1.Neutralization of anti-venom IgY against main activities of Deinagkistrodon acutus venom
Jinhua LIU ; Heng LI ; Qiyi HE ; Yingfeng ZHANG ; Diancheng CHEN ; Cong LUO ; Xiaodong YU
Chinese Pharmacological Bulletin 2017;33(1):58-62
Aim To evaluate the potency of anti-D. acutus venom IgY neutralizing the main activities of D. acutus venom.Methods After mixing the different a-mounts of IgY with snake venom and incubating togeth-er,the main activities of snake venom were assayed by biochemical methods.Results The in vitro assays in-dicated that anti-D.acutus venom IgY obviously neu-tralized the activities of PLA2 ,5′-nucleotidase,hyalu-ronidase,metalloprotease and serine proteinase (fi-brinogenase)in D.acutus venom.Mouse experiments showed that the ED50 value of IgY for mouse was 1 131.09 μg.Conclusion Anti-D.acutus venom IgY antibodies have good effects in neutralizing D.acutus venom without the toxicities themselves.
2.Effect of Gehua Jiejiu Dizhi Decoction on energy metabolism in liver tissue of alcoholic liver disease mice
Rui LIU ; Xu YI ; Xueli WU ; Shuoshi WANG ; Diancheng HE ; Shaowei YOU
Journal of Beijing University of Traditional Chinese Medicine 2024;47(5):662-671
Objective To detect the level of related indexes of energy metabolism in liver tissue of alcoholic liver disease(ALD)mice,and to explore the intervention effect of Gehua Jiejiu Dizhi Decoction.Methods Forty male C57BL/6J mice were randomly divided into the normal control group,the model group,the Gehua Jiejiu Dizhi Decoction high-dose group(4.94 g/kg),the Gehua Jiejiu Dizhi Decoction low-dose group(2.47 g/kg),and the resveratrol group(0.40 g/kg),with 8 mice in each group.Except the normal control group,the mice in other groups were fed with Lieber-DeCarli control liquid diet for five days,followed by Lieber-DeCarli alcohol liquid diet for ten days,and on the 16th day,the mice were given 31.5%alcohol solution through gavage to establish the ALD model.From the second day after modeling,the rats in the intervention groups were given the corresponding drugs by gavage once a day for nine consecutive days.Hematoxylin and eosin staining and oil red O staining were used to observe the liver steatosis in liver tissue.The activities of Na+K+-ATPase and Ca2+Mg2+-ATPase,and the contents of succinate dehydrogenase(SDH)and hepatic glycogen in liver tissue were detected using spectrophotometry.The contents of ATP,ADP,AMP,the AMP/ATP value,total adenosine pool(TAN)content,and energy charge(EC)in liver tissue were detected by reversed phase high performance liquid chromatography method.The mRNA expressions of NAD dependent deacetylase Sirtuin-1(SIRT1)and AMP-activated protein kinase(AMPK)α2 in liver tissue were detected by real-time PCR.The protein expressions of SIRT1,AMPKα2,and AMPKβ1 in liver tissue were detected by Western blotting.Results Compared with the normal control group,the model group mice showed significant hepatic steatosis,significantly decreased Ca2+Mg2+-ATPase activity and SDH content in liver tissue,significantly increased hepatic glycogen content,significantly decreased EC and AMP/ATP value,significantly increased ATP,ADP,AMP,and TAN content,significantly decreased mRNA expressions of SIRT1 and AMPKα2,significantly increased protein expression of AMPKβ1(P<0.05).Compared with the model group,the Gehua Jiejiu Dizhi Decoction high-and low-dose groups significantly reduced liver tissue steatosis,and the activity of Na+K+-ATPase in liver tissue was significantly reduced,the EC and the mRNA expressions of SIRT1 and AMPKα2 were increased(P<0.05);the activity of Ca2+Mg2+-ATPase,SDH and ATP contents were increased in the Gehua Jiejiu Dizhi Decoction low-dose group(P<0.05);the AMP/ATP value was increased in the Gehua Jiejiu Dizhi Decoction high-dose group(P<0.05);and the protein expression of SIRT1 was increased in the the Gehua Jiejiu Dizhi Decoction high-and low-dose groups and the resveratrol group(P<0.05);the protein expression of AMPKα2 in the Gehua Jiejiu Dizhi Decoction low-dose group and the resveratrol group was increased(P<0.05).Compared with the Gehua Jiejiu Dizhi Decoction high-dose group,the Gehua Jiejiu Dizhi Decoction low-dose group and the resveratrol group showed a significant increase in ATP,TAN contents,and EC in liver tissue,while the AMP/ATP value decreased(P<0.05);mRNA expressionin of AMPKα2 in the Gehua Jiejiu Dizhi Decoction low-dose group was decreased(P<0.05);and the protein expressions of SIRT1 and AMPKα2 in the resveratrol group were increased(P<0.05).Compared with the Gehua Jiejiu Dizhi Decoction low-dose group,the protein expression of AMPKβ1 was decreased in the resveratrol group(P<0.05).Conclusion The changes of energy metabolism caused by chronic alcohol intake may be related to the occurrence of ALD,and the intervention of Gehua Jiejiu Dizhi Decoction can improve the abnormal energy metabolism in the liver of ALD mice.
