41 results on '"Maff"'
Search Results
2. PROTAC technology as a novel tool to identify the target of lathyrane diterpenoids.
- Author
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Wu, Yanli, Yang, Yueying, Wang, Wang, Sun, Dejuan, Liang, Jing, Zhu, Man, Li, Hua, and Chen, Lixia
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DITERPENES - Published
- 2022
- Full Text
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3. BAP1-mediated MAFF deubiquitylation regulates tumor growth and is associated with adverse outcomes in colorectal cancer.
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Xie, Zhongdong, Lin, Hanbin, Huang, Ying, Wang, Xiaojie, Lin, Hongyue, Xu, Meifang, Wu, Jiashu, Wu, Yuecheng, Shen, Hao, Zhang, Qiongying, Chen, Jinhua, Deng, Yu, Xu, Zongbin, Chen, Zhiping, Lin, Yu, Han, Yuting, Lin, Lin, Yan, Linzhu, Li, Qingyun, and Lin, Xinjian
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PROTEINS , *RISK assessment , *IN vitro studies , *PHENOMENOLOGICAL biology , *PHOSPHORYLATION , *COLORECTAL cancer , *CELLULAR signal transduction , *ENZYMES , *CANCER patients , *QUANTITATIVE research , *BIOCHEMISTRY , *IN vivo studies , *GENE expression , *GAIN-of-function mutations , *RNA , *LONGITUDINAL method , *PROTEOMICS , *RESEARCH , *NONSENSE mutation , *MOLECULAR biology , *PROGRESSION-free survival , *BIOMARKERS , *GENETIC testing , *SEQUENCE analysis ,RESEARCH evaluation - Abstract
Despite improvements in colorectal cancer (CRC) treatment, the prognosis for advanced CRC patients remains poor. Disruption of protein stability is one of the important factors in cancer development and progression. In this study, we aim to identify and analyze novel dysregulated proteins in CRC, assessing their significance and the mechanisms. Using quantitative proteomics, expression pattern analysis, and gain-of-function/loss-of-function experiments, we identify novel functional protein dysregulated by ubiquitin-proteasome axis in CRC. Prognostic significance was evaluated in a training cohort of 546 patients and externally validated in 794 patients. Mechanistic insights are gained through molecular biology experiments, deubiquitinating enzymes (DUBs) expression library screening, and RNA sequencing. MAFF protein emerged as the top novel candidate substrate regulated by ubiquitin-proteasome in CRC. MAFF protein was preferentially downregulated in CRC compared to adjacent normal tissues. More importantly, multicenter cohort study identified reduced MAFF protein expression as an independent predictor of overall and disease-free survival in CRC patients. The in vitro and vivo assays showed that MAFF overexpression inhibited CRC growth, while its knockdown had the opposite effect. Intriguingly, we found the abnormal expression of MAFF protein was predominantly regulated via ubiquitination of MAFF, with K48-ubiquitin being dominant. BAP1 as a nuclear deubiquitinating enzyme (DUB), bound to and deubiquitinated MAFF, thereby stabilizing it. Such stabilization upregulated DUSP5 expression, resulting in the inhibition of ERK phosphorylation. This study describes a novel BAP1-MAFF signaling axis which is crucial for CRC growth, potentially serving as a therapeutic target and a promising prognostic biomarker for CRC. • MAFF protein is preferentially downregulated in CRC. • MAFF protein signature segregates CRC patient survival. • The K48-linked ubiquitination affects aberrant MAFF expression in CRC. • BAP1 suppresses CRC growth via deubiquitylation of MAFF at K92 and K110 residue. • DUSP5 is required for MAFF's CRC growth suppression through ERK phosphorylation. [ABSTRACT FROM AUTHOR]
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- 2024
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4. miR-320a induces pancreatic β cells dysfunction in diabetes by inhibiting MafF
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Hengzhi Du, Zhongwei Yin, Yanru Zhao, Huaping Li, Beibei Dai, Jiahui Fan, Mengying He, Xiang Nie, Cong-Yi Wang, Dao Wen Wang, and Chen Chen
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miRNA ,pancreatic islet ,β cells ,diabetes ,MafF ,Therapeutics. Pharmacology ,RM1-950 - Abstract
A variety of studies indicate that microRNAs (miRNAs) are involved in diabetes. However, the direct role of miR-320a in the pathophysiology of pancreatic β cells under diabetes mellitus remains unclear. In the current study, islet transplantation and hyperglycemic clamp assays were performed in miR-320a transgenic mice to explore the effects of miR-320a on pancreatic β cells in vivo. Meanwhile, β cell-specific overexpression or inhibition of miR-320a was delivered by adeno-associated virus (AAV8). In vitro, overexpression or downregulation of miR-320a was introduced in cultured rat islet tumor cells (INS1). RNA immunoprecipitation sequencing (RIP-Seq), luciferase reporter assay, and western blotting were performed to identify the target genes. Results showed that miR-320a was increased in the pancreatic β cells from high-fat-diet (HFD)-treated mice. Overexpression of miR-320a could not only deteriorate the HFD-induced pancreatic islet dysfunction, but also initiate pancreatic islet dysfunction spontaneously in vivo. Meanwhile, miR-320a increased the ROS level, inhibited proliferation, and induced apoptosis of cultured β cells in vitro. Finally, we identified that MafF was the target of miR-320a that responsible for the dysfunction of pancreatic β cells. Our data suggested that miR-320a could damage the pancreatic β cells directly and might be a potential therapeutic target of diabetes.
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- 2021
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5. Identification of the Transcription Factor ATF3 as a Direct and Indirect Regulator of the LDLR.
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Bauer, Sabine, Eigenmann, Jana, Zhao, Yuqi, Fleig, Julia, Hawe, Johann S., Pan, Calvin, Bongiovanni, Dario, Wengert, Simon, Ma, Angela, Lusis, Aldons J., Kovacic, Jason C., Björkegren, Johan L. M., Maegdefessel, Lars, Schunkert, Heribert, and von Scheidt, Moritz
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TRANSCRIPTION factors ,HOMEOSTASIS ,CORONARY artery bypass ,CHOLESTEROL metabolism ,LIPOPROTEIN receptors ,LIVER cells ,CORONARY artery disease - Abstract
Coronary artery disease (CAD) is a complex, multifactorial disease caused, in particular, by inflammation and cholesterol metabolism. At the molecular level, the role of tissue-specific signaling pathways leading to CAD is still largely unexplored. This study relied on two main resources: (1) genes with impact on atherosclerosis/CAD, and (2) liver-specific transcriptome analyses from human and mouse studies. The transcription factor activating transcription factor 3 (ATF3) was identified as a key regulator of a liver network relevant to atherosclerosis and linked to inflammation and cholesterol metabolism. ATF3 was predicted to be a direct and indirect (via MAF BZIP Transcription Factor F (MAFF)) regulator of low-density lipoprotein receptor (LDLR). Chromatin immunoprecipitation DNA sequencing (ChIP-seq) data from human liver cells revealed an ATF3 binding motif in the promoter regions of MAFF and LDLR. siRNA knockdown of ATF3 in human Hep3B liver cells significantly upregulated LDLR expression (p < 0.01). Inflammation induced by lipopolysaccharide (LPS) stimulation resulted in significant upregulation of ATF3 (p < 0.01) and subsequent downregulation of LDLR (p < 0.001). Liver-specific expression data from human CAD patients undergoing coronary artery bypass grafting (CABG) surgery (STARNET) and mouse models (HMDP) confirmed the regulatory role of ATF3 in the homeostasis of cholesterol metabolism. This study suggests that ATF3 might be a promising treatment candidate for lowering LDL cholesterol and reducing cardiovascular risk. [ABSTRACT FROM AUTHOR]
- Published
- 2022
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6. PRMT1 promotes epigenetic reprogramming associated with acquired chemoresistance in pancreatic cancer.
