Assessment of the Levels of Level of Biomarkers of Bone Matrix Glycoproteins and Inflammatory Cytokines from Saudi Parkinson Patients.

Background. Parkinson's disease (PD) is the second most commonly neurodegenerative disease after Alzheimer's disease which occurs to nearly 1% of the population > 50 years old. Inflammatory and bone biomarkers have both become valuable tools for PD diagnosis and prognosis. However, no studies have examined these markers in Saudi patients diagnosed with PD. Objectives. To assess the biomarkers and proinflammatory cytokines from blood with PD in serum. Methods. In our study, we included 26 patients with PD and 24 controls. Blood samples were withdrawn from subjects with PD and their matched controls. Biomarkers multiplex assay from Milliplex was used to assess the levels of IL-1B, IL-6, TNF-α, osteoprotegerin (OPG), osteopontin (OPN), and PTH (parathyroid hormone). Data was analyzed using the Statistical Package, GraphPad Prism. Results. We found that IL-1ß cytokine is significantly higher in patients with PD (p value = 0.0014). However, there are no statistically significant variances found among the two studied groups with regard to the IL-6 and TNF-α cytokines levels. We also found that levels of PTH are decreased in the PD subjects than the age-matched controls (p value= 0.003). Also, the bone matrix glycoproteins, including osteoprotegerin (OPG) and osteopontin (OPN), are significantly upregulated (p value= 0.04 for OPG and p value= 0.003 for OPN), as compared to the controls. Conclusions. Our findings are reliable with the possibility that inflammatory and bone markers can be used as biomarkers in PD prognosis. However, to clarify the natural role and consequence of these markers in PD pathology, further larger cohort studies are needed.

Ligands of toll-like receptors 2/4 differentially alter markers of inflammation, adhesion and angiogenesis by monocytes from women with pre-eclampsia in co-culture with endothelial cells.

Pre-eclampsia (PE) is characterized by an exaggerated systemic inflammatory response and generalized endothelial dysfunction. We have recently demonstrated that fibrinogen, an endogenous ligand of Toll-like receptor (TLR) 4, activates monocytes from women with pre-eclampsia (Al-ofi et al., 2014). Using an experimental co-culture model of primary human monocytes (derived from 9 women with PE (GA=33.18±5.8) and 9 normotensive pregnant women, NP (GA=33.15±4.0)) and human umbilical venous endothelial cells (HUVECs), we compared the effects of fibrinogen and lipopolysaccharide (LPS, bacterial ligand to TLR4) on the expression levels of inflammatory cytokines (IL-6 and IL-1ß), chemokines (IL-8 and MCP-1), and anti-angiogenic factor (soluble fms-like tyrosine kinase-1,sFLT-1), as well as the soluble vascular cell adhesion molecule-1 (sVCAM-1). Cytokines, VEGF and sVCAM-1 were measured in the supernatant media by cytometric array. The levels of sFLT-1 were measured by ELISA. Fibrinogen induced greater expression levels of IL-1ß and VCAM-1 from PE HUVEC-monocyte co-culture than from NP HUVEC-monocyte co-culture (P<0.05), similar to the effects of LPS. In contrast, unlike LPS, fibrinogen suppressed IL-6, IL-8, MCP-1 and sFLT-1 production by co-cultures that included PE monocytes compared to those with NP monocytes (P<0.05). In conclusion, fibrinogen promotes monocyte-endothelial cell adhesion and angiogenesis and suppresses the expression of some inflammatory markers in pre-eclampsia. Although the physiological implications of these intriguing observations are unclear our findings suggest that fibrinogen contributes to the regulation of cell adhesion, angiogenesis and inflammation by mechanisms not wholly dependent on TLR4 stimulation.