Objective To identify biomarkers that characterize its bitter-cold properties of Scutellaria Radix on the basis of evaluating its cold and hot properties,as well as possible metabolic pathways and related targets;To explore its molecular mechanism.Methods Totally 40 mice were randomly divided into a control group and a treatment group,and were orally administered with normal saline and Scutellaria Radix decoction,respectively,for 4 consecutive days.The cold and hot plate differential method was used to evaluate the cold and hot tendencies of the mice;UPLC-MS/MS technology was used to analyze mouse blood samples,differential metabolites were screened using principal component analysis,partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis methods,and metabolic pathway analysis was performed;network modular analysis of differential metabolites was performed using Cytoscape 3.9.0 software to identify potential molecular targets.Results On the second day of administration,the anal temperature of mice in the treatment group decreased significantly compared to the control group(P<0.01);in the cold and hot tendency test,the mice in the treatment group showed an overall increase in high-temperature tendency and a higher proportion of high-temperature zone retention.There was a statistically significant difference(P<0.01,P<0.05)between the treatment group and the control group on the 2nd and 3rd day of treatment;the pattern recognition analysis of serum metabolome data showed that the serum samples of the treatment group and the control group could be completely separated,and a total of 14 differential metabolites were screened out;metabolic pathway analysis identified 16 related pathways,including unsaturated fatty acid biosynthesis,linoleic acid metabolism,citric acid cycle(TCA cycle),arachidonic acid metabolism,glycine,serine and threonine metabolism,steroid hormone biosynthesis,etc.;a total of 16 modules were obtained through network modular analysis,among which the arachidonic acid metabolism pathway and linoleic acid metabolism pathway modules were larger;the nodal degree values of arachidonic acid and linoleic acid were greater than the mean,involving arachidonic acid metabolism and linoleic acid metabolism pathways;by screening 26 genes associated with the cytochrome P450 enzyme system were obtained.Conclusion Scutellaria Radix may regulate the body's energy metabolism,achieve its biological effects,and characterize its medicinal properties by intervening in metabolic pathways such as arachidonic acid and linoleic acid.

Objective To identify biomarkers that characterize its bitter-cold properties of Scutellaria Radix on the basis of evaluating its cold and hot properties,as well as possible metabolic pathways and related targets;To explore its molecular mechanism.Methods Totally 40 mice were randomly divided into a control group and a treatment group,and were orally administered with normal saline and Scutellaria Radix decoction,respectively,for 4 consecutive days.The cold and hot plate differential method was used to evaluate the cold and hot tendencies of the mice;UPLC-MS/MS technology was used to analyze mouse blood samples,differential metabolites were screened using principal component analysis,partial least squares discriminant analysis and orthogonal partial least squares discriminant analysis methods,and metabolic pathway analysis was performed;network modular analysis of differential metabolites was performed using Cytoscape 3.9.0 software to identify potential molecular targets.Results On the second day of administration,the anal temperature of mice in the treatment group decreased significantly compared to the control group(P<0.01);in the cold and hot tendency test,the mice in the treatment group showed an overall increase in high-temperature tendency and a higher proportion of high-temperature zone retention.There was a statistically significant difference(P<0.01,P<0.05)between the treatment group and the control group on the 2nd and 3rd day of treatment;the pattern recognition analysis of serum metabolome data showed that the serum samples of the treatment group and the control group could be completely separated,and a total of 14 differential metabolites were screened out;metabolic pathway analysis identified 16 related pathways,including unsaturated fatty acid biosynthesis,linoleic acid metabolism,citric acid cycle(TCA cycle),arachidonic acid metabolism,glycine,serine and threonine metabolism,steroid hormone biosynthesis,etc.;a total of 16 modules were obtained through network modular analysis,among which the arachidonic acid metabolism pathway and linoleic acid metabolism pathway modules were larger;the nodal degree values of arachidonic acid and linoleic acid were greater than the mean,involving arachidonic acid metabolism and linoleic acid metabolism pathways;by screening 26 genes associated with the cytochrome P450 enzyme system were obtained.Conclusion Scutellaria Radix may regulate the body's energy metabolism,achieve its biological effects,and characterize its medicinal properties by intervening in metabolic pathways such as arachidonic acid and linoleic acid.

