The mechanism of emodin inhibiting YAP1 and FOXD1 in gastric cancer AGS cells and its related study / 实用医学杂志

Objective To explore the possible mechanism of emodin in inhibiting proliferation,migration,and invasion of AGS cells and in suppressing the expressions of YAP1 and FOXD1.Methods Normal gastric cell GES-1 and gastric cancer cell AGS were cultured with different concentrations of emodin.CCK8 test,scratch test and Transwell assay were used to verify changes in the biological phenotype of AGS cells.TCGA database was applied to analyze expressions of HK2,YAP1 and FOXD1 in gastric cancer tissues and normal gastric tissues.Western blotting method was used to detect the impacts of emodin on HK2,YAP1 and FOXD1 proteins in AGS cells.Exogenous pyruvic acid was added to verify the changes in YAP1 and FOXD1.Results The IC50 of emodin was significantly higher in GES-1 cells than in AGS cells(P<0.05).CCK8 proliferation test,scratch test,and Transwell assay showed that emodin significantly inhibited the biological abilities of AGS(P<0.05 for comparisons).Analysis on the TCGA bioinformatics database found that the expression of key enzymes HK2 in the glycolysis pathway and oncogenes YAP1 and FOXD1 was significantly higher in gastric cancer tissues than in normal gastric tissues(P<0.05 for comparisons).Emodin significantly inhibited the protein expressions of key glycolytic enzymes HK2 and oncogenes YAP1 and FOXD1(P<0.05 for comparisons).With supplement of exogenous glycolytic metabolite pyruvate,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased(P<0.05 for comparisons).Conclusions Emodin has a significant pharmacological inhibitory effect on gastric cancer AGS cells,markedly suppressing their biological phenotype.Emodin not only significantly inhibits the key enzyme HK2 in glycolysis metabolism,but also the protein expressions of oncogenes YAP1 and FOXD1.With the addition of exogenous pyruvate to enhance the glycolytic metabolic pathway,the protein expressions of oncogenes YAP1 and FOXD1 significantly increased.The above results suggest a close association of YAP1 and FOXD1 with glycolytic metabolism.Emodin may inhibit oncogenes YAP1 and FOXD1 through the glycolytic metabolism of gastric cancer AGS cells.

VEGF-C Promotes Cervical Cancer Invasion via Regulation of microRNA-145/Smad Interacting Protein 1 / 中山大学学报(医学科学版)

[Objective]To investigate the role of microRNA-145/Smad interacting protein 1(SIP 1)in VEGF-C-enhanced cervical cancer metastasis.[Methods]Cervical cancer cell line SiHa cells were cultured and treated with VEGF-C to observe its effect on the expression of miR-145 and SIP1. After transfection with specific SIP1 siRNA,the invasion number of cultured cells were calculated by transwell chamber assay.[Results]Treatment with VEGF-C(100 ng/mL)for 12 h,24 h and 48 h all reduced miR-145 expression,with the expression abundance of(82.4±6.4)% (P<0.05),(72.5±7.2)%(P<0.01),and(60.6±9.6)%(P<0.001),respectively,when compared to control.Meanwhile, the same treatment with VEGF-C also increased SIP1 protein expression,with the expression abundance of(142.4 ± 16.5)%(P<0.05),(183.6 ± 11.4)%(P<0.01)and(220.8 ± 15.7)%(P<0.001),respectively. The transfection of miR-145 mimic significantly impaired VEGF-C effect on SIP1 expression. Finally,VEGF-C promoted SiHa cell invasion,which was largely inhibited by the tranfection of SIP siRNA with the inhibitory rate of(56.6±10.3)%(P<0.01).[Conclusion]VEGF-C downregulates miR-145,thus increases SIP1 expression and promotes cervical cancer cell invasion,which may contributes to cervical cancer malignant progression.

