37 results on '"Ting Shao"'
Search Results
2. A taste for new psychoactive substances : wastewater analysis study of 10 countries
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Richard Bade, Jason M. White, Maulik Ghetia, Santosh Adiraju, Sangeet Adhikari, Lubertus Bijlsma, Tim Boogaerts, Daniel A. Burgard, Sara Castiglioni, Alberto Celma, Andrew Chappell, Adrian Covaci, Erin M. Driver, Rolf U. Halden, Felix Hernandez, Heon-Jun Lee, Alexander L. N. van Nuijs, Jeong-Eun Oh, Marco A. Pineda Castro, Noelia Salgueiro-Gonzalez, Bikram Subedi, Xue-Ting Shao, Viviane Yargeau, Ettore Zuccato, Cobus Gerber, Bade, Richard, White, Jason M., Ghetia, Maulik, Adiraju, Santosh, and Gerber, Cobus
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health authorities ,Chemistry ,Ecology ,Health, Toxicology and Mutagenesis ,New psychoactive substances (NPS) ,Environmental Chemistry ,forensic toxicology ,Pollution ,Waste Management and Disposal ,Biology ,drug enforcement agencies ,Water Science and Technology - Abstract
New psychoactive substances (NPS) are compounds designed to mimic both licit and illicit drugs, and these substances are being discovered each year through forensic toxicology, drug enforcement agencies, and health authorities. However, there is limited information surrounding their international popularity. In this work, influent wastewater samples (n = 144) were collected from 25 sites in 10 countries: Australia, Belgium, Canada, China, Fiji, Italy, New Zealand, Republic of Korea, Spain, and the United States over the 2020-2021 New Year period. All samples were extracted in the country of origin then shipped and analyzed centrally at the University of South Australia using validated liquid chromatography-mass spectrometry methods. This study focused on 28 NPS stimulants, with 11 detected. The emerging substances eutylone and 3-methylmethcathinone (3-MMC) were detected most frequently and with the highest mass loads, indicating international popularity. Interestingly, the "older"generation stimulants, para-methoxyamphetamine (PMA), methylone, and mephedrone, were also detected. From the sites monitored in this work, areas in New Zealand had the highest loads of NPS stimulant consumption. Results here show that wastewater analysis can elucidate the dynamic nature of the NPS market, providing near real-time information on changing consumption patterns whose information can be used to minimize public risk. Refereed/Peer-reviewed
- Published
- 2022
3. A New Phenanthrene Derivative from Pleione praecox
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Ya-Ting Shao, Yu-Peng Li, and Rong-Ping Zhang
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biology ,010405 organic chemistry ,Chemistry ,Positive control ,Plant Science ,General Chemistry ,Phenanthrene ,biology.organism_classification ,01 natural sciences ,General Biochemistry, Genetics and Molecular Biology ,0104 chemical sciences ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Phenanthrene derivative ,medicine ,Organic chemistry ,Pleione ,Acarbose ,medicine.drug - Abstract
A new phenanthrene, 2,6-dihydroxy-5,8-dimethoxyphenanthrene (1), was isolated from Pleione praecox. The structure of the new compound was determined on the basis of NMR (1D and 2D) and HR-ESI-MS data. The new compound was also evaluated for its α-glucosidase inhibitory activity. Compared with the positive control acarbose, the new compound exhibited appreciable effect.
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- 2021
4. Diurnal expression of circadian clock genes period 1 and period 3 in Pelteobagrus vachellii
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He Yang, Hu Peng, Wang Jun, Ting Shao, Qin Chuanjie, and Xufeng Liao
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Open reading frame ,PER3 ,Complementary DNA ,Circadian clock ,Circadian rhythm ,Biology ,Oceanography ,Nuclear export signal ,Gene ,Water Science and Technology ,PER1 ,Cell biology - Abstract
Circadian clock genes are crucial for generating and sustaining most rhythmic daily functions in the animal kingdom, which entrain the rhythms of biochemical, physiological, and behavioural processes. To better understand the molecular oscillations of the circadian rhythms in darkbarbel catfish (Pelteobagrus vachellii), we isolated and characterized two circadian clock genes in P. vachellii, period 1 (per1), and period 3 (per3). The circadian clock gene per1 was found to encode a 1 428-amino acid polypeptide, including PER-ARNT-SIM (PAS) dimerisation domains, a PAS-associated C-terminal motif (PAC), a short mutable domain (S/M), and a nuclear export signal (NES). The 4 902-bp per3 cDNA includes an open reading frame encoding a 1 292-amino acid residue polypeptide with a PER-ARNT-SIM (PAS) domain, cytoplasmic localisation domain (CLD), interaction site (TIS), and a nuclear localisation signal (NLS). The per1 and per3 gene was constitutively expressed in all examined tissues. Moreover, per1 expression within a light/dark cycles showed rhythmic expression in the diencephalon, brain, liver and intestine, with the acrophase at 15:15, 12:52, 7:51, and 12:55, respectively. Daily expression of per3 was rhythmic in the diencephalon, brain, liver and intestine, with the acrophase at 8:15, 9:54, 10:39, and 10:25 h, respectively. These findings expand our understanding of circadian mechanism at the molecular level in this species.
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- 2020
5. Effects of feeding time on complement component C7 expression in Pelteobagrus vachellii subject to bacterial challenge
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Fanglan Ge, Chuanjie Qin, Huiguo Duan, Yuan Dengyue, Zhengyong Wen, Jun Wang, and Ting Shao
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0301 basic medicine ,Messenger RNA ,Head Kidney ,Spleen ,04 agricultural and veterinary sciences ,Metabolism ,Biology ,Oceanography ,biology.organism_classification ,Andrology ,03 medical and health sciences ,Aeromonas hydrophila ,Open reading frame ,030104 developmental biology ,Immune system ,medicine.anatomical_structure ,Complementary DNA ,040102 fisheries ,medicine ,0401 agriculture, forestry, and fisheries ,Water Science and Technology - Abstract
Shifting the feeding time for fish from daytime to nighttime could alter their digestive behavior, disturb their metabolism, and may affect immune-related genes. This study aimed to clone complement component C7 and analyze the different expression of C7 mRNA in fish fed during either the day or at night and then challenged with Aeromonas hydrophila infection. The Pv-C7 cDNA of Pelteobagrus vachellii contained 2 647 bp with an open reading frame encoding a protein of 818 amino acids. Multiple sequences analysis indicated that Pv-C7 included eight domains, which was similar to results for other species. Quantitative PCR analysis showed that Pv-C7 was mainly expressed in the liver, spleen, intestine and head kidney tissues of healthy P. vachellii. Quantitative PCR analysis showed that C7 mRNA transcript in the liver, spleen and head kidney also increased significantly when the fish were fed at nighttime (20:00). In addition, the expression of Pv-C7 mRNA significantly increased with A. hydrophila challenge in the liver (48–96 h), spleen and head kidney (12–96 h) tissues of P. vachellii. Pv-C7 mRNA expression of the fish fed at nighttime showed significant higher than that in the fish fed at day time at 12–48 h in head kidney and 12–24 h in spleen. This study indicates that altering the feeding time from daytime to nighttime could increase Pv-C7 mRNA expression, and feeding time may affect the immune response involving C7.
- Published
- 2018
6. SYNCRIP facilitates porcine parvovirus viral DNA replication through the alternative splicing of NS1 mRNA to promote NS2 mRNA formation
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Ting Shao, Xiujuan Zhang, Qian Du, Dewen Tong, Lingling Chang, Nannan Chen, Songbiao Chen, Xuezhi Zhang, Bichen Miao, Yong Huang, and Caiyi Chen
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0301 basic medicine ,DNA Replication ,Porcine parvovirus ,Swine ,Veterinary medicine ,viruses ,Sus scrofa ,PPV ,Viral Nonstructural Proteins ,Heterogeneous-Nuclear Ribonucleoproteins ,NS2 mRNA ,Parvoviridae Infections ,NS1 mRNA ,03 medical and health sciences ,In vivo ,SYNCRIP ,SF600-1100 ,Animals ,RNA, Messenger ,Swine Diseases ,Messenger RNA ,030102 biochemistry & molecular biology ,General Veterinary ,biology ,Alternative splicing ,virus diseases ,biochemical phenomena, metabolism, and nutrition ,Parvovirus, Porcine ,biology.organism_classification ,Molecular biology ,In vitro ,Alternative Splicing ,030104 developmental biology ,Capsid ,Cytoplasm ,RNA splicing ,DNA, Viral ,Research Article - Abstract
Porcine Parvovirus (PPV), a pathogen causing porcine reproductive disorders, encodes two capsid proteins (VP1 and VP2) and three nonstructural proteins (NS1, NS2 and SAT) in infected cells. The PPV NS2 mRNA is from NS1 mRNA after alternative splicing, yet the corresponding mechanism is unclear. In this study, we identified a PPV NS1 mRNA binding protein SYNCRIP, which belongs to the hnRNP family and has been identified to be involved in host pre-mRNA splicing by RNA-pulldown and mass spectrometry approaches. SYNCRIP was found to be significantly up-regulated by PPV infection in vivo and in vitro. We confirmed that it directly interacts with PPV NS1 mRNA and is co-localized at the cytoplasm in PPV-infected cells. Overexpression of SYNCRIP significantly reduced the NS1 mRNA and protein levels, whereas deletion of SYNCRIP significantly reduced NS2 mRNA and protein levels and the ratio of NS2 to NS1, and further impaired replication of the PPV. Furthermore, we found that SYNCRIP was able to bind the 3′-terminal site of NS1 mRNA to promote the cleavage of NS1 mRNA into NS2 mRNA. Taken together, the results presented here demonstrate that SYNCRIP is a critical molecule in the alternative splicing process of PPV mRNA, while revealing a novel function for this protein and providing a potential target of antiviral intervention for the control of porcine parvovirus disease. Supplementary Information The online version contains supplementary material available at 10.1186/s13567-021-00938-6.
- Published
- 2020
7. Bioinformatic Identification of Potential Hub Genes in Muscle-Invasive Bladder Urothelial Carcinoma
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Minghui Li, Fengjun Liu, Zhiming Gao, Changgang Guo, Dadong Wei, Chunsheng Li, Ting Shao, and Guochang Bao
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COL1A1 ,Microarray ,COL1A2 ,COL3A1 ,Urinary Bladder ,Biomedical Engineering ,COL5A2 ,lcsh:Medicine ,Disease ,Biology ,medicine.disease_cause ,Collagen Type I ,Metastasis ,Gene expression ,medicine ,Humans ,KEGG ,Gene ,Transplantation ,muscle-invasive bladder carcinoma ,lcsh:R ,Computational Biology ,Cell Biology ,medicine.disease ,Gene expression profiling ,Collagen Type I, alpha 1 Chain ,Collagen Type III ,Cancer research ,gene expression profile ,Original Article ,Carcinogenesis ,Transcriptome ,Protein Binding - Abstract
Despite aggressive treatment approaches, muscle-invasive bladder urothelial carcinoma (MIBC) patients still have a 50% chance of developing general incurable metastases. Therefore, there is an urgent need for candidate markers to enhance diagnosis and generate effective treatments for this disease. We evaluated four mRNA microarray datasets to find differences between non-MIBC (NMIBC) and MIBC tissues. Through a gene expression profile analysis via the Gene Expression Omnibus database, we identified 56 differentially expressed genes (DEGs). Enrichment analysis of gene ontology, Kyoto Encyclopedia of Genes and Genomes, and Reactome pathways revealed the interactions between these DEGs. Next, we established a protein-protein interaction network to determine the interrelationship between the DEGs and selected 10 hub genes accordingly. Bladder urothelial carcinoma (BLCA) patients with COL1A2, COL5A1, and COL5A2 alterations showed poor disease-free survival rates, while BLCA patients with COL1A1 and LUM alterations showed poor overall survival rates. Oncomine analysis of MIBC versus NMIBC tissues showed that COL1A1, COL5A2, COL1A2, and COL3A1 were consistently among the top 20 overexpressed genes in different studies. Using the TCGAportal, we noted that the high expression of each of the four genes led to shorter BLCA patient overall survival. It was evident that BLCA patients with an elevated high combined gene expression had significantly shorter overall survival and relapse-free survival than those with low combined gene expression using PROGgeneV2. Using Gene Expression Profiling Interactive Analysis, we noted that COL1A1, COL1A2, COL3A1, and COL5A2 were positively correlated with each other in BLCA. These genes are considered as clinically relevant genes, suggesting that they may play an important role in the carcinogenesis, development, invasion, and metastasis of MIBC. However, considering we adopted a bioinformatic approach, more research is crucial to confirm our results. Nonetheless, our findings may have important prospective clinical implementations.
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- 2020
8. Construction of paclitaxel-based antibody–drug conjugates with a PEGylated linker to achieve superior therapeutic index
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Tianzhi Chen, Ting Shao, Xiaoyue Liu, Li Hui, Dianwen Ju, Yuning Chen, Qi Wang, Guo Maojun, Zhu Tong, Yi-Li Chen, and Chunhe Wang
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Drug ,Cancer Research ,Immunoconjugates ,Letter ,Paclitaxel ,media_common.quotation_subject ,Mice, Nude ,lcsh:Medicine ,Drug development ,Pharmacology ,Polyethylene Glycols ,Mice ,chemistry.chemical_compound ,Antineoplastic Agents, Immunological ,Therapeutic index ,Cell Line, Tumor ,Genetics ,Animals ,Humans ,lcsh:QH301-705.5 ,media_common ,biology ,lcsh:R ,Neoplasms, Experimental ,Xenograft Model Antitumor Assays ,lcsh:Biology (General) ,chemistry ,biology.protein ,Experimental pathology ,Antibody ,Linker ,Conjugate - Published
- 2020
9. Autophagy Promotes Porcine Parvovirus Replication and Induces Non-Apoptotic Cell Death in Porcine Placental Trophoblasts
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Jie Zhang, Bichen Miao, Ting Shao, Songbiao Chen, Dewen Tong, Yong Huang, Xiujuan Zhang, Zhenyu Wang, Yingli Xiong, and Qian Du
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0301 basic medicine ,Programmed cell death ,Porcine parvovirus ,autophagy ,replication ,genetic structures ,Swine ,Placenta ,ATG5 ,Apoptosis ,Biology ,Virus Replication ,Article ,Cell Line ,Parvoviridae Infections ,03 medical and health sciences ,non-apoptotic cell death ,0302 clinical medicine ,Pregnancy ,Virology ,Animals ,Swine Diseases ,Gene knockdown ,Parvovirus ,Autophagy ,parvovirus ,Autophagosomes ,Parvovirus, Porcine ,biology.organism_classification ,Cell biology ,Trophoblasts ,030104 developmental biology ,Infectious Diseases ,Viral replication ,030220 oncology & carcinogenesis ,Female ,Lysosomes ,Biomarkers - Abstract
Autophagy plays important roles in the infection and pathogenesis of many viruses, yet the regulatory roles of autophagy in the process of porcine parvovirus (PPV) infection remain unclear. Herein, we show that PPV infection induces autophagy in porcine placental trophoblasts (PTCs). Induction of autophagy by rapamycin (RAPA) inhibited the occurrence of apoptotic cell death, yet promoted viral replication in PPV-infected cells, inhibition of autophagy by 3-MA or ATG5 knockdown increased cellular apoptosis and reduced PPV replication. Interestingly, we found that in the presence of caspase-inhibitor zVAD-fmk, PPV induces non-apoptotic cell death that was characterized by lysosomal damage and associated with autophagy. Induction of complete autophagy flux by RAPA markedly promoted PPV replication compared with incomplete autophagy induced by RAPA plus bafilomycin (RAPA/BAF) in the early phase of PPV infection (24 h.p.i.). Meanwhile, induction of complete autophagy with RAPA increased lysosomal damage and non-apoptotic cell death in the later phase of PPV infection. Therefore, our data suggest that autophagy can enhance PPV replication and promote the occurrence of lysosomal-damage-associated non-apoptotic cell death in PPV-infected porcine placental trophoblasts.
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- 2019
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10. Molecular characterization and expression of toll-like receptor 5 genes from Pelteobagrus vachellii
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Yuan Dengyue, Zhengyong Wen, Quan Gong, Huatao Li, Chuanjie Qin, and Ting Shao
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Fish Proteins ,0301 basic medicine ,Toll-Like Receptor Pathway ,Aquatic Science ,Biology ,Fish Diseases ,03 medical and health sciences ,Complementary DNA ,Animals ,Environmental Chemistry ,Amino Acid Sequence ,Gene ,Catfishes ,Phylogeny ,Toll-like receptor ,Innate immune system ,Gene Expression Profiling ,04 agricultural and veterinary sciences ,General Medicine ,Molecular biology ,Immunity, Innate ,Aeromonas hydrophila ,Toll-Like Receptor 5 ,Open reading frame ,030104 developmental biology ,Gene Expression Regulation ,TLR5 ,040102 fisheries ,biology.protein ,0401 agriculture, forestry, and fisheries ,Gram-Negative Bacterial Infections ,Sequence Alignment ,Flagellin - Abstract
Toll-like receptor 5 (TLR5) is an important pathogen recognition receptor (PRR) that recognizes the flagellin protein of pathogenic bacteria and plays a fundamental role in activating the innate immune response. In this study, full-length pvTLR5m (membrane) and pvTLR5s (soluble) genes were cloned from darkbarbel catfish Pelteobagrus vachellii, and their expression and that of downstream genes were analyzed following exposure to the Aeromonas hydrophila pathogen. The 3009 bp pvTLR5m cDNA includes a 2652 bp open reading frame (ORF) encoding 884 amino acids. The 2422 bp pvTLR5s cDNA includes a 1944 bp ORF encoding a predicted protein of 648 amino acids. The genes are most closely related to TLR5m (75%) and TLR5s (69%) from Ictalurus punctatus, respectively, and both have a typical TLR structure. Both genes were constitutively expressed in all examined tissues, and most abundantly in the head kidney and spleen. Following pathogen challenge, pvTLR5m and pvTLR5s expression was increased significantly (P0.05) and peaked at 24 and 12 h post-exposure in the liver, 24 and 12 h in the head kidney, and 48 and 24 h in the spleen, respectively. The downstream genes interleukin-1β (IL-1β), IL-12 and tumor necrosis factor-alpha (TNF-α) were significantly up-regulated following pathogen exposure in spleen, and the NF-kB inhibitor (IκB) was down-regulated. These findings indicated that pvTLR5 may play an important role in the immune responses to A. hydrophila. These results provide new insight to elucidate the immune signalling pathways of fish TLR.
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- 2018
11. Effect of ammonia-N on histology and expression of immunoglobulin M and component C3 in the spleen and head kidney of Pelteobagrus vachellii
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Yong-ming Wang, Chuan-jie Qin, quan Gong, Ting Shao, Qin Yang, and Ping Bu
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0301 basic medicine ,medicine.medical_specialty ,Lysozyme ,Spleen ,Aquatic Science ,lcsh:Aquaculture. Fisheries. Angling ,03 medical and health sciences ,chemistry.chemical_compound ,Immune system ,Ammonia ,Internal medicine ,medicine ,Pelteobagrus vachellii ,Component C3 ,lcsh:SH1-691 ,Head Kidney ,biology ,Aquatic animal ,Histology ,04 agricultural and veterinary sciences ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,Immunoglobulin M ,chemistry ,040102 fisheries ,biology.protein ,0401 agriculture, forestry, and fisheries ,Animal Science and Zoology ,Catfish - Abstract
Ammonia-N is toxic to many aquatic animals and serves as a key stress factor in aquatic environments. The effects of ammonia-N stress on the immune response of darkbarbel catfish Pelteobagrus vachellii were investigated in this study. Changes in overall histology, and in the expression of complement C3 and immunoglobulin M (IgM) in spleen and head kidney, and lysozyme and C3 in serum, were measured in 1 and 5 mg/L ammonia-N. Hyperemia, melano-macrophage assembly and loose splenosis were evident in spleen tissue. Both lysozyme and component C3 were significantly reduced in serum (P 0.05). IgM expression also increased significantly at 6–12 h in spleen and 6–24 h in head kidney after the 1 mg/L treatment (P
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- 2017
12. Chemical constituents of Bulbophyllum wendlandianum (Kraenzl.) Dammer and their chemotaxonomic significance
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Jia-Duo Yu, Xiao-Rong Zhou, Yu-Peng Li, Xia Zhao, Ya-Ting Shao, and Ya-Ping Chen
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Lignan ,Stigmasterol ,Ergosterol peroxide ,010405 organic chemistry ,Biology ,biology.organism_classification ,01 natural sciences ,Biochemistry ,0104 chemical sciences ,Bulbophyllum ,010404 medicinal & biomolecular chemistry ,chemistry.chemical_compound ,Bulbophyllum wendlandianum ,chemistry ,Pinoresinol ,Bibenzyl ,Organic chemistry ,Phenols ,Ecology, Evolution, Behavior and Systematics - Abstract
Phytochemical investigation of Bulbophyllum wendlandianum (Kraenzl.) Dammer led to the isolation of twenty-three compounds 1–23 (flavanthrinin 1, coelonin 2, lusianthridin 3, densiflorol B 4, plicatol B 5, batatasin-lll 6, gigantol 7, 5-hydroxy-3,3′-dimethoxy-2-(p-hydroxybenzyl) bibenzyl 8, 2,2-dimethyl-5-hydroxy-6-carboxy-7-(2-phenylethyl) 9, tristin 10, p-hydroxybenzyl ethyl ether 11, p-hydroxybenzaldehyde 12, hydroquinone 13, coniferaldehyde 14, p-hydroxybenzyl alcohol 15, 3,4-dihydroxy benzaldehyde 16, stigmasterol 17, β-sitosterol 18, ergosterol peroxide 19, (+)pinoresinol 20, n-butyl sulfoxide 21, tridec-4E-en-l-yl acetate 22, ethyl linolate 23) including five phenanthrenes 1–5, five bibenzyls 6–10, six phenols 11–16, three sterols 17–19, one lignan 20, one n-butyl sulfoxide 21 and two fatty acids 22–23. The structures of these compounds were elucidated by spectroscopic analyses. This is the first report of isolation of compounds 1–23 from Bulbophyllum wendlandianum and compounds 8–9, 11, 13, 15–16 and 19–23 within genus Bulbophyllum. Compound 21 is a new natural product, isolated from a natural source for the first time. Furthermore, the chemotaxonomic significance of the isolates was also discussed.
- Published
- 2021
13. Effect of ammonia-N and pathogen challenge on complement component 8α and 8β expression in the darkbarbel catfish Pelteobagrus vachellii
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Yuan Dengyue, Zhengyong Wen, Daxian Zhao, Huatao Li, Ting Shao, Huiguo Duan, Chuanjie Qin, and Qi Zemin
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Fish Proteins ,0301 basic medicine ,DNA, Complementary ,Aquatic Science ,Fish Diseases ,Random Allocation ,03 medical and health sciences ,Immune system ,Ammonia ,Gene expression ,Animals ,Environmental Chemistry ,Amino Acid Sequence ,RNA, Messenger ,Cloning, Molecular ,Catfishes ,Phylogeny ,chemistry.chemical_classification ,MACPF ,biology ,04 agricultural and veterinary sciences ,General Medicine ,Complement C8 ,Molecular biology ,Aeromonas hydrophila ,Amino acid ,Open reading frame ,030104 developmental biology ,Perforin ,chemistry ,Immunology ,040102 fisheries ,biology.protein ,0401 agriculture, forestry, and fisheries ,Gram-Negative Bacterial Infections ,Complement membrane attack complex ,Sequence Alignment ,Catfish - Abstract
The complement components C8α and C8β mediate the formation of the membrane attack complex (MAC) to resist pathogenic bacteria and play important roles in innate immunity. Full-length complement C8α (Pv-C8α) and C8β (Pv-C8β) cDNA were identified in the darkbarbel catfish Pelteobagrus vachellii, and their mRNA expression levels were analyzed after ammonia-N and pathogen treatment. The Pv-C8α gene contained 1983 bp, including a 1794-bp open reading frame (ORF) encoding 598 amino acids. The Pv-C8β gene contained 1952 bp, including a 1761-bp ORF encoding 587 amino acids. Pv-C8α and Pv-C8β had the highest amino acid identity with rainbow trout Oncorhynchus mykiss C8α (62%) and Japanese flounder Paralichthys olivaceus C8β (83%), respectively. Sequence analysis indicated that both Pv-C8α and Pv-C8β contained a thrombospondin type-1 (TSP1) domain, a low-density lipoprotein receptor class A (LDLR-A) domain, a membrane attack complex/perforin (MACPF) domain and an epidermal growth factor-like (EGF-like) domain. In addition, Pv-C8α and Pv-C8β were mainly distributed in the liver, head kidney, spleen, and eggs. Under ammonia-N stress, the Pv-C8α and Pv-C8β mRNA levels significantly decreased (P
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- 2017
14. Vimentin is important in the neural differentiation of PC12 cells promoted by sialylation
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Li Hui Wu, Min Peng, Qi Chen, Nanbert Zhong, Jing Pan, Yi Wei Dong, Hui Sun, Qian Qian Cai, Xing Zhong Wu, Jun Xia Guo, Xiao Mei Yan, Xiao Ting Shao, and Zhong Yi Chen
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0301 basic medicine ,Glycosylation ,Neurite ,Neuronal Outgrowth ,Vimentin ,PC12 Cells ,Biochemistry ,03 medical and health sciences ,chemistry.chemical_compound ,Lectins ,Neurites ,Animals ,Molecular Biology ,biology ,Lectin ,Cell Biology ,Transfection ,Molecular biology ,Rats ,Sialic acid ,Blot ,030104 developmental biology ,chemistry ,Mutation ,Sialic Acids ,biology.protein ,Ectopic expression ,Protein Processing, Post-Translational - Abstract
Sialic acid modification is a kind of post-translational modification. To investigate the regulation effect of sialic acid on neural differentiation, we used CycloManN propanyl perac (CycloManN pro), a metabolic precursor of sialic acid, to treat PC12 cells. We noted that CycloManN pro indeed robustly promoted global sialylation detected by MAL II lectin blot in PC12 cells. Simultaneously, we interestingly found that the neurite outgrowth of PC12 cells was significantly promoted by the CycloManN pro treatment. The profile analysis of sialylated proteins showed that a protein band at 55KD was greatly enhanced especially in PC12L cells after CycloManN pro treatment. After enrichment with lectin MAL II, the proteins in this band were analyzed by mass spectrometry. The results showed that 23 proteins were in the band, but the score of vimentin was the highest among them. To investigate further the role of vimentin in the process of neurite differentiation, vimentin construct was transfected into PC12 cells. We interestingly observed that ectopic expression of vimentin significantly enhanced the neurite outgrowth induced by CycloManN pro. However, after three potential glycosylation sites (Ser-7, Thr-33, Ser-34:) of vimentin were mutated to alanine, overexpression of the mutated vimentin completely lost the enhancement activity for the neural differentiation even in the presence of CycloManN pro. Taken together, our study demonstrated that vimentin was important in the induction of neural differentiation by CycloManN pro.
- Published
- 2016
15. mTORC2 promotes type I insulin-like growth factor receptor and insulin receptor activation through the tyrosine kinase activity of mTOR
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Ting Luo, Qian Wang, Minjing Li, Yancun Yin, Shu Liu, Jiao Wang, Yangfu Jiang, Hui Hua, Qingbin Kong, Yuanming Luo, and Ting Shao
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0301 basic medicine ,endocrine system ,Mechanistic Target of Rapamycin Complex 2 ,mTORC1 ,Biology ,mTORC2 ,Receptor, IGF Type 1 ,03 medical and health sciences ,chemistry.chemical_compound ,Cell Line, Tumor ,Humans ,Phosphorylation ,Kinase activity ,Molecular Biology ,PI3K/AKT/mTOR pathway ,Cell Proliferation ,Sirolimus ,TOR Serine-Threonine Kinases ,RPTOR ,nutritional and metabolic diseases ,Tyrosine phosphorylation ,Hep G2 Cells ,Cell Biology ,Protein-Tyrosine Kinases ,Receptor, Insulin ,Insulin receptor ,HEK293 Cells ,Rapamycin-Insensitive Companion of mTOR Protein ,030104 developmental biology ,chemistry ,Multiprotein Complexes ,Cancer research ,biology.protein ,Tyrosine ,Original Article ,Carrier Proteins ,Tyrosine kinase ,hormones, hormone substitutes, and hormone antagonists - Abstract
Mammalian target of rapamycin (mTOR) is a core component of raptor-mTOR (mTORC1) and rictor-mTOR (mTORC2) complexes that control diverse cellular processes. Both mTORC1 and mTORC2 regulate several elements downstream of type I insulin-like growth factor receptor (IGF-IR) and insulin receptor (InsR). However, it is unknown whether and how mTOR regulates IGF-IR and InsR themselves. Here we show that mTOR possesses unexpected tyrosine kinase activity and activates IGF-IR/InsR. Rapamycin induces the tyrosine phosphorylation and activation of IGF-IR/InsR, which is largely dependent on rictor and mTOR. Moreover, mTORC2 promotes ligand-induced activation of IGF-IR/InsR. IGF- and insulin-induced IGF-IR/InsR phosphorylation is significantly compromised in rictor-null cells. Insulin receptor substrate (IRS) directly interacts with SIN1 thereby recruiting mTORC2 to IGF-IR/InsR and promoting rapamycin- or ligand-induced phosphorylation of IGF-IR/InsR. mTOR exhibits tyrosine kinase activity towards the general tyrosine kinase substrate poly(Glu-Tyr) and IGF-IR/InsR. Both recombinant mTOR and immunoprecipitated mTORC2 phosphorylate IGF-IR and InsR on Tyr1131/1136 and Tyr1146/1151, respectively. These effects are independent of the intrinsic kinase activity of IGF-IR/InsR, as determined by assays on kinase-dead IGF-IR/InsR mutants. While both rictor and mTOR immunoprecitates from rictor(+/+) MCF-10A cells exhibit tyrosine kinase activity towards IGF-IR and InsR, mTOR immunoprecipitates from rictor(-/-) MCF-10A cells do not induce IGF-IR and InsR phosphorylation. Phosphorylation-deficient mutation of residue Tyr1131 in IGF-IR or Tyr1146 in InsR abrogates the activation of IGF-IR/InsR by mTOR. Finally, overexpression of rictor promotes IGF-induced cell proliferation. Our work identifies mTOR as a dual-specificity kinase and clarifies how mTORC2 promotes IGF-IR/InsR activation.