Objective To explore the role of ethyl pyruvate (EP) on E-cadherin of airway epithelium and airway inflammation in a TDI-induced mouse asthma model. Methods 30 male BALB/c mice were randomly divided into control group , asthma group and EP group. On day 1 and 8 , mice in asthma group and EP group were treated with 0.3%TDI on the dorsum of both ears for sensitization. And on day 15 , 18 and 21 the mice underwent an aerosol inhalation of 3% TDI, and saline (100 mg/kg) was injected intraperitoneally 1 hour before inhalation. The control group underwent acetone and olive oil (AOO) sensitization on day 1 and 8, AOO challenge on day 15, 18 and 21. Saline (100 mg/kg) was injected intraperitoneally 1 hour before challenge. One hour before each challenge, mice were given EP (100mg/kg) or vehicle via intraperitoneal injection. On day 22, airway reactivity, IL-4 , IFN-γand IgE in the serum were detected , immunohistochemistry and WB were used to assess E-cadherin levels. Results Airway reactivity, IL-4, IFN-γin and IgE in the serum in asthma group are significantly higher than that in control group (P<0.05). Treatment with EP dramatically decreased airway hyperresponsiveness in TDI-challenged mice, as well as IL-4, IFN-γ and IgE (P < 0.05). E-cadherin in control group was distributed evenly at the connection of epithelial cells. E-cadherinin distribution was chaotic and its expression was decreased in asthma group. EP intervention can ameliorate the damage of E-cadherinin. Conclusions EP can ameliorate the destruction of E-cadherin in airway epithilum by TDI.

OBJECTIVETo test the effect of high-mobility group box protein 1 (HMGB1) alone or in synergy with interleukin-1β (IL-1β) on the expression of IL-8 in human airway epithelial cells in vitro.

METHODSHuman airway epithelial 16HBE and A549 cell lines were incubated with HMGB1 (100 ng/ml) in the absence or presence of IL-1β (10 ng/ml) for 24 h, and the changes of IL-8 mRNA and protein expressions were assessed using quantitative PCR and enzyme-linked immunosorbent assay (ELISA).

RESULTSIn the two human airway epithelial cell lines, HMGB1 alone did not produce obvious effect on the expression of IL-8, but in the presence of IL-1β, HMGB1 caused a significant increase of IL-8 expressions at both the mRNA and protein levels.

CONCLUSIONHMGB1 in synergy with IL-1β increases the expression of IL-8 in human airway epithelial cells, which provides new evidence that HMGB1 contributes to neutrophilic airway inflammation by regulating IL-8 expression.

Bronchi ; cytology ; drug effects ; Cell Line ; Epithelial Cells ; drug effects ; metabolism ; HMGB1 Protein ; pharmacology ; Humans ; Inflammation ; Interleukin-1beta ; pharmacology ; Interleukin-8 ; metabolism ; RNA, Messenger

AIM: To investigate the expression of peroxisome proliferator-activated receptors (PPARs) in human endothelial cells, and their effects on plasminogen activator inhibitor-1 transcription. METHODS: The expression of three types of PPARs in mRNA level were detected in human umbilical vein endothelial cells(HUVECs) by using RT-PCR. Cultured endothelial cells line-ECV304 were transfected with PAI-1 promoter controlling CAT reporter gene and co-transfected with varying doses (250, 500, 1 000 ng) of expression vectors PPAR? or PPAR?.The transcripton activity of PAI-1 promoter were detected with ELISA. RESULTS: There were all three types of PPARs mRNA expression in HUVECs, while the expression of PPAR? was less than that of PPAR?( P