目的:研究IGF1 rs5742612位点的基因多态性与中国青岛地区汉族人群中MASLD发病风险之间的相关性。方法:纳入2022年12月到2023年12月于青岛市市立医院就诊的确诊为MASLD的中国汉族患者205人作为研究的病例组;同时纳入130名健康体检者作...目的:研究IGF1 rs5742612位点的基因多态性与中国青岛地区汉族人群中MASLD发病风险之间的相关性。方法:纳入2022年12月到2023年12月于青岛市市立医院就诊的确诊为MASLD的中国汉族患者205人作为研究的病例组;同时纳入130名健康体检者作为对照组。收集纳入研究的患者的基本临床信息,进行生化指标的临床检测及基因组DNA的提取和IGF1 rs5742612位点基因型测定。利用χ2检验来检验两组间基因型频率和等位基因频率是否存在差异。基于显性和隐性模型,采用Logistic回归分析基因型和等位基因与疾病发生风险的关联。结果:IGF1 rs5742612位点基因型频率(χ2 = 0.286, P = 0.867)和等位基因频率(χ2 = 0.083, P = 0.773)在两组之间的分布无统计学差异。显性和隐性模型均提示该位点与MASLD之间关联不存在统计学意义(P均 P均 > 0.05)。结论:IGF1 rs5742612多态性与MASLD发病无显著相关性。Objective: To investigate the correlation between genetic polymorphisms at the IGF1 rs5742612 locus and the risk of developing MASLD in the Han Chinese population in Qingdao, China. Methods: A total of 205 Chinese Han patients diagnosed with MASLD who attended Qingdao Municipal Hospital from December 2022 to December 2023 were included as the case group of the study;130 healthy medical check-ups were also included as the control group. The basic clinical information of the patients included in the study was collected, and clinical tests of biochemical indexes as well as genomic DNA extraction and genotyping at the IGF1 rs5742612 locus were performed. The χ2 test was used to test whether there were differences in genotype frequencies and allele frequencies between the two groups. Based on the dominant and recessive models, logistic regression was used to analyse the association between genotype and allele and the risk of disease occurrence. Results: The distribution of genotype frequencies (χ2 = 0.286, P = 0.867) and allele frequencies (χ2 = 0.083, P = 0.773) at the IGF1 rs5742612 locus were not statistically different between the two groups. Both dominant and recessive models suggested that the association between this locus and MASLD was not statistically significant (both P P > 0.05). Conclusion: There was no significant correlation between IGF1 rs5742612 polymorphism and the development of MASLD.展开更多
diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.human umbilical cord mesen...diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red“O”staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.展开更多
BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The reg...BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.展开更多
文摘目的:研究IGF1 rs5742612位点的基因多态性与中国青岛地区汉族人群中MASLD发病风险之间的相关性。方法:纳入2022年12月到2023年12月于青岛市市立医院就诊的确诊为MASLD的中国汉族患者205人作为研究的病例组;同时纳入130名健康体检者作为对照组。收集纳入研究的患者的基本临床信息,进行生化指标的临床检测及基因组DNA的提取和IGF1 rs5742612位点基因型测定。利用χ2检验来检验两组间基因型频率和等位基因频率是否存在差异。基于显性和隐性模型,采用Logistic回归分析基因型和等位基因与疾病发生风险的关联。结果:IGF1 rs5742612位点基因型频率(χ2 = 0.286, P = 0.867)和等位基因频率(χ2 = 0.083, P = 0.773)在两组之间的分布无统计学差异。显性和隐性模型均提示该位点与MASLD之间关联不存在统计学意义(P均 P均 > 0.05)。结论:IGF1 rs5742612多态性与MASLD发病无显著相关性。Objective: To investigate the correlation between genetic polymorphisms at the IGF1 rs5742612 locus and the risk of developing MASLD in the Han Chinese population in Qingdao, China. Methods: A total of 205 Chinese Han patients diagnosed with MASLD who attended Qingdao Municipal Hospital from December 2022 to December 2023 were included as the case group of the study;130 healthy medical check-ups were also included as the control group. The basic clinical information of the patients included in the study was collected, and clinical tests of biochemical indexes as well as genomic DNA extraction and genotyping at the IGF1 rs5742612 locus were performed. The χ2 test was used to test whether there were differences in genotype frequencies and allele frequencies between the two groups. Based on the dominant and recessive models, logistic regression was used to analyse the association between genotype and allele and the risk of disease occurrence. Results: The distribution of genotype frequencies (χ2 = 0.286, P = 0.867) and allele frequencies (χ2 = 0.083, P = 0.773) at the IGF1 rs5742612 locus were not statistically different between the two groups. Both dominant and recessive models suggested that the association between this locus and MASLD was not statistically significant (both P P > 0.05). Conclusion: There was no significant correlation between IGF1 rs5742612 polymorphism and the development of MASLD.
基金supported by the Peak Disciplines(Type IV)of Institutions of Higher Learning in Shanghai,the Discipline Leader Program of Pudong New District Health and Family Planning Commission(No.PWRd2018-02)the Natural Science Foundation of Jiangxi Province(Nos.20181ACB20021 and 20181BAB205044),China.
文摘diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red“O”staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.
文摘BACKGROUND Gastrointestinal stromal tumors(GISTs)are typical gastrointestinal tract neoplasms.Imatinib is the first-line therapy for GIST patients.Drug resistance limits the long-term effectiveness of imatinib.The regulatory effect of insulin-like growth factor 2(IGF2)has been confirmed in various cancers and is related to resistance to chemotherapy and a worse prognosis.AIM To further investigate the mechanism of IGF2 specific to GISTs.METHODS IGF2 was screened and analyzed using Gene Expression Omnibus(GEO:GSE225819)data.After IGF2 knockdown or overexpression by transfection,the phenotypes(proliferation,migration,invasion,apoptosis)of GIST cells were characterized by cell counting kit 8,Transwell,and flow cytometry assays.We used western blotting to evaluate pathway-associated and epithelial-mesenchymal transition(EMT)-associated proteins.We injected transfected cells into nude mice to establish a tumor xenograft model and observed the occurrence and metastasis of GIST.RESULTS Data from the GEO indicated that IGF2 expression is high in GISTs,associated with liver metastasis,and closely related to drug resistance.GIST cells with high expression of IGF2 had increased proliferation and migration,invasiveness and EMT.Knockdown of IGF2 significantly inhibited those activities.In addition,OEIGF2 promoted GIST metastasis in vivo in nude mice.IGF2 activated IGF1R signaling in GIST cells,and IGF2/IGF1R-mediated glycolysis was required for GIST with liver metastasis.GIST cells with IGF2 knockdown were sensitive to imatinib treatment when IGF2 overexpression significantly raised imatinib resistance.Moreover,2-deoxy-D-glucose(a glycolysis inhibitor)treatment reversed IGF2 overexpressionmediated imatinib resistance in GISTs.CONCLUSION IGF2 targeting of IGF1R signaling inhibited metastasis and decreased imatinib resistance by driving glycolysis in GISTs.
