Cíl: Protože kardiovaskulární onemocnění jsou příčinou závažné morbidity a mortality, je třeba zjišťovat jejich přítomnost a začít je včas léčit. Proto byla pro stanovení rizika vypracována řada stupnic, v současnosti se však rutinně nepoužívá žádný biochemický marker pro stanovení kardiovaskulárního rizika. Ateroskleróza je nejzávažnější příčinou rozvoje kardiovaskulárních onemocnění a v patofyziologii aterosklerózy hraje jistou úlohu zánět cév. Řada studií prokázala, že mnoho kroků v procesu rozvoje tohoto zánětu ovlivňují hodnoty YKL-40 v séru. Evropská kardiologická společnost používá pro stanovení desetiletého kardiovaskulárního rizika skórovací systém SCORE2. V naší studii jsme zkoumali vztah mezi algoritmem pro toto riziko a hodnotou biochemického markeru YKL-40 v séru. Materiál a metody: Do studie bylo zařazeno 87 dobrovolníků ve věku 40–70 let, kteří se dostavili na naši kliniku, v minulosti neprodělali kardiovaskulární příhodu, měli však rizikové faktory pro rozvoj kardiovaskulárního onemocnění. Pomocí predikčního modelu SCORE2 bylo stanoveno jejich kardiovaskulární riziko a současně změřeny hodnoty YKL-40 v séru. Tyto hodnoty se mění s věkem bez ohledu na přítomnost či nepřítomnost nemoci, což platilo pro naši studii stejně jako pro jiné studie. Abychom eliminovali toto paradigma, hodnotili jsme hodnoty YKL-40 v séru pomocí statistického modelu společně s věkem. Výsledky: Naše základní analýza nezjistila významný vztah mezi hodnotami YKL-40 a všemi parametry v algoritmu predikčního modelu SCORE2. Nicméně po porovnání výsledku analýzy s výsledkem statistického modelu s použitím věku se ukázalo se, že hodnota YKL-40 představuje biochemický marker, který lze použít, podobně jako systém SCORE2, při stanovování kardiovaskulárního rizika (R2 : 0,72; p < 0,001).

Objective: Since cardiovascular diseases are a cause of serious morbidity and mortality, it is important to detect and treat them in advance. For this reason, many risk scales have been created, but there is currently no biochemical marker in routine use to estimate cardiovascular risk. Atherosclerosis is the most important reason for the development of cardiovascular disease, and vascular inflammation plays a role in the pathophysiology of atherosclerosis. It has been observed in many studies that the serum YKL-40 level has an effect on many steps in the development process of this inflammation. SCORE2 are used by the European Society of Cardiology to estimate 10-year cardiovascular risk. In our study, we investigated the relationship between this risk algorithm and the serum YKL-40 level, which is a biochemical marker. Material and methods: 87 volunteers between the ages of 40-70 who applied to our clinic, who had not yet experienced a cardiovascular event but had risk factors for cardiovascular diseases, were included in the study. SCORE2 cardiovascular disease risk was calculated for the patients and serum YKL-40 levels were gaged. Serum YKL-40 levels change with age, regardless of the disease, in our study as in many studies. In order to eliminate this paradigm, we examined serum YKL-40 levels with a statistical model that evaluates them jointly with age. Results: We could not detect a significant relationship with YKL-40 levels in the basal analysis performed by considering all parameters of SCORE2 algorithm. However, result of the statistical model that we evaluated with age, we found that the YKL-40 level is a biochemical parameter that can be used like SCORE2 in cardiovascular disease risk estimation (R2 : 0.72, p < 0.001).

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.

• 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

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
• 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

• MeSH
• biologické markery MeSH
• chrupavka metabolismus   patofyziologie   MeSH
• glykoproteiny biosyntéza   krev   MeSH
• lidé MeSH
• nemoci chrupavky diagnóza   etiologie   metabolismus   MeSH
• Check Tag
• lidé 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.

• 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

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

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.

• 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

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.

