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.     

Milk from cows fed a diet with a high forage:concentrate ratio improves inflammatory state,oxidative stress,and mitochondrial function in rats

Excessive energy intake may evoke complex biochemical processes characterized by inflammation, oxidative stress, and impairment of mitochondrial function that represent the main factors underlying noncommunicable diseases. Because cow milk is widely used for human nutrition and in food industry processing, the nutritional quality of milk is of special interest with respect to human health. In our study, we analyzed milk produced by dairy cows fed a diet characterized by a high forage:concentrate ratio (high forage milk, HFM). In view of the low n-6:n-3 ratio and high content of conjugated linoleic acid of HFM, we studied the effects of this milk on lipid metabolism, inflammation, mitochondrial function, and oxidative stress in a rat model. To this end, we supplemented for 4 wk the diet of male Wistar rats with HFM and with an isocaloric amount (82 kJ, 22 mL/d) of milk obtained from cows fed a diet with low forage:concentrate ratio, and analyzed the metabolic parameters of the animals. Our results indicate that HFM may positively affect lipid metabolism, leptin:adiponectin ratio, inflammation, mitochondrial function, and oxidative stress, providing the first evidence of the beneficial effects of HFM on rat metabolism.     

Application of chitosan–alginate microspheres for the sustained release of bacteriophage in simulated gastrointestinal conditions

This study was designed to evaluate the acid stability, release property and antimicrobial efficacy of Escherichia coli O157:H7 bacteriophages encapsulated in chitosan–alginate microspheres under the simulated gastrointestinal conditions. The bacteriophages belonging to Myoviridae family were stable at the pH above 4 in trypticase soy broth. The chitosan–alginate microspheres exhibited protective effect on the viability of bacteriophages in the simulated gastric conditions at pH 2.0 and pH 2.5, showing 4.8 and 5.6 log PFU mL^‐1, respectively, after 1 h of incubation at 37 °C. The release per cent of bacteriophages from microspheres gradually increased up to 65% in the simulated intestinal condition (pH 7.5) at 37 °C for 6 h. The lytic efficacy of chitosan‐ and alginate‐encapsulated bacteriophages against E. coli O157:H7 was significantly maintained in the simulated intestinal conditions to 10 h of incubation (1.3 log reduction). The results suggest that the chitosan–alginate microspheres can be used as a reliable delivery system for bacteriophages.     

Role of Nd-Ni on structural,spectral and dielectric properties of strontium-barium based nano-sized X-type ferrites

The influence of neodymium and nickel substitution on structural and dielectric parameters was investigated in strontium-barium X-type hexagonal ferrites having composition SrBaCu_2?xNi_xNd_yFe_28?yO₄₆ (x = 0, 0.2, 0.4, 0.6, 0.8, 1 and y = 0, 0.02, 0.04, 0.06, 0.08, 0.1). Sol-gel method was employed for synthesizing these hexagonal ferrites. The XRD plots of all studied materials which were annealed at 1250 °C show single phase characteristics. Lattice parameter ‘c’ increased as a consequence of larger radius of rare earth ion (Nd³⁺) as compared to (Fe³⁺), while lattice parameter ‘a’ showed very small variation. The cell volume was obtained in the range 2508.32–2523.75 (ų). The inclusion of Nd-Ni also affected X-ray density, bulk density and porosity. The FTIR spectroscopy indicated the particular absorption peaks of hexagonal ferrites and it was performed in the range of 500–700 cm^?1. On account of Nd-Ni doping, the dielectric constant, dielectric loss and AC-conductivity showed decreasing trend. The occupancy of Nd³⁺ ions at octahedral site impedes the valence alternation of Fe³⁺; therefore there was decrease in dielectric permittivity. Ac conductivity has been decreased from 9.14 to 6.49 (Ω cm)^?1 at frequency of 2.7 GHz. The Cole-Cole plots of synthesized materials noticeably revealed grain boundary contribution. The appearance of single semi-circle in impedance Cole-Cole graphs confirms the exceptional role of grain boundaries in the conduction process. The considerably lower dielectric parameters of investigated nano X-type ferrites propose their feasibility for high-frequency applications (phase shifters, dielectric resonators, stealth technology etc).     

Zein-based anti-browning cling wraps for fresh-cut apple slices

The usage of cling wraps is emerging as an easy and cost-effective approach to protect fresh-cut fruits and vegetables from dust, whilst improving visual appeal on retail counters. This study focused on developing an alternate, protein-based packaging material as a food grade cling wrap for food packaging applications. Zein-based cling wraps were produced, and their physical and mechanical characteristics were evaluated and compared with conventionally used chitosan biopolymer films and commercial synthetic polymer films. Antioxidant potential of the prepared films was studied, and the effectiveness of the developed films as anti-browning cling wraps was evaluated using studies conducted on fresh-cut apple slices at ambient conditions. Anti-browning effects were in par with polymeric counterparts; however, zein cling wraps could better prevent weight loss in apple slices. Zein-based films can be adopted as biodegradable food grade cling wraps as an alternative to chitosan and synthetic polymeric materials.