16 results on '"Xue, Yu-Fan"'
Search Results
2. Multiresolution Hierarchical Target Detection in High-resolution Maritime Surveillance Radars
- Author
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Zhang, Xiao-Jun, primary, Chang, Si-Yuan, additional, Xue, Yu-Fan, additional, and Shui, Peng-Lang, additional
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- 2024
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- View/download PDF
3. Long-time Adaptive Coherent Detection of Small Targets in Sea Clutter by Fast Inversion Algorithm of Block Tridiagonal Speckle Covariance Matrices
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Zhang, Xiao-Jun, primary, Shui, Peng-Lang, additional, and Xue, Yu-Fan, additional
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- 2023
- Full Text
- View/download PDF
4. Cinobufacini retards progression of pancreatic ductal adenocarcinoma through targeting YEATS2/TAK1/NF-κB axis
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Tian Lan, Hang-fei Chen, Fang Zheng, Hui Huang, Qi Wu, Xue-yu Fan, Si-wei Wang, and Feng Zhang
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Pharmacology ,Complementary and alternative medicine ,Drug Discovery ,Pharmaceutical Science ,Molecular Medicine - Abstract
Cinobufacini, a sterilized hot water extract of dried toad skin, had significant effect against several human cancers. However, there are few studies reporting the effect of cinobufacini on pancreatic cancer.To investigate the effects of cinobufacini on the progress of pancreatic ductal adenocarcinoma and the underlying mechanisms.Cell counting, EdU incorporation and flow Cytometry were performed to evaluate the effect of cinobufacini on cell cycle and growth. MIA-PaCa2 cells were implanted into the nude mice to determine whether cinobufacini represses PDAC progression in vivo. Luciferase reporter assay, western blotting and qPCR were carried out to measure the activity of NF-κB pathway and the alteration of YEATS2 and TAK1. Ectopic gene expression introduced by plasmids was used to verify the molecular mechanism.Our results showed that cinobufacini induced cell cycle arrest and inhibited the growth of PDAC cell in vitro, and repressed MIA-derived PDAC in vivo. Cinobufacini inhibited the phosphorylation of IKK, IκB and NF-κB p65 in PDAC cells. Furthermore, cinobufacini decreased the abundance of intracellular YEATS2 and total TAK1 protein in a time- and dose dependent manner. Ectopic expression of YEATS2 re-elevated the level of TAK1 and phosphorylated IKKα/β, IκBα and p65 after cinobufacini treatment in PANC-1 cells.Cinobufacini retards the growth and progression of PDAC in vitro and in vivo through YEATS2/TAK1/NF-κB axis.
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- 2023
5. Neohesperidin enhances PGC-1α-mediated mitochondrial biogenesis and alleviates hepatic steatosis in high fat diet fed mice
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Xue-Yu Fan, Li-jun Lou, Yuan-Yuan Weng, Hao Sheng, Si-wei Wang, Yong-Feng Bai, and Feng Zhang
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0301 basic medicine ,Blood Glucose ,Male ,medicine.medical_specialty ,Endocrinology, Diabetes and Metabolism ,Mitochondrion ,AMP-Activated Protein Kinases ,Diet, High-Fat ,Article ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Insulin resistance ,Non-alcoholic Fatty Liver Disease ,Internal medicine ,Nonalcoholic fatty liver disease ,Internal Medicine ,medicine ,Animals ,Humans ,Obesity ,Beta oxidation ,lcsh:RC620-627 ,Organelle Biogenesis ,business.industry ,Hesperidin ,AMPK ,Type 2 diabetes ,Hep G2 Cells ,Translational research ,medicine.disease ,Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha ,humanities ,Mitochondria ,Fatty Liver ,Mice, Inbred C57BL ,lcsh:Nutritional diseases. Deficiency diseases ,030104 developmental biology ,Endocrinology ,Mitochondrial biogenesis ,030220 oncology & carcinogenesis ,Organelle biogenesis ,Steatosis ,Insulin Resistance ,business - Abstract
Backgrounds Mitochondria plays a critical role in the development and pathogenesis of nonalcoholic fatty liver disease (NAFLD). Neohesperidin (NHP) could lower blood glucose and prevent obesity in mice. However, the direct effect of NHP on hepatic steatosis has not been reported. Methods Mice were fed with either a chow diet or HFD with or without oral gavage of NHP for 12 weeks. A variety of biochemical and histological indicators were examined. In vitro cell culture model was utilized to demonstrate underlying molecular mechanism of the effect induced by NHP treatment. Results NHP increases mitochondrial biogenesis, improves hepatic steatosis and systematic insulin resistance in high fat diet (HFD) fed mice. NHP elevates hepatic mitochondrial biogenesis and fatty acid oxidation by increasing PGC-1α expression. Mechanistically, the activation of AMP-activated protein kinase (AMPK) is involved in NHP induced PGC-1α expression. Conclusions PGC-1α-mediated mitochondrial biogenesis plays a vital role in the mitigation of hepatic steatosis treated by NHP. Our result suggests that NHP is a good candidate to be dietary supplement for the auxiliary treatment of NAFLD.
