The biology of sialic acids has been an object of interest in many models of acquired and inherited skeletal muscle pathology. The present study focuses on the sialylation changes in mouse skeletal muscle after invasion by the parasitic nematode Trichinella spiralis (Owen, 1835). Asynchronous infection with T. spiralis was induced in mice that were sacrificed at different time points of the muscle phase of the disease. The amounts of free sialic acid, sialylated glycoproteins and total sialyltransferase activity were quantified. Histochemistry with lectins specific for sialic acid was performed in order to localise distribution of sialylated glycoconjugates and to clarify the type of linkage of the sialic acid residues on the carbohydrate chains. Elevated intracellular accumulation of α-2,3- and α-2,6-sialylated glycoconjugates was found only within the affected sarcoplasm of muscle fibres invaded by the parasite. The levels of free and protein-bound sialic acid were increased and the total sialyltransferase activity was also elevated in the skeletal muscle tissue of animals with trichinellosis. We suggest that the biological significance of this phenomenon might be associated with securing integrity of the newly formed nurse cell within the surrounding healthy skeletal muscle tissue. The increased sialylation might inhibit the affected muscle cell contractility through decreased membrane ion gating, helping the parasite accommodation process.
- Keywords
- sialylace,
- MeSH
- Staining and Labeling statistics & numerical data MeSH
- Fluorescence MeSH
- Glycoproteins biosynthesis MeSH
- Histological Techniques MeSH
- Muscle Fibers, Skeletal parasitology pathology ultrastructure MeSH
- Sialic Acids * analysis biosynthesis MeSH
- Lectins analysis biosynthesis classification MeSH
- Models, Animal MeSH
- Mice MeSH
- Statistics as Topic MeSH
- Trichinella spiralis * immunology isolation & purification MeSH
- Check Tag
- Mice MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't 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.
- MeSH
- Adipokines biosynthesis MeSH
- Biomarkers MeSH
- Demyelinating Diseases diagnosis MeSH
- Adult MeSH
- Lectins biosynthesis MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Brain metabolism pathology MeSH
- Follow-Up Studies MeSH
- Prognosis MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Young Adult MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't 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
- Adipokines biosynthesis blood genetics MeSH
- Astrocytoma metabolism pathology therapy MeSH
- Adult MeSH
- Glioblastoma metabolism pathology therapy MeSH
- Glioma metabolism pathology therapy MeSH
- Combined Modality Therapy MeSH
- Lectins biosynthesis blood genetics MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Messenger biosynthesis genetics MeSH
- Neoplasm Proteins biosynthesis blood genetics MeSH
- Brain Neoplasms metabolism pathology therapy MeSH
- Prognosis MeSH
- Gene Expression Regulation, Neoplastic MeSH
- RNA, Neoplasm biosynthesis genetics MeSH
- Aged MeSH
- Case-Control Studies MeSH
- Neoplasm Grading MeSH
- Up-Regulation MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Účel přehledu: Existuje fenotyp chronické obstrukční plicní nemoci (CHOPN) s častým výskytem exacerbací nezávislým na závažnosti onemocnění. Klíčový význam má vývoj metod umožňujících rozpoznávání pacientů ohrožených častými exacerbacemi. Cílem tohoto přehledového článku je podat kritický přehled o publikacích z poslední doby vztahujících se k predikci exacerbací CHOPN a navrhnout doporučení ohledně budoucího výzkumu. Nové poznatky: Ačkoli existuje mnoho studií, v nichž byly k predikci budoucích exacerbací využívány zánětlivé biomarkery, je pravděpodobné, že tyto biomarkery představují spíše důsledek než příčinu těchto exacerbací. Do kauzálních drah jsou zapojeny genetické prediktory. Chceme‑li tedy porozumět mechanismu exacerbací a vyvíjet nové léčebné postupy, musíme se zaměřit na genetické aspekty CHOPN. S výskytem exacerbací mají spojitost některé jednonukleotidové polymorfismy, přičemž jedinci s genotypy chránícími před infekcí jsou méně náchylní k exacerbacím. Sami jsme naopak publikovali zjištění, že se sníženým rizikem exacerbací CHOPN souvisí ztráta lektinu Siglec‑14, který je pravděpodobně zapojen do obrany hostitele. Souhrn: Měli bychom vzít v úvahu, že protein zapojený do obrany hostitele, jakým je Siglec‑14, jenž může rovněž spouštět nadměrnou imunologickou odpověď, může rovněž generovat nežádoucí lokální a systémový zánět, potenciálně ohrožující hostitele, a může vést k rozvoji fenotypu CHOPN s častými exacerbacemi, k progresi této nemoci a k výskytu komorbidit.
- Keywords
- patogeneze, varianty počtu kopií,
- MeSH
- Biomarkers MeSH
- Pulmonary Disease, Chronic Obstructive * diagnosis etiology genetics prevention & control therapy MeSH
- Genetic Markers MeSH
- Genotype MeSH
- Immunophenotyping MeSH
- Respiratory Tract Infections etiology pathology prevention & control MeSH
- Lectins * biosynthesis diagnostic use immunology secretion adverse effects MeSH
- Humans MeSH
- Disease Progression * MeSH
- Inflammation physiopathology prevention & control MeSH
- Check Tag
- Humans MeSH
- Publication type
- Research Support, Non-U.S. Gov't MeSH
- Review MeSH
Omentin is a novel adipokine with insulin-sensitizing effects expressed predominantly in visceral fat. We investigated serum omentin levels and its mRNA expression in subcutaneous adipose tissue (SCAT) of 11 women with type 2 diabetes mellitus (T2DM), 37 obese non-diabetic women (OB) and 26 healthy lean women (C) before and after various weight loss interventions: 2-week very-low-calorie diet (VLCD), 3-month regular exercise and laparoscopic sleeve gastrectomy (LSG). At baseline, both T2DM and OB groups had decreased serum omentin concentrations compared with C group while omentin mRNA expression in SCAT did not significantly differ among the groups. Neither VLCD nor exercise significantly affected serum omentin concentrations and its mRNA expression in SCAT of OB or T2DM group. LSG significantly increased serum omentin levels in OB group. In contrast, omentin mRNA expression in SCAT was significantly reduced after LSG. Baseline fasting serum omentin levels in a combined group of the studied subjects (C, OB, T2DM) negatively correlated with BMI, CRP, insulin, LDL-cholesterol, triglycerides and leptin and were positively related to HDL-cholesterol. Reduced circulating omentin levels could play a role in the etiopathogenesis of obesity and T2DM. The increase in circulating omentin levels and the decrease in omentin mRNA expression in SCAT of obese women after LSG might contribute to surgery-induced metabolic improvements and sustained reduction of body weight.
- MeSH
- Cytokines biosynthesis blood MeSH
- Diabetes Mellitus, Type 2 blood epidemiology therapy MeSH
- Adult MeSH
- Gastrectomy methods MeSH
- GPI-Linked Proteins biosynthesis blood MeSH
- Caloric Restriction methods MeSH
- Laparoscopy methods MeSH
- Lectins biosynthesis blood MeSH
- Middle Aged MeSH
- Humans MeSH
- RNA, Messenger biosynthesis MeSH
- Obesity, Morbid blood epidemiology therapy MeSH
- Follow-Up Studies MeSH
- Subcutaneous Fat metabolism MeSH
- Motor Activity physiology MeSH
- Gene Expression Regulation MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