- Published
- 2015
16. The Clock gene clone and its circadian rhythms in Pelteobagrus vachelli
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Chuanjie Qin and Ting Shao
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Genetics ,CLOCK ,Period (gene) ,Clone (cell biology) ,Zeitgeber ,Circadian rhythm ,Biology ,Oceanography ,Pelteobagrus ,biology.organism_classification ,Molecular clock ,Water Science and Technology ,Catfish - Abstract
The Clock gene, a key molecule in circadian systems, is widely distributed in the animal kingdom. We isolated a 936-bp partial cDNA sequence of the Clock gene (Pva-clock) from the darkbarbel catfish Pelteobagrus vachelli that exhibited high identity with Clock genes of other species of fish and animals (65%–88%). The putative domains included a basic helix-loop-helix (bHLH) domain and two period-ARNT-single-minded (PAS) domains, which were also similar to those in other species of fish and animals. Pva-Clock was primarily expressed in the brain, and was detected in all of the peripheral tissues sampled. Additionally, the pattern of Pva-Clock expression over a 24-h period exhibited a circadian rhythm in the brain, liver and intestine, with the acrophase at zeitgeber time 21:35, 23:00, and 23:23, respectively. Our results provide insight into the function of the molecular Clock of P. vachelli.
- Published
- 2015
17. BRD1-Mediated Acetylation Promotes Integrin αV Gene Expression Via Interaction with Sulfatide
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Yi Wei Dong, Rong Wang, Xing Zhong Wu, Zhong Yi Chen, Xiao-Ting Shao, Bao Mei He, Qian Qian Cai, and Bing Qi
- Subjects
0301 basic medicine ,Male ,Models, Molecular ,Cancer Research ,Carcinoma, Hepatocellular ,Integrin ,03 medical and health sciences ,Cell Line, Tumor ,Humans ,Histone Chaperones ,Neoplasm Metastasis ,ORC1 ,Molecular Biology ,Histone Acetyltransferases ,Regulation of gene expression ,Gene knockdown ,Sulfoglycosphingolipids ,biology ,Chemistry ,Liver Neoplasms ,Nuclear Proteins ,Acetylation ,Integrin alphaV ,Prognosis ,Survival Analysis ,Bromodomain ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Histone acetyltransferase binding ,030104 developmental biology ,Histone ,Oncology ,Tissue Array Analysis ,Cancer research ,biology.protein ,Female - Abstract
Integrin αV gene expression is often dysregulated in cancers especially in hepatocellular carcinoma (HCC); however, the mechanism of regulation is poorly understood. Here, it is demonstrated that sulfatide activated integrin αV gene transcription, through histone H3K9/14 acetylation at the promoter, and high integrin αV expression are closely associated with poor prognosis. To elucidate the mechanism of regulation of acetylation, sulfatide-bound proteins were screened by mass spectrometry (MS), and bromodomain containing protein 1 (BRD1) was identified as an interacting protein that also colocalized with sulfatide in HCC cells. BRD1 was also formed a complex with Sp1, which was recruited to the integrin αV gene promoter. Sulfatide was also found to induce BRD1, monocytic leukemia zinc finger (MOZ) and histone acetyltransferase binding to ORC1 (HBO1) acetyltransferase multiprotein complex recruitment to the integrin αV promoter, which is responsible for histone H3K9/14 acetylation. Finally, knockdown of BRD1 limited sulfatide-induced H3K9/14 acetylation and occupancy of MOZ or HBO1 on integrin αV gene promoter. Implications: This study demonstrates that sulfatide interaction with BRD1 mediates acetylation and is important for regulation of integrin αV gene expression. Mol Cancer Res; 16(4); 610–22. ©2018 AACR.
- Published
- 2017
18. Transcriptome analysis of the spleen of the darkbarbel catfish Pelteobagrus vachellii in response to Aeromonas hydrophila infection
- Author
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Chuanjie Qin, Yuan Dengyue, Ting Shao, Quan Gong, Huatao Li, Zhengyong Wen, and Jun Wang
- Subjects
0301 basic medicine ,Fish Proteins ,Spleen ,Aquatic Science ,Microbiology ,Transcriptome ,03 medical and health sciences ,Fish Diseases ,Immune system ,Immunity ,medicine ,Environmental Chemistry ,Animals ,KEGG ,Receptor ,Gene ,Catfishes ,biology ,Gene Expression Profiling ,04 agricultural and veterinary sciences ,General Medicine ,biology.organism_classification ,Immunity, Innate ,Aeromonas hydrophila ,030104 developmental biology ,medicine.anatomical_structure ,040102 fisheries ,0401 agriculture, forestry, and fisheries ,Gram-Negative Bacterial Infections - Abstract
Intensive aquaculture has increased the susceptibility of fish to Aeromonas hydrophila, and this has led to severe economic damage. There has been little study of the host defense mechanism against A. hydrophila infection in scaleless fish. Therefore, in the present study, the transcriptome profiles of the spleen of Pelteobagrus vachellii were examined after infection with A. hydrophila. In total, 37,730 unigenes from 322 KEGG pathways were identified. Following A. hydrophila infection, 27,803 differentially expressed genes were identified, including 13,934 upregulated and 13,869 downregulated genes. Significant enrichment analysis of these differentially expressed unigenes showed that the major immune pathways were involved, including toll-like receptor pathways, B-cell receptor signaling pathways, Fcγ receptor-mediated phagocytosis, complement and coagulation cascades, and natural killer cell-mediated cytotoxicity pathways. From these pathways, 59 key immune-related differentially expressed genes were selected: 53 genes that were upregulated, including those coding for complement components, interferons, and interleukins, and six DEGs that were downregulated, including inhibitor of nuclear factor kappa-B kinase. Finally, nine DEGs, which were randomly selected, were confirmed by qRT-PCR to be differentially expressed. The results indicated that complement components, interferons and Fcγ receptor-mediated phagocytosis played key role in the response to A. hydrophila infection in the spleen of P. vachellii, which may prove useful in the future for the development of therapeutic regimens.
- Published
- 2017
19. The natural agent rhein induces β-catenin degradation and tumour growth arrest
- Author
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Peiying Song, Qingbin Kong, Hui Hua, Ting Shao, Yangfu Jiang, Ting Luo, Jiao Wang, and Shu Liu
- Subjects
0301 basic medicine ,Cell cycle checkpoint ,Anthraquinones ,S Phase ,HeLa ,chemistry.chemical_compound ,0302 clinical medicine ,Neoplasms ,MG132 ,beta Catenin ,Gene knockdown ,Mice, Inbred BALB C ,biology ,Hep G2 Cells ,Neoplasm Proteins ,030220 oncology & carcinogenesis ,Molecular Medicine ,β‐catenin ,cancer therapy ,Female ,Original Article ,medicine.drug ,Proteasome Endopeptidase Complex ,Mice, Nude ,Antineoplastic Agents ,Natural product ,rhein ,03 medical and health sciences ,Downregulation and upregulation ,medicine ,Animals ,Humans ,RNA, Messenger ,Protein kinase B ,Cell Proliferation ,Biological Products ,Glycogen Synthase Kinase 3 beta ,Cell growth ,Cell Biology ,Cell Cycle Checkpoints ,Original Articles ,biology.organism_classification ,Xenograft Model Antitumor Assays ,030104 developmental biology ,chemistry ,Proteolysis ,Proteasome inhibitor ,Cancer research ,Proto-Oncogene Proteins c-akt ,HeLa Cells - Abstract
The natural agent rhein is an ananthraquinone derivative of rhubarb, which has anticancer effects. To determine the mechanisms underlying the anticancer effects of rhein, we detected the effect of rhein on several oncoproteins. Here, we show that rhein induces β‐catenin degradation in both hepatoma cell HepG2 and cervical cancer cell Hela. Treatment of HepG2 and Hela cells with rhein shortens the half‐life of β‐catenin. The proteasome inhibitor MG132 blunts the downregulation of β‐catenin by rhein. The induction of β‐catenin degradation by rhein is dependent on GSK3 but independent of Akt. Treatment of HepG2 and Hela cells with GSK3 inhibitor or GSK3β knockdown abrogates the effect of rhein on β‐catenin. GSK3β knockdown compromises the inhibition of HepG2 and Hela cell growth by rhein. Furthermore, rhein dose not downregulate β‐catenin mutant that is deficient of phosphorylation at multiple residues including Ser33, Ser37, Thr41 and Ser45. Moreover, rhein induces cell cycle arrest at S phase in both HepG2 and Hela cells. Intraperitoneal administration of rhein suppresses tumour cells proliferation and tumour growth in HepG2 xenografts model. Finally, the levels of β‐catenin are reduced in rhein‐treated tumours. These data demonstrate that rhein can induce β‐catenin degradation and inhibit tumour growth.
- Published
- 2017
20. Study on Biofortification in Vertical Flow Constructed Wetland
- Author
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Ji Ku Zhang, Hui Ting Shao, Yue Ming, and Hui Ye Wang
- Subjects
Pollution ,geography ,geography.geographical_feature_category ,biology ,Microorganism ,media_common.quotation_subject ,General Engineering ,Biofortification ,Environmental engineering ,Wetland ,biology.organism_classification ,Substrate (marine biology) ,Nitrifying bacteria ,Constructed wetland ,Environmental science ,Microbial inoculant ,media_common - Abstract
The methods of dosing composite microbial inoculants are used in vertical flow constructed wetlands for biofortification. The removal of the main pollution indicators by substrate microorganisms was studied. The results show that compared with the blank system, the number of bacteria and nitrifying bacteria was higher in the substrate of constructed wetland by biofortification. At the hydraulic loading rate (HLR) of about 0.8 m3/(m2·d), relationship between total number of bacteria and the removal rate of COD was significant in Device A and Device B. Relationship with TP removal rate is not evident. Correlation between the number of nitrifying bacteria and TN removal rate was obvious. The biofortification is feasible on technology and economy.
- Published
- 2014
21. Antifatigue effect of Gracilaria eucheumoides in mice
- Author
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Lu Bin Zheng, Mei Yan Wang, and Jin Ting Shao
- Subjects
Cancer Research ,medicine.medical_specialty ,biology ,Glycogen ,Cholesterol ,General Medicine ,chemistry.chemical_compound ,Real-time polymerase chain reaction ,Endocrinology ,Immunology and Microbiology (miscellaneous) ,chemistry ,AMP-activated protein kinase ,Apoptosis ,Lactate dehydrogenase ,Internal medicine ,Immunology ,Gene expression ,biology.protein ,medicine ,Protein kinase A - Abstract
Gracilaria eucheumoides Linn (Gracilariaceae; G. eucheumoides) is abundant in dietary fiber, which aids the clearance of excess cholesterol from the blood and maintains stable blood glucose levels. The aim of the present study was to investigate the antifatigue effect of G. eucheumoides in mice and the physiological and molecular mechanisms underlying this effect. Mice were randomly divided into four groups and three of the groups were administered different doses of G. eucheumoides extract. A loaded swimming test demonstrated that the swimming times of the low-, medium- and high-dose groups were longer than those of the control group. Examinations revealed that the liver and muscle glycogen, lactate dehydrogenase and blood glucose concentration levels of the treatment groups were higher than those of the control group (P 0.05). Quantitative polymerase chain reaction showed that the gene expression levels of glucose transport protein 4 and AMP-activated protein kinase in the medium-dose group exhibited the largest increases, compared with the other treatment groups, and were 3.0- and 1.8-fold higher than those in the control group, respectively. The results of the present study indicated that G. eucheumoides exerts an antifatigue effect on mice.
- Published
- 2013
22. Research on Influencing Factors of Photoreactivation in Urban Sewage Treatment by UV Disinfection
- Author
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Hui Ye Wang, Zhi Biao Dong, Ji Ku Zhang, and Hui Ting Shao
- Subjects
biology ,business.industry ,Chemistry ,Environmental engineering ,Sewage ,General Medicine ,medicine.disease_cause ,biology.organism_classification ,Environmental chemistry ,medicine ,Sewage treatment ,Uv disinfection ,Photolyase ,business ,Ultraviolet ,Bacteria - Abstract
Test using CS-type UV sterilizer to do experimental study on the urban sewage , mainly research the influence of the placement time under natural light and the UV dose on photoreactivation. The results show that when disinfection ultraviolet dose is equal, bacteria photoreactivation phenomenon is more obvious with the increase of the placement time of water samples under natural light . When the placement time reaches at 3h, bacteria photoreactivation phenomenon is the most obvious. Under the same placement time, the ratio of bacteria photoreactivation decreases gradually with the increase of UV dose. When UV dose reaches at 80mJ /cm2 or the higher doses, the bacteria does not basically happen photoreactivation phenomenon. Photoreactivation phenomenon in E. coli is more obvious than that in bacteria under the same conditions.
- Published
- 2013
23. Involvement of hydrogen peroxide in heat shock- and cadmium-induced expression of ascorbate peroxidase and glutathione reductase in leaves of rice seedlings
- Author
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Yun-Yang Chao, Ting-Shao Chou, and Ching Huei Kao
- Subjects
inorganic chemicals ,Physiology ,Glutathione reductase ,Plant Science ,Gene Expression Regulation, Enzymologic ,chemistry.chemical_compound ,Ascorbate Peroxidases ,Gene Expression Regulation, Plant ,Gene expression ,Hydrogen peroxide ,NADPH oxidase ,Oryza sativa ,biology ,Chemistry ,food and beverages ,Oryza ,Hydrogen Peroxide ,Glutathione ,APX ,Plant Leaves ,Glutathione Reductase ,Biochemistry ,Seedlings ,biology.protein ,Agronomy and Crop Science ,Heat-Shock Response ,Cadmium ,Peroxidase - Abstract
Hydrogen peroxide (H2O2) is considered a signal molecule inducing cellular stress. Both heat shock (HS) and Cd can increase H2O2 content. We investigated the involvement of H2O2 in HS- and Cd-mediated changes in the expression of ascorbate peroxidase (APX) and glutathione reductase (GR) in leaves of rice seedlings. HS treatment increased the content of H2O2 before it increased activities of APX and GR in rice leaves. Moreover, HS-induced H2O2 production and APX and GR activities could be counteracted by the NADPH oxidase inhibitors dipehenylene iodonium (DPI) and imidazole (IMD). HS-induced OsAPX2 gene expression was associated with HS-induced APX activity but was not regulated by H2O2. Cd-increased H2O2 content and APX and GR activities were lower with than without HS. Cd did not increase the expression of OsAPX and OsGR without HS treatment. Cd increased H2O2 content by Cd before it increased APX and GR activities without HS. Treatment with DPI and IMD effectively inhibited Cd-induced H2O2 production and APX and GR activities. Moreover, the effects of DPI and IMD could be rescued with H2O2 treatment. H2O2 may be involved in the regulation of HS- and Cd-increased APX and GR activities in leaves of rice seedlings.
- Published
- 2012
24. Effects of a human plasma membrane-associated sialidase siRNA on prostate cancer invasion
- Author
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Xuejian Zhao, Chen Shao, De-Qi Xu, Baofeng Guo, Yue-ting Shao, Na Li, Ling Zhang, Bo Wang, Zuowen Liang, Xiao-jie Li, and Yang Li
- Subjects
Male ,Salmonella typhimurium ,Cell ,Biophysics ,Neuraminidase ,Biology ,Transfection ,Sialidase ,Biochemistry ,Metastasis ,Mice ,Prostate cancer ,Cell Movement ,In vivo ,Cell Line, Tumor ,medicine ,Animals ,Humans ,Neoplasm Invasiveness ,RNA, Messenger ,RNA, Small Interfering ,Molecular Biology ,Mice, Inbred BALB C ,Prostatic Neoplasms ,Bone metastasis ,Genetic Therapy ,Cell Biology ,medicine.disease ,Molecular biology ,Blot ,medicine.anatomical_structure ,Cell culture - Abstract
Human plasma membrane-associated sialidase (Neu3) is one of several sialidases that hydrolyze sialic acids in the terminal position of the carbohydrate groups of glycolipids and glycoproteins. Neu3 is mainly localized in plasma membranes and plays crucial roles in the regulation of cell surface functions. In this study, we investigated the effects and molecular mechanisms of Neu3 on cell invasion and migration in vivo and in vitro. Initially, we found that the levels of Neu3 expression were higher in prostate cancer tissues and cell lines than in normal prostate tissues based on RT-PCR and Western blotting analyses. We then applied a Neu3 siRNA approach to block Neu3 signaling using PC-3M cells as model cells. Transwell invasion assays and wound assays showed significantly decreased invasion and migration potential in the Neu3 siRNA-transfected cells. RT-PCR and Western blotting analyses revealed that Neu3 knockdown decreased the expressions of the matrix metalloproteinases MMP-2 and MMP-9. In vivo, mice injected with PC-3M cell tumors were evaluated by SPECT/CT to determine the presence of bone metastases. Mice treated with attenuated Salmonella carrying the Neu3 siRNA developed fewer bone metastases than mice treated with attenuated Salmonella carrying a control Scramble siRNA, attenuated Salmonella alone or PBS. The results for bone metastasis detection by pathology were consistent with the data obtained by SPECT/CT. Tumor blocks were evaluated by histochemical, RT-PCR and Western blotting analyses. The results revealed decreased expressions of MMP-2 and MMP-9 at the mRNA and protein levels. Taken together, the present findings suggest that Neu3 is a promising molecular target for the prevention of prostate cancer metastasis.
- Published
- 2011
25. Involvement of abscisic acid and hydrogen peroxide in regulating the activities of antioxidant enzymes in leaves of rice seedlings under magnesium deficiency
- Author
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Ching Huei Kao, Ting-Shao Chou, and Yun-Yang Chao
- Subjects
chemistry.chemical_classification ,NADPH oxidase ,Antioxidant ,biology ,Physiology ,Chemistry ,medicine.medical_treatment ,fungi ,Glutathione reductase ,food and beverages ,Plant Science ,Superoxide dismutase ,chemistry.chemical_compound ,Enzyme ,Biochemistry ,Catalase ,biology.protein ,medicine ,Agronomy and Crop Science ,Abscisic acid ,Peroxidase - Abstract
Magnesium (Mg) deficiency in plants is a widespread problem, affecting productivity and quality in agriculture. The mechanism of Mg deficiency inducing antioxidant enzyme activities has not been elucidated in rice. We examined the relationship among abscisic acid (ABA), H2O2, and antioxidant enzymes in the leaves of rice seedlings grown under conditions of Mg deficiency. The expression of OsRab16A, an ABA responsive gene, was used to determine the content of ABA. Mg deficiency resulted in increased ABA content in leaves of rice seedlings. The production of H2O2 was examined by 3,3-diaminobenzidine staining and a colorimetric method. Mg deficiency also induced H2O2 production in leaves, which was blocked by dipehnyleneiodonium chloride (DPI), an NADPH oxidase inhibitor. Tungstate (Tu), an ABA biosynthesis inhibitor, was effective in reducing Mg deficiency-increased ABA content, as well as Mg deficiency-induced H2O2 production. Both Tu and DPI were effective in reducing Mg deficiency-induced activities of superoxide dismutase, ascorbate peroxidase, glutathione reductase, and catalase in the leaves. Mg deficiency-induced ABA accumulation may trigger increased production of H2O2, which may involve plasma-membrane NADPH oxidase, and, in turn, up-regulates the activities of antioxidant enzymes in leaves of rice seedlings.
- Published
- 2011
26. Effect of magnesium deficiency on antioxidant status and cadmium toxicity in rice seedlings
- Author
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Chwan-Yang Hong, Yun-Yang Chao, Wen-Dar Huang, Ting-Shao Chou, and Ching Huei Kao
- Subjects
Chlorophyll ,Time Factors ,Antioxidant ,Physiology ,Iron ,medicine.medical_treatment ,Glutathione reductase ,Ascorbic Acid ,Plant Science ,Biology ,Plant Roots ,Antioxidants ,Superoxide dismutase ,chemistry.chemical_compound ,Ascorbate Peroxidases ,Hydroponics ,Paraquat ,Botany ,medicine ,Magnesium ,Biomass ,Superoxide Dismutase ,food and beverages ,Oryza ,Glutathione ,Catalase ,Oxidative Stress ,Zinc ,Horticulture ,Glutathione Reductase ,chemistry ,Seedlings ,Shoot ,Toxicity ,biology.protein ,Agronomy and Crop Science ,Plant Shoots ,Cadmium - Abstract
Cadmium (Cd) is one of the most toxic heavy metals and inhibits physiological processes of plants. Magnesium (Mg) is known as one of the essential nutrients for plants. Mg deficiency in plants affects metabolic processes. Plants grown in the field may encounter several abiotic stresses, rather than a single stress. Thus, the relationship between Mg nutrition and Cd toxicity is of ecological importance. In this study, effects of Mg deficiency on antioxidant systems and Cd toxicity in rice seedlings were investigated. Mg deficiency significantly decreased Mg concentrations in shoot and roots of rice seedlings. However, fresh weight and dry weight of rice seedlings were not affected by Mg deficiency. The contents of ascorbate and glutathione (GSH), the ratio of GSH/oxidized glutathione, and the activities of superoxide dismutase, ascorbate peroxidase, glutathione reductase, and catalase in Mg-deficient leaves were higher than respective control leaves. Cd toxicity was judged by the decrease in biomass production, decrease in chlorophyll, and induction of oxidative stress. Based on these criteria, we demonstrated that Mg deficiency protected rice seedlings from Cd stress. Moreover, chlorophyll destruction by paraquat was higher in detached leaves from Mg-sufficient than Mg-deficient seedlings. Cd concentration was higher in Mg-deficient shoot and roots than their respective control shoot and roots, suggesting that the protective effect of Mg deficiency against Cd toxicity is not due to reduction of Cd uptake. Moreover, we observed that Cd-decreased Fe and Zn contents in Mg-deficient seedlings were more pronounced than that in Mg-sufficient seedlings. Of particular interest is the finding that the increase in OsIRT1, OsZIP1, and OsZIP3 transcripts caused by Cd in Mg-deficient roots was greater than that in control roots.
- Published
- 2011
27. Enhanced tumor suppression in vitro and in vivo by co-expression of survivin-specific siRNA and wild-type p53 protein
- Author
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F Li, Yue-ting Shao, D Zhao, Xin Li, Y Liu, Dhananjaya V. Kalvakolanu, De-Qi Xu, Ling Zhang, Dennis J. Kopecko, Jiadi Hu, Libo Sun, Yang Li, Xuejian Zhao, and C Shao
- Subjects
Male ,Cancer Research ,Survivin ,Mice, Nude ,Biology ,Article ,Inhibitor of Apoptosis Proteins ,Small hairpin RNA ,Mice ,Prostate cancer ,Nude mouse ,Prostate ,Cell Line, Tumor ,Gene expression ,medicine ,Animals ,Humans ,RNA, Small Interfering ,Molecular Biology ,Cell Proliferation ,Kinase ,Cell growth ,Prostatic Neoplasms ,medicine.disease ,biology.organism_classification ,Repressor Proteins ,medicine.anatomical_structure ,Cancer research ,Molecular Medicine ,Tumor Suppressor Protein p53 ,Microtubule-Associated Proteins - Abstract
The development of malignant prostate cancer involves multiple genetic alterations. For example, alterations in both survivin and p53 are reported to have crucial roles in prostate cancer progression. However, little is known regarding the interrelationships between p53 and survivin in prostate cancer. Our data demonstrate that the expression of survivin is inversely correlated with that of wtp53 protein (r(s)=0.548) in prostate cancer and in normal prostate tissues. We have developed a therapeutic strategy, in which two antitumor factors, small interfering RNA-survivin and p53 protein, are co-expressed from the same plasmid, and have examined their effects on the growth of PC3, an androgen-independent prostate cancer cell line. When p53 was expressed along with a survivin-specific short hairpin RNA (shRNA), tumor cell proliferation was significantly suppressed and apoptosis occurred. In addition, this combination also abrogated the expression of downstream target molecules such as cyclin-dependent kinase 4 and c-Myc, while enhancing the expression of GRIM19. These changes in gene expression occurred distinctly in the presence of survivin-shRNA/wtp53 compared with control or single treatment groups. Intratumoral injection of the co-expressed construct inhibited the growth and survival of tumor xenografts in a nude mouse model. These studies revealed evidence of an interaction between p53 and survivin proteins plus a complex signaling network operating downstream of the wtp53-survivin pathway that actively controls tumor cell proliferation, survival and apoptosis.
- Published
- 2010
28. Aflatoxin B1 induces Src phosphorylation and stimulates lung cancer cell migration
- Author
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Qingbin Kong, Yangfu Jiang, Hui Hua, Ting Luo, Anguo Cui, Ting Shao, and Peiying Song
- Subjects
Aflatoxin B1 ,Lung Neoplasms ,Cell migration ,General Medicine ,Biology ,medicine.disease ,IRS1 ,Gene Expression Regulation, Neoplastic ,src-Family Kinases ,Growth factor receptor ,Cell Movement ,Cell Line, Tumor ,Cancer research ,medicine ,Insulin Receptor Substrate Proteins ,Quinazolines ,Phosphorylation ,Humans ,Benzodioxoles ,Lung cancer ,Protein kinase B ,Carcinogen ,Proto-oncogene tyrosine-protein kinase Src ,Signal Transduction - Abstract
AflatoxinB1 (AFB1) is well known as a potent carcinogen. Epidemiological studies have shown an association between AFB1 exposure and lung cancer in humans. AFB1 can induce the mutations of genes such as tumor suppressor p53 through its metabolite AFB1-8,9-exo-epoxide, which acts as a mutagen to react with DNA. In addition, recent study demonstrates AFB1 positively regulates type I insulin-like growth factor receptor (IGF-IR) signaling in hepatoma cells. The current study aims to determine the effects of AFB1 on Src kinase and insulin receptor substrate (IRS) in lung cancer cells and the effects of AFB1 on lung cancer cell migration. To this end, the effects of AFB1 on IRS expression, Src, Akt, and ERK phosphorylation were measured by Western blot analysis. The migration of lung cancer cells was detected by wound-healing assay. AFB1 downregulates IRS1 but paradoxically upregulates IRS2 through positive regulation of the stability of IRS2 and the proteasomal degradation of IRS1 in lung cancer cell lines A549 and SPCA-1. In addition, AFB1 induces Src, Akt, and ERK1/2 phosphorylation. Treatment of lung cancer cells with Src inhibitor saracatinib abrogates AFB1-induced IRS2 accumulation. Moreover, AFB1 stimulates lung cancer cell migration, which can be inhibited by saracatinib. We conclude that AFB1 may upregulate IRS2 and stimulate lung cancer cell migration through Src.
- Published
- 2014
29. Inhibition of STAT3 expression by siRNA suppresses growth and induces apoptosis in laryngeal cancer cells
- Author
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Yue-ting Shao, Xing-yi Zhang, De-Qi Xu, Xuejian Zhao, Lian-ji Wen, and Lifang Gao
- Subjects
STAT3 Transcription Factor ,Cell ,Apoptosis ,Biology ,Transfection ,chemistry.chemical_compound ,Cell Line, Tumor ,medicine ,Humans ,Pharmacology (medical) ,RNA, Messenger ,Northern blot ,RNA, Small Interfering ,Laryngeal Neoplasms ,Cell Proliferation ,Pharmacology ,Cell growth ,General Medicine ,Molecular biology ,DNA-Binding Proteins ,medicine.anatomical_structure ,Proto-Oncogene Proteins c-bcl-2 ,chemistry ,Cell culture ,Cancer cell ,Trans-Activators ,Cancer research ,RNA Interference ,Growth inhibition - Abstract
To determine the inhibitory effect of the synthetic STAT3 siRNA on the expression of STAT3 gene in human laryngeal cancer cell lines Hep2 and to investigate the effect of STAT3 siRNA on growth and apoptosis in Hep2 cells. A pair of DNA templates coding siRNA against STAT3-mRNA was synthesized to reconstruct plasmid of pSilencer1.0-U6 siRNA-STAT3. Hep2 cells were transfected with RPMI-1640 media (untreated), plasmid (empty), and STAT3 siRNA, respectively. Northern blot and Western blot analysis of STAT3 and pTyr-STAT3 expression in Hep2 cells and Western blot analysis of Bcl-2 expression in the Hep2 cell was performed 72 h after transfection. MTT, flow cytometry, and AO/EB assay were used for determination of cells proliferation and apoptosis in Hep2 cells. pTyr-STAT3 was markedly expressed in untreated Hep2 cells and the vector-treated Hep2 cells, whereas pTyr-STAT3 expression was significantly reduced in STAT3 siRNA-transfected Hep2 cells, indicating that STAT3 siRNA inhibited the activity of STAT3. Transfection of Hep2 cells with STAT3 siRNA significantly inhibited STAT3 expression at both mRNA and protein level in Hep2 cells and the inhibition was characterized by time-dependent transfection. Treatment of Hep2 cells with STAT3 siRNA resulted in dose-dependent growth inhibition of Hep2, this significantly increased apoptotic cell rate, and decreased Bcl-2 expression level in Hep2 cells. STAT3 siRNA had an effect on induction of either early or late stage apoptosis. This study demonstrates that STAT3 siRNA effectively inhibits STAT3 gene expression in Hep2 cells leading to growth suppression and induction of apoptosis in Hep2 cells. The use of siRNA technique may provide a novel therapeutic approach to treat laryngeal cancer and other malignant tumors expressing constitutively activated STAT3.
- Published
- 2005
30. GSK3 protein positively regulates type I insulin-like growth factor receptor through forkhead transcription factors FOXO1/3/4
- Author
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Xiaodong Huo, Yangfu Jiang, Shu Liu, Ting Shao, Qingbin Kong, Hui Hua, Ting Luo, and Jiao Wang
- Subjects
Transcriptional Activation ,animal structures ,Blotting, Western ,FOXO1 ,Cell Cycle Proteins ,macromolecular substances ,Biology ,Biochemistry ,Receptor, IGF Type 1 ,Transactivation ,Glycogen Synthase Kinase 3 ,Forkhead Transcription Factors ,Growth factor receptor ,GSK-3 ,Cell Line, Tumor ,Humans ,Insulin-Like Growth Factor I ,Phosphorylation ,Extracellular Signal-Regulated MAP Kinases ,Promoter Regions, Genetic ,Molecular Biology ,Protein kinase B ,Transcription factor ,Cell Proliferation ,Glycogen Synthase Kinase 3 beta ,Models, Genetic ,Forkhead Box Protein O1 ,Reverse Transcriptase Polymerase Chain Reaction ,Forkhead Box Protein O3 ,Cell Biology ,Gene Expression Regulation, Neoplastic ,Cancer research ,RNA Interference ,Signal transduction ,Proto-Oncogene Proteins c-akt ,Protein Binding ,Transcription Factors ,Signal Transduction - Abstract
Glycogen synthase kinase-3 (GSK3) has either tumor-suppressive roles or pro-tumor roles in different types of human tumors. A number of GSK3 targets in diverse signaling pathways have been uncovered, such as tuberous sclerosis complex subunit 2 and β-catenin. The O subfamily of forkhead/winged helix transcription factors (FOXO) is known as tumor suppressors that induce apoptosis. In this study, we find that FOXO binds to type I insulin-like growth factor receptor (IGF-IR) promoter and stimulates its transcription. GSK3 positively regulates the transactivation activity of FOXO and stimulates IGF-IR expression. Although kinase-dead GSK3β cannot up-regulate IGF-IR, the constitutively active GSK3β induces IGF-IR expression in a FOXO-dependent manner. Serum starvation or Akt inhibition leads to an increase in IGF-IR expression, which could be blunted by GSK3 inhibition. GSK3β knockdown or GSK3 inhibitor suppresses IGF-I-induced IGF-IR, Akt, and ERK1/2 phosphorylation. Moreover, knockdown of GSK3β or FOXO1/3/4 leads to a decrease in cellular proliferation and abrogates IGF-I-induced hepatoma cell proliferation. These results suggest that GSK3 and FOXO may positively regulate IGF-I signaling and hepatoma cell proliferation.
- Published
- 2014
31. Prioritizing candidate disease miRNAs by topological features in the miRNA target-dysregulated network: case study of prostate cancer
- Author
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Jun Ying Lv, Xia Li, Yan Zou, Lihua Wang, Xiao Huo, Yun Xiao, Huan Ren, Chuanxing Li, Ting Ting Shao, Qing Lian Han, Xiang Li, Yongsheng Li, and Juan Xu
- Subjects
Male ,Cancer Research ,Computational biology ,Disease ,Biology ,medicine.disease_cause ,Molecular oncology ,Mirna target ,Prostate cancer ,Cell Line, Tumor ,microRNA ,medicine ,Humans ,Molecular Targeted Therapy ,Gene ,Oligonucleotide Array Sequence Analysis ,Genetics ,Sequence Analysis, RNA ,Gene Expression Profiling ,Prostatic Neoplasms ,Transfection ,medicine.disease ,Gene Expression Regulation, Neoplastic ,MicroRNAs ,Oncology ,Carcinogenesis ,Algorithms - Abstract
Recently, microRNAs (miRNA), small noncoding RNAs, have taken center stage in the field of human molecular oncology. However, their roles in tumor biology remain largely unknown. According to the assumption that miRNAs implicated in a specific tumor phenotype will show aberrant regulation of their target genes, we introduce an approach based on the miRNA target–dysregulated network (MTDN) to prioritize novel disease miRNAs. Target genes have predicted binding sites for any miRNA. The MTDN is constructed by combining computational target prediction with miRNA and mRNA expression profiles in tumor and nontumor tissues. Application of the proposed method to prostate cancer reveals that known prostate cancer miRNAs are characterized by a greater number of dysregulations and coregulators and the tendency to coregulate with each other and that they share a higher proportion of targets with other prostate cancer miRNAs. Support vector machine classifier, based on these features and changes in miRNA expression, is constructed and gives an average overall prediction accuracy of 0.8872 in cross-validation tests. The classifier is then applied to miRNAs in the MTDN. Functions enriched by dysregulated targets of novel predicted miRNAs are closely associated with oncogenesis. In addition, predicted cancer miRNAs within families or from different families show combinatorial dysregulation of target genes, as revealed by analysis of the MTDN modular organization. Finally, 3 miRNA target regulations are verified to hold in prostate cancer cells by transfection assays. These results show that the network-centric method could prioritize novel disease miRNAs and model how oncogenic lesions are mediated by miRNAs, providing important insights into tumorigenesis. Mol Cancer Ther; 10(10); 1857–66. ©2011 AACR.
- Published
- 2011
32. Synergistic suppression of prostatic cancer cells by coexpression of both murine double minute 2 small interfering RNA and wild-type p53 gene in vitro and in vivo
- Author
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Yanan Liu, Yue-ting Shao, Chen Shao, Bo Wang, De-Qi Xu, Xuejian Zhao, Ling Zhang, Jiadi Hu, Kun Ji, Yang Li, Xin Li, Lu Cai, and Xiao-jie Li
- Subjects
Male ,Small interfering RNA ,Mice, Nude ,Biology ,Mice ,Random Allocation ,In vivo ,Cell Line, Tumor ,Animals ,Humans ,RNA, Small Interfering ,Pharmacology ,Gene knockdown ,Cell growth ,Prostatic Neoplasms ,Proto-Oncogene Proteins c-mdm2 ,Transfection ,Genes, p53 ,Molecular biology ,Xenograft Model Antitumor Assays ,In vitro ,Gene Expression Regulation, Neoplastic ,Lipofectamine ,Cancer cell ,Cancer research ,Molecular Medicine - Abstract
Our objective was to evaluate cell growth and death effects by inhibiting Murine Double Minute 2 (MDM2) expression in human prostate cancer cells overexpressing the wild-type (WT) p53 gene. Prostate PC-3 tumor cells were transfected with a plasmid containing either mdm2 small interfering (Si-mdm2) or the WT p53 gene (Pp53) alone, or both (Pmp53), using Lipofectamine in vitro and attenuated Salmonella enterica serovar Typhi vaccine strain Ty21a (Salmonella Typhi Ty21a) in vivo. Cell growth, apoptosis, and the expression of related genes and proteins were examined in vitro and in vivo by flow cytometry and Western blot assays. We demonstrated that human prostate tumors had increased expression of MDM2 and mutant p53 proteins. Transfection of the PC-3 cells with the Pmp53 plasmid in vitro offered significant inhibition of cell growth and an increase in apoptotic cell death compared with that of the Si-mdm2 or Pp53 group. These effects were associated with up-regulation of p21 and down-regulation of hypoxia-inducible factor 1α expression in Pmp53-transfected cells. To validate the in vitro findings, the nude mice implanted with PC-3 cells were treated with attenuated Salmonella Typhi Ty21a carrying the plasmids, which showed that the Pmp53 plasmid significantly inhibited the tumor growth rate in vivo compared with that of the Si-mdm2 or Pp53 plasmid alone. Tumor tissues from mice treated with the Pmp53 plasmid showed increased expression of p21 and decreased expression of hypoxia-inducible factor 1α proteins, with an increased apoptotic effect. These results suggest that knockdown of mdm2 expression by its specific small interfering RNA with overexpression of the WT p53 gene offers synergistic inhibition of prostate cancer cell growth in vitro and in vivo.
- Published
- 2011
33. MiRNA-miRNA synergistic network: construction via co-regulating functional modules and disease miRNA topological features
- Author
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Yunpeng Zhang, Juan Xu, Ting Ting Shao, Jun Ying Lv, Yun Xiao, Xia Li, Liang De Xu, Ye Ma, Yongsheng Li, Lei Du, Chuanxing Li, Chunquan Li, Yingying Wang, and Wei Jiang
- Subjects
Genetics ,Network construction ,Gene ontology ,Gene regulatory network ,Computational Biology ,Disease ,Biology ,Topology ,Mirna target ,MicroRNAs ,RNA interference ,Interaction network ,microRNA ,Humans ,Gene Regulatory Networks ,RNA Interference ,Algorithms - Abstract
Synergistic regulations among multiple microRNAs (miRNAs) are important to understand the mechanisms of complex post-transcriptional regulations in humans. Complex diseases are affected by several miRNAs rather than a single miRNA. So, it is a challenge to identify miRNA synergism and thereby further determine miRNA functions at a system-wide level and investigate disease miRNA features in the miRNA–miRNA synergistic network from a new view. Here, we constructed a miRNA–miRNA functional synergistic network (MFSN) via co-regulating functional modules that have three features: common targets of corresponding miRNA pairs, enriched in the same gene ontology category and close proximity in the protein interaction network. Predicted miRNA synergism is validated by significantly high co-expression of functional modules and significantly negative regulation to functional modules. We found that the MFSN exhibits a scale free, small world and modular architecture. Furthermore, the topological features of disease miRNAs in the MFSN are distinct from non-disease miRNAs. They have more synergism, indicating their higher complexity of functions and are the global central cores of the MFSN. In addition, miRNAs associated with the same disease are close to each other. The structure of the MFSN and the features of disease miRNAs are validated to be robust using different miRNA target data sets.
- Published
- 2010
34. Bacterial Delivery of siRNAs: A New Approach to Solid Tumor Therapy
- Author
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Lifang Gao, Yue-ting Shao, De-Qi Xu, Baofeng Guo, Ling Zhang, Lijing Zhao, and Dennis J. Kopecko
- Subjects
Small hairpin RNA ,Small interfering RNA ,In vivo ,RNA interference ,Genetic enhancement ,Cancer research ,Gene silencing ,Transfection ,Biology ,Genetically modified organism - Abstract
RNAi is a powerful research tool for specific gene silencing and may also lead to promising novel therapeutic strategies. However, the development of RNAi-based therapies has been slow due to the lack of targeted delivery methods. The biggest challenge in the use of siRNA-based therapies is the delivery to target cells. There are many additional obstacles to in vivo delivery of siRNAs, such as degradation by endogenous enzymes and interaction with blood components leading to nonspecific uptake into cells, which govern biodistribution and availability of siRNA in the body. Naked unmodified synthetic siRNA including plasmid-carried-shRNA-expression constructs cannot penetrate cellular membranes, and therefore, systemic application is unlikely to be successful. The success of gene therapy by siRNAs relies on the development of safe, economical, and efficacious in vivo delivery systems into the target cells. Attenuated Salmonella have been employed recently as vectors to deliver silencing hairpin RNA (shRNA) expression plasmids into mammalian cells. This approach has achieved gene silencing in vitro and in vivo. The facultative anaerobic, invasive Salmonella have a natural tropism for solid tumors including metastatic tumors. Genetically modified, attenuated Salmonella have been used recently both as potential antitumor agents by themselves, and to deliver specific tumoricidal therapies. This chapter describes the use of attenuated bacteria as tumor-targeting delivery systems for cancer therapy.
- Published
- 2008
35. Effects of plasmid-based Stat3-specific short hairpin RNA and GRIM-19 on PC-3M tumor cell growth
- Author
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Ling Zhang, Kun Ji, Jiadi Hu, Yue-ting Shao, Dennis J. Kopecko, Xuejian Zhao, Hao Yu, Guimiao Lin, Lifang Gao, De-Qi Xu, Yang Li, and Dhananjaya V. Kalvakolanu
- Subjects
Male ,STAT3 Transcription Factor ,Cancer Research ,Transcription, Genetic ,Mice, Nude ,Apoptosis ,Small hairpin RNA ,chemistry.chemical_compound ,Mice ,Transcription (biology) ,RNA interference ,Cell Line, Tumor ,Gene silencing ,Animals ,Humans ,NADH, NADPH Oxidoreductases ,RNA, Small Interfering ,STAT3 ,Cell Proliferation ,Regulation of gene expression ,Mice, Inbred BALB C ,biology ,Prostate ,RNA ,Prostatic Neoplasms ,Molecular biology ,Xenograft Model Antitumor Assays ,Gene Expression Regulation, Neoplastic ,Oncology ,chemistry ,Cancer research ,biology.protein ,Growth inhibition ,Apoptosis Regulatory Proteins ,Plasmids - Abstract
Purpose: Persistent activation of signal transducers and activators of transcription 3 (Stat3) and its overexpression contribute to the progression and metastasis of several different tumor types. For this reason, Stat3 is a reasonable target for RNA interference–mediated growth inhibition. Blockade of Stat3 using specific short hairpin RNAs (shRNA) can significantly reduce prostate tumor growth in mice. However, RNA interference does not fully ablate target gene expression in vivo, owing to the idiosyncrasies associated with shRNAs and their targets. To enhance the therapeutic efficacy of Stat3-specific shRNA, we applied a combination treatment involving gene associated with retinoid-IFN–induced mortality 19 (GRIM-19), another inhibitor of STAT3, along with shRNA.Experimental Design: The coding sequences for GRIM-19, a cellular STAT3-specific inhibitor, and Stat3-specific shRNAs were used to create a dual expression plasmid vector and used for prostate cancer therapy in vitro and in mouse xenograft models in vivo.Results: The coexpressed Stat3-specific shRNA and GRIM-19 synergistically and more effectively suppressed prostate tumor growth and metastases when compared with treatment with either single agent alone.Conclusion: The simultaneous use of two specific, but mechanistically different, inhibitors of STAT3 activity exerts enhanced antitumor effects.
- Published
- 2008
36. Knockdown of Stat3 expression using RNAi inhibits growth of laryngeal tumors in vivo
- Author
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Lian-ji Wen, Yue-ting Shao, Yan Meng, Hao Yu, Xuejian Zhao, Ling Zhang, De-Qi Xu, and Lifang Gao
- Subjects
STAT3 Transcription Factor ,Survivin ,H&E stain ,Mice, Nude ,Apoptosis ,Inhibitor of Apoptosis Proteins ,Mice ,Cyclin D1 ,Cell Line, Tumor ,Medicine ,Animals ,Humans ,Pharmacology (medical) ,RNA, Messenger ,RNA, Small Interfering ,STAT3 ,Laryngeal Neoplasms ,Pharmacology ,Gene knockdown ,TUNEL assay ,biology ,business.industry ,General Medicine ,Molecular biology ,Neoplasm Proteins ,Blot ,Transplantation ,Proto-Oncogene Proteins c-bcl-2 ,biology.protein ,RNA Interference ,business ,Microtubule-Associated Proteins ,Neoplasm Transplantation - Abstract
Aim: To study the effect of pSilencer 1.0-U6-siRNA-stat3 on the growth of human laryngeal tumors in nude mice. Methods: Hep2 cells were transplanted into nude mice, then at the time of tumor formation, growth rates were observed. After the tumor formed, pSilencer 1.0-U6-siRNA- stat3 was injected. Tumor volumes were calculated, and growth curves were plotted. Representative histological sections were taken from mice bearing transplantation tumors in both treated and control groups, and start3 , pTyr-stat3 , Bcl-2 , cyclin D1 , and surviving expression were detected by Western blotting. survivin mRNA levels were detected by Northern blotting, hematoxylin and eosin staining and terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling (TUNEL) assay to confirm the apoptosis of tumors. Results: In nude mice, pSilencer 1.0-U6-siRNA-stat3 significantly suppressed the growth of tumors compared with controls ( P BcL2 , cyclin D1 , and surviving expression within the tumor. This significantly induced apoptosis of the tumors. Conclusion: pSilencer 1.0-U6-siRNA- stat3 was able to inhibit the growth of transplanted human laryngeal tumors in nude mice and induce apoptosis.
- Published
- 2006
37. Down-regulation of signal transducer and activator of transcription 3 expression using vector-based small interfering RNAs suppresses growth of human prostate tumor in vivo
- Author
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Yue-ting Shao, Dhananjaya V. Kalvakolanu, Feng Li, Dan Zhao, Ling Zhang, De-Qi Xu, Jiadi Hu, Lifang Gao, Dennis J. Kopecko, and Xuejian Zhao
- Subjects
Male ,STAT3 Transcription Factor ,Cancer Research ,Small interfering RNA ,Genetic Vectors ,Molecular Sequence Data ,Down-Regulation ,Mice, Nude ,Apoptosis ,Biology ,Proto-Oncogene Proteins c-myc ,Mice ,RNA interference ,LNCaP ,Gene expression ,Tumor Cells, Cultured ,Gene silencing ,Animals ,Humans ,Cyclin D1 ,RNA, Small Interfering ,Base Pairing ,Cell Proliferation ,Gene knockdown ,Base Sequence ,Cell Cycle ,RNA ,Prostatic Neoplasms ,DNA-Binding Proteins ,Oncology ,Proto-Oncogene Proteins c-bcl-2 ,Cancer cell ,Cancer research ,Trans-Activators - Abstract
Purpose: Signal transducer and activator of transcription 3 (Stat3) is constitutively activated in a variety of cancers and it is a common feature of prostate cancer. Thus, Stat3 represents a promising molecular target for tumor therapy. We applied a DNA vector–based Stat3-specific RNA interference approach to block Stat3 signaling and to evaluate the biological consequences of Stat3 down-modulation on tumor growth using a mouse model. Experimental Design: To investigate the therapeutic potential of blocking Stat3 in cancer cells, three small interfering RNAs (siRNA; Stat3-1, Stat3-2, and Stat3-3) specific for different target sites on Stat3 mRNA were designed and used with a DNA vector–based RNA interference approach expressing short hairpin RNAs to knockdown Stat3 expression in human prostate cancer cells in vitro as well as in vivo. Results: Of the three equivalently expressed siRNAs, only Stat3-3 and Stat3-2, which target the region coding for the SH2 domain and the coiled-coil domain, respectively, strongly suppressed the expression of Stat3 in PC3 and LNCaP cells. The Stat3-1 siRNA, which targeted the DNA-binding domain, exerted no effect on Stat3 expression, indicating that the gene silencing efficiency of siRNA may be dependent on the local structure of Stat3 mRNA. The Stat3 siRNAs down-regulated the expression of Bcl-2 (an antiapoptotic protein), and cyclin D1 and c-Myc (cell growth activators) in prostate cancer cells. Inhibition of Stat3 and its related genes was accompanied by growth suppression and induction of apoptosis in cancer cells in vitro and in tumors implanted in nude mice. Conclusions: These data indicate that Stat3 signaling is a promising molecular target for prostate cancer therapy and that vector-based Stat3 siRNA may be useful as a therapeutic agent for treatment of prostate cancer.
- Published
- 2005
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