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In this paper, three varieties of Elaeagnus conferta Roxb fruits prepared by ultrasonic-assisted extraction from a subtropical region southwest of China were utilized as raw materials to investigate their phenolic profiles, antioxidant activities, and protective effects on injured human umbilical vein endothelial cells (HUVECs). The ultra performance liquid chromatography-electrospray ionization tandem mass spectrometry (UPLC-ESI-MS/MS) findings revealed that fifteen substances, including seven phenolic acids, seven flavonoids, and one gallic acid derivative, were discovered. The dihydromyricetin, ellagic acid, gallic acid were the predominant phenolic compounds in all E.conferta fruits. These E.conferta fruits extracts shown excellent antioxidant activity varied from 2.258 ± 0.03 ~ 7.844 ± 0.39 µM Trolox/g and protective effect on HUVECs injured by H2O2 through decrease the level of ROS, MDA, LDH and enhance the SOD level. These finding indicate that E.conferta is a valuable source of high-capacity antioxidants that might be used as an alternative material for food industries.
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The metastasis-associated lung adenocarcinoma transcription 1 (Malat1) is a long non-coding RNA (lncRNA), exerts oncogenic role in multiple cancers, including hepatocellular carcinoma (HCC). This study was aimed to investigate its posttranscriptional regulation in HCC cells. RT-PCR was performed to monitor the expression levels of Malat1 in normal liver and HCC cell lines. The expression of Malat1, microRNA (miR)-195, and epidermal growth factor receptor (EGFR) in HepG2 and MHCC97 cells was respectively or synchronously altered by transfection. Then the changes in cell viability, apoptotic cell rate, cell cycle distribution, migration, and invasion were respectively assessed. As a result, we found that Malat1 was highly expressed in HCC cell lines when compared to normal liver cells. Malat1 silence suppressed HCC cells viability, migration and invasion, induced apoptosis, and arrested more cells in G0/G1 phase. Malat1 acted as a circular endogenous RNA (ceRNA) for miR-195. Malat1 silence could not suppress HCC cell growth and motility when miR-195 was knocked down. EGFR was a direct target of miR-195. miR-195 overexpression could not suppress HCC cell growth and motility when the 3'UTR site of EGFR was overexpressed. Furthermore, Malat1 silence blocked the activation of PI3K/AKT and JAK/STAT pathways, while EGFR overexpression activated them. Our study demonstrates Malat1-miR-195-EGFR axis plays a critical role in HCC cells which provided a better understanding of Malat1 in HCC.
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Carcinoma Hepatocelular/genética , Receptores ErbB/genética , Técnicas de Silenciamento de Genes , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Sobrevivência Celular , Regulação Neoplásica da Expressão Gênica , Células Hep G2 , HumanosRESUMO
The fireworks industry has long struggled with the problem of safety. Scientific, reasonable, and operable evaluation models are prerequisites of reducing risk. Based on the data from over 100 fireworks production safety accidents in China from 2010 to 2022, two evaluation models were established from the perspective of safety risk definition. Firstly, a weight calculation derivative method, the frequency-based analytic network process (ANP), was proposed creatively. This method optimized the importance ranking index calculation process in the ANP by considering the causal frequency of risk factors in the historical accident samples, thus determining how much each indicator affects the likelihood of accidents. Secondly, utilizing the historical accident samples as the dataset, a back propagation neural network (BPNN) model was developed to extract the mathematical relationship between each risk factor and the severity of accident consequence. Finally, the frequency-based ANP and BPNN models were combined to determine the safety risk level of the fireworks production enterprises. Meanwhile, the safety evaluation research samples were used as the comparison set for empirical study with historical accident samples, involving 100 fireworks production enterprises in China evaluated from 2017 to 2020. The significance result of zero shows that there is a statistically significant difference between the likelihood evaluation results of the accident and non-accident companies. Additionally, the severity evaluation model exhibits an excellent result, revealing a classification accuracy of 98.21 %, a mean square error of 8.97 × 10-4, a percent bias of 1.24 %, and a correlation coefficient and Nash-Sutcliffe efficiency coefficient both of 0.96. The frequency-based ANP and BPNN models integrate self-learning, self-adaptive, and fuzzy information processing, obtaining more accurate and objective evaluation results. This work provides a new strategy for the promotion and application of artificial intelligence in the field of safety risk evaluation, thus offering real-time safety risk evaluation and decision support of the safety management for the enterprises.
