Nutrition of infants and young children (one to three years) and its effect on later health: A systematic review of current recommendations (EarlyNutrition project)

Background. EarlyNutrition (www.project-earlynutrition.eu) is an international research project investigating the effects of early nutrition on metabolic programming.

Objective. To summarize, by performing a systematic review, current standards, recommendations, guidelines, and regulations (hereafter, referred to as documents) on the nutrition of children up to three years of age. Special emphasis was placed on long-term effects of early nutrition, such as the risk of cardiovascular disease, hypertension, overweight, obesity, metabolic syndrome, diabetes, or glucose intolerance.

Methods. MEDLINE, selected databases, and websites were searched for documents published between 2008 and January 2013.

Results. Forty two documents met the inclusion criteria. The strongest and most consistent evidence for a protective, long-term effect was documented for breastfeeding. Also, limiting the intake of sodium and rapidly absorbed carbohydrates, use of a specific meal pattern, reducing the consumption of saturated fatty acids by replacing them with polyunsaturated fatty acids, and lowering the intake of trans fatty acids, seems beneficial. Many documents did not evaluate long-term outcomes of interest to us, or reported insufficient or imprecise data. Inconsistency in recommendations for some outcomes and research gaps were identified.

Conclusions. Our findings may serve as a helpful tool in planning further research, preventive actions against important diet-related diseases, and guidelines improvement.     

Multielement stable isotope ratios (H,C, N,S) of honey from different European regions

The aim of this study as a part of the food traceability project “TRACE” funded by the EU was to investigate if honeys produced in regions with different climatic and geological characteristics could be discriminated on the basis of the isotopic data. The hydrogen, carbon, nitrogen and sulphur stable isotope ratios of 516 authentic honeys from 20 European regions are presented and discussed. As honey contains only small quantities of nitrogen and sulphur, the honey protein was precipitated in order to obtain measurable amounts of these elements. The mean hydrogen isotopic ratios of the honey protein were found to be significantly correlated with the mean hydrogen isotopic ratios of precipitation and groundwater in the production regions. Carbon isotopic ratios were influenced by climate. The sulphur stable isotope composition is clearly influenced by geographical location (sea spray effect) and surface geology of the production regions. The results show that the stable isotope ratios of the four bio-elements carbon, nitrogen, hydrogen and sulphur in honey protein can be applied to verify the origin of honey. Carbon and sulphur were identified by canonical discriminant analysis as providing the maximum discrimination between honey samples. For seven regions the percentage of correct classified samples is greater than 70%. It was concluded that the methodology in its current state can be used to provide reliable origin information.     

Combining Radiation- with Immunotherapy in Prostate Cancer: Influence of Radiation on T Cells

Radiation of tumor cells can lead to the selection and outgrowth of tumor escape variants. As radioresistant tumor cells are still sensitive to retargeting of T cells, it appears promising to combine radio- with immunotherapy keeping in mind that the radiation of tumors favors the local conditions for immunotherapy. However, radiation of solid tumors will not only hit the tumor cells but also the infiltrated immune cells. Therefore, we wanted to learn how radiation influences the functionality of T cells with respect to retargeting to tumor cells via a conventional bispecific T cell engager (BiTE) and our previously described modular BiTE format UNImAb. T cells were irradiated between 2 and 50 Gy. Low dose radiation of T cells up to about 20 Gy caused an increased release of the cytokines IL-2, TNF and interferon-γ and an improved capability to kill target cells. Although radiation with 50 Gy strongly reduced the function of the T cells, it did not completely abrogate the functionality of the T cells.     

Inhalative as well as Intravenous Administration of H2S Provides Neuroprotection after Ischemia and Reperfusion Injury in the Rats’ Retina

