目的探讨食管鳞癌组织中microRNA let-7a-3甲基化状态与血浆中类胰岛素样生长因子2(Insulin like growth factor 2,IGF-Ⅱ)表达的相关性。方法采用甲基化特异性PCR法(Methylation specific PCR,qMSP)检测83例食管癌及相对应的癌旁正常...目的探讨食管鳞癌组织中microRNA let-7a-3甲基化状态与血浆中类胰岛素样生长因子2(Insulin like growth factor 2,IGF-Ⅱ)表达的相关性。方法采用甲基化特异性PCR法(Methylation specific PCR,qMSP)检测83例食管癌及相对应的癌旁正常组织中let-7a-3甲基化状态,采用酶联免疫吸附试验(Enzyme linked immunosorbent assay,ELISA)检测血浆中IGF-Ⅱ的表达水平。结果83例食管鳞癌患者癌组织中的microRNA let-7a-3甲基化程度显著高于癌旁正常组织(P<0.001)。83例食管鳞癌患者血浆中IGF-Ⅱ的表达水平与let-7a-3基因的甲基化程度总体上呈正相关,具有统计学意义(r=0.600,P<0.001)。结论microRNA let-7a-3可能通过对下游分子的甲基化调控参与食管鳞癌的发生发展,这对了解食管鳞癌形成的机制具有重要意义,可为食管鳞癌的诊断和预后提供依据。展开更多
目的 探究脑出血患者脑组织中Nod样受体蛋白-3 (NLRP3)、NIMA相关蛋白激酶7 (NEK7)表达水平与疾病严重程度的相关性。方法 前瞻性选取2017年1月至2020年12月郑州颐和医院诊治的80例脑出血患者进行研究,取皮层造瘘通道靠近血肿0.5 cm处...目的 探究脑出血患者脑组织中Nod样受体蛋白-3 (NLRP3)、NIMA相关蛋白激酶7 (NEK7)表达水平与疾病严重程度的相关性。方法 前瞻性选取2017年1月至2020年12月郑州颐和医院诊治的80例脑出血患者进行研究,取皮层造瘘通道靠近血肿0.5 cm处的脑组织为靠近组,另取远离血肿位置的脑组织为远离组。依据脑出血患者出血量将其分为少量组(出血量<15 mL) 29例、中量组(出血量15~30 m L) 27例和大量组(出血量>30 mL)24例;按美国国立卫生研究院卒中量表(NIHSS)评分将患者分为轻型组(1~4分) 30例、中型组(5~15分) 27例和重型组(>15分) 23例。采用实时荧光定量PCR (qRT-PCR)法测定各组脑组织中NEK7 m RNA、NLRP3 m RNA表达水平;采用Pearson法分析脑出血患者血肿0.5 cm处脑组织中NEK7 m RNA表达水平与NLRP3 m RNA表达水平的相关性;比较不同出血量、不同严重程度的脑出血患者距离血肿0.5 cm处脑组织中NEK7 m RNA、NLRP3 m RNA表达水平。结果 靠近组患者脑组织中NEK7 m RNA、NLRP3 m RNA表达水平分别为1.72±0.58、1.69±0.57,明显高于远离组的1.03±0.34、1.01±0.33,差异均有统计学意义(P<0.05);脑出血患者血肿0.5 cm处脑组织中NEK7 m RNA表达水平与NLRP3 mRNA表达水平呈正相关(r=0.563,P<0.05);脑出血患者距离血肿0.5 cm处脑组织中NEK7m RNA、NLRP3 m RNA表达水平随着出血量的增加而升高,差异均有统计学意义(P<0.05);脑出血患者距离血肿0.5 cm处脑组织中NEK7 mRNA、NLRP3 m RNA表达水平随着NIHSS评分的增加而升高,差异均有统计学意义(P<0.05)。结论 脑出血患者距离血肿0.5 cm处脑组织中NEK7、NLRP3表达水平明显升高,两者均与出血量和疾病严重程度显著相关,检测距离血肿0.5 cm处脑组织NEK7、NLRP3有利于判断脑出血严重程度及出血情况。展开更多
Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various disea...Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.展开更多
文摘目的 探究脑出血患者脑组织中Nod样受体蛋白-3 (NLRP3)、NIMA相关蛋白激酶7 (NEK7)表达水平与疾病严重程度的相关性。方法 前瞻性选取2017年1月至2020年12月郑州颐和医院诊治的80例脑出血患者进行研究,取皮层造瘘通道靠近血肿0.5 cm处的脑组织为靠近组,另取远离血肿位置的脑组织为远离组。依据脑出血患者出血量将其分为少量组(出血量<15 mL) 29例、中量组(出血量15~30 m L) 27例和大量组(出血量>30 mL)24例;按美国国立卫生研究院卒中量表(NIHSS)评分将患者分为轻型组(1~4分) 30例、中型组(5~15分) 27例和重型组(>15分) 23例。采用实时荧光定量PCR (qRT-PCR)法测定各组脑组织中NEK7 m RNA、NLRP3 m RNA表达水平;采用Pearson法分析脑出血患者血肿0.5 cm处脑组织中NEK7 m RNA表达水平与NLRP3 m RNA表达水平的相关性;比较不同出血量、不同严重程度的脑出血患者距离血肿0.5 cm处脑组织中NEK7 m RNA、NLRP3 m RNA表达水平。