YKL-40 is structurally similar to chitotriosidase (CHIT1), an active chitinase, but it lacks chitin-degrading activity while retaining chitin-binding capability. Elevated YKL-40 levels are associated with inflammatory diseases and cancers, making it a valuable biomarker. We previously reported that the W69T substitution in YKL-40 significantly reduces its chitin-binding affinity, identifying W69 as a crucial binding site. In this study, we establish a novel chitin-binding affinity evaluation method using a three-step buffer system to assess the binding strength and specificity of chitin-binding proteins and apply it to characterize YKL-40's binding mechanism. Our findings confirm that YKL-40, through its key residue W69, exhibits highly specific and robust affinity to chitin. Unlike CHIT1, which has both a catalytic domain (CatD) and a chitin-binding domain (CBD) that allow for diverse binding and degradation activities, YKL-40 lacks a CBD and is specialized for specific chitin recognition without degrading it. Comparative analysis with YKL-39, which does not contain a corresponding W69 residue, highlights the unique role of this residue in YKL-40's chitin-binding activity that is potentially linked to immune and inflammatory responses. Our evaluation method clarifies YKL-40's binding properties and provides a versatile approach applicable to other chitin-binding proteins.

• Klíčová slova
• W69 residue, YKL-39, YKL-40, catalytic domain (CatD), chitin, chitin-binding activity, chitin-binding affinity assay, chitin-binding domain (CBD), chitinase-like proteins (CLPs), chitotriosidase (CHIT1),
• MeSH
• chitin * metabolismus   chemie   MeSH
• hexosaminidasy * metabolismus   chemie   MeSH
• katalytická doména MeSH
• lidé MeSH
• protein CHI3L1 * metabolismus   MeSH
• vazba proteinů * MeSH
• vazebná místa MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• CHI3L1 protein, human MeSH Prohlížeč
• chitin * MeSH
• chitotriosidase MeSH Prohlížeč
• hexosaminidasy * MeSH
• protein CHI3L1 * MeSH

YKL-40, also known as human cartilage glycoprotein-39 (HC-gp39) or CHI3L1, shares structural similarities with chitotriosidase (CHIT1), an active chitinase, but lacks chitinase activity. Despite being a biomarker for inflammatory disorders and cancer, the reasons for YKL-40's inert chitinase function have remained elusive. This study reveals that the loss of chitinase activity in YKL-40 has risen from multiple sequence modifications influencing its chitin affinity. Contrary to the common belief associating the lack of chitinase activity with amino acid substitutions in the catalytic motif, attempts to activate YKL-40 by creating two amino acid mutations in the catalytic motif (MT-YKL-40) proved ineffective. Subsequent exploration that included creating chimeras of MT-YKL-40 and CHIT1 catalytic domains (CatDs) identified key exons responsible for YKL-40 inactivation. Introducing YKL-40 exons 3, 6, or 8 into CHIT1 CatD resulted in chitinase inactivation. Conversely, incorporating CHIT1 exons 3, 6, and 8 into MT-YKL-40 led to its activation. Our recombinant proteins exhibited properly formed disulfide bonds, affirming a defined structure in active molecules. Biochemical and evolutionary analysis indicated that the reduced chitinase activity of MT-YKL-40 correlates with specific amino acids in exon 3. M61I and T69W substitutions in CHIT1 CatD diminished chitinase activity and increased chitin binding. Conversely, substituting I61 with M and W69 with T in MT-YKL-40 triggered chitinase activity while reducing the chitin-binding activity. Thus, W69 plays a crucial role in a unique subsite within YKL-40. These findings emphasize that YKL-40, though retaining the structural framework of a mammalian chitinase, has evolved to recognize chitin while surrendering chitinase activity.

