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INTRODUCTION: We investigated blood DNA methylation patterns associated with 15 well‐established cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) pathophysiology, neuroinflammation, and neurodegeneration. METHODS: We assessed DNA methylation in 885 blood samples from the European Medical Information Framework for Alzheimer's Disease (EMIF‐AD) study using the EPIC array. RESULTS: We identified Bonferroni‐significant differential methylation associated with CSF YKL‐40 (five loci) and neurofilament light chain (NfL; seven loci) levels, with two of the loci associated with CSF YKL‐40 levels correlating with plasma YKL‐40 levels. A co‐localization analysis showed shared genetic variants underlying YKL‐40 DNA methylation and CSF protein levels, with evidence that DNA methylation mediates the association between genotype and protein levels. Weighted gene correlation network analysis identified two modules of co‐methylated loci correlated with several amyloid measures and enriched in pathways associated with lipoproteins and development. DISCUSSION: We conducted the most comprehensive epigenome‐wide association study (EWAS) of AD‐relevant CSF biomarkers to date. Future work should explore the relationship between YKL‐40 genotype, DNA methylation, and protein levels in the brain. Highlights: Blood DNA methylation was assessed in the EMIF‐AD MBD study.Epigenome‐wide association studies (EWASs) were performed for 15 Alzheimer's disease (AD)–relevant cerebrospinal fluid (CSF) biomarker measures.Five Bonferroni‐significant loci were associated with YKL‐40 levels and seven with neurofilament light chain (NfL).DNA methylation in YKL‐40 co‐localized with previously reported genetic variation.DNA methylation potentially mediates the effect of single‐nucleotide polymorphisms (SNPs) in YKL‐40 on CSF protein levels. [ABSTRACT FROM AUTHOR]

Objective: To investigate the relationship between serum programmed cell death molecule 5 (PDCD5), CXC chemokine ligand 8 (CXCL8), human cartilage glycoprotein 39 (YKL-40) and disease condition and clinical outcome in influenza A virus pneumonia. Methods: 165 patients with influenza A virus pneumonia who were admitted to Jilin Fifth People's Hospital from March 2021 to May 2023 were selected as observation group, and 50 healthy subjects who underwent physical examination during the same period were selected as control group. The PDCD5, CXCL8 and YKL-40 of patients and subjects were detected, and the differences of each index level between groups were compared, and the levels of each index of patients with influenza A virus pneumonia in different conditions were compared. The clinical outcomes of patients were statistically analyzed, and patients were divided into death group and survival group, the levels of PDCD5, CXCL8 and YKL-40 were compared between two groups, the risk factors and protective factors of death in patients with influenza A virus pneumonia were analyzed by univariate and multivariate Logistic analysis. Results: The levels of PDCD5, CXCL8 and YKL-40 in observation group were higher than those in control group (P<0.05). The levels of PDCD5, CXCL8 and YKL-40 in severe group were higher than those in mild group (P<0.05). After follow-up observation, 39 patients died, and the levels of PDCD5, CXCL8 and YKL-40 in death group were higher than those in survival group (P<0.05). Univariate analysis showed that, there was no significant difference in gender, body mass index (BMI), smoking history, drinking history, hypertension history, diabetes history, hyperlipidemia history and course of disease between two groups (P>0.05). The age, PDCD5, CXCL8 and YKL-40 in death group were higher than those in survival group, and the forced vital capacity(FVC), peak expiratory flow (PEF) and maximum middle expiratory flow rate (MMEF) were lower than those in survival group (P<0.05). Logistic multivariate analysis showed that, age, PDCD5, CXCL8 and YKL-40 were independent risk factors for the prognosis of patients with influenza A virus pneumonia, and FVC, PEF and MMEF were protective factors for the prognosis of patients. Conclusion: Serum PDCD5, CXCL8 and YKL-40 are involve in the occurrence and progression of influenza A virus pneumonia, and are closely relate to the clinical outcome of patients, together with age, they constitute a risk factor for the prognosis of patients, while FVC, PEF and MMEF are protective factors for the prognosis of patients [ABSTRACT FROM AUTHOR]

Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne viral disease. YKL-40 (also known as chitinase-3-like-1 protein) is an acute phase protein released by various immune cells. The purpose of this study was to investigate the relationship between YKL-40 level and the clinical course and prognosis of CCHF. The study included 78 patients who were admitted to our hospital between April 15 and 30 August 2022 and had a positive polymerase chain reaction test result for CCHF. The patients were divided into two groups, severe and non-severe. In addition, a control group consisting of 22 healthy people was established. Mean serum YKL-40 levels were significantly higher in patients than controls (106.8 ng/mL ± 91.2 and 47.1 ng/mL ± 35.3, respectively; p < 0.001). However, mean YKL-40 levels were also significantly higher in patients with severe CCHF compared to non-severe cases (173.3 ± 112.3 and 67.5 ± 41.7, respectively; p < 0.001). A comparison of the 10 exitus patients and the 68 survivors revealed significantly higher YKL-40 levels in the exitus group (mean: 214.0 ± 139.0 and 92.8 ± 73.6, respectively; p = 0.001). A receiver operating characteristic analysis for YKL-40 levels to distinguish between severe and non-severe patients found an area under the curve of 0.925. YKL-40 levels were measured with a sensitivity of 97% and a specificity of 84% with a cutoff value of 90.7 ng/mL. YKL-40 levels measured at the time of hospital presentation in patients with CCHF can be used as a biomarker for clinical course and prognosis. [ABSTRACT FROM AUTHOR]

Abstract A growing body of evidence indicates there is an increasing incidence of cognitive dysfunction in patients after coronavirus disease 2019 (COVID-19) infection. However, still lack diagnostic tools, which allow us to predict prognosis in such cases and improve the stratification of the disease. This study aims to evaluate the usefulness of the biomarkers that could allow to predict the severity and progression of COVID-19 in patients with post-COVID syndrome and cognitive problems. Data regarding clinical history, pre-existing conditions, chest CT scan, and therapy (remdesivir, steroids) were acquired. A total of 44 patients with hospitalized COVID-19, and healthy controls were enrolled in the investigation, and serum blood was obtained. After 6 months of observations, patients with COVID-19 were divided into two groups: first - without post-COVID syndrome and memory complaints, and second - with post-COVID and cognitive problems. Measurements of YKL-40 and MR-pro-ADM were taken in the serum with enzyme immunoassay kits at the time of admission (visit 1) and 6 months after discharge from the hospital (visit 2). Significantly higher concentrations of YKL-40 were found in patients with COVID-19 as compared to healthy individuals (p = 0.016). Moreover, YKL-40 ratio allowed to differentiate patients with and without post-COVID syndrome (median: 0.94 vs. 1.55, p = 0.004). Additionally, COVID-19 patients with dyspnea presented significantly elevated levels of MR-pro-ADM as compared to the group of COVID-19 survivors without dyspnea (p = 0.015). In the group of patients without post-COVID syndrome, the concentrations of YKL-40 and MR-pro-ADM decreased after treatment as compared to levels before therapy (77 vs. 36 ng/ml and 607 vs. 456 pmol/L). However, in patients with post-COVID syndrome and cognitive problems, the levels of both markers did not alter 6 months after hospital discharge in comparison to basal levels. Furthermore, after dexamethasone treatment the YKL-40 concentrations declined significantly (p = 0.003) in patients with COVID-19. This study demonstrated the predictive usefulness of YKL-40 as an indicator of successful treatment in patients with COVID-19 infection allowing risk stratification of hospitalized patients. It seems that indicators of neuroinflammation might have the potential to track development of cognitive complaints, however, it requires further investigations.

