1.Research about the activity of CYP2A6 that related to regulative mechanism
Chinese Pharmacological Bulletin 2003;0(12):-
CYP2A6 is an important drug metabolic enzyme that plays a central role in pharmacology and toxicology.Coumarin and nicodine are mainly metabolized by it.CYP2A6 also have a close connection with diseases that related to smoking.While hnRNP A1 is a protein that shows an important regulative action on some specific genes at post-transcription level.Recently,researchers are paying more and more attention to the relationship between the activity of CYP2A6 and the expression of hnRNPA1.In order to master the change rule of CYP2A6 activity,we try to explain the regulative effect on CYP2A6 by hnRNP A1 at post-transcription level,which will bring an important effect on guiding clinical medicine treatments and smoking addictive therapy.
2.Advance in flavin-containing monooxygenase 3(FMO3):structure/function and genetic polymorphisms
Hao CHEN ; Zhirong TAN ; Honghao ZHOU
Chinese Pharmacological Bulletin 2003;0(10):-
Flavin-containing monooxygenase 3 (FMO3) is an important hepatic microsomal enzyme that oxidizes a number of drugs,xenobiotics and other chemicals.Many variants in the gene encoding FMO3 have been identified,some of which result in altered enzymatic activity,consenquently,altered substrate metabolism.Studies also implicate individual and ethnic differences in FMO3.Thus,it is anticipated that knowledge regarding functionally-relevant FMO3 genetic variability will become increasingly important for drug development and patient therapeutic choices.
3.Management of metacarpophalangeal bone defects after hand trauma by distraction osteogenesis with mini external fixation
Honghao CHEN ; Yachao JIA ; Qinglin KANG
Chinese Journal of Orthopaedic Trauma 2016;18(12):1015-1021
Objective To evaluate the outcomes of distraction osteogenesis with mini external fixation in management of metacarpophalangeal bone defects after hand trauma.Methods From June 2010 to December 2015,16 patients with metacarpophalangeal bone defects after hand trauma received distraction osteogenesis at our department.They were 11 men and 5 women,from 20 to 45 years of age (average,32.5 years).There were altogether 20 bone defects:8 cases had single metacarpal bone defect,2 unilateral second and third metacarpal bone defects and 6 phalangeal shortening after repair of digital stump (involving thumb in 4 cases,index finger in one and index and middle fingers in one).The metacarpophalangeal bone defects averaged 1.8 cm (from 1.0 to 3.1 cm).Under the fluoroscopic guide,4 or 6 mini half-pins in one line were directly drilled into the dorsal aspect of the involved metacarpophalangeal bone before the Orthofix fixator was mounted.The proximal (18 digits) or distal (2 digits) osteotomy between the second and third pinholes was performed via the dorsal approach,The external fixator and pins were removed without anesthesia after callus maturation.Results Average follow-up period was 12.2 months (range,from 9 to 26 months).All the metacarpal bone defects were reconstructed and all the phalangeal shortenings were lengthened;the bony callus was completely calcified at the lengthened part.The mean lengthening was 1.9 cm (from 1.0 to 3.1 cm);the percentage of lengthening ranged from 26% to 51% (average,34%).The bone lengthening index (time cost by average 1 cm) was 70.9 d/cm (from 60.0 to 87.1 d/cm).According to the Tentative Assessment Criteria for Upper Extremity Function by Hand Surgery Society,Chinese Medical Association,the total activity of motion (TAM) was excellent in 13 cases,good in 4,fair in 2,and poor in one,yielding an excellent to good rate of 85.0%.Conclusion Distraction lengthening using mini external fixation is a valid option with a minor rate of complications which allows for early functional exercise to help restore the appearance and function of the affected fingers.