3.Transformation of Chronic Atrophic Gastritis into Gastric Cancer and Prevention and Treatment: Based on Spleen Deficiency and Pathogen Stagnation
Shaowei YOU ; Yamei ZHAN ; Wensu WANG ; Diancheng HE ; Xingzhu PENG ; Xueyong WANG
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(21):188-195
Gastric ''inflammation-cancer'' transformation stars from inflammation and ends as gastric cancer (GC), and the pathogenesis is still unclear. In China, GC features high morbidity and mortality and poor prognosis, influencing the quality of life and physical and mental health of patients. Therefore, it is of great significance to construct the prevention and treatment system for GC. Chronic atrophic gastritis (CAG) plays a key role in the occurrence, development, and outcome of gastric ''inflammation-cancer'' transformation. Modern therapies for CAG generally aim at eliminating causes and alleviating clinical symptoms, which show satisfactory short-term efficacy, but the reverse and recurrence are common. Based on the holistic view, syndrome differentiation-based treatment, and the ''inflammation-cancer'' transformation in modern medicine, traditional Chinese medicine emphasizes both prevention and treatment, with individualized therapies for CAG and GC to control the transformation. According to the pathogenesis of CAG-asthenia in origin and sthenia in superficiality and deficiency-excess in complexity, this study proposed the theory of spleen deficiency and pathogen stagnation in CAG, and believed spleen deficiency, pathogen, and stagnation are respectively the root cause of, the main factor of, and the key to ''inflammation-cancer'' transformation, respectively. Spleen deficiency and pathogen stagnation are closely related to the process of the transformation. For the treatment, the spleen-invigorating and pathogen-eliminating method should be used for invigorating the spleen to consolidate original Qi, improve the blood supply in stomach, and regulate immunity, and eliminating the pathogen to relieve stagnation, reduce the occurrence of non-controllable inflammation, and improve inflammatory micro-environment. As a result, the gastric inflammation is controlled at the early stage and the gastric ''inflammation-cancer'' transformation is blocked. The gastric mucosal lesions are blocked, delayed, or even reversed. This study provides a new idea in clinical diagnosis and treatment of CAG and in the prevention of GC.
