3.Metabolic pathway and metabolites of total diterpene acid isolated from Pseudolarix kaempferi.
Peng LIU ; Hong-Zhu GUO ; Jiang-Hao SUN ; Man XU ; Hui GUO ; Shi-Feng SUN ; De-An GUO
Acta Pharmaceutica Sinica 2014;49(8):1169-1174
The preliminary metabolic profile of total diterpene acid (TDA) isolated from Pseudolarix kaempferi was investigated by using in vivo and in vitro tests. Pseudolaric acid C2 (PC2) was identified as the predominant metabolite in plasma, urine, bile and feces after both oral and intravenous administrations to rats using HPLC-UV and HPLC-ESI/MS(n), and demethoxydeacetoxypseudolaric acid B (DDPB), a metabolite proposed to be the glucoside of PC2 (PC2G), as well as pseudolaric acid C (PC), pseudolaric acid A (PA), pseudolaric acid A O-beta-D glucopyranoside (PAG), pseudolaric acid B O-beta-D glucopyranoside (PBG) and deacetylpseudolaric acid A (DPA) originated from TDA could also be detected. It was demonstrated by tests that the metabolism of TDA is independent of intestinal microflora, and neither of pepsin and trypsin is in charge of metabolism of TDA, TDA is also stable in both pH environments of gastric tract and intestinal tract. The metabolites of TDA in whole blood in vitro incubation were found to be PC2, DDPB and PC2G, which demonstrated that the metabolic reaction of TDA in vivo is mainly occurred in blood and contributed to be the hydrolysis of plasma esterase to ester bond, as well as the glucosylation reaction. These results clarified the metabolic pathway of TDA for the first time, which is of great significance to the in vivo active form and acting mechanism research of P. kaempferi.
Animals
;
Chromatography, High Pressure Liquid
;
Diterpenes
;
metabolism
;
Glucosides
;
metabolism
;
Hydrolysis
;
Mass Spectrometry
;
Metabolic Networks and Pathways
;
Pinaceae
;
chemistry
;
Rats
4.Platelet Count Doubling after One Course of Demethylated Drug Therapeutic Predicts the Treatment Response and Efficacy of Patients with Myelodysplastic Syndrome
Hui HUI ; Hao-Yuan YU ; De-Peng LI
Journal of Experimental Hematology 2024;32(1):184-189
Objective:To investigate the predictive value of platelet doubling(platelet count doubling)after one course of hypomethylating agents(HMA)on the treatment response and efficacy of myelodysplastic syndrome(MDS).Methods:Clinical and pathological data of 75 patients who received HMA in our hospital from January 2017 to March 2022 were collected and analyzed.All patients were divided into two groups according to whether their platelet count doubled after one course of treatment,including platelet doubling group and non-doubling group,and statistical analysis was performed to compare the treatment response and efficacy between the two groups.In addition,platelet count changes were compared between azacitidine and decitabine therapy.Results:Compared with the non-doubling platelet count group,the ORR of the doubling platelet group was significantly better after 3 courses of treatment(P=0.002),and there was a statistically significant difference in the number of HI between the two groups(P=0.005).In addition,the median survival time(MST)was 26 months in the platelet doubling group and 11 months in the non-doubling group(P=0.001).The overall survival(OS)and 1-and 2-year survival rates of the platelet doubling group were also significantly better than those of the non-doubing group.Multivariate COX analysis showed that platelet count doubling was an independent predictor of OS in MDS patients after 1 course of treatment(P=0.013).There was no significant difference in the response rate of platelet count doubling between MDS patients treated with azacitidine and decitabine(33.3%vs 23.8%,P>0.05).Conclusion:Platelet count doubling after one course of treatment can be used as a predictor of response rate and survival of demethylated drug therapy in MDS patients.In addition,there was no significant difference in the response rate of platelets in MDS patients treated with azacitidine or dicetabine.
5.The effect of cell killing by ABT-737 synergized with docetaxel in human prostate cancer PC-3 cells.
Jian-wei HAO ; Xiao-peng MAO ; De-gang DING ; Guang-hui DU ; Zhong-hua LIU
Chinese Journal of Surgery 2012;50(2):161-165
OBJECTIVETo investigate the synergistical killing effect of docetaxel combined with ABT-737 on human prostate cancer cell line PC-3 by inducing apoptosis and further to determine the mechanism underlying such effect.
METHODSPC-3 cells were treated with various concentrations of docetaxel or (and) ABT-737. Cell viability was determined using MTT assay. Apoptosis was assessed by fluorescence microscopy analysis of cells with condensed and segmented nuclei following staining with 4',6-diamidino-2-phenylindole (DAPI). Cellular DNA was stained with propidium iodide and flow cytometric analysis was performed to analyze the cell cycle distribution. Bcl-2, Bax, Bcl-xL and Mcl-1 protein changes were detected by Western blot. The activity of caspase-3 was measured using a colorimetric assay.
