AIM: To investigate the association of the functional monocyte chemotactic protein-1(MCP-1) promoter polymorphism(A-2518G) with spontaneous bacterial peritonitis(SBP).METHODS: Fifty patients with post-hepatitis C live...AIM: To investigate the association of the functional monocyte chemotactic protein-1(MCP-1) promoter polymorphism(A-2518G) with spontaneous bacterial peritonitis(SBP).METHODS: Fifty patients with post-hepatitis C liver cirrhosis and ascites were categorized into two groups; group Ⅰ included 25 patients with SBP and group Ⅱ included 25 patients free from SBP. In addition, a group of 20 healthy volunteers were included. We assessed the MCP-1 gene polymorphism and gene expression as well as interleukin(IL)-10 levels in both blood and ascitic fluid. RESULTS: A significant MCP-1 gene polymorphism was detected in groups Ⅰ and Ⅱ(P = 0.001 and 0.02 respectively). Group Ⅰ was associated with a significantly higher frequency of AG genotype [control 8(40%) vs SBP 19(76.0%), P < 0.001], and group Ⅱ was associated with a significantly higher frequency of GG genotype when compared to healthy volunteers [control 1(5%) vs cirrhotic 16(64%), P < 0.001]. Accordingly, the frequency of G allele was significantly higher in both groups(Ⅰ and Ⅱ) [control 10(25%) vs SBP 27(54%), P < 0.001 and vs cirrhotic 37(74.0%), P < 0.001, respectively]. The total blood and ascetic fluid levels of IL-10 and MCP-1 gene expression were significantly higher in group Ⅰ than in group Ⅱ. Group Ⅰ showed significant reductions in the levels of MCP-1 gene expression and IL-10 in the whole blood and ascetic fluid after therapy. CONCLUSION: MCP-1 GG genotype and G allele may predispose HCV infected patients to a more progressive disease course, while AG genotype may increase the susceptibility to SBP. Patients carrying these genotypes should be under supervision to prevent or restrict further complications.展开更多
AIM:To investigate the expression and prognostic value of CCL2 in gastric cancer,as well as its relationshipwith tumor hypoxia.METHODS:Tumor tissues from 68 gastric cancer patients(GC)were analyzed,and the expression ...AIM:To investigate the expression and prognostic value of CCL2 in gastric cancer,as well as its relationshipwith tumor hypoxia.METHODS:Tumor tissues from 68 gastric cancer patients(GC)were analyzed,and the expression of CCL2and hypoxia-inducible factor 1 alpha(HIF-1α)in tumortissues was detected by immunohistochemistry.Statistical evaluations that were used included univariate logrank tests of Kaplan-Meier curves and multivariate Coxregression model analysis.RESULTS:CCL2 was highly expressed in 66.2%(45/68)of gastric cancer specimens.The distribution of CCL2expression in tumor tissue was consistent with thatof HIF-1α.Patients with high CCL2 expression in GChad a lower overall survival rate[50.6 mo(95%CI:44.44-56.93)vs 64.6 mo(95%CI:60.27-68.94),P=0.013].CONCLUSION:CCL2 expression correlates closely with HIF-1αexpression in gastric cancer.CCL2 may be an independent prognostic marker for GC.展开更多
AIM:To investigate a genetic polymorphism of the monocyte chemotactic protein-1 (MCP-1 ) gene in patients with spontaneous bacterial peritonitis (SBP).METHODS:MCP-1 genotyping was performed in 23 patients with SBP and...AIM:To investigate a genetic polymorphism of the monocyte chemotactic protein-1 (MCP-1 ) gene in patients with spontaneous bacterial peritonitis (SBP).METHODS:MCP-1 genotyping was performed in 23 patients with SBP and 83 cirrhotic control patients with non-infected ascites.RESULTS:The frequency of carriers of the G-allele was lower in SBP patients but this difference did not reach statistical significance. However,in the subgroup of patients with alcoholic cirrhosis (n=80),carriers of the G-allele were significantly less frequent in SBP-patients (38.1%) than in cirrhotic controls (67.8%,P=0.021). CONCLUSION:In patients with alcoholic liver cirrhosis,the-2518 MCP-1 genotype AA is a risk factor for the development of SBP.展开更多
