Chitinase-like Protein Research Articles

Significance of chitinase-3-like protein 1 in the pathogenesis of inflammatory diseases and cancer.

Chitinase-3-like protein 1 (CHI3L1) is a secreted glycoprotein that mediates inflammation, macrophage polarization, apoptosis, and carcinogenesis. The expression of CHI3L1 is strongly upregulated by various inflammatory and immunological diseases, including several cancers, Alzheimer's disease, and atherosclerosis. Several studies have shown that CHI3L1 can be considered as a marker of disease diagnosis, prognosis, disease activity, and severity. In addition, the proinflammatory action of CHI3L1 may be mediated via responses to various proinflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, interleukin-6, and interferon-γ. Therefore, CHI3L1 may contribute to a vast array of inflammatory diseases. However, its pathophysiological and pharmacological roles in the development of inflammatory diseases remain unclear. In this article, we review recent findings regarding the roles of CHI3L1 in the development of inflammatory diseases and suggest therapeutic approaches that target CHI3L1.

Serum CHI3L1 Levels Predict Overall Survival of Hepatocellular Carcinoma Patients after Hepatectomy.

Objective: The Chitinase 3-like protein 1 (CHI3L1) is currently used as a biomarker for the diagnosis of liver fibrosis. However, its prognostic value for hepatocellular carcinoma (HCC) patients remains controversial. In this study, we aimed to investigate the prognostic value of the CHI3L1 in HCC patients after hepatectomy. Methods: In total, 753 HCC patients who underwent curative hepatectomy between January 2017 to August 2021 were retrospectively recruited. The probability of overall survival (OS) was evaluated by the Kaplan-Meier method and compared between groups using the log-rank test. Cox proportional hazard regression analysis was used to determine the independent prognostic factors. A prognostic nomogram was constructed for further examine the clinical utility of CHI3L1 in HCC. Results: Kaplan-Meier analysis revealed that elevated serum CHI3L1 levels were associated with worse overall survival of HCC patients. Multivariate Cox regression analysis showed that the high-CHI3L1 group (≥198.94 ng/ml) was associated with a shorter survival time compared with that in the low-CHI3L1 group (< 198.94 ng/ml) after adjustment for potential confounding factors (HR =1.43, 95% CI = 1.05-1.94, P = 0.024). Additionally, the nomogram had sufficient calibration and discriminatory power in the training cohort, with C-indexes of 0.723 (95% CI: 0.673-0.772). The validation cohort showed similar results. Finally, we demonstrated that the AUC of the nomogram was 0.752 (95% CI: 0.683-0.821), which had better predictive ability than AFP (AUC: 0.644, 95% CI: 0.577-0.711). Conclusion: Our results confirmed that the CHI3L1 could serve as an independent predictor for OS in HCC patients after hepatectomy. The nomogram showed a good performance in prognosis prediction of HCC.

CHI3L1 on fibrinolytic system imbalance in chronic rhinosinusitis with nasal polyp.

Chronic rhinosinusitis (CRS) is an inflammatory disease affecting more than 10% of the global adult population. It is classified into Th1, Th2, and Th17 endotypes and eosinophilic and non-eosinophilic types. Th2-based inflammation and eosinophilic CRS (ECRS) are associated with tissue remodeling and fibrinolytic system impairment. To elucidate the role of eosinophils in inducing fibrin deposition in CRS nasal polyp tissues and explore potential regulatory mechanisms. We analyzed the expression of genes related to the serpin family and fibrinolytic system using Gene Expression Omnibus and Next-generation sequencing data. Differentially expression genes (DEGs) analysis was used to compare control and nasal polyp tissues, followed by KEGG and Gene ontology (GO) analysis. We measured the expression and correlation of plasminogen activator-1 (PAI-1), tissue plasminogen activator (t-PA), urokinase plasminogen activator (u-PA), and urokinase plasminogen activator surface receptor (u-PAR) in CRS tissues, and evaluated the effect of eosinophils on the fibrinolytic system using a cytokine array and co-culture. Nasal polyp tissues showed upregulated PAI-1, u-PA, and u-PAR expression and downregulated t-PA expression. Fibrinolytic system-related genes positively correlated with Th2 cytokines, except for t-PA. Eosinophil-derived Chitinase-3-like protein 1 (CHI3L1) increased PAI-1 expression and decreased t-PA levels in fibroblasts and epithelial cells. The inhibition of CHI3L1 suppresses these alterations. CHI3L1 contributes to fibrin deposition by impairing the fibrinolytic system during nasal polyp formation. The regulation of CHI3L1 expression may inhibit fibrin deposition and edema in ECRS, presenting a potential treatment for this condition.

