Recurrent implantation failure (RIF) is considered to be one of the major limiting factors of assisted reproductive technology (ART) programme success. The current study focused on the investigation of matrix metalloproteinases (MMPs), tissue inhibitors of MMPs (TIMPs), cytokines and cell adhesion molecules in peripheral blood (PB) and follicular fluid (FF) obtained from 44 women aged between 25 and 39 years old and undergoing intracytoplasmic sperm injection (ICSI). These women were divided into two groups: 22 RIF women with embryo implantation failures after the transfer of at least four fresh or frozen–thawed good quality embryos in a minimum of three ICSI cycles, and 22 ICSI success women (controls) who achieved a clinical pregnancy at their first ICSI attempt. The PB and FF samples were obtained from each patient on the day of oocyte retrieval. MMP-1, -2, -3, -7, -9, TIMP-1, -2, vascular endothelial growth factor (VEGF), leukaemia inhibitory factor (LIF), vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecules 1 (ICAM1) were analyzed using enzyme-linked immunosorbent assay of PB and FF. Our results showed significant decreases in PB MMP-7 and PB VEGF in the RIF group compared with controls [281.11 (33–614) pg/ml vs 119.92 (27–441) pg/ml; P-value = 0.030] and [82.54 (25.94–210.20) pg/ml vs 30.93 (13.62–193.33) pg/ml; P-value = 0.022; respectively]. Receiver operating characteristic (ROC) curve analysis showed informative area under the curve values for PB MMP-7, as well as for PB VEGF, making them able to be proposed as biomarkers of the RIF. Therefore, circulating MMP-7 and VEGF seem to play an interesting role in embryo implantation in in vitro fertilization (IVF)/ICSI cycles and could be proposed as circulating biomarkers of the RIF. These results could be helpful for clinicians and patients to choose the best rescue strategy and treatment to minimize implantation failure in women undergoing IVF/ICSI procedures after the first attempt.

The hypovitaminosis D kyphotic pig provides a reliable model to study the initiation of bone lesions caused by maternal vitamin D (D) deficiencies. Matrix metalloproteinases (MMP; specifically, MMP9 and MMP13) and vascular endothelial growth factor (VEGF) are important in endochondral ossification and are potentially regulated by D. Fibroblast growth factor 23 (FGF23) is interrelated with D homoeostasis and bone mineralisation. Relative mRNA expression of MMP9, MMP13, VEGF and FGF23 was measured in pig femur and vertebra. Sows (n 37) were fed diets with 0 (−D), 8·125 (+D) or 43·750 (++D) µg D3/kg throughout gestation and lactation. At weaning (3 weeks), pigs were fed diets with 0 (−D) or 7·0 (+D) µg D3/kg, each with 75 and 95 % (LCaP) or 150 and 120 % (HCaP) of the Ca and P requirements. Pigs at birth (n 27), 3 weeks (n 27) and after the nursery period (7 weeks; n 72) were euthanised for analysis. At 3 weeks, femur MMP9 expression of pigs produced by +D or ++D sows was reduced (P<0·05) to 0·5-fold and VEGF expression to 0·4-fold compared with pigs from –D sows. At 7 weeks, MMP9 expression was reduced (P<0·05) to 0·45-fold in femur and 0·58-fold in vertebra from pigs produced by +D or ++D sows compared with pigs from −D sows. Pig femur VEGF expression was reduced to 0·75-fold in pigs produced by ++D sows. MMP9 and VEGF mRNA expression offer potential markers for the initiation of bone lesions in the hypovitaminosis D kyphotic pig model.