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
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
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
AIM:To investigate the effect of Danzhijiangtang capsule(DJC) on monocyte chemoattractant protein-1(MCP-1) mRNA expression in newly diagnosed type 2 diabetes mellitus(T2DM) subclinical vascular lesions.METHODS:Sixty-t...AIM:To investigate the effect of Danzhijiangtang capsule(DJC) on monocyte chemoattractant protein-1(MCP-1) mRNA expression in newly diagnosed type 2 diabetes mellitus(T2DM) subclinical vascular lesions.METHODS:Sixty-two patients with newly diagnosed T2DM subclinical vascular lesions were randomly divided into a control group and treatment group of 31 cases each.Oral antidiabetic therapy with routine western medicine was conducted in both groups,and the treatment group was additionally treated with DJCs.The treatment course for both groups was 12 wk.Before and after treatment,the total efficiency and traditional Chinese medicine(TCM) syndrome score were calculated.The fasting plasma glucose(FPG),2-h plasma glucose(2hPG),fasting insulin(FINS),insulin resistance index(IRI),hemoglobin(Hb)A1c,blood lipids,and hemorheology indices were determined.In addition,the levels of vascular endothelial growth factors including thrombomodulin(TM),von Willebrand factor(vWF),P-selectin and MCP-1 mRNA were determined.RESULTS:After 12 wk of treatment,the TCM syndrome score was significantly decreased compared to before treatment in both groups.After treatment,FPG,2hPG,HbA1c,FINS,IRI,total cholesterol,triglycerides,low-density lipoprotein,high-density lipoprotein,whole blood low shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA were significantly improved compared to before treatment in both groups.After treatment,the total efficiency and TCM syndrome score in the treatment group were better than in the control group.FINS,IRI,whole blood high shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA level in the treatment group were significantly reduced after treatment compared with control group.CONCLUSION:DJCs are efficacious in supplementing qi,nourishing yin and invigorating blood circulation,and upregulate MCP-1 mRNA expression in patients with T2DM subclinical vascular lesions.展开更多
To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore t...To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.展开更多
Objective:To investigate the effect of malarial pigment(hemozoin,HZ) on expression of heat shock proteins(HSPs) and cell viability in human monocytes by using a stable cell line(THP-1 cells).Methods:THP-1 cells were f...Objective:To investigate the effect of malarial pigment(hemozoin,HZ) on expression of heat shock proteins(HSPs) and cell viability in human monocytes by using a stable cell line(THP-1 cells).Methods:THP-1 cells were fed with native HZ or treated with pro-apoptotic molecule gliotoxin for 9 h.Thereafter,the protein expression of HSP-27 and HSP-70 was evaluated by western blotting.Alternatively,HZ-fed cells were cultured up to 72 h and cell viability parameters(survival,apoptosis and necrosis rates) were measured by flow cytometric analysis. Results:HZ increased basal protein levels of HSP-27 without altering those of HSP-70 in THP-1 cells,and promoted long-term cell survival without inducing apoptosis.As expected,gliotoxin inhibited HSP-27 protein expression and promoted long-term cell apoptosis.Conclusions: Present data show that HZ prevents cell apoptosis and enhances the expression of anli-apoptotic HSP-27 in THP-1 cells,confirming the previous evidences obtained from HZ-fed immunopurified monocytes.Since the use of a stable cell line is pivotal to perform HSP-27 silencing experiments, monocytic THP-1 cells could be a good candidate line for such an approach,which is heavily required to clarify the role of HSP-27 in survival of impaired HZ-fed monocytes during falciparum malaria.展开更多
