Transient down-regulation of beta1 integrin subtypes on kidney carcinoma cells is induced by mechanical contact with endothelial cell membranes

Adhesion molecules of the integrin beta1 family are thought to be involved in the malignant progression renal cell carcinoma (RCC). Still, it is not clear how they contribute to this process. Since the hematogenous phase of tumour dissemination is the rate-limiting step in the metastatic process, we explored beta1 integrin alterations on several RCC cell lines (A498, Caki1, KTC26) before and after contacting vascular endothelium in a tumour-endothelium (HUVEC) co-culture assay. Notably, alpha2, alpha3 and alpha5 integrins became down-regulated immediately after the tumour cells attached to HUVEC, followed by re-expression shortly thereafter. Integrin down-regulation on RCC cells was caused by direct contact with endothelial cells, since the isolated endothelial membrane fragments but not the cell culture supernatant contributed to the observed effects. Integrin loss was accompanied by a reduced focal adhesion kinase (FAK) expression, FAK activity and diminished binding of tumour cells to matrix proteins. Furthermore, intracellular signalling proteins RCC cells were altered in the presence of HUVEC membrane fragments, in particular 14-3-3 epsilon, ERK2, PKCdelta, PKCepsilon and RACK1, which are involved in regulating tumour cell motility. We, therefore, speculate that contact of RCC cells with the vascular endothelium converts integrin-dependent adhesion to integrin-independent cell movement. The process of dynamic integrin regulation may be an important part in tumour cell migration strategy, switching the cells from being adhesive to becoming motile and invasive

Antimicrobial activity against pathogenic bacteria, antioxidant and cytotoxic activity of cosmos caudatus

Cosmos caudatus is a traditional medicinal herb commonly found in Southeast Asia. This herb has been reported as a potential antioxidant and antimicrobial agent as it contains a variety of bioactive compounds.However, its cytotoxic effects on cancer still lack empirical evidence. Thus, this study aimed to investigate antimicrobial and antioxidant potentials of Cosmos caudatus as well as its cytotoxic effects on cancer cell lines. Ethanol and water extracts of Cosmos caudatus were tested for its antimicrobial activities against pathogenic bacteria, Staphylococcus aureus, Salmonella sp., Pseudomonas aeruginosa and Escherichia coli using agar well diffusion method. Antioxidant properties of the extracts were evaluated by 2,2-diphenyl-1-picryl-hydrazyl radical scavenging assay while cytotoxic activity of the extracts on colorectal carcinoma cell line, HCT 116 was determined by (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The findings indicated that conventional Soxhlet extraction with water as solvent extracted more efficiently than ethanolic maceration and ultrasonic assisted extraction. In antioxidants assay, both ethanolic and water extracts obtained through ultrasonic extraction exhibited the highest DPPH free radical scavenging capacity compared to maceration and Soxhlet extraction method. As for antimicrobial assay, both water and ethanol extracts showed no inhibitory action against the tested pathogenic bacteria. For anticancer activity, the F2, F7 and F8 fractions showed potent dose dependent cytotoxicity on HCT 116 cells with IC50 value of 15.53 ± 0.4, 32.72 ± 0.3 and 34.16 ± 1.4 μg/mL, respectively

Determinants of the Incidence of Hand, Foot and Mouth Disease in China Using Geographically Weighted Regression Models

Child population density and climate factors are potential determinants of the HFMD incidence in most areas in China. The strength and direction of association between these factors and the incidence of HFDM is spatially heterogeneous at the local geographic level, and child population density has a greater influence on the incidence of HFMD than the climate factors

Nonlinear analysis of reinforced concrete hollow beam with GFRP bars and stirrups using finite element method under cyclic load

