BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive deterioration of upper and lower motor neurons. A definitive diagnostic test or biomarker for ALS is currently unavailable, leading to a diagnostic delay following the onset of initial symptoms. Our study focused on cerebrospinal fluid (CSF) concentrations of clusterin, tau protein, phosphorylated tau protein, and beta-amyloid1-42 in ALS patients and a control group. METHODS: Our study involved 54 ALS patients and 58 control subjects. Among the ALS patients, 14 presented with bulbar-onset ALS, and 40 with limb-onset ALS. We quantified biomarker levels using enzyme-linked immunosorbent assay (ELISA) and compared the results using the Mann-Whitney U-test. RESULTS: Significant elevations in neurodegenerative markers, including tau protein (p < 0.0001), phosphorylated tau protein (p < 0.0001), and clusterin (p = 0.038), were observed in ALS patients compared to controls. Elevated levels of tau protein and phosphorylated tau protein were also noted in both bulbar and limb-onset ALS patients. However, no significant difference was observed for beta-amyloid1-42. ROC analysis identified tau protein (AUC = 0.767) and p-tau protein (AUC = 0.719) as statistically significant predictors for ALS. CONCLUSION: Our study demonstrates that neurodegenerative marker levels indicate an ongoing neurodegenerative process in ALS. Nonetheless, the progression of ALS cannot be predicted solely based on these markers. The discovery of a specific biomarker could potentially complement existing diagnostic criteria for ALS.
- MeSH
- amyotrofická laterální skleróza * diagnóza MeSH
- biologické markery MeSH
- klusterin MeSH
- lidé MeSH
- opožděná diagnóza MeSH
- proteiny tau MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
This mini-review aims to introduce the association between Secretory clusterin/apolipoprotein J (sCLU) and diverse musculoskeletal diseases. A comprehensive review of the literature was performed to identify basic science and clinical studies, which implied the therapeutic and prognostic role of sCLU in diverse musculoskeletal diseases. sCLU is a multifunctional glycoprotein that is ubiquitously expressed in various tissues and is implicated in many pathophysiological processes. Dysregulated expression of sCLU had been reported to be assocaited with proliferative or apoptotic molecular processes and inflammatory responses, which participated in many pathophysiological processes such as degenerative musculoskeletal diseases including ischemic osteonecrosis, osteoarthritis (OA) and degenerative cervical myelopathy (spinal cord injury), neoplastic musculoskeletal diseases, inflammatory and autoimmune musculoskeletal diseases including Rheumatoid arthritis (RA), joint damage induced by Brucella abortus, Sjogren's syndrome, idiopathic inflammatory myopathies, muscle glucose metabolism, insulin sensitivity and traumatic musculoskeletal diseases. Recent findings of sCLU in these musculoskeletal diseases provides insights on the therapeutic and prognostic role of sCLU in these musculoskeletal diseases. sCLU may serve as a promising therapeutic target for ischemic osteonecrosis, OA and spinal cord injury as well as a potential prognostic biomarker for OA and RA. Moreover, sCLU could act as a prognostic biomarker for osteosarcoma (OS) and a promising therapeutic target for OS resistance. Although many studies support the potential therapeutic and prognostic role of sCLU in some inflammatory and autoimmune-mediated musculoskeletal diseases, more future researches are needed to explore the molecular pathogenic mechanism mediated by sCLU implied in these musculoskeletal diseases.
Clusterin (CLU; also known as apolipoprotein J, ApoJ) is a protein of inconstant structure known to be involved in diverse processes inside and outside of brain cells. CLU can act as a protein chaperon or protein solubilizer, lipid transporter as well as redox sensor and be anti- or proapoptotic, depending on context. Primary structure of CLU is encoded by CLU gene which contains single nucleotide polymorphisms (SNP's) associated with the risk of late-onset Alzheimer's disease (LOAD). Studying a sample of Czech population and using the case-control association approach we identified C allele of the SNP rs11136000 as conferring a reduced risk of LOAD, more so in females than in males. Additionally, data from two smaller subsets of the population sample suggested a possible association of rs11136000 with diabetes mellitus. In a parallel study, we found no association between rs11136000 and mild cognitive impairment (MCI). Our findings on rs11136000 and LOAD contradict those of some previous studies done elsewhere. We discuss the multiple roles of CLU in a broad range of molecular mechanisms that may contribute to the variability of genetic studies of CLU in various ethnic groups. The above discordance notwithstanding, our conclusions support the association of rs1113600 with the risk of LOAD.
