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( Fei-liang Zhong ),( Rui Ma ),( Mingliang Jiang ),( Wei-wei Dong ),( Jun Jiang ),( Songquan Wu ),( Donghao Li ),( Lin-hu Quan ) 한국미생물 · 생명공학회 2016 Journal of microbiology and biotechnology Vol.26 No.10
The ginsenoside-hydrolyzing β-glucosidase gene (bgy2) was cloned from Lactobacillus brevis. We expressed this gene in Escherichia coli BL21(DE3), isolated the resulting protein, and then utilized the enzyme for the biotransformation of ginsenosides. The bgy2 gene contains 2,223 bp, and encodes a protein of 741 amino acids that is a member of glycosyl hydrolase family 3. β-Glucosidase (Bgy2) cleaved the outer glucose moieties of ginsenosides at the C-20 position, and the inner glucose at the C-3 position. Under optimal conditions (pH 7.0, 30˚C), we used 0.1 mg/ml Bgy2 in 20 mM sodium phosphate buffer (PBS) for enzymatic studies. In these conditions, 1.0 mg/ml ginsenoside Rb1 and ginsenoside F2 were converted into 0.59 mg/ml ginsenoside Rd and 0.72mg/ml compound K, with molar conversion productivities of 69% and 91%, respectively. In pharmaceutical and commercial industries, this recombinant Bgy2 would be suitable for producting ginsenoside Rd and compound K.
C1420T Polymorphism of Cytosolic Serine Hydroxymethyltransferase and Risk of Cancer: a Meta-analysis
Zhong, Shan-Liang,Zhang, Jun,Hu, Qing,Chen, Wei-Xian,Ma, Teng-Fei,Zhao, Jian-Hua Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.5
A series of studies have explored the role of cytosolic serine hydroxymethyltransferase (SHMT1) C1420T polymorphism in cancer risk, but their results were conflicting rather than conclusive. To derive a more precise estimation of the association between C1420T and cancer risk, the present meta-analysis of 28 available studies with 15,121 cases and 18,023 controls was conducted. The results revealed that there was no significant association between the polymorphism and cancer risk overall. In stratified analysis by cancer type (breast cancer, gastrointestinal cancer, leukemia, lymphoma, and others), the results showed that 1420T allele was associated with decreased risk in leukemia (CT vs. CC: OR= 0.825, 95% CI =0.704-0.966; and CT+TT vs. CC: OR= 0.838, 95% CI = 0.722-0.973), but the same results were not present for other cancer types. When subgroup analysis was performed by source of control (population-based [PB] and hospital-based [HB]), a borderline inverse association was observed for the HB subgroup (CT vs. CC: OR= 0.917, 95% CI = 0.857-0.982) but not for the PB subgroup. Stratifying by geographic area (America, Asia and Europe), significant inverse association was only found in Asia subgroup (CT vs. CC: OR= 0.674, 95% CI = 0.522-0.870). In summary, the findings suggest that SHMT1 C1420T polymorphism is not associated with overall cancer development, but might decrease cancer susceptibility of Asians as well as reduce leukemia risk. Large well-designed epidemiological studies will be necessary to validate the risk identified in the current meta-analysis.
MACC1 Expression Correlates with PFKFB2 and Survival in Hepatocellular Carcinoma
Ji, Dong,Lu, Zhong-Tang,Li, Yao-Qing,Liang, Zhe-Yong,Zhang, Peng-Fei,Li, Chao,Zhang, Jun-Li,Zheng, Xin,Yao, Ying-Min Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.2
Objective: To validate the relationship between MACC1 and 6-phosphofructo-2-kinase/fructose 2, 6 bisphosphatase (PFKFB2) expression as well as its clinicopathological features and prognostic significance in hepatocellular carcinoma. Methods: By using immunohistochemistry, we investigated the MACC1 and PFKFB2 protein expression in 60 pairs of hepatocellular carcinoma and corresponding non-tumor tissues. Using the Mann-Whitney U test, the Chi-square test, Kaplan-Meier survival analysis, Cox proportional hazard regression analysis and Spearman analysis, we studied the relationship between MACC1 and PFKFB2 protein expression and postoperative overall survival (OS) of the HCC patients. Results: MACC1 and PFKFB2 positive staining rates were significantly higher in hepatocellular carcinoma than in the corresponding nontumor tissues (P=0.012 and 0.04, respectively). The clinicopathological features evaluation revealed that positive expression of MACC1 was associated with a high Edmondson classification (P=0.007) and advanced TNM stage (P=0.027). Similar findings were evident for PFKFB2 expression (P=0.002 and P=0.027). MACC1 and PFKFB2 positive expression was associated with a lower OS rate (P=0.004 and 0.03, respectively). Kaplan-Meier survival and Cox proportional hazard regression analyses revealed MACC1 positive expression to be a prognostic factor for postoperative OS, but PFKFB was not. Conclusion: Highly expressed MACC1 and PFKFB2 protein were associated with TNM stage, Edmondson-Steier classification and overall survival. MACC1 may affect tumor metabolism partly through expression and phophorylation of PFKFB2.