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).METHODS: Fifty patients with post-hepatitis C liver cirrhosis and ascites were categorized into two groups; group Ⅰ included 25 patients with SBP and group Ⅱ included 25 patients free from SBP. In addition, a group of 20 healthy volunteers were included. We assessed the MCP-1 gene polymorphism and gene expression as well as interleukin(IL)-10 levels in both blood and ascitic fluid. RESULTS: A significant MCP-1 gene polymorphism was detected in groups Ⅰ and Ⅱ(P = 0.001 and 0.02 respectively). Group Ⅰ was associated with a significantly higher frequency of AG genotype [control 8(40%) vs SBP 19(76.0%), P < 0.001], and group Ⅱ was associated with a significantly higher frequency of GG genotype when compared to healthy volunteers [control 1(5%) vs cirrhotic 16(64%), P < 0.001]. Accordingly, the frequency of G allele was significantly higher in both groups(Ⅰ and Ⅱ) [control 10(25%) vs SBP 27(54%), P < 0.001 and vs cirrhotic 37(74.0%), P < 0.001, respectively]. The total blood and ascetic fluid levels of IL-10 and MCP-1 gene expression were significantly higher in group Ⅰ than in group Ⅱ. Group Ⅰ showed significant reductions in the levels of MCP-1 gene expression and IL-10 in the whole blood and ascetic fluid after therapy. CONCLUSION: MCP-1 GG genotype and G allele may predispose HCV infected patients to a more progressive disease course, while AG genotype may increase the susceptibility to SBP. Patients carrying these genotypes should be under supervision to prevent or restrict further complications.
基金Supported by National Natural Science Foundation of China,No.81101739China International Medical Foundation,No.CIMF-F-H001-023
文摘AIM:To investigate the expression and prognostic value of CCL2 in gastric cancer,as well as its relationshipwith tumor hypoxia.METHODS:Tumor tissues from 68 gastric cancer patients(GC)were analyzed,and the expression of CCL2and hypoxia-inducible factor 1 alpha(HIF-1α)in tumortissues was detected by immunohistochemistry.Statistical evaluations that were used included univariate logrank tests of Kaplan-Meier curves and multivariate Coxregression model analysis.RESULTS:CCL2 was highly expressed in 66.2%(45/68)of gastric cancer specimens.The distribution of CCL2expression in tumor tissue was consistent with thatof HIF-1α.Patients with high CCL2 expression in GChad a lower overall survival rate[50.6 mo(95%CI:44.44-56.93)vs 64.6 mo(95%CI:60.27-68.94),P=0.013].CONCLUSION:CCL2 expression correlates closely with HIF-1αexpression in gastric cancer.CCL2 may be an independent prognostic marker for GC.
文摘AIM:To investigate a genetic polymorphism of the monocyte chemotactic protein-1 (MCP-1 ) gene in patients with spontaneous bacterial peritonitis (SBP).METHODS:MCP-1 genotyping was performed in 23 patients with SBP and 83 cirrhotic control patients with non-infected ascites.RESULTS:The frequency of carriers of the G-allele was lower in SBP patients but this difference did not reach statistical significance. However,in the subgroup of patients with alcoholic cirrhosis (n=80),carriers of the G-allele were significantly less frequent in SBP-patients (38.1%) than in cirrhotic controls (67.8%,P=0.021). CONCLUSION:In patients with alcoholic liver cirrhosis,the-2518 MCP-1 genotype AA is a risk factor for the development of 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.
