Dihydrotanshinone,a Natural Diterpenoid,Preserves Blood-Retinal Barrier Integrity via P2X7 Receptor

Activation of P2X7 signaling, due to high glucose levels, leads to blood retinal barrier (BRB) breakdown, which is a hallmark of diabetic retinopathy (DR). Furthermore, several studies report that high glucose (HG) conditions and the related activation of the P2X7 receptor (P2X7R) lead to the over-expression of pro-inflammatory markers. In order to identify novel P2X7R antagonists, we carried out virtual screening on a focused compound dataset, including indole derivatives and natural compounds such as caffeic acid phenethyl ester derivatives, flavonoids, and diterpenoids. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) rescoring and structural fingerprint clustering of docking poses from virtual screening highlighted that the diterpenoid dihydrotanshinone (DHTS) clustered with the well-known P2X7R antagonist JNJ47965567. A human-based in vitro BRB model made of retinal pericytes, astrocytes, and endothelial cells was used to assess the potential protective effect of DHTS against HG and 2′(3′)-O-(4-Benzoylbenzoyl)adenosine-5′-triphosphate (BzATP), a P2X7R agonist, insult. We found that HG/BzATP exposure generated BRB breakdown by enhancing barrier permeability (trans-endothelial electrical resistance (TEER)) and reducing the levels of ZO-1 and VE-cadherin junction proteins as well as of the Cx-43 mRNA expression levels. Furthermore, HG levels and P2X7R agonist treatment led to increased expression of pro-inflammatory mediators (TLR-4, IL-1β, IL-6, TNF-α, and IL-8) and other molecular markers (P2X7R, VEGF-A, and ICAM-1), along with enhanced production of reactive oxygen species. Treatment with DHTS preserved the BRB integrity from HG/BzATP damage. The protective effects of DHTS were also compared to the validated P2X7R antagonist, JNJ47965567. In conclusion, we provided new findings pointing out the therapeutic potential of DHTS, which is an inhibitor of P2X7R, in terms of preventing and/or counteracting the BRB dysfunctions elicited by HG conditions.     

High SPARC Expression Starting from Dysplasia,Associated with Breast Carcinoma,Is Predictive for Bone Metastasis without Enhancement of Plasma Levels

In order to become established in the skeleton, metastatic cells disseminating from the breast carcinoma need to acquire organ-specific traits. There are no effective predictors for who will develop bone metastasis to guide long-term predictive therapy. Our purpose was to individuate events critical for bone colonization to make a molecular classification of breast carcinoma useful for bone-metastasis outcome. In dysplasia adjacent to carcinoma and in pair-matched specimens of bone metastasis we examined SPARC expression and localization as well as Endothelin 1/ET_AR signals by immunohistochemistry, and the evaluation of plasma levels of SPARC by ELISA was also performed. In patients with breast carcinoma metastasizing to bone, SPARC and Endothelin 1/ET_AR axis were highly expressed from dysplasia until bone metastasis, but the SPARC plasma level was as low as that of normal women, in contrast to patients that never develop bone metastasis, suggesting that circulating SPARC was counter adhesive. Altogether, the early identification of SPARC/Endothelin 1/ET_AR in dysplastic lesions would be important to devise therapies preventing metastasis engraftment, since often carcinoma cells spread to distant organs at the time or even before patients present with cancer.     

Precooked sorghum flour as proper vehicle of ACE-I and DPP-IV inhibitory sorghum peptides

Sorghum flour was heat treated for producing an instant dispersion ingredient. The precooked sorghum flour was added with ACE-I and DPP-IV inhibitory sorghum peptides (3.0 g peptide 100 g⁻¹). The product was reconstituted in water, and peptide bioaccessibility was evaluated by equilibrium dialysis method after simulated gastrointestinal digestion. Total peptide dialysability of precooked sorghum flour added with sorghum peptides was higher than those obtained for precooked sorghum flour (315.9 ± 14.8 vs. 45.2 ± 5.6 µmol, respectively) (P < 0.05). The ACE-I and DPP-IV-IC₅₀ values of the bioaccessible peptides from the bioactive product were lower than those obtained for precooked sorghum flour ingredient (1.04 ± 0.12 vs. 1.82 ± 0.09 and 0.86 ± 0.02 vs. 2.12 ± 0.08 mg protein mL⁻¹, for ACE-I and DPP-IV, respectively) indicating a higher activity. Precooked sorghum flour was a good vehicle since it did not affect the bioaccessibility of ACE-I and DPP-IV inhibitory peptides provided by sorghum protein hydrolysate.     

Assessment of reference values for mercury in urine: the results of an Italian polycentric study

The results of a polycentric study to assess the reference values of urinary mercury (U-Hg) in four Italian cities are presented. A total of 383 subjects were selected on the basis of standardised criteria by a questionnaire on personal habits, lifestyle, occupational or non-occupational exposure to Hg, medical history, number and area of dental amalgams. U-Hg was determined by hydride generation atomic absorption method (HG-AAS), with a detection limit of 0.5 microg/l and by flow injection (FI) inductively coupled plasma mass spectrometry (ICP-MS), with a detection limit of 0.03 microg/l. The median value of U-Hg, determined by HG-AAS, was 0.78 microg/g creatinine (0.75 for males and 0.83 for females), with 5 degrees and 95 degrees percentiles, respectively, of 0.17 and 3.66 microg/g creatinine. When determined by FI ICP-MS, the median value was 0.79 microg/g creatinine (0.77 for males and 0.79 for females) with 5 degrees and 95 degrees percentiles of, respectively, 0.12 and 5.02 microg/g creatinine. Among the independent variables, city of origin, area of dental amalgams, fish intake and tobacco smoking significantly influenced the U-Hg levels. The U-Hg reference values from this survey are lower than those from other recent investigations, probably due to characteristics and selection of the examined individuals and to the strict control of pre-analytical and analytical factors of variability.     