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- 2020
6. Inhibition of histone acetyltransferase by naringenin and hesperetin suppresses Txnip expression and protects pancreatic β cells in diabetic mice
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Yuan-yuan Weng, Xue-yu Fan, Jing-qi Fu, Fang Zheng, Yong-feng Bai, Hao Sheng, Si-wei Wang, and Feng Zhang
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Naringenin ,Male ,Citrus ,Pharmaceutical Science ,Pharmacology ,Diabetes Mellitus, Experimental ,Histones ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,Thioredoxins ,Insulin-Secreting Cells ,Drug Discovery ,Animals ,Hypoglycemic Agents ,Epigenetics ,030304 developmental biology ,Histone Acetyltransferases ,0303 health sciences ,biology ,Chemistry ,Hesperidin ,Hesperetin ,Acetylation ,Histone acetyltransferase ,Rats ,Mice, Inbred C57BL ,Histone ,Complementary and alternative medicine ,Diabetes Mellitus, Type 2 ,Cell culture ,030220 oncology & carcinogenesis ,Flavanones ,biology.protein ,Molecular Medicine ,Carrier Proteins ,TXNIP ,Drugs, Chinese Herbal - Abstract
Background The damage of pancreatic β cells is a major pathogenesis of the development and progression of type 2 diabetes and there is still no effective therapy to protect pancreatic β cells clinically. In our previous study, we found that Quzhou Fructus Aurantii (QFA), which is rich in flavanones, had the protective effect of pancreatic β cells in diabetic mice. However, the underlying mechanism is still unclear. Purpose In the current study, we administered naringenin and hesperetin, two major active components of QFA, to protect pancreatic β cells and to investigate the underlying molecular mechanism focusing on the epigenetic modifications. Methods We used diabetic db/db mouse and INS-1 pancreatic β cell line as in vivo and in vitro models to investigate the protective effect of naringenin and hesperetin on pancreatic β cells under high glucose environment and the related mechanism. The phenotypic changes were evaluatedby immunostaining and the measurement of biochemical indexes. The molecular mechanism was explored by biological techniques such as western blotting, qPCR, ChIP-seq and ChIP-qPCR, flow cytometry and lentivirus infection. Results We found that naringenin and hesperetin had an inhibitory effect on histone acetylation. We showed that naringenin and hesperetin protected pancreatic β cells in vivo and in vitro, and this effect was independent of their direct antioxidant capacity. The further study found that the inhibition of thioredoxin-interacting protein (Txnip) expression regulated by histone acetylation was critical for the protective role of naringenin and hesperetin. Mechanistically, the histone acetylation inhibition by naringenin and hesperetin was achieved through regulating AMPK-mediated p300 inactivation. Conclusion These findings highlight flavanones and the phytomedicine rich in flavanones as important dietary supplements in protecting pancreatic β cells in advanced diabetes. In addition, targeting histone acetylation by phytomedicine is a potential strategy to delay the development and progression of diabetes.
