ABSTRACT
Polyphyllin Ⅰ(PPⅠ)and polyphyllin Ⅱ(PⅡ)are the main active substances in the Paris polyphylla.However,liver toxicity of these compounds has impeded their clinical application and the potential hepatotoxicity mechanisms remain to be elucidated.In this work,we found that PPⅠ and PⅡ exposure could induce significant hepatotoxicity in human liver cell line L-02 and zebrafish in a dose-dependent manner.The results of the proteomic analysis in L-02 cells and transcriptome in zebrafish indicated that the hepa-totoxicity of PPⅡ and PⅡwas associated with the cholesterol biosynthetic pathway disorders,which were alleviated by the cholesterol biosynthesis inhibitor lovastatin.Additionally,3-hydroxy-3-methy-lglutaryl CoA reductase(HMGCR)and squalene epoxidase(SQLE),the two rate-limiting enzymes in the choles-terol synthesis,selected as the potential targets,were confirmed by the molecular docking,the over-expression,and knockdown of HMGCR or SQLE with siRNA.Finally,the pull-down and surface plasmon resonance technology revealed that PPⅠ could directly bind with SQLE but not with HMGCR.Collectively,these data demonstrated that PPⅠ-induced hepatotoxicity resulted from the direct binding with SQLE protein and impaired the sterol-regulatory element binding protein 2/HMGCR/SQLE/lanosterol synthase pathways,thus disturbing the cholesterol biosynthesis pathway.The findings of this research can contribute to a better understanding of the key role of SQLE as a potential target in drug-induced hepatotoxicity and provide a therapeutic strategy for the prevention of drug toxic effects with similar structures in the future.
ABSTRACT
Objective To investigate the application value of combined detection of four diarrhea viral antigens (rotavirus ,enteric adenovirus ,norovirus ,astrovirus) in suspected food poisoning .Methods One hundred and seventy-six stool samples from the pa-tients with acute phase of suspected food poisoning were collected and performed the 4-item viral antigen detection by adopting the immunofluorescence chromatography ,and at the same time the culture and identification of pathogenic bacteria at the same time were performed .Results Among 176 stool samples of patients with suspected food poisoning ,one strain of Shigella was detected and other pathogens were not detected out ;the detection rates of four viral antigens of rotavirus ,enteric adenovirus ,norovirus and astrovirus were 9 .66% ,1 .70% ,14 .77% and 2 .84% respectively .Conclusion The combined detection of four diarrhea viral anti-gens can definite viral pathogens ,timely identify and early warn food-borne disease outbreaks .
ABSTRACT
Feeding intolerance in preterm infants,which is an important issue that the neonatal pediatri-cians have to work out,leads to malnutrition of early preterm infants and growth restriction which have an impact on later behavioral and cognitive outcomes. Feeding intolerance is related to the immature of gastrointestinal function,perinatal asphyxia,infection and other diseases. Minimal enteral feeding,prokinetic agents and supple-mentation of the enteral probiotics,are used generally,but at present there is no guidelines for the prevention and treatment.
ABSTRACT
From the perspective of modern medicine, we analyzed the relationship between procedure of diabetes and the hepatic physiological functions as well as pathological mechanisms. Liver dysfunction played a key role in each stage of type 2 diabetes. It's the basis for disorders of nervous, endocrine and immune systems. Using TCM methods to protect the liver can be useful to interfere the development of diabetes and achieve sound therapeutic effects.