The Association Between Serum Levels of Glial Biomarkers, Clinical Severity and Electro-encephalography Features in Idiopathic West and Lennox-Gastaut Syndromes.

Although the contribution of enhanced glial activity in seizure induction is increasingly recognized, the role of glia-induced neuroinflammation in the physiopathology of epileptic encephalopathy (EE) has been scarcely investigated. To delineate the contribution of glial activity in EE, we measured levels of glia-derived mediators with previously described biomarker value, including glial fibrillary acidic protein (GFAP), high mobility group box 1 (HMGB1), chitinase-3-like protein 1 (CHI3L1), soluble CD163 (sCD163) and triggering receptor expressed on myeloid cells 2 (TREM2) by ELISA in sera of patients with idiopathic West syndrome (WS, n=18), idiopathic Lennox-Gastaut syndrome (LGS, n=13) and healthy controls (n=31). Patients with EE showed significantly higher CHI3L1 levels compared to healthy controls. Levels of HMGB1, CHI3L1, sCD163 and TREM2 were higher in LGS patients than WS patients and/or healthy controls. One or more of the investigated mediators were associated with treatment responsiveness, disease severity and presence of pathological features on electroencephalography (EEG). To our knowledge, our findings provide the initial patient-based evidence that astrocyte- and microglia-mediated neuroinflammation might be involved in the pathogenesis of LGS and WS. Moreover, glial mediators may serve as prognostic biomarkers in patients with idiopathic EE.

Predictive value of serum HIF-1α/HIF-2α and YKL-40 levels for vascular invasion and prognosis of follicular thyroid cancer

ObjectiveThis study investigated the significance of serum hypoxia-inducible factor (HIF)-1α/HIF-2 α and Chitinase 3-Like protein 1 (YKL-40) levels in the assessment of vascular invasion and prognostic outcomes in patients with Follicular Thyroid Cancer (FTC). MethodsThis prospective study comprised 83 patients diagnosed with FTC, who were subsequently categorized into a recurrence group (17 cases) and a non-recurrence group (66 cases). The pathological features of tumor vascular invasion were classified. Serum HIF-1α/HIF-2α and YKL-40 were quantified using a dual antibody sandwich enzyme-linked immunosorbent assay, while serum Thyroglobulin (Tg) levels were measured using an electrochemiluminescence immunoassay method. The Spearman test was employed to assess the correlation between serum factors, and the predictive value of diagnostic factors was determined using receiver operating characteristic curve analysis. A Cox proportional hazards regression model was utilized to analyze independent factors influencing prognosis. ResultsSerum HIF-1α, HIF-2α, YKL-40, and Tg were elevated in patients exhibiting higher vascular invasion. A significant positive correlation was observed between Tg and HIF-1α, as well as between HIF-1α and YKL-40. The cut-off values for HIF-1α and YKL-40 in predicting recurrence were 48.25 pg/mL and 60.15 ng/mL, respectively. Patients exceeding these cut-off values experienced a lower recurrence-free survival rate. Furthermore, serum levels surpassing the cut-off value, in conjunction with vascular invasion (v2+), were identified as independent risk factors for recurrence in patients with FTC. ConclusionSerum HIF-1α/HIF-2α and YKL-40 levels correlate with vascular invasion in FTC, and the combination of HIF-1α and YKL-40 predicts recurrence in patients with FTC.

Toxoplasma gondii chitinase-like protein TgCLP1 regulates the parasite cyst burden.