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- 2020
7. The flavonoid-rich Quzhou Fructus Aurantii extract modulates gut microbiota and prevents obesity in high-fat diet-fed mice
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Feng Zhang, Xiao-Xiao Wang, Hao Sheng, Li-jun Lou, Yuan-Yuan Weng, Xue-Yu Fan, Si-wei Wang, Yong-Feng Bai, and Xin-Tian Zhu
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Blood Glucose ,0301 basic medicine ,Firmicutes ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,Flavonoid ,Gut flora ,Pharmacology ,Diet, High-Fat ,Article ,Mice ,03 medical and health sciences ,Lactobacillus ,Internal Medicine ,medicine ,Animals ,Obesity ,Alistipes ,lcsh:RC620-627 ,Nutrition ,Flavonoids ,chemistry.chemical_classification ,030109 nutrition & dietetics ,Bacteria ,biology ,Plant Extracts ,business.industry ,Prebiotic ,digestive, oral, and skin physiology ,food and beverages ,Type 2 diabetes ,Akkermansia ,biology.organism_classification ,medicine.disease ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Disease Models, Animal ,lcsh:Nutritional diseases. Deficiency diseases ,Cholesterol ,030104 developmental biology ,chemistry ,Insulin Resistance ,business - Abstract
Background Flavonoids are reported to modulate the composition of gut microbiota, which play an important role in preventing obesity and associated metabolic diseases. In this study, we investigated the effect of Total Flavonoids of Quzhou Fructus Aurantii Extract (TFQ) on gut microbial community in mice fed with a high-fat diet (HFD). Methods C57BL/6J mice were fed with either a chow diet or HFD with or without oral gavage of TFQ (300 mg/kg/day) for 12 weeks. Results Our data indicate TFQ significantly reduced obesity, inflammatio,n and liver steatosis. TFQ elevates the expression of tight junction proteins and reduces metabolic endotoxemia. In addition, TFQ treatment reverses HFD-induced gut dysbiosis, as indicated by the reduction of Firmicutes to Bacteroidetes ratio, the increase of genera Akkermansia and Alistipes, and the decrease of genera Dubosiella, Faecalibaculum, and Lactobacillus. Conclusion These findings support a prebiotic role of TFQ as a dietary supplement for the intervention of gut dysbiosis and obesity-related metabolic disorders.
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- 2019
8. Cinobufacini Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice through Inhibiting M1 Macrophage Polarization
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Yuan-yuan Weng, Feng Zhang, Hui Huang, Yong-feng Bai, Yi Xu, Si-wei Wang, Fang Zheng, and Xue-yu Fan
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0301 basic medicine ,Male ,Population ,Macrophage polarization ,Pharmacology ,Proinflammatory cytokine ,03 medical and health sciences ,Mice ,0302 clinical medicine ,In vivo ,medicine ,Animals ,Colitis ,Medicine, Chinese Traditional ,education ,education.field_of_study ,Mice, Inbred ICR ,biology ,Chemistry ,CD68 ,Macrophages ,Dextran Sulfate ,Cell Polarity ,medicine.disease ,Nitric oxide synthase ,030104 developmental biology ,RAW 264.7 Cells ,biology.protein ,Amphibian Venoms ,Molecular Medicine ,Tumor necrosis factor alpha ,Inflammation Mediators ,030217 neurology & neurosurgery - Abstract
Cinobufacini is a traditional Chinese medicine used clinically that has antitumor and anti-inflammatory effects. It improves colitis outcomes in the clinical setting, but the mechanism underlying its function yet to be uncovered. We investigated the protective effects and mechanisms of cinobufacini on colitis using a dextran sulfate sodium (DSS)-induced colitis mouse model, mainly focusing on the impact of macrophage polarization. Our results showed that cinobufacini dramatically ameliorated DSS-induced colitis in mice. Cinobufacini treatment reduced the infiltration of activated F4/80+ and/or CD68+ macrophages into the colon in DSS-induced colitis mice. More importantly, cinobufacini significantly decreased the quantity of M1 macrophages and the expression of proinflammatory cytokines such as interleukin-6, tumor necrosis factor α, and inducible nitric oxide synthase. Cinobufacini also increased the population of M2 macrophages and the expression of anti-inflammatory factors such as interleukin-10 and arginase-1 in DSS-induced colitis mice. Furthermore, our study demonstrated that cinobufacini inhibited M1 macrophage polarization in lipopolysaccharide-induced RAW 264.7 cells. Mechanistically, our in vivo and in vitro results showed that cinobufacini inhibition of M1 macrophage polarization may be associated with the suppression of nuclear factor κB activation. Our study suggests that cinobufacini could ameliorate DSS-induced colitis in mice by inhibiting M1 macrophage polarization.