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It is important to investigate how to achieve carbon unlocking in the transport sector, especially in transport infrastructure, in order to contribute to the achievement of carbon neutrality targets and the 2030 Sustainable Development Goals. This study aims to investigate the necessary and sufficient conditions to achieve carbon unlocking in transport infrastructure. To achieve this, a combination of partial least squares structural equation modeling (PLS-SEM) and necessary condition analysis (NCA) methods have been used to examine whether there are unidentified necessity factors beyond the currently recognized 'technology-in-institution' (TIC) lock-in. This study also explores how the carbon unlocking of transport infrastructure can be achieved through the unlocking of relevant factors. The study includes 366 points from a subjective questionnaire from the government, transport infrastructure researchers, and relevant businesspeople. We found that, at the adequacy level, achieving institutional and technological unlocking is sufficient and economic factors have little impact on transport infrastructure (0.06), and that institutional and technical factors have a large impact on carbon unlocking (0.453, 0.280); however, from the necessary point of view, carbon unlocking at the economic level is necessary to achieve the goal of a medium to high level of carbon unlocking. To achieve carbon unlocking at this level (over 50%), a combination of technological, institutional, and economic factors is required. To achieve full carbon unlocking, the technology, system, and economy need to be at least 0.533, 0.791, and 0.63 unlocked. Therefore, we can conclude that by using the joint analysis of PLS-SEM and NCA, we have achieved an extension of the traditional TIC and identified sufficient and necessary conditions to achieve a medium to high degree of carbon unlocking.
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Carbono , Desenvolvimento Sustentável , Análise dos Mínimos Quadrados , Análise de Classes Latentes , TecnologiaRESUMO
Public health and effective risk response cannot be promoted without a coordinated emergency process during a natural disaster. One primary problem with the emergency relief chain is the homogeneous layout of rescue organizations and reserves. There is a need for government-enterprise coordination to enhance the systemic resilience and demand orientation. Therefore, a bi-level multi-phase emergency plan model involving procurement, prepositioning and allocation is proposed. The tradeoff of efficiency, economy and fairness is offered through the multi-objective cellular genetic algorithm (MOCGA). The flood emergency in Hunan Province, China is used as a case study. The impact of multi-objective and coordination mechanisms on the relief chain is discussed. The results show that there is a significant boundary condition for the coordinated location strategy of emergency facilities and that further government coordination over the transition phase can generate optimal relief benefits. Demand orientation is addressed by the proposed model and MOCGA, with the realization of the process coordination in multiple reserves, optimal layout, and transition allocation. The emergency relief chain based on government-enterprise coordination that adapts to the evolution of disasters can provide positive actions for integrated precaution and health security.
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Planejamento em Desastres , Desastres , Serviços Médicos de Emergência , Planejamento em Desastres/métodos , Inundações , GovernoRESUMO
Public safety and health cannot be secured without the comprehensive recognition of characteristics and reliable emergency response schemes under the disaster chain. Distinct from emergency resource allocation that focuses primarily on a single disaster, dynamic response, periodic supply, and assisted decision-making are necessary. Therefore, we propose a multiobjective emergency resource allocation model considering uncertainty under the natural disaster chain. Resource allocation was creatively combined with path planning through the proposed multiobjective cellular genetic algorithm (MOCGA) and the improved A* algorithm with avoidance of unexpected road elements. Furthermore, timeliness, efficiency, and fairness in actual rescue were optimized by MOCGA. The visualization of emergency trips and intelligent avoidance of risk areas were achieved by the improved A* algorithm. The effects of logistics performance, coupling of disaster factors, and government regulation on emergency resource allocation were discussed based on different disaster chain scenarios. The results show that disruption in infrastructure support, cascading effect of disasters, and time urgency are additional environmental challenges. The proposed model and algorithm work in obtaining the optimal solution for potential regional coordination and resilient supply, with a 22.2% increase in the total supply rate. Cooperative allocation complemented by political regulation can be a positive action for successfully responding to disaster chains.