Toxoplasma, an important intracellular parasite of humans and animals, causes life-threatening toxoplasmosis in immunocompromised individuals. Although Toxoplasma secretory proteins during acute infection (tachyzoite, which divides rapidly and causes inflammation) have been extensively characterized, those involved in chronic infection (bradyzoite, which divides slowly and is surrounded by a cyst wall) remain uncertain. Regulation of the cyst wall is essential to the parasite life cycle, and polysaccharides, such as chitin, in the cyst wall are necessary to sustain latent infection. Toxoplasma secretory proteins during the bradyzoite stage may have important roles in regulating the cyst wall via polysaccharides. Here, we focused on characterizing the hypothetical T. gondii chitinase, chitinase-like protein 1 (TgCLP1). We found that the chitinase-like domain containing TgCLP1 is partially present in the bradyzoite microneme and confirmed, albeit partially, its previous identification in the tachyzoite microneme. Furthermore, although parasites lacking TgCLP1 could convert from tachyzoites to bradyzoites and make an intact cyst wall, they failed to convert from bradyzoites to tachyzoites, indicating that TgCLP1 is necessary for bradyzoite reactivation. Taken together, our findings deepen our understanding of the molecular basis of recrudescence and could contribute to the development of novel strategies for the control of toxoplasmosis.

Clinical Significance of Chitinase-3-like Protein 1 Gene Expression in Patients With Locally Advanced Gastric Cancer.

Chitinase-3-like protein 1 (CHI3L1), encoded by CHI3L1, is thought to be involved in growth, invasion, migration, and resistance to chemotherapy in cancer. This study aimed to investigate the clinical significance of CHI3L1 expression as a biomarker in gastric cancer (GC) tissues of patients with locally advanced GC after curative resection. Quantitative polymerase chain reaction (PCR) was used to determined CHI3L1 expression in GC tissues and adjacent normal gastric mucosa of 253 patients with pStage II/III GC who underwent curative resection. We compared the expression levels in GC tissues and adjacent normal gastric mucosa, and examined the relationship between expression in GC tissues and clinicopathological factors and overall survival (OS) in these patients. CHI3L1 expression was significantly associated with lymph-node metastasis and venous invasion. OS rate was significantly lower in the high- than in the low-CHI3L1 expression group (5-year survival 55.5% vs. 72.6%; p=0.009). Furthermore, in multivariate analysis, high CHI3L1 gene expression was an independent factor for poor OS (hazard ratio=2.030; 95% confidence interval=1.318-3.127; p=0.001). In patients with locally advanced GC after curative resection, expression of the CHI3L1 in GC tissue may be a useful prognostic marker.

Role and mechanisms of CHI3L1 in coronary artery lesions in a mouse model of Kawasaki disease-like vasculitis

To explore the role and potential mechanisms of chitinase-3-like protein 1 (CHI3L1) in coronary artery lesions in a mouse model of Kawasaki disease (KD)-like vasculitis. Four-week-old male SPF-grade C57BL/6 mice were randomly divided into a control group and a model group, with 10 mice in each group. The model group mice were intraperitoneally injected with 0.5 mL of lactobacillus casei cell wall extract (LCWE) to establish a mouse model of KD-like vasculitis, while the control group mice were injected with an equal volume of normal saline. The general conditions of the mice were observed on the 3rd, 7th, and 14th day after injection. Changes in coronary artery tissue pathology were observed using hematoxylin-eosin staining. The level of CHI3L1 in mouse serum was measured by enzyme-linked immunosorbent assay. Immunofluorescence staining was used to detect the expression and localization of CHI3L1, von Willebrand factor (vWF), and α-smooth muscle actin (α-SMA) in coronary artery tissue. Western blot analysis was used to detect the expression of CHI3L1, vWF, vascular endothelial cadherin (VE cadherin), Caspase-3, B cell lymphoma-2 (Bcl-2), Bcl-2 associated X protein (Bax), nuclear factor κB (NF-κB), and phosphorylated NF-κB (p-NF-κB) in coronary artery tissue. The serum level of CHI3L1 in the model group was significantly higher than that in the control group (P<0.05). Compared to the control group, the expression of CHI3L1 in the coronary artery tissue was higher, while the expression of vWF was lower in the model group. The relative expression levels of CHI3L1, Bax, Caspase-3, NF-κB, and p-NF-κB were significantly higher in the model group than in the control group (P<0.05). The relative expression levels of vWF, VE cadherin, and Bcl-2 were lower in the model group than in the control group (P<0.05). In the LCWE-induced mouse model of KD-like vasculitis, the expression levels of CHI3L1 in serum and coronary arteries increase, and it may play a role in coronary artery lesions through endothelial cell apoptosis mediated by inflammatory reactions.

