Background Erythropoietin （EPO） functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production and neuron protection. This study aimed to determine the neuron protective ef...Background Erythropoietin （EPO） functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production and neuron protection. This study aimed to determine the neuron protective effect of erythropoietin on experimental rats enduring spinal cord injury （SCI） by assessing thrombospondin-1 （TSP-1） level and transforming growth factor-β （TGF-β） in the development of a rat model of SCI. Methods Sixty Sprague-Dawley rats were randomly assigned to three groups： sham operation control group, SCI group and EPO treatment group. By using a weight-drop contusion SCI model, the rats in the SCI group and EPO treatment group were sacrificed at 24 hours and 7 days subsequently. The Basso, Beattie, and Bresnahan （BBB） scores were examined for locomotor function. Pathological changes were observed after HE staining. The expressions of thrombospondin-2 （TSP-1） and TGF-β were determined by immunohistochemical staining and Western blotting. Results Slighter locomotor dysfunction was discovered and it was recovered abruptly as higher BBB scores were found in the EPO treatment group than in the SCI group （P 〈0.01）. Pathologically, progressive disruption of the dorsal white matter and regeneration of a few neurons were also observed in SCI rats. TSP-1 and TGF-β expression increased at 24 hours and 7 days after SCI in the injured segment, and it was higher in the SCI group than in the EPO treatment group. Spinal cord samples from the animals demonstrated a TSP-1 optical density of 112.2±6.8 and TSP-1 positive cells of 5.7±1.3 respectively. After injury, the TSP-1 optical density and cell number increased to 287.2±14.3/mm^2 and 23.2±2.6/mm^2 at 24 hours and to 232.1±13.2/mm^2 and 15.2±2.3/mm^2 at 7 days respectively. When EPO treated rats compared with the SCI rats, the TSP-1 optical density and cell number decreased to 213.1 ±11.6/mm^2 and 11.9±1.6/mm^2 at 24 hours and to 189.9±10.5/mm^2 and 9.3±1.5/mm^2 at 7 days, respectively （P 〈0.01）. In the SCI rats, the TGF-β optical density and positive neuron number were 291.4±15.2/mm^2 and 28.8±4.9/mm^2 at 24 hours and 259.1±12.3/mm^2 and 23.9±4.1/mm^2 at 7 days respectively. They decreased in the EPO treated rats to 222.8±11.9/mm^2 and 13.7±2.1/mm^2 at 24 hours and to 196.5±9.7/mm^2 and 8.7±2.2/mm^2 at 7 days （P 〈0.01）. Conclusions Increased expression of TSP-1 and TGF-β can be found in the injured segment of the spinal cord at 24 hours and 7 days after injury. EPO treatment can effectively prevent pathological alterations from severe spinal cord injury by reduced expression of TSP-1 and TGF-β.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
目的：探讨杜仲多糖治疗肝纤维化（HF）作用,并探讨其相关的作用机制。方法：将60只健康SD大鼠随机分成2组,正常组（10只）和肝纤维化造模组（50只）。造模组采用40%四氯化碳（CCl4）腹腔注射制备HF动物模型,造模成功后将其随机分为5个...目的：探讨杜仲多糖治疗肝纤维化（HF）作用,并探讨其相关的作用机制。方法：将60只健康SD大鼠随机分成2组,正常组（10只）和肝纤维化造模组（50只）。造模组采用40%四氯化碳（CCl4）腹腔注射制备HF动物模型,造模成功后将其随机分为5个组,分别为模型组,杜仲多糖高、中、低剂量组及秋水仙碱组每组10只。秋水仙碱组（1.0×10^-4g·kg^-1）,杜仲多糖高、中、低剂量组（0.14,0.07,0.035 g·kg^-1）分别连续灌胃给药8周后收集样本,测定法大鼠体质量及计算肝脏系数;采用酶联免疫吸附测定（ELISA）检测血清白细胞介素-6（IL-6）,高迁移率族蛋白B1（high-mobility group box 1,HMGB1）,脂多糖（LPS）,肝组织基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制因子-1（TIMP-1）水平;逆转录聚合酶链式反应（RT-PCR）技术分析各组大鼠肝组织Ⅰ,Ⅲ型胶原蛋白,MMP-1,TIMP-1及转化生长因子-β1（TGF-β1）mRNA表达情况。结果：与正常组比较,CCl4能显著降低实验大鼠体质量（P〈0.01）,提高肝脏系数（P〈0.01）;杜仲多糖能显著增加HF模型的体质量（P〈0.01）,显著降低HF模型肝脏系数（P〈0.01）;ELISA检测表明,杜仲多糖能显著降低肝纤维化大鼠血清IL-6,HMGB1及LPS含量（P〈0.01）;RT-PCR检测结果显示,杜仲多糖及秋水仙碱能显著降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA含量（P〈0.05）,明显提高MMP-1含量（P〈0.05,P〈0.01）,且呈量效关系。结论：杜仲多糖具有显著的抗肝纤维化作用,其作用机制可能与抑制降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA表达有关。展开更多
基金This study was supported by grants from the Major Science Research Program of Zhejiang Province （No. 2006C23029）, Medical Science Foundation of Zhejiang Province （No. 2005HN007） and Zhejiang Provincial Program for the Cultivation of High-level Innovative Health Talents.