- Author
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Nguyen, Chan D.K., Colón-Emeric, Benjamín A., Murakami, Shigekazu, Shujath, Mia N.Y., and Yi, Chunling
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Pancreatic ductal adenocarcinoma (PDAC) carries a dismal prognosis due to therapeutic resistance. We show that PDAC cells undergo global epigenetic reprogramming to acquire chemoresistance, a process that is driven at least in part by protein arginine methyltransferase 1 (PRMT1). Genetic or pharmacological PRMT1 inhibition impairs adaptive epigenetic reprogramming and delays acquired resistance to gemcitabine and other common chemo drugs. Mechanistically, gemcitabine treatment induces translocation of PRMT1 into the nucleus, where its enzymatic activity limits the assembly of chromatin-bound MAFF/BACH1 transcriptional complexes. Cut&Tag chromatin profiling of H3K27Ac, MAFF, and BACH1 suggests a pivotal role for MAFF/BACH1 in global epigenetic response to gemcitabine, which is confirmed by genetically silencing MAFF. PRMT1 and MAFF/BACH1 signature genes identified by Cut&Tag analysis distinguish gemcitabine-resistant from gemcitabine-sensitive patient-derived xenografts of PDAC, supporting the PRMT1-MAFF/BACH1 epigenetic regulatory axis as a potential therapeutic avenue for improving the efficacy and durability of chemotherapies in patients of PDAC. [Display omitted] • Epigenetic reprogramming is associated with acquired chemoresistance • PRMT1 is a central driver of acquired chemoresistance in PDAC • PRMT1 inhibits chemo-induced chromatin recruitment of the MAFF/BACH1 complex • PRMT1 gene signatures segregate PDAC patient survival and chemo response Nguyen et al. investigate mechanisms of acquired chemotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). By identifying the PRMT1-MAFF/BACH1 axis as a key mechanism of response to chemotherapy, Nguyen et al. demonstrate a promising pathway for improving the efficacy of chemotherapy treatments in PDAC. [ABSTRACT FROM AUTHOR]
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- 2024
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7. RBFOX1 Regulates the Permeability of the Blood-Tumor Barrier via the LINC00673/MAFF Pathway
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Shuyuan Shen, Chunqing Yang, Xiaobai Liu, Jian Zheng, Yunhui Liu, Libo Liu, Jun Ma, Teng Ma, Ping An, Yang Lin, Heng Cai, Di Wang, Zhen Li, Lini Zhao, and Yixue Xue
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glioma ,blood-tumor barrier ,RBFOX1 ,LINC00673 ,MAFF ,STAU1 ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
The blood-tumor barrier limits the delivery of therapeutic drugs to brain tumor tissues. Selectively opening the blood-tumor barrier is considered crucial for effective chemotherapy of glioma. RNA-binding proteins have emerged as crucial regulators in various biologic processes. This study found that RNA-binding Fox-1 homolog 1 (RBFOX1) was downregulated in glioma vascular endothelial cells derived from glioma tissues, and in glioma endothelial cells obtained by co-culturing endothelial cells with glioma cells. Overexpression of RBFOX1 impaired the integrity of the blood-tumor barrier and increased its permeability. Additionally, RBFOX1 overexpression decreased the expression of tight junction proteins ZO-1, occludin, and claudin-5. Subsequent analysis of the mechanism indicated that the overexpression of RBFOX1 increased musculoaponeurotic fibrosarcoma protein basic leucine zipper [bZIP] transcription factor F (MAFF) expression by downregulating LINC00673, which stabilized MAFF messenger RNA (mRNA) through Staufen1-mediated mRNA decay. Moreover, MAFF could bind to the promoter region and inhibit the promoter activities of ZO-1, occludin, and claudin-5, which reduced its expression. The combination of RBFOX1 upregulation and LINC00673 downregulation promoted doxorubicin delivery across the blood-tumor barrier, resulting in apoptosis of glioma cells. In conclusion, this study indicated that overexpression of RBFOX1 increased blood-tumor barrier permeability through the LINC00673/MAFF pathway, which might provide a new useful target for future enhancement of blood-tumor barrier permeability.
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- 2020
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8. MafF Is an Antiviral Host Factor That Suppresses Transcription from Hepatitis B Virus Core Promoter.
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Ibrahim, Marwa K., Abdelhafez, Tawfeek H., Takeuchi, Junko S., Wakae, Kosho, Masaya Sugiyama, Masataka Tsuge, Masahiko Ito, Koichi Watashi, Kassas, Mohamed El, Takanobu Kato, Asako Murayama, Tetsuro Suzuki, Kazuaki Chayama, Kunitada Shimotohno, Masamichi Muramatsu, Aly, Hussein H., and Takaji Wakita
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HEPATITIS B virus , *HEPATITIS B , *TUMOR necrosis factors , *SMALL interfering RNA , *PEPTIDE antibiotics , *INTERLEUKIN-1 - Abstract
Hepatitis B virus (HBV) is a stealth virus that exhibits only minimal induction of the interferon system, which is required for both innate and adaptive immune responses. However, 90% of acutely infected adults can clear the virus, suggesting the presence of additional mechanisms that facilitate viral clearance. Here, we report that Maf bZIP transcription factor F (MafF) promotes host defense against infection with HBV. Using a small interfering RNA (siRNA) library and an HBV/NanoLuc (NL) reporter virus, we screened to identify anti-HBV host factors. Our data showed that silencing of MafF led to a 6-fold increase in luciferase activity after HBV/NL infection. Overexpression of MafF reduced HBV core promoter transcriptional activity, which was relieved upon mutation of the putative MafF binding region. Loss of MafF expression through CRISPR/Cas9 editing (in HepG2-hNTCP-C4 cells) or siRNA silencing (in primary hepatocytes [PXB cells]) induced HBV core RNA and HBV pregenomic RNA (pgRNA) levels, respectively, after HBV infection. MafF physically binds to the HBV core promoter and competitively inhibits HNF-4a binding to an overlapping sequence in the HBV enhancer II sequence (EnhII), as seen by chromatin immunoprecipitation (ChIP) analysis. MafF expression was induced by interleukin-1b (IL-1b) or tumor necrosis factor alpha (TNF-a) treatment in both HepG2 and PXB cells, in an NF-κBdependent manner. Consistently, MafF expression levels were significantly enhanced and positively correlated with the levels of these cytokines in patients with chronic HBV infection, especially in the immune clearance phase. [ABSTRACT FROM AUTHOR]
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- 2021
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9. Multi-Response Optimization of Magnetic Abrasive Flow Finishing Process on Aluminum (6061-T6) Using Utility Concept Embedded Firefly's Algorithm.
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Yadav, Pawan Kumar and Jayswal, S. C.
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FINISHES & finishing ,SURFACE finishing ,WATER jet cutting ,MAGNETIC flux density ,UTILITY theory ,SURFACES (Technology) - Abstract
Surface finish is the most desired properties of any sophisticated machinery parts for its proper functioning and long endurance. The surface finish must be in the order of micrometer to nanometer for most of the machinery parts. The nontraditional surface finish processes prepare these parts; in these processes, the uses of electromagnet play a vital role in the surface finishing mechanism. Magnetic abrasive flow finishing (MAFF) is such a hybrid process, which gives a combined effect of abrasive flow finishing (AFF) and magnetic abrasive finishing (MAF). In this method, a pair of electromagnets are attached to the AFF setup. By using electromagnet in the AFF process, it enhanced material removal and surface finishing. The main process parameters selected in the MAFF process were magnetic flux density, number of cycles, percentage abrasive content, piston speed, and corresponding responses selected were material removal, percentage improvement in surface finish. In this research paper, the responses were optimized by a combination of utility theory and meta-heuristic firefly's algorithm. The utility theory based-firefly algorithm's predicted global optimum parameters set, which was more suitable for reducing the finishing time and required surface finish. The confirmatory test validated this optimized parameter set and it was revealed that the meta-heuristic firefly algorithm embedded with utility theory had given optimized results in the MAFF process. [ABSTRACT FROM AUTHOR]
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- 2021
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10. MafF Is Regulated via the circ-ITCH/miR-224-5p Axis and Acts as a Tumor Suppressor in Hepatocellular Carcinoma.
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Wu, Minhua, Deng, Xubin, Zhong, Yu, Hu, Li, Zhang, Xiujuan, Liang, Yanqin, Li, Xiaofang, and Ye, Xiaoxia
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HEPATOCELLULAR carcinoma ,LEUCINE zippers ,CIRCULAR RNA ,TRANSCRIPTION factors ,APOPTOSIS - Abstract
MafF is a member of the basic leucine zipper (bZIP) transcription factor Maf family and is commonly downregulated in multiple cancers. But the expression and function of MafF in hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the relationship between endogenous MafF expression and HCC progression and explored the regulatory mechanism of MafF expression in HCC. We found that MafF decreased in HCC tissues and cells. Lentivirus-mediated MafF overexpression inhibited HCC cell proliferation and induced cell apoptosis. Bioinformatics analysis and luciferase assay identified MafF as a direct target of miR-224-5p. RNA pull-down assay demonstrated that circular RNA circ-ITCH could sponge miR-224-5p specifically in HCC. The rescue experiments further elucidated that the expression and antitumor effects of MafF could be regulated via the circ-ITCH/miR-224-5p axis. This study verified that MafF acted as a tumor suppressor in HCC and revealed the upstream regulation mechanism of MafF, which provided a new perspective for potential therapeutic targets of HCC. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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11. Regulation of CXCL1 chemokine and CSF3 cytokine levels in myometrial cells by the MAFF transcription factor.
