Effects of artesunate on schistosomal liver fibrosis in mice / 中国药理学通报

Aim: To study the role and the molecular mechanism of artesunate in anti-schistosomal liver fibrosis in vivo. Methods: Mouse model of liver fibrosis due to Schistosoma japonica infection was established by placing the coverglass with cercaria on the hairless belly. Mice were started on a 8-week regimen of artesunate (ART) daily in 16th week post infection. Mice were observed for four weeks after ART treatment course. The expression of fibrosis genes and CHI3L1/ERK pathway related genes were detected by quantitative PCR and Western blot. Results: Mouse model of schistosomal liver fibrosis was established successfully. Evidence of pathological changes was found for effectiveness of artesunate in the treatment of schistosomal liver fibrosis. The expression of tissue inhibitors of metaslloproteinases 1 (TIMP1) and type IH collagen of mice in treatment group were significantly reduced compared those of model group. The CHI3L1 and ERK1/2 gene expression level of mice in treatment group decreased significantly compared to that of model group. The phosphorylation level of ERK was also significantly inhibited. Conclusions: ART suppresses liver fibrosis of schistosomiasis japonica in vivo and the mechanism for the liver protective effect is related to the inhibition of collagen production and the transmission of CHI3L1/ERK pathway.

Correlation between molecular features and genetic subtypes of Glioblastoma: critical analysis in 109 cases / Correlação entre as características moleculares e os subtipos genéticos dos glioblastomas: análise crítica de 109 casos

OBJECTIVE: Glioblastoma, the most common and lethal brain tumor, is also one of the most defying forms of malignancies in terms of treatment. Integrated genomic analysis has searched deeper into the molecular architecture of GBM, revealing a new sub-classification and promising precision in the care for patients with specific alterations. METHOD: Here, we present the classification of a Brazilian glioblastoma cohort into its main molecular subtypes. Using a high-throughput DNA sequencing procedure, we have classified this cohort into proneural, classical and mesenchymal sub-types. Next, we tested the possible use of the overexpression of the EGFR and CHI3L1 genes, detected through immunohistochemistry, for the identification of the classical and mesenchymal subtypes, respectively. RESULTS: Our results demonstrate that genetic identification of the glioblastoma subtypes is not possible using single targeted mutations alone, particularly in the case of the Mesenchymal subtype. We also show that it is not possible to single out the mesenchymal cases through CHI3L1 expression. CONCLUSION: Our data indicate that the Mesenchymal subtype, the most malignant of the glioblastomas, needs further and more thorough research to be ensure adequate identification.

OBJETIVO: O glioblastoma (GBM), o tumor cerebral mais comum e mais letal, é também um dos tipos de tumores de mais difícil tratamento. Análises genômicas integradas têm contribuído para um melhor entendimento da arquitetura molecular dos GBMs, revelando uma nova subclassificação com a promessa de precisão no tratamento de pacientes com alterações específicas. Neste estudo, nós apresentamos a classificação de uma casuística brasileira de GBMs dentro dos principais subtipos do tumor. MÉTODO: Usando sequenciamento de DNA em larga escala, foi possível classificar os tumores em proneural, clássico e mesenquimal. Em seguida, testamos o possível uso da hiperexpressão de EGFR e CHI3L1 para a identificação dos subtipos clássico e mesenquimal, respectivamente. RESULTADOS: Nossos resultados deixam claro que a identificação genética dos subtipos moleculares de GBM não é possível utilizando-se apenas um único tipo de mutação, em particular nos casos de GBMs mesenquimais. Da mesma forma, não é possível distinguir os casos mesenquimais apenas com a expressão de CHI3L1. CONCLUSÃO: Nossos dados indicam que o subtipo mesenquimal, o mais maligno dos GBMs, necessita de uma análise mais aprofundada para sua identificação.

Clinical Application Value of Chitinase-3-like Protein 1 in Patients with Different Liver Diseases / 现代检验医学杂志