- MeSH
- Alzheimerova nemoc etiologie genetika MeSH
- genetická predispozice k nemoci MeSH
- jednonukleotidový polymorfismus MeSH
- klusterin genetika MeSH
- kognitivní dysfunkce etiologie genetika MeSH
- lidé MeSH
- rizikové faktory MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- senioři nad 80 let MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Česká republika MeSH
OBJECTIVES: The aim of this cross-sectional study was to explore the circulating and skeletal muscle expression of clusterin (CLU) in inflammatory myopathies (IIM) and its potential implication in pathogenetic mechanisms of the disease. METHODS: A total of 85 IIM patients and 86 healthy controls (HC) were recruited. In addition, 20 IIM patients and 21 HC underwent a muscle biopsy. Circulating CLU was measured by ELISA. Serum cytokine profile of patients and HC was assessed by Cytokine 27-plex Assay. Immunohistochemical localisation of CLU was assessed in 10 IIM and 4 control muscle tissue specimens. The expression of CLU and myositis related cytokines in muscle was determined by qPCR. RESULTS: Serum levels of CLU were significantly increased in IIM patients compared to controls (86.2 (71.6-99.0) vs. 59.6 (52.6-68.4) μg/mL, p<0.0001) and positively correlated with myositis disease activity assessment (MYOACT) (r=0.337, p=0.008), myositis intention-to-treat activity index (MITAX) (r=0.357, p=0.004) and global disease assessment evaluated by physician (r=0.309, p=0.015). Moreover, serum CLU correlated with cytokines and chemokines involved in IIM and their combined effect on disease activity was revealed by multivariate redundancy analysis. In muscle tissue, CLU mRNA was increased in IIM patients compared to controls (p=0.032) and CLU accumulated in the cytoplasm of regenerating myofibres. CONCLUSIONS: We suggest that the up-regulation of clusterin in circulation and skeletal muscle of IIM patients may be an inflammation and atrophy induced response of the organism intended to limit the environment, favouring further muscle damage.
- MeSH
- cytokiny MeSH
- klusterin * genetika MeSH
- kosterní svaly MeSH
- lidé MeSH
- myozitida * MeSH
- průřezové studie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Clusterin (CLU) is a molecular chaperone that participates in a variety of biological processes. Recent studies indicate its possible involvement in the development of bone erosions and autoimmunity. The aim of this study was to investigate its serum concentrations in patients with early rheumatoid arthritis (RA) and to explore their potential relationship with disease activity and treatment response. Serum levels of CLU were measured in 52 patients before and 3 months after the initiation of treatment and in 52 healthy individuals. CLU levels at baseline were significantly increased in patients with early RA compared with healthy subjects (p < 0.0001). After 3 months of treatment, the levels of CLU decreased and reached concentrations comparable to those in controls. Even though there was no relationship between CLU levels and disease activity at baseline, CLU levels positively correlated with disease activity at months 3, 6 and 12 after treatment initiation. Using ROC analysis, lower CLU baseline levels predicted achieving the therapeutic target of low disease activity and remission at months 3, 6 and 12. In summary, we found increased serum concentrations of clusterin in treatment-naïve patients with early rheumatoid arthritis, and we suggest clusterin as a predictive biomarker of disease activity and treatment response.
- MeSH
- biologické markery krev MeSH
- dospělí MeSH
- klusterin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- revmatoidní artritida krev terapie MeSH
- senioři MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- klinické zkoušky MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
Apolipoprotein J (clusterin) is a component of high-density lipoproteins, the high level of which is reversely correlated with the risk of coronary heart disease. In addition, it exerts anti-inflammatory and anti-apoptotic effects on endothelial cells and inhibits smooth muscle cell migration and proliferation, indicating that it may play a protective role in cardiovascular disease. However, the exact mechanisms by which this occurs remain unclear. This study aimed to clarify these underlying protective mechanisms by researching the inhibitory effects of apolipoprotein J via the NOD-like receptor protein 3 pathway on the inflammation induced by cholesterol crystals in THP‐1 macrophages. In culture, THP-1 macrophages were infected with adenoviral vectors containing apolipoprotein J genes and subsequently treated with cholesterol crystals. The inflammatory cytokines interleukin‐1β, interleukin 18 and tumour necrosis factor α were quantitatively measured with ELISA kits. NOD-like receptor protein 3, cysteinyl aspartate specific proteinase 1 and interleukin 1β were evaluated by Western blot and PCR analysis. As a result, apolipoprotein J expression was found to remarkably decrease the levels of inflammatory cytokines, including tumour necrosis factor α, interleukin 18 and interleukin 1β, secreted by THP‐1 macrophages. It was also found capable of inhibiting the levels of NOD-like receptor protein 3, cysteinyl aspartate-specific proteinase 1 and interleukin 1β both at the protein and mRNA levels. In the current study, we revealed that over-expression of apolipoprotein J attenuated the inflammation induced by cholesterol crystals through inhibition of the NOD-like receptor protein 3 inflammasome pathway.