Influence of pH on colour and iron content of peptide fractions obtained from bovine Hb concentrate hydrolysates

The effect of pH on colour and iron content (Fe) of peptide fractions obtained from bovine haemoglobin concentrate (BHC) hydrolysates was studied. Four hydrolysates were obtained using three enzymes: Protex‐6‐L (P), Fungal–Protease–Concetrate (FC) and Flavourzyme (F). BHC and its hydrolysates (P, FC, P + F, FC + F) were fractioned at pH 4.5, 7.0 and 9.5. Solubility and Fe from different fractions were measured. Correlations between CIELAB colour parameters and Fe from different fractions were analysed. The colour from different fractions varied from red to yellow (a* and b* positives). Lightness values (L*) ranged from twenty‐four to seventy. FC4.5 and FC + F4.5 fractions were the clearest and yellow (higher L*, b*, h), while BHC9.5 and P + F9.5 fractions had the lowest values of L*, b* and h. There was an inverse linear relationship between b* and L* parameters and Fe from fractions. This relationship could be associated with the pH of extraction. As pH increases Fe significantly increases and lower b* and L* values were obtained.     

Cyclic invariance for discrete time-delay systems

This technical communique introduces a new concept of set invariance with respect to linear discrete time dynamics affected by delay. We are interested in the definition and characterization of sequences of cyclically invariant subsets in the state space. The algebraic conditions established in the late ’80s for linear dynamics are generalized to invariance analysis in the presence of delays for given sequences of polyhedral sets.     

Physical and nutritional properties of extruded products based on whole grain with the addition of wild legumes (Vicia lutea subsp. lutea var. hirta and Vicia sativa subsp. sativa)

Flour blends based on whole corn and rice with two added wild legumes at 15% level of cereal replacement were extruded to produce whole grain snacks. Extrusion temperature was 175 °C, and the moisture content was adjusted to 14%. The extruded products were evaluated for their physical, chemical and nutritional properties. Results showed that the addition of legumes produces a decrease in expansion in rice‐containing samples and an increase in solubility in corn‐containing samples. With only 15% of legume added to cereal, a significant increase in protein content and quality was obtained. An increase in fibre, polyphenol, iron and zinc content was also obtained. Protein digestibility was in the range of 81.8–85.3%. Mineral availability ranged from 6.4 to 16.3% for iron and 10–16.3% for zinc. The performance of each mixture during extrusion and the physical properties of the extruded products were considered to be similar to those expected for snack‐type products and described in the literature.     

Bed Sediment Characteristics in the Paraná and Paraguay Rivers

ABSTRACT

This paper presents a granulometric characterization of the Paraná and Paraguay rivers bed sediments. Samples obtained along 2,900 km of the thalweg of those rivers form the basis of this study. The main results and other features of the study are as follows: a) the bed sediment of both rivers is composed mainly of medium to fine well-sorted sands, with sizes in the Paraná slightly higher than those in the Paraguay river; b) the variations of mean diameters for both rivers are well correlated with the energy slopes. The correlation coefficient in the Paraguay river increases notably if the discharge and width/depth relationship variations along the channel are included in the regression; and, c) the origin of the transported sands could be related to the geologic characteristics of the Paraná river basin. An explanation is also suggested for the different bed sediment texture found in the Paraná de las Palmas and Paraná Guazú rivers in the lower delta. The explanation is based on the geomorphic processes that built that region of the Paraná river.     

Micromechanics of spatially uniform heterogeneous media: A critical review and emerging approaches

Outside of the classical microstructural detail-free estimates of effective moduli, micromechanical analyses of macroscopically uniform heterogeneous media may be grouped into two categories based on different geometric representations of material microstructure. Analysis of periodic materials is based on the repeating unit cell (RUC) concept and the associated periodic boundary conditions. This contrasts with analysis of statistically homogeneous materials based on the representative volume element (RVE) concept and the associated homogeneous boundary conditions. In this paper, using the above classification framework we provide a critical review of the various micromechanical approaches that had evolved along different paths, and outline recent emerging trends. We begin with the basic framework for the solution of micromechanics problems independent of microstructural representation, and then clarify the often confused RVE and RUC concepts. Next, we describe classical models, including the available RVE-based models, and critically examine their limitations. This is followed by discussion of models based on the concept of microstructural periodicity. In the final part, two recent unit cell-based models, which continue to evolve, are outlined. First, a homogenization technique called finite-volume direct averaging micromechanics theory is presented as a viable and easily implemented alternative to the mainstream finite-element based asymptotic homogenization of unit cells. The recent incorporation of parametric mapping into this approach has made it competitive with the finite-element method. Then, the latest work based on locally-exact solutions of unit cell problems is described. In this approach, the interior unit cell problem is solved exactly using the elasticity approach. The exterior problem is tackled with a new variational principle that successfully overcomes the non-separable nature of the overall unit cell problem.