RESUMO
Human infections with Salmonella enterica subspecies enterica serovar Senftenberg are often associated with exposure to poultry flocks, farm environments, or contaminated food. The recent emergence of multidrug-resistant isolates has raised public health concerns. In this study, comparative genomics and phenotypic analysis were used to characterize 14 Salmonella Senftenberg clinical isolates recovered from multiple outbreaks in Shenzhen and Shanghai, China, between 2002 and 2011. Single-nucleotide polymorphism analyses identified two phylogenetically distinct clades of S Senftenberg, designated SC1 and SC2, harboring variations in Salmonella pathogenicity island 1 (SPI-1) and SPI-2 and exhibiting distinct biochemical and phenotypic signatures. Although the two variants shared the same serotype, the SC2 isolates of sequence type 14 (ST14) harbored intact SPI-1 and -2 and hence were characterized by possessing efficient invasion capabilities. In contrast, the SC1 isolates had structural deletion patterns in both SPI-1 and -2 that correlated with an impaired capacity to invade cultured human cells and also the year of their isolation. These atypical SC1 isolates also lacked the capacity to produce hydrogen sulfide. These findings highlight the emergence of atypical Salmonella Senftenberg variants in China and provide genetic validation that variants lacking SPI-1 and regions of SPI-2, which leads to impaired invasion capacity, can still cause clinical disease. These data have identified an emerging public health concern and highlight the need to strengthen surveillance to detect the prevalence and transmission of nontyphoidal Salmonella species.
Assuntos
Surtos de Doenças , Infecções por Salmonella/epidemiologia , Infecções por Salmonella/microbiologia , Salmonella enterica/classificação , Salmonella enterica/isolamento & purificação , Sorogrupo , Adulto , Idoso , Técnicas de Tipagem Bacteriana , China/epidemiologia , Análise por Conglomerados , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Filogenia , Polimorfismo de Nucleotídeo Único , Salmonella enterica/genética , Adulto JovemRESUMO
A new object tracking mask-based novel-look-up-table (OTM-NLUT) method is proposed and implemented on graphics-processing-units (GPUs) for real-time generation of holographic videos of three-dimensional (3-D) scenes. Since the proposed method is designed to be matched with software and memory structures of the GPU, the number of compute-unified-device-architecture (CUDA) kernel function calls and the computer-generated hologram (CGH) buffer size of the proposed method have been significantly reduced. It therefore results in a great increase of the computational speed of the proposed method and enables real-time generation of CGH patterns of 3-D scenes. Experimental results show that the proposed method can generate 31.1 frames of Fresnel CGH patterns with 1,920 × 1,080 pixels per second, on average, for three test 3-D video scenarios with 12,666 object points on three GPU boards of NVIDIA GTX TITAN, and confirm the feasibility of the proposed method in the practical application of electro-holographic 3-D displays.
RESUMO
1. Minocycline, memantine,and glycoconjugate were assessed for their ability to protect cultured primary cortical neurons against double-stranded RNA-induced neurotoxicity. 2. Minocycline but not memantine or glycoconjugate protected cultured cells and warrants further investigation.
Assuntos
Antibacterianos/farmacologia , Minociclina/farmacologia , Fármacos Neuroprotetores/farmacologia , Síndromes Neurotóxicas/prevenção & controle , Análise de Variância , Apoptose , Caspase 3/metabolismo , Linhagem Celular Tumoral , Encefalite Japonesa/complicações , Antagonistas de Aminoácidos Excitatórios/farmacologia , Glicoconjugados/farmacologia , Humanos , L-Lactato Desidrogenase/metabolismo , Memantina/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/enzimologia , Neurônios/patologia , Síndromes Neurotóxicas/enzimologia , Síndromes Neurotóxicas/etiologia , RNA de Cadeia DuplaRESUMO
The term "human papillomavirus" has been used as the keyword during searching titles, abstracts, and keywords based on the online version of Science Citation Index (SCI), Web of Science from 1993 to 2008. Twelve document types were found among the 14,943 papers published in 1,072 journals that were listed in 99 SCI subject categories. All the articles referring to human papillomavirus were assessed by using the following aspects: characteristics of publication output, distribution of output in journals, publication output of source country, source institute, and analysis of word clusters in title, author keywords, and keywords plus. The results have shown that the USA ranked first using five publication indicators including total, single country, international, first author, and corresponding author publications. China has had the sharpest rise of publications since 2004. The top four European countries in 2008 were France, Germany, the UK, and Italy, respectively. Trend studies with word cluster analysis were performed with regards to the areas of immunology, screening methodology, behavioral sciences, economics, and meta-analysis. All those areas have shown a sharp upward rise since 2004. In addition, hypermethylation-induced inactivation of the p16 gene in the early stages of oncogenesis has been getting more interest in recent years.
