9 results on '"Lu, Lihui"'
Search Results
2. LMO2 promotes the development of AML through interaction with transcription co-regulator LDB1
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Lu, Lihui, Wang, Jianwei, Fang, Fang, Guo, Ailian, Jiang, Shuting, Tao, Yanfang, Zhang, Yongping, Li, Yan, Zhang, Kunlong, Zhang, Zimu, Zhuo, Ran, Chu, Xinran, Li, Xiaolu, Tian, Yuanyuan, Ma, Li, Sang, Xu, Chen, Yanling, Yu, Juanjuan, Yang, Yang, Cao, Haibo, Gao, Jizhao, Lu, Jun, Hu, Shaoyan, Pan, Jian, and He, Hailong
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- 2023
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3. Colocalized, bidirectional optogenetic modulations in freely behaving mice with a wireless dual-color optoelectronic probe
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Li, Lizhu, Lu, Lihui, Ren, Yuqi, Tang, Guo, Zhao, Yu, Cai, Xue, Shi, Zhao, Ding, He, Liu, Changbo, Cheng, Dali, Xie, Yang, Wang, Huachun, Fu, Xin, Yin, Lan, Luo, Minmin, and Sheng, Xing
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- 2022
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4. Luteolin-7-O-β-d-Glucuronide Attenuated Cerebral Ischemia/Reperfusion Injury: Involvement of the Blood–Brain Barrier.
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Fan, Xing, Song, Jintao, Zhang, Shuting, Lu, Lihui, Lin, Fang, Chen, Yu, Li, Shichang, Jin, Xinxin, and Wang, Fang
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CEREBRAL ischemia ,REPERFUSION injury ,BLOOD-brain barrier ,CORONARY heart disease treatment ,CEREBRAL infarction ,ELLAGIC acid ,HYDROCEPHALUS - Abstract
Ischemic stroke is a common cerebrovascular disease with high mortality, high morbidity, and high disability. Cerebral ischemia/reperfusion injury seriously affects the quality of life of patients. Luteolin-7-O-β-d-glucuronide (LGU) is a major active flavonoid compound extracted from Ixeris sonchifolia (Bge.) Hance, a Chinese medicinal herb mainly used for the treatment of coronary heart disease, angina pectoris, cerebral infarction, etc. In the present study, the protective effect of LGU on cerebral ischemia/reperfusion injury was investigated in an oxygen–glucose deprivation/reoxygenation (OGD/R) neuronal model and a transient middle cerebral artery occlusion (tMCAO) rat model. In in vitro experiments, LGU was found to improve the OGD/R-induced decrease in neuronal viability effectively by the MTT assay. In in vivo experiments, neurological deficit scores, infarction volume rates, and brain water content rates were improved after a single intravenous administration of LGU. These findings suggest that LGU has significant protective effects on cerebral ischemia/reperfusion injury in vitro and in vivo. To further explore the potential mechanism of LGU on cerebral ischemia/reperfusion injury, we performed a series of tests. The results showed that a single administration of LGU decreased the content of EB and S100B and ameliorated the abnormal expression of tight junction proteins ZO-1 and occludin and metalloproteinase MMP-9 in the ischemic cerebral cortex of the tMCAO 24-h injury model. In addition, LGU also improved the tight junction structure between endothelial cells and the degree of basement membrane degradation and reduced the content of TNF-α and IL-1β in the brain tissue. Thereby, LGU attenuated cerebral ischemia/reperfusion injury by improving the permeability of the blood–brain barrier. The present study provides new insights into the therapeutic potential of LGU in cerebral ischemia. [ABSTRACT FROM AUTHOR]
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- 2024
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5. BRD4 PROTAC degrader MZ1 exhibits anti-B-cell acute lymphoblastic leukemia effects via targeting CCND3.
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Ma, Li, Wang, Jianwei, Yang, Yang, Lu, Jun, Ling, Jing, Chu, Xinran, Zhang, Zimu, Tao, Yanfang, Li, Xiaolu, Tian, Yuanyuan, Li, Zhiheng, Zhang, Yongping, Sang, Xu, Lu, Lihui, Wan, Xiaomei, Zhang, Kunlong, Chen, Yanling, Yu, Juanjuan, Zhuo, Ran, and Wu, Shuiyan
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LYMPHOBLASTIC leukemia ,ACUTE leukemia ,GENE expression ,HEMATOLOGIC malignancies ,CELL cycle - Abstract
B-cell acute lymphoblastic leukemia (B-ALL) is the most prevalent malignant tumor affecting children. While the majority of B-ALL patients (90%) experience successful recovery, early relapse cases of B-ALL continue to exhibit high mortality rates. MZ1, a novel inhibitor of Bromodomains and extra-terminal (BET) proteins, has demonstrated potent antitumor activity against hematological malignancies. The objective of this study was to examine the role and therapeutic potential of MZ1 in the treatment of B-ALL. In order to ascertain the fundamental mechanism of MZ1, a sequence of in vitro assays was conducted on B-ALL cell lines, encompassing Cell Counting Kit 8 (CCK8) assay, Propidium iodide (PI) staining, and Annexin V/PI staining. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) were employed to examine protein and mRNA expression levels. Transcriptomic RNA sequencing (RNA-seq) was utilized to screen the target genes of MZ1, and lentiviral transfection was employed to establish stably-expressing/knockdown cell lines. MZ1 has been observed to induce the degradation of Bromodomain Containing 4 (BRD4), Bromodomain Containing 3 (BRD3), and Bromodomain Containing 2 (BRD2) in B-ALL cell strains, leading to inhibited cell growth and induction of cell apoptosis and cycle arrest in vitro. These findings suggest that MZ1 exhibits cytotoxic effects on two distinct molecular subtypes of B-ALL, namely 697 (TCF3/PBX1) and RS4;11 (MLL-AF4) B-ALL cell lines. Additionally, RNA-sequencing analysis revealed that MZ1 significantly downregulated the expression of Cyclin D3 (CCND3) gene in B-ALL cell lines, which in turn promoted cell apoptosis, blocked cell cycle, and caused cell proliferation inhibition. Our results suggest that MZ1 has potential anti-B-ALL effects and might be a novel therapeutic target. [ABSTRACT FROM AUTHOR]
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- 2023
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6. Super Enhancer Regulatory Gene FYB1 Promotes the Progression of T Cell Acute Lymphoblastic Leukemia by Activating IGLL1.
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Zhang, Kunlong, Lu, Jun, Fang, Fang, Zhang, Yongping, Yu, Juanjuan, Tao, Yanfang, liu, Wenyuan, Lu, Lihui, Zhang, Zimu, Chu, Xinran, Wang, Jianwei, Li, Xiaolu, Tian, Yuanyuan, Li, Zhiheng, Li, Qian, Sang, Xu, Ma, Li, Wang, Ningling, Pan, Jian, and Hu, Shaoyan
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REGULATOR genes ,LYMPHOBLASTIC leukemia ,ACUTE leukemia ,T cells ,GENE enhancers - Abstract
Background. Arising from T progenitor cells, T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematologic malignant tumor, accounting for 15% of childhood ALL and 25% of adult ALL. Composing of putative enhancers in close genomic proximity, super enhancer (SE) is critical for cell identity and the pathogenesis of multiple cancers. Belonging to the cytosolute linker protein group, FYB1 is essential for TCR signaling and extensively studied in terms of tumor pathogenesis and metastasis. Dissecting the role of FYN binding protein 1 (FYB1) in T-ALL holds the potential to improve the treatment outcome and prognosis of T-ALL. Methods. In this study, SEs were explored using public H3K27ac ChIP-seq data derived from T-ALL cell lines, AML cell lines and hematopoietic stem and progenitor cells (HSPCs). Downstream target of FYB1 gene was identified by RNA-seq. Effects of shRNA-mediated downregulation of FYB1 and immunoglobulin lambda-like polypeptide 1 (IGLL1) on self-renewal of T-ALL cells were evaluated in vitro and/or in vivo. Results. As an SE-driven gene, overexpression of FYB1 was observed in T-ALL, according to the Cancer Cell Line Encyclopedia database. In vitro, knocking down FYB1 led to comprised growth and enhanced apoptosis of T-ALL cells. In vivo, downregulation of FYB1 significantly decreased the disease burden by suppressing tumor growth and improved survival rate. Knocking down FYB1 resulted in significantly decreased expression of IGLL1 that was also an SE-driven gene in T-ALL. As a downstream target of FYB1, IGLL1 exerted similar role as FYB1 in inhibiting growth of T-ALL cells. Conclusion. Our results suggested that FYB1 gene played important role in regulating self-renewal of T-ALL cells by activating IGLL1, representing a promising therapeutic target for T-ALL patients. [ABSTRACT FROM AUTHOR]
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- 2023
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7. BRD4 Inhibitor GNE-987 Exerts Anticancer Effects by Targeting Super-Enhancer-Related Gene LYL1 in Acute Myeloid Leukemia.
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Sang, Xu, Zhang, Yongping, Fang, Fang, Gao, Li, Tao, Yanfang, Li, Xiaolu, Zhang, Zimu, Wang, Jianwei, Tian, Yuanyuan, Li, Zhiheng, Yao, Di, Wu, Yumeng, Chu, Xinran, Zhang, Kunlong, Ma, Li, Lu, Lihui, Chen, Yanling, Yu, Juanjuan, Zhuo, Ran, and Wu, Shuiyan
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ACUTE myeloid leukemia ,POLY(ADP-ribose) polymerase ,GENE targeting ,ANTINEOPLASTIC agents ,INHIBITION of cellular proliferation ,SUPER enhancers ,PROTEINS ,NUCLEAR proteins ,ANIMAL experimentation ,CELL cycle proteins ,CELL physiology ,APOPTOSIS ,TRANSCRIPTION factors ,CELL lines ,MICE - Abstract
Background: AML (acute myeloid leukemia) is a common hematological malignancy in children with poor treatment effects and poor prognosis. Recent studies have shown that as a novel BRD4 (bromodomain containing 4) PROTACs (proteolysis targeting chimeras) degrader, GNE-987 can slow down the growth of various tumors and increase apoptosis, with promising clinical prospects. However, the function and molecular mechanism of GNE-987 in AML remain unclear. This study is aimed at investigating the therapeutic effect of GNE-987 on AML and its underlying mechanism.Methods: The association between BRD4 and AML was assessed by studying public databases. After GNE-987 was added to AML cells, cell proliferation slowed down, the cycle was disturbed, and apoptosis increased. Western blotting was used to detect BRD2 (bromodomain containing 2), BRD3 (bromodomain containing 3), BRD4, and PARP (poly ADP-ribose polymerase) proteins. The effect of GNE-987 on AML cells was analyzed in vivo. RNA-seq (RNA sequencing) and ChIP-seq (chromatin immunoprecipitation sequencing) validated the function and molecular pathways of GNE-987 in processing AML.Results: BRD4 expression was significantly elevated in pediatric AML samples compared with healthy donors. GNE-987 inhibited AML cell proliferation by inhibiting the cell cycle and inducing apoptosis. BRD2, BRD3, and BRD4 were consistent with decreased VHL (Von Hippel Lindau) expression in AML cells. In an AML xenograft model, GNE-987 significantly reduced the hepatosplenic infiltration of leukemia cells and increased the mouse survival time. Based on analysis of RNA-seq and ChIP-seq analyses, GNE-987 could target multiple SE- (super-enhancer-) related genes, including LYL1 (lymphoblastic leukemia 1), to inhibit AML.Conclusions: GNE-987 had strong antitumor activity in AML. GNE-987 could effectively inhibit the expression of SE-related oncogenes including LYL1 in AML. Our results suggested that GNE-987 had broad prospects in the treatment of AML. [ABSTRACT FROM AUTHOR]- Published
- 2022
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8. BRD4 PROTAC degrader MZ1 exerts anticancer effects in acute myeloid leukemia by targeting c-Myc and ANP32B genes.
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Ma, Li, Wang, Jianwei, Zhang, Yongping, Fang, Fang, Ling, Jing, Chu, Xinran, Zhang, Zimu, Tao, Yanfang, Li, Xiaolu, Tian, Yuanyuan, Li, Zhiheng, Sang, Xu, Zhang, Kunlong, Lu, Lihui, Wan, Xiaomei, Chen, Yanling, Yu, Juanjuan, Zhuo, Ran, Wu, Shuiyan, and Lu, Jun
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ACUTE myeloid leukemia ,ANTINEOPLASTIC agents ,BLOOD diseases ,PROTEOLYSIS ,SUBSTANCE abuse relapse - Abstract
Acute myeloid leukemia (AML) is a highly cancerous and aggressive hematologic disease with elevated levels of drug resistance and relapse resulting in high mortality. Recently, bromodomains and extra-terminal (BET) protein inhibitors have been extensively researched in hematological tumors as potential anticancer agents. MZ1 is a novel BET inhibitor that mediates selective proteins degradation and suppression of tumor growth through proteolysis-targeting chimeras (PROTAC) technology. Accordingly, this study aimed to investigate the role and therapeutic potential of MZ1 in AML. In this study, we first identified that AML patients with high BRD4 expression had poor overall survival than those with low expression group. MZ1 inhibited AML cell growth and induced apoptosis and cycle arrest in vitro. MZ1 induced degradation of BRD4, BRD3 and BRD2 in AML cell strains. Additionally, MZ1 also initiated the cleavage of poly-ADP-ribose polymerase (PARP), which showed cytotoxic effects on NB4 (PML-RARa), K562 (BCR-ABL), Kasumi-1 (AML1-ETO), and MV4-11 (MLL-AF4) cell lines representing different molecular subtypes of AML. In AML mouse leukemia model, MZ1 significantly decreased leukemia cell growth and increased the mouse survival time. According to the RNA-sequencing analysis, MZ1 led to c-Myc and ANP32B genes significant downregulation in AML cell lines. Knockdown of ANP32B promoted AML cell apoptosis and inhibited cell growth. Overall, our data indicated that MZ1 had broad anti-cancer effects on AML cell lines with different molecular lesions, which might be exploited as a novel therapeutic strategy for AML patients. [ABSTRACT FROM AUTHOR]
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- 2022
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9. A Novel BRD Family PROTAC Inhibitor dBET1 Exerts Great Anti-Cancer Effects by Targeting c-MYC in Acute Myeloid Leukemia Cells.
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Zhang K, Gao L, Wang J, Chu X, Zhang Z, Zhang Y, Fang F, Tao Y, Li X, Tian Y, Li Z, Sang X, Ma L, Lu L, Chen Y, Yu J, Zhuo R, Wu S, Pan J, and Hu S
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- Humans, Cell Cycle Proteins metabolism, Cell Line, Tumor, Intercellular Signaling Peptides and Proteins, Proteolysis, Proto-Oncogene Proteins c-myc, Transcription Factors metabolism, Leukemia, Myeloid, Acute pathology, Nuclear Proteins metabolism
- Abstract
Acute myeloid leukemia (AML) represents an aggressive hematopoietic malignancy with a prognosis inferior to that of other leukemias. Recent targeted therapies offer new opportunities to achieve better treatment outcomes. However, due to the complex heterogeneity of AML, its prognosis remains dismal. In this study, we first identified the correlation between high expression of BRD4 and overall survival of patients with AML. Targeted degradation of BRD2, BRD3, and BRD4 proteins by dBET1, a proteolysis-targeting chimera (PROTAC) against the bromodomain and extra-terminal domain (BET) family members, showed cytotoxic effects on Kasumi (AML1-ETO), NB4 (PML-RARa), THP-1 (MLL-AF9), and MV4-11 (MLL-AF4) AML cell lines representing different molecular subtypes of AML. Furthermore, we determined that dBET1 treatment arrested cell cycling and enhanced apoptosis and c-MYC was identified as the downstream target. Collectively, our results indicated that dBET1 had broad anti-cancer effects on AML cell lines with different molecular lesions and provided more benefits to patients with AML., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhang, Gao, Wang, Chu, Zhang, Zhang, Fang, Tao, Li, Tian, Li, Sang, Ma, Lu, Chen, Yu, Zhuo, Wu, Pan and Hu.)
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- 2022
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