BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its me...BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF.展开更多
AIM: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP).
AIM: To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer(CRC) and benign patients and postoperatively after CRC resection.METHODS: A plasma bank was screened for minimally i...AIM: To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer(CRC) and benign patients and postoperatively after CRC resection.METHODS: A plasma bank was screened for minimally invasive colorectal cancer resection(MICR) for CRC and benign disease(BEN) patients for whom preoperative, early postoperative, and 1 or more late postoperative samples(postoperative day 7-27) were available. Monocyte chemotactic protein-1(MCP-1) levels(pg/mL) were determined via enzyme linked immuno-absorbent assay. RESULTS: One hundred and two CRC and 86 BEN patients were studied. The CRC patient's median preoperative MCP-1 level(283.1, CI: 256.0, 294.3) was higher than the BEN group level(227.5, CI: 200.2, 245.2; P = 0.0004). Vs CRC preoperative levels, elevated MCP-1 plasma levels were found on postoperative day 1(446.3, CI: 418.0, 520.1), postoperative day 3(342.7, CI: 320.4, 377.4), postoperative day 7-13(326.5, CI: 299.4, 354.1), postoperative day 14-20(361.6, CI: 287.8, 407.9), and postoperative day 21-27(318.1, CI: 287.2, 371.6; P < 0.001 for all). CONCLUSION: Preoperative MCP-1 levels were higher in CRC patients(vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.展开更多
I read with great interest the article by Gbele et al published in issue 44 of World J Gastroenterol 2009.The results of their study indicate that-2518 Monocyte chemotactic protein-1(MCP-1)genotype AA is a risk fact...I read with great interest the article by Gbele et al published in issue 44 of World J Gastroenterol 2009.The results of their study indicate that-2518 Monocyte chemotactic protein-1(MCP-1)genotype AA is a risk factor for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.However,there are some items that need to be discussed.展开更多
Objective：To investigate the effect of MCP-1 on mesenchymal stem cells（MSCs） homing to injured myocardium in a rat myocardial infarction（MI） model. Methods：Rat myocardial infarction model was established by perm...Objective：To investigate the effect of MCP-1 on mesenchymal stem cells（MSCs） homing to injured myocardium in a rat myocardial infarction（MI） model. Methods：Rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with BrdU. The Rats were divided into two groups. Monocyte chemotactic protein I（MCP-1） expression were measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1, 2, 4, 7, 14 and 28 days post operation in MCP-1 detection group. The rats were injected with MCP-1, anti-MCP-1 antibody or saline 4 days after myocardial infarction in intervention group. Then, a total of 5 × 10^6 cells in 2.5 ml of PBS were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and blood vessel density were assessed 28 days post injection. Results：Self-generating MCP-1 expression was increased at the first day, peaked at the 7^th day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than that in the non-MI group（P= 0.000）, the MSCs enrichment in the host hearts were more abundant in the MCP-1 injected group than that in the anti-MCP-1 antibody and saline injected groups （P = 0.000）. Cardiac function was improved more in MCP-1 injected group than anti-MCP-1 antibody and saline injected groups（P= 0.000）. Neovascularization in MCP-1 injected group significantly increased compared with that of other groups（P = 0.000）. Conclusion： Myocardial MCP-1 expression was increased only in the early phase post MI. MCP-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization.展开更多
Objective: To explore the effect of Irbesartan and Metformin on tumor necrosis factor receptor 1 and monocyte chemoattractant protein-1 in patients with early diabetic nephropathy. Methods: A total of 162 patients wit...Objective: To explore the effect of Irbesartan and Metformin on tumor necrosis factor receptor 1 and monocyte chemoattractant protein-1 in patients with early diabetic nephropathy. Methods: A total of 162 patients with early diabetic nephropathy who had been admitted to the Hospital between February 2017 and February 2018 were randomly assigned into a Metformin group, an Irbesartan group, and a combination therapy group. The Metformin group were treated with oral Metformin, those in the Irbesartan group were given oral Irbesartan for treatment, and the combination therapy group was treated with Metformin combined with Irbesartan. After 3 months of continuous treatment, the levels of sTNFR1, high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, glucose metabolism index, proteinuria, and serum creatinine levels in the two groups were compared. Results:After treatment, the levels of sTNFR1, sICAM-1, hs-CRP, and MCP-1 in the three groups decreased compared with those before treatment, and the levels in the combination therapy group were all shown to be lower than those of the Metformin group and the Irbesartan group, with statistically significant differences (P<0.05). The levels of glycosylated hemoglobin and fasting blood glucose in the three groups were significantly lower than before treatment, and those in the combination therapy group were lower than the Metformin group and Irbesartan group, where the difference was statistically significant (P<0.05). The 24-hour urinary protein quantification, urinary albumin excretion rate, and serum creatinine in the combination therapy group were lower than those in the Metformin group and in the Irbesartan group, where the differences were statistically significant (P<0.05). Conclusion: The effects of metformin combined with irbesartan on early diabetic nephropathy patients were significant, which can effectively reduce the levels of serum sTNFR1 and MCP-1, relieve inflammation and improve glucose metabolism and proteinuria level.展开更多
