Effect of toll-like receptor 3 agonist poly I:C on intestinal mucosa and epithelial barrier function in mouse models of acute colitis

AIM To investigate potential effects of poly I:C on mucosal injury and epithelial barrier disruption in dextran sulfate sodium(DSS)-induced acute colitis.METHODS Thirty C57BL/6 mice were given either regular drinking water(control group) or 2%(w/v) DSS drinking water(model and poly I:C groups) ad libitum for 7 d. Poly I:C was administrated subcutaneously (20 μg/mouse) 2 h prior to DSS induction in mice of the poly I:C group. Severity of colitis was evaluated by disease activity index, body weight, colon length, histology and myeloperoxidase (MPO) activity, as well as the production of proinflammatory cytokines, including tumor necrosis factor-α(TNF-α), interleukin 17(IL-17) and interferon-γ (IFN-γ). Intestinal permeability was analyzed by the fluorescein isothiocyanate labeleddextran (FITC-D) method. Ultrastructural features of the colon tissue were observed under electron microscopy. Expressions of tight junction(TJ) proteins, including zo-1, occludin and claudin-1, were measured by immunohistochemistry/immunofluorescence, Western blot and real-time quantitative polymerase chain reaction(RT-qPCR).RESULTS DSS caused significant damage to the colon tissue in the model group. Administration of poly I:C dramatically protected against DSS-induced colitis, as demonstrated by less body weight loss, lower disease activity index score, longer colon length, colonic MPO activity, and improved macroscopic and histological scores. It also ameliorated DSS-induced ultrastructural changes of the colon epithelium, as observed under scanning electron microscopy, as well as FITC-D permeability. The m RNA and protein expressions of TJ protein, zo-1, occludin and claudin-1 were also found to be significantly enhanced in the poly I:C group, as determined by immunohistochemistry/immunofluorescence, Western blot and RT-q PCR. By contrast, poly I:C pretreatment markedly reversed the DSS-induced up-regulated expressions of the inflammatory cytokines TNF-α, IL-17 and IFN-γ.CONCLUSION Our study suggested that poly I:C may protect against DSS-induced colitis through maintaining integrity of the epithelial barrier and regulating innate immune responses, which may shed light on the therapeutic potential of poly I:C in human colitis.

The relationship between serum miR-21 levels and left atrium dilation in elderly patients with essential hypertension

BACKGROUND MicroRNA-21(miR-21)is related to hypertension and cardiac remodelling.Left atrium(LA)dilation is highly sensitive to small haemodynamic changes in the left ventricle(LV)that are induced by hypertension.This study aimed to elucidate the relationship between miR-21 expression and LA dilation in elderly patients with essential hypertension(EH).METHODS In this cross-sectional study,one hundred elderly patients with EH were recruited for the study.According to their left atrium diameters(LADs),the patients were divided into the LA dilation group[42 patients(42%)]and the no-LA dilation group[58 patients(58%)].The serum levels of miR-21 and chemical biomarkers used in the clinic,such as creatinine,blood urea nitrogen,uric acid,fasting blood glucose,total cholesterol(TC),triglyceride(TG),high-density lipoprotein cholesterol(HDLC),low-density lipoprotein cholesterol(LDL-C),very-low-density lipoprotein cholesterol,Lp(a),apolipoprotein A1(apoA1),and apolipoprotein B,were measured.All the patients underwent echocardiographic examination,and the LAD,interventricular septum(IVS),right atrium diameter(RAD),right ventricle diameter(RVD),left ventricular end-systolic diameter(LVESD),left ventricular end-systolic diameter(LVEDD)and left ventricular ejection fraction(LVEF)were measured.RESULTS The levels of miR-21[8.02(5.21,14.39)vs.6.05(3.81,8.95),P=0.011]and LVEF(67.02±3.82 vs.64.14±4.43,P=0.001)were higher in the LA dilation group.The levels of creatinine[70.40(64.45,80.15)vs.63.9(60.1,73.43)],P=0.020]were higher in the no-LA dilation group.The levels of HDLC(r=-0.209,P=0.037),apoA1(r=-0.269,P=0.007)and RAD(r=0.203,P=0.043)were significantly correlated with miR-21 expression.The LAD was significantly correlated with the RAD(r=0.287,P=0.004),RVD(r=0.450,P<0.001),LVEDD(r=0.248,P=0.013)and LVEF(r=0.232,P=0.020).Multivariate logistic regression revealed that miR-21 significantly influenced LA dilation in elderly patients with EH(P<0.05).CONCLUSIONS Circulating serum levels of miR-21 are increased in elderly patients with EH with LA dilation.miR-21 levels are significantly correlated with LA dilation in elderly patients with EH,and miR-21 may be a factor related to the clinical pathophysiological occurrence of and treatment for the progression of hypertension-related early heart damage in EH patients.

Study on the medication rules of traditional Chinese medicine in the treatment of sleep disorder after stroke based on data mining

Objective:To explore the medication rule of Traditional Chinese Medicine(TCM)in the treatment of sleep disorder after stroke by using data mining technology.Methods:A computer search was used to search the electronic database of clinical literature on the treatment of sleep disorders after stroke by TCM from January 2000 to January 2021.Excel was used to establish the database,and the prescription information was described and analyzed statistically.Using IBM SPSS Modeler 18.0 software,Apriori algorithm was used for TCM association analysis,and IBM SPSS 22.0 software was used for systematic cluster analysis of high-frequency TCM.Results:A total of 67 literatures were included,covering 131 traditional Chinese medicines.The medecines with a higher frequency of sodium use include Ziziphi Spinosae Semen(Suanzaoren),Angelicae Sinensis Radix(Danggui),Ligusticum(Chuanxiong),liquorice(Gancao),Poria cocos(Fuling),and so on.From the effect point of view,deficiency-tonifying medicine,sedative medicine and blood-activating and stasis-removing medicine are commonly used.The medicinal properties are mainly cold,mild and warm.The main medicine flavor are sweet and bitter.The medicines mostly belong to the liver,heart and spleen Meridian.Thirty-three association rules were obtained for medicine pairs and medicine groups from the correlation analysis,and the core combinations were"Ziziphi Spinosae Semen(Suanzaoren)-Tuber fleeceflower stem(Yejiaoteng)","Ziziphi Spinosae Semen(Suanzaoren)-Polygala(Yuanzhi)","Ziziphi Spinosae Semen(Suanzaoren)-Cortex albiziae(Hehuanpi)"and"Angelicae Sinensis Radix(Danggui)-Radix bupleuri(Chaihu)-Radix Paeoniae Alba(Baishao)"and so on.Seven medicine aggregation groups were obtained by medicine cluster analysis.Conclusion:In the treatment of sleep disorder after stroke by TCM,the main method is to calm the heart and mind.Meanwhile,according to different syndrome types,the treatment methods of tonifying the heart and spleen,nourishing the liver and kidney,soothing the liver and softening the liver,clearing heat and resolving phlegm,nourishing the blood and promoting blood circulation are selected,which provide certain reference for clinical treatment.