• Klíčová slova
• YKL-40, asthma, biomarker, cartilage biology, chitin, chitin-binding, chitinase, enzyme inactivation, inflammation, tumor marker,
• MeSH
• chitin * metabolismus   chemie   MeSH
• chitinasy metabolismus   genetika   chemie   MeSH
• exony MeSH
• hexosaminidasy metabolismus   chemie   genetika   MeSH
• katalytická doména MeSH
• lidé MeSH
• molekulární evoluce MeSH
• protein CHI3L1 * metabolismus   genetika   chemie   MeSH
• sekvence aminokyselin MeSH
• substituce aminokyselin MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CHI3L1 protein, human MeSH Prohlížeč
• chitin * MeSH
• chitinasy MeSH
• chitotriosidase MeSH Prohlížeč
• hexosaminidasy MeSH
• protein CHI3L1 * MeSH

Malignant gliomas are the most common type of primary malignant brain tumours, characterized by extreme proliferation and aggressive invasion. There is evidence for over-expression of the YKL40 gene in high-grade gliomas. The high serum levels of the glycoprotein are associated with poor prognosis of various inflammatory and tumour processes. We investigated the YKL40 mRNA level and protein expression in the tumour site and in the serum of high-grade glioma patients. The YKL-40 expression in 36 patients with glial tumours (astrocytoma grade III, glioblastoma) and 33 age-matched healthy persons was measured by gene analysis, immunohistochemistry and ELISA. YKL-40 serum levels in high-grade glioma patients compared to healthy subjects were significantly increased (P ≤ 0.05). A wide range of variability in YKL40 mRNA expression was found. YKL-40 staining in situ was more abundant in glioblastoma tissue than in anaplastic astrocytoma, with the lowest level in normal brain tissue. Our gene analysis revealed that in general, YKL40 mRNA in glioma patients was over-expressed versus normal brain. A significant correlation between YKL40 transcript and protein levels was observed (P ≤ 0.05). It could be speculated that the YKL-40 protein might contribute to glioblastomas' specific biological characteristics that distinguish them from grade III gliomas. A complex investigation of YKL40 expression was performed at the molecular and cellular levels in human high-grade gliomas. Serum YKL-40 concentrations increased with tumour grade and correlated positively with transcript rate, being the highest in glioblastoma. We provide evidence for a relationship between YKL40 expression and the malignancy of glial tumours.

• MeSH
• adipokiny biosyntéza   krev   genetika   MeSH
• astrocytom metabolismus   patologie   terapie   MeSH
• dospělí MeSH
• glioblastom metabolismus   patologie   terapie   MeSH
• gliom metabolismus   patologie   terapie   MeSH
• kombinovaná terapie MeSH
• lektiny biosyntéza   krev   genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA biosyntéza   genetika   MeSH
• nádorové proteiny biosyntéza   krev   genetika   MeSH
• nádory mozku metabolismus   patologie   terapie   MeSH
• prognóza MeSH
• protein CHI3L1 MeSH
• regulace genové exprese u nádorů MeSH
• RNA nádorová biosyntéza   genetika   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň nádoru MeSH
• upregulace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adipokiny MeSH
• CHI3L1 protein, human MeSH Prohlížeč
• lektiny MeSH
• messenger RNA MeSH
• nádorové proteiny MeSH
• protein CHI3L1 MeSH
• RNA nádorová MeSH