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Saliba, James, Coutaud, Baptiste, Solovieva, Vera, Lu, Fangshi, and Blank, Volker
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PARTURITION ,TRANSCRIPTION factors ,GENE regulatory networks ,CELL physiology ,MESSENGER RNA ,PREMATURE labor - Abstract
Cytokines play key roles in a variety of reproductive processes including normal parturition as well as preterm birth. Our previous data have shown that MAFF, a member of the MAF family of bZIP transcription factors, is rapidly induced by pro‐inflammatory cytokines in PHM1‐31 myometrial cells. We performed loss‐of‐function studies in PHM1‐31 cells to identify MAFF dependent genes. We showed that knockdown of MAFF significantly decreased CXCL1 chemokine and CSF3 cytokine transcript and protein levels. Using chromatin immunoprecipitation analyzes, we confirmed CXCL1 and CSF3 genes as direct MAFF targets. We also demonstrated that MAFF function in PHM1‐31 myometrial cells is able to control cytokine and matrix metalloproteinase gene expression in THP‐1 monocytic cells in a paracrine fashion. Our studies provide valuable insights into the MAFF dependent transcriptional network governing myometrial cell function. The data suggest a role of MAFF in parturition and/or infection‐induced preterm labour through modulation of inflammatory processes in the microenvironment. [ABSTRACT FROM AUTHOR]
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- 2019
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12. miR-320a induces pancreatic β cells dysfunction in diabetes by inhibiting MafF
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Zhongwei Yin, Cong-Yi Wang, Beibei Dai, Mengying He, Dao Wen Wang, Jiahui Fan, Xiang Nie, Chen Chen, Yanru Zhao, Hengzhi Du, and Huaping Li
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Genetically modified mouse ,geography ,geography.geographical_feature_category ,diabetes ,Chemistry ,RM1-950 ,pancreatic islet ,MafF ,medicine.disease ,Islet ,β cells ,Transplantation ,Blot ,Downregulation and upregulation ,Apoptosis ,Diabetes mellitus ,Drug Discovery ,microRNA ,Cancer research ,medicine ,Molecular Medicine ,Original Article ,Therapeutics. Pharmacology ,miRNA - Abstract
A variety of studies indicate that microRNAs (miRNAs) are involved in diabetes. However, the direct role of miR-320a in the pathophysiology of pancreatic β cells under diabetes mellitus remains unclear. In the current study, islet transplantation and hyperglycemic clamp assays were performed in miR-320a transgenic mice to explore the effects of miR-320a on pancreatic β cells in vivo. Meanwhile, β cell-specific overexpression or inhibition of miR-320a was delivered by adeno-associated virus (AAV8). In vitro, overexpression or downregulation of miR-320a was introduced in cultured rat islet tumor cells (INS1). RNA immunoprecipitation sequencing (RIP-Seq), luciferase reporter assay, and western blotting were performed to identify the target genes. Results showed that miR-320a was increased in the pancreatic β cells from high-fat-diet (HFD)-treated mice. Overexpression of miR-320a could not only deteriorate the HFD-induced pancreatic islet dysfunction, but also initiate pancreatic islet dysfunction spontaneously in vivo. Meanwhile, miR-320a increased the ROS level, inhibited proliferation, and induced apoptosis of cultured β cells in vitro. Finally, we identified that MafF was the target of miR-320a that responsible for the dysfunction of pancreatic β cells. Our data suggested that miR-320a could damage the pancreatic β cells directly and might be a potential therapeutic target of diabetes., Graphical abstract, Overexpression of miR-320a spontaneously initiated pancreatic islet dysfunction in vivo. Meanwhile, miR-320a suppressed the insulin secretion and induced apoptosis in pancreatic β cells via targeting MafF. These findings suggested that miR-320a was a key regulator in diabetes which could potentially serve as a new therapeutic target.
- Published
- 2021
13. Meta-Analysis of Parkinson's Disease and Alzheimer's Disease Revealed Commonly Impaired Pathways and Dysregulation of NRF2-Dependent Genes.
- Author
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Qian Wang, Wen-Xing Li, Shao-Xing Dai, Yi-Cheng Guo, Fei-Fei Han, Jun-Juan Zheng, Gong-Hua Li, Jing-Fei Huang, Wang, Qian, Li, Wen-Xing, Dai, Shao-Xing, Guo, Yi-Cheng, Han, Fei-Fei, Zheng, Jun-Juan, Li, Gong-Hua, and Huang, Jing-Fei
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PARKINSON'S disease , *ALZHEIMER'S disease , *MITOCHONDRIAL pathology , *OXIDATIVE stress , *META-analysis , *PROTEIN metabolism , *CELLULAR signal transduction , *COMPARATIVE studies , *RESEARCH methodology , *MEDICAL cooperation , *PROTEINS , *RESEARCH , *EVALUATION research , *NUCLEAR proteins ,BRAIN metabolism - Abstract
Many lines of evidence suggest that Parkinson's disease (PD) and Alzheimer's disease (AD) have common characteristics, such as mitochondrial dysfunction and oxidative stress. As the underlying molecular mechanisms are unclear, we perform a meta-analysis with 9 microarray datasets of PD studies and 7 of AD studies to explore it. Functional enrichment analysis revealed that PD and AD both showed dysfunction in the synaptic vesicle cycle, GABAergic synapses, phagosomes, oxidative phosphorylation, and TCA cycle pathways, and AD had more enriched genes. Comparing the differentially expressed genes between AD and PD, we identified 54 common genes shared by more than six tissues. Among them, 31 downregulated genes contained the antioxidant response element (ARE) consensus sequence bound by NRF2. NRF2 is a transcription factor, which protects cells against oxidative stress through coordinated upregulation of ARE-driven genes. To our surprise, although NRF2 was upregulated, its target genes were all downregulated. Further exploration found that MAFF was upregulated in all tissues and significantly negatively correlated with the 31 NRF2-dependent genes in diseased conditions. Previous studies have demonstrated over-expressed small MAFs can form homodimers and act as transcriptional repressors. Therefore, MAFF might play an important role in dysfunction of NRF2 regulatory network in PD and AD. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
14. Reduced SUMOylation of Nrf2 signaling contributes to its inhibition induced by amyloid-β.
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Wang, Peng, Wang, Xiaoxuan, Qiao, Ke, Zhang, Yu, Nie, Qian, Cui, Jing, Sun, Jing, and Li, Liang
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NUCLEAR factor E2 related factor , *SMALL ubiquitin-related modifier proteins , *SMALL interfering RNA , *AMYLOID , *PSYCHOLOGICAL stress , *ALZHEIMER'S disease - Abstract
• Chronic oxidative stress injury by Aβ inhibited Nrf2 signaling. • Reduced SUMOylation of Nrf2 signal contributed to its inhibition induced by Aβ. • Overexpression of Ubc9 might protected cells against Aβ-induced injury. Oxidative stress induced by amyloid-β (Aβ) has been considered as one of the important mechanisms in the development of Alzheimer disease (AD). The inhibition of endogenous antioxidant Nrf2 signaling in the brain of AD patients aggravates the oxidative damage, however, the causes of Nrf2 signaling inhibition are unclear. It is reported that small ubiquitin-like modification (SUMOylation) is involved in the process of oxidative injury. To investigate whether and how SUMOylation was involved in the inhibition of Nrf2 signaling pathway induced by Aβ, Aβ intrahippocampal injection rat model and Aβ treated SH-SY5Y cell model were used in the current study. Small interfering RNA and lentivirus transfection were used to intervene SUMOylation, and the level of SUMOylation was assessed by immunoprecipitation. The present in vivo and in vitro studies revealed that SUMOylation levels of Nrf2 and MafF, as well as the overall SUMOylation level were reduced under long-term Aβ insult. Meanwhile, the binding of Nrf2 to MafF was decreased, accompanied by low interaction with antioxidant response element (ARE) area of gene. Down-regulation of SUMO protein exacerbated the Aβ-induced inhibition of Nrf2 signaling pathway, while, enhancement of SUMOylation of Nrf2 and MafF by overexpression of Ubc9 reversed this process. These results imply that reduction in SUMOylation induced by Aβ contributed to the inhibition of Nrf2 signaling, and SUMOylation might be a potential therapeutic target of AD. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
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15. Worldwide Trends in Agricultural Extension Scinario-An Overview
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Kumar, Rajeev and Singh, S.P.
