Biological activities of phenolic compounds present in virgin olive oil

The Mediterranean diet is associated with a lower incidence of atherosclerosis, cardiovascular disease, neurodegenerative diseases and certain types of cancer. The apparent health benefits have been partially ascribed to the dietary consumption of virgin olive oil by Mediterranean populations. Much research has focused on the biologically active phenolic compounds naturally present in virgin olive oils to aid in explaining reduced mortality and morbidity experienced by people consuming a traditional Mediterranean diet. Studies (human, animal, in vivo and in vitro) have demonstrated that olive oil phenolic compounds have positive effects on certain physiological parameters, such as plasma lipoproteins, oxidative damage, inflammatory markers, platelet and cellular function, antimicrobial activity and bone health. This paper summarizes current knowledge on the bioavailability and biological activities of olive oil phenolic compounds.

Antimicrobial, antioxidant and anti-inflammatory phenolic activities in extra virgin olive oil

The Mediterranean diet is associated with a lower incidence of chronic degenerative diseases and higher life expectancy. These health benefits have been partially attributed to the dietary consumption of extra virgin olive oil (EVOO) by Mediterranean populations, and more specifically the phenolic compounds naturally present in EVOO. Studies involving humans and animals (in vivo and in vitro) have demonstrated that olive oil phenolic compounds have potentially beneficial biological effects resulting from their antimicrobial, antioxidant and anti-inflammatory activities. This paper summarizes current knowledge on the biological activities of specific olive oil phenolic compounds together with information on their concentration in EVOO, bioavailability and stability over time.

Generation of mutant leukaemia inhibitory factor (LIF)-IgG heavy chain fusion proteins as bivalent antagonists of LIF

Two leukaemia inhibitory factor (LIF) mutants, designated MH35-BD and LIF05, have been shown to have a capacity to inhibit the biological activities of not only human LIF (hLIF) but also other interleukin-6 (IL-6) subfamily cytokines such as human oncostatin M (hOSM). These cytokines share the same receptor complex in which the glycoprotein 130 (gp130) subunit is a common constituent. However, at low concentrations and in their monomeric forms, such molecules have a relatively short plasma half-life due to rapid clearance from the kidneys. Here, to prolong their serum half-lives, we have used a multi-step polymerase chain reaction (PCR) to fuse each of the LIF05 and MH35-BD cDNA fragments to a sequence encoding the Fc portion, and the hinge region, of the human immunoglobulin G (hIgG) heavy chain. The linking was achieved through an oligomer encoding a thrombin-sensitive peptide linker thus generating MH35-BD:Fc and LIF05:Fc, respectively. Both Fc fusion constructs were expressed in insect cell Sf21 and the proteins were purified by two successive affinity chromatography steps using nickel–nitrilotriacetic acid (Ni–NTA) agarose and protein A beads. The Ba/F3 cell-based proliferation assay was used to confirm that the proteins were biologically active. In addition, preliminary pharmacokinetics indicates that the Fc fusion constructs have a longer serum half-life compared to their non-fusion counterparts.

Identification of novel genes differentially expressed in haemopoietic progenitor cells