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AIM:To investigate the effect of Danzhijiangtang capsule(DJC) on monocyte chemoattractant protein-1(MCP-1) mRNA expression in newly diagnosed type 2 diabetes mellitus(T2DM) subclinical vascular lesions.METHODS:Sixty-two patients with newly diagnosed T2DM subclinical vascular lesions were randomly divided into a control group and treatment group of 31 cases each.Oral antidiabetic therapy with routine western medicine was conducted in both groups,and the treatment group was additionally treated with DJCs.The treatment course for both groups was 12 wk.Before and after treatment,the total efficiency and traditional Chinese medicine(TCM) syndrome score were calculated.The fasting plasma glucose(FPG),2-h plasma glucose(2hPG),fasting insulin(FINS),insulin resistance index(IRI),hemoglobin(Hb)A1c,blood lipids,and hemorheology indices were determined.In addition,the levels of vascular endothelial growth factors including thrombomodulin(TM),von Willebrand factor(vWF),P-selectin and MCP-1 mRNA were determined.RESULTS:After 12 wk of treatment,the TCM syndrome score was significantly decreased compared to before treatment in both groups.After treatment,FPG,2hPG,HbA1c,FINS,IRI,total cholesterol,triglycerides,low-density lipoprotein,high-density lipoprotein,whole blood low shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA were significantly improved compared to before treatment in both groups.After treatment,the total efficiency and TCM syndrome score in the treatment group were better than in the control group.FINS,IRI,whole blood high shear specific viscosity,plasma specific viscosity,TM,vWF,P-selectin and MCP-1 mRNA level in the treatment group were significantly reduced after treatment compared with control group.CONCLUSION:DJCs are efficacious in supplementing qi,nourishing yin and invigorating blood circulation,and upregulate MCP-1 mRNA expression in patients with T2DM subclinical vascular lesions.
基金This project was supported by a grant from the NationalNatural Sciences Foundation of China (No .30470713)
文摘To observe the effects of simvastatin on nuclear factor kappaB （NF-kB）-DNA binding activity and on the expression of monocyte chemoattractant protein-1 （MCP-1） in atherosclerotic plaque in rabbits and to explore the anti-atherosclerotic properties beyond its lipid-lowering effects. Thirty-six New Zealand male rabbits were randomly divided into low-cholesterol group （LC）, high- cholesterol group （HC）, high-cholesterol＋ simvastatin group （HC＋S） and then were fed for 12 weeks. At the end of the experiment, standard enzymatic assays, electrophoretic mobility shift as- say （EMSA）, immunohistochemical staining, and morphometry were performed to observe serum lipids, NF-kB-DNA binding activity, MCP-1 protein expression, intirna thickness and plaque area of aorta respectively in all three groups. Our results showed that the serum lipids, NF-kB-DNA binding activity, expression of MCP-1 protein, intima thickness, and plaque area of aorta in the LC and HC＋S groups were significantly lower than those in the HC group （P〈0.05）. There was no significant difference in the serum lipids between the LC and HC＋S groups （P〉0.05）, but the NF-kB-DNA binding activity, the expression of MCP-1 protein and the intirna thickness and plaque area of aorta in the HC＋S group were significantly decreased as compared to the LC group （P〈0. 05）. This study demonstrated that simvastatin could decrease atherosclerosis by inhibiting the NF-kB-DNA binding activity and by reducing the expression of MCP-1 protein.
基金supported by University of Torino Intramural Funds to GG and by grants to MP from the Compagnia di San Paolo,Torino,in the context of the Italian Malaria Network
文摘Objective:To investigate the effect of malarial pigment(hemozoin,HZ) on expression of heat shock proteins(HSPs) and cell viability in human monocytes by using a stable cell line(THP-1 cells).Methods:THP-1 cells were fed with native HZ or treated with pro-apoptotic molecule gliotoxin for 9 h.Thereafter,the protein expression of HSP-27 and HSP-70 was evaluated by western blotting.Alternatively,HZ-fed cells were cultured up to 72 h and cell viability parameters(survival,apoptosis and necrosis rates) were measured by flow cytometric analysis. Results:HZ increased basal protein levels of HSP-27 without altering those of HSP-70 in THP-1 cells,and promoted long-term cell survival without inducing apoptosis.As expected,gliotoxin inhibited HSP-27 protein expression and promoted long-term cell apoptosis.Conclusions: Present data show that HZ prevents cell apoptosis and enhances the expression of anli-apoptotic HSP-27 in THP-1 cells,confirming the previous evidences obtained from HZ-fed immunopurified monocytes.Since the use of a stable cell line is pivotal to perform HSP-27 silencing experiments, monocytic THP-1 cells could be a good candidate line for such an approach,which is heavily required to clarify the role of HSP-27 in survival of impaired HZ-fed monocytes during falciparum malaria.
