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Influenza virus-like particles (VLPs) were produced in Sf9 insect cells by co-expressing the matrix protein M1 and the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) using the recombinant baculovirus expression sy...
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Influenza virus-like particles (VLPs) were produced in Sf9 insect cells by co-expressing the matrix protein M1 and the surface glycoproteins hemagglutinin (HA) and neuraminidase (NA) using the recombinant baculovirus expression system. The VLPs were morphologically similar to influenza virions. Both HA and NA proteins were incorporated into VLPs and these proteins retained their functional activities. Further, influenza VLPs but not inactivated influenza viruses (IIV) stimulated secretion of inflammatory cytokines from mouse bone marrow-derived dendritic cells (BMDC). Immunogenicity of influenza VLPs and their protective efficacies against lethal influenza virus challenge were evaluated in young and aged mice. Immunization with influenza VLPs induced strong antibody responses against HA that inhibited hemagglutination by influenza virus, similar to IIV vaccines. Compared to young mice, antibody responses in aged mice immunized with a low dose of either influenza VLPs or IIV vaccines exhibited markedly reduced avidity for HA. However, immunization of aged mice with a high dose of influenza VLPs induced antibody responses with high avidity similar to those in young mice. Furthermore, all vaccinated animals survived a lethal challenge by a mouse-adapted influenza virus (A/PR/8/34), indicating that influenza VLPs are highly efficacious for protection against influenza virus infection in both young and aged mice.
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BACKGROUND: Suicide has been identified as one of the three leading causes of death in adolescents and young adults. No previous study in China has tested the association between protective factors and urban adolescents' suicidal ...
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BACKGROUND: Suicide has been identified as one of the three leading causes of death in adolescents and young adults. No previous study in China has tested the association between protective factors and urban adolescents' suicidal behaviours. In this study we tested the hypothesis that suicidal behaviours would be associated with multiple protective factors. METHODS: A stratified random of 9015 students from 100 junior middle schools in Beijing, Hangzhou, Wuhan and Urumqi completed the Chinese version of Global School-Based Student Health Survey. RESULTS: Overall, 17.4% of students had seriously considered attempting suicide, and 8.1% had made a specific plan to attempt suicide during the 12 months preceding the survey. The students in Wuhan (18.7%) and Urumqi (20.8%) cities were significantly more likely than students in Beijing (14.4%) and Hangzhou (14.4%) to have suicidal ideation (chi2 = 45.9, P < 0.001). Female students were significantly more likely than male students to have suicidal ideation and have made suicide attempts [odds ratio (OR) = 1.4, P < 0.001]. Results indicated that the rates of suicidal ideation and suicide attempts increased with age (OR = 1.44, P < 0.001). Multivariate logistic regression models showed that suicide risk tended to decrease significantly when 'days of missed classes or school without permission were less than one', and when students thought students in their school were kind and helpful most of the time or always', 'parents or guardians checked to see if homework was done most of the time or always', 'parents or guardians understood their problems and worries most of the time or always' and 'parents or guardians really know what they are doing with their free time most of the time or always'. CONCLUSIONS: Adolescent suicide behaviour should be a serious problem. Measures can be taken to prevent suicide by observing the factors significantly linked to suicidal behaviour. Steps can then be taken to identify adolescents who have serious suicidal ideation so that intervention can be taken to reduce the suicidal rate.
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BACKGROUND: Vascular endothelial growth inhibitor (VEGI) has been implicated in the regulation of tumour-related vasculature in certain solid tumours. However, its role in urothelial tumours is still unclear. In the present study,...
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BACKGROUND: Vascular endothelial growth inhibitor (VEGI) has been implicated in the regulation of tumour-related vasculature in certain solid tumours. However, its role in urothelial tumours is still unclear. In the present study, the role played by VEGI in urothelial tumours of the bladder was investigated. MATERIALS AND METHODS: The expression of VEGI was examined in cancer human bladder tissues and in a serial of cell lines using immunochemical staining and RT-PCR respectively. The biological impact of modifying VEGI expression in urothelial cancer cells was evaluated using in vitro models. RESULTS: VEGI mRNA was expressed in a wide variety of human cell lines. VEGI expression was seen in normal urothelial and stromal cells, but was found to be reduced or absent in urothelial cancer cells. The positive staining in normal tissue (6/7) was significantly higher than that of urothelial cancer tissues (2/12), p=0.006. Moreover, overexpression of VEGI reduced the motility and adhesion of urothelial cancer cells in vitro. However, the overexpression of VEGI had no bearing on the growth and invasion of urothelial cancer cells. CONCLUSION: VEGI has an inhibitory effect on cellular motility and adhesion in bladder cancer cells. Taken together with the expression pattern of VEGI in urothelial cancer of the bladder, it suggests that VEGI functions as a negative regulator of aggressiveness during development and progression of bladder cancer.
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Resveratrol is a natural occurring phytoalexin present in grapes and berries, that has been shown to have chemopreventive/therapeutic activity. But the precise mechanism of resveratrol involved in leukemia is not well understood. ...