Objective: To explore the relationship between YKL-40 level, telomere length, and different subtypes of insomnia disorder. Methods: A total of 145 individuals suffering from insomnia were enrolled and divided into four groups according to the insomniac subtypes: difficulty initiating sleep, early morning awakening, difficulty maintaining sleep, and mixed symptoms. Eighty healthy controls were also collected at the same time. Peripheral leukocyte genomic DNA was extracted, relative telomere lengths were measured using the real-time quantitative polymerase chain reaction method, and YKL-40 levels were determined using enzyme-linked immunoassay. Logistic regression modeling was used to analyze the correlation between different insomnia subtypes, YKL-40 level, and telomere length. Results: People with telomere lengths in the lowest tertile were more likely to have trouble falling asleep (odds ratio (OR) 2.13, 95% confidence interval (CI) 1.22-3.63; p = 0.03) and had a higher frequency of mixed symptoms (OR 1.49, 95% CI 1.30-2.81; p = 0.04). People in the highest tertile of YKL-40 level had an increased chance of waking up early (OR 2.98, 95% CI 1.54-5.33; p = 0.01) and more mixed symptoms (OR 1.47, 95% CI 1.22-2.79; p = 0.02). Furthermore, using receiver operating characteristic curve analysis, the area under the curve of YKL-40 level and telomere length was 0.806 and 0.746, respectively. Conclusions: Telomere length in patients with difficulty initiating sleep and mixed symptoms was significantly shortened and the level of YKL-40 in people who have early morning awakening and mixed symptoms was significantly increased. Our findings provide the first evidence that leukocyte telomere length and YKL-40 level are individually linked to mixed symptoms. [ABSTRACT FROM AUTHOR]

Abstract Background Recent trials of anti-amyloid-β (Aβ) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits and their use comes with a significant risk of serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD and several AD risk genes related to immune response, including but not restricted to CD33 and TREM2. Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers and their role in characterizing the pathophysiology of AD. Main body Neuroinflammation is recognized to be a crucial and contributing component of AD pathogenesis. The fact that neuroinflammation is most likely present from earliest pre-stages of AD and co-occurs with the deposition of Aβ reinforces the need to precisely define the sequence and nature of neuroinflammatory events. Numerous clinical trials involving anti-inflammatory drugs previously yielded unfavorable outcomes in early and mild-to-moderate AD. Although the reasons behind these failures remain unclear, these may include the time and the target selected for intervention. Indeed, in our review, we observed a stage-dependent neuroinflammatory process in the AD brain. While the initial activation of glial cells counteracts early brain Aβ deposition, the downregulation in the functional state of microglia occurs at more advanced disease stages. To address this issue, personalized neuroinflammatory modulation therapy is required. The emergence of reliable blood-based neuroinflammatory biomarkers, particularly glial fibrillary acidic protein, a marker of reactive astrocytes, may facilitate the classification of AD patients based on the ATI(N) biomarker framework. This expands upon the traditional classification of Aβ (“A”), tau (“T”), and neurodegeneration (“N”), by incorporating a novel inflammatory component (“I”). Conclusions The present review outlines the current knowledge on potential neuroinflammatory biomarkers and, importantly, emphasizes the role of longitudinal analyses, which are needed to accurately monitor the dynamics of cerebral inflammation. Such a precise information on time and place will be required before anti-inflammatory therapeutic interventions can be considered for clinical evaluation. We propose that an effective anti-neuroinflammatory therapy should specifically target microglia and astrocytes, while considering the individual ATI(N) status of patients.

Background: The inflammatory factor YKL-40 is associated with various inflammatory diseases and is key to remodeling inflammatory cells and tissues. YKL-40 (Chi3l1) promotes the activation of tissue factor (TF), leading to intrahepatic vascular coagulation (IAOC) and liver injury. TF is a key promoter of the exogenous coagulation cascade and is also involved in several signaling involving cell proliferation, apoptosis, charring,migration and inflammatory diseases pathways. However, the effect of YKL-40-induced TF- PAR1 pathway on the expression of downstream chemokines remains unknown. Methods: We established a liver injury model using Concanavalin A (ConA) in C57 BL/6 mice. By adopting various experimental techniques, the effect of YKL-40 induced TF-PAR1 pathway on the expression of downstream chemokine ligand 2 (CCL2) and IP-10 was verified. Results: We found that overexpression of YKL-40 increased the expression of TF, protease-activated receptor 1 (PAR1), CCL2 and IP-10 inmice and exacerbated the severity of liver injury. However, blocking the expression of TF significantly reversed the extent of liver injury. Conclusion: We found that YKL-40 promotes the expression of downstream chemokines ligand 2 (CCL2) and IP-10 by activating the TF-PAR1 pathway, leading to increased recruitment of inflammatory cells and exacerbating the progression of liver injury. This provides a new approach for the clinical treatment of drug- induced liver injury. [ABSTRACT FROM AUTHOR]

• YKL-40 levels were associated with the risk of stroke-specific mortality. • Drinking status modified the effect of YKL-40 levels on stroke-specific mortality. • Elevated amount of alcohol consumption amplified the impact of YKL-40 on mortality. Our study aimed to evaluate the association between plasma human cartilage glycoprotein-39 (YKL-40) and stroke-specific mortality at two years in acute ischemic stroke patients according to the drinking status and amount of alcohol consumption. We further investigated the effect of the interaction between these conditions and YKL-40 levels on the outcome. We measured plasma YKL-40 levels in 3267 participants from the China Antihypertensive Trial in Acute Ischemic Stroke. Outcome data on stroke-specific mortality were collected at two years after stroke onset. During the two years of follow-up, 208 (6.4 %) patients, including 44 drinkers and 164 nondrinkers, died of stroke-specific causes. The patients in the highest quartile of YKL-40 had a 3.52-fold (95 % CI: 1.15–10.76, P for trend = 0.006) risk of stroke-specific mortality compared with those in the lowest quartile among drinkers. However, no significant association between YKL-40 and the outcome was observed among nondrinkers (HR: 1.18, 95 % CI: 0.75–1.86, P for trend = 0.08). Alcohol drinking modified the effect of YKL-40 on the outcome (P for interaction = 0.04). Subgroup analyses revealed that each 1-unit increase in log-transformed YKL-40 was associated with a 72 % greater risk of stroke-specific mortality for light drinkers. This association was amplified with a 226 % increased risk of the outcome among heavy drinkers. Elevated YKL-40 levels were associated with an increased risk of stroke-specific mortality at two years among drinkers with ischemic stroke. Drinking status substantially modified the effect of plasma YKL-40 levels on the outcome. This effect was amplified with the increased amount of alcohol consumption. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01840072. [ABSTRACT FROM AUTHOR]

YKL-40 is a glycoprotein synthesized by several cell types, including macrophages, neutrophils, and endothelial cells. It plays a role in several biological processes, such as tissue remodeling, inflammation, and cell proliferation. Research findings have shown that levels of YKL-40 tend to be higher in individuals diagnosed with cardiovascular diseases (CVDs), including atherosclerosis. Elevated concentrations of YKL-40 have been associated with detrimental CV outcomes. In general, while the precise function of YKL-40 in CVDs is still under investigation, it is evident that this glycoprotein has significant potential as a biomarker for CVDs. Furthermore, CVD treatment has the potential to specifically target the protein YKL-40. [ABSTRACT FROM AUTHOR]

Background: Interstitial lung disease (ILD) is a common pulmonary manifestation of rheumatoid arthritis (RA) and is associated with a poor prognosis. However, the role of blood biomarkers in RA-associated interstitial lung disease (RA-ILD) is ill-defined. We aim to evaluate the role of YKL-40 and Krebs von den Lungen-6 (KL-6) in the diagnosis and severity evaluation of RA-ILD. Methods: 45 RA-non-ILD patients and 38 RA-ILD patients were included. The clinical data and the levels of YKL-40 and KL-6 were measured and collected for all patients. The risk factors for RA-ILD were analyzed and their correlation with relevant indicators and predictive value for RA-ILD was explored. Results: The levels of YKL-40 and KL-6 in RA-ILD patients were higher than RA-non-ILD patients (p <.001). Both YKL-40 and KL-6 were correlated with the incidence of RA-ILD. The predictive power of combined KL-6 and YKL-40 for the presence of ILD was 0.789, with a sensitivity and specificity at 73.7% and 73.3%, respectively. In RA-ILD patients, both YKL-40 and KL-6 were positively correlated with the Scleroderma Lung Study (SLS) I score and negatively correlated with pulmonary function. Conclusions: KL-6 and YKL-40 might be a useful biomarker in the diagnosis and severity evaluation of RA-ILD. [ABSTRACT FROM AUTHOR]

