Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chem...Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.展开更多
目的探讨ABI家族成员3结合蛋白(ABI family member 3-binding protein,ABI3BP)在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导内皮祖细胞功能障碍中的作用及机制。方法为探讨ABI3BP在AngⅡ诱导内皮祖细胞功能障碍中的作用,将细胞分为4组,sh-N...目的探讨ABI家族成员3结合蛋白(ABI family member 3-binding protein,ABI3BP)在血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导内皮祖细胞功能障碍中的作用及机制。方法为探讨ABI3BP在AngⅡ诱导内皮祖细胞功能障碍中的作用,将细胞分为4组,sh-NC组[转染阴性对照短发夹RNA(LV-scramble-shRNA)+磷酸盐缓冲液(phosphate buffered saline,PBS)]、sh-ABI3BP组[转染ABI3BP shRNA(LV-ABI3BP-shRNA)+PBS]、sh-NC+AngⅡ组(LV-scramble-shRNA+AngⅡ)和sh-ABI3BP+AngⅡ组(LV-ABI3BP-shRNA+AngⅡ)。采用Transwell实验检测细胞迁移能力,黏附实验检测细胞黏附能力,Matrigel检测细胞成管能力,原位末端标记法检测细胞凋亡。Western blot检测整合素β1-黏着斑激酶(focal adhesion kinase,FAK)-P53信号通路变化情况。结果与sh-NC组比较,sh-NC+AngⅡ组迁移细胞数量、黏附细胞数量、小管形成数量显著降低,细胞凋亡率、整合素β1、磷酸化FAK(p-FAK)/FAK及P53蛋白表达显著增高,差异有统计学意义(P<0.05)。与sh-NC+AngⅡ组比较,sh-ABI3BP+AngⅡ组迁移细胞数量[(88.67±8.33)个vs(62.33±7.37)个]、黏附细胞数量[(104.33±6.03)个vs(68.33±10.05)个]、小管形成数量[(36.33±3.21)个vs(19.33±3.06)个]显著增高,细胞凋亡率、整合素β1、p-FAK/FAK及P53蛋白表达水平显著降低,差异有统计学意义(P<0.05)。结论AngⅡ可上调ABI3BP表达,敲低ABI3BP基因表达可改善AngⅡ诱导的内皮祖细胞功能障碍,其机制可能与抑制整合素β1-FAK-P53信号通路有关。展开更多
目的探究H型原发性高血压(高血压)患者血清诱骗受体3(decoy receptor 3,DcR3)、含1型血小板反应蛋白基序的去整合素金属蛋白酶13(A disintegrin and metalloproteinase with A thrombospondin type 1 motif member 13,ADAMTS13)浓度与...目的探究H型原发性高血压(高血压)患者血清诱骗受体3(decoy receptor 3,DcR3)、含1型血小板反应蛋白基序的去整合素金属蛋白酶13(A disintegrin and metalloproteinase with A thrombospondin type 1 motif member 13,ADAMTS13)浓度与其心血管功能及预后的关系。方法选取大庆市人民医院2020年6月至2022年6月收治的132例高血压患者作为观察对象,根据同型半胱氨酸(homocysteine,Hcy)浓度分为非H型高血压组40例和H型高血压组92例,根据预后情况将H型高血压患者分为预后良好组和预后不良组,并选择同期来大庆市人民医院健康体检的成年人70名作为对照组。采用酶联免疫吸附试验法检测受试者血清中DcR3、ADAMTS13浓度,Pearson法分析血清中DcR3、ADAMTS13浓度与心血管功能指标的相关性,多因素Logistic回归分析H型高血压患者1年预后不良的影响因素。绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清DcR3、ADAMTS13浓度对H型高血压患者1年预后不良的预测价值。结果与对照组[(122.28±32.34)mmHg(1 mmHg=0.133 kPa)、(48.16±8.65)mmHg、(8.59±1.25)mm、(118.34±34.25)g/m2、(1.48±0.34)g/L、(57.15±14.94)mg/L、(1.45±0.31)、70.28%±15.21%]比较,H型高血压组患者的收缩压[(139.35±38.21)mmHg]、脉压[(57.37±11.75)mmHg]、左心室后壁厚度(posterior wall thickness,PWT)[(11.69±2.00)mm]以及左心室质量指数(left ventricular mass index,LVMI)[(148.54±38.22)g/m2]显著升高,DcR3[(0.74±0.19)g/L]、ADAMTS13浓度[(14.13±4.62)mg/L]、二尖瓣舒张早期血流峰值/二尖瓣舒张晚期血流峰值(E-peak to A-peak of the mitral flow spectrum,E/A)(0.65±0.13)、左心室射血分数(left ventricular ejection fraction,LVEF)(64.26%±12.75%)显著降低,差异有统计学意义(P<0.05);与非H型高血压组患者组比较,H型高血压组患者的DcR3、ADAMTS13浓度及E/A显著降低,LVMI显著升高,差异有统计学意义(P<0.05)。H型高血压组患者血清中DcR3、ADAMTS13浓度均与收缩压、脉压和LVMI呈负相关(P<0.05),而与E/A、LVEF呈正相关(P<0.05)。预后不良组患者的年龄显著高于预后良好组,E/A(0.38±0.07)、DcR3[(0.45±0.13)g/L]、ADAMTS13浓度[(8.45±2.11)mg/L]显著低于预后良好组[0.75±0.11、(0.85±0.27)g/L、(16.25±4.85)mg/L],差异有统计学意义(P<0.05)。DcR3、ADAMTS13是H型高血压患者预后不良的保护因素(P<0.05)。血清DcR3、ADAMTS13浓度单独及二者联合预测H型高血压患者1年发生预后不良的曲线下面积(area under the curve,AUC)分别为0.906、0.844、0.950。结论H型高血压疾病患者血清DcR3、ADAMTS13浓度降低,与心血管功能及预后密切相关,对该疾病的预后评估有重要价值。展开更多
BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPI...BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPINH1 in colorectal cancer(CRC)remain largely elusive.AIM To investigate the effects of SERPINH1 on CRC cells and its specific mechanism.METHODS Quantitative real-time polymerase chain reaction,western blotting analysis,The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues.A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC.RESULTS SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues,manifested at both mRNA and protein tiers.Elevated SERPINH1 levels correlated closely with advanced T stage,lymph node involvement,and distant metastasis,exhibiting a significant association with poorer overall survival among CRC patients.Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation,invasion,and migration in vitro,while conversely,SERPINH1 knockdown elicited the opposite effects.Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation.Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation,thereby facilitating CRC cell invasion and migration.CONCLUSION These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC,potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.展开更多
Recent exploration results indicate that a significant exploration potential remains in the Dongying Depression of the Bohai Bay Basin and the undiscovered oil and gas are largely reservoired in subtle traps including...Recent exploration results indicate that a significant exploration potential remains in the Dongying Depression of the Bohai Bay Basin and the undiscovered oil and gas are largely reservoired in subtle traps including turbidite litholigcal traps of the Sha-3 Member. In order to effectively guide the exploration program targeting turbidites, this study will focus on the depositional models of the Sha-3 Member turbidites and oil/gas accumulation characteristics in these turbidites. Two corresponding relationships were found. One is that the East African Rift Valley provides a modern analog for the depositional systems in the Dongying Depression. The other is that the depositional models of line-sourced slope aprons, single point-source submarine fan and multiple source ramp turbidite, established for deep-sea turbidites, can be applied to interpret the depositional features of the turbidite fans of three different origins: slope turbidite aprons, lake floor turbidite fans and delta-fed turbidite fans in the Sha-3 Member. Updip sealing integrity is the key factor determining whether oil/gas accumulates or not in the slope aprons and lake floor fans. The factors controlling oil/gas migration and accumulation in the delta-fed turbidite fans are not very clear. Multiple factors rather than a single factor probably played significant roles in these processes.展开更多
基金National Yang Ming Chiao Tung University Far Eastern Memorial Hospital Joint Research Programs(NYCU-FEMH 109DN03,110DN06,111DN04,112DN05).