The biochemical and molecular processes that maintain the stem cell pool, and govern the proliferation and differentiation of haemopoietic stem/progenitor cells (HSPCs) have been widely investigated but are incompletely understood. The purpose of this study was to identify and characterise novel genes that may play a part in regulating the mechanisms that control the proliferation, differentiation and self-renewal of human HSPCs. Reverse transcription differential display polymerase chain reaction (dd-PCR) was used to identify differences in gene expression between a HSPC population defined by expression of the CD34 phenotype, and the more mature CD34 depleted populations. A total of 6 differentially expressed complementary deoxyribonucleic acid (cDNA) sequences were identified. Four of these transcripts were homologous to well characterised genes, while two (band 1 and band 20) were homologous to unknown and uncharacterised partial gene sequences on the GenBank database and were thus chosen for further investigation. The partial cDNA sequences for band 1 and band 20 were designated ORP-3 and MERP-1 (respectively) due to homologies with other well-characterised gene families. Differential expression of the ORP-3 and MERP-1 genes was confirmed using Taqman™ real-time polymerase chain reaction (PCR) with 3 - 4-fold and 4-10 -fold higher levels in the CD34+ fractions of haemopoietic cells compared to CD34- populations respectively. Additionally, expression of both these genes was down regulated with proliferation and differentiation of CD34+ cells further confirming higher expression in a less differentiated subset of haemopoietic cells. The full coding sequences of ORP-3 and MERP-1 were elucidated using bioinformatics, rapid amplification of cDNA ends (RACE) and PCR amplification. The MERP-1 cDNA is 2600 nucleotides (nt) long, and localizes by bioinformatics to chromosome 7.. It consists of three exons and 2 introns spanning an entire length of 31.4 kilobases (kb). The MERP-1 open reading frame (ORF) codes for a putative 344 amino acid (aa) type II transmembrane protein with an extracellular C-terminal ependymin like-domain and an intracellular N-terminal sequence with significant homology to the cytoplasmic domains of members of the protocadherin family of transmembrane glycoproteins. Ependymins and protocadherins are well-characterised calcium-dependant cell adhesion glycoproteins. Although the function of MERP-1 remains to be elucidated, it is possible that MERP-1 like its homologues plays a role in calcium dependent cell adhesion. Differential expression of the MERP-1 gene in haemopoietic cells suggests a role in haemopoietic stem cell proliferation and differentiation, however, its broad tissue distribution implies that it may also play a role in many cell types. Characterization of the MERP-1 protein is required to elucidate these possible roles. The ORP-3 cDNA is 6631nt long, and localizes by bioinformatics to chromosome 7pl5-p21. It consists of 23 exons and 22 introns spanning an entire length of 183.5kb. The ORP-3 ORF codes for a putative 887aa protein which displays the consensus sequence for a highly conserved oxysterol-binding domain. Other well-characterised proteins expressing these domains have been demonstrated to bind oxysterols (OS) in a dose dependant fashion. OS are hydroxylated derivatives of cholesterol Their biological activities include inhibition of cholesterol biosynthesis and cell proliferation in a variety of cell types, including haemopoietic cells. Differential expression of the ORP-3 gene in haemopoietic cells suggests a possible role in the transduction of OS effects on haemopoietic cells, however, its broad tissue distribution implies that it may also play a role in many cell types. Further investigation of ORP-3 gene expression demonstrates a significant correlation with CD34+ sample purity, and 2-fold higher expression in a population of haemopoietic cells defined by the CD34+38- phenotype compared to more mature CD34+38+ cells. This finding, taken together with the previous observation of down-regulation of ORP-3 expression with proliferation and differentiation of CD34+ cells, indicates that ORP-3 expression may be higher in a less differentiated subset of cells with a higher proliferative capacity. This hypothesis is supported by the observation that expression of the ORP-3 gene is approximately 2-fold lower in differentiated HL60 promyelocytic cells compared to control, undifferentiated cells. ORP-3 expression in HL60 cells during normal culture conditions was also found to vary with expression positively correlated with cell number. This indicates a possible cell cycle effect on ORP-3 gene expression with levels highest when cell density, and therefore the percentage of cells in G(0)/G(1) phase of the cell cycle is highest. This observation also correlates with the observation of higher ORP-3 expression in CD34+38-cells, and in CD34+ and HL60 cells undergoing OS induced and camptothecin induced apoptosis that is preceded by cell cycle arrest at G(0)/G(1). Expression of the ORP-3 gene in CD34+ HSPCs from UCB was significantly decreased to approximately half the levels observed in control cells after 24 hours incubation in transforming growth factor beta-1 (TGFâl). As ≥90% of these cells are stimulated into cell cycle entry by TGFâl, this observation further supports the hypothesis that ORP-3 expression is highest when cells reside in the G(0)/G(1) phase of the cell cycle. Data obtained from investigation of ORP-3 gene expression in synchronised HL60 cells however does not support nor disprove this hypothesis. Culture of CD34+ enriched HSPCs and HL60 cells with 25-OHC significantly increased ORP-3 gene expression to approximately 1.5 times control levels. However, as 25-OHC treatment also increased the percentage of apoptotic cells in these experiments, it is not valid to make any conclusions regarding the regulation of ORP-3 gene expression by OS. Indeed, the observation that camptothecin induced apoptosis also increased ORP-3 gene expression in HL60 cells raises the possibility that up-regulation of ORP-3 gene expression is also associated with apoptosis, Taken together, expression of the ORP-3 gene appears to be regulated by differentiation and apoptosis of haemopoietic progenitors, and may also be positively associated with proliferative and G(0)/G(1) cell cycle status indicating a possible role in all of these processes. Given the important regulatory role of apoptosis in haemopoiesis and differential expression of the ORP-3 gene in haemopoietic progenitors, final investigations were conducted to examine the effects OS on human HSPCs. Granulocyte/macrophage colony forming units (CFU-GM) generated from human bone marrow (ABM) and umbilical cord blood (UCB) were grown in the presence of varying concentrations of three different OS - 7keto-cholesterol (7K-C), 7beta-hydroxycholesterol (7p-OHC) and 25-hydroxycholesterol (25-OHC). Similarly, the effect of OS on HL60 and CD34+ cells was investigated using annexin-V staining and flow cytometry to measure apoptosis. Reduction of nitroblue tetrazolium (NBT) was used to assess differentiative status of HL60 cells. CFU-GM from ABM and HL60 growth was inhibited by all three OS tested, with 25-OHC being the most potent. 25-OHC inhibited ≥50% of bone marrow CFU-GM and ≥95% of HL60 cell growth at a level of 1 ug/ml. Compared to UCB, CFU-GM derived from ABM were more sensitive to the effects of all OS tested. Only 25-OHC and 7(5-OHC significantly inhibited growth of UCB derived CFU-GM. OS treatment increased the number of annexin-V CD34+ cells and NBT positive HL60 cells indicating that OS inhibition of CFU-GM and HL60 cell growth can be attributed to induction of apoptosis and differentiation. From these studies, it can be concluded that dd-PCR is an excellent tool for the discovery of novel genes expressed in human HSPCs. Characterisation of the proteins encoded by the novel genes ORP-3 and MERP-1 may reveal a regulatory role for these genes in haemopoiesis. Finally, investigations into the effects of OS on haemopoietic progenitor cells has revealed that OS are a new class of inhibitors of HSPC proliferation of potential relevance in vivo and in vitro.

Microwave-assisted direct amination : rapid access to multi-functionalized N6-substituted adenosines

Analogues of adenosine have a range of interesting biological activities and potential therapeutic applications. A method for the efficient preparation of highly functionalized N6-substituted adenosines has been developed from the corresponding tert-butyldimethylsilyl-protected inosine. The key step in this procedure is a microwave-assisted amination reaction between an appropriately substituted inosine and an amine in the presence of PyBroP. High yields of desired N6-substituted adenosines were achieved with hindered amines and the reaction was also found to accommodate a range of substituents on the inosine precursor.

Fouling in reverse osmosis (RO) membrane in water recovery from secondary effluent : a review

Reverse osmosis (RO) is the most preferable process for water recovery from secondary effluent (SE) because of its higher rejection of impurities with lower associated cost and higher quality of product. Fouling still is a major challenge during the water recovery due to higher contaminant loadings in SE and high rejection capability of this membrane. The presence of suspended solids, colloidal and organic matters, and high level of biological activities in SE further elevate fouling potentiality. This review was performed to identify major foulants causing hindrance in sustainable application of reverse osmosis and to present available pre-treatment options for these foulants. There are four fouling types present in RO namely; bio-fouling, inorganic/scaling, organic, and particulate fouling. Among them; bio-fouling is less understood but dominant since the pre-treatment options are not well developed. Other fouling mechanisms have been overcome by well developed pre-treatments. The major foulants for RO are dissolved and macromolecular organic substances, sparingly soluble inorganic compounds, colloidal and suspended particles, and micro-organisms. Some of these potential fouling water quality parameters (PFWQPs) are interrelated with each others such as electrical conductivity is a surrogate measure of total dissolved solids with established stable relationship. Most of these PFWQPs such as total suspended solids, turbidity, chemical oxygen demand can be removed by conventional pre-treatment; some such as colloidal particles and micro-organisms by modern options and even others such as endocrine disrupting compounds, pharmaceutical and personal care products are still challenging for current pre-treatments. These foulants need to be identified properly to integrate appropriate pre-treatments for minimizing fouling potentiality to increase water recovery at minimal costs.