Autism spectrum disorder (ASD) is associated with multiple physiological abnormalities. Current laboratory and clinical evidence most commonly report mitochondrial dysfunction, oxidative stress, and immunological imbalance in almost every cell type of the body. The present work aims to evaluate oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and inflammation-related molecules such as Cyclooxygenase-2 (COX-2), chitinase 3-like protein 1 (YKL-40), Interleukin-1 beta (IL-1β), Interleukin-9 (IL-9) in ASD children with and without regression compared to healthy controls. Children with ASD (n = 56) and typically developing children (TDC, n = 12) aged 1.11 to 11 years were studied. Mitochondrial activity was examined in peripheral blood mononuclear cells (PBMCs) isolated from children with ASD and from the control group, using a metabolic analyzer. Gene and protein levels of IL-1β, IL-9, COX-2, and YKL-40 were investigated in parallel. Our results showed that PBMCs of the ASD subgroup of regressed patients (ASD R(+), n = 21) had a specific pattern of mitochondrial activity with significantly increased maximal respiration, respiratory spare capacity, and proton leak compared to the non-regressed group (ASD R(-), n = 35) and TDC. Furthermore, we found an imbalance in the studied proinflammatory molecules and increased levels in ASD R(-) proving the involvement of inflammatory changes. The results of this study provide new evidence for specific bioenergetic profiles of immune cells and elevated inflammation-related molecules in ASD. For the first time, data on a unique metabolic profile in ASD R(+) and its comparison with a random group of children of similar age and sex are provided. Our data show that mitochondrial dysfunction is more significant in ASD R(+), while in ASD R(-) inflammation is more pronounced. Probably, in the group without regression, immune mechanisms (immune dysregulation, leading to inflammation) begin initially, and at a later stage mitochondrial activity is also affected under exogenous factors. On the other hand, in the regressed group, the initial damage is in the mitochondria, and perhaps at a later stage immune dysfunction is involved. [ABSTRACT FROM AUTHOR]

Background: Vascular calcification (VC) is highly prevalent and predicts cardiovascular mortality in dialysis patients. The mechanisms are still unclear. Inflammation is a well-known inducer of VC. YKL-40 has been suggested as a novel biomarker of inflammation and has been demonstrated to be associated with cardiovascular mortality in hemodialysis patients. This study aims to evaluate the relationship between serum YKL-40 and VC in hemodialysis (HD) patients. Methods: A total of 109 HD patients and 31 healthy controls were enrolled in the study from September 2014 to December 2014. We evaluated the abdominal aortic calcification (AAC) score by plain X-ray films of the abdomen and measured serum YKL-40 concentrations using enzyme-linked immunosorbent assay. We also examined the relationship between YKL-40 levels and AAC scores in HD patients. Results: Serum YKL-40 levels in HD patients were significantly higher than those in healthy controls [199.8 (144.8, 288.7) vs. 71.9 (52.8, 89.3) ng/ml; P < 0.001]. There was a tendency that YKL-40 levels in diabetic hemodialysis patients were higher than those in nondiabetic patients [217.8 (155.3, 335.8) vs. 192.9 (135.9, 274.4) ng/ml; P = 0.093]. A significant positive correlation was found between serum YKL-40 level and AAC score in these patients (r = 0.410, P = 0.003). Multiple regression analysis showed that Ln(YKL-40) was independently associated with AAC score in HD patients (P = 0.044). Conclusion: This study showed high serum YKL-40 concentrations in chronic HD patients and that YKL-40 was independently associated with increased AAC in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Background: Recent trials of anti-amyloid-β (Aβ) monoclonal antibodies, including lecanemab and donanemab, in early Alzheimer disease (AD) showed that these drugs have limited clinical benefits and their use comes with a significant risk of serious adverse events. Thus, it seems crucial to explore complementary therapeutic approaches. Genome-wide association studies identified robust associations between AD and several AD risk genes related to immune response, including but not restricted to CD33 and TREM2. Here, we critically reviewed the current knowledge on candidate neuroinflammatory biomarkers and their role in characterizing the pathophysiology of AD. Main body: Neuroinflammation is recognized to be a crucial and contributing component of AD pathogenesis. The fact that neuroinflammation is most likely present from earliest pre-stages of AD and co-occurs with the deposition of Aβ reinforces the need to precisely define the sequence and nature of neuroinflammatory events. Numerous clinical trials involving anti-inflammatory drugs previously yielded unfavorable outcomes in early and mild-to-moderate AD. Although the reasons behind these failures remain unclear, these may include the time and the target selected for intervention. Indeed, in our review, we observed a stage-dependent neuroinflammatory process in the AD brain. While the initial activation of glial cells counteracts early brain Aβ deposition, the downregulation in the functional state of microglia occurs at more advanced disease stages. To address this issue, personalized neuroinflammatory modulation therapy is required. The emergence of reliable blood-based neuroinflammatory biomarkers, particularly glial fibrillary acidic protein, a marker of reactive astrocytes, may facilitate the classification of AD patients based on the ATI(N) biomarker framework. This expands upon the traditional classification of Aβ ("A"), tau ("T"), and neurodegeneration ("N"), by incorporating a novel inflammatory component ("I"). Conclusions: The present review outlines the current knowledge on potential neuroinflammatory biomarkers and, importantly, emphasizes the role of longitudinal analyses, which are needed to accurately monitor the dynamics of cerebral inflammation. Such a precise information on time and place will be required before anti-inflammatory therapeutic interventions can be considered for clinical evaluation. We propose that an effective anti-neuroinflammatory therapy should specifically target microglia and astrocytes, while considering the individual ATI(N) status of patients. [ABSTRACT FROM AUTHOR]

This study investigates the correlation between serum levels of YKL-40, LXRs, PPM1A, and TGF-β1 and airway remodeling and lung function in bronchial asthma patients. The study involved 80 bronchial asthma patients and 92 healthy individuals. Serum cytokines, airway remodeling, and lung function markers were compared across mild, moderate, and severe asthma cases using high-resolution CT, t-tests, ANOVA, and Pearson correlation analysis. Asthmatic patients exhibited higher levels of serum YKL-40, LXRα, LXRβ, TGF-β1, airway wall thickness (T)/outer diameter (D), and WA% of total cross-sectional area compared to controls. Conversely, their serum PPM1A, Peak Expiratory Flow (PEF), and Forced Expiratory Volume in 1 s (FEV1) were lower. Serum YKL-40 and TGF-β1 levels were positively correlated with T/D and WA%, and negatively correlated with PEF and FEV1. PPM1A levels were strongly associated with T/D, WA%, PEF, and FEV1. The severity of bronchial asthma is associated with increased serum levels of YKL-40, LXRα, LXRβ, and TGF-β1 and decreased PPM1A. The levels of YKL-40, PPM1A, and TGF-β1 have a significant correlation with airway remodeling and lung function. [ABSTRACT FROM AUTHOR]

Around 30–60% of patients with rheumatoid arthritis (RA) present treatment failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Chitinase-like proteins (CLPs) (YKL-40, YKL-39, SI-CLP) might play a role, as they are associated with the inflammatory process. This study aimed to evaluate CLP utility as a biomarker in the treatment failure of csDMARDs. A case–control study included 175 RA patients classified into two groups based on therapeutic response according to DAS28-ESR: responders (DAS28 < 3.2); non-responders (DAS28 ≥ 3.2). CLP serum levels were determined by ELISA. Multivariable logistic regression and receiver operating characteristic (ROC) curves were used to evaluate CLPs' utility as biomarkers of treatment failure. Non-responders presented higher levels of YKL-40, YKL-39, and SI-CLP compared with responders (all: p < 0.001). YKL-40 correlated positively with YKL-39 (rho = 0.39, p < 0.001) and SI-CLP (rho = 0.23, p = 0.011) and YKL-39 with SI-CLP (rho = 0.34, p < 0.001). The addition of CLPs to the regression models improves diagnostic accuracy (AUC 0.918) compared to models including only clinical classical variables (AUC 0.806) p < 0.001. Non-responders were positive for all CLPs in 35.86%. Conclusions: CLPs could be considered as a useful biomarker to assess treatment failure, due to their association with clinical variables and improvement to the performance of regression models. [ABSTRACT FROM AUTHOR]

Chitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma, and indicates that these molecules can open new perspectives on antiproliferative action and anticancer therapy. This study analyzes how different chitosan conformations, such as α-chitosan (CH) or β-oligochitosan (CO), with various degrees of deacetylation (DDA) and molar mass (MM), both in different concentrations and in CH–CO mixtures, influence the cellular processes of SK-MEL-28 melanocytes, to estimate the reactivity of these cells to the applied treatments. The in vitro evaluation was carried out, aiming at the cellular metabolism (MTT assay), cellular morphology, and chitinase-like glycoprotein YKL-40 expression. The in vitro effect of the CH–CO mixture application on melanocytes is obvious at low concentrations of α-chitosan/β-oligochitosan (1:2 ratio), with the cell's response supporting the hypothesis that β-oligo-chitosan amplifies the effect. This oligochitosan mixture, favored by the β conformation and its small size, penetrates faster into the cells, being more reactive when interacting with some cellular components. Morphological effects expressed by the loss of cell adhesion and the depletion of YKL-40 synthesis are significant responses of melanocytes. β-oligochitosan (1.5 kDa) induces an extension of cytophysiological effects and limits the cell viability compared to α-chitosan (400–900 kDa). Statistical analysis using multivariate techniques showed differences between the CH samples and CH–CO mixtures. [ABSTRACT FROM AUTHOR]

