Inhibition of integrin β3, a binding partner of kallistatin,leads to reduced viability,invasion and proliferation in NCI-H446 cells

Background

Kallistatin is a serine proteinase inhibitor and heparin-binding protein. It is considered an endogenous angiogenic inhibitor. In addition, multiple studies demonstrated that kallistatin directly inhibits cancer cell growth. However, the molecular mechanisms underlying these effects remain unclear.

Methods

Pull-down, immunoprecipitation, and immunoblotting were used for binding experiments. To elucidate the mechanisms, integrin β3 knockdown (siRNA) or blockage (antibody treatment) on the cell surface of small the cell lung cancer NCI-H446 cell line was used.

Results

Interestingly, kallistatin was capable of binding integrin β3 on the cell surface of NCI-H446 cells. Meanwhile, integrin β3 knockdown or blockage resulted in loss of antitumor activities induced by kallistatin. Furthermore, kallistatin suppressed tyrosine phosphorylation of integrin β3 and its downstream signaling pathways, including FAK/-Src, AKT and Erk/MAPK. Viability, proliferation and migration of NCI-H446 cells were inhibited by kallistatin, with Bcl-2 and Grb2 downregulation, and Bax, cleaved caspase-9 and caspase 3 upregulation.

Conclusions

These findings reveal a novel role for kallistatin in preventing small cell lung cancer growth and mobility, by direct interaction with integrin β3, leading to blockade of the related signaling pathway.

     

Dispersal mode,shade tolerance,and phytogeographical affinity of tree species during secondary succession in tropical montane cloud forest

Secondary succession following land abandonment, represented by a chronosequence of 15 old fields (0–80 years old) and two old-growth forests, was studied in the tropical montane cloud forest region of Veracruz, Mexico. The objective was to determine successional trajectories in forest structure and species richness of trees ≥5 cm DBH, in terms of differences in seed dispersal mode, shade tolerance, and phytogeographical affinity. Data were analyzed using AIC model selection and logistic regressions. Mean and maximum canopy height reached values similar to old-growth forest at 35 and 80 years, respectively. Species richness and diversity values were reached earlier (15 and 25 years, respectively) while basal area and stem density tended to reach old-growth forest values within 80 years. Along the chronosequence, the proportion of species and individuals of wind-dispersed trees declined, that of bird dispersed small seeded trees remained constant, while that of gravity and animal dispersed large seeded trees increased; shade-intolerant species and individuals declined, while intermediate and shade-tolerant trees increased. Shade-tolerant canopy trees were rare during succession, even in the old-growth forest. Tropical tree species were more frequent than temperate ones throughout the chronosequence, but temperate tree individuals became canopy dominants at intermediate and old-growth forest stages.     

Characterization of <Emphasis Type="Italic">Prototheca zopfii</Emphasis> Associated with Outbreak of Bovine Clinical Mastitis in Herd of Beijing,China

Prototheca zopfii (P. zopfii) has become an important cause of bovine mastitis in many countries. In the present study, to better understand the occurrence of one clinical mastitis (CM) outbreak due to P. zopfii, the molecular characterization and resistance patterns of the microalga were described. P. zopfii strains were isolated from 17 of 23 quarters, which suffered CM in the outbreak, and 7 of 46 CM recovered quarters before the outbreak, as well as 2 of 75 environmental samples in the dairy farm. All strains were identified as genotype 2 by genotype-specific PCR analysis. Results of in vitro antimicrobial and antifungal susceptibility tests indicated that these strains were resistant to majority of tested drugs, with the only exception of amphotericin B, nystatin, streptomycin, gentamicin, and amikacin. This is the first report about CM outbreak caused by P. zopfii in China. These data suggest that P. zopfii may represent a serious risk in the studied herd, and this microalga could be an important potential pathogen causing mastitis in dairy herds of Beijing.     

Icelandic lampreys (<Emphasis Type="Italic">Petromyzon marinus</Emphasis>): where do they come from?

The recent discovery of sea lamprey wounds on salmonids in Icelandic rivers prompted an investigation on the origin of sea lampreys in Icelandic waters. Using a mitochondrial DNA fragment, the origin of the lampreys examined was assigned to the European stock and not to the North American one.     

Modeling Optimal Age-Specific Vaccination Strategies Against Pandemic Influenza

In the context of pandemic influenza, the prompt and effective implementation of control measures is of great concern for public health officials around the world. In particular, the role of vaccination should be considered as part of any pandemic preparedness plan. The timely production and efficient distribution of pandemic influenza vaccines are important factors to consider in mitigating the morbidity and mortality impact of an influenza pandemic, particularly for those individuals at highest risk of developing severe disease. In this paper, we use a mathematical model that incorporates age-structured transmission dynamics of influenza to evaluate optimal vaccination strategies in the epidemiological context of the Spring 2009 A (H1N1) pandemic in Mexico. We extend previous work on age-specific vaccination strategies to time-dependent optimal vaccination policies by solving an optimal control problem with the aim of minimizing the number of infected individuals over the course of a single pandemic wave. Optimal vaccination policies are computed and analyzed under different vaccination coverages (21%–77%) and different transmissibility levels (R₀\mathcal{R}_{0} in the range of 1.8–3). The results suggest that the optimal vaccination can be achieved by allocating most vaccines to young adults (20–39 yr) followed by school age children (6–12 yr) when the vaccination coverage does not exceed 30%. For higher R₀\mathcal{R}_{0} levels ($\mathcal{R}_{0}>=2.4$\mathcal{R}_{0}>=2.4), or a time delay in the implementation of vaccination (>90 days), a quick and substantial decrease in the pool of susceptibles would require the implementation of an intensive vaccination protocol within a shorter period of time. Our results indicate that optimal age-specific vaccination rates are significantly associated with R₀\mathcal{R}_{0}, the amount of vaccines available and the timing of vaccination.     

Antioxidant system in programmed cell death of sycamore (<Emphasis Type="Italic">Acer pseudoplatanus</Emphasis> L.) cultured cells

Reactive oxygen species (ROS) have pleiotropic effects in plants. ROS can lead to cellular damage and death or play key roles in control and regulation of biological processes, such as programmed cell death (PCD). This dual role of ROS, as toxic or signalling molecules, is possible because plant antioxidant system (AS) is able to achieve a tight control over ROS cellular levels, balancing properly their production and scavenging. AS response in plant PCD has been clearly described only in the hypersensitive response in incompatible plant–pathogen interactions and in the senescence process and has not been completely unravelled. In sycamore (Acer pseudoplatanus L.) cultured cells PCD can be induced by Fusicoccin (Fc), Tunicamycin (Tu), and Brefeldin A (Ba). These chemicals induce comparable PCD time course and extent, while H₂O₂ production is detectable only in Fc- and, to a lesser extent, in Ba-treated cells. In this paper the AS has been investigated during PCD of sycamore cells, measuring the effects of the three inducers on the cellular levels of non-enzymatic and enzymatic antioxidants. Results show that the AS behaviour is different in the PCD induced by the three chemicals. In Fc-treated cells AS is mainly devoted to decrease the concentration of toxic intracellular H₂O₂ levels. On the contrary, in cells treated with Tu and Ba, the cell redox state is shifted to a more reduced state and the enzymatic AS is partially down-regulated, allowing ROS to act as signalling molecules.