目的:探讨重复经颅磁刺激(r TMS)对抑郁症患者的疗效及对患者外周血PDLIM5基因转录水平的影响。方法:正常健康者24例纳入正常组,抑郁症患者27例纳入抑郁组。抑郁组患者接受r TMS治疗2周。于治疗前、后,行汉密尔顿抑郁量表(HAMD)评分,并...目的:探讨重复经颅磁刺激(r TMS)对抑郁症患者的疗效及对患者外周血PDLIM5基因转录水平的影响。方法:正常健康者24例纳入正常组,抑郁症患者27例纳入抑郁组。抑郁组患者接受r TMS治疗2周。于治疗前、后,行汉密尔顿抑郁量表(HAMD)评分,并检测外周血中PDLIM5 m RNA转录水平。结果:抑郁组HAMD总分明显高于对照组(P<0.05)。r TMS治疗后,抑郁组"有效"13例(48.1%),"明显缓解"8例(29.6%);HAMD总分较治疗前明显下降(P<0.01),但仍高于对照组(P<0.05)。治疗前抑郁组外周血PDLIM5 m RNA转录水平明显低于对照组(P<0.05),治疗后抑郁者组外周血PDLIM5 m RNA表达水平与治疗前差异无统计学意义(P>0.05)。治疗前后,抑郁组HAMD总分与外周血PDLIM5 m RNA转录水平无明显相关性(P>0.05)。结论:r TMS治疗抑郁症有效,对外周血PDLIM5转录水平无影响。展开更多
BACKGROUND Abnormal type I collagen(COL1)expression is associated with the development of many cardiovascular diseases.The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression,...BACKGROUND Abnormal type I collagen(COL1)expression is associated with the development of many cardiovascular diseases.The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression,but the underlying molecular mechanisms are still not fully understood.METHODS Gain-and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen(COL1A2).Co-immunoprecipitation assay was performed to observe the interaction between two proteins.RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5.RESULTS In this study,we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells(VSMCs).We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway.CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta.Mechanistically,circZBTB46 mediates the interaction between Smad2 and PDLIM5,resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression.Furthermore,we found that the expression of TGFbeta and COL1A2 is decreased,while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues,indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development.CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs,highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.展开更多
Objective:Cognitive impairment is a core deficit of schizophrenia and current antipsychotic treatments have no or only very limited effects on cognitive impairment.Clinical studies have found that about 50%~90%of all ...Objective:Cognitive impairment is a core deficit of schizophrenia and current antipsychotic treatments have no or only very limited effects on cognitive impairment.Clinical studies have found that about 50%~90%of all psychiatric patients are smokers,and the high rate of smoking may be due to the fact that the patients smoke tobacco to reduce their cognitive symptoms.Nicotine is the key psychoactive component and various studies have reported that nicotine can improve cognition under some circumstances.Therefore,we propose our hypothesis that nicotine alleviates schizophreniainduced cognitive impairment.Our published results confirmed that nicotine treatment significantly improved rat’s working memory in the delayed alternate T maze task(DAT).Methods:In this current study,MK-801 was applied to induce schizophrenia-like behavior which was confi rmed by pre-pulse inhibition(PPI)and T-maze used to assess cognitive performance.Results:Our data showed that MK-801 caused cognitive impairment accompanied by an increase of Pdlim5,anadaptor protein that is critically associated with schizophrenia in medial prefrontal cortex(mPFC).Of note,chronic nicotine treatment attenuates MK-801-induced schizophrenia-like symptom as well as cognitive impairment by regulating Pdlim5.In addition,nicotine treatment also reduced MK-801-induced decrease of CREBregulated transcription coactivator 1(CRTC1),a coactivator of CREB which has been shown to play an important role in cognition.More important,MK-801 neither induced schizophrenia-like behavior in pdlim5-/-mice,nor decreased CRTC1 in mPFC.Conclusion:Our results showed that chronic nicotine treatment alleviates schizophrenia-induced memory defi cit through regulating Pdlim5 and CRTC1 in mice.展开更多
文摘目的:探讨重复经颅磁刺激(r TMS)对抑郁症患者的疗效及对患者外周血PDLIM5基因转录水平的影响。方法:正常健康者24例纳入正常组,抑郁症患者27例纳入抑郁组。抑郁组患者接受r TMS治疗2周。于治疗前、后,行汉密尔顿抑郁量表(HAMD)评分,并检测外周血中PDLIM5 m RNA转录水平。结果:抑郁组HAMD总分明显高于对照组(P<0.05)。r TMS治疗后,抑郁组"有效"13例(48.1%),"明显缓解"8例(29.6%);HAMD总分较治疗前明显下降(P<0.01),但仍高于对照组(P<0.05)。治疗前抑郁组外周血PDLIM5 m RNA转录水平明显低于对照组(P<0.05),治疗后抑郁者组外周血PDLIM5 m RNA表达水平与治疗前差异无统计学意义(P>0.05)。治疗前后,抑郁组HAMD总分与外周血PDLIM5 m RNA转录水平无明显相关性(P>0.05)。结论:r TMS治疗抑郁症有效,对外周血PDLIM5转录水平无影响。
基金This study was supported by the National Natural Science Foundation of China(No.31671182&No.31871152&No.81770285&No.81971328&No.82271624)the Natural Science Foundation of Hebei Province of China(No.H2022206074&No.H2021206459)the Medical Science Research Project in Hebei Province Foundation of Health Commission of Hebei Province of China(No.20230065).