Assuntos
Papillomaviridae , Publicações Periódicas como Assunto , Pesquisa , Humanos , Bibliometria , Publicações Periódicas como Assunto/tendências , Pesquisa/tendênciasAssuntos
Citocinas/metabolismo , Hipocampo/efeitos dos fármacos , Minociclina/administração & dosagem , Fármacos Neuroprotetores/administração & dosagem , Animais , Citocinas/administração & dosagem , Hipocampo/metabolismo , Masculino , Minociclina/farmacologia , Neuroglia/metabolismo , Neuropeptídeos/metabolismo , Fármacos Neuroprotetores/farmacologia , Ratos , Ratos Sprague-Dawley , Proteínas tau/metabolismoRESUMO
Recent studies suggest that glutaredoxin-1 (Glrx-1) may serve as therapeutic target for diabetic hearts. As the level of reactive oxygen species (ROS) is increased in the pathologic hearts including ischemia/reperfusion (I/R) and diabetes, we assumed that upregulation of Glrx-1 could reduce the cardiac risk factors associated with I/R and/or diabetes. Diabetes was induced in mice by i.p. injection of streptozotocin (150 mg kg(-1)). Eight days after when the blood glucose was elevated to 400 mg per 100 ml, the animals were randomly assigned to one of the following three groups, which received either empty vector, or LacZ or Glrx-1 adenoviral construct. Four days later, isolated working hearts were subjected to 30 min ischemia followed by 2 h reperfusion. Glrx-1 gene therapy significantly enhanced the Glrx-1 level, which prevented I/R-mediated reduction of ventricular recovery, increased myocardial infarct size and cardiomyocyte apoptosis in diabetic myocardium. In concert, Glrx-1 prevented diabetes and ischemia-reperfusion induced reduction of cardioprotective proteins including Akt, FoxO-1, and hemeoxygenase-1, and abolished the death signal triggered by Jnk, p38 mitogen-activated protein kinase, and c-Src. Glrx-1 gene therapy seems to prevent cardiac complications in diabetic heart due to the I/R by switching the death signal into survival signal by activating Akt-FoxO-signaling network.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Terapia Genética/métodos , Glutarredoxinas/metabolismo , Traumatismo por Reperfusão/terapia , Transdução de Sinais/genética , Adenoviridae , Animais , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Glutarredoxinas/genética , Heme Oxigenase-1/metabolismo , Imuno-Histoquímica , Camundongos , Miocárdio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Traumatismo por Reperfusão/genéticaRESUMO
Human monocytes use the products of phosphoinositide hydrolysis (1,2-diacylglycerol and inositol 1,4,5-triphosphate) as second messengers to trigger rapid cellular activation during the occupancy of chemoattractant receptors. The effect of chemoattractants on modulation of gene expression in monocytes was examined in this study. The chemoattractants FMLP and platelet-activating factor induced the progressive increase of c-fos RNA to 6-15-fold over those of control within 30 min after treatment. Similar kinetics of c-fos gene activation was also observed when cells were treated with PMA or sn-1,2-dioctanoylglycerol, but not with the calcium mobilizer ionomycin, suggesting a role for protein kinase C in gene regulation by chemoattractant receptors. Activation of c-fos gene expression by FMLP is mediated through a pertussis toxin-sensitive G protein, since pertussis toxin treatment of the cells blocked the induction of the c-fos gene by FMLP but not PMA. The level of c-myc RNA was slightly decreased after 1 h of treatment with chemoattractants, but not with PMA or diacylglycerol. This implies that chemoattractant receptor occupancy generates signals beyond protein kinase C activation that are capable of selectively downregulating monocyte gene expression. The effect of FMLP and PMA on the accumulation of c-fos RNA appears to result from altering both the rate of transcription and message stability. These observations indicate that signals generated through chemoattractant receptor occupancy may regulate monocyte function at the genetic level.
