Clitocine potentiates TRAIL-mediated apoptosis in human colon cancer cells by promoting Mcl-1 degradation

Among anti-cancer candidate drugs, TRAIL might be the most specific agent against cancer cells due to its low toxicity to normal cells. Unfortunately, cancer cells usually develop drug resistance to TRAIL, which is a major obstacle for its clinical application. One promising strategy is co-administrating with sensitizer to overcome cancer cells resistance to TRAIL. Clitocine, a natural amino nucleoside purified from wild mushroom, is recently demonstrated that can induce apoptosis in multidrug-resistant human cancer cells by targeting Mcl-1. In the present study,we found that pretreatment with clitocine dramatically enhances TRAIL lethality in its resistant human colon cancer cells by inducing apoptosis. More importantly, combination of clitocine and TRAIL also effectively inhibits xenograft growth and induces tumor cells apoptosis in athymic mice. The disruption of the binding between Mcl-1 and Bak as well as mitochondrial translocation of Bax mediated by clitocine are identified as the key underlying mechanisms, which leading to mitochondrial membrane permeabilization. Enforced exogenous Mcl-1 can effectively attenuate clitocine/TRAIL-induced apoptosis by suppressing the activation of intrinsic apoptotic pathway. Furthermore, clitocine regulates Mcl-1 expression at the posttranslational level as no obvious change is observed on mRNA level and proteasome inhibitor MG132 almost blocks the Mcl-1 suppression by clitocine. In fact, more ubiquitinated Mcl-1 was detected under clitocine treatment. Our findings indicate that clitocine is potentially an effective adjuvant agent in TRAIL-based cancer therapy.     

重楼属植物甾体皂甙的高效液相色谱分析

应用高效液相层析技术,对重楼属十八个种植物的甾体皂甙进行了定性、定量分析。植物用甲醇提取,抽出物经DIAION柱,以90％甲醇洗出总甙。在HPLC上,用ODS柱先将总甙以用醇:水(9:1)洗脱分为三馏段,每馏再在ODS柱或Rp-8柱上以甲醇:水(8:2;7:3.5)洗脱,使各个皂甙成分完全分离。被分离的每个色谱峰与已知重楼皂甙的保留时间进行比较并配合HPLC的加入法,TLC分析及用HPLC制备少量样品做MS测定来加以定性鉴定。定量采用内标及校正曲线法。     

Role of hypoxia in the hallmarks of human cancer

Hypoxia has been recognized as one of the fundamentally important features of solid tumors and plays a critical role in various cellular and physiologic events, including cell proliferation, survival, angiogenesis, immunosurveillance, metabolism, as well as tumor invasion and metastasis. These responses to hypoxia are at least partially orchestrated by activation of the hypoxia‐inducible factors (HIFs). HIF‐1 is a key regulator of the response of mammalian cells to oxygen deprivation and plays critical roles in the adaptation of tumor cells to a hypoxic microenvironment. Hypoxia and overexpression of HIF‐1 have been associated with radiation therapy and chemotherapy resistance, an increased risk of invasion and metastasis, and a poor clinical prognosis of solid tumors. The discovery of HIF‐1 signaling has led to a rapidly increasing understanding of the complex mechanisms involved in tumor hypoxia and has helped greatly in screening novel anticancer agents. In this review, we will first introduce the cellular responses to hypoxia and HIF‐1 signaling pathway in hypoxia, and then summarize the multifaceted role of hypoxia in the hallmarks of human cancers. J. Cell. Biochem. 107: 1053–1062, 2009. © 2009 Wiley‐Liss, Inc.     

Lysophosphatidic Acid Increases the Electrophysiological Instability of Adult Rabbit Ventricular Myocardium by Augmenting L-Type Calcium Current

Lysophosphatidic acid (LPA) has diverse actions on the cardiovascular system and is widely reported to modulate multiple ion currents in some cell types. However, little is known about its electrophysiological effects on cardiac myocytes. This study investigated whether LPA has electrophysiological effects on isolated rabbit myocardial preparations. The results indicate that LPA prolongs action potential duration at 90% repolarization (APD₉₀) in a concentration- and frequency-dependent manner in isolated rabbit ventricular myocytes. The application of extracellular LPA significantly increases the coefficient of APD₉₀ variability. LPA increased L-type calcium current (I_Ca,L) density without altering its activation or deactivation properties. In contrast, LPA has no effect on two other ventricular repolarizing currents, the transient outward potassium current (I_to) and the delayed rectifier potassium current (I_K). In arterially perfused rabbit left ventricular wedge preparations, the monophasic action potential duration, QT interval, and Tpeak-end are prolonged by LPA. LPA treatment also significantly increases the incidence of ventricular tachycardia induced by S₁S₂ stimulation. Notably, the effects of LPA on action potentials and I_Ca,L are PTX-sensitive, suggesting LPA action requires a G_i-type G protein. In conclusion, LPA prolongs APD and increases electrophysiological instability in isolated rabbit myocardial preparations by increasing I_Ca,L in a G_i protein-dependent manner.     

Factors influencing Chinese male's willingness to undergo circumcision: a cross-sectional study in western China

Background

Male circumcision (MC) has been shown to reduce the risk of female to male transmission of HIV. The goal of this survey was to explore the acceptability of MC among the Chinese and to identify factors associated with circumcision preference.

Methods

A cross-sectional survey was conducted between September 2009 and December 2010. We interviewed 2,219 male community participants, from three high HIV prevalence provinces in western China. A structured questionnaire was used to collect data on MC knowledge, willingness to accept MC, reasons to accept or refuse MC, and sexual behaviors and health. For those who refused MC, a health education intervention providing information on the benefits of circumcision was conducted. We used multiple logistic regression models to identify factors associated with the acceptability of MC.

