1.Research progress in therapeutic targets and drugs for eosinophilic gastroenteritis
Xinyi ZHANG ; Yinru JIANG ; Ziyuan ZHAO ; Longrui WANG ; Wenjing SUN ; Guanhua DU ; Linglei KONG
Chinese Journal of Pharmacology and Toxicology 2025;39(7):538-549
Eosinophilic gastroenteritis(EG)is a rare disease characterized by abnormal infiltration of eosinophils(Eos)in gastrointestinal tissues.Due to the unclear pathogenesis of EG and the lack of effective therapeutic drugs,research on its novel mechanisms,targets and drugs is critical.This article starts by outlining the research progress in the pathogenesis of EG,involving IgE mediated typeⅠimmediate allergic reactions and T helper 2 cell(Th2)mediated delayed allergic reactions.Then,the related targets of EG are summarized,including Th2 cytokines and factors regulating Eos function,but there has been no breakthrough in the treatment of these targets.Finally,the therapeutic drugs for EG are reviewed,such as glucocorticoids,antiallergic drugs and biologics.The advantages and disadvantages of various drugs are also described.However,these drugs cannot meet the current demands of clinical treatment and there is an urgent need to develop novel therapeutic drugs.It is believed that multi-target therapy is an ideal treatment for EG,and that traditional Chinese medicine and natural products should be the priorities of research and development for EG therapeutic drugs in the future.This review is expected to provide new ideas for the clinical treatment strategies and drug development of EG.
2.Effects of salvianolic acid A on functions of neutrophils after activation in vitro
Longrui WANG ; Ziyuan ZHAO ; Yinru JIANG ; Zhaowei LI ; Wenjing SUN ; Guanhua DU ; Linglei KONG
Chinese Journal of Pharmacology and Toxicology 2025;39(7):518-526
OBJECTIVE To investigate the effect of salvianolic acid A(SAA)on functions of neutro-phils after activation in vitro.METHODS Rat neutrophils were extracted and activated by lipopolysac-charide(LPS)at 0.3,1,3 mg·L-1,and the number of adherent neutrophils and myeloperoxidase(MPO)activity were detected to determine the concentration of LPS.Neutrophils were divided into the control,model,model+4-aminobenzohydrazide(ABH)20 μmol·L-1,and model+SAA 1,3 and 10 μmol·L-1 groups.LPS was stimulated with 3 mg·L-1 for 30 min,and the neutrophil adhesion rate was detected by immunofluorescence after 1 h of drug incubation.After 2 h of drug incubation,phagocytosis of neutro-phils was detected by immunofluorescence and fluorescein isothiocyanate-immunoglobulin G.After 3 h of drug incubation,the neutrophil adhesion rate to endothelial cells was detected by colorimetric assay.Intracellular MPO activity and hypochlorous acid(HOCl)production were investigated by colorimetric assay in response to the degranulation function.Intracellular reactive oxygen species(ROS)levels were detected by probe assay,and mitochondrial membrane potential by JC-1 assay.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and total antioxidant capacity(T-AOC)were measured to reflect oxidation function of neutrophils.RESULTS LPS increased the number of adherent cells and MPO activity in a concentration-dependent manner,with 3 mg·L-1 of LPS showing the most significant effect,which was used for subsequent experiments.Compared with the control group,LPS-activated neutrophil adhesion and phagocytosis were significantly enhanced.MPO activity and HOCl production significantly increased.The levels of ROS and MDA in LPS-activated neutrophils were significantly increased while the mitochondrial membrane potential and the levels of SOD,GSH,T-AOC were significantly decreased,indicating that the oxidative stress ability was enhanced.Compared with the model group,SAA dose-dependently inhibited LPS-induced adhesion,phagocytosis,degranu-lation,and ROS generation of neutrophils,with significant effects at medium and high doses.CONCLU-SION SAA can inhibit different functions of neutrophils after activation,which may be a potential drug for targeting neutrophil function regulation.
3.Research progress in therapeutic targets and drugs for eosinophilic gastroenteritis
Xinyi ZHANG ; Yinru JIANG ; Ziyuan ZHAO ; Longrui WANG ; Wenjing SUN ; Guanhua DU ; Linglei KONG
Chinese Journal of Pharmacology and Toxicology 2025;39(7):538-549
Eosinophilic gastroenteritis(EG)is a rare disease characterized by abnormal infiltration of eosinophils(Eos)in gastrointestinal tissues.Due to the unclear pathogenesis of EG and the lack of effective therapeutic drugs,research on its novel mechanisms,targets and drugs is critical.This article starts by outlining the research progress in the pathogenesis of EG,involving IgE mediated typeⅠimmediate allergic reactions and T helper 2 cell(Th2)mediated delayed allergic reactions.Then,the related targets of EG are summarized,including Th2 cytokines and factors regulating Eos function,but there has been no breakthrough in the treatment of these targets.Finally,the therapeutic drugs for EG are reviewed,such as glucocorticoids,antiallergic drugs and biologics.The advantages and disadvantages of various drugs are also described.However,these drugs cannot meet the current demands of clinical treatment and there is an urgent need to develop novel therapeutic drugs.It is believed that multi-target therapy is an ideal treatment for EG,and that traditional Chinese medicine and natural products should be the priorities of research and development for EG therapeutic drugs in the future.This review is expected to provide new ideas for the clinical treatment strategies and drug development of EG.
