Many people engagingin medical scienceasked me,"You’ve beenworking on the exploration of Holistic Integrated Medicine（HIM）for quite awhile.What is the progressyou have made in your research?Have you got your article published?May I beyour first reader?"
目的 从c-JUN调控的糖基化角度探究追毒方逆转三阴性乳腺癌(TNBC)耐药的机制.方法 MTT检测细胞增殖,采用Western blot检测c-JUN、β3GnT8和ppGalNAc-T1/2、CD147、耐药蛋白BCRP和MDR1的表达.采用转染c-JUN质粒建立过表达c-JUN的MDA-MB-231/ADR细胞.体内实验采用耐药TNBC原位移植裸鼠模型.结果 追毒方可显著抑制MDA-MB-231/ADR细胞的增殖(P<0.01),具有时效和量效关系;可明显抑制耐药TNBC原位移植裸鼠的肿瘤质量(P<0.01);降低耐药蛋白BCRP和MDR1表达(P<0.01),并同时明显降低c-JUN、β3GnT8和ppGalNAc-T1/2、CD147蛋白的表达(P<0.05).过表达c-JUN后,与空白质粒对照组比较,β3GnT8、ppGalNAc T1/2、CD147、BCRP和MDR1的表达均显示增加(P<0.05,P<0.01).而空白质粒对上述蛋白的表达无影响.追毒方可以显著降低过表达c-JUN后的上述蛋白的表达,但其表达水平还是显著高于空白质粒加药组(P<0.05,P<0.01).结论 追毒方通过作用于调控因子c-JUN,下调β3GnT8和ppGalNAc-T1/2的激活,从而抑制CD147的糖基化修饰,导致耐药蛋白BCRP和MDR1下调而逆转TNBC耐药.
OBJECTIVE To investigate the potential of glycyrrhizic acid(GL)to improve the solubility and bioavailability of ost-hole(Ost),and to explore the underlying mechanism of the potential solubility and pharmacokinetic interactions.METHODS Male Sprague-Dawley rats were orally given osthole(20 mg·kg-1)alone or with glycyrrhizic acid(45 mg·kg-1).Blood and liver samples were collected at specific time points and determined by an LC-MS/MS method.The effect of glycyrrhizic acid on the solubility of ost-hole,and physical characterizations,including X-ray diffraction(XRD)and Fourier transform infrared(FT-IR)spectroscopy,were performed to reveal the mechanism of the solubilization of GL.In addition,bidirectional transport study using Caco-2 cell monolayer model was employed to study the effects of glycyrrhizic acid and its active metabolite glycyrrhetinic acid(GC)on the absorption of ost-hole.In incubation studies,rat enterocyte S9 and liver S9 were used to explore the potential effect of GL and GC on the metabolism of osthole.RESULTS The results of pharmacokinetics in rats showed that co-administration of glycyrrhizic acid could significantly in-crease the AUC of osthole as compared with osthole administered alone.The results of rat liver tissue samples indicated that glycyrrhizic acid increased the distribution of osthol in liver tissue.Solubility study found that glycyrrhizic acid could significantly enhance the solu-bility of osthole in water due to the decreased crystallinity of osthole and the formation of hydrogen bonding between Ost and GL.Caco-2 cell monolayer model demonstrated that neither GL nor GC could enhance osthole absorption.Further in vitro incubation study re-vealed that there was little metabolic interaction between osthole and GL or GC in phaseⅠmetabolism.CONCLUSION Increased AUC and liver concentration of osthole are probably due to the increased solubility of osthole by GL.The current study has significant implications for further investigation on the potential combination use of natural solubilizing agent GL and drugs with solubility as the rate-limiting step to absorption from the gastrointestinal tract.
OBJECTIVE To identify Magnoliae Flos and its related species using DNA barcoding technology,so as to establish a rapid,accurate and convenient method for identification of Magnoliae Flos.METHODS Genomic DNA of 21 Magnoliae Flos and their related species were extracted,and ITS,ITS2,psb A-trn H,mat K and rbc L gene sequences were amplified and sequenced.MEGA7.0 software was used for sequence comparison,and the intraspecific and interspecific genetic distance was calculated based on Kimura-2-Parameter(K2P)model to evaluate Barcoding gap,and the NJ phylogenetic trees were constructed to react identification re-sults.RESULTS Among the 5 primers,psb A-trn H and mat K could normally amplify the target gene,and the success rate of them was higher than 98%,while the success rate of rbc L sequencing was 38.1%only.The mat K sequence had the highest number of varia-tion sites,and psb A-trn H had the most prominent species discriminatory on Barcoding gap analysis relative to mat K and rbc L.The NJ phylogenetic tree showed that psb A-trn H+mat K barcode sequence could accurately identify 9 varieties,and distinguish Magnoliae Flos and its relatives.In addition,we applied it to the molecular identification of Magnolia grafting rootstocks for the first time.CONCLU-SION The sequence combination of psb A-trn H+mat K can realize the accurate identification of Magnoliae Flos,and can be applied to the rapid identification of Magnolia grafting rootstocks.
Yigong powder is one of the classic famous prescriptions published in the Catalogue of Ancient Classical Famous Pre-scriptions(the Second Batch of Pediatrics).Through systematically collating textual research and analyzing ancient literatures and clini-cal literatures on Yigong decoction,the key issues of prescription origin,composition,drug base,processing method,usage and dos-age,efficacy and indications of Yigong powder were summarized,providing literature data support for the development and clinical ap-plication of the classic pediatric prescription of Yigong powder.According to the analysis and research,Yigong powder comes from Qian Yi's Key to Diagnosis and Treatment of Children's Diseases and is consisted of ginseng,poria cocos,atractylodes,tangerine peel and licorice,with ginger and jujube being used as guiding medicine.The medicinal base follows the 2020 edition of Chinese Pharmaco-poeia.Ginseng,poria cocos,and orange peel are used as raw products,atractylodes is used as bran fried atractylodes,licorice is used as processed licorice.Children should be differentiated from adults in terms of drug dosage.The dosage for children is 1.4—1.7 g each for ginseng,poria cocos,atractylodes,tangerine peel and licorice,and the dosage for adults is 5.6 g—6.8 g each.The method of making and taking medicine is to file drugs down,take 300 mL water,add ginger and jujube and fry to 210 mL,take warm medicine before meals and adjust the frequency according to the actual situation.The ancient prescription was often used in children anorexia,diarrhea and other diseases.After the innovation of later generations of doctors,it is also used for digestive system diseases,recurrent respiratory tract infections in children,allergic rhinitis and so on.