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- 2018
9. Hesperetin, a SIRT1 activator, inhibits hepatic inflammation via AMPK/CREB pathway
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Feng Zhang, Xin-Tian Zhu, Xue-Yu Fan, Zheng-Cai Xu, Yuan-Yuan Weng, Si-wei Wang, Yong-Feng Bai, Wen Wang, Fang Zheng, and Hao Sheng
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Male ,0301 basic medicine ,Immunology ,Flavonoid ,Anti-Inflammatory Agents ,Regulator ,Galactosamine ,Inflammation ,AMP-Activated Protein Kinases ,Pharmacology ,CREB ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Sirtuin 1 ,medicine ,Animals ,Humans ,Immunology and Allergy ,Cyclic AMP Response Element-Binding Protein ,chemistry.chemical_classification ,Mice, Inbred BALB C ,biology ,Chemistry ,Activator (genetics) ,Hesperidin ,Macrophages ,Transcription Factor RelA ,Hesperetin ,food and beverages ,AMPK ,Acetylation ,Enzyme Activation ,Disease Models, Animal ,HEK293 Cells ,RAW 264.7 Cells ,030104 developmental biology ,Liver ,030220 oncology & carcinogenesis ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Chemical and Drug Induced Liver Injury ,medicine.symptom ,Protein Processing, Post-Translational ,hormones, hormone substitutes, and hormone antagonists ,Signal Transduction - Abstract
Silent mating type information regulation 2 homolog 1 (SIRT1) is an important inflammatory regulator, which epigenetically reprograms inflammation by altering the acetylation of NF-κB. Hesperetin, as a common flavonoid, has been proven to have a significant effect on acute inflammatory diseases. However, the detailed molecular mechanism by which hesperetin alleviates inflammatory response and accompanied tissue injury is poorly understood. Our results show that SIRT1 is required for the inhibitory effect of hesperetin on inflammation. Hesperetin suppresses the acetylation of RelA/p65 to reduce NF-κB activity by inducing SIRT1 expression. Mechanistically, hesperetin increases SIRT1 expression through AMPK/CREB pathway. Additionally, the protective effect of hesperetin against LPS/D-GalN-induced hepatitis in mice is also dependent on SIRT1. Our study suggests that hesperetin is an SIRT1 activator and could be potential candidates for the treatments of inflammatory conditions.
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- 2020
10. Astilbin ameliorates cisplatin-induced nephrotoxicity through reducing oxidative stress and inflammation
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Xue-yu Fan, Feng Zhang, Xiao-yan Zheng, Li-jun Lou, Yong-feng Bai, Si-wei Wang, Yi Xu, and Yuan-yuan Weng
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0301 basic medicine ,Male ,Flavonols ,Inflammation ,Antineoplastic Agents ,Apoptosis ,Pharmacology ,Toxicology ,medicine.disease_cause ,Kidney ,Nephrotoxicity ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,medicine ,Animals ,Humans ,chemistry.chemical_classification ,Reactive oxygen species ,biology ,General Medicine ,Nitric oxide synthase ,Mice, Inbred C57BL ,Oxidative Stress ,030104 developmental biology ,HEK293 Cells ,chemistry ,biology.protein ,Tumor necrosis factor alpha ,Kidney Diseases ,Astilbin ,medicine.symptom ,Cisplatin ,Oxidative stress ,Food Science - Abstract
Oxidative stress and inflammation are considered to be the main pathogenesis of cisplatin nephrotoxicity. Astilbin, a flavonoid with anti-oxidation and anti-inflammation function, has been used to treat heavy metal induced kidney injury. In this study, we investigated the protective effects of astilbin on cisplatin-induced nephrotoxicity and its underlying mechanisms. Our results showed that astilbin markedly inhibited cisplatin-induced cell apoptosis and recovered cell growth. Astilbin significantly decreased reactive oxygen species (ROS) accumulation and alleviated ROS-induced activation of p53, MAPKs and AKT signaling cascades, which in turn attenuated cisplatin-induced HEK-293 cell apoptosis. Astilbin effectively enhanced NRF2 activation and transcription of its targeting antioxidant genes to reduce ROS accumulation in cisplatin-induced HEK-293 cells. Furthermore, we found that astilbin obviously suppressed tumor necrosis factor alpha (TNF-α) expression and NF-κB activation, and also inhibited the expression of induced nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Finally, we confirmed that the effect of astilbin to improve renal oxidative stress and inflammation in cisplatin induced acute nephrotoxic mice. In conclusion, our study suggests that astilbin could ameliorate the cisplatin-induced nephrotoxicity by reducing oxidative stress and inflammation.