Background: The biological function of YKL-40 is not well determined in different inflammatory and autoimmune diseases; however, some data highlighted its possible connection with disease activity. Aim: We investigated the diagnostic utility of serum YKL-40 in patients with SLE and examined its correlation with disease activity. Additionally, we examined any differences in serum YKL-40 levels between juvenile and adult SLE patients. Methods: We included 78 female patients with SLE and 42 controls. The level of YKL-40 in serum was measured by ELISA. Results: The serum YKL-40 level in SLE patients was significantly higher compared to the control group (9 (3) ng/mL vs. 5.5 (0.1) ng/mL; p < 0.001). YKL-40 showed excellent diagnostic utility with an AUC of 1 (p < 0.001) and a cutoff point of 5.6, providing sensitivity and specificity of 100%. YKL-40 was higher in adolescents and those with a positive family history of SLE (p = 0.01 for both) and positively correlated with disease duration (r = 0.45, p < 0.001). YKL-40 level was significantly higher in patients with photosensitivity, fever, vasculitis, blood disorders, positive anti-dsDNA, and APL ab (p < 0.05 for all). Conversely, patients with skin manifestations had a significantly lower YKL-40 (p = 0.004). In juvenile SLE, the AUC was 0.65 and a p-value of 0.01, and at a cutoff value of (8.7) ng/mL, the sensitivity and specificity were 72% and 60%, respectively. Conclusion: YKL-40 in serum could be a promising biomarker in patients with SLE, especially in adolescent-onset cases. It is independently influenced by disease duration, anemia, thrombocytopenia, positive anti-dsDNA, and APL ab features. [ABSTRACT FROM AUTHOR]

Central nervous system infections continue to be a public health concern owing to the high mortality and the significant neurological sequelae among survivors. The diverse etiology with overlapping clinical and laboratory abnormalities makes the management of such patients challenging. Neuroinflammation plays an essential role in triggering oxidative stress and autophagy dysregulation. Impaired autophagy may lead to abnormal protein aggregation resulting in neurodegeneration. YKL-40 is a secreted glycoprotein, involved in several diseases accompanied by inflammation. The lysosome-associated membrane proteins (LAMPs) 1 and 2 exhibit diverse expression levels in a range of cell processes (including autophagy) and clinical conditions but the complete picture of their biological function is still unknown. This review highlights the role of YKL-40 and LAMPs in central nervous system infections. We suggest that these biomolecules might have a promising value as biomarkers or targets for therapy and could provide additional evidence for inflammatory activity in different neurological diseases.

Background: Neuroinflammation is a major cause of secondary brain injury in intracerebral hemorrhage (ICH). To date, the prognostic value of YKL-40 (chitinase-3-like-1 protein), a biomarker of neuroinflammation, in cerebral amyloid angiopathy-related intracerebral hemorrhage (CAA-ICH) remains undiscovered. Objective: To evaluate the relationships between serum YKL-40 and CAA-ICH recurrence. Methods: Clinical and imaging information of 68 first-onset probable CAA-ICH cases and 95 controls were collected at baseline. Serum YKL-40 was measured by Luminex assay. Cox proportional hazards model was used to analyze the associations between YKL-40 level and CAA-ICH recurrence. Results: Serum YKL-40 level was significantly higher in CAA-ICH cases than healthy controls (median [interquartile range, IQR], 46.1 [19.8, 93.4] versus 24.4 [13.9, 59.0] ng/mL, p = 0.004). Higher level of YKL-40 predicted increased risk of CAA-ICH recurrence adjusted for age, ICH volume and enlarged perivascular space score (ePVS) (above versus below 115.5 ng/ml, adjusted hazard ratios 4.721, 95% confidence intervals 1.829–12.189, p = 0.001) within a median follow-up period of 2.4 years. Adding YKL-40 to a model of only MRI imaging markers including ICH volume and ePVS score improved the discriminatory power (concordance index from 0.707 to 0.772, p = 0.001) and the reclassification power (net reclassification improvement 28.4%; integrated discrimination index 11.0%). Conclusions: Serum YKL-40 level might be a candidate prognostic biomarker for CAA-ICH recurrence. [ABSTRACT FROM AUTHOR]

YKL-40 is implicated in inflammation and tissue repair, but no reports have investigated its involvement in myositis in polymyositis (PM) and dermatomyositis (DM). Therefore, we aimed to investigate the relationship between YKL-40 and PM/DM. We retrospectively enrolled 35 patients diagnosed with PM/DM along with 26 healthy controls (HCs). Both PM and DM were diagnosed according to Bohan and Peter's criteria. Serum YKL-40 levels were measured, age-corrected to YKL-40 percentile values, and compared to HCs. Patients with myositis without interstitial lung disease were also enrolled and compared to HCs. Immunofluorescence staining was performed to identify YKL-40-positive inflammatory cells in muscle biopsy samples from two patients each with PM and DM. Age-corrected serum YKL-40 levels were significantly higher in patients with PM/DM compared to HCs with and without lung disease; however, these levels decreased significantly after treatment. Immunohistochemical analysis showed infiltration of YKL-40-positive inflammatory cells into the intramuscular sheath and perimuscular membrane. Immunofluorescence staining showed CD68 expression in YKL-40-positive inflammatory cells, suggesting that these cells were macrophages. To the best of our knowledge, this is the first study to demonstrate that YKL-40-positive macrophages are present in PM and DM, indicating that YKL-40 may be involved in PM/DM. [ABSTRACT FROM AUTHOR]

AbstractYKL-40 is implicated in inflammation and tissue repair, but no reports have investigated its involvement in myositis in polymyositis (PM) and dermatomyositis (DM). Therefore, we aimed to investigate the relationship between YKL-40 and PM/DM. We retrospectively enrolled 35 patients diagnosed with PM/DM along with 26 healthy controls (HCs). Both PM and DM were diagnosed according to Bohan and Peter’s criteria. Serum YKL-40 levels were measured, age-corrected to YKL-40 percentile values, and compared to HCs. Patients with myositis without interstitial lung disease were also enrolled and compared to HCs. Immunofluorescence staining was performed to identify YKL-40-positive inflammatory cells in muscle biopsy samples from two patients each with PM and DM. Age-corrected serum YKL-40 levels were significantly higher in patients with PM/DM compared to HCs with and without lung disease; however, these levels decreased significantly after treatment. Immunohistochemical analysis showed infiltration of YKL-40-positive inflammatory cells into the intramuscular sheath and perimuscular membrane. Immunofluorescence staining showed CD68 expression in YKL-40-positive inflammatory cells, suggesting that these cells were macrophages. To the best of our knowledge, this is the first study to demonstrate that YKL-40-positive macrophages are present in PM and DM, indicating that YKL-40 may be involved in PM/DM.

Abstract Glial cell-mediated neuroinflammation and neuronal attrition are highly correlated with cognitive impairment in Alzheimer’s disease. YKL-40 is a secreted astrocytic glycoprotein that serves as a diagnostic biomarker of Alzheimer’s disease. High levels of YKL-40 are associated with either advanced Alzheimer’s disease or the normal aging process. However, the functional role of YKL-40 in Alzheimer’s disease development has not been firmly established. In a 5xFAD mouse model of Alzheimer’s disease, we observed increased YKL-40 expression in the cerebrospinal fluid of 7-month-old mice and was correlated with activated astrocytes. In primary astrocytes, Aβ1-42 upregulated YKL-40 in a dose-dependent manner and was correlated with PI3-K signaling pathway activation. Furthermore, primary neurons treated with YKL-40 and/or Aβ1-42 resulted in significant synaptic degeneration, reduced dendritic complexity, and impaired electrical parameters. More importantly, astrocyte-specific knockout of YKL-40 over a period of 7 days in symptomatic 5xFAD mice could effectively reduce amyloid plaque deposition in multiple brain regions. This was also associated with attenuated glial activation, reduced neuronal attrition, and restored memory function. These biological phenotypes could be explained by enhanced uptake of Aβ1-42 peptides, increased rate of Aβ1-42 degradation and acidification of lysosomal compartment in YKL-40 knockout astrocytes. Our results provide new insights into the role of YKL-40 in Alzheimer’s disease pathogenesis and demonstrate the potential of targeting this soluble biomarker to alleviate cognitive defects in symptomatic Alzheimer’s disease patients.