结果 靠近组患者脑组织中NEK7 m RNA、NLRP3 m RNA表达水平分别为1.72±0.58、1.69±0.57,明显高于远离组的1.03±0.34、1.01±0.33,差异均有统计学意义(P<0.05);脑出血患者血肿0.5 cm处脑组织中NEK7 m RNA表达水平与NLRP3 mRNA表达水平呈正相关(r=0.563,P<0.05);脑出血患者距离血肿0.5 cm处脑组织中NEK7m RNA、NLRP3 m RNA表达水平随着出血量的增加而升高,差异均有统计学意义(P<0.05);脑出血患者距离血肿0.5 cm处脑组织中NEK7 mRNA、NLRP3 m RNA表达水平随着NIHSS评分的增加而升高,差异均有统计学意义(P<0.05)。结论 脑出血患者距离血肿0.5 cm处脑组织中NEK7、NLRP3表达水平明显升高,两者均与出血量和疾病严重程度显著相关,检测距离血肿0.5 cm处脑组织NEK7、NLRP3有利于判断脑出血严重程度及出血情况。
基金supported by National Natural Science Foundation of China,No.32102745(to XL).
文摘Traumatic brain injury is a severe health problem leading to autophagy and apoptosis in the brain.3,6-Dibromo-beta-fluoro-N-(3-methoxyphenyl)-9H-carbazole-9-propanamine(P7C3-A20)can be neuroprotective in various diseases,including ischemic stroke and neurodegenerative diseases.However,whether P7C3-A20 has a therapeutic effect on traumatic brain injury and its possible molecular mechanisms are unclear.Therefore,in the present study,we investigated the therapeutic effects of P7C3-A20 on traumatic brain injury and explored the putative underlying molecular mechanisms.We established a traumatic brain injury rat model using a modified weight drop method.P7C3-A20 or vehicle was injected intraperitoneally after traumatic brain injury.Severe neurological deficits were found in rats after traumatic brain injury,with deterioration in balance,walking function,and learning memory.Furthermore,hematoxylin and eosin staining showed significant neuronal cell damage,while terminal deoxynucleotidyl transferase mediated dUTP nick end labeling staining indicated a high rate of apoptosis.The presence of autolysosomes was observed using transmission electron microscope.P7C3-A20 treatment reversed these pathological features.Western blotting showed that P7C3-A20 treatment reduced microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ)autophagy protein,apoptosis-related proteins(namely,Bcl-2/adenovirus E1B 19-kDa-interacting protein 3[BNIP3],and Bcl-2 associated x protein[Bax]),and elevated ubiquitin-binding protein p62(p62)autophagy protein expression.Thus,P7C3-A20 can treat traumatic brain injury in rats by inhibiting excessive autophagy and apoptosis.