Insufficient knowledge on using fibre-reinforced polymer (FRP) materials in hollow members limits their application. Torsional load results in the less efficient hollow section that plays an important role in hollow members. This load is generated on the members by an external load. The torsional load in hollow members that are reinforced longitudinally with FRP has been discussed for years. However, research on high-strength concrete (HSC) reinforced with glass fibre-reinforced polymer (GFRP) is scarce. Therefore, in this study, the behaviour of hollow beam internally reinforced with GFRP bars under cyclic load is investigated. For this purpose, the HSC-reinforced concrete hollow beam with GFRP bars and hollow beam with normal reinforcement are considered and finite element model is developed and nonlinear dynamic analysis has been conducted by applying cyclic loads to the developed models. In addition, reinforced concrete (RC) solid beam with HSC material is tested experimentally in order to verify and validate the ability of finite element software to predict the result. The analysis results are investigated in terms of the hysteresis loop, stress and strain distribution in the beam and it is indicated that the performance of hollow beam reinforced with GFRP bars and stirrups has improved in comparison with HSC beam with GFRP bars and also HSC beam with normal steel reinforcement. Therefore, based on this research, it is recommended to implement GFRP bars and stirrup for strengthening the concrete members in the high humidity areas where use of normal steel is not feasible due to corrosion threat

Angiostatin generating capacity and anti-tumour effects of D-penicillamine and plasminogen activators

BACKGROUND: Upregulation of endogenous angiostatin levels may constitute a novel anti-angiogenic, and therefore anti-tumor therapy. In vitro, angiostatin generation is a two-step process, starting with the conversion of plasminogen to plasmin by plasminogen activators (PAs). Next, plasmin excises angiostatin from other plasmin molecules, a process requiring a donor of a free sulfhydryl group. In previous studies, it has been demonstrated that administration of PA in combination with the free sulfhydryl donor (FSD) agents captopril or N-acetyl cysteine, resulted in angiostatin generation, and anti-angiogenic and anti-tumour activity in murine models. METHODS: In this study we have investigated the angiostatin generating capacities of several FSDs. D-penicillamine proved to be most efficient in supporting the conversion of plasminogen to angiostatin in vitro. Next, from the optimal concentrations of tPA and D-penicillamine in vitro, equivalent dosages were administered to healthy Balb/c mice to explore upregulation of circulating angiostatin levels. Finally, anti-tumor effects of treatment with tPA and D-penicillamine were determined in a human melanoma xenograft model. RESULTS: Surprisingly, we found that despite the superior angiostatin generating capacity of D-penicillamine in vitro, both in vivo angiostatin generation and anti-tumour effects of tPA/D-penicillamine treatment were impaired compared to our previous studies with tPA and captopril. CONCLUSION: Our results indicate that selecting the most appropriate free sulfhydryl donor for anti-angiogenic therapy in a (pre)clinical setting should be performed by in vivo rather than by in vitro studies. We conclude that D-penicillamine is not suitable for this type of therapy

Comparative Evaluation of Light-Trap Catches, Electric Motor Mosquito Catches and Human Biting Catches of Anopheles in the Three Gorges Reservoir

The mosquito sampling efficiency of light-trap catches and electric motor mosquito catches were compared with that of human biting catches in the Three Gorges Reservoir. There was consistency in the sampling efficiency between light-trap catches and human biting catches for Anopheles sinensis (r = 0.82, P<0.01) and light-trap catches were 1.52 (1.35–1.71) times that of human biting catches regardless of mosquito density (r = 0.33, P>0.01), while the correlation between electric motor mosquito catches and human biting catches was found to be not statistically significant (r = 0.43, P>0.01) and its sampling efficiency was below that of human biting catches. It is concluded that light-traps can be used as an alternative to human biting catches of Anopheles sinensis in the study area and is a promising tool for sampling malaria vector populations

Situação epidemiológica e a relação com variáveis meteorológicas da HFMD em Guangzhou, sul da China, 2008-2012

