目的研究肉毒碱棕榈酰基转移酶1A (CPT1A)在肺癌转移中的调控作用。方法首先,利用实时定量PCR (qRT-PCR)与Western blot实验检测11对肺癌原发灶与转移灶组织中CPT1A分子的mRNA与蛋白表达,以明确CPT1A在肺癌转移过程中的表达是否发生改变...目的研究肉毒碱棕榈酰基转移酶1A (CPT1A)在肺癌转移中的调控作用。方法首先,利用实时定量PCR (qRT-PCR)与Western blot实验检测11对肺癌原发灶与转移灶组织中CPT1A分子的mRNA与蛋白表达,以明确CPT1A在肺癌转移过程中的表达是否发生改变;其次,用细胞划痕实验检测下调CPT1A表达对肺癌A549细胞迁移能力的影响;最后,用Transwell侵袭实验检测下调CPT1A表达对肺癌A549细胞侵袭能力的影响。结果肺癌转移灶组织中CPT1A表达在m RNA与蛋白水平均明显高于原发灶组织[mRNA水平:(1.00±0.14)vs (1.83±0.75);蛋白水平:(1.00±0.26) vs (2.25±0.63)],差异均有统计学意义(P<0.05);与对照组细胞相比,下调CPT1A表达可显著抑制肺癌细胞的迁移能力[siCtrl vs siCPT1A-1 vs siCPT1A-2=(1.00±0.12) vs (0.39±0.04) vs (0.38±0.03)],差异均有统计学意义(P<0.05);与对照组相比,下调CPT1A表达可显著抑制肺癌细胞的侵袭能力[siCtrl vs siCPT1A vs siCPT1A-2=(23.00±3.00) vs (12.00±2.00) vs (13.00±1.00)],差异均有统计学意义(P<0.05)。结论 CPT1A在肺癌转移过程中表达显著上调;CPT1A可同时促进肺癌细胞的迁移与侵袭能力,提示CPT1A是肺癌治疗潜在的分子靶标。展开更多
BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarniti...BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarnitine is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)patients.In contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without HCC.AIM To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients.METHODS Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this study.Blood samples were obtained from patients at the time of admission.The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry.The levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent assay.Univariate and multivariate analyses were used to determine early diagnostic factors of HCC.RESULTS The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without HCC.The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC.The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC.Further studies are warranted to investigate 展开更多
目的:分析1例肉碱棕榈酰转移酶1A(CPT1A)缺乏症患儿的临床和基因突变特点,提高对该病的认识。方法:收集该患儿的临床资料,血液串联质谱分析酰基肉碱谱。抽取患儿及其父母的外周静脉血3 m L,提取DNA,通过测序技术,对CPT1A基因所有外显子...目的:分析1例肉碱棕榈酰转移酶1A(CPT1A)缺乏症患儿的临床和基因突变特点,提高对该病的认识。方法:收集该患儿的临床资料,血液串联质谱分析酰基肉碱谱。抽取患儿及其父母的外周静脉血3 m L,提取DNA,通过测序技术,对CPT1A基因所有外显子及相邻内含子(侧翼区域)序列进行直接测序,检测突变。结果:患儿临床表现为腹泻、发热、抽搐,随后出现意识障碍,发育倒退。血生化示转氨酶、心肌酶升高,低血糖,血氨增高,血液相串联质谱仪分析示游离肉碱(C0)193.61(参考值10.00~90.00),棕榈酰肉碱(C16)0.06(0.20~3.00),棕榈烯酰肉碱(C16:1)0.01(0.02~0.30),十八碳酰肉碱(C18)0.07(0.10~1.50),十八碳烯酰肉碱(C18:1)0.04(0.20~2.80),十八碳二烯酰肉碱(C18:2)0.02(0.10~1.10),C0/(C16+C18)为1595.54(6.50~100)。基因检测示CPT1A基因存在c.281+1G>A(Intron3)剪接突变与15-18号外显子杂合缺失,患儿母亲携带CPT1A基因c.281+1G>A(Intron3)剪接突变,患儿父亲携带CPT1A基因15-18号外显子杂合缺失。父母亲均为杂合突变,临床表型正常,为该突变的携带者。结论:CPT1A缺乏症临床表现为低酮性低血糖、肝损伤伴肝大、高血氨、凝血功能异常、惊厥、昏迷等,其临床表现多样且缺乏特异性,易误诊。血酰基肉碱谱分析、基因检查有助于早期明确诊断。展开更多
