Atherosclerosis: immunopathogenesis and strategies for immunotherapy.

Atherosclerosis, a chronic inflammatory condition in which atheroma accumulates within the intima of the arterial wall, is a life-threatening manifestation of cardiovascular disease, due to atheroma rupture, chronic luminal narrowing and thrombosis. Current knowledge of the role of a protective immune response in atherosclerotic lesions has provided promising opportunities to develop new immunotherapeutic strategies. In particular, Tregs exert an atheroprotective role by releasing anti-inflammatory cytokines (IL-10/TGF-β) and suppressing autoreactive T lymphocytes.

Identification of Potential Kinase Inhibitors within the PI3K/AKT Pathway of Species.

Leishmaniasis is a public health disease that requires the development of more effective treatments and the identification of novel molecular targets. Since blocking the PI3K/AKT pathway has been successfully studied as an effective anticancer strategy for decades, we examined whether the same approach would also be feasible in due to their high amount and diverse set of annotated proteins. Here, we used a best reciprocal hits protocol to identify potential protein kinase homologues in an annotated human PI3K/AKT pathway.

Submerged cultivation, characterization and in vitro antitumor activity of polysaccharides from Schizophyllum radiatum.

Production of polysaccharides by white-rot-fungi in submerged cultivation has several advantages due to process control. This work deals with the submerged cultivation, extraction and antitumor activity of polysaccharides from a wild strain of Schizophyllum radiatum isolated from a tropical forest of Colombia. The mushroom was cultivated in laboratory conditions, and classified by classical and molecular taxonomy.

Biotechnological production, characterization and in vitro antitumor activity of polysaccharides from a native strain of Lentinus crinitus.

This work deals with the submerged cultivation, extraction and antitumor activity of polysaccharides from Lentinus crinitus. The fungus was isolated from a tropical forest (Antioquia, Colombia), cultivated in laboratory conditions, and classified by classical and molecular taxonomy. Then, it was cultivated in a bioreactor of 5 L using a ligninolytic residue as substrate.

Antitumor activity of Lepidium latifolium and identification of the epithionitrile 1-cyano-2,3-epithiopropane as its major active component.

Consumption of Brassica (Cruciferae) vegetables is associated with a reduced risk of cancer, but identification of the active components and insights into the underlying molecular events are scarce. Here we found that an extract of Lepidium latifolium, a cruciferous plant native to southern Europe, Mediterranean countries and Asia, showed in vitro cytotoxic activity, inducing caspase-dependent apoptosis, in a variety of human tumor cells, and the plant juice showed in vivo antitumor activity in a HT-29 human colon cancer xenograft mouse model. The epithionitrile 1-cyano-2,3-epithiopropane (CETP) was identified as the major active cancer cell-killing principle of L.

Mitochondria and lipid raft-located FOF1-ATP synthase as major therapeutic targets in the antileishmanial and anticancer activities of ether lipid edelfosine.

Background: Leishmaniasis is the world's second deadliest parasitic disease after malaria, and current treatment of the different forms of this disease is far from satisfactory. Alkylphospholipid analogs (APLs) are a family of anticancer drugs that show antileishmanial activity, including the first oral drug (miltefosine) for leishmaniasis and drugs in preclinical/clinical oncology trials, but their precise mechanism of action remains to be elucidated.

Methodology/principal Findings: Here we show that the tumor cell apoptosis-inducer edelfosine was the most effective APL, as compared to miltefosine, perifosine and erucylphosphocholine, in killing Leishmania spp.

Interleukin-10 production and T cell-suppressive capacity in B cell subsets from atherosclerotic apoE mice.

The evidence regarding the role of regulatory B cells (Breg) in atherosclerosis are scarce, and there are contradictory data about their atheroprotective properties. Due to the demonstrated protective function of Breg in different inflammatory diseases mainly through interleukin-10 (IL-10) production, the knowledge of their participation in atherosclerosis immunopathology would be very valuable. To further study which B cell subsets participate in IL-10 production and their regulatory role, splenocytes from apolipoprotein-E-deficient mice were evaluated by ex vivo and in vitro cultures.

Data in support of dyslipidemia-associated alterations in B cell subpopulations frequency and phenotype during experimental atherosclerosis.

Cardiovascular diseases are the most common cause of death in the world, atherosclerosis being its main underlying disease. Information about the role of B cells during atherosclerotic process is scarce, but both proatherogenic and atheroprotective properties have been described in the immunopathology of this disease. Frequency and phenotype of B cell subpopulations were studied in wild type and apolipoprotein-E-deficient (apoE (-/-) ) mice fed or not with high-fat diet (HFD), by flow cytometry.

Dyslipidemia-associated alterations in B cell subpopulation frequency and phenotype during experimental atherosclerosis.