YKL-40 as a biomarker in various inflammatory diseases: A review.

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.

Serum YKL-40 (chitinase 3-like protein 1) levels in migraine patients during an attack

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&gt;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.

Increased Circulating Levels of YKL-40 Protein in Children and Adolescents with Hemophilia: Correlation with the Degree of Hemophilic Arthropathy

Introduction: Hemophilia A and B are rare X-linked inherited bleeding disorders caused by complete or partial deficiency of coagulation factors VIII and IX, respectively. Recurrent joint bleeding (hemarthrosis) is the most frequent clinical manifestation of severe hemophilia. Unless appropriately managed, even subclinical hemarthrosis can lead to hemophilic arthropathy, that severely affects the quality of life of patients. Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a 40-kDa heparin-human cartilage glycoprotein without enzymatic activity, that is encoded by the CHI3L1 gene in humans and its name derives from the one letter code for the three terminal amino acids - tyrosine (Y), lysine (K) and leucine (L). YKL-40 is secreted in vitro and in vivo in the arthritic joint by various cell types, such as activated macrophages, chondrocytes, synoviocytes and neutrophils. Actually, it is a major protein that has been identified in the chondrocytes from arthritic knee joints.In fact, synovial as well as serum YKL-40 levels are found increased in joint diseases like rheumatoid arthritis and osteoarthritis, indicating its potential role as a biomarker of inflammation and tissue remodeling or degradation, whereas it is absent in normal joints. In our knowledge, there are not any reports linking YKL-40 expression with hemophilic arthropathy, thus we aimed to investigate if this protein could be implicated in hemophilic arthropathy severity, by measuring its circulating levels and correlate them with hemophilic arthropathy features and laboratory parameters in children and adolescents with hemophilia A and B. Patients and Methods: Eighty children and adolescents (median age:14 years, range 10-18 years) with severe (n= 60), moderate (n= 8) and mild (n= 12) hemophilia A or B (n= 7), on prophylaxis or on demand treatment (n= 12) were included in the study, while 35 apparently healthy male individuals matched for age served as controls. No signs of hemophilic arthropathy (NHAP), i.e. Hemophilia Joint Health Score 2.1 ≤ 2 and Hemophilia Early Detection Arthropathy with Ultrasound Score ≤ 1, were detected in 34/80 patients with median age of 13.5 years. In 37/80 patients with median age of 14.25 years arthropathy (HAP) was confirmed, while 18/80 patients with median age of 15.75 years presented with acute bleeding (AB)-hemarthrosis or muscle bleed- at the time of the laboratory evaluation. In patients and controls YKL-40 concentrations were determined by means of an immunoenzymatic technique. Results: We found that: a) Circulating YKL-40 levels in patients with hemophilia were significantly higher compared to controls, 21.9±2.3 ng/mL (95% Confidence Intervals of the mean (CI): 19.6;24.2 ng/mL) vs 17.0±2.5 ng/mL (CI: 14.5;19.4 ng/mL), respectively, p=0.003. b) Patients with arthropathy (HAP) tend to express higher circulating YKL-40 levels (25.5±2.0 ng/mL) than patients without arthropathy (NHAP)(20.1±1.8 ng/mL) and patients with acute bleeding (AB) (19.7±2.4 ng/mL), respectively, p-trend=0.06. Conclusions: To the best of our knowledge, this is the first study to evaluate the potential clinical significance of circulating YKL-40 levels in patients with hemophilia and demonstrated that it could reflect hemophilic arthropathy activity in clinical or even in subclinical level. As YKL-40 in synovial fluid is derived from cells in the inflamed/damaged synovium, such as chondrocytes, we postulate that it may be involved in the pathophysiology of the hemophilic arthropathy processes and reflect local disease activity. Further studies are essential on the role of YKL-40 in the evolution of hemophilic arthropathy, in order to fully elucidate its clinical significance and prognostic utility.