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Planejamento em Desastres , Desastres , Desastres Naturais , Algoritmos , Planejamento em Desastres/métodos , Alocação de RecursosRESUMO
BACKGROUND: Pancreatic carcinoma (PC) is one of the most aggressive cancers affecting human health. It is essential to identify candidate biomarkers for the diagnosis and prognosis of PC. The present study aimed to investigate the diagnosis and prognosis biomarkers of PC. METHODS: Differentially expressed genes (DEGs) were identified from the mRNA expression profiles of GSE62452, GSE28735 and GSE16515. Functional analysis and the protein-protein interaction network analysis was performed to explore the biological function of the identified DEGs. Diagnosis markers for PC were identified using ROC curve analysis. Prognosis markers were identified via survival analysis of TCGA data. The protein expression pattern of the identified genes was verified in clinical tissue samples. A retrospective clinical study was performed to evaluate the correlation between the expression of candidate proteins and survival time of patients. Moreover, comprehensive analysis of the combination of multiple genes/proteins for the prognosis prediction of PC was performed using both TCGA data and clinical data. In vitro studies were undertaken to elaborate the potential roles of these biomarkers in clonability and invasion of PC cells. FINDINGS: In total, 389 DEGs were identified. These genes were mainly associated with pancreatic secretion, protein digestion and absorption, cytochrome P450 drug metabolism, and energy metabolism pathway. The top 10 genes were filtered out following Fisher's exact test. ROC curve analysis demonstrated that TMPRSS4, SERPINB5, SLC6A14, SCEL, and TNS4 could be used as biomarkers for the diagnosis of PC. Survival analysis of TCGA data and clinical data suggested that TMC7, TMPRSS4, SCEL, SLC2A1, CENPF, SERPINB5 and SLC6A14 can be potential biomarkers for the prognosis of PC. Comprehensive analysis show that a combination of identified genes/proteins can predict the prognosis of PC. Mechanistically, the identified genes attributes to clonability and invasiveness of PC cells. INTERPRETATION: We synthesized several sets of public data and preliminarily clarified pathways and functions of PC. Candidate molecular markers were identified for diagnosis and prognosis prediction of PC including a novel gene, TMC7. Moreover, we found that the combination of TMC7, TMPRSS4, SCEL, SLC2A1, CENPF, SERPINB5 and SLC6A14 can serve as a promising indicator of the prognosis of PC patients. The candidate proteins may attribute to clonability and invasiveness of PC cells. This research provides a novel insight into molecular mechanisms as well as diagnostic and prognostic markers of PC. FUND: National Natural Science Foundation of China [No. 81602646 &81802339], Natural Science Foundation of Guangdong Province [No. 2016A030310254] and China Postdoctoral Science Foundation [No. 2016M600648].
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Biomarcadores Tumorais , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Ontologia Genética , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/mortalidade , Prognóstico , Modelos de Riscos Proporcionais , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas , Curva ROC , Transcriptoma , Neoplasias PancreáticasRESUMO
Hepatocellular carcinoma (HCC) is a leading cause of tumour-associated mortality worldwide, but no significant improvement in treating HCC has been reported with currently available systemic therapies. Immunotherapy represents a new frontier in tumour therapy. Therefore, the immunobiology of hepatocarcinoma has been under intensive investigation. Decoy receptor 3 (DcR3), a member of the tumour necrosis factor receptor (TNFR) superfamily, is an immune suppressor associated with tumourigenesis and cancer metastasis. However, little is known about the role of DcR3 in the immunobiology of hepatocarcinoma. In this study, we found that overexpression of DcR3 in HCC is mediated by the TGFß3-Smad-Sp1 signalling pathway, which directly targets DcR3 promoter regions. Moreover, overexpression of DcR3 in HCC tissues is associated with tumour invasion and metastasis and significantly promotes the differentiation and secretion of Th2 and Treg cells while inhibiting the differentiation and secretion of Th1 cells. Conversely, knockdown of DcR3 expression in HCC significantly restored the immunity of CD4+ T cells. Inhibition of DcR3 expression may provide a novel immunotherapeutic approach to restoring immunity in HCC patients.
