Pharmacokinetics and Metabolism Investigation of Oleocanthal.

Oleocanthal is a secoiridoid found in olive oil, which lately gained great scientific interest due to its important pharmacological spectrum and biological properties. However, limited data exist on the metabolic fate of oleocanthal , a commonly underestimated aspect in natural products research. Especially, its pharmacokinetic (PK) characteristics have never been described so far.

Direct In Vitro Comparison of the Anti-Leishmanial Activity of Different Olive Oil Total Polyphenolic Fractions and Assessment of Their Combined Effects with Miltefosine.

The bioactive compounds present in the edible products of the olive tree have been extensively studied and their favorable effects on various disease risk factors have been demonstrated. The aim of this study was to perform a comparative analysis of the anti-leishmanial effects of total phenolic fractions (TPFs) derived from extra virgin olive oil with different phenolic contents and diverse quantitative patterns. Moreover, the present study investigated their association with miltefosine, a standard anti-leishmanial drug, against both extracellular promastigotes and intracellular amastigotes of a viscerotropic and a dermotropic strain.

Exploring the Immunotherapeutic Potential of Oleocanthal against Murine Cutaneous Leishmaniasis.

Leishmaniasis is a major tropical disease with increasing global incidence. Due to limited therapeutic options with severe drawbacks, the discovery of alternative treatments based on natural bioactive compounds is important. In our previous studies we have pointed out the antileishmanial activities of olive tree-derived molecules.

Development of autogenous vaccines for farmed European seabass against Aeromonas veronii using zebrafish as a model for efficacy assessment.

Aeromonas veronii bv. sobria is an emerging pathogen for the European seabass cultured in the Aegean Sea (Mediterranean) causing significant problems in the Greek and Turkish aquaculture industry since no licensed vaccine is currently available for the disease. A bivalent vaccine was developed based on two phenotypically distinct strains of the pathogen, PDB (motile, pigment-producing strain) and NS (non-motile, non-pigment-producing).

Total Phenolic Fraction (TPF) from Extra Virgin Olive Oil: Induction of apoptotic-like cell death in Leishmania spp. promastigotes and in vivo potential of therapeutic immunomodulation.

Background: Leishmaniasis is a serious multifactorial parasitic disease with limited treatment options. Current chemotherapy is mainly consisted of drugs with serious drawbacks such as toxicity, variable efficacy and resistance. Alternative bioactive phytocompounds may provide a promising source for discovering new anti-leishmanial drugs.

Quantification of Nitric Oxide and Reactive Oxygen Species in -infected J774A.1 Macrophages as a Response to the treatment with a Natural Product Compound.

Leishmaniasis is a parasitic disease caused by the obligatory intracellular protozoa spp. Current therapeutic options are limited and thus, drug discovery against leishmaniasis is very important. Nevertheless, there is a great difficulty to develop therapeutic strategies against the disease because the parasite deploys various mechanisms to evade the immune system and multiply inside the host.

Screening of Antileishmanial Activity of Natural Product Compounds: Determination of IC, CC and SI Values.

Neglected tropical diseases gain the scientific interest of numerous research programs in an attempt to achieve their effective control or elimination. In this attempt, more cutting-edge public health policies and research are needed for the discovery of new, safer and effective drugs originated from natural products. Here, we describe protocols for the screening of a natural product-derived compound required for the determination of its antileishmanial potency.

New Insights on the Adjuvant Properties of the Eukaryotic Initiation Factor.

Vaccination is the most effective tool against infectious diseases. Subunit vaccines are safer compared to live-attenuated vaccines but are less immunogenic and need to be delivered with an adjuvant. Adjuvants are essential for enhancing vaccine potency by improving humoral and cell-mediated immune responses.

Leishmania infantum LeIF and its recombinant polypeptides induce the maturation of dendritic cells in vitro: An insight for dendritic cells based vaccine.