Assuntos
Regulação da Expressão Gênica/efeitos dos fármacos , Monócitos/efeitos dos fármacos , N-Formilmetionina Leucil-Fenilalanina/farmacologia , Fator de Ativação de Plaquetas , Proto-Oncogenes , Cicloeximida/farmacologia , Dactinomicina/farmacologia , Proteínas de Ligação ao GTP/fisiologia , Humanos , Monócitos/metabolismo , Toxina Pertussis , Biossíntese de Proteínas , Proteína Quinase C/análise , Acetato de Tetradecanoilforbol/farmacologia , Transcrição Gênica/efeitos dos fármacos , Ativação Transcricional , Fatores de Virulência de Bordetella/farmacologia , Microglobulina beta-2/genéticaRESUMO
BACKGROUND AND OBJECTIVE: Local persistent infection by Porphyromonas gingivalis leads to inflammatory systemic diseases, such as atherosclerosis. We have reported previously that avirulent P. gingivalis fimbriae-dependent invasion into endothelial cells might be involved in progression of atherosclerosis. Although interleukin-6 (IL-6) regulates progression of atherosclerosis, little is known about the relationship of P. gingivalis fimbriae-dependent invasion to IL-6 regulation in endothelial cells. MATERIAL AND METHODS: We examined the secretion of IL-6 and the expression of the IL-6 signal transducer gp130 in human umbilical vein endothelial cells (HUVEC) infected with the wild-type FDC381 strain of P. gingivalisand a fimbriae-deficient mutant (fimA) by enzyme-linked immunosorbent assay, quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometry (fluorescence-activated cell sorting, FACS) analysis. RESULTS: Coculture of HUVEC with P. gingivalis resulted in increase of IL-6 secretion at 24 h postinfection. Interestingly, the increase was inhibited significantly in HUVEC infected with the P. gingivalis fimA mutant. In addition, the increase of IL-6 secretion induced by P. gingivalis infection was significantly impaired by the meiosis specific kinase 1 inhibitor, PD98059, or the nuclear factor kappaB inhibitor, Bay11-7082. Furthermore, we demonstrated that gp130 expression increased with P. gingivalis infection. Importantly, gp130 expression was significantly impaired by P gingivalis fimA mutant infection compared with wild-type P. gingivalis infection, as assessed by both quantitative RT-PCR and FACS analysis. CONCLUSION: Our findings indicate that P. gingivalis fimbriae are important factors in the autocrine regulation of IL-6, by increasing gp130 in endothelial cells.
Assuntos
Comunicação Autócrina/imunologia , Receptor gp130 de Citocina/imunologia , Células Endoteliais/imunologia , Endotélio Vascular/imunologia , Fímbrias Bacterianas/imunologia , Interleucina-6/imunologia , Porphyromonas gingivalis/imunologia , Proteínas Quinases Dependentes de Cálcio-Calmodulina/antagonistas & inibidores , Células Cultivadas , Técnicas de Cocultura , Receptor gp130 de Citocina/análise , Células Endoteliais/microbiologia , Endotélio Vascular/microbiologia , Inibidores Enzimáticos/farmacologia , Proteínas de Fímbrias/genética , Proteínas de Fímbrias/imunologia , Flavonoides/farmacologia , Humanos , Interleucina-6/análise , Mutação/genética , NF-kappa B/antagonistas & inibidores , Nitrilas/farmacologia , Pili Sexual/genética , Pili Sexual/imunologia , Porphyromonas gingivalis/genética , Sulfonas/farmacologia , Veias Umbilicais/patologiaRESUMO
Novel biosorbent 'maize bran' has been successfully utilized for the removal of Cr(VI) from aqueous solution. The effect of different parameters such as contact time, sorbate concentration, pH of the medium and temperature were investigated and maximum uptake of Cr(VI) was 312.52 (mgg(-1)) at pH 2.0, initial Cr(VI) concentration of 200mgL(-1) and temperature of 40 degrees C. Effect of pH showed that maize bran was not only removing Cr(VI) from aqueous solution but also reducing toxic Cr(VI) into less toxic Cr(III). The sorption kinetics was tested with first order reversible, pseudo-first order and pseudo-second order reaction and it was found that Cr(VI) uptake process followed the pseudo-second order rate expression. Mass transfer of Cr(VI) from bulk to the solid phase (maize bran) was studied at different temperatures. Different thermodynamic parameters, viz., DeltaG degrees , DeltaH degrees and DeltaS degrees have also been evaluated and it has been found that the sorption was feasible, spontaneous and endothermic in nature. The Langmuir and Freundlich equations for describing sorption equilibrium were applied and it was found that the process was well described by Langmuir isotherm. Desorption studies was also carried out and found that complete desorption of Cr(VI) took place at pH of 9.5.
