Transplantation of amniotic membrane in corneal ulcers and persistant epithelial defects

Amniotic membrane transplantation (AMT) leads to reduction of inflammatory symptoms and causes faster epithelisation in corneal ulcers and persistant epithelial defect. 21 patients with corneal ulcer (n = 18) or non-healing epithelial defect (n = 3) unresponsive to conventional treatment were included in the study. All patients were treated by AMT. Corneal epithelial cells in patients suffering from corneal ulcer secreted 3.51 +/- 1.79 of IL-1alpha, 64.27 +/- 31.53 pg/mL of TNFalpha and 209.07 +/- 201.82 pg/mL of VEGF. Levels of all 3 investigated cytokines were significantly higher as compared to controls (p < 0.005). Amniotic membranes that were used contained 775.69 +/- 613.98 pg/mL of IL-1alpha, 0.036 +/- 0.033 pg/mL of sTNF and 175.01 +/- 166.63 pg/mL of VEGF-R. Supporting effect of the AMT could be explained by the fact that AM secretes its natural antinflammatory antagonists IL-1ra, sTNF and VEGF-R.     

Consensus statement understanding health and malnutrition through a systems approach: the ENOUGH program for early life

Nutrition research, like most biomedical disciplines, adopted and often uses experimental approaches based on Beadle and Tatum’s one gene—one polypeptide hypothesis, thereby reducing biological processes to single reactions or pathways. Systems thinking is needed to understand the complexity of health and disease processes requiring measurements of physiological processes, as well as environmental and social factors, which may alter the expression of genetic information. Analysis of physiological processes with omics technologies to assess systems’ responses has only become available over the past decade and remains costly. Studies of environmental and social conditions known to alter health are often not connected to biomedical research. While these facts are widely accepted, developing and conducting comprehensive research programs for health are often beyond financial and human resources of single research groups. We propose a new research program on essential nutrients for optimal underpinning of growth and health (ENOUGH) that will use systems approaches with more comprehensive measurements and biostatistical analysis of the many biological and environmental factors that influence undernutrition. Creating a knowledge base for nutrition and health is a necessary first step toward developing solutions targeted to different populations in diverse social and physical environments for the two billion undernourished people in developed and developing economies.     

Design,synthesis, biological evaluation and QSAR analysis of novel N-substituted benzimidazole derived carboxamides

As a result of our previous research focussed on benzimidazoles, herein we present design, synthesis, QSAR analysis and biological activity of novel N-substituted benzimidazole derived carboxamides. Carboxamides were designed to study the influence of the number of methoxy groups, the type of the substituent placed at the benzimidazole core on biological activity. Pronounced antioxidative activity displayed unsubstituted 28 (IC₅₀ ≈ 3.78 mM, 538.81 mmolFe²⁺/mmolC) and dimethoxy substituted derivative 34 (IC₅₀ ≈ 5.68 mM, 618.10 mmolFe²⁺/mmolC). Trimethoxy substituted 43 and unsubstituted compound 40 with isobutyl side chain at N atom showed strong activity against HCT116 (IC₅₀ ≈ 0.6 µM, both) and H 460 cells (IC₅₀ ≈ 2.5 µM; 0.4 µM), being less cytotoxic towards non-tumour cell. Antioxidative activity in cell generally confirmed relatively modest antioxidant capacity obtained in DPPH/FRAP assays of derivatives 34 and 40. The 3D-QSAR models were generated to explore molecular properties that have the highest influence on antioxidative activity.     

A Targeted LC‐MS Strategy for Low‐Abundant HLA Class‐I‐Presented Peptide Detection Identifies Novel Human Papillomavirus T‐Cell Epitopes

For rational design of therapeutic vaccines, detailed knowledge about target epitopes that are endogenously processed and truly presented on infected or transformed cells is essential. Many potential target epitopes (viral or mutation‐derived), are presented at low abundance. Therefore, direct detection of these peptides remains a challenge. This study presents a method for the isolation and LC‐MS³‐based targeted detection of low‐abundant human leukocyte antigen (HLA) class‐I‐presented peptides from transformed cells. Human papillomavirus (HPV) was used as a model system, as the HPV oncoproteins E6 and E7 are attractive therapeutic vaccination targets and expressed in all transformed cells, but present at low abundance due to viral immune evasion mechanisms. The presented approach included preselection of target antigen‐derived peptides by in silico predictions and in vitro binding assays. The peptide purification process was tailored to minimize contaminants after immunoprecipitation of HLA‐peptide complexes, while keeping high isolation yields of low‐abundant target peptides. The subsequent targeted LC‐MS³ detection allowed for increased sensitivity, which resulted in successful detection of the known HLA‐A2‐restricted epitope E7_11–19 and ten additional E7‐derived peptides on the surface of HPV16‐transformed cells. T‐cell reactivity was shown for all the 11 detected peptides in ELISpot assays, which shows that detection by our approach has high predictive value for immunogenicity. The presented strategy is suitable for validating even low‐abundant candidate epitopes to be true immunotherapy targets.     