Lymphocytes, the cellular effectors of adaptive immunity, are involved in the chronic inflammatory process known as atherosclerosis. Proatherogenic and atheroprotective properties have been ascribed to B cells. However, information regarding the role of B cells during atherosclerosis is scarce.

C-Geranylated flavonoids from Paulownia tomentosa fruits with antimicrobial potential and synergistic activity with antibiotics.

Context C-6-Geranylated flavonoids possess promising biological activities. These substances could be a source of lead compounds for the development of therapeutics. Objective The study was designed to evaluate their antibacterial and antileishmanial activity.

Complete inhibition of extranodal dissemination of lymphoma by edelfosine-loaded lipid nanoparticles.

Background: Lipid nanoparticles (LNs) made of synthetic lipids Compritol(®) 888 ATO and Precirol(®) ATO 5 were developed with an average size of 110.4 ± 2.1 and 103.

In vitro and in vivo efficacy of ether lipid edelfosine against Leishmania spp. and SbV-resistant parasites.

Background: The leishmaniases are a complex of neglected tropical diseases caused by more than 20 Leishmania parasite species, for which available therapeutic arsenal is scarce and unsatisfactory. Pentavalent antimonials (SbV) are currently the first-line pharmacologic therapy for leishmaniasis worldwide, but resistance to these compounds is increasingly reported. Alkyl-lysophospoholipid analogs (ALPs) constitute a family of compounds with antileishmanial activity, and one of its members, miltefosine, has been approved as the first oral treatment for visceral and cutaneous leishmaniasis.

New polyether triterpenoids from Laurencia viridis and their biological evaluation.

The red seaweed Laurencia viridis is a rich source of secondary metabolites derived from squalene. New polyethers, such as iubol (2), 22-hydroxy-15(28)- dehydrovenustatriol (3), 1,2-dehydropseudodehydrothyrsiferol (4), and secodehydrothyrsiferol (5) have been isolated and characterized from this alga. The structures were determined through the interpretation of NMR spectroscopic data and the relative configuration was proposed on the basis of NOESY spectrum and biogenetic considerations.

Cytotoxic oxasqualenoids from the red alga Laurencia viridis.

Three new polyether squalene derivatives 15-dehydroxythyrsenol A (2), prethyrsenol A (3) and 13-hydroxyprethyrsenol A (4) have been isolated from the red alga Laurencia viridis. Their structures were determined through the interpretation of NMR spectroscopic data and chemical correlations. In addition, four semi-synthetic compounds modulating the solubility of the lead compound dehydrothyrsiferol (1) were prepared without loss of activity.

Involvement of mitochondrial and B-RAF/ERK signaling pathways in berberine-induced apoptosis in human melanoma cells.

The natural isoquinoline alkaloid berberine exhibits a wide spectrum of biological activities including antitumor activity, but its mechanism of action remains to be fully elucidated. Here, we report that berberine induced apoptosis in human melanoma cells, through a process that involved mitochondria and caspase activation. Berberine-induced activation of a number of caspases, including caspases 3, 4, 7, 8, and 9.

Selective fusion of azurophilic granules with Leishmania-containing phagosomes in human neutrophils.

Leishmania parasites use polymorphonuclear neutrophils as intermediate hosts before their ultimate delivery to macrophages following engulfment of parasite-infected neutrophils. This leads to a silent and unrecognized entry of Leishmania into the macrophage host cell. Neutrophil function depends on its cytoplasmic granules, but their mobilization and role in how Leishmania parasites evade intracellular killing in neutrophils remain undetermined.

Synthesis and cytotoxic activity of a new potential DNA bisintercalator: 1,4-Bis{3-[N-(4-chlorobenzo[g]phthalazin-1-yl)aminopropyl]}piperazine.

The synthesis of new 1,4-bisalkylamino (2-4) and 1-alkylamino-4-chloro (5-6) substituted benzo[g]phthalazines is reported. Compounds 2-4 and 6 were prepared both in the free and heteroaromatic ring protonated forms. Bifunctional 6 contains the 1,4-bisaminopropylpiperazine chain as a linker between the two heteroaromatic units, whereas 5 is its monofunctional analogue.

In vitro and In vivo selective antitumor activity of Edelfosine against mantle cell lymphoma and chronic lymphocytic leukemia involving lipid rafts.

Purpose: Mantle cell lymphoma (MCL) and chronic lymphocytic leukemia (CLL) remain B-cell malignancies with limited therapeutic options. The present study investigates the in vitro and in vivo effect of the phospholipid ether edelfosine (1-O-octadecyl-2-O-methyl-rac-glycero-3-phosphocholine) in MCL and CLL.

Experimental Design: Several cell lines, patient-derived tumor cells, and xenografts in severe combined immunodeficient mice were used to examine the anti-MCL and anti-CLL activity of edelfosine.