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- 2017
11. Analyses of the Similarity and Difference of Global Gene Expression Profiles in Cortex Regions of Three Neurodegenerative Diseases: Sporadic Creutzfeldt-Jakob Disease (sCJD), Fatal Familial Insomnia (FFI), and Alzheimer’s Disease (AD)
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Ge Meng, Chan Tian, Hans A. Kretzschmar, Di Liu, Wei Li, Xue-Yu Fan, Wei Xiang, Xiao-Ping Dong, Chen Gao, Yin Xu, Hui Wang, and Qinglan Sun
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medicine.medical_specialty ,Neurology ,Genotype ,Microarray ,Neuroscience (miscellaneous) ,Disease ,Bioinformatics ,Insomnia, Fatal Familial ,Creutzfeldt-Jakob Syndrome ,Cellular and Molecular Neuroscience ,Alzheimer Disease ,Humans ,Medicine ,Genetic Predisposition to Disease ,Neuropeptide signaling pathway ,Gene ,Neurons ,Fatal familial insomnia ,business.industry ,Microarray analysis techniques ,Brain ,medicine.disease ,Transcriptome ,business - Abstract
Neurodegenerative disease is a general designation for the disorders that are progressive loss of structure or function and final death of neurons, including Alzheimer's, Parkinson's, Huntington's, prion diseases, etc. In this study, we comparatively analyzed 21 individual microarray data sets of the cortex tissues from 11 sporadic Creutzfeldt-Jakob disease (sCJD), 3 fatal familial insomnia (FFI), 3 Alzheimer's disease (AD), and 4 normal controls. After normalization, a collection of 730 differently expressed sets (DESets) were obtained by comparison of the data of three diseases with their original controls. Principal component analysis (PCA) showed a background-related distribution within the groups of FFI, AD, and normal control, but two apparently different subgroups within the group of sCJD were observed. Review of the clinical materials of 11 sCJD patients identified the difference in brain PrP(Sc) deposits between two subgroups. Hierarchical cluster analysis illustrated the relatively independent clusters of normal controls, FFIs, six sCJD cases (subgroup 1) with more PrP(Sc) deposits, respectively, while an overlapped cluster of five cases of sCJD2 (subgroup 2) with less PrP(Sc) deposits and AD patients. Despite of the presence of special gene expressions, many common features were found among those neurodegenerative diseases. The most commonly changed biological processes (BPs) were signal transduction, synaptic transmission, and neuropeptide signaling pathway. The most commonly changed pathways were MAPK signaling pathway, Parkinson's disease, and oxidative phosphorylation. Our data here provide the similarity and difference in global gene expressions among the patients with sCJD, FFI, and AD, which may help to understand the common mechanism of neurodegenerative diseases.