Abstract Background The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients. Aims To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice. Methods We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p

Objective: To study the predictive value of three-dimensional energy Doppler ultrasound combined with serum human epididymal protein 4 (HE4), thymidine kinase 1 (TK1) and chitinase protein 40 (YKL-40) for endometrial cancer in postmenopausal bleeding patients. Methods: 150 postmenopausal bleeding patients who were admitted from October 2019 to October 2022 in the our hospital were selected. They were divided into endometrial carcinoma group (31 cases) and endometrial benign hyperplasia group (119 cases) according to the difference of pathological examination results. Three-dimensional energy Doppler ultrasound was performed in all patients, and serum HE4, TK1, YKL-40 levels were detected. The efficacy of three-dimensional energy Doppler ultrasound combined with serum HE4, TK1, and YKL-40 levels in predicting endometrial cancer in postmenopausal bleeding patients was analyzed by receiver operating characteristic curve (ROC). Results: Blood flow index (FI), angiogenesis index (VI), angiogenesis - blood flow index (VFI) and the composite index I constructed by these three parametersin endometrial cancer group were higher than those in endometrial benign hyperplasia group (all P<0.05). The serum levels of HE4, TK1 and YKL-40 in endometrial cancer group were higher than those in endometrial benign hyperplasia group (all P<0.05). Through ROC curve analysis found that the area under the curve(AUC), sensitivity, specificity and Yoden index of three-dimensional energy Doppler ultrasound combined with serum HE4, TK1 and YKL-40 levels in predicting endometrial cancer in postmenopausal bleeding patients were higher than those of the four independent predictions. Conclusion: Three-dimensional energy Doppler ultrasound combined with serum HE4, TK1 and YKL-40 levels were more effective in predicting endometrial cancer in postmenopausal bleeding patients. [ABSTRACT FROM AUTHOR]

Purpose: The number of studies conducted on the role of neuroinflammation in the etiopathogenesis of bipolar disorder has been increasing in recent years. The role of Galectin‐1, Galectin‐9, and YKL‐40, which are considered to play roles in neuroinflammation and the etiopathogenesis of bipolar disorder, and the relationship of these parameters with cognitive functions were investigated in the present study. Method: Serum Galectin‐1, Galectin‐9, and YKL‐40 levels were measured with the ELISA Method in 64 bipolar euthymic patients and 64 healthy controls. The Stroop and trail‐making tests were administered to assess cognitive functions in all participants. Results: Serum Galectin‐1, Galectin‐9, and YKL‐40 levels were statistically and significantly lower in the patient group when compared to the healthy control group. The scores of the Stroop test and trail‐making tests were statistically higher in the patient group than in the healthy control group. There was a weak and positive correlation between serum Galectin‐1, Galectin‐9, and YKL‐40 levels and cognitive performance in all participants. Discussion and conclusion: Statistically significant low levels of serum Galectin‐1, Galectin‐9, and YKL‐40 detected in the patient group suggest that these parameters have important roles in neuroinflammation. The statistically higher Stroop and trail‐making test scores of the patient group compared to the control group indicates that the cognitive performance of the patient group was weaker. Also, the positive correlation between Galectin‐1, Galectin‐9, and YKL‐40 levels and cognitive performance suggests that these molecules may have a neuroprotective role. We think that the present study will contribute to this field where there is very limited data in the literature. There are studies reporting that neuroinflammation plays a role in the etiopathogenesis of bipolar disorder. We examined molecules associated with inflammation that have not been studied before in bipolar disorder and their relationship with cognition. [ABSTRACT FROM AUTHOR]

YKL-40 or Chitinase-3-Like Protein 1 (CHI3L1) is a highly conserved glycoprotein that binds heparin and chitin in a non-enzymatic manner. It is a member of the chitinase protein family 18, subfamily A, and unlike true chitinases, YKL-40 is a chitinase-like protein without enzymatic activity for chitin. Although its accurate function is yet unknown, the pattern of its expression in the normal and disease states suggests its possible engagement in apoptosis, inflammation and remodeling or degradation of the extracellular matrix. During an inflammatory response, YKL-40 is involved in a complicated interaction between host and bacteria, both promoting and attenuating immune response and potentially being served as an autoantigen in a vicious circle of autoimmunity. Based on its pathophysiology and mechanism of action, the aim of this review was to summarize research on the growing role of YKL-40 as a persuasive biomarker for inflammatory diseases' early diagnosis, prediction and follow-up (e.g., cardiovascular, gastrointestinal, endocrinological, immunological, musculoskeletal, neurological, respiratory, urinary, infectious) with detailed structural and functional background of YKL-40. [ABSTRACT FROM AUTHOR]

Background:YKL-40 is a new marker that plays a role in tissue remodeling and airway inflammatory processes. Objective: The objective wasevaluatingYKL-40 serum levels in children with bronchial asthma, its predictive value for asthma exacerbation, and its correlation with other inflammatory parameters. Patients and Methods: 84 patients with bronchial asthma (34 acute, 50 stable) and 60 healthy children as controls were recruited. YKL-40 levels were measured using an ELISA kit, analyzing correlations with inflammatory parameters. Results:Serum YKL-40 levels in asthmatic patients were significantly higher than in non-asthmatic individuals (p < 0.001), demonstrating excellent diagnostic accuracy; the area under the curve (AUC) was 1. At a cutoff of 11.9 ng/mL, YKL-40 exhibited 100% sensitivity and 98% specificity. Higher levels were observed in patients with exacerbations (p < 0.001) and a history of hospitalizations or intensive care unit (ICU) admissions (p = 0.03, p < 0.001 respectively). Positive correlations were found with ICU admissions (r = 0.34, p < 0.001) and inverse correlations with asthma control test (ACT) score (r = -0.62, p < 0.001). YKL-40 was also associated with inflammatory markers and predicted exacerbations (AUC = 0.73, p < 0.001) at a cutoff of 20.2 ng/mL (sensitivity 79%, specificity 65%). Conclusion:YKL-40 could serve as a potential biomarker for asthma exacerbation prediction and may provide valuable insights into disease severity and inflammation. [ABSTRACT FROM AUTHOR]

Background: The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to choose the best personalized therapy for their patients. Aims: To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice. Methods: We designed a real-life study with 2 years of follow-up (TRAZELGA [GEE-ELI-2017-01]) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant. Main Results: Thirty patients were enrolled in the study. The median age was 41.5 years and the male–female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy. Conclusion: In summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy. [ABSTRACT FROM AUTHOR]

Glial cell-mediated neuroinflammation and neuronal attrition are highly correlated with cognitive impairment in Alzheimer's disease. YKL-40 is a secreted astrocytic glycoprotein that serves as a diagnostic biomarker of Alzheimer's disease. High levels of YKL-40 are associated with either advanced Alzheimer's disease or the normal aging process. However, the functional role of YKL-40 in Alzheimer's disease development has not been firmly established. In a 5xFAD mouse model of Alzheimer's disease, we observed increased YKL-40 expression in the cerebrospinal fluid of 7-month-old mice and was correlated with activated astrocytes. In primary astrocytes, Aβ1-42 upregulated YKL-40 in a dose-dependent manner and was correlated with PI3-K signaling pathway activation. Furthermore, primary neurons treated with YKL-40 and/or Aβ1-42 resulted in significant synaptic degeneration, reduced dendritic complexity, and impaired electrical parameters. More importantly, astrocyte-specific knockout of YKL-40 over a period of 7 days in symptomatic 5xFAD mice could effectively reduce amyloid plaque deposition in multiple brain regions. This was also associated with attenuated glial activation, reduced neuronal attrition, and restored memory function. These biological phenotypes could be explained by enhanced uptake of Aβ1-42 peptides, increased rate of Aβ1-42 degradation and acidification of lysosomal compartment in YKL-40 knockout astrocytes. Our results provide new insights into the role of YKL-40 in Alzheimer's disease pathogenesis and demonstrate the potential of targeting this soluble biomarker to alleviate cognitive defects in symptomatic Alzheimer's disease patients. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to investigate YKL-40 in migraine patients during migraine attacks. Methods: In this prospective study, 30 migraine patients with aura (MWA) and 30 migraine patients without aura (MWOA) who presented to the Neurological Outpatient Department of Konya City Hospital during a migraine episode as well as 28 healthy controls were included. According to the manufacturer's recommendations, serum YKL-40 levels were determined using an ELISA kit (FineTest). Statistical analysis of the data was performed with the IBM SPSS version 20.0 program. Results: The mean gender and age were similar between groups (p>0.05). The serum YKL-40 level was 3575 ± 604.975 pg/ml in the MWA group, 3339 ± 492.689 pg/ml in the MWOA group and 3190 ± 544.018 pg/ml in the control group. YKL-40 levels were significantly higher in MWA than in the control group (p=0.028). YKL-40 levels were similar in the MWA and MWOA groups (p=0.302). No significant difference was found between the group with MWOA and the control group (p=0.915). Conclusion: Although YKL-40 levels are increased in patients with migraine with aura during an attack, comprehensive studies with a larger sample are needed to clarify the relationship between YKL-40 and migraine. [ABSTRACT FROM AUTHOR]