Potential Roles and Future Perspectives of Chitinase 3-like 1 in Macrophage Polarization and the Development of Diseases.

Chitinase-3-like protein 1 (CHI3L1), a chitinase-like protein family member, is a secreted glycoprotein that mediates macrophage polarization, inflammation, apoptosis, angiogenesis, and carcinogenesis. Abnormal CHI3L1 expression has been associated with multiple metabolic and neurological disorders, including diabetes, atherosclerosis, and Alzheimer's disease. Aberrant CHI3L1 expression is also reportedly associated with tumor migration and metastasis, as well as contributions to immune escape, playing important roles in tumor progression. However, the physiological and pathophysiological roles of CHI3L1 in the development of metabolic and neurodegenerative diseases and cancer remain unclear. Understanding the polarization relationship between CHI3L1 and macrophages is crucial for disease progression. Recent research has uncovered the complex mechanisms of CHI3L1 in different diseases, highlighting its close association with macrophage functional polarization. In this article, we review recent findings regarding the various disease types and summarize the relationship between macrophages and CHI3L1. Furthermore, this article also provides a brief overview of the various mechanisms and inhibitors employed to inhibit CHI3L1 and disrupt its interaction with receptors. These endeavors highlight the pivotal roles of CHI3L1 and suggest therapeutic approaches targeting CHI3L1 in the development of metabolic diseases, neurodegenerative diseases, and cancers.

Evaluation of the Effect of Oral Isotretinoin on the Level of Serum YKL40 in Acne Vulgaris Patients: A Cross-Sectional Case-Control.

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. 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. 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. 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.

Serum YKL-40 in coronary heart disease: linkage with inflammatory cytokines, artery stenosis, and optimal cut-off value for estimating major adverse cardiovascular events.

YKL-40, previously known as chitinase-3-like protein 1 (CHI3L1), is an inflammation-related glycoprotein that promotes atherosclerosis, but its application and optimal cut-off value as a prognostic biomarker in coronary heart disease (CHD) require more clinical evidence. Thus, this prospective study aimed to evaluate the linkage of serum YKL-40 with disease features, inflammatory cytokines, and major adverse cardiovascular events (MACEs) in CHD patients. A total of 410 CHD patients were enrolled for serum YKL-40 determination via enzyme-linked immunosorbent assay. Meanwhile, serum YKL-40 levels in 100 healthy controls (HCs) were also quantified. YKL-40 level was higher in CHD patients compared with that in HCs (P < 0.001). YKL-40 was positively linked with hyperlipidemia (P = 0.014), diabetes mellitus (P = 0.001), fasting blood glucose (P = 0.045), C-reactive protein (P < 0.001), the Gensini score (P < 0.001), and stenosis degree (graded by the Gensini score) (P < 0.001) in CHD patients. In addition, an elevated YKL-40 level was associated with increased levels of tumor necrosis factor alpha (P = 0.001), interleukin (IL)-1β (P = 0.001), IL-6 (P < 0.001), and IL-17A (P = 0.002) in CHD patients. The 1-/2-/3-year cumulative MACE rates of CHD patients were 5.5%, 14.4%, and 25.0%, respectively. Regarding the prognostic capability, YKL-40 ≥100 ng/ml (the median cut-off value) (P = 0.003) and YKL-40 ≥150 ng/ml (the third interquartile cut-off value) (P = 0.021) reflected an elevated accumulating MACE rate, whereas accumulating MACE was not different between CHD patients with YKL-40 ≥80 and <80 ng/ml (the first interquartile cut-off value) (P = 0.083). Serum YKL-40 is positively linked with inflammatory cytokines and the Gensini score, whose high expression cut-off by 100 and 150 ng/ml estimates a higher MACE risk in CHD patients.

STAT6-induced production of mucus and resistin-like molecules in lung Club cells does not protect against helminth or influenza A virus infection.

