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Zhongguo Zhong Yao Za Zhi ; 46(16): 4265-4273, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467741


To systematically evaluate the efficiency and safety of Tanreqing Injection in the treatment of stroke-associated pneumonia(SAP). Seven domestic and foreign databases(CNKI, Wanfang, VIP, CBM, PubMed, Cochrane Library, EMbase) were retrieved from the establishment to July 2020. According to the inclusion and exclusion criteria, randomized controlled trial of the effect of Tanreqing Injection in the treatment of SAP was selected. NoteExpress software was used to screen out literatures. RevMan 5.4 software was used for data analysis. GRADE system was used to evaluate the evidence quality of the outcome indicators. A total of 1 755 cases in 21 studies were retrieved, including 879 cases in experimental group and 876 cases in control group. In general, the quality of stu-dies received was not high. According to Meta-analysis,(1) in terms of shortening the length of hospital stay, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(MD=-4.04, 95%CI[-4.43,-3.65], P<0.000 01);(2) in terms of increasing effective rate, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(RR=1.22, 95%CI[1.17, 1.27], P<0.000 01);(3) in terms of reducing inflammation indicators, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(MD_(CRP)=-10.75, 95%CI[-15.61,-5.88], P<0.000 01; MD_(WBC count)=-1.62, 95%CI[-2.55,-0.69], P=0.000 6; MD_(PCT)=-0.58, 95%CI[-0.89,-0.26], P=0.000 3];(4) in terms of improving symptoms and signs, Tanreqing Injection combined with conventional wes-tern medicine was better than conventional western medicine(MD_(cough)=-2.73, 95%CI[-4.93,-0.53], P=0.02; MD_(antipyretic)=-1.07, 95%CI[-1.17,-0.98), P<0.000 01];(5) in terms of decreasing the NIHSS scores, Tanreqing Injection combined with conventional western medicine was better than conventional western medicine(MD=-3.02, 95%CI[-4.91,-1.13], P=0.002);(6) in terms of adverse reactions, there was no statistically significant difference between Tanreqing Injection combined with conventio-nal western medicine compared with conventional western medicine treatment(RR=1.19, 95%CI[0.61,2.29], P=0.61). GRADE system showed that the evidence levels of above outcome indicators were low and extremely low. The results proved that Tanreqing Injection combined with conventional western medicine had a good advantage in the treatment of SAP, with better observation indicators better than western medicine conventional treatment, and no increase in the incidence of adverse reactions. However, this study had certain limitations. The overall quality of the included studies was low, which affected the reliability of the results. Therefore, the conclusions of this study shall be used cautiously.

Medicamentos de Ervas Chinesas , Pneumonia , Acidente Vascular Cerebral , Humanos , Pneumonia/tratamento farmacológico , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico
Cereb Cortex ; 28(9): 3309-3321, 2018 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-28968688


Long-term memory formation has been proven to require gene expression and new protein synthesis. MicroRNAs (miRNAs), as an endogenous small non-coding RNAs, inhibit the expression of their mRNA targets, through which involve in new memory formation. In this study, elevated miR-181a levels were found to be responsible for hippocampal contextual fear memory consolidation. Using a luciferase reporter assay, we indicated that miR-181a targets 2 upstream molecules of mTOR pathway, namely, PRKAA1 and REDD1. Upregulated miR-181a can downregulate the PRKAA1 and REDD1 protein levels and promote mTOR activity to facilitate hippocampal fear memory consolidation. These results indicate that miR-181a is involved in hippocampal contextual fear memory by activating the mTOR signaling pathway. This work provides a novel evidence for the role of miRNAs in memory formation and demonstrates the implication of mTOR signaling pathway in miRNA processing in the adult brain.

Regulação da Expressão Gênica/genética , Memória/fisiologia , MicroRNAs/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Animais , Medo/fisiologia , Camundongos , Camundongos Endogâmicos C57BL
J Neurosci ; 37(25): 5978-5995, 2017 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-28500221