RESULTSDocetaxel (20 nmol/L) combination with ABT-737 (400 nmol/L) for 48 hours, the cell viability was decreased to 19.7% ± 3.2% to compare with 44.2% ± 4.4% (t = 4.45) of docetaxel and 93.2% ± 1.8% of ABT-737 separately and there was a synergistic effect between the two drugs (CI = 0.8). Apoptosis rate of the combination group was higher than other two drugs. Docetaxel increased the cell number arrested in G(2)/M phase compared with control group (P < 0.05), but the combination treatment resulted in a significant arrest in the G(0)/G(1) phase. The combination treatment could significantly reduced the Bcl-2, Bcl-xL and Mcl-1 expression (F = 369.53, 57.89 and 32.77, all P < 0.05) and enhanced the activity of caspase-3 (419.7% ± 15.6%) (F = 207.33, P < 0.05).
CONCLUSIONSThe combination of ABT-737 with docetaxel can synergistically inhibit the proliferation of PC-3 cells through inducing apoptosis, which may be associated with cell cycle arrest, down-regulation of Bcl-2, Bcl-xL and Mcl-1 expression and activation of caspase-3.
Apoptosis ; drug effects ; Biphenyl Compounds ; pharmacology ; Caspase 3 ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Drug Synergism ; Humans ; Male ; Myeloid Cell Leukemia Sequence 1 Protein ; metabolism ; Nitrophenols ; pharmacology ; Piperazines ; pharmacology ; Prostatic Neoplasms ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism ; Sulfonamides ; pharmacology ; Taxoids ; pharmacology ; bcl-X Protein ; metabolism
6.Image integration system to guide catheter ablation of atrial tachycardia with a multi-key-isthmus reentrant in a patient with a repaired atrial septal defect: a case report.
Rong-hui YU ; Jian-zeng DONG ; Xing-peng LIU ; De-yong LONG ; Jun-ping KANG ; Chang-sheng MA
Chinese Medical Journal 2008;121(9):859-861
7.Clinical observation on hemiplegia early rehabilitation effects of different acupuncture programs.
Long-ming LEI ; Jun PANG ; Jia-xing CHEN ; De-hui PENG ; Ze-tao WANG
Chinese Acupuncture & Moxibustion 2005;25(4):233-236
OBJECTIVETo observe early rehabilitation of two different acupuncture programs for hemiplegia due to stroke.
METHODSSeventy cases of early hemiplegia due to stroke were randomly divided into a treatment group and a control group. The treatment group were treated by acupuncture at acupoints of both the healthy and affected sides, twice each day, respectively, and the control group by acupuncture at the affected side, once daily. Their therapeutic effects were evaluated by the brief Fugl-Meyer movement scale and the modified Barthel indexes.
RESULTSThe patients with over grade IV for FMA accounted for 68.6% and the good rate for ADL was 74.3% in the treatment group, and 31.4% and 42.8% in the control group, respectively, the therapeutic effect of the treatment group being better than that of the control group (P<0.01 or P<0.05).
CONCLUSIONThe acupuncture program in which acupoints at both the healthy and affected sides are applied alternately is more beneficial to recovery of motor function and activity daily living (ADL) of the patient with hemiplegia due to stroke.
Activities of Daily Living ; Acupuncture Points ; Acupuncture Therapy ; Hemiplegia ; therapy ; Humans ; Stroke ; therapy
8.Application of green light laser in complex posterior urethral stricture after surgical treatment of benign prostatic hyperplasia
Mu-Wen WANG ; Xun-Bo JIN ; Yong ZHAO ; Qing-Hua XIA ; Shao-Bo JIANG ; Hui XIONG ; Peng SUN ; Xiu-de CHEN ; Zheng WANG
Chinese Journal of Urology 2000;0(12):-
Objective To investigate the effect of green light laser in complex posterior urethral stricture after surgical treatment of benign prostatic hyperplasia (BPH).Methods Green light laser was applied in treating 20 cases of complex iatrogenic posterior urethral stricture.Of these cases,12 had false passages,5 had more than 2 strictures and 5 had concurrently urethratresia.The scar tissues were transure- thrally vaporized and resected.The in-dwelling urethral catheter time was 1-2 months after operation. Results All the patients were initially cured without serious complications.The mean operative time was 39 rain (range,30-65 min).During the follow-up of 2-10 months,1 case had mild incontinence:another case (Q_(max)<9ml/s 2 weeks after surgery) got satisfactory results(Q_(max)>15ml/s)after the scheduled urethral dilatation.The other 18 cases were treated successfully and voided fluently with postoperative Q_(max)>15ml/s in all.Conclusions It is suggested that transurethral green light laser procedure is not only safe and ef- fective,but also simple and minimally iuvasive for complex posterior urethral stricture following surgical treat- ment of BPH.