Early events of HIV-1 infection : can signalling be the next therapeutic target?

Intracellular signaling events are signposts of biological processes, which govern the direction and action of biological activities. Through millions of years of evolution, pathogens, such as viruses, have evolved to hijack host cell machinery to infect their targets and are therefore dependent on host cell signaling for replication. This review will detail our current understanding of the signaling events that are important for the early steps of HIV-1 replication. More specifically, the therapeutic potential of signaling events associated with chemokine coreceptors, virus entry, viral synapses, and post-entry processes will be discussed. We argue that these pathways may represent novel targets for antiviral therapy.

Maternal supplementation with LGG reduces vaccine-specific immune responses in infants at high-risk of developing allergic disease

Probiotics are defined as live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Among their pleiotropic effects, inhibition of pathogen colonization at the mucosal surface as well as modulation of immune responses are widely recognized as the principal biological activities of probiotic bacteria. In recent times, the immune effects of probiotics have led to their application as vaccine adjuvants, offering a novel strategy for enhancing the efficacy of current vaccines. Such an approach is particularly relevant in regions where infectious disease burden is greatest and where access to complete vaccination programs is limited. In this study, we report the effects of the probiotic, Lactobacillus rhamnosus GG (LGG) on immune responses to tetanus, Haemophilus influenzae type b (Hib) and pneumococcal conjugate (PCV7) vaccines in infants. This study was conducted as part of a larger clinical trial assessing the impact of maternal LGG supplementation in preventing the development of atopic eczema in infants at high-risk for developing allergic disease. Maternal LGG supplementation was associated with reduced antibody responses against tetanus, Hib, and pneumococcal serotypes contained in PCV7 (N = 31) compared to placebo treatment (N = 30) but not total IgG levels. Maternal LGG supplementation was also associated with a trend to increased number of tetanus toxoid-specific T regulatory in the peripheral blood compared to placebo-treated infants. These findings suggest that maternal LGG supplementation may not be beneficial in terms of improving vaccine-specific immunity in infants. Further clinical studies are needed to confirm these findings. As probiotic immune effects can be species/strain specific, our findings do not exclude the potential use of other probiotic bacteria to modulate infant immune responses to vaccines.

Oleocanthal, a phenolic derived from virgin olive oil: a review of the beneficial effects on inflammatory disease

Virgin olive oil (VOO) is credited as being one of many healthful components of the Mediterranean diet. Mediterranean populations experience reduced incidence of chronic inflammatory disease states and VOO is readily consumed as part of an everyday dietary pattern. A phenolic compound contained in VOO, named oleocanthal, shares unique perceptual and anti-inflammatory characteristics with Ibuprofen. Over recent years oleocanthal has become a compound of interest in the search for naturally occurring compounds with pharmacological qualities. Subsequent to its discovery and identification, oleocanthal has been reported to exhibit various modes of action in reducing inflammatory related disease, including joint-degenerative disease, neuro-degenerative disease and specific cancers. Therefore, it is postulated that long term consumption of VOO containing oleocanthal may contribute to the health benefits associated with the Mediterranean dietary pattern. The following paper summarizes the current literature on oleocanthal, in terms of its sensory and pharmacological properties, and also discusses the beneficial, health promoting activities of oleocanthal, in the context of the molecular mechanisms within various models of disease.

Bioactive proteins and peptides from soybeans.

Dietary proteins from soybeans have been shown to offer health benefits in vivo and/or in vitro either as intact proteins or in partially digested forms also called bioactive peptides. Upon oral administration and absorption, soy-derived bioactive peptides may induce several physiological responses such as antioxidative, antimicrobial, antihypertensive, anticancer and immunomodulatory effects. There has therefore been a mounting research interest in the therapeutic potential of soy protein hydrolysates and their subsequent incorporation in functional foods and 'Food for Specified Health Uses' (FOSHU) related products where their biological activities may assist in the promotion of good health or in the control and prevention of diseases. This mini review discusses relevant patents and gives an overview on bioactive proteins and peptides obtainable from soybeans. Processes for the production and formulation of these peptides are given, together with specific examples of their therapeutic potential and possible areas of application.

