蠕虫及其来源分子干预炎症性疾病的研究进展

炎症是由机体应对病原体入侵或组织损伤产生的一种复杂的保护性反应,心血管疾病、糖尿病、哮喘、肥胖症等均为炎症相关疾病。近年来,大量证据表明,蠕虫及其来源分子对炎症性疾病具有有效的干预作用,故提出了"蠕虫疗法"这一概念。由于接种活体蠕虫面临较大伦理及安全性方面的争议,目前研究热点聚焦于蠕虫源性抗炎效应分子的筛选、结构解析、抗炎活性的鉴定及验证等方面。本文对蠕虫来源的抗炎活性分子及其干预炎症性疾病作用机制的最新进展进行综述。

Changes of the cytokine profile in inflammatory bowel diseases

Cytokines are indispensable signals of the mucosaassociated immune system for maintaining normal gut homeostasis.An imbalance of their profile in favour of inflammation initiation may lead to disease states,such as that is observed in inflammatory bowel diseases(IBD).Although Crohn's disease(CD) is often described as a prototype of T-helper 1-type diseases,and ulcerative colitis(UC) is traditionally viewed as a T-helper 2-mediated condition,the classic paradigm,which categorises cytokines into pro-and anti-inflammatory groups,has recently been changed.The inflammation regulatory pathways may not be mutually exclusive as individual cytokines can have diverse and even opposing functions in various clinical and immunological settings.None the less there are many common immunological responses in IBD that are mediated by cytokines.Although they regulate and influence the development,course and recurrence of the inflammatory process,the concrete pathogenic role of these small signaling molecules is sometimes not unambiguous in the subtypes of the disease.Our aim is to review the current information about pro-and anti-inflammatory effects of traditionally studied and recently discovered cytokines in the pathogenesis of UC and CD.The better understanding of their production and functional activity may lead to the development of new therapeutic modalities.

Amelioration of experimental colitis by Astragalus membranaceus through anti-oxidation and inhibition of adhesion molecule synthesis

AIM: To investigate the protective effects of Astragalus membranaceus(Am) against hapten-induced colitis in male Sprague-Dawley rats as well as its underlying mechanism.METHODS: Experimental colitis was induced in rats by enema administration of 2,4-dinitrobenzene sulfonic acid (DNBS). Rats were either pretreated with Am extract (2 or 4 g/kg, p.o. once daily) starting from 10 d before DNBS enema, or received Am post-treatment (2 or 4 g/kg, p.o.twice daily) on the three consecutive days following DNBS administration. Colonic lesion area and histological damage were determined, while the activities of myeloperoxidase (MPO) and xanthine oxidase, as well as reduced glutathione (GSH) content were measured in the excised colonic tissues. Besides, protein expression of inducible nitrite oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1) and P-selectin was also detected by Western blot analysis.RESULTS: Our findings had shown that both macroscopic lesion area and histological colonic damage induced by DNBS were significantly reduced by both Am pre- and post-treatments. These were accompanied by attenuation of the elevated colonic MPO activity and downregulation of the iNOS, P-selectin, and ICAM-1 protein expression.Besides, deprivation of colonic GSH level under colitis condition was also preserved.CONCLUSION: These results demonstrate that Am possesses both preventive and therapeutic potential in experimental colitis. The anti-inflammatory actions involve anti-oxidation along with inhibition of adhesion molecule synthesis in the colonic tissues.

Molecular mechanisms of insulin resistance in chronic hepatitis C

It is now widely recognized that chronic hepatitis C (CHC)is associated with insulin resistance(IR)and type 2 diabetes,so can be considered a metabolic disease.IR is most strongly associated with hepatitis C virus(HCV)genotype 1,in contrast to hepatic steatosis, which is associated with genotype 3 infection.Apart from the well-described complications of diabetes,IR in CHC predicts faster progression to fibrosis and cirrhosis that may culminate in liver failure and hepatocellular carcinoma.More recently,it has been recognized that IR in CHC predicts a poor response to antiviral therapy. The molecular mechanisms for the association between IR and HCV infection are not well defined.This review will elaborate on the clinical associations between CHC and IR and summarize current knowledge regarding the molecular mechanisms that potentially mediate HCV-associated IR.

Crohn’s disease:Evidence for involvement of unregulated transcytosis in disease etio-pathogenesis

Crohn’s disease(CD)is a chronic inflammatory bowel disease.Research has identified genetic predisposition and environmental factors as key elements in the development of the disease.However,the precise mechanism that initiates immune activation remains undefined.One pathway for luminal antigenic molecules to enter the sterile lamina propria and activate an immune response is via transcytosis.Transcytosis,although tightly regulated by the cell,has the potential for transepithelial transport of bacteria and highly antigenic luminal molecules whose uncontrolled translocation into the lamina propria can be the source of immune activation.Viewed as a whole,the evidence suggests that unregulated intestinal epithelial transcytosis is involved in the inappropriate presentation of immunogenic luminal macromolecules to the intestinal lamina propria.Thus fulfilling the role of an early pre-morbid mechanism that can result in antigenic overload of the lamina propria and initiate an immune response culminating in chronic inflammation characteristic of this disease.It is the aim of this paper to present evidence implicating enterocyte transcytosis in the early etio-pathogenesis of CD.

Research Progress on Molecular Mechanism of Moxibustion in the Treatment of Ankylosing Spondylitis

As an important part of traditional Chinese medicine (TCM) nursing technology, moxibustion plays a unique role in improving the symptoms of ankylosing spondylitis (AS). The research on the mechanism of moxibustion intervention in AS mainly focuses on anti-inflammatory effects, immune regulation, bone metabolism regulation, intestinal flora regulation, and so on. Molecular medicine is of great significance to further clarify the mechanism of moxibustion intervention in AS. However, there are still some problems in the research on the molecular mechanism of moxibustion intervention in AS: the existing biomedical research methods only explore from a specific field and lack the exploration of moxibustion-targeted molecules based on biomedical network. In the future, the molecular network effect of moxibustion on AS can be discussed comprehensively and systematically with the help of omics technology and the construction of biological information interaction network between omics. The effect of moxibustion on upstream osteogenic transcription factors and related signaling pathways such as WNT, β-catenin, and BMP/Smads is not yet clear. Future research can focus on the relevant signal targets of bone reconstruction and clarify the mechanism of moxibustion against the new bone formation. In addition, there is a lack of research on the molecular mechanism of moxibustion in the treatment of AS from the perspective of metabolites. It is necessary to further explore the mechanism of moxibustion in the treatment of AS with the help of metabonomics technology.