Treatment of depression using sleep electroencephalogram modulated repetitive transcranial magnetic stimulation / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>As a treatment of depression, the efficacy of conventional repetitive transcranial magnetic stimulation (rTMS) is limited, and symptoms recurrence is easy to occur after the treatment. This study aimed to examine the efficacy and safety of sleep electroencephalogram modulated repetitive rTMS (SEM-rTMS) in the treatment of depression.</p><p><b>METHODS</b>After 7 days without psychoactive medication, 164 patients with clinically defined depression were randomly divided into 3 groups: SEM-rTMS group (n = 57), conventional rTMS (C-rTMS, n = 55) group and sham-rTMS group (n = 52). Every patient was treated with the corresponding method for 30 minutes everyday for 10 days. Before and after scores on the 24-item Hamilton rating scale for depression (HAMD-24) and the clinical outcome on the 10th day of therapy for all subjects were analyzed.</p><p><b>RESULTS</b>Twenty-two cases in the SEM-rTMS group obtained improved mood as compared to 6 in the C-rTMS group and 2 in the sham-rTMS group (χ(2) = 15.89, P = 0.0004). After completion of the rTMS phase of the protocol, a (51 ± 5)% reduction of HAMD-24 scores from the baseline in the SEM-rTMS group was found compared with a (34 ± 4)% in the C-rTMS group (q = 26.09, P = 0.001) and a (14 ± 3)% in sham-rTMS group (q = 57.53, P = 0.000). The 88% total effective rate in the SEM-rTMS group was significantly higher than 68% in the C-rTMS group and 20% in the sham-rTMS group (χ(2) = 12.01, P = 0.0025). No significant side effects were noted.</p><p><b>CONCLUSION</b>SEM-rTMS is an effective and safe way for treating depression with repetitive transcranial magnetic stimulation (ChiCTR-TRC-00000438).</p>

Distribution behavior of lipophilic drugs in the oil-in-water microemulsions / 药学学报

Distribution behavior of lipophilic drugs in the oil-in-water (O/W) microemulsions was studied. Fluorescence spectra analysis was performed to investigate the effect of the compositions of microemulsions on the fluorescence spectra of armillarisin and ofloxacin which were used as the model drugs. The fluorescence spectra of the model drugs in the microemulsions with various amount of the compositions were compared. The results showed that the armillarisin were both localized in the interfacial film of microemulsion systems with both phenylmethanol and PEG 400 as the co-surfactants, separately. Ofloxacin was localized in the interfacial film of microemulsion systems with Gradamol GTCC as the oil phase, but in the oil pool of microemulsion systems with oleic acid/olive oil (OA/OO) (1:1) as the oil phase. Besides, it was found that the drug would have the tendency to locate in the microenvironment where the composition with the largest solubility to model drug is located, and its actual localized position would be dependent on the amount of this composition. The results indicate that the localized region of lipophilic drug in the O/W microemulsion systems is related with the solubility of the model drug in various compositions.

Systematic studies on quality of main species of Herba epimedii / 中国中药杂志

<p><b>OBJECTIVE</b>To achieve the quality control of Herba Epimedii, and to evaluate the quality of medical materials of the 8 official species including the 5 species recorded in 'Chinese Pharmacopoeia' including Epimedium brevicornum, E. sagittatum, E. pubescens, E. koreanum and E. wushanense, and the 3 other species (E. acuminatum, E. myrianthum, E. leptorrhizum) recorded in 'Guizhou Quality Criteria for Traditional Chinese Medical Material and Nationality Medical Material', and E. pseudowushanuse (new species) which is used as E. wushanense for a long time.</p><p><b>METHOD</b>The contents of icariin and total flavonoids of 102 samples of 9 officinal species of Herba Epimedii were determined by HPLC and UV, respectively.</p><p><b>RESULT AND CONCLUSION</b>The contents of icariin in about 30% of the samples of the 5 species recorded in 'Chinese Pharmacopoeia' were lower than 0.5%, which is acceptable quality recorded in 'Chinese Pharmacopoeia'. Refering the literatures, we suggested the total contents of epimedin A, B, C and icariin (epi-medium multi-glycosides, ABCI) should be established as a new standard instead of the content of icariin. The content of total flavonoids, not less than 5.0%, and ABCI, not less than 1.3%, could be used to evaluate the quality of the above medical materials efficiently.</p>