Assuntos
Agricultura , Cromo/isolamento & purificação , Resíduos Industriais , Zea mays , Difusão , Concentração de Íons de Hidrogênio , Cinética , Soluções , Termodinâmica , Água/químicaRESUMO
OBJECTIVES: The highly infectious human papillomavirus (HPV) causes both genital warts and cervical cancer in women. In 2009, the prevalence of genital warts in Hong Kong was 203.7 per 100,000 person-years. Cervical cancer, more seriously, was the eight most common cancer among women and girls in Hong Kong, accounting for 2.3% of all new cancer cases in females in 2014. Cervical cancer is a significant global public health problem and HPV is a major risk factor leading to the development of cervical cancer. HPV is also the most common sexually transmitted disease among university students. This is the first study to examine the acceptability of HPV vaccines and associations with perceptions related to HPV and HPV vaccines among the male baccalaureate student population locally. METHODS: A self-administrative cross-sectional survey was used to assess whether male baccalaureate students from eight local Hong Kong universities intended to be immunized for HPV. The study also asked questions concerning how its subjects perceived HPV and HPV vaccines using the Health Belief Model. Data collection spanned from June to September 2015. A multiple stepwise regression model was used to examine associations between cognitive factors and subjects' intention to take up the HPV vaccine. RESULTS: A total of 1,004 (83.7%) students aged 18 and 26 participated in this study. 23.3% found vaccinating for HPV acceptable, a level correlating with a number of indicators. Subjects were more likely to find vaccinating acceptable if 1) they knew something about HPV vaccines; 2) they understood that men were susceptible to infection by HPV; 3) they realised they could benefit by HPV vaccination, and 4) they were aware of the arguments for and against HPV vaccination, as disseminated by either the media or peers. CONCLUSIONS: HPV remains a significant public health concern in Hong Kong and China more broadly. This study's findings show a disconnect between the perceived and actual risk of being infected with the HPV vaccine among male baccalaureate students. This disconnect may be bridged by informing young men of the benefits of their being vaccinated against HPV, by removing the psychological and financial barriers that prevent them from taking up the vaccine and by improving how primary healthcare providers motivate them to get immunized.
Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Infecções por Papillomavirus/prevenção & controle , Vacinas contra Papillomavirus/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde , Estudantes/estatística & dados numéricos , Adolescente , Adulto , Estudos Transversais , Hong Kong , Humanos , Intenção , Masculino , Infecções por Papillomavirus/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Estudantes/psicologia , Inquéritos e Questionários , Universidades/estatística & dados numéricos , Adulto JovemRESUMO
There are considerable challenges in directly targeting the mutant p53 protein, given the large heterogeneity of p53 mutations in the clinic. An alternative approach is to exploit the altered fitness of cells imposed by loss-of-wild-type p53. Here we identify niclosamide through a HTS screen for compounds selectively killing p53-deficient cells. Niclosamide impairs the growth of p53-deficient cells and of p53 mutant patient-derived ovarian xenografts. Metabolome profiling reveals that niclosamide induces mitochondrial uncoupling, which renders mutant p53 cells susceptible to mitochondrial-dependent apoptosis through preferential accumulation of arachidonic acid (AA), and represents a first-in-class inhibitor of p53 mutant tumors. Wild-type p53 evades the cytotoxicity by promoting the transcriptional induction of two key lipid oxygenation genes, ALOX5 and ALOX12B, which catalyzes the dioxygenation and breakdown of AA. Therefore, we propose a new paradigm for targeting cancers defective in the p53 pathway, by exploiting their vulnerability to niclosamide-induced mitochondrial uncoupling.