9.Construction of WISP3 gene's mutants in SEDT-PA and their expression in COS-7 cells.
Min WANG ; Yi-qun PENG ; Hou-de ZHOU ; Mu-xu ZHAI ; Yu-ling HE ; Hui XIE
Journal of Central South University(Medical Sciences) 2008;33(1):8-15
OBJECTIVE:
To construct two types of Wnt-inducible secreted protein 3(WISP3) gene's mutants(1000T/C,840delT) found in spondyloepiphyseal dysplasia tarda with progressive anthopathy (SEDT-PA) patients, and to observe their expression in COS-7 cells.
METHODS:
Full-length cDNA of wild type WISP3 gene(WT-WISP3) was amplified from human chondrocytes by RT-PCR, and site-directed mutagenesis was used to obtain full-length cDNAs of the mutated WISP3 genes(MUT1000T/C and MUT840delT). The recombined plasmids WT-WISP3/pcDNA3.1(+), MUT1000T/C/pcDNA3.1(+) and MUT840delT/pcDNA3.1(+) were transfected transiently into COS-7 cells by liposome-mediated method, and pcDNA3.1(+) vector was used as a control. The total RNA and protein of the transfected COS-7 cells were extracted after 48 hours of transfection. The expression of WISP3 gene in the transfected COS-7 cells was detected by semi-quantitative RT-PCR and Western blot.
RESULTS:
By restriction endonuclease analysis and sequencing, the sequence of MUT1000T/C and MUT840delT were consistent with that mutated in SEDT-PA, and the open reading frames matched with the vector sequence. Semi-quantitative RT-PCR and Western blot showed that the recombined plasmids were highly expressed in COS-7 cells.
CONCLUSION
WISP3 gene's mutants of SEDT-PA are successfully constructed by genetic recombination, and expressed in COS-7 cells, which lays the foundation for the further study on its molecular functions in SEDT-PA.
Animals
;
Base Sequence
;
CCN Intercellular Signaling Proteins
;
COS Cells
;
metabolism
;
Chlorocebus aethiops
;
Humans
;
Insulin-Like Growth Factor Binding Proteins
;
biosynthesis
;
genetics
;
Molecular Sequence Data
;
Mutagenesis, Site-Directed
;
Mutation
;
Osteochondrodysplasias
;
genetics
;
metabolism
;
Transfection
10.Relations between serum adipocyte fatty acid-binding protein and type 2 diabetes in a community population.
Wen-hui YE ; Xiang-hang PENG ; Ya-qin AI ; Hong CHEN ; Hua ZHANG ; De-hong CAI
Journal of Southern Medical University 2011;31(3):508-511
OBJECTIVETo study the relationship between the serum levels of adipocyte fatty acid-binding protein (A-FABP) level and type 2 diabetes mellitus in a community population.
METHODSA total of 255 residents (aged 45-85 years) were randomly selected from 4 communities in Guangzhou to examine the fasting plasma glucose (FPG), 2-hour postprandial blood glucose (2hPG), glycosylated hemoglobin (HbA1c), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR), blood pressure (BP), triglyceride (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C). The insulin resistance index (HOMA-IR) was calculated and enzyme-linked immunosorbent assay (ELISA) was used to determine serum A-FABP and fasting insulin (FINs) levels. The cases were divided into 3 groups according to blood glucose level, namely the normal group (group A, n=90), impaired glucose tolerance group (group B, n=85), and diabetic group (group C, n=80), and the A-FABP levels were compared between them.
RESULTSCompared with group A, the subjects in groups B and C showed significantly increased FPG, 2hPGh, HbA1C, HOMA-IR, systolic blood pressure (SBP), and waist circumference (P=0.000) as well as FINs, WHR, diastolic blood pressure (DBP) , TG, and HDL-C (P=0.038, 0.047, 0.01, and 0.046, respectively). Compared with group B, group C showed significantly higher FPG, 2hPG, HbA1c, TG, and SBP (P=0.00), with also higher levels of FINs, BMI, WC, DBP, and HDL-C (P=0.012, 0.006, 0.03, 0.019, and 0.029, respectively). A-FABP increased significantly in the order of group A, B, and C (P=0.00), and this result was not affected by the differences in age between the 3 groups (P>0.05). A-FABP level was positively correlated to FPB, 2hPG, FINS, WHR, BMI, WC, SBP, and HOMA-IR, but inversely to TG and HDL-C (P=0.00).
CONCLUSIONElevated serum A-FABP is closely related to glucose metabolism disorder, and A-FABP may serve as a useful marker for the occurrence and development of type 2 diabetes in the community population.
Adipocytes ; chemistry ; Aged ; Aged, 80 and over ; Diabetes Mellitus, Type 2 ; blood ; etiology ; Fatty Acid-Binding Proteins ; blood ; Female ; Humans ; Male ; Middle Aged ; Serum ; metabolism