Aim To establish a LC-MS/MS method for determination of 5-HT, NE, DA and observe the con-centration of 5-HT, NE, DA in rat plasma of CUMS. Methods Twenty-two male SD rats were divided into control group and model group. Model group was given 9 kinds chronic unpredictable mild stimulating factors every day. 21 days later, behavior and orbital blood were measured before and after modeling. Using benzo-yl chloride as a pre-column derivatization reagent, three analytes and IS were derivatized before LC-MS/MS detection. Change in three kinds of neurotransmit-ter concentration was measured in rat plasma before and after modeling. Results After modeling, com-pared with control group, the weight of rats in model group was declined significantly ( P<0. 05 ) . Horizon-tal scores, vertical scores and sugar consumption were declined significantly ( P <0. 01 ) . Calibration curves of 5-HT, NE, DA were linear between 1. 47 ~752, 1. 75 ~898 , 2. 05 ~1 053 μg · L-1 and LOQ were 1. 47, 1. 75, 2. 046μg·L-1 ,respectively. The recov-ery of 5-HT, NE, DA from plasma was over than 70%, and RSD of inter-day and intra-day assay was limited in 15%. Compared with control group, the con-centration of 5-HT, NE, DA in rat plasma of model group was declined to ( 3. 99 ± 1. 21 ) , ( 6. 24 ± 1. 94), (6. 07 ± 1. 98) μg·L-1(P <0. 01). Con-clusion After making CUMS model of depression, three kinds of neurotransmitters in rat plasma are de-creased.

This study aimed to explore the impact of depression caused by chronic unpredictable mild stress (CUMS) on in vivo activity of six kinds of CYP450 isoforms in rats. According to 'Katz' method, the model of CUMS was established. Tolbutamide, chlorzoxazone, theophylline, midazolam, omeprazole and dextromethorphan were chosen as probe substrates of CYP2C6, CYP2E1, CYP1A2, CYP3A2, CYP2D1 and CYP2D2 of rats. Plasma concentration of six kinds of CYP450 in control group and model group were determined by LC-MS/MS and computed pharmacokinetic parameters. Consequently, metabolism of theophylline and chlorzoxazone accelerated significantly (P < 0.01), but tolbutamide, dextromethorphan, omeprazole and midazolam had no significant difference. The present study proved that depression caused by CUMS had strong induction to CYP1A2 and medium induction to CYP2E1.

Objective To investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA). Methods Equilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions. Results The binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16±2.82)%, (33.42±4.21)%, and (34.61±3.42)%, and those of and Rb1 were (50.13±2.34)%, (51.23±3.23)%, and (53.11± 3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13 ± 2.72)%, (21.42 ± 3.22)%, and (25.45 ± 3.52)%, and those of Rb1 to (40.13 ± 3.24)%, (41.25 ± 4.15)%, and (43.11 ± 3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA. Conclusion Clopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.

Objective To investigate the effect of clopidogrel on the binding rate of ginsenosides with rat serum proteins (RSA). Methods Equilibrium dialysis and liquid chromatography-mass spectrometry were employed to quantify the concentration of ginsenoside Rg1 and Rb1. The protein-binding rates of Rg1 and Rb1 in the presence or absence of clopidogrel (1.0 mg/L) were determined. A molecular simulation model (consisting of homology modeling and molecular docking interaction) was used to reveal the target protein-compound interactions. Results The binding rates of ginsenosides Rg1 (0.4, 1.0, and 2.0 mg/L) with RSA were (30.16±2.82)%, (33.42±4.21)%, and (34.61±3.42)%, and those of and Rb1 were (50.13±2.34)%, (51.23±3.23)%, and (53.11± 3.26)%, respectively. In the presence of clopidogrel, the binding rates of Rg1 decreased to (22.13 ± 2.72)%, (21.42 ± 3.22)%, and (25.45 ± 3.52)%, and those of Rb1 to (40.13 ± 3.24)%, (41.25 ± 4.15)%, and (43.11 ± 3.31)%, receptively. The molecular docking suggested that these compounds competed to bind with RSA. Conclusion Clopidogrel can competitively bind to RSA with ginsenosides to lower the plasma protein binding rates of ginsenosides.

PURPOSE: Breast cancer is the most frequently diagnosed malignancy in women worldwide. MicroRNAs (miRNAs) are thought to serve as potential biomarkers in various cancers, including breast cancer. METHODS: We evaluated the miRNA expression profiles in 1,083 breast cancer samples and 104 normal breast tissues from The Cancer Genome Atlas database. We used the edgeR package of R software to analyze the differentially expressed miRNAs in normal and cancer tissues, and screened survival-related miRNAs by Kaplan-Meier analysis. A receiver operating characteristic curve was generated to evaluate the accuracy of these miRNAs as molecular markers for breast cancer diagnosis. Furthermore, the functional role of these miRNAs was verified using cell experiments. Targets of candidate miRNAs were predicted using 9 online databases, and Gene Ontology (GO) functional annotation and pathway analyses were conducted using Database for Annotation, Visualization and Integrated Discovery online tool. RESULTS: A total of 68 miRNAs showed significantly different expression patterns between the groups (p < 0.001), and 13 of these miRNAs were significantly associated with poor survival (p < 0.05). Three miRNAs with high specificity and sensitivity, namely, miR-148b-3p, miR-190b, and miR-429, were selected. In vitro experiments showed that the overexpression of these 3 miRNAs significantly promoted the proliferation and migration of MDA-MB-468 and T47D cells and reduced the apoptosis of T47D cells. GO and pathway enrichment analyses revealed that the targets of these dysregulated miRNAs were involved in many critical cancer-related biological processes and pathways. CONCLUSION: The miR-148b-3p, miR-190b, and miR-429 may serve as potential diagnostic and prognostic markers for breast cancer. This study demonstrated the roles of these 3 miRNAs in the initiation and progression of breast cancer.
Apoptosis ; Biological Phenomena ; Biological Processes ; Biomarkers ; Breast Neoplasms ; Breast ; Diagnosis ; Female ; Gene Ontology ; Genome ; Humans ; In Vitro Techniques ; Kaplan-Meier Estimate ; MicroRNAs ; ROC Curve ; Sensitivity and Specificity