Circulating sRANKL, Periostin, and Osteopontin as Biomarkers for the Assessment of Activated Osteoclastogenesis in Myeloma Related Bone Disease.

The hallmark of multiple myeloma is myeloma related bone disease. Interactions between myeloma plasma cells (MPCs), stromal cells, and the bone marrow (BM) microenvironment play a critical role in the pathogenesis of MBD. Bone remodeling is severely dysregulated with the prevalence of osteoclast activity. We aimed to assess circulating levels of sRANKL, periostin, and osteopontin as osteoclast activators in NDMM patients at diagnosis and in the course of treatment, correlations with clinical and laboratory data, and to evaluate their potential as additional biomarkers for the assessment of MBD. The current study involved 74 subjects (41 NDMM patients, 33 controls). MBD was assessed by whole-body low-dose computed tomography. sRANKL, periostin, and osteopontin were assayed by commercial ELISA kits. At diagnosis, all tested parameters were significantly higher in NDMM patients compared to the controls (p < 0.0001), correlating with disease stage, MBD grade, and BM infiltration by MPCs. During therapy, the serum levels of all tested proteins decrease, most prominently after autologous stem cell transplantation (p < 0.0001). A significant reduction was established in patients achieving complete and very-good partial response compared to all others (p < 0.05). In conclusion, sRANKL, periostin, and osteopontin reflect MBD severity and could be promising markers for MBD monitoring and the effect of myeloma treatment.

Circulating uncarboxylated matrix Gla protein in patients with atrial fibrillation or heart failure with preserved ejection fraction.

CONTEXT: Circulating uncarboxylated matrix Gla protein (ucMGP) is possibly related to coronary arterial calcification (CAC) in cardiovascular disease (CVD) patients. OBJECTIVE: We aimed to evaluate the relationships between circulating ucMGP, CVD pathology and CAC and its interplay with CVD risk factors. MATERIALS AND METHODS: ucMGP was measured in 99 CVD-patients. CAC score was determined by multislice computed tomography. Circulating ucMGP, uncarboxylated (ucOC) and carboxylated osteocalcin (cOC) were assayed by ELISA kits. Vitamin-K status was evaluated by ucOC/cOC ratio. RESULTS: A tendency for decreased ucMGP was observed for CAC ≥ 100 AU vs. CAC = 1-99 AU after exclusion of the patients on vitamin K-antagonist anticoagulants. Significant inverse correlations between ucMGP and vitamin-K status were indicated for the entire cohort and according to CAC score. Significant associations were found between ucMGP and risk factors for CVD. CONCLUSION: Circulating ucMGP may reflect certain stages of CVD and CAC. Future studies are needed to clarify its role as potential biomarker.

Ferrum phosphoricum D12 Treatment Affects J774A.1 Cell Proliferation, Transcription Levels of Iron Metabolism, Antioxidant Defense, and Inflammation-related Genes.

BACKGROUND: Ferrum phosphoricum (FP) is prescribed as a homeopathic remedy to treat the early stages of fever and inflammation in cases of colds or flu, muscle fatigue and anemia. We aimed to analyze the molecular mechanisms of action of FP D12 on cell proliferation and mRNA expression of iron metabolism, antioxidant defense and inflammation-related genes in mouse J774A.1 macrophages. METHODS: Cell proliferation was examined using the MTT test. RT-qPCR analyses were performed to estimate gene expression changes. Relative gene expression levels were calculated using the 2-ΔΔCt method. The effect of treatment using FP D12 tablets was compared with that using placebo tablets (PT). RESULTS: FP D12 in low concentrations (0.0125 mg/mL to 0.025 mg/mL) significantly stimulated proliferation of J774A.1 cells by up to 11% (p < 0.01) versus control untreated cells and by up to 40% (p < 0.01) versus PT-treated cells in the respective concentration. FP D12 versus PT induced a significant increase in mRNA expression of ferritin light chain (Ftl1) (by 8-fold, p < 0.01), ß-2-microglobulin (B2m) (by 2.5-fold, p < 0.05) and iron-responsive element binding protein 2 (Ireb2) (by 4-fold, p < 0.05), and induced a slight decrease in myosin IE (Myo1e) mRNA expression levels (by 0.4-fold, p < 0.01) in macrophages. A highly significant (r2 = 0.99, p < 0.05) correlation was observed between Ireb2 and B2m transcription levels. Significant stimulation of antioxidant enzyme Gpx-1 (by 1.27-fold, p < 0.01) in cells by 0.025 mg/mL FP D12, but a slight decrease (by 0.12-fold, p < 0.05) in 0.0125 mg/mL-treated cells, was observed. A significant increase in the gene expression of IL-1ß (by 3.5-fold, р < 0.05) in macrophages was also detected. CONCLUSION: Ferrum phosphoricum in D12 dilution potentially exhibits iron retention, antioxidant and immunomodulation activities, possibly by modulating transcription levels of related genes in non-stimulated mouse macrophages.

Effects of sulphur-containing mineral water intake on oxidative status and markers for inflammation in healthy subjects.

CONTEXT: Sulphurous mineral waters (SMW) have a wide range of applications. Sulphur content of mineral waters is considered as possible determinant for their anti-inflammatory or pro-inflammatory effects. OBJECTIVE: To explore the healing properties of Varna basin mineral water by analysing possible antioxidative and anti-inflammatory effects. MATERIALS AND METHODS: An intervention with Varna SMW intake was performed with healthy volunteers. Total thiols, total glutathione and its fractions, reactive oxygen metabolites, malondialdehyde, intracellular adhesion molecule (ICAM-1) and vascular cell adhesion molecule (VCAM-1) were measured. Expression of γ-gluthamyl-cysteinyl ligase (GCL) and sICAM-1 genes was also analysed. RESULTS: A significantly increased total glutathione and total thiols were observed at the end of the intervention. GCL and sICAM-1 gene expressions were increased after the intervention. CONCLUSION: SMW consumption improved redox status of the body. We suggested that these beneficial effects may be attributed to the established high levels of sulphur-containing compounds in Varna mineral water.