文摘目的观察复方贞术调脂方(FTZ)对高脂饮食致非酒精性脂肪肝的预防作用,并探讨其相关机制。方法 20只雄性C57BL/6j小鼠按随机数表法分为模型组及FTZ组,每组10只。两组均予高脂饮食喂养,同时模型组予5%阿拉伯树胶水溶液灌胃,FTZ组予FTZ浸膏粉溶液灌胃(每日1.17 g/kg,以5%阿拉伯树胶水溶液为溶剂,10 m L/kg灌胃给药),两组每日1次给药,共给药5个月。监测小鼠进食量及体重情况,检测治疗前后小鼠血糖、血脂水平,治疗后进行口服糖耐量实验(OGTT),并计算曲线下面积(AUC)。观察肝脏病理情况,测定肝脏脂质含量,Real-time PCR法检测肝内过氧化物酶体增殖物激活受体α(PPARα)、肉碱脂酰转移酶1(CPT1)m RNA表达。结果两组小鼠进食量相近,差异无统计学意义(P>0.05),但是高脂喂养3个月后FTZ组小鼠体重明显低于模型组(P<0.05)。治疗前,两组TG、TC及空腹血糖比较差异无统计学意义(P>0.05)。治疗后,与模型组比较,FTZ组小鼠TC、TG、空腹血糖、肝脏TC、TG水平降低(P<0.05),OGTT实验AUC明显减少(P<0.05),肝脏中PPARα及CPT1 m RNA表达升高(P<0.05,P<0.01)。两组小鼠肝脏重量、内脏脂肪及腹股沟脂肪称重结果比较,差异无统计学意义(P>0.05)。模型组小鼠可观察到肝脏明显脂质沉积,汇管区周围、中央静脉周围可见大量肝细胞空泡变性及水样变性,淋巴细胞浸润,少量肝细胞点状坏死。而FTZ组肝脏空泡变性及水样变性程度明显轻于模型组。结论 FTZ可延缓高脂饮食所致的非酒精性脂肪肝的发生,其机制与上调肝PPARα及其下游基因CPT1,促进脂肪酸氧化,改善胰岛素敏感性有关。
文摘目的研究肉毒碱棕榈酰基转移酶1A (CPT1A)在肺癌转移中的调控作用。方法首先,利用实时定量PCR (qRT-PCR)与Western blot实验检测11对肺癌原发灶与转移灶组织中CPT1A分子的mRNA与蛋白表达,以明确CPT1A在肺癌转移过程中的表达是否发生改变;其次,用细胞划痕实验检测下调CPT1A表达对肺癌A549细胞迁移能力的影响;最后,用Transwell侵袭实验检测下调CPT1A表达对肺癌A549细胞侵袭能力的影响。结果肺癌转移灶组织中CPT1A表达在m RNA与蛋白水平均明显高于原发灶组织[mRNA水平:(1.00±0.14)vs (1.83±0.75);蛋白水平:(1.00±0.26) vs (2.25±0.63)],差异均有统计学意义(P<0.05);与对照组细胞相比,下调CPT1A表达可显著抑制肺癌细胞的迁移能力[siCtrl vs siCPT1A-1 vs siCPT1A-2=(1.00±0.12) vs (0.39±0.04) vs (0.38±0.03)],差异均有统计学意义(P<0.05);与对照组相比,下调CPT1A表达可显著抑制肺癌细胞的侵袭能力[siCtrl vs siCPT1A vs siCPT1A-2=(23.00±3.00) vs (12.00±2.00) vs (13.00±1.00)],差异均有统计学意义(P<0.05)。结论 CPT1A在肺癌转移过程中表达显著上调;CPT1A可同时促进肺癌细胞的迁移与侵袭能力,提示CPT1A是肺癌治疗潜在的分子靶标。
文摘BACKGROUND Early diagnosis of hepatocellular carcinoma(HCC)is necessary to improve the prognosis of patients.However,the currently available tumor biomarkers are insufficient for the early detection of HCC.Acylcarnitine is essential in fatty acid metabolic pathways.A recent study reported that a high level of acylcarnitine may serve as a useful biomarker for the early diagnosis of HCC in steatohepatitis(SH)patients.In contrast,another study reported that the level of acetylcarnitine(AC2)-one