We previously showed that recombinant Leishmania infantum eukaryotic initiation factor (LieIF) was able to induce the secretion of cytokines IL-12, IL-10 and TNF-α by human monocytes. In this study, we explored in vitro the potential of LieIF to induce phenotypic maturation and functional differentiation of murine bone-marrow derived dendritic cells (BM-DCs). Moreover, in order to identify potential immunnomodulatory regions of LieIF, eight recombinant overlapping protein fragments covering the whole amino acid sequence of protein, were constructed and assessed in vitro for their ability to induce maturation of BM-DCs.

The Role of Tissue Oxygen Tension in Dengue Virus Replication.

Low oxygen tension exerts a profound effect on the replication of several DNA and RNA viruses. In vitro propagation of Dengue virus (DENV) has been conventionally studied under atmospheric oxygen levels despite that in vivo, the tissue microenvironment is hypoxic. Here, we compared the efficiency of DENV replication in liver cells, monocytes, and epithelial cells under hypoxic and normoxic conditions, investigated the ability of DENV to induce a hypoxia response and metabolic reprogramming and determined the underlying molecular mechanism.

Evaluation of total phenolic fraction derived from extra virgin olive oil for its antileishmanial activity.

Background: Leishmaniasis is a neglected and emerging disease with varying clinical manifestations. The current treatment options rely on limited chemotherapy with serious drawbacks. Thus, there is an increasing interest in the identification of new candidates for designing potent, less toxic and low-cost drugs.

Evaluation of Protective Efficacy of Selected Immunodominant B-Cell Epitopes within Virulent Surface Proteins of Streptococcus pneumoniae.

Four previously identified immunodominant B-cell epitopes, located within known virulent pneumococcal proteins CbpD, PhtD, PhtE, and ZmpB, had shown promising immunological characteristics, indicating their potential to be used as vaccine antigens. In this study, we further evaluated the opsonophagocytic activity of antibodies against these epitopes and their capacity to protect mice from pneumococcal sepsis. An opsonophagocytic killing assay (OPKA) revealed that OPKA titers of human anti-peptide antibodies against pneumococcal serotypes 1, 3, and 19A were significantly higher ( < 0.

Phlebotomine sandflies and factors associated with their abundance in the leishmaniasis endemic area of Attiki, Greece.

Leishmaniasis is a parasitic disease of animals and humans caused by several Leishmania species and transmitted by phlebotomine sandflies. The aim of the present study was to identify the species of field collected phlebotomine sandflies in the endemic area of the Attiki during 4 consecutive years, to isolate the Leishmania parasites from the infected sandflies, and identify possible factors associated with sandfly abundance in the area. A total of 542 trappings were made in 46 collection sites, in purely urban areas, periurban areas, and purely rural areas in Attiki.

In silico analysis and in vitro evaluation of immunogenic and immunomodulatory properties of promiscuous peptides derived from Leishmania infantum eukaryotic initiation factor.

It is generally considered as imperative the ability to control leishmaniasis through the development of a protective vaccine capable of inducing long-lasting and protective cell-mediated immune responses. In this current study, we demonstrated potential epitopes that bind to H2 MHC class I and II molecules by conducting the in silico analysis of Leishmania infantum eukaryotic Initiation Factor (LieIF) protein, using online available algorithms. Moreover, we synthesized five peptides (16-18 amino acids long) which are part of the N-terminal portion of LieIF and contain promising MHC class I and II-restricted epitopes and afterwards, their predicted immunogenicity was evaluated in vitro by monitoring peptide-specific T-cell responses.

The leishmanicidal activity of oleuropein is selectively regulated through inflammation- and oxidative stress-related genes.

Background: Much research effort has been focused on investigating new compounds derived from low-cost sources, such as natural products, for treating leishmaniasis. Oleuropein derived from numerous plants, particularly from the olive tree, Olea europaea L. (Oleaceae), is a biophenol with many biological activities.

Mannan-conjugated myelin peptides prime non-pathogenic Th1 and Th17 cells and ameliorate experimental autoimmune encephalomyelitis.

Antigen presenting cells (APC) are critical for regulating immune responses. We tested mannan-peptide conjugates for targeting myelin peptides to APC to induce T cell tolerance and resistance to experimental autoimmune encephalomyelitis (EAE). Myelin peptides conjugated to mannan in oxidized (OM) or reduced (RM) forms protected mice against EAE in prophylactic and therapeutic protocols, with OM-conjugated peptides giving best results.