4.Effects of salvianolic acid A on functions of neutrophils after activation in vitro
Longrui WANG ; Ziyuan ZHAO ; Yinru JIANG ; Zhaowei LI ; Wenjing SUN ; Guanhua DU ; Linglei KONG
Chinese Journal of Pharmacology and Toxicology 2025;39(7):518-526
OBJECTIVE To investigate the effect of salvianolic acid A(SAA)on functions of neutro-phils after activation in vitro.METHODS Rat neutrophils were extracted and activated by lipopolysac-charide(LPS)at 0.3,1,3 mg·L-1,and the number of adherent neutrophils and myeloperoxidase(MPO)activity were detected to determine the concentration of LPS.Neutrophils were divided into the control,model,model+4-aminobenzohydrazide(ABH)20 μmol·L-1,and model+SAA 1,3 and 10 μmol·L-1 groups.LPS was stimulated with 3 mg·L-1 for 30 min,and the neutrophil adhesion rate was detected by immunofluorescence after 1 h of drug incubation.After 2 h of drug incubation,phagocytosis of neutro-phils was detected by immunofluorescence and fluorescein isothiocyanate-immunoglobulin G.After 3 h of drug incubation,the neutrophil adhesion rate to endothelial cells was detected by colorimetric assay.Intracellular MPO activity and hypochlorous acid(HOCl)production were investigated by colorimetric assay in response to the degranulation function.Intracellular reactive oxygen species(ROS)levels were detected by probe assay,and mitochondrial membrane potential by JC-1 assay.The levels of malondialdehyde(MDA),superoxide dismutase(SOD),glutathione(GSH)and total antioxidant capacity(T-AOC)were measured to reflect oxidation function of neutrophils.RESULTS LPS increased the number of adherent cells and MPO activity in a concentration-dependent manner,with 3 mg·L-1 of LPS showing the most significant effect,which was used for subsequent experiments.Compared with the control group,LPS-activated neutrophil adhesion and phagocytosis were significantly enhanced.MPO activity and HOCl production significantly increased.The levels of ROS and MDA in LPS-activated neutrophils were significantly increased while the mitochondrial membrane potential and the levels of SOD,GSH,T-AOC were significantly decreased,indicating that the oxidative stress ability was enhanced.Compared with the model group,SAA dose-dependently inhibited LPS-induced adhesion,phagocytosis,degranu-lation,and ROS generation of neutrophils,with significant effects at medium and high doses.CONCLU-SION SAA can inhibit different functions of neutrophils after activation,which may be a potential drug for targeting neutrophil function regulation.
5.Association of the DJ-1 gene polymorphism with sporadic Parkinson's disease in Sichuan province of China.
Wenjun CHEN ; Rong PENG ; Tao LI ; Yan WU ; Jinhong ZHANG ; Yincheng WANG ; Guanggu YUAN ; Yinru GOU ; Quying JIANG
Chinese Journal of Medical Genetics 2008;25(5):566-569
OBJECTIVETo investigate the frequencies of three polymorphisms in DJ-1 (g.168-185del; SNP405, refSNP ID:rs3766606 and 293 G/A) and their association with sporadic Parkinson's disease.
METHODSAn association study was performed to determine the genotype of each subject using polymerase chain reaction, restriction fragment length polymorphism and sequence analysis in 192 patients with sporadic Parkinson's disease and 198 healthy controls.
RESULTSIn the g.168-185del locus, the Ins/Ins genotype was common and the frequency of Del allele was very low (0.38%). The SNP of 293G/A was not detected in both groups. In the SNP405 G/T site, the GT genotype frequency was significantly higher in patients with age of onset before 40 years than in controls (18.75% vs 5.54%, P=0.004, OR=6.30 95%CI:1.96-20.18).
CONCLUSIONThe results suggest that the frequencies of the g.168-185del and 293G/A polymorphisms might be different between Chinese and European. The SNP405 GT genotype might be a risk factor for sporadic Parkinson's disease with early age of onset in Sichuan Han population.
Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Asian Continental Ancestry Group ; genetics ; Base Sequence ; Case-Control Studies ; China ; Female ; Gene Frequency ; Genotype ; Humans ; Intracellular Signaling Peptides and Proteins ; genetics ; Male ; Middle Aged ; Oncogene Proteins ; genetics ; Parkinson Disease ; genetics ; pathology ; Polymorphism, Genetic ; Protein Deglycase DJ-1

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