BACKGROUND: The aim of this study is to investigate the association between hepatic activity index (HAI) and fibrosis score (FS) with inflammation biomarkers in non-uremic and uremic hepatitis C positive patients. METHODS: Fifty chronic hepatitis C (cHepC) positive patients, having a liver biopsy were included in this study. Liver biopsies were scored according to modified ISHAC scoring system. 25 healthy controls of similar age and gender were also enrolled as control group. Serum YKL-40, neutrophil/lymphocyte ratio (NLR), thrombocyte/lymphocyte ratio (PLR), CRP and Immunoglobulin (IgG, A and M) levels were used to determine inflammation. AST to Platelet Ratio Index (APRI) score was also evaluated. According to biopsy findings patients were divided into 2 groups: low (0-2) and severe (3-6) FS. RESULTS: Patients with cHepC had increased inflammation compared to the healthy controls. End-stage renal disease (ESRD) patients had higher levels of inflammation markers (NLR, IgG, CRP and YKL-40) and lower HCV RNA levels, HAI and FS compared to non-uremic patients. When patients were grouped into 2 according to FS as mild and severe, IgG (p < 0.001), YKL-40 (p = 0.02) levels and APRI score (p = 0.002) were significantly higher compared to mild FS (p = 0.002). YKL-40 levels (t value: 3.48; p = 0.001) and APRI score (t value: 4.57, p < 0.001) were found as independent associated with FS in non-uremic patients. However, in adjusted models, only APRI score (t value: 3.98, p = 0.002) was an independent associated with FS in ESRD patients. CONCLUSION: In non-uremic cHepC patients, YKL-40 levels and APRI score may be valuable markers of FS. In ESRD patients, there is not sufficient data for prediction of HAI and FS. In these patients, APRI score may provide better information.

• Klíčová slova
• APRI score, YKL-40, end-stage renal disease, hepatitis C, inflammation biomarkers, liver histopathology,
• MeSH
• biologické markery metabolismus   MeSH
• biopsie MeSH
• chronická hepatitida C patofyziologie   MeSH
• dospělí MeSH
• játra patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• neutrofily metabolismus   MeSH
• počet leukocytů MeSH
• počet lymfocytů MeSH
• protein CHI3L1 krev   MeSH
• senioři MeSH
• studie případů a kontrol MeSH
• stupeň závažnosti nemoci MeSH
• trombocyty metabolismus   MeSH
• uremie komplikace   MeSH
• zánět patofyziologie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• biologické markery MeSH
• CHI3L1 protein, human MeSH Prohlížeč
• protein CHI3L1 MeSH

STUDY OBJECTIVES: To study prognostic value of different biochemical markers for morphological progression of early knee osteoarthritis. DESIGN: A total of 89 patients with knee osteoarthritis (OA) were enroled into the study. The follow-up period was 2 years. Radiological OA progression was evaluated by measuring joint space width. Pentosidine was detected using the HPLC method described earlier, cartilage oligomeric matrix protein (COMP) using the method published by our team. MMP-9, tissue inhibitors of metalloproteinases (TIMP), YKL-40 and hyaluronic acid were detected using commercially available kits. RESULTS: In the group of patients suffering from knee OA, higher serum levels of pentosidine (P=0.04), MMP-9 (P=0.02), TIMP (P=0.04) and COMP (P=0.05) were detected compared with healthy control subjects. Using a correlation analysis method, it has been found that the patients with higher basic serum levels of hyaluronic acid had a faster radiological progression (r=0.56, P<0.005), as well as the patients with higher basic serum pentosidine levels (r=0.30, P<0.005). Other biochemical markers had no statistically significant prognostic value. CONCLUSIONS: In our study, serum levels of hyaluronic acid and pentosidine had a predictive value for further development of knee OA in that further joint space narrowing was detected in the patients with knee OA in the next 2 years.