• 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

The prognostic role of cerebrospinal fluid molecular biomarkers determined in early pathogenic stages of multiple sclerosis has yet to be defined. In the present study, we aimed to investigate the prognostic value of chitinase 3 like 1 (CHI3L1), neurofilament light chain, and oligoclonal bands for conversion to clinically isolated syndrome and to multiple sclerosis in 75 patients with radiologically isolated syndrome. Cerebrospinal fluid levels of CHI3L1 and neurofilament light chain were measured by enzyme-linked immunosorbent assay. Uni- and multivariable Cox regression models including as covariates age at diagnosis of radiologically isolated syndrome, number of brain lesions, sex and treatment were used to investigate associations between cerebrospinal fluid CHI3L1 and neurofilament light chain levels and time to conversion to clinically isolated syndrome and multiple sclerosis. Neurofilament light chain levels and oligoclonal bands were independent risk factors for the development of clinically isolated syndrome (hazard ratio = 1.02, P = 0.019, and hazard ratio = 14.7, P = 0.012, respectively) and multiple sclerosis (hazard ratio = 1.03, P = 0.003, and hazard ratio = 8.9, P = 0.046, respectively). The best cut-off to classify cerebrospinal fluid neurofilament light chain levels into high and low was 619 ng/l, and high neurofilament light chain levels were associated with a trend to shorter time to clinically isolated syndrome (P = 0.079) and significant shorter time to multiple sclerosis (P = 0.017). Similarly, patients with radiologically isolated syndrome presenting positive oligoclonal bands converted faster to clinically isolated syndrome and multiple sclerosis (P = 0.005 and P = 0.008, respectively). The effects of high neurofilament light chain levels shortening time to clinically isolated syndrome and multiple sclerosis were more pronounced in radiologically isolated syndrome patients with ≥37 years compared to younger patients. Cerebrospinal fluid CHI3L1 levels did not influence conversion to clinically isolated syndrome and multiple sclerosis in radiologically isolated syndrome patients. Overall, these findings suggest that cerebrospinal neurofilament light chain levels and oligoclonal bands are independent predictors of clinical conversion in patients with radiologically isolated syndrome. The association with a faster development of multiple sclerosis reinforces the importance of cerebrospinal fluid analysis in patients with radiologically isolated syndrome.

• MeSH
• biologické markery MeSH
• demyelinizační nemoci diagnóza   MeSH
• dospělí MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• neparametrická statistika MeSH
• neurofilamentové proteiny MeSH
• oligoklonální proužky MeSH
• prognóza MeSH
• protein CHI3L1 MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Evropa MeSH

Glioma is the most pernicious cancer of the nervous system, with histological grade influencing the survival of patients. Despite many studies on the multimodal treatment approach, survival time remains brief. In this study, a novel two-stage ensemble of an ensemble-type machine learning-based predictive framework for glioma detection and its histograde classification is proposed. In the proposed framework, five characteristics belonging to 135 subjects were considered: human telomerase reverse transcriptase (hTERT), chitinase-like protein (YKL-40), interleukin 6 (IL-6), tissue inhibitor of metalloproteinase-1 (TIMP-1) and neutrophil/lymphocyte ratio (NLR). These characteristics were examined using distinctive ensemble-based machine learning classifiers and combination strategies to develop a computer-aided diagnostic system for the non-invasive prediction of glioma cases and their grade. In the first stage, the analysis was conducted to classify glioma cases and control subjects. Machine learning approaches were applied in the second stage to classify the recognised glioma cases into three grades, from grade II, which has a good prognosis, to grade IV, which is also known as glioblastoma. All experiments were evaluated with a five-fold cross-validation method, and the classification results were analysed using different statistical parameters. The proposed approach obtained a high value of accuracy and other statistical parameters compared with other state-of-the-art machine learning classifiers. Therefore, the proposed framework can be utilised for designing other intervention strategies for the prediction of glioma cases and their grades.

• MeSH
• gliom * diagnóza   MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• nádory mozku * diagnóza   MeSH
• strojové učení * MeSH
• stupeň nádoru MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH