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Garcinol, an Acetyltransferase Inhibitor, Suppresses Proliferation of Breast Cancer Cell Line MCF-7 Promoted by 17β-Estradiol

  • Ye, Xia;Yuan, Lei;Zhang, Li;Zhao, Jing;Zhang, Chun-Mei;Deng, Hua-Yu
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.5001-5007
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    • 2014
  • The acetyltransferase inhibitor garcinol, a polyisoprenylated benzophenone, is extracted from the rind of the fruit of Garcinia indica, a plant found extensively in tropical regions. Anti-cancer activity has been suggested but there is no report on its action via inhibiting acetylation against cell proliferation, cell cycle progression, and apoptosis-inhibtion induced by estradiol ($E_2$) in human breast cancer MCF-7 cells. The main purposes of this study were to investigate the effects of the acetyltransferase inhibitor garcinol on cell proliferation, cell cycle progression and apoptosis inhibition in human breast cancer MCF-7 cells treated with estrogen, and to explore the significance of changes in acetylation levels in this process. We used a variety of techniques such as CCK-8 analysis of cell proliferation, FCM analysis of cell cycling and apoptosis, immunofluorescence analysis of NF-${\kappa}B$/p65 localization, and RT-PCR and Western blotting analysis of ac-H3, ac-H4, ac-p65, cyclin D1, Bcl-2 and Bcl-xl. We found that on treatment with garcinol in MCF-7 cells, $E_2$-induced proliferation was inhibited, cell cycle progression was arrested at G0/G1 phase, and the cell apoptosis rate was increased. Expression of ac-H3, ac-H4 and NF-${\kappa}B$/ac-p65 proteins in $E_2$-treated MCF-7 cells was increased, this being inhibited by garcinol but not ac-H4.The nuclear translocation of NF-${\kappa}B$/p65 in $E_2$-treated MCF-7 cells was also inhibited, along with cyclin D1, Bcl-2 and Bcl-xl in mRNA and protein expression levels. These results suggest that the effect of $E_2$ on promoting proliferation and inhibiting apoptosis is linked to hyperacetylation levels of histones and nonhistone NF-${\kappa}B$/p65 in MCF-7 cells. The acetyltransferase inhibitor garcinol plays an inhibitive role in MCF-7 cell proliferation promoted by $E_2$. Mechanisms are probably associated with decreasing ac-p65 protein expression level in the NF-${\kappa}B$ pathway, thus down-regulating the expression of cyclin D1, Bcl-2 and Bcl-xl.

Dynamics and Liver Disease Specific Aspects of Quality of Life Among Patients with Chronic Liver Disease in Yunnan, China

  • Che, Yan-Hua;You, Jing;Chongsuvivatwong, Virasakdi;Li, Li;Sriplung, Hucha;Yan, Yuan-Zhi;Ma, Si-Jia;Zhang, Xiaoli;Shen, Ting;Chen, He-Min;Rao, Shao-Feng;Zhang, Ru-Yi
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.12
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    • pp.4765-4771
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    • 2014
  • Background: Patients with chronic liver diseases (CLD) may have compromised health related quality of life (HRQoL). Hepatitis B virus (HBV) infection has long been the leading cause of CLD including liver cancer and cirrhosis. Knowledge on different symptom profiles of CLD should help in development of comprehensive treatment and patient care plans. Objective: To access the facets of HRQoL in chronic liver diseases throughout their spectrum of severity. Materials and Methods: A cross-sectional study was conducted in the First Affiliated Hospital of Kunming Medical University in Yunnan Province of China. Both out- and inpatients undergoing treatment protocols for different HBV related liver disease states were consecutively collected from December 2012 to June 2013. ANOVA was used to compare the mean scores of EQ-5D and chronic liver disease questionnaire (CLDQ) among 5 disease groups. The relationship between demographic variables predicting global CLDQ scores and the domains of CLDQ was analysed. Results: A total of 1040 patients including 520 without complications, 91 with compensated cirrhosis, 198 with decompensated cirrhosis, 131 with HCC and 100 with liver failure were recruited. All domains of CLDQ, the means of EQ-5D value and EQ VAS exhibited significant decline with worsening of disease severity from uncomplicated HBV to liver failure. The multivariate regression demonstrated the reduction of mean scores of CLDQ domain at advanced stage. Patients with liver failure and HCC had more HRQoL impairment than other disease states. No effect of patient gender was found. Patient age was associated with 'fatigue' and 'worry' domains (p=0.006; p=0.004) but not with other domains and global scores of CLDQ and ED-5D. Conclusions: The HRQoL in chronic hepatitis B patients is greatly affected by disease states. Care for HBV-related diseases should consider not only the outcomes of treatment strategies but also improvement in patient wellbeing.