- Published
- 2014
12. Activation of the AMPK-ULK1 pathway plays an important role in autophagy during prion infection
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Chan Tian, Xue-Yu Fan, Bao-Yun Zhang, Qi-Xiang Shao, Hui Wang, Yangjing Zhao, Qi Shi, Xiao-Ping Dong, Yin Xu, Ge Meng, Chen Gao, Lubin Zhang, and Ke Ren
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Prions ,AMP-Activated Protein Kinases ,Protein Serine-Threonine Kinases ,Article ,Cell Line ,Mice ,AMP-activated protein kinase ,Cricetinae ,Autophagy ,Animals ,Humans ,Protein kinase A ,PI3K/AKT/mTOR pathway ,Multidisciplinary ,biology ,TOR Serine-Threonine Kinases ,Brain ,AMPK ,ULK1 ,Cell biology ,Gene Knockdown Techniques ,biology.protein ,Phosphorylation ,Signal transduction ,Signal Transduction - Abstract
AMPK is a serine/threonine protein kinase that acts as a positive regulator of autophagy, by phosphorylating ULK1 at specific sites. A previous study demonstrated activation of the macroautophagic system in scrapie-infected experimental rodents and in certain human prion diseases, in which the essential negative regulator mTOR is severely inhibited. In this study, AMPK and ULK1 in the brains of hamsters infected with scrapie strain 263 K and in the scrapie-infected cell line SMB-S15 were analysed. The results showed an up-regulated trend of AMPK and AMPK-Thr172, ULK1 and ULK1-Ser555. Increases in brain AMPK and ULK1 occurred at an early stage of agent 263 K infection. The level of phosphorylated ULK1-Ser757 decreased during mid-infection and was only negligibly present at the terminal stage, a pattern that suggested a close relationship of the phosphorylated protein with altered endogenous mTOR. In addition, the level of LKB1 associated with AMPK activation was selectively increased at the early and middle stages of infection. Knockdown of endogenous ULK1 in SMB-S15 cells inhibited LC3 lipidation. These results showed that, in addition to the abolishment of the mTOR regulatory pathway, activation of the AMPK-ULK1 pathway during prion infection contributes to autophagy activation in prion-infected brain tissues.
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- 2015
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13. Polo-like kinase 3 (PLK3) mediates the clearance of the accumulated PrP mutants transiently expressed in cultured cells and pathogenic PrP(Sc) in prion infected cell line via protein interaction
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Xiao-Ping Dong, Chen Gao, Qi-Xiang Shao, Yang-Jing Zhao, Qi Shi, Li-Na Chen, Lubin Zhang, Chan Tian, Cao Chen, Xue-Yu Fan, Jing Sun, Jing Wang, Yan Lv, and Hui Wang
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PrPSc Proteins ,Prions ,Scrapie ,Polo-like kinase ,Biology ,Protein Serine-Threonine Kinases ,Transfection ,Biochemistry ,PLK3 ,Cell Line ,Prion Diseases ,Mice ,Cricetinae ,Animals ,Humans ,Kinase activity ,Mesocricetus ,Kinase ,Tumor Suppressor Proteins ,Cell Biology ,Cell cycle ,Virology ,Cell biology ,Mice, Inbred C57BL ,HEK293 Cells ,Protein kinase domain ,Cell culture ,Mutant Proteins ,Protein Binding - Abstract
Polo-like kinases (PLKs) family has long been known to be critical for cell cycle and recent studies have pointed to new dimensions of PLKs function in the nervous system. Our previous study has verified that the levels of PLK3 in the brain are severely downregulated in prion-related diseases. However, the associations of PLKs with prion protein remain unclear. In the present study, we confirmed that PrP protein constitutively interacts with PLK3 as determined by both in vitro and in vivo assays. Both the kinase domain and polo-box domain of PLK3 were proved to bind PrP proteins expressed in mammalian cell lines. Overexpression of PLK3 did not affect the level of wild-type PrP, but significantly decreased the levels of the mutated PrPs in cultured cells. The kinase domain appeared to be responsible for the clearance of abnormally aggregated PrPs, but this function seemed to be independent of its kinase activity. RNA-mediated knockdown of PLK3 obviously aggravated the accumulation of cytosolic PrPs. Moreover, PLK3 overexpression in a scrapie infected cell line caused notable reduce of PrP(Sc) level in a dose-dependent manner, but had minimal effect on the expression of PrP(C) in its normal partner cell line. Our findings here confirmed the molecular interaction between PLK3 and PrP and outlined the regulatory activity of PLK3 on the degradation of abnormal PrPs, even its pathogenic isoform PrP(Sc). We, therefore, assume that the recovery of PLK3 in the early stage of prion infection may be helpful to prevent the toxic accumulation of PrP(Sc) in the brain tissues.
