15,16-Dihydrotanshinone I, a Compound of Salvia miltiorrhiza Bunge, Induces Apoptosis through Inducing Endoplasmic Reticular Stress in Human Prostate Carcinoma Cells

5,16-dihydrotanshinone I (DHTS) is extracted from Salvia miltiorrhiza Bunge (tanshen root) and was found to be the most effective compound of tanshen extracts against breast cancer cells in our previous studies. However, whether DHTS can induce apoptosis through an endoplasmic reticular (ER) stress pathway was examined herein. In this study, we found that DHTS significantly inhibited the proliferation of human prostate DU145 carcinoma cells and induced apoptosis. DHTS was able to induce ER stress as evidenced by the upregulation of glucose regulation protein 78 (GRP78/Bip) and CAAT/enhancer binding protein homologous protein/growth arrest- and DNA damage-inducible gene 153 (CHOP/GADD153), as well as increases in phosphorylated eukaryotic initiation factor 2α (eIF2α), c-jun N-terminal kinase (JNK), and X-box-binding protein 1 (XBP1) mRNA splicing forms. DHTS treatment also caused significant accumulation of polyubiquitinated proteins and hypoxia-inducible factor (HIF)-1α, indicating that DHTS might be a proteasome inhibitor that is known to induce ER stress or enhance apoptosis caused by the classic ER stress-dependent mechanism. Moreover, DHTS-induced apoptosis was reversed by salubrinal, an ER stress inhibitor. Results suggest that DHTS can induce apoptosis of prostate carcinoma cells via induction of ER stress and/or inhibition of proteasome activity, and may have therapeutic potential for prostate cancer patients

Sonoporation-mediated gene transfer into adult rat dorsal root ganglion cells

<p>Abstract</p> <p>Background</p> <p>Gene transfer into many cell types has been successfully used to develop alternative and adjunct approaches to conventional medical treatment. However, effective transfection of postmitotic neurons remains a challenge. The aim of this study was to develop a method for gene transfer into rat primary dorsal root ganglion neurons using sonoporation.</p> <p>Methods</p> <p>Dissociated cells from adult rat dorsal root ganglion (DRG) cells were sonicated for 1-8 s at 2.5-10 W to determine the optimal ultrasound duration and power for gene transfection and cell survival. Transfection efficiency was compared between sonoporation, liposome and lentiviral vector gene transfer techniques.</p> <p>Results</p> <p>The optimum ultrasound intensity was 5 W for 2 s and yielded an efficiency of gene transfection of 31% and a survival rate of 35%.</p> <p>Conclusions</p> <p>Sonoporation can be optimized to minimize cell death and yield a high percentage of transfected neurons and that this technique can be easily applied to primary cultures of rat dorsal root ganglion neurons.</p

Switch activation of PI-PLC downstream signals in activated macrophages with wortmannin

AbstractPhosphatidylinositol (4,5)-bisphosphate (PtdIns(4,5)P2) has been known to serve as a substrate for phosphatidylinositol 3-kinase (PI3K) and phosphoinositide-specific phospholipase C (PI-PLC), which can produce PtdIns(3,4,5)P3 and inositol 1,4,5-trisphosphate (Ins(1,4,5)P3) and diacylglycerol (DAG), respectively. In this study, we elucidated the role of PI-PLC during the LPS-activated mouse macrophages RAW264.7 treated with PI3K inhibitor wortmannin. First, wortmannin treatment enhanced Ins(1,4,5)P3 production and iNOS expression in LPS-activated macrophages. Inhibition of PI3K by p85 siRNA also showed an enhancement of iNOS expression. On the other hand, overexpression of PI3K by ras-p110 expression plasmid significantly decreased iNOS expression in LPS-activated macrophages. In addition, overexpression of wild-type or dominant-negative Akt expression plasmid did not affect the iNOS expression in LPS-activated macrophages. Second, treatment of PI-PLC inhibitor U73122 reversed the enhancement of iNOS expression, the increase of phosphorylation level of ERK, JNK and p38, and the increase of AP-1-dependent gene expression in wortmannin-treated and LPS-activated macrophages. However, NF-κB activity determined by EMSA assay and reporter plasmid assay did not change during LPS-activated macrophages with or without wortmannin. We propose that the inhibition of PI3K by wortmannin in mouse macrophages enhances the PI-PLC downstream signals, and subsequently increases the LPS induction of iNOS expression independently of Akt pathway

Low Cost Seismic Network Practical Applications for Producing Quick Shaking Maps in Taiwan

Two major earthquakes of ML greater than 6.0 occurred in Taiwan in the first half of 2013. The vibrant shaking brought landslides, falling rocks and casualties. This paper presents a seismic network developed by National Taiwan University (NTU) with 401 Micro-Electro Mechanical System (MEMS) accelerators. The network recorded high quality strong motion signals from the two events and produced delicate shaking maps within one minute after the earthquake occurrence. The high shaking regions of the intensity map produced by the NTU system suggest damage and casualty locations. Equipped with a dense array of MEMS accelerometers, the NTU system is able to accommodate 10% signals loss from part of the seismic stations and maintain its normal functions for producing shaking maps. The system also has the potential to identify the rupture direction which is one of the key indices used to estimate possible damage. The low cost MEMS accelerator array shows its potential in real-time earthquake shaking map generation and damage avoidance