Effects of processing method on the pharmacokinetics and tissue distribution of orally administered ginseng

  • Chen, Jianbo;Li, Meijia;Chen, Lixue;Wang, Yufang;Li, Shanshan;Zhang, Yuwei;Zhang, Lei;Song, Mingjie;Liu, Chang;Hua, Mei;Sun, Yinshi
    • Journal of Ginseng Research
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    • v.42 no.1
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    • pp.27-34
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    • 2018
  • Background: The use of different methods for the processing of ginseng can result in alterations in its medicinal properties and efficacy. White ginseng (WG), frozen ginseng (FG), and red ginseng (RG) are produced using different methods. WG, FG, and RG possess different pharmacological properties. Methods: WG, FG, and RG extracts and pure ginsenosides were administered to rats to study the pharmacokinetics and tissue distribution characteristics of the following ginsenosides-DRg1, Re, Rb1, and Rd. The concentrations of the ginsenosides in the plasma and tissues were determined using UPLC-MS/MS. Results: The rate and extent of absorption of Rg1, Re, Rb1, and Rd appeared to be affected by the different methods used in processing the ginseng samples. The areas under the plasma drug concentration-time curves (AUCs) of Rg1, Re, Rb1, and Rd were significantly higher than those of the pure ginsenosides. In addition, the AUCs of Rg1, Re, Rb1, and Rd were different for WG, FG, and RG. The amounts of Rg1, Re, Rd, and Rb1 were significantly (p < 0.05) higher in the tissues than those of the pure ginsenosides. The amounts of Re, Rb1, and Rd from the RG extract were significantly higher than those from the WG and FG extracts in the heart, lungs, and kidneys of the rats. Conclusion: Our results show that the use of different methods to process ginseng might affect the pharmacokinetics and oral bioavailability of ginseng as well as the tissue concentrations of Rg1, Re, Rd, and Rb1.

Prognostic Significance of C-reactive Protein in Urological Cancers: a Systematic Review and Meta-analysis

  • Dai, Jin;Tang, Kun;Xiao, Wei;Yu, Gan;Zeng, Jin;Li, Wei;Zhang, Ya-Qun;Xu, Hua;Chen, Zhi-Qiang;Ye, Zhang-Qun
    • Asian Pacific Journal of Cancer Prevention
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    • v.15 no.8
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    • pp.3369-3375
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    • 2014
  • Background: C-reactive protein (CRP), considered as a prototypical inflammatory cytokine, has been proposed to be involved in tumor progression through inflammation. Recent studies have indicated CRP as a progostic predictor for urological cancers, but the results remain controversial. Materials and Methods: A systematic search of Medline, Scopus and the Cochrane Library was performed to identify eligible studies published between Jan 1, 2001 and Sep 1, 2013. Outcomes of interest were collected from studies comparing overall survival (OS), cancer-specific survival (CSS) and relapse-free survival (RFS) in patients with elevated CRP levels and those having lower levels. Studies were pooled, and combined hazard ratio (HR) of CRP with its 95% confidence interval (CI) for survival were used for the effect size estimate. Results: A total of 43 studies (7,490 patients) were included in this meta-analysis (25 for RCC, 10 for UC, and 8 for PC). Our pooled results showed that elevated serum CRP level was associated with poor OS (HR: 1.26, 95%CI: 1.22-1.30) and RFS (HR: 1.38 95%CI: 1.29-1.47), respectively. For CSS the pooled HR (HR: 1.33, 95%CI: 1.28-1.39) for higher CRP expression could strongly predict poorer survival in urological cancers. Simultaneously, elevated serum CRP was also significantly associated with poor prognosis in the subgroup analysis. Conclusions: Our pooled results demonstrate that a high serum level of CRP as an inflammation biomarker denotes a poor prognosis of patients with urological cancers. Further large prospective studies should be performed to confirm whether CRP, as a biomarker of inflammation, has a prognostic role in urological cancer progression.

Identification of Specific Gene Modules in Mouse Lung Tissue Exposed to Cigarette Smoke

  • Xing, Yong-Hua;Zhang, Jun-Ling;Lu, Lu;Li, De-Guan;Wang, Yue-Ying;Huang, Song;Li, Cheng-Cheng;Zhang, Zhu-Bo;Li, Jian-Guo;Xu, Guo-Shun;Meng, Ai-Min
    • Asian Pacific Journal of Cancer Prevention
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    • v.16 no.10
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    • pp.4251-4256
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    • 2015
  • Background: Exposure to cigarette may affect human health and increase risk of a wide range of diseases including pulmonary diseases, such as chronic obstructive pulmonary disease (COPD), asthma, lung fibrosis and lung cancer. However, the molecular mechanisms of pathogenesis induced by cigarettes still remain obscure even with extensive studies. With systemic view, we attempted to identify the specific gene modules that might relate to injury caused by cigarette smoke and identify hub genes for potential therapeutic targets or biomarkers from specific gene modules. Materials and Methods: The dataset GSE18344 was downloaded from the Gene Expression Omnibus (GEO) and divided into mouse cigarette smoke exposure and control groups. Subsequently, weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network for each group and detected specific gene modules of cigarette smoke exposure by comparison. Results: A total of ten specific gene modules were identified only in the cigarette smoke exposure group but not in the control group. Seven hub genes were identified as well, including Fip1l1, Anp32a, Acsl4, Evl, Sdc1, Arap3 and Cd52. Conclusions: Specific gene modules may provide better understanding of molecular mechanisms, and hub genes are potential candidates of therapeutic targets that may possible improve development of novel treatment approaches.

Gene Cloning, Expression and Immunogenicity of the Protective Antigen Subolesin in Dermacentor silvarum

  • Hu, Yonghong;Zeng, Hua;Zhang, Jincheng;Wang, Duo;Li, Dongming;Zhang, Tiantian;Yang, Shujie;Liu, Jingze
    • Parasites, Hosts and Diseases
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    • v.52 no.1
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    • pp.93-97
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    • 2014
  • Subolesin (4D8), the ortholog of insect akirins, is a highly conserved protective antigen and thus has the potential for development of a broad-spectrum vaccine against ticks and mosquitoes. To date, no protective antigens have been characterized nor tested as candidate vaccines against Dermacentor silvarum bites and transmission of associated pathogens. In this study, we cloned the open reading frame (ORF) of D. silvarum 4D8 cDNA (Ds4D8), which consisted of 498 bp encoding 165 amino acid residues. The results of sequence alignments and phylogenetic analysis demonstrated that D. silvarum 4D8 (Ds4D8) is highly conserved showing more than 81% identity of amino acid sequences with those of other hard ticks. Additionally, Ds4D8 containing restriction sites was ligated into the pET-32(a+) expression vector and the recombinant plasmid was transformed into Escherichia coli rosetta. The recombinant Ds4D8 (rDs4D8) was induced by isopropyl ${\beta}$-D-thiogalactopyranoside (IPTG) and purified using Ni affinity chromatography. The SDS-PAGE results showed that the molecular weight of rDs4D8 was 40 kDa, which was consistent with the expected molecular mass considering 22 kDa histidine-tagged thioredoxin (TRX) protein from the expression vector. Western blot results showed that rabbit anti-D. silvarum serum recognized the expressed rDs4D8, suggesting an immune response against rDs4D8. These results provided the basis for developing a candidate vaccine against D. silvarum ticks and transmission of associated pathogens.

FOLLOW-UP OBSERVATIONS TOWARD PLANCK COLD CLUMPS WITH GROUND-BASED RADIO TELESCOPES

  • LIU, TIE;WU, YUEFANG;MARDONES, DIEGO;KIM, KEE-TAE;MENTEN, KARL M.;TATEMATSU, KEN;CUNNINGHAM, MARIA;JUVELA, MIKA;ZHANG, QIZHOU;GOLDSMITH, PAUL F;LIU, SHENG-YUAN;ZHANG, HUA-WEI;MENG, FANYI;LI, DI;LO, NADIA;GUAN, XIN;YUAN, JINGHUA;BELLOCHE, ARNAUD;HENKEL, CHRISTIAN;WYROWSKI, FRIEDRICH;GARAY, GUIDO;RISTORCELLI, ISABELLE;LEE, JEONG-EUN;WANG, KE;BRONFMAN, LEONARDO;TOTH, L. VIKTOR;SCHNEE, SCOTT;QIN, SHENGLI;AKHTER, SHAILA
    • Publications of The Korean Astronomical Society
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    • v.30 no.2
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    • pp.79-82
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    • 2015
  • The physical and chemical properties of prestellar cores, especially massive ones, are still far from being well understood due to the lack of a large sample. The low dust temperature (< 14 K) of Planck cold clumps makes them promising candidates for prestellar objects or for sources at the very initial stages of protostellar collapse. We have been conducting a series of observations toward Planck cold clumps (PCCs) with ground-based radio telescopes. In general, when compared with other star forming samples (e.g. infrared dark clouds), PCCs are more quiescent, suggesting that most of them may be in the earliest phase of star formation. However, some PCCs are associated with protostars and molecular outflows, indicating that not all PCCs are in a prestellar phase. We have identified hundreds of starless dense clumps from a mapping survey with the Purple Mountain Observatory (PMO) 13.7-m telescope. Follow-up observations suggest that these dense clumps are ideal targets to search for prestellar objects.

The Up-Regulation of miR-199b-5p in Erythroid Differentiation Is Associated with GATA-1 and NF-E2

  • Li, Yuxia;Bai, Hua;Zhang, Zhongzu;li, Weihua;Dong, Lei;Wei, Xueju;Ma, Yanni;Zhang, Junwu;Yu, Jia;Sun, Guotao;Wang, Fang
    • Molecules and Cells
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    • v.37 no.3
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    • pp.213-219
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    • 2014
  • MicroRNAs (miRNAs) represent a class of small non-coding regulatory RNAs that play important roles in normal hematopoiesis, including erythropoiesis. Although studies have identified several miRNAs that regulate erythroid commitment and differentiation, we do not understand the mechanism by which the crucial erythroid transcription factors, GATA-1and NF-E2 directly regulate and control differentiation via miRNA pathways. In this study, we identified miR-199b-5p as a key regulator of human erythropoiesis, and its expression was up-regulated during the erythroid differentiation of K562 cells. Furthermore, the increase of miR-199b-5p in erythroid cells occurred in a GATA-1- and NF-E2-dependent manner during erythrocyte maturation. Both GATA-1 and NF-E2 bound upstream of the miR-199b gene locus and activated its transcription. Forced expression of miRNA-199b-5p in K562 cells affected erythroid cell proliferation and maturation. Moreover, we identified c-Kit as a direct target of miR-199b-5p in erythroid cells. Taken together, our results establish a functional link among the erythroid transcription factors GATA-1/NF-E2, miR-199b-5p and c-Kit, and provide new insights into the coupling of transcription and post-transcription regulation in erythroid differentiation.

