The new member of the IL-1 family, interleukin-33 (IL-33), participates in the progression of a variety of diseases through binding with its receptor ST2. Recently, much clinical evidence and experimental data have indicated that IL-33 is associated with various liver diseases. This review primarily addresses the relationship between IL-33 and several hepatic diseases. IL-33 can alleviate high-fat diet- (HFD-) induced hepatic steatosis and insulin resistance, and IL-33 acts as an alarmin, which quickly triggers the immune system to respond to virus invasion and toxic damage to the liver. However, when liver injury is chronic, IL-33 promotes Th2 reactions and hepatic stellate cell (HSC) activity, facilitating progression to liver fibrosis. The complicated functions of IL-33 should be considered before its clinical application.
Alcoholic liver disease (ALD) is a complication that is a burden on global health and economy. Interleukin‐33 (IL‐33) is a newly identified member of the IL‐1 cytokine family and is released as an “alarmin” during inflammation. Soluble suppression of tumourigenicity 2 (sST2), an IL‐33 decoy receptor, has been reported as a new biomarker for the severity of systemic and highly inflammatory diseases. Here, we found the levels of plasma sST2, increased with the disease severity from mild to severe ALD. Importantly, the plasma sST2 levels in ALD patients not only correlated with scores for prognostic models (Maddrey's discriminant function, model for end‐stage liver disease and Child‐Pugh scores) and indexes for liver function (total bilirubin, international normalized ratio, albumin, and cholinesterase) but also correlated with neutrophil‐associated factors as well as some proinflammatory cytokines. In vitro, lipopolysaccharide‐activated monocytes down‐regulated transmembrane ST2 receptor but up‐regulated sST2 mRNA and protein expression and produced higher levels of tumour necrosis factor‐α (TNF‐α). By contrast, monocytes pretreated with recombinant sST2 showed decreased TNF‐α production. In addition, although plasma IL‐33 levels were comparable between healthy controls and ALD patients, we found the IL‐33 expression in liver tissues from ALD patients was down‐regulated at both RNA and protein levels. Immunohistochemical staining further showed that the decreased of IL‐33‐positive cells were mainly located in liver lobule area. These results suggested that sST2, but not IL‐33, is closely related to the severity of ALD. Consequently, sST2 could be used as a potential biomarker for predicting the prognosis of ALD.
Alcoholic liver disease ( ALD ) is a progressive liver disease that can cause a series of complications, including cirrhosis, liver failure and hepatocellular carcinoma. Granulocytic myeloid‐derived suppressor cell ( gMDSC ) populations have been observed to expand in various liver diseases and to inhibit innate and adaptive immunity in patients with liver disease. However, the characteristics of gMDSC s in patients with ALD have not been studied. We studied 24 healthy controls ( HC s) and 107 patients with ALD and found an accumulation of gMDSC s in the peripheral blood of patients with alcoholic liver cirrhosis ( ALC ). Furthermore, ALC patients with a poor prognosis displayed a significant increase in peripheral gMDSC s and showed an increased capacity for arginase I production compared to HC s. In contrast, plasma arginase I levels in ALC patients were negatively correlated with total bilirubin and international normalized ratio, two key parameters of liver damage. Importantly, gMDSC s accumulated in the livers of ALC patients, and the frequency of liver gMDSC s significantly correlated with that of peripheral gMDSC s. In addition, gMDSC enrichment in vitro significantly inhibited the function of natural killer ( NK ) cells, perhaps preventing the NK ‐induced apoptosis of hepatic stellate cells. In summary, increased peripheral and intrahepatic gMDSC populations are present in patients with ALC and may contribute to enhancing the severity of liver cirrhosis.
Moracins, a kind of 2-phenyl-benzofuran compound from Moraceae, serve as phytoalexins with antimicrobial, anti-inflammatory, antitumor, and antidiabetes activities and respond to biotic and abiotic stresses, while their biosynthetic pathway and regulatory mechanism remain unclear. Here, we report a de novo transcriptome sequencing for different tissues of seedlings, as well as leaves under different stresses, in M. alba L. A total of 88 282 unigenes were assembled with an average length of 937 bp, and 82.2% of them were annotated. On the basis of the differential expression analysis and enzymatic activity assays in vitro , moracins were traced to the phenylpropanoid pathway, and a putative biosynthetic pathway of moracins was proposed. Unigenes coding key enzymes in the pathway were identified and their expression levels were verified by real-time quantitative reverse transcription PCR (qRT-PCR). Particularly, a p -coumaroyl CoA 2′-hydroxylase was presumed to be involved in the biosynthesis of stilbenes and deoxychalcones in mulberry. Additionally, the transcription factors that might participate in the regulation of moracin biosynthesis were obtained by coexpression analysis. These results shed light on the putative biosynthetic pathway of moracins, providing a basis for further investigation in functional characterization and transcriptional regulation of moracin biosynthesis in mulberry.
Multiple primary malignant neoplasms (MPMNs) were referred to as the synchronous carcinoma (SC) or metachronous carcinoma (MC) of two or more types of primary malignant tumours in one or more organs and tissues in the same patient. 1 The incidence of MPMNs was variable because of ethnic areas, local medical care, awareness of MPMNS, statistical methods and literature publication. According to the different time sequences of occurrence, MPMNs were divided into SC and MC. The time interval of more than 2 kinds of malignant tumours occurring successively less than 6 months as SC. 2 Meanwhile, MC was defined while the carcinoma interval time was more than 6 months. 3 Most studies have shown that MC cases were much more than SC cases.The prognosis of MPMNs was influenced by the interval between carcinomas, the type of pathology, the organs involved, the degree
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