基金Supported by the National Natural Science Foundation of China,No.81570543 and No.81560104
文摘BACKGROUND Massive hepatocyte death is the core event in acute liver failure(ALF).Gasdermin D(GSDMD)-mediated pyroptosis is a type of highly inflammatory cell death.However,the role of hepatocyte pyroptosis and its mechanisms of expanding inflammatory responses in ALF are unclear.AIM To investigate the role and mechanisms of GSDMD-mediated hepatocyte pyroptosis through in vitro and in vivo experiments.METHODS The expression of pyroptosis pathway-associated proteins in liver tissues from ALF patients and a hepatocyte injury model was examined by Western blot.GSDMD short hairpin RNA(shRNA)was used to investigate the effects of downregulation of GSDMD on monocyte chemotactic protein 1(MCP1)and its receptor CC chemokine receptor-2(CCR2)in vitro.For in vivo experiments,we used GSDMD knockout mice to investigate the role and mechanism of GSDMD in a D-galactose/lipopolysaccharide(D-Galn/LPS)-induced ALF mouse model.RESULTS The levels of pyroptosis pathway-associated proteins in liver tissue from ALF patients and a hepatocyte injury model increased significantly.The level of GSDMD-N protein increased most obviously(P<0.001).In vitro,downregulation of GSDMD by shRNA decreased the cell inhibition rate and the levels of MCP1/CCR2 proteins(P<0.01).In vivo,GSDMD knockout dramatically eliminated inflammatory damage in the liver and improved the survival of DGaln/LPS-induced ALF mice(P<0.001).Unlike the mechanism of immune cell pyroptosis that involves releasing interleukin(IL)-1βand IL-18,GSDMDmediated hepatocyte pyroptosis recruited macrophages via MCP1/CCR2 to aggravate hepatocyte death.However,this pathological process was inhibited after knocking down GSDMD.CONCLUSION GSDMD-mediated hepatocyte pyroptosis plays an important role in the pathogenesis of ALF,recruiting macrophages to release inflammatory mediators by upregulating MCP1/CCR2 and leading to expansion of the inflammatory responses.GSDMD knockout can reduce hepatocyte death and inflammatory responses,thus alleviating ALF.
文摘AIM: To investigate the association of the functional monocyte chemotactic protein-1 (MCP-1) promoter polymorphism (A-2518G) with spontaneous bacterial peritonitis (SBP).
文摘AIM: To investigate plasma Monocyte Chemotactic Protein-1 levels preoperatively in colorectal cancer(CRC) and benign patients and postoperatively after CRC resection.METHODS: A plasma bank was screened for minimally invasive colorectal cancer resection(MICR) for CRC and benign disease(BEN) patients for whom preoperative, early postoperative, and 1 or more late postoperative samples(postoperative day 7-27) were available. Monocyte chemotactic protein-1(MCP-1) levels(pg/mL) were determined via enzyme linked immuno-absorbent assay. RESULTS: One hundred and two CRC and 86 BEN patients were studied. The CRC patient's median preoperative MCP-1 level(283.1, CI: 256.0, 294.3) was higher than the BEN group level(227.5, CI: 200.2, 245.2; P = 0.0004). Vs CRC preoperative levels, elevated MCP-1 plasma levels were found on postoperative day 1(446.3, CI: 418.0, 520.1), postoperative day 3(342.7, CI: 320.4, 377.4), postoperative day 7-13(326.5, CI: 299.4, 354.1), postoperative day 14-20(361.6, CI: 287.8, 407.9), and postoperative day 21-27(318.1, CI: 287.2, 371.6; P < 0.001 for all). CONCLUSION: Preoperative MCP-1 levels were higher in CRC patients(vs BEN). After MICR for CRC, MCP-1 levels were elevated for 1 mo and may promote angiogenesis, cancer recurrence and metastasis.
文摘I read with great interest the article by Gbele et al published in issue 44 of World J Gastroenterol 2009.The results of their study indicate that-2518 Monocyte chemotactic protein-1(MCP-1)genotype AA is a risk factor for spontaneous bacterial peritonitis in patients with alcoholic cirrhosis.However,there are some items that need to be discussed.
文摘Objective：To investigate the effect of MCP-1 on mesenchymal stem cells（MSCs） homing to injured myocardium in a rat myocardial infarction（MI） model. Methods：Rat myocardial infarction model was established by permanent left anterior descending branch ligation. Mesenchymal stem cells from donor rats were cultured in IMDM and labeled with BrdU. The Rats were divided into two groups. Monocyte chemotactic protein I（MCP-1） expression were measured by in situ hybridization and immunohistochemistry in the sham operated or infarcted hearts at 1, 2, 4, 7, 14 and 28 days post operation in MCP-1 detection group. The rats were injected with MCP-1, anti-MCP-1 antibody or saline 4 days after myocardial infarction in intervention group. Then, a total of 5 × 10^6 cells in 2.5 ml of PBS were injected through the tail vein. The number of the labeled MSCs in the infarcted hearts was counted 3 days post injection. Cardiac function and blood vessel density were assessed 28 days post injection. Results：Self-generating MCP-1 expression was increased at the first day, peaked at the 7^th day and decreased thereafter post MI and remained unchanged in sham operated hearts. The MSCs enrichment in the host hearts were more abundant in the MI groups than that in the non-MI group（P= 0.000）, the MSCs enrichment in the host hearts were more abundant in the MCP-1 injected group than that in the anti-MCP-1 antibody and saline injected groups （P = 0.000）. Cardiac function was improved more in MCP-1 injected group than anti-MCP-1 antibody and saline injected groups（P= 0.000）. Neovascularization in MCP-1 injected group significantly increased compared with that of other groups（P = 0.000）. Conclusion： Myocardial MCP-1 expression was increased only in the early phase post MI. MCP-1 may enhance MSCs homing to the injured heart and improve cardiac function by promoting neovascularization.