• MeSH
• adipokiny MeSH
• adjuvancia imunologická krev   MeSH
• arginin analogy a deriváty   krev   MeSH
• artróza kolenních kloubů krev   diagnostické zobrazování   MeSH
• biologické markery krev   MeSH
• chrupavkový oligomerní matrixový protein MeSH
• extracelulární matrix - proteiny krev   MeSH
• glykoproteiny krev   MeSH
• kloubní chrupavka metabolismus   MeSH
• kolenní kloub diagnostické zobrazování   MeSH
• kyselina hyaluronová krev   MeSH
• lektiny MeSH
• lidé středního věku MeSH
• lidé MeSH
• lysin analogy a deriváty   krev   MeSH
• matriliny MeSH
• matrixová metaloproteinasa 9 krev   MeSH
• prognóza MeSH
• progrese nemoci MeSH
• protein CHI3L1 MeSH
• radiografie MeSH
• reagencia zkříženě vázaná analýza   MeSH
• tkáňové inhibitory metaloproteinas krev   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adipokiny MeSH
• adjuvancia imunologická MeSH
• arginin MeSH
• biologické markery MeSH
• CHI3L1 protein, human MeSH Prohlížeč
• chrupavkový oligomerní matrixový protein MeSH
• extracelulární matrix - proteiny MeSH
• glykoproteiny MeSH
• kyselina hyaluronová MeSH
• lektiny MeSH
• lysin MeSH
• matriliny MeSH
• matrixová metaloproteinasa 9 MeSH
• pentosidine MeSH Prohlížeč
• protein CHI3L1 MeSH
• reagencia zkříženě vázaná MeSH
• tkáňové inhibitory metaloproteinas MeSH
• TSP5 protein, human MeSH Prohlížeč

PURPOSE OF THE STUDY: Both synovial and bone forms of osteoarthritis (OA) are characterized by inflammatory processes in the articular compartment. Increasing evidence suggests that changes in bone tissue are important for the deterioration or loss of joint function. Therefore it is reasonable to shift emphasis from research on cartilage to that on other articular tissues, particularly on subchondral bone. The aim of the study was to demonstrate the involvement of several cytokines in OA development and, on the basis of changes of joint markers, to assess the extent of inflammatory process. MATERIAL: A total of 60 patients with an osseous form of osteoarthritis of the knee joint (28 patients) or the hip joining (32 patients) underwent total knee or hip arthroplasty. The mean age of our patients was 66.7 +/- 10.4 years. Preoperative clinical and radiographic examinations were carried out as well as routine laboratory tests on blood and urine. Samples of urine, blood serum (BS) and synovial fluid (SF), extracts from cartilage (CA) and synovial membrane (SM) and granulation bone tissue were analysed for markers indicating the presence of inflammatory processes in joints. METHOD: The following markers of inflammatory activity in the bone compartment were investigated: pyridinoline (PYR), deoxypyridinoline (D-PYR), bone alkaline phosphatase (BAP) and chondrex (CHON). The levels of cytokines IL-1 alpha, IL-8, IL-10 and TNF-alpha were assayed by immunoanalysis (ELISA and IMMULITE system) in BS, CA, SM, GT and SF. The tissue samples were obtained during arthroplasty. RESULTS: In the patients with osteoarthritis, the urinary levels of PYR and D-PYR were higher than control values (70.33 +/- 34.93 vs (41.6 +/- 10.6 nmol/mmol creatinine). No significant differences were found between pre- and post-operative levels. Similarly, the serum levels of BAP and CHON compared with control values were higher (27.65 +/- 12.21 vs 12.2 +/- 2.7 U/L and (96.35 +/- 58.83 vs 43.2 +/- 14.5 ng/ml, respectively). In all articular compartments and in synovial fluid, the level of cytokine IL-8 exceeded concentrations of the other cytokines. In blood serum, only IL-10 levels were markedly increased as against the control group (17.35 +/- 5.82 vs 9.80 +/- 4.40 pg/ml). DISCUSSION: Primary osteoarthritis is the most common joint disease that deteriorates with age. Its symptoms are pain and a lower range of motion in the joint affected. The initial involvement of articular cartilage progresses to degenerative changes involving synovial and bony structures. This degenerative disease gradually develops into an inflammatory disease. At this stage, osseous tissue shows an increase in metabolism and bone destruction results. In the control of inflammatory reactions by the immune system, cytokines, among other proteins, play an important role: some may enhance inflammation by activating leukocytes (IL-1, TNF-alpha, IL-8) while others, such as IL-10, have anti-inflammatory effects. CONCLUSION: During osteoarthritis, the articular compartment shows high metabolic processes that, in some patients, may increase and even persist some time after arthroplasty.