Multiple studies have established that brain-derived neurotrophic factor (BDNF) plays a critical role in the regulation of synaptic plasticity via its receptor, TrkB. In addition to being phosphorylated, TrkB has also been demonstrated to be ubiquitinated. However, the mechanisms of TrkB ubiquitination and its biological functions remain poorly understood. In this study, we demonstrate that ubiquitin C-terminal hydrolase L1 (UCH-L1) promotes contextual fear conditioning learning and memory via the regulation of ubiquitination of TrkB. We provide evidence that UCH-L1 can deubiquitinate TrkB directly. K460 in the juxtamembane domain of TrkB is the primary ubiquitination site and is regulated by UCH-L1. By using a peptide that competitively inhibits the association between UCH-L1 and TrkB, we show that the blockade of UCH-L1-regulated TrkB deubiquitination leads to increased BDNF-induced TrkB internalization and consequently directs the internalized TrkB to the degradation pathway, resulting in increased degradation of surface TrkB and attenuation of TrkB activation and its downstream signaling pathways. Moreover, injection of the peptide into the DG region of mice impairs hippocampus-dependent memory. Together, our results suggest that the ubiquitination of TrkB is a mechanism that controls its downstream signaling pathways via the regulation of its endocytosis and postendocytic trafficking and that UCH-L1 mediates the deubiquitination of TrkB and could be a potential target for the modulation of hippocampus-dependent memory.SIGNIFICANCE STATEMENT Ubiquitin C-terminal hydrolase L1 (UCH-L1) has been demonstrated to play important roles in the regulation of synaptic plasticity and learning and memory. TrkB, the receptor for brain-derived neurotrophic factor, has also been shown to be a potent regulator of synaptic plasticity. In this study, we demonstrate that UCH-L1 functions as a deubiquitinase for TrkB. The blockage of UCH-L1-regulated deubiquitination of TrkB eventually results in the increased degradation of surface TrkB and decreased activation of TrkB and its downstream signaling pathways. In vivo, UCH-L1-regulated TrkB deubiquitination is necessary for hippocampus-dependent memory. Overall, our study provides novel insights into the mechanisms of UCH-L1-mediated neurobiological functions and suggests that ubiquitination is an important regulatory signal for TrkB functions.

Hipocampo/fisiologia , Memória/fisiologia , Receptor trkB/metabolismo , Ubiquitina Tiolesterase/metabolismo , Ubiquitinação/fisiologia , Animais , Azepinas/farmacologia , Benzamidas/farmacologia , Fator Neurotrófico Derivado do Encéfalo/metabolismo , Fator Neurotrófico Derivado do Encéfalo/farmacologia , Condicionamento Operante/fisiologia , Endocitose/genética , Endocitose/fisiologia , Medo/psicologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora/efeitos dos fármacos , Atividade Motora/genética , Atividade Motora/fisiologia , Neurônios/metabolismo , Receptor trkB/antagonistas & inibidores , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Ubiquitina Tiolesterase/genética , Ubiquitinação/genética
J Neurosci ; 37(14): 3848-3863, 2017 04 05.
Artigo em Inglês | MEDLINE | ID: mdl-28283560


Histone acetylation, an epigenetic modification, plays an important role in long-term memory formation. Recently, histone deacetylase (HDAC) inhibitors were demonstrated to promote memory formation, which raises the intriguing possibility that they may be used to rescue memory deficits. However, additional research is necessary to clarify the roles of individual HDACs in memory. In this study, we demonstrated that HDAC7, within the dorsal hippocampus of C57BL6J mice, had a late and persistent decrease after contextual fear conditioning (CFC) training (4-24 h), which was involved in long-term CFC memory formation. We also showed that HDAC7 decreased via ubiquitin-dependent degradation. CBX4 was one of the HDAC7 E3 ligases involved in this process. Nur77, as one of the target genes of HDAC7, increased 6-24 h after CFC training and, accordingly, modulated the formation of CFC memory. Finally, HDAC7 was involved in the formation of other hippocampal-dependent memories, including the Morris water maze and object location test. The current findings facilitate an understanding of the molecular and cellular mechanisms of HDAC7 in the regulation of hippocampal-dependent memory.SIGNIFICANCE STATEMENT The current findings demonstrated the effects of histone deacetylase 7 (HDAC7) on hippocampal-dependent memories. Moreover, we determined the mechanism of decreased HDAC7 in contextual fear conditioning (CFC) through ubiquitin-dependent protein degradation. We also verified that CBX4 was one of the HDAC7 E3 ligases. Finally, we demonstrated that Nur77, as one of the important targets for HDAC7, was involved in CFC memory formation. All of these proteins, including HDAC7, CBX4, and Nur77, could be potential therapeutic targets for preventing memory deficits in aging and neurological diseases.

Medo/fisiologia , Histona Desacetilases/metabolismo , Ligases/metabolismo , Memória/fisiologia , Complexo Repressor Polycomb 1/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Ubiquitinação/fisiologia , Animais , Condicionamento Psicológico/fisiologia , Medo/psicologia , Células HEK293 , Hipocampo/metabolismo , Humanos , Masculino , Aprendizagem em Labirinto/fisiologia , Camundongos , Camundongos Endogâmicos C57BL