Relationship of epigenetic variability of miR-124 to extracellular matrix remodelling and age-related MMP-3 expression in rheumatoid arthritis.

The aim of study was to examine relation among miR-124 and serum levels of selected cytokines and chemokines, MMP-3, production of auto-antibodies, and factors describing clinical activity (DAS28) and radiographic progression in rheumatoid arthritis (RA). A total of 80 RA patients according to the ACR classification criteria, and 32 control subjects were recruited into study. The measurements of miR-124 and U-6 expression, CRP, anti-CCP, rheumatoid factors (RFs), radiographs of both hands with calculation of total sharp score (TSS), DAS28 and cytokines, chemokines and MMP levels in serum were obtained from all RA patients. miR-124 was down-regulated in RA patients compared to controls (7-fold decrease). The miR-124 expression correlated to MMP-3 levels (p < 0.001), which were in multivariate analysis associated to age of RA onset. Higher levels were detected in younger subjects. No relation of miR-124 expression to measures of RA activity (DAS28 score; TSS), auto-antibodies (anti-CCP, RF, RF IgG, RF IgA, RF IgM), acute inflammatory markers (CRP, IL-6), and other cytokine and chemokines (IL-13, IL-15, IL-8, TNF-α, MCP-1, RANTES) was observed. In conclusion, we present a down-regulation of miR-124 in RA patients and its correlation to MMP-3 levels, which associated to age of RA onset.

Osteoarthritic process modifies expression response to NiTi alloy presence.

Nickel-titanium alloy (nitinol, NiTi) is a biomaterial with unique thermal shape memory, superelasticity and high damping properties. Therefore NiTi has been used in medical applications. In this in vitro study, the effect of NiTi alloy (with two surface modifications - helium and hydrogen) on gene expression profile of selected interleukins (IL-1ß, IL-6 and IL-8) and matrix metalloproteinases (MMP-1 and MMP-2) in human physiological osteoblasts and human osteoarthritic osteoblasts was examined to respond to a question of the different behavior of bone tissue in the implantation of metallic materials in the presence of cells affected by the osteoarthritic process. The cells were cultivated in contact with NiTi and with or without LPS (bacterial lipolysaccharide). Changes in expression of target genes were calculated by 2-ΔΔCt method. An increased gene expression of IL-1ß in osteoarthritic osteoblasts, with even higher expression in cells collected directly from the metal surface was observed. In case of physiological osteoblasts, the change in expression was detected after LPS treatment in cells surrounding the disc. Higher expression levels of IL-8 were observed in osteoarthritic osteoblasts after NiTi treatment in contact with alloy, and in physiological osteoblasts without relation to location in combination of NiTi and LPS. IL-6 was slightly increased in physiological osteoblastes after application of LPS. MMP-1 expression level was obviously significantly higher in osteoarthritic osteoblasts with differences regarding the metal surface and location. MMP-2 expression was decreased in both cell lines after LPS treatment. In conclusion, results of present study show that the NiTi alloy and the treatment by LPS, especially repeated doses of LPS, change the gene expression of selected ILs and MMPs in human osteoblast cell cultures. Some of the changes were depicted solely to osteoarthritic osteoblasts.

Biocompatibility of NiTi alloys in the cell behaviour.

Metallic biomaterial alloys composed of nickel and titanium have unique thermal shape memory, superelastic, and high damping properties, which are widely used in the medicine. The major parameter evaluated in the studies regarding the behaviour of the material in the contact with organism or cells is biocompatibility. The aim of the studies is to clarify the differences in the proliferation, growth, and morphology especially in the cell cultures. The cytotoxicity is affected among other by release of the metal ions in the presence of the metal alloy, which is further dependent on the possible treatments of the material and the corrosive properties. To evaluate the cytotoxicity, wide range of tests including the Sulforhodamine B assay and MTT tests, expression profiles, cell survival tests such as apoptotic test are used. The review compares the cell behaviour in contact with the material alloys composed of nickel and titanium with respect to different materials composition and different surface treatment that affects the ion release. Even though the results published so far are controversial, almost all data suggest sufficient biocompatibility in medical use.

Soluble ST2 levels in patients with cardiogenic and septic shock are not predictors of mortality.

BACKGROUND: Soluble ST2 (sST2) is an interleukin-33 receptor. sST2 was found to be an independent prognostic factor in patients with myocardial infarction, sepsis and heart failure. OBJECTIVES: To assess sST2 levels in patients with cardiogenic shock (CS) and septic shock (SS), and to evaluate the prognostic value of sST2 for short-term mortality. METHODS: The present prospective observational study evaluated 32 patients with CS, 17 patients with SS and 61 patients with ST segment elevation myocardial infarction (STEMI )(control group). Samples of serum were collected eight times and the follow-up time was three months. RESULTS: sST2 levels were elevated from admission in SS patients relative to patients with CS and STEMI, who exhibited peak sST2 levels 24 h after admission. On admission, CS patients had a median (5th percentile; 95th percentile) sST2 level of 62.5 pg/mL (8.3 pg/mL; 315.8 pg/mL) and SS patients had a median sST2 level of 216.4 pg/mL (46.8 pg/mL; 364.4 pg/mL). ROC analysis found sST2 to be a biomarker that could distinguish between CS and SS at admission (area under the curve [AUC] 0.813; P<0.01) with a cut-off value of 210.4 pg/mL. Patients with STEMI had significantly lower sST2 levels at admission (20.3 pg/mL (4.2 pg/mL; 339.8 pg/mL) compared with CS patients. The AUC of the ROC analysis was 0.671 (P=0.007) for the detection of CS in patients with STEMI. Only a weak correlation was observed between sST2 and B-type natriuretic peptide (r=0.376, P=0.05) and sST2 and N-terminal pro-B-type natriuretic peptide (r=0.496, P=0.019). No statistically significant differences were observed in sST2 levels in patients with CS and SS relative to three-month mortality. CONCLUSION: Levels of sST2 at admission are significantly higher in patients with SS compared with CS. sST2 could be a diagnostic marker to distinguish SS and CS as well as CS and STEMI at the time of admission. Levels of sST2 are related to levels of natriuretic peptides in CS but not in SS. sST2 levels are not a suitable prognostic marker for patients with CS and SS.