Pasture vs. Coop: Biomarker Insights into Free-Range and Conventional Broilers.

Identifying blood components influenced by rearing systems that serve as biomarkers to distinguish free-range from conventional broilers can improve animal health, welfare, and productivity. The current study aimed to evaluate specific blood parameters related to immune function and tissue stress, as biomarkers to differentiate free-range, slow-growing Sasso broilers from conventionally raised fast-growing Ross 308 broilers. For this purpose, serum IgM Natural Antibodies (NAbs) targeting actin and lipopolysaccharides (LPS) as key immunological parameters of natural immunity, along with creatine phosphokinase (CPK) and other significant stress and tissue-related biochemical parameters, were measured in a total of 300 broilers (150 per group) raised under industrial scale rearing systems, by standard methodology.

Levels of Circulating IgM and IgY Natural Antibodies in Broiler Chicks: Association with Genotype and Farming Systems.

Naturally occurring antibodies (NAbs), which are major components of innate immunity, exist in circulation under healthy conditions without prior antigenic stimulation and are able to recognize both self- and non-self-constituents. The present study aimed at identifying potential immunological differences between commercial fast- and slow-growth broilers ( = 555) raised in conventional and free-range systems, respectively, through the use of the specificity, isotypes and levels of circulating NAbs. The possible beneficial effect of oregano-based dietary supplementation was also evaluated.

Multidrug Resistance Protein 4 (MRP4/ABCC4): A Suspected Efflux Transporter for Human's Platelet Activation.

The main role of platelets is to contribute to hemostasis. However, under pathophysiological conditions, platelet activation may lead to thrombotic events of cardiovascular diseases. Thus, anti-thrombotic treatment is important in patients with cardiovascular disease.

Synergistic effect of peptide inhibitors derived from the extracellular and intracellular domain of α subunit of integrin αβ on platelet activation and aggregation.

αβ, the major platelet integrin, plays a central role in hemostasis and thrombosis. Upon platelet activation, conformation of αβ changes and allows fibrinogen binding and, subsequently, platelet aggregation. It was previously shown that a lipid-modified platelet permeable peptide, which corresponds to the intracellular acidic membrane distal sequence LEEDDEEGE of α (pal-K-LEEDDEEGE or pal-K-1000-1008), inhibits thrombin-induced human platelet aggregation, by inhibiting talin association with the integrin.

Inhibition of αIIbβ3 Ligand Binding by an αIIb Peptide that Clasps the Hybrid Domain to the βI Domain of β3.

Agonist-stimulated platelet activation triggers conformational changes of integrin αIIbβ3, allowing fibrinogen binding and platelet aggregation. We have previously shown that an octapeptide, p1YMESRADR8, corresponding to amino acids 313-320 of the β-ribbon extending from the β-propeller domain of αIIb, acts as a potent inhibitor of platelet aggregation. Here we have performed in silico modelling analysis of the interaction of this peptide with αIIbβ3 in its bent and closed (not swing-out) conformation and show that the peptide is able to act as a substitute for the β-ribbon by forming a clasp restraining the β3 hybrid and βI domains in a closed conformation.

Palmitoylated peptide, being derived from the carboxyl-terminal sequence of the integrin αIIb cytoplasmic domain, inhibits talin binding to αIIbβ₃.

The αIIb cytoplasmic domain of platelet integrin αIIbβ3 contains an unorganized acidic membrane-distal (1000)LEEDDEEGE(1008) region. We have shown that a platelet permeable peptide corresponding to the above region the palmitoyl-K-LEEDDEEGE (pal-K-1000-1008) inhibits platelet aggregation induced by thrombin or by pal-K-989-995, a palmitoylated peptide corresponding to the membrane-proximal αIIb cytoplasmic domain (989)KVGFFKR(995). We now tested the anti-aggregatory activity of (i) a lipid-modified scrambled acidic peptide (pal-K-GDDEELEEE), (ii) two smaller peptides derived from the acidic amino sequence: palmitoyl-K-(1000)LEEDDE(1005) (pal-K-1000-1005) and palmitoyl-K-(1005)EEGE(1008) (pal-K-1005-1008) and (iii) lipid-modified palmitoyl-acidic peptides with alanine (Ala) substitution at residues 1001, 1003, 1004 and 1005 and one peptide with a double Ala substitution at residues 1001 and 1004 of the 1000-1008 sequence.

A palmitoylated peptide, derived from the acidic carboxyl-terminal segment of the integrin alphaIIb cytoplasmic domain, inhibits platelet activation.

Platelet integrin alpha(IIb)beta(3) contains an acidic membrane distal motif, 1000LEEDDEEGE1008, in the cytoplasmic domain of the alpha(IIb) subunit. We showed that a lipid-modified peptide corresponding to the above region, palmitoyl-K-LEEDDEEGE (pal-K-1000-1008), is platelet permeable and has inhibited platelet aggregation induced by 0.4 U/ml of thrombin (IC50 = 164 microM).

Effect of fast-food Mediterranean-type diet on human plasma oxidation.

Oxidation of lipoproteins, particularly of low-density lipoprotein (LDL), is of prime importance in the initiation and progression of atherosclerosis. The Mediterranean diet has been associated with an unexpectedly low rate of cardiovascular events. Type 2 diabetic patients are at high risk of developing atherosclerosis.

Investigation of the role of adjacent amino acids to the 313-320 sequence of the alphaIIb subunit on platelet activation and fibrinogen binding to alphaIIbbeta3.

The platelet integrin receptor alphaIIbbeta3 plays a critical role in thrombosis and haemostasis by mediating interactions between platelets and several ligands, primarily fibrinogen. We have previously shown that the synthetic peptide YMESRADRKLAEVGRVYLFL corresponding to residues 313-332 of alphaIIb, is a potent inhibitor of platelet aggregation and fibrinogen binding to alphaIIbbeta3, interacting with fibrinogen rather than the receptor. Furthermore, we have demonstrated that the biological activities of the above peptide are due to the sequence YMESRADR, which corresponds to residues 313-320.

Molecular and mechanistic characterization of platelet-activating factor-like bioactivity produced upon LDL oxidation.

Oxidation of LDL is thought to be involved in both initiating and sustaining atherogenesis through the formation of proinflammatory lipids and the covalent modification of LDL particles. Platelet-activating factor (PAF; 1-0-alkyl-2-acetyl-sn-glycero-3-phosphocholine) is a potent phospholipid mediator involved in inflammation. Upon oxidation of LDL, oxidized phospholipids with PAF-like structure are generated, and some of them may act via the PAF receptor.

The relative orientation of the Arg and Asp side chains defined by a pseudodihedral angle as a key criterion for evaluating the structure-activity relationship of RGD peptides.

The ability of an integrin to distinguish between the RGD-containing extracellular matrix proteins is thought to be due partially to the variety of RGD conformations. Three criteria have been proposed for the evaluation of the structure-activity relationship of RGD-containing peptides. These include: (i) the distance between the charged centres, (ii) the distance between the Arg Cbeta and Asp Cbeta atoms, and (iii) the pseudo-dihedral angle defining the Arg and Asp side-chain orientation formed by the Arg Czeta, Arg Calpha, Asp Calpha and Asp Cgamma atoms.

Non-enzymatic platelet-activating factor formation by acetylated proteins.

Substantial amounts of platelet-activating factor (PAF 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine), the potent phospholipid mediator of allergic and inflammatory reactions, are formed upon incubation of acetylated low-density lipoprotein, acetylated bovine serum albumin (BSA) and acetylated apolipoprotein A-I with 1-0-hexadecyl-sn-glycero-3-phosphocholine (lyso-PAF). Acetylated BSA produced 0.3 nmol PAF/mg of protein after a 6 h incubation period with 40 microM lyso-PAF.

Effect of synthetic peptides corresponding to residues 313-332 of the alphaIIb subunit on platelet activation and fibrinogen binding to alphaIIbbeta3.

The platelet integrin receptor alphaIIbbeta3 plays a critical role in thrombosis and haemostasis by mediating interactions between platelets and several ligands but primarily fibrinogen. It has been shown previously that the YMESRADR KLAEVGRVYLFL (313-332) sequence of the alphaIIb subunit plays an important role in platelet activation, fibrinogen binding and alphaIIbbeta3-mediated outside-in signalling. Furthermore, we recently showed that the 20-residue peptide (20-mer) alphaIIb 313-332, is a potent inhibitor of platelet aggregation and fibrinogen binding to alphaIIbbeta3, interacting with fibrinogen rather than the receptor.

Mapping the binding domains of the alpha(IIb) subunit. A study performed on the activated form of the platelet integrin alpha(IIb)beta(3).

alpha(IIb)beta(3), a member of the integrin family of adhesive protein receptors, is the most abundant glycoprotein on platelet plasma-membranes and binds to adhesive proteins via the recognition of short amino acid sequences, for example the ubiquitous RGD motif. However, elucidation of the ligand-binding domains of the receptor remains controversial, mainly owing to the fact that integrins are conformationally labile during purification and storage. In this study, a detailed mapping of the extracellular region of the alpha(IIb) subunit is presented, using overlapping 20-peptides, in order to identify the binding sites of alpha(IIb) potentially involved in the platelet-aggregation event.