4.Study on the role of NR1H4 in chronic atrophic gastritis and drug prediction based on bioinformatics
Xiaoting PENG ; Wensu WANG ; Diancheng HE ; Yamei ZHAN ; Shaowei YOU
China Modern Doctor 2024;62(4):5-10,23
Objective To explore the differential gene expression profile and small molecule drugs for chronic atrophic gastritis(CAG)by bioinformatics technology.Methods Two gene expression samples of CAG chips(GSE27411,GSE116312)were obtained through the Gene Expression Synthesis(GEO)database,screen the differentially expressed genes(DEGs)of CAG by R language,and CAG immune-related genes were obtained for gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Protein-protein interaction(PPI)network was constructed using STRING database to screen out core genes,further study on immune invasion of core genes based on GSE27411 dataset,small molecular compounds interacting with core genes were predicted,molecular docking was carried out by MOE2022,and survival analysis was carried out by GEPIA2 website.Results A total of 517 DEGs were screened out based on GEO database.GO function enrichment analysis found that it mainly involved in granulocyte chemotaxis、leukocyte chemotaxis and neutrophil chemotaxis biological processes.KEGG pathway enrichment analysis showed that it mainly involved in cytokine-cytokine receptor interaction、nuclear factor kappa B signaling pathway、interleukin-17 signaling pathway.Six key genes of NR1H4、CCK、CCL20、CXCL1、LCN2、SAA1 were obtained by PPI network,through relevant verification,NR1H4 was regarded as the core gene.Immune cell infiltration analysis showed that central memory CD8 T cell、effector memeory CD4 T cell、gamma delta T cell、natural killer T cell、neutrophil and other immune cells may be involved in the development of CAG,and the neutrophil was positively correlated with NR1H4.It was predicted that six small molecular drugs,corilagin,stigmasterol,geniposide,tangeretin,chenodeoxycholic acid and epigallocatechin 3-gallate,have good binding force with NR1H4.Conclusion The potential mechanism of CAG is preliminarily explored in this study,the key gene of NR1H4 and neutrophil may play an important role in the"inflammatory cancer transformation"process of CAG,which can provide a certain reference for the study of the"inflammatory cancer transformation"mechanism of CAG.
5.Mechanism of Weiwei Tongtiao Decoction Against Chronic Atrophic Gastritis in Rats: Based on NF-κB Signaling Pathway
Shaowei YOU ; Xu YI ; Qi ZHAO ; Wensu WANG ; Ling YANG ; Diancheng HE ; Pingzhen TONG ; Xueyong WANG ; Yamei ZHAN
Chinese Journal of Experimental Traditional Medical Formulae 2023;29(2):88-97
ObjectiveTo explore the effect of Weiwei Tongtiao decoction (WTD) on chronic atrophic gastritis (CAG) rats and the underlying mechanism. MethodA total of 90 SD rats were randomized into normal control group, model group, high-dose, medium-dose, and low-dose WTD groups (18, 9, 4.5 g·kg-1·d-1 WTD, respectively, ig), and weifuchun control group (0.45 g·kg-1·d-1 weifuchun aqueous solution, ig), with 15 rats in each group. The N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) was employed to induced CAG in rats. After the modeling (identified by histopathological examination), the administration began and lasted 12 weeks. Then, gastric mucosa tissues of the rats were collected and stained with hematoxylin and eosin (HE), and the pathological changes of gastric mucosa were observed under the optical microscope. Real-time PCR, immunohistochemistry (IHC), and Western blotting were applied to examine the mRNA and protein expression of indexes in nuclear factor kappa-B (NF-κB) signaling pathway in the gastric mucosa of rats. ResultCAG rats showed irregular arrangement and morphology of the inherent glands in gastric mucosa and the glands decreased or disappeared. In addition, inflammatory cell infiltration was observed in the lamina propria of CAG rats, and about 48.4% presented intestinal metaplasia. WTD significantly alleviated the reduction of the glands and intestinal metaplasia in a dose-dependent manner. Compared with the normal control group, the model group demonstrated increase in the mRNA expression of cyclooxygenase-2 (COX-2), NF-κB p65, interleukin (IL)-1α, IL-1β, IL-10, IL-8α, and IL-8β, and protein expression of COX-2, NF-κB p65, and IL-10 (P<0.01). WTD and weifuchun lowered the mRNA expression of COX-2, NF-κB p65, IL-1α, IL-1β, IL-10, IL-8α, and IL-8β, and the protein expression of COX-2, NF-κB p65, and IL-10 in gastric mucosa of CAG rats (P<0.01). The expression of the above indexes after the intervention with high-dose WTD was close to that of the normal control group. ConclusionWTD can improve or even reverse the diseased gastric mucosa of CAG rats, and the mechanism is the likelihood that WTD down-regulates the mRNA and protein expression of the indexes in NF-κB signaling pathway in gastric mucosa of CAG rats.