• MeSH
• adipokiny MeSH
• alkalická fosfatasa analýza   MeSH
• artróza kolenních kloubů metabolismus   MeSH
• artróza kyčelních kloubů metabolismus   MeSH
• cytokiny analýza   MeSH
• glykoproteiny analýza   MeSH
• kloubní chrupavka MeSH
• kloubní pouzdro chemie   MeSH
• kolenní kloub MeSH
• kyčelní kloub MeSH
• lektiny MeSH
• lidé MeSH
• protein CHI3L1 MeSH
• senioři MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adipokiny MeSH
• alkalická fosfatasa MeSH
• CHI3L1 protein, human MeSH Prohlížeč
• cytokiny MeSH
• glykoproteiny MeSH
• lektiny MeSH
• protein CHI3L1 MeSH

Chitinase 3-like 1 (CHI3L1) has been proposed as a biomarker associated with the conversion to clinically definite multiple sclerosis in patients with clinically isolated syndromes, based on the finding of increased cerebrospinal fluid CHI3L1 levels in clinically isolated syndrome patients who later converted to multiple sclerosis compared to those who remained as clinically isolated syndrome. Here, we aimed to validate CHI3L1 as a prognostic biomarker in a large cohort of patients with clinically isolated syndrome. This is a longitudinal cohort study of clinically isolated syndrome patients with clinical, magnetic resonance imaging, and cerebrospinal fluid data prospectively acquired. A total of 813 cerebrospinal fluid samples from patients with clinically isolated syndrome were recruited from 15 European multiple sclerosis centres. Cerebrospinal fluid CHI3L1 levels were measured by enzyme-linked immunosorbent assay. Multivariable Cox regression models were used to investigate the association between cerebrospinal fluid CHI3L1 levels and time to conversion to multiple sclerosis and time to reach Expanded Disability Status Scale 3.0. CHI3L1 levels were higher in patients who converted to clinically definite multiple sclerosis compared to patients who continued as clinically isolated syndrome (P = 8.1 × 10(-11)). In the Cox regression analysis, CHI3L1 levels were a risk factor for conversion to multiple sclerosis (hazard ratio = 1.7; P = 1.1 × 10(-5) using Poser criteria; hazard ratio = 1.6; P = 3.7 × 10(-6) for McDonald criteria) independent of other covariates such as brain magnetic resonance imaging abnormalities and presence of cerebrospinal fluid oligoclonal bands, and were the only significant independent risk factor associated with the development of disability (hazard ratio = 3.8; P = 2.5 × 10(-8)). High CHI3L1 levels were associated with shorter time to multiple sclerosis (P = 3.2 × 10(-9) using Poser criteria; P = 5.6 × 10(-11) for McDonald criteria) and more rapid development of disability (P = 1.8 × 10(-10)). These findings validate cerebrospinal fluid CHI3L1 as a biomarker associated with the conversion to multiple sclerosis and development of disability and reinforce the prognostic role of CHI3L1 in patients with clinically isolated syndrome. We propose that determining cerebrospinal fluid chitinase 3-like 1 levels at the time of a clinically isolated syndrome event will help identify those patients with worse disease prognosis.

• Klíčová slova
• biomarker, clinically isolated syndrome, disability progression, multiple sclerosis,
• MeSH
• adipokiny biosyntéza   mozkomíšní mok   MeSH
• biologické markery mozkomíšní mok   MeSH
• demyelinizační nemoci mozkomíšní mok   diagnóza   MeSH
• dospělí MeSH
• lektiny biosyntéza   mozkomíšní mok   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mozek metabolismus   patologie   MeSH
• následné studie MeSH
• prognóza MeSH
• protein CHI3L1 MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adipokiny MeSH
• biologické markery MeSH
• CHI3L1 protein, human MeSH Prohlížeč
• lektiny MeSH
• protein CHI3L1 MeSH

