Objective : To investigate the effects of sinapine on lung tissue inflammation and mucus hypersecretion in asthmatic mice. Methods: Eight-week-old female C57BL/6J mice were randomly divided into Control group, ovalbumin(OVA) group, Sinapine group, and Sinapine+OVA group. The asthmatic mice model were established by intraperitoneal injection of OVA combined with aluminum hydroxide [Al(OH)3] suspension and OVA nasal stimulation. One hour before OVA nasal stimulation, the mice in Sinapine+OVA group and Sinapine group were intraperitoneally injected with sinapine solution, and the mice in OVA group and Control group were treated with the same dose of 0.9% sodium chloride solution. 24 hours after the last OVA stimulation, the inflammation of lung tissue of mice were observed by HE staining; the mucus secretion were evaluated by PAS staining; the mRNA expression levels of Interleukin-4(IL-4), Interleukin-5(IL-5), Interleukin-13(IL-13), tumor necrosis factor-alpha(TNF-α), Mucin 5ac(Muc5ac), and the mRNA of the key genes of Notch pathway such as Notch receptor 1(Notch1), Notch receptor 2(Notch2), Notch receptor 3(Notch3), and hes family bHLH transcription factor 1(Hes1) in lung tissues were detected by real-time fluorescent quantitative PCR(RT-qPCR); the expression levels of Notch1, Notch2, Notch3 and Hes1 proteins were determined by Western blot. Results : Compared with Control group, the inflammation score and PAS score of lung tissues of mice in OVA group increased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in OVA group were enhanced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in OVA group significantly increased(P<0.001), while there was no significant difference in the mRNA and protein expression levels of Notch1. Compared with OVA group, the inflammation score and PAS score of lung tissues of mice in Sinapine+OVA group decreased(P<0.001); the mRNA expression levels of IL-4, IL-5, IL-13, TNF-α, and Muc5ac of mice in Sinapine+OVA group were reduced(P<0.05); the mRNA and protein expression levels of Notch2, Notch3, and Hes1 of mice in Sinapine+OVA group were downregulated(P<0.05), while there was no significant difference in the mRNA and protein expression levels of Notch1. Conclusion Sinapine can alleviate the lung tissue inflammation and mucus hypersecretion in asthmatic mice, and its mechanism may be related to the inhibition of Notch2/Notch3-Hes1 signal pathway.

Objective To explore the expression level of serum CD73 in Parkinson's disease(PD)patients and the correlation be-tween serum CD73 and the severity of motor dysfunction.Methods A total of 97 PD patients and 71 healthy controls were included.Bas-ic data of the subjects were collected,including age,gender,smoking history,and the condition of dose taking.Disease course,H&Y stage,and UPDRS-Ⅲ score of PD patients were also collected.PD patients were divided into mild PD group,and moderate and severe PD group according to H&Y stage.The fasting venous blood of the subjects was collected for serum CD73detection.Binary Logistic regres-sion analysis was used to analyze the correlation between PD and factors such as age,gender,and serum CD73.Receiver operating char-acteristic curve analysis was used to predict the diagnostic value of serum CD73.Pearson correlation was used to analyze the correlation between serum CD73 level,H&Y stage,and UPDRS-Ⅲ score in PD patients.Results The level of serum CD73 in PD patients was significantly lower than that in healthy controls.Binary Logistic regression showed that the decrease in the level of serum CD73 was an in-dependent risk factor for PD.The level of serum CD73 lower than 2.85U/L was more sensitive to the diagnosis of PD.In PD patients,the higher the H&Y stage,the lower the serum CD73 level;Pearson correlation analysis showed that the serum CD73 level was negatively cor-related with the H&Y stage and UPDRS-Ⅲ score.Conclusion The reduction of serum CD73 level can significantly increase the risk of PD,and the lower the level of serum CD73,the more serious the motor dysfunction of PD patients.