Objctive To explore the clinical value of Chitinase-3-like protein 1(CHI3L1)in patients with chronic hepatitis B (CHB),liver cirrhosis and liver cancer.Methods 96 clinically diagnosed patients in Department of Infectious Diseases Hos-pital of Anhui Provincial Hospital from Jan 2016 to Feb 2017(28CHB,44livercirrhosis,24liver cancer,15healthy controls) were analyzed.The serum level of CHI3L1 was measured by enzyme-linked immunosorbentassay(ELISA).The Golgi pro-tein(GP73)was tested by double-antibody sandwich immunochromatographic assay.The Alpha-fetoprotein(AFP)was tested by means of chemical luminescence.Results There were significant differences between the groups of chronic hepati-tis B(CHB),liver cirrhosis,liver cancer and healthy controls on the CHI3L1 level(χ2=70.249,P<0.001).The CHI3L1 level of the liver cirrhosis group and the liver cancer group increased significantly compared with that of the healthy controls (P<0.001).The GP73 levels of these groups were significantly different(χ2=44.963,P<0.001).The GP73 levels of the CHB group,the liver cirrhosis group and the liver cancer group all increased significantly compared with that of the healthy controls(P<0.05).The AFP levels of these groups were significantly different(χ2=57.606,P<0.001).The AFP level of the liver cancer group increased significantly compared with that of the CHB group,the liver cirrhosis group and the healthy controls(P<0.001).Based on the receiver operating characteristic(ROC)curve of CHI3L1,GP73 and AFP in the CHB group and the liver cirrhosisgroup,the Area Under roc Curve(AUC)of CHI3L1 was 0.953(95%CI:0.902~1.000),the sensitivity was 88.6%,and the specificity was 92.9%,which was higher than GP73 and AFP.Based on the ROC curve of CHI3L1,GP73 and AFP in the liver cirrhosis group and the liver cancer group,the AUC of AFP was 0.930(95% CI:0.871~0.989),the sensitivity was 75.0%,and the specificity was 97.7%,which was higher than CHI3L1 and GP73.The corre-lation between the CHI3L1,GP73 and AFP in CHB,liver cirrhosis and liver cancer groups were analyzed.There was a posi-tive correlation between AFP and GP73(rs=0.491,P<0.001),a positive correlation between AFP and CHI3L1(rs=0.452,P<0.001),a positive correlation between GP73 and CHI3L1(rs=0.554,P<0.001).Conclusion CHI3L1 is good at diagnosis of liver cirrhosism,better than GP73 and AFP.And AFP could be more beneficial in patients with liver cancer, better than CHI3L1 and GP73.

The roles of YKL-40 in atherosclerosis / 国际脑血管病杂志

YKL-40 (human cartilage glycoprotein 39) is a newly discovered inflammatory cytokine, which belongs to the member of 18 glycosyl hydrolase of mammal family. Previous studies have indicated that YKL-40 is associated with the acute or chronic inflammatory diseases and tumors. Studies in recent years have suggested that YKL-40 may be involved in the occurrence and development of atherosclerotic plaques, and it is correlated with the plaque instability. The physiological function and the mechanisms of YKL-40 are not fully understood. It may have the roes of promoting vascular smooth muscle migration and proliferation, promoting cell adhesion and proliferation, as well as regulating extracellular matrix remodeling The detection of YKL-40 may have some significance in the aided diagnosis, predicting prognosis, prevention of cardiocerebrovascular diseases, and even the establishment of new therapeutic strategies.

Role of breast regression protein-39/YKL-40 in asthma and allergic responses

BRP-39 and its human homolog YKL-40 have been regarded as a prototype of chitinase-like proteins (CLP) in mammals. Exaggerated levels of YKL-40 protein and/or mRNA have been noted in a number of diseases characterized by inflammation, tissue remodeling, and aberrant cell growth. Asthma is an inflammatory disease characterized by airway hyperresponsiveness and airway remodeling. Recently, the novel regulatory role of BRP-39/YKL-40 in the pathogenesis of asthma has been demonstrated both in human studies and allergic animal models. The levels of YKL-40 are increased in the circulation and lungs from asthmatics where they correlate with disease severity, and CHI3L1 polymorphisms correlate with serum YKL-40 levels, asthma and abnormal lung function. Animal studies using BRP-39 null mutant mice demonstrated that BRP-39 was required for optimal allergen sensitization and Th2 inflammation. These studies suggest the potential use of BRP-39 as a biomarker as well as a therapeutic target for asthma and other allergic diseases. Here, we present an overview of chitin/chitinase biology and summarize recent findings on the role of BRP-39 in the pathogenesis of asthma and allergic responses.

The Molecular Mechanism of LPS-induced CHI3L1 Expression / 生物化学与生物物理进展

Treatment of chronic osteomyelitis has become a difficult problem in clinical medicine due to its extended pathological process,high occurrence of complication and recurrence of disease.The major pathogenesis mechanism is Gram-negative bacteria infection,such as staphylococci.LPS is an important substance found in the cell wall of Gram-negative bacteria and administration of LPS to skeleton relevant cells in vitro could simulate the pathological characteristics of osteomyelitis patients.The results of quantitative real-time PCR and Western blot showed that CHI3L1 was up-regulated obviously in the infected bone tissues of osteomyelitis patients and LPS-stimulated osteoblasts.Analysis of the luciferase activity of NF-?B reporter gene vector revealed that LPS could activate NF-?B.Bay11-7082,an inhibitor of NF-?B activation,suppressed the elevation of CHI3L1 expression induced by LPS.Pre-incubation of osteoblasts with anti-TNF-? antibody or silencing TNF-? receptor expression by siRNA inhibited the induction effect of LPS on CHI3L1.Inhibition of NF-?B activation also prevented up-regulation of TNF-? induced by LPS.In conclusion,LPS stimulated TNF-? expression through activating NF-?B,then TNF-? induced CHI3L1 expression.It was demonstrated for the first time that CHI3L1 expression is promoted in osteomyelitis and LPS-treated osteoblasts and investigates the molecular mechanism of LPS-induced CHI3L1 expression in osteoblasts.