- Published
- 2008
16. Identification of the Transcription Factor ATF3 as a Direct and Indirect Regulator of the LDLR
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Sabine Bauer, Jana Eigenmann, Yuqi Zhao, Julia Fleig, Johann S. Hawe, Calvin Pan, Dario Bongiovanni, Simon Wengert, Angela Ma, Aldons J. Lusis, Jason C. Kovacic, Johan L. M. Björkegren, Lars Maegdefessel, Heribert Schunkert, and Moritz von Scheidt
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ATF3 ,atherosclerosis ,cardiovascular disease ,coronary artery disease ,gene expression ,inflammation ,LDLR ,lipid metabolism ,liver metabolism ,LPS ,MAFF ,transcription factor ,Article ,Endocrinology, Diabetes and Metabolism ,Atf3 ,Atherosclerosis ,Cardiovascular Disease ,Coronary Artery Disease ,Gene Expression ,Inflammation ,Ldlr ,Lipid Metabolism ,Liver Metabolism ,Lps ,Maff ,Transcription Factor ,Molecular Biology ,Biochemistry ,ddc - Abstract
Coronary artery disease (CAD) is a complex, multifactorial disease caused, in particular, by inflammation and cholesterol metabolism. At the molecular level, the role of tissue-specific signaling pathways leading to CAD is still largely unexplored. This study relied on two main resources: (1) genes with impact on atherosclerosis/CAD, and (2) liver-specific transcriptome analyses from human and mouse studies. The transcription factor activating transcription factor 3 (ATF3) was identified as a key regulator of a liver network relevant to atherosclerosis and linked to inflammation and cholesterol metabolism. ATF3 was predicted to be a direct and indirect (via MAF BZIP Transcription Factor F (MAFF)) regulator of low-density lipoprotein receptor (LDLR). Chromatin immunoprecipitation DNA sequencing (ChIP-seq) data from human liver cells revealed an ATF3 binding motif in the promoter regions of MAFF and LDLR. siRNA knockdown of ATF3 in human Hep3B liver cells significantly upregulated LDLR expression (p < 0.01). Inflammation induced by lipopolysaccharide (LPS) stimulation resulted in significant upregulation of ATF3 (p < 0.01) and subsequent downregulation of LDLR (p < 0.001). Liver-specific expression data from human CAD patients undergoing coronary artery bypass grafting (CABG) surgery (STARNET) and mouse models (HMDP) confirmed the regulatory role of ATF3 in the homeostasis of cholesterol metabolism. This study suggests that ATF3 might be a promising treatment candidate for lowering LDL cholesterol and reducing cardiovascular risk.
- Published
- 2021
17. Policy on the hoof: the handling of the foot and mouth disease outbreak in the UK 2001
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Taylor, Ian
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- 2003
- Full Text
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18. Small Maf proteins (MafF, MafG, MafK): History, structure and function.
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Katsuoka, Fumiki and Yamamoto, Masayuki
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PROTEIN analysis , *LEUCINE zippers , *TRANSCRIPTION factors , *DNA-binding proteins , *HOMODIMERS , *HETERODIMERS - Abstract
The small Maf proteins (sMafs) are basic region leucine zipper (bZIP)-type transcription factors. The basic region of the Maf family is unique among the bZIP factors, and it contributes to the distinct DNA-binding mode of this class of proteins. MafF, MafG and MafK are the three vertebrate sMafs, and no functional differences have been observed among them in terms of their bZIP structures. sMafs form homodimers by themselves, and they form heterodimers with cap ‘n’ collar (CNC) proteins (p45 NF-E2, Nrf1, Nrf2, and Nrf3) and also with Bach proteins (Bach1 and Bach2). Because CNC and Bach proteins cannot bind to DNA as monomers, sMafs are indispensable partners that are required by CNC and Bach proteins to exert their functions. sMafs lack the transcriptional activation domain; hence, their homodimers act as transcriptional repressors. In contrast, sMafs participate in transcriptional activation or repression depending on their heterodimeric partner molecules and context. Mouse genetic analyses have revealed that various biological pathways are under the regulation of CNC-sMaf heterodimers. In this review, we summarize the history and current progress of sMaf studies in relation to their partners. [ABSTRACT FROM AUTHOR]
- Published
- 2016
- Full Text
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19. Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion
- Author
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Tsuchiya, Hiroyuki, Oura, Seiya, Tsuchiya, Hiroyuki, and Oura, Seiya
- Abstract
Retinoids exert antitumor effects through the retinoic acid receptor α (RARα). In the present study, we sought to identify the factors involved in the RARα-mediated transcriptional regulation of the tumor suppressor gene and the tissue factor pathway inhibitor 2 (TFPI2) in hepatocellular carcinoma (HCC). All-trans-retinoic acid (ATRA) was used in the in vitro experiments. Cell invasiveness was measured using trans-well invasion assay. ATRA significantly increased TFPI2 expression through RARα in a human HCC cell line known as HuH7. TFPI2 was vital in the ATRA-mediated suppression of HuH7 cell invasion. The musculo-aponeurotic fibrosarcoma oncogene homolog B (MAFB) significantly enhanced the activation of the TFPI2 promoter via RARα while MAFF inhibited it. The knockdown of RARα or MAFB counteracted the ATRA-mediated suppression of HuH7 cell invasion while the knockdown of MAFF inhibited the invasion. TFPI2 expression in HCC tissues was significantly downregulated possibly due to the decreased expression of RARβ and MAFB. Patients with HCC expressing low MAFB and high MAFF levels showed the shortest disease-free survival time. These results suggest that MAFB and MAFF play critical roles in the antitumor effects of retinoids by regulating the expression of retinoid target genes such as TFPI2 and can be promising for developing therapies to combat HCC invasion.
- Published
- 2021
20. A Comparative Analysis of Reactive Müller Glia Gene Expression After Light Damage and microRNA-Depleted Müller Glia—Focus on microRNAs
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Stefanie G. Wohl, Thomas A. Reh, Monica Andrade, Daniel Larbi, Sara Reardon, and Seoyoung Kang
- Subjects
Microarray ,injury ,Maff ,Cell and Developmental Biology ,let-7 ,Gene expression ,microRNA ,medicine ,lcsh:QH301-705.5 ,Gene ,Original Research ,biology ,miR-125 ,stress response ,Cell Biology ,Cell biology ,gliosis ,medicine.anatomical_structure ,lcsh:Biology (General) ,Gliosis ,retinal degeneration ,biology.protein ,GADD45B ,medicine.symptom ,Gadd45b ,Muller glia ,Dicer ,Developmental Biology - Abstract
Müller glia (MG) are the predominant glia in the neural retina and become reactive after injury or in disease. microRNAs (miRNAs) are translational repressors that regulate a variety of processes during development and are required for MG function. However, no data is available about the MG miRNAs in reactive gliosis. Therefore, in this study, we aimed to profile miRNAs and mRNAs in reactive MG 7 days after light damage. Light damage was performed for 8 h at 10,000 lux; this leads to rapid neuronal loss and strong MG reactivity. miRNAs were profiled using the Nanostring platform, gene expression analysis was conducted via microarray. We compared the light damage dataset with the dataset of Dicer deleted MG in order to find similarities and differences. We found: (1) The vast majority of MG miRNAs declined in reactive MG 7 days after light damage. (2) Only four miRNAs increased after light damage, which included miR-124. (3) The top 10 genes found upregulated in reactive MG after light damage include Gfap, Serpina3n, Ednrb and Cxcl10. (4) The miRNA decrease in reactive MG 7 days after injury resembles the profile of Dicer-depleted MG after one month. (5) The comparison of both mRNA expression datasets (light damage and Dicer-cKO) showed 1,502 genes were expressed under both conditions, with Maff , Egr2, Gadd45b, and Atf3 as top upregulated candidates. (6) The DIANA-TarBase v.8 miRNA:RNA interaction tool showed that three miRNAs were found to be present in all networks, i.e., after light damage, and in the combined data set; these were miR-125b-5p, let-7b and let-7c. Taken together, results show there is an overlap of gene regulatory events that occur in reactive MG after light damage (direct damage of neurons) and miRNA-depleted MG (Dicer-cKO), two very different paradigms. This suggests that MG miRNAs play an important role in a ubiquitous MG stress response and manipulating these miRNAs could be a first step to attenuate gliosis.
- Published
- 2021
- Full Text
- View/download PDF
21. RBFOX1 Regulates the Permeability of the Blood-Tumor Barrier via the LINC00673/MAFF Pathway
- Author
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Jun Ma, Shuyuan Shen, Yixue Xue, Teng Ma, Yang Lin, Yunhui Liu, Xiaobai Liu, Libo Liu, Zhen Li, Heng Cai, Jian Zheng, Ping An, Di Wang, Chunqing Yang, and Lini Zhao
- Subjects
0301 basic medicine ,Cancer Research ,blood-tumor barrier ,LINC00673 ,Occludin ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,Glioma ,glioma ,medicine ,Pharmacology (medical) ,Fibrosarcoma ,RBFOX1 ,Transcription factor ,Messenger RNA ,Tight junction ,Chemistry ,MAFF ,stability ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,medicine.disease ,Cell biology ,030104 developmental biology ,Oncology ,Apoptosis ,030220 oncology & carcinogenesis ,STAU1 ,Molecular Medicine - Abstract
The blood-tumor barrier limits the delivery of therapeutic drugs to brain tumor tissues. Selectively opening the blood-tumor barrier is considered crucial for effective chemotherapy of glioma. RNA-binding proteins have emerged as crucial regulators in various biologic processes. This study found that RNA-binding Fox-1 homolog 1 (RBFOX1) was downregulated in glioma vascular endothelial cells derived from glioma tissues, and in glioma endothelial cells obtained by co-culturing endothelial cells with glioma cells. Overexpression of RBFOX1 impaired the integrity of the blood-tumor barrier and increased its permeability. Additionally, RBFOX1 overexpression decreased the expression of tight junction proteins ZO-1, occludin, and claudin-5. Subsequent analysis of the mechanism indicated that the overexpression of RBFOX1 increased musculoaponeurotic fibrosarcoma protein basic leucine zipper [bZIP] transcription factor F (MAFF) expression by downregulating LINC00673, which stabilized MAFF messenger RNA (mRNA) through Staufen1-mediated mRNA decay. Moreover, MAFF could bind to the promoter region and inhibit the promoter activities of ZO-1, occludin, and claudin-5, which reduced its expression. The combination of RBFOX1 upregulation and LINC00673 downregulation promoted doxorubicin delivery across the blood-tumor barrier, resulting in apoptosis of glioma cells. In conclusion, this study indicated that overexpression of RBFOX1 increased blood-tumor barrier permeability through the LINC00673/MAFF pathway, which might provide a new useful target for future enhancement of blood-tumor barrier permeability., Graphical Abstract, In this article, the authors systematically elucidate the molecular network between RNA-binding proteins and lncRNAs and its functional role in regulating the permeability of the blood-tumor barrier at the molecular level. Additionally, this article provides a new theoretical basis and strategies for the clinical treatment of glioma.