Objective:To discuss the effect of Aspergillus fumigatus(Af)on DNA damage and interleukin(IL)-33 expression in the human bronchial epithelial cells,and to clarify its related mechanism.Methods:Different concentrations(1,5,and 10 mg·L-1)of Af were used to stimulate the bronchial epithelial BEAS-2B cells to select the appropriate stimulation concentration.When the BEAS-2B cells were treated with N-acetylcysteine(NAC)and Af,the cells were divided into control group,Af group,NAC group,and Af+NAC group.When the BEAS-2B cells were treated with DNA double-strand break repair inhibitor NU7441 and Af,the cells were divided into control group,Af group,NU7441 group,and Af+NU7441 group.The comet assay was used to detect the percentages of comet tail DNA of cells in various groups;immunofluorescence method was used to detect the expression levels of DNA damage-related protein phosphorylated H2AX(yH2AX)in the cells in various groups;2,7-dichlorofluorescein diacetate(DCFH-DA)fluorescence probe was used to detect the levels of reactive oxygen species(ROS)in the cells in various groups;real-time fluorescence quantitative PCR(RT-qPCR)method was used to detect the expression levels of interleukih-33(IL-33),thymic stromal lymphopoietin(TSLP),and interleukih-25(IL-25)mRNA in the cells in various groups;Western blotting method was used to detect the expression levels of phosphorylated nuclear factor κB(p-NF-κB),phosphorylated ataxia telangiectasia mutated(p-ATM),and γH2AX proteins in the cells in various groups.Results:Compared with control group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 1 mg·L-1 Af group showed no significant difference(P＞0.05),while the percentage of comet tail DNA and the expression level of γH2AX in the cells in 5 mg·L-1 Af group were significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the percentage of comet tail DNA and the expression level of γH2AX in the cells in 10 mg·L-1 Af group were significantly increased(P＜0.01).Compared with control group,the ROS levels in the bronchial epithelial cells in 1 mg·L-1 Af group was significantly increased(P＜0.05);compared with 1 mg·L-1 Af group,the ROS level in the cells in 5 mg·L-1 Af group was significantly increased(P＜0.01);compared with 5 mg·L-1 Af group,the ROS level in the cells in 10 mg·L-1 Af group was significantly increased(P＜0.05).After treatment of NAC,compared with Af group,the percentage of comet tail DNA(P＜0.01),the expression level of γH2AX(P＜0.05),and the ROS level(P＜0.01)in the cells in Af+NAC group were significantly decreased;after treatment of NU7441,compared with Af group,the percentage of comet tail DNA and the expression level of yH2AX in the cells in Af+NU7441 group were significantly increased(P＜0.01).The RT-qPCR results showed that after treatment of NAC,compared with control group,the expression level of IL-33 mRNA in the cells in Af group was significantly increased(P＜0.05);compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NAC group was significantly decreased(P＜0.05);after treatment of NU7441,compared with Af group,the expression level of IL-33 mRNA in the cells in Af+NU7441 group was significantly increased(P＜0.05).The Western blotting results showed that after treatment of NAC,compared with control group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af group were significantly increased(P＜0.05);after treatment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NAC group were significantly decreased(P＜0.05);After treat ment of NU7441,compared with Af group,the expression levels of p-NF-κB,p-ATM,and γH2AX proteins in the cells in Af+NU7441 group were significantly increased(P＜0.05).Conclusion:Af promotes the IL-33 expression in the human bronchial epithelial cells by causing DNA damage,and its mechanism may be related to the activation of ATM/NF-κB signaling pathway.

An in vitro blood-brain barrier (BBB) model is critical for enabling rapid screening of the BBB permeability of the drugs targeting on the central nervous system. Though many models have been developed, their reproducibility and renewability remain a challenge. Furthermore, drug transport data from many of the models do not correlate well with the data for in vivo BBB drug transport. Induced-pluripotent stem cell (iPSC) technology provides reproducible cell resources for in vitro BBB modeling. Here, we generated a human in vitro BBB model by differentiating the human iPSC (hiPSC) line GM25256 into brain endothelial-type cells. The model displayed BBB characteristics including tight junction proteins (ZO-1, claudin-5, and occludin) and endothelial markers (von Willebrand factor and Ulex), as well as high trans-endothelial electrical resistance (TEER) (1560 Ω.cm ± 230 Ω.cm) and γ-GTPase activity. Co-culture with primary rat astrocytes significantly increased the TEER of the model (2970 Ω.cm to 4185 Ω.cm). RNAseq analysis confirmed the expression of key BBB-related genes in the hiPSC-derived endothelial cells in comparison with primary human brain microvascular endothelial cells, including P-glycoprotein (Pgp) and breast cancer resistant protein (BCRP). Drug transport assays for nine CNS compounds showed that the permeability of non-Pgp/BCRP and Pgp/BCRP substrates across the model was strongly correlated with rodent in situ brain perfusion data for these compounds (R = 0.982 and R = 0.9973, respectively), demonstrating the functionality of the drug transporters in the model. Thus, this model may be used to rapidly screen CNS compounds, to predict the in vivo BBB permeability of these compounds and to study the biology of the BBB.

Objective To investigate the effect of the multi-material artifact reduction (MMAR) algorithm of wide-detector CT system in reducing the beam hardening artifacts in brain CT imaging. Methods Nine tubes with various iodine concentrations (0.1-16.0 mgI/ml) were placed in a uniform phantom filled with soft-tissue equivalent material. The phantom was scanned using different combinations of the tube voltage and current as follows:80 kV/530 mA, 100 kV/295 mA, 120 kV/190 mA and 140 kV/135 mA. The scanning was performed using the GE Discovery 750 and GE Revolution CT scanners, respectively. The CT values and standard deviations of the uniform areas between tubes were measured. The artifact index (AI) was calculated by using the standard deviation value outside the tubes as background noise. The artifact index values under different kV/mA combinations with different scanners were compared. CT brain images of 36 patients (n=18 on Discovery CT and n=18 on Revolution CT) were randomly selected. CT values of normal brain tissue and dark bands areas in the posterior fossa were measured for each case. The AI was calculated for these cases as for the phantom study. Paired t test was performed for phantom data analysis, and independent t test was performed for the clinical cases data analysis. Results The average AI values with Revolution CT(4.96±1.39, 4.80±1.57, 4.56±1.45, 4.76±1.57) were smaller than those of Discovery 750 (11.90 ± 6.61, 11.17 ± 5.61, 8.85 ± 4.59, 8.77 ± 3.85) under different tube voltage settings(t=3.714, 4.186, 3.745, 4.634,P<0.001). The higher the iodine concentration difference between tube pairs was, the higher the artifact index;As for clinical data, the difference in AI values between Revolution CT(2.31 ± 0.95) and Discovery 750(3.91 ± 1.32) was found statistically significant(t=4.066,P<0.001). Conclusion The multi-material artifact reduction algorithm implemented on the wide-detector Revolution CT scanner can significantly reduce beam hardening artifacts.

