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 'Molecular Medicine' source. Mon, 06 Feb 2012 16:52:16 +0100 http://www.medworm.com/index.php?rid=5620641&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22252712%26dopt%3DAbstract Authors: Sancho-Pelluz J, Tosi J, Hsu CW, Lee F, Wolpert K, Tabacaru MR, Greenberg JP, Tsang SH, Lin CS Abstract Rhodopsin is the G protein-coupled receptor in charge of initiating signal transduction in rod photoreceptor cells upon the arrival of the photon. D190N, a missense mutation in rhodopsin, causes autosomal dominant retinitis pigmentosa (adRP) in humans. Affected patients present hyperfluorescent retinal rings and progressive rod photoreceptor degeneration. Studies in humans cannot reveal the molecular processes causing the earliest stages of the condition, thus necessitating the creation of an appropriate animal model. A knock-in mouse model with the D190N mutation was engineered to study the pathogenesis of the disease. Electrophysiological and histological findings in t... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5620641 Wed, 11 Jan 2012 05:00:00 +0100 5620641 http://www.medworm.com/index.php?rid=5620640&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22252713%26dopt%3DAbstract Authors: Kim TH, Yoon SJ, Lee SM Abstract The pathogenesis of sepsis is characterized by overwhelming inflammatory responses that lead to tissue damage and organ failure. Toll-like receptor (TLR) signaling is crucial for induction of hyperinflammatory responses and tissue injury during sepsis. Genipin, a aglycon of geniposide, has antiinflammatory and antimicrobial activities. The purpose of this study was to test the hypothesis that genipin reduces multiple organ dysfunction and mortality during sepsis through inhibition of TLR signaling. Male ICR were subjected to sepsis by cecal ligation and puncture (CLP), or endotoxemia by lipopolysaccharide (LPS). Various doses of genipin (1, 2.5, and 5 mg/kg) or a vehicle were administered intravenously immediately after CLP or intraperitone... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5620640 Wed, 11 Jan 2012 05:00:00 +0100 5620640 http://www.medworm.com/index.php?rid=5620639&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22252714%26dopt%3DAbstract Authors: Silva HM, Takenaka MC, Moraes-Vieira PM, Monteiro SM, Hernandez MO, Chaara W, Six A, Agena F, Sesterheim P, Barbé-Tuana FM, Saitovitch D, Lemos F, Kalil J, Coelho V Abstract Transplanted individuals in operational tolerance (OT) maintain long term stable graft function after completely stopping immunosuppression. Understanding the mechanisms involved in OT can provide valuable information about pathways to human transplantation tolerance. Here we report that operationally tolerant individuals display quantitative and functional preservation of the B cell compartment in renal transplantation. OT exhibited normal numbers of circulating total B cells, naive, memory and regulatory B cells (Bregs), as well as a preserved B cell receptor repertoire, similar to healthy individua... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5620639 Wed, 11 Jan 2012 05:00:00 +0100 5620639 http://www.medworm.com/index.php?rid=5598768&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22245800%26dopt%3DAbstract We reported that A1AT protects lung endothelial cells from apoptosis and inhibits caspase-3 activity. It is not clear if cigarette smoking or A1AT mutations alter the caspase-3 inhibitory activity of A1AT and if this serpin alters the function of other caspases. We tested the hypothesis that the caspase-3 inhibitory activity of A1AT is impaired by cigarette smoking and that the A1AT reactive center loop, the key anti-protease domain of the serpin, is required for its interaction with caspase. We examined the caspase-3 inhibitory activity of human A1AT purified from plasma of actively smoking and non-smoking individuals, either affected or unaffected with COPD. We also tested the caspase inhibitory activity of two mutant forms of A1AT, the recombinant human piZZ and the reactive center loop... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5598768 Tue, 10 Jan 2012 05:00:00 +0100 5598768 http://www.medworm.com/index.php?rid=5598770&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22231732%26dopt%3DAbstract Authors: Reay DP, Niizawa GA, Watchko JF, Daood M, Reay JC, Raggi E, Clemens PR Abstract Gene therapy studies for Duchenne muscular dystrophy (DMD) have focused on viral vector-mediated gene transfer to provide therapeutic protein expression or treatment with drugs to limit dystrophic changes in muscle. The pathological activation of the nuclear factor κB (NF-κB) signaling pathway has emerged as an important cause of dystrophic muscle changes in muscular dystrophy. Furthermore, activation of NF-κB may inhibit gene transfer by promoting inflammation in response to the transgene or vector. Therefore, we hypothesized that inhibition of pathological NF-κB activation in muscle would complement the therapeutic benefits of dystrophin gene transfer in the mdx mouse model of DMD. System... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5598770 Thu, 05 Jan 2012 05:00:00 +0100 5598770 http://www.medworm.com/index.php?rid=5598769&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22231733%26dopt%3DAbstract EXPRESSION OF INTERLEUKIN-8 (IL-8) RECEPTOR CXCR2 AND SUPPRESSOR OF CYTOKINE SIGNALING-3 (SOCS-3) IN ASTROCYTIC TUMORS. Mol Med. 2012 Jan 4; Authors: Korkolopoulou P, Levidou G, El-Habr EA, Adamopoulos C, Samaras V, Zisakis A, Kavantzas N, Boviatsis E, Fragkou P, Papavassiliou AG, Patsouris E, Piperi C Abstract The aim was to expand recently published information regarding the significance of IL-8/p-STAT-3 pathway in astrocytomas, focusing on IL-8 receptor, CXCR2, and STAT-3 inhibitor, SOCS-3. 91 paraffin-embedded human astrocytoma tissues (grades II to IV) were investigated for the association of SOCS-3 and CXCR2 expression with clinicopathologic and morphometric microvascular characteristics, vascular endothelial growth factor (VEGF), IL-8 and p-STAT-3 expression, and pat... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5598769 Wed, 04 Jan 2012 05:00:00 +0100 5598769 http://www.medworm.com/index.php?rid=5548801&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21327296%26dopt%3DAbstract Authors: Frankenberger M, Eder C, Hofer TP, Heimbeck I, Skokann K, Kassner G, Weber N, Möller W, Ziegler-Heitbrock L Abstract Small sputum macrophages represent highly active cells that increase in the airways of patients with inflammatory diseases such as chronic obstructive pulmonary disease (COPD). It has been reported often that levels of cytokines, chemokines and pro-teases are increased in sputum supernatants of these patients. In COPD, the small sputum macrophages may contribute to these supernatant proteins and recruit additional cells via specific chemokine expression patterns. We therefore investigated the expression profile of chemokines in sputum macrophages obtained from COPD patients in comparison to cells from healthy donors and cells isolated after inhalation of li... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548801 Thu, 29 Dec 2011 07:24:03 +0100 5548801 http://www.medworm.com/index.php?rid=5548800&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21327297%26dopt%3DAbstract Authors: Jiang L, Lai YK, Zhang J, Wang H, Lin MC, He ML, Kung HF Abstract S100P was recently found to be overexpressed in a variety of cancers and is considered a potential target for cancer therapy, but the functional role or mechanism of action of S100P in colon cancer is not fully understood. In the present study, we knocked down the gene expression of S100P in colon cancer cells using lentivirus-mediated RNA interference. This step resulted in significant inhibition of cancer cell growth, migration and invasion in vitro and tumor growth and liver metastasis in vivo. Moreover, S100P downstream target proteins were identified by proteomic analysis in colon cancer DLD-1 cells with deletion of S100P. Knockdown of S100P led to downregulation of thioredoxin 1 and β-tubulin and upre... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548800 Thu, 29 Dec 2011 07:24:03 +0100 5548800 http://www.medworm.com/index.php?rid=5548799&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21327300%26dopt%3DAbstract Authors: Pavicic W, Perkiö E, Kaur S, Peltomäki P Abstract MicroRNAs (miRNAs) are small noncoding RNAs that contribute to tumorigenesis by acting as oncogenes or tumor suppressor genes and may be important in the diagnosis, prognosis and treatment of cancer. Many miRNA genes have associated CpG islands, suggesting epigenetic regulation of their expression. Compared with sporadic cancers, the role of miRNAs in hereditary or familial cancer is poorly understood. We investigated 96 colorectal carcinomas, 58 gastric carcinomas and 41 endometrial carcinomas, occurring as part of inherited DNA mismatch repair (MMR) deficiency (Lynch syndrome), familial colorectal carcinoma without MMR gene mutations or sporadically. Methylation-specific multiplex ligation-dependent probe amplification ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548799 Thu, 29 Dec 2011 07:24:03 +0100 5548799 http://www.medworm.com/index.php?rid=5548798&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21327301%26dopt%3DAbstract Authors: Martini WZ Abstract Hemorrhagic coagulopathy (without neurological injuries) constitutes 40% of injury-related death in civilian hospitals and on the battlefield, and the underlying contributing mechanisms remain unclear. The purpose of this study is to investigate the effects of fibrinogen availability on coagulation function after hemorrhage in pigs. Sixteen crossbred commercial Yorkshire swine were randomized into the control group (group C) (n = 8) and hemorrhage group (group H) (n = 8). Hemorrhage was induced in group H by bleeding 35% of the estimated total blood volume, followed by resuscitation with lactated Ringer solution at three times the bled volume. Pigs in group C were not hemorrhaged or resuscitated. Blood samples were withdrawn at baseline, 15 min, 3 h, 6 ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548798 Thu, 29 Dec 2011 07:24:03 +0100 5548798 http://www.medworm.com/index.php?rid=5548797&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21365122%26dopt%3DAbstract In conclusion, the combined use of autologous MSCs and low-dose CsA exerted a synergistic immunosuppressive effect in an islet allograft model, suggesting a role for autologous MSCs as an immune modulator. PMID: 21365122 [PubMed - indexed for MEDLINE] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548797 Thu, 29 Dec 2011 07:24:03 +0100 5548797 http://www.medworm.com/index.php?rid=5548796&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21365123%26dopt%3DAbstract Authors: Pfeiffer MJ, Smit FP, Sedelaar JP, Schalken JA Abstract Considerable levels of testosterone and dihydrotestosterone (DHT) are found in prostate cancer (PCa) tissue after androgen deprivation therapy. Treatment of surviving cancer-initiating cells and the ability to metabolize steroids from precursors may be the keystones for the appearance of recurrent tumors. To study this hypothesis, we assessed the expression of several steroidogenic enzymes and stem cell markers in clinical PCa samples and cell cultures during androgen depletion. Gene expression profiles were determined by microarray or qRT-PCR. In addition, we measured cell viability and analyzed stem cell marker expression in DuCaP cells by immunocytochemistry. Seventy patient samples from different stages of PCa, an... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548796 Thu, 29 Dec 2011 07:24:03 +0100 5548796 http://www.medworm.com/index.php?rid=5548795&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21365124%26dopt%3DAbstract Authors: Bishop DF, Clavero S, Mohandas N, Desnick RJ Abstract Congenital erythropoietic porphyria (CEP) is an autosomal recessive disorder due to the deficient activity of uroporphyrinogen III synthase (UROS). Knock-in mouse models were generated for the common, hematologically severe human genotype, C73R/C73R, and milder genotypes (C73R/V99L and V99L/V99L). The specific activities of the UROS enzyme in the livers and erythrocytes of these mice averaged approximately 1.2%, 11% and 19% of normal, respectively. C73R/C73R mice that survived fetal life to weaning age (~12%) had a severe microcytic hypochromic anemia (hemoglobin 7.9 g/dL, mean cellular volume 26.6 fL, mean cellular hemoglobin content 27.4 g/dL, red cell distribution width 37.7%, reticulocytes 19%) and massively accumul... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548795 Thu, 29 Dec 2011 07:24:03 +0100 5548795 http://www.medworm.com/index.php?rid=5548794&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21373720%26dopt%3DAbstract Authors: Chartoumpekis DV, Habeos IG, Ziros PG, Psyrogiannis AI, Kyriazopoulou VE, Papavassiliou AG Abstract Fibroblast growth factor-21 (FGF21) is a pleiotropic protein involved in glucose, lipid metabolism and energy homeostasis, with main tissues of expression being the liver and adipose tissue. Brown adipose tissue (BAT) is responsible for cold-induced thermogenesis in rodents. The role of FGF21 in BAT biology has not been investigated. In the present study, wild-type C57BL/6J mice as well as a brown adipocyte cell line were used to explore the potential role of cold exposure and β3-adrenergic stimulation in the expression of FGF21 in BAT. Our results demonstrate that short-term exposure to cold, as well as β3-adrenergic stimulation, causes a significant induction of FGF21 mR... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548794 Thu, 29 Dec 2011 07:24:03 +0100 5548794 http://www.medworm.com/index.php?rid=5548793&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21380479%26dopt%3DAbstract In conclusion, these data support a potential role for HMGB1 as a biomarker and diagnostic tool for the differential diagnosis of asthma and COPD. The importance of this observation on asthma and COPD mechanisms and outcomes should be further investigated in large prospective studies. PMID: 21380479 [PubMed - indexed for MEDLINE] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548793 Thu, 29 Dec 2011 07:24:03 +0100 5548793 http://www.medworm.com/index.php?rid=5548792&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21394384%26dopt%3DAbstract In conclusion, expression of IL-1F members is more pronounced in adipose compared with liver tissue in patients with severe obesity. Excessive weight loss changes the adipose and liver expression profile of IL-1F members toward a more antiinflammatory direction. PMID: 21394384 [PubMed - indexed for MEDLINE] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548792 Thu, 29 Dec 2011 07:24:03 +0100 5548792 http://www.medworm.com/index.php?rid=5548791&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21424106%26dopt%3DAbstract In this study, we showed that MSCs increase proliferation of tumor cells in vitro and promote tumor growth in vivo. We also further analyzed the mechanisms that underlie these effects. For use in in vitro and in vivo experiments, we established a bone marrow-derived mesenchymal stromal cell line from cells isolated in C57BL/6 mice. Effects of murine MSCs on tumor cell proliferation in vitro were analyzed in a coculture model with B16-LacZ cells. Both coculture with MSCs and treatment with MSC-conditioned media led to enhanced growth of B16-LacZ cells, although the magnitude of growth stimulation in cocultured cells was greater than that of cells treated with conditioned media. Co-injection of B16-LacZ cells and MSCs into syngeneic mice led to increased tumor size compared with injection of... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548791 Thu, 29 Dec 2011 07:24:03 +0100 5548791 http://www.medworm.com/index.php?rid=5548790&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21424107%26dopt%3DAbstract Authors: Leung M, Rosen D, Fields S, Cesano A, Budman DR Abstract The hereditary forms of breast cancer identified by BRCA1 and BRCA2 genes have a defect in homologous DNA repair and demonstrate a dependence on alternate DNA repair processes by base excision repair, which requires poly(ADP-ribose) polymerase 1 (PARP-1). siRNA and deletion mutations demonstrate that interference with PARP-1 function results in enhanced cell death when the malignancy has a defect in homologous recombination. These findings resulted in a plethora of agents in clinical trials that interfere with DNA repair, and these agents offer the potential of being more selective in their effects than classic chemotherapeutic drugs. An electronic search of the National Library of Medicine for published articles wri... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548790 Thu, 29 Dec 2011 07:24:03 +0100 5548790 http://www.medworm.com/index.php?rid=5548789&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21424108%26dopt%3DAbstract Authors: Guan Q, Ma Y, Hillman CL, Qing G, Ma AG, Weiss CR, Zhou G, Bai A, Warrington RJ, Bernstein CN, Peng Z Abstract Interleukin (IL)-12 and IL-23 both share the p40 subunit and are key cytokines in the pathogenesis of Crohn's disease. Previously, we have developed and identified three mouse p40 peptide-based and virus-like particle vaccines. Here, we evaluated the effects and immune mechanisms of the optimal vaccine in downregulating intestinal inflammation in murine acute and chronic colitis, induced by intrarectal administrations of trinitrobenzene sulfonic acid (TNBS). Mice were injected subcutaneously with vaccine, vaccine carrier or saline three times, and then intrarectally administered TNBS weekly for 2 wks (acute colitis) or 7 wks (chronic colitis). The severity of coli... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548789 Thu, 29 Dec 2011 07:24:03 +0100 5548789 http://www.medworm.com/index.php?rid=5548788&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21424109%26dopt%3DAbstract This study reaffirms the importance of classic inflammation pathways, such as MAPK and TGFβ signaling and reveals less known involvement of glycogen synthase kinase 3β (GSK-3β), AKT and SRC signaling cassettes in pneumonia. PMID: 21424109 [PubMed - indexed for MEDLINE] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548788 Thu, 29 Dec 2011 07:24:03 +0100 5548788 http://www.medworm.com/index.php?rid=5548787&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21431247%26dopt%3DAbstract Authors: Subirán N, Casis L, Irazusta J Abstract Endogenous opioid peptides are substances involved in cell communication. They are present in various organs and tissues of the male and female reproductive tract, suggesting that they may regulate some of the processes involved in reproductive function. In fact, the opioid system that operates as a multi-messenger system can participate in the regulation of reproductive physiology at multiple levels, for example, at the levels of the central nervous system, at the testes level and at sperm level. A better understanding of the implication of the opioid system in reproductive processes may contribute to clarifying the etiology of many cases of infertility and the effect of opiate abuse on fertility. Indeed, a novel biochemical tool f... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548787 Thu, 29 Dec 2011 07:24:03 +0100 5548787 http://www.medworm.com/index.php?rid=5548786&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21442128%26dopt%3DAbstract Authors: Ferreira A, Bigio EH Abstract Tau dysfunction has been associated with a host of neurodegenerative diseases called tauopathies. These diseases share, as a common pathological hallmark, the presence of intracellular aggregates of hyperphosphorylated tau in affected brain areas. Aside from tau hyperphosphorylation, little is known about the role of other posttranslational modifications in tauopathies. Recently, we obtained data suggesting that calpain-mediated tau cleavage leading to the generation of a neurotoxic tau fragment might play an important role in Alzheimer's disease. In the current study, we assessed the presence of this tau fragment in several tauopathies. Our results show high levels of the 17-kDa tau fragment and enhanced calpain activity in the temporal corte... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548786 Thu, 29 Dec 2011 07:24:03 +0100 5548786 http://www.medworm.com/index.php?rid=5548785&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21442129%26dopt%3DAbstract In this study we explored the effects of a high-glucose environment on the innate immunity of keratinocytes by focusing on β defensin-3 (BD3) using in vivo and in vitro models. Our results demonstrated that the perilesional skins of diabetic rats failed to show enhanced BD3 expression after wounding. In addition, high-glucose treatment reduced human BD3 (hBD3) expression of cultured human keratinocytes. This pathogenic process involved inhibition of p38MAPK signaling, an event that resulted from increased formation of advanced glycation end products. On the other hand, toll-like receptor-2 expression and function of cultured keratinocytes were not significantly affected by high-glucose treatment. In summary, high-glucose conditions inhibited the BD3 expression of epidermal keratinocytes, ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548785 Thu, 29 Dec 2011 07:24:03 +0100 5548785 http://www.medworm.com/index.php?rid=5548784&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21442130%26dopt%3DAbstract In this study, we investigated the function of the FASN signaling pathway in a large series of Middle Eastern EOC patient samples, a panel of cell lines and nude mouse model. Using immunohistochemistry, we detected overexpression of FASN in 75.5% (114/151) of the tumor samples. Overexpression of FASN was associated significantly with tumor proliferative marker Ki-67 (P = 0.0009), activated AKT (P = 0.0117) and XIAP (P = 0.0046). Treatment of EOC cell lines with C-75, a selective inhibitor of FASN, caused inhibition of EOC cell viability via induction of apoptosis. Inhibition of FASN by C-75 led apoptosis via the mitochondrial pathway. FASN inhibition caused downregulation of activated AKT and its downstream targets. In addition, inhibition by FASN siRNA caused downregulation of FASN and ac... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548784 Thu, 29 Dec 2011 07:24:03 +0100 5548784 http://www.medworm.com/index.php?rid=5548783&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21448509%26dopt%3DAbstract Authors: Kurtovic S, Paloschi V, Folkersen L, Gottfries J, Franco-Cereceda A, Eriksson P Abstract Impaired regulation of the transforming growth factor-β (TGFβ) signaling pathway has been linked to thoracic aortic aneurysm (TAA). Previous work has indicated that differential splicing is a common phenomenon, potentially influencing the function of proteins. In the present study we investigated the occurrence of differential splicing in the TGFβ pathway associated with TAA in patients with bicuspid aortic valve (BAV) and tricuspid aortic valve (TAV). Affymetrix human exon arrays were applied to 81 intima/media tissue samples from dilated (n = 51) and nondilated (n = 30) aortas of TAV and BAV patients. To analyze the occurrence of alternative splicing in the TGFβ pathway, multivar... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548783 Thu, 29 Dec 2011 07:24:03 +0100 5548783 http://www.medworm.com/index.php?rid=5548782&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21487639%26dopt%3DAbstract The objective of this study was to determine if the herpes virus carrying an enhanced green fluorescent protein (EGFP) could detect rare cancer cells in body fluids against millions of normal cells. Human cancer cells suspended with normal murine cells were infected with NV1066 at a multiplicity of infection (MOI) of 0.5 and 1.0 for 18 h. Fluorescent microscopy and flow cytometry were used for EGFP detection of cancer cells. EGFP-expressing cells were confirmed as cancer cells with specific markers by immunohistochemistry staining. Limits of detection of cancer cells in body fluid were measured by serial dilutions. Applicability of technique was confirmed with samples from patients with malignant pleural effusions. NV1066 expressed EGFP in 111 human cancer cell lines detected by fluorescen... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548782 Thu, 29 Dec 2011 07:24:03 +0100 5548782 http://www.medworm.com/index.php?rid=5548781&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21519633%26dopt%3DAbstract In this study, the VEGF status in CLL was assessed by enzyme-linked immunosorbent assay and immunofluorescence. VEGF receptor 2 (VEGFR2) phosphorylation was determined flow cytometrically and by immunofluorescence. For co-culture, CLL cells were cultivated on a monolayer of the bone marrow-derived stromal cell (BMSC) line HS5. Secreted VEGF was neutralized using the monoclonal antibody mAb293 (R&D Systems, Minneapolis, MN, USA). To block protein secretion, we used Brefeldin A. VEGF was downregulated in BMSCs by small interfering RNA (siRNA), and we assessed survival by annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining. CLL cells express and secrete VEGF and possess phosphorylated VEGFR2. This positive VEGF status is not sufficient to prevent spontaneous apoptos... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548781 Thu, 29 Dec 2011 07:24:03 +0100 5548781 http://www.medworm.com/index.php?rid=5548780&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21519634%26dopt%3DAbstract We report 26 cMV proteome profiles from male and female stroke-prone and non-stroke-prone rats at 2 months and 4.5 months of age prior to overt stroke events. We identified 1,934 proteins by two or more peptides. Metaprotein pathway analysis detected age-associated changes in energy metabolism and cell-to-microenvironment interactions, as well as sex-specific changes in energy metabolism and endothelial leukocyte transmigration pathways. Stroke susceptibility was associated independently with multiple protein changes associated with ischemia, angiogenesis or involved in blood brain barrier (BBB) integrity. Immunohistochemical analysis confirmed aquaporin-4 and laminin-α1 induction in cMVs, representative of proteomic changes with >65 Bayes factor (BF), associated with stroke susceptibi... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548780 Thu, 29 Dec 2011 07:24:03 +0100 5548780 http://www.medworm.com/index.php?rid=5548779&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21519635%26dopt%3DAbstract Authors: Gehrau R, Maluf D, Archer K, Stravitz R, Suh J, Le N, Mas V Abstract Acute cellular rejection (ACR) and hepatitis C virus (HCV) recurrence (HCVrec) are common complications after liver transplantation (LT) in HCV patients, who share common clinical and histological features, making a differential diagnosis difficult. Fifty-three liver allograft samples from unique HCV LT recipients were studied using microarrays, including a training set (n = 32) and a validation set (n = 19). Two no-HCV-ACR samples from LT recipients were also included. Probe set intensity values were obtained using the robust multiarray average method (RMA) method. Analysis of variance identified statistically differentially expressed genes (P ≤ 0.005). The limma package was used to fit the mixed-effec... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548779 Thu, 29 Dec 2011 07:24:03 +0100 5548779 http://www.medworm.com/index.php?rid=5548778&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21528155%26dopt%3DAbstract In conclusion, our results provide an empirical basis for the development of a pharmacological ASD treatment strategy based on retinoids. PMID: 21528155 [PubMed - indexed for MEDLINE] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548778 Thu, 29 Dec 2011 07:24:03 +0100 5548778 http://www.medworm.com/index.php?rid=5548777&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21541441%26dopt%3DAbstract Authors: Fuhler GM, Diks SH, Peppelenbosch MP, Kerr WG Abstract Multiple myeloma (MM) is a neoplasm of plasma cell origin that is largely confined to the bone marrow (BM). Chromosomal translocations and other genetic events are known to contribute to deregulation of signaling pathways that lead to transformation of plasma cells and progression to malignancy. However, the tumor stroma may also provide trophic support and enhance resistance to therapy. Phosphorylation of proteins on tyrosine, serine and threonine residues plays a pivotal role in cell growth and survival. Therefore, knowing the status of phosphorylation-based signaling pathways in cells may provide key insights into how cell growth and survival is promoted in tumor cells. To provide a more comprehensive molecular anal... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548777 Thu, 29 Dec 2011 07:24:03 +0100 5548777 http://www.medworm.com/index.php?rid=5548776&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21556483%26dopt%3DAbstract Authors: Finney CA, Hawkes CA, Kain DC, Dhabangi A, Musoke C, Cserti-Gazdewich C, Oravecz T, Liles WC, Kain KC Abstract Cerebral malaria (CM) is associated with excessive inflammatory responses and endothelial activation. Sphingosine 1-phosphate (S1P) is a signaling sphingolipid implicated in regulating vascular integrity, inflammation and T-cell migration. We hypothesized that altered S1P signaling during malaria contributes to endothelial activation and inflammation, and show that plasma S1P levels were decreased in Ugandan children with CM compared with children with uncomplicated malaria. Using the Plasmodium berghei ANKA (PbA) model of experimental CM (ECM), we demonstrate that humanized S1P lyase (hS1PL)(-/-) mice with reduced S1P lyase activity (resulting in increased bio-av... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548776 Thu, 29 Dec 2011 07:24:03 +0100 5548776 http://www.medworm.com/index.php?rid=5548775&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21738953%26dopt%3DAbstract Authors: Satapathy SK, Ochani M, Dancho M, Hudson LK, Rosas-Ballina M, Valdes-Ferrer SI, Olofsson PS, Harris YT, Roth J, Chavan S, Tracey KJ, Pavlov VA Abstract Obesity, a serious and growing health threat, is associated with low-grade inflammation that plays a role in mediating its adverse consequences. Previously, we have discovered a role for neural cholinergic signaling in controlling inflammation, and demonstrated that the cholinergic agent galantamine suppresses excessive proinflammatory cytokine release. The main objective of this study was to examine the efficacy of galantamine, a clinically-approved drug, in alleviating obesity-related inflammation and associated complications. After 8 wks on a high-fat diet, C57BL/6J mice were treated with either galantamine (4 mg/kg, int... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548775 Thu, 29 Dec 2011 07:24:03 +0100 5548775 http://www.medworm.com/index.php?rid=5548774&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22193356%26dopt%3DAbstract CONCLUSIONS: We provide both in vitro and in vivo evidence that low-dose methotrexate inhibits MAT genes, proteins, and enzyme activity independent of folate depletion. Since polyglutamated methotrexate stays in the hepatocytes, if methotrexate inhibits MAT in the liver, the efficacy of clinical folinate rescue with respect to maintaining hepatic S-adenosylmethionine synthesis and normalizing the methylation reactions would be limited. These findings raise concerns on perturbed methylation reactions in humans on low-dose methotrexate. Future studies on the clinical physiological consequences of MAT inhibition by methotrexate and the potential benefits of S-adenosylmethionine supplementation on methyl group homeostasis in clinical methotrexate therapies are warranted. PMID: 22193356 [Pu... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5548774 Mon, 19 Dec 2011 05:00:00 +0100 5548774 http://www.medworm.com/index.php?rid=5533220&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22183893%26dopt%3DAbstract Authors: Olofsson P, Katz D, Rosas-Ballina M, Levine Y, Ochani M, Valdés-Ferrer S, Pavlov V, Tracey K, Chavan S Abstract The immune response to infection or injury coordinates host defense and tissue repair, but also has the capacity to damage host tissues. Recent advances in understanding protective mechanisms have found neural circuits that suppress release of damaging cytokines. Stimulation of the vagus nerve protects from excessive cytokine production and ameliorates experimental inflammatory disease. This mechanism, the inflammatory reflex, requires the alpha7 nicotinic acetylcholine receptor (α7nAChR), a ligand gated ion channel expressed on macrophages, lymphocytes, neurons, and other cells. To investigate cell-specific function of α7nAChR in the inflammatory reflex, we c... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533220 Fri, 16 Dec 2011 05:00:00 +0100 5533220 http://www.medworm.com/index.php?rid=5533221&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22183892%26dopt%3DAbstract Authors: Brines M, Cerami A Abstract Tissue injury, hypoxia, and significant metabolic stress activate innate immune responses driven by TNFα and other pro-inflammatory cytokines that typically increase damage surrounding a lesion. In a compensatory protective response, erythropoietin (EPO) is synthesized in surrounding tissues, which subsequently triggers anti-inflammatory and anti-apoptotic processes that delimit injury and promote repair. What we refer to as the sequelae of injury or disease are often the consequences of this intentionally discoordinated, primitive system that employs a "scorched earth" strategy to rid the invader at the expense of a serious lesion. The EPO-mediated tissue protective system depends upon receptor expression that is up-regulated by inflammation a... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533221 Thu, 15 Dec 2011 05:00:00 +0100 5533221 http://www.medworm.com/index.php?rid=5533219&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22183894%26dopt%3DAbstract In conclusion, our study demonstrated that GNMT regulates the homeostasis of cholesterol metabolism and hepatic cholesterol accumulation may result from down-regulation of GNMT and instability of its interactive protein-NPC2. Novel therapeutics for steatohepatitis and HCC may be developed through using this concept. PMID: 22183894 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533219 Thu, 15 Dec 2011 05:00:00 +0100 5533219 http://www.medworm.com/index.php?rid=5533223&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160392%26dopt%3DAbstract We examined the proliferative, survival, and anabolic effects of the rAAV-hIGF-I treatment in primary human normal and OA chondrocytes in vitro and in explant cultures in situ compared with control (reporter) vector delivery. Efficient, prolonged IGF-I secretion via rAAV stimulated the biological activities of OA chondrocytes in all the systems evaluated over extended periods of time, especially in situ where it allowed for the long-term reconstruction of OA cartilage (at least for 90 days). Remarkably, production of high, stable amounts of IGF-I in OA cartilage using rAAV advantageously modulated the expression of central effectors of the IGF-I axis by downregulating IGF-I inhibitors (IGFBP3, IGFBP4) while upregulating key potentiators (IGFBP5, the IGF-I receptor and downstream MAPK/ERK-1... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533223 Fri, 09 Dec 2011 05:00:00 +0100 5533223 http://www.medworm.com/index.php?rid=5533222&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160393%26dopt%3DAbstract Authors: Wang L, Chen S, Xue M, Zhong J, Wang X, Gan L, Lam EK, Liu X, Zhang J, Zhou T, Yu J, Jin H, Si J Abstract Homeobox D10 (HoxD10) gene plays a critical role in cell differentiation and morphogenesis during development. However, the function of HoxD10 in tumor progression remains largely unknown. We demonstrated that the expression of HoxD10 was commonly downregulated in gastric cancer tissues (n=33) and cell lines (n=8) relative to normal stomach tissues. Functionally, re-expression of HoxD10 results in significant inhibition of cell survival, induction of cell apoptosis, and impairment of cell migration and invasion. Moreover, ectopic expression of HoxD10 suppresses gastric tumor growth in a mouse xenograft model. To identify target candidates of HoxD10, we performed cDNA m... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533222 Thu, 08 Dec 2011 05:00:00 +0100 5533222 http://www.medworm.com/index.php?rid=5533224&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160303%26dopt%3DAbstract Authors: Qi L, Cui X, Dong W, Barrera R, Nicastro J, Coppa GF, Wang P, Wu R Abstract Traumatic brain injury (TBI) and hemorrhagic shock often occur concomitantly due to multiple injuries. Gastrointestinal dysfunction occurs frequently in patients with TBI. However, whether alterations in the gastrointestinal system are involved in modulating neuronal damage and recovery after TBI is largely neglected. Ghrelin is a 'gut-brain' hormone with multiple functions including anti-inflammation and anti-apoptosis. The purpose of this study was to determine whether ghrelin attenuates brain injury in a rat model of TBI and uncontrolled hemorrhage (UH). To study this, brain injury was induced by dropping a 450 g weight from 1.5 m onto a steel helmet attached to the skull of male adult rats. Imm... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533224 Tue, 06 Dec 2011 05:00:00 +0100 5533224 http://www.medworm.com/index.php?rid=5533229&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160217%26dopt%3DAbstract Authors: Taneri B, Asilmaz E, Gaasterland T Abstract Splicing is a cellular mechanism, which dictates eukaryotic gene expression by removing the non-coding introns and ligating the coding exons in the form of a messenger RNA molecule. Alternative splicing adds a major level of complexity to this mechanism and thus to the regulation of gene expression. This widespread cellular phenomenon generates multiple messenger RNA isoforms from a single gene, by utilizing alternative splice-sites and promoting different exon-intron inclusions and exclusions. Alternative splicing greatly increases the coding potential of eukaryotic genomes and hence contributes to the diversity of eukaryotic proteomes. Mutations that lead to disruptions of either constitutive or alternative splicing cause sever... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533229 Thu, 01 Dec 2011 05:00:00 +0100 5533229 http://www.medworm.com/index.php?rid=5533228&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160218%26dopt%3DAbstract In conclusion, GNMT regulates HCC growth in part through interacting with DEPDC6/DEPTOR and modulating mTOR/Raptor signaling pathway. Both GNMT and DEPDC6/DEPTOR are potential targets for the development of therapeutics for HCC. PMID: 22160218 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533228 Thu, 01 Dec 2011 05:00:00 +0100 5533228 http://www.medworm.com/index.php?rid=5533227&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160219%26dopt%3DAbstract BETA-AMYLOID CARRYING THE DUTCH MUTATION HAS DIVERSE EFFECTS ON CALPAIN-MEDIATED TOXICITY IN HIPPOCAMPAL NEURONS. Mol Med. 2011 Dec 1; Authors: Nicholson AM, Wold LA, Walsh DM, Ferreira A Abstract Hereditary cerebral hemorrhage with amyloidosis-Dutch type is a disorder associated with a missense mutation (E693Q) in the beta-amyloid (Aβ)-coding region of the amyloid precursor protein. This familial disease is characterized by cognitive deficits secondary to intracerebral hemorrhage and, in some cases, progressive Alzheimer disease (AD)-like dementia. Although this mutation was the first ever reported in the human APP gene, little is known about the molecular mechanisms underlying the direct toxic effects of this mutated Aβ on central neurons. In the present study, we asses... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533227 Thu, 01 Dec 2011 05:00:00 +0100 5533227 http://www.medworm.com/index.php?rid=5533226&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160220%26dopt%3DAbstract Authors: Murillo-Cuesta S, Camarero G, González-Rodríguez A, La Rosa LR, Burks DJ, Avendaño C, Valverde AM, Varela-Nieto I Abstract The insulin receptor substrate proteins are key mediators of insulin and insulin-like growth factor 1 signaling. Protein tyrosine phosphatase 1B dephosphorylates and inactivates both insulin and IGF-1 receptors. IRS2-deficient mice present altered hepatic insulin signaling and β-cell failure, and develop type 2-like diabetes. In addition, IRS2 deficiency leads to developmental defects in the nervous system. IGF1 gene mutations cause syndromic sensorineural hearing loss in men and mice. However, the involvement of IRS2 and PTP1B, two IGF-1 downstream signaling mediators, in hearing onset and loss has not been studied. Our objective was to study the ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533226 Thu, 01 Dec 2011 05:00:00 +0100 5533226 http://www.medworm.com/index.php?rid=5533225&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22160221%26dopt%3DAbstract Authors: Naert G, Rivest S Abstract Monocytes emigrate from bone marrow, can infiltrate into brain, differentiate into microglia and clear amyloid beta (Aβ) from the brain of mouse models of Alzheimer's disease (AD). Here we show that these mechanisms specifically require CC-chemokine receptor 2 (CCR2) expression in bone marrow cells (BMC). Disease progression was exacerbated in APP(Swe)/PS1 mice harboring CCR2-deficient BMC. Indeed, transplantation of CCR2-deficient BMC enhanced mnesic deficit, increased amount of soluble Aβ and expression of TGF-β1 and TGF-β receptors. By contrast, transplantation of WT bone marrow stem cells restored memory capacities and diminished soluble Aβ accumulation in APP(Swe)/PS1 and APP(Swe)/PS1/CCR2(-/-) mice. Finally, gene therapy using lentivir... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533225 Tue, 29 Nov 2011 05:00:00 +0100 5533225 http://www.medworm.com/index.php?rid=5533235&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113494%26dopt%3DAbstract Authors: Nogueira-Silva C, Carvalho-Dias E, Piairo P, Nunes S, Baptista MJ, Moura RS, Correia-Pinto J Abstract Antenatal stimulation of lung growth is a reasonable approach to treat congenital diaphragmatic hernia (CDH), a disease characterized by pulmonary hypoplasia and hypertension. Several evidences from the literature demonstrated a possible involvement of renin-angiotensin system (RAS) during fetal lung development. Thus, the expression pattern of renin, angiotensin-converting enzyme, angiotensinogen, type 1 (AT(1)) and type 2 (AT(2)) receptors of angiotensin II (ANGII) was assessed by immunohistochemistry throughout gestation, whereas the function of RAS in the fetal lung was evaluated using fetal rat lung explants. These were morphometrically analyzed and intracellular path... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533235 Fri, 18 Nov 2011 05:00:00 +0100 5533235 http://www.medworm.com/index.php?rid=5533233&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113496%26dopt%3DAbstract Authors: Lucs AV, Wu R, Mullooly V, Abramson AL, Steinberg BM Abstract Recurrent respiratory papillomatosis (RRP) is caused by human papillomaviruses (HPV), primarily types 6 and 11. The disease is characterized by multiple recurrences of airway papillomas, resulting in high levels of morbidity and significant mortality. The prevalence of latent HPV in the larynx of the general population is much greater than the prevalence of RRP, suggesting a host-susceptibility factor for disease. Here we report that the oncogene Rac1 and its downstream product COX-2 are both constitutively expressed at high levels throughout the airway of these patients, independent of active HPV infection. Use of the COX-2 inhibitor celecoxib in primary papilloma cell culture resulted in the down-regulation of... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533233 Fri, 18 Nov 2011 05:00:00 +0100 5533233 http://www.medworm.com/index.php?rid=5533234&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113495%26dopt%3DAbstract In this study we tested the salutary effect of RSV following T-H and its influence on Sirt1 expression. Rats were subjected to T-H or sham operation. RSV (8 mg/Kg body wt, intravenously) or vehicle was administered 10 minutes after the onset of resuscitation and sacrificed 2 hours following resuscitation. Sirtinol, a Sirt1 inhibitor, was administered five minutes prior to RSV administration. Cardiac contractility (±dP/dt) was measured and heart tissue was tested for Sirt1, Pgc-1α, c-Myc, cytosolic cytochrome C expression and ATP level. Left ventricular function, after T-H, was improved (p<0.05) following RSV treatment with significantly elevated expression of Sirt1 (p<0.05) and Pgc-1α (p<0.05), and decreased c-Myc (p<0.05). We also observed significantly higher cardiac ATP c... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533234 Wed, 16 Nov 2011 05:00:00 +0100 5533234 http://www.medworm.com/index.php?rid=5533232&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113497%26dopt%3DAbstract Authors: Zhang Y, Talwar A, Tsang D, Bruchfeld A, Sadoughi A, Hu M, Omonuwa K, Cheng KF, Al-Abed Y, Miller EJ Abstract Pulmonary hypertension (PH) is a devastating disease leading to progressive hypoxemia, right ventricular failure, and death. Hypoxia can play a pivotal role in PH etiology, inducing pulmonary vessel constriction and remodeling. These events lead to increased pulmonary vessel wall thickness, elevated vascular resistance and right ventricular hypertrophy. The current study examined the association of the inflammatory cytokine macrophage migration inhibitory factor (MIF) with chronic lung disease and its role in the development of hypoxia-induced PH. We found that plasma MIF in patients with primary PH or PH secondary to interstitial lung disease (ILD) was significant... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533232 Wed, 16 Nov 2011 05:00:00 +0100 5533232 http://www.medworm.com/index.php?rid=5533231&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113498%26dopt%3DAbstract Authors: Bu R, Uddin S, Ahmed M, Hussain AR, Alsobhi S, Amin T, Al-Nuaim A, Al-Dayel F, Abubaker J, Bavi P, Al-Kuraya KS Abstract The Met receptor tyrosine kinase is overexpressed and/or activated in variety of human malignancies. Previously we have shown that c-Met is overexpressed in Middle Eastern Papillary Thyroid Carcinoma (PTC) and significantly associated with aggressive phenotype, but its role has not been fully elucidated in PTC. The aim was to deteremine the functional link between c-Met/AKT signaling pathway and Death Receptor 5 (DR5) in a large cohort of PTC in a tissue microarray format followed by functional studies using PTC cell lines and Nude mice. Our data show that high expression of p-Met and DR5 were significantly associated with aggressive phenotype of PTC and... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533231 Wed, 16 Nov 2011 05:00:00 +0100 5533231 http://www.medworm.com/index.php?rid=5533230&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22113499%26dopt%3DAbstract Authors: Issazadeh-Navikas S, Teimer R, Bockermann R Abstract It is no longer a myth that a balanced diet is fundamental for general health. Common dietary components including vitamins A and D, omega-3 and probiotics are now widely accepted to be essential to protect against many diseases with an inflammatory nature. On the other hand, high fat diets are documented to exert multiple deleterious effects, including fatty liver diseases. Here we discuss the effect of dietary components on regulatory T cell (Tregs) homeostasis, a central element of the immune system to prevent chronic tissue inflammation. Accordingly, evidence bearing on the impact of dietary components on diseases in which Tregs play a seminal role will be discussed. Among chronic diseases where dietary factors could... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5533230 Wed, 16 Nov 2011 05:00:00 +0100 5533230 http://www.medworm.com/index.php?rid=5439160&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105606%26dopt%3DAbstract Authors: Souza-Fonseca-Guimaraes F, Adib-Conquy M, Cavaillon JM Abstract Natural killer (NK) cells were first described as immune leukocytes able to kill tumor cells and soon after reported to kill virus-infected cells. In the mid 1980's, ten years after their discovery, NK cells were also demonstrated contributing to the fight against bacterial infection, particularly thanks to their crosstalk with other leukocytes. A wide variety of immune cells are now recognized to interact with NK cells, particularly through the production of cytokines such as IL-2, IL-12, IL-15, and IL-18, which boost NK cell activities. The recent demonstration that NK cells express pattern recognition receptors (PRRs), namely Toll-like and Nod-like receptors, led to the understanding that these cells are no... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5439160 Thu, 10 Nov 2011 05:00:00 +0100 5439160 http://www.medworm.com/index.php?rid=5439161&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105605%26dopt%3DAbstract Authors: Zhang L, Cardinal JS, Bahar R, Evankovich J, Huang H, Nace G, Billiar TR, Rosengart MR, Pan P, Tsung A Abstract The pathogenesis of sepsis is complex and unfortunately poorly understood. The cellular process of autophagy is believed to play a protective role in sepsis; however, the mechanisms responsible for its regulation in this setting are ill defined. In the present study, interferon regulatory factor-1 (IRF-1) was found to regulate the autophagic response in LPS stimulated macrophages. In vivo, tissue macrophages obtained from LPS stimulated IRF-1 knockout (KO) mice demonstrated increased autophagy and decreased apoptosis compared to those isolated from IRF-1 wild type (WT) mice. In vitro, LPS stimulated peritoneal macrophages obtained from IRF-1 KO mice experienced i... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5439161 Wed, 09 Nov 2011 05:00:00 +0100 5439161 http://www.medworm.com/index.php?rid=5439162&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105604%26dopt%3DAbstract Authors: Yang H, Lundbäck P, Ottosson L, Erlandsson-Harris H, Venereau E, Bianchi ME, Al-Abed Y, Andersson U, Tracey KJ, Antoine DJ Abstract High mobility group box 1 (HMGB1) is a nuclear protein with extracellular inflammatory cytokine activity. It is passively released during cell injury and necrosis, and actively secreted by immune cells. HMGB1 contains three conserved redox-sensitive cysteine residues: C23 and C45 can form an intra-molecular disulfide bond, whereas C106 is unpaired and is essential for the interaction with Toll-Like Receptor (TLR) 4. However, a comprehensive characterization of the dynamic redox states of each cysteine residue and of their impacts on innate immune responses is lacking. Using tandem mass-spectrometric analysis we have now established that the C... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5439162 Mon, 07 Nov 2011 05:00:00 +0100 5439162 http://www.medworm.com/index.php?rid=5439159&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22105607%26dopt%3DAbstract Authors: Wilfried P, Stefan P, Thomas L, Birgit W, Adam F, Holger B, Cornelia LF, Heribert S, Doris W Abstract Although rapidly becoming a valuable tool for gene silencing, regulation or editing in vitro, the direct transfer of siRNAs into cells is still an unsolved problem for in vivo applications. For the first time, we show that specific modifications of antisense oligomers allow autonomous passage into cell lines and primary cells without further adjuvant or coupling to a cell-penetrating peptide. For this reason, we termed the specifically modified oligonucleotides 'cell membrane-crossing oligomers' (CMCOs). CMCOs targeted to various conserved regions of HIV-1 were tested and compared to non-targeting CMCOs. Analyses of uninfected and infected cells incubated with labeled CMCO... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5439159 Mon, 07 Nov 2011 05:00:00 +0100 5439159 http://www.medworm.com/index.php?rid=5418924&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22076467%26dopt%3DAbstract Authors: Canzi L, Castellaneta V, Navone S, Nava S, Dossena M, Zucca I, Mennini T, Bigini P, Parati EA Abstract Mesenchymal stem cell (MSCs) therapy is considered one of the most promising approaches for treatment of different neurodegenerative disorders, including Amyotorophic Lateral Sclerosis (ALS). We previously characterized a sub-population of human skeletal muscle-derived stem cells (SkmSCs) with MSCs-like characteristics that are able to differentiate in to the neurogenic lineage in vitro. In the present study, we evaluated the SkmSCs'therapeutic effects in the most characterized model of spontaneous motor neuron degeneration, the Wobbler mouse (Wr). Before evaluating the therapeutic efficacy in Wr, we followed the route of SkmSCs at different times after intracerebroventri... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5418924 Fri, 04 Nov 2011 04:00:00 +0100 5418924 http://www.medworm.com/index.php?rid=5418923&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22076468%26dopt%3DAbstract Authors: Hreggvidsdóttir HS, Lundberg AM, Aveberger AC, Klevenvall L, Andersson U, Harris HE Abstract The nuclear protein HMGB1 promotes inflammation upon extracellular release. HMGB1 induces proinflammatory cytokine production in macrophages via TLR4 signaling in a redox dependent fashion. Independent of its redox state and endogenous cytokine-inducing ability, HMGB1 can form highly immunostimulatory complexes by interaction with certain proinflammatory mediators. Such complexes have the ability to enhance the induced immune response up to hundred-fold, as compared to induction by the ligand alone. In order to clarify the mechanisms for these strong synergistic effects we have here studied receptor requirements. IL-6 production was assessed in supernatants from cultured peritonea... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5418923 Fri, 04 Nov 2011 04:00:00 +0100 5418923 http://www.medworm.com/index.php?rid=5418927&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22064970%26dopt%3DAbstract CONCLUSION: We have identified a new effect of Calcitriol in FLS invasion. This discovery suggests that the reduced levels of vitamin D and its metabolites commonly seen in RA might increase risk for FLS-mediated cartilage and bone invasion and erosions. Treatment with vitamin D or its analogs has the potential to become a helpful adjuvant aimed at preventing or reducing joint destruction. PMID: 22064970 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5418927 Wed, 02 Nov 2011 04:00:00 +0100 5418927 http://www.medworm.com/index.php?rid=5418926&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22064971%26dopt%3DAbstract Authors: Wang H, Wang ZH, Kong J, Yang MY, Jiang GH, Wang XP, Zhong M, Zhang Y, Deng JT, Zhang W Abstract The fundamental mechanisms that underlie platelet activation in atherothrombosis are still obscure. Oxidative stress is involved in central features of atherosclerosis. Platelet-derived microvesicles (PMVs) could be important mediators between oxidative stress and platelet activation. CD36 could be a receptor of PMVs, thus generating a PMV-CD36 complex. We aimed to investigate the detailed pathway by which oxidative damage contributes to platelet activation by the PMV-CD36 complex. We found that oxidized low-density lipoprotein (oxLDL) stimulated the generation of PMVs. PMVs enhanced normal platelet activation, as assessed by the expression of integrin α(IIb)β(3), secretion o... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5418926 Wed, 02 Nov 2011 04:00:00 +0100 5418926 http://www.medworm.com/index.php?rid=5418925&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22064972%26dopt%3DAbstract Authors: Zhao GJ, Yin K, Fu YC, Tang CK Abstract Reverse cholesterol transport (RCT) has been characterized as a crucial step for anti-atherosclerosis, which is initiated by ATP-binding cassette A1 (ABCA1) to mediate the efflux of cellular phospholipids and cholesterol to lipid-free apolipoprotein A-I (apoA-I), however, the mechanisms underlying apoA-I/ABCA1 interaction to lead to the lipidation of apoA-I are poorly understood. There are several models proposed for the interaction of apoA-I with ABCA1 as well as lipidation of apoA-I mediated by ABCA1. ApoA-I markedly increases the levels of ABCA1 protein, ABCA1 inturn can stabilize apoA-I. The interaction of apoA-I with ABCA1 could activate signaling molecules that modulate post-translational ABCA1 activity or lipid transport activ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5418925 Wed, 02 Nov 2011 04:00:00 +0100 5418925 http://www.medworm.com/index.php?rid=5379198&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22045221%26dopt%3DAbstract Authors: Ahmed MN, Zhang Y, Codipilly C, Zaghloul N, Patel D, Wolin M, Miller EJ Abstract Hypoxia leads to free radical production which has a pivotal role in the pathophysiology of pulmonary hypertension (PH). We hypothesized that treatment with extracellular superoxide dismutase (EC-SOD) could ameliorate the development of PH induced by hypoxia. In vitro studies using pulmonary microvascular endothelial cells showed that cells transfected with EC-SOD had significantly less accumulation of xanthine oxidase and reactive oxygen species compared to non-transfected cells after hypoxia exposure for 24 hour. To study the prophylactic role of EC-SOD, adult male wild type (WT) and transgenic mice (TG), with lung-specific overexpression of hEC-SOD, were exposed to FiO(2)10% for 10d. After ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379198 Fri, 28 Oct 2011 04:00:00 +0100 5379198 http://www.medworm.com/index.php?rid=5379199&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22033729%26dopt%3DAbstract Authors: Klinker MW, Lundy SK Abstract Suppression of the immune system following the resolution of infection or inflammation is an important process that limits immune-mediated pathogenesis and autoimmunity. Several mechanisms of immune suppression have received a great deal of attention in the past three decades. These include mechanisms related to suppressive cytokines, IL-10 and TGFβ, produced by regulatory cells, and mechanisms related to apoptosis mediated by death ligands, FasL and TRAIL, expressed by killer or cytotoxic cells. Despite many lines of evidence supporting an important role for B lymphocytes as both regulatory and killer cells in many inflammatory settings, relatively little attention has been given to understanding the biology of these cells, their relative im... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379199 Mon, 24 Oct 2011 04:00:00 +0100 5379199 http://www.medworm.com/index.php?rid=5379200&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22033676%26dopt%3DAbstract Authors: Tsukimura T, Kawashima I, Togawa T, Kodama T, Suzuki T, Watanabe T, Chiba Y, Jigami Y, Fukushige T, Kanekura T, Sakuraba H Abstract To economically produce recombinant human α-galactosidase A (GLA) with a cell culture system that does not require bovine serum, we chose methylotrophic yeast cells with the OCH1 gene deleted and overexpressing the MNN4 gene as a host cell line. The enzyme (yr-hGLA) produced with the gene-manipulated yeast cells has almost the same enzymological parameters as those of the recombinant human GLA produced with cultured human fibroblasts (agalsidase alfa), which is currently used for enzyme replacement therapy for Fabry disease. However, the basic structures of their sugar chains are quite different. yr-hGLA has a high content of phosphorylated N... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379200 Fri, 21 Oct 2011 04:00:00 +0100 5379200 http://www.medworm.com/index.php?rid=5379202&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22033674%26dopt%3DAbstract This study evaluates in vivo cellular and molecular modifications induced by irinotecan, a topoisomerase I-directed agent, in patient-derived colon tumors subcutaneously implanted in athymic nude mice. Irinotecan was given at 40 mg/kg i.p. q5dx5 and expression profiles were evaluated at day 25 in tumors from treated and untreated animal. Unexpectedly, the in vivo antitumor activity of irinotecan was closely linked to a downregulation of hypoxia-inducible factor-1alpha (HIF1A)-target genes along with an inhibition of HIF1A protein accumulation. The consequence was a decrease in tumor angiogenesis leading to tumor size stabilization. These results highlight molecular basis for the antitumor activity of a widely used anticancer agent and the method used opens the way for mechanistic studies o... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379202 Wed, 19 Oct 2011 04:00:00 +0100 5379202 http://www.medworm.com/index.php?rid=5379201&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22033675%26dopt%3DAbstract In conclusion, this study shows that inhibition of SHIP1 and SHIP2 may have broad clinical application in the treatment of multiple tumors. PMID: 22033675 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379201 Wed, 19 Oct 2011 04:00:00 +0100 5379201 http://www.medworm.com/index.php?rid=5379204&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22027904%26dopt%3DAbstract We present evidence suggesting TF plays a detrimental role in this disease via signal transduction dependent KC production in colon epithelial cells, which provokes granulocyte influx leading to subsequent inflammation and organ damage. We agree with Gambone et al. that experiments using genetically modified mice should ideally be performed with littermate controls. Unfortunately, intercrosses of 50% TF mice are problematic and employing this strategy resulted in insufficient TFlow (1%) mice within a similar age category as littermate wildtype controls. Consequently, we opted for an experimental set-up in which littermate 1% and 50% TF mice were compared with non-littermate C57Bl/6 wildtypes. The 1 and 50% TF mice had been backcrossed for 6 generations with C57BL/6 mice and are thus largel... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379204 Tue, 18 Oct 2011 04:00:00 +0100 5379204 http://www.medworm.com/index.php?rid=5379203&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22027905%26dopt%3DAbstract Comment on "Tissue factor-dependent chemokine production aggravates experimental colitis' Mol Med. 2011 Oct 18; Authors: Gambone JE, Owens Iii AP, Mackman N Abstract The article by Queiroz and colleagues in the September-October 2011 issue of Molecular Medicine (1) uses a genetic approach to examine the role of tissue factor (TF) in colitis. The authors conclude that TF contributes to colitis by enhancing KC expression leading to granulocyte recruitment. Three experimental groups of mice are used: C57BL/6; TF(+/-)/hTF(+) (50% mice); and TF(-/-)/hTF(+) (1% mice). The 50% and 1% mice generated by our laboratory (2) are on a genetic background that is not fully C57BL/6. These mice were created by backcrossing 6 generations with C57BL/6 mice. However, an increase in spontaneous... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379203 Tue, 18 Oct 2011 04:00:00 +0100 5379203 http://www.medworm.com/index.php?rid=5379205&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22009279%26dopt%3DAbstract Authors: Zitta K, Meybohm P, Bein B, Heinrich C, Renner J, Cremer J, Steinfath M, Scholz J, Albrecht M Abstract Remote ischemic preconditioning (RIPC) can be induced by transient occlusion of blood flow to a limb with a blood-pressure cuff and exerts multiorgan protection from ischemia/reperfusion (I/R) injury. I/R-injury in the intestinal tract leads to intestinal barrier dysfunction and can result in multiple organ failure. Here we employed an intestinal cell line (CaCo-2) to evaluate the effects of RIPC conditioned patient sera on hypoxia-induced cell damage in-vitro and to identify serum factors that mediate RIPC effects. Patient sera (N=10) derived before RIPC (T0), directly after RIPC (T1) and 1h after RIPC (T2) were added to the culture medium at the onset of hypoxia until 4... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379205 Fri, 14 Oct 2011 04:00:00 +0100 5379205 http://www.medworm.com/index.php?rid=5379206&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22009278%26dopt%3DAbstract Authors: Gochuico BR, Huizing M, Golas GA, Scher CD, Tsokos M, Denver SD, Frei-Jones MJ, Gahl WA Abstract Pulmonary fibrosis develops in Hermansky-Pudlak syndrome (HPS) types 1 and 4. Limited information is available about lung disease in HPS type 2 (HPS-2), which is characterized by abnormal function of the adaptor protein-3 (AP-3) complex. To define lung disease in HPS-2, one child and two adults with HPS-2 were evaluated at the National Institutes of Health on at least two visits, and another child was evaluated at University of Texas Health Science Center San Antonio. All four subjects with HPS-2 had findings of interstitial lung disease (ILD) on high-resolution computed tomography scan of the chest. The predominant feature was ground glass opacification. Subject 1, a fourteen ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379206 Wed, 12 Oct 2011 04:00:00 +0100 5379206 http://www.medworm.com/index.php?rid=5379208&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21989947%26dopt%3DAbstract Authors: Dou GR, Wang L, Wang YS, Han H Abstract Ocular angiogenesis, characterized by the formation of new blood vessels in the avascular area in eyes, is a highly coordinated process involved in retinal vasculature formation and several ocular diseases such as age-related macular degeneration (AMD), proliferative diabetic retinopathy (PDR) and retinopathy of prematurity (ROP). This process is orchestrated by complicated cellular interactions and vascular growth factors, during which endothelial cells acquire heterogeneous phenotypes and distinct cellular destinations. To date, while vascular endothelial growth factor has been identified as the most critical angiogenic agent with a remarkable therapeutic value, the Notch signaling pathway appears to be a similarly important regula... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379208 Wed, 05 Oct 2011 04:00:00 +0100 5379208 http://www.medworm.com/index.php?rid=5379207&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21989948%26dopt%3DAbstract Authors: He G, Hu J, Li T, Ma X, Meng J, Jia M, Lu J, Ohtsu H, Chen Z, Luo X Abstract The role of histamine as a newly recognized sympathetic neurotransmitter has been presented previously, and its postsynaptic effects greatly depended on the activities of sympathetic nerves. Cardiac sympathetic nerves become overactivated under acute myocardial ischemic conditions and release neurotransmitters in large amounts, inducing ventricular arrhythmia. Therefore, it is proposed that cardiac sympathetic histamine, in addition to norepinephrine, may have a significant arrhythmogenic effect. To test this hypothesis, we observed the release of cardiac sympathetic histamine and associated ventricular arrhythmogenesis that was induced by acute ischemia in isolated mouse hearts. Mast cell deficie... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5379207 Wed, 05 Oct 2011 04:00:00 +0100 5379207 http://www.medworm.com/index.php?rid=5296197&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21979753%26dopt%3DAbstract Authors: Fecteau JF, Bharati IS, O'hayre M, Handel TM, Kipps TJ, Messmer D Abstract We have previously shown that sorafenib, a multi-kinase inhibitor, exhibits cytotoxic effects on CLL cells. Since the cellular microenvironment can protect CLL cells from drug-induced apoptosis it is important to evaluate the effect of novel drugs in this context. Here we characterized the in vitro cytotoxic effects of sorafenib on CLL cells and the underlying mechanism in the presence of marrow stromal cells (MSCs) and nurse-like cells (NLCs). One single dose of 10 μM or the repeated addition of 1 μM sorafenib caused caspase-dependent apoptosis and reduced levels of phosphorylated B-RAF, C-RAF, ERK, STAT3, and Mcl-1 in CLL cells in the presence of the microenvironment. We show that the RAF/MEK/ER... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5296197 Tue, 04 Oct 2011 04:00:00 +0100 5296197 http://www.medworm.com/index.php?rid=5296198&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21979752%26dopt%3DAbstract Authors: Yan K, Deng X, Zhai X, Zhou M, Jia X, Luo L, Niu M, Zhu H, Qiang H, Zhou Y Abstract Leptin, a key hormone in regulating energy homeostasis, is mainly produced by adipocyte. Cogent evidence indicates a unique role of leptin in the promotion of liver fibrosis. Hepatic stellate cell (HSC) activation is a pivotal step in the process of liver fibrosis. Sterol regulatory element binding protein-1c (SREBP-1c), a critical transcription factor for lipid synthesis and adipocyte differentiation, function as a key transcription factor in inhibition of HSC activation. SREBP-1c is highly expressed in quiescent HSC and down-regulated upon HSC activation. The aim of this study is to examine the effect of leptin on SREBP-1c gene expression in HSCs in vitro and in vivo and elucidate the und... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5296198 Mon, 03 Oct 2011 04:00:00 +0100 5296198 http://www.medworm.com/index.php?rid=5276794&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21923696%26dopt%3DAbstract Conclusions  Sitagliptin significantly improved overall glucose control, including postprandial and 24-h glucose control, in adult patients with Type 1 diabetes, while significantly reducing prandial insulin requirements. Further investigation is warranted in patients with Type 1 diabetes in a larger cohort designed to assess both clinical outcomes and mechanism of action. PMID: 21923696 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5276794 Sat, 01 Oct 2011 04:00:00 +0100 5276794 http://www.medworm.com/index.php?rid=5276793&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21953418%26dopt%3DAbstract Authors: Chu CC, Zhang L, Dhayalan A, Agagnina BM, Magli AR, Fraher G, Didier S, Johnson LP, Kennedy WJ, Damle RN, Yan XJ, Patten PE, Teichberg S, Koduru P, Kolitz JE, Allen SL, Rai KR, Chiorazzi N Abstract An infectious etiology has been proposed for many human cancers, but rarely have specific agents been identified. One difficulty has been the need to propagate cancer cells in vitro to produce the infectious agent in detectable quantity. We hypothesized that genome amplification from small numbers of cells could be adapted to circumvent this difficulty. A patient with concomitant chronic lymphocytic leukemia (CLL) and polycythemia vera (PV) requiring therapeutic phlebotomy donated a large amount of phlebotomized blood to test this possibility. Using genome amplification methods,... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5276793 Wed, 21 Sep 2011 04:00:00 +0100 5276793 http://www.medworm.com/index.php?rid=5276792&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21953419%26dopt%3DAbstract CONCLUSION: Analysis of activation patterns stratified by performance accuracy, differences in co-morbid disease, corticosteroid doses or disease activity suggest that these observed differences are attributable to SLE effects on the central nervous system (CNS) exclusive of vascular disease or other confounding influences. Our hypothesis is further supported by the lack of correlation between regional brain abnormalities on fMRI and the SLICC damage index. PMID: 21953419 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5276792 Wed, 21 Sep 2011 04:00:00 +0100 5276792 http://www.medworm.com/index.php?rid=5276791&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21953420%26dopt%3DAbstract This study investigates the direct effect of SAA on promoting the formation of atherosclerosis in apolipoprotein E-deficient (ApoE(-/-)) mice. Murine SAA lentivirus was constructed and injected into ApoE(-/-) mice intravenously. Then, experimental mice were fed a chow diet (5% fat and no added cholesterol) for 14 weeks. Aortic atherosclerotic lesion area was larger with than without SAA treatment. With increased SAA level, the plasma levels of interleukin-6 and tumor necrosis factor-α were significantly increased. Macrophage infiltration in atherosclerotic regions was enhanced with SAA treatment. Migration assay revealed prominent dose-dependent chemotaxis of SAA to macrophages. Furthermore, the expression of monocyte chemotactic protein-1 and vascular cell adhesion molecule-1 (VCAM-1) wa... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5276791 Wed, 21 Sep 2011 04:00:00 +0100 5276791 http://www.medworm.com/index.php?rid=5218365&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21604128%26dopt%3DAbstract Authors: Schilling O, auf dem Keller U, Overall CM Abstract Protease specificity profiling using proteome-derived, database-searchable peptide libraries is a novel approach to define the active site specificity of proteolytic enzymes we call PICS (Proteomic Identification of protease Cleavage Sites). Proteome-derived peptide libraries are generated by trypsin, GluC, or chymotrypsin digestion of biologically relevant proteomes, such as cytosolic lysates, to generate three separate libraries that each differ from the others in their C-terminal amino acid residues according to the protease specificity. Primary amines of all peptides are then chemically protected so that after incubation with a test protease, the neo-N-termini of the prime-side cleavage products with exposed α-amines ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218365 Wed, 14 Sep 2011 12:24:03 +0100 5218365 http://www.medworm.com/index.php?rid=5218364&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21912807%26dopt%3DAbstract CONCLUSION: DGF is a poor marker for organ quality and transplant outcome. In contrast, pre-implant gene expression profiles identify "poor quality" grafts and may eventually improve organ allocation. PMID: 21912807 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218364 Tue, 06 Sep 2011 04:00:00 +0100 5218364 http://www.medworm.com/index.php?rid=5218362&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21912809%26dopt%3DAbstract Authors: Karamouzis MV, Papavassiliou AG Abstract It has long been shown that many of the presently used anticancer drugs exert their effects partly through modulating the activity of vital transcription factors. The intricacy of transcriptional regulation still represents the main obstacle for the design of transcription factor-directed agents. Systematic mapping of tumor-specific transcriptional networks and application of new molecular tools have reinforced research interest and efforts on this venue. The case of breast cancer is discussed as a representative example. PMID: 21912809 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218362 Tue, 06 Sep 2011 04:00:00 +0100 5218362 http://www.medworm.com/index.php?rid=5218363&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21912808%26dopt%3DAbstract Authors: Ehrenreich H, Kästner A, Weissenborn K, Streeter J, Sperling S, Wang KK, Worthmann H, Hayes RL, Von Ahsen N, Kastrup A, Jeromin A, Herrmann M Abstract The German Multicenter EPO Stroke Trial, investigating safety and efficacy of erythropoietin (EPO) treatment in ischemic stroke, had formally to be declared a negative study. Exploratory subgroup analysis, however, revealed that patients not receiving thrombolysis most likely benefited from EPO regarding clinical recovery - a result reproducing findings of the Göttingen EPO Stroke Study. The present work investigated whether the positive signal on clinical outcome in this patient subgroup is mirrored by respective post-stroke biomarker profiles. All patients of the German Multicenter EPO Stroke Trial non-qualifying for thr... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5218363 Fri, 02 Sep 2011 04:00:00 +0100 5218363 http://www.medworm.com/index.php?rid=5141112&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843303%26dopt%3DAbstract Conclusions  Despite increased age, parity, obesity and social disadvantage, women with Type 2 diabetes had better glycaemic control, fewer large-for-gestational-age infants, fewer preterm deliveries and fewer neonatal care admissions. Better tools are needed to improve glycaemic control and reduce the rates of large for gestational age, particularly in Type 1 diabetes. PMID: 21843303 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5141112 Fri, 19 Aug 2011 18:14:19 +0100 5141112 http://www.medworm.com/index.php?rid=5141111&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843305%26dopt%3DAbstract Conclusions  Results of this observational study demonstrate combined glycaemic and health-related quality of life benefits of initiating insulin glargine in patients with Type 2 diabetes in routine primary care. PMID: 21843305 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5141111 Fri, 19 Aug 2011 18:14:15 +0100 5141111 http://www.medworm.com/index.php?rid=5141110&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21843308%26dopt%3DAbstract Discussion  These data highlight the economic and clinical benefits of moderate weight loss in Type 2 diabetes. PMID: 21843308 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5141110 Fri, 19 Aug 2011 18:14:10 +0100 5141110 http://www.medworm.com/index.php?rid=5141117&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21196696%26dopt%3DAbstract CONCLUSION: TOR treatment did not increase intracellular concentrations of triglyceride, although TAM treatment did so. PMID: 21196696 [PubMed - indexed for MEDLINE] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5141117 Fri, 19 Aug 2011 18:14:03 +0100 5141117 http://www.medworm.com/index.php?rid=5141113&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21833457%26dopt%3DAbstract Authors: Holden NJ, Savage CO, Young SP, Wakelam MJ, Harper L, Williams JM Abstract Dysregulated release of neutrophil azurophilic granules causes increased tissue damage and amplified inflammation during autoimmune disease. Anti-neutrophil cytoplasmic antibodies (ANCA) are implicated in the pathogenesis of small vessel vasculitis and promote adhesion and exocytosis in neutrophils. ANCA activate specific signal transduction pathways in neutrophils that have the potential to be modulated therapeutically to prevent neutrophil activation by ANCA. We have investigated a role for diacylglycerol kinase (DGK) and its downstream product phosphatidic acid (PA) in ANCA induced neutrophil exocytosis. Neutrophils incubated with the DGK inhibitor R59022, prior to treatment with ANCA, exhibited ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5141113 Sun, 07 Aug 2011 23:00:00 +0100 5141113 http://www.medworm.com/index.php?rid=5141114&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21826374%26dopt%3DAbstract Authors: Wang N, Shen N, Vyse TJ, Anand V, Gunnarson I, Sturfelt G, Rantapää-Dahlqvist S, Elvin K, Truedsson L, Andersson BA, Dahle C, Ortqvist E, Gregersen PK, Behrens TW, Hammarström L Abstract Selective IgA deficiency (IgAD) is the most common primary immunodeficiency in Caucasians. It has previously been suggested to be associated with a variety of concomitant autoimmune diseases. In this review, we present data on the prevalence of IgAD in patients with Graves' disease (GD), systemic lupus erythematosus (SLE), type 1 diabetes (T1D), celiac disease (CD), myasthenia gravis (MG) and rheumatoid arthritis (RA) based both on our own, recent, large scale screening results and literature data. Genetic factors are important for the development of both IgAD and various autoimmune dis... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5141114 Wed, 03 Aug 2011 23:00:00 +0100 5141114 http://www.medworm.com/index.php?rid=5141116&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21826372%26dopt%3DAbstract This study demonstrates that insertional mutagenesis can contribute to immortalization of mature T cells, although this is a rare event. Furthermore, the results show that signaling of the IL-2 receptor and the proto-oncogene LMO2 can act synergistically in malignization of mature T lymphocytes. PMID: 21826372 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5141116 Tue, 26 Jul 2011 23:00:00 +0100 5141116 http://www.medworm.com/index.php?rid=5141115&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21826373%26dopt%3DAbstract In this study, we further found that endogenous levels of let-7b and let-7i miRNAs are inversely correlated with levels of estrogen receptor (ER)-α36, a new variant of ER-α66, in the FFPE tissue set. Bioinformatic analysis suggested that ER-α36 may be another target of let-7 miRNAs. To test this hypothesis, co-transfection of let-7 mimics or inhibitors together with full-length or a fragment of ER-α36 3' UTR luciferase construct was performed, and we found that let-7b and i mimics suppressed significantly the activity of reporter gene, which was enhanced remarkably by let-7b and i inhibitors. Both mRNA and protein expression of ER-α36 were inhibited by let-7 mimics and enhanced by let-7 inhibitors. Furthermore, ER-α36 mediated non-genomic MAPK and Akt pathways were weakened by let-7b... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5141115 Tue, 26 Jul 2011 23:00:00 +0100 5141115 http://www.medworm.com/index.php?rid=5097507&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21792478%26dopt%3DAbstract Authors: Wang Y, Wang DH To investigate the effects of the transient receptor potential vanilloid type 1 (TRPV1) channel on renal extracellular matrix (ECM) protein expression including collagen deposition and the TGF-β/Smad signaling pathway during salt-dependent hypertension, wild-type (WT) and TRPV1-null mutant (TRPV1(-/-)) mice were uninephrectomized and given deoxycorticosterone acetate (DOCA)-salt for 4 weeks. TRPV1 gene ablation exaggerated DOCA-salt-induced impairment of renal function as evidenced by increased albumin excretion (μg/24 h) compared to WT mice (83.7±7.1 vs. 28.3±4.8, P<0.05), but had no apparent effect on mean arterial pressure (mmHg) as determined by radiotelemetry (141±4 vs. 138±3, P>0.05). Morphological analysis showed that DOCA-salt-induced glomer... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097507 Thu, 21 Jul 2011 23:00:00 +0100 5097507 http://www.medworm.com/index.php?rid=5097460&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21792480%26dopt%3DAbstract Authors: Nolte A, Walker T, Schneider M, Deniz O, Avci-Adali M, Ziemer G, Wendel HP Over recent years, drug eluting stents have demonstrated new concepts to improve outcomes of intravascular interventions. A novel technique may arise by designing gene silencing stents that elute specific siRNAs for better vascular wall regeneration. Although siRNAs have surpassed expectations in in vitro experiments to alter gene expression, the functional and local delivery of siRNAs is still the major obstacle for the in vivo application of RNAi. This preliminary in vitro study describes a surface immobilized siRNA delivery technique that would be readily adaptable for local intravascular applications in vivo.The transfection potency of gelatin coatings consisting of a specific siRNA complexed with p... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097460 Thu, 21 Jul 2011 23:00:00 +0100 5097460 http://www.medworm.com/index.php?rid=5097477&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21792479%26dopt%3DAbstract Authors: Bond JE, Bergeron A, Thurlow P, Selim MA, Bowers EV, Kuang A, Levinson H Aberrant fibroblast migration in response to fibrogenic peptides plays a significant role in keloid pathogenesis. Angiotensin II (Ang II) is an octapeptide hormone recently implicated as a mediator of organ fibrosis and cutaneous repair. Ang II promotes cell migration but its role in keloid fibroblast phenotypic behavior has not been studied. Here, we investigated Ang II signaling in keloid fibroblast behavior as a potential mechanism of disease. Primary human keloid fibroblasts were stimulated to migrate in the presence of Ang II and Ang II receptor 1 (AT(1)), Ang II receptor 2 (AT(2)), or non muscle myosin II (NMM II) antagonists. Keloid and surrounding normal dermis was immunostained for NMM IIA, NMM I... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097477 Wed, 20 Jul 2011 23:00:00 +0100 5097477 http://www.medworm.com/index.php?rid=5097568&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21785809%26dopt%3DAbstract Authors: Liu Y, Sun L, Pan Z, Bai Y, Wang N, Zhao J, Xu C, Li Z, Li B, Du Z, Lu Y, Gao X, Yang B The present study was designed to investigate the cardiac beneficial effects of M(3) muscarinic receptor (M(3)-mAChR) over-expression and whether these effects are related to the regulation of the inward rectifying K(+) channel by microRNA-1 (miR-1) in a conditional over-expression mouse model. A cardiac-specific M(3)-mAChR transgenic mouse model was successfully established for the first time in this study using microinjection, and the over-expression was confirmed by both RT-PCR and Western blot techniques. We demonstrated that M(3)-mAChR over-expression dramatically reduced the incidence of arrhythmias and decreased the mortality in a mouse model of myocardial ischemia-reperfusion (I/R).... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097568 Tue, 12 Jul 2011 23:00:00 +0100 5097568 http://www.medworm.com/index.php?rid=5097561&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21785810%26dopt%3DAbstract Authors: Ghiotto F, Marcatili P, Tenca C, Calevo MG, Yan XJ, Albesiano E, Bagnara D, Colombo M, Cutrona G, Chu CC, Morabito F, Bruno S, Ferrarini M, Tramontano A, Fais F, Chiorazzi N B-cell chronic lymphocytic leukemia (CLL) patients display leukemic clones bearing either germline or somatically mutated IGHV genes. Most information on CLL Igs, such as the definition of stereotyped BCRs, was derived from germline unmutated Igs. In particular, detailed studies on the distribution and nature of mutations in paired heavy and light chain domains of CLL clones bearing mutated Igs are lacking. To address the somatic hypermutation dynamics of CLL Igs, we analyzed the mutation pattern of paired IGHV-D-J and IGK/LV-J rearrangements of 193 leukemic clones that displayed ≥ 2% mutations in at lea... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097561 Tue, 12 Jul 2011 23:00:00 +0100 5097561 http://www.medworm.com/index.php?rid=5097513&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21785811%26dopt%3DAbstract Authors: Li L, Miao Z, Liu R, Yang M, Liu H, Yang G Liraglutide is a glucagon-like peptide-1 (GLP-1) analogue that reduces blood glucose levels, increases insulin secretion, and improves insulin sensitivity through mechanisms have not been completely understood. Therefore, we aimed to evaluate the metabolic impact and underlying mechanisms of liraglutide in a hypoadiponectinemia and high fat diet (HFD)-induced insulin resistance (IR) model. Adiponectin gene targeting was achieved using adenovirus-transduced RNAi and was used to lower plasma adiponectin levels, and liraglutide (1mg/kg ) was given twice daily for eight weeks to HFD fed ApoE(-/-) mice. Insulin sensitivity was examined by euglycaemic-hyperinsulinaemic clamp. Gene mRNA and protein expressions were measured by Quantitative r... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5097513 Sun, 10 Jul 2011 23:00:00 +0100 5097513 http://www.medworm.com/index.php?rid=5000851&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21712799%26dopt%3DAbstract Authors: Norrby KC The adult rat mesentery window angiogenesis assay is biologically appropriate and is exceptionally well suited to the study of sprouting angiogenesis in vivo [see review papers], which is the dominating form of angiogenesis in human tumors and non-tumor tissues, as discussed in invited review papers(1,2). Angiogenesis induced in the membranous mesenteric parts by intraperitoneal (i.p.) injection of a pro-angiogenic factor can be modulated by subcutaneous (s.c.), intravenous (i.v.) or oral (p.o.) treatment with modifying agents of choice. Each membranous part of the mesentery is translucent and framed by fatty tissue, giving it a window-like appearance. The assay has the following advantageous features: (i) the test tissue is natively vascularized, albeit sparsely, an... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5000851 Thu, 07 Jul 2011 08:45:03 +0100 5000851 http://www.medworm.com/index.php?rid=5000850&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21717034%26dopt%3DAbstract Authors: Fabelo N, Martín V, Santpere G, Marín R, Torrent L, Ferrer I, Díaz M SUMMARY: Lipid rafts are cholesterol- and sphingomyelin-enriched microdomains that provide a highly saturated and viscous physicochemical microenvironment to promote protein-lipid and protein-protein interactions. We have purified lipid rafts from human frontal cortex from normal, early motor stages of Parkinson disease (PD) and incidental Parkinson disease (iPD) subjects, and analyzed their lipid composition. We have observed that lipid rafts from PD and iPD cortices exhibit dramatic reductions in their contents of n-3 and n-6 LCPUFA, especially docosahexaenoic acid (22:6-n3) and arachidonic acid (20:4n-6). Also, saturated fatty acids (16:0 and 18:0) were significantly higher than in control brains. Paral... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5000850 Tue, 21 Jun 2011 23:00:00 +0100 5000850 http://www.medworm.com/index.php?rid=5000849&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21717035%26dopt%3DAbstract Authors: Queiroz KC, Van 't Veer C, Van Den Berg Y, Duitman J, Versteeg HH, Aberson HL, Groot AP, Verstege MI, Roelofs JJ, Te Velde AA, Spek CA Tissue factor (TF) is traditionally known as the initiator of blood coagulation but TF also exerts an important role in inflammatory processes. Considering the pivotal role of coagulation in inflammatory bowel disease, we assessed whether genetic ablation of TF limits experimental colitis. To this end, wildtype and TF deficient (TFlow) mice were treated with 1.5% DSS for 7 days and effects on disease severity, cytokine production and leukocyte recruitment were examined. Clinical and histological parameters showed that the severity of colitis was reduced in both heterozygous and homozygous TFlow mice compared to controls. Most notably, edema, gr... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5000849 Tue, 21 Jun 2011 23:00:00 +0100 5000849 http://www.medworm.com/index.php?rid=5000853&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21695351%26dopt%3DAbstract CONCLUSION: At high doses P4 effectively inhibits the growth of solid neuroblastoma tumor, has high bioavailability, selective toxicity and a high margin of safety, making it a possible candidate for further study as a potential clinical treatment of neuroblastoma. PMID: 21695351 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5000853 Thu, 16 Jun 2011 23:00:00 +0100 5000853 http://www.medworm.com/index.php?rid=5000852&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21695352%26dopt%3DAbstract Authors: Chaung WW, Wu R, Ji Y, Wang Z, Dong W, Cheyuo C, Qi L, Qiang X, Wang H, Wang P Stroke is a leading cause of death and the primary medical cause of acquired adult disability worldwide. The progressive brain injury after acute stroke is partly mediated by ischemia-elicited inflammatory responses. The vasoactive hormone adrenomedullin (AM), upregulated under various inflammatory conditions, counter-balances inflammatory responses. However, regulation of AM activity in ischemic stroke remains largely unknown. Recent studies have demonstrated the presence of a specific AM binding protein (i.e., AMBP-1) in mammalian blood. AMBP-1 potentiates AM biological activities. Using a rat model of focal cerebral ischemia induced by permanent middle cerebral artery occlusion (MCAO), we found t... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5000852 Thu, 16 Jun 2011 23:00:00 +0100 5000852 http://www.medworm.com/index.php?rid=4955309&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21687917%26dopt%3DAbstract Authors: Bogachev O, Majdalawieh A, Pan X, Zhang L, Ro HS Atherogenesis is a long-term process that involves inflammatory response coupled with metabolic dysfunction. Foam cell formation and macrophage inflammatory response are two key events in atherogenesis. Adipocyte enhancer-binding protein 1 (AEBP1) has been shown to impede macrophage cholesterol efflux, promoting foam cell formation, via PPARγ1 and LXRα down-regulation. Moreover, AEBP1 has been shown to promote macrophage inflammatory responsiveness by inducing NF-κB activity via IκBα down-regulation. LPS-induced suppression of pivotal macrophage cholesterol efflux mediators, leading to foam cell formation, has been shown to mediate by AEBP1. Herein, we showed that AEBP1-transgenic mice (AEBP1(TG)) with macrophage-specific A... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4955309 Mon, 13 Jun 2011 23:00:00 +0100 4955309 http://www.medworm.com/index.php?rid=4955310&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21670849%26dopt%3DAbstract Authors: Liao YC, Wang YS, Guo YC, Ozaki K, Tanaka T, Lin HF, Chang MH, Chen KC, Yu ML, Sheu SH, Juo SH The BRCA-1 associated protein gene (BRAP) was recently identified as a susceptibility gene for myocardial infarction (MI). The present study aims at deciphering (1) the association between the BRAP polymorphism and carotid atherosclerosis, and (2) the mechanism beneath its pro-atherogenic effect. A total of 1749 stroke/MI-free volunteers received carotid ultrasonic examinations for the measurement of intimal-medial thickness (IMT) and plaque. The promoter polymorphism rs11066001 was selected because it affected the transcription of BRAP. We found that the GG genotype was associated with a 1.58-fold increased risk for having at least one plaque in comparison to the A allele carriers (... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4955310 Thu, 09 Jun 2011 23:00:00 +0100 4955310 http://www.medworm.com/index.php?rid=4955312&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21670847%26dopt%3DAbstract Authors: Medina RJ, O'neill CL, O'doherty TM, Knott H, Guduric-Fuchs J, Gardiner TA, Stitt AW Endothelial progenitor cells (EPCs) promote angiogenesis and clinical trials have shown such cell therapy to be feasible for treating ischaemic disease. However clinical outcomes have been contradictory due to the diverse range of EPC types used. We recently characterised two EPC subtypes, and identified outgrowth endothelial cells (OECs) as the only EPC type with true progenitor and endothelial characteristics. By contrast, MACs were shown to be monocytic cells without endothelial characteristics despite being widely described as "EPCs". In the current study we demonstrate that, although MACs do not become endothelial cells or directly incorporate into a microvascular network; they can signif... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4955312 Tue, 07 Jun 2011 23:00:00 +0100 4955312 http://www.medworm.com/index.php?rid=4955311&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21670848%26dopt%3DAbstract Authors: Galit S, Hadas M, Eyal O, Mark M, Avishag A, Lewis EC Anti-inflammatory clinical-grade, plasma-derived human alpha-1 antitrypsin (hAAT) protects islets from allorejection, as well as from autoimmune destruction. hAAT was also shown to interfere with disease progression in experimental autoimmune encephalomyelitis (EAE) and in collagen-induced arthritis (CIA) mouse models. hAAT increases IL-1 receptor antagonist expression in human mononuclear cells, and T-regulatory cell population size in animal models. Clinical-grade hAAT contains plasma impurities, multiple hAAT isoforms and various states of inactive hAAT. We thus wished to establish islet-protective activities and effect on Tregs of plasmid-derived circulating hAAT in whole animals. The previously reported plasmid, pEF-hA... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4955311 Tue, 07 Jun 2011 23:00:00 +0100 4955311 http://www.medworm.com/index.php?rid=4955314&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21666956%26dopt%3DAbstract Authors: Schierbeck H, Lundbäck P, Palmblad K, Klevenvall L, Erlandsson-Harris H, Andersson U, Ottosson L HMGB1 is a DNA-binding nuclear protein that can be released from dying cells and activated myeloid cells. Extracellularly, HMGB1 promotes inflammation. Experimental studies demonstrate HMGB1 to be a pathogenic factor in many inflammatory conditions including arthritis. HMGB1-blocking therapies in arthritis models alleviate disease and confer significant protection against cartilage and bone destruction. So far, the most successful HMGB1-targeted therapies have been demonstrated with HMGB1-specific polyclonal antibodies and with recombinant A Box protein, a fragment of HMGB1. The present study is the first to evaluate the potential of a monoclonal anti-HMGB1 antibody (2G7, mouse Ig... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4955314 Mon, 06 Jun 2011 23:00:00 +0100 4955314 http://www.medworm.com/index.php?rid=4955313&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21666957%26dopt%3DAbstract Authors: Menzel CL, Sun Q, Loughran PA, Pape HC, Billiar TR, Scott MJ Adaptive immune responses are induced in liver after major stresses such as hemorrhagic shock (HS) and trauma. There is emerging evidence that the inflammasome, the multiprotein platform that induces caspase-1 activation and promotes IL1β and IL18 processing, is activated in response to cellular oxidative stress, such as after hypoxia, ischemia and HS. Additionally, danger-associated molecular patterns (DAMPs) such as those released following injury, have been shown to activate the inflammasome and caspase-1 through the NOD-like receptor (NLR) NLRP3. However, the role of the inflammasome in organ injury following HS and trauma is unknown. We therefore investigated inflammatory responses and end-organ injury in WT an... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4955313 Mon, 06 Jun 2011 23:00:00 +0100 4955313 http://www.medworm.com/index.php?rid=4905728&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21647536%26dopt%3DAbstract Authors: Vingtdeux V, Chandakkar P, Zhao H, Davies P, Marambaud P AMP-activated protein kinase (AMPK) is a sensor and regulator of cellular energy metabolism potentially implicated in a broad range of conditions, including obesity and Alzheimer's disease. Its role in the control of key metabolic enzymes makes this kinase a central player in glucose and lipid homeostasis. Recently, by screening a library of synthetic small-molecules selected for their structural similarity with the natural polyphenol resveratrol, we identified RSVA314 and RSVA405 as potent indirect activators of AMPK (EC(50) = 1 μM in cell-based assays). Here we show that RSVA314 and RSVA405 can significantly activate AMPK and inhibit acetyl-CoA carboxylase (ACC), one target of AMPK and key regulator of fatty acid biog... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4905728 Tue, 31 May 2011 23:00:00 +0100 4905728 http://www.medworm.com/index.php?rid=4905727&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21647537%26dopt%3DAbstract In conclusion we show that although DCs generated under atmospheric or physiological oxygen conditions are mostly similar in function and phenotype, DCs differentiated under physiological oxygen secrete larger amounts of IL-12(p70). This could have implications for the use of ex vivo generated DCs for clinical studies, as DCs differentiated at physiological oxygen could induce increased Th1 responses in vivo. PMID: 21647537 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4905727 Tue, 31 May 2011 23:00:00 +0100 4905727 http://www.medworm.com/index.php?rid=4804010&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21532541%26dopt%3DAbstract Authors: Cuocolo A The 10th National Congress of the Italian Association of Nuclear Medicine and Molecular Imaging (AIMN) took place in Rimini on March 18-21, 2011 under the chairmanship of Professor Stefano Fanti. The program was of excellent quality and put a further step for the settlement of the standardized AIMN congress structure. A large industrial exhibition demonstrated the latest technological innovations and developments within the field. The congress was a great success with more than 1100 total participants and more than 360 abstracts received. Of these, 40 abstracts were accepted for oral and 285 for poster presentations. The original investigations presented were related to different areas of nuclear medicine and molecular imaging, with particular focus on advances in in... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804010 Tue, 10 May 2011 19:45:21 +0100 4804010 http://www.medworm.com/index.php?rid=4804022&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21480964%26dopt%3DAbstract Conclusions  Good or acceptable metabolic control is achievable in the majority of patients with Type 1 diabetes or other causes of absolute insulin deficiency in routine diabetes care while limiting the risk for severe hypoglycaemia. PMID: 21480964 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804022 Sat, 30 Apr 2011 23:00:00 +0100 4804022 http://www.medworm.com/index.php?rid=4804021&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21480967%26dopt%3DAbstract Conclusions  In a population at risk for diabetes, the HbA(1c) strategy could lead to diagnosing more cases of dysglycaemia and to treating more patients with metformin than the oral glucose tolerance test strategy. The consistency of either diagnostic criteria was low. The patients with the highest a priori risk of diabetes and cardiovascular disease were those fulfilling both oral glucose tolerance test and HbA(1c) criteria. PMID: 21480967 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804021 Sat, 30 Apr 2011 23:00:00 +0100 4804021 http://www.medworm.com/index.php?rid=4804020&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21480968%26dopt%3DAbstract Conclusions  This model estimates that the prevalence of total diabetes (diagnosed and undiagnosed) in England is higher than previously suggested. An ageing population and increasing prevalence of obesity imply that the prevalence of diabetes will continue to rise and health services should be planned accordingly. PMID: 21480968 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804020 Sat, 30 Apr 2011 23:00:00 +0100 4804020 http://www.medworm.com/index.php?rid=4804019&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21480969%26dopt%3DAbstract Conclusions  These results suggest nearly a doubling in the prevalence of diabetes over 5 years in Scotland. PMID: 21480969 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804019 Sat, 30 Apr 2011 23:00:00 +0100 4804019 http://www.medworm.com/index.php?rid=4804009&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21541441%26dopt%3DAbstract Authors: Fuhler GM, Diks SH, Peppelenbosch MP, Kerr WG Multiple myeloma (MM) is a neoplasm of plasma cell origin that is largely confined to the bone marrow (BM). Chromosomal translocations and other genetic events are known to contribute to deregulation of signaling pathways that lead to transformation of plasma cells and progression to malignancy. However, the tumor stroma may also provide trophic support and enhance resistance to therapy. Phosphorylation of proteins on tyrosine, serine and threonine residues plays a pivotal role in cell growth and survival. Therefore, knowing the status of phosphorylation-based signaling pathways in cells may provide key insights into how cell growth and survival is promoted in tumor cells. To provide a more comprehensive molecular analysis of signa... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804009 Wed, 27 Apr 2011 23:00:00 +0100 4804009 http://www.medworm.com/index.php?rid=4804008&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21541442%26dopt%3DAbstract In this study, we focused on seven CLL cases with stereotyped BcR Subset #8 found among a cohort of 700 patients; in six, the cells expressed IgG and utilized IGHV4-39 and IGKV1-39/IGKV1D-39 genes, as reported for Subset #8 BcR. One case exhibited special features, including expression of IgM or IgG by different subclones consequent to an isotype switch, allelic inclusion at the IGH locus in the IgM expressing cells and a particular pattern of cytogenetic lesions. Collectively, the data indicate a process of antigenic stimulation/selection of the fully transformed CLL cells leading to the expansion of the Subset #8-IgG bearing sub-clone. PMID: 21541442 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804008 Wed, 27 Apr 2011 23:00:00 +0100 4804008 http://www.medworm.com/index.php?rid=4804007&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21541443%26dopt%3DAbstract Authors: Zhang Y, Lin X, Koga K, Takahashi K, Linge HM, Mello A, Laragione T, Gulko PS, Miller EJ Pulmonary infection is a major cause of mortality and morbidity, and the magnitude of the lung inflammatory response correlates with patient survival. Previously, we have shown that neutrophil migration into joints is regulated by arthritis severity quantitative trait loci (QTLs). However, it is unclear whether these QTLs contribute to the regulation of lung inflammation in pneumonias. Therefore, in this study, we examined two inbred rat strains that differ in these QTLs and their susceptibility to joint inflammation, DA and F344, to more clearly define the factors regulating acute inflammatory responses in the lung. Staphylococcal cell wall components lipoteichoic acid (LTA) and peptidogl... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804007 Wed, 27 Apr 2011 23:00:00 +0100 4804007 http://www.medworm.com/index.php?rid=4804012&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21528154%26dopt%3DAbstract In conclusion, this report is the first study on the regulation of asporin expression by different cytokines in HAC. Our data indicate that the expression of this gene is finely regulated in cartilage, and suggest a major role of Sp1. PMID: 21528154 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804012 Sun, 24 Apr 2011 23:00:00 +0100 4804012 http://www.medworm.com/index.php?rid=4804011&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21528155%26dopt%3DAbstract In conclusion, our results provide an empirical basis for the development of a pharmacological treatment strategy in ASD based on retinoids. PMID: 21528155 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804011 Sun, 24 Apr 2011 23:00:00 +0100 4804011 http://www.medworm.com/index.php?rid=4804013&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21519635%26dopt%3DAbstract Authors: Gehrau R, Maluf D, Archer K, Stravitz R, Suh J, Le N, Mas V Acute cellular rejection (ACR) and HCV recurrence (HCVrec) are common complications post-liver transplantation (LT) in HCV patients that share common clinical and histological features, turning difficult the differential diagnosis.Fifty-three liver allograft samples from unique HCV LT recipients were studied using microarrays, including a training set (n=32) and a validation set (n=19). Two no-HCV-ACR samples from LT recipients were also included. Probe sets (Psets) intensity values were obtained using RMA method. ANOVA analysis identified statistically differential expressed genes (p ≤ 0.005). The limma package was used to fit the mixed effects models using restricted maximum likelihood procedure. LASSO model was f... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804013 Tue, 19 Apr 2011 23:00:00 +0100 4804013 http://www.medworm.com/index.php?rid=4804015&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21519633%26dopt%3DAbstract In this study the VEGF-status in CLL was assessed by ELISA and immunofluorescence. VEGF-receptor 2 (VEGFR2) phosphorylation was determined flow cytometrically and by immunofluorescence. For coculture CLL cells were cultivated on a monolayer of the bone marrow-derived stromal cell (BMSC) line HS5. Secreted VEGF was neutralized using the monoclonal antibody mAb293 (R&D Systems). To block protein secretion Brefeldin A was used. VEGF was downregulated in BMSCs by siRNA. Survival was assessed by annexin-V FITC/PI staining. CLL cells express and secrete VEGF and possess phosphorylated VEGFR2. This positive VEGF-status is not sufficient to prevent spontaneous apoptosis in vitro. Coculture with BMSCs, which secrete vast amounts of VEGF, maintains in vitro CLL cell survival. Blockage of secrete... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804015 Wed, 13 Apr 2011 23:00:00 +0100 4804015 http://www.medworm.com/index.php?rid=4804014&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21519634%26dopt%3DAbstract We report twenty-six cMV proteome profiles from male and female stroke-prone and non-stroke prone rats at 2-month and 4.5-months of age prior to overt stroke events. We identified 1934 proteins by two or more peptides. Metaprotein-pathway analysis detected age-associated changes in energy metabolism and cell-microenvironment interactions; as well as sex-specific changes in energy metabolism and endothelial leukocyte transmigration pathways. Stroke susceptibility was independently associated with multiple protein changes associated with ischemia, angiogenesis, or involved in blood brain barrier integrity. Immunohistochemical analysis confirmed aquaporin-4 and laminin-α1 induction in cMVs, representative of proteomic changes with >65 BayesFactor, associated with stroke susceptibility. Al... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804014 Wed, 13 Apr 2011 23:00:00 +0100 4804014 http://www.medworm.com/index.php?rid=4804016&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21494752%26dopt%3DAbstract In this study, we examine mechanisms related to the effect of AAT on neutrophil responses. We report a previously unknown function of AAT to inactivate calpain I (μ-calpain) and to induce a rapid cell polarization and random migration. These effects of AAT coincided with transient rise in intracellular calcium, increase in intracellular lipids, activation of the Rho GTPases, Rac1 and Cdc42, and extracellular signal-regulated kinase (ERK1/2). Furthermore, AAT caused a significant inhibition of non-stimulated as well as formyl-met-leu-phe (fMLP)-stimulated neutrophil adhesion to fibronectin, strongly inhibited lipopolysaccharide (LPS)-induced IL-8 release and slightly delayed neutrophil apoptosis. The results presented here broaden our understanding of the regulation of calpain-related neut... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804016 Sun, 10 Apr 2011 23:00:00 +0100 4804016 http://www.medworm.com/index.php?rid=4804018&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21487638%26dopt%3DAbstract In conclusion, we have demonstrated that treatment with JJ316 has a dramatic therapeutic effect on an experimental crescentic GN, probably due to expansion and activation of Treg cells. PMID: 21487638 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804018 Thu, 07 Apr 2011 23:00:00 +0100 4804018 http://www.medworm.com/index.php?rid=4804017&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21487639%26dopt%3DAbstract The objective of this study was to determine if herpes virus carrying an EGFP protein could detect rare cancer cells in body fluids against millions of normal cells. Human cancer cells suspended with normal murine cells were infected with NV1066 at an MOI (multiplicity of infection) of 0.5 and 1.0 for 18 hours. Fluorescent microscopy and flow cytometry were used for EGFP detection of cancer cells. EGFP-expressing cells were confirmed as cancer cells with specific markers by immunohistochemistry staining. Limits of detection of cancer cells in body fluid were measured by serial dilutions. Applicability of technique was confirmed with samples from patients with malignant pleural effusions. NV1066 expressed EGFP in 111 human cancer cell lines detected by fluorescent microscopy at an MOI of 0.... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4804017 Thu, 07 Apr 2011 23:00:00 +0100 4804017 http://www.medworm.com/index.php?rid=4578750&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21392060%26dopt%3DAbstract Conclusions  Current evidence shows that the real-time continuous glucose monitoring system has a beneficial effect on glycaemic control in adult diabetes patients, without an increase in the incidence of hypoglycaemia. Studies in well-selected patient groups (pregnancy, history of severe hypoglycaemias, Type 2 diabetes) are lacking. PMID: 21392060 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4578750 Sun, 13 Mar 2011 18:45:41 +0100 4578750 http://www.medworm.com/index.php?rid=4578749&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21392066%26dopt%3DAbstract Conclusions  Results pooled from the included trials provided strong evidence that mobile phone intervention led to statistically significant improvement in glycaemic control and self-management in diabetes care, especially for Type 2 diabetes patients. PMID: 21392066 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4578749 Sun, 13 Mar 2011 18:45:30 +0100 4578749 http://www.medworm.com/index.php?rid=4578748&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21392067%26dopt%3DAbstract Conclusions  The HbA(1c) was significantly and meaningfully reduced by both doses of PF-734200, but 20 mg appears to be the more appropriate therapeutic dose for Type 2 diabetes mellitus, contingent upon confirmation by long-term controlled studies. PMID: 21392067 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4578748 Sun, 13 Mar 2011 18:45:18 +0100 4578748 http://www.medworm.com/index.php?rid=4578751&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21380479%26dopt%3DAbstract CONCLUSION: These data support a potential role for HMGB1 as a biomarker and diagnostic tool for the differential diagnosis of asthma and COPD. The importance of this observation on asthma and COPD mechanisms and outcomes should be further investigated in large prospective studies. PMID: 21380479 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4578751 Thu, 03 Mar 2011 00:00:00 +0100 4578751 http://www.medworm.com/index.php?rid=4578747&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21394384%26dopt%3DAbstract In conclusion, expression of IL-1F members is more pronounced in adipose compared to liver tissue in patients with severe obesity. Excessive weight loss changes the adipose and liver expression profile of IL-1F members towards a more anti-inflammatory direction. PMID: 21394384 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4578747 Wed, 02 Mar 2011 00:00:00 +0100 4578747 http://www.medworm.com/index.php?rid=4578746&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21394385%26dopt%3DAbstract Authors: Jingzhou C, Yi S, Ziyu L, Hui Y, Yu H, Xiaojian W, Kai S, Tao Y, Kejia L, Yan S, Yinhui Z, Yisong Z, Guiguo Z, Ying H, Jiafu J, Rutai H The IC53 gene has been reported to be upregulated in the colon adenocarcinoma cell line SW480. Here, we show that the expression level of IC53 is positively correlated with the grade and depth of invasion in adenocarcinoma of the colon. Injection of IC53-stably transfected HCT-116 cells into athymic nude mice promoted tumor growth. Furthermore, overexpression of IC53 increased cell invasive growth, which could be dramatically prevented by knocking down IC53 with siRNA. These effects of IC53 on cell invasive growth were mediated by upregulation of integrins, activation of phosphatidylinositol 3-kinase and phosphorylation of Akt. A single-nucleo... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4578746 Wed, 02 Mar 2011 00:00:00 +0100 4578746 http://www.medworm.com/index.php?rid=4470688&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21309842%26dopt%3DAbstract Conclusions  Injectable liraglutide may lead to greater treatment satisfaction than oral sitagliptin, potentially by facilitating greater improvement in glycaemic control, weight loss and/ or perception of greater treatment efficacy. PMID: 21309842 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4470688 Sun, 13 Feb 2011 09:00:18 +0100 4470688 http://www.medworm.com/index.php?rid=4470687&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21309843%26dopt%3DAbstract Conclusions  Social deprivation was associated with low uptake and poor success of insulin intensification and this appeared to be largely mediated via lower educational levels. PMID: 21309843 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4470687 Sun, 13 Feb 2011 09:00:11 +0100 4470687 http://www.medworm.com/index.php?rid=4470690&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21308150%26dopt%3DAbstract Authors: Consalvi S, Saccone V, Giordani L, Minetti G, Mozzetta C, Puri PL Histone deacetylases inhibitors (HDACi) include a growing number of drugs that share the ability to inhibit the enzymatic activity of some or all the HDACs. Experimental and preclinical evidence indicates that these epigenetic drugs can be effective in the treatment of malignancies, inflammatory and degenerative disorders, but also genetic diseases, such as muscular dystrophies. The ability of HDACi to counter the progression of muscular dystrophies points to HDACs as a crucial link between specific genetic mutations and downstream determinants of disease progression. It also suggests the contribution of epigenetic events to the pathogenesis of muscular dystrophies. Here we describe the experimental evidence sup... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4470690 Mon, 07 Feb 2011 00:00:00 +0100 4470690 http://www.medworm.com/index.php?rid=4470693&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21308147%26dopt%3DAbstract In conclusion, a molecular signature defined by 4 genes represents a promising diagnostic tool for the identification of MIBC patients at high risk of progression. PMID: 21308147 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4470693 Fri, 04 Feb 2011 00:00:00 +0100 4470693 http://www.medworm.com/index.php?rid=4470692&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21308148%26dopt%3DAbstract Authors: Chogle A, Bu HF, Wang X, Brown JB, Chou PM, Tan XD Milk fat globule-EGF factor 8 (MFG-E8) has been shown to play an important role in maintaining the integrity of the intestinal mucosa and accelerate healing of the mucosa in septic mice. Herein, we (1) analyzed the expression of MFG-E8 in the gut of wild type C57BL/6 (MFG-E8(+/+)) mice with and without dextran sulfate sodium (DSS)-induced colitis, (2) characterized the pathological changes in intestinal mucosa of MFG-E8(+/+) and MFG-E8(-/-) mice with DSS-induced colitis, and (3) examined the therapeutic role of MFG-E8 in inflammatory bowel disease using DSS-induced colitis model. Our data documented that there was an increase in colonic and rectal MFG-E8 expression in MFG-E8(+/+) mice during the development of DSS colitis. MFG... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4470692 Fri, 04 Feb 2011 00:00:00 +0100 4470692 http://www.medworm.com/index.php?rid=4470691&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21308149%26dopt%3DAbstract Authors: Cornu JN, Drouin S, Cancel-Tassin G, Bigot P, Azzouzi AR, Koutlidis N, Cormier L, Gaffory C, Rouprêt M, Sèbe P, Bitker MO, Haab F, Cussenot O Single Nucleotide Polymorphisms (SNPs) have been associated to prostate cancer (PCa) risk and tumor aggressiveness in retrospective studies. To assess value of genotyping in a clinical setting, we prospectively evaluated the correlation between three genotypes (rs1447295 and rs6983267(8q24) and rs4054823(17p12)) and prostatic biopsy outcome in a French population of Caucasian men. 598 patients with Prostatic Specific Antigen (PSA) >4ng/mL or abnormal digital rectal examination (DRE) participated in this prospective, multicentre study. Age, familial history of PCa, body mass index (BMI), data of DRE, International Prostate Symptom Sc... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4470691 Fri, 04 Feb 2011 00:00:00 +0100 4470691 http://www.medworm.com/index.php?rid=4470689&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21308151%26dopt%3DAbstract Authors: Vojinovic J, Damjanov N Rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) are heterogeneous autoimmune diseases characterized by chronic joint inflammation. Methotrexate is used as the gold standard to treat rheumatoid arthritis, but yet there are many patients in whom the disease cannot be controlled or who experience unacceptable intolerance. Most of the biologics currently used are effective but mostly if combined with methotrexate. Long term possible side effects such as impaired host defense mechanisms against infection and lymphoma are distinct disadvantages and major concern of anti-cytokine therapies. Parenteral administration is a problem, particularly in children. Thus, there is a need to explore new treatment options. Here we review the properties of... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4470689 Fri, 04 Feb 2011 00:00:00 +0100 4470689 http://www.medworm.com/index.php?rid=4335608&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21219421%26dopt%3DAbstract Conclusions  Lower insulin sensitivity is associated with a more atherogenic lipid profile in both youths and adults with Type 1 diabetes. PMID: 21219421 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4335608 Wed, 12 Jan 2011 21:45:24 +0100 4335608 http://www.medworm.com/index.php?rid=4335607&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21219434%26dopt%3DAbstract Conclusion  Nearly half of insulin-treated patients do not use an injection-meal interval. We found no significant association between adherence to injection-meal interval and HbA(1c) in patients with Type 1 diabetes, but a slightly lower HbA(1c) in patients with Type 2 diabetes who always use an injection-meal interval. PMID: 21219434 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4335607 Wed, 12 Jan 2011 21:45:20 +0100 4335607 http://www.medworm.com/index.php?rid=4335606&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21219435%26dopt%3DAbstract Conclusions  Our data show that meals with the same carbohydrate content but a different glycaemic index produce clinically significant differences in postprandial blood glucose. PMID: 21219435 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4335606 Wed, 12 Jan 2011 21:45:16 +0100 4335606 http://www.medworm.com/index.php?rid=4335605&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21219880%26dopt%3DAbstract Authors: Ganesan L, Margolles-Clark E, Song Y, Buchwald P Following our observation that Erythrosine B (FD&C Red No. 3) is a relatively potent inhibitor of the TNF-R-TNFα and CD40-CD154 protein-protein interactions (J. Mol. Med. 2009, 87, 1133), we investigated whether this inhibitory activity extends to any other protein-protein interactions (PPI) as well as whether any other approved food colors possess such inhibitory activity. We found erythrosine, a poly-iodinated xanthene dye, to be a non-specific promiscuous inhibitor ofa number of PPIs within the tumor necrosis factor superfamily (TNF-R-TNFα, CD40-CD154, BAFF-R-BAFF, RANK-RANK-L, OX40-OX40L, 4-1BB-4-1BBL) as well as outside of it (EGF-R-EGF) with a remarkably consistent median inhibitory concentration (IC(50)) in the 2-20... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4335605 Fri, 07 Jan 2011 00:00:00 +0100 4335605 http://www.medworm.com/index.php?rid=4335610&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21210072%26dopt%3DAbstract This article summarizes state of the art of inflammatory modulation by fibrin(ogen) and fibrin fragments. However, further research is required to gain better understanding of the entire role, fibrin fragments play during inflammation and possibly disease development. PMID: 21210072 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4335610 Tue, 04 Jan 2011 00:00:00 +0100 4335610 http://www.medworm.com/index.php?rid=4335611&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21210071%26dopt%3DAbstract In conclusion, we demonstrated novel findings that restoring GNMT assists methylfolate-dependent reactions and ameliorates the consequences of folate depletion. GNMT expression in vivo improves folate retention and bioavailability in the liver. Studies on how GNMT expression impacts the distribution of different folate cofactors and the regulation of specific folate dependent reactions are underway. PMID: 21210071 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4335611 Mon, 03 Jan 2011 00:00:00 +0100 4335611 http://www.medworm.com/index.php?rid=4335609&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21210073%26dopt%3DAbstract Authors: Sandu N, Pöpperl G, Toubert ME, Spiriev T, Arasho B, Orabi M, Schaller BJ Energy metabolism measurements in spinal cord tumors as well as in osseous spinal tumors/metastasis in vivo are only rarely performed as molecular imaging (MI) by positron emission tomography (PET). This imaging modality has developed from a small number of basic and later also clinical science investigations that have cross fertilized each other. Apart from precise anatomical localization by co-registration of morphological imaging and quantification, the most intriguing advantage of such imaging is the opportunity to investigate the time course (dynamics) of disease-specific molecular events in the intact organism. Most importantly, MI represents one of the key-technologies in translational molecular ... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4335609 Mon, 03 Jan 2011 00:00:00 +0100 4335609 http://www.medworm.com/index.php?rid=4335604&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21220499%26dopt%3DAbstract In conclusion, we found that sorafenib exerts a potent inhibitory activity against the EMT by inhibiting MAPK signaling and SNAI1 expression in HCC. Our findings may provide a novel insight into the anti-EMT effect of tyrosine kinase inhibitors in cancer cells. Mol Cancer Ther; 10(1); 169-77. ©2011 AACR. PMID: 21220499 [PubMed - in process] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4335604 Sat, 01 Jan 2011 00:00:00 +0100 4335604 http://www.medworm.com/index.php?rid=4276169&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21166843%26dopt%3DAbstract Conclusions  Of those with diabetes diagnosis based on two oral glucose tolerance tests during the Diabetes Prevention Study follow-up, 60% would have remained undiagnosed if diagnosis had been based on HbA(1c) ≥ 6.5% (≥ 48 mmol/mol) criterion. PMID: 21166843 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4276169 Tue, 21 Dec 2010 16:31:33 +0100 4276169 http://www.medworm.com/index.php?rid=4276161&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21166848%26dopt%3DAbstract Conclusions  In secondary prevention, patients with diabetes and HbA(1c) levels < 7.0% (< 53 mmol/mol) had a lower incidence of subsequent ischaemic events and a lower mortality than those with HbA(1c) levels > 7.0% (> 53 mmol/mol). These differences appeared only in patients with coronary artery disease. PMID: 21166848 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4276161 Tue, 21 Dec 2010 16:30:53 +0100 4276161 http://www.medworm.com/index.php?rid=4276160&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21166851%26dopt%3DAbstract Conclusions  In patients with Type 2 diabetes with early renal disease, we found no statistical difference in renal function between those taking high- or low-dose atorvastatin over 2 years. We cannot exclude a beneficial effect of < 1.6 ml min(-1)  1.73 m(-2) year(-1) on Modification of Diet in Renal Disease estimated glomerular filtration rate, or if blood pressure management or if renin-angiotensin system blocker use had not been optimized. PMID: 21166851 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4276160 Tue, 21 Dec 2010 16:30:22 +0100 4276160 http://www.medworm.com/index.php?rid=4061864&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20931388%26dopt%3DAbstract Authors: Wang Z MiRNA-masking antisense oligonucleotides technology (miR-mask) is an anti-microRNA antisense oligodeoxyribonucleotide (AMO) approach of a different sort. A standard miR-mask is single-stranded 2'-O-methyl-modified oligoribonucleotide (or other chemically modified) that is a 22-nt antisense to a protein-coding mRNA as a target for an endogenous miRNA of interest. Instead of binding to the target miRNA like an AMO, an miR-mask does not directly interact with its target miRNA but binds to the binding site of that miRNA in the 3' UTR of the target mRNA by fully complementary mechanism. In this way, the miR-mask covers up the access of its target miRNA to the binding site so as to derepress its target gene (mRNA) via blocking the action of its target miRNA. The anti-miRNA ac... Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4061864 Wed, 13 Oct 2010 22:35:07 +0100 4061864 http://www.medworm.com/index.php?rid=4061867&cid=s_33577_67_f&fid=33577&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20927484%26dopt%3DAbstract This study showed that PLSCR1 protein levels were significantly elevated in both the cancer tissue and plasma of CRC patients. Moreover, the plasma levels of PLSCR1 were significantly elevated in patients with early-stage CRC, compared with healthy individuals, suggesting that PLSCR1 might represent a noninvasive serological biomarker for the early diagnosis of CRC. PMID: 20927484 [PubMed - as supplied by publisher] (Source: Molecular Medicine) Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4061867 Mon, 04 Oct 2010 23:00:00 +0100 4061867