Airway epithelial cells contribute to a variety of lung diseases including allergic asthma, where IL-4 and IL-13 promote activation of the transcription factor STAT6. This leads to goblet cell hyperplasia and the secretion of effector molecules by epithelial cells. However, the specific effect of activated STAT6 in lung epithelial cells is only partially understood. Here, we created a mouse strain to selectively investigate the role of constitutively active STAT6 in Club cells, a subpopulation of airway epithelial cells. CCSP-Cre_STAT6vt mice and bronchiolar organoids derived from these show an enhanced expression of the chitinase-like protein Chil4 (Ym2) and resistin-like molecules (Relm-α, -β, -γ). In addition, goblet cells of these mice spontaneously secrete mucus into the bronchi. However, the activated epithelium resulted neither in impaired lung function nor conferred a protective effect against the migrating helminth Nippostrongylus brasiliensis. Moreover, CCSP-Cre_STAT6vt mice showed similar allergic airway inflammation induced by live conidia of the fungus Aspergillus fumigatus and similar recovery after influenza A virus infection compared to control mice. Together these results highlight that STAT6 signaling in Club cells induces the secretion of Relm proteins and mucus without impairing lung function, but this is not sufficient to confer protection against helminth or viral infections.

Diagnostic Significance of Chemerin and Chitinase 3-Like Protein 1 Levels in Cholelithiasis

Diagnostic Significance of Chemerin and Chitinase 3-Like Protein 1 Levels in Cholelithiasis

Correlations of special AT-rich sequence binding protein 2 and chitinase-3-like protein-1 with sensitivity to paclitaxel chemotherapy for gastric cancer

Abstract Background: Our objective was to examine the associations between special AT-rich sequence binding protein 2 (SATB2) and chitinase-3-like protein-1 (CHI3L1) and the responsiveness to paclitaxel treatment in individuals with gastric cancer. Methods: From March 2018 to October 2020, our hospital collected gastric cancer samples along with adjacent gastric mucosal tissues located more than 5 cm away from the cancerous margin. These samples were obtained from 90 patients who underwent chemotherapy regimens containing paclitaxel. To assess the rates of positive expression of CHI3L1 and SATB2 in gastric cancer and adjacent tissues, the immunohistochemical streptavidin-peroxidase (SP) technique was utilized. Results: The positive expression rate of CHI3L1 was higher in gastric cancer tissues compared to adjacent tissues, while the positive expression rate of SATB2 was lower (P&lt;0.05). Risk factors that influenced the positive expression of CHI3L1 in gastric cancer tissues included the level of differentiation, tumor-node-metastasis (TNM) stage, and the presence of lymph node metastasis (OR&gt;1, P&lt;0.05). Additionally, the positive expression of SATB2 was also affected by TNM stage and lymph node metastasis, which were identified as risk factors (OR&gt;1, P&lt;0.05). In gastric cancer tissues, there was a negative correlation observed between the expressions of CHI3L1 and SATB2 (r&lt;0, P&lt;0.05). According to the analysis results of Kendall’s tau-b (K), it was found that the presence of CHI3L1 had an inverse relationship with the responsiveness to paclitaxel-based chemotherapy in gastric cancer (r=-0.498, P=0.000), while SATB2 exhibited a positive correlation with the sensitivity (r=0.513, P=0.000). During the 3-year follow-up after chemotherapy, the survival rate was 55.55% (50/90). Conclusions: The findings indicate a strong correlation between SATB2 and CHI3L1 with the TNM stage, lymph node metastasis, response to paclitaxel-based chemotherapy, and the overall survival rate of individuals.

CHI3L1 signaling impairs hippocampal neurogenesis and cognitive function in autoimmune-mediated neuroinflammation.

