Neuroprotective effects of Ellagic acid on Neonatal Hypoxic Brain Injury via Inhibition of Inflammatory Mediators and Down-regulation of JNK/p38 MAPK Activation

Purpose: To investigate if ellagic acid exerts neuroprotective effects in hypoxic ischemic (HI) brain injury by inhibiting apoptosis and inflammatory responses.Methods: Separate groups of rat pups from post-natal day 4 (D4) were administered with ellagic acid (10, 20 or 40 mg/kg body weight) orally till post- natal day 10 (D10). On D10, the rats were subjected to HI brain injury. Following HI injury, infarct size, weight and volume of the brain were measured. Apoptosis was assessed by Fluoro-Jade C staining. Expression of caspases (caspase-3, 8 and 9), apoptotic pathway proteins (Bax, Bad, Bcl-2 and Bcl-xL), MAPKs, NF κB(p65) and p-IK-Bα were assessed by western blotting. mRNA levels of inflammatory mediators (TNF-α, IL-1α, IL-1β, iNOS, COX-2) were analyzed.Results: Ellagic acidmarkedly (p < 0.05) reduced infarct size, volume and tissue loss. Significant (p < 0.05) reduction in neuroapoptosis was observed on pre treatment with ellagic acid. Expression levels of caspases, apoptotic pathway proteins and MAPK proteins were down-regulated with marked (p < 0.05) suppression of inflammatory mediators, NF-κB(p65) and p-IK-Bα.Conclusion: Ellagic acid affords neuroprotection in HI brain injury by inhibiting apoptosis, inflammatory responses and modulating the proteins of apoptotic and MAPK pathways. Thus, ellagic acid may be a potent candidate for the treatment of HI injury.Keywords: Brain injury, Ellagic acid, Hypoxia, Inflammatory mediators, Mitogen activated protein kinases, Neuroprotectiv

Anisotropic g factors of the tetragonal Cu²⁺ monomer in Tl-2223 superconductor

The gyromagnetic factors of the Cu²⁺ monomer in Tl-2223 superconductor are quantitatively investigated from the perturbation formulas of these factors for a 3d⁹ ion in a tetragonally elongated octahedron. The local tetragonal distortion of the system is attributable to the axial elongation along c axis, corresponding to the five-fold coordinated Cu²⁺(2) site with almost 30% longer Cu–O bond length for the apical oxygen as compared to the four planar ones. The significant anisotropic behaviors of the EPR spectra perpendicular to and parallel with the ab (CuO₂) layers are analyzed on the basis of the local tetragonal elongation

Causal structures and causal boundaries

We give an up-to-date perspective with a general overview of the theory of causal properties, the derived causal structures, their classification and applications, and the definition and construction of causal boundaries and of causal symmetries, mostly for Lorentzian manifolds but also in more abstract settings.Comment: Final version. To appear in Classical and Quantum Gravit

Robust estimation of bacterial cell count from optical density

Optical density (OD) is widely used to estimate the density of cells in liquid culture, but cannot be compared between instruments without a standardized calibration protocol and is challenging to relate to actual cell count. We address this with an interlaboratory study comparing three simple, low-cost, and highly accessible OD calibration protocols across 244 laboratories, applied to eight strains of constitutive GFP-expressing E. coli. Based on our results, we recommend calibrating OD to estimated cell count using serial dilution of silica microspheres, which produces highly precise calibration (95.5% of residuals <1.2-fold), is easily assessed for quality control, also assesses instrument effective linear range, and can be combined with fluorescence calibration to obtain units of Molecules of Equivalent Fluorescein (MEFL) per cell, allowing direct comparison and data fusion with flow cytometry measurements: in our study, fluorescence per cell measurements showed only a 1.07-fold mean difference between plate reader and flow cytometry data

Studies on the axial shift and the spin Hamiltonian parameters for Cr

The axial shift and the spin Hamiltonian parameters (zero-field splitting D, g factors and hyperfine structure constants) for Cr+ in BeO are theoretically studied in this work. The calculations are carried out by using the perturbation formulas of these parameters for a 3d5 ion under trigonally distorted tetrahedra based on the cluster approach containing both the crystal-field and charge transfer contributions. It is found that the impurity Cr+ may not occupy exactly the host Be2+ site but experience a small outward shift 0.01 Å away from the ligand triangle along the C3 axis. The above impurity axial shift leads to much smaller trigonal distortion than the host Be2+ site in BeO. The theoretical spin Hamiltonian parameters based on the above impurity axial shift are in good agreement with the observed values

Birkhoff and Taub theorems generalized to metrics with conformal symmetries

SIGLEITItal

Syntheses and Biological Evaluation of Costunolide, Parthenolide, and Their Fluorinated Analogues

Inspired by the biosynthesis of sesquiterpene lactones (SLs), herein we report the asymmetric total synthesis of the germacrane ring (<b>24</b>). The synthetic strategy features a selective aldol reaction between β,γ-unsaturated chiral sulfonylamide <b>15a</b> and aldehyde <b>13</b>, as well as the intramolecular α-alkylation of sulfone <b>21</b> to construct a 10-membered carbocylic ring. The key intermediate <b>24</b> can be used to prepare the natural products costunolide and parthenolide (PTL), which are the key precursors for transformation into other SLs. Furthermore, the described synthetic sequences are amenable to the total synthesis of SL analogues, such as trifluoromethylated analogues <b>32</b> and <b>45</b>. Analogues <b>32</b> and <b>45</b> maintained high activities against a series of cancer cell lines compared to their parent PTL and costunolide, respectively. In addition, <b>32</b> showed enhanced tolerance to acidic media compared with PTL. To our surprise, PTL and <b>32</b> showed comparable half-lives in rat plasma and in the presence of human liver microsomes