Background: YKL-40, which is also known as Chitiniase 3-like 1, has been found to be upregulated in many autoimmune diseases including asthma, systemic sclerosis and systemic lupus, etc. However, the relationship between serum levels of YKL-40 and one another common autoinmmue thyroid disease - Graves' disease (GD) has not yet been investigated. Objective: The current study was performed to investigate the correlation of serum YKL-40 levels with disease severity of initially diagnosed GD. Methods: A total of 142 newly diagnosed active GD and 137 healthy individuals were enrolled in the study. Methimazole was given to 55 GD patients and then 2-month study of follow-up was performed. A commercial ELISA kit was applied for the detection of YKL-40 in serum. Degree of goiter was assessed according to Pérez's Grade. Receiver operating characteristic (ROC) curve analysis was carried out to detect the diagnostic value of serum YKL-40 with regard to goiter degree. The velocity of the peak systolic blood-flow and the thyroid tissue blood flow (TBF) were examined using Color Flow Doppler ultrasonography (CFDU). Results: The patients with GD exhibited dramatically higher YKL-40 in serum compared to those of healthy controls (606.1 ± 149.8 pg/mL vs. 397.4 ± 95.1 pg/mL, P < 0.001). Positive associations of YKL-40 with free T3 (FT3) and T4 (FT4), as well as the negative correlation of YKL-40 with TSH in serum, were observed. Additionally, the YKL-40 in serum was dramatically reduced after methimazole intervention, and the correlation of the decline with the reduced FT3 and FT4 was also found (all P < 0.001). Serum YKL-40 levels were positively correlated with goiter degree. ROC curve analysis demonstrated that serum YKL-40 concentration may act as a decent marker for goiter degree. The positive correlations of YKL-40 in serum with the average superior thyroid artery velocity (STV) and thyroid tissue blood flow (TBF) were also observed. Conclusion: Our findings implicated that YKL-40 may be closely connected to the pathogenesis of GD. Increased YKL-40 levels are linked with disease severity of initially diagnosed GD. [ABSTRACT FROM AUTHOR]

YKL-40 is a secreted glycoprotein that can promote invasion, angiogenesis and inhibit apoptosis, and was highly expressed in a variety of tumours. In this paper, we investigated the impacts of YKL-40 on proliferation and invasion in HTR-8/SVneo cells during placenta accreta spectrum disorders (PAS) development. The levels of YKL-40 protein in late-pregnant placental tissue were detected using immunohistochemistry and Western blotting, and gene expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion and apoptosis abilities of HTR-8/SVneo cells were detected by cell counting kit-8 (CCK-8), Transwell, scratch assay, and flow cytometry, respectively. Our current results showed that YKL-40 was significantly increased in the PAS group compared to the normal control group (P < 0.01). Biological function experiments showed that YKL-40 significantly promoted the proliferation, migration and invasion of HTR-8/SVneo cells, and inhibited cell apoptosis. Knockdown of YKL-40 inhibited the activation of Akt/MMP9 signalling in trophoblast cells. These data suggested that YKL-40 might be involved in the progression of PAS, which may be attributed to the regulation of Akt/MMP9 signalling pathway. What is already known on this subject? YKL-40 is a secretory glycoprotein that can promote invasion, angiogenesis, and inhibit apoptosis and was highly expressed in a variety of tumours. Trophoblast cells resemble tumour cells in their migration and invasion. What the results of this study add? YKL-40 expression was significantly up-regulated in PAS. CCK-8 assays showed that YKL-40 remarkably enhanced the viability of HTR-8/SVneo cells. Scratch and Transwell assays demonstrated that YKL-40 significantly promoted the migration and invasion of HTR-8/SVneo cells. Additionally, YKL-40 attenuated apoptosis in HTR-8/SVneo cells. What the implications are of these findings for clinical practice and/or further research? Akt/MMP9 was involved in the regulation of YKL-40 on trophoblast invasion, which may provide theoretical basis and new ideas for the drug blocking intervention of placenta accreta. [ABSTRACT FROM AUTHOR]

Тhe poor prognosis of patients initially diagnosed at an advanced stage of colorectal cancer (CRC) and the heterogeneity within the same tumor stage define the need for additional predictive biomarkers. Tumor buds are proposed as a poor prognostic factor for CRC, however, they are still not implemented into routine pathology reporting. In turn, the chitinase-3-like protein 1 (CHI3L1) also known as YKL-40, is regarded as a candidate circulating biomarker and therapeutic target in CRC. The aim of our study was to investigate tissue YKL-40 localization and tumor budding in CRC. Thirty-one CRC patients and normal colonic tissues were examined. The correlation between YKL-40 levels, tumor budding and clinocopathological parameters was evaluated by polychoric correlation analysis. The immunohistochemical assessment revealed high YKL-40 expression in CRC in contrast to normal mucosa. Specifically, intense YKL-40 staining was detected in the front of tumor invasion compared with tumor parenchyma and noncancerous tissue. We present novel data for increased YKL-40 expression in tumor buds within the front of tumor invasion. We assume that the combination of this morphological parameter with the tissue level of the pleotropic YKL-40 glycoprotein could serve as a future prognostic biomarker for CRC stratification and treatment.

Mahmoud Ahmed Ali,1 Moustafa Adam El Taieb,1 Eisa Mohamed Hegazy,2 Hassan M Ibrahim,2 Alshimaa Abbas Mohamed,1 Mohamed Amer Ahmed Abdellatif,1 Nour Mohammed Ahmed,3 Ali Mohamed Younis1 1Dermatology, Venereology, and Andrology Department, Faculty of Medicine, Aswan University, Aswan, Egypt; 2Dermatology, Venereology, and Andrology Department, Faculty of Medicine South Valley University, Qena, Egypt; 3Clinical Pathology Department, Faculty of Medicine, Aswan University, Aswan, EgyptCorrespondence: Mahmoud Ahmed Ali, Dermatology, Venereology, and Andrology Department, Faculty of Medicine, Aswan University, Aswan, 81528, Egypt, Tel +201002364902, Email dr.mahmoudali8051@gmail.comBackground: In the entire world, acne vulgaris (AV) is the most prevalent skin condition. Approximately 9.4% of people worldwide have acne vulgaris. This study compared the blood levels of chitinase 3-like protein 1 (YKL-40) in acne vulgaris patients before and after oral isotretinoin therapy.Patients and Methods: The design of the study was cross-sectional case-control. Forty patients with moderate to severe acne vulgaris and twenty healthy participants participated in this study. Using the Global Acne Grading System (GAGS) score, patients with acne vulgaris were evaluated both before and after concluding their treatment. Using the enzyme-linked immunosorbent assay (ELISA), the serum levels of YKL-40 were measured before and after oral isotretinoin therapy in healthy controls and acne patients.Results: Patients with acne vulgaris had considerably greater serum levels of YKL-40 than healthy control subjects (p 0.001) did. After three months of oral isotretinoin medication, the GAGS score and blood levels of YKL-40 in acne vulgaris patients both significantly decreased.Conclusion: The conclusion of this study was that reducing the blood levels of YKL-40 and the GAGS score in patients with acne vulgaris who took oral isotretinoin for three months was a crucial strategy.Keywords: acne vulgaris, YKL-40, isotretinoin, GAGS

Objective(s): Neuropathy, retinopathy, and nephropathy, known as the triopathy of diabetes, are the consequences of microvascular complications of diabetes. The present study aimed to investigate the potential protective effects of oleanolic acid (OA) administration against diabetic nephropathy considering biochemical and histopathological parameters.Materials and Methods: The rats with fasting blood glucose levels of 200 mg/dl and above were considered diabetic after induction of diabetes via injecting STZ. The other half of the rats were not injected with STZ (healthy rats). Both healthy and diabetic rats were then divided randomly into two subgroups to be administered with either OA (5 mg/kg) with 1 ml tap water by oral gavage or 1 ml tap water in the same route for 21 days. Serum urea-N, Ca, P, and Mg as well as renal tissue MDA, SOD, NF-κB, IL-6, IL-18, AMPK, YKL-40, and KIM-1 levels were measured.Results: OA administration partially decreased levels of serum urea-N and P, as well as levels of renal tissue MDA and inflammation markers (NF-κB, IL-6, IL-18, YKL-40, and KIM-1) in the diabetic rats. It also partially increased serum Ca and renal tissue AMPK levels in diabetic rats. These positive effects were also seen in renal tissue histopathology.Conclusion: OA treatment partially alleviated renal damage inflammatory and oxidative profiles in diabetic rats.