- Published
- 2020
22. MafF Is Regulated via the circ-ITCH/miR-224-5p Axis and Acts as a Tumor Suppressor in Hepatocellular Carcinoma
- Author
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Li Hu, Yu Zhong, Xiaoxia Ye, Xiujuan Zhang, Minhua Wu, Xiaofang Li, Xubin Deng, and Yanqin Liang
- Subjects
0301 basic medicine ,Cancer Research ,Carcinoma, Hepatocellular ,miR-224-5p ,Ubiquitin-Protein Ligases ,circ-ITCH ,Apoptosis ,Biology ,Article ,law.invention ,03 medical and health sciences ,0302 clinical medicine ,Circular RNA ,law ,Cell Movement ,Cell Line, Tumor ,medicine ,Humans ,Luciferase ,MafF Transcription Factor ,Hepatocellular carcinoma (HCC) ,Cell Proliferation ,Cell growth ,Liver Neoplasms ,RNA ,Nuclear Proteins ,General Medicine ,Transcription Factor Maf ,RNA, Circular ,MafF ,medicine.disease ,digestive system diseases ,Gene Expression Regulation, Neoplastic ,Repressor Proteins ,MicroRNAs ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Hepatocellular carcinoma ,Cancer research ,Suppressor ,RNA Interference - Abstract
MafF is a member of the basic leucine zipper (bZIP) transcription factor Maf family and is commonly downregulated in multiple cancers. But the expression and function of MafF in hepatocellular carcinoma (HCC) remain unclear. In this study, we investigated the relationship between endogenous MafF expression and HCC progression and explored the regulatory mechanism of MafF expression in HCC. We found that MafF decreased in HCC tissues and cells. Lentivirus-mediated MafF overexpression inhibited HCC cell proliferation and induced cell apoptosis. Bioinformatics analysis and luciferase assay identified MafF as a direct target of miR-224-5p. RNA pull-down assay demonstrated that circular RNA circ-ITCH could sponge miR-224-5p specifically in HCC. The rescue experiments further elucidated that the expression and antitumor effects of MafF could be regulated via the circ-ITCH/miR-224-5p axis. This study verified that MafF acted as a tumor suppressor in HCC and revealed the upstream regulation mechanism of MafF, which provided a new perspective for potential therapeutic targets of HCC.
- Published
- 2020
23. Simulation for the prediction of surface roughness in magnetic abrasive flow finishing (MAFF)
- Author
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Wani, Amit M., Yadava, Vinod, and Khatri, Atul
- Subjects
- *
SIMULATION methods & models , *SURFACE roughness measurement , *FRICTION , *FINISHES & finishing - Abstract
Abstract: The final machining (or finishing) of precision parts with high level of surface finish and close tolerance is making the application of magnetic abrasive finishing technology increasingly important. Magnetic abrasive flow finishing (MAFF) is a new abrasive finishing process combining the features of abrasive flow finishing (AFF) and magnetic abrasive finishing (MAF). MAFF provides a high level of surface finish and close tolerances for wide range of industrial application. This paper focuses on the modeling and simulation for the prediction of surface roughness on the workpiece surface finished by MAFF process. A finite element model is developed to find the magnetic potential distribution in the magnetic abrasive brush formed during finishing action and then it is used to evaluate machining pressure, surface finish and material removal. The simulation results are compared with the experimental results available in the literature. The simulated workpiece surface roughness shows features similar in nature to the experimental results. [Copyright &y& Elsevier]
- Published
- 2007
- Full Text
- View/download PDF
24. Comparison of maf gene expression patterns during chick embryo development
- Author
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Lecoin, Laure, Sii-Felice, Karine, Pouponnot, Celio, Eychène, Alain, and Felder-Schmittbuhl, Marie-Paule
- Subjects
- *
GENE expression , *LEUCINE zippers , *TRANSCRIPTION factors , *GENES , *EMBRYOS , *EMBRYOLOGY - Abstract
Maf proteins are basic-leucine zipper transcription factors belonging to the AP1 superfamily. Several developmental processes require Maf proteins yet, the redundancy or complementarity of their respective roles in common processes has been only partially investigated. We present for the first time a complete comparative analysis of maf gene expression patterns in vertebrates. Expression of c-maf, mafB/kreisler, mafA/L-maf, mafF, mafG and mafK was analyzed by whole-mount in situ hybridization within chick embryos and their extraembryonic tissues ranging from embryonic day (E) 1 to 7. We carefully examined the extent of overlap between distinct maf genes and report that the developing lens, kidney, pancreas and apoptotic zones of limb buds show sustained co-expression of large maf genes. Small maf genes also exhibit overlap, for example in the dermomyotome. We also describe so far unidentified sites of maf gene expression. mafA is found in the developing neural tube and dorsal root ganglia. c-maf hybridization is detected in the neuroretina, the notochord and the endothelium of extraembryonic blood vessels. [Copyright &y& Elsevier]
- Published
- 2004
- Full Text
- View/download PDF
25. An update on vitamin K: contribution of MAFF-funded research.
- Author
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Buttriss, Judy, Bundy, Rafe, and Hughes, Joyce
- Subjects
- *
VITAMIN K - Abstract
Summary This paper summarises the findings with respect to vitamin K of the British Nutrition Foundation’s recent review of MAFF's Optimal Nutrition Status research programme. As well as providing an overview of current knowledge about the role that vitamin K plays in human health, the paper places in context the contribution to current knowledge of the MAFF-funded research and summarises the priorities for future research recommended in the final report submitted to the Joint Food Safety and Standards Group, now the Foods Standards Agency. [ABSTRACT FROM AUTHOR]
- Published
- 2000
- Full Text
- View/download PDF
26. Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion
- Author
-
Hiroyuki Tsuchiya and Seiya Oura
- Subjects
0301 basic medicine ,Transcription, Genetic ,Cell ,Kaplan-Meier Estimate ,0302 clinical medicine ,Cell Movement ,Tumor Cells, Cultured ,Retinoid ,Promoter Regions, Genetic ,Spectroscopy ,Gene knockdown ,education.field_of_study ,Retinoic Acid Receptor alpha ,Liver Neoplasms ,MAFF ,Nuclear Proteins ,General Medicine ,hepatocellular carcinoma ,MAFB ,invasion ,Prognosis ,Computer Science Applications ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,030220 oncology & carcinogenesis ,Disease Progression ,Carcinoma, Hepatocellular ,Tumor suppressor gene ,retinoids ,medicine.drug_class ,MafB Transcription Factor ,Biology ,Catalysis ,Article ,Inorganic Chemistry ,TFPI2 ,03 medical and health sciences ,Cell Line, Tumor ,medicine ,Humans ,MafF Transcription Factor ,Physical and Theoretical Chemistry ,education ,Molecular Biology ,neoplasms ,Glycoproteins ,Oncogene ,organic chemicals ,Organic Chemistry ,RARα ,biological factors ,Tissue-factor-pathway inhibitor 2 ,digestive system diseases ,Retinoic acid receptor ,030104 developmental biology ,Cancer research ,RAR alpha - Abstract
Retinoids exert antitumor effects through the retinoic acid receptor α (RARα). In the present study, we sought to identify the factors involved in the RARα-mediated transcriptional regulation of the tumor suppressor gene and the tissue factor pathway inhibitor 2 (TFPI2) in hepatocellular carcinoma (HCC). All-trans-retinoic acid (ATRA) was used in the in vitro experiments. Cell invasiveness was measured using trans-well invasion assay. ATRA significantly increased TFPI2 expression through RARα in a human HCC cell line known as HuH7. TFPI2 was vital in the ATRA-mediated suppression of HuH7 cell invasion. The musculo-aponeurotic fibrosarcoma oncogene homolog B (MAFB) significantly enhanced the activation of the TFPI2 promoter via RARα while MAFF inhibited it. The knockdown of RARα or MAFB counteracted the ATRA-mediated suppression of HuH7 cell invasion while the knockdown of MAFF inhibited the invasion. TFPI2 expression in HCC tissues was significantly downregulated possibly due to the decreased expression of RARβ and MAFB. Patients with HCC expressing low MAFB and high MAFF levels showed the shortest disease-free survival time. These results suggest that MAFB and MAFF play critical roles in the antitumor effects of retinoids by regulating the expression of retinoid target genes such as TFPI2 and can be promising for developing therapies to combat HCC invasion.