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Resveratrol is a natural occurring phytoalexin present in grapes and berries, that has been shown to have chemopreventive/therapeutic activity. But the precise mechanism of resveratrol involved in leukemia is not well understood. In this study, we examine its anti-leukemia effect both in vitro and in vivo. Our data indicate that resveratrol contributes to inhibiting growth, inducing apoptosis and cell cycle arrest in the three leukemia cell lines (Jurkat, SUP-B15, and Kasumi-1), and reducing the phosphorylation of STAT3, meanwhile modulating the expression of Bcl-2 and Bax. In vivo, resveratrol could prolong the life span of Kasumi-1-bearing mice, and attenuate the activity of STAT3. Taken altogether, this investigation focuses on signaling pathways involved in STAT3 by resveratrol and to delineate its molecular mechanisms underlying anti-leukemia effect.
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Hepatitis C virus nonstructural protein 4B (NS4B) is an endoplasmic reticulum (ER) membrane associated protein and a potent causative factor of ER stress. Here we reported that unfolded protein response (UPR) can be activated by H...
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Hepatitis C virus nonstructural protein 4B (NS4B) is an endoplasmic reticulum (ER) membrane associated protein and a potent causative factor of ER stress. Here we reported that unfolded protein response (UPR) can be activated by HCV NS4B through inducing both XBP1 mRNA splicing and ATF6 cleavage in human hepatic cells. Flow cytometric analysis revealed that HCV NS4B stimulates the production of reactive oxygen species (ROS) by perturbing intracellular Ca(2+) homeostasis. Luciferase assay showed that HCV NS4B also activates the multifunctional transcription factor, NF-kappaB, in a dose-dependent manner through Ca(2+) signaling and ROS. Further immunoblot analysis showed that HCV NS4B promotes NF-kappaB translocation into the nucleus via protein-tyrosine kinase (PTK) mediated phosphorylation and subsequent degradation of IkappaBalpha. These studies provide an important insight into the implication of NS4B in HCV life cycle and HCV-associated liver disease by affecting host intracellular signal transduction pathways.
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BACKGROUND: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public-private consortia have been formed with the goal of improving chemical safety assessment by the means of high-through...
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BACKGROUND: Accurate prediction of in vivo toxicity from in vitro testing is a challenging problem. Large public-private consortia have been formed with the goal of improving chemical safety assessment by the means of high-throughput screening. OBJECTIVE: A wealth of available biological data requires new computational approaches to link chemical structure, in vitro data, and potential adverse health effects. METHODS AND RESULTS: A database containing experimental cytotoxicity values for in vitro half-maximal inhibitory concentration (IC(50)) and in vivo rodent median lethal dose (LD(50)) for more than 300 chemicals was compiled by Zentralstelle zur Erfassung und Bewertung von Ersatz- und Ergaenzungsmethoden zum Tierversuch (ZEBET; National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments). The application of conventional quantitative structure-activity relationship (QSAR) modeling approaches to predict mouse or rat acute LD(50) values from chemical descriptors of ZEBET compounds yielded no statistically significant models. The analysis of these data showed no significant correlation between IC(50) and LD(50). However, a linear IC(50) versus LD(50) correlation could be established for a fraction of compounds. To capitalize on this observation, we developed a novel two-step modeling approach as follows. First, all chemicals are partitioned into two groups based on the relationship between IC(50) and LD(50) values: One group comprises compounds with linear IC(50) versus LD(50) relationships, and another group comprises the remaining compounds. Second, we built conventional binary classification QSAR models to predict the group affiliation based on chemical descriptors only. Third, we developed k-nearest neighbor continuous QSAR models for each subclass to predict LD(50) values from chemical descriptors. All models were extensively validated using special protocols. CONCLUSIONS: The novelty of this modeling approach is that it uses the relationships between in vivo and in vitro data only to inform the initial construction of the hierarchical two-step QSAR models. Models resulting from this approach employ chemical descriptors only for external prediction of acute rodent toxicity.
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OBJECTIVE: Wnt5a is generally considered a non-canonical Wnt family member and plays an important role in the development of several tissues through regulation of cell fate, proliferation, migration, polarity and death. This study...
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OBJECTIVE: Wnt5a is generally considered a non-canonical Wnt family member and plays an important role in the development of several tissues through regulation of cell fate, proliferation, migration, polarity and death. This study investigates its expression mode in human tooth development and the involved cell signal transduction pathways, as they remain unclear. DESIGN: The expression of Wnt5a was analyzed by immunohistochemistry method. Recombinant adenovirus encoding full-length Wnt5a cDNA was constructed to investigate four cell signal pathways and nine dentinogenesis nuclear transcription factors in response to Wnt5a in human dental papilla cells (HDPCs). RESULTS: Immunostaining revealed that Wnt5a was expressed in enamel epithelium cells from the bud stage, and in odontoblast layers and dental papilla tissues from early bell stage of human tooth development onward. Western blot analysis indicated that p42/44 MAPK, p38 MAPK, JNK and AKT signal pathways could be phosphorylated by WNT5A. RT-PCR analysis showed that Wnt5a increased the expression of DLX1, DLX2, LEF1, MSX2, PAX9 and RUNX2 mRNA, but decreased BARX1 and PITX2 mRNA. CONCLUSIONS: It was concluded that WNT5A is expressed in human tooth development, and that p42/44 MAPK, p38 MAPK, JNK and AKT signal pathways and DLX1, DLX2, LEF1, MSX2, PAX9, RUNX2 could be activated by Wnt5a.
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BACKGROUND: The categories of recognized transferable quinolone resistance determinants have been increasing sharply. The rapid horizontal transfer of these quinolone resistance genes has caused concern since they bring new dissem...
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BACKGROUND: The categories of recognized transferable quinolone resistance determinants have been increasing sharply. The rapid horizontal transfer of these quinolone resistance genes has caused concern since they bring new dissemination possibilities for quinolone resistance. METHODS: In total, 579 clinical Escherichia coli isolates were subjected to antimicrobial susceptibility testing, screening for qnr alleles, qepA and aac-(6')-Ib-cr by PCR amplification and DNA sequence analysis. Isolates containing transferable quinolone resistance determinants were further characterized by mutation analysis in the quinolone resistance determining regions (QRDRs) of GyrA and ParC, phylogenetic typing and PFGE to determine their genetic relatedness. RESULTS: After PCR screening and sequence analysis, transferable quinolone resistance determinants were identified in 74 of 579 E. coli isolates (12.8%). The antimicrobial resistance profiles and phylogenetic groups differed between isolates containing different categories of transferable quinolone resistance determinant. Most of the isolates containing qepA alone were highly resistant to ciprofloxacin (MIC >or= 512 mg/L) and belonged to phylogenetic group D (22/25), while most of the isolates containing aac-(6')-Ib-cr alone belonged to phylogenetic group A (17/35) or D (16/35). Of 74 E. coli isolates containing transferable quinolone resistance determinants, 69 PFGE patterns and 19 clusters were identified. CONCLUSIONS: The great genetic variation of E. coli hosts containing transferable quinolone resistance determinants demonstrated the high transmission capacity of these mechanisms. It is urgent to characterize and block their transmission routes in order that the utility of quinolones is preserved.
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BACKGROUND: The impact of STAT-3 expression on the apoptosis of human hepatomas cell SMMC-7721 line induced by X-ray and carbon ion irradiations was investigated. METHODS: Human hepatoma SMMC-7721 cells were irradiated with a carb...
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BACKGROUND: The impact of STAT-3 expression on the apoptosis of human hepatomas cell SMMC-7721 line induced by X-ray and carbon ion irradiations was investigated. METHODS: Human hepatoma SMMC-7721 cells were irradiated with a carbon ion beam and X-ray. Cell survival was determined by a standard colony-forming assay. STAT-3 protein expression was analysed by Western Immunoblots. Cell cycle and apoptosis were performed by flow cytometry. RESULTS: The viability of SMMC-7721 cells decreased with increasing dose of the carbon ion beam, and the high-LET carbon ion beam led to the cells getting arrested at G(2)/M phase. Western Blot analyses show that STAT-3 expression increased with increasing radiation dose. The carbon ion irradiation induced cell apoptosis and significantly promoted the expression of STAT-3 gene compared with the X-ray irradiation. The apoptosis rate is correlated with the expression of STAT-3 in human hepatoma SMMC-7721 cells after exposure to different doses of X-ray and heavy ion beam. CONCLUSIONS: Heavy ion irradiation increases the expression of STAT-3 gene, makes SMMC-7721 cells arrested at G(2)/M phase and increases cell apoptosis in comparison with that induced by low-LET X-ray. The STAT-3 expression may be regarded as a protected reaction when the cancerous cells suffer a strong stimulus such as high-LET irradiation. The interaction of STAT-3 expression and other cytokines in human hepatoma and the relationship between STAT-3 and radiation-induced apoptosis remain to be clarified in the future.
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Vascular endothelial growth inhibitor (VEGI), also known as tumour necrosis factor superfamily member 15 (TNFSF15) and TNF ligand related molecule 1 (TL1), is a recently identified anti-angiogenic cytokine that belongs to the TNF ...
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Vascular endothelial growth inhibitor (VEGI), also known as tumour necrosis factor superfamily member 15 (TNFSF15) and TNF ligand related molecule 1 (TL1), is a recently identified anti-angiogenic cytokine that belongs to the TNF superfamily. Three isoforms of VEGI, VEGI 174, 192, and 251 have been documented, all sharing 151 common C-terminal amino acids but differing in their N-terminal regions. The investigations into the biological functions of VEGI have pointed to a potential cancer inhibitory role for the cytokine. The inhibitory effects of VEGI on cancer are manifested in three main areas, the direct effect on cancer cells, the anti-angiogenic effects on endothelial cells, and stimulation of maturation of dendric cells. The clinical aspect of VEGI in cancer is also being explored in recent years. The present article overviews the recent progress on this molecule and discusses the value of VEGI as a potential therapeutic target in cancer therapy.
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