Objective:To investigate the effect of compound matrine injection on morphine tolerance in mice with lung cancer in situ and the expressions of multidrug resistance gene 1 (MDR1) and P-glycoprotein (P-gp).Methods:A mouse model of lung cancer in situ and morphine tolerance mode was established. The mice were injected with gradient concentration of compound matrine. The pain thresholds under different conditions were measured by thermal radiation tail-flick method. The mRNA level of MDR1 was tested by reverse transcription polymerase chain reaction (RT-PCR) and the protein level of P-gp was detected by western blot. The DNA binding activity of cyclophosphoadenosine response element binding protein (CREB) to the promoter of MDR1 gene was detected by electrophoretic mobility shift assay (EMSA).Results:The maximum analgesic percentage (MPE) of the mice in the morphine group was (85.21±6.53)% on the 8th day, and decreased to (38.45±5.52)% and (28.14±4.52)% on the 10th and 12th day, respectively, which indicated the morphine tolerance of mice with lung cancer in situ.The MPE of the mice in the group treated with morphine and compound matrine injection (300 mg/kg) was (79.34±6.50)% on the 8th day, and decreased to (62.16±5.53)% and (40.20±4.50)% on the 10th and 12th day, respectively.The results of RT-PCR assay showed that the relative expression levels of MDR1 mRNA in the brain tissues of mice in the morphine group, saline group, morphine combined with compound matrine injection (300 mg/kg) group and compound matrine injection (200 mg/kg) group were 2.33±0.79, 1.04±0.38, 1.37±0.38, and 1.43±0.53, respectively. There were statistically significant differences between the morphine group and the normal saline group, the morphine group and the morphine combined with compound matrine injection (300 mg/kg) group ( P<0.05). There was no significant difference between the normal saline group and the compound matrine injection (200 mg/kg) group ( P=0.05). The results of western blot showed that the relative expression levels of P-gp protein in the brain tissue of mice in the morphine group, saline group, and morphine combined with compound matrine injection (300 mg/kg) group were 1.86±0.40, 1.00±0.23, and 1.27±0.27, respectively. The expression of P-gp protein in the morphine group was significantly higher than those of the normal saline group and the morphine combined with compound matrine injection (300 mg/kg) group ( P<0.05). The DNA-binding activity of CREB in the saline group was (0.23±0.07) Pu, significantly lower than (0.89±0.23) Pu of morphine combined with naloxone group and (0.80±0.23) Pu of morphine group ( P<0.05). While the CREB DNA binding activity of morphine combined with compound matrine injection (300 mg/kg) group was (0.79±0.21) Pu, implicated that compound matrine had marginal effect on the DNA-binding activity of CREB ( P>0.05). Conclusion:Compound matrine injection can significantly improve morphine tolerance and drug resistance of lung cancer through inhibiting the upregulations of MDR1 and P-gp induced by morphine.

Objective:To investigate the effect of compound matrine injection on morphine tolerance in mice with lung cancer in situ and the expressions of multidrug resistance gene 1 (MDR1) and P-glycoprotein (P-gp).Methods:A mouse model of lung cancer in situ and morphine tolerance mode was established. The mice were injected with gradient concentration of compound matrine. The pain thresholds under different conditions were measured by thermal radiation tail-flick method. The mRNA level of MDR1 was tested by reverse transcription polymerase chain reaction (RT-PCR) and the protein level of P-gp was detected by western blot. The DNA binding activity of cyclophosphoadenosine response element binding protein (CREB) to the promoter of MDR1 gene was detected by electrophoretic mobility shift assay (EMSA).Results:The maximum analgesic percentage (MPE) of the mice in the morphine group was (85.21±6.53)% on the 8th day, and decreased to (38.45±5.52)% and (28.14±4.52)% on the 10th and 12th day, respectively, which indicated the morphine tolerance of mice with lung cancer in situ.The MPE of the mice in the group treated with morphine and compound matrine injection (300 mg/kg) was (79.34±6.50)% on the 8th day, and decreased to (62.16±5.53)% and (40.20±4.50)% on the 10th and 12th day, respectively.The results of RT-PCR assay showed that the relative expression levels of MDR1 mRNA in the brain tissues of mice in the morphine group, saline group, morphine combined with compound matrine injection (300 mg/kg) group and compound matrine injection (200 mg/kg) group were 2.33±0.79, 1.04±0.38, 1.37±0.38, and 1.43±0.53, respectively. There were statistically significant differences between the morphine group and the normal saline group, the morphine group and the morphine combined with compound matrine injection (300 mg/kg) group ( P<0.05). There was no significant difference between the normal saline group and the compound matrine injection (200 mg/kg) group ( P=0.05). The results of western blot showed that the relative expression levels of P-gp protein in the brain tissue of mice in the morphine group, saline group, and morphine combined with compound matrine injection (300 mg/kg) group were 1.86±0.40, 1.00±0.23, and 1.27±0.27, respectively. The expression of P-gp protein in the morphine group was significantly higher than those of the normal saline group and the morphine combined with compound matrine injection (300 mg/kg) group ( P<0.05). The DNA-binding activity of CREB in the saline group was (0.23±0.07) Pu, significantly lower than (0.89±0.23) Pu of morphine combined with naloxone group and (0.80±0.23) Pu of morphine group ( P<0.05). While the CREB DNA binding activity of morphine combined with compound matrine injection (300 mg/kg) group was (0.79±0.21) Pu, implicated that compound matrine had marginal effect on the DNA-binding activity of CREB ( P>0.05). Conclusion:Compound matrine injection can significantly improve morphine tolerance and drug resistance of lung cancer through inhibiting the upregulations of MDR1 and P-gp induced by morphine.