White adipose tissue reference network: a knowledge resource for exploring health-relevant relations

Optimal health is maintained by interaction of multiple intrinsic and environmental factors at different levels of complexity—from molecular, to physiological, to social. Understanding and quantification of these interactions will aid design of successful health interventions. We introduce the reference network concept as a platform for multi-level exploration of biological relations relevant for metabolic health, by integration and mining of biological interactions derived from public resources and context-specific experimental data. A White Adipose Tissue Health Reference Network (WATRefNet) was constructed as a resource for discovery and prioritization of mechanism-based biomarkers for white adipose tissue (WAT) health status and the effect of food and drug compounds on WAT health status. The WATRefNet (6,797 nodes and 32,171 edges) is based on (1) experimental data obtained from 10 studies addressing different adiposity states, (2) seven public knowledge bases of molecular interactions, (3) expert’s definitions of five physiologically relevant processes key to WAT health, namely WAT expandability, Oxidative capacity, Metabolic state, Oxidative stress and Tissue inflammation, and (4) a collection of relevant biomarkers of these processes identified by BIOCLAIMS (http://bioclaims.uib.es). The WATRefNet comprehends multiple layers of biological complexity as it contains various types of nodes and edges that represent different biological levels and interactions. We have validated the reference network by showing overrepresentation with anti-obesity drug targets, pathology-associated genes and differentially expressed genes from an external disease model dataset. The resulting network has been used to extract subnetworks specific to the above-mentioned expert-defined physiological processes. Each of these process-specific signatures represents a mechanistically supported composite biomarker for assessing and quantifying the effect of interventions on a physiological aspect that determines WAT health status. Following this principle, five anti-diabetic drug interventions and one diet intervention were scored for the match of their expression signature to the five biomarker signatures derived from the WATRefNet. This confirmed previous observations of successful intervention by dietary lifestyle and revealed WAT-specific effects of drug interventions. The WATRefNet represents a sustainable knowledge resource for extraction of relevant relationships such as mechanisms of action, nutrient intervention targets and biomarkers and for assessment of health effects for support of health claims made on food products.

Electronic supplementary material

The online version of this article (doi:10.1007/s12263-014-0439-x) contains supplementary material, which is available to authorized users.     

Relations of the morphological characteristic latent structure and body posture indicators in children aged seven to nine years

With the aim of determining the connection between the indicators of body posture and latent structure of morphological variables in children aged 7 and 8 years, first and second grade of primary school, a set of 17 morphological measures and 12 body posture indicators were longitudinally applied to a sample of 110 boys and 114 girls. The latent structure of morphological variables in both sexes was defined by three factors but at a different order of significance: in boys, the order was longitudinal dimensionality, voluminosity, mass and subcutaneous fat tissue and transverse dimensionality, whereas in girls the order was voluminosity, mass and subcutaneous fat tissue, longitudinal dimensionality and transverse dimensionality. The latent structure of torax body posture indicator was defined by two factors, the status of body posture of the rear part of the thorax, and status of the body posture of the front part of the thorax. The results obtained by canonical correlation analysis between predictive variables, morphological latent structure and criterion variables, latent structure of thorax body posture indicators with two posture indicators of the chest and one of the foot status, showed two important pairs of canonical roots on each measurement, suggesting a significant association between these two sets of parameters.     

Growth Conditions in In Vitro Culture Can Induce Oxidative Stress in <Emphasis Type="Italic">Mammillaria gracilis</Emphasis> Tissues

In vitro propagated plants of Mammillaria gracilis Pfeiff. (Cactaceae) develop calli without any exogenous growth regulators. This habituated tissue spontaneously regenerates morphologically normal as well as hyperhydric shoots. In this study, a possible involvement of activated oxygen metabolism in habituation and hyperhydricity in in vitro propagated plants of Mammillaria gracilis Pfeiff. (Cactaceae) was investigated. Significantly higher malondialdehyde (MDA) and carbonyl contents as well as hydrogen peroxide (H₂O₂) production were observed in habituated callus (HC), hyperhydric regenerated shoots (HS), and tumors (TT) in comparison to normal regenerated shoots (NS). Lipoxygenase (LOX) activity showed a similar trend, with a clear increase in activity in HC and HS. The activities of antioxidative enzymes, namely, peroxidase (POX), ascorbate peroxidase (APX), and catalase (CAT), were also higher in HC, HS, and TT, whereas an increase in superoxide dismutase (SOD) activity was observed in HC and HS. The majority of antioxidative isoenzymes were common to all cactus tissues, although a few tissue-specific bands were noticed. Significant decreases in phenylalanine ammonia lyase (PAL) activity, total phenolic content, and lignification were found in HS, HC, and TT in comparison to NS. Our results showed the appearance of a prominent oxidative stress in HC, HS, and TT as well as a strong induction of the antioxidant system indicating that activated oxygen metabolism could be involved in habituation and hyperhydricity and linked to the loss of tissue organization in M. gracilis. B. Balen and M. Tkalec contributed equally to this work.     

Antioxidant and antimicrobial properties of the lichens <Emphasis Type="Italic">Anaptychya ciliaris,Nephroma parile,Ochrolechia tartarea</Emphasis> and <Emphasis Type="Italic">Parmelia centrifuga</Emphasis>

The aim of this study was to characterize the antioxidant and antimicrobial activity of the methanol extracts of: Anaptychya ciliaris, Nephroma parile, Ochrolechia tartarea and Parmelia centrifuga. The methanol extract of the P. centrifuga showed a strong antioxidant activity, in comparison to the extracts from A. ciliaris, O. tartarea and N. parile which were relatively weaker. Furthermore, the methanol extract of the lichen P. centrifuga was shown to contain the highest total phenol content (54.19 mg/g of the dry extract). Interestingly, a statistically significant positive relationship between the antioxidant activity and the total phenol content was observed. The minimum inhibitory concentration (MIC) against six bacterial and eleven fungi was established for the methanol extracts from each of species of lichens. The methanol extracts of the lichens P. centrifuga and O. tartarea showed the strongest both antibacterial and antifungal activity. Taken together, the results from this study suggest that the lichens P. centrifuga and O. tartarea may be used as a natural source of antioxidants in addition to providing certain antimicrobial features.