The Critical Role of the Branched Chain Amino Acids (BCAAs) Catabolism-Regulating Enzymes,Branched-Chain Aminotransferase (BCAT) and Branched-Chain α-Keto Acid Dehydrogenase (BCKD), in Human Pathophysiology

Branched chain amino acids (BCAAs), leucine, isoleucine and valine, are essential amino acids widely studied for their crucial role in the regulation of protein synthesis mainly through the activation of the mTOR signaling pathway and their emerging recognition as players in the regulation of various physiological and metabolic processes, such as glucose homeostasis. BCAA supplementation is primarily used as a beneficial nutritional intervention in chronic liver and kidney disease as well as in muscle wasting disorders. However, downregulated/upregulated plasma BCAAs and their defective catabolism in various tissues, mainly due to altered enzymatic activity of the first two enzymes in their catabolic pathway, BCAA aminotransferase (BCAT) and branched-chain α-keto acid dehydrogenase (BCKD), have been investigated in many nutritional and disease states. The current review focused on the underlying mechanisms of altered BCAA catabolism and its contribution to the pathogenesis of a numerous pathological conditions such as diabetes, heart failure and cancer. In addition, we summarize findings that indicate that the recovery of the dysregulated BCAA catabolism may be associated with an improved outcome and the prevention of serious disease complications.     

In Vitro Assessment of Poly-N-Vinylpyrrolidone/Acrylic Acid Nanoparticles Biocompatibility in a Microvascular Endothelium Model

An amphiphilic copolymer of N-vinyl-2-pyrrolidone and acrylic acid—namely, p(VP-AA)-OD6000 (p(VP-AA))—was synthesized to prepare p(VP-AA) nanoparticles (NPs). Furthermore, the copolymer was linked with CFSE, and the so-prepared nanoparticles were loaded with the DiI dye to form D nanoparticles (DNPs). In this study, as demonstrated by immunofluorescence microscopy, immunofluorescence, and confocal microscopy, DNPs were readily taken up by human microvascular endothelial cells (HMEC-1) cells in a concentration-dependent manner. Upon uptake, both the CFSE dye (green stain) and the DiI dye (red stain) were localized to the cytoplasm of treated cells. Treatment with p(VP-AA) did not affect the viability of normal and challenged with LPS, HMEC-1 cells at 0.010 mg/mL and induced a dose-dependent decrease of these cells’ viability at the higher concentrations of 0.033 and 0.066 mg/mL (p ≤ 0.01; p ≤ 0.001, respectively). Furthermore, we focused on the potential immunological activation of HMEC-1 endothelial cells upon p(VP-AA) NPs treatment by assessing the expression of adhesion molecules (E-Selectin, ICAM-1, and V-CAM). NPs treatments at concentrations utilized (p = NS) did not affect individual adhesion molecules’ expression. p(VP-AA) NPs do not activate the endothelium and do not affect its viability at pharmacologically relevant concentrations.     

Exhausted but Not Senescent T Lymphocytes Predominate in Lupus Nephritis Patients

Lupus nephritis (LN), a chronic inflammatory disease, is characterized by the substantial disruption of immune homeostasis. This study examines its effects on the T lymphocyte phenotype and, particularly, its senescence- and exhaustion-related immune alterations. T cell subpopulations were determined with flow cytometry in 30 LN patients and 20 healthy controls (HCs), according to the expression of senescence- (CD45RA, CCR7, CD31, CD28, CD57), and exhaustion- (PD1) related markers. The immune phenotype was associated with disease activity and renal histology. LN patients were characterized by pronounced lymphopenia, mainly affecting the CD4 compartment, with a concurrent reduction in the naïve, central and effector memory subsets compared to the HCs. In the CD8 compartment, the naïve subsets were significantly lower than that of the HCs, but a shift in the T cells occurred towards the central memory population. CD4+PD1+ and CD8+PD1+ cells were increased in the LN patients compared to the HCs. However, in CD4 T cells, the increase was limited to CD45RA+, whereas in CD8 T cells, both CD45RA+ and CD45RA− subsets were affected. Disease activity was correlated with CD4+PD1+ and highly differentiated CD4+CD28-CD57+ cells. Histology was only associated with CD4 T cell disturbances, with stage IV presenting reduced naïve and increased senescent subsets. Exhausted T lymphocyte subpopulations predominate within LN patients, while the T cell phenotype varies depending on disease activity.     

