Effect of Xifeng Capsule on blood stasis in patients with rheumatoid arthritis by regulating miR-126-VEGF/PI3K/AKT signaling pathway

Objective:From the perspective of miR-126-vascular endothelial cytokine(VEGF)/phosphatidylinositol 3-kinase(PI3K)/ser-threonine protein kinase(AKT)signaling pathway,Xinfeng Capsule(XFC)can improve rheumatoid arthritis(RA))The mechanism of the patient's blood stasis state.Methods:Sixty RA patients meeting the diagnostic criteria were selected and divided into XFC treatment group 30 cases and Leflunomide(LEF)control group 30 cases according to the random number table method.The treatment group took Xinfeng Capsules(3 capsules each time,3 times/d),and the control group took Leflunomide(1 capsule each time,1 times/d).Observe the blood stasis symptom scores of RA patients,and detect the laboratory indicators erythrocyte sedimentation rate(ESR),c-reactive protein(CRP),rheumatoid factor(RF),anti-cyclic citrullinated peptide antibody(CCP),thrombin time(TT),part prothrombin time(APTT),prothrombin time(PT),D dimer(DD),fibrinogen(FBG),platelets(PLT),mean platelet volume(MPV),platelet distribution width(PDW)levels.Real-time fluorescent quantitative PCR method was used to detect the level of miR-126,and the ELISA method was used to detect the levels of tumor necrosis factor(TNF-α),interleukin-6(IL-6),IL-35,VEGF,PI3K,and AKT.Spearman method was used to analyze the correlation between the total score of blood stasis symptoms,blood stasis-related indicators and disease activity indicators,cytokines,miR-126,VEGF,PI3K,and AKT in RA patients.Results:Comparing the two groups after treatment,the XFC group improved blood stasis symptoms,disease activity indicators,decreased miR-126,VEGF,PI3K,AKT,TNF-α,IL-6,D-D,FBG,PLT,and increased IL-35 The level was significantly better than the LEF group,with statistical significance(P<0.05,P<0.01).Correlation analysis showed that there was a certain correlation between the total score of blood stasis symptoms,blood stasis related indicators and disease activity indicators,cytokines,miR-126,VEGF,PI3K,and AKT in RA patients.Conclusion:There is blood stasis in RA patients.XFC may improve the cytokine network disorder of patients through miR-126-VEGF/PI3K/AKT signaling pathway,thereby improving the blood stasis status of RA patients.

Tetramethylpyrazine and paeoniflorin combination(TMP-PF)inhibits angiogenesis in atherosclerosis via miR-126/VEGF/VEGFR2 signaling pathway

Angiogenesis in atherosclerosis(AS)promotes plaque destabilization.miR-126 has a significant role in angiogenesis.Tetramethylpyrazine(TMP)and paeoniflorin(PF)have anti-atherosclerotic effects.However,the miR-126-related mechanisms of TMP and PF combination(TMP-PF)on angiogenesis in AS have not been understood.To explore the mechanism of TMP-PF on angiogenesis in AS targeting miR-126.Human umbilical vein endothelial cells(HUVECs)were assigned into the control,model,TMP-PF,TMP-PF+miR-126 inhibitor,and simvastatin groups.HUVECs were transfected with miR-126 inhibitor or negative control,incubated with oxidized low-density lipoprotein(ox-LDL)to establish AS model,and then treated with TMP-PF or simvastatin.Cell proliferation,migration,and tube formation assays are conducted,and the expression of angiogenesis-related factors were detected by enzyme-linked immunosorbent assay(ELISA)and Western blotting.The expression level of miR-126 was confirmed by polymerase chain reaction(PCR).0x-LDL promoted HUVECs proliferation,migration,and tube formation,downregulated miR-126 expression,and increased the expression of VEGF,VEGFR2,bFGF,and FGFR1.TMP-PF inhibited proliferation,migration,and tube formation,upregulated miR-126 expression and decreased the expression of VEGF,VEGFR2,bFGF,and FGFR1 in ox-LDL-induced HUVECs.However,the effects of TMP-PF on angiogenesis and the expression of miR-126,VEGF,VEGFR2,and FGFR1 were abolished by miR-126 inhibitor.TMP-PF suppressed angiogenesis in AS by regulating miR-126/VEGF/VEGFR2 pathway,which might elucidate the underlying mechanism of TMP-PF in alleviating AS.

Vascular endothelial growth factor: an attractive target in the treatment of hypoxic/ischemic brain injury

Cerebral hypoxia or ischemia results in cell death and cerebral edema, as well as other cellular reactions such as angiogenesis and the reestablishment of functional microvasculature to promote recovery from brain injury. Vascular endothelial growth factor is expressed in the central nervous system after hypoxic/ischemic brain injury, and is involved in the process of brain repair via the regulation of angiogenesis, neurogenesis, neurite outgrowth, and cerebral edema, which all require vascular endothelial growth factor signaling. In this review, we focus on the role of the vascular endothelial growth factor signaling pathway in the response to hypoxic/ischemic brain injury, and discuss potential therapeutic interventions.