- Published
- 2018
27. miR-320a induces pancreatic β cells dysfunction in diabetes by inhibiting MafF.
- Author
-
Du H, Yin Z, Zhao Y, Li H, Dai B, Fan J, He M, Nie X, Wang CY, Wang DW, and Chen C
- Abstract
A variety of studies indicate that microRNAs (miRNAs) are involved in diabetes. However, the direct role of miR-320a in the pathophysiology of pancreatic β cells under diabetes mellitus remains unclear. In the current study, islet transplantation and hyperglycemic clamp assays were performed in miR-320a transgenic mice to explore the effects of miR-320a on pancreatic β cells in vivo . Meanwhile, β cell-specific overexpression or inhibition of miR-320a was delivered by adeno-associated virus (AAV8). In vitro , overexpression or downregulation of miR-320a was introduced in cultured rat islet tumor cells (INS1). RNA immunoprecipitation sequencing (RIP-Seq), luciferase reporter assay, and western blotting were performed to identify the target genes. Results showed that miR-320a was increased in the pancreatic β cells from high-fat-diet (HFD)-treated mice. Overexpression of miR-320a could not only deteriorate the HFD-induced pancreatic islet dysfunction, but also initiate pancreatic islet dysfunction spontaneously in vivo . Meanwhile, miR-320a increased the ROS level, inhibited proliferation, and induced apoptosis of cultured β cells in vitro . Finally, we identified that MafF was the target of miR-320a that responsible for the dysfunction of pancreatic β cells. Our data suggested that miR-320a could damage the pancreatic β cells directly and might be a potential therapeutic target of diabetes., Competing Interests: The authors declare no conflicts of interest., (© 2021 The Author(s).)
- Published
- 2021
- Full Text
- View/download PDF
28. A Comparative Analysis of Reactive Müller Glia Gene Expression After Light Damage and microRNA-Depleted Müller Glia-Focus on microRNAs.
- Author
-
Kang S, Larbi D, Andrade M, Reardon S, Reh TA, and Wohl SG
- Abstract
Müller glia (MG) are the predominant glia in the neural retina and become reactive after injury or in disease. microRNAs (miRNAs) are translational repressors that regulate a variety of processes during development and are required for MG function. However, no data is available about the MG miRNAs in reactive gliosis. Therefore, in this study, we aimed to profile miRNAs and mRNAs in reactive MG 7 days after light damage. Light damage was performed for 8 h at 10,000 lux; this leads to rapid neuronal loss and strong MG reactivity. miRNAs were profiled using the Nanostring platform, gene expression analysis was conducted via microarray. We compared the light damage dataset with the dataset of Dicer deleted MG in order to find similarities and differences. We found: (1) The vast majority of MG miRNAs declined in reactive MG 7 days after light damage. (2) Only four miRNAs increased after light damage, which included miR-124. (3) The top 10 genes found upregulated in reactive MG after light damage include Gfap, Serpina3n, Ednrb and Cxcl10 . (4) The miRNA decrease in reactive MG 7 days after injury resembles the profile of Dicer-depleted MG after one month. (5) The comparison of both mRNA expression datasets (light damage and Dicer-cKO) showed 1,502 genes were expressed under both conditions, with Maff , Egr2, Gadd45b , and Atf3 as top upregulated candidates. (6) The DIANA-TarBase v.8 miRNA:RNA interaction tool showed that three miRNAs were found to be present in all networks, i.e., after light damage, and in the combined data set; these were miR-125b-5p, let-7b and let-7c. Taken together, results show there is an overlap of gene regulatory events that occur in reactive MG after light damage (direct damage of neurons) and miRNA-depleted MG (Dicer-cKO), two very different paradigms. This suggests that MG miRNAs play an important role in a ubiquitous MG stress response and manipulating these miRNAs could be a first step to attenuate gliosis., 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 © 2021 Kang, Larbi, Andrade, Reardon, Reh and Wohl.)
- Published
- 2021
- Full Text
- View/download PDF
29. RBFOX1 Regulates the Permeability of the Blood-Tumor Barrier via the LINC00673/MAFF Pathway.
- Author
-
Shen S, Yang C, Liu X, Zheng J, Liu Y, Liu L, Ma J, Ma T, An P, Lin Y, Cai H, Wang D, Li Z, Zhao L, and Xue Y
- Abstract
The blood-tumor barrier limits the delivery of therapeutic drugs to brain tumor tissues. Selectively opening the blood-tumor barrier is considered crucial for effective chemotherapy of glioma. RNA-binding proteins have emerged as crucial regulators in various biologic processes. This study found that RNA-binding Fox-1 homolog 1 (RBFOX1) was downregulated in glioma vascular endothelial cells derived from glioma tissues, and in glioma endothelial cells obtained by co-culturing endothelial cells with glioma cells. Overexpression of RBFOX1 impaired the integrity of the blood-tumor barrier and increased its permeability. Additionally, RBFOX1 overexpression decreased the expression of tight junction proteins ZO-1, occludin, and claudin-5. Subsequent analysis of the mechanism indicated that the overexpression of RBFOX1 increased musculoaponeurotic fibrosarcoma protein basic leucine zipper [bZIP] transcription factor F (MAFF) expression by downregulating LINC00673, which stabilized MAFF messenger RNA (mRNA) through Staufen1-mediated mRNA decay. Moreover, MAFF could bind to the promoter region and inhibit the promoter activities of ZO-1, occludin, and claudin-5, which reduced its expression. The combination of RBFOX1 upregulation and LINC00673 downregulation promoted doxorubicin delivery across the blood-tumor barrier, resulting in apoptosis of glioma cells. In conclusion, this study indicated that overexpression of RBFOX1 increased blood-tumor barrier permeability through the LINC00673/MAFF pathway, which might provide a new useful target for future enhancement of blood-tumor barrier permeability., (© 2020 The Author(s).)
- Published
- 2020
- Full Text
- View/download PDF
30. Involvement of MAFB and MAFF in Retinoid-Mediated Suppression of Hepatocellular Carcinoma Invasion.
- Author
-
Tsuchiya, Hiroyuki and Oura, Seiya
- Subjects
- *
RETINOIDS , *ANTINEOPLASTIC agents , *RETINOIC acid receptors , *LIVER cancer , *TRETINOIN - Abstract
Retinoids exert antitumor effects through the retinoic acid receptor α (RARα). In the present study, we sought to identify the factors involved in the RARα-mediated transcriptional regulation of the tumor suppressor gene and the tissue factor pathway inhibitor 2 (TFPI2) in hepatocellular carcinoma (HCC). All-
trans -retinoic acid (ATRA) was used in the in vitro experiments. Cell invasiveness was measured using trans-well invasion assay. ATRA significantly increased TFPI2 expression through RARα in a human HCC cell line known as HuH7. TFPI2 was vital in the ATRA-mediated suppression of HuH7 cell invasion. The musculo-aponeurotic fibrosarcoma oncogene homolog B (MAFB) significantly enhanced the activation of the TFPI2 promoter via RARα while MAFF inhibited it. The knockdown of RARα or MAFB counteracted the ATRA-mediated suppression of HuH7 cell invasion while the knockdown of MAFF inhibited the invasion. TFPI2 expression in HCC tissues was significantly downregulated possibly due to the decreased expression of RARβ and MAFB. Patients with HCC expressing low MAFB and high MAFF levels showed the shortest disease-free survival time. These results suggest that MAFB and MAFF play critical roles in the antitumor effects of retinoids by regulating the expression of retinoid target genes such as TFPI2 and can be promising for developing therapies to combat HCC invasion. [ABSTRACT FROM AUTHOR]- Published
- 2018
- Full Text
- View/download PDF
31. Radionuclides at MAFF
- Author
-
Nebel, Florian M., Krücken, Reiner (Prof. Dr.), and Zimmer, Oliver (Prof. Dr.)
- Subjects
Physik ,ddc:530 ,MAFF ,Aktivitätsverteilung ,Aktivität ,Ionenoptik ,Activity ,Distribution ,ionoptic - Abstract
The purpose of this work was to re-evaluate and improve important parts of the concept of the Munich Accelerator for Fission Fragments (MAFF) to the point, where the realization and authorization procedure can be started. MAFF is a reactor based next generation radioactive ion beam facility dedicated to the production of neutron-rich rare isotopes for science, medicine, and industry, with ion beam intensities about thousand times higher compared to present installations. In order to produce fission fragments in an ion source close to the reactor core and extract them out of the reactor environment it is necessary to move ion source and extraction optics on rail-bound trollies into the through going vacuum tube. After the extraction, the ions are mass-separated and transported to low and high energy experiments. Within the scope of this work all safety and user relevant aspects of MAFF have been studied with a clear emphasis on radiation safety and ion beam handling. The outcome of this studies influenced the re-design of the MAFF system. The ion optic design for the complete low energy beam transport system, from the ion source to the ion beam coolers, has been studied in detail. Special attention had to be paid to the challenges arising from the installation of the facility at a reactor environment, particularly for the design of the in-pile beam transport system. For the design of the mass separator, an in-depth study of a modified Mattauch-Herzog type layout and its unique features has been performed. For the slit system in the focal plane of the mass separator a new concept has been developed, where the slits are designed as electrostatic detectors, in order to change the mass ratio of the transmitted beams. This would lead to a higher flexibility in the combination of future high and low energy experiments. For the transport of low and high mass beams to the dedicated low and high energy beam coolers, located in the Reactor-Building East, a feasible layout has been developed, giving the possibility to switch the low and high mass beam between the two beam coolers, using electrostatic deflectors. With respect to radiation safety the spacial distribution and temporal evolution of radionuclides within the MAFF system has been studied. Thereby, special attention has been paid to evaluate the chances of uncontrolled radiation release from the system via multiple routes. A concept of operation accounting for these possibilities has been developed, in addition analyses and risk assessments of conceivable emergency scenarios have been performed. Emergencies are detected by a specially adapted early warning concept. For the time after an emergency has occurred suggestions for reasonable follow-up procedures are made. Finally, technical investigations of several key components crucial for a safe operation of MAFF have been undertaken. For the surface of the slit system a material was searched for and found, which reduces the sputter factor, and hence the release of previously implanted radionuclides, from the slit system into the vacuum chamber by a factor of thousand. Furthermore, the mechanical behavior and reliability of the two trollies and related systems were investigated at the example of the lens trolley. Also the mechanical properties of gadolinium have been investigated with the aim to verify the possibility of using gadolinium as a neutron absorber at MAFF. It is the outcome of this work, that it is possible to handle the additional safety challenges of a next generation radioactive ion beam facility, such as MAFF, if new safety features and special operational modes are applied. Der Zweck dieser Arbeit war es, wichtige Teile des Konzeptes des Münchner Spaltfragmentbeschleunigers, MAFF (Munich Accelerator for Fission Fragments), im Hinblick auf die technische Realisierung und das anvisierte Genehmigungsverfahren zu verbessern und zu überarbeiten. Bei MAFF handelt es sich um eine an einem Kernreaktor stationierte Anlage zur Produktion neutronenreicher, radioaktiver Ionen für die Verwendung in Forschung, Medizin und Industrie. Als Einrichtung der nächsten Generation bietet MAFF ca. 1000-fach intensivere Ionenstrahlen als gegenwärtige Anlagen. Um die Spaltprodukte aus dem Reaktorbereich extrahieren zu können, werden bei MAFF Ionenquelle und Extraktionsoptik mit auf Schienen fahrenden Wagen in den durchgehenden Neutronenleiter eingebracht. Die extrahierten Ionen werden massensepariert und zu den Nieder- und Hochenergie-Experimenten transportiert. Im Rahmen dieser Arbeit wurden alle sicherheits- und anwenderrelevanten Aspekte unter dem Gesichtspunkt Strahlenschutz und Strahlhandhabung untersucht. Die Ergebnisse dieser Untersuchungen sind in die Überarbeitung des MAFF Konzeptes eingeflossen, dessen Aufbau in dieser Arbeit in einem überblick dargestellt wird. Das komplette ionenoptische System für die Niederenergie-Strahlführung, von der Ionenquelle bis zu den Strahlkühlern, wurde im Detail untersucht. Dabei mussten die Randbedingungen, die sich aus der Installation an einem Reaktor ergeben, besonders bei dem Design des Strahltransportes innerhalb des Reaktors berücksichtigt werden. Als Massenseparator wurde eine Modifikation des Mattauch-Herzog Massenseparators mit ihren besonderen Eigenschaften untersucht. Für das Schlitzsystem hinter dem Massenseparator wurde ein neues Konzept entwickelt, das die Konstruktion der Schlitze selbst als elektrostatische Deflektoren vorsieht und so die Möglichkeit bietet, das Massenverhältnis der transmittierten Strahlen zu verändern, was eine größere Flexibilität bei der Kombination zukünftiger Experimente ermöglicht. Für den anschließenden Transport der Ionenstrahlen leichter und schwerer Masse zu den dedizierten Nieder- und Hochenergie-Strahlkühlern im Reaktorgebäude Ost wurde eine mögliche Anordnung entwickelt, die auch eine Möglichkeit vorsieht die Ionenstrahlen leichter und schwerer Masse zwischen den Strahlkühlern umzuschalten. Zur besseren Beurteilung der Belastung durch -Strahlung wurde die räumliche Ausbreitung sowie die zeitliche Entwicklung der Radionuklide innerhalb des MAFF Systems untersucht. Dabei wurde besonderer Wert auf die Beurteilung der Wahrscheinlichkeiten für unkontrollierte Freisetzung von Strahlung über verschiedenste Wege gelegt, woraus ein Betriebskonzept, welches diese Möglichkeiten in Betracht zieht, entwickelt wurde. Zusätzlich wurden vorstellbare Notfallszenarien analysiert, die mittels eines speziell angepassten Frühwarnsystems detektiert werden. Darüber hinaus werden Vorschläge für zweckdienliche Folgemaßnahmen gemacht, die in der Zeit nach einem eventuellen Störfall einzuleiten sind. Des weiteren wurden technische Untersuchungen zahlreicher Schlüsselkomponenten durchgeführt, die für den sicheren Betrieb von MAFF unerlässlich sind. Um die Menge an Radionukliden, die vom Schlitzsystem durch Oberflächenabtrag freigesetzt werden, zu reduzieren, wurde eine experimentelle Suche nach einem Material erfolgreich abgeschlossen, das nur ein tausendstel der einfallenden Radionuklide wieder freisetzt. Darüber hinaus wurde das mechanische Verhalten und die Zuverlässigkeit der Wagen und zugehöriger Teilkomponenten am Beispiel des Linsenwagens untersucht. Eine Materialstudie der mechanischen Eigenschaften von Gadolinium wurde mit dem Ziel begonnen, die Möglichkeiten auszuloten, Gadolinium zur Neutronenabschirmung zu benutzen. Als Ergebnis dieser Arbeit kann festgestellt werden, dass die zusätzlichen sicherheitstechnischen Anforderungen, die sich für den Betrieb von MAFF ergeben, gemeistert werden können, wenn neue Methoden der Radioaktivitätshandhabung und Betriebsweise angewendet werden.
- Published
- 2007
32. Foot and Mouth Disease: The 1967 outbreak and its aftermath, vol. 18
- Author
-
Reynolds, LA and Tansey, EM
- Subjects
Foot-and-Mouth disease ,FMD ,Northumberland Committee ,MAFF ,State Veterinarian Service ,Pirbright ,vaccination ,World Vaccine Bank - Abstract
In 1967/8 Britain experienced the worst FMD epidemic of the 20th century. Attributed to pig swill containing infected Argentine lamb, 2228 outbreaks were recorded during a nine-month period, resulting in the slaughter of nearly 450 000 animals, statistics only surpassed by the 2001 FMD epidemic. In this Witness Seminar, Lord Soulsby led the discussion by veterinarians, virologists, academics and farmers of MAFF’s State Veterinary Service procedures and their subsequent investigations for the Northumberland Committee (1969); the contribution of Pirbright and the establishment of the World Vaccine Bank for FMD; the hardship endured by the farmers and political views of the historic slaughter policy alongside the debate over vaccination, both in Westminster and in Europe Participants included: Miss Mary Brancker, Mr Keith Meldrum, Dr Noel Mowat, Lord Plumb, Mr Howard Rees, Dr Robert Sellers, Mr Angus Taylor and Mr Ken Tyrrell.
- Published
- 2003
33. Meta-Analysis of Parkinson's Disease and Alzheimer's Disease Revealed Commonly Impaired Pathways and Dysregulation of NRF2-Dependent Genes.
- Author
-
Wang Q, Li WX, Dai SX, Guo YC, Han FF, Zheng JJ, Li GH, and Huang JF
- Subjects
- Alzheimer Disease metabolism, Brain metabolism, Humans, MafF Transcription Factor genetics, MafF Transcription Factor metabolism, NF-E2-Related Factor 2 metabolism, Nuclear Proteins genetics, Nuclear Proteins metabolism, Parkinson Disease metabolism, Signal Transduction, Alzheimer Disease genetics, NF-E2-Related Factor 2 genetics, Parkinson Disease genetics
- Abstract
Many lines of evidence suggest that Parkinson's disease (PD) and Alzheimer's disease (AD) have common characteristics, such as mitochondrial dysfunction and oxidative stress. As the underlying molecular mechanisms are unclear, we perform a meta-analysis with 9 microarray datasets of PD studies and 7 of AD studies to explore it. Functional enrichment analysis revealed that PD and AD both showed dysfunction in the synaptic vesicle cycle, GABAergic synapses, phagosomes, oxidative phosphorylation, and TCA cycle pathways, and AD had more enriched genes. Comparing the differentially expressed genes between AD and PD, we identified 54 common genes shared by more than six tissues. Among them, 31 downregulated genes contained the antioxidant response element (ARE) consensus sequence bound by NRF2. NRF2 is a transcription factor, which protects cells against oxidative stress through coordinated upregulation of ARE-driven genes. To our surprise, although NRF2 was upregulated, its target genes were all downregulated. Further exploration found that MAFF was upregulated in all tissues and significantly negatively correlated with the 31 NRF2-dependent genes in diseased conditions. Previous studies have demonstrated over-expressed small MAFs can form homodimers and act as transcriptional repressors. Therefore, MAFF might play an important role in dysfunction of NRF2 regulatory network in PD and AD.
- Published
- 2017
- Full Text
- View/download PDF
34. Služba pro archivaci webového obsahu
- Author
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Polčák, Libor, Veselý, Vladimír, Polčák, Libor, and Veselý, Vladimír
- Abstract
Tato bakalářská práce řeší návrh a implementaci webových služeb pro archivaci obsahu se zaměřením na stránky z deep webu. Zabývá se seznámením se s principy aplikačních protokolů HTTP a HTTPS a dále bude nastíněna architektura webových služeb. Čtenář bude seznámen s existujícím řešením frameworku pro archivaci a rekonstrukci webu Lemmiwinks. S využitím tohoto frameworku je navržen a implementován systém webových služeb, které lze využít pro archivaci zvoleného webového obsahu do formátu MAFF., This bachelor's thesis deals with the design of web microservices for web archiving, mainly focused on deep web pages. The HTTP and HTTPS protocols will be explained in detail as well as web services design and architecture. The reader will learn about web archiving frameworks, especially the Lemmiwinks framework. This framework will be used as a basis for web services designed for archiving into the MAFF archive.
35. Služba pro archivaci webového obsahu
- Author
-
Polčák, Libor, Veselý, Vladimír, Polčák, Libor, and Veselý, Vladimír
- Abstract
Tato bakalářská práce řeší návrh a implementaci webových služeb pro archivaci obsahu se zaměřením na stránky z deep webu. Zabývá se seznámením se s principy aplikačních protokolů HTTP a HTTPS a dále bude nastíněna architektura webových služeb. Čtenář bude seznámen s existujícím řešením frameworku pro archivaci a rekonstrukci webu Lemmiwinks. S využitím tohoto frameworku je navržen a implementován systém webových služeb, které lze využít pro archivaci zvoleného webového obsahu do formátu MAFF., This bachelor's thesis deals with the design of web microservices for web archiving, mainly focused on deep web pages. The HTTP and HTTPS protocols will be explained in detail as well as web services design and architecture. The reader will learn about web archiving frameworks, especially the Lemmiwinks framework. This framework will be used as a basis for web services designed for archiving into the MAFF archive.
36. Služba pro archivaci webového obsahu
- Author
-
Serečun, Viliam, Polčák, Libor, Serečun, Viliam, and Polčák, Libor
- Abstract
Tato bakalářská práce řeší návrh a implementaci webových mikroslužeb pro archivaci obsahu se zaměřením na stránky z deep webu. Zabývá se seznámením se s principy aplikačních protokolů HTTP a HTTPS a dále bude nastíněna architektura webových služeb. Čtenář bude seznámen s existujícím řešením frameworku pro archivaci a rekonstrukci webu Lemmiwinks. S využitím tohoto frameworku je navržen a implementován systém webových služeb, které lze využít pro archivaci zvoleného webového obsahu do formátu MAFF., This bachelor's thesis deals with the design of web microservices for web archiving, mainly focused on deep web pages. The HTTP and HTTPS protocols will be explained in detail as well as web services design and architecture. The reader will learn about web archiving frameworks, especially the Lemmiwinks framework. This framework will be used as a basis for web services designed for archiving into the MAFF archive.
37. Služba pro archivaci webového obsahu
- Author
-
Serečun, Viliam, Polčák, Libor, Serečun, Viliam, and Polčák, Libor
- Abstract
Tato bakalářská práce řeší návrh a implementaci webových mikroslužeb pro archivaci obsahu se zaměřením na stránky z deep webu. Zabývá se seznámením se s principy aplikačních protokolů HTTP a HTTPS a dále bude nastíněna architektura webových služeb. Čtenář bude seznámen s existujícím řešením frameworku pro archivaci a rekonstrukci webu Lemmiwinks. S využitím tohoto frameworku je navržen a implementován systém webových služeb, které lze využít pro archivaci zvoleného webového obsahu do formátu MAFF., This bachelor's thesis deals with the design of web microservices for web archiving, mainly focused on deep web pages. The HTTP and HTTPS protocols will be explained in detail as well as web services design and architecture. The reader will learn about web archiving frameworks, especially the Lemmiwinks framework. This framework will be used as a basis for web services designed for archiving into the MAFF archive.
38. Služba pro archivaci webového obsahu
- Author
-
Polčák, Libor, Veselý, Vladimír, Polčák, Libor, and Veselý, Vladimír
- Abstract
Tato bakalářská práce řeší návrh a implementaci webových služeb pro archivaci obsahu se zaměřením na stránky z deep webu. Zabývá se seznámením se s principy aplikačních protokolů HTTP a HTTPS a dále bude nastíněna architektura webových služeb. Čtenář bude seznámen s existujícím řešením frameworku pro archivaci a rekonstrukci webu Lemmiwinks. S využitím tohoto frameworku je navržen a implementován systém webových služeb, které lze využít pro archivaci zvoleného webového obsahu do formátu MAFF., This bachelor's thesis deals with the design of web microservices for web archiving, mainly focused on deep web pages. The HTTP and HTTPS protocols will be explained in detail as well as web services design and architecture. The reader will learn about web archiving frameworks, especially the Lemmiwinks framework. This framework will be used as a basis for web services designed for archiving into the MAFF archive.
39. Služba pro archivaci webového obsahu
- Author
-
Serečun, Viliam, Polčák, Libor, Serečun, Viliam, and Polčák, Libor
- Abstract
Tato bakalářská práce řeší návrh a implementaci webových mikroslužeb pro archivaci obsahu se zaměřením na stránky z deep webu. Zabývá se seznámením se s principy aplikačních protokolů HTTP a HTTPS a dále bude nastíněna architektura webových služeb. Čtenář bude seznámen s existujícím řešením frameworku pro archivaci a rekonstrukci webu Lemmiwinks. S využitím tohoto frameworku je navržen a implementován systém webových služeb, které lze využít pro archivaci zvoleného webového obsahu do formátu MAFF., This bachelor's thesis deals with the design of web microservices for web archiving, mainly focused on deep web pages. The HTTP and HTTPS protocols will be explained in detail as well as web services design and architecture. The reader will learn about web archiving frameworks, especially the Lemmiwinks framework. This framework will be used as a basis for web services designed for archiving into the MAFF archive.
40. Služba pro archivaci webového obsahu
- Author
-
Serečun, Viliam, Polčák, Libor, Matuš, Adam, Serečun, Viliam, Polčák, Libor, and Matuš, Adam
- Abstract
Tato bakalářská práce řeší návrh a implementaci webových mikroslužeb pro archivaci obsahu se zaměřením na stránky z deep webu. Zabývá se seznámením se s principy aplikačních protokolů HTTP a HTTPS a dále bude nastíněna architektura webových služeb. Čtenář bude seznámen s existujícím řešením frameworku pro archivaci a rekonstrukci webu Lemmiwinks. S využitím tohoto frameworku je navržen a implementován systém webových služeb, které lze využít pro archivaci zvoleného webového obsahu do formátu MAFF., This bachelor's thesis deals with the design of web microservices for web archiving, mainly focused on deep web pages. The HTTP and HTTPS protocols will be explained in detail as well as web services design and architecture. The reader will learn about web archiving frameworks, especially the Lemmiwinks framework. This framework will be used as a basis for web services designed for archiving into the MAFF archive.
41. Služba pro archivaci webového obsahu
- Author
-
Polčák, Libor, Veselý, Vladimír, Matuš, Adam, Polčák, Libor, Veselý, Vladimír, and Matuš, Adam
- Abstract
Tato bakalářská práce řeší návrh a implementaci webových služeb pro archivaci obsahu se zaměřením na stránky z deep webu. Zabývá se seznámením se s principy aplikačních protokolů HTTP a HTTPS a dále bude nastíněna architektura webových služeb. Čtenář bude seznámen s existujícím řešením frameworku pro archivaci a rekonstrukci webu Lemmiwinks. S využitím tohoto frameworku je navržen a implementován systém webových služeb, které lze využít pro archivaci zvoleného webového obsahu do formátu MAFF., This bachelor's thesis deals with the design of web microservices for web archiving, mainly focused on deep web pages. The HTTP and HTTPS protocols will be explained in detail as well as web services design and architecture. The reader will learn about web archiving frameworks, especially the Lemmiwinks framework. This framework will be used as a basis for web services designed for archiving into the MAFF archive.
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