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.

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.

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.

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.

Objective To analyze the impacts of curcumin on the inflammation and activation of microglia in dorsal horn of spinal cord in rats with lumbar disc herniation(LDH)by regulating the CXC chemokine ligand 12(CXCL12)/CXC chemokine receptor 4(CXCR4)signaling pathway.Methods Rats were randomly separated into sham surgery group,model group,curcumin low,medium,and high-dose groups,and curcumin high-dose+NUCC-390(CXCL12/CXCR4 signaling pathway activator)group.The motor function and scores of rats in each group were observed.Pain hypersensitivity experiment was applied to determine the mechanical stimulation foot contraction reflex threshold(PWMT)and the thermal stimulation foot contraction reflex latency(PWTL).HE staining was applied to observe pathological changes in the spinal dorsal horn tissue.Immunofluorescence staining was applied to observe the expression of Iba-1.ELISA was applied to detect levels of TNF-α,IL-8,and IL-2.Western blot was applied to detect the expression of Iba-1,CXCL12,and CXCR4 pathway proteins.Results Compared with the sham surgery group,the nerve cells of rats in the LDH group shrank,and the nuclei and Nissl bodies decreased,the motor function score,TNF-α,IL-8,IL-2,Iba-1,CXCL12,and CXCR4 expression elevated,PWMT and PWML decreased(P＜0.05).Compared with the LDH group,the morphology of nerve cells in the curcumin low,medium,and high dose groups recovered,nucleoli were clear,and Nissl bodies increased,the motor function score,TNF-α,IL-8,IL-2,Iba-1,CXCL12,and CXCR4 expression decreased,PWMT and PWML increased(P＜0.05).Compared with the curcumin high-dose group,the curcumin high-dose+NUCC-390 group showed nerve cell damage,the motor function score,TNF-α,IL-8,IL-2,Iba-1,CXCL12,and CXCR4 expression elevated,PWMT and PWML decreased(P＜0.05).Conclusion Curcumin can inhibit inflammatory response and the activation of microglia in spinal dorsal horn in LDH rats,and the mechanism of action may be related to the inhibition of the CXCL12/CXCR4 signaling pathway.

Objective To analyze the impacts of curcumin on the inflammation and activation of microglia in dorsal horn of spinal cord in rats with lumbar disc herniation(LDH)by regulating the CXC chemokine ligand 12(CXCL12)/CXC chemokine receptor 4(CXCR4)signaling pathway.Methods Rats were randomly separated into sham surgery group,model group,curcumin low,medium,and high-dose groups,and curcumin high-dose+NUCC-390(CXCL12/CXCR4 signaling pathway activator)group.The motor function and scores of rats in each group were observed.Pain hypersensitivity experiment was applied to determine the mechanical stimulation foot contraction reflex threshold(PWMT)and the thermal stimulation foot contraction reflex latency(PWTL).HE staining was applied to observe pathological changes in the spinal dorsal horn tissue.Immunofluorescence staining was applied to observe the expression of Iba-1.ELISA was applied to detect levels of TNF-α,IL-8,and IL-2.Western blot was applied to detect the expression of Iba-1,CXCL12,and CXCR4 pathway proteins.Results Compared with the sham surgery group,the nerve cells of rats in the LDH group shrank,and the nuclei and Nissl bodies decreased,the motor function score,TNF-α,IL-8,IL-2,Iba-1,CXCL12,and CXCR4 expression elevated,PWMT and PWML decreased(P＜0.05).Compared with the LDH group,the morphology of nerve cells in the curcumin low,medium,and high dose groups recovered,nucleoli were clear,and Nissl bodies increased,the motor function score,TNF-α,IL-8,IL-2,Iba-1,CXCL12,and CXCR4 expression decreased,PWMT and PWML increased(P＜0.05).Compared with the curcumin high-dose group,the curcumin high-dose+NUCC-390 group showed nerve cell damage,the motor function score,TNF-α,IL-8,IL-2,Iba-1,CXCL12,and CXCR4 expression elevated,PWMT and PWML decreased(P＜0.05).Conclusion Curcumin can inhibit inflammatory response and the activation of microglia in spinal dorsal horn in LDH rats,and the mechanism of action may be related to the inhibition of the CXCL12/CXCR4 signaling pathway.

In the present study, the specifically knockdown models of P-gp or MRP2 were constructed by using a series of chemically synthesized small interfering RNA (siRNA) in vitro. The expression of P-gp and MRP2 was measured by real-time PCR and Western blot, and the function was evaluated by applying P-gp and MRP2 substrate, rhodamine and methotrexate. The results showed that MRP2 siRNA-3 or P-gp siRNA-2 significantly decreased the mRNA expression of MRP2 or P-gp, the inhibition ratio was 68% or 84%; MRP2 siRNA-3 or P-gp siRNA-2 at a dose of 80 nmol x L(-1) significantly reduced the protein expression of MRP2 or P-gp at 48 h after treatment, the inhibition ratio was 62% or 70%. Meanwhile, other transporters were not influenced by siRNA. When pretreatment with MRP2 siRNA-3 or P-gp siRNA-2, the efflux of methotrexate or rhodamine decreased significantly and the intra-cellular concentration increased. The results suggested that chemically synthesized siRNA could significantly inhibit the expression and function of MRP2 and P-gp, and the model of RNAi in vitro could be used to evaluate the role of efflux transporters in transportation of drugs.

Cardiac hypertrophy is a major adaptational mechanism in stresses such as pressure overload and neurohumoral stimulation.As powerful vasoconstrictor peptides in cardiovascular system,especially the vascular endothelium,smooth muscle cells and cardiocyte,ETs play important physiological roles in the regulation of normal cardiovascular function.Excessive generation of ETs in local cardiac muscle has been linked to myocardial hypertrophy.Endothelin-1(ET-1) in cardiac muscle exerts its actions in the development of myocardial hypertrophy through binding to specific receptors and interacting with other vasoactive substance of local tissues.ET-1 can induce the hypertrophy for cardiocytes and the proliferation for cardiac fibroblasts by ETA.ETB receptors are implicated both in initiating and maintaining myocardial hypertrophy.As a new target of drug,ET receptors have become the research focus,and great progress has been made on the development of the ET antagonists.