Assuntos
Mitocôndrias/efeitos dos fármacos , Niclosamida/uso terapêutico , Ionóforos de Próton/uso terapêutico , Proteína Supressora de Tumor p53/deficiência , Animais , Apoptose , Araquidonato 12-Lipoxigenase/metabolismo , Araquidonato 5-Lipoxigenase/metabolismo , Ácido Araquidônico , Cálcio/metabolismo , Técnicas de Cocultura , Células HCT116 , Humanos , Metabolismo dos Lipídeos , Metaboloma/efeitos dos fármacos , Camundongos , Niclosamida/farmacologia , Ionóforos de Próton/farmacologia , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Adriamycin (ADR) is a potent anticancer drug known to cause severe cardiac toxicity. Although ADR generates free radicals, the role of free radicals in the development of cardiac toxicity and the intracellular target for ADR-induced cardiac toxicity are still not well understood. We produced three transgenic mice lines expressing increased levels of human manganese superoxide dismutase (MnSOD), a mitochondrial enzyme, as an animal model to investigate the role of ADR-mediated free radical generation in mitochondria. The human MnSOD was expressed, functionally active, and properly transported into mitochondria in the heart of transgenic mice. The levels of copper-zinc SOD, catalase, and glutathione peroxidase did not change in the transgenic mice. Electron microscopy revealed dose-dependent ultrastructural alterations with marked mitochondrial damage in nontransgenic mice treated with ADR, but not in the transgenic littermates. Biochemical analysis indicated that the levels of serum creatine kinase and lactate dehydrogenase in ADR-treated mice were significantly greater in nontransgenic than their transgenic littermates expressing a high level of human MnSOD after ADR treatment. These results support a major role for free radical generation in ADR toxicity as well as suggesting mitochondria as the critical site of cardiac injury.
Assuntos
Doxorrubicina/toxicidade , Coração/efeitos dos fármacos , Mitocôndrias Cardíacas/efeitos dos fármacos , Superóxido Dismutase/metabolismo , Animais , Radicais Livres/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos C3H , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias Cardíacas/enzimologia , Miocárdio/enzimologia , Miocárdio/patologia , Proteínas Recombinantes/metabolismo , Superóxido Dismutase/genéticaRESUMO
The role of Cu/Zn-superoxide dismutase (SOD) in myocardial ischemic reperfusion injury was studied by using a mouse model with targeted disruption of the mouse Sod I gene. Inactivation of the functional mouse Sod I gene in hearts by gene targeting (Sod I(+/-)) resulted in a 50% reduction of Cu/Zn-SOD mRNA and significant reduction of Cu/Zn-SOD enzyme activity compared with that of wild-type Sod I(+/+) mice. Cu/Zn-SOD mRNA could not be detected in Sod I(-/-) heart. The isolated buffer-perfused hearts from the knockout mice devoid of any functional copy of the Sod I (Sod I(-/-)) and matched nontransgenic control mice were subjected to 30 minutes of global ischemia followed by 2 hours of reperfusion. For both groups of mice, the postischemic functional recovery for the hearts was lower than the baseline, but the recovery for the Sod I(-/-) was less compared with the wild-type mice. Thus, the postischemic recovery of the developed force and the maximum first derivative of the developed force were consistently lower for the Sod I(-/-) mouse hearts compared with wild-type control hearts. The coronary flow was lower compared with the baseline levels for both groups of hearts, but there was no significant difference between the groups. The myocardial infarction determined from the ratio of infarct size/area of risk was higher for the Sod I(-/-) mice compared with the control mice. The amount of creatine kinase release from the wild-type mouse hearts was less compared with the Sod I(-/-) mouse hearts. In concert, a reduced amount of oxidative stress was found in the hearts of wild-type mice compared with Sod I(-/-) mouse hearts. These results documented that Sod I(-/-) mouse hearts were more susceptible to ischemic reperfusion injury compared with corresponding wild-type mouse hearts, suggesting that the Sod I gene constitutes an important defense element for the hearts.