OBJECTIVES: Chitinase 3-like 1 (CHI3L1) is an extracellular monomeric single-chain glycoprotein expressed by many types of cells. Its elevated levels were found in cerebrospinal fluid in central nervous system (CNS) inflammatory diseases patients. The aim of the study was 1) to validate the reference interval of cerebrospinal fluid (CSF) CHI3L1 in a control group; 2) to measure the CHI3L1 concentration in different diagnosis groups .including multiple sclerosis (MS); and 3) to correlate those values with other biomarkers of axonal damage or neuroinflammation in different grous. METHODS: The study included 132 CSF samples sent to the Department of Clinical Biochemistry, Institute of Laboratory Diagnostics, University Hospital Ostrava. Concentrations of CHI3L1, CXCL13 chemokine, neurofilament light chains, and phosphorylated neurofilament heavy chains were determined by enzyme-linked immunosorbent assays. IgG oligoclonal bands were detected by isoelectric focusing in agarose gels followed by immunofixation. IgM and FLC oligoclonal bands were analyzed by IEF followed by affinity immunoblotting. The group consisted of 42 patients with multiple sclerosis, 14 with clinically isolated syndrome, 11 with other central nervous system inflammatory diseases, 46 with non-inflammatory diseases of the central nervous system, 4 with inflammatory diseases of the peripheral nervous system, and 15 controls. RESULTS: The estimated reference values of CHI3L1 were 28.6-182.5 μg.L-1. Statistically significant differences of CSF CHI3L1 concentrations were found among diagnosis groups (p < 0.0001), after age adjustment (p = 0.002). There was a statistically significant relationship between CHI3L1 and NFL in the MS group (rs = 0.460; P = 0.002), and between CHI3L1 and pNFH in the MS group (rs = 0.691; P < 0.001). No statistically significant difference was found in the categorical comparison of CHI3L1 in the MS group and other diagnostic groups as well as when using the Mann-Whitney U test for CHI3L1 with additional parameters with and without oligoclonal bands present. CONCLUSIONS: CSF CHI3L1 values differ depending on diagnosis and correlate significantly with concentrations of the axonal damage markers CSF neurofilament light chains, and CSF phosphorylated neurofilament heavy chains, but not with CSF concentrations of the inflammatory marker CXCL13. Thus, CSF CHI3L1 could be another promising prognostic, albeit probably etiologically nonspecific, biomarker of MS.

• MeSH
• biologické markery mozkomíšní mok   MeSH
• demyelinizační nemoci mozkomíšní mok   diagnóza   MeSH
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• prognóza MeSH
• protein CHI3L1 mozkomíšní mok   MeSH
• roztroušená skleróza mozkomíšní mok   diagnóza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• biologické markery MeSH
• CHI3L1 protein, human MeSH Prohlížeč
• protein CHI3L1 MeSH

AIMS: The aim of this study was to evaluate the association of serum neurofilament heavy chain (sNfH) and chitinase 3-like 1 (sCHI3L1) with treatment response and disease activity in multiple sclerosis (MS). METHODS: This single-center, prospective, observational cohort study was conducted at the MS Centre, University Hospital Ostrava, Czech Republic, from May 2020 to August 2023. sNfH and sCHI3L1 were determined using ELISA. A mixed-effects linear model with a log-transformed outcome variable was applied. RESULTS: We analyzed 459 samples from 57 people with MS. Patients were sampled an average of 8.05 times during 21.9 months of follow-up. Those experiencing a relapse at sampling had a sNfH concentration 50 % higher than those in remission (exp(β) 1.5, 95 % CI 1.15-1.96). A longer duration of treatment was associated with lower sNfH (exp(β) 0.95, 95 % CI 0.94-0.96). Patients switched from low- to high-efficacy disease-modifying therapies (DMTs) had higher sNfH than patients treated with low-efficacy DMTs only (exp(β) 1.95, 95 % CI 1.35-2.81). Higher sCHI3L1 was associated with older age (exp(β) 1.01, 95 % CI 1.00-1.02) and longer DMT use (exp(β) 1.01, 95 % CI 1.00-1.02). sCHI3L1 values were not associated with relapse at the time of sampling, renal function, sex, or type of DMT. CONCLUSION: In contrast to sCHI3L1, sNfH may be a potential biomarker for monitoring treatment response and confirming clinical relapse in MS. Further research is needed to determine the long-term dynamics of sNfH and develop related treatment strategies.