Objective To investigate the effect of the multi-material artifact reduction (MMAR) algorithm of wide-detector CT system in reducing the beam hardening artifacts in brain CT imaging. Methods Nine tubes with various iodine concentrations (0.1-16.0 mgI/ml) were placed in a uniform phantom filled with soft-tissue equivalent material. The phantom was scanned using different combinations of the tube voltage and current as follows:80 kV/530 mA, 100 kV/295 mA, 120 kV/190 mA and 140 kV/135 mA. The scanning was performed using the GE Discovery 750 and GE Revolution CT scanners, respectively. The CT values and standard deviations of the uniform areas between tubes were measured. The artifact index (AI) was calculated by using the standard deviation value outside the tubes as background noise. The artifact index values under different kV/mA combinations with different scanners were compared. CT brain images of 36 patients (n=18 on Discovery CT and n=18 on Revolution CT) were randomly selected. CT values of normal brain tissue and dark bands areas in the posterior fossa were measured for each case. The AI was calculated for these cases as for the phantom study. Paired t test was performed for phantom data analysis, and independent t test was performed for the clinical cases data analysis. Results The average AI values with Revolution CT(4.96±1.39, 4.80±1.57, 4.56±1.45, 4.76±1.57) were smaller than those of Discovery 750 (11.90 ± 6.61, 11.17 ± 5.61, 8.85 ± 4.59, 8.77 ± 3.85) under different tube voltage settings(t=3.714, 4.186, 3.745, 4.634,P<0.001). The higher the iodine concentration difference between tube pairs was, the higher the artifact index;As for clinical data, the difference in AI values between Revolution CT(2.31 ± 0.95) and Discovery 750(3.91 ± 1.32) was found statistically significant(t=4.066,P<0.001). Conclusion The multi-material artifact reduction algorithm implemented on the wide-detector Revolution CT scanner can significantly reduce beam hardening artifacts.

OBJECTIVETo investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats.

METHODSThe permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp).

RESULTSCompared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected.

CONCLUSIONCapsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.

ATP-Binding Cassette, Sub-Family B, Member 1 ; metabolism ; Animals ; Capsaicin ; pharmacology ; Colon ; metabolism ; Fluorescein ; pharmacokinetics ; Ileum ; metabolism ; Intestinal Absorption ; Jejunum ; metabolism ; Male ; Permeability ; Rats ; Rats, Sprague-Dawley ; Rhodamine 123 ; pharmacokinetics

Objective To investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats. Methods The permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp). Results Compared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected. Conclusion Capsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.

Objective To investigate the role of capsaicin in regulating permeation of P-gp substrate rhodamine 123 (R123) across the jejunum, ileum and colon membranes of rats. Methods The permeability of R123 or fluorescein sodium (CF) across the jejunum, ileum and colon membranes of male SD rats was evaluated using a Ussing chamber. The concentration of R123 or CF in the receptor was determined using fluorospectrophotometry to calculate the apparent permeability coefficient (Papp). Results Compared with the blank control group, capsaicin increased the permeability of R123 across jejunal membranes in the mucosal-to-serosal (M-S) direction and decreased its permeability in the serosal-to-mucosal (S-M) direction, but produced no obvious effect on R123 transport across the ileum or colon membranes. Capsaicin caused a regional increase in the permeability of CF across the jejunal membranes compared with the control group, but CF transport across the ileum and colon membranes was not affected. Conclusion Capsaicin can affect the transport of R123 and CF across rat jejunal membranes, and this effect is shows an obvious intestine segment-related difference probably because of the different distribution of P-gp or tight junction in the intestines. This finding suggests that capsaicin is a weak P-gp inhibitor and an improver of mucous membrane channels.

OBJECTIVETo investigate the chemical constituents of Euphorbia pekinensis roots. METHODS Column and liquid chromatography were used for the isolation of chemical constituents, and their chemical structures were determined using a spectroscopic method.

RESULTS AND CONCLUSIONFour compounds were isolated and identified as ziyu glycoside I (1), 3β-α-L-arabinopyranosyloxyurs-12,19(29)-dien-28-oic acid 28-β-D-glucopyranosyl ester (2), lithospermic acid B (3), and senarguine B (4), which were obtained for the first time from the roots of Euphorbia pekinensis.

Benzofurans ; chemistry ; isolation & purification ; Depsides ; chemistry ; isolation & purification ; Euphorbia ; chemistry ; Glycosides ; chemistry ; isolation & purification ; Plant Roots ; chemistry