- Published
- 2014
14. FBXW7-Induced MTOR Degradation Forces Autophagy to Counteract Persistent Prion Infection
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Cao Chen, Chan Tian, Ke Wang, Yu-E Yan, Xue-Yu Fan, Qi Shi, Hui Wang, Jin Zhang, Yin Xu, Xiao-Ping Dong, Jing Sun, and Ke Ren
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0301 basic medicine ,F-Box-WD Repeat-Containing Protein 7 ,PrPSc Proteins ,animal diseases ,Ubiquitin-Protein Ligases ,ATG5 ,Neuroscience (miscellaneous) ,mTORC1 ,Biology ,Protein degradation ,Mechanistic Target of Rapamycin Complex 1 ,Cell Line ,Prion Diseases ,03 medical and health sciences ,Cellular and Molecular Neuroscience ,Mice ,Cricetinae ,Autophagy ,Animals ,PI3K/AKT/mTOR pathway ,Gene knockdown ,Innate immune system ,Mesocricetus ,F-Box Proteins ,TOR Serine-Threonine Kinases ,RPTOR ,Brain ,nervous system diseases ,Cell biology ,030104 developmental biology ,Neurology ,Multiprotein Complexes - Abstract
Autophagy is an important protein degradation pathway and a part of the innate immune system that is activated in the brain tissue during animal and human prion diseases. However, the possible mechanism by which prion infection triggers autophagy and the significance of activated autophagy on prion accumulation remain unknown. Here, we demonstrated that autophagic flux was enhanced in the persistent prion-infected cell line, SMB-S15. Knockdown of ATG5 and the presence of three autophagic inhibitors resulted in a significant increase of PrP(Sc). The mammalian target of rapamycin (MTOR) levels in SMB-S15 cells were also markedly decreased, in direct relation to PrP(Sc) accumulation. F-box and WD repeat domain containing 7 (FBXW7) levels in SMB-S15 cells and in the brains of scrapie-agent 263K-infected hamsters were upregulated at the early stage of infection, leading to active ubiquitination and degradation of MTOR. Knockdown of FBXW7 in SMB-S15 cells remarkably inhibited autophagic flux and increased PrP(Sc) accumulation. Thus, we conclude that prion infection induced the expression of FBXW7, which mediated MTOR ubiquitination and degradation, further altering phosphorylation status through cross talk between MTORC1 and AMPK and increasing autophagic flux. Autophagy may serve as innate immunity to degrade PrP(Sc) and maintain prion homeostasis.
- Published
- 2014
15. Remarkable reductions of PAKs in the brain tissues of scrapie-infected rodent possibly linked closely with neuron loss
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Ge Meng, Xiao-Ping Dong, Qi Shi, Cao Chen, Ming-Ming Xue, Chen Gao, Bao-Yun Zhang, Yin Xu, Kang Xiao, Ke Ren, Hui Wang, Jing Wang, Chan Tian, and Xue-Yu Fan
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Microbiology (medical) ,Pathology ,medicine.medical_specialty ,Time Factors ,Immunology ,Blotting, Western ,Scrapie ,CDC42 ,Biology ,Cell Line ,Mice ,PAK1 ,Cricetulus ,medicine ,Immunology and Allergy ,Animals ,p21-activated kinases ,cdc42 GTP-Binding Protein ,Neurons ,Kinase ,Gene Expression Profiling ,Brain ,General Medicine ,Immunohistochemistry ,Cell biology ,Proto-Oncogene Proteins c-raf ,Cdc42 GTP-Binding Protein ,Gliosis ,p21-Activated Kinases ,Signal transduction ,medicine.symptom - Abstract
Prion diseases are irreversible progressive neurodegenerative diseases characterized in the brain by PrP(Sc) deposits, neuronal degeneration, gliosis and by cognitive, behavioral and physical impairments, leading to severe incapacity and inevitable death. Proteins of the p21-activated kinase (PAK) family are noted for roles in gene transcription, cytoskeletal dynamics, cell cycle progression and survival signaling. In the present study, we aimed to identify the potential roles of PAKs during prion infection, utilizing the brains of scrapie agent-infected hamsters. Western blots and immunohistochemical assays showed that brain levels of PAK3 and PAK1, as well as their upstream activator Rac/cdc42 and downstream substrate Raf1, were remarkably reduced at terminal stage. Double-stained immunofluorescent assay demonstrated that PAK3 was expressed mainly in neurons. Dynamic analyses of the brain samples collected at the different time points during the incubation period illustrated successive decreases of PAK3, PAK1 and Raf1, especially phosphor Raf1, which correlated well with neuron loss. Rac/cdc42 in the brain tissues increased at early stage and reached to the top at mid-late stage, but diminished at final stage. Unlike the alteration of PAKs in vivo, PAK3 and PAK1, as well as Rac/cdc42 and Raf1 in the prion-infected cell line SMB-S15 remained unchanged compared with those of its normal cell line SMB-PS. Our data here indicate that the functions of PAKs and their associated signaling pathways are seriously affected in the brains of prion disease, which appear to associate closely with the extensive neuron loss.