Experimental Validation of Multi-Epitope Peptides Including Promising MHC Class I- and II-Restricted Epitopes of Four Known Leishmania infantum Proteins.

Leishmaniasis is a significant worldwide health problem for which no vaccine exists. Activation of CD4(+) and CD8(+) T cells is crucial for the generation of protective immunity against parasite. Recent trend in vaccine design has been shifted to epitope-based vaccines that are more specific, safe, and easy to produce.

Leishmania eukaryotic initiation factor (LeIF) inhibits parasite growth in murine macrophages.

The leishmaniases constitute neglected global public health problems that require adequate control measures, prophylactic clinical vaccines and effective and non-toxic drug treatments. In this study, we explored the potential of Leishmania infantum eukaryotic initiation factor (LieIF), an exosomal protein, as a novel anti-infective therapeutic molecule. More specifically, we assessed the efficacy of recombinant LieIF, in combination with recombinant IFN-γ, in eliminating intracellular L.

Anthropometric, hemodynamic, metabolic, and renal responses during 5 days of food and water deprivation.

Background: Although there is considerable research in the field of fasting and fluid restriction, little is known about the impact of food and water deprivation (FWD) on body circumferences and vital parameters.

Methods: During 5 days of FWD in 10 healthy adults, hemodynamic, metabolic, and renal parameters, such as weight, 5 circumferences at neck, waist, hip, chest at axilla, chest at nipples, and 1 new oblique hip circumference were measured daily. For each circumference, new quotients of daily circumference-to-weight decrease were calculated.

Leishmanicidal activity assessment of olive tree extracts.

Leishmaniasis, a protozoan parasitic disease that remains a major worldwide health problem with high endemicity in developing countries, is prevalent around the Mediterranean basin. High cost, systemic toxicity, and diminished efficacy due to development of parasite resistance are the serious drawbacks of current treatment options. Thus, identifying new, effective, and safer anti-leishmanial drug(s) is of paramount importance.

Cellular FLIP long isoform transgenic mice overcome inherent Th2-biased immune responses to efficiently resolve Leishmania major infection.

c-FLIP(L) expression in T cells is required for mounting effective T cell responses and can also be critical for effector T cell differentiation, as has recently been shown by a number of in vivo studies in conditional knockout and transgenic mouse systems. Available data supports therefore a novel immunomodulatory role of this anti-apoptotic protein besides its traditionally proposed function in homeostatic maintenance of T cell populations. In this study, the responses to infection with Leishmania major of mice over-expressing FLIP(L) specifically in the T cell compartment (TgFLIP(L)) are assessed.

Function of CD8+ T lymphocytes in a self-curing mouse model of visceral leishmaniasis.

CD8+ T lymphocytes play an important role in the control of visceral leishmaniasis in non self-cure mice (e.g. BALB/c).

CD8(+) T cells with parasite-specific cytotoxic activity and a Tc1 profile of cytokine and chemokine secretion develop in experimental visceral leishmaniasis.

Recently, a prominent role for CD8(+) T cells in immunity against pathogens has emerged. The mode of action of CD8(+) T cells in murine visceral leishmaniasis and their contribution to the clearance of the parasite has been addressed in the present study. We showed that during the course of experimental infection cytotoxic clones specific for Leishmania infantum antigens developed in the spleen of susceptible BALB/c mice, showed an activated phenotype and became susceptible to apoptotic cell death late in the course of the disease.

Idiotype-anti-idiotype circuit in non-autoimmune mice after immunization with the epitope and complementary epitope 289-308aa of La/SSB: implications for the maintenance and perpetuation of the anti-La/SSB response.

Background: Antibodies to La/SSB are usually found in sera of patients with Sjogren's Syndrome (SS) and Systemic Lupus Erythematosus (SLE). Recent work from our laboratory (Mol Med 2002;8:293-305) revealed that an active idiotypic network involving antibodies to epitopes of La/SSB and their anti-idiotypes exist in human sera. The anti-idiotypic antibodies were detected using complementary peptides to B-cell epitopes of the autoantigen.