Ming-Chen Ba,Hui Long,Xiang-Liang Zhang,Yuan-Feng Gong,Zhao-Fei Yan,Shuai Wang,Yun-Qiang Tang,Shu-Zhong Cui 연세대학교의과대학 2017 Yonsei medical journal Vol.58 No.3
Purpose: CO2 leakage along the trocar (chimney effect) has been proposed to be an important factor underlying port-site metastasisafter laparoscopic surgery. This study aimed to test this hypothesis by comparing the incidence of port-site metastasis betweenB-ultrasound-guided and laparoscopically-assisted hyperthermic intraperitoneal perfusion chemotherapy (HIPPC). Materials and Methods: Sixty-two patients with malignant ascites induced by gastrointestinal or ovarian cancer were divided into two groups to receive either B-ultrasound-guided or laparoscopically-assisted HIPPC. Clinical efficacy was assessed from the objective remission rate (ORR), the Karnofsky Performance Status (KPS) score, and overall survival. The incidence of port-site metastasis was compared between the two groups. Results: Patients in the B-ultrasound (n=32) and laparoscopy (n=30) groups were comparable in terms of age, sex, primary diseasetype, volume of ascites, and free cancer cell (FCC)-positive ascites. After HIPPC, there were no significant differences between the B-ultrasound and laparoscopy groups in the KPS score change, ORR, and median survival time. The incidence of port-site metastasis after HIPPC was not significantly different between the B-ultrasound (3 of 32, 9.36%) and laparoscopy (3 of 30, 10%) groups, but significantly different among pancreatic, gastric, ovarian, and colorectal cancer (33.33, 15.79, 10.00, and 0.00%, p<0.001). Conclusion: The chimney effect may not be the key reason for port-site metastasis after laparoscopy. Other factors may play a role, including the local microenvironment at the trocar site and the delivery of viable FCCs (from the tumor or malignant ascites) to the trauma site during laparoscopic surgery.
Dong, Wei-Wei,Zhao, Jinhua,Zhong, Fei-Liang,Zhu, Wen-Jing,Jiang, Jun,Wu, Songquan,Yang, Deok-Chun,Li, Donghao,Quan, Lin-Hu The Korean Society of Ginseng 2017 Journal of Ginseng Research Vol.41 No.4
Background: In general, after Panax ginseng is administered orally, intestinal microbes play a crucial role in its degradation and metabolization process. Studies on the metabolism of P. ginseng by microflora are important for obtaining a better understanding of their biological effects. Methods: In vitro biotransformation of P. ginseng extract by rat intestinal microflora was investigated at $37^{\circ}C$ for 24 h, and the simultaneous determination of the metabolites and metabolic profile of P. ginseng saponins by rat intestinal microflora was achieved using LC-MS/MS. Results: A total of seven ginsenosides were detected in the P. ginseng extract, including ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd. In the transformed P. ginseng samples, considerable amounts of deglycosylated metabolite compound K and Rh1 were detected. In addition, minimal amounts of deglycosylated metabolites (ginsenosides Rg2, F1, F2, Rg3, and protopanaxatriol-type ginsenosides) and untransformed ginsenosides Re, Rg1, and Rd were detected at 24 h. The results indicated that the primary metabolites are compound K and Rh1, and the protopanaxadiol-type ginsenosides were more easily metabolized than protopanaxatriol-type ginsenosides. Conclusion: This is the first report of the identification and quantification of the metabolism and metabolic profile of P. ginseng extract in rat intestinal microflora using LC-MS/MS. The current study provided new insights for studying the metabolism and active metabolites of P. ginseng.