文摘Hepatocellular carcinoma(HCC)is a leading cause of death worldwide.Current therapies are effective for HCC patients with early disease,but many patients suffer recurrence after surgery and have a poor response to chemotherapy.Therefore,new therapeutic targets are needed.We analyzed gene expression profiles between HCC tissues and normal adjacent tissues from public databases and found that the expression of genes involved in lipid metabolism was significantly different.The analysis showed that AKR1C3 was upregulated in tumors,and high AKR1C3 expression was associated with a poorer prognosis in HCC patients.In vitro,assays demonstrated that the knockdown of AKR1C3 or the addition of the AKR1C3 inhibitor indomethacin suppressed the growth and colony formation of HCC cell lines.Knockdown of AKR1C3 in Huh7 cells reduced tumor growth in vivo.To explore the mechanism,we performed pathway enrichment analysis,and the results linked the expression of AKR1C3 with prostaglandin F2 alpha(PGF2a)downstream target genes.Suppression of AKR1C3 activity reduced the production of PGF2a,and supplementation with PGF2a restored the growth of indomethacin-treated Huh7 cells.Knockdown of the PGF receptor(PTGFR)and treatment with a PTGFR inhibitor significantly reduced HCC growth.We showed that indomethacin potentiated the sensitivity of Huh7 cells to sorafenib.In summary,our results indicate that AKR1C3 upregulation may promote HCC growth by promoting the production of PGF2α,and suppression of PTGFR limited HCC growth.Therefore,targeting the AKR1C3-PGF2a-PTGFR axis may be a new strategy for the treatment of HCC.
文摘目的探究H型原发性高血压(高血压)患者血清诱骗受体3(decoy receptor 3,DcR3)、含1型血小板反应蛋白基序的去整合素金属蛋白酶13(A disintegrin and metalloproteinase with A thrombospondin type 1 motif member 13,ADAMTS13)浓度与其心血管功能及预后的关系。方法选取大庆市人民医院2020年6月至2022年6月收治的132例高血压患者作为观察对象,根据同型半胱氨酸(homocysteine,Hcy)浓度分为非H型高血压组40例和H型高血压组92例,根据预后情况将H型高血压患者分为预后良好组和预后不良组,并选择同期来大庆市人民医院健康体检的成年人70名作为对照组。采用酶联免疫吸附试验法检测受试者血清中DcR3、ADAMTS13浓度,Pearson法分析血清中DcR3、ADAMTS13浓度与心血管功能指标的相关性,多因素Logistic回归分析H型高血压患者1年预后不良的影响因素。绘制受试者工作特征曲线(receiver operating characteristic curve,ROC)分析血清DcR3、ADAMTS13浓度对H型高血压患者1年预后不良的预测价值。结果与对照组[(122.28±32.34)mmHg(1 mmHg=0.133 kPa)、(48.16±8.65)mmHg、(8.59±1.25)mm、(118.34±34.25)g/m2、(1.48±0.34)g/L、(57.15±14.94)mg/L、(1.45±0.31)、70.28%±15.21%]比较,H型高血压组患者的收缩压[(139.35±38.21)mmHg]、脉压[(57.37±11.75)mmHg]、左心室后壁厚度(posterior wall thickness,PWT)[(11.69±2.00)mm]以及左心室质量指数(left ventricular mass index,LVMI)[(148.54±38.22)g/m2]显著升高,DcR3[(0.74±0.19)g/L]、ADAMTS13浓度[(14.13±4.62)mg/L]、二尖瓣舒张早期血流峰值/二尖瓣舒张晚期血流峰值(E-peak to A-peak of the mitral flow spectrum,E/A)(0.65±0.13)、左心室射血分数(left ventricular ejection fraction,LVEF)(64.26%±12.75%)显著降低,差异有统计学意义(P<0.05);与非H型高血压组患者组比较,H型高血压组患者的DcR3、ADAMTS13浓度及E/A显著降低,LVMI显著升高,差异有统计学意义(P<0.05)。H型高血压组患者血清中DcR3、ADAMTS13浓度均与收缩压、脉压和LVMI呈负相关(P<0.05),而与E/A、LVEF呈正相关(P<0.05)。预后不良组患者的年龄显著高于预后良好组,E/A(0.38±0.07)、DcR3[(0.45±0.13)g/L]、ADAMTS13浓度[(8.45±2.11)mg/L]显著低于预后良好组[0.75±0.11、(0.85±0.27)g/L、(16.25±4.85)mg/L],差异有统计学意义(P<0.05)。DcR3、ADAMTS13是H型高血压患者预后不良的保护因素(P<0.05)。血清DcR3、ADAMTS13浓度单独及二者联合预测H型高血压患者1年发生预后不良的曲线下面积(area under the curve,AUC)分别为0.906、0.844、0.950。结论H型高血压疾病患者血清DcR3、ADAMTS13浓度降低,与心血管功能及预后密切相关,对该疾病的预后评估有重要价值。
基金Supported by Ruian Natural Science Foundation,No.MS2021008.