AIM: To explore the mechanism of action of alkaloid components of compound kushen Injection (CKI) in the treatment of lung cancer based on serum metabolomics, network pharmacology, and molecular docking techniques. METHODS: A lung cancer model was established in C57 mice by inoculation of Lewis mouse lung cancer tumor strain. Thirty male mice were randomly divided into normal group, model group and CKI group. The drug was administered by tail vein injection once daily for 17 consecutive days. Mouse serum was examined by ultrahigh performance liquid chromatography tandem mass spectrometry (LC-MS) metabolomics, and several multivariate statistical analyses including principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA), combined with databases such as the human metabolic database (HMDB) and related literature to identify and identify differential metabolites, the relevant metabolic pathways were searched for by the metaboanalyst online tool. Using network pharmacology, construct the“component-target-disease”network of CKI in the treatment of lung cancer. Molecular docking method was used to verify the interaction between potential active ingredients and core targets. Serum metabolomics was jointly analyzed with network pharmacology to construct a“metabolite-germinal-enzyme-gene” network. RESULTS: Through metabolomics technology, 16 differential metabolites associated with lung cancer were screened from serum, and CKI addback these differential metabolite levels compared with the model group. Metabolic pathways mainly involve retinol metabolism, tryptophan metabolism, glycerophospholipid metabolism and other metabolic pathways. Network pharmacology analysis indicated that CKI treatment of lung cancer mainly targets STAT3, MAPK3, and MAPK1, which are closely related to proteoglycans, cellular senescence, and HIF − 1 signaling pathways in cancer. CONCLUSION: This article explains the mechanism of CKI in treating lung cancer from the perspective of metabonomics and network pharmacology, and provides basis for further study of CKI.

AIM: To study the effect of Qingdaipowder Gel (QDPG) on mice specific dermatitis (AD) model and the antibacterial effect of the ethanol extract of Qingdaipowder. METHODS: AD model of mice was established by repeated skin induction with 2,4-dinitrochlorobenzene (DNCB). Fifty-six mice were randomly divided into blank group, model group, Hydrocortisone Butyrate Cream group (Hyd, 1.5 mg/cm

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can cause acute respiratory distress syndrome, hypercoagulability, hypertension, and multiorgan dysfunction. Effective antivirals with safe clinical profile are urgently needed to improve the overall prognosis. In an analysis of a randomly collected cohort of 124 patients with COVID-19, we found that hypercoagulability as indicated by elevated concentrations of D-dimers was associated with disease severity. By virtual screening of a U.S. FDA approved drug library, we identified an anticoagulation agent dipyridamole (DIP) , which suppressed SARS-CoV-2 replication . In a proof-of-concept trial involving 31 patients with COVID-19, DIP supplementation was associated with significantly decreased concentrations of D-dimers ( < 0.05), increased lymphocyte and platelet recovery in the circulation, and markedly improved clinical outcomes in comparison to the control patients. In particular, all 8 of the DIP-treated severely ill patients showed remarkable improvement: 7 patients (87.5%) achieved clinical cure and were discharged from the hospitals while the remaining 1 patient (12.5%) was in clinical remission.