Accumulation of environmental chitin in the lungs can lead to pulmonary fibrosis, characterized by inflammatory infiltration and fibrosis in acidic chitinase (Chia)-deficient mice. Transgenic expression of Chia in these mice ameliorated the symptoms, indicating the potential of enzyme supplementation as a promising therapeutic strategy for related lung diseases. This study focuses on utilizing hyperactivated human Chia, which exhibits low activity. We achieved significant activation of human Chia by incorporating nine amino acids derived from the crab-eating monkey (Macaca fascicularis) Chia, known for its robust chitin-degrading activity. The modified human Chia retained high activity across a broad pH spectrum and exhibited enhanced thermal stability. The amino acid substitutions associated with hyperactivation of human Chia activity occurred species specifically in monkey Chia. This discovery highlights the potential of hyperactivated Chia in treating pulmonary diseases resulting from chitin accumulation in human lungs.

• MeSH
• aktivace enzymů účinky léků   MeSH
• chitin metabolismus   chemie   MeSH
• chitinasy * metabolismus   genetika   chemie   MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• Macaca fascicularis MeSH
• myši MeSH
• plíce metabolismus   patologie   enzymologie   MeSH
• stabilita enzymů MeSH
• substituce aminokyselin MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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).

• MeSH
• biologické markery krev   MeSH
• dospělí MeSH
• kardiovaskulární nemoci krev   prevence a kontrola   MeSH
• lidé středního věku MeSH
• lidé MeSH
• prognóza MeSH
• protein CHI3L1 * krev   MeSH
• rizikové faktory kardiovaskulárních chorob * MeSH
• senioři MeSH
• statistika jako téma MeSH
• ukazatele zdravotního stavu MeSH
• věkové faktory MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• klinická studie 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

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

Alzheimer's disease (AD) is the most common form of progressively disabling dementia. The chitinases CHI3L1 and CHI3L2 have long been known as biomarkers for microglial and astrocytic activation in neurodegeneration. Here, we collected microarray datasets from the National Center for Biotechnology Information (NCBI) brain samples of non-demented controls (NDC) (n = 460), and of deceased patients with AD (n = 697). The AD patients were stratified according to sex. Comparing the high CHI3L1 and CHI3L2 expression group (75th percentile), and low CHI3L1 and CHI3L2 expression group (25th percentile), we obtained eight signatures according to the sex of patients and performed a genomic deconvolution analysis using neuroimmune signatures (NIS) belonging to twelve cell populations. Expression analysis revealed significantly higher CHI3L1 and CHI3L2 expression in AD compared with NDC, and positive correlations of these genes with GFAP and TMEM119. Furthermore, deconvolution analysis revealed that CHI3L1 and CHI3L2 high expression was associated with inflammatory signatures in both sexes. Neuronal activation profiles were significantly activated in AD patients with low CHI3L1 and CHI3L2 expression levels. Furthermore, gene ontology analysis of common genes regulated by the two chitinases unveiled immune response as a main biological process. Finally, microglia NIS significantly correlated with CHI3L2 expression levels and were more than 98% similar to microglia NIS determined by CHI3L1. According to our results, high levels of CHI3L1 and CHI3L2 in the brains of AD patients are associated with inflammatory transcriptomic signatures. The high correlation between CHI3L1 and CHI3L2 suggests strong co-regulation.

• MeSH
• Alzheimerova nemoc * genetika   metabolismus   MeSH
• biologické markery metabolismus   MeSH
• chitinasy * genetika   metabolismus   MeSH
• lidé MeSH
• mozek metabolismus   MeSH
• transkriptom genetika   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chitin, the second most abundant biopolymer on earth after cellulose, is composed of β-1,4-N-acetylglucosamine (GlcNAc) units. It is widely distributed in nature, especially as a structural polysaccharide in the cell walls of fungi, the exoskeletons of crustaceans, insects, and nematodes. However, the principal commercial source of chitin is the shells of marine or freshwater invertebrates. Microbial chitinases are largely responsible for chitin breakdown in nature, and they play an important role in the ecosystem's carbon and nitrogen balance. Several microbial chitinases have been characterized and are gaining prominence for their applications in various sectors. The current review focuses on chitinases of microbial origin, their diversity, and their characteristics. The applications of chitinases in several industries such as agriculture, food, the environment, and pharmaceutical sectors are also highlighted.

• MeSH
• bezobratlí metabolismus   MeSH
• chitin chemie   metabolismus   MeSH
• chitinasy * MeSH
• ekosystém * MeSH
• houby metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

The accumulation of chitin waste from the seafood industry is a serious environmental problem. However, this residue can be degraded by chitinases and its subproducts, such as chitosan, economically exploited. In this study, a chitinase producer bacteria, identified as Paenibacillus illinoisensis, was isolated from the Brazilian coastal city of Terra de Areia - Rio Grande Do Sul (RS) and was immobilized within alginate beads to evaluate its chitinase production. The alginate beads containing cells presented an average size of 4 mm, 99% of immobilization efficiency and increased the enzymatic activity in 40.71% compared to the free cells. The biomass during enzymatic production increased 62.01% and the total cells leaked from the alginate beads corresponded to 6.46% after 96 h. Immobilized cells were reused in a sequential batch system and remained stable for production for up to four 96-h cycles, decreasing only 21.04% of the initial activity at the end of the fourth cycle. Therefore, the methodology used for cell immobilization resulted in adequate beads to maintain cell viability during the enzymatic production, increasing enzymatic activity, showing low cell leakage from the support and appropriate recyclable capacity.