4.Hepatectomy combined with intraarterial and intraportal chemotherapy for the treatment of hepatocellular carcinoma
Honghao LI ; Jisheng CHEN ; Haigang LI
Chinese Journal of General Surgery 2001;0(08):-
Objective To evaluate irregular hepatectomy combined with removal of tumor thrombi, postoperative hepatic artery chemotherapy(HAC) and portal vein chemotherapy (PVC) for the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombi (PVTT). Methods From Jan. 1987 to Dec. 1996, 62 HCC cases with PVTT underwent the combined therapy. Among them HAC and PVC were given in 40 cases. 59 patients were followed up for over 3 years. Results 6 cases died of postoperative hepatic and renal failure in 3 months. Recurrent rate and survival rate at 1, 2, 3 year was 46%(18/39), 59%(23/39),79%(31/39)and 69%(27/39),51%(20/39), 31%(12/39) respectively in group of combined HAC and PVC compared with 80%(16/20),90%(18/20),100%(20/20)and 30%(6/20),10%(2/20), 5%(1/20)in group without postoperative HAC and PVC. Conclusions Irregular hepatectomy with removal of tumor thrombi is an effective treatment for HCC with PVTT. Postoperative use of HAC and PVC significantly reduces the recurrence rate and improves survival.
5.Cloning and characterization of a cDNA coding 3-hydroxy-3-methylglutary CoA reductase involved in glycyrrhizic acid biosynthesis in Glycyrrhiza uralensis.
Ying LIU ; Qiaoxian XU ; Peiyu XI ; Honghao CHEN ; Chunsheng LIU
Acta Pharmaceutica Sinica 2013;48(5):773-9
The roots of Glycyrrhiza uralensis are widely used in Chinese medicine for their action of clearing heat, detoxicating, relieving cough, dispelling sputum and tonifying spleen and stomach. The reason why Glycyrrhiza uralensis has potent and significant actions is that it contains various active secondary metabolites, especially glycyrrhizic acid. In the present study, we cloned the cDNA coding 3-hydroxy-3-methylglutary CoA reductase (HMGR) involved in glycyrrhizic acid biosynthesis in Glycyrrhiza uralensis. The corresponding cDNA was expressed in Escherichia coli as fusion proteins. Recombinant HMGR exhibited catalysis activity in reduction of HMG-CoA to mevalonic acid (MVA) just as HMGR isolated from other species. Because HMGR gene is very important in the biosynthesis of glycyrrhizic acid in Glycyrrhiza uralensis, this work is significant for further studies concerned with strengthening the efficacy of Glycyrrhiza uralensis by means of increasing glycyrrhizic acid content and exploring the biosynthesis of glycyrrhizic acid in vitro.
6.Mechanism of genuineness of Glycyrrhiza uralensis based on SNP of β-Amyrin synthase gene.
Yimei ZANG ; Yanpeng LI ; Jing QIAO ; Honghao CHEN ; Chunsheng LIU
Acta Pharmaceutica Sinica 2015;50(7):906-9
β-Amyrin synthase (β-AS) genes of Glycyrrhiza uralensis from 6 different regions were analyzed by PCR-SSCP and sequenced, then the correlationship between β-AS SNP and regions of Glycyrrhiza uralensis were determined. According to the 1 coding single nucleotide polymorphism on the first exon of β-AS gene at 94 bp site, Glycyrrhiza uralensis could be divided into 3 genotypes. In these genotypes, the percentage of 94A type in genuine regions was much higher, and it had significant differences with the percentage in non-genuine regions (P < 0.001). The results of the experiment proved that different β-AS genotypes at 94 bp site from different regions may be one of the important reasons to result in the genuineness of Glycyrrhiza uralensis.
7.Basic research and clinical translation of precision medicine
Zhangren CHEN ; Fazhong HE ; Honghao ZHOU ; Wei ZHANG
Chinese Pharmacological Bulletin 2015;(12):1629-1632
Since the late twentieth century,the progress of ge-nomics,proteomics and other areas has promoted modern medi-cine from the era of evidence-based medicine to the era of preci-sion medicine.With the studies of the relationships between ge-nomic information and clinical phenotypes,precise medicine,to improve clinical outcomes and minimize unnecessary side effects,develops and implements individualized medicine ac-cording to patients’personalized specificities through pharma-cogenomics.Basic research and clinical translation of precision medicine do help to improve the health system of our country.