文摘BACKGROUND Abnormal type I collagen(COL1)expression is associated with the development of many cardiovascular diseases.The TGF-beta/Smad signaling pathway and circRNAs have been shown to regulate COL1 gene expression,but the underlying molecular mechanisms are still not fully understood.METHODS Gain-and loss-of-function experiments were prformed to study the effect of circZBTB46 on the expression of alpha 2 chain of type I collagen(COL1A2).Co-immunoprecipitation assay was performed to observe the interaction between two proteins.RNA immunoprecipitation assay and biotin pull-down assay were performed to observe the interaction of circZBTB46 with PDLIM5.RESULTS In this study,we investigated the role of circZBTB46 in regulating COL1A2 expression in human vascular smooth muscle cells(VSMCs).We found that circZBTB46 is expressed in VSMCs and that TGF-beta inhibits circZBTB46 formation by downregulating KLF4 expression through activation of the Smad signaling pathway.CircZBTB46 inhibits the expression of COL1A2 induced by TGF-beta.Mechanistically,circZBTB46 mediates the interaction between Smad2 and PDLIM5,resulting in the inhibition of Smad signaling and the subsequent downregulation of COL1A2 expression.Furthermore,we found that the expression of TGFbeta and COL1A2 is decreased,while circZBTB46 expression is increased in human abdominal aortic aneurysm tissues,indicating that circZBTB46-mediated regulation of TGF-beta/Smad signaling and COL1A2 synthesis in VSMCs plays a crucial role in vascular homeostasis and aneurysm development.CONCLUSIONS CircZBTB46 was identified as a novel inhibitor of COL1 synthesis in VSMCs,highlighting the importance of circZBTB46 and PDLIM5 in regulating TGF-beta/Smad signaling and COL1A2 expression.
文摘Objective:Cognitive impairment is a core deficit of schizophrenia and current antipsychotic treatments have no or only very limited effects on cognitive impairment.Clinical studies have found that about 50%~90%of all psychiatric patients are smokers,and the high rate of smoking may be due to the fact that the patients smoke tobacco to reduce their cognitive symptoms.Nicotine is the key psychoactive component and various studies have reported that nicotine can improve cognition under some circumstances.Therefore,we propose our hypothesis that nicotine alleviates schizophreniainduced cognitive impairment.Our published results confirmed that nicotine treatment significantly improved rat’s working memory in the delayed alternate T maze task(DAT).Methods:In this current study,MK-801 was applied to induce schizophrenia-like behavior which was confi rmed by pre-pulse inhibition(PPI)and T-maze used to assess cognitive performance.Results:Our data showed that MK-801 caused cognitive impairment accompanied by an increase of Pdlim5,anadaptor protein that is critically associated with schizophrenia in medial prefrontal cortex(mPFC).Of note,chronic nicotine treatment attenuates MK-801-induced schizophrenia-like symptom as well as cognitive impairment by regulating Pdlim5.In addition,nicotine treatment also reduced MK-801-induced decrease of CREBregulated transcription coactivator 1(CRTC1),a coactivator of CREB which has been shown to play an important role in cognition.More important,MK-801 neither induced schizophrenia-like behavior in pdlim5-/-mice,nor decreased CRTC1 in mPFC.Conclusion:Our results showed that chronic nicotine treatment alleviates schizophrenia-induced memory defi cit through regulating Pdlim5 and CRTC1 in mice.