SARS Exposure and Emergency Department Workers

Of 193 emergency department workers exposed to severe acute respiratory syndrome (SARS), 9 (4.7%) were infected. Pneumonia developed in six workers, and assays showed anti-SARS immunoglobulin (Ig) M and IgG. The other three workers were IgM-positive and had lower IgG titers; in two, mild illness developed, and one remained asymptomatic

Study on the Repetitive Innovation of Medical Education in a Medical University

培育優質之醫師影響醫療照護品質進而攸關國人全面健康之提昇。隨著經濟發展及社會進步，過去單純之醫療環境漸趨複雜。醫學大學之醫學系肩負醫學生畢業前之醫學教育，更需要與時俱進，不斷創新，以符合民眾及社會期待。 台北醫學大學醫學系自2009年起，依循整合、多元、自主之理念，對醫學系展開課程變革。其中三至四年級由原本之學科主導授課，改為器官系統為主之整合課程，內容貫穿融合基礎與臨床內容。五年級上學期增加47項臨床核心技能課程及核心技能臨床案例討論，讓同學及早接觸醫院之教學環境。六年級進入醫院後，新增整合客觀結構式臨床技能測驗iOSCE (integrated objective structured clinical examination)教學，結合標準化病人及電腦自學軟體。七年級亦新增跨領域團隊合作訓練TRM(team resource management)，包括小組討論及模擬演練，使同學熟悉臨床情境。利用質、量性分析方法，我們發現醫學系課程變革對clerkship (五至六年級)的效用較明顯。而整合課程滿意度較高之同學，和一階國考通過比例成有意義之正相關。 本研究亦運用VPS (vision, positioning, scenario)創新循環理論，來說明醫學生於畢業前包括進入醫院前、後之醫學教育改革。在跳脫現今思維、化不可能為可能、物超所值之理念下，應用VPS創新循環不斷提升。最後，利用價值創新循環(value creation cycle)，說明在現今醫療之作業環境下，未來如何充分掌握醫療與資訊科技的發展、利用雲端趨勢、社群分享、協同合作，發現創新的泉源，規劃及落實住院醫師及醫學生訓練，持續不斷的發現、創造、及實現價值循環。Cultivating high standard physician affects quality of patient care and subsequently health promotion to our fellow citizens. Along with the economic development and social progress, the health care environment is becoming more complex. School of medicine of medical university is responsible for the medical education before medical student graduation. Therefore, to meet the people and social expectations, it is imperative that school of medicine requires constant progress and innovation. Under the ideas of integration, multivariate, and self-directed learning, curriculum reform in School of Medicine of Taipei Medical University was started since 2009. Multi-disciplinary curriculum for year 3-4 medical students was shifted into organ-system-based curriculum which integrated basic and clinical knowledge. To let the year 5 medical students encounter the clinical environment earlier, 47 core clinical skills and case-based discussion curriculum were engaged in our teaching hospitals. Novel iOSCE which combined standardized patients and computer programs was added for the year 6 medical students to promote self-direct learning. TRM which includes small group discussion and simulation programs was implicated for the year 7 medical students to familiar with real clinical situations. Using qualitative and quantitative methods, we demonstrate that curriculum reform in School of Medicine of TMU is more effective for clerkship (year 5-6) students. Moreover, for the clerkship, the course satisfaction is significantly associated with the increased passing rate for the stage one national physician examination of Taiwan. In this study, we also apply VPS (vision, positioning, scenario) innovation theory to demonstrate the feasibility of medical education reform for medical students either learning at school or hospital before graduation. The vision, position, and scenario of our curriculum reform fit the cores of innovation: 「Never thought of before」,「Impossible makes possible」 and 「Heart-touching」, respectively. Finally, under present health care environment, we examine the advances of medical care and information technology, the trend of cloud infrastructure development, and the possibility of social sharing and online collaboration to explore the sources for repetitive innovations. We then use value creation cycle to show how we plan and implement the future training for residents and medical students with the notion that the discovery, creation and realization of value will be a continued cycling process

Decellularized Lymph Node Scaffolding as a Carrier for Dendritic Cells to Induce Anti-Tumor Immunity

In recent decades, the decellularized extracellular matrix (ECM) has shown potential as a promising scaffold for tissue regeneration. In this study, an organic acid decellularized lymph node (dLN) was developed as a carrier for dendritic cells (DCs) to induce antitumor immunity. The dLNs were prepared by formic acid, acetic acid, or citric acid treatment. The results showed highly efficient removal of cell debris from the lymph node and great preservation of ECM architecture and biomolecules. In addition, bone marrow dendritic cells (BMDCs) grown preferably inside the dLN displayed the maturation markers CD80, CD86, and major histocompatibility complex (MHC)-II, and they produced high levels of interleukin (IL)-1&beta;, IL-6, and IL-12 cytokines when stimulated with ovalbumin (OVA) and CpG oligodeoxynucleotides (CPG-ODN). In an animal model, the BMDC-dLN completely rejected the E.G7-OVA tumor. Furthermore, the splenocytes from BMDC-dLN-immunized mice produced more interferon gamma, IL-4, IL-6, and IL-2, and they had a higher proliferation rate than other groups when re-stimulated with OVA. Hence, BMDC-dLN could be a promising DC-based scaffold for in vivo delivery to induce potent antitumor immunity