Autism spectrum disorder (ASD) is associated with multiple physiological abnormalities. Current laboratory and clinical evidence most commonly report mitochondrial dysfunction, oxidative stress, and immunological imbalance in almost every cell type of the body. The present work aims to evaluate oxygen consumption rate (OCR), extracellular acidification rate (ECAR), and inflammation-related molecules such as Cyclooxygenase-2 (COX-2), chitinase 3-like protein 1 (YKL-40), Interleukin-1 beta (IL-1β), Interleukin-9 (IL-9) in ASD children with and without regression compared to healthy controls. Children with ASD (n = 56) and typically developing children (TDC, n = 12) aged 1.11 to 11 years were studied. Mitochondrial activity was examined in peripheral blood mononuclear cells (PBMCs) isolated from children with ASD and from the control group, using a metabolic analyzer. Gene and protein levels of IL-1β, IL-9, COX-2, and YKL-40 were investigated in parallel. Our results showed that PBMCs of the ASD subgroup of regressed patients (ASD R(+), n = 21) had a specific pattern of mitochondrial activity with significantly increased maximal respiration, respiratory spare capacity, and proton leak compared to the non-regressed group (ASD R(-), n = 35) and TDC. Furthermore, we found an imbalance in the studied proinflammatory molecules and increased levels in ASD R(-) proving the involvement of inflammatory changes. The results of this study provide new evidence for specific bioenergetic profiles of immune cells and elevated inflammation-related molecules in ASD. For the first time, data on a unique metabolic profile in ASD R(+) and its comparison with a random group of children of similar age and sex are provided. Our data show that mitochondrial dysfunction is more significant in ASD R(+), while in ASD R(-) inflammation is more pronounced. Probably, in the group without regression, immune mechanisms (immune dysregulation, leading to inflammation) begin initially, and at a later stage mitochondrial activity is also affected under exogenous factors. On the other hand, in the regressed group, the initial damage is in the mitochondria, and perhaps at a later stage immune dysfunction is involved.

Around 30–60% of patients with rheumatoid arthritis (RA) present treatment failure to conventional synthetic disease-modifying antirheumatic drugs (csDMARDs). Chitinase-like proteins (CLPs) (YKL-40, YKL-39, SI-CLP) might play a role, as they are associated with the inflammatory process. This study aimed to evaluate CLP utility as a biomarker in the treatment failure of csDMARDs. A case–control study included 175 RA patients classified into two groups based on therapeutic response according to DAS28-ESR: responders (DAS28 < 3.2); non-responders (DAS28 ≥ 3.2). CLP serum levels were determined by ELISA. Multivariable logistic regression and receiver operating characteristic (ROC) curves were used to evaluate CLPs’ utility as biomarkers of treatment failure. Non-responders presented higher levels of YKL-40, YKL-39, and SI-CLP compared with responders (all: p < 0.001). YKL-40 correlated positively with YKL-39 (rho = 0.39, p < 0.001) and SI-CLP (rho = 0.23, p = 0.011) and YKL-39 with SI-CLP (rho = 0.34, p < 0.001). The addition of CLPs to the regression models improves diagnostic accuracy (AUC 0.918) compared to models including only clinical classical variables (AUC 0.806) p < 0.001. Non-responders were positive for all CLPs in 35.86%. Conclusions: CLPs could be considered as a useful biomarker to assess treatment failure, due to their association with clinical variables and improvement to the performance of regression models.

Chitosan is a natural polymer with numerous biomedical applications. The cellular activity of chitosan has been studied in various types of cancer, including melanoma, and indicates that these molecules can open new perspectives on antiproliferative action and anticancer therapy. This study analyzes how different chitosan conformations, such as α-chitosan (CH) or β-oligochitosan (CO), with various degrees of deacetylation (DDA) and molar mass (MM), both in different concentrations and in CH–CO mixtures, influence the cellular processes of SK-MEL-28 melanocytes, to estimate the reactivity of these cells to the applied treatments. The in vitro evaluation was carried out, aiming at the cellular metabolism (MTT assay), cellular morphology, and chitinase-like glycoprotein YKL-40 expression. The in vitro effect of the CH–CO mixture application on melanocytes is obvious at low concentrations of α-chitosan/β-oligochitosan (1:2 ratio), with the cell’s response supporting the hypothesis that β-oligo-chitosan amplifies the effect. This oligochitosan mixture, favored by the β conformation and its small size, penetrates faster into the cells, being more reactive when interacting with some cellular components. Morphological effects expressed by the loss of cell adhesion and the depletion of YKL-40 synthesis are significant responses of melanocytes. β-oligochitosan (1.5 kDa) induces an extension of cytophysiological effects and limits the cell viability compared to α-chitosan (400–900 kDa). Statistical analysis using multivariate techniques showed differences between the CH samples and CH–CO mixtures.

YKL-40 is a secreted glycoprotein that can promote invasion, angiogenesis and inhibit apoptosis, and was highly expressed in a variety of tumours. In this paper, we investigated the impacts of YKL-40 on proliferation and invasion in HTR-8/SVneo cells during placenta accreta spectrum disorders (PAS) development. The levels of YKL-40 protein in late-pregnant placental tissue were detected using immunohistochemistry and Western blotting, and gene expression using reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion and apoptosis abilities of HTR-8/SVneo cells were detected by cell counting kit-8 (CCK-8), Transwell, scratch assay, and flow cytometry, respectively. Our current results showed that YKL-40 was significantly increased in the PAS group compared to the normal control group (P

Parkinson's disease (PD) is the second most common neurodegenerative disease worldwide. A growing body of evidence suggests that mitochondrial dysfunction and inflammation play a crucial role as a pathogenetic mechanism in PD. The glycoprotein YKL-40 (CHI3L1) is a potential biomarker involved in inflammation and tumor processes. The aim of the present study was to investigate the metabolic profile of PBMCs from PD patients and to search for a possible relationship between cellular bioenergetics and YKL-40. The study included 18 naïve PD patients and an age-matched control group (HC, n = 7). Patients were diagnosed according to the MDS-PD, the UPDRS, and the Hoen–Yahr scales. Mitochondrial activity was measured by a metabolic analyzer on isolated PBMCs from PD patients. Gene (qPCR) and protein (ELISA) expression levels of YKL40 were investigated. New data are reported revealing changes in the mitochondrial activity and YKL-40 levels in PD patients. Bioenergetic parameters showed increased respiratory reserve capacity in PD compared to HC. The protein levels of YKL-40 were threefold higher in PD. We found a correlation between the YKL-40 protein levels and basal respiration and between YKL-40 and ATP production. These observations suggest an interplay between YKL-40 and mitochondrial function in PD. We assume that the YKL-40 gene and protein levels in combination with changes in mitochondrial function might serve as an additional tool to monitor the clinical course of PD. [ABSTRACT FROM AUTHOR]