Background: Neuronal ischemia-reperfusion injury (IRI), such as it can occur in glaucoma or strokes, is associated with neuronal cell death and irreversible loss of function of the affected tissue. Hydrogen sulfide (H₂S) is considered a potentially neuroprotective substance, but the most effective route of application and the underlying mechanism remain to be determined. Methods: Ischemia-reperfusion injury was induced in rats by a temporary increase in intraocular pressure (1 h). H₂S was then applied by inhalation (80 ppm at 0, 1.5, and 3 h after reperfusion) or by intravenous administration of the slow-releasing H₂S donor GYY 4137. After 24 h, the retinas were harvested for Western blotting, qPCR, and immunohistochemical staining. Retinal ganglion cell survival was evaluated 7 days after ischemia. Results: Both inhalative and intravenously delivered H₂S reduced retinal ganglion cell death with a better result from inhalative application. H₂S inhalation for 1.5 h, as well as GYY 4137 treatment, increased p38 phosphorylation. Both forms of application enhanced the extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation, and inhalation showed a significant increase at all three time points. H₂S treatment also reduced apoptotic and inflammatory markers, such as caspase-3, intracellular adhesion molecule 1 (ICAM-1), vascular endothelial growth factor (VEGF), and inducible nitric oxide synthase (iNOS). The protective effect of H₂S was partly abolished by the ERK1/2 inhibitor PD98059. Inhalative H₂S also reduced the heat shock response including heme oxygenase (HO-1) and heat shock protein 70 (HSP-70) and the expression of radical scavengers such as superoxide dismutases (SOD1, SOD2) and catalase. Conclusion: Hydrogen sulfide acts, at least in part, via the mitogen-activated protein kinase (MAPK) ERK1/2 to reduce apoptosis and inflammation. Both inhalative H₂S and intravenous GYY 4137 administrations can improve neuronal cell survival.     

Turning Seashell Waste into Electrically Conductive Particles

Biomaterials such as seashells are intriguing due to their remarkable properties, including their hierarchical structure from the nanometer to the micro- or even macroscopic scale. Transferring this nanostructure to generate nanostructured polymers can improve their electrical conductivity. Here, we present the synthesis of polypyrrole using waste seashell powder as a template to prepare a polypyrrole/CaCO₃ composite material. Various synthesis parameters were optimized to produce a composite material with an electrical conductivity of 2.1 × 10⁻⁴ ± 3.2 × 10⁻⁵ S/cm. This work presents the transformation of waste seashells into sustainable, electronically conductive materials and their application as an antistatic agent in polymers. The requirements of an antistatic material were met for a safety shoe sole.     

Structure-Dependent Toxicokinetics of Selected Pyrrolizidine Alkaloids In Vitro

Phytochemicals like pyrrolizidine alkaloids (PAs) can affect the health of humans and animals. PAs can occur for example in tea, honey or herbs. Some PAs are known to be cytotoxic, genotoxic, and carcinogenic. Upon intake of high amounts, hepatotoxic and pneumotoxic effects were observed in humans. This study aims to elucidate different toxicokinetic parameters like the uptake of PAs and their metabolism with in vitro models. We examined the transport rates of differently structured PAs (monoester, open-chained diester, cyclic diester) over a model of the intestinal barrier. After passing the intestinal barrier, PAs reach the liver, where they are metabolized into partially instable electrophilic metabolites interacting with nucleophilic centers. We investigated this process by the usage of human liver, intestinal, and lung microsomal preparations for incubation with different PAs. These results are completed with the detection of apoptosis as indicator for bioactivation of the PAs. Our results show a structure-dependent passage of PAs over the intestinal barrier. PAs are structure-dependently metabolized by liver microsomes and, to a smaller extent, by lung microsomes. The detection of apoptosis of A549 cells treated with lasiocarpine and monocrotaline following bioactivation by human liver or lung microsomes underlines this result. Conclusively, our results help to shape the picture of PA toxicokinetics which could further improve the knowledge of molecular processes leading to observed effects of PAs in vivo.     

Pre-Activated Granulocytes from an Autoimmune Uveitis Model Show Divergent Pathway Activation Profiles upon IL8 Stimulation In Vitro

In the pathophysiology of autoimmune-mediated uveitis, granulocytes have emerged as possible disease mediators and were shown to be pre-activated in equine recurrent uveitis (ERU), a spontaneous disease model. We therefore used granulocytes from ERU horses to identify early molecular mechanisms involved in this dysregulated innate immune response. Primary granulocytes from healthy and ERU horses were stimulated with IL8, and cellular response was analyzed with differential proteomics, which revealed significant differences in protein abundance of 170 proteins in ERU. Subsequent ingenuity pathway analysis identified three activated canonical pathways “PKA signaling”, “PTEN signaling” and “leukocyte extravasation”. Clustered to the leukocyte extravasation pathway, we found the membrane-type GPI-anchored protease MMP25, which was increased in IL8 stimulated ERU granulocytes. These findings point to MMP25 as a possible regulator of granulocyte extravasation in uveitis and a role of this molecule in the impaired integrity of the blood-retina-barrier. In conclusion, our analyses show a clearly divergent reaction profile of pre-activated granulocytes upon IL8 stimulation and provide basic information for further in-depth studies on early granulocyte activation in non-infectious ocular diseases. This may be of interest for the development of new approaches in uveitis diagnostics and therapy. Raw data are available via ProteomeXchange with identifier PXD013648.