• Klíčová slova
• Chitinase 3-like 1, ELISA, Multiple sclerosis, Neurofilament heavy chain,
• MeSH
• biologické markery * krev   MeSH
• dospělí MeSH
• hodnocení výsledků zdravotní péče MeSH
• imunologické faktory aplikace a dávkování   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• následné studie MeSH
• neurofilamentové proteiny * krev   MeSH
• prospektivní studie MeSH
• protein CHI3L1 * krev   MeSH
• roztroušená skleróza krev   farmakoterapie   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• pozorovací studie MeSH
• Názvy látek
• biologické markery * MeSH
• CHI3L1 protein, human MeSH Prohlížeč
• imunologické faktory MeSH
• neurofilament protein H MeSH Prohlížeč
• neurofilamentové proteiny * MeSH
• protein CHI3L1 * MeSH

AIM: Chitinase-3-like protein 1 (CHI3L1) is involved in tissue remodelling and inflammatory processes. Plasma levels are elevated in patients with insulin resistance and T2DM. We recently showed that CHI3L1 and its receptor protease-activated receptor 2 (PAR-2) are expressed in skeletal muscle. Activation of PAR-2 by CHI3L1 protects against TNF-α-induced inflammation and insulin resistance. However, the effect of exercise on CHI3L1 and PAR-2 signalling remains unknown. The aim of this work was to study the impact of exercise on CHI3L1 production and the effect of CHI3L1/PAR-2 signalling on skeletal muscle growth and repair. METHODS: Three human exercise studies were used to measure CHI3L1 plasma levels (n = 32). In addition, muscle and adipose tissue CHI3L1 mRNA expression was measured in response to acute and long-term exercise (n = 24). Primary human skeletal muscle cells were differentiated in vitro, and electrical pulse stimulation was applied. In addition, myoblasts were incubated with CHI3L1 protein and activation of MAP kinase signalling as well as proliferation was measured. RESULTS: Circulating CHI3L1 levels and muscle CHI3L1 mRNA were increased after acute exercise. In addition, CHI3L1 mRNA expression as well as CHI3L1 secretion was enhanced in electrically stimulated cultured myotubes. Incubation of cultured human myoblasts with CHI3L1 protein leads to a strong activation of p44/42, p38 MAPK and Akt as well as enhanced myoblast proliferation. CONCLUSION: Our findings suggest that CHI3L1 is induced by acute exercise and that CHI3L1/PAR-2 signalling activates myocyte proliferation, which is important for restructuring of skeletal muscle in the response to exercise training.

• Klíčová slova
• chitinase-3-like protein 1, exercise, skeletal muscle,
• MeSH
• cvičení fyziologie   MeSH
• dospělí MeSH
• kosterní svaly metabolismus   MeSH
• kvantitativní polymerázová řetězová reakce MeSH
• lidé středního věku MeSH
• lidé MeSH
• messenger RNA analýza   MeSH
• mladý dospělý MeSH
• proliferace buněk fyziologie   MeSH
• protein CHI3L1 metabolismus   MeSH
• senioři MeSH
• signální transdukce fyziologie   MeSH
• svalové buňky metabolismus   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• CHI3L1 protein, human MeSH Prohlížeč
• messenger RNA MeSH
• protein CHI3L1 MeSH