8.Bone formation mediated by local administration of thymosin β4 in distraction osteogenesis
Honghao CHEN ; Yachao JIA ; Qinglin KANG ; Chuan LIANG ; Yimin CHAI
Chinese Journal of Orthopaedic Trauma 2016;18(9):791-797
Objective To explore the effect and mechanism of local administration of thymosin β4 (Tβ4) on bone regeneration in a distraction osteogenesis model of rat fenur.Methods Sixty Sprague-Dawley rats were randomly divided into groups A,B and C in this study.A distraction osteogenesis model was established in the left femur after osteotomy.At the end of distraction period,the bone regeneration area in group A was subjected to no treatment,that in group B to injection of phosphate buffer saline (PBS),and that in group C to injection of Tβ4.On days 22,29 and 43 postoperatively,the rats from each group were randomly sacrificed and processed for observation of bone regeneration in the distraction osteogenesis area using radiography,Micro-CT,histology and immunohistochemical staining.RT-PCR was used to detect the expression of related genes as well.Results Radiography revealed that the bone regeneration in group C was superior to that in groups A and B on days 22,29 and 43 postoperatively.Micro-CT examination showed significantly increased bone volume (BV),bone mineral density (BMD) and ratio of bone volume to tissue volume (BV/TV) in group C on days 22,29 and 43 postoperatively,and significantly decreased ratio of bone surface area to bone volume on postoperative day 43 in comparison with groups A and B(P < 0.05).HE staining indicated that local capillary density was significantly higher in group C than in groups A and B after local administration of Tβ4 in the distraction osteogenesis.Immunohistochemical staining showed that the capillary density and osteoblasts in group C were higher than in groups A and B.RT-PCR results revealed significantly higher expression of eNOS and Osterix mRNA in the local callus in group C on postoperative day 22 than in groups A and group B (P < 0.05).Conclusion Local administration of thymosin β4 may promote bone formation,which is probably related to the increased expression of eNOS and Osterix.
9.The anti-apoptotic effects of Caspase inhibitor Ⅰ on cultured hepatocytes
Hongwei ZHANG ; Jie WANG ; Erwei SONG ; Honghao LI ; Jisheng CHEN ;
Chinese Journal of General Surgery 2000;0(11):-
0 05) Under the same treatment concentration of rsFasL or granzyme B, percentage in TUNEL positive staining and Caspase 3 activity in the experimental group were much lower than those in the control group ( P
10.Enhancing the accumulation of beta-amyrin in Saccharomyces cerevisiae by co-expression of Glycyrrhiza uralensis squalene synthase 1 and beta-amyrin synthase genes.
Ying LIU ; Honghao CHEN ; Hao WEN ; Ya GAO ; Liqiang WANG ; Chunsheng LIU
Acta Pharmaceutica Sinica 2014;49(5):734-41
Glycyrrhiza uralensis Fisch. ex DC is widely used in traditional Chinese medicine (TCM). Among its various active components, glycyrrhizic acid is believed to be the marker component. Squalene synthase (SQS) and beta-amyrin synthase (beta-AS) are key enzymes in the biosynthetic pathway of glycyrrhizic acid in G uralensis. To reveal the effects of co-expression of SQS1 and beta-AS genes on this pathway, 7 yeast expression vectors harboring different SQS1 variants and beta-AS were constructed and expressed in Saccharomyces cerevisiae as fusion proteins. TLC and GC-MS results showed that co-expression of SQS1 and beta-AS enhanced the accumulation of beta-amyrin. The effects of SQS12 were more obvious than the other two SQS1 variants. This study is significant for further investigations concerned with exploring the biosynthesis of glycyrrhizic acid in vitro and strengthening the efficacy of G. uralensis by means of increasing the content of glycyrrhizic acid.