Biotransformation of Panax ginseng extract by rat intestinal microflora
Wei-Wei Dong,Jinhua Zhao,Fei-Liang Zhong,Wen-Jing Zhu,Jun Jiang,Songquan Wu,Deok-Chun Yang,Donghao Li,Lin-Hu Quan 고려인삼학회 2017 Journal of Ginseng Research Vol.41 No.4
Background: In general, after Panax ginseng is administered orally, intestinal microbes play a crucial role in its degradation and metabolization process. Studies on the metabolism of P. ginseng by microflora are important for obtaining a better understanding of their biological effects. Methods: In vitro biotransformation of P. ginseng extract by rat intestinal microflora was investigated at 37C for 24 h, and the simultaneous determination of the metabolites and metabolic profile of P. ginseng saponins by rat intestinal microflora was achieved using LCeMS/MS. Results: A total of seven ginsenosides were detected in the P. ginseng extract, including ginsenosides Rg1, Re, Rf, Rb1, Rc, Rb2, and Rd. In the transformed P. ginseng samples, considerable amounts of deglycosylated metabolite compound K and Rh1 were detected. In addition, minimal amounts of deglycosylated metabolites (ginsenosides Rg2, F1, F2, Rg3, and protopanaxatriol-type ginsenosides) and untransformed ginsenosides Re, Rg1, and Rd were detected at 24 h. The results indicated that the primary metabolites are compound K and Rh1, and the protopanaxadiol-type ginsenosides were more easily metabolized than protopanaxatriol-type ginsenosides. Conclusion: This is the first report of the identification and quantification of the metabolism and metabolic profile of P. ginseng extract in rat intestinal microflora using LCeMS/MS. The current study provided new insights for studying the metabolism and active metabolites of P. ginseng.
Down-regulation of miRNA-452 is Associated with Adriamycin-resistance in Breast Cancer Cells
Hu, Qing,Gong, Jian-Ping,Li, Jian,Zhong, Shan-Liang,Chen, Wei-Xian,Zhang, Jun-Ying,Ma, Teng-Fei,Ji, Hao,Lv, Meng-Meng,Zhao, Jian-Hua,Tang, Jin-Hai Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.13
Adriamycin (ADR) is an important chemotherapeutic agent frequently used in treatment of breast cancer. However, resistance to ADR results in treatment failure in many patients. Recent studies have indicated that microRNAs (miRNAs) may play an important role in such drug-resistance. In the present study, microRNA-452 (miR-452) was found to be significantly down-regulated in adriamycin-resistant MCF-7 cells (MCF-7/ADR) compared with the parental MCF-7 cells by miRNA microarray and real-time quantitative PCR (RT-qPCR). MiR-452 mimics and inhibitors partially changed the adriamycin-resistance of breast cancer cells, as also confirmed by apoptosis assay. In exploring the potential mechanisms of miR-452 in the adriamycin-resistance of breast cancer cells, bioinformatics analysis, RT-qPCR and Western blotting showed that dysregulation of miR-452 played an important role in the acquired adriamycin-resistance of breast cancer, maybe at least in part via targeting insulin-like growth factor-1 receptor (IGF-1R).
Jin, Xin,Zhang, Ke-Jin,Guo, Xu,Myers, Ronald,Ye, Zhong,Zhang, Zhi-Pei,Li, Xiao-Fei,Yang, Hu-Shan,Xing, Jin-Liang Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.17
Over-expression of de novo lipogenesis (DNL) genes is associated with the prognosis of various types of cancers. However, the effects of single nucleotide polymorphisms (SNPs) in these genes on recurrence and survival of non-small cell lung cancer (NSCLC) patients after surgery are still unknown. In this study, a total of 500 NSCLC patients who underwent surgery treatment were included. Eight SNPs in 3 genes (ACACA, FASN and ACLY) of the DNL pathway were examined using the Sequenom iPLEX genotyping system. Multivariate Cox proportional hazards regression and Kaplan-Meier curves were used to analyze the association of SNPs with patient survival and tumour recurrence. We found that two SNPs in the FASN gene were significantly associated with the recurrence of NSCLC. SNP rs4246444 had a significant association with lung cancer recurrence under additive model (hazard ratio [HR], 0.82; 95% confidence interval [95%CI], 0.67-1.00; p=0.05). Under the dominant model, rs4485435 exhibited a significant association with recurrence (HR, 0.75; 95%CI, 0.56-1.01; p=0.05). Additionally, SNP rs9912300 in ACLY gene was significantly associated with overall survival in lung cancer patients (HR, 1.41; 95%CI, 1.02-1.94, p=0.04) under the dominant model. Further cumulative effect analysis showed moderate dose-dependent effects of unfavorable SNPs on both survival and recurrence. Our data suggest that the SNPs in DNL genes may serve as independent prognostic markers for NSCLC patients after surgery.