Introduction: One goal of the Longitudinal Early Onset Alzheimer's Disease Study (LEADS) is to define the fluid biomarker characteristics of early‐onset Alzheimer's disease (EOAD). Methods: Cerebrospinal fluid (CSF) concentrations of Aβ1‐40, Aβ1‐42, total tau (tTau), pTau181, VILIP‐1, SNAP‐25, neurogranin (Ng), neurofilament light chain (NfL), and YKL‐40 were measured by immunoassay in 165 LEADS participants. The associations of biomarker concentrations with diagnostic group and standard cognitive tests were evaluated. Results: Biomarkers were correlated with one another. Levels of CSF Aβ42/40, pTau181, tTau, SNAP‐25, and Ng in EOAD differed significantly from cognitively normal and early‐onset non‐AD dementia; NfL, YKL‐40, and VILIP‐1 did not. Across groups, all biomarkers except SNAP‐25 were correlated with cognition. Within the EOAD group, Aβ42/40, NfL, Ng, and SNAP‐25 were correlated with at least one cognitive measure. Discussion: This study provides a comprehensive analysis of CSF biomarkers in sporadic EOAD that can inform EOAD clinical trial design. [ABSTRACT FROM AUTHOR]

The pathogenesis associated with Alzheimer's disease (AD) is particularly complicated, and early diagnosis and course monitoring of the disease are not ideal based on the available core biomarkers. As a biomarker closely related to neuroinflammation, YKL-40 provides a potential scalable approach in AD, but its association remains controversial and inconclusive with AD. We conducted this study to assess the utility of YKL-40 levels in peripheral blood and cerebrospinal fluid (CSF) of AD patients and healthy controls (HCs) by meta-analysis. We systematically searched and screened relevant trials for comparing YKL-40 levels between AD patients and HCs in PubMed, Embase, Cochrane, and Web of Science, with a search deadline of 14 March 2023 for each database. A total of 17 eligible and relevant studies involving 1811 subjects, including 949 AD patients and 862 HCs, were included. The results showed that YKL-40 levels in the peripheral blood of AD patients and HCs did not possess significant differences. Subgroup analysis showed YKL-40 significantly differed in plasma (SMD = 0.527, 95%CI: [0.302, 0.752]; p = 0.000), but did not in serum. In the case of comparison with HCs, YKL-40 was significantly higher in CSF of AD patients (SMD = 0.893, 95%CI: [0.665, 1.121]; p = 0.000). Besides that, when we performed a combined analysis of total YKL-40 in both peripheral blood and CSF, overall YKL-40 concentrations were also significantly increased among AD patients (SMD = 0.608, 95%CI: [0.272, 0.943]; p = 0.000). YKL-40 provides support and rationale for the neuroinflammatory pathogenesis of AD. The significance of CSF levels of YKL-40 for early screening of AD is definite. Plasma levels of YKL-40 also appear to assist in discriminating AD patients from HCs, which facilitates early screening and monitoring of the natural course of AD. [ABSTRACT FROM AUTHOR]

Objective(s): Neuropathy, retinopathy, and nephropathy, known as the triopathy of diabetes, are the consequences of microvascular complications of diabetes. The present study aimed to investigate the potential protective effects of oleanolic acid (OA) administration against diabetic nephropathy considering biochemical and histopathological parameters. Materials and Methods: The rats with fasting blood glucose levels of 200 mg/dl and above were considered diabetic after induction of diabetes via injecting STZ. The other half of the rats were not injected with STZ (healthy rats). Both healthy and diabetic rats were then divided randomly into two subgroups to be administered with either OA (5 mg/kg) with 1 ml tap water by oral gavage or 1 ml tap water in the same route for 21 days. Serum urea-N, Ca, P, and Mg as well as renal tissue MDA, SOD, NF-κB, IL-6, IL-18, AMPK, YKL-40, and KIM-1 levels were measured. Results: OA administration partially decreased levels of serum urea-N and P, as well as levels of renal tissue MDA and inflammation markers (NF-κB, IL-6, IL-18, YKL-40, and KIM-1) in the diabetic rats. It also partially increased serum Ca and renal tissue AMPK levels in diabetic rats. These positive effects were also seen in renal tissue histopathology. Conclusion: OA treatment partially alleviated renal damage inflammatory and oxidative profiles in diabetic rats. [ABSTRACT FROM AUTHOR]

Background: The diagnosis of advanced endometriosis remains challenging with considerable limitations in the diagnosis of retroperitoneal and deep infiltrating lesions. Thus, a well-defined panel of inexpensive, noninvasive inflammatory biomarkers could be a crucial tool for appropriate staging for women with suspected endometriosis. The aim of this work is to explore the potential use of serum YKL-40, interleukin-37 (IL-37), and cancer antigen 125 (CA125) for noninvasive staging of endometriosis patients for proper intervention and most optimal management of the condition. Methods: This study was conducted on 90 women, who had undergone laparoscopic or laparotomy surgery due to suspected pelvic endometriosis. Blood samples for serum YKL-40, IL-37, and CA125 levels assay were taken from all participants at admission for laparoscopy or laparotomy. After histopathological confirmation of the diagnosis, the selected cases were immunostained for YKL-40, IL-37, and CA125. Results: YKL-40, IL-37, and CA125 serum levels were significantly elevated in patients with endometriosis than healthy controls. Moreover, the association between the serum level and immunoexpression and grading of endometriosis. A triple combination panel of serum YKL-40, IL-37, and CA125 was found to have the best sensitivity and specificity (96.67% and 100.0%, respectively) compared to any single serum marker alone or double combination panel in predicting the severity of endometriosis. Conclusions: A triple combination panel of serum YKL-40, IL-37, and CA125 could be used in the future for predicting endometriosis stage, providing a practical reference for making better-informed decisions on the best treatment plan. [ABSTRACT FROM AUTHOR]

Background: YKL-40, also known as chitinase-3-like protein 1 (CHI3L1), is a secreted glycoprotein produced by various cell types including stromal, immune, and cancer cells. It contributes to cancer progression through tumor-promoting inflammation and has been shown to inhibit the cytotoxicity of T and NK lymphocytes. In vivo studies have demonstrated synergistic anti-cancer effects of blocking YKL-40 in combination with immune checkpoint inhibitors (ICIs). Biomarkers for the prediction of the response to ICIs are highly needed. We investigated the association between plasma YKL-40 and clinical benefit and survival in patients with metastatic pancreatic cancer (mPC) receiving ICIs and stereotactic body radiotherapy (SBRT). Methods: Blood samples were collected from 84 patients with mPC who participated in the randomized phase II CheckPAC study, in which patients received nivolumab with or without ipilimumab combined with a single fraction of SBRT. Plasma YKL-40 was measured using a commercial ELISA kit. Results: Elevated baseline plasma YKL-40 was an independent predictor of shorter overall survival (OS) (HR 2.19, 95% CI 1.21-3.95). A ≥ 40% decrease in plasma YKL-40 during treatment was associated with longer progression-free survival (p = 0.009) and OS (p = 0.0028). There was no correlation between plasma YKL-40 and the tumor burden marker CA19-9 at baseline or during treatment. Conclusion: This study contributes new knowledge regarding YKL-40 as a predictor of clinical benefit from ICIs and radiotherapy. These exploratory results warrant further investigation of YKL-40 as a biomarker for patients treated with immunotherapies. Clinical trial registration: Clinicaltrials.gov, identifier NCT02866383. [ABSTRACT FROM AUTHOR]

Little information exists on YKL-40—a key protein in tissue remodeling—and complete blood count (CBC) parameters during acute exacerbations of advanced chronic obstructive pulmonary disease (COPD). This pilot exploratory study (August 2020–January 2021) investigated the connection between serum YKL-40 levels and CBC profile in sex- and age-matched individuals with severe COPD (GOLD stage III, n = 23, median age = 66 years, 65.21% males) and very severe COPD (GOLD stage IV, n = 24, median age = 66.5 years, 74.81% males). The measured parameters were serum YKL-40, absolute leukocyte count (ALLC), absolute neutrophil count (ANC), neutrophil percentage, absolute lymphocyte count (ALC), lymphocyte percentage, neutrophil-to-lymphocyte ratio (NLR), absolute eosinophil count (AEC), eosinophil percentage, absolute monocyte count (AMC), monocyte percentage, absolute basophil count (ABC), basophil percentage, hemoglobin levels, and hematocrit concentrations. No significant inter-group differences were observed. However, high YKL-40 subjects (n = 23)—as stratified via median YKL-40 (3934.5 pg/mL)—showed significantly increased neutrophil percentage and NLR but significantly lower lymphocyte-, eosinophil-, and basophil-related parameters compared to low YKL-40 patients (n = 24). These results reveal multidimensional, YKL-40-associated changes in leukocyte profile of patients with advanced COPD during acute exacerbations, with potential implications for personalized treatment. [ABSTRACT FROM AUTHOR]