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OBJECTIVE: To investigate the relapse of patients with chronic hepatitis B (CHB) undergoing first and repeated recombinant interferon-alpha (rIFN-alpha) therapy during long-term follow up. METHOD: Five hundred and twenty three patients with chronic hepatitis B including 403 hepatitis B e-antigen (HBeAg) positive patients and 120 HBeAg negative ones were treated with 5MU recombinant interferon-alpha 1b (rIFN-alpha1b) subcutaneously thrice weekly for 6 - 25 (median 10) months. For each patient, serum alanine aminotransferase (ALT) was measured biochemically and serum HBV DNA level was detected by fluorescent-quantitative PCR, HBeAg with enzyme immunoassay every 1 - 3 month during therapy and every 3 - 6 month during the follow up period. Some of the individuals who relapsed during the follow-up period were treated with interferon-alpha repeatedly. RESULTS: Ratios of early response to interferon-alpha were similar in HBeAg positive patients (55.8%, 225/403), and HBeAg negative patients (64.2%, 77/120) at the end of naive treatment (chi(2) = 2.633, P = 0.105). 39.4% (119/302) of early responders relapsed during 39 +/- 22-month follow up, and relapse rates in HBeAg negative group (55.8%, 43/77) were higher than those in HBeAg positive group (33.8%, 76/225) at the end of follow up (chi(2) = 19.335, P = 0.000). Divided the follow-up period into six fragments as 1 - 12 months, 13 - 24 months, 25 - 36 months, 37 - 48 months, 48 - 60 months and > or = 61 months, we found that the differences of relapse incidence were significant (chi(2) = 73.518, df = 5, P = 0.000), and accumulative relapse rates were significant too (chi(2) = 32.167, df = 5, P = 0.000) in all follow-up periods. Constituent ratios of HBeAg in relapsed patients of every follow-up period were similar. 57 relapsed individuals (25 in HBeAg positive group and 32 in HBeAg negative group) were retreated with interferon-alpha, and complete response were achieved in all cases at the end of repeated therapy. The relapse rates in HBeAg positive group (52.0%, 13/25) were higher than in HBeAg negative group (21.9%, 7/32) during the follow-up period after the end of retreatment (chi(2) = 5.592, P = 0.018). CONCLUSION: Rates of early response to interferon-alpha therapy were similar in HBeAg positive and HBeAg negative patients at the end of nave treatment, and relapse rates in HBeAg negative group were higher than in HBeAg positive group during long term follow-up. Combined response was achieved in all relapse cases received repeated interferon-alpha therapy at the end of retreatment. The relapse rates in HBeAg positive group were higher than in HBeAg negative group during the follow-up period after repeated therapy.
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Vírus da Hepatite B/efeitos dos fármacos , Hepatite B Crônica/tratamento farmacológico , Interferon Tipo I/uso terapêutico , Adulto , Alanina Transaminase/sangue , Antivirais/uso terapêutico , DNA Viral/sangue , DNA Viral/genética , Feminino , Seguimentos , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Hepatite B Crônica/patologia , Hepatite B Crônica/virologia , Humanos , Técnicas Imunoenzimáticas , Masculino , Reação em Cadeia da Polimerase , Proteínas Recombinantes , Recidiva , Fatores de Tempo , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the relationship of virological breakthrough and production of neutralizing anti-interferon antibody (NAb) in chronic hepatitis B patients treated with recombinant interferon-alpha (rIFN-alpha). METHOD: Four hundred eighty-five patients with histological proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha1b) thrice weekly for 6-37 months (median 10). Serum HBV DNA, HBeAg and NAb levels of the patients were detected by fluorescent-quantitative PCR, enzymoimmunoassay and antiviral neutralizing biological assay respectively during the therapy. RESULTS: Virological breakthrough occurred in 66 patients (13.6%), and NAb was found in 98 patients (20.2%) of the total 485 patients. The rate of NAb positivity was higher in patients with viral breakthrough than those without it (68.2%, 45/66, vs 12.6%, 53/419, chi(2)=109.06, P < 0.01), and viral breakthrough occurred more in patients with positive NAb than with negative NAb (45.9%, 45/98, vs 5.4%, 21/387, chi(2)=109.06, P < 0.01). The time of the viral breakthrough occurrence and the time of NAb production had a significant correlation (P < 0.01). The occurrence of viral breakthrough was also influenced by the age of patients (P < 0.05) and HBeAg status (P < 0.01) before they were treated. CONCLUSION: Viral breakthrough occurred in 13.6% of our 485 chronic hepatitis B patients treated with recombinant interferon-alpha. Their viral breakthrough and production of NAb production had a significant correlation.
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Anticorpos Anti-Hepatite B/biossíntese , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/virologia , Interferon Tipo I/uso terapêutico , Adulto , Anticorpos Neutralizantes/biossíntese , Feminino , Vírus da Hepatite B/imunologia , Humanos , Masculino , Proteínas Recombinantes , Adulto JovemRESUMO
Dysregulation of microRNAs (miRNAs) is actively involved in the pathogenesis and tumorigenicity of hepatocellular carcinoma (HCC). miR-489 was found to play either oncogenic or tumor suppressive roles in human cancers. Recent study reported that the levels of miR-489 in late recurrent HCC patients were evidently higher than that in early recurrent cases, suggesting that miR-489 may function as a tumor suppressive miRNA in HCC. Yet, the clinical value and biological function of miR-489 remain rarely known in HCC. Here, we presented that miR-489 level in HCC tissues was notably reduced compared to matched non-cancerous specimens. Its decreased level was evidently correlated with adverse clinical parameters and poor prognosis of HCC patients. Accordingly, the levels of miR-489 were obviously down-regulated in HCC cells. Ectopic expression of miR-489 in HCCLM3 and MHCC97H cells prominently inhibits the migration and invasion of tumor cells and reduced lung metastases in vivo, while miR-489 knockdown increased these behaviors of HepG2 and MHCC97L cells. Mechanically, miR-489 negatively regulated matrix metalloproteinase-7 (MMP7) abundance in HCC cells. Herein, MMP7 was found to be a downstream molecule of miR-489 in HCC. An inversely correlation between miR-489 and MMP7 was confirmed in HCC specimens. MMP7 knockdown prohibited cell migration and invasion while MMP7 overexpression showed opposite effects on HCC cells. Furthermore, restoration of MMP7 expression could abrogate the anti-metastatic effects of miR-489 on HCCLM3 cells with enhanced cell migration and invasion. Altogether, miR-489 potentially acts as a prognostic predictor and a drug-target for HCC patients.
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Drug resistance to sorafenib is common in patients with hepatocellular carcinoma(HCC). We examined the effects of a combination of sorafenib and fluvastatin on HCC using in vitro and in vivo models. The dual treatment induced apoptosis and reduced cellular viability in HCC more effectively than either drug alone. The combination treatment also inhibited activation of hepatic stellate cells, whereas single drug treatments did not. On a molecular level, combined treatment inhibited activation of the MAPK and NF-κB pathways via Toll-like receptor 4 in HCC cells. Combined treatment also inhibited expression of stromal cell-derived factor 1α in HCC cells, which further inhibited the MAPK pathway in hepatic stellate cells. These results suggest that a combination of sorafenib and fluvastatin may be a promising therapeutic strategy for patients with advanced HCC.
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Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Hepatocelular/tratamento farmacológico , Ácidos Graxos Monoinsaturados/farmacologia , Indóis/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Adulto , Animais , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sinergismo Farmacológico , Ácidos Graxos Monoinsaturados/administração & dosagem , Feminino , Fluvastatina , Células Hep G2 , Humanos , Indóis/administração & dosagem , Neoplasias Hepáticas/patologia , Masculino , Pessoa de Meia-Idade , Niacinamida/administração & dosagem , Niacinamida/farmacologia , Compostos de Fenilureia/administração & dosagem , Ratos , Ratos Wistar , Transdução de Sinais , SorafenibeRESUMO
Zinc finger and BTB domain-containing 20 (ZBTB20) is a new BTB/POZ-domain gene and a member of the POK family of transcriptional repressors. Notably, the role of ZBTB20 and its underlying mechanisms involved in hepatocarcinogenesis are poorly investigated. In this study, the expression of ZBTB20 was significantly overexpressed in hepatocellular carcinoma (HCC) tissues. The positive expression of ZBTB20 was associated with large tumor size, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage. Additionally, HCC patients with positive expression of ZBTB20 had a poorer 5-year survival. Multivariate analyses revealed that ZBTB20 overexpression was an independent prognostic factor for HCC. Gain- and loss-of-function experiments demonstrated that ZBTB20 promoted HCC cell viability, proliferation, tumorigenicity, and cell cycle progression. Mechanistically, Cyclin D1 and Cyclin E were increased, while p21 and p27 were decreased by ZBTB20 in HCC cells. FoxO1 was inversely correlated with ZBTB20 protein expression in the same cohort of HCC specimens. We further revealed that FoxO1 was transcriptionally repressed by ZBTB20 in HCC. Moreover, restoration of FoxO1 expression partially abrogated ZBTB20-induced HCC cell proliferation and growth entry in vitro and in vivo. Collectively, these results indicate that ZBTB20 may serve as a prognostic marker and promotes tumor growth of HCC via transcriptionally repressing FoxO1.
