferon.METHODS:Seventy-four patients(46 males,28 females) aged 40-66 years(mean 53±13 years) participated in the study.The patients were affected by chronic liver diseases with cirrhosis which was proven histologically(n=58);by chronic active hepatitis C(n=4),chronic active hepatitis B(n=2),and chronic persistent hepatitis C(n=6).In the four patients lacking histology,cirrhosis was diagnosed from anamnesis,serum laboratory tests,esophageal varices and ascites.Patients were assigned to colchicine(1 mg/d) or standard treatment as control in a randomized,double-blind trial,and followed for 4.4 years with clinical and laboratory evaluation.RESULTS:Survival at the end of the study was 94.6% in the colchicine group and 78.4% in the control group(P=0.001).Serum N-terminal peptide of type Ⅲ procollagen levels fell from 34.0 to 18.3 ng/mL(P=0.0001),and pseudocholinesterase levels rose from 4.900 to 5.610 mU/mL(P=0.0001) in the colchicine group,while no signif icant change was seen in controls.Best results were obtained in patients with chronic hepatitis C and in alcoholic cirrhotics.CONCLUSION:Colchicine is an effective and safe antifibrotic drug for long-term treatment of chronic liver disease in which fi brosis progresses towards cirrhosis.
基金This study was supported by the grant from the Guangdong Provincial Science and Technology Foundation (No. A 1999--198).
文摘OBJECTIVE: To assess the significance of serum hyaluronic acid (HA), proeollagen type Ⅲ (PCⅢ), collagen type Ⅳ (CⅣ) in the histological diagnosis of liver fibrosis. METHODS: The concentrations of serum HA, PCⅢ, CⅣ in 253 patients with chronic liver diseases were measured by radioimmunoassay. Liver biopsies were performed in all patients at the same time. The liver was pathologically evaluated by a pathologist according to a scoring system. Combined with the results of liver pathological diagnosis, the accuracy of serum HA, PCⅢ, CⅣ in diagnosing patients with hepatic fibrosis (staging≥S_2) or cirrhosis (S_4) was assessed using the receiver operating curve (ROC). RESULTS: The cutoff values of serum HA, PCⅢ and CⅣ for identifying patients with hepatic fibrosis (≥S_2) or cirrhosis (S_4) were determined. The cutoff values of serum HA, PCⅢ and CⅣ for detecting patients with fibrosis (stage≥S_2) were 90μg/L, 90μg/L, 75μg/L, respectively; their sensitivity (Se) was 80.4%, 82%, 63.1%; their specificity (Spe) was 70.2%, 60.8%, 83.8%; their positive predictive values (PPV) were 86.7%, 83.5%, 90.4%; their negative predictive values (NPV) were 59.8%, 58.4%, 48.4%, respectively. The cutoff values for detecting patients with liver cirrhosis were 210μg/L for HA, 96.2% for Se, 85.3% for Spe, 65.4% for PPV, 98.8% for NPV; 150μg/L for PCⅢ, 76.4% for Se, 68.7% for Spe, 40.4% for PPV, 91.3% for NPV; 90μg/L for CⅣ, 80% for Se, 75.8% for Spe, 47.8% for PPV, 93.2% for NPV, respectively. CONCLUSIONS: Serum HA, PCⅢ and CⅣ can be determined for an accurate diagnosis of hepatic fibrosis in various stages. HA is the best for screening liver cirrhosis.
文摘Objective To explore the role of serum fibrotic indices including hyaluronic acid （HA）, procollagen type Ⅲ NH2-terminal peptide （PCIIIP）, and laminin （LN） in assessing the severity of myocardial fibrosis in chronic congestive heart failure （CHF）. Methods Serum levels of HA, PCIIIP, and LN in 39 patients with CHF E [14 with New York Heart Association （NYHA） functional class II, 21 with class Ⅲ, 4 with class Ⅳ] and in 46 patients with NYHA functional class I were assessed by radioimmunoassay. Results The serum concentrations of HA, PCMP, and LN were 359.75 ± 84.59 μg/L, 77.88 ± 24. 67 μg/L, 86. 73 ± 23.90 μg/L in CHF group, and 211.60 ±54. 80 μg/L, 64.82 ±23.99 μg/L, 82. 26 ±23.98 μg/L in NYHA functional class Ⅰ group, respectively. The HA level was significantly higher in CHF patients as compared with NYHA functional class Ⅰ group （ P 〈 0.05 ）. However, no difference was found in the levels of PCIIIP and LN between CHF group and NYHA functional class Ⅰ group. The serum HA concentration was negatively correlated with left ventricular ejection fraction （ r = - 0.71, P 〈 0.05 ）. Conclusion Serum HA level may act as an indicator for myocardial fibrosis.
基金Supported by the National Natural Science Foundation of China(No.81770963No.81770964)。
文摘AIM:To investigate the role of procollagen C-proteinase enhancer 1(PCPE1)in retinal angiogenesis and relevant mechanisms.METHODS:The Pcolce1-knockout(KO)mice were used to explore the effect of PCPE1 on retinal angiogenesis in vivo.Pcolce1 si RNA were designed,cell count kit 8(CCK8)assays and tube formation assays were performed to investigate the cell proliferation and tube formation abilities of retinal microvascular endothelial cells(h RMECs)in vitro.Mouse embryo fibroblasts(MEF)cells were isolated and cultured to analyze the effect of PCPE1 on enhancing procollagen cleavage.RESULTS:In vivo studies showed that the retinal vascular density of Pcolce1-/-mice was significantly lower than that of the control group.Furthermore,silencing of Pcolce1 inhibited cell proliferation and tube formation abilities of h RMECs in vitro.Additionally,much more procollagen was found in Pcolce1-/-MEF cells,compared to wild type MEF cells.CONCLUSION:PCPE1 may promote physiological retinal angiogenesis by regulating the processing of collagen,which may provide a potential therapeutic target of retinal vascular disease.
基金supported by the Ministry of Trade,Industry&Energy,Korea Institute for Advancement of Technology and Busan Institute For Regional Program Evaluation through the Encouragement Program for the Social and Economic Innovation Growth(project number,P0008724)
文摘Objective:To determine the effect of Lentinula edodes extract on ultraviolet(UV)A and UVB-induced changes in matrix metalloproteinase(MMP)and type I procollagen expression using human immortalized HaCaT keratinocytes.Methods:Lentinula edodes ethanol extract(LEE)was obtained by extraction with 80%ethanol for 4 h at 80℃.Effect of LEE on UVinduced alteration on the expression and production of MMPs and type I procollagen in keratinocytes was investigated using ELISA,RT-PCR,and Western blotting assay.To determine the underlying mechanism of LEE-mediated effects,mitogen-activated protein kinase(MAPK)and activator protein 1 signaling pathways were analysed by Western blotting assay.Results:LEE significantly inhibited the expression of MMP-1 and MMP-9 and increased the expression of type I procollagen in UVA and UVB-irradiated HaCaT keratinocytes.The phosphorylation levels of p38 were significantly inhibited by LEE whereas it did not affect c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation.Suppression of p38 phosphorylation was also accompanied by downregulation of UVA and UVB-induced increase in c-Fos.Conclusions:LEE effectively inhibits the expression of MMP-1 and MMP-9 and increases type I procollagen production through the p38 MAPK/c-Fos signaling pathway in UVA and UVB-irradiated HaCaT keratinocytes.This findings suggest that Lentinula edodes may be developed as a cosmetic material to suppress UV exposuremediated skin aging.
文摘Objective:To investigate the effect of TGFβ, IFNs and TNFα on promoter activities in mouse α2(I )procollagen gene. Methods: Recombinant constructions PCOL 0. 4, pCOL0. 8, pAZ1009 containing CAT reportergene fused respectively with 400, 800 and 2 000 hp length of the 5'--flanking region in mouse α2(Ⅰ) procollagengene were used for transfection. Promoter activities were determined by CAT reporter gene assay(CAT--ELISA) intransfected cells treated with different cytokines. Results: TGFβ(2 ng/ml ) increased the activities of -- 2kb-- +54hp, -- 780~ + 54hp and -- 348~ +54 hp fragments as promoter respectively, with the increase of activity of 2kb -- + 54hp being most evident. TNFα (100 u/ml ) decreased the activity of -- 2kb ~ + 54hp sequence aspromoter. A slight increase, but not decrease of CAT activities was found in cells treated with IFNα(1000 u/ml)or IFNγ(1 000 u/ml) when pAZ1009 was trans feeted. But CAT expression was decreased more greatly if IFNα orIFNγ was used in combination with TNFα compared with TNFα treatment alone. The same change was seen ifPCOLO. 4 or PCOLO. 8 was used for transfection. Conclusion: Positive TGFβ--responsive elements exist within Zkbflanking region in mouse α2 (Ⅰ ) procollagen gene mediating the fibrogenic effect, while some negative elementsmediate the antifibrotic effect of TNFα. The target antifibrotic effect of IFNs might lie outside this 2kb-- +54bpregion or posttranscriptionally.
文摘Progressive inflammation and fibrosis are the central processes in the pathogenesis of pulmonary fibrosis. It is believed that macrophages in areas of chronically inflamed lung play a key role in fibrotic response. Therefore, we investigated the effects of alveolar macrophage (AmΦ) conditioned media from interstitial lung disease (ILD) patients on lung fibroblast proliferation and procollagen mRNA expression. After stimulating with AmΦ conditioned media from ILD patients, the fibroblast proliferation increased 71. 4 % compared with the control, but for media from bronchial carcinoma (BC) patients, it just increased 14. 3%. There is a significant difference between the two groups (P<0. 05). The procollagen a1 (Ⅰ) mRNA in fibroblasts stimulated with AmΦ conditioned media from ILD patients was increased 21. 3 %, and a1 ( Ⅲ) was 37. 2% higher than control (P<0.05). It increased 6. 8% and 12. 8% for media from BC patients respectively, but there was no difference when compared to the control. We considered that AmΦ from ILD patients might be in an activated state and could release some growth factors to stimulate fibroblast proliferation and promote collagen DNA expression.
文摘The current study revealed that increased synthesis and secretion of collagen types I and III play major roles in arterial wall remodeling, aneurysm formation, and atherosclerotic cap stability. The aim is to investigate the age-related changes of the procollagen alpha polypeptide gene mRNA and protein expression in the vascular smooth muscle cells (VSMCs) in rats, as well as the possible underlying mechanisms. We tested in vitro culture of VSMC from the thoracoabdominal aorta in neonate and 9-month-old healthy male Wistar rats;procollagen alpha polypeptide mRNA and procollagen alpha polypeptide protein expression were detected, using RT-PCR, VG staining, Western blot and ELISA methods. Semi-quantitative analysis displayed that, in the real-time reverse transcription polymerase chain reaction (RT-PCR), the type I collagen α polypeptide chain mRNA increased in the adult group, but not significantly (<em>P</em> = 0.05). Further, there was no significant difference between the two groups of type III collagen α polypeptide chain mRNA (<em>P</em> > 0.05). Both the type I and type III procollagen alpha polypeptide protein expression were increased significantly in the older group as compared with the young group (<em>P</em> < 0.05). This phenomenon mainly lies in the fact that the regulatory pathway on age-related changes of procollagen alpha polypeptides may be one of the molecular mechanisms in vascular remodeling during aging.
文摘Objectives To evaluate the changes of serum intact terminal peptide of procollagen in patients with chronic Keshan disease (KD) and investigate their clinical significance. Methods The concentrations of serum intact N-terminal peptide of type procollagen (P NP) and intact N-terminal peptide of type procollagen were measured by radioimmunoassay in 35 patients with chronic KD and 31 normal control. Doppler ultrasounds was used to determine several parameters of left ventricular systole and diastole functions. Results The concentration of serum P NP (74.07±16.74)μg/L and the ratio of P NP/ P NP (18.02 ±4.60) in chronic KD were significantly increased as compared to the control (39.63±12.07 μg/L, 12.12±4.24; P< 0.001). Serum P NP (4.19±0.64)μg/L in chronic KD was higher than that in the control (3.36±0.65 μg/L,P < 0.001) too. The higher of serum concentration of P NP and the ratio of P NP/ P NP, the worse of cardiac function in patients with chronic KD. A negative correlation was found between serum P NP/ P NP, P NP and VE/VA, LVEF (γ=-0.4502, -0.4608, P< 0.01 and γ=-0.3936, -0.3904, respectively; P<0.05). Conclusions These findings suggested that tissue synthesis of collagen type and type was abnormally increased in chronic KD. On the other hand, our results indicated that P NP and P NP were related to several functional alterations of the left ventricle. Serum procollagen peptide measurements might therefore provide indirectly diagnostic information on myocardial fibrosis associated with chronic KD.
文摘目的:探讨急性髓系白血病(AML)患者采用DCAG方案化疗后血清同源盒基因A9(HOXA9)、可溶性E钙黏蛋白(SE-CAD)及Ⅲ型前胶原蛋白(PCⅢ)水平的变化及其与预后的关系。方法:回顾性分析2018年3月至2021年12月经本院确诊并收治的80例复发难治性AML患者的资料,按照治疗方案不同将其分为DCAG组(n=40)与CAG组(n=40),对比治疗前后各组的临床疗效及HOXA9、SE-CAD、PCⅢ水平的变化;另按照临床疗效将所有患者分为缓解组(n=58)与未缓解组(n=22),通过单因素和多因素分析影响AML患者预后的危险因素;采用ROC曲线分析HOXA9、SE-CAD、PCⅢ三项单一指标及三者联合对预后的预测效能。结果:相比于治疗前,DCAG组与CAG组患者在治疗后的HOXA9、SE-CAD、PCⅢ水平均有所下降,但DCAG组患者各指标的改善效果明显优于CAG组,且DCAG组患者在治疗后的临床疗效显著优于CAG组(均P<0.05);多因素分析结果显示,骨髓原始细胞比率、HOXA9 m RNA、SE-CAD及PCⅢ水平升高是影响AML患者化疗疗效的独立危险因素(均P<0.05);ROC曲线分析显示,HOXA9 m RNA、SE-CAD及PCⅢ联合能够有效预测AML预后情况,其敏感度为84.80%、特异度为88.20%。结论:应用DCAG的化疗方案能够显著改善AML患者的HOXA9 m RNA、SE-CAD及PCⅢ水平;且这三项指标作为影响AML患者预后的危险因素,通过联合检测能够对AML患者的预后情况进行有效预测。