Genetic Variability and Phylogeny of High Risk HPV Type 16, 18, 31, 33 and 45 L1 Gene in Greek Women

The present study explores nucleotide variability, phylogeny and association with cervical neoplasia in high risk HPV types 16, 18, 31, 33 and 45 collected from Greek women. Of the 1894 women undergoing routine cervical cytology examination, 160 samples test positive for single infections of HPV type 16 (n = 104), HPV 31 (n = 40), HPV 33 (n = 7), HPV 18 (n = 5), and HPV 45 (n = 4) were typed by microarrays method, amplified by PCR then sequenced and phylogenetically analyzed. For HPV 16, 9 variants with nucleotide variations were included into the study. For HPV 31, 33, 18 and 45, nucleotide variations were identified in 6, 4, 2 and 3 variants, respectively. The Bayesian inference and Maximum Parsimony methods were used in order to construct the phylogenetic trees. When types were analyzed independently HPV 16 (European and non-European) and HPV 18 (African and non-African) formed distinct clades. The genomic characterization of HPV variants will be important for illuminating the geographical relatedness and biological differences and for the determination of their risk.     

New Affordable Methods for Large-Scale Isolation of Major Olive Secoiridoids and Systematic Comparative Study of Their Antiproliferative/Cytotoxic Effect on Multiple Cancer Cell Lines of Different Cancer Origins

Olive oil phenols (OOPs) are associated with the prevention of many human cancers. Some of these have been shown to inhibit cell proliferation and induce apoptosis. However, no systematic comparative study exists for all the investigated compounds under the same conditions, due to difficulties in their isolation or synthesis. Herein are presented innovative methods for large-scale selective extraction of six major secoiridoids from olive oil or leaves enabling their detailed investigation. The cytotoxic/antiproliferative bioactivity of these six compounds was evaluated on sixteen human cancer cell lines originating from eight different tissues. Cell viability with half-maximal effective concentrations (EC₅₀) was evaluated after 72 h treatments. Antiproliferative and pro-apoptotic effects were also assessed for the most bioactive compounds (EC₅₀ ≤ 50 μM). Oleocanthal (1) showed the strongest antiproliferative/cytotoxic activity in most cancer cell lines (EC₅₀: 9–20 μM). The relative effectiveness of the six OOPs was: oleocanthal (1) > oleuropein aglycone (3a,b) > ligstroside aglycone (4a,b) > oleacein (2) > oleomissional (6a,b,c) > oleocanthalic acid (7). This is the first detailed study comparing the bioactivity of six OOPs in such a wide array of cancer cell lines, providing a reference for their relative antiproliferative/cytotoxic effect in the investigated cancers.     

Shocks in economic growth = shocking effects for food security?

The recent economic and financial turmoil raises the question on how global economic growth affects agricultural commodity markets and, hence, food security. To address this question, this paper assesses the potential impacts of faster economic growth in developed and emerging economies on the one hand and a replication of the recent economic downturn on the other hand. The empirical analysis uses AGLINK-COSIMO, a recursive-dynamic, partial equilibrium, supply–demand model. Simulation results demonstrate that higher economic growth influences demand more than supply, resulting in higher world market prices for agricultural commodities. Emerging economies tend to import more and to stock less in order to cover their demand needs, while the rest of the world increases its exports. The modelled faster economic growth also helps developing countries to improve their trade balance, but does not necessarily give them the incentive to address domestic food security concerns by boosting domestic consumption. A replication of an economic downturn leads to lower world prices, and while the magnitude of the effects decreases over time, markets do not regain their baseline levels within a 5-year period. Due to the lower world market prices, developing countries import more and increase their per capita food calorie intake. However, as developing countries become more import dependent, this also implies that they become more vulnerable to disruptions in agricultural world markets.     

A proposed enhanced scheme for the dynamic frequency hopping performance in the IEEE 802.22 standard

This paper presents an integrated scheme for the dynamic‐frequency‐hopping (DFH) technique provided in literature for the IEEE 802.22 standard supporting wireless regional area networks (WRANs). The performance of DFH is analyzed thoroughly for various channel models and for a multiple‐input multiple‐output systems. The core of this research is based on the coexistence of digital terrestrial TV broadcasting and the WRANs in the TV white space. The proposed technique aims at protecting the incumbent users from interfering with the cognitive broadband access in the TV spectrum. In order to achieve this, spectrum sensing is performed in the intended working channel in DFH while spectrum monitoring with an energy‐ratio (ER) algorithm is applied during the WRAN data transmission in the working channel. Hence, in the DFH‐ER algorithm, the reappearance of a digital terrestrial TV signal in a band occupied by the WRANs would be detected immediately. This will provide interference free performance for the licensed signal as well as reliable data transmission for the unlicensed ones. Both analyses and simulation results of the proposed DFH‐ER technique compared with the conventional DFH scenario exemplify the enhancement of the WRAN data transmission while protecting the digital terrestrial TV users. Copyright © 2016 John Wiley & Sons, Ltd.