MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'exp Mol Med' source. Mon, 06 Feb 2012 16:52:05 +0100 http://www.medworm.com/index.php?rid=5620129&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257881%26dopt%3DAbstract Authors: Jing K, Lim K Abstract The process of macroautophagy (referred to hereafter as autophagy), is generally characterized by the prominent formation of autophagic vesicles in the cytoplasm. In the past decades, studies of autophagy have been vastly expanded. As an essential process to main cellular homeostasis and functions, autophagy is responsible for the lysosome-mediated degradation of damaged proteins and organelles, and thus misregulation of autophagy can result in a variety of pathological conditions in human beings. Although our understanding of regulatory pathways that control autophagy is still limited, an increasing number of studies have shed light on the importance of autophagy in a wide range of physiological processes and human diseases. The goal of the reviews ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5620129 Thu, 19 Jan 2012 05:00:00 +0100 5620129 http://www.medworm.com/index.php?rid=5620128&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257882%26dopt%3DAbstract Authors: Pyo JO, Nah J, Jung YK Abstract Autophagy is a self-degradation system of cellular components through an autophagosomal-lysosomal pathway. Over the last 15 years, yeast genetic screens led to the identification of a number of genes involved in the autophagic pathway. Most of these autophagy genes are present in higher eukaryotes and regulate autophagy process for cell survival and homeostasis. Significant progress has recently been made to better understand the molecular mechanisms of the autophagy machinery. Especially, autophagy process, including the induction of autophagy through mTOR and the nucleation and elongation in autophagosome formation through Beclin1 complex and ubiquitin-like conjugation systems, becomes evident. While many unanswered questions remain to be ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5620128 Thu, 19 Jan 2012 05:00:00 +0100 5620128 http://www.medworm.com/index.php?rid=5620127&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257883%26dopt%3DAbstract Authors: Quan W, Lim YM, Lee MS Abstract Type 2 diabetes mellitus is characterized by insulin resistance and failure of pancreatic b-cells producing insulin. Autophagy plays a crucial role in cellular homeostasis through degradation and recycling of organelles such as mitochondria or ER. Here we discussed the role of b-cell autophagy in development of diabetes, based on our own studies using mice with b-cell-specific deletion of Atg7 (autophagy-related 7), an important autophagy gene, and studies by others. b-cell-specific Atg7-null mice showed reduction in b-cell mass and pancreatic insulin content. Insulin secretory function ex vivo was also impaired, which might be related to organelles dysfunction associated with autophagy deficiency. As a result, b-cell-specific Atg7-null mice... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5620127 Thu, 19 Jan 2012 05:00:00 +0100 5620127 http://www.medworm.com/index.php?rid=5620126&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257884%26dopt%3DAbstract Authors: Son JH, Shim JH, Kim KH, Ha JY, Han JY Abstract Autophagy is a dynamic cellular pathway involved in the turnover of proteins, protein complexes, and organelles through lysosomal degradation. The integrity of postmitotic neurons is heavily dependent on high basal autophagy compared to non-neuronal cells as misfolded proteins and damaged organelles cannot be diluted through cell division. Moreover, neurons contain the specialized structures for intercellular communication, such as axons, dendrites and synapses, which require the reciprocal transport of proteins, organelles and autophagosomes over significant distances from the soma. Defects in autophagy affect the intercellular communication and subsequently, contributing to neurodegeneration. The presence of abnormal autoph... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5620126 Thu, 19 Jan 2012 05:00:00 +0100 5620126 http://www.medworm.com/index.php?rid=5620125&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257885%26dopt%3DAbstract Authors: Yuk JM, Yoshimori T, Jo EK Abstract Autophagy is a housekeeping process that maintains cellular homeostasis through recycling of nutrients and degradation of damaged or aged cytoplasmic constituents. Over the past several years, accumulating evidence has suggested that autophagy can function as an intracellular innate defense pathway in response to infection with a variety of bacteria and viruses. Autophagy plays a role as a specialized immunologic effector and regulates innate immunity to exert antimicrobial defense mechanisms. Numerous bacterial pathogens have developed the ability to invade host cells or to subvert host autophagy to establish a persistent infection. In this review, we have summarized the recent advances in our understanding of the interaction between an... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5620125 Thu, 19 Jan 2012 05:00:00 +0100 5620125 http://www.medworm.com/index.php?rid=5620124&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257886%26dopt%3DAbstract Authors: Choi KS Abstract Basal autophagy plays a critical role in maintaining cellular homeostasis and genomic integrity by degrading aged or malfunctioning organelles and damaged or misfolded proteins. However, autophagy also plays a complicated role in tumorigenesis and treatment responsiveness. It can be tumor-suppressing during the early stages of tumorigenesis (i.e., it is an anti-tumor mechanism), as reduced autophagy is found in tumor cells and may be associated with malignant transformation. In this case, induction of autophagy would seem to be beneficial for cancer prevention. In established tumors, however, autophagy can be tumor-promoting (i.e., it is a pro-tumor mechanism), and cancer cells can use enhanced autophagy to survive under metabolic and therapeutic stress. T... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5620124 Thu, 19 Jan 2012 05:00:00 +0100 5620124 http://www.medworm.com/index.php?rid=5620123&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22257887%26dopt%3DAbstract Authors: Im JE, Song SH, Kim JY, Kim KL, Baek SH, Lee DR, Suh W Abstract We previously reported the successful establishment of embryonic stem cell (ESC)-like multipotent spermatogonial stem cells (mSSCs) from neonatal mouse testis. Here, we examined the ability of mSSCs to differentiate into vascular endothelial cells and smooth muscle cells, and compared to that of mouse ESCs. We used real-time reverse transcriptase polymerase chain reaction and immunohistochemistry to examine gene expression profiles of mSSCs and ESCs during in vitro vascular differentiation. Both mSSCs and ESCs exhibited substantial increase in the expression of mesodermal markers, such as Brachyury, Flk1, Mesp1, Nkx2.5, and Islet1, and a decrease in the expression of pluripotency markers, such as Oct3/4 and Na... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5620123 Thu, 19 Jan 2012 05:00:00 +0100 5620123 http://www.medworm.com/index.php?rid=5620130&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22248567%26dopt%3DAbstract Authors: Lee ES, Jeong MS, Singh R, Jung J, Yoon H, Min JK, Kim KH, Hong HJ Abstract Intrahepatic cholangiocarcinoma (ICC), a malignant tumor derived from the intrahepatic bile duct epithelium, has a poor prognosis and is refractory to conventional chemotherapy and radiation therapy. Thus, there is an urgent need to develop new effective therapeutic strategies for this disease. We previously found that L1 cell adhesion molecule (L1CAM) plays an important role in tumor progression of ICC, and we generated a murine mAb, A10-A3 (IgG1), that binds to the Ig1 domain of L1CAM. In the present study, we further characterized A10-A3, constructed a chimeric A10-A3 antibody (cA10-A3) containing the constant regions of human IgG1, and evaluated the therapeutic potential in a human ICC xenograf... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5620130 Tue, 17 Jan 2012 05:00:00 +0100 5620130 http://www.medworm.com/index.php?rid=5577844&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22228176%26dopt%3DAbstract Authors: Falco SD Abstract Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration (Carmeliet and Jain, 2011). Among the several molecular players involved in angiogenesis, some members of VEGF family, VEGF-A, VEGF-B and placental growth factor (PlGF), and the related receptors VEGF receptor 1 (VEGFR-1,... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5577844 Mon, 09 Jan 2012 05:00:00 +0100 5577844 http://www.medworm.com/index.php?rid=5577845&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22228119%26dopt%3DAbstract In this study, using microarray analysis and Ingenuity Pathways AnalysisTM, we identified genes (up- or down-regulated, ≥1.5 fold, P ≤ 0.001), functions and signaling pathways that were altered following treatment with an inhibitory concentration of genistein (50 mg/ml) in UtLM cells. Downregulation of TGF-b signaling pathway genes, activin A, activin B, Smad3, TGF-b2 and genes related to cell cycle regulation, with the exception of the upregulation of the CDK inhibitor P15, were identified and validated by real-time reverse transcriptase-polymerase chain reaction studies. Western blot analysis further demonstrated decreased protein expression of activin A and Smad3 in genistein-treated UtLM cells. Moreover, we found that activin A stimulated the growth of UtLM cells, and the inhibitor... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5577845 Fri, 06 Jan 2012 05:00:00 +0100 5577845 http://www.medworm.com/index.php?rid=5577848&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217446%26dopt%3DAbstract Authors: Li M, Song L, Gao X, Chang W, Qin X Abstract Type 1 diabetes mellitus is caused by the autoimmune destruction of β cells within the islets. In recent years, innate immunity has been proposed to play a key role in this process. High-mobility group box 1 (HMGB1), an inflammatory trigger in a number of autoimmune diseases, activates proinflammatory responses following its release from necrotic cells. Our aim was to determine the significance of HMGB1 in the natural history of diabetes in non-obese diabetic (NOD) mice. We observed that the rate of HMGB1 expression in the cytoplasm of islets was much greater in diabetic mice compared with non-diabetic mice. The majority of cells positively stained for toll-like receptor 4 (TLR4) were β cells; few α cells were stained for TLR... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5577848 Thu, 05 Jan 2012 05:00:00 +0100 5577848 http://www.medworm.com/index.php?rid=5577847&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217447%26dopt%3DAbstract Authors: Uhm TG, Lee SK, Kim BS, Kang JH, Park CS, Rhim TY, Chang HS, Kim DJ, Chung IY Abstract DNA methylation may regulate gene expression by restricting the access of transcription factors. We have previously demonstrated that GATA-1 regulates the transcription of the CCR3 gene by dynamically interacting with both positively and negatively acting GATA elements of high affinity binding in the proximal promoter region including exon 1. Exon 1 has three CpG sites, two of which are positioned at the negatively acting GATA elements. We hypothesized that the methylation of these two CpGs sites might preclude GATA-1 binding to the negatively acting GATA elements and, as a result, increase the availability of GATA-1 to the positively acting GATA element, thereby contributing to an incre... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5577847 Thu, 05 Jan 2012 05:00:00 +0100 5577847 http://www.medworm.com/index.php?rid=5577846&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22217448%26dopt%3DAbstract Authors: Kim KJ, Co CS, Kim WU Abstract Accumulating evidences have documented that angiogenesis is closely linked to inflammation and regulators of angiogenesis play key roles in various inflammatory conditions. PlGF is an angiogenic protein belonging to the VEGF family and is upregulated mainly in pathologic conditions. In recent, PlGF was discovered having a proinflammatory role in inflammatory arthritis and its serum level drew attention not only as a useful surrogate biomarker but also a potential therapeutic target in atherosclerosis and various cancers. Particularly, PlGF has attractive clinical values because endogenous PlGF is redundant for vascular development and physiological vessel maintenance in healthy adults. However, there have been conflicting results about the ef... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5577846 Thu, 05 Jan 2012 05:00:00 +0100 5577846 http://www.medworm.com/index.php?rid=5548396&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198295%26dopt%3DAbstract In this study, we investigated the role of p53, ATM, and DNA-PKcs in tetraploid G1 arrest induced by actin damage. Treatment with actin-damaging agents including pectenotoxin-2 (PTX-2) increases phosphorylation of ser-15 and ser-37 residues of p53, but not ser-20 residue. Knockdown of ATM and DNA-PKcs do not affect p53 phosphorylation induced by actin damage. However, while ATM knockdown does not affect tetraploid G1 arrest, knockdown of DNA-PKcs not only perturbs tetraploid G1 arrest, but also results in formation of polyploidy and induction of apoptosis. These results indicate that DNA-PKcs is essential for the maintenance of actin damage induced- tetraploid G1 arrest in a p53-independent manner. Furthermore, actin damage-induced p53 expression is not observed in cells synchronized at G1... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5548396 Mon, 26 Dec 2011 05:00:00 +0100 5548396 http://www.medworm.com/index.php?rid=5548395&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198296%26dopt%3DAbstract In this study, we determined whether or not ANT2 suppression could also be effective in inducing cell death of breast cancer stem-like cells. A sub-population (SP; CD44+/CD24-) of breast cancer cells has been reported to have stem/progenitor cell properties. We utilized the adeno-ANT2 shRNA virus to inhibit ANT2 expression and then observed the treatment effect in a SP of breast cancer cell line. In this study, MCF7, MDA-MB-231 cells, and breast epithelial cells (MCF10A) mesenchymally-transdifferentiated through E-cadherin knockdown were used. ANT2 expression was high in both stem-like cells and non-stem-like cells of MCF7 and MDA-MB-231 cells, and was induced and up-regulated by mesenchymal transdifferentiation in MCF10A cells (MCF10AEMT). Knockdown of ANT2 by adeno-shRNA virus efficientl... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5548395 Mon, 26 Dec 2011 05:00:00 +0100 5548395 http://www.medworm.com/index.php?rid=5548394&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22198297%26dopt%3DAbstract Authors: Paik SH, Kim HJ, Son HY, Lee S, Im SW, Ju YS, Yeon JH, Jo SJ, Eun HC, Seo JS, Kwon OS, Kim JI Abstract To elucidate the genes responsible for constitutive human skin color, we measured the extent of skin pigmentation in the buttock, representative of lifelong non-sun-exposed skin, and conducted a gene mapping study on skin color in an isolated Mongolian population composed of 344 individuals from 59 families who lived in Dashbalbar, Mongolia. The heritability of constitutive skin color was 0.82, indicating significant genetic association on this trait. Through the linkage analysis using 1,039 short tandem repeat (STR) microsatellite markers, we identified a novel genomic region regulating constitutive skin color on 11q24.2 with an logarithm of odds (LOD) score of 3.39. In ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5548394 Mon, 26 Dec 2011 05:00:00 +0100 5548394 http://www.medworm.com/index.php?rid=5548398&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192927%26dopt%3DAbstract Authors: Lee MJ, Xu DY, Li H, Yu GR, Leem SH, Chu IS, Kim IH, Kim DG Abstract NM23 is a family of structurally and functionally conserved proteins known as nucleoside diphosphate kinases (NDPK). There is abundant mRNA expression of NM23-H1, NM23-H2, or a read through transcript (NM23-LV) in the primary sites of hepatocellular carcinoma (HCC). Although the NM23-H1 protein is implicated as a metastasis suppressor, the role of NM23-H2 appears to be less understood. Thus, the aim of this study was to examine whether NM23-H2 is associated with hepatocarcinogenesis. The level of NM23-H2 expression in tumor tissues and the surrounding matrix appeared to be independent of etiology and tumor differentiation. Its subcellular localization was confined to mainly the cytoplasm and to a lesser e... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5548398 Thu, 22 Dec 2011 05:00:00 +0100 5548398 http://www.medworm.com/index.php?rid=5548397&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22192928%26dopt%3DAbstract Authors: Kwon HB, Choi YK, Lim JJ, Kwon SH, Her S, Kim HJ, Lim KJ, Ahn JC, Kim YM, Bae MK, Park JA, Jeong CH, Mochizuki N, Kim KW Abstract The integrity of blood vessels controls vascular permeability and extravasation of blood cells, across the endothelium. Thus, the impairment of endothelial integrity leads to hemorrhage, edema, and inflammatory infiltration. However, the molecular mechanism underlying vascular integrity has not been fully understood. Here, we demonstrate an essential role for A-kinase anchoring protein 12 (AKAP12) in the maintenance of endothelial integrity during vascular development. Zebrafish embryos depleted of akap12 (akap12 morphants) exhibited severe hemorrhages. In vivo time-lapse analyses suggested that disorganized interendothelial cell-cell adhesions ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5548397 Thu, 22 Dec 2011 05:00:00 +0100 5548397 http://www.medworm.com/index.php?rid=5532883&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22179105%26dopt%3DAbstract Authors: Jang J, Yoo JE, Lee JA, Lee DR, Kim JY, Huh YJ, Kim DS, Hwang DY, Kim HS, Kang HC, Kim DW Abstract The generation of disease-specific induced pluripotent stem cell (iPSC) lines from patients with incurable diseases is a promising approach for studying disease mechanisms and drug screening. Such innovation enables to obtain autologous cell sources in regenerative medicine. Herein, we report the generation and characterization of iPSCs from fibroblasts of patients with sporadic or familial diseases, including Parkinson's disease (PD), Alzheimer's disease (AD), juvenile-onset, type I diabetes mellitus (JDM), and Duchenne type muscular dystrophy (DMD), as well as from normal human fibroblasts (WT). As an example to modeling disease using disease-specific iPSCs, we also discuss... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5532883 Mon, 19 Dec 2011 05:00:00 +0100 5532883 http://www.medworm.com/index.php?rid=5532885&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22170034%26dopt%3DAbstract Authors: Wang Y, Lin L, Zheng C Abstract Orai1 is the key subunit of the Ca2+-release-activated Ca2+ channel. Our previous report has demonstrated that Orai1 expression in the airway was upregulated in the ovalbumin (OVA)-induced allergic rhinitis (AR) mouse models. To observe whether inhibition of Orai1 expression in the airway could suppress symptoms in a murine model of AR and to assess the impacts of this inhibition on the responses of local and systemic immunocytes, we administered recombinant lentivirus vectors that encoded shRNA against ORAI1 (lenti-ORAI1) into the nostrils of OVA-sensitized mice before the challenges, and analyzed its effect on allergic responses, as compared with the unsensitized mice and untreated AR mice. Administration of lenti-ORAI1 into the nasal cavi... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5532885 Wed, 14 Dec 2011 05:00:00 +0100 5532885 http://www.medworm.com/index.php?rid=5532884&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22170035%26dopt%3DAbstract Authors: Chung BH, Kim S, Kim JD, Lee JJ, Baek YY, Jeoung D, Lee H, Choe J, Ha KS, Won MH, Kwon YG, Kim YM Abstract Nitric oxide (NO) produced by endothelial NO synthase (eNOS) plays an important role in vascular functions, including vasorelaxation. We here investigated the pharmacological effect of the natural product syringaresinol on vascular relaxation and eNOS-mediated NO production as well as its underlying biochemical mechanism in endothelial cells. Treatment of aortic rings from wild type, but not eNOS-/- mice, with syringaresinol induced endothelium-dependent relaxation, which was abolished by addition of the NOS inhibitor NG-monomethyl-L-arginine. Treatment of human endothelial cells and mouse aortic rings with syringaresinol increased NO production, which was correlated ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5532884 Wed, 14 Dec 2011 05:00:00 +0100 5532884 http://www.medworm.com/index.php?rid=5492765&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22139526%26dopt%3DAbstract We examined the accumulation of argpyrimidine, a methylglyoxal-derived AGE, and the expression of apoptosis-related molecules including nuclear factor-kappaB (NF-κB), Bax, and Bcl-2 in the human LEC line HLE-B3 and in cataractous lenses of Zucker diabetic fatty (ZDF) rats, an animal model of type 2 diabetes. In cataractous lenses from twenty-one-week-old ZDF rats, LEC apoptosis was markedly increased, and the accumulation of argpyrimidine as well as subsequent activation of NF-κB in LECs were significantly enhanced. The ratio of Bax to Bcl-2 protein levels was also increased. In addition, the accumulation of argpyrimidine triggered apoptosis in methylglyoxal-treated HLE-B3 cells. However, the presence of pyridoxamine (an AGEs inhibitor) and pyrrolidine dithiocarbamate (a NF-κB inhibitor... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5492765 Mon, 05 Dec 2011 05:00:00 +0100 5492765 http://www.medworm.com/index.php?rid=5474185&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22127053%26dopt%3DAbstract Authors: Kim KH, Kim YM, Lee MJ, Ko HC, Kim MB, Kim JH Abstract Sphingosylphosphorylcholine (SPC) induces differentiation of human adipose tissue-derived mesenchymal stem cells (hASCs) into smooth muscle-like cells expressing α-smooth muscle actin (α-SMA) via transforming growth factor-β1/Smad2- and RhoA/Rho kinase-dependent mechanisms. 3-Hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins) have been known to have beneficial effects in the treatment of cardiovascular diseases. In the present study, we examined the effects of simvastatin on the SPC-induced α-SMA expression and Smad2 phosphorylation in hASCs. Simvastatin inhibited the SPC-induced α-SMA expression and sustained phosphorylation of Smad2 in hASCs. SPC treatment caused RhoA activation via a simvastatin... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5474185 Wed, 30 Nov 2011 05:00:00 +0100 5474185 http://www.medworm.com/index.php?rid=5474186&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113134%26dopt%3DAbstract In this study, we report that leukocytes from GC patients express lower levels of membrane HVEM (mHVEM) and have lower LIGHT-induced bactericidal activities than those from healthy controls (HC). In contrast, levels of soluble HVEM (sHVEM) in the sera of GC patients were significantly higher than in those of HC. We found that monocyte membrane-bound HVEM is released into the medium when cells are activated by proinflammatory cytokines such as TNF-a and IL-8, which are elevated in the sera of GC patients. mHVEM level dropped in parallel with the release of sHVEM, and release was completely blocked by the metalloprotease inhibitor, GM6001. We also found that the low level of mHVEM on GC patient leukocytes was correlated with low LIGHT-induced bactericidal activities against H. pylori and S. ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5474186 Thu, 24 Nov 2011 05:00:00 +0100 5474186 http://www.medworm.com/index.php?rid=5474187&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113105%26dopt%3DAbstract In this study, we examined whether p190RhoGEF and a downstream effector molecule RhoA are required for B cell differentiation. Expression of p190RhoGEF positively correlated with the expression of surface markers and transcriptional regulators that are characteristic of mature B cells with plasma cell (PC) phenotypes. Moreover, either the overexpression of p190RhoGEF or the expression of a constitutively active RhoA drove cellular differentiation toward PC phenotypes. B cell maturation was abrogated in cells that overexpressed p190RhoGEF and a dominant-negative form of RhoA simultaneously. CD40-mediated maturation events were also abrogated in cells that overexpressed either dominant-negative p190RhoGEF or RhoA. Together, these data provide evidence that p190RhoGEF signaling through RhoA i... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5474187 Wed, 23 Nov 2011 05:00:00 +0100 5474187 http://www.medworm.com/index.php?rid=5474190&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089087%26dopt%3DAbstract Authors: Lee HJ, Hong CY, Kim MH, Lee YK, Nguyen-Pham TN, Park BC, Yang DH, Chung IJ, Kim HJ, Lee JJ Abstract Anterior gradient-2 (AGR2) promotes tumor growth, cell migration, and cellular transformation, and is one of the specific mRNA markers for circulating tumor cells in patients with gastrointestinal cancer. We investigated the feasibility of AGR2 as a potent antigen for tumor immunotherapy against colorectal cancer (CRC) cells using dendritic cells (DCs) transduced with a recombinant adenovirus harboring the AGR2 gene (AdAGR2). DCs transduced with a recombinant adenovirus encoding the AGR2 gene (AdAGR2/DCs) were characterized. These genetically-modified DCs expressed AGR2 mRNA as well as AGR2 protein at a multiplicity of infection of 1,000 without any significant alterations ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5474190 Wed, 16 Nov 2011 05:00:00 +0100 5474190 http://www.medworm.com/index.php?rid=5474189&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089088%26dopt%3DAbstract This study investigated the genetic association of the EGR2 gene with BD and schizophrenia (SPR) in Korea. In 946 subjects (350 healthy controls, 352 patients with BD, and 244 with SPR), nine single nucleotide polymorphisms (SNPs) in the EGR2 gene region were genotyped. Five SNPs showed nominally significant allelic associations with BD (rs2295814, rs61865882, rs10995315, rs2297488, and rs2297489), and the positive associations of all except rs2297488 remained significant after multiple testing correction. Linkage disequilibrium structure analysis revealed two haplotype blocks. Among the common identified haplotypes (frequency > 5%), 'T-G-A-C-T (block 1)' and 'A-A-G-C (block 2)' haplotypes were over-represented, while 'C-G-G-T-T (block 1)' haplotype was under-represented in BD. In contr... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5474189 Wed, 16 Nov 2011 05:00:00 +0100 5474189 http://www.medworm.com/index.php?rid=5474188&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22089089%26dopt%3DAbstract In this study, we identified three novel peptides by screening a synthetic hexapeptide combinatorial library. The identified peptides GMMWAI, MMHWAM, and MMHWFM caused an increase in intracellular Ca2+ in a concentration-dependent manner via phospholipase C activity in human neutrophils. The three peptides acted specifically on neutrophils and monocytes and not on other non-leukocytic cells. As a physiological characteristic of the peptides, we observed that the three peptides induced chemotactic migration of neutrophils as well as stimulated superoxide anion production. Studying receptor specificity, we observed that two of the peptides (GMMWAI and MMHWFM) acted on formyl peptide receptor (FPR)1 while the other peptide (MMHWAM) acted on FPR2. Since the three novel peptides were specific a... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5474188 Wed, 16 Nov 2011 05:00:00 +0100 5474188 http://www.medworm.com/index.php?rid=5418707&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22064379%26dopt%3DAbstract Authors: Chang KH, Kim MS, Hong GW, Shin YN, Kim SH Abstract Epidermal growth factor receptor (EGFR) is an attractive target for tumor therapy because it is overexpressed in the majority of solid tumors and the increase in receptor expression levels has been linked with a poor clinical prognosis. Also it is well established that blocking the interaction of EGFR and the growth factors could lead to the arrest of tumor growth and possibly result in tumor cell death. mAb A13 is a murine monoclonal antibody (mAb) that specifically binds to various sets of EGFR-expressing tumor cells and inhibits EGF-induced EGFR phosphorylation. We isolated human immunoglobulin genes by guided selection based on the mAb A13. Four different human scFvs were isolated from from hybrid scFv libraries conta... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5418707 Tue, 08 Nov 2011 05:00:00 +0100 5418707 http://www.medworm.com/index.php?rid=5418715&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22056625%26dopt%3DAbstract In this study, in order to evaluate the reno-protective effects of wortmannin in early DN by regulating Rac1 and Cdc42, streptozotocin (STZ)-induced proteinuric renal disease (SPRD) rats were treated with wortmannin. The albuminuria value of the SPRD group was 3.55±0.56 mg/day, whereas wortmannin group was 1.77±0.48 mg/day. Also, the ACR value of the SPRD group was 53.08±10.82 mg/g, whereas wortmannin group was 20.27±6.41 mg/g. Changes in the expression level of nephrin, podocin and Rac1/Cdc42, which is related to actin cytoskeleton in podocytes, by wortmannin administration were confirmed by Western blotting. The expression levels of nephrin (79.66±0.02), podocin (87.81±0.03) and Rac1/Cdc42 (86.12±0.02) in the wortmannin group were higher than the expression levels of nephrin (55.3... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5418715 Thu, 03 Nov 2011 04:00:00 +0100 5418715 http://www.medworm.com/index.php?rid=5360858&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22033101%26dopt%3DAbstract Authors: Kwak DH, Ryu JS, Kim CH, Ko K, Ma JY, Hwang KA, Choo YK Abstract The human colorectal carcinoma-associated GA733 antigen epithelial cell adhesion molecule (EpCAM) was initially described as a cell surface protein selectively expressed in some myeloid cancers. Gangliosides are sialic acid-containing glycosphingolipids involved in inflammation and oncogenesis. We have demonstrated that treatment with anti-EpCAM mAb and RAW264.7 cells significant inhibited the cell growth in SW620 cancer cells, but neither anti-EpCAM mAb nor RAW264.7 cells alone induced cytotoxicity. The relationship between ganglioside expression and the anti-cancer effects of anti-EpCAM mAb and RAW264.7 was investigated by high-performance thin-layer chromatography. The results demonstrated that expression ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5360858 Fri, 28 Oct 2011 04:00:00 +0100 5360858 http://www.medworm.com/index.php?rid=5360859&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22024541%26dopt%3DAbstract Authors: Suh EJ, Kabir MH, Kang UB, Lee JW, Yu J, Noh DY, Lee C Abstract Breast cancer is the most common cancer in women worldwide. It is necessary to identify biomarkers for early detection, to make accurate prognoses, and to monitor for any recurrence of the cancer. In order to identify potential breast cancer biomarkers, we analyzed the plasma samples of women diagnosed with breast cancer and age-matched normal healthy women by mTRAQ-based stable isotope-labeling mass spectrometry. We identified and quantified 204 proteins including thrombospondin-1 (THBS1) and bromodomain and WD repeat-containing protein 3 (BRWD3) which were increased by more than 5-fold in breast cancer plasma. The plasma levels of the two proteins were evaluated by Western blot assay to confirm for their dia... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5360859 Mon, 24 Oct 2011 04:00:00 +0100 5360859 http://www.medworm.com/index.php?rid=5360860&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22020533%26dopt%3DAbstract In this study, we report a 3-stage method to induce the differentiation of skin fibroblasts into insulin-producing cells (IPCs). In stage 1, we establish the isolation, expansion and characterization of mesenchymal stem cells from human labia minora dermis-derived fibroblasts (hLMDFs) (stage 1: MSC expansion). hLMDFs express the typical mesenchymal stem cell marker proteins and can differentiate into adipocytes, osteoblasts, chondrocytes or muscle cells. In stage 2, DMEM/F12 serum-free medium with ITS mix (insulin, transferrin, and selenite) is used to induce differentiation of hLMDFs into endoderm-like cells, as determined by the expression of the endoderm markers Sox17, Foxa2, and PDX1 (stage 2: mesenchymal-endoderm transition). In stage 3, cells in the mesenchymal-endoderm transition st... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5360860 Fri, 21 Oct 2011 04:00:00 +0100 5360860 http://www.medworm.com/index.php?rid=5360861&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22020445%26dopt%3DAbstract Authors: Park SJ, Shin S, Koo OJ, Moon JH, Jang G, Ahn C, Lee BC, Yoo YJ Abstract Transplantation of islet cells into diabetic patients is a promising therapy, provided that the islet cells are able to evade host immune rejection. With improved islet viability, this strategy may effectively reverse diabetes. We applied 2% calcium alginate to generate small and large capsules to encapsulate porcine neonatal pancreatic cell clusters (NPCCs) using an air-driven encapsulator. After encapsulation, the viability was assessed at 1, 4, 7, 14 and 28 days and secretion of functional insulin in response to glucose stimulation were tested at days 14 and 28. Selective permeability of the small alginate capsules was confirmed using various sizes of isothiocyanate-labeled dextran (FITC-dextran). ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5360861 Wed, 19 Oct 2011 04:00:00 +0100 5360861 http://www.medworm.com/index.php?rid=5296171&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975281%26dopt%3DAbstract In conclusion, it was suggested that FA have protective and therapeutic effects on diabetic nephropathy by reducing oxidative stress and inflammation. PMID: 21975281 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5296171 Thu, 06 Oct 2011 04:00:00 +0100 5296171 http://www.medworm.com/index.php?rid=5296170&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21975282%26dopt%3DAbstract In conclusion, inhibition of NF-κB activity prevented high glucose-induced VSMC proliferation and PAI-1 expression. PMID: 21975282 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5296170 Thu, 06 Oct 2011 04:00:00 +0100 5296170 http://www.medworm.com/index.php?rid=5296172&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21971413%26dopt%3DAbstract In this study, we investigated the underlying molecular mechanism of the synergistic effect of rottlerin on interleukin1b (IL-1b)-induced COX-2 expression in MDA-MB-231 human breast cancer cell line. Treatment with rottlerin enhanced IL-1b-induced COX-2 expression at both the protein and mRNA levels. Combined treatment with rottlerin and IL-1b significantly induced COX-2 expression, at least in part, through the enhancement of COX-2 mRNA stability. In addition, rottlerin and IL-1b treatment drove sustained activation of p38 Mitogen-activated protein kinase (MAPK), which is involved in induced COX-2 expression. Also, a pharmacological inhibitor of p38 MAPK (SB 203580) and transient transfection with inactive p38 MAPK inhibited rottlerin and IL-1b-induced COX-2 upregulation. However, suppres... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5296172 Wed, 05 Oct 2011 04:00:00 +0100 5296172 http://www.medworm.com/index.php?rid=5276553&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21734448%26dopt%3DAbstract In conclusion, survivin appeared to play an important role in the up-regulation of uPA induced by HGF via JunB and might contribute to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy. PMID: 21734448 [PubMed - in process] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5276553 Fri, 30 Sep 2011 04:00:00 +0100 5276553 http://www.medworm.com/index.php?rid=5276552&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21734449%26dopt%3DAbstract Authors: Kim H, Lee SW, Baek KM, Park JS, Min JH Abstract Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride; PQ), an effective and widely used herbicide, was commercially introduced in 1962. It is reduced by the electron donor NADPH, and then reduced PQ transfers the electrons to molecular oxygen, resulting in the production of reactive oxygen species (ROS), which are related to cellular toxicity. However, the influence of continuous hypoxia on PQ-induced ROS production has not fully been investigated. We evaluated in vitro the protective effect of continuous hypoxia on PQinduced cytotoxicity in the human carcinogenic alveolar basal epithelial cell line (A549 cells) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and live and dead assay,... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5276552 Fri, 30 Sep 2011 04:00:00 +0100 5276552 http://www.medworm.com/index.php?rid=5228408&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21918362%26dopt%3DAbstract Authors: Yun JH, Park SJ, Jo A, Kang JL, Jou I, Park JS, Choi YH Abstract Recent evidence supports a neuroprotective role of Src homology 2-containing protein tyrosine phosphatase 2 (SHP-2) against ischemic brain injury. However, the molecular mechanisms of SHP-2 activation and those governing how SHP-2 exerts its function under oxidative stress conditions are not well understood. Recently we have reported that reactive oxygen species (ROS)-mediated oxidative stress promotes the phosphorylation of endogenous SHP-2 through lipid rafts, and that this phosphorylation strongly occurs in astrocytes, but not in microglia. To investigate the molecules involved in events leading to phosphorylation of SHP-2, raft proteins were analyzed using astrocytes and microglia. Interestingly, caveolin... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5228408 Thu, 15 Sep 2011 04:00:00 +0100 5228408 http://www.medworm.com/index.php?rid=5228407&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21918363%26dopt%3DAbstract Authors: Hong KS, Kim HS, Kim SH, Lim DJ, Park JY, Kim SD Abstract In an oxygen-depleted environment, endothelial cells initiate an adaptive pattern of synthesis, which may enable them to survive hypoxic crises. Using high-resolution two-dimensional gel electrophoresis in conjunction with mass spectroscopy, we obtained a 24 differential display of proteins in the pancreatic endothelial cell line, MS-1, at four time points following induction of hypoxia. The induction of wee1 under hypoxia was confirmed both at the mRNA and protein levels. The phosphorylation of cell division cycle 2, which is downstream of wee1, was also increased after hypoxic exposure. In addition, pre-exposure to hypoxia attenuated a decrease in hydrogen peroxide-induced cell number. The induction of bax (a pro-... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5228407 Thu, 15 Sep 2011 04:00:00 +0100 5228407 http://www.medworm.com/index.php?rid=5218287&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21904110%26dopt%3DAbstract Authors: Suh BY, Jung JJ, Park N, Seong CH, Im HJ, Kwon Y, Kim D, Chun YJ Abstract Steroid sulfatase (STS) is responsible for the hydrolysis of aryl and alkyl steroid sulfates and has a pivotal role in regulating the formation of biologically active estrogens. STS may be considered a new promising drug target for treating estrogen-mediated carcinogenesis. However, the molecular mechanism of STS expression is not well-known. To investigate whether tumor necrosis factor (TNF)-α is able to regulate gene transcription of STS, we studied the effect of TNF-α on STS expression in PC-3 human prostate cancer cells. RT-PCR and Western blot analysis showed that TNF-α significantly induced the expression of STS mRNA and protein in a concentration- and time-dependent manner. Treatment with T... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5218287 Fri, 09 Sep 2011 04:00:00 +0100 5218287 http://www.medworm.com/index.php?rid=5174912&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21869593%26dopt%3DAbstract In this study, we investigated the role of short hairpin RNA (shRNA) targeting E2F-1 gene on human gastric cancer MGC-803 cell growth in vivo, and preliminarily revealed the mechanism. Thus, we constructed recombinant pGCSIL-GFP-shRNA-E2F-1 lentiviral vector to knock down E2F-1 expression in human gastric cancer MGC-803 cells in vivo, and studied the effect of E2F-1 shRNA on growth of MGC-803 tumor and evaluated its treatment efficacy. Our data demonstrated that in a mouse model of established gastric cancer, intratumor injection of lentiviral shRNA targeting E2F-1 definitely decreased the endogenous E2F-1 mRNA and protein expression in MGC-803 tumor, and inhibited tumor growth and promoted tumor cells apoptosis. Moreover, we found that E2F-1 shRNA increased the expression of phosphatase a... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5174912 Thu, 25 Aug 2011 23:00:00 +0100 5174912 http://www.medworm.com/index.php?rid=5174913&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21865860%26dopt%3DAbstract Authors: Chung BH, Oh HJ, Piao SG, Sun IO, Kang SH, Choi SR, Park HS, Choi BS, Choi YJ, Park CW, Kim YS, Cho ML, Yang CW Abstract The aim of this study was to evaluate whether the Th17 and Treg cell infiltration into allograft tissue is associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens were immunostained for FOXP3 and IL-17. The allograft function was assessed at biopsy by measuring serum creatinine (Scr) concentration, and by applying the modified diet in renal disease (MDRD) formula, which provides the estimated glomerular filtration rate (eGFR). The severity of allograft tissue injury was assessed by calculating tissue injur... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5174913 Tue, 23 Aug 2011 23:00:00 +0100 5174913 http://www.medworm.com/index.php?rid=5141044&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21847007%26dopt%3DAbstract Authors: Yang HS, Shin J, Bhang SH, Shin JY, Park J, Im GI, Kim CS, Kim BS Abstract Platelet-rich plasma (PRP) contains growth factors that promote tissue regeneration. Previously, we showed that heparin-conjugated fibrin (HCF) exerts the sustained release of growth factors with affinity for heparin. Here, we hypothesize that treatment of skin wound with a mixture of PRP and HCF exerts sustained release of several growth factors contained in PRP and promotes skin wound healing. The release of fibroblast growth factor 2, platelet-derived growth factor-BB, and vascular endothelial growth factor contained in PRP from HCF was sustained for a longer period than those from PRP, calcium-activated PRP (C-PRP), or a mixture of fibrin and PRP (F-PRP). Treatment of full-thickness skin wounds ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5141044 Tue, 16 Aug 2011 23:00:00 +0100 5141044 http://www.medworm.com/index.php?rid=5141043&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21847008%26dopt%3DAbstract Authors: Baek SJ, Kang SK, Ra JC Abstract The homing properties of adipose tissue-derived mesenchymal stem cells (AdMSCs) have stimulated intravenous applications for their use in stem cell therapy. However, the soluble factors and corresponding cellular receptors responsible for inducing chemotaxis of AdMSCs have not yet been reported. In the present study, the migration capacity of human AdMSCs (hAdMSCs) toward various cytokines or growth factors (GFs) and the expression of their receptors were determined. When compared in an in vitro migration assay, PDGF-AB, TGF-β1 and TNF-α showed the most chemoattractant activity. Human AdMSCs were prestimulated with a select chemokine or GF and were allowed to migrate toward medium containing 10% FBS. Those hAdMSCs prestimulated with TNF-Î... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5141043 Tue, 16 Aug 2011 23:00:00 +0100 5141043 http://www.medworm.com/index.php?rid=5141045&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21844665%26dopt%3DAbstract Authors: Hu HJ, Jin EH, Yim SH, Yang SY, Jung SH, Shin SH, Kim WU, Shim SC, Kim TG, Chung YJ Abstract Although the genetic component in the etiology of rheumatoid arthritis (RA) has been consistently suggested, many novel genetic loci remain to uncover. To identify RA risk loci, we performed a genome-wide association study (GWAS) with 100 RA cases and 600 controls using Affymetrix SNP array 5.0. The candidate risk locus (APOM gene) was re-sequenced to discover novel promoter and coding variants in a group of the subjects. Replication was performed with the independent case-control set comprising of 578 RAs and 711 controls. Through GWAS, we identified a novel SNP associated with RA at the APOM gene in the MHC class III region on 6p21.33 (rs805297, odds ratio (OR) = 2.28, P = 5.20 x... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5141045 Mon, 15 Aug 2011 23:00:00 +0100 5141045 http://www.medworm.com/index.php?rid=5141046&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21832867%26dopt%3DAbstract In this study, we analyzed whether simvastatin can inhibit RANKL-induced osteoclastogenesis through suppression of the subsequently formed ROS and investigated whether simvastatin can inhibit H2O2-induced signaling pathways in osteoclast differentiation. We found that simvastatin decreased expression of tartrate-resistant acid phosphatase (TRAP), a genetic marker of osteoclast differentiation, and inhibited intracellular ROS generation in RAW 264.7 cell lines. ROS generation activated IkBα, protein kinases B (AKT), mitogen-activated protein kinases (MAPKs) signaling pathways such as c-JUN N-terminal kinases (JNK), p38 MAP kinases (P38) as well as extracellular signal-regulated kinase (ERK). Simvastatin was found to suppress these H2O2-induced signaling pathways in osteoclastogenesis. Toge... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5141046 Tue, 09 Aug 2011 23:00:00 +0100 5141046 http://www.medworm.com/index.php?rid=5141047&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21825834%26dopt%3DAbstract Authors: Ahn I, Bae SE, Son HS Abstract We compared genetic variations in the VP1 gene of foot-and-mouth disease viruses (FMDVs) isolated since 2000 according to the region of the world from. We analyzed relative synonymous codon usage (RSCU) and phylogenetic relationship between geographical regions, and calculated the genetic substitution patterns between Korean isolate and those from other countries. We calculated the ratios of synonymously substituted codons (SSC) to all observed substitutions and developed a new analytical parameter, EMC (the ratio of exact matching codons within each synonymous substitution group) to investigate more detailed substitution patterns within each synonymous codon group. We observed that FMDVs showed distinct RSCU patterns according to phylogeneti... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5141047 Mon, 08 Aug 2011 23:00:00 +0100 5141047 http://www.medworm.com/index.php?rid=5141048&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21822049%26dopt%3DAbstract Authors: Kim CY, Park SH, Jeong M, Kwon OS, Doh H, Kang SH, Robbins PD, Kim BM, Seol DW, Kim BG Abstract Malignant glioma is the most frequent type in brain tumors. The prognosis of this tumor has not been significantly improved for the past decades and the average survival of patients is less than one year. Thus, an effective novel therapy is urgently needed. TNF-related apoptosis inducing ligand (TRAIL), known to have tumor cell-specific killing activity, has been investigated as a novel therapeutic for cancers. We have developed Ad-stTRAIL, an adenovirus-based gene therapy delivering secretable trimeric TRAIL and demonstrated the potential to treat malignant gliomas. Currently, this Ad-stTRAIL gene therapy is under phase I clinical trial for malignant gliomas. Here, we report pr... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5141048 Sun, 07 Aug 2011 23:00:00 +0100 5141048 http://www.medworm.com/index.php?rid=5141049&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21817852%26dopt%3DAbstract Authors: Park WH, Pak YK Abstract Cholesterol 7α-hydroxylase (CYP7A1) regulates the balance between cholesterol supply and matabolism by catalyzing the rate-limiting step of bile acid biosynthesis. The transcriptional activity of CYP7A1 is tightly controlled by various nuclear receptors. A forkhead transcription factor O1 (FOXO1) plays a critical role in metabolism, and insulin inactivates FOXO1 through Akt-dependent phosphorylation and nuclear exclusion. We investigated the role of insulin- Akt-FOXO1 signaling pathway in CYP7A1 transcriptional regulation since we found putative insulin-response elements, FOXO1 binding sequences, in both rat and human CYP7A1 promoters. However, ectopic expression of FOXO1 increased the rat CYP7A1-, but mildly reduced human CYP7A1-promoter activiti... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5141049 Wed, 03 Aug 2011 23:00:00 +0100 5141049 http://www.medworm.com/index.php?rid=5097489&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21811090%26dopt%3DAbstract Authors: Shim H To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5097489 Tue, 02 Aug 2011 23:00:00 +0100 5097489 http://www.medworm.com/index.php?rid=5097508&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21795829%26dopt%3DAbstract Authors: Woo YJ, Joo YB, Jung YO, Ju JH, Cho ML, Oh HJ, Jhun JY, Park MK, Park JS, Kang CM, Sung MS, Park SH, Kim HY, Min JK Osteoarthritis (OA) is an age-related joint disease that is characterized by degeneration of articular cartilage and chronic pain. Oxidative stress is considered one of the pathophysiological factors in the progression of OA. We investigated the effects of grape seed proanthocyanidin extract (GSPE), which is an antioxidant, on monosodium iodoacetate (MIA)-induced arthritis of the knee joint of rat, which is an animal model of human OA. GSPE (100 mg/kg or 300 mg/kg) or saline was given orally three times per week for 4 weeks after the MIA injection. Pain was measured using the paw withdrawal latency (PWL), the paw withdrawal threshold (PWT) and the hind limb weigh... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5097508 Wed, 27 Jul 2011 23:00:00 +0100 5097508 http://www.medworm.com/index.php?rid=5097514&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21778808%26dopt%3DAbstract Authors: Jung GA, Shin BS, Jang YS, Sohn JB, Woo SR, Kim JE, Choi G, Lee KM, Min BH, Lee KH, Park GH Protein arginine methylation is important for a variety of cellular processes including transcriptional regulation, mRNA splicing, DNA repair, nuclear/cytoplasmic shuttling and various signal transduction pathways. However, the role of arginine methylation in protein biosynthesis and the extracellular signals that control arginine methylation are not fully understood. Basic fibroblast growth factor (bFGF) has been identified as a potent stimulator of myofibroblast dedifferentiation into fibroblasts. We demonstrated that symmetric arginine dimethylation of eukaryotic elongation factor 2 (eEF2) is induced by bFGF without the change in the expression level of eEF2 in mouse embryo fibroblas... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5097514 Wed, 20 Jul 2011 23:00:00 +0100 5097514 http://www.medworm.com/index.php?rid=5051419&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21765237%26dopt%3DAbstract Authors: Cho SC, Rhim JH, Choi HR, Son YH, Lee SJ, Song KY, Park SC Although 4,4'-diaminodiphenylsulfone (DDS, dapsone) has been used to treat several dermatologic conditions, including Hansen disease, for the past several decades, its mode of action has remained a topic of debate. We recently reported that DDS treatment significantly extends the lifespan of the nematode C. elegans by decreasing the generation of reactive oxygen species. Additionally, in in vitro experiments using non-phagocytic human fibroblasts, we found that DDS effectively counteracted the toxicity of paraquat (PQ). In the present study, we extended our work to test the protective effect of DDS against PQ in vivo using a mouse lung injury model. Oral administration of DDS to mice significantly attenuated the lung t... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5051419 Sun, 17 Jul 2011 23:00:00 +0100 5051419 http://www.medworm.com/index.php?rid=5051420&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21743278%26dopt%3DAbstract In this study, we evaluated the interaction of ligand advanced glycation end products (AGE) with RAGE during the epithelial to myofibroblast transition in rat AECs. Our results indicate that AGE inhibited the TGF-β-dependent alveolar EMT by increasing Smad7 expression, and that the effect was abolished by RAGE siRNA treatment. Thus, the induction of Smad7 by the AGE-RAGE interaction limits the development of pulmonary fibrosis by inhibiting TGF-β-dependent signaling in AECs. PMID: 21743278 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5051420 Sun, 10 Jul 2011 23:00:00 +0100 5051420 http://www.medworm.com/index.php?rid=5051421&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21737995%26dopt%3DAbstract Authors: Seo JM, Lee JY, Ji GE, You JC We have investigated the effect of various forms of phosphodiester cytidine-phosphate-guanosine oligodeoxynucleotides (CpG ODNs) on the production of pro-inflammatory cytokines and related genes in RAW 264.7 macrophages. Treatment with the CpG ODNs increased the expression of tumor necrosis factor α (TNF-α), IL-6, and inducible nitric oxide synthase but not interleukin-1β (IL-1β). We also investigated the effect of CpG ODNs on the expression of ATP-binding cassette transporter A1 (ABCA1) and G1 (ABCG1) genes which are known to facilitate cholesterol efflux from macrophages for anti-atherosclerosis. CpG 2006 significantly reduced the levels of ABCG1 mRNA as determined by real-time polymerase chain reaction, whereas ABCA1 mRNA was not. Western b... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5051421 Thu, 07 Jul 2011 23:00:00 +0100 5051421 http://www.medworm.com/index.php?rid=5051423&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21734448%26dopt%3DAbstract In conclusion, survivin appeared to play an important role in the up-regulation of uPA induced by HGF via JunB and might contribute to HGF-mediated tumor invasion and metastasis, which may serve as a promising target for gastric cancer therapy. PMID: 21734448 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5051423 Tue, 05 Jul 2011 23:00:00 +0100 5051423 http://www.medworm.com/index.php?rid=5051422&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21734449%26dopt%3DAbstract Authors: Kim H, Lee SW, Bak KM, Park JS, Min JH Paraquat (1,1'-dimethyl-4,4'-bipyridinium dichloride; PQ), an effective and widely used herbicide, was commercially introduced in 1962. It is reduced by the electron donor NADPH, and then reduced PQ transfers the electrons to molecular oxygen, resulting in the production of reactive oxygen species (ROS), which are related to cellular toxicity. However, the influence of continuous hypoxia on PQ-induced ROS production has not fully been investigated. We evaluated in vitro the protective effect of continuous hypoxia on PQ-induced cytotoxicity in the human carcinogenic alveolar basal epithelial cell line (A549 cells) by using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and live and dead assay, and by measu... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5051422 Tue, 05 Jul 2011 23:00:00 +0100 5051422 http://www.medworm.com/index.php?rid=5000879&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21697645%26dopt%3DAbstract Authors: Liu BQ, Meng X, Li C, Gao YY, Li N, Niu XF, Guan Y, Wang HQ Glucosamine, a naturally occurring amino monosaccharide, has been reported to play a role in the regulation of apoptosis more than half century. However the effect of glucosamine on tumor cells and the involved molecular mechanisms have not been thoroughly investigated. Glucosamine enters the hexosamine biosynthetic pathway (HBP) downstream of the rate-limiting step catalyzed by the GFAT (glutamine:fluctose-6-phosphate amidotransferase), providing UDP-GlcNAc substrates for O-linked b-N-acetylglucosamine (O-GlcNAc) protein modification. Considering that O-GlcNAc modification of proteasome subunits inhibits its activity, we examined whether glucosamine induces growth inhibition via affecting proteasomal activity. In the... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5000879 Wed, 22 Jun 2011 23:00:00 +0100 5000879 http://www.medworm.com/index.php?rid=5000880&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21694495%26dopt%3DAbstract Authors: Park JH, Yoon JY, Ko SM, Jin SA, Kim JH, Cho CH, Kim JM, Lee JH, Choi SW, Seong IW, Jeong JO Cardiac lymphatic system in the remodeling after acute myocardial infarction (AMI) has been overlooked. We wanted to investigate the role of bone marrow (BM)-derived endothelial progenitor cells (EPCs) and their contribution to lymphatic distribution in myocardial remodeling after AMI. Mouse (C57bl/6J) MI models were created by ligation of the left anterior descending coronary artery and were treated with phosphate buffered saline (PBS) or EPCs. Real-time RT-PCR with 2- to 4-week myocardial tissue samples revealed that lymphangiogenetic factors such as vascular endothelial growth factor (VEGF)-C (8.5 fold, p<0.05), VEGF-D (6.1 fold, p<0.05), Lyve-1 (15 fold, p<0.05), and Prox-... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=5000880 Tue, 21 Jun 2011 23:00:00 +0100 5000880 http://www.medworm.com/index.php?rid=4955448&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21691142%26dopt%3DAbstract In conclusion, HMB-TZD ameliorates atherosclerotic lesion formation possibly by reducing the expression of proinflammatory molecules and monocyte/macrophage recruitment to the lesion. These results suggest that HMB-TZD, and benzylidenethiazole analogs in general, may have therapeutic potential as treatments for atherosclerosis. PMID: 21691142 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4955448 Mon, 20 Jun 2011 23:00:00 +0100 4955448 http://www.medworm.com/index.php?rid=4955449&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21685723%26dopt%3DAbstract Authors: Cho IH, Lee KW, Ha HY, Han PL We previously reported that mice lacking JSAP1 (jsap1-/-) were lethal and the brain of jsap1-/- at E18.5 exhibited multiple types of developmental defects, which included impaired axon projection of the corpus callosum and anterior commissures. In the current study, we examined whether the early telencephalic commissures were formed abnormally from the beginning of initial development or whether they arose normally, but have been progressively lost their maintenance in the absence of JSAP1. The early corpus callosum in the brain of jsap1+/+ at E15.5-E16.5 was found to cross the midline with forming a distinct U-shaped tract, whereas the early axonal tract in jsap1-/- appeared to cross the midline in a diffuse manner, but the lately arriving axons ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4955449 Sun, 19 Jun 2011 23:00:00 +0100 4955449 http://www.medworm.com/index.php?rid=4955450&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21677506%26dopt%3DAbstract Authors: Kim D, Choi B, Song J, Kim S, Oh S, Jin EH, Kang SS, Jin EJ Vertically aligned, laterally spaced nanoscale titanium nanotubes were grown on a titanium surface by anodization, and the growth of chondroprogenitors on the resulting surfaces was investigated. Surfaces bearing nanotubes of 70 to 100 nm in diameter were found to trigger the morphological transition to a cortical actin pattern and rounded cell shape (both indicative of chondrocytic differentiation), as well as the up-regulation of type II collagen and integrin b4 protein expression through the down-regulation of Erk activity. Inhibition of Erk signaling reduced stress fiber formation and induced the transition to the cortical actin pattern in cells cultured on 30-nm-diameter nanotubes, which maintained their fibrobla... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4955450 Wed, 15 Jun 2011 23:00:00 +0100 4955450 http://www.medworm.com/index.php?rid=4955451&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21654189%26dopt%3DAbstract This study aimed to unravel the mechanisms involving the failure to activate tolerogenic IDO in the inflamed joint. We demonstrate that both poly (I:C) and lipopolysaccharide (LPS) induce expression of IDO in synovial fibroblasts. However, inflammatory cytokines such as IL-17, TNF-a, IL-12, IL-23 and IL-16 did not induce IDO expression. Poly (I:C) appeared to induce higher IDO expression than did LPS. Surprisingly, toll-like receptor (TLR)4-mediated IDO expression was upregulated after depletion of myeloid differentiation primary response protein 88 (MyD88) in synovial fibroblasts using small interfering RNA (siRNA). IDO, TLR3 and TLR4 were highly expressed in synovial tissue of RA patients compared with that of osteoarthritis patients. In addition, RA patients with severe disease activity... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4955451 Tue, 07 Jun 2011 23:00:00 +0100 4955451 http://www.medworm.com/index.php?rid=4955453&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21654187%26dopt%3DAbstract This study demonstrated that IPoC induced protection was associated with increased expression of MIP2. Both MIP2 overexpression and MIP2 suppression can influence the IPoC induced protection. PMID: 21654187 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4955453 Mon, 06 Jun 2011 23:00:00 +0100 4955453 http://www.medworm.com/index.php?rid=4955452&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21654188%26dopt%3DAbstract Authors: Kwak DH, Seo BB, Chang KT, Choo YK Gangliosides have been suggested to play important roles in various functions such as adhesion, cell differentiation, growth control, and signaling. Mouse follicular development, ovulation, and luteinization during the estrous cycle are regulated by several hormones and cell-cell interactions; in addition, spermatogenesis in seminiferous tubules of adult testes is also regulated by several hormones, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and cell-cell interactions. The regulation of these processes by hormones and cell-cell interactions provides evidence for the importance of surface membrane components, including gangliosides. During preimplantation embryo development, a mammalian embryo undergoes a series ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4955452 Mon, 06 Jun 2011 23:00:00 +0100 4955452 http://www.medworm.com/index.php?rid=4905863&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21646846%26dopt%3DAbstract In this study, we conducted LC-MS/MS to analyze serum samples depleted of the six most abundant proteins from normal and PE-affected pregnancies to profile serum proteins. A total of 237 proteins were confidently identified with <1% FDR from the two groups of duplicate analysis. The expression levels of those identified proteins were compared semiquantitatively by spectral counting. To further validate the candidate proteins with a quantitative mass spectrometric method, selective reaction monitoring (SRM) and enzyme linked immune assay (ELISA) of serum samples collected from pregnant women with severe PE (n=8) or normal pregnant women (n=5) was conducted. Alpha2-HS-glycoprotein (AHSG), Retinol binding protein4 (RBP4) and alpha-1-microglobulin/bikunin (AMBP) and Insulin like growth fact... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4905863 Thu, 02 Jun 2011 23:00:00 +0100 4905863 http://www.medworm.com/index.php?rid=4905868&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21633183%26dopt%3DAbstract Authors: Kim KH, Yoo HY, Joo KM, Jung Y, Jin J, Kim Y, Yoon SJ, Choi SH, Seol HJ, Park WY, Nam DH Radiation is the most useful treatment modality for cancer patients. It initiates a series of signal cascades such as DNA damage response (DDR) signaling for repairing damaged DNA, arresting the cell cycle, and inducing cell death. Until now, few genes have been found to be regulated by radiation, which explains the molecular mechanisms of cellular responses to radiation. Although the transcriptional changes caused by radiation have been widely investigated, little is known about the direct evidence for the transcriptional control of DDR-related genes. Here, we examined the radiosensitivity of two non-small cell lung cancer cell lines (H460 and H1299), which have different p53 status. With... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4905868 Wed, 01 Jun 2011 23:00:00 +0100 4905868 http://www.medworm.com/index.php?rid=4905867&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21633184%26dopt%3DAbstract Authors: Jin S, Park JY, Hong JM, Kim TH, Shin HI, Park EK, Kim SY Tumor necrosis factor-α (TNF-α) and inflammatory cytokines released from activated macrophages in response to particulate debris greatly impact periprosthetic bone loss and consequent implant failure. In the present study, we found that a major polyphenolic component of green tea, (-)-epigallocatechin gallate (EGCG), inhibited Ti particle-induced TNF-α release in macrophages in vitro and calvarial osteolysis in vivo. The Ti stimulation of macrophages released TNF-α in a dose- and time-dependent manner, and EGCG substantially suppressed Ti particle-induced TNF-α release. Analysis of signaling pathway showed that EGCG inhibited the Ti-induced c-Jun N-terminus kinase (JNK) activation and inhibitory κB (IκB) degradat... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4905867 Wed, 01 Jun 2011 23:00:00 +0100 4905867 http://www.medworm.com/index.php?rid=4905871&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21628990%26dopt%3DAbstract Authors: Kim DN, Song YJ, Lee SK Epstein-Barr Virus (EBV) microRNAs (miRNAs) are expressed in EBV-associated tumors and cell lines, but the regulation mechanism of their expression is unclear, yet. We investigated whether the expression of EBV miRNAs is epigenetically regulated in EBV-infected B cell lines. The expression of BART miRNAs was inversely related with the methylation level of the BART promoter at both steady-state and following 5-aza-2'-deoxycytidine treatment of the cells. The expression of BHRF1 miRNAs also became detectable with the demethylation of Cp/Wp in latency I EBV-infected cell lines. Furthermore, in vitro methylation of the BART and Cp promoters reduced the promoter-driven transactivation. In contrast, tricostatin A had little effect on the expression of EBV miR... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4905871 Tue, 31 May 2011 23:00:00 +0100 4905871 http://www.medworm.com/index.php?rid=4905870&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21628991%26dopt%3DAbstract Authors: Lee EJ, Kim KJ, Kim HN, Bok J, Jung SC, Kim EK, Lee JY, Kim HL Granular corneal dystrophy, type II (CGD2; Avellino corneal dystrophy) is the most common corneal dystrophy among Koreans, but its pathophysiology is still poorly understood. Many reports showed that even though the causative mutation is the same TGFBI R124H mutation, there are severe and mild phenotypes of the corneal dystrophy. We also observed the phenotype differences in our samples. For this reason, we focused our effort on the identification of unknown genetic factor related to phenotype variation. A total 551 individuals from 59 families were genotyped with SNP chip and used in genome-wide linkage analysis. From single-point linkage analyses, we confirmed the known 5q31 region for TGFBI gene, and selected no... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4905870 Tue, 31 May 2011 23:00:00 +0100 4905870 http://www.medworm.com/index.php?rid=4905869&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21628992%26dopt%3DAbstract In this study, we demonstrate that p41-Arc can induce senescent phenotypes when it is overexpressed in human tumor cell line, SaOs-2, which is deficient in p53 and Rb tumor suppressor genes, implying that p41 can induce senescence in a p53-independent way. p41-Arc overexpression causes a change in actin filaments, accumulating actin filaments in nuclei. Therefore, these results imply that a change in actin filament can trigger an intrinsic senescence program in the absence of p53 and Rb tumor suppressor genes. PMID: 21628992 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4905869 Tue, 31 May 2011 23:00:00 +0100 4905869 http://www.medworm.com/index.php?rid=4804048&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21540635%26dopt%3DAbstract Authors: Shen M, Zhang L, Lee KM, Vermeulen R, Hosgood HD, Li G, Yin S, Rothman N, Chanock S, Smith MT, Lan Q Benzene, a recognized hematotoxicant and carcinogen, can damage the human immune system. We studied the association between single nucleotide polymorphisms (SNPs) in genes involved in innate immunity and benzene hematotoxicity in a cross-sectional study of workers exposed to benzene (250 workers and 140 controls). A total of 1,236 tag SNPs in 149 gene regions of six pathways were included in the analysis. Six gene regions were significant for their association with white blood cell (WBC) counts (MBP, VCAM1, ALOX5, MPO, RAC2, and CRP) based on gene-region (P < 0.05) and SNP analyses (FDR < 0.05). VCAM1 rs3176867, ALOX5 rs7099684, and MPO rs2071409 were the three most signi... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4804048 Mon, 02 May 2011 23:00:00 +0100 4804048 http://www.medworm.com/index.php?rid=4804049&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21532314%26dopt%3DAbstract Authors: Kang KS, Lee SJ, Lee H, Moon W, Cho DW We observed how combined mechanical stimuli affect the proliferation and differentiation of pre-osteoblasts. For this research, a bioreactor system was developed that can simultaneously stimulate cells with cyclic strain and ultrasound, each of which is known to effectively stimulate bone tissue regeneration. MC3T3-E1 cells, which are pre-osteoblasts, were chosen for bone tissue engineering due to their osteoblast-like characteristics. 3-D scaffolds were fabricated with PCL and PLLA using the salt leaching method. They were stimulated by the bioreactor with cyclic strain and ultrasound. The bioreactor was set at a frequency of 1.0 Hz and 10 % strain for cyclic strain and 1.0 MHz and 30 mW/cm2 for ultrasound. Three experimental groups (ult... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4804049 Sun, 01 May 2011 23:00:00 +0100 4804049 http://www.medworm.com/index.php?rid=4804050&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21519184%26dopt%3DAbstract Authors: Shen Y, Li Y, Ye F, Wang F, Wan X, Lu W, Xie X Quantitative real-time RT-PCR (RT-qPCR) is being widely used in microRNA expression research. However, few reports detailed a robust identification and validation strategy for suitable reference genes for normalisation in microRNA RT-qPCR studies. The aim of this study was to identify the most stable reference gene(s) for quantification of microRNA expression analysis in cervical tissues. A microarray was performed on 6 pairs of cervical tissues to identify the candidate reference genes. The stability of candidate reference genes was assessed by RT-qPCR in 23 pairs of cervical tissues. The identified most stable reference genes were further validated in other cohort of 108 clinic cervical samples: (HR-HPV- normal, n=21; HR-HPV+ no... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4804050 Mon, 25 Apr 2011 23:00:00 +0100 4804050 http://www.medworm.com/index.php?rid=4751940&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21515993%26dopt%3DAbstract Authors: Woo YJ, Yoon BY, Jhun JY, Oh HJ, Min S, Cho ML, Park SH, Kim HY, Ki Min J B cells play an important role in the pathogenesis of rheumatoid arthritis (RA). High levels of B cell activating factor belonging to the tumor necrosis factor family (BAFF) are detected in autoimmune diseases. BAFF and BAFF receptor (BAFF-R) are expressed in B and T cells of RA synovium. The study was undertaken to identify the NF-kB signal pathway involved in the induction of BAFF-R in human B cells. Immunohistochemical staining of NF-kB p65, NF-kB p50, BAFF, and BAFF-R was performed on sections of synovium from severe and mild RA and osteoarthritis (OA) patients. Peripheral blood mononuclear cells (PBMCs) were isolated from control and RA patients and B cells were isolated from controls. BAFF-R was an... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4751940 Sun, 24 Apr 2011 23:00:00 +0100 4751940 http://www.medworm.com/index.php?rid=4751942&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21499011%26dopt%3DAbstract Authors: Paik YH, Yoon YJ, Lee HC, Jung MK, Kang SH, Chung SI, Kim JK, Cho JY, Lee KS, Han KH Magnesium lithospermate B (MLB) is one of the major active components of Salvia miltiorrhizae. The anti-oxidative effects of Salvia miltiorrhizae have been previously reported. The aim of this study was to investigate the effect of purified MLB on hepatic fibrosis in rats and on the fibrogenic responses in hepatic stellate cells (HSCs). Hepatic fibrosis was induced in rats by intraperitoneal thioacetamide (TAA) injections over a period of 8 or 12 weeks. MLB was orally administered daily by gavage tube. Serum AST and ALT levels in TAA + MLB group were significantly lower than those in TAA only group at week 8. Hepatic fibrosis was significantly attenuated in TAA + MLB group than in TAA only gro... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4751942 Sun, 17 Apr 2011 23:00:00 +0100 4751942 http://www.medworm.com/index.php?rid=4751941&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21499012%26dopt%3DAbstract In this study, we observed that the cell number and GAG formation dramatically decreased with aging. Also, gene expression in the annulus fibrosus(AF) and nucleus pulposus(NP) cells changed with aging. The level of MMP-1 mRNA increased with age and both type I, II collagens decreased with age. The level of aggrecan mRNA was highest in the mature group and decreased significantly with aging. In the mature group, MMP-1 expression was minimal compared to the newborn group. In AF cells, type II collagen was expressed at a high level in the mature group with a higher level of aggrecan, when aged NP showed a decrease in type II collagen. The model of IVD degeneration in the porcine disc shows many changes in gene expression with age that have been previously documented for human and may serve as... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4751941 Sun, 17 Apr 2011 23:00:00 +0100 4751941 http://www.medworm.com/index.php?rid=4751943&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21499010%26dopt%3DAbstract Authors: Kim BH, Min YS, Choi JS, Baeg GH, Kim Y, Shin JW, Kim TY, Ye SK Persistently activated JAK/STAT3 signaling pathway plays a pivotal role in various human cancers including major carcinomas and hematologic tumors, and is implicated in cancer cell survival and proliferation. Therefore, inhibition of JAK/STAT3 signaling may be a clinical application in cancer therapy. Here, we report that 2-cyclohexylimino-6-methyl-6,7-dihydro-5H-benzo[1,3]oxathiol-4-one (BOT-4-one), a small molecule inhibitor of JAK/STAT3 signaling, induces apoptosis through inhibition of STAT3 activation. BOT-4-one suppressed cytokine (upd)-induced tyrosine phosphorylation and transcriptional activity of STAT92E, the sole Drosophila STAT homolog. Consequently, BOT-4-one significantly inhibited STAT3 tyrosine pho... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4751943 Thu, 14 Apr 2011 23:00:00 +0100 4751943 http://www.medworm.com/index.php?rid=4751944&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21483230%26dopt%3DAbstract Authors: Kim W, Seong KM, Youn B Radiotherapy, frequently used for treatment of solid tumors, carries two main obstacles including acquired radioresistance in cancer cells during radiotherapy and normal tissue injury. Phenylpropanoids, which are naturally occurring phytochemicals found in plants, have been identified as potential radiotherapeutic agents due to their anti-cancer activity and relatively safe levels of cytotoxicity. Various studies have proposed that these compounds could not only sensitize cancer cells to radiation resulting in inhibition of growth and cell death but also protect normal cells against radiation-induced damage. This review is intended to provide an overview of recent investigations on the usage of phenylpropanoids in combination with radiotherapy in cancer... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4751944 Sun, 10 Apr 2011 23:00:00 +0100 4751944 http://www.medworm.com/index.php?rid=4751945&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21483229%26dopt%3DAbstract This study assessed the long-term efficacy of MET on suppression of tumor growth and spontaneous metastasis in a rat model of HCC induced by administration of diethylnitrosamine for 16 weeks. The rats were divided into 3 groups: MTD group received intraperitoneal (i.p.) injections of 40 mg/kg cyclophosphamide on days 1, 3, and 5 of a 21-day cycle; Control and MET groups received i.p. injections of saline and 20 mg/kg cyclophosphamide twice a week, respectively. Anti-tumor and anti-angiogenic effects and anti-metastatic mechanisms including matrix metalloproteinases (MMPs) and tissue inhibitors of MMPs (TIMPs) were evaluated. Twelve weeks of MET therapy resulted in a significant reduction in intrahepatic tumors than control or MTD therapy. The MET group had fewer proliferating cell nuclear ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4751945 Thu, 07 Apr 2011 23:00:00 +0100 4751945 http://www.medworm.com/index.php?rid=4697444&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21467839%26dopt%3DAbstract Authors: Cho CH Studies of epilepsy have mainly focused on the membrane proteins that control neuronal excitability. Recently, attention has been shifting to intracellular proteins and their interactions, signaling cascades and feedback regulation as they relate to epilepsy. The mTOR (mammalian target of rapamycin) signal transduction pathway, especially, has been suggested to play an important role in this regard. These pathways are involved in major physiological processes as well as in numerous pathological conditions. Here, involvement of the mTOR pathway in epilepsy will be reviewed by presenting; an overview of the pathway, a brief description of key signaling molecules, a summary of independent reports and possible implications of abnormalities of those molecules in epilepsy, a ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4697444 Tue, 05 Apr 2011 23:00:00 +0100 4697444 http://www.medworm.com/index.php?rid=4697447&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21464588%26dopt%3DAbstract Authors: Arora H, Qureshi R, Jin S, Park AK, Park WY The activation of nuclear factor-kappa B1 (NFKB1) in cancer cells may confer resistance to ionizing radiation (IR). To enhance the therapeutic efficiency of IR in lung cancer, we screened for microRNAs (miRNAs) that suppress NFKB1 and observed their effects on radiosensitivity in a human lung cancer cell line. From time series data of miRNA expression in g-irradiated H1299 human lung cancer cells, we found that the expression of miR-9 was inversely correlated with that of NFKB1. Overexpression of miR-9 down-regulated the level of NFKB1 in H1299 cells, and the surviving fraction of γ-irradiated cells was decreased. Interestingly, let-7g also suppressed the expression of NFKB1, although there was no canonical target site for let-7g in... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4697447 Mon, 04 Apr 2011 23:00:00 +0100 4697447 http://www.medworm.com/index.php?rid=4697446&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21464589%26dopt%3DAbstract Authors: Lee Y, Kim SJ, Min HJ, Jo JY, Park EH, Koh SS Pancreatic cancer is a notorious disease with a poor prognosis and low survival rates, which is due to limited advances in understanding of the molecular mechanism and inadequate development of effective treatment options over the decades. In previous studies, we demonstrated that a novel soluble protein named PAUF (Pancreatic Adenocarcinoma Up-regulated Factor) acts on tumor and immune cells and plays an important role in metastasis and progression of pancreatic cancer. Here we show that PAUF promotes adhesiveness of pancreatic cancer cells to various extracellular matrix (ECM). Our results further support a positive correlation of activation and expression of FAK, a key player in tumor cell metastasis and survival, with PAUF expr... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4697446 Mon, 04 Apr 2011 23:00:00 +0100 4697446 http://www.medworm.com/index.php?rid=4697445&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21464590%26dopt%3DAbstract In this study, we have established an MHC class II molecule-expressing B16F1 murine melanoma cell line (B16F1-CIITA) by transduction of the CIITA (Class II transactivator) gene. Exosomes from B16-CII cells (CIITA-Exo) contained a high amount of MHC class II as well as a tumor antigen TRP2. When loaded on dendritic cells (DCs), CIITA-Exo induced the increased expression of MHC class II molecules and CD86 than the exosomes from the parental cells (Exo). In vitro assays using co-culture of immunized splenocytes and exosome-loaded DCs demonstrated that CIITA-Exo enhanced the splenocyte proliferation and IL-2 secretion. Consistently, compared to B16-Exo, CIITA-Exo induced the increased mRNA levels of inflammatory cytokines such as TNF-α, chemokine receptor CCR7 and the production of Th1-polari... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4697445 Mon, 04 Apr 2011 23:00:00 +0100 4697445 http://www.medworm.com/index.php?rid=4638041&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21415590%26dopt%3DAbstract Authors: Bang BR, Chun E, Shim EJ, Lee HS, Lee SY, Cho SH, Min KU, Kim YY, Park HW The role of alveolar macrophages (AMs) in the pathogenesis of asthma is still unknown. The aim of the present study was to investigate the effects of AM in the murine model of asthma. AMs were selectively depleted by liposomes containing clodronate just before allergen challenges, and changes in inflammatory cells and cytokine concentrations in bronchoalveolar lavage (BAL) fluid were measured. AMs were then adoptively transferred to AM-depleted sensitized mice and changes were measured. Phenotypic changes in AMs were evaluated after in vitro allergen stimulation. AM-depletion after sensitization significantly increased the number of eosinophils and lymphocytes and the concentrations of IL-4, IL-5 and GM-... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4638041 Fri, 18 Mar 2011 00:00:00 +0100 4638041 http://www.medworm.com/index.php?rid=4638040&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21415591%26dopt%3DAbstract Authors: Lee HS, Kim CK Alveolar type II cells are main target of hyperoxia-induced lung injury. The authors investigated whether lysosomal protease, cathepsin B (CB), is activated in fetal alveolar type II cells in the transitional period from the canalicular to saccular stages during 65%-hyperoxia and whether CB is related to fetal alveolar type II cell (FATIIC) death secondary to hyperoxia. FATIICs were isolated from embryonic day 19 rats and exposed to 65%-oxygen for 24 h and 36 h. The cells exposed to room air were used as controls. Cell cytotoxicity was assessed by lactate dehydrogenase-release and flow cytometry, and apoptosis was analyzed by TUNEL assay and flow cytometry. CB activity was assessed by colorimetric assay, qRT-PCR and western blots. 65%-hyperoxia induced FATIIC de... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4638040 Fri, 18 Mar 2011 00:00:00 +0100 4638040 http://www.medworm.com/index.php?rid=4638039&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21415592%26dopt%3DAbstract Authors: Lee HJ, Baek SM, Ho DH, Suk JE, Cho ED, Lee SJ Parkinson's disease (PD) is characterized by selective and progressive degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNpc) and by abnormal aggregation of a-synuclein. Previous studies have suggested that DA can interact with a-synuclein, thus modulating the aggregation process of this protein; this interaction may account for the selective vulnerability of DA neurons in patients with PD. However, the relationship between DA and a-synuclein, and the role in progressive degeneration of DA neurons remains elusive. We have shown that in the presence of DA, recombinant human a-synuclein produces non-fibrillar, sodium dodesylsulfate (SDS)-resistant oligomers, while b-sheet-rich fibril formation i... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4638039 Fri, 18 Mar 2011 00:00:00 +0100 4638039 http://www.medworm.com/index.php?rid=4578764&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21389766%26dopt%3DAbstract Authors: Seo JB, Choe SS, Jeong HW, Park SW, Shin HJ, Choi SM, Park JY, Choi EW, Kim JB, Seen DS, Jeong JY, Lee TG Lysimachia foenum-graecum has been used as an oriental medicine with anti-inflammatory effect. The anti-obesity effect of L. foenum-graecum extract (LFE) was first discovered in our screening of natural product extract library against adipogenesis. To characterize its anti-obesity effects and to evaluate its potential as an anti-obesity drug, we performed various obesity-related experiments in vitro and in vivo. In adipogenesis assay, LFE blocked the differentiation of 3T3-L1 preadipocyte in a dose-dependent manner with an IC50 of 2.5 mg/mL. In addition, LFE suppressed the expression of lipogenic genes, while increasing the expression of lipolytic genes in vitro at 10 mg/m... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4578764 Thu, 10 Mar 2011 00:00:00 +0100 4578764 http://www.medworm.com/index.php?rid=4578766&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21372631%26dopt%3DAbstract Authors: Li Y, Sun M, Cheng H, Li S, Liu L, Qiao H, Hua S, Lu J To determine the impact of IL-23 knockdown by RNA interference (RNAi) on the development and severity of ovalbumin (OVA)-induced asthmatic inflammation, and the potential mechanisms in mice, the IL-23-specific RNAi-expressing pSRZsi-IL-23p19 plasmid was constructed and inhaled into OVA-sensitized mice before each challenge, as compared with that ofcontrol mice treated with alum or budesonide. Inhalation of the pSRZsi-IL-23p19, significantly reduced the levels of OVA-challenge induced IL-23 in the lung tissues by nearly 75%, determined by reverse transcription polymerase chain reaction (RT-PCR). In addition, knockdown of IL-23 expression dramatically reduced the numbers of eosinophils and neutrophils in BALF and mitigated i... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4578766 Fri, 04 Mar 2011 00:00:00 +0100 4578766 http://www.medworm.com/index.php?rid=4578765&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21372632%26dopt%3DAbstract Authors: Wang MF, Liao YF, Hung YC, Lin CL, Hour TC, Lue KH, Hung HC, Liu GY Ornithine decarboxylase (ODC) is the rate-limiting enzyme in polyamine biosynthesis and a target for chemoprevention. Hydroxydibenzoylmethane (HDB), a derivative of dibenzoylmethane of licorice, is a promising chemopreventive agent. In this paper, we investigated whether HDB would inhibit the ODC pathway to enhance apoptosis in human promyelocytic leukemia HL-60 cells. We found ODC enzyme activity was reduced during HDB treatment. Overexpression of ODC in HL-60 parental cells could reduce HDB-induced apoptosis, which leads to loss of mitochondrial membrane potential (Δym), through lessening intracellular ROS. Furthermore, ODC overexpression protected cytochrome c release and the activation of caspase-3 follow... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4578765 Fri, 04 Mar 2011 00:00:00 +0100 4578765 http://www.medworm.com/index.php?rid=4525325&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21350328%26dopt%3DAbstract Authors: Chung JH, Im EK, Jin T, Lee SM, Kim SH, Choi EY, Shin MJ, Lee KH, Jang Y Gene transfer of basic fibroblast growth factor (bFGF) has been shown to induce significant endothelial migration and angiogenesis in ischemic disease models. Here, we investigate what factors are secreted from skeletal muscle cells (SkMCs) transfected with bFGF gene and whether they participate in endothelial cell migration. We constructed replication-defective adenovirus vectors containing the human bFGF gene (Ad/bFGF) or a control LacZ gene (Ad/LacZ) and obtained conditioned media, bFGF-CM and LacZ-CM, from SkMCs infected by Ad/bFGF or Ad/LacZ, respectively. Cell migration significantly increased in HUVECs incubated with bFGF-CM compared to cells incubated with LacZ-CM. Interestingly, HUVEC migration i... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4525325 Thu, 24 Feb 2011 00:00:00 +0100 4525325 http://www.medworm.com/index.php?rid=4525327&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21339696%26dopt%3DAbstract Authors: Aoyagi Y, Kuroda M, Asada S, Bujo H, Tanaka S, Konno S, Tanio M, Ishii I, Aso M, Saito Y The development of clinically applicable scaffolds is important for the application of cell transplantation in various human diseases. The aims of this study are to evaluate fibrin glue in a novel protein replacement therapy using proliferative adipocytes and to develop a mouse model system to monitor the delivery of the transgene product into the blood and the fate of the transduced cells after transplantation. Proliferative adipocytes from mouse adipose tissue were transduced by a retroviral vector harboring the human lecithin-cholesterol acyltransferase (lcat) gene, and were subcutaneously transplanted into mice combined with fibrin glue. The lcat gene transduction efficiency and the su... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4525327 Tue, 22 Feb 2011 00:00:00 +0100 4525327 http://www.medworm.com/index.php?rid=4525326&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21339697%26dopt%3DAbstract Authors: Kim SK, Kim H, Yang YR, Suh PG, Chang JS Phosphatidylinositolphosphates (PtdInsPs) are ubiquitous membrane phospholipids that play diverse roles in cell growth and differentiation. To clarify the regulation mechanism acting on neurofilament light chain (NF-L) self assembly, we examined the effects of various PtdInsPs on this process. We found that PtdInsPs, including PI(4,5)P2, directly bind to the positively charged Arg54 of murine NF-L, and this binding promotes NF-L self assembly in vitro. Mutant NF-L (R53A/R54A) proteins lacking binding affinity to PtdInsPs did not have the same effect, but the mutant NF-L proteins showed greater self assembly than the wild-type in the absence of any PtdInsP. These results collectively suggest that Arg54 plays a pivotal role in NF-L self a... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4525326 Tue, 22 Feb 2011 00:00:00 +0100 4525326 http://www.medworm.com/index.php?rid=4470698&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21297377%26dopt%3DAbstract Authors: Lee BJ, Moon HG, Shin TS, Jeon SG, Lee EY, Gho YS, Lee CG, Zhu Z, Elias JA, Kim YK Recent clinical evidence indicates that the non-eosinophilic subtype of severe asthma is characterized by fixed airway obstruction, which may be related to emphysema. Transgenic studies have demonstrated that high levels of IFN-gamma in the airways induce emphysema. FGF2, which is the downstream mediator of TGF-beta, is important in wound healing. We investigated the role of FGF2 in IFN-gamma-induced emphysema and the therapeutic effects of recombinant FGF2 in the prevention of emphysema in a severe non-eosinophilic asthma model. To evaluate the role of FGF2 in IFN-gamma-induced emphysema, lung targeted IFN-gamma transgenic mice were cross-bred with FGF2-deficient mice. A severe non-eosinophilic... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4470698 Mon, 07 Feb 2011 00:00:00 +0100 4470698 http://www.medworm.com/index.php?rid=4470697&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21297378%26dopt%3DAbstract Authors: Zhu W, Fu A, Hu J, Wang T, Luo Y, Peng M, Ma Y, Wei Y, Chen L Our previous report has demonstrated that 5-formylhonokiol (FH), a derivative of honokiol (HK), exerts more potent anti-proliferative activities than honokiol in several tumor cell lines. In present study, we first explored the antiangiogenic activities of 5-formylhonokiol on proliferation, migration and tube formation of human umbilical vein endothelial cells (HUVECs) for the first time in vitro. Then we investigated the in vivo antiangiogenic effect of 5-formylhonokiol on zebrafish angiogenesis model. In order to clarify the underlying molecular mechanism of 5-formylhonokiol, we investigated the signaling pathway involved in controlling the angiogenesis process by western blotting assay. Wound-healing results show... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4470697 Mon, 07 Feb 2011 00:00:00 +0100 4470697 http://www.medworm.com/index.php?rid=4470696&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21297379%26dopt%3DAbstract Authors: Moon MH, Jeong JK, Seo JS, Seol JW, Lee YJ, Park SY Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of the TNF superfamily of cytokines, is one of the most promising candidates for cancer therapeutics. However, many osteosarcomas are resistant to TRAIL. Bisphosphonates are very effective in the treatment of bone problems associated with malignancies; the antitumor effects are due to the inhibition of protein prenylation that is essential for cell function and survival. The purpose of this study was to determine the effects of bisphosphonates on TRAIL-resistant MG 63 human osteosarcoma cells. The cells showed no response to TRAIL alone; however, pre-treatment with bisphosphonates significantly increased TRAIL-mediated apoptosis and cellular activ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4470696 Mon, 07 Feb 2011 00:00:00 +0100 4470696 http://www.medworm.com/index.php?rid=4470701&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21270506%26dopt%3DAbstract Authors: Dong C CD4+ T lymphocytes play a major role in regulation of adaptive immunity. Upon activation, naïve T cells differentiate into different functional subsets. In addition to the classical Th1 and Th2 cells, several novel effector T cell subsets have been recently identified, including Th17 cells. There has been rapid progress in characterizing the development and function of Th17 cells. Here I summarize and discuss on the genetic controls of their differentiation and emerging evidence on their plasticity. This information may benefit understanding and treating immune diseases. PMID: 21270506 [PubMed - in process] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4470701 Mon, 31 Jan 2011 00:00:00 +0100 4470701 http://www.medworm.com/index.php?rid=4470700&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21270507%26dopt%3DAbstract Authors: Jun HO, Kim DH, Lee SW, Lee HS, Seo JH, Kim JH, Kim JH, Yu YS, Min BH, Kim KW Clusterin is a secretory glycoprotein, which is highly up-regulated in a variety of normal and injury tissues undergoing apoptosis including infarct region of the myocardium. Here, we report that clusterin protects H9c2 cardiomyocytes from H2O2-induced apoptosis by triggering the activation of Akt and GSK-3β. Treatment with H2O2 induces apoptosis of H9c2 cells by promoting caspase cleavage and cytochrome c release from mitochondria. However, co-treatment with clusterin reverses the induction of apoptotic signaling by H2O2, thereby recovers cell viability. The protective effect of clusterin on H2O2-induced apoptosis is impaired by PI3K inhibitor LY294002, which effectively suppresses clusterin-induce... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4470700 Mon, 31 Jan 2011 00:00:00 +0100 4470700 http://www.medworm.com/index.php?rid=4470699&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21278483%26dopt%3DAbstract We examined the possibility that transient forebrain ischemia (TFI) causes the blood-brain barrier (BBB) to become permeable to blood cells, possibly via dysfunction and degeneration of endothelial cells in rats. Extravasation of Evans blue and immunoglobulin G (IgG) was observed in the hippocampal CA1-2 areas within 8 h after TFI, and peaked at 48 h. This extravasation was accompanied by loss of tight junction (TJ) proteins, occludin, and zonula occludens (ZO)-1, and degeneration of endothelial cells in the CA1-2 areas. Iron overload and mitochondrial free radical production were evident in the microvessel endothelium of the hippocampus before endothelial cell damage occurred. Administration of deferoxamine (DFO), an iron chelator, or Neu2000, an antioxidant, blocked free radical producti... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4470699 Mon, 31 Jan 2011 00:00:00 +0100 4470699 http://www.medworm.com/index.php?rid=4400243&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21252614%26dopt%3DAbstract In this study, the role of BLT2, a receptor for leukotriene B4 (LTB4) and 12(S)-hydroxyeicosatetraenoic acid (HETE), in the survival of bladder cancer 253J-BV cells was investigated. We found that the expression of BLT2 is highly elevated in bladder cancer cells. Also, we observed that blockade of BLT2 with an antagonist or BLT2 siRNA resulted in cell cycle arrest and apoptotic cell death, suggesting a role of BLT2 in the survival of human bladder cancer 253J-BV cells. Further experiments aimed at elucidating the mechanism by which BLT2 mediates survival revealed that enhanced level of reactive oxygen species (ROS) are generated via a BLT2-dependent up-regulation of NADPH oxidase members NOX1 and NOX4. Additionally, we observed that inhibition of ROS generation by either NOX1/4 siRNAs or t... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4400243 Thu, 20 Jan 2011 00:00:00 +0100 4400243 http://www.medworm.com/index.php?rid=4335778&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21209554%26dopt%3DAbstract Authors: Kwak I, Shin YH, Kim M, Cha HY, Nam HJ, Lee BS, Chaudhary SC, Pai KS, Lee JH Aberrant activation of hepatocyte growth factor/scatter factor (HGF/SF) and its receptor, Met, is involved in the development and progression of many human cancers. In the cell-based screening assay, (-) Epigallocatechin-3-gallate (EGCG) inhibited HGF/SF-Met signaling as indicated by its inhibitory activity on HGF/SF-induced cell scattering and uPA activation (IC50 = 15.8 mg/ml). Further analysis revealed that EGCG at low doses specifically inhibited HGF/SF-induced tyrosine phosphorylation of Met but not epidermal growth factor (EGF)-induced phosphorylation of EGF receptor (EGFR). On the other hand, high-dose EGCG decreased both Met and EGFR proteins. We also found that EGCG did not act on the intrace... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4335778 Wed, 05 Jan 2011 00:00:00 +0100 4335778 http://www.medworm.com/index.php?rid=4335789&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21200133%26dopt%3DAbstract We describe an alternative ROS production pathway that is triggered by CD40 ligation, involves 5-lipoxygenase (5-LO), and results in activation of p38 MAPK. Our studies in Raji human B lymphomas revealed that CD40-induced ROS production by 5-LO also requires the activities of PI3K and Rac1. In contrast to the NADPH oxidase pathway, however, TRAF molecules are not required for the CD40-induced ROS production by 5-LO. The association of CD40 with 5-LO is dependent on CD40 ligation in Raji B cells, and co-immunoprecipitation experiments using epitope-tagged proteins transiently expressed in human embryonic kidney 293T cells revealed the role of the regulatory subunit of PI3K, p85, in this association. Collectively, these data suggest a separate pathway for the CD40-induced ROS production in B... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4335789 Tue, 04 Jan 2011 00:00:00 +0100 4335789 http://www.medworm.com/index.php?rid=4335779&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21200134%26dopt%3DAbstract Authors: Park K, Chung YJ, So H, Kim K, Park J, Oh M, Jo M, Choi K, Lee EJ, Choi YL, Song SY, Bae DS, Kim BG, Lee JH Ovarian cancer is a leading cause of death in women. Early detection of ovarian cancer is essential to decrease mortality. However, the early diagnosis of ovarian cancer is difficult due to a lack of clinical symptoms and suitable molecular diagnostic markers. Thus, identification of meaningful tumor biomarkers with potential clinical application is clearly needed. To search for a biomarker for the early detection of ovarian cancer, we identified human anterior gradient 2 (AGR2) from our systematic analysis of paired normal and ovarian tumor tissue cDNA microarray. We noted a marked overexpression of AGR2 mRNA and protein in early stage mucinous ovarian tumors compared t... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4335779 Tue, 04 Jan 2011 00:00:00 +0100 4335779 http://www.medworm.com/index.php?rid=4335792&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21196815%26dopt%3DAbstract Authors: Cho IR, Koh SS, Min HJ, Kim SJ, Lee Y, Park EH, Ratakorn S, Jhun BH, Oh S, Johnston RN, Chung YH It is not yet understood how the enhanced expression of pancreatic adenocarcinoma up-regulated factor (PAUF; a novel oncogene identified in our recent studies), contributes to the oncogenesis of pancreatic cells. We herein report that PAUF up-regulates the expression and transcriptional activity of b-catenin while the suppression of PAUF by shRNA down-regulates b-catenin. The induction of b-catenin by PAUF is mediated by the activities of Akt and GSK-3b, but inhibition of downstream ERK does not reduce b-catenin expression. To test whether PAUF emulates either the Wnt3a-mediated or the protein kinaseA-mediated signaling pathway for the stabilization of b-catenin, we examined the ph... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4335792 Fri, 31 Dec 2010 00:00:00 +0100 4335792 http://www.medworm.com/index.php?rid=4335818&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21187701%26dopt%3DAbstract Authors: Kim BJ, Kim SY, Cho YS, Kim BJ, Han BG, Park EK, Lee SH, Kim HY, Kim GS, Lee JY, Koh JM There is increasing evidence of a biochemical link between lipid oxidation and bone metabolism. Paraoxonase 1 (PON1) prevents the oxidation of low-density lipoprotein (LDL) and metabolizes biologically active phospholipids in oxidized LDLs. Here, we performed association analyses of genetic variation in PON1 to ascertain its contribution to osteoporotic fractures (OFs) and bone mineral density (BMD). We directly sequenced the PON1 gene in 24 Korean individuals and identified 26 sequence variants. A large population of Korean postmenopausal women (n = 1,329) was then genotyped for eight selected PON1 polymorphisms. BMD at the lumbar spine and femoral neck was measured using dual-energy X-ray... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4335818 Tue, 28 Dec 2010 00:00:00 +0100 4335818 http://www.medworm.com/index.php?rid=4335793&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21187702%26dopt%3DAbstract In this study, we tested the development of genetic therapeutic options to treat atopic dermatitis using bacteria expressing miRNA. We constructed a recombinant strain of Salmonella typhimurium expressing CCL22 miRNA (ST-miRCCL22) for the in vivo knockdown of CCL22. The CCL22 gene was downregulated with CCL22 miRNA in activated lymphocytes. In mice with a cutaneous disease similar to atopic dermatitis, interleukin-4 (IL-4) was inhibited and interferon-γ (IFN-γ) was induced after treatments with ST-miRCCL22. Furthermore, CCL22 levels were suppressed in the atopic mice treated with ST-miRCCL22. These results suggest that ST-miRCCL22 may be an effective genetic agent for treating atopic dermatitis. PMID: 21187702 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4335793 Tue, 28 Dec 2010 00:00:00 +0100 4335793 http://www.medworm.com/index.php?rid=4335821&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21178390%26dopt%3DAbstract Authors: Lee KY, Joo EJ, Ji YI, Kim DH, Park J, Chung IW, Lee SI, Joo YH, Ahn YM, Song JY, Kim YS The dysregulation of the dopaminergic system has been implicated in the pathophysiology of major psychosis, including schizophrenia, with dopamine receptor genes (DRDs) presently targeted as the most promising candidate genes. We investigated DRD1-5 for association with schizophrenia using a multi-stage approach in a Korean sample. One hundred forty-two SNPs in DRD1-5 were selected from the dbSNP, and the associations of each SNP were then screened and typed by MALDI-TOF mass spectrometry using pooled DNA samples from 150 patients with major psychosis and 150 controls. Each of the suggested SNPs was then genotyped and tested for an association within the individual samples comprising each ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4335821 Tue, 21 Dec 2010 00:00:00 +0100 4335821 http://www.medworm.com/index.php?rid=4276211&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21169725%26dopt%3DAbstract This study, with OVA-sensitized and OVA-challenged mice, revealed the following typical histopathologic features of allergic diseases: increased inflammatory cells of the airway, airway hyperresponsiveness, and increased levels of TNF-α, intercellular adhesion molecule (ICAM)- 1, and vascular cellular adhesion molecule (VCAM)-1. However, the histopathologic features and levels of ICAM-1 and VCAM-1 proteins in W/Wv mice after OVA challenges were significantly inhibited. Moreover, mast cell-reconstituted W/Wv mice showed restoration of histopathologic features and recovery of ICAM-1 and VCAM-1 protein levels that were similar to those found in +/+ mice. Intratracheal administration of TNF-α resulted in increased ICAM-1 and VCAM-1 protein levels in W/Wv mice. These results suggest that mast... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4276211 Mon, 20 Dec 2010 00:00:00 +0100 4276211 http://www.medworm.com/index.php?rid=4276212&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21150246%26dopt%3DAbstract Authors: Kang YJ, Kim IY, Kim EH, Yoon MJ, Kim SU, Kwon TK, Choi KS Tumor necrosis factor-related apoptosis-induced ligand (TRAIL) induces apoptosis selectively in cancer cells while sparing normal cells. However, many cancer cells are resistant to TRAIL-induced cell death. Here, we report that paxilline, an indole alkaloid from Penicillium paxilli, can sensitize various glioma cells to TRAIL-mediated apoptosis. While treatment with TRAIL alone caused partial processing of caspase-3 to its p20 intermediate in TRAIL-resistant glioma cell lines, co-treatment with TRAIL and subtoxic doses of paxilline caused complete processing of caspase-3 into its active subunits. Paxilline treatment markedly upregulated DR5, a receptor of TRAIL, through a CHOP/GADD153-mediated process. In addition, pax... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4276212 Fri, 10 Dec 2010 00:00:00 +0100 4276212 http://www.medworm.com/index.php?rid=4276213&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21150245%26dopt%3DAbstract Authors: Im SW, Kim HJ, Lee MK, Yi JH, Jargal G, Sung J, Cho SI, Kim JI Anthropometric traits for eyes and nose are complex quantitative traits influenced by genetic and environmental factors. To date, there have been few reports on the contribution of genetic influence to these traits in Asian populations. The aim of this study was to determine the genetic effect and quantitative trait locus (QTL) of seven traits eyes- and nose-related anthropometric measurements in an isolated Mongolian population. Frontal and lateral photographs were obtained from 1,014 individuals (434 males and 580 females) of Mongolian origin. A total of 349 short tandem repeat markers on 22 autosomes were genotyped for each individual. Heritability estimates of the seven ocular and nasal traits, adjusted for sig... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4276213 Thu, 09 Dec 2010 00:00:00 +0100 4276213 http://www.medworm.com/index.php?rid=4217995&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21099244%26dopt%3DAbstract Authors: Kim SY, Kang HT, Choi HR, Park SC Biliverdin reductase A (BLVRA), an enzyme that converts biliverdin to bilirubin, has recently emerged as a key regulator of the cellular redox cycle. However, the role of BLVRA in the aging process remains unclear. To study the role of BLVRA in the aging process, we compared the stress responses of young and senescent human diploid fibroblasts (HDFs) to the reactive oxygen species (ROS) inducer, hydrogen peroxide (H2O2). H2O2 markedly induced BLVRA activity in young HDFs, but not in senescent HDFs. Additionally, depletion of BLVRA reduced the H2O2-dependent induction of heme oxygenase-1 (HO-1) in young HDFs, but not in senescent cells, suggesting an aging-dependent differential modulation of responses to oxidative stress. The role of BLVRA in ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4217995 Wed, 24 Nov 2010 00:00:00 +0100 4217995 http://www.medworm.com/index.php?rid=4200961&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21088470%26dopt%3DAbstract Authors: Lee HG, Won SM, Gwag BJ, Lee YB The possibility that P2X7 receptor (P2X7R) expression in microglia would mediate neuronal damage via reactive oxygen species (ROS) production was examined in the APPswe/PS1dE9 mouse model of Alzheimer's disease (AD). P2X7R was predominantly expressed in CD11b-immunopositive microglia from 3 months of age before Aβ plaque formation. In addition, gp91phox, a catalytic subunit of NADPH oxidase, and ethidium fluorescence were detected in P2X7R-positive microglial cells of animals at 6 months of age, indicating that P2X7R-positive microglia could produce ROS. Postsynaptic density 95-positive dendrites showed significant damage in regions positive for P2X7R in the cerebral cortex of 6 month-old mice. Taken together, up-regulation of P2X7R activation ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4200961 Fri, 19 Nov 2010 00:00:00 +0100 4200961 http://www.medworm.com/index.php?rid=4166074&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21072003%26dopt%3DAbstract In this study, we have shown the gene expression of human GD3 synthase (hST8Sia I) suppressed by triptolide (TPL) in human melanoma SK-MEL-2 cells. To elucidate the mechanism underlying the downregulation of hST8Sia I gene expression in TPL-treated SK-MEL-2 cells, we characterized the TPL-inducible promoter region within the hST8Sia I gene using luciferase constructs carrying 5'-deletions of the hST8Sia I promoter. Functional analysis of the 5'-flanking region of the hST8Sia I gene demonstrated that the -1146 to -646 region, which contains putative binding sites for transcription factors c-Ets-1, CREB, AP-1 and NF-kB, functions as the TPL-inducible promoter of hST8Sia I in SK-MEL-2 cells. Site-directed mutagenesis and ChIP analysis indicated that the NF-kB binding site at -731 to -722 is c... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4166074 Thu, 11 Nov 2010 00:00:00 +0100 4166074 http://www.medworm.com/index.php?rid=4166073&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21072004%26dopt%3DAbstract In this study, we have used for the first time Multiplex Ligation-dependent Probe Amplification (MLPA) and Comparative Multiplex Dosage Analysis (CMDA) to search for large deletions affecting the UBE3A gene. Using this approach, we identified a novel causative deletion involving exon 8 in an affected sibling. Based on our results, we propose the use of MLPA as a fast, accurate and inexpensive test to detect large deletions in the UBE3A gene in a small but significant percentage of AS patients. PMID: 21072004 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4166073 Thu, 11 Nov 2010 00:00:00 +0100 4166073 http://www.medworm.com/index.php?rid=4123183&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20980790%26dopt%3DAbstract In this study, we showed that HSP90 regulated angiotensin II-induced hypertrophy via maintenance of the IkB kinase (IKK) complex stability in cardiac cells. An HSP90 inhibitor, geldanamycin (GA), significantly suppressed angiotensin II-induced [3H]leucine incorporation and atrial natriuretic factor expression in cardiac cells. GA also inhibited the NF-κB activation induced by angiotensin II. Importantly, treatment with GA caused a degradation of IKKα/β; on the other hand, a proteasome-specific inhibitor restored the level of IKKα/β. We also found that GA prevented HSP90-IKKs complex induced by angiotensin II in cardiac cells. The small interfering RNA (siRNA)-mediated knockdown of HSP90 expression significantly inhibited angiotensin II-induced cell hypertrophy and NF-κB activation. T... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4123183 Sun, 31 Oct 2010 00:00:00 +0100 4123183 http://www.medworm.com/index.php?rid=4107875&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20966635%26dopt%3DAbstract Authors: Kim C, Ryu HC, Kim JH Skin exposure to low-dose ultraviolet B (UVB) light up-regulates the expression of matrix metalloproteinase-1 (MMP-1), thus contributing to premature skin aging (photo-aging). Although cyclooxygenase-2 (COX-2) and its product, prostaglandin E2 (PGE2), have been associated with UVB-induced signaling to MMP expression, very little are known about the roles of lipoxygenases and their products (especially leukotriene B4 (LTB4) and 12(S)-hydroxyeicosatetraenoic acid (12(S)-HETE)) in MMP-1 expression in skin keratinocytes. In the present study, we demonstrate that BLT2, a cell surface receptor for LTB4 and 12(S)-HETE, plays a critical role in UVB-mediated MMP-1 upregulation in human HaCaT keratinocytes. Moreover, our results demonstrated that BLT2-mediated MMP-... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4107875 Thu, 21 Oct 2010 23:00:00 +0100 4107875 http://www.medworm.com/index.php?rid=4088273&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20962566%26dopt%3DAbstract Authors: Jeong HK, Jou I, Joe EH It has been suggested that brain inflammation is important in aggravation of brain damage and/or that inflammation causes neurodegenerative diseases including Parkinson's disease (PD). Recently, systemic inflammation has also emerged as a risk factor for PD. In the present study, we evaluated how systemic inflammation induced by intravenous (iv) lipopolysaccharides (LPS) injection affected brain inflammation and neuronal damage in the rat. Interestingly, almost all brain inflammatory responses, including morphological activation of microglia, neutrophil infiltration, and mRNA/protein expression of inflammatory mediators, appeared within 4?8 h, and subsided within 1?3 days, in the substantia nigra (SN), where dopaminergic neurons are located. More import... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4088273 Mon, 18 Oct 2010 23:00:00 +0100 4088273 http://www.medworm.com/index.php?rid=4088274&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20959717%26dopt%3DAbstract Authors: Choi JH, Choi AY, Yoon H, Choe W, Yoon KS, Ha J, Yeo EJ, Kang I Baicalein is one of the major flavonoids in Scutellaria baicalensis Georgi and possesses various effects, including cytoprotection and anti-inflammation. Because endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, and cerebral ischemia, we investigated the effects of baicalein on apoptotic death of HT22 mouse hippocampal neuronal cells induced by thapsigargin (TG) and brefeldin A (BFA), two representative ER stress inducers. Apoptosis, reactive oxygen species (ROS) production, and mitochondrial membrane potential (MMP) were measured by flow cytometry. Expression level and phosphorylation status of ER stress-associated proteins and a... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4088274 Sun, 17 Oct 2010 23:00:00 +0100 4088274 http://www.medworm.com/index.php?rid=4076973&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20948279%26dopt%3DAbstract Authors: Kim WK, Sul OJ, Kwak JS, Hur HY, Latour AM, Koller BH, Kwon BS, Jeong CS Tumor Necrosis Factor Receptor- Related 2 (TR2, HVEM or TNFRSF-14) plays an important role in immune responses, however, the mechanisms regulating its expression are unclear. To understand the control of TR2 gene expression, we studied the upstream region of the gene. Gel supershift assays revealed inducible binding of nuclear factor of activated T cells(NFAT) to a putative NFAT site within the TR2 promoter. Furthermore, cotransfection of a dominant negative NFAT construct, or siRNA for NFAT, resulted in increased expression of a TR2 reporter gene. Our findings demonstrate that NFAT negatively regulates TR2 expression in activated T cells. PMID: 20948279 [PubMed - as supplied by publisher] (Source: ex... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4076973 Wed, 13 Oct 2010 23:00:00 +0100 4076973 http://www.medworm.com/index.php?rid=4061883&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20938215%26dopt%3DAbstract In conclusion, the modulation of HO-1 expression substantially improved the anticancer effect of PTL. The combination of PTL and Ro could prove to be a valuable chemotherapeutic strategy for CC. PMID: 20938215 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4061883 Sun, 10 Oct 2010 23:00:00 +0100 4061883 http://www.medworm.com/index.php?rid=4061885&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20926918%26dopt%3DAbstract In this study, we observed the role of 2-deoxy-D-glucose (2DG) on inflammation of chondrocytes. 2DG is well known as an inducer of ER stress, via inhibition of glycolysis and glycosylation. Treatment of 2DG in chondrocytes considerably induced ER stress in a dose- and time-dependent manner, which was demonstrated by a reduction of glucose regulated protein of 94 kDa (grp94), an ER stress-inducible protein, as determined by a Western blot analysis. In addition, induction of ER stress by 2DG led to the expression of COX-2 protein with an apparent molecular mass of 66- 70kDa as compared with the normally expressed 72-74 kDa protein. The suppression of ER stress with salubrinal (Salub), a selective inhibitor of eif2-alpha dephosphorylation, successfully prevented grp94 induction and efficientl... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4061885 Tue, 05 Oct 2010 23:00:00 +0100 4061885 http://www.medworm.com/index.php?rid=4061884&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20926919%26dopt%3DAbstract In this study, we investigated the molecular mechanism by using broiler pulmonary arterial endothelial cells (PAECs). Our results showed that genistein stimulated a rapid phosphorylation of eNOS at Ser1179 which was associated with activation of eNOS/NO axis. Further study indicated that the activation of eNOS was not mediated through estrogen receptors or tyrosine kinase inhibition, but via a phosphatidyl inositol 3 kinase (PI3K)/Akt-dependent signaling pathway, as the eNOS activity and related NO release were largely abolished by pharmacological inhibitors of PI3K or Akt. Thus, our findings revealed a critical function of Akt in mediating genistein-stimulated eNOS activity in PAECs, partially accounting for the beneficial effects of genistein on the development of cardiovascular diseases... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4061884 Tue, 05 Oct 2010 23:00:00 +0100 4061884 http://www.medworm.com/index.php?rid=4042506&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20890087%26dopt%3DAbstract Authors: Yang S, He S, Zhou X, Liu M, Zhu H, Wang Y, Zhang W, Yan S, Quan L, Bai J, Xu N The abnormality of serine/threonine kinase Aurora-A is seen in many types of cancers. Although in physiological context it has been shown to play a vital role in cellular mitosis, how this oncogene contributes to tumorigenesis remains unclear. Here we demonstrate that Aurora-A overexpression enhances both the expression level and transcriptional activity of c-Myc. The inhibition of c-Myc expression by RNA interference significantly impaired the oncogenic potential of Aurora-A, resulting in attenuated cellular proliferation and transformation rates as well as fewer centrosomal aberrancies. Furthermore, downregulation of c-Myc effectively overcame Aurora-A-induced resistance to cisplatin in esophagea... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4042506 Thu, 30 Sep 2010 23:00:00 +0100 4042506 http://www.medworm.com/index.php?rid=4042505&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20890088%26dopt%3DAbstract In this study, the expression of four putative reference genes (hsa-miR-16, hsa-miR-130b, RNU6-2, SNORD7) was examined with regard to their use as normalizer. After SNORD7 was already shown an inappropriate reference gene in preliminary experiments using total RNA pools, we studied the expression of the putative reference genes in tissue and normal adjacent tissue sample pairs from 76 men with untreated prostate carcinoma collected after radical prostatectomy. Hsa-miR-130b and RNU6-2 showed no significantly different expression between the matched malignant and non-malignant tissue samples, whereas hsa-miR-16 was significantly underexpressed in malignant tissue. Softwares geNorm and Normfinder predicted hsa-miR-130b and the geometric mean of hsa-miR-130b and RNU6-2 as the most stable refer... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4042505 Thu, 30 Sep 2010 23:00:00 +0100 4042505 http://www.medworm.com/index.php?rid=4026367&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20881452%26dopt%3DAbstract Authors: Zhu H, Wang J, Jiang H, Ma Y, Pan S, Reddy S, Sun X Nonspecific inflammatory response is the major cause for failure of islet grafts at the early phase of intraportal islet transplantation (IPIT). Bilirubin, a natural product of heme catabolism, has displayed anti-oxidative and anti-inflammatory activities. The present study has demonstrated that bilirubin protected islet grafts by inhibiting nonspecific inflammatory response in a syngeneic rat model of IPIT. The inflammation-induced cell injury was mimicked by exposing cultured rat insulinoma INS-1 cells to cytokines (IL-1β, TNF-α and IFN-γ) in in vitro assays. At appropriate lower concentrations, bilirubin significantly attenuated the reduced cell viability and enhanced cell apoptosis induced by cytokines, and prote... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4026367 Wed, 29 Sep 2010 23:00:00 +0100 4026367 http://www.medworm.com/index.php?rid=4003596&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20871212%26dopt%3DAbstract Authors: Min G The nuclear receptors, steroid and xenobiotic receptor (SXR) and constitutive androstane receptor (CAR) play important functions in mediating lipid and drug metabolism in the liver. The present study demonstrates modulatory actions of estrogen in transactivations of SXR-mediated liver X receptor response element (LXRE) and CAR-mediated phenobarbital response element (PBRU). When human estrogen receptor (hERα) and SXR were exogenously expressed, treatment with either rifampicin or corticosterone promoted significantly the SXR-mediated transactivation of LXRE reporter gene in HepG2. However, combined treatment with estrogen plus either rifampicin or corticosterone resulted in less than 50% of the mean values of the transactivation by rifampicin or corticosterone alone. ... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4003596 Sun, 26 Sep 2010 23:00:00 +0100 4003596 http://www.medworm.com/index.php?rid=4003814&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20844341%26dopt%3DAbstract This study examined in vitro ubiquitination of different regions of SHP fragments and sumoylation of SHP proteins. Whereas SHP fragments 1-92 and 160-260 decreased in ubiquitinated forms, the 92-160 region showed stronger and even greater forms than SHP wild type. However, SHP did not demonstrate sumoylation in wild type or SHP mutants. Whereas the single point mutation K123R significantly enhanced the repressive activity of SHP on hCYP7A1 transactivation in HepG2 cells, the double point mutation K122/123R did not. Consistent with this finding, the double mutation K122/123R did not affect the transactivation of GAL4-TATA-luciferase reporter in Hepa1c1c7 cells. These results suggest that the conformational protein structure may influence on the ubiquitinations of SHP, and the Lys residues a... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=4003814 Wed, 15 Sep 2010 23:00:00 +0100 4003814 http://www.medworm.com/index.php?rid=3973331&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20841959%26dopt%3DAbstract Authors: Shin TS, Lee BJ, Tae YM, Kim YS, Jeon SG, Gho YS, Choi DC, Kim YK Asthma is characterized by airway inflammation induced by immune dysfunction to inhaled antigens. Although respiratory viral infections are the most common cause of asthma exacerbation, immunologic mechanisms underlying virus-associated asthma exacerbation are controversial. Clinical evidence indicates that nitric oxide (NO) levels in exhaled air are increased in exacerbated asthma patients compared to stable patients. Here, we evaluated the immunologic mechanisms and the role of NO synthases (NOSs) in the development of virus-associated asthma exacerbation. A murine model of virus-associated asthma exacerbation was established using intranasal challenge with ovalbumin (OVA) plus dsRNA for 4 weeks in mice sensit... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3973331 Tue, 14 Sep 2010 23:00:00 +0100 3973331 http://www.medworm.com/index.php?rid=3955097&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20820112%26dopt%3DAbstract Authors: Kwon B Graft-versus-host disease (GVHD) is mediated by mature donor T cells contained in the hematopoietic stem cell graft. During the development of GVHD, signaling through a variety of costimulatory receptors plays an important role in allogeneic T cell responses. Even though delivery of costimulatory signals is a prerequisite for full activation of donor T cells in the phase of their interactions with host APCs, their involvement with GVHD might occur over multiple stages. Like many other aspects of GVHD, promise of therapeutic interventions with costimulatory pathways has been gleaned from preclinical models. In this review, I summarize some of the advances in roles of costimulatory molecules in GVHD pathophysiology and discuss preclinical approaches that warrant further e... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3955097 Mon, 06 Sep 2010 23:00:00 +0100 3955097 http://www.medworm.com/index.php?rid=3934015&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20739833%26dopt%3DAbstract Authors: Lim EJ, Park DW, Lee JG, Lee CH, Bae YS, Hwang YC, Jeong JW, Chin BR, Baek SH Synthetic oligodeoxynucleotides (ODN) with a CpG-motif are recognized by toll-like receptor 9 (TLR9) and pleiotropic immune responses are elicited. Stimulation of macrophages with TLR9 agonist prevented apoptosis induced by serum deprivation through increased expression of FLICE-like inhibitory protein (FLIP). CpG ODN-mediated anti-apoptosis depended on the TLR9-Akt-FoxO3a signaling pathway. Inhibition of TLR9 by small interfering RNA or an inhibitor suppressed CpG ODN-mediated anti-apoptosis. Analysis of signaling pathways revealed that the anti-apoptotic effect of CpG ODN required phosphorylation of FoxO3a and translocation from the nucleus to the cytosol of FoxO3a. Overexpression of FoxO3a increas... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3934015 Wed, 25 Aug 2010 23:00:00 +0100 3934015 http://www.medworm.com/index.php?rid=3900181&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20733350%26dopt%3DAbstract Authors: Paek AR, Kim SH, Kim SS, Kim KT, You HJ Expression of zinc-finger protein 143 (ZNF143), a human homolog of the Xenopus transcriptional activator protein Staf, is induced by various DNA-damaging agents including etoposide, doxorubicin, and gamma-irradiation. ZNF143 binds to cisplatin-modified DNA, and its levels are increased in cancer cells that are resistant to anticancer drugs, including cisplatin, suggesting that it plays a role in carcinogenesis and cancer cell survival. However, the mechanism of ZNF143 induction in cancer cells remains unclear. Both insulin-like growth factor-1 (IGF-1) and its receptor (IGF-1R) have been reported to be overexpressed in cancer cells and to be related to anticancer drug resistance, but the identity of the relevant signaling mediators is sti... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3900181 Mon, 23 Aug 2010 23:00:00 +0100 3900181 http://www.medworm.com/index.php?rid=3900182&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20733349%26dopt%3DAbstract This study suggests that bFGF gene transfection is effective in treating experimental OA. Multiple gene transfection has better biologic effects on OA. PMID: 20733349 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3900182 Sun, 22 Aug 2010 23:00:00 +0100 3900182 http://www.medworm.com/index.php?rid=3900183&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20720456%26dopt%3DAbstract Authors: Lee SY, Kim B, Yoon S, Kim YJ, Liu T, Woo JH, Chwae YJ, Joe EH, Jou I In brain tissue, astrocytes play defensive roles in central nervous system integrity by mediating immune responses against pathological conditions. Type I phosphatidylinositol 4-phosphate 5-kinase a (PIP5Ka) that is responsible for production of phosphatidylinositol 4,5-bisphosphate (PI[4,5]P2) regulates many important cell functions at the cell surface. Here, we have examined whether PIP5Ka is associated with astrocyte inflammatory responses. Gangliosides are releasable from damaged cell membranes of neurons and capable of inducing inflammatory responses. We found that treatment of primary cultured astrocytes with gangliosides significantly enhanced PIP5Ka mRNA and protein expression levels. PI(4,5)P2 imagi... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3900183 Wed, 18 Aug 2010 23:00:00 +0100 3900183 http://www.medworm.com/index.php?rid=3882282&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20716902%26dopt%3DAbstract This study conducted proteomic analyses to find proteins that were significantly altered in response to allo-HSCT. Sera from five representative patients who underwent allo-HSCT were analyzed by 2-DE and LC-MS/MS, and were measured on a weekly basis before and after allo-HSCT in additional 78 patients. Fourteen protein spots showing changes in expression were further examined, and most proteins were identified as acute phase proteins (APPs). Studies of 78 additional patients confirmed that CRP and haptoglobin undergo expression changes during allo-HSCT and thus may have the potential to serve as representative markers of clinical events after allo-HSCT. Maximal CRP level affected the development of major transplant-related complications (MTCs) and other problems such as fever of unknown or... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3882282 Tue, 17 Aug 2010 23:00:00 +0100 3882282 http://www.medworm.com/index.php?rid=3855054&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20689364%26dopt%3DAbstract Authors: Jung SH, Park D, Park JH, Kim YM, Ha KS Atomic force microscopy (AFM) is an emerging technique for a variety of uses involving the analysis of cells. AFM is widely applied to obtain information about both cellular structural and subcellular events. In particular, a variety of investigations into membrane proteins and microfilaments were performed with AFM. Here, we introduce applications of AFM to molecular imaging of membrane proteins, and various approaches for observation and identification of intracellular microfilaments at the molecular level. These approaches can contribute to many applications of AFM in cell imaging. PMID: 20689364 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3855054 Thu, 05 Aug 2010 23:00:00 +0100 3855054 http://www.medworm.com/index.php?rid=3824112&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20676023%26dopt%3DAbstract In this study, we investigate the role of TG2 in apoptosis induced by Ca2+-overload. Overexpression of TG2 inhibited the A23187-induced apoptosis through suppression of caspase-3 and -9 activities, cytochrome c release into cytosol, and mitochondria membrane depolarization. Conversely, down-regulation of TG2 caused the increases of cell death, caspase-3 activity and cytochrome c in cytosol in response to Ca2+-overload. Western blot analysis of Bcl-2 family proteins showed that TG2 reduced the expression level of Bax protein. Moreover, overexpression of Bax abrogated the anti-apoptotic effect of TG2, indicating that TG2-mediated suppression of Bax is responsible for inhibiting cell death under Ca2+-overloaded conditions. Our findings revealed a novel anti-apoptotic pathway involving TG2, an... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3824112 Sun, 01 Aug 2010 23:00:00 +0100 3824112 http://www.medworm.com/index.php?rid=3824113&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20661005%26dopt%3DAbstract Authors: Song MY, Jeong GS, Kwon KB, Ka SO, Jang HY, Park JW, Kim YC, Park BH NF-kappaB activation has been implicated as a key signaling mechanism for pancreatic beta-cell damage. Sulfuretin is one of the main flavonoids produced by Rhus verniciflua, which is reported to inhibit the inflammatory response by suppressing the NF-kappaB pathway. Therefore, we isolated sulfuretin from Rhus verniciflua and evaluated if sulfuretin could inhibit cytokine- or streptozotocin-induced beta-cell damage. Rat insulinoma RINm5F cells and isolated rat islets were treated with IL-1beta and IFN-gamma to induce cytotoxicity. Incubation of cells and islets with sulfuretin resulted in a significant reduction of cytokine-induced NF-kappaB activation and its downstream events, iNOS expression, and nitric oxi... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3824113 Mon, 26 Jul 2010 23:00:00 +0100 3824113 http://www.medworm.com/index.php?rid=3777282&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20644344%26dopt%3DAbstract Authors: Woo JS, Cho CH, Kim DH, Lee EH During membrane depolarization associated with skeletal excitation-contraction (EC) coupling, dihydropyridine receptor (DHPR, a L-type Ca2+ channel in the transverse (t)-tubule membrane) undergoes conformational changes that are transmitted to ryanodine receptor 1 (RyR1, an internal Ca2+-release channel in the sarcoplasmic reticulum (SR) membrane) causing Ca2+ release from the SR. Canonical-type transient receptor potential cation channel 3 (TRPC3), an extracellular Ca2+-entry channel in the t-tubule and plasma membrane, is required for full-gain of skeletal EC coupling. To examine additional role(s) for TRPC3 in skeletal muscle other than mediation of EC coupling in the present study, we created a stable myoblast line with reduced TRPC3 expressi... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3777282 Sun, 18 Jul 2010 23:00:00 +0100 3777282 http://www.medworm.com/index.php?rid=3777278&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20644345%26dopt%3DAbstract Authors: Nguyen TL, Kim CK, Cho JH, Lee KH, Ahn JY Neurotrophins protect neurons against excitotoxicity; however the signaling mechanisms for this protection remain to be fully elucidated. Here we report that activation of the phosphatidyl inositol 3 kinase (PI3K)/Akt pathway is critical for protection of hippocampal cells from staurosporine (STS) induced apoptosis, characterized by nuclear condensation and activation of the caspase cascade. Both nerve growth factor (NGF) and brain-derived growth factor (BDNF) prevent STS-induced apoptotic morphology and caspase-3 activity by upregulating phosphorylation of the tropomyosin receptor kinase (Trk) receptor. Inhibition of Trk receptor by K252a altered the neuroprotective effect of both NGF and BDNF whereas inhibition of the p75 neurotrophi... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3777278 Sun, 18 Jul 2010 23:00:00 +0100 3777278 http://www.medworm.com/index.php?rid=3759178&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20631490%26dopt%3DAbstract Authors: Nam EH, Park SR, Kim PH Angiogenesis is a multi-step process that involves the activation, proliferation, and migration of endothelial cells. We have recently shown that TGF-b1 can induce mouse macrophages to produce VEGF, a potent angiogenic factor. In the present study, we explored whether TGF-b1 has a similar effect on mouse dendritic cells. First, we show that under hypoxic conditions, TGF-b1 induced the expression of VEGF transcripts in bone marrow-derived dendritic cells. Overexpression of Smad3/4 further augmented TGF-b1-induced VEGF transcription, while overexpression of DN-Smad3 decreased VEGF transcription in DC2.4 cells, a mouse dendritic cell line. We also show that TGF-b1 and Smads are involved in the induction of VEGF protein secretion. Interestingly, under the s... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3759178 Wed, 14 Jul 2010 23:00:00 +0100 3759178 http://www.medworm.com/index.php?rid=3759179&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20628269%26dopt%3DAbstract Authors: Jin X, Beck S, Sohn YW, Kim JK, Kim SH, Yin J, Pian X, Kim SC, Choi YJ, Kim H Although human telomerase catalytic subunit (TERT) has several cellular functions including telomere homeostasis, genomic stability, cell proliferation, and tumorigenesis, the molecular mechanism underlying anti-apoptosis regulated by TERT remains to be elucidated. Here, we show that ectopic expression of TERT in spontaneously immortalized human fetal fibroblast (HFFS) cells, which are a telomerase- and p53-positive, leads to increases of cell proliferation and transformation, as well as a resistance to DNA damage response and inactivation of p53 function. We found that TERT and a mutant TERT (no telomerase activity) induce expression of basic fibroblast growth factor (bFGF), and ectopic expression o... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3759179 Tue, 13 Jul 2010 23:00:00 +0100 3759179 http://www.medworm.com/index.php?rid=3759180&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20628268%26dopt%3DAbstract Authors: Song HY, Kim MY, Kim KH, Lee IH, Shin SH, Lee JS, Kim JH Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disorder that causes the immune system to attack the joints. Transforming growth factor-b1 (TGF-b1) is a secreted protein that promotes differentiation of synovial fibroblasts to alpha-smooth muscle actin (a-SMA)-positive myofibroblasts to repair the damaged joints. Synovial fluid from patients with RA (RA-SF) induced expression of alpha-SMA in human adipose tissue-derived mesenchymal stem cells (hASCs). RA-SF-induced a-SMA expression was abrogated by immunodepletion of TGF-b1 from RA-SF with anti-TGF-b1 antibody. Furthermore, pretreatment of hASCs with the TGF-b type I receptor inhibitor SB431542 or lentiviral small hairpin RNA-mediated silencing of TGF-b t... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3759180 Mon, 12 Jul 2010 23:00:00 +0100 3759180 http://www.medworm.com/index.php?rid=3759181&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20625243%26dopt%3DAbstract In conclusion, rebamipide-induced downregulation of PLD may contribute to the inhibition of inflammation and proliferation in gastric cancer. <b></b> PMID: 20625243 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3759181 Sun, 11 Jul 2010 23:00:00 +0100 3759181 http://www.medworm.com/index.php?rid=3742568&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20610917%26dopt%3DAbstract In this study, we investigated the effect of CD1d-restricted NKT cells in the Tol-APCs-mediated suppression of autoimmune disease using a murine CIA model. When CIA-induced mice were treated with Tol-APCs obtained from CD1d+/- or CD1d-/- mice, unlike CD1d+/- APCs, CD1d-/- Tol-APCs failed to suppress CIA. More specifically, CD1d-/- Tol-APCs failed to suppress the production of inflammatory cytokines and the induction of Th2 responses by antigen-specific CD4 T cells both in vitro and in vivo. Our results demonstrate that the presence of CD1d-restricted NKT cells is critical for the induction of Tol-APCs-mediated suppression of CIA. PMID: 20610917 [PubMed - as supplied by publisher] (Source: exp Mol Med) exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3742568 Tue, 06 Jul 2010 23:00:00 +0100 3742568 http://www.medworm.com/index.php?rid=3719517&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20592486%26dopt%3DAbstract Authors: Kim YS, Choi SJ, Choi JP, Jeon SG, Oh SY, Lee BJ, Gho YS, Lee CG, Zhu Z, Elias JA, Kim YK IL-4 and IL-13 are closely related cytokines that are produced by Th2 cells. However, IL-4 and IL-13 have different effects on the development of asthma phenotypes. Here, we evaluated downstream molecular mechanisms involved in the development of Th2 type asthma phenotypes. A murine model of Th2 asthma was used that involved intraperitoneal sensitization with an allergen (ovalbumin) plus alum and then challenge with ovalbumin alone. Asthma phenotypes, including airway-hyperresponsiveness (AHR), lung inflammation, and immunologic parameters were evaluated after allergen challenge in mice deficient in candidate genes. The present study showed that methacholine AHR and lung inflammation deve... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3719517 Wed, 30 Jun 2010 23:00:00 +0100 3719517 http://www.medworm.com/index.php?rid=3659760&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20543547%26dopt%3DAbstract Authors: Woo A, Min B, Ryoo S Arginase competitively inhibits nitric oxide synthase (NOS) via use of the common substrate L-Arginine. Arginase II has recently reported as a novel therapeutic target for the treatment of cardiovascular diseases such as atherosclerosis. Here, we demonstrate that piceatannol-3'-O-beta-D-glucopyranoside(PG), a potent component of stilbenes, inhibits the activity of arginase I and II prepared from mouse liver and kidney lysates, respectively, in a dose-dependent manner. In HUVECs, incubation of PG markedly blocked arginase activity and increased NOx production, as measured by Griess assay. The PG effect was associated with increase of eNOS dimer ratio, although the protein levels of arginase II or eNOS were not changed. Furthermore, isolated mice aortic ring... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3659760 Sun, 13 Jun 2010 23:00:00 +0100 3659760 http://www.medworm.com/index.php?rid=3659759&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20543548%26dopt%3DAbstract Authors: Kim JW, Kim TD, Hong BS, Kim OY, Yoon WH, Chae CB, Gho YS Angiogenesis is critical and indispensable for tumor progression. Since VEGF is known to play a central role in angiogenesis, the disruption of VEGF-VEGF receptor system is a promising target for anti-cancer therapy. Previously, we reported that a hexapeptide (RRKRRR, RK6) blocked the growth and metastasis of tumor by inhibiting VEGF binding to its receptors. In addition, dRK6, the D-form derivative of RK6, retained its biological activity with improved serum stability. In the present study, we developed a serum-stable branched dimeric peptide (MAP2-dRK6) with enhanced anti-VEGF and anti-tumor activity. MAP2-dRK6 is more effective than dRK6 in many respects: inhibition of VEGF binding to its receptors, VEGF- and tumor c... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3659759 Sun, 13 Jun 2010 23:00:00 +0100 3659759 http://www.medworm.com/index.php?rid=3655399&cid=s_30450_67_f&fid=30450&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20530983%26dopt%3DAbstract We examined the effects of 2DG on dedifferentiation with a focus on the beta-catenin pathway in rabbit articular chondrocytes. The rabbit articular chondrocytes were treated with 5 mM 2DG for the indicated time periods or with various concentrations of 2DG for 24 h, and the expression of type II collagen, c-jun and beta-catenin was determined by Western blot, RT-PCR, immunofluorescence staining and immunohistochemical staining and reduction of sulfated proteoglycan synthesis detected by Alcain blue staining. Luciferase assay using a TCF (T cell factor)/LEF (lymphoid enhancer factor) reporter construct was used to demonstrate the transcriptional activity of beta-catenin. We found that 2DG treatment caused a decrease of type II collagen expression. 2DG induced dedifferentiation was dependent... exp Mol Med journals http://www.medworm.com/rss/comments.php?id=3655399 Mon, 07 Jun 2010 23:00:00 +0100 3655399