Study on the mechanism of action of Feng-Liao-Chang-Wei-Kang combined with 5-fluorouracil in the treatment of colitis-associated colon cancer

Objective:To investigate the therapeutic effects and mechanisms of Feng-Liao-Chang-Wei-Kang combined with 5-fluorouracil administration in mice with colitis-associated colon cancer.Methods:To establish a colitis-associated colon cancer mouse model and observe the behavior and activity of mice after Feng-Liao-Chang-Wei-Kang and 5-fluorouracil administration;HE staining to observe the pathological changes of mouse colonic tissue;Western blot was used to detect the expression of mouse colon tissue in IL-6/STAT3 pathway-related proteins.Results:The survival rate of mice in the co-administered group was significantly increased,and the intestinal wall thickening and interstitial inflammation of mice were significantly reduced.Western blot results showed that the expression levels of P-STAT3 and IL-6 were significantly increased in the colonic tissue of mice after modeling,and the combined administration inhibited the expression of Cyclin D1,CDK4 and Bcl-2 protein in the IL-6/STAT3 pathway and upregulated the expression of Bax(P<0.05).Conclusion:Feng-Liao-Chang-Wei-Kang combined with 5-fluorouracil inhibits IL-6/STAT3 pathway to exert inhibition of colitis-associated colon cancer inhibition of colitis-associated colon cancer.

Study on Acute Toxicity of Purified Protein HAS1 Expression in KM Mice

[Objectives]The antifungal protein HAS1 newly obtained was evaluated for acute toxicity safety in KM mice according to relevant national regulations,so as to eliminate people s concerns about the safety of transgenic plants.[Methods]The acute toxicity of the purified protein HAS1 was observed by intragastric administration of mice,and the poisoning symptoms,poisoning degree,recovery and death were observed.[Results]No abnormal toxicity symptoms were observed in the test group,the vehicle control group and the blank control group.The main tissues and organs were not abnormal in gross anatomy.The average body weight of each group showed an increasing trend compared with before administration at 1,3,7,11 and 14 d after administration.It was found that after giving the purified protein HAS1 to KM mice at a cumulative dose of 64 mg/kg a day,no obvious toxicity was observed in the acute toxicity test,indicating that the test substance was non-toxic by oral administration.[Conclusions]This study provides a basis for further use of the protein and its coding genes.

Skin Anaphylaxis Test of Purified Protein HAS1 in Cavies

The antifungal protein HAS1 is a new antifungal protein isolated from the genome of Bacillus subtilis HAS,which has a good inhibitory effect on various pathogenic fungi in sugarcane.This study aimed at evaluating the immunological transfer reaction of the test sample through repeated skin contact by observing whether the cavy skin repeatedly exposed to purified protein HAS1 suffers from allergic reaction and how strong is the allergic reaction.The results showed that the test group and the vehicle control group exhibited no allergic reaction in the skin immediately and at 24,48 and 72 h and had an mean reaction score and a sensitization rate both of 0,so the results of the naked eye observation were both nonallergenic to cavy skin;and in the positive control group,the cavies were observed to be highly sensitized immediately after removing the drug,mildly sensitized at 24 h,and not sensitized at 48 and 72 h,which meant the skin allergy was alleviated with the observation time.It is suggested that the purified protein HAS1 is negative for cavy skin anaphylaxis test (nonallergenic to cavy skin),which provides an experimental basis for further utilization of the protein and its coding gene.

Development and Application of Network Toxicology in Safety Research of Chinese Materia Medica

Network toxicology that is an important branch of the network pharmacology emerges on the basis of network biology. It refers to study on the toxicological features of a constructed network model which is used to analyze toxic substances and their interaction and regulation in biological systems, particularly investigate the toxic effects of drugs and/or compatibility of medicines on body, and clarify the mechanism of toxicity. Network toxicology currently develops rapidly in safety prediction of Chinese materia medica （CMM）. The application of network toxicology to safety and toxicology study on CMM is extremely beneficial to identify the toxic components and potential incompatibility of CMM. Since CMM is a complex system with multi-components, multi-targets, and multi-interactions, the network toxicology in safety prediction of CMM faces three great challenges, including integration studies of bioinformatics, innovation of methods, and tools and risk assessment in future development of the network toxicology in CMM research. In this paper, relevant database, approaches and tools that network toxicology utilized in the safety study of CMM were carefully reviewed. Based on the progress made, the scientific development and modernization of CMM will be greatly enhanced.

Xenobiotic receptors in mediating the effect of sepsis on drug metabolism

Sepsis is an infection-induced systemic inflammatory syndrome.The immune response in sepsis is characterized by the activation of both proinflammatory and anti-inflammatory pathways.When sepsis occurs,the expression and activity of many inflammatory cytokines are markedly affected.Xenobiotic receptors are chemical-sensing transcription factors that play essential roles in the transcriptional regulation of drug-metabolizing enzymes(DMEs).Xenobiotic receptors mediate the functional crosstalk between sepsis and drug metabolism because the inflammatory cytokines released during sepsis can affect the expression and activity of xenobiotic receptors and thus impact the expression and activity of DMEs.Xenobiotic receptors in turn may affect the clinical outcomes of sepsis.Thisreview focuses on the sepsis-induced inflammatory response and xenobiotic receptors such as pregnane X receptor(PXR),aryl hydrocarbon receptor(AHR),glucocorticoid receptor(GR),and constitutive androstane receptor(CAR),DMEs such as CYP1A,CYP2B6,CYP2C9,and CYP3A4,and drug transporters such as p-glycoprotein(P-gp),and multidrug resistance-associated protein(MRPs)that are affected by sepsis.Understanding the xenobiotic receptor-mediated effect of sepsis on drug metabolism will help to improve the safe use of drugs in sepsis patients and the development of new xenobiotic receptor-based therapeutic strategies for sepsis.