文摘Objective: To explore the effect of Irbesartan and Metformin on tumor necrosis factor receptor 1 and monocyte chemoattractant protein-1 in patients with early diabetic nephropathy. Methods: A total of 162 patients with early diabetic nephropathy who had been admitted to the Hospital between February 2017 and February 2018 were randomly assigned into a Metformin group, an Irbesartan group, and a combination therapy group. The Metformin group were treated with oral Metformin, those in the Irbesartan group were given oral Irbesartan for treatment, and the combination therapy group was treated with Metformin combined with Irbesartan. After 3 months of continuous treatment, the levels of sTNFR1, high-sensitivity C-reactive protein, monocyte chemoattractant protein-1, glucose metabolism index, proteinuria, and serum creatinine levels in the two groups were compared. Results:After treatment, the levels of sTNFR1, sICAM-1, hs-CRP, and MCP-1 in the three groups decreased compared with those before treatment, and the levels in the combination therapy group were all shown to be lower than those of the Metformin group and the Irbesartan group, with statistically significant differences (P<0.05). The levels of glycosylated hemoglobin and fasting blood glucose in the three groups were significantly lower than before treatment, and those in the combination therapy group were lower than the Metformin group and Irbesartan group, where the difference was statistically significant (P<0.05). The 24-hour urinary protein quantification, urinary albumin excretion rate, and serum creatinine in the combination therapy group were lower than those in the Metformin group and in the Irbesartan group, where the differences were statistically significant (P<0.05). Conclusion: The effects of metformin combined with irbesartan on early diabetic nephropathy patients were significant, which can effectively reduce the levels of serum sTNFR1 and MCP-1, relieve inflammation and improve glucose metabolism and proteinuria level.
文摘目的探究凝血指标联合血清单核细胞趋化蛋白-1(monocyte chemotactic protein-1,MCP-1)对慢性肾脏病患者急性肾损伤的预测价值。方法选择2021年1月─2023年6月于联勤保障部队第九〇八医院收治的慢性肾脏病患者155例为研究对象,比较急性肾损伤组(40例)及急性肾损伤未发生组(115例)患者的临床基本资料、凝血指标、MCP-1水平。探究影响慢性肾脏病患者急性肾损伤发生的主要风险因素及凝血指标、MCP-1预测慢性肾脏病患者急性肾损伤的临床价值。结果急性肾损伤组患者的凝血酶时间(TT)、活化部分凝血酶时间(APTT)、凝血酶原时间(PT)、MCP-1水平较未发生组升高(t=20.506、20.551、21.120、16.230;均P<0.001);急性肾损伤组患者纤维蛋白原(FIB)水平较未发生组降低(t=8.441;P<0.001)。慢性肾脏病患者急性肾损伤与年龄、性别、体质量指数(body mass index,BMI)、糖尿病无关(t=0.521、0.760、0.648、2.399;P=0.477、0.383、0.341、0.121),与舒张压、收缩压、血尿酸、空腹血糖、总胆固醇(TC)、血肌酐(Scr)、三酰甘油(TAG)、高脂血症、高血压有关(t=15.681、12.942、11.694、6.914、12.836、8.392、9.724、14.856、11.372;均P<0.001)。以慢性肾脏病患者发生急性肾损伤为因变量,临床资料中P<0.05的变量为自变量行多因素Logistic回归分析,结果显示收缩压、舒张压、空腹血糖、血尿酸、TC、TAG、Scr、高血压、高脂血症、PT、TT、FIB、APTT、MCP-1为慢性肾脏病患者急性肾损伤发生的主要危险因素(OR值分别为:3490、3.357、3.050、2.980、3.264、2.861、3.287、2.939、3.466、9.196、3.350、3.281、2.974、3.404;95%CI分别为:2.210~4.770、1.947~4.767、1.862~4.238、1.838~4.122、2.104~4.424、1.751~3.971、2.065~4.510、1.813~4.065、2.416~4.516、1.982~4.410、2.082~4.618、2.103~4.459、1.780~4.168、2.092~4.716;P值分别为:0.002、0.004、0.005、0.002、<0.001、<0.001、<0.001、0.007、0.002、<0.001、<0.001、<0.001、<0.001、<0.001)。结论TT、APTT、PT、FIB、MCP-1水平与患者急性肾损伤发生有关,对慢性肾脏病患者急性肾损伤有较好的预测价值。