Results

Of the respondents (n = 2,219), 44.6% (989/2,219) reported they would accept MC for the following reasons: promotion of female partners'' hygiene (60.3%), redundant foreskin (59.4%), prevention of penile cancer (50.2%), enhanced sexual pleasure (41.4%), and protection against HIV and STDs (34.2%). The multivariable logistic regression showed that five factors were associated with MC willingness: long foreskin (OR = 15.98), residing in Xinjiang province (OR = 3.69), being younger than 25 (OR = 1.60), knowing hazards of redundant foreskin (OR = 1.78), and having a friend who underwent circumcision (OR = 1.36).

Conclusion

The acceptability of male circumcision was high among the general population in China. Our study elucidates the factors associated with circumcision preference and suggests that more health education campaigns about positive health effects are necessary to increase the MC rate in China.     

Toll-like receptor 9 agonists up-regulates the expression of cyclooxygenase-2 via activation of NF-κB in prostate cancer cells

CpG-oligonucleotides (CpG-ODNs), mimicking bacterial DNA, have recently been shown to stimulate prostate cancer invasion in vitro via Toll-like receptor 9 (TLR9). Since cyclooxygenase 2 (COX-2), frequently overexpressed in multiple tumor types including prostate cancer, is a causal factor for tumor development, invasion and metastasis, an interesting question is raised whether TLR9 regulates COX-2 expression in prostate cancer cells. To address this question, herein we examined COX-2 expression in PC-3 cells stimulated with different doses and time courses of CpG-ODNs. The regulatory role of NF-κB in TLR9-mediated COX-2 expression was also investigated. CpG-ODN was found to up-regulate the expression of COX-2 in PC-3 cells in a dose- and time-dependent manner, but have little impact on COX-1 expression. Moreover, CpG-ODN also promoted nuclear translocation and activation of NF-κB, which appeared to be required for COX-2 induction by CpG-ODN. Overall, TLR9 up-regulates COX-2 expression in prostate cancer cells, at least partially through the activation of NF-κB, which may be implicated in tumor invasion and metastasis.     

不同佐剂对含S+PreS1融合抗原的乙型肝炎病毒颗粒疫苗免疫原性的影响

本研究在前期工作基础上,用CHO细胞表达的含PreS1+S融合抗原的新型基因工程HBV颗粒疫苗(HBSS1)与Al(OH)3、CpG及CpG+Al(OH)3等佐剂配伍,在Balb/C小鼠模型上研究不同佐剂对HBV颗粒疫苗肌肉注射后免疫应答的影响,主要包括抗体滴度、抗体亚型分类及特异性细胞免疫(γ-IFNELISpot检测)。结果表明:CpG佐剂结合HBSS1颗粒疫苗可快速诱导(单针免疫)高水平的抗PreS1及S抗体,IgG2a/IgG1比率1,同时可诱导较高抗原特异的细胞免疫应答;Al(OH)3+CpG双佐剂组一次免疫后可诱导产生最高的抗S抗体滴度(1:105),其产生的抗体亚类包括IgG1、IgG2a与IgG2b;在S抗原N端(13~49aa)存在优势CTL表位。结论:CpG佐剂结合HBSS1颗粒疫苗应是发展新型治疗性乙肝疫苗的较佳选项。     

Effects of microclimate,litter type,and mesh size on leaf litter decomposition along an elevation gradient in the Wuyi Mountains,China

Litter decomposition is an important ecosystem process regulated by both biotic factors (e.g., decomposers and litter types) and abiotic factors (e.g., temperature and moisture). This study examined the regulatory effects of soil fauna and microclimate on decomposition of two substrates (Castanopsis carlesii and Pinus taiwanensis) along an elevation gradient in four ecosystems of zonal vegetation types in southeastern China: evergreen broadleaf forest (EVB), coniferous forest (COF), dwarf forest (DWF), and alpine meadow (ALM). Our objective was to identify the mechanisms by which microclimate, substrate, and fauna control litter decomposition, especially where variations in ecosystem structure and environment are markedly shown across an elevation gradient. The hypotheses were as follows: (1) litter decomposition within the same litter type would decrease across the elevation gradient, (2) litter decomposition would be lower in poorer nutrient quality substrate across the four sites, and (3) litter dynamics, influenced by strong interactions among ecosystem type, litter type, and decomposers, would vary by elevation gradient due to microclimate effects (i.e., temperature and moisture). The decomposition rates of C. carlesii were significantly higher than those of P. taiwanensis at EVB, COF, and DWF sites; however, they were not significantly different at the ALM site. Low elevation forests possessed a microclimate (warm and humid) that favors decomposer activities and also appeared to possess a decomposer community adapted to consuming large amounts of leaf litter, as indicated by the rapid leaf litter loss. Litter decomposition in micro-mesh bags proceeded more slowly compared to litter in meso-mesh and macro-mesh litterbags across the elevation gradient, indicating that restricting some detritivore access to litter reduced litter mass loss. We suggest that microclimate and faunal contributions to plant litter decomposition differ markedly across the ecosystems in the Wuyi Mountains.     

江苏云台山野生珍稀濒危中药植物初步研究

通过查阅资料,访问及实地调查等方法,报道了云台山野生珍稀濒危中药植物24科37种,对它们的生长环境、药效及现在情况做了介绍,并分析了云台山野生中药植物资源被破坏的主要原因,提出了对云台山野生药用植物资源进行保护的具体措施。