of the acylcarnitine species-in non-SH patients with HCC was decreased vs that reported in those without HCC.AIM To investigate the usefulness of acylcarnitine as a biomarker for the early diagnosis of HCC in non-SH patients.METHODS Thirty-three non-SH patients(14 with HCC and 19 without HCC)were enrolled in this study.Blood samples were obtained from patients at the time of admission.The levels of acylcarnitine and AC2 in the serum were determined through tandem mass spectrometry.The levels of vascular endothelial growth factor(VEGF)and VEGF receptor 2(VEGFR-2)were determined by enzymelinked immunosorbent assay.Univariate and multivariate analyses were used to determine early diagnostic factors of HCC.RESULTS The level of acylcarnitine was significantly lower in non-SH patients with HCC vs those without HCC(P<0.05).In contrast,the level of lens culinaris agglutininreactive fraction ofα-fetoprotein(AFP)-AFP-L3%-was significantly higher in non-SH patients with HCC vs those without HCC(P<0.05).However,the levels of total carnitine,free carnitine,AFP,des-γ-carboxy prothrombin,VEGF,and VEGFR-2 were not different between patients with and without HCC.The multivariate analysis showed that a low level of acylcarnitine was the only independent factor for the early diagnosis of HCC.The patients with a low level of AC2 had a significantly higher level of VEGF vs those with a high level of AC2(P<0.05).CONCLUSION The metabolic pathways of fatty acids may differ between SH HCC and non-SH HCC.Further studies are warranted to investigate
文摘目的:分析1例肉碱棕榈酰转移酶1A(CPT1A)缺乏症患儿的临床和基因突变特点,提高对该病的认识。方法:收集该患儿的临床资料,血液串联质谱分析酰基肉碱谱。抽取患儿及其父母的外周静脉血3 m L,提取DNA,通过测序技术,对CPT1A基因所有外显子及相邻内含子(侧翼区域)序列进行直接测序,检测突变。结果:患儿临床表现为腹泻、发热、抽搐,随后出现意识障碍,发育倒退。血生化示转氨酶、心肌酶升高,低血糖,血氨增高,血液相串联质谱仪分析示游离肉碱(C0)193.61(参考值10.00~90.00),棕榈酰肉碱(C16)0.06(0.20~3.00),棕榈烯酰肉碱(C16:1)0.01(0.02~0.30),十八碳酰肉碱(C18)0.07(0.10~1.50),十八碳烯酰肉碱(C18:1)0.04(0.20~2.80),十八碳二烯酰肉碱(C18:2)0.02(0.10~1.10),C0/(C16+C18)为1595.54(6.50~100)。基因检测示CPT1A基因存在c.281+1G>A(Intron3)剪接突变与15-18号外显子杂合缺失,患儿母亲携带CPT1A基因c.281+1G>A(Intron3)剪接突变,患儿父亲携带CPT1A基因15-18号外显子杂合缺失。父母亲均为杂合突变,临床表型正常,为该突变的携带者。结论:CPT1A缺乏症临床表现为低酮性低血糖、肝损伤伴肝大、高血氨、凝血功能异常、惊厥、昏迷等,其临床表现多样且缺乏特异性,易误诊。血酰基肉碱谱分析、基因检查有助于早期明确诊断。
