Etude De Quelques Proprietes Biologiques De Ocimum Gratissimum L., Une Lamiaceae Recoltee A Daloa (Côte d'Ivoire)

Introduction: Ocimum gratissimum is used in traditional Ivorian medicine for its multiple therapeutic virtues. Scope: Evaluate the biological properties of the essential oil of this plant. Methods: Antitumor activity was assessed using the MTS colorimetric assay on six (06) cell lines, the antifungal activity was evaluated by double dilution slant method on four (04) strains of clinical fungi, the potential antioxidant was determined by the DPPH test. Results: The strongest cytotoxic activity was obtained on Jurkat (T lymphoma) with an IC50 = 80 μg / ml. The best antifungal activity was observed on C. albicans with MIC and FMC values obtained at 12.5 μg / ml. Antioxidant activity was evaluated at F = 187 ± 1.57 mM Trolox / ml or (I = 38 ± 0.74%). Conclusion: The essential oil has interesting biological properties like as cytotoxic, antifungal and antioxidan

Original Contribution Nitric oxide activates an Nrf2/sulfiredoxin antioxidant pathway in macrophages

a b s t r a c t a r t i c l e i n f o Peroxiredoxins (Prx's) are a family of peroxidases that maintain thiol homeostasis by catalyzing the reduction of organic hydroperoxides, H 2 O 2 , and peroxynitrite. Under conditions of oxidative stress, eukaryotic Prx's can be inactivated by the substrate-dependent oxidation of the catalytic cysteine to sulfinic acid, which may regulate the intracellular messenger function of H 2 O 2 . A small redox protein, sulfiredoxin (Srx), conserved only in eukaryotes, has been shown to reduce sulfinylated 2-Cys Prx's, adding to the complexity of the H 2 O 2 signaling network. In this study, we addressed the regulation of Srx expression in immunostimulated primary macrophages that produce both reactive oxygen species (ROS) and nitric oxide (NO • ). We present genetic evidence that NO-mediated Srx up-regulation is mediated by the transcription factor nuclear factor erythroid 2-related factor (Nrf2). We also show that the NO • /Srx pathway inhibits generation of ROS. These results reveal a link between innate immunity and H 2 O 2 signaling. We propose that an NO • /Nrf2/Srx pathway participates in the maintenance of redox homeostasis in cytokine-activated macrophages and other inflammatory settings

Performance of Pyridylthiourea-Polyethylenimine Polyplex for siRNA-Mediated Liver Cancer Therapy in Cell Monolayer, Spheroid, and Tumor Xenograft Models

Medical application of siRNAs relies on methods for delivering nucleic acids into the cytosol. Synthetic carriers, which assemble with nucleic acids into delivery systems, show promises for cancer therapy but efficiency remains to be improved. In here, the effectiveness of pyridylthiourea‐polyethylenimine (πPEI), a siRNA carrier that favors both polyplex disassembly and endosome rupture upon sensing the acidic endosomal environment, in 3 experimental models of hepatocellular cancer is tested. The πPEI‐assisted delivery of a siRNA targeting the polo‐like kinase 1 into Huh‐7 monolayer produces a 90% cell death via a demonstrated RNA interference mechanism. Incubation of polyplex with Huh‐7 spheroids leads to siRNA delivery into the superficial first cell layer and a 60% reduction in spheroid growth compared to untreated controls. Administration of polyplexes into mice bearing subcutaneous implanted Huh‐7Luc tumors results in a reduced tumor progression, similar to the one observed in the spheroid model. Altogether, these results support the in vivo use of synthetic and dedicated polymers for increasing siRNA‐mediated gene knockdown, and their clinical promise in cancer therapeutics