A doença de mão-pé-e-boca (HFMD) está se tornando doença extremamente comum transmitida pelo ar e contato em Guangzhou, sul da China, levando preocupação às autoridades de saúde pública acerca da sua incidência aumentada. Neste estudo foi usada parte ecológica e regressão binomial negativa para identificar o status epidêmico da HFMD e sua relação com variáveis meteorológicas. Durante 2008-2012 um total de 173.524 casos confirmados de HFMD foram apresentados, 12 com morte, elevando o índice de fatalidade a 0,69 por 10.000. As incidências anuais de 2008 a 2010 foram 60,56, 132,44, 311,40, 402,76 e 468,59 por 100.000, respectivamente, mostrando tendência de rápido aumento. Cada 1 °C de aumento da temperatura correspondeu a aumento de 9,47% (95% CI 9,36% a 9,58%) no número semanal de casos de HFMD, enquanto a 1 hPa de aumento da pressão atmosférica correspondeu a decréscimo no número de casos de 7,53% (95% CI - 7,60% a - 7,45%). De maneira semelhante cada aumento de 1% na humidade relativa correspondeu a aumento de 1,48% ou 3,3% e a um aumento de 1 metro por hora na velocidade do vento correspondeu a um aumento de 2,18% ou 4,57%, no número de casos semanais de HFMD, dependendo das variáveis consideradas no modelo. Estes achados revelaram que o status epidêmico do HFMD em Guangzhou é caracterizado por alta morbidade, mas baixa fatalidade. Fatores referentes ao tempo tiveram influência significante na incidência do HFMD.Hand-foot-and-mouth disease (HFMD) is becoming one of the extremely common airborne and contact transmission diseases in Guangzhou, southern China, leading public health authorities to be concerned about its increased incidence. In this study, it was used an ecological study plus the negative binomial regression to identify the epidemic status of HFMD and its relationship with meteorological variables. During 2008-2012, a total of 173,524 HFMD confirmed cases were reported, 12 cases of death, yielding a fatality rate of 0.69 per 10,000. The annual incidence rates from 2008 to 2012 were 60.56, 132.44, 311.40, 402.76, and 468.59 (per 100,000), respectively, showing a rapid increasing trend. Each 1 °C rise in temperature corresponded to an increase of 9.47% (95% CI 9.36% to 9.58%) in the weekly number of HFMD cases, while a one hPa rise in atmospheric pressure corresponded to a decrease in the number of cases by 7.53% (95% CI -7.60% to -7.45%). Similarly, each one percent rise in relative humidity corresponded to an increase of 1.48% or 3.3%, and a one meter per hour rise in wind speed corresponded to an increase of 2.18% or 4.57%, in the weekly number of HFMD cases, depending on the variables considered in the model. These findings revealed that epidemic status of HFMD in Guangzhou is characterized by high morbidity but low fatality. Weather factors had a significant influence on the incidence of HFMD

Functional Crosstalk between Type I and II Interferon through the Regulated Expression of STAT1

Small "priming" quantities of type I interferon enhance cellular responses to type II interferon by maintaining basal levels of STAT1, explaining the observed crosstalk between these two cytokines

The dominant Anopheles vectors of human malaria in the Asia-Pacific region: occurrence data, distribution maps and bionomic précis

<p>Abstract</p> <p>Background</p> <p>The final article in a series of three publications examining the global distribution of 41 dominant vector species (DVS) of malaria is presented here. The first publication examined the DVS from the Americas, with the second covering those species present in Africa, Europe and the Middle East. Here we discuss the 19 DVS of the Asian-Pacific region. This region experiences a high diversity of vector species, many occurring sympatrically, which, combined with the occurrence of a high number of species complexes and suspected species complexes, and behavioural plasticity of many of these major vectors, adds a level of entomological complexity not comparable elsewhere globally. To try and untangle the intricacy of the vectors of this region and to increase the effectiveness of vector control interventions, an understanding of the contemporary distribution of each species, combined with a synthesis of the current knowledge of their behaviour and ecology is needed.</p> <p>Results</p> <p>Expert opinion (EO) range maps, created with the most up-to-date expert knowledge of each DVS distribution, were combined with a contemporary database of occurrence data and a suite of open access, environmental and climatic variables. Using the Boosted Regression Tree (BRT) modelling method, distribution maps of each DVS were produced. The occurrence data were abstracted from the formal, published literature, plus other relevant sources, resulting in the collation of DVS occurrence at 10116 locations across 31 countries, of which 8853 were successfully geo-referenced and 7430 were resolved to spatial areas that could be included in the BRT model. A detailed summary of the information on the bionomics of each species and species complex is also presented.</p> <p>Conclusions</p> <p>This article concludes a project aimed to establish the contemporary global distribution of the DVS of malaria. The three articles produced are intended as a detailed reference for scientists continuing research into the aspects of taxonomy, biology and ecology relevant to species-specific vector control. This research is particularly relevant to help unravel the complicated taxonomic status, ecology and epidemiology of the vectors of the Asia-Pacific region. All the occurrence data, predictive maps and EO-shape files generated during the production of these publications will be made available in the public domain. We hope that this will encourage data sharing to improve future iterations of the distribution maps.</p