文摘BACKGROUND Serpin peptidase inhibitor clade H member 1(SERPINH1)was initially recognized as an oncogene implicated in various human malignancies.Nevertheless,the clinical relevance and functional implications of SERPINH1 in colorectal cancer(CRC)remain largely elusive.AIM To investigate the effects of SERPINH1 on CRC cells and its specific mechanism.METHODS Quantitative real-time polymerase chain reaction,western blotting analysis,The Cancer Genome Atlas data mining and immunohistochemistry were employed to examine SERPINH1 expression in CRC cell lines and tissues.A series of in-vitro assays were performed to demonstrate the function of SERPINH1 and its possible mechanisms in CRC.RESULTS SERPINH1 demonstrated elevated expression levels in both CRC cells and tissues,manifested at both mRNA and protein tiers.Elevated SERPINH1 levels correlated closely with advanced T stage,lymph node involvement,and distant metastasis,exhibiting a significant association with poorer overall survival among CRC patients.Subsequent investigations unveiled that SERPINH1 overexpression notably bolstered CRC cell proliferation,invasion,and migration in vitro,while conversely,SERPINH1 knockdown elicited the opposite effects.Gene set enrichment analysis underscored a correlation between SERPINH1 upregulation and genes associated with cell cycle regulation.Our findings underscored the capacity of heightened SERPINH1 levels to expedite G1/S phase cell cycle progression via phosphatidylinositol 3-kinase/AKT/mechanistic target of rapamycin pathway activation,thereby facilitating CRC cell invasion and migration.CONCLUSION These findings imply a crucial involvement of SERPINH1 in the advancement and escalation of CRC,potentially positioning it as a novel candidate for prognostic assessment and therapeutic intervention in CRC management.
文摘Recent exploration results indicate that a significant exploration potential remains in the Dongying Depression of the Bohai Bay Basin and the undiscovered oil and gas are largely reservoired in subtle traps including turbidite litholigcal traps of the Sha-3 Member. In order to effectively guide the exploration program targeting turbidites, this study will focus on the depositional models of the Sha-3 Member turbidites and oil/gas accumulation characteristics in these turbidites. Two corresponding relationships were found. One is that the East African Rift Valley provides a modern analog for the depositional systems in the Dongying Depression. The other is that the depositional models of line-sourced slope aprons, single point-source submarine fan and multiple source ramp turbidite, established for deep-sea turbidites, can be applied to interpret the depositional features of the turbidite fans of three different origins: slope turbidite aprons, lake floor turbidite fans and delta-fed turbidite fans in the Sha-3 Member. Updip sealing integrity is the key factor determining whether oil/gas accumulates or not in the slope aprons and lake floor fans. The factors controlling oil/gas migration and accumulation in the delta-fed turbidite fans are not very clear. Multiple factors rather than a single factor probably played significant roles in these processes.