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Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/patologia , Proteína Forkhead Box O1/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Proteínas do Tecido Nervoso/metabolismo , Fatores de Transcrição/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Proliferação de Células , Feminino , Proteína Forkhead Box O1/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Proteínas do Tecido Nervoso/genética , Prognóstico , Regiões Promotoras Genéticas , Taxa de Sobrevida , Fatores de Transcrição/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , Dedos de ZincoRESUMO
Decoy receptor 3 (DcR3), a novel member of the tumor necrosis factor receptor (TNFR) family, was recently reported to be associated with tumorigenesis and metastasis. However, the role of DcR3 in human colorectal cancer (CRC) has not been fully elucidated. In this study, we found that DcR3 expression was significantly higher in human colorectal cancer tissues than in paired normal tissues, and that DcR3 expression was strongly correlated with tumor invasion, lymph node metastases and poor prognoses. Moreover, DcR3 overexpression significantly enhanced CRC cell proliferation and migration in vitro and tumorigenesis in vivo. Conversely, DcR3 knockdown significantly repressed CRC cell proliferation and migration in vitro, and DcR3 deficiency also attenuated CRC tumorigenesis and metastasis in vivo. Functionally, DcR3 was essential for TGF-ß3/SMAD-mediated epithelial-mesenchymal transition (EMT) of CRC cells. Importantly, cooperation between DcR3 and TGF-ß3/SMAD-EMT signaling-related protein expression was correlated with survival and survival time in CRC patients. In conclusion, our results demonstrate that DcR3 may be a prognostic biomarker for CRC and that this receptor facilitates CRC development and metastasis by participating in TGF-ß3/SMAD-mediated EMT of CRC cells.
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Neoplasias Colorretais/patologia , Transição Epitelial-Mesenquimal , Membro 6b de Receptores do Fator de Necrose Tumoral/genética , Membro 6b de Receptores do Fator de Necrose Tumoral/metabolismo , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HCT116 , Células HT29 , Humanos , Camundongos , Transplante de Neoplasias , Prognóstico , Transdução de Sinais , Proteínas Smad/metabolismo , Fator de Crescimento Transformador beta3/metabolismo , Regulação para CimaRESUMO
OBJECTIVE: To explore the patterns of temperature changes of patients with the severe acute respiratory syndrome (SARS) and the effect of glucocorticoid hormone on the temperature of these patients. METHODS: The clinical data of 94 SARS cases treated during the outbreak of SARS in South China in 2003 were collected for a retrospective review. According to different treatment regimens, the patients were divided into hormone group (n=35) and non-hormone group (n=59). The control groups consisted of 65 patients with interstitial pneumonia, 78 with bacterial pneumonia and 57 with upper respiratory tract infection. The changes in body temperature were compared between the SARS patients and those with other respiratory diseases and the effect of glucocorticoid hormone on controlling body temperature of the SARS patients was explored. RESULTS: The body temperature of patients with the 4 diseases all exhibited obvious reduction 7 days after hospitalization (P<0.001) with only subsequent mild fluctuation within the basically normal range. At each time point of measurement, the body temperature of SARS patients was significantly higher than that of patients with other diseases (P<0.03), with a fluctuation of 0.2 to 0.5 degrees C; and following a pattern of variation similar to those of the other diseases. Of the 4 time points of daily measurement, namely 6, 10, 14 and 18 o'clock, the temperature measured at 14 o'clock was significantly higher than those at the other 3 time points (P<0.001). Hormone therapy did not significantly affect the temperature of SARS patients (P=0.180), who had longer duration of high fever. CONCLUSION: SARS patients have higher body temperature and longer duration of high fever. Hormone therapy may not produce significant effect in controlling the temperature of SARS patients.
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Regulação da Temperatura Corporal/efeitos dos fármacos , Febre/tratamento farmacológico , Glucocorticoides/uso terapêutico , Síndrome Respiratória Aguda Grave/tratamento farmacológico , Adulto , Feminino , Febre/etiologia , Humanos , Masculino , Estudos RetrospectivosRESUMO
OBJECTIVE: To study the causes of poorer antiviral response to neutralizing anti-interferon-alpha antibodies (NA) in male chronic hepatitis B patients treated with recombinant interferon-alpha (rIFN-alpha). METHODS: Two hundred sixty-nine patients (198 males and 71 females) with histologically proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha 1b) subcutaneously thrice weekly for 6-37 (median 10.0) months. For each patient, serum HBV DNA levels were detected with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay, and NA with an antiviral neutralizing biological assay during therapy. RESULTS: NA was found in 70 (35.4%) of the 198 males and in 15 (21.1%) of the 71 females during treatment (x2 = 4.894, P = 0.027). At the end of treatment combined-response was achieved in 21 (24.7%) of the 85 NA-positive patients and in 100 (54.3%) of the 184 NA-negative cases (x2 = 20.642). Stratification analysis by NA showed that combined-response rate was significantly lower in males than in females (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among NA-positive patients while it was similar in males and in females (50.8%, 65/128, vs. 62.5%, 35/56, x2 = 2.156) among NA-negative patients. In stratification analysis by gender, it was significantly lower in NA-positive patients than in NA-negative ones (18.6%, 13/70 vs. 53.3%, 8/15, x2 = 8.024) among males but there was no significant difference between combined-response rates among females. CONCLUSION: The poorer antiviral response to recombinant interferon-alpha in male chronic hepatitis B patients than in female patients is related to the neutralizing anti-interferon antibodies.
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Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/imunologia , Interferon Tipo I/uso terapêutico , Anticorpos/sangue , Antivirais/imunologia , DNA Viral/sangue , Feminino , Humanos , Interferon Tipo I/imunologia , Masculino , Testes de Neutralização , Proteínas Recombinantes , Fatores Sexuais , Resultado do TratamentoRESUMO
Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. Aberrant expression of miRNAs contributes to HCC development. Here, we observed elevated miR-520g expression in tumor samples from HCC patients with relapse and metastasis, and this high miR-520g expression was correlated with poor survival. Through gain- and loss-of-function studies, miR-520g was demonstrated to facilitate HCC cell migration, invasion and epithelial-mesenchymal transition (EMT). SMAD7 was identified as a direct target of miR-520g. Accordingly, we conclude that high miR-520g expression promotes HCC cell mobility and EMT by targeting SMAD7, and this is correlated with reduced survival in HCC patients.
Assuntos
Carcinoma Hepatocelular/metabolismo , Transição Epitelial-Mesenquimal , Neoplasias Hepáticas/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Neoplásico/metabolismo , Proteína Smad7/metabolismo , Adulto , Idoso , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/patologia , Intervalo Livre de Doença , Feminino , Células Hep G2 , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Metástase Neoplásica , Proteínas de Neoplasias/genética , RNA Neoplásico/genética , Proteína Smad7/genética , Taxa de SobrevidaRESUMO
OBJECTIVE: To discuss the diagnostic value of ultrasonic examination in patients with early liver cirrhosis and the relation with different stages of liver fibrosis. METHODS: In the series, 263 patients with chronic hepatitis B were under taken liver biopsy and ultrasonic examination of type B for determination of liver cirrhosis images, width of the main portal vein and the splenic vein, tumefaction of the spleen. Data were analysed statistically. RESULTS: Sixties of 263 patients were diagnosed as early liver cirrhosis. The diagnostic sensitivity, specificity, misdiagnostic rate, missed diagnostic rate, and Jonden's index of ultrasonic examination for early liver cirrhosis were 52.5%, 88.3%, 11.7%, 47.5%, and 0.508, respectively. The width of the main portal vein with liver fibrosis of S1, S2, S3, and S4 were 10.93 mm +/- 1.25 mm, 11.35 mm +/- 1.06 mm,11.29 mm +/- 1.52 mm, and 11.4 8mm +/- 1.25 mm, respectively with statistic difference between S4 and S1 (P=0.03). The width of the spleen vein of S1, S2, S3, and S4 were 6.518 mm +/- 2.033 mm, 7.190 mm +/- 1.569 mm, 7.444 mm +/- 1.805 mm and 8.406 mm +/- 2.227 mm, respectively with statistic difference between S4 and S2 (P=0.035). The incidence of tumefaction of the spleen was increased with the degree of liver fibrosis. CONCLUSIONS: The diagnostic sensitivity of ultrasonic examination for early liver cirrhosis is low. The width of the main portal vein, the spleen vein and the incidence of tumefaction of the spleen are related with the degree of liver fibrosis. The regeneration node of liver cirrhosis may contribute to the development of portal hypertension.
