AIM:To investigate the role of hepatopoietin Cn(HPPCn) in apoptosis of hepatocellular carcinoma(HCC)cells and its mechanism. METHODS:Two human HCC cell lines,SMMC7721 and HepG2,were used in this study.Immunostaining, ...AIM:To investigate the role of hepatopoietin Cn(HPPCn) in apoptosis of hepatocellular carcinoma(HCC)cells and its mechanism. METHODS:Two human HCC cell lines,SMMC7721 and HepG2,were used in this study.Immunostaining, Western blotting and enzyme linked immunosorbent assay were conducted to identify the expression of HPPCn and the existence of an autocrine loop of HPPCn/ HPPCn receptor in SMMC7721 and HepG2.Apoptotic cells were detected using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium iodide.RESULTS:The HPPCn was highly expressed in human HCC cells and secreted into culture medium(CM). FITC-labeled recombinant human protein(rhHPPCn) could specifically bind to its receptor on HepaG2 cells. Treatment with 400 ng/mL rhHPPCn dramatically increased the viability of HCC-derived cells from 48.1% and 36.9%to 85.6%and 88.4%,respectively(P< 0.05).HPPCn silenced by small-interfering RNA reduced the expression and secretion of HPPCn and increased the apoptosis induced by trichostatin A.Additionally, HPPCn could up-regulate the expression of myeloid cell leukemia-1(Mcl-1)in HCC cells via mitogen-activated protein kinase(MAPK)and sphingosine kinase-1. CONCLUSION:HPPCn is a novel hepatic growth factor that can be secreted to CM and suppresses apoptosis of HCC cells by up-regulating Mcl-1 expression.展开更多
Objective： To investigate the association between the T cell inhibitory receptor programmed death 1（PD-1）and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia（AML） and AML in c...Objective： To investigate the association between the T cell inhibitory receptor programmed death 1（PD-1）and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia（AML） and AML in complete remission（CR）.Methods：Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3＋,CD4＋ and CD8＋ T cells from peripheral blood samples from 20 newly diagnosed,untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry.Twenty-three healthy individuals served as control.Results：A significantly higher percentage of PD-1＋ cells were found for CD3＋ T cells in the de novo AML group compared with healthy controls.In addition,an increased level of PD-1＋ CD8＋ T cells,but not PD-1＋ CD4＋,was found for CD3＋ T cells in the de novo AML and AML-CR samples.A higher percentage of CD244＋ CD4＋,CD244＋ CD8＋,CD57＋ CD4＋ and CD57＋ CD8＋ T cells was found in CD3＋ T cells in samples from those with de novo AML compared with those from healthy controls.Strong increased PD-1＋ CD244＋ and PD-1＋ CD57＋ coexpression was found for CD4＋ and CD8＋ T cells in the de novo AML group compared with healthy controls.Conclusions：We characterized the major T cell defects,including co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML,and found a particular influence on CD8＋ T cells,suggesting a poor anti-leukemia immune response in these patients.展开更多
目的探究急性缺血性脑卒中(AIS)患者血清间α胰蛋白酶抑制因子重链4(ITIH4)、髓样细胞白血病因子-1(MCL-1)表达与病情程度及预后的关系。方法纳入2019年7月—2022年7月河南科技大学附属黄河医院神经内科诊治AIS患者128例为AIS组。根据...目的探究急性缺血性脑卒中(AIS)患者血清间α胰蛋白酶抑制因子重链4(ITIH4)、髓样细胞白血病因子-1(MCL-1)表达与病情程度及预后的关系。方法纳入2019年7月—2022年7月河南科技大学附属黄河医院神经内科诊治AIS患者128例为AIS组。根据入院时美国国立卫生研究院卒中量表(NIHSS)评分,分为轻度亚组(NIHSS<6分,n=42)、中度亚组(NIHSS 6~<14分,n=52)和重度亚组(NIHSS≥14分,n=34)。根据出院3个月时AIS患者改良Rankins评分,分为预后不良亚组(mRS评分>2分,30例)和预后良好亚组(mRS评分≤2分,98例)。另选取同期医院体检的健康人70例为健康对照组。酶联免疫吸附试验检测血清ITIH4、MCL-1水平。Pearson相关分析血清ITIH4、MCL-1水平与病情程度及预后的相关性;多因素Logistic回归分析影响AIS患者预后的因素;受试者工作特征曲线分析血清ITIH4、MCL-1对AIS患者预后的预测价值。结果AIS组患者血清ITIH4、MCL-1水平显著低于健康对照组(t/P=43.211/<0.001,43.191/<0.001);病情程度越重,AIS患者血清ITIH4/MCL-1水平越低(F/P=107.796/<0.001,297.976/<0.001);预后不良亚组梗死面积、入院24 h NIHSS评分高于预后良好亚组(t/P=9.637/<0.001,9.752/<0.001),血清ITIH4、MCL-1水平及出院3个月简易智能状态量表(MMSE)评分、蒙特利尔认知评估量表(MoCA)评分低于预后良好亚组(t/P=26.723/<0.001,11.709/<0.001,13.674/<0.001,10.782/<0.001);AIS患者血清ITIH4、MCL-1与梗死面积、入院24 h NIHSS评分呈负相关(r/P=-0.705/<0.001,-0.685/<0.001;-0.761/<0.001,-0.619/<0.001),与出院3个月MMSE评分、MoCA评分呈正相关(r/P=0.656/<0.001,0.632/<0.001;0.751/<0.001,0.789/<0.001);出院3个月MMSE评分高、出院3个月MoCA评分高是影响AIS患者预后不良的独立保护因素[0.622(0.446~0.868),0.606(0.427~0.861)],血清ITIH4低、MCL-1低、梗死面积大、入院24 h NIHSS评分高是危险因素[OR(95%CI)=1.467(1.150~1.870),1.415(1.094~1.829),1.605(1.168~2.205),1.765(1.233~2.526)];血清ITIH4、MCL-1及两项联合预测AIS预后不良的AUC分别为0.811、0.835、0.923,两项联合预测AIS预后不良的AUC大于单一指标,差异具有统计学意义(Z=4.258、4.119,P均<0.001)。结论AIS患者血清ITIH4、MCL-1表达下调,两者表达水平与病情严重程度有关,两者联合对AIS患者预后具有较高的预测价值。展开更多
Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL....Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL. The study aimed to clarify the prognostic role of MCL-1, BCL-2 and BCL-2/ Bax ratio in B-CLL. Patients & method: Estimation of MCL-1, BCL-2 and Bax expressions by a flow cytometry in 45 B-CLL patients and the prognostic value of these markers were correlated with other well-known established prognostic markers and treatment response. Results: MCL-1 was expressed in 60% of cases while BCL-2 was expressed in 82.2% of cases. MCL-1 expression was significantly high in male gender, short lymphocyte doubling time (LDT), and high expression of CD 38 (p β2M, CD38 expression), low ZAP-70 expression, splenomegaly and higher Rai stage were significantly increased in patients with high expression of BCL-2 (p β2M, high C-D38 expression, low ZAP-70 expression, the poor cytogenetic and splenomegaly in patients with high expression of BCL-2/ Bax ratio (p In conclusion: MCL-1, BCL-2 expressions and BCL-2/Bax ratio could be useful potential predictive and prognostic markers in B-CLL.展开更多
基金Supported by(in part)Grants From the National Natural Science Foundation of China,No.30800558 and No.30930041the Chinese Major Special Science&Technology Project for Development of Major New Drugs,No.2009ZX09103-617
文摘AIM:To investigate the role of hepatopoietin Cn(HPPCn) in apoptosis of hepatocellular carcinoma(HCC)cells and its mechanism. METHODS:Two human HCC cell lines,SMMC7721 and HepG2,were used in this study.Immunostaining, Western blotting and enzyme linked immunosorbent assay were conducted to identify the expression of HPPCn and the existence of an autocrine loop of HPPCn/ HPPCn receptor in SMMC7721 and HepG2.Apoptotic cells were detected using fluorescein isothiocyanate (FITC)-conjugated Annexin V and propidium iodide.RESULTS:The HPPCn was highly expressed in human HCC cells and secreted into culture medium(CM). FITC-labeled recombinant human protein(rhHPPCn) could specifically bind to its receptor on HepaG2 cells. Treatment with 400 ng/mL rhHPPCn dramatically increased the viability of HCC-derived cells from 48.1% and 36.9%to 85.6%and 88.4%,respectively(P< 0.05).HPPCn silenced by small-interfering RNA reduced the expression and secretion of HPPCn and increased the apoptosis induced by trichostatin A.Additionally, HPPCn could up-regulate the expression of myeloid cell leukemia-1(Mcl-1)in HCC cells via mitogen-activated protein kinase(MAPK)and sphingosine kinase-1. CONCLUSION:HPPCn is a novel hepatic growth factor that can be secreted to CM and suppresses apoptosis of HCC cells by up-regulating Mcl-1 expression.
基金supported by grants from the National Natural Science Foundation of China (No. 81570143 and 91642111)the Guangdong Provincial Basic Research Program (No. 2015B020227003)+3 种基金the Guangdong Provincial Applied Science and Technology Research & Development Program (No. 2016B020237006)the Guangzhou Science and Technology Project (No. 201510010211)the Fundamental Research Funds for the Central Universities (No. 21616108)the Medical Scientific Research Foundation of Guangdong Province, China (No. A2016045)
文摘Objective： To investigate the association between the T cell inhibitory receptor programmed death 1（PD-1）and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia（AML） and AML in complete remission（CR）.Methods：Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3＋,CD4＋ and CD8＋ T cells from peripheral blood samples from 20 newly diagnosed,untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry.Twenty-three healthy individuals served as control.Results：A significantly higher percentage of PD-1＋ cells were found for CD3＋ T cells in the de novo AML group compared with healthy controls.In addition,an increased level of PD-1＋ CD8＋ T cells,but not PD-1＋ CD4＋,was found for CD3＋ T cells in the de novo AML and AML-CR samples.A higher percentage of CD244＋ CD4＋,CD244＋ CD8＋,CD57＋ CD4＋ and CD57＋ CD8＋ T cells was found in CD3＋ T cells in samples from those with de novo AML compared with those from healthy controls.Strong increased PD-1＋ CD244＋ and PD-1＋ CD57＋ coexpression was found for CD4＋ and CD8＋ T cells in the de novo AML group compared with healthy controls.Conclusions：We characterized the major T cell defects,including co-expression of PD-1 and CD244,CD57-exhausted T cells in patients with de novo AML,and found a particular influence on CD8＋ T cells,suggesting a poor anti-leukemia immune response in these patients.
文摘目的探究急性缺血性脑卒中(AIS)患者血清间α胰蛋白酶抑制因子重链4(ITIH4)、髓样细胞白血病因子-1(MCL-1)表达与病情程度及预后的关系。方法纳入2019年7月—2022年7月河南科技大学附属黄河医院神经内科诊治AIS患者128例为AIS组。根据入院时美国国立卫生研究院卒中量表(NIHSS)评分,分为轻度亚组(NIHSS<6分,n=42)、中度亚组(NIHSS 6~<14分,n=52)和重度亚组(NIHSS≥14分,n=34)。根据出院3个月时AIS患者改良Rankins评分,分为预后不良亚组(mRS评分>2分,30例)和预后良好亚组(mRS评分≤2分,98例)。另选取同期医院体检的健康人70例为健康对照组。酶联免疫吸附试验检测血清ITIH4、MCL-1水平。Pearson相关分析血清ITIH4、MCL-1水平与病情程度及预后的相关性;多因素Logistic回归分析影响AIS患者预后的因素;受试者工作特征曲线分析血清ITIH4、MCL-1对AIS患者预后的预测价值。结果AIS组患者血清ITIH4、MCL-1水平显著低于健康对照组(t/P=43.211/<0.001,43.191/<0.001);病情程度越重,AIS患者血清ITIH4/MCL-1水平越低(F/P=107.796/<0.001,297.976/<0.001);预后不良亚组梗死面积、入院24 h NIHSS评分高于预后良好亚组(t/P=9.637/<0.001,9.752/<0.001),血清ITIH4、MCL-1水平及出院3个月简易智能状态量表(MMSE)评分、蒙特利尔认知评估量表(MoCA)评分低于预后良好亚组(t/P=26.723/<0.001,11.709/<0.001,13.674/<0.001,10.782/<0.001);AIS患者血清ITIH4、MCL-1与梗死面积、入院24 h NIHSS评分呈负相关(r/P=-0.705/<0.001,-0.685/<0.001;-0.761/<0.001,-0.619/<0.001),与出院3个月MMSE评分、MoCA评分呈正相关(r/P=0.656/<0.001,0.632/<0.001;0.751/<0.001,0.789/<0.001);出院3个月MMSE评分高、出院3个月MoCA评分高是影响AIS患者预后不良的独立保护因素[0.622(0.446~0.868),0.606(0.427~0.861)],血清ITIH4低、MCL-1低、梗死面积大、入院24 h NIHSS评分高是危险因素[OR(95%CI)=1.467(1.150~1.870),1.415(1.094~1.829),1.605(1.168~2.205),1.765(1.233~2.526)];血清ITIH4、MCL-1及两项联合预测AIS预后不良的AUC分别为0.811、0.835、0.923,两项联合预测AIS预后不良的AUC大于单一指标,差异具有统计学意义(Z=4.258、4.119,P均<0.001)。结论AIS患者血清ITIH4、MCL-1表达下调,两者表达水平与病情严重程度有关,两者联合对AIS患者预后具有较高的预测价值。
文摘Background: High levels of MCL-1 and BCL-2 proteins have been found in Chronic Lymphocytic Leukemia (CLL), and inversely correlated with response to treatment. BCL-2/Bax ratio is the main director of apoptosis in CLL. The study aimed to clarify the prognostic role of MCL-1, BCL-2 and BCL-2/ Bax ratio in B-CLL. Patients & method: Estimation of MCL-1, BCL-2 and Bax expressions by a flow cytometry in 45 B-CLL patients and the prognostic value of these markers were correlated with other well-known established prognostic markers and treatment response. Results: MCL-1 was expressed in 60% of cases while BCL-2 was expressed in 82.2% of cases. MCL-1 expression was significantly high in male gender, short lymphocyte doubling time (LDT), and high expression of CD 38 (p β2M, CD38 expression), low ZAP-70 expression, splenomegaly and higher Rai stage were significantly increased in patients with high expression of BCL-2 (p β2M, high C-D38 expression, low ZAP-70 expression, the poor cytogenetic and splenomegaly in patients with high expression of BCL-2/ Bax ratio (p In conclusion: MCL-1, BCL-2 expressions and BCL-2/Bax ratio could be useful potential predictive and prognostic markers in B-CLL.