• MeSH
• algináty chemie   MeSH
• chitinasy * MeSH
• kyseliny hexuronové chemie   MeSH
• půda MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Brazílie MeSH

BACKGROUND: The possibility to better predict the severity of the disease in a patient newly diagnosed with multiple sclerosis would allow the treatment strategy to be personalized and lead to better clinical outcomes. Prognostic biomarkers are highly needed. OBJECTIVE: To assess the prognostic value of intrathecal IgM synthesis, cerebrospinal fluid and serum IL-2, IL-6, IL-10, chitinase 3-like 2 and neurofilament heavy chains obtained early after the onset of the disease. METHODS: 58 patients after the first manifestation of multiple sclerosis were included. After the initial diagnostic assessment including serum and cerebrospinal fluid biomarkers, all patients initiated therapy with either glatiramer acetate, teriflunomide, or interferon beta. To assess the evolution of the disease, we followed the patients clinically and with MRI for two years. RESULTS: The IL-2:IL-6 ratio (both in cerebrospinal fluid) <0.48 (p = 0.0028), IL-2 in cerebrospinal fluid ≥1.23pg/ml (p = 0.026), and chitinase 3-like 2 in cerebrospinal fluid ≥7900pg/ml (p = 0.033), as well as baseline EDSS ≥1.5 (p = 0.0481) and age <22 (p = 0.0312), proved to be independent markers associated with shorter relapse free intervals. CONCLUSION: The IL-2:IL-6 ratio, IL-2, and chitinase 3-like 2 (all in cerebrospinal fluid) might be of value as prognostic biomarkers in early phases of multiple sclerosis.

• MeSH
• biologické markery mozkomíšní mok   MeSH
• chitinasy metabolismus   MeSH
• chronická nemoc MeSH
• interleukin-2 metabolismus   MeSH
• interleukin-6 metabolismus   MeSH
• lidé MeSH
• recidiva MeSH
• roztroušená skleróza * mozkomíšní mok   diagnóza   farmakoterapie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Chitooligosaccharides exhibit several biomedical activities, such as inflammation and tumorigenesis reduction in mammals. The mechanism of the chitooligosaccharides' formation in vivo has been, however, poorly understood. Here we report that mouse acidic chitinase (Chia), which is widely expressed in mouse tissues, can produce chitooligosaccharides from deacetylated chitin (chitosan) at pH levels corresponding to stomach and lung tissues. Chia degraded chitin to produce N-acetyl-d-glucosamine (GlcNAc) dimers. The block-type chitosan (heterogenous deacetylation) is soluble at pH 2.0 (optimal condition for mouse Chia) and was degraded into chitooligosaccharides with various sizes ranging from di- to nonamers. The random-type chitosan (homogenous deacetylation) is soluble in water that enables us to examine its degradation at pH 2.0, 5.0, and 7.0. Incubation of these substrates with Chia resulted in the more efficient production of chitooligosaccharides with more variable sizes was from random-type chitosan than from the block-type form of the molecule. The data presented here indicate that Chia digests chitosan acquired by homogenous deacetylation of chitin in vitro and in vivo. The degradation products may then influence different physiological or pathological processes. Our results also suggest that bioactive chitooligosaccharides can be obtained conveniently using homogenously deacetylated chitosan and Chia for various biomedical applications.

• MeSH
• chitinasy chemie   metabolismus   MeSH
• chitosan chemie   metabolismus   MeSH
• difrakce rentgenového záření MeSH
• hydrolýza MeSH
• koncentrace vodíkových iontů * MeSH
• myši MeSH
• oligosacharidy chemie   metabolismus   MeSH
• orgánová specificita MeSH
• plíce metabolismus   MeSH
• substrátová specifita MeSH
• žaludek metabolismus   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Commensal bacterium Clostridium paraputrificum J4 produces several extracellular chitinolytic enzymes including a 62 kDa chitinase Chit62J4 active toward 4-nitrophenyl N,N'-diacetyl-β-d-chitobioside (pNGG). We characterized the crude enzyme from bacterial culture fluid, recombinant enzyme rChit62J4, and its catalytic domain rChit62J4cat. This major chitinase, securing nutrition of the bacterium in the human intestinal tract when supplied with chitin, has a pH optimum of 5.5 and processes pNGG with Km = 0.24 mM and kcat = 30.0 s-1. Sequence comparison of the amino acid sequence of Chit62J4, determined during bacterial genome sequencing, characterizes the enzyme as a family 18 glycosyl hydrolase with a four-domain structure. The catalytic domain has the typical TIM barrel structure and the accessory domains-2x Fn3/Big3 and a carbohydrate binding module-that likely supports enzyme activity on chitin fibers. The catalytic domain is highly homologous to a single-domain chitinase of Bacillus cereus NCTU2. However, the catalytic profiles significantly differ between the two enzymes despite almost identical catalytic sites. The shift of pI and pH optimum of the commensal enzyme toward acidic values compared to the soil bacterium is the likely environmental adaptation that provides C. paraputrificum J4 a competitive advantage over other commensal bacteria.

• MeSH
• bakteriální proteiny genetika   metabolismus   MeSH
• chitin metabolismus   MeSH
• chitinasy chemie   genetika   metabolismus   MeSH
• Clostridium růst a vývoj   izolace a purifikace   metabolismus   MeSH
• katalytická doména MeSH
• koncentrace vodíkových iontů MeSH
• lidé MeSH
• rekombinantní proteiny genetika   metabolismus   MeSH
• střevní mikroflóra MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH