Antioxidant, antibacterial and cell toxicity effects of polyphenols Fromahmeur bouamer grape seed extracts

In this work and for the first time, significant concentrations of total polyphenols and flavonoids from Vitis vinifera L. grape seed extracts were obtained (256.15 ± 17.40 mg GAE/gdm and 14.08 ± 0.64 mg CE/gdm, respectively).The LC/MS analysis revealed richness in procyanidins. For antioxidant, antimicrobial and antifungal effects, the grape seed extract (GSE) responded positively. At 100 μg/mL, GSE induced a moderate toxicity of the order of 3.88% on 3T6 cells at the first 24 hours of treatment, whereas, its prolonged effect to 48 hours reduced this toxicity to less than 0.5%. As for the anti-proliferative effect on tumoral cell lines, a cell death of 18.39% to 23.79% and 10.30% to 20.37% was registered respectively for HeLa and BCPAP cells during 24 and 48 hours of treatment. Consequently, it is possible to consider using GSE at lower concentrations as an anti-proliferative agent without losing sight of its benefic effect on healthy cells.Keywords: grape seed extract, 3T6 cell, antioxidant, antibacterial, anti-proliferation

Publication Recommendations to Report Laboratory Data of Neonates - a Modified Delphi Approach

Background: Clinical and analytical information on laboratory data of neonates in scientific publications is sparse and incomplete. Furthermore, interpreting neonatal laboratory data can be complex due to their time-dependent and developmental physiology, and paucity of well-established age-appropriate reference ranges for neonates. This study aims to develop publication recommendations to report laboratory data of neonates to enhance the quality of these data in research and clinical care. Methods: A modified Delphi approach was used to develop recommendations in cooperation with the International Neonatal Consortium. A Core Group, including different stakeholders, was responsible for developing the recommendations, in collaboration with a Reflection Group, responsible for providing additional input. Results: The recommendations were classified into three categories: ‘Clinical Characteristics’, ‘Bio-analytical Information’ and ‘Data-analytical Information’. These were each divided into ‘Core Data’ (always to be reported) and ‘Supplemental Considerations’ (to be reported when considered relevant to the study). Conclusion: Our recommendations provide guidance on standardization of neonatal laboratory data in publications. This will enhance the comparison, replication, and application of study results in research initiatives and clinical practice. Furthermore, these recommendations also serve as foundational work to develop reference ranges for neonatal laboratory values by standardizing the quality of information needed for such efforts. Impact: Standardized reporting of neonatal laboratory data in scientific publications will enhance the comparison, replication, and application of study results in research initiatives and clinical practice, as well as improve reporting to regulatory agencies. To integrate multistakeholder perspectives, a modified Delphi approach was used to develop publication recommendations which strengthens the applicability of the recommendations. Implementation of standardization will likely improve the overall quality of neonatal clinical research and neonatal healthcare. In addition, these recommendations are foundational to develop reference ranges for neonatal laboratory values by standardizing the quality of information needed for such efforts.</p

Bifunctional Gd(III) and Tb(III) chelates based on a pyridine-bis(iminodiacetate) platform, suitable contrast agents for magnetic resonance and optical imaging

peer reviewe

Lanthanide(III) Complexes of Novel Mixed Carboxylic-Phosphorus Acid Derivatives of Diethylenetriamine: A Step towards More Efficient MRI Contrast Agents

Three novel phosphorus-containing analogues of H5DTPA (DTPA = diethylenetriaminepentaacetate) were synthesised (H6L1, H5L2, H5L3). These compounds have a -CH2-P(O)(OH)-R function (R = OH, Ph, CH2NBn2) attached to the central nitrogen atom of the diethylenetriamine backbone. An NMR study reveals that these ligands bind to lanthanide(III) ions in an octadentate fashion through the three nitrogen atoms, a P-O oxygen atom and four carboxylate oxygen atoms. The complexed ligand occurs in several enantiomeric forms due to the chirality of the central nitrogen atom and the phosphorus atom upon coordination. All lanthanide complexes studied have one coordinated water molecule. The residence times (tau) of the coordinated water molecules in the gadolinium(III) complexes of H6L1 and H5L2 are 88 and 92 ns, respectively, which are close to the optimum. This is particularly important upon covalent and noncovalent attachment of these Gd3+ chelates to polymers. The relaxivity of the complexes studied is further enhanced by the presence of at least two water molecules in the second coordination sphere of the Gd3+ ion, which are probably bound to the phosphonate/phosphinate moiety by hydrogen bonds. The complex [Gd(L3)(H2O)]2- shows strong binding ability to HSA, and the adduct has a relaxivity comparable to MS-325 (40 s-1 mM-1 at 40 MHz, 37 °C) even though it has a less favourable tauM value (685 ns). Transmetallation experiments with Zn2+ indicate that the complexes have a kinetic stability that is comparable to - or better than - those of [Gd(dtpa)(H2O)]2- and [Gd(dtpa-bma)(H2O)]

In Vivo Detection of Inflammation Using Pegylated Iron Oxide Particles Targeted at E-Selectin A Multimodal Approach Using MR Imaging and EPR Spectroscopy

peer reviewedObjectives: Ultrasmall particles of iron oxide (USPIO) possess superparamagnetic properties and are used as negative contrast agent in magnetic resonance imaging (MRI) because of their strong T-2 and T-2* effects. Besides this method, electron paramagnetic resonance (EPR) offers the unique capability to quantify these particles. The objective of this study was to evaluate a molecular marker for non invasive diagnosis and monitoring of inflammation. During inflammation cell adhesion molecules such as E-selectin are expressed on the endothelial cell surface. An E-selectin ligand was coupled to pegylated USPIO particles. Materials and Methods: Inflammation was induced by intramuscular injection of Freund's Complete Adjuvant in male NMRI mice. After intravenous injection of grafted or ungrafted USPIO particles, iron concentration in inflamed muscles was quantified ex vivo by X-band EPR. Particle accumulation was also assessed in vivo by L-Band EPR, as well as by T-2-Weighted MRI. Results: We determined the mean iron oxide concentration in inflamed muscles after injection of grafted or ungrafted UPSIO particles, which was 0.8% and 0.4% of the initially injected dose, respectively. By L-band EPR, we observed that the concentration of the grafted USPIO particles in inflamed muscles was twice higher than for the ungrafted particles. Using MRI experiments, a higher signal loss was clearly observed in the inflamed muscle when grafted particles were injected in comparison with the ungrafted particles. Conclusion: Even taking into account a non specific accumulation of iron oxides, the targeting of USPIO particles with E-selectin ligands significantly improved the sensitivity of detection of inflamed tissues

Mn2+ Complexes with Pyclen-Based Derivatives as Contrast Agents for Magnetic Resonance Imaging: Synthesis and Relaxometry Characterization

Magnetic resonance imaging (MRI) has a leading place in medicine as an imaging tool of high resolution for anatomical studies and diagnosis of diseases, in particular for soft tissues that cannot be accessible by other modalities. Many research works are thus focused on improving the images obtained with MRI. This technique has indeed poor sensitivity, which can be compensated by using a contrast agent (CA). Today, the clinically approved CAs on market are solely based on gadolinium complexes that may induce nephrogenic systemic fibrosis for patients with kidney failure, whereas more recent studies on healthy rats also showed Gd retention in the brain. Consequently, researchers try to elaborate other types of safer MRI CAs like manganese-based complexes. In this context, the synthesis of Mn2+ complexes of four 12-membered pyridine-containing macrocyclic ligands based on the pyclen core was accomplished and described herein. Then, the properties of these Mn(II) complexes were studied by two relaxometric methods, 17O NMR spectroscopy and 1H NMR dispersion profiles. The time of residence (τM) and the number of water molecules (q) present in the inner sphere of coordination were determined by these two experiments. The efficacy of the pyclen-based Mn(II) complexes as MRI CAs was evaluated by proton relaxometry at a magnetic field intensity of 1.41 T near those of most medical MRI scanners (1.5 T). Both the 17O NMR and the nuclear magnetic relaxation dispersion profiles indicated that the four hexadentate ligands prepared herein left one vacant coordination site to accommodate one water molecule, rapidly exchanging, in around 6 ns. Furthermore, it has been shown that the presence of an additional amide bond formed when the paramagnetic complex is conjugated to a molecule of interest does not alter the inner sphere of coordination of Mn, which remains monohydrated. These complexes exhibit r1 relaxivities, large enough to be used as clinical MRI CAs (1.7–3.4 mM–1·s–1, at 1.41 T and 37 °C)

Modulation of Cytosolic Phospholipase A2 as a Potential Therapeutic Strategy for Alzheimer's Disease.

peer reviewedBACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder lacking any curative treatment up to now. Indeed, actual medication given to the patients alleviates only symptoms. The cytosolic phospholipase A2 (cPLA2-IVA) appears as a pivotal player situated at the center of pathological pathways leading to AD and its inhibition could be a promising therapeutic approach. OBJECTIVE: A cPLA2-IVA inhibiting peptide was identified in the present work, aiming to develop an original therapeutic strategy. METHODS: We targeted the cPLA2-IVA using the phage display technology. The hit peptide PLP25 was first validated in vitro (arachidonic acid dosage [AA], cPLA2-IVA cellular translocation) before being tested in vivo. We evaluated spatial memory using the Barnes maze, amyloid deposits by MRI and immunohistochemistry (IHC), and other important biomarkers such as the cPLA2-IVA itself, the NMDA receptor, AβPP and tau by IHC after i.v. injection in APP/PS1 mice. RESULTS: Showing a high affinity for the C2 domain of this enzyme, the peptide PLP25 exhibited an inhibitory effect on cPLA2-IVA activity by blocking its binding to its substrate, resulting in a decreased release of AA. Coupled to a vector peptide (LRPep2) in order to optimize brain access, we showed an improvement of cognitive abilities of APP/PS1 mice, which also exhibited a decreased number of amyloid plaques, a restored expression of cPLA2-IVA, and a favorable effect on NMDA receptor expression and tau protein phosphorylation. CONCLUSION: cPLA2-IVA inhibition through PLP25 peptide could be a promising therapeutic strategy for AD

Studies on preparation and characterization of novel MRI contrast agents for targeting organs and blood vessels

peer reviewedTo improve the poor properties of currently clinically used MRI contrast agent of Gd-DTPA (Gadolinium-Diethylenetriamine-N,N,N',N',N'-pentaacetic acid) complex, sugar dendritic derivatives which contains Gd-DTPA as the core part and four or twelve sugars as the terminal part, dendrimer 8(Gd-DTPA-D1Glc(OAc)) or dendrimer 10(Gd-DTPA-D2Glc(OAc)), respectively, were prepared. From the result of relaxivity profile of these Gd complexes depending on temperature and magnitude of magnetic field, the smaller size MRI contrast agent of Gd-DTPA, 8(Gd-DTPA-D1Glc(OAc)), showed similar behavior to that of Gd-DTPA and the dendrimer constructs DDS of Gd-DTPA and was proven to have the improved properties for MR imaging of blood vessel (MRA) as well as for targeting specific organs