Dendritic cells regulate angiogenesis associated with liver fibrogenesis

During liver fibrogenesis the immune response and angiogenesis process are fine-tuned resulting in activation of hepatic stellate cells that produce an excess of extracellular matrix proteins. Dendritic cells (DC) play a central role modulating the liver immunity and have recently been implicated to favour fibrosis regression; although their ability to influence the development of fibrogenesis is unknown. Therefore, we explored whether the depletion of DC during early stages of liver injury has an impact in the development of fibrogenesis. Using the CD11c.DTR transgenic mice, DC were depleted in two experimental models of fibrosis in vivo. The effect of anti-angiogenic therapy was tested during early stages of liver fibrogenesis. DC depletion accelerates the development of fibrosis and as a consequence, the angiogenesis process is boosted. We observed up-regulation of pro-angiogenic factors together with an enhanced vascular endothelial growth factor (VEGF) bioavailability, mainly evidenced by the decrease of anti-angiogenic VEGF receptor 1 (also known as sFlt-1) levels. Interestingly, fibrogenesis process enhanced the expression of Flt-1 on hepatic DC and administration of sFlt-1 was sufficient to abrogate the acceleration of fibrogenesis upon DC depletion. Thus, DC emerge as novel players during the development of liver fibrosis regulating the angiogenesis process and thereby influencing fibrogenesis.     

Discrete nanoparticles induce loss of Legionella pneumophila biofilms from surfaces

Nanoparticles (NPs) have been shown to induce dispersal events in microbial biofilms but the mechanism of the dispersal is unknown. Biofilms contaminate many man-made aquatic systems such as cooling towers, spas and dental lines. Within these biofilms, Legionella pneumophila is a primary pathogen, leading to these environments serving as sources for disease outbreaks. Here we show a reduction in biofilm bio-volume upon treatment with citrate-coated 6-nm platinum NPs, polyethylene glycol (PEG)-coated 11-nm gold NPs, and PEG-coated 8-nm iron oxide NPs. Treatment with citrate-coated 8-nm silver NPs, however, did not reduce biomass. The synthesis of NPs that remain dispersed and resist irreversible aggregation in the exposure media appears to be a key factor in the ability of NPs to induce biofilm dispersal.     

Some are more equal than others

The microbial communities found in the mammalian large intestine and rumen efficiently degrade many recalcitrant substrates that are resistant to the host’s digestive enzymes. These communities are known from molecular profiling to be highly diverse at the species and strain level, but it may be that only certain specialized organisms (“keystone species”) have the ability to initiate degradation of such substrates, thus releasing energy on which the rest of the community depends. We have recently reported that Ruminococcus bromii has a superior ability to degrade certain forms of particulate resistant starch (RS) when compared with other highly abundant species of amylolytic bacteria found in the human colon and have presented evidence that this bacterium provides an example of a keystone species within the microbial community with respect to RS fermentation. The concept of keystone species can be equally relevant to other activities, e.g., those involved in stabilizing the community.     

Animal and human dentin microstructure and elemental composition

Animal teeth are a common model in studies on dentin adhesive materials. The aim of this study was to compare microstructural parameters (density and diameter of dentinal tubules (DT), peritubular dentin (PTD) thickness, PTD and intertubular dentin (ITD) surface area) and chemical characteristics of canine, porcine, equine, and human root dentin. The middle layers of dentin were harvested just below a cemento-enamel junction from incisors and investigated by means of scanning electron microscopy (SEM) and energy dispersive X-ray spectroscopy (EDXS). SEM evaluation of the specimens revealed, that porcine dentin shared most similarities with human dentin. When comparing the density of DTs, canine dentin was also found to be similar to human dentin. Elemental composition of the root dentin did not differ significantly in porcine, equine and human dentin, but in canine dentin higher magnesium value in PTD compared to ITD was found. It is known that microstructural and chemical characteristics affect the strength of the adhesive bonds created among restorative materials and dentin. According to the results of this study, porcine dentin seems to be the most appropriate model to study dental materials to be used in human restorative dentistry.     

Beta toxin catalyzes formation of nucleoprotein matrix in staphylococcal biofilms

Biofilms are surface-associated communities of microbes encompassed by an extracellular matrix. It is estimated that 80% of all bacterial infections involve biofilm formation, but the structure and regulation of biofilms are incompletely understood. Extracellular DNA (eDNA) is a major structural component in many biofilms of the pathogenic bacterium Staphylococcus aureus, but its role is enigmatic. Here, we demonstrate that beta toxin, a neutral sphingomyelinase and a virulence factor of S. aureus, forms covalent cross-links to itself in the presence of DNA (we refer to this as biofilm ligase activity, independent of sphingomyelinase activity) producing an insoluble nucleoprotein matrix in vitro. Furthermore, we show that beta toxin strongly stimulates biofilm formation in vivo as demonstrated by a role in causation of infectious endocarditis in a rabbit model. Together, these results suggest that beta toxin cross-linking in the presence of eDNA assists in forming the skeletal framework upon which staphylococcal biofilms are established.