- MeSH
- cholesterol metabolismus MeSH
- cytokiny metabolismus MeSH
- endoteliální buňky metabolismus patologie MeSH
- inflamasomy * metabolismus farmakologie MeSH
- interleukin-18 metabolismus MeSH
- interleukin-1beta metabolismus MeSH
- klusterin metabolismus farmakologie MeSH
- kyselina aspartová metabolismus farmakologie MeSH
- lidé MeSH
- makrofágy metabolismus MeSH
- proteasy metabolismus farmakologie MeSH
- protein NLRP3 * metabolismus MeSH
- TNF-alfa metabolismus MeSH
- zánět patologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Psoriasis is a pathological condition characterized by immune system dysfunction and inflammation. Patients with psoriasis are more likely to develop a wide range of disorders associated with inflammation. Serum levels of various substances and their combinations have been associated with the presence of the disease (psoriasis) and have shown the potential to reflect its activity. The aim of the present study is to contribute to the elucidation of pathophysiological links between psoriasis, its pro-inflammatory comorbidity metabolic syndrome (MetS), and the expression of clusterin and elafin, which are reflected in the pathophysiological "portfolio" of both diseases. MATERIAL AND METHODS: Clinical examinations (PASI score), ELISA (clusterin, elafin), and biochemical analyses (parameters of MetS) were performed. RESULTS: We found that patients with psoriasis were more often afflicted by MetS, compared to the healthy controls. Clusterin and elafin levels were higher in the patients than in the controls but did not correlate to the severity of psoriasis. CONCLUSION: Our data suggest that patients with psoriasis are more susceptible to developing other systemic inflammatory diseases, such as MetS. The levels of clusterin and elafin, which are tightly linked to inflammation, were significantly increased in the patients, compared to the controls, but the presence of MetS in patients did not further increase these levels.
- MeSH
- dospělí MeSH
- elafin genetika MeSH
- index tělesné hmotnosti MeSH
- klusterin genetika MeSH
- komorbidita MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolický syndrom komplikace genetika metabolismus patologie MeSH
- psoriáza komplikace genetika metabolismus patologie MeSH
- regulace genové exprese genetika MeSH
- studie případů a kontrol MeSH
- stupeň závažnosti nemoci MeSH
- zánět genetika metabolismus patologie MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: The aims of this study were to analyse the serum concentrations of clusterin (CLU) in patients with hand osteoarthritis (OA) and in healthy controls, to compare CLU levels between patients with erosive and non-erosive disease, and to examine the association of CLU levels with clinical and laboratory parameters. METHODS: A total of 135 patients with hand OA (81 with erosive and 54 with non-erosive disease) and 53 healthy individuals were included in this study. All patients underwent clinical and hand joint ultrasound examination. The Australian/Canadian (AUSCAN) hand osteoarthritis index, algofunctional index and a visual analogue scale (VAS) for the measurement of pain were assessed. Serum levels of CLU were measured by an enzyme-linked immunosorbent assay (ELISA). RESULTS: Serum levels of CLU were significantly lower in patients with hand OA than in control subjects (p < 0.0001). In addition, patients with erosive hand OA had significantly lower CLU levels than those with non-erosive disease (p = 0.044). Negative correlations between CLU levels and pain as assessed by the AUSCAN score and the VAS were found in patients with erosive hand OA (r = - 0.275; p = 0.013 and r = - 0.220; p = 0.049, respectively). CONCLUSION: The present study demonstrates that lower concentrations of CLU are found in hand OA patients than in healthy individuals, especially in those with erosive disease, and that CLU concentrations have a negative association with hand pain.