Assuntos
Cirrose Hepática/diagnóstico por imagem , Ultrassonografia Doppler em Cores/métodos , Adolescente , Adulto , Criança , Feminino , Hepatite B Crônica/complicações , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/patologia , Masculino , Veia Porta/diagnóstico por imagem , Veia Porta/patologia , Sensibilidade e Especificidade , Veia Esplênica/diagnóstico por imagem , Veia Esplênica/patologiaRESUMO
OBJECTIVE: To investigate the clinical significance of neutralizing anti-interferon-alpha antibodies (NA) in chronic hepatitis B patients treated with recombinant interferon-alpha(rIFN-alpha). METHODS: One hundred and eighty-one patients (128 male and 53 female) with histological proven chronic hepatitis B were treated with 5 MU recombinant interferon-alpha 1b (rIFN-alpha 1b) subcutaneously thrice weekly for 6 to 37 (median 10) months. For each patient, Specific detection of serum HBV DNA level with fluorescent-quantitative PCR, HBeAg with enzymoimmunoassay and NA with an antiviral neutralizing biological assay were performed during therapy. RESULTS: NA was found in 61 (33.7%) of 181 patients. At the end of treatment, complete-response was achieved in 17 (27.9%) of 61 patients with NA and in 54 (45.0%) of 120 patients without NA, respectively (chi2=4.979). For NA positive patients, the complete-response rate was significantly lower in those who had not achieved partial-response prior to or at the same time as NA occurred than in those who did (3.8%, 1/26, vs. 45.7%, 16/35, chi2 = 7.457). Moreover, it was lower in patients who either had 20pg/ml of serum HBV DNA or above or HBV DNA had being reduced by less than 60% recent 3 months, but higher in those who had less than 20pg/ml of HBV DNA and HBV DNA had being reduced by 60% or above (20.0%, 9/45, vs. 56.3%, 9/16, chi2 = 11.009). CONCLUSION: NA may negate the antiviral effects of rIFN-alpha in chronic hepatitis B patients treated with rIFN-alpha, especially if they appear before partial-response or at the occasion at which serum HBV DNA level was not below 20pg/ml or HBV DNA had being reduced by less than 60% recent 3 months.
Assuntos
Anticorpos/sangue , Hepatite B Crônica/tratamento farmacológico , Interferon-alfa/imunologia , Interferon-alfa/uso terapêutico , DNA Viral/sangue , Feminino , Hepatite B Crônica/virologia , Humanos , Masculino , Proteínas Recombinantes/uso terapêuticoRESUMO
A combination of nucleos(t)ides and hepatitis B immunoglobulin (HBIg) has been found to be effective for the prevention of hepatitis B viral (HBV) reinfection after liver transplantation (LT), but its administration is costly, and not always available. We report the case of a male, 33-year-old cirrhotic patient who has tested positive for serum HBsAg, and HBeAg, with 9.04 × 10(7) copies/mL of HBV DNA. He suffered from acute liver failure and was near death before undergoing emergency LT. No HBIg was available at the time, so only lamivudine was used. He routinely received immunosuppression medication. Serum HBV DNA and HBsAg still showed positive post-LT, and the graft re-infected. Hepatitis B flared three months later. Adefovir dipivoxil was added to the treatment, but in the 24(th) mo of treatment, the patient developed lamivudine resistance and a worsening of the hepatitis occurred shortly thereafter. The treatment combination was then changed to a double dosage of entecavir and the disease was gradually resolved. After 60-mo of post-LT nucleos(t)ide analogue therapy, anti-HBs seroconverted, and the antiviral was stopped. By the end of a 12-mo follow-up, the patient had achieved sustained recovery. In conclusion, the case seems to point to evidence that more potent and less resistant analogues like entecavir might fully replace HBIg as an HBV prophylaxis and treatment regimen.