Antioxidative peptides derived from food proteins

The search for natural antioxidants is an ongoing endeavour as an aid to combat the harmful effects of free radicals. Research advances in the past few decades have shown that, by controlled enzymatic hydrolysis, natural antioxidants can be produced from food proteins. In this chapter, the role of certain antioxidative peptides derived from food proteins is discussed in relation to their prospect in the prevention of oxidative stress. The molecular diversity of these food peptides is described together with their pharmacological effects and mechanisms of action in relation to antioxidation. The production of these peptides and the elucidation of their antioxidative peptides are also presented. Owing to their therapeutic potential, antioxidative peptides derived from food proteins can be incorporated as ingredients in functional foods, nutraceuticals and pharmaceuticals, where their biological activities may inhibit product oxidation or assist in the control and prevention of diseases induced by free radicals. However, further insightful research is needed to overcome certain scientific challenges and thereby increase and promote consumer acceptance of these natural antioxidants.

Perspectives of engineered marine derived polymers for biomedical nanoparticles

Marine environment exhibits an enormous diversity of organisms which contains an abundant source of polysaccharides. As polymer matrix carriers, marine-based polymers possess several valuable properties including high stability, non-toxicity, hydrophilicity, biodegradability, with low production cost. Despite notable biological activities of these natural polymers, there are certain limitations in exploring their functions in applications of nano-sized drug delivery systems. The review aims to demonstrate exceptional characteristics of marine-based polymers including fucoidan, alginate, carrageenan, hyaluronic acid, chondroitin sulfate, and chitosan as well as provide perspectives of current publications on their nanoparticle formulations for biomedical applications.

Food-derived multifunctional bioactive proteins and peptides: sources and production

Multifunctional proteins and peptides from food proteins have been studied over the past few decades to elucidate their biological potency and the beneficial roles they play in human health. Owing to their multiple biological activities, these peptides have a wider role in modulating physiological functions such as antioxidative, antimicrobial, antihypertensive, cytomodulatory, anxiolytic, anorexic, and immunomodulatory activities in living body systems. Highlighted in this chapter is the biological role of some multifunctional peptides as well as the food proteins and enzyme(s) that are responsible for their release. Other challenges to the bioprocessing of multifunctional peptides and the need for research to address them are also discussed.

Simulation of oleuropein structural conformation in vacuum, water and triolein-water systems using molecular dynamics

Oleuropein, the main phenolic compound of olive leaves, exhibits a unique blend of biological activities and has been shown to locate itself at the oil-water (O/W) interface. This behavior could influence the physico-chemical properties of dispersed systems such as emulsions. In this work, we study the effect of the microenvironment (vacuum, water, and triolein-water) on the conformational preferences of oleuropein using molecular dynamics (MD) simulations at 300K for at least 30ns. The seven torsions that describe the flexible skeleton of oleuropein were monitored together with the distance between the glucose (Glu) and hydroxytyrosol (Hyd) moieties (dglu-hyd) of the molecule. The obtained trajectories demonstrated that oleuropein adopts different conformations that depend on the environment. The preferential conformers in each system were analyzed for their molecular geometry and internal energy. In vacuum, the oleuropein preferential conformation is tight with the glucose moiety in close proximity with the hydroxytyrosol moiety. In water, oleuropein preferential conformers presented large differences in their structural properties, varying from a close like U form, and a semi-opened form, to an opened form characterized by high fluctuations in dglu-hyd values. In a triolein-water system, oleuropein tends to adopt a more open form where the glucose moiety could be approximately aligned with the hydroxytyrosol and elenolic acid moieties. Based on a calculation at the HF/6-31G* level, these flexibilities of oleuropein required energy of 19.14kcal/mol in order to adopt the conformation between water and triolein-water system. A radial distribution function (RDF) analysis showed that specific hydroxyl groups of Hyd and Glu interact with water molecules, enabling us to understand the amphiphilic character of oleuropein at the triolein-water interface. MD calculations together with interfacial tension measurements revealed that the oleuropein binding at O/W interface is an enthalpy driven mechanism.