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951.
Wei-Qing Li Hong-Yu Yu Yi-Ming Li Xiang Wang Jin He Hong-Zhu Yan Dao-Hua Yang Xiao-Jun Wu Li-Jun Hou Hui-Min Liu Chun-Yan Xia Yi-Cheng Lu 《Biochemical and biophysical research communications》2014
Previous studies from this laboratory indicated that microRNA-21 (miR-21) contributes to chemoresistance of glioblastoma multiforme (GBM) cells to teniposide, a type II topoisomerase inhibitor. We also showed that LRRFIP1 is a target of miR-21. In this study, we found that higher baseline LRRFIP1 expression in human GBM tissue (n = 60) is associated with better prognosis upon later treatment with teniposide. Experiments in cultured U373MG cells showed enhanced toxicity of teniposide against U373MG cells transfected with a vector that resulted in LRRFIP1 overexpression (vs. cells transfected with control vector). Experiments in nude mice demonstrated better response of LRRFIP1 overexpressing xenografts to teniposide. These findings indicate that high baseline LRRFIP1 expression in GBM is associated with better response to teniposide, and encourage exploring LRRFIP1 as a target for GBM treatment. 相似文献
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Nan Cheng Chang Jin Ping Jin Dan Zhu Zuoxu Hou 《Journal of cellular and molecular medicine》2021,25(13):6137-6147
High glucose promoted expression of AKT3, a direct target gene of miR-29b, by regulating circHIPK3 that functioned as ceRNA to sponge and down-regulate miR-29b. As a potential target gene of miR-29b, AKT3 plays a crucial role in the pathogenesis of myocardial ischaemia/reperfusion (I/R) injury, and this study aimed to investigate the potential role of high glucose in the outcome of I/R injury. qPCR and luciferase assay were carried out to investigate the relationship between the expression of circHIPK3, miR-29b and ATK3 mRNA. Immunohistochemistry and TUNEL were performed to analyse the relationship between AKT3 expression and apoptosis of myocardiocytes in vivo. No obvious difference in myocardial functions was observed between I/R and control rats under hyperglycaemia (HG) and normal glucose (NG) conditions, except that the infarct size/area at risk (IS/AR) ratio and the amount of h-FABP expression were different under HG and NG conditions. The expression of circHIPK3 and ATK3 was significantly elevated in the rats preconditioned by NG, whereas the expression of miR-29a was remarkably decreased. Meanwhile, the apoptosis of myocardial tissue was reduced in the rats preconditioned by NG. Luciferase assay confirmed that miR-29a played a repressive role in the expression of circHIPK3 and ATK3. And subsequent study indicated that the over-expressed AKT3 could rescue the increased cell apoptosis rate induced by the knockdown of circHIPK3. In this study, we demonstrated that high glucose protects cardiomyocytes against I/R associated injury by suppressing apoptosis and high glucose promoted the expression of AKT3 by regulating the expression of circHIPK3/miR-29b. 相似文献
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Lu Wang Bin Deng Panpan Yan Huanghui Wu Chunhui Li Hongrui Zhu Jiwei Du Lichao Hou 《Journal of cellular and molecular medicine》2021,25(7):3449-3459
Tumour necrosis factor-α (TNF-α), a crucial cytokine, has various homeostatic and pathogenic bioactivities. The aim of this study was to assess the neuroprotective effect of ketamine against TNF-α-induced motor dysfunction and neuronal necroptosis in male C57BL/6J mice in vivo and HT-22 cell lines in vitro. The behavioural testing results of the present study indicate that ketamine ameliorated TNF-α-induced neurological dysfunction. Moreover, immunohistochemical staining results showed that TNF-α-induced brain dysfunction was caused by necroptosis and microglial activation, which could be attenuated by ketamine pre-treatment inhibiting reactive oxygen species production and mixed lineage kinase domain-like phosphorylation in hippocampal neurons. Therefore, we concluded that ketamine may have neuroprotective effects as a potent inhibitor of necroptosis, which provides a new theoretical and experimental basis for the application of ketamine in TNF-α-induced necroptosis-associated diseases. 相似文献
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Jiaxing Li Chaoquan Hu Hui Chao Yu Zhang Yong Li Jing Hou Limin Huang 《Journal of cellular and molecular medicine》2021,25(19):9183-9198
Nasopharyngeal carcinoma (NPC), a subclass of cancers of the neck and head, is a predominant cause of cancer-associated death worldwide. Hence, there is a critical need for research into NPC-related treatment strategies. Cisplatin is a promising therapy option for NPCs and other cancers that is frequently utilized. Some patients acquire resistance to cisplatin therapy, which complicates the successful use of cisplatin treatment in NPCs. Although exosomal transfer of oncogenic miRNAs has been shown to improve recipient cell proliferation, metastasis and chemoresistance, the molecular mechanism behind this effect on NPC has yet to be fully understood. Exosomal microRNAs (miRNAs) from cisplatin-resistant cells were identified as significant mediators of chemoresistance in NPC cells in this investigation. Initially, we found that exosomal miR-106a-5p levels in the serum of chemoresistant and last-cycle patients were greater than in that of non-resistant and first-cycle patients. Also, exosomal miR-106a-5p enhanced the proliferative ability of NPC cells. Mechanistically, exosomal miR-106a-5p targets ARNT2, which further activates AKT phosphorylation, and thus promotes NPC cell proliferation, decreases apoptosis and in turn regulates tumorigenesis. We found similar results using in vivo NPC models, where exosomal miR-106a-5p through regulation of ARNT2 (aryl hydrocarbon receptor nuclear translocator 2) promoted tumorigenesis. Taken together, these findings indicate that exosomal miR-106a-5p could be a promising diagnostic biomarker and drug target for patients with NPC. 相似文献
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Chien-Wei Hou 《Journal of biomedical science》2011,18(1):75
Background
Pu-Erh tea is one of the most-consumed beverages due to its taste and the anti-anxiety-producing effect of the gamma-aminobutyric acid (GABA) if contains. However the protective effects of Pu-Erh tea and its constituent, GABA to kainic acid (KA)-induced seizure have not been fully investigated. 相似文献960.
The accuracy of protein synthesis relies on the ability of aminoacyl-tRNA synthetases (aaRSs) to discriminate among true and near cognate substrates. To date, analysis of aaRSs function, including identification of residues of aaRS participating in amino acid and tRNA discrimination, has largely relied on the steady state kinetic pyrophosphate exchange and aminoacylation assays. Pre-steady state kinetic studies investigating a more limited set of aaRS systems have also been undertaken to assess the energetic contributions of individual enzyme-substrate interactions, particularly in the adenylation half reaction. More recently, a renewed interest in the use of rapid kinetics approaches for aaRSs has led to their application to several new aaRS systems, resulting in the identification of mechanistic differences that distinguish the two structurally distinct aaRS classes. Here, we review the techniques for thermodynamic and kinetic analysis of aaRS function. Following a brief survey of methods for the preparation of materials and for steady state kinetic analysis, this review will describe pre-steady state kinetic methods employing rapid quench and stopped-flow fluorescence for analysis of the activation and aminoacyl transfer reactions. Application of these methods to any aaRS system allows the investigator to derive detailed kinetic mechanisms for the activation and aminoacyl transfer reactions, permitting issues of substrate specificity, stereochemical mechanism, and inhibitor interaction to be addressed in a rigorous and quantitative fashion. 相似文献