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Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. A growing body of evidence suggests that mitochondrial dysfunction and inflammation play a crucial role as a pathogenetic mechanism in PD. The glycoprotein YKL-40 (CHI3L1) is a potential biomarker involved in inflammation and tumor processes. The aim of the present study was to investigate the metabolic profile of PBMCs from PD patients and to search for a possible relationship between cellular bioenergetics and YKL-40. The study included 18 naïve PD patients and an age-matched control group (HC, n = 7). Patients were diagnosed according to the MDS-PD, the UPDRS, and the Hoen–Yahr scales. Mitochondrial activity was measured by a metabolic analyzer on isolated PBMCs from PD patients. Gene (qPCR) and protein (ELISA) expression levels of YKL40 were investigated. New data are reported revealing changes in the mitochondrial activity and YKL-40 levels in PD patients. Bioenergetic parameters showed increased respiratory reserve capacity in PD compared to HC. The protein levels of YKL-40 were threefold higher in PD. We found a correlation between the YKL-40 protein levels and basal respiration and between YKL-40 and ATP production. These observations suggest an interplay between YKL-40 and mitochondrial function in PD. We assume that the YKL-40 gene and protein levels in combination with changes in mitochondrial function might serve as an additional tool to monitor the clinical course of PD. [ABSTRACT FROM AUTHOR]

YKL-40 is a heparin- and chitin-binding glycoprotein that belongs to the family of glycosyl hydrolases but lacks enzymatic properties. It affects different (patho)physiological processes, including cancer. In different tumors, YKL-40 gene overexpression has been linked to higher cell proliferation, angiogenesis, and vasculogenic mimicry, migration, and invasion. Because, in colorectal cancer (CRC), the serological YKL-40 level may serve as a risk predictor and prognostic biomarker, we investigated the underlying mechanisms by which it may contribute to tumor progression and the clinical significance of its tissue expression in metastatic CRC. We demonstrated that high-YKL-40-expressing HCT116 and Caco2 cells showed increased motility, invasion, and proliferation. YKL-40 upregulation was associated with EMT signaling activation. In the AOM/DSS mouse model, as well as in tumors and sera from CRC patients, elevated YKL-40 levels correlated with high-grade tumors. In retrospective analyses of six independent cohorts of CRC patients, elevated YKL-40 expression correlated with shorter survival in patients with advanced CRC. Strikingly, high YKL-40 tissue levels showed a predictive value for a better response to cetuximab, even in patients with stage IV CRC and mutant KRAS, and worse sensitivity to oxaliplatin. Taken together, our findings establish that tissue YKL-40 overexpression enhances CRC metastatic potential, highlighting this gene as a novel prognostic candidate, a predictive biomarker for therapy response, and an attractive target for future therapy in CRC. [ABSTRACT FROM AUTHOR]

Objectives: Systemic sclerosis (SSc) is an autoimmune disease with incompletely revealed etiology and pathophysiology. There are still no specific and reliable biomarkers. Here we examined YKL-40 as a biomarker of inflammation and fibrosis, and suggest a possible mechanism for its regulation. Methods: Forty female patients with SSc (26 with diffuse cutaneous (dcSSc) and 14 with limited cutaneous SSc (lcSSc)) and 14 healthy female controls were enrolled in this cross-sectional study. Bioinformatic tools identified miR-214 binding site in the 30-untranslated region (3'UTR) of YKL-40 mRNA. Serum levels of YKL-40 were examined by ELISA, while YKL-40 mRNA and miR-214 was measured by qPCR. Results: The in silico analysis revealed several microRNAs (miRNAs) targeting YKL-40 mRNA, from which miR-214 was selected. YKL-40 serum levels were significantly higher in patients compared to controls (p=.0042). In contrary, miR-214 expression in plasma of SSc patients was significantly downregulated compared to controls (p=.0058). Receiver operating characteristic (ROC) and area under the curve (AUC) analysis showed that both serum YKL-40 and plasma miR-214 levels had good capacity to distinguish patients with SSc, dcSSc and lcSSc from healthy subjects. Conclusion: YKL-40 and miR-214 have different expression profile in SSc. Increased serum levels of YKL-40 could be associated with down-regulation of miR-214 expression in plasma. Both, YKL-40 concentrations and miR-214 plasma fold change values might serve as possible biomarkers in SSc. [ABSTRACT FROM AUTHOR]

Systemic sclerosis (SSc) is a rare connective tissue disease characterized by vascular, immune and fibrotic abnormalities in the skin and in many internal organs. New biomarkers with predictive value associated with target organ involvement are needed. The up-regulation of IL-6 production is associated with the disease activity and in the development of cardiopulmonary manifestations in SSc patients. The protein YKL-40 is a promising and intensively investigated biomarker related to inflammatory and tumor diseases. The objective of the study was to investigate how serum levels of YKL-40 and IL-6 correlate with articular and periarticular involvement in patients with SSc assessed by high-frequency ultrasonography. 59 SSc patients (56 women, 3 men) and 23 age-matched healthy subjects (21 women and 2 men) were investigated for serum YKL-40 and IL-6 (by ELISA). All the patients and healthy controls underwent clinically and high-frequency ultrasound assessment of articular and periarticular structures. Joint involvement was scored according to the new US10SSc score. Clinical data about the SSc patients showed significantly higher mRSS in the dcSSc patients (p = 0.015). Clinical synovitis was diagnosed in 16.9% of all patients: 22.5% of the dcSSc group and 10.7% of the lcSSc group (p = 0.306). On the other hand, US synovitis was detected in a higher percentage: 44% of all SSc patients; 54.8% of the dcSSc group and 32% of the lcSSc patients (p = 0.116). Clinical tenosynovitis was established in 6.7% of all patients: 9.7% of the dcSSc group and 3.5% of the lcSSc group (p = 0.614). US tenosynovitis was detected at a higher rate: 27% of all patients; 32.25% of the dcSSc group and 21.4% of the lcSSc group (p = 0.393). Serum level of YKL-40 was significantly higher in SSc patients (115.62 ng/ml ± 89.51, median 86.76) compared to the healthy controls (46.28 ng/ml ± 18.91, median 44.02), p < 0.001. IL-6 level was also significantly higher in the patient group (27.60 ± 48.80 pg/ml; median 8.32) vs. the healthy controls (5.79 ± 2.46 pg/ml, median 5.52). In the patient subgroups, YKL-40 and IL-6 levels were significantly elevated in dcSSc compared to lcSSc patients: YKL-40 dcSSc (159.52 ng/ml ± 102.81; median 136.20 ng/ml) vs. lcSSc patients (89.31 ng/ml ± 50.36; median 68.03 ng/ml;), p < 0.001; IL-6 dcSSc patients (49.64 pg/ml ± 46.37; median 16.36 pg/ml) vs. lcSSc patients (13.22 pg/ml ± 8.95; median 8.65 pg/ml), p = 0.048. A statistically significant correlation of high magnitude (rs = 0.884, p < 0.001) was observed between YKL-40 and the ultrasound 10 Systemic sclerosis score (US10SSc) and between IL-6 and the US10SSc score (rs = 0.808, p < 0.001). Serum YKL-40 and IL-6 in combination with US may have a potential role in defining disease activity and stratification, predicting organ involvement, and in the prognosis of SSc. [ABSTRACT FROM AUTHOR]

The aim of our study was to analyze the level of the glycoprotein YKL-40 in patients with active knee osteoarthritis (OA) and to search possible correlations with local inflammation and ultrasound (US) findings.Material and Methods: A prospective study with fifty consecutive patients with active knee OA (diagnosed based on the American College of Rheumatology criteria for OA with radiographic confirmation) was performed. Concentrations of YKL-40 in serum and synovial fluid were measured by ELISA. US examinations - Gray scale (GS) US and Power Doppler (PD) US - of the knee was performed according to international guidelines. The suprapatellar, medial and lateral parapatellar recesses were scanned in each knee to evaluate synovial hypertrophy and vascularization.Results: Forty women (mean age 61.50±11.33 years old) and 10 men (aged 68.50±6.60 years old) were enrolled. We found that the synovial level of the glycoprotein (237.80±104.08 ng/ml) was significantly higher compared to the serum concentration (112.83±60.61 ng/ml, p<0.001). The serum concentration in OA patients was higher comparing with age-matched healthy controls (84.19±11.39 ng/ml) (p<0.05). A statistically significant association between YKL- 40 in synovial fluid and serum levels was shown. We determined a moderately positive linear relationship between the synovial level of the glycoprotein and the serum concentration. No association between the levels of inflammatory markers - erythrocyte sedimentation rate and C-reactive protein - and YKL-40 concentrations was detected. Our study revealed a strong relationship between YKL-40 in synovial fluid and GS US and feeble with PD US. YKL-40 correlated with inflammatory activity in knee joints and neovascularization detected by US.Conclusions: YKL-40 is involved in the pathogenesis of OA synovitis. Evaluation of YKL-40 levels in parallel with US might provide more sensitive and reliable information for the diagnosis and understanding of OA. [ABSTRACT FROM AUTHOR]

YKL-40, also known as human cartilage glycoprotein 39, is a member of the 'mammalian chitinase-like proteins' family without chitinase activity. Increased serum concentrations are associated with inflammatory processes and several types of cancer. In this study, we evaluated YKL-40 levels in serum and synovial fluid of patients with rheumatoid arthritis in comparison with the ultrasonographic findings. YKL-40 levels were measured by enzyme-linked immunosorbent assay in 25 patients with active rheumatoid arthritis and in 40 healthy subjects. B mode and power Doppler were performed to determine synovial thickening and vascularization. Serum YKL-40 level in patients was significantly higher than the concentration in healthy controls ( P < 0.01). In patients with rheumatoid arthritis, the level of the glycoprotein in synovial fluid was remarkably elevated compared to the serum level ( P = 0.003). The B mode and power Doppler scores correlated to YKL-40 in serum and synovial fluid ( P = 0.07). Serum YKL-40 levels were related positively to serum markers of inflammation such as C-reactive protein ( P = 0.004) and erythrocyte sedimentation rate ( P = 0.003). This study is the first to demonstrate a relationship between YKL-40 levels and ultrasonographic examinations in Bulgarian patients with rheumatoid arthritis. The findings suggest that YKL-40 might be implicated in the pathogenesis of the disease and could indicate the level of joint inflammation. [ABSTRACT FROM AUTHOR]