- MeSH
- artralgie krev diagnostické zobrazování patofyziologie MeSH
- biologické markery krev MeSH
- down regulace MeSH
- ELISA MeSH
- klouby ruky diagnostické zobrazování metabolismus patofyziologie MeSH
- klusterin krev MeSH
- lidé středního věku MeSH
- lidé MeSH
- měření bolesti MeSH
- osteoartróza krev diagnostické zobrazování patofyziologie MeSH
- prediktivní hodnota testů MeSH
- průřezové studie MeSH
- senioři MeSH
- studie případů a kontrol MeSH
- ultrasonografie MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- srovnávací studie MeSH
OBJECTIVE: The aim of this study was to evaluate clusterin concentrations in amniotic fluid in pregnancies complicated by preterm prelabor rupture of membranes (PPROM) with respect to the presence of the microbial invasion of the amniotic cavity (MIAC), intra-amniotic inflammation (IAI) and microbial-associated IAI. METHODS: One hundred thirty-six women with singleton pregnancies complicated by PPROM were included in this study. Amniotic fluid samples were obtained by transabdominal amniocentesis. Amniotic fluid clusterin concentrations were assessed by enzyme-linked immunosorbent assay. MIAC was determined by a non-cultivation approach. IAI was defined as an amniotic fluid bedside interleukin-6 concentration ≥745 pg/mL. Microbial-associated IAI was characterized as the presence of both MIAC and IAI. RESULT: Women with MIAC, IAI and microbial-associated IAI had lower amniotic fluid clusterin concentrations than women without these complications (with MIAC: median 1314 ng/mL versus without MIAC: median 1633 ng/mL, p = 0.003; with IAI: median 1281 ng/mL versus without IAI: median 1575 ng/mL, p = 0.04; with microbial associated-IAI: median 1220 ng/mL versus without microbial-associated IAI: median 1575 pg/mL; p = 0.008). A week negative correlation between amniotic fluid clusterin concentrations and gestational age at sampling was revealed (rho= -0.30; p = 0.0005). CONCLUSIONS: The presence of MIAC, IAI and microbial-associated IAI was characterized by lower amniotic fluid clusterin concentrations in pregnancies complicated by PPROM.
- MeSH
- chorioamnionitida metabolismus mikrobiologie MeSH
- dospělí MeSH
- gestační stáří MeSH
- klusterin metabolismus MeSH
- lidé MeSH
- mladý dospělý MeSH
- plodová voda metabolismus MeSH
- předčasný odtok plodové vody metabolismus MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Alzheimer's disease (AD) is the most common type of dementia, with a prevalence that is rising every year. AD is associated with type 2 diabetes mellitus (T2DM) and insulin resistance, and is therefore sometimes called "type 3 diabetes mellitus". The aim of this study was to examine whether the variants of some candidate genes involved in the development of AD, namely BIN1 (rs744373), CLU (rs11136000), CR1 (rs3818361), and PICALM (rs3851179), are related to several disorders of glucose metabolism-gestational diabetes (GDM), T2DM and impaired glucose tolerance (IGT). Our study included 550 women with former GDM and 717 control women, 392 patients with T2DM and 180 non-diabetic controls, and 117 patients with IGT and 630 controls with normal glucose tolerance. Genotyping analysis was performed using specially-designed TaqMan assays. No significant associations of the genetic variants rs744373 in BIN1, rs11136000 in CLU, or rs3818361 in CR1 were found with GDM, T2DM or IGT, but rs3851179 in PICALM was associated with an increased risk of GDM. The frequency of the AD risk-associated C allele was significantly higher in the GDM group compared to controls: OR 1.21; 95% CI (1.03-1.44). This finding was not apparent in T2DM and IGT; conversely, the C allele of the PICALM SNP was protective for IGT: OR 0.67; 95% CI (0.51-0.89). This study demonstrates an association between PICALM rs3851179 and GDM as well as IGT. However, elucidation of the possible role of this gene in the pathogenesis of GDM requires further independent studies.
- MeSH
- adaptorové proteiny signální transdukční krev genetika MeSH
- alely MeSH
- Alzheimerova nemoc komplikace genetika MeSH
- běloši genetika MeSH
- diabetes mellitus 2. typu genetika MeSH
- dospělí MeSH
- frekvence genu MeSH
- genetická predispozice k nemoci MeSH
- genetická variace MeSH
- genetické asociační studie metody MeSH
- gestační diabetes genetika metabolismus MeSH
- jaderné proteiny krev genetika MeSH
- jednonukleotidový polymorfismus genetika MeSH
- klusterin krev genetika MeSH
- lidé středního věku MeSH
- lidé MeSH
- monomerní proteiny vytvářející klathrin krev genetika MeSH
- nádorové supresorové proteiny krev genetika MeSH
- odds ratio MeSH
- porucha glukózové tolerance genetika metabolismus MeSH
- receptory komplementu 3b krev genetika MeSH
- rizikové faktory MeSH
- senioři MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- senioři MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