文摘Background Erythropoietin （EPO） functions as a tissue-protective cytokine in addition to its crucial hormonal role in red cell production and neuron protection. This study aimed to determine the neuron protective effect of erythropoietin on experimental rats enduring spinal cord injury （SCI） by assessing thrombospondin-1 （TSP-1） level and transforming growth factor-β （TGF-β） in the development of a rat model of SCI. Methods Sixty Sprague-Dawley rats were randomly assigned to three groups： sham operation control group, SCI group and EPO treatment group. By using a weight-drop contusion SCI model, the rats in the SCI group and EPO treatment group were sacrificed at 24 hours and 7 days subsequently. The Basso, Beattie, and Bresnahan （BBB） scores were examined for locomotor function. Pathological changes were observed after HE staining. The expressions of thrombospondin-2 （TSP-1） and TGF-β were determined by immunohistochemical staining and Western blotting. Results Slighter locomotor dysfunction was discovered and it was recovered abruptly as higher BBB scores were found in the EPO treatment group than in the SCI group （P 〈0.01）. Pathologically, progressive disruption of the dorsal white matter and regeneration of a few neurons were also observed in SCI rats. TSP-1 and TGF-β expression increased at 24 hours and 7 days after SCI in the injured segment, and it was higher in the SCI group than in the EPO treatment group. Spinal cord samples from the animals demonstrated a TSP-1 optical density of 112.2±6.8 and TSP-1 positive cells of 5.7±1.3 respectively. After injury, the TSP-1 optical density and cell number increased to 287.2±14.3/mm^2 and 23.2±2.6/mm^2 at 24 hours and to 232.1±13.2/mm^2 and 15.2±2.3/mm^2 at 7 days respectively. When EPO treated rats compared with the SCI rats, the TSP-1 optical density and cell number decreased to 213.1 ±11.6/mm^2 and 11.9±1.6/mm^2 at 24 hours and to 189.9±10.5/mm^2 and 9.3±1.5/mm^2 at 7 days, respectively （P 〈0.01）. In the SCI rats, the TGF-β optical density and positive neuron number were 291.4±15.2/mm^2 and 28.8±4.9/mm^2 at 24 hours and 259.1±12.3/mm^2 and 23.9±4.1/mm^2 at 7 days respectively. They decreased in the EPO treated rats to 222.8±11.9/mm^2 and 13.7±2.1/mm^2 at 24 hours and to 196.5±9.7/mm^2 and 8.7±2.2/mm^2 at 7 days （P 〈0.01）. Conclusions Increased expression of TSP-1 and TGF-β can be found in the injured segment of the spinal cord at 24 hours and 7 days after injury. EPO treatment can effectively prevent pathological alterations from severe spinal cord injury by reduced expression of TSP-1 and TGF-β.
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.
文摘目的：探讨杜仲多糖治疗肝纤维化（HF）作用,并探讨其相关的作用机制。方法：将60只健康SD大鼠随机分成2组,正常组（10只）和肝纤维化造模组（50只）。造模组采用40%四氯化碳（CCl4）腹腔注射制备HF动物模型,造模成功后将其随机分为5个组,分别为模型组,杜仲多糖高、中、低剂量组及秋水仙碱组每组10只。秋水仙碱组（1.0×10^-4g·kg^-1）,杜仲多糖高、中、低剂量组（0.14,0.07,0.035 g·kg^-1）分别连续灌胃给药8周后收集样本,测定法大鼠体质量及计算肝脏系数;采用酶联免疫吸附测定（ELISA）检测血清白细胞介素-6（IL-6）,高迁移率族蛋白B1（high-mobility group box 1,HMGB1）,脂多糖（LPS）,肝组织基质金属蛋白酶-1（MMP-1）和金属蛋白酶组织抑制因子-1（TIMP-1）水平;逆转录聚合酶链式反应（RT-PCR）技术分析各组大鼠肝组织Ⅰ,Ⅲ型胶原蛋白,MMP-1,TIMP-1及转化生长因子-β1（TGF-β1）mRNA表达情况。结果：与正常组比较,CCl4能显著降低实验大鼠体质量（P〈0.01）,提高肝脏系数（P〈0.01）;杜仲多糖能显著增加HF模型的体质量（P〈0.01）,显著降低HF模型肝脏系数（P〈0.01）;ELISA检测表明,杜仲多糖能显著降低肝纤维化大鼠血清IL-6,HMGB1及LPS含量（P〈0.01）;RT-PCR检测结果显示,杜仲多糖及秋水仙碱能显著降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA含量（P〈0.05）,明显提高MMP-1含量（P〈0.05,P〈0.01）,且呈量效关系。结论：杜仲多糖具有显著的抗肝纤维化作用,其作用机制可能与抑制降低HF肝脏中Ⅰ,Ⅲ型胶原蛋白,TIMP-1及TGF-β1mRNA表达有关。