How Polydopamine Modulates Biological Responses to PTFE Prostheses

International audienceDiaphragm repair after congenital diaphragmatic hernia is associated with hernia recurrence due to prosthesis failure. Expanded polytetrafluoroethylene (e-PTFE), a synthetic non-degradable biomaterial, is currently used for those diaphragmatic defect repairs. The drawback of e-PTFE is its poor wettability that leads to coating difficulties, bonding that could favor implant integration. However, polydopa-mine (PDA) can be deposited as well on organic as on inorganic substrates. Therefore, we assessed the biological responses of a clinically used e-PTFE bio-material treated with PDA in two different manners: one impregnated with PDA and the other coated with a one side PDA film. Mechanical properties of the raw e-PTFE, the PDA soaked biomaterial and the PDA coated surface were characterized by colloidal probe atomic force microscopy. Behaviors of primary human fibroblasts and Wharton's jelly stem cells were investigated by electron micro-scopy. Findings reveal that the mechanical properties at the microscopic scale are not modified by the PDA treatments. Cells spread onto both PDA functionalized substrates. In addition, microscopic observations disclose numerous focal cell contacts, evidencing cell attachment, and cytoplasmic projections particularly with the nanoscale PDA coating. Results clearly suggest that PDA in general but above all the PDA coating enhance cellular colonization of the implant material

Optimization of peptide-based cancer vaccine compositions, by sequential screening, using versatile liposomal platform

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Polyarginine as a Simultaneous Antimicrobial, Immunomodulatory, and miRNA Delivery Agent within Polyanionic Hydrogel

Implantation of biomedical devices is followed by immune response to the implant, as well as occasionally bacterial, yeast, and/or fungal infections. In this context, new implant materials and coatings that deal with medical device-associated complications are required. Antibacterial and anti-inflammatory materials are also required for wound healing applications, especially in diabetic patients with chronic wounds. In this work, hyaluronic acid (HA) hydrogels with triple activity: antimicrobial, immunomodulatory, and miRNA delivery agent, are presented. It is demonstrated that polyarginine with a degree of polymerization of 30 (PAR30), which is previously shown to have a prolonged antibacterial activity, decreases inflammatory response of lipopolysaccharide-stimulated macrophages. In addition, PAR30 accelerates fibroblast migration in macrophage/fibroblast coculture system, suggesting a positive effect on wound healing. Furthermore, PAR30 allows to load miRNA into HA hydrogels, and then to deliver them into the cells. To the authors knowledge, this study is the first describing miRNA-loaded hydrogels with antibacterial effect and anti-inflammatory features. Such system can become a tool for the treatment of infected wounds, e.g., diabetic ulcers, as well as for foreign body response modulation. Keywords: anti-inflammatory; antibacterial; biomaterials; hydrogels; miRNA

β-Cyclodextrin-Functionalized Chitosan/Alginate Compact Polyelectrolyte Complexes (CoPECs) as Functional Biomaterials with Anti-Inflammatory Properties

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Liposomes as tunable platform to decipher the antitumor immune response triggered by TLR and NLR agonists

Liposomes are powerful tools for the optimization of peptides and adjuvant composition in cancer vaccines. Here, we take advantage of a liposomal platform versatility to develop three vaccine candidates associating a peptide from HA influenza virus protein as CD4 epitope, a peptide from HPV16 E7 oncoprotein as CD8 epitope and TLR4, TLR2/6 or NOD1 agonists as adjuvant. Liposomal vaccine containing MPLA (TLR4 liposomes), are the most effective treatment against the HPV-transformed orthotopic lung tumor mouse model, TC-1. This vaccine induces a potent Th1-oriented antitumor immunity, which lead to a significant reduction in tumor growth and a prolonged survival of mice, even when injected after tumor appearance. This efficacy is dependent on CD8+ T cells. Subcutaneous injection of this treatment induces the migration of skin DCs to draining lymph nodes. Interestingly, TLR2/6 liposomes trigger a weaker Th1-immune response which is not sufficient for the induction of a prolonged antitumor activity. Although NOD1 liposome treatment results in the control of early tumor growth, it does not extend mice survival. Surprisingly, the antitumor activity of NOD1 vaccine is not associated with a specific adaptive immune response. This study shows that our modulable platform can be used for the strategical development of vaccines