Chitinase-3-like protein 1 (CHI3L1) is primarily secreted by activated astrocytes in the brain and is known as a reliable biomarker for inflammatory central nervous system (CNS) conditions such as neurodegeneration and autoimmune disorders like neuromyelitis optica (NMO). NMO is an astrocyte disease caused by autoantibodies targeting the astroglial protein aquaporin 4 (AQP4) and leads to vision loss, motor deficits, and cognitive decline. In this study examining CHI3L1's biological function in neuroinflammation, we found that CHI3L1 expression correlates with cognitive impairment in our NMO patient cohort. Activated astrocytes secrete CHI3L1 in response to AQP4 autoantibodies, and this inhibits the proliferation and neuronal differentiation of neural stem cells. Mouse models showed decreased hippocampal neurogenesis and impaired learning behaviors, which could be rescued by depleting CHI3L1 in astrocytes. The molecular mechanism involves CHI3L1 engaging the CRTH2 receptor and dampening β-catenin signaling for neurogenesis. Blocking this CHI3L1/CRTH2/β-catenin cascade restores neurogenesis and improves cognitive deficits, suggesting the potential for therapeutic development in neuroinflammatory disorders.

Dauricine regulates prostate cancer progression by inhibiting PI3K/AKT-dependent M2 polarization of macrophages

M2 type tumor-associated macrophages, an essential component of the tumor microenvironment (TME), have been proved to contribute to tumor metastasis. Dauricine (Dau) has recently received widespread attention due to its multiple targets and low price. However, the effect of Dau on macrophage polarization of TME remains unclear. In this study, we investigated the effect of Dau on prostate cancer (PCa) metastasis and specifically its correlation to macrophage polarization. Our results showed that Dau efficiently suppressed M2 polarization of macrophages induced by interleukin (IL) −4 and IL-13. Mechanistically, Dau inhibited the activity of PI3K/AKT signaling pathway, which subsequently suppressed macrophage differentiation to M2 type. Importantly, our study indicated that Dau decreased the release of chitinase 3-like protein 1 (CHI3L1) from M2 macrophages, which ultimately inhibited the M2 macrophage-mediated progression of PCa cells in vitro and in vivo. Taken together, our data demonstrated that Dau suppressed M2 polarization of macrophages via downregulation of the PI3K/AKT signaling pathway, in turn, preventing proliferation, epithelial–mesenchymal transition, migration, and invasion of PCa cells. Thus, this study reveals a previously unrecognized function of Dau in inhibition of PCa progression via intervention in M2 polarization of macrophages.

SerpinA1 levels in amyotrophic lateral sclerosis patients: An exploratory study.

SerpinA1, a serine protease inhibitor, is involved in the modulation of microglial-mediated inflammation in neurodegenerative diseases. We explored SerpinA1 levels in cerebrospinal fluid (CSF) and serum of amyotrophic lateral sclerosis (ALS) patients to understand its potential role in the pathogenesis of the disease. SerpinA1, neurofilament light (NfL) and heavy (NfH) chain, and chitinase-3-like protein-1 (CHI3L1) were determined in CSF and serum of ALS patients (n = 110) and healthy controls (n = 10) (automated next-generation ELISA), and correlated with clinical parameters, after identifying three classes of progressors (fast, intermediate, slow). Biomarker levels were analyzed for diagnostic power and association with progression and survival. SerpinA1serum was significantly decreased in ALS (median: 1032 μg/mL) compared with controls (1343 μg/mL) (p = 0.02). SerpinA1CSF was elevated only in fast progressors (8.6 μg/mL) compared with slow (4.43 μg/mL, p = 0.01) and intermediate (4.42 μg/mL, p = 0.03) progressors. Moreover, SerpinA1CSF correlated with neurofilament and CHI3L1 levels in CSF. Contrarily to SerpinA1CSF , neurofilament and CHI3L1 concentrations in CSF correlated with measures of disease progression in ALS, while SerpinA1serum mildly related with time to generalization (rho = 0.20, p = 0.04). In multivariate analysis, the ratio between serum and CSF SerpinA1 (SerpinA1 ratio) and NfHCSF were independently associated with survival. Higher SerpinA1CSF levels are found in fast progressors, suggesting SerpinA1 is a component of the neuroinflammatory mechanisms acting upon fast-progressing forms of ALS. Both neurofilaments or CHI3L1CSF levels outperformed SerpinA1 at predicting disease progression rate in our cohort, and so the prognostic value of SerpinA1 alone as a measure remains inconclusive.