- Published
- 2014
16. [Determination of ten bisphenols and five parabens in urine by solid supported liquid-liquid extraction and liquid chromatography-tandem mass spectrometry].
- Author
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Xue YF, Shang T, Cui JT, Zhao LJ, Li P, Zeng XY, and Yu ZQ
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- Humans, Benzhydryl Compounds urine, Chromatography, Liquid methods, Chromatography, High Pressure Liquid methods, Tandem Mass Spectrometry methods, Liquid-Liquid Extraction methods, Phenols urine, Phenols analysis, Parabens analysis
- Abstract
Bisphenols (BPs) and parabens (PBs) are of great concern for environmental pollution and human health because of their endocrine-disrupting effects and potential health hazards. Urinary biomonitoring of BPs and PBs can provide basic data for human internal exposure evaluation, which is a prerequisite for accurately assessing their health risks. In this study, we developed a new pretreatment procedure based on solid supported liquid-liquid extraction (SLE) for the simultaneous separation of ten BPs and five PBs in human urine, followed by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis. In the instrumental analysis, the HPLC conditions and MS/MS parameters were comprehensively optimized. Accurate qualitative and quantitative determination of ten BPs and five PBs was achieved by introducing a ternary gradient elution system of water, methanol, and acetonitrile for LC separation. During sample pretreatment, the extraction solvent and elution volume were optimized. Specifically, urine samples were held at room temperature and centrifuged at 3000 r/min for 10 min. The supernatant (2 mL) was then transferred to a glass tube, and the pH was adjusted to 5.0 using HCl (0.5 mL; 0.1 mol/L) and NaAc-HAc buffer (1.5 mL). Thereafter, β -glucuronidase-arylsulfatase (20 μL) and surrogate standard solutions (10 ng;
13 C12 -BPS,13 C12 -BPAF,13 C6 -MeP, and13 C6 -BuP) were added, and the mixture was incubated in a shaker bath in the dark at 37 ℃ for 16 h. After incubation, the hydrolyzed sample (4 mL) was loaded onto an SLE cartridge and equilibrated for a minimum of 5 min to ensure the solution was completely absorbed by the packing material. Subsequently, the target chemicals were eluted with a mixed ethyl acetate/ n -hexane solution (3∶7, v/v; 15 mL). Separation of the targets was performed on a ZORBAX SB-C18 reversed-phase column (250 mm×4.6 mm, 5 μm) using an acetonitrile-methanol-water system as the mobile phase. The method was verified by spiking mixed urine samples at three levels (1, 5, and 50 μg/L), with the recoveries ranging from 84.3% to 119.8%. Except for bisphenols (BPS), whose matrix effect was calculated as -21.8%, the matrix effects of other analytes were lower than 20%, indicating low matrix interference. The linear ranges of the analytes varied from 0.1-500 μg/L to 1-500 μg/L, with correlation coefficients higher than 0.995. The method limits of quantification for target chemicals ranged from 0.03 to 0.30 μg/L, and the relative standard deviations of intra- and inter-day experiments were 1.4%-8.4% and 5.7%-14.6%, respectively, suggesting high stability and reproducibility. The method was successfully applied to the determination of ten BPs and five PBs in 10 urine samples from a general population. The concentrations of target chemicals in the human urine samples varied. Methylparaben (MeP), ethylparaben (EtP), propylparaben (PrP), and bisphenol A (BPA) were detected in all samples, with median mass concentrations of 1.10, 0.60, 0.21, and 0.55 μg/L, respectively. The detection rates of the other chemicals were less than 50%, which may be related to the production and use of specific chemicals, their bioavailability, and biological metabolism in humans.- Published
- 2024
- Full Text
- View/download PDF
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