Olive oil (OO) is the primary source of fat in the Mediterranean diet and has been associated with longevity and a lower incidence of chronic diseases, particularly CHD. Cardioprotective effects of OO consumption have been widely related with improved lipoprotein profile, endothelial function and inflammation, linked to health claims of oleic acid and phenolic content of OO. With CVD being a leading cause of death worldwide, a review of the potential mechanisms underpinning the impact of OO in the prevention of disease is warranted. The current body of evidence relies on mechanistic studies involving animal and cell-based models, epidemiological studies of OO intake and risk factor, small- and large-scale human interventions, and the emerging use of novel biomarker techniques associated with disease risk. Although model systems are important for mechanistic research nutrition, methodologies and experimental designs with strong translational value are still lacking. The present review critically appraises the available evidence to date, with particular focus on emerging novel biomarkers for disease risk assessment. New perspectives on OO research are outlined, especially those with scope to clarify key mechanisms by which OO consumption exerts health benefits. The use of urinary proteomic biomarkers, as highly specific disease biomarkers, is highlighted towards a higher translational approach involving OO in nutritional recommendations.

Background: Deposition of amyloid β in senile plaques and in cerebral blood vessels is one hallmark of the pathogenesis of Alzheimer's disease (AD). The ability of several matrix metalloproteinases (MMPs) to degrade amyloid precursor protein leading to aggregation of amyloid β, as well as the increased expression of MMPs in post mortem brain tissue of Alzheimer's patients, indicate that MMPs play an important role in the pathogenesis of AD.

Methods: We investigated levels of MMP-2,-3,-9 and -10 in plasma and cerebrospinal fluid (CSF) of AD patients (n = 14) by gelatin and casein zymography. Comparisons between AD patients and controls relative to levels of MMP-2, MMP-3, MMP-9, and MMP-10 were made with Wilcoxon rank statistics. Pearson correlations were computed as measures of association.

Results: MMP-3 in AD was significantly elevated in plasma (p = 0.006) and there was a trend towards increase in CSF (p = 0.05). MMP-2 in CSF of AD patients was significantly decreased (p = 0.02) while levels in plasma remained unchanged. MMP-9 and MMP-10 could not be detected in CSF; MMP-10 was unchanged in plasma, but MMP-9 was significantly decreased (p = 0.02).

Conclusions: These findings constitute further evidence for the important role of MMPs in the pathogenesis of AD.

Theileria annulata infects and reversibly transforms bovine leucocytes. The parasite-transformed cells are immortalized, metastatic and express a number of metalloproteinases including matrix metalloproteinase 9 which they secrete. All the metalloproteinases observed on substrate gels are inhibited by tissue inhibitor of metalloproteinase 1 and 4 synthetic inhibitors BB94, GM6001, BRL29808AI and Ro31–4724. We have adapted an in vitro assay for metastatic behaviour that measures the ability of parasitized cells to cross reconstituted basement membrane, Matrigel™. Using this we demonstrated that macroschizont-infected cells are invasive in vitro and that their invasive properties can be almost eliminated by the same specific inhibitors of metalloproteinases as used in the substrate gels. This demonstrates that the metastatic behaviour of the infected cells is due in part to metalloproteinase activity and strongly suggests a role for the metalloproteinases we observed on gels. This is further supported by the fact that an attenuated vaccine line which shows much reduced metalloproteinase activity also exhibits a marked reduction in metastatic behaviour. We suggest that these metalloproteinases are virulence factors mediating some pathological features of the disease and their loss in the vaccine line could provide an explanation for attenuation.

Matrix metalloproteinases (MMPs) are a family of zinc and calcium-dependent endopeptidases that play a key role in extracellular matrix (ECM) degradation. MMPs are known to be important in normal remodelling processes. Overexpression and activation of MMPs or an imbalance of active MMPs and tissue inhibitors of metalloproteinases (TIMPs) has been linked with a number of specific disease states associated with the breakdown and remodelling of the extracellular matrix. MMPs and TIMPs play a role in the development and progression of conditions such as acute and chronic otitis media, nasal polyposis and Sjogren’s disease of salivary glands. Their role in allergic rhinitis has not been proven although they do appear to have a role in asthma, a condition closely linked to rhinitis. The use of a broad spectrum MMP inhibitor has been shown to alter the outcome of acute otitis media and otitis media with effusion. Therapeutic strategies with anti-MMP molecules are currently being developed and may play a role in modulating the course of non-neoplastic otorhinolaryngological disease in the future.