Myeloid-Derived Suppressor Cells Are Associated with Viral Persistence and Downregulation of TCR ζ Chain Expression on CD8+ T Cells in Chronic Hepatitis C Patients

  • Zeng, Qing-Lei;Yang, Bin;Sun, Hong-Qi;Feng, Guo-Hua;Jin, Lei;Zou, Zheng-Sheng;Zhang, Zheng;Zhang, Ji-Yuan;Wang, Fu-Sheng
    • Molecules and Cells
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    • v.37 no.1
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    • pp.66-73
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    • 2014
  • Myeloid-derived suppressor cells (MDSCs) play an important role in impairing the function of T cells. We characterized MDSCs in two chronic hepatitis C (CHC) cohorts: a cross-sectional group that included 61 treatment-naive patients with CHC, 14 rapid virologic response (RVR) cases and 22 early virologic response (EVR) cases; and a longitudinal group of 13 cases of RVR and 10 cases of EVR after pegylated-interferon-${\alpha}$/ribavirin treatment for genotype 1b HCV infection. Liver samples from 32 CHC patients and six healthy controls were subjected to immunohistochemical analysis. MDSCs frequency in treatment-naive CHC was significantly higher than in RVR, EVR, or healthy subjects and was positively correlated with HCV RNA. Patients infected with HCV genotype 2a had a significantly higher frequency of MDSCs than those infected with genotype 1b. Decreased T cell receptor (TCR) ${\zeta}$ expression on $CD8^+$ T cells was significantly associated with an increased frequency of MDSCs in treatment-naive CHC patients and was restored by L-arginine treatment in vitro. Increased numbers of liver arginase-$1^+$ cells were closely associated with the histological activity index in CHC. The TCR ${\zeta}$ chain was significantly downregulated on hepatic $CD8^+$ T cells in CHC. During antiviral follow up, MDSCs frequency in peripheral blood mononuclear cells was directly correlated with the HCV RNA load in the plasma and inversely correlated with TCR ${\zeta}$ chain expression in $CD8^+$ T cells in both RVR and EVR cases. Notably, the RVR group had a higher frequency of MDSCs at baseline than the EVR group. Collectively, this study provides evidence that MDSCs might be associated with HCV persistence and downregulation of CD8 ${\zeta}$ chain expression.

Effects of adaptation time and inclusion level of sugar beet pulp on nutrient digestibility and evaluation of ileal amino acid digestibility in pigs

  • Zhang, Ze Yu;Zhang, Shuai;Lai, Chang Hua;Zhao, Jin Biao;Zang, Jian Jun;Huang, Cheng Fei
    • Asian-Australasian Journal of Animal Sciences
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    • v.32 no.9
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    • pp.1414-1422
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    • 2019
  • Objective: Two experiments were conducted to determine the effects of adaptation time and inclusion level of sugar beet pulp (SBP) on nutrient digestibility and to evaluate the ileal amino acid digestibility of SBP fed to pigs. Methods: In Exp. 1, thirty-six crossbred barrows ($85.0{\pm}2.1kg$) were allotted to 6 diets in a completely randomized design with six replicates per diet. Diets included a corn-soybean meal diet and 5 test diets containing 14.6%, 24.4%, 34.2%, 43.9%, or 53.7% SBP, respectively. The adaptation time consisted 7, 14, 21, or 28 d consecutively for each pig followed by 5 d for fecal collection. Feces were collected from d 8 to 13, d 15 to 20, d 22 to 27, and d 29 to 34, respectively. In Exp. 2, six pigs ($35.1{\pm}1.7kg$) with T-cannulas at the terminal ileum were fed to 3 diets in a replicated $3{\times}3$ Latin square design with 3 periods and 2 replicate pigs per diet. Each period consisted 5 d for diet adaptation followed by 2 d for digesta collection. Results: The digestible energy (DE) value and the apparent total tract digestibility (ATTD) of gross energy (GE), dry matter (DM), ash, and organic matter in diets linearly decreased (p<0.05) as the adaptation time increased or as the dietary SBP increased, while the ATTD of neutral detergent fibre and acid detergent fibre in diets linearly increased (p<0.01) as the dietary SBP increased. The DE value and the ATTD of GE and crude protein (CP) in SBP linearly increased (p<0.05) as the adaptation time increased, while the ATTD of CP in SBP linearly decreased (p<0.01) as the inclusion level increased. The standardized ileal digestibility of Lys, Met, Thr, and Trp in SBP was 37.03%, 51.62%, 40.68%, and 46.22%, respectively. Conclusion: The results of this study indicated that the ATTD of energy and nutrients were decreased as inclusion rate of SBP increased.