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 'Journal of Molecular Medicine' source. Thu, 09 Feb 2012 16:56:46 +0100 http://www.medworm.com/index.php?rid=5673924&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy602171721091612%2F Abstract  Expansions of a polyalanine (polyA) stretch in the coding region of the PHOX2B gene cause congenital central hypoventilation syndrome (CCHS), a neurocristopathy characterized by the absence of adequate control of autonomic breathing. Expansion of polyA in PHOX2B leads to protein misfolding and accumulation into inclusions. The mechanisms that regulate mutant protein degradation and turnover have been poorly elucidated. Here, we investigate the regulation of degradation of wild-type and polyA-expanded PHOX2B. We show that expanded PHOX2B is targeted for degradation through the ubiquitin–proteasome system, resulting in lowered levels of the mutant protein relative to its wild-type counterpart. Moreover, we show that mutant PHOX2B forms ubiquitin-positive inclusions... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673924 Fri, 03 Feb 2012 17:52:37 +0100 5673924 http://www.medworm.com/index.php?rid=5673925&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7g0w8532212044p4%2F Abstract  Atherosclerosis has been established as a chronic inflammatory disease of the vessel wall. Among the mononuclear cell types recruited to the lesions, specialized dendritic cells (DCs) have gained increasing attention, and their secretory products and interactions shape the progression of atherosclerotic plaques. The regulation of DC functions by microRNAs (miRNAs) may thus be of primary importance in disease. We here systematically summarize the biogenesis and functions of miRNAs and provide an overview of miRNAs in DCs, their targets, and potential implications for atherosclerosis, with a particular focus on the best characterized miRNAs in DCs, namely, miR-155 and miR-146. MiRNA functions in DCs range from regulation of lipid uptake to cytokine production and T ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673925 Fri, 03 Feb 2012 17:52:36 +0100 5673925 http://www.medworm.com/index.php?rid=5673926&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe2q1k3772h33623v%2F Abstract  Increasing evidences suggest that the type I interferon α (IFNα) plays a critical role in the etiopathogenesis of systemic lupus erythematosus (SLE), which makes it a promising therapeutic target for the treatment of the disease. By screening a large size non-immune human antibody library, we have developed a human single-chain antibody (ScFv) AIFNα1bScFv01 and corresponding whole antibody AIFNα1bIgG01 to human interferon α1b (IFNα1b) with high specificity and high affinity. The IgG antibody could down-regulate the expression of ISG15 and IFIT-1 induced by either recombinant IFNα1b or naïve IFNα from SLE patients’ sera, and reduced total serum IgG and IgM antibodies level in a pristane-primed lupus-like mouse model. The crystal structure of AIFNα1bScFv0... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673926 Fri, 03 Feb 2012 17:52:35 +0100 5673926 http://www.medworm.com/index.php?rid=5643834&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh42r00u547n14266%2F In conclusion, srVSV is a promising platform for virotherapeutic approaches and also for VSV-based vector vaccines, combining improved safety with an increased coding capacity for therapeutic transgenes, potentially allowing for multipronged approaches. Content Type Journal ArticleCategory Original ArticlePages 1-12DOI 10.1007/s00109-012-0863-6Authors Alexander Muik, Georg-Speyer-Haus, 60596 Frankfurt am Main, GermanyCatherine Dold, Institute for Virology, Innsbruck Medical University, Fritz-Pregl-Str. 3, A-6020 Innsbruck, AustriaYvonne Geiß, Georg-Speyer-Haus, 60596 Frankfurt am Main, GermanyAndreas Volk, Georg-Speyer-Haus, 60596 Frankfurt am Main, GermanyMarina Werbizki, Georg-Speyer-Haus, 60596 Frankfurt am Main, GermanyUrsula Dietrich, Georg-Speyer-Haus, 60596 Frankfurt am Mai... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5643834 Fri, 27 Jan 2012 17:53:02 +0100 5643834 http://www.medworm.com/index.php?rid=5635406&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Frl631407053n4457%2F Content Type Journal ArticleCategory Clinical ImplicationsPages 1-3DOI 10.1007/s00109-012-0862-7Authors Friedrich C. Luft, Experimental and Clinical Research Center, Max-Delbrück Center and Charité Medical Faculty, Lindenbergerweg 80, 13125 Berlin, Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5635406 Tue, 24 Jan 2012 12:27:18 +0100 5635406 http://www.medworm.com/index.php?rid=5635408&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq7513432662408g0%2F Abstract  During the last 10 years, a series of exciting observations has led to a new theory of pathophysiology using insights from evolutionary biology and neuroendocrine immunology to understand the sequelae of chronic inflammatory disease. According to this theory, disease sequelae can be explained based on redirection of energy-rich fuels from storage organs to the activated immune system. These disease sequelae are highly diverse and include the following: sickness behavior, anorexia, malnutrition, muscle wasting–cachexia, cachectic obesity, insulin resistance with hyperinsulinemia, dyslipidemia, increase of adipose tissue near inflamed tissue, alterations of steroid hormone axes, elevated sympathetic tone and local sympathetic nerve fiber loss, decreased paras... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5635408 Tue, 24 Jan 2012 06:54:52 +0100 5635408 http://www.medworm.com/index.php?rid=5635407&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq87p862712v18600%2F Abstract  Intrauterine growth restriction (IUGR) is a risk factor for impairment of lung function in adolescence and adulthood. Inflammatory and proliferative processes linking IUGR and perturbed extracellular matrix (ECM) as an underlying mechanism have not been addressed so far. Therefore, in this study, we aimed to investigate the developmental regulation of inflammatory and profibrotic processes in the lung subsequent to IUGR. IUGR was induced in rats by isocaloric protein restriction during gestation. Lung function was assessed with direct plethysmography at postnatal day (P) 28 and P70. Lungs were obtained at P1, P42, and P70 for assessment of mRNA, protein expression, immunohistochemistry, and gelatinolytic activity. Both respiratory system resistance and compliance ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5635407 Tue, 24 Jan 2012 06:54:52 +0100 5635407 http://www.medworm.com/index.php?rid=5617011&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6255566312611151%2F Abstract  Reactive oxygen species (ROS) are strongly implicated in melanoma development, and treatment with antioxidants has shown efficacy in suppressing malignant transition and progression. Here, we investigated the significance of the glutamate-l-cysteine ligase catalytic subunit (GCLC) expression, a key regulator of glutathione synthesis, for malignant melanoma. A large set of melanoma cell lines (n = 36) was analyzed, and higher GCLC levels were associated with lower presence of intracellular ROS and interestingly also lower rates of cell proliferation. Moreover, treatment with the antioxidant N-acetylcysteine efficiently reduced the growth speed of several investigated malignant cells. In addition GCLC expression was significantly linked to a prominent set of cellu... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5617011 Tue, 17 Jan 2012 07:09:03 +0100 5617011 http://www.medworm.com/index.php?rid=5603989&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F02715hq237m7u728%2F Abstract  Despite substantial progress, mortality and morbidity of the acute respiratory distress syndrome (ARDS), a severe form of acute lung injury (ALI), remain unacceptably high. There is no effective treatment for ARDS/ALI. The renin–angiotensin system (RAS) through Angiotensin-converting enzyme (ACE)-generated Angiotensin II contributes to lung injury. ACE2, a recently discovered ACE homologue, acts as a negative regulator of the RAS and counterbalances the function of ACE. We hypothesized that ACE2 prevents Bleomycin (BLM)-induced lung injury. Fourteen to 16-week-old ACE2 knockout mice—male (ACE2−/y) and female (ACE2−/−)—and age-matched wild-type (WT) male mice received intratracheal BLM (1.5U/kg). Male ACE2−/y BLM injured mice exhibited poorer exercise c... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5603989 Fri, 13 Jan 2012 16:50:02 +0100 5603989 http://www.medworm.com/index.php?rid=5593011&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F224l5134gq57176t%2F Abstract  We previously reported that mesenchymal stem cells (MSC) co-expressing Akt and angiopoietin-1 (Ang-1) preserved infarcted heart function via angiomyogenesis. The present study determined the mechanism of co-overexpression of Akt and Ang-1 in promoting endothelial commitment of MSC. The cells were transduced with vectors encoding for Akt (AktMSC), Ang-1 (Ang-1MSC), and both Akt and Ang-1 (AAMSC) using Empty vector transduced MSC (EmpMSC) as control. Molecular studies indicated a coordinated interaction between Akt and Ang-1 in AAMSC and led to non-hypoxic stabilization of hypoxia inducible factor-1α (HIF-Iα) which accentuated under 4-h anoxia. We also observed HIF-Iα dependent induction of hemeoxygenase-1, endothelial specific markers and VEGF in AAMSC. Vascular co... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5593011 Wed, 11 Jan 2012 17:54:17 +0100 5593011 http://www.medworm.com/index.php?rid=5593012&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu4rv372086052357%2F Abstract  Intratumoral hypoxia, a frequent finding in metastatic cancer, results in the activation of hypoxia-inducible factors (HIFs). HIFs are implicated in many steps of breast cancer metastasis, including metastatic niche formation through increased expression of lysyl oxidase (LOX) and lysyl oxidase-like (LOXL) proteins, enzymes that remodel collagen at the metastatic site and recruit bone marrow-derived cells (BMDCs) to the metastatic niche. We investigated the effect of two chemically and mechanistically distinct HIF inhibitors, digoxin and acriflavine, on breast cancer metastatic niche formation. Both drugs blocked the hypoxia-induced expression of LOX and LOXL proteins, collagen cross-linking, CD11b+ BMDC recruitment, and lung metastasis in an orthotopic breast canc... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5593012 Mon, 09 Jan 2012 19:37:55 +0100 5593012 http://www.medworm.com/index.php?rid=5593013&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb385u4m1666257w1%2F Content Type Journal ArticleCategory Retraction NotePages 1-1DOI 10.1007/s00109-011-0850-3Authors Michel Azizi, Faculté de Médecine, Université Paris Descartes; Assistance Publique Hôpitaux de Paris, Hôpital Européen Georges Pompidou; INSERM, Clinical Investigation Center 9201, Paris, France Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5593013 Mon, 09 Jan 2012 19:37:54 +0100 5593013 http://www.medworm.com/index.php?rid=5593016&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9357j6484742k316%2F Abstract  Important causes for modern epidemics such as obesity, diabetes, and cardiovascular disease are over- and malnutrition. Dietary as well as endogenous lipids are transported through the bloodstream in lipoproteins, and disturbances in lipoprotein metabolism are associated with atherosclerosis, heart disease, and diabetes. Recent findings reveal biological principles—how lipoproteins, in particular triglyceride-rich lipoproteins, are metabolized and what factors regulate their processing. The fate of triglycerides delivered by lipoproteins is quite simple: either they can be stored or they can be utilized for combustion or biosynthetic pathways. In the healthy state, fatty acids derived from triglycerides can be burned in the heart, muscle, and other organs for ac... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5593016 Mon, 09 Jan 2012 19:37:52 +0100 5593016 http://www.medworm.com/index.php?rid=5593015&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F26r1060044t401ux%2F Abstract  Colon cancer affects millions of individuals in Western countries. Cannabidiol, a safe and non-psychotropic ingredient of Cannabis sativa, exerts pharmacological actions (antioxidant and intestinal antinflammatory) and mechanisms (inhibition of endocannabinoid enzymatic degradation) potentially beneficial for colon carcinogenesis. Thus, we investigated its possible chemopreventive effect in the model of colon cancer induced by azoxymethane (AOM) in mice. AOM treatment was associated with aberrant crypt foci (ACF, preneoplastic lesions), polyps, and tumour formation, up-regulation of phospho-Akt, iNOS and COX-2 and down-regulation of caspase-3. Cannabidiol-reduced ACF, polyps and tumours and counteracted AOM-induced phospho-Akt and caspase-3 changes. In colorectal ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5593015 Mon, 09 Jan 2012 19:37:52 +0100 5593015 http://www.medworm.com/index.php?rid=5593014&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa243m68352w34mp1%2F Abstract  Multiple Sclerosis (MS) and Rheumatoid Arthritis (RA) are amongst the most common autoimmune diseases in the northern hemisphere. There is mounting evidence that in both afflictions, not only environmental and genetic factors influence disease, but cellular components such as autoreactive T cells also contribute to pathology. Animal models are key in the study and subsequent therapeutic development for human autoimmune diseases. As patient material is often difficult to obtain and in some cases—as in MS, where the central nervous system (CNS) is concerned—even not accessible, animal models provide a multifaceted tool to explore disease-underlying mechanisms. The pro-inflammatory T cell cytokine IL-17 has recently moved to center stage due to its crucial role in... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5593014 Mon, 09 Jan 2012 19:37:52 +0100 5593014 http://www.medworm.com/index.php?rid=5593017&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv06p47750386710v%2F Abstract  Increased and decreased methylation at specific sequences (hypermethylation and hypomethylation, respectively) is characteristic of tumor DNA compared to normal DNA and promotes carcinogenesis in multiple ways including genomic instability. Long interspersed element (LINE), an abundant class of retrotransposons, provides a surrogate marker for global hypomethylation. We developed methylation-specific multiplex ligation-dependent probe amplification assays to study LINE-1 methylation in cases of colorectal, gastric, and endometrial cancer (N = 276), stratified by patient category [sporadic; Lynch syndrome (LS); familial colorectal cancer type X (FCCX)] and microsatellite instability status. Within each patient group, LINE-1 showed lower methylation in tumor DNA ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5593017 Sat, 07 Jan 2012 16:55:24 +0100 5593017 http://www.medworm.com/index.php?rid=5576668&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc25m4730r0621m81%2F Abstract  The wound healing response after myocardial infarction (MI) involves a cascade of molecular and cellular events that lead to a replacement of the necrotic area with a collagen-rich scar. Clearance of necrotic debris by neutrophils, monocytes, and macrophages is a critical component of infarct healing; however, tight control and timely repression of this inflammatory response is important to prevent excessive tissue degradation leading to infarct expansion and heart failure. Genetic ablation or blockade of anti-inflammatory pathways tends to be detrimental after MI, whereas genetic ablation of pro-inflammatory pathways tends to be beneficial. Accordingly, therapies enhancing endogenous anti-inflammatory pathways or blocking endogenous pro-inflammatory pathways have... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5576668 Fri, 06 Jan 2012 16:47:48 +0100 5576668 http://www.medworm.com/index.php?rid=5576669&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu1681l060l381535%2F Abstract  Human anion exchanger 2 (AE2) is a plasma membrane protein that regulates intracellular pH and cell volume. AE2 contributes to transepithelial transport of chloride and bicarbonate in normal colon and other epithelial tissues. We now report that AE2 overexpression in colon cancer cells is correlated with expression of the nuclear proliferation marker, Ki67. Survival analysis of 24 patients with colon cancer in early stage or 33 patients with tubular adenocarcinoma demonstrated that expression of AE2 is correlated with poor prognosis. Cellular and molecular experiments indicated that AE2 expression promoted proliferation of colon cancer cells. In addition, we found that transcription factor EGR1 underlies AE2 upregulation and the AE2 sequester p16INK4a (P16) in the... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5576669 Fri, 06 Jan 2012 16:47:46 +0100 5576669 http://www.medworm.com/index.php?rid=5576670&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx67j4p153p7345ml%2F Abstract  Celiac patient-derived anti-transglutaminase 2 (TG2) antibodies disturb several steps in angiogenesis, but the detailed molecular basis is not known. Therefore, we here analyzed by microarray technology the expression of a set of genes related to angiogenesis and endothelial cell biology in order to identify factors that could explain our previous data related to vascular biology in the context of celiac disease. To this end, in vitro models using human umbilical vein endothelial cells (HUVECs) or in vivo models of angiogenesis were used. A total of 116 genes were analyzed after treatment with celiac patient autoantibodies against TG2. Compared to treatment with control IgA celiac patient, total IgA induced a consistent expression change of 10 genes, the up-regula... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5576670 Thu, 05 Jan 2012 17:07:55 +0100 5576670 http://www.medworm.com/index.php?rid=5568839&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff76536q67887w530%2F Abstract  The mitogen-activated protein kinase (MAPK) and PI3K pathways are regulated by extensive crosstalk, occurring at different levels. In tumors, transactivation of the alternate pathway is a frequent “escape” mechanism, suggesting that combined inhibition of both pathways may achieve synergistic antitumor activity. Here we show that, in the M14 melanoma model, simultaneous inhibition of both MEK and mammalian target of rapamycin (mTOR) achieves synergistic effects at suboptimal concentrations, but becomes frankly antagonistic in the presence of relatively high concentrations of MEK inhibitors. This observation led to the identification of a novel crosstalk mechanism, by which either pharmacologic or genetic inhibition of constitutive MEK signaling restores phosph... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5568839 Wed, 04 Jan 2012 06:58:43 +0100 5568839 http://www.medworm.com/index.php?rid=5568840&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx222730122p82135%2F Abstract  Type II collagen is a marker of articular cartilage encoded by the COL2A1 gene. The nature of the trans factors involved in the upregulation of this gene by insulin-like growth factor-I (IGF-I) remains unclear. We found that IGF-I increased type II collagen synthesis by a transcriptional control mechanism involving a 715-bp region within the COL2A1 first-intron specific enhancer. The overproduction of L-Sox5/Sox6/Sox9 and Sp1 and decoy experiments targeting these factors demonstrated their action in concert in IGF-I trans-activation. These results were supported by the data obtained in knockdown experiments in which siRNA against Sox9/Sox6 and Sp1 prevented the IGF-I-induced increase in collagen II production. Indeed, each of these trans-activators increased the expr... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5568840 Wed, 04 Jan 2012 06:58:42 +0100 5568840 http://www.medworm.com/index.php?rid=5568841&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9146ln0114560217%2F This study aimed to evaluate the therapeutic efficacy of BKM120 in multiple myeloma (MM). BKM120 induces cell growth inhibition and apoptosis in both MM cell lines and freshly isolated primary MM cells. However, BKM120 only shows limited cytotoxicity toward normal lymphocytes. The presence of MM bone marrow stromal cells, insulin-like growth factor, or interleukin-6 does not affect BKM120-induced tumor cell apoptosis. More importantly, BKM120 treatment significantly inhibits tumor growth in vivo and prolongs the survival of myeloma-bearing mice. In addition, BKM120 shows synergistic cytotoxicity with dexamethasone in dexamethasone-sensitive MM cells. Low doses of BKM120 and dexamethasone, each of which alone has limited cytotoxicity, induce significant cell apoptosis in MM.1S and ARP... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5568841 Fri, 30 Dec 2011 07:09:18 +0100 5568841 http://www.medworm.com/index.php?rid=5556785&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F3392237728176173%2F In this study, we investigate the cytotoxic effect of the natural substance cnicin in multiple myeloma. Cnicin treatment reveals potent antiproliferative effects and induces cell death in cell lines and primary myeloma cells even in the presence of survival cytokines and the tumor microenvironment. Other cell lines of hematopoietic origin also succumb to cell death whereas stromal cells and endothelial cells are unaffected. We show that activation of caspases, accumulation of reactive oxygen species and downregulation of nuclear factor kappa-light-chain-enhancer of activated B cell contribute to the cytotoxic effects of cnicin. Microarray analysis reveals downregulation of Pim-2, a serine/threonine kinase. We provide evidence that Pim-2 constitutes a new survival kinase for myeloma c... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5556785 Wed, 28 Dec 2011 16:45:02 +0100 5556785 http://www.medworm.com/index.php?rid=5542207&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F246vq9l51r834726%2F In this study, we found that in the same model, the CB2 agonist JWH-015 enhances neuronal nitric oxide synthase (nNOS) expression in axotomized neurons and that CB2-mediated neuroprotection is abrogated by pharmacological inhibition of nNOS. JWH-015 prevented the axotomy-induced upregulation of inducible NOS (iNOS) in astrocytes but had no effect on endothelial NOS (eNOS). In addition, we observed that JWH-015 significantly reduces hemicerebellectomy-induced neuroinflammatory responses and oxidative/nitrative stress. With regard to the signaling pathways of CB2/nNOS-mediated neuroprotection, we noted nNOS-dependent modulation of the expression of anti-oxidative (Hsp70) and anti-apoptotic (Bcl-2) proteins. These findings shed light on the interactions between the endocannabinoid and nit... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5542207 Fri, 23 Dec 2011 16:55:13 +0100 5542207 http://www.medworm.com/index.php?rid=5542208&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu04n188171546342%2F Abstract  Activation of ERK signaling may promote cardioprotection from ischemia–reperfusion (I/R) injury. ZnT-1, a protein that confers resistance from zinc toxicity, was found to interact with Raf-1 kinase through its C-terminal domain, leading to downstream activation of ERK. In the present study, we evaluated the effects of ZnT-1 in cultured murine cardiomyocytes (HL-1 cells) that were exposed to simulated-I/R. Cellular injury was evaluated by lactate dehydrogenase (LDH) release and by staining for pro-apoptotic caspase activation. Overexpression of ZnT-1 markedly reduced LDH release and caspase activation following I/R. Knockdown of endogenous ZnT-1 augmented the I/R-induced release of LDH and increased caspase activation following I/R. Phospho-ERK levels were signif... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5542208 Thu, 22 Dec 2011 16:37:47 +0100 5542208 http://www.medworm.com/index.php?rid=5542209&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy6306074p7tkq434%2F Abstract  To meet the growing need for tissue replacement materials for our aging population, the development of new adaptive biomaterials is essential. The tissues with the highest demand for implant materials are skin and bone. These tissues share various similarities, including signaling pathways and extracellular matrix composition. Glycosaminoglycans such as hyaluronan and chondroitin sulfate are the major organic extracellular matrix components. They modulate the attraction of skin and bone precursor cells and their subsequent differentiation and gene expression and regulate the action of proteins essential to bone and skin regeneration. The precise action of glycosaminoglycans varies according to their structural composition mainly in respect to the degree of sulfati... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5542209 Tue, 20 Dec 2011 16:46:57 +0100 5542209 http://www.medworm.com/index.php?rid=5512423&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fp4026g2256867725%2F Abstract  Cystic fibrosis (CF) is the most common lethal inherited disease in Caucasians and is caused by mutations in the CFTR gene. The disease is incurable and medical treatment is limited to the amelioration of symptoms or secondary complications. A comprehensive understanding of the disease mechanisms and the development of novel treatment options require appropriate animal models. Existing CF mouse models fail to reflect important aspects of human CF. We thus generated a CF pig model by inactivating the CFTR gene in primary porcine cells by sequential targeting using modified bacterial artificial chromosome vectors. These cells were then used to generate homozygous CFTR mutant piglets by somatic cell nuclear transfer. The homozygous CFTR mutants lack CFTR protein expres... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5512423 Wed, 14 Dec 2011 16:41:42 +0100 5512423 http://www.medworm.com/index.php?rid=5501083&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F256238u338v6k5t7%2F Content Type Journal ArticleCategory Clinical ImplicationsPages 1-3DOI 10.1007/s00109-011-0838-zAuthors Friedrich C. Luft, Experimental and Clinical Research Center, Charité Medical Faculty and Max-Delbrück Center for Molecular Medicine, Lindenbergerweg 80, 13125 Berlin, Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5501083 Fri, 09 Dec 2011 17:09:36 +0100 5501083 http://www.medworm.com/index.php?rid=5492614&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fkvn7803g32451632%2F Abstract  MicroRNAs (miRNAs) are a novel class of small, non-coding, single-stranded RNAs that negatively regulate gene expression via translational inhibition or mRNA degradation followed by protein synthesis repression. Many miRNAs are expressed in a tissue- and/or cell-specific manner and their expression patterns are reflective of underlying patho-physiologic processes. miRNAs can be detected in serum or in plasma in a remarkably stable form, making them attractive biomarkers for human diseases. This review describes the progress of identifying circulating miRNAs as novel biomarkers for diverse cardiovascular diseases, including acute myocardial infarction, heart failure, coronary artery disease, diabetes, stroke, essential hypertension, and acute pulmonary embolism. In... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5492614 Wed, 07 Dec 2011 10:48:17 +0100 5492614 http://www.medworm.com/index.php?rid=5454058&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg521t404343333l4%2F Abstract  The bromodomain protein BRD4 is involved in cell proliferation and cell cycle progression, primarily through its role in acetylated chromatin-dependent regulation of transcription at targeted loci. Here, we show that BRD4 is frequently downregulated by aberrant promoter hypermethylation in human colon cancer cell lines and primary tumors. Ectopic re-expression of BRD4 in these colon cancer cell lines markedly reduced in vivo tumor growth, suggesting a role of BRD4 in human colon cancer. Content Type Journal ArticleCategory Original ArticlePages 1-9DOI 10.1007/s00109-011-0837-0Authors R. M. Rodriguez, Cancer Epigenetics Laboratory, Instituto Universitario de Oncología del Principado de Asturias (IUOPA), HUCA, Universidad de Oviedo, Oviedo, SpainC. Huidobro, Ca... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5454058 Sat, 26 Nov 2011 16:48:01 +0100 5454058 http://www.medworm.com/index.php?rid=5454059&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv737r14420u21251%2F Abstract  Timely and accurate diagnosis of pancreatic ductal adenocarcinoma (PDAC) is critical in order to provide adequate treatment to patients. However, the clinical signs and symptoms of PDAC are shared by several types of malignant or benign tumors which may be difficult to differentiate from PDAC with conventional diagnostic procedures. Among others, these include ampullary cancers, solid pseudopapillary tumors, and adenocarcinomas of the distant bile duct, as well as inflammatory masses developing in chronic pancreatitis. Here, we report an approach to accurately differentiate between these different types of pancreatic masses based on molecular analysis of biopsy material. A total of 156 bulk tissue and fine needle aspiration biopsy samples were analyzed using a ded... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5454059 Fri, 25 Nov 2011 17:59:55 +0100 5454059 http://www.medworm.com/index.php?rid=5454060&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg23311234p6m3017%2F In this study we demonstrated that the expression of Erbin was upregulated in the tubular epithelia of 5/6-nephrectomized rats. We also showed here that TGF-β1 upregulated Erbin expression in NRK52E cells during their EMT phenotype acquisition. Importantly, elevated expression of Erbin inhibited ERK signaling and partial reversed EMT stimulated by TGF-β1. In the mean time, reducing Erbin expression enhanced ERK phosphorylation, promoted the E-cadherin suppression, and induced α-SMA expression and fibronection secretion in response to TGF-β1, which could be rescued if cells were treated with the inhibitor of MEK1/2 U0126. However, in the absence of TGF-β1, Erbin failed to affect ERK activation and EMT process. These results suggest that Erbin is a negative feedback molecule indu... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5454060 Thu, 24 Nov 2011 17:49:57 +0100 5454060 http://www.medworm.com/index.php?rid=5454061&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F870811vh395140u4%2F In this study, we have investigated the level of DLX3 expression in idiopathic FGR-affected placentae and determined its functional role in villous trophoblast differentiation. FGR-affected placentae (n = 25) were collected based on well-defined clinical criteria and matched for gestation with control uncomplicated pregnancies (n = 25). Real-time polymerase chain reaction and immunoblotting showed increased DLX3 mRNA and protein expression in FGR-affected placentae compared with gestation-matched controls. Qualitative immunohistochemistry revealed DLX3 localisation in the syncytiotrophoblast, cytotrophoblasts and endothelial cells surrounding the foetal capillaries in both FGR-affected and control placentae. Down-regulation of DLX3 in primary villous trophoblast cells and a tro... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5454061 Wed, 23 Nov 2011 17:42:23 +0100 5454061 http://www.medworm.com/index.php?rid=5447627&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F15356451q3214019%2F Abstract  Rapamycin, a specific inhibitor for mTOR complex 1, is an FDA-approved immunosuppressant for organ transplant. Recent developments have raised the prospect of using rapamycin to treat cancer or diabetes and to delay aging. It is therefore important to assess how rapamycin treatment affects glucose homeostasis. Here, we show that the same rapamycin treatment reported to extend mouse life span significantly impaired glucose homeostasis of aged mice. Moreover, rapamycin treatment of lean C57B/L6 mice reduced glucose-stimulated insulin secretion in vivo and ex vivo as well as the insulin content and beta cell mass of pancreatic islets. Confounding the diminished capacity for insulin release, rapamycin decreased insulin sensitivity. The multitude of rapamycin effects t... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5447627 Mon, 21 Nov 2011 18:04:34 +0100 5447627 http://www.medworm.com/index.php?rid=5437246&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm82q02j118800690%2F Abstract  Leukocyte recruitment into tissue forms the basis of immune surveillance and direct immune defense. It proceeds in a cascade-like fashion. The first contact of leukocytes with the endothelium is mediated by selectins and their counter receptors, followed by rolling and integrin-mediated arrest. While rolling, neutrophils collect different inflammatory signals which can activate several signaling pathways leading to leukocyte adhesion to the endothelium and transmigration through the blood vessel wall into the inflamed tissue. Whereas inflammatory reactions are beneficial and necessary for host defense, they need to be balanced and controlled to prevent harmful consequences and tissue destruction. In this article, we discuss the different signaling pathways that en... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5437246 Fri, 18 Nov 2011 17:32:44 +0100 5437246 http://www.medworm.com/index.php?rid=5437247&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcw2002228032r722%2F In this study, we spearheaded noninvasive detection of ovarian cancer by salivary transcriptomic biomarkers, and evaluated the clinical utilities of discovered biomarkers using a clinical case–control study. To find salivary mRNA biomarkers, salivary transcriptomes in 11 ovarian cancer patients and 11 matched controls were profiled by Affymetrix HG-U133-Plus-2.0 array. The biomarker candidates selected from the microarray results were then subjected to clinical validation by RT-qPCR using an independent sample cohort including 21 ovarian cancer patients and 35 healthy controls. Seven downregulated mRNA biomarkers were validated. The logistic regression model revealed the combination of five validated biomarkers (AGPAT1, B2M, BASP2, IER3, and IL1B) can significantly discriminate ova... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5437247 Fri, 18 Nov 2011 06:58:29 +0100 5437247 http://www.medworm.com/index.php?rid=5437248&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbm437541727735th%2F Abstract  Kinase domains are the type of protein domain most commonly found in genes associated with tumorigenesis. Because of this, the human kinome (the protein kinase component of the genome) represents a promising source of cancer biomarkers and potential targets for novel anti-cancer therapies. Alterations in the human colon kinome during the progression from normal colon (NC) through adenoma (AD) to adenocarcinoma (AC) were investigated using integrated transcriptomic and proteomic datasets. Two hundred thirty kinase genes and 42 kinase proteins showed differential expression patterns (fold change ≥ 1.5) in at least one tissue pair-wise comparison (AD vs. NC, AC vs. NC, and/or AC vs. AD). Kinases that exhibited similar trends in expression at both the mRNA and p... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5437248 Fri, 18 Nov 2011 06:58:27 +0100 5437248 http://www.medworm.com/index.php?rid=5428033&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft78m1l3878n26503%2F Abstract  Obstructive sleep apnea (OSA) is a prevalent disorder characterized by intermittent hypoxia (IH) during sleep. OSA is strongly associated with obesity and dysregulation of metabolism—yet the molecular pathways linking the effects of IH on adipocyte biology remain unknown. We hypothesized that exposure to IH would activate distinct, time-dependent transcriptional programs in visceral adipose tissue of mice. We exposed 36 mice to IH or normoxia for up to 13 days. We transcriptionally profiled visceral fat tissue harvested from the animals and performed functional enrichment and network analysis on differentially expressed genes. We identified over 3,000 genes with significant expression patterns during the time course of IH exposure. The most enriched pathway... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5428033 Tue, 15 Nov 2011 16:48:42 +0100 5428033 http://www.medworm.com/index.php?rid=5417605&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa476865677757373%2F Abstract  Pattern recognition scavenger receptor SRA/CD204, primarily expressed on specialized antigen-presenting cells (APCs), including dendritic cells (DCs) and macrophages, has been implicated in multiple physiological and pathological processes, including atherosclerosis, Alzheimer’s disease, endotoxic shock, host defense, and cancer development. SRA/CD204 was also recently shown to function as an attenuator of vaccine response and antitumor immunity. Here, we, for the first time, report that SRA/CD204 knockout (SRA−/−) mice developed a more robust CD4+ T cell response than wild-type mice after ovalbumin immunization. Splenic DCs from the immunized SRA−/− mice were much more efficient than those from WT mice in stimulating naïve OT-II cells, indicating that th... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5417605 Mon, 14 Nov 2011 16:51:23 +0100 5417605 http://www.medworm.com/index.php?rid=5404732&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj127480253w80763%2F Abstract  Giant cell tumor (GCT) of bone is a benign type of tumor, but the presence of hyperactive multinucleated giant osteoclasts cause local osteolytic lesions, increasing morbidity in patients. To specifically target hyperactive multinucleated giant osteoclasts in GCTs, one would envisage the usage of osteoclast inhibitors or genetic modulation of osteoclastogenesis. Recently, we have found that the translationally regulated balance between the transcription factor C/EBPβ long (LAP) and short (LIP) protein isoforms regulates osteoclast differentiation. Here, we report that GCTs express high levels of the LIP C/EBPβ isoform, which in mice cause giant osteoclast formation. In mice, inhibition of mTOR activity by rapamycin decreased osteoclast differentiation by shiftin... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5404732 Wed, 09 Nov 2011 17:51:56 +0100 5404732 http://www.medworm.com/index.php?rid=5404733&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F1630328p25000200%2F Abstract  Solar lights encompass ultraviolet (UV), visible, and infrared spectrum. Most previous studies focused on the harmful UV effects, and the biologic effects of lights at other spectrums remained unclear. Recently, lights at visible region have been used for regenerative purposes. Using the process of vitiligo repigmentation as a research model, we focused on elucidating the pro-differentiation effects induced by visible light. We first showed that helium–neon (He–Ne) laser (632.8 nm) irradiation stimulated differentiation of primitive pigment cells, an effect not replicable by UVB treatment even at high and damaging doses. In addition, significant increases of mitochondrial DNA copy number and the regulatory genes for mitochondrial biogenesis were induced b... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5404733 Tue, 08 Nov 2011 19:13:00 +0100 5404733 http://www.medworm.com/index.php?rid=5404734&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0t30x286n5k758n0%2F Abstract  The aim of this study was to construct a promoter containing DNA motifs for an endogenous transcription factor associated with inflammation along with motifs for pharmacological regulation factors. We demonstrate in transfected cells that expression of a gene of interest is induced by hypoxic conditions or through pharmacological induction, and also show pharmacological repression. In vivo studies utilised electroporation of plasmid to mouse paws, a delivery method shown to be effective by bioluminescence imaging. For gene therapy, the promoter was used to drive expression of IL-1Ra in a paw inflammation model with therapeutic effect observed which was further enhanced when the promoter was additionally induced with a pharmacological activator. One of the most imp... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5404734 Tue, 08 Nov 2011 19:12:58 +0100 5404734 http://www.medworm.com/index.php?rid=5396797&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk5435g017744820q%2F Content Type Journal ArticleCategory Clinical ImplicationsPages 1-3DOI 10.1007/s00109-011-0827-2Authors Friedrich C. Luft, Experimental and Clinical Research Center, Charité Medical Faculty and Max-Delbrück Center for Molecular Medicine, Berlin, Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5396797 Thu, 03 Nov 2011 16:53:17 +0100 5396797 http://www.medworm.com/index.php?rid=5375295&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4r872755602504px%2F In this study, we found that NAD-dependent protein deacetylase SIRT1 is differentially expressed in both human bone marrow-derived MSCs (B-MSCs) and adipose tissue-derived MSCs after increasing passages of cell culture. Using lentiviral shRNA we demonstrated that selective knockdown of SIRT1 in human MSCs at early passage slows down cell growth and accelerates cellular senescence. Conversely, overexpression of SIRT1 delays senescence in B-MSCs that have undergone prolonged in vitro culturing and the cells do not lose adipogenic and osteogenic potential. In addition, we found that the delayed accumulation of the protein p16 is involved in the effect of SIRT1. However, resveratrol, which has been used as an activator of SIRT1 deacetylase activity, only transiently promotes proliferatio... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5375295 Sat, 29 Oct 2011 05:43:39 +0100 5375295 http://www.medworm.com/index.php?rid=5375296&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F63r43220511pw769%2F Abstract  Systemic sclerosis (SSc) is a connective tissue disease characterised by exaggerated collagen deposition in the skin and visceral organs. Adenosine A2A receptor stimulation (A2Ar) promotes dermal fibrosis, while the cannabinoid system modulates fibrogenesis in vitro and in animal models of SSc. Moreover, evidence in central nervous system suggests that A2A and cannabinoid (CB1) receptors may physically and functionally interact. On this basis, we investigated A2Ar expression and function in modulating collagen biosynthesis from SSc dermal fibroblasts and analysed the cross-talk with cannabinoid receptors. In sclerodermic cells, A2Ar expression (RT-PCR, Western blotting) was evaluated together with the effects of A2A agonists and/or antagonists on collagen biosynth... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5375296 Fri, 28 Oct 2011 06:04:40 +0100 5375296 http://www.medworm.com/index.php?rid=5343502&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F21710q48315123w3%2F Abstract  Intronic single-nucleotide polymorphisms (SNPs) are commonly associated with complex diseases but exhibit unknown biologic functionality. Myosin light-chain kinase (MLCK), a central cytoskeletal regulator encoded by MYLK, plays a key pathophysiological role in complex diseases including acute lung injury (ALI) and asthma. We studied the potential regulatory roles of two intronic MYLK SNPs (rs936170 and rs820336) previously associated with ALI and asthma. Due to their genomic location at the junction encoding the non-muscle and smooth muscle MLCK (smMLCK) isoforms, we first identified the transcription start site (TSS) of the smMLCK isoform, and isolated a 2,954-bp DNA fragment upstream of the smMLCK TSS. Serial 5′ deletion of the fragment revealed a proximal prom... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5343502 Thu, 20 Oct 2011 15:47:40 +0100 5343502 http://www.medworm.com/index.php?rid=5343503&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fbk776u24kh41t051%2F Abstract  RU486 (Mifepristone) has been known as antiprogesterone and antiglucocorticoid agent. RU486 is also used for treatment of several cancers, such as breast, ovarian, prostate, and glaucoma. Here, we investigated the effect of RU486 on TRAIL-induced apoptosis in human renal carcinoma Caki cells. Low dose of RU486 (30–50 μM) alone had no effect on apoptosis, but RU486 markedly sensitized Caki cells to TRAIL-induced apoptosis. We found that up-regulation of death receptor 5 (DR5; receptor for TRAIL ligand), and down-regulation of Bcl-2 and c-FLIP (caspase regulator) contributes to RU-486 induced TRAIL sensitization. Down-regulation of DR5 by siRNA also blocked RU486 induced TRAIL sensitization. Furthermore, overexpression of Bcl-1 or c-FLIP(L) inhibited the cel... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5343503 Wed, 19 Oct 2011 05:54:43 +0100 5343503 http://www.medworm.com/index.php?rid=5330602&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd07451rq1r405j24%2F Abstract  Colorectal cancer (CRC) is one of the most common cancers worldwide. More than half of all CRC patients will develop metastases, which represents the major cause of death for CRC patients. CRC metastases confined in other organs are potentially resectable, and patients who receive curative resections appear to have better outcomes. Thus, the early detection of metastasis in CRC patients could improve their survival rate after curative surgery. Here, we report the use of Cy-dye labeling combined with multi-dimensional fractionation and mass spectrometry as a proteomics-based approach for identifying CRC metastasis-associated biomarker(s) in plasma samples collected from three CRC patients upon diagnosis of their primary and metastatic tumors. Among the eight identi... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5330602 Thu, 13 Oct 2011 15:50:45 +0100 5330602 http://www.medworm.com/index.php?rid=5321507&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F201ul55115486725%2F Abstract  Tuberculosis (TB) caused by Mycobacterium tuberculosis (Mtb) is one of the most deadly infectious diseases, with approximately two million people dying of TB annually. An effective therapeutic method for activating dendritic cells (DCs) and driving Th1 immune responses would improve host defenses and further the development of a TB vaccine. Given the importance of DC maturation in eliciting protective immunity against TB, we investigated whether Rv0315, a newly identified Mtb antigen, can prompt DC maturation. We found that Rv0315 functionally activated DCs by augmenting the expression of the co-stimulatory molecules CD80 and CD86 as well as MHC class I/II molecules. Moreover, it increased DC secretion of the pro-inflammatory cytokines IL-6, IL-1β, and TNF-α. Unl... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5321507 Wed, 12 Oct 2011 16:32:29 +0100 5321507 http://www.medworm.com/index.php?rid=5281464&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fxx684613651t0497%2F Abstract  Immune disorders are linked to the development of type 2 diabetes (T2D) and its complications. The relationship of CD4+CD25hi T regulatory cells (Treg) and pro-inflammatory Th17 and Th1 subsets in T2D patients with metabolic disorders and complications need to be determined. The ratios of CD4+CD25hi Treg/Th17 cells and CD4+CD25hi Treg/Th1 cells, but not Th17/Th1 cells, were significantly decreased in T2D patients. The thymic output CD4+Foxp3+Helios+ Tregs were normal but peripheral induced CD4+Foxp3+Helios− Tregs were decreased in T2D patients. The Bcl-2/Bax ratio decreased in CD4+CD25hi Tregs in T2D patients, supporting the increased sensitivity to cell death of these cells in T2D. CD4+CD25hiCD127− Tregs in T2D patients with microvascular complications were signif... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5281464 Sat, 01 Oct 2011 05:48:22 +0100 5281464 http://www.medworm.com/index.php?rid=5257268&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk241720702m15552%2F Abstract  There is a considerable inter-individual variation in response to statin therapy and one third of patients do not meet their treatment goals. We aimed to identify differentially expressed genes that might be involved in the effects of statin treatment and to suggest potential markers to guide statin therapy. Forty-six healthy Korean subjects received atorvastatin; their whole-genome expression profiles in peripheral blood were analyzed before and after atorvastatin administration in relation with changes in lipid profiles. The expression patterns of the differentially expressed genes were also compared with the data of familial hypercholesterolemia (FH) patients and controls. Pairwise comparison analyses revealed differentially expressed genes involved in diverse ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5257268 Fri, 23 Sep 2011 15:51:45 +0100 5257268 http://www.medworm.com/index.php?rid=5257269&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fy0173410468154x6%2F In this study, we found 36 mass-to-charge-ratio (m/z) species that specifically distinguished metastatic from non-metastatic tumors, among which m/z 11,608 was identified as thioredoxin, m/z 11,184 as S100-A10, and m/z 10,094 as S100-A6. Furthermore, using IHC on the validation set, we showed that the overexpression of these three proteins was highly associated with lymph node metastasis in PTC (p < 0.005). For functional analysis of the metastasis-specific proteins, we performed an Ingenuity Pathway Analysis and discovered a strong relationship of all candidates with the TGF-β-dependent EMT pathway. Our results demonstrated the potential application of the MALDI-IMS proteomic approach in identifying protein markers of metastasis in PTC. The novel protein markers identified in ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5257269 Thu, 22 Sep 2011 05:52:49 +0100 5257269 http://www.medworm.com/index.php?rid=5233428&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd464307n41q92707%2F Abstract  Deregulation of Ras/ERK signaling in myeloid leukemias makes this pathway an interesting target for drug development. Myeloid leukemia cell lines were screened for idarubicin-induced apoptosis, cell-cycle progression, cell-cycle-dependent MAP kinase kinase (MEK-1/2) activation, and Top2 expression. Cell-cycle-dependent activation of MEK/ERK signaling was blocked using farnesyltransferase inhibitor (FTI) BMS-214,662 and dual prenyltransferase inhibitor (DPI) L-778,123 to disrupt Ras signaling. Idarubicin caused a G2/M cell-cycle arrest characterized by elevated diphosphorylated MEK-1/2 and Top2α expression levels. The FTI/DPIs elicited distinct effects on Ras signaling, protein prenylation, cell cycling and apoptosis. Combining these FTI/DPIs with idarubicin syner... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5233428 Wed, 14 Sep 2011 05:52:38 +0100 5233428 http://www.medworm.com/index.php?rid=5233427&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm410u04772q38553%2F Abstract  IRX-2, a natural cytokine biological with multiple components, has been used in preclinical and clinical studies to promote antitumor activity of T lymphocytes. To define cellular mechanisms responsible for antitumor effects of IRX-2, its ability to induce effector T cells (Teff) was examined in a model simulating the tumor microenvironment. An in vitro model containing conventional CD4+CD25− cells co-cultured with autologous immature dendritic cells, irradiated tumor cells, and cytokines was used to study differentiation and expansion of regulatory T cells (Treg) and Teff in the presence and absence of IRX-2. Phenotype, suppressor function, signaling, and cytokine production were serially measured using flow cytometry, Western blots, CFSE-based suppressor assays... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5233427 Wed, 14 Sep 2011 05:52:38 +0100 5233427 http://www.medworm.com/index.php?rid=5233429&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F602254758232854r%2F In conclusion, IL-1 beta is significantly linked to poor prognosis for patients with esophageal cancer and may be a promising molecular target for therapeutic intervention for esophageal SCC. Content Type Journal ArticleCategory Original ArticlePages 1-12DOI 10.1007/s00109-011-0809-4Authors Miao-Fen Chen, Department of Radiation Oncology, Chang Gung Memorial Hospital at Chia-Yi, Chia-Yi, TaiwanMing-Shian Lu, Department of Thoracic & Cardiovascular Surgery, Chang Gung Memorial Hospital at Chia-Yi, Chia-Yi, TaiwanPing-Tsung Chen, Department of Hematology and Oncology, Chang-Gung Memorial Hospital, Chia-Yi, #6, Chia-Pu Rd, Putz City, Chia-Yi Hsien, TaiwanWen-Cheng Chen, Department of Radiation Oncology, Chang Gung Memorial Hospital at Chia-Yi, Chia-Yi, TaiwanPaul-Yang Lin, Department ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5233429 Mon, 12 Sep 2011 15:50:50 +0100 5233429 http://www.medworm.com/index.php?rid=5217682&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fqj525550535t88k3%2F Abstract  Intermedin (IMD) is a novel member of the calcitonin/calcitonin gene-related peptide family. We aimed to explore whether the cardioprotective effect of IMD is mediated by inhibiting myocardial endoplasmic reticulum (sarcoplasmic reticulum) stress (ERS). In vitro, IMD1–53 (10−9, 10−8, and 10−7 mol/l) directly inhibited the upregulation of ERS markers such as glucose-regulated protein 78, CCAAT/enhancer binding protein homologous protein, and caspase-12 induced by the ERS inducers tunicamycin (Tm, 10 mg/ml) or dithiothreitol (DTT, 2 mmol/l) in cardiac tissue. IMD1–53 also inhibited Tm- or DTT-induced upregulation of cleaved activating transcription factor 6 and 4. These inhibitory effects of IMD1–53 were abolished by the IMD receptor antago... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5217682 Sat, 10 Sep 2011 15:48:35 +0100 5217682 http://www.medworm.com/index.php?rid=5217683&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff1371662n3011t76%2F In this study, we investigated the effect of bortezomib on the expression, activity and localization of HIF-1α in LNCaP (AD) and PC3 (AI) PCa cells. First, we show that hypoxic upregulation of HIF-1α protein levels and activity involves both the PI3K/Akt/mTOR and p44/42 MAPK pathways. Second, bortezomib inhibits expression of HIF-1α protein under both normoxic and hypoxic conditions, represses HIF-1 transcriptional activity and attenuates the release of vascular endothelial growth factor. These effects correlate with the ability of bortezomib to cause dephosphorylation of phospho-Akt, phospho-p70S6K, and phospho-S6RP, thus inactivating a pathway known to be required for HIF-1α protein expression at the translational level. Furthermore, bortezomib also abrogates p44/42 MAPK phosph... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5217683 Sat, 10 Sep 2011 06:01:58 +0100 5217683 http://www.medworm.com/index.php?rid=5217684&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F63n33306304126v7%2F Abstract  Ischemic stroke is a devastating disease which, in most cases, is caused by thrombotic occlusion of brain arteries. The molecular mechanisms involved in microvascular thrombus formation during focal cerebral ischemia are not well understood. As a consequence, the current antithrombotic drugs used to treat acute stroke or prevent stroke recurrence either show limited efficacy or put patients at risk for serious bleeding complications. The serine protease blood coagulation factor XII (FXII) initiates the intrinsic pathway of coagulation which, together with the extrinsic pathway, culminates in the formation of fibrin. A physiological function of FXII in clot formation and hemostasis in vivo has been questioned for more than 50 years. This was mainly due to the ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5217684 Fri, 09 Sep 2011 16:46:38 +0100 5217684 http://www.medworm.com/index.php?rid=5204145&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8h35104w28n35j30%2F Abstract  Biotin (vitamins H and B7) is an important micronutrient as defects in its availability, metabolism or adsorption can cause serious illnesses, especially in the young. A key molecule in the biotin cycle is holocarboxylase synthetase (HLCS), which attaches biotin onto the biotin-dependent enzymes. Patients with congenital HLCS deficiency are prescribed oral biotin supplements that, in most cases, reverse the clinical symptoms. However, some patients respond poorly to biotin therapy and have an extremely poor long-term prognosis. Whilst a small number of mutations in the HLCS gene have been implicated, the molecular mechanisms that lead to the biotin-unresponsive phenotype are not understood. To improve our understanding of HLCS, limited proteolysis was performed to... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5204145 Tue, 06 Sep 2011 05:48:26 +0100 5204145 http://www.medworm.com/index.php?rid=5204146&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb135kmhl138671r7%2F Abstract  Nonalcoholic fatty liver disease (NAFLD) is a metabolic disorder including simple steatosis and nonalcoholic steatohepatitis (NASH). Advanced stages of NASH result ultimately in fibrosis, cirrhosis, and hepatocarcinoma. A diagnosis of NASH entails an increased risk of both liver-related and cardiovascular mortality as worsening of the metabolic syndrome. Because of its escalation, many investigations have been performed to elucidate the pathophysiologic origins of the disease progression. Human epidemiologic studies describing polymorphisms in a number of genes involved in metabolic dysfunctions have contributed to clarify the causes leading to the disease evolution. In this review, we attempt to outline critically the most recently identified genetic variants in ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5204146 Mon, 05 Sep 2011 16:16:42 +0100 5204146 http://www.medworm.com/index.php?rid=5194787&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ff7j15256x435m757%2F Content Type Journal ArticleCategory Clinical ImplicationsPages 1-3DOI 10.1007/s00109-011-0810-yAuthors Jan Fritzsche, Department of Medicine/Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, GermanyPhilipp Stawowy, Department of Medicine/Cardiology, Deutsches Herzzentrum Berlin, Augustenburger Platz 1, 13353 Berlin, Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5194787 Fri, 02 Sep 2011 05:50:38 +0100 5194787 http://www.medworm.com/index.php?rid=5194786&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F826433863l851815%2F In this study, we observed heightened TLR4 levels in GBM tumor samples as compared to adjacent normal tissue. Since the pro-inflammatory cytokine tumor necrosis factor (TNF)α induces NF-κB activation in GBM, and as several common signaling mediators are involved in TNFα and TLR4-mediated NF-κB activation, we investigated the role of TLR4 in the regulation of NF-κB activation and inflammatory responses in TNFα-treated glioma cells. TNFα elevated TLR4 expression and inhibition of TLR4 signaling by either signaling inhibitor, neutralizing antibody, or small interfering RNA (siRNA)-attenuated TNFα-induced NF-κB activation. TLR4-mediated NF-κB activation was independent of canonical myeloid differentiation factor 88 signaling but involved toll/IL-1R homology domain-containing ad... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5194786 Fri, 02 Sep 2011 05:50:38 +0100 5194786 http://www.medworm.com/index.php?rid=5173928&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fpj5q71428613536v%2F Abstract  Right ventricular hypertrophy (RVH) and RV failure are major determinants of prognosis in pulmonary hypertension and congenital heart disease. In RVH, there is a metabolic shift from glucose oxidation (GO) to glycolysis. Directly increasing GO improves RV function, demonstrating the susceptibility of RVH to metabolic intervention. However, the effects of RVH on fatty acid oxidation (FAO), the main energy source in adult myocardium, are unknown. We hypothesized that partial inhibitors of FAO (pFOXi) would indirectly increase GO and improve RV function by exploiting the reciprocal relationship between FAO and GO (Randle’s cycle). RVH was induced in adult Sprague-Dawley rats by pulmonary artery banding (PAB). pFOXi were administered orally to prevent (trimetazidine... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5173928 Sat, 27 Aug 2011 15:48:07 +0100 5173928 http://www.medworm.com/index.php?rid=5173929&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fu23033073p645263%2F We report that the NK cell percentage within RCC-infiltrating lymphocytes, as determined by flow cytometry, allows ccRCC subgrouping in NKhigh/NKlow tissues independent of TNMG classification. Quantitative reverse transcriptase polymerase chain reaction using whole-tissue RNA identified four markers (NKp46, perforin, CX3CL1, and CX3CR1) whose transcript levels reproduced the NKhigh/NKlow tissue distinction identified by flow cytometry with high selectivity and specificity. Combined in a multiplex profile and analyzed using neural network, the accuracy of predicting the NKhigh/NKlow groups was 87.8%, surpassing that of each single marker. The tissue transcript signature, based on a robust high-throughput methodology, is easily amenable to archive material and clinical translation. This ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5173929 Thu, 25 Aug 2011 15:48:03 +0100 5173929 http://www.medworm.com/index.php?rid=5155612&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6t805r855522m714%2F Abstract  The human intestine harbors a large number of bacteria that are constantly interacting with the intestinal immune system, eliciting non-pathological basal level immune responses. Increasing evidence points to dysbiosis of microbiota in the intestine as an underlying factor in inflammatory bowel disease susceptibility. Loss-of-function mutations in NOD2 are among the stronger genetic factors linked to ileal Crohn’s disease. Indeed, Nod2 is a key regulator of microbiota in the intestine, as microflora in the terminal ileum is dysregulated in Nod2-deficient mice. Nod2 is highly expressed in Paneth cells, which are responsible for the regulation of ileal microflora by anti-microbial compounds, and Nod2-deficient ileal intestinal epithelia are unable to kill bacteria ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5155612 Mon, 22 Aug 2011 16:06:40 +0100 5155612 http://www.medworm.com/index.php?rid=5155613&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0kj72487235141u3%2F In this study, we employed the FcγRs to target DCs both in vitro and in vivo. We designed a recombinant molecule (HER2-Fc) composed of the immunogenic sequence of the human tumor-associated antigen HER2 (aa 364–391) and the Fc domain of a human IgG1. In a mouse model, HER2-Fc cDNA vaccination activated significant T cell-mediated immune responses towards HER2 peptide epitopes as detected by IFN-γ ELIspot and induced longer tumor latency as compared to Ctrl-Fc-vaccinated control mice. Human in vitro studies indicated that the recombinant HER2-Fc immunogen efficiently targeted human DCs through the FcγRs resulting in protein cross-processing and in the activation of autologous HER2-specific CD8+ T cells from breast cancer patients. Content Type Journal ArticleCategory Original... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5155613 Tue, 16 Aug 2011 06:08:28 +0100 5155613 http://www.medworm.com/index.php?rid=5137794&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2m6v4383202vq268%2F We report that while the metalloproteinase membrane type 1-metalloprotease (MT1-MMP) has an essential role in human HSPC trafficking during granulocyte colony-stimulating factor (G-CSF)-induced mobilization, its inhibitor reversion-inducing cysteine-rich protein with Kazal motifs (RECK) and the adhesion molecule CD44 are required for HSPC retention to the BM in steady-state conditions. The nervous system via Wnt signaling along with HGF/c-Met signaling and the complement cascade play a major role in regulating MT1-MMP increased activity, CD44 cleavage, and RECK-reduced expression during G-CSF-induced mobilization. This review will elaborate on the opposite roles of MT1-MMP and RECK in HSPC migration and retention and suggest targeting them in order to facilitate HSPC mobilization an... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5137794 Sat, 13 Aug 2011 06:08:14 +0100 5137794 http://www.medworm.com/index.php?rid=5137793&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa8487p4732486004%2F Abstract  Endothelial cell-dependent vascular relaxation plays an important role in the regulation of blood pressure. Here, we show that stimulation of vascular endothelial cells with platelet-derived growth factor (PDGF) results in vascular relaxation through Akt1-dependent activation of endothelial nitric oxide synthase (eNOS) and nitric oxide (NO) production. Stimulation of both human umbilical artery endothelial cells and abdominal aortic vessels with PDGF induced NO production. PDGF-dependent production of NO was completely abolished by inhibition of phosphatidylinositol 3-kinase with wortmannin (100 nM). Stimulation of aortic vessels with PDGF resulted in the activation of Akt phosphorylation and eNOS phosphorylation: however, eNOS phosphorylation and production ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5137793 Sat, 13 Aug 2011 06:08:14 +0100 5137793 http://www.medworm.com/index.php?rid=5129932&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F5521351871658515%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s00109-011-0789-4Authors Sharon Bakalash, Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, IsraelGil Ben-Shlomo, Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot, IsraelEyal Aloni, Department of Ophthalmology, Kaplan Medical Center, Rehovot, IsraelIftach Shaked, Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, IsraelLarry Wheeler, Department of Biological Sciences, Allergan Pharmaceuticals, Irvine, CA, USARon Ofri, Koret School of Veterinary Medicine, The Hebrew University of Jerusalem, Rehovot, IsraelMichal Schwartz, Department of Neurobiology, The Weizmann Institute of Science, 76100 Rehovot, Israel Journal Journal of Molecular MedicineOnli... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5129932 Thu, 11 Aug 2011 06:56:47 +0100 5129932 http://www.medworm.com/index.php?rid=5124411&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F824n681964u30113%2F Abstract  Natriuretic peptides (NPs) exert well-characterized protective effects on the cardiovascular system, such as vasorelaxation, natri- and diuresis, increase of endothelial permeability, and inhibition of renin–angiotensin–aldosterone system. It has been reported that they also possess antihypertrophic and antifibrotic properties and contribute actively to cardiac remodeling. As a consequence, they are involved in several aspects of cardiovascular diseases. Antihypertrophic and antifibrotic actions of NPs appear to be mediated by specific signaling pathways within a more complex cellular network. Elucidation of the molecular mechanisms underlying the effects of NPs on cardiac remodeling represents an important research objective in order to gain more insights on ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5124411 Mon, 08 Aug 2011 19:55:14 +0100 5124411 http://www.medworm.com/index.php?rid=5117078&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn6lx1l73ttm65211%2F Abstract  The molecular functions and pathophysiologic role of the lymphocyte α-kinase gene (ALPK1) in gout are unknown. We aimed to examine ALPK1 expression in patients with gout and investigate its role in monosodium urate monohydrate (MSU)-induced inflammatory responses. Microarray data mining was performed with six datasets containing three clinical gout and three volunteer samples. Real-time quantitative polymerase chain reaction (qPCR) assay was used to profile ALPK1 mRNA expression in 62 independent samples. RNA interference for ALPK1 suppression in THP1 cells (human monocytic cell line) was used to scrutinize the functional role of ALPK1 in MSU-mediated inflammatory responses, and ALPK1 expression in MSU-treated THP1 cells was determined by qPCR and Western blot analys... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5117078 Sun, 07 Aug 2011 05:52:39 +0100 5117078 http://www.medworm.com/index.php?rid=5117081&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2089360vt7125r41%2F Abstract  Cell death in bacteria can be triggered by activation of self-inflicted molecular mechanisms. Pathogenic bacteria often make use of suicide mechanisms in which the death of individual cells benefits survival of the population. Important elements for programmed cell death in bacteria are proteinaceous toxin–antitoxin systems. While the toxin generally resides dormant in the bacterial cytosol in complex with its antitoxin, conditions such as impaired de novo synthesis of the antitoxin or nutritional stress lead to antitoxin degradation and toxin activation. A widespread toxin–antitoxin family consists of the ε/ζ systems, which are distributed over plasmids and chromosomes of various pathogenic bacteria. In its inactive state, the bacteriotoxic ζ toxin protein... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5117081 Sat, 06 Aug 2011 05:59:56 +0100 5117081 http://www.medworm.com/index.php?rid=5117080&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa515804811r61630%2F This study demonstrates for the first time that andrographolide possesses a novel role of antiplatelet activity, which may involve the activation of the eNOS-NO/cyclic GMP pathway, resulting in the inhibition of the PI3 kinase/Akt-p38 MAPK and PLCγ2–PKC cascades, thereby leading to inhibition of platelet aggregation. Content Type Journal ArticlePages 1-13DOI 10.1007/s00109-011-0800-0Authors Wan-Jung Lu, Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei, TaiwanJie-Jen Lee, Department of Surgery, Mackay Memorial Hospital, Taipei, TaiwanDuen-Suey Chou, Department of Pharmacology, School of Medicine, College of Medicine, Taipei Medical University, 250 Wuxing St., Taipei, 11031 TaiwanThanasekaran Jayakumar, Graduate Institute of Medical ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5117080 Sat, 06 Aug 2011 05:59:56 +0100 5117080 http://www.medworm.com/index.php?rid=5117079&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fjp8722203624q6q1%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00109-011-0791-xAuthors Friedrich C. Luft, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Lindenbergerweg 80, 13125 Berlin, Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5117079 Sat, 06 Aug 2011 05:59:56 +0100 5117079 http://www.medworm.com/index.php?rid=5117082&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F948131h313215n50%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00109-011-0799-2Authors Jalees Rehman, Section of Cardiology, Department of Medicine and Department of Pharmacology, College of Medicine, University of Illinois at Chicago, (M/C 868) 835 S. Wolcott Ave. Rm. E403, Chicago, IL 60612, USA Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5117082 Sat, 06 Aug 2011 05:59:52 +0100 5117082 http://www.medworm.com/index.php?rid=5106086&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fd1250n3176l72029%2F Abstract  Central angiotensin II (AngII) plays an important role in the regulation of the sympathetic nervous system. The underlining molecular mechanisms are largely unknown. Spinophilin (SPL) is a regulator of G protein-coupled receptor signaling. Deletion of SPL induces sympathetically mediated arterial hypertension in mice. We tested the hypothesis that SPL restrains blood pressure (BP) by regulating AngII activity. We equipped SPL−/− and SPL+/+ mice with telemetric devices and applied AngII (1.0 mg kg−1 day−1, minipumps) or the AngII subtype 1 receptor (AT1-R) blocker valsartan (50 mg kg−1 day−1, gavage). We assessed autonomic nervous system activity through intraperitoneal application of trimethaphan, metoprolol, and atropine. W... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5106086 Fri, 05 Aug 2011 05:52:57 +0100 5106086 http://www.medworm.com/index.php?rid=5106085&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmr065k9083w37663%2F Abstract  Macroautophagy is a catabolic process by which the cell degrades cytoplasmic components through the lysosomal machinery. While initially acknowledged as a rather unspecific bulk degradation process, growing lines of evidence indicate the selectivity of macroautophagy pathways in the removal of misfolded or aggregated proteins. How such substrates are recognized and specifically targeted to the macroautophagy machinery has become a hotspot of investigation, and recent evidence suggests that here molecular chaperones and co-chaperones play a central role. One emerging pathway is mediated by the co-chaperone protein Bcl-2-associated athanogene 3 (BAG 3) which seems to utilize the specificity of molecular chaperones (heat-shock proteins) towards non-native proteins as... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5106085 Fri, 05 Aug 2011 05:52:57 +0100 5106085 http://www.medworm.com/index.php?rid=5106087&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa35753u256212584%2F In conclusion, these data imply that cell apoptosis contributes to the pathogenesis of NASH, during which HSS expression is downregulated. Increasing HSS expression in hepatocytes may forestall cell apoptosis as result of fatty acid insult. Content Type Journal ArticlePages 1-11DOI 10.1007/s00109-011-0790-yAuthors Ying Jiang, Department of Cell Biology and Municipal Laboratory for Liver Protection and Regulation of Liver Regeneration, Capital Medical University, 10 You An Men Wai Xi Tou Tiao, 100069 Beijing, ChinaMiaoyun Zhao, Department of Cell Biology and Municipal Laboratory for Liver Protection and Regulation of Liver Regeneration, Capital Medical University, 10 You An Men Wai Xi Tou Tiao, 100069 Beijing, ChinaWei An, Department of Cell Biology and Municipal Laboratory for Live... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5106087 Thu, 04 Aug 2011 15:23:28 +0100 5106087 http://www.medworm.com/index.php?rid=5102757&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fg53j445141r3m749%2F Abstract  Pulmonary arterial hypertension (PAH) is a vascular remodeling disease characterized by enhanced proliferation and suppressed apoptosis of pulmonary artery smooth muscle cells (PASMC). This apoptosis resistance is characterized by PASMC mitochondrial hyperpolarization [in part, due to decreased pyruvate dehydrogenase (PDH) activity], decreased mitochondrial reactive oxygen species (mROS), downregulation of Kv1.5, increased [Ca++]i, and activation of the transcription factor nuclear factor of activated T cells (NFAT). Inflammatory cells are present within and around the remodeled arteries and patients with PAH have elevated levels of inflammatory cytokines, including tumor necrosis factor-α (TNFα). We hypothesized that the inflammatory cytokine TNFα inhibits PASM... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5102757 Tue, 02 Aug 2011 05:54:18 +0100 5102757 http://www.medworm.com/index.php?rid=5061493&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fq47t3298814520g1%2F We examined whether NB54 administration rescued CFTR protein and function in clinically relevant CF models. In a fluorescence-based halide efflux assay, NB54 partially restored halide efflux in a CF bronchial epithelial cell line (CFTR genotype W1282X/F508del), but not in a CF epithelial cell line lacking a PTC (F508del/F508del). In polarized airway epithelial cells expressing either a CFTR-W1282X or -G542X cDNA, treatment with NB54 increased stimulated short-circuit current (I SC) with greater efficiency than gentamicin. NB54 and gentamicin induced comparable increases in forskolin-stimulated I SC in primary airway epithelial cells derived from a G542X/F508del CF donor. Systemic administration of NB54 to Cftr−/− mice expressing a human CFTR-G542X transgene restored 15–17% of the... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5061493 Thu, 21 Jul 2011 17:56:42 +0100 5061493 http://www.medworm.com/index.php?rid=5061494&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ftt37351261001555%2F We report the analysis of CPI-613, the first member of a large set of analogs of lipoic acid (lipoate) we have investigated as potential anticancer agents. CPI-613 strongly disrupts mitochondrial metabolism, with selectivity for tumor cells in culture. This mitochondrial disruption includes activation of the well-characterized, lipoate-responsive regulatory phosphorylation of the E1α pyruvate dehydrogenase (PDH) subunit. This phosphorylation inactivates flux of glycolysis-derived carbon through this enzyme complex and implicates the PDH regulatory kinases (PDKs) as a possible drug target. Supporting this hypothesis, RNAi knockdown of the PDK protein levels substantially attenuates CPI-613 cancer cell killing. In both cell culture and in vivo tumor environments, the observed strong m... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5061494 Tue, 19 Jul 2011 05:49:55 +0100 5061494 http://www.medworm.com/index.php?rid=5048281&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F96742130l5648042%2F Abstract  Pulmonary arterial hypertension (PAH) is a disease of the pulmonary vasculature characterized by constricted and remodeled pulmonary arteries. This phenomenon is associated with enhanced pulmonary artery smooth muscle cells proliferation and suppressed apoptosis, metabolism shift, inflammation, and several other features that are considered as hallmarks of cancer. Since oncogenes, tumor suppressors, and miRNAs are the major regulators of signaling in the cancer phenotype, we studied if the same type of regulation is operative in PAH. From the discovery of BMPR2 mutation in familial forms of PAH, oncogenic pathways activation like MAPK were identified. Recently, the Src/STAT3/Pim1 axis was also described as playing a critical role in PAH pathogenesis. Moreover, thr... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5048281 Thu, 14 Jul 2011 16:50:34 +0100 5048281 http://www.medworm.com/index.php?rid=5035409&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx5g1532585852302%2F Abstract  RNA interference (RNAi) represents a powerful post-transcriptional gene silencing network which fine-tunes gene expression in all eukaryotic cells. The endogenous triggers of RNAi, microRNAs (miRNAs), are proposed to regulate expression of up to a third of all protein-coding genes, and have been shown to have critical roles in developmental processes including in the central nervous system and skeletal muscle. Further, many have been reported to display differential expression in various disease states. Here we describe present understanding of the biogenesis and function of miRNAs, review current knowledge of miRNA abnormalities in both human neurological and skeletal muscle disease and discuss their potential as novel disease biomarkers. Finally, we highlight th... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5035409 Wed, 13 Jul 2011 06:01:19 +0100 5035409 http://www.medworm.com/index.php?rid=5035410&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fem811q6xp326r853%2F Abstract  Liberation of damage-associated molecular patterns (DAMPs) following tissue injury and necrotic cell death leads to the induction of sterile inflammation. A hallmark of acute inflammation is the recruitment of neutrophils to injured tissues. This review focuses on the journey of neutrophils to sites of sterile inflammation and the cellular and molecular mechanisms that choreograph this complex voyage. We review the pathway of leukocyte recruitment, with emphasis on recent additions to our understanding of intravascular neutrophil migration. The contributions of various tissue-resident sentinel cell populations to the detection of danger signals (DAMPs) and coordination of neutrophil recruitment and migration are discussed. In addition, we highlight recent data on ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5035410 Wed, 13 Jul 2011 06:01:18 +0100 5035410 http://www.medworm.com/index.php?rid=5017805&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F723502r340740772%2F Content Type Journal ArticlePages 1-4DOI 10.1007/s00109-011-0783-xAuthors Todd M. Kolb, Division of Pulmonary and Critical Care Medicine and Department of Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, 5th Floor, Baltimore, MD 21205, USARachel L. Damico, Division of Pulmonary and Critical Care Medicine and Department of Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, 5th Floor, Baltimore, MD 21205, USAPaul M. Hassoun, Division of Pulmonary and Critical Care Medicine and Department of Medicine, Johns Hopkins University School of Medicine, 1830 East Monument Street, 5th Floor, Baltimore, MD 21205, USA Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medi... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5017805 Thu, 07 Jul 2011 05:50:12 +0100 5017805 http://www.medworm.com/index.php?rid=5017806&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F640xl76m5913103t%2F Abstract  The number of circulating endothelial progenitor cells (EPCs) inversely correlates with cardiovascular risk and clinical outcome, and thus has been proposed as a valuable biomarker for risk assessment, disease progression, and response to therapy. However, current strategies for isolation of these rare cells are limited to complex, laborious approaches. The goal of this study was the design and validation of a disposable microfluidic platform capable of selectively capturing and enumerating EPCs directly from human whole blood in healthy and diseased subjects, eliminating sample preprocessing. We then applied the “EPC capture chip” clinically and determined EPC numbers in blood from patients with pulmonary arterial hypertension (PAH). Blood was collected in tu... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5017806 Thu, 07 Jul 2011 05:50:10 +0100 5017806 http://www.medworm.com/index.php?rid=4997151&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn45761543xg0h3wx%2F In conclusion, dietary MK-7 supplementation increased vitamin K tissue levels in the PXE mouse model but failed to counteract ectopic calcification. Hence, we obtained no support for the hypothesis that Abcc6 transports vitamin K and that PXE can be cured by increasing tissue levels of vitamin K. Content Type Journal ArticlePages 1-11DOI 10.1007/s00109-011-0782-yAuthors Theo G. M. F. Gorgels, Department of Clinical and Molecular Ophthalmogenetics, The Netherlands Institute for Neuroscience (NIN), an Institute of the Royal Netherlands Academy of Arts and Sciences (KNAW), Meibergdreef 47, 1105 BA Amsterdam, The NetherlandsJan H. Waarsing, Department of Orthopaedics, Erasmus Medical Center, Dr. Molewaterplein 50-60, Rotterdam, The NetherlandsMarjolein Herfs, VitaK and Cardiovascular ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4997151 Fri, 01 Jul 2011 17:43:16 +0100 4997151 http://www.medworm.com/index.php?rid=4967578&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F325613801l5466q7%2F Abstract  Suicide gene therapy is a promising concept in oncology. We have recently introduced a novel suicide gene, TK.007, which was shown to excel established herpes simplex virus thymidine kinase (HSVtk) variants when used for donor-lymphocyte modification in adoptive immunotherapy models. Here, the potential of TK.007 in killing cancer cells was studied. Initially, we transduced tumour cell lines derived from different neoplasias (glioblastoma, melanoma, lung cancer, colon cancer) with lentiviral LeGO vectors encoding TK.007 or the splice-corrected (sc)HSVtk together with an eGFP/Neo-marker. Based on direct in vitro comparison, we found that TK.007 facilitates more efficient tumour cell killing at significantly lower ganciclovir doses in all tumour cell lines tested. A... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4967578 Wed, 22 Jun 2011 15:57:48 +0100 4967578 http://www.medworm.com/index.php?rid=4967577&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb7528422l3705883%2F Abstract  Allergic contact hypersensitivity responses to the transition metal nickel (Ni2+) affect millions of people worldwide despite extensive legislatory efforts to ban the use of Ni2+ in products coming into direct contact with the skin. Like other contact allergens, Ni2+ triggers a T lymphocyte-driven delayed-type hypersensitivity reaction that is characterized by leukocyte infiltration at sites of allergen exposure. The last years have revealed that besides a hapten-specific T cell response, Ni2+ can also directly trigger an innate immune response in resident skin cells that is necessary for mounting an allergic hypersensitivity reaction to Ni2+. Recently, the receptor for the bacterial membrane component lipopolysaccharide, Toll-like receptor 4, has been identified as ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4967577 Wed, 22 Jun 2011 15:57:48 +0100 4967577 http://www.medworm.com/index.php?rid=4959255&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj07330rh05540562%2F Abstract  Hyperhomocysteinemia is an independent risk factor for ischemic cardiovascular diseases, but its causal role in atherothrombosis remains controversial. Proatherogenic and/or prothrombotic effects may underlie the potential causal relation between hyperhomocysteinemia and cardiovascular events. Here, the effects of selective lowering of plasma homocysteine, plasma cholesterol, or both on endothelial function and on atherogenesis in male hyperlipidemic and hyperhomocysteinemic C57BL/6 low-density lipoprotein receptor (LDLr)−/−/cystathionine-β-synthase (CBS)+/−-deficient mice were investigated. Second, we evaluated whether selective homocysteine lowering has anti-thrombotic effects in a model of arterial thrombosis. A hyperhomocysteinemic and atherogenic diet wa... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4959255 Sat, 18 Jun 2011 05:41:44 +0100 4959255 http://www.medworm.com/index.php?rid=4951341&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc122w833k74k324x%2F Abstract  Proprotein convertase (PC) 5/6 belongs to a family of secretory proteases involved in proprotein proteolysis. Several studies suggest a role for PC5/6 in cardiovascular disease. Because lethality at birth of mice lacking PC5/6 precluded elucidation of its function in the adult, we generated mice in which the gene of PC5/6 (pcsk5) is specifically inactivated in endothelial cells (ecKO), which are viable and do not exhibit overt abnormalities. In order to uncover the function of PC5/6 in the cardiovascular system, the effect of ecKO was studied in aging mice. In 16 to 18-month-old ecKO mice, the left ventricle (LV) mass, media cross-sectional area of aorta and coronary arteries, and media-to-lumen ratio of mesenteric arteries were decreased. The LV presented decrease... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4951341 Fri, 17 Jun 2011 11:59:58 +0100 4951341 http://www.medworm.com/index.php?rid=4951342&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj43j7g54g644058x%2F Abstract  Targeting of pathways downstream of RAS represents a promising therapeutic strategy for pancreatic cancer, the fourth leading cause of cancer-related death in the USA, since activation of the Raf-MEK-ERK and PI3K-AKT pathways is found frequently in this disease and is associated with poor prognosis. Taking advantage of a panel of human PDAC cell lines and specific inhibitors of PI3K and/or mTOR, we systematically address the question whether dual-targeted inhibition of the PI3K and mTOR pathways offers advantages over single-targeted inhibition of PI3K in PDAC. We observe greater overall susceptibility of cell lines to dual inhibition compared to targeting PI3K alone. However, we find that dual inhibition of PI3K and mTOR induces autophagy to a greater extent than... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4951342 Thu, 16 Jun 2011 05:51:43 +0100 4951342 http://www.medworm.com/index.php?rid=4932242&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F87085252527n3004%2F Abstract  MicroRNAs are single-stranded small non-coding RNA molecules which regulate mammalian cell growth, differentiation, and apoptosis by altering the expression of other genes and play a role in tumor genesis and progression. MiR-106a is upregulated in several types of malignancies and provides a pro-tumorigenic effect. However, its role in glioma is largely unknown. Our findings demonstrate that the low expression of miR-106a in human glioma specimens is significantly correlated with high levels of E2F1 protein and high-grade glioma. Here, we present the first evidence that miR-106a provides a tumor-suppressive effect via suppressing proliferation of and inducing apoptosis in human glioma cells. We further show that E2F1 is a direct functional target of miR-106a, sug... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4932242 Thu, 09 Jun 2011 05:44:29 +0100 4932242 http://www.medworm.com/index.php?rid=4901271&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F2050471735351237%2F In this study, we show that Nrf2-dependent gene expression is affected by the apoE genotype. ApoE4 vs. apoE3 mice exhibited lower hepatic Nrf2 nuclear protein levels. Furthermore, mRNA and protein levels of Nrf2 target genes including glutathione-S-transferase, heme oxygenase-1 and NAD(P)H dehydrogenase, quinone 1 were significantly lower in apoE4 as compared to apoE3 mice. Lower hepatic mRNA levels of phase II enzymes, as observed in apoE4 vs. apoE3 mice, were accompanied by higher mRNA levels of phase I enzymes including Cyp26a1 and Cyp3a16. Furthermore, miRNA-144, miRNA-125b, and miRNA-29a involved in Nrf2 signaling, inflammation, and regulation of phase I enzyme gene expression were affected by the apoE genotype. We provide first evidence that Nrf2 is differentially regulated in ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4901271 Fri, 27 May 2011 18:13:03 +0100 4901271 http://www.medworm.com/index.php?rid=4901272&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw715053427672416%2F Abstract  Human ischemic cardiomyopathy is characterized by de novo cardiomyogenesis, which is limited to the surviving portion of the ventricle, and by organ hypertrophy that develops as a chronic response to ischemic injury. Although myocyte hypertrophy and myocyte regeneration restore the original myocardial mass, the coronary vasculature remains defective and the extent and regulation of myocardial perfusion are severely impaired. Recently, vascular stem cells (VSCs) have been identified in the coronary circulation. VSCs express c-kit and the vascular endothelial growth factor receptor-2, KDR. These cells are self-renewing, clonogenic, and multipotent in vitro and in vivo. In animal models of critical coronary artery stenosis, VSCs form large conductive coronary arterie... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4901272 Mon, 23 May 2011 16:49:41 +0100 4901272 http://www.medworm.com/index.php?rid=4901273&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Flh36h70q02402754%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00109-011-0772-0Authors Friedrich C. Luft, Experimental and Clinical Research Center, a joint cooperation between the Charité Medical Faculty and the Max-Delbrück Center for Molecular Medicine, Berlin, Lindenbergerweg 80, 13125 Berlin, Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4901273 Mon, 23 May 2011 16:49:37 +0100 4901273 http://www.medworm.com/index.php?rid=4901274&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4708783863621731%2F This study presents a comprehensive transcriptional analysis of stroke-associated CPs and demonstrates a significant transcriptome difference between stroke-associated and asymptomatic CPs. Follow-up studies on the identified genes are needed to define whether they could be used as biomarkers of symptomatic CPs or have a role in plaque destabilization. Content Type Journal ArticlePages 1-12DOI 10.1007/s00109-011-0773-zAuthors Jani Saksi, Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, P.O. Box700, Haartmaninkatu 8, FI-00290 Helsinki, FinlandPetra Ijäs, Research Programs Unit, Molecular Neurology, Biomedicum Helsinki, University of Helsinki, P.O. Box700, Haartmaninkatu 8, FI-00290 Helsinki, FinlandKrista Nuotio, Research Programs Unit, Mo... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4901274 Mon, 23 May 2011 16:49:36 +0100 4901274 http://www.medworm.com/index.php?rid=4852261&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl8464v8q77u6lw51%2F Abstract  Activated oncogenes evoke cellular fail-safe programs such as apoptosis, senescence, or autophagy to protect the organism from the expansion of damaged and potentially harmful cells. Non-cell-autonomous interactions between tumor cells and nonmalignant bystander cells add to cell-autonomous modes of tumor suppression during tumor development and progression. In particular, the role of stroma or host immune cells converting tumor-generated signals into a response that feeds back to the tumor cell population has been experimentally underappreciated. Using the Eμ-myc transgenic mouse lymphoma model, we elucidated how constitutive Myc signaling indirectly promotes cellular senescence via cytokines that were released by nonmalignant cells in response to oncogene-evoked... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4852261 Wed, 18 May 2011 18:18:26 +0100 4852261 http://www.medworm.com/index.php?rid=4852262&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F4024v042n22755k8%2F Abstract  Cellular senescence, which can be induced by various stimuli, is a stress response that manifests as irreversible cell cycle arrest. Recent studies have revealed that cellular senescence can serve as a critical barrier for cancer development. Induction of cellular senescence by oncogenic insults, such as Ras overexpression or by inactivation of PTEN tumor suppressor, triggers an ARF/p53-dependent tumor-suppressive effect which can significantly restrict cancer progression. Given the important role of the ARF/p53 pathway in cellular senescence and tumor suppression, drugs that stabilize p53 expression have been developed and tested in clinical trials. However, a major hurdle for p53 targeting in cancer treatment arises from the frequent deficiency or mutation of AR... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4852262 Wed, 18 May 2011 18:18:25 +0100 4852262 http://www.medworm.com/index.php?rid=4852263&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Ft748u123764tm304%2F This study suggests that ATO treatment or survivin inhibition could be a novel therapeutic strategy in malignant gliomas. Content Type Journal ArticlePages 1-15DOI 10.1007/s00109-011-0763-1Authors Hui-Wen Chiu, Department of Environmental and Occupational Health, National Cheng Kung University Medical College, 138 Sheng-Li Road, Tainan, 704 TaiwanYuan-Soon Ho, School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, TaiwanYing-Jan Wang, Department of Environmental and Occupational Health, National Cheng Kung University Medical College, 138 Sheng-Li Road, Tainan, 704 Taiwan Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4852263 Wed, 18 May 2011 18:18:24 +0100 4852263 http://www.medworm.com/index.php?rid=4839661&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fa18034p037q71h80%2F Abstract  Synaptic plasticity in the spinal cord and the cortex is believed to be important for the amplification of painful information in chronic pain conditions. The investigation of molecular mechanism responsible for maintaining injury-related plastic changes, such as through the study of long-term potentiation in these structures, provides potential novel targets for designing new medicine for chronic pain. Recent studies using integrative neurobiological approaches demonstrate that protein kinase M zeta (PKMζ) maintains pain-induced persistent changes in the anterior cingulate cortex (ACC), and inhibiting PKMζ by ζ-pseudosubstrate inhibitory peptide produces analgesic effects in animal models of chronic pain. We propose that targeting PKMζ, or its up- or downstre... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4839661 Mon, 16 May 2011 08:42:24 +0100 4839661 http://www.medworm.com/index.php?rid=4839662&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh260324436p12086%2F Abstract  Extensive cell death with consecutive release of danger signals can cause immune-mediated tissue destruction. The abundance of cell death is likely to determine the relevance of the danger signals as physiological mechanisms that counteract immune activation may be overruled. Such constellation is conceivable in chemo-/radiotherapy-induced tissue damage, reperfusion injury, trauma, and severe infection. Studies on graft-versus-host disease (GvHD) development have to consider the effects of chemo-/radiotherapy-related tissue damage leading to the release of exogenous and endogenous danger signals. Our previous work has demonstrated a role for adenosine-5′-triphosphate (ATP) as an endogenous danger signal in GvHD. Besides ATP, uric acid or soluble extracellular ma... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4839662 Sat, 14 May 2011 15:53:37 +0100 4839662 http://www.medworm.com/index.php?rid=4839663&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F6213864p62653044%2F Abstract  Group 1 allergen from Dermatophagoid pteronyssinus (Der p 1) belongs to the papain-like cysteine protease family and is a major cause of allergic rhinitis and asthma. An anti-Der p 1 monoclonal antibody, mAb W108, was selected and isolated from Der p-specific IgG2b-producing hybridoma clones. Two-dimensional electrophoresis and immunoblotting showed that mAb W108 reacted with four components of Der p extracts with a molecular mass of 35 kDa and pI values varying from 4 to 6; it also reacted with IgE antibodies in the sera of Der p-sensitive patients. In the competitive assay and using azocasein as a substrate, we found that mAb W108 inhibited not only the binding of Der p 1, but also its cysteine protease activity in a dose-dependent manner. The two peptide se... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4839663 Thu, 12 May 2011 16:38:36 +0100 4839663 http://www.medworm.com/index.php?rid=4819652&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F9h23m52811520001%2F Abstract  Lymph node metastasis is a strong predictor of poor outcome in cancer patients. Animal studies of lymph node metastasis are constrained by difficulties in the establishment of appropriate animal models, limitations in the noninvasive monitoring of lymph node metastasis progression, and challenges in the pathologic confirmation of lymph node metastases. In this comprehensive review, we summarize available preclinical animal cancer models for noninvasive imaging and identification of lymph node metastases of non-hematogenous cancers. Furthermore, we discuss the strengths and weaknesses of common noninvasive imaging modalities used to identify tumor-bearing lymph nodes and provide guidelines for their pathological confirmation. Content Type Journal ArticlePages 1... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4819652 Tue, 10 May 2011 06:03:12 +0100 4819652 http://www.medworm.com/index.php?rid=4819653&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F821p45831m014n23%2F Abstract  Cell-mediated immunity is critical to the clearance of Mycobacterium tuberculosis due to the primarily intracellular niche of this pathogen. Adoptive transfer of M. tuberculosis-specific effector T cells has been shown to confer immunity to M. tuberculosis-infected recipients resulting in M. tuberculosis clearance. However, it is difficult to generate sufficient numbers of M. tuberculosis antigen-specific T cells in a short time. Recent studies have developed T cell receptor (TCR) gene-modified T cells that allow for the rapid generation of large numbers of antigen-specific T cells. Many TCRs that target various tumor and viral antigens have now been isolated and shown to have functional activity. Nevertheless, TCRs specific for intracellular bacterial antigens (incl... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4819653 Tue, 10 May 2011 06:03:11 +0100 4819653 http://www.medworm.com/index.php?rid=4819654&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe245x1q8116373n6%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00109-011-0765-zAuthors Friedrich C. Luft, Experimental and Clinical Research Center, Charité Medical, Faculty and Max-Delbrück Center for Molecular Medicine, Berlin, Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4819654 Mon, 09 May 2011 05:34:57 +0100 4819654 http://www.medworm.com/index.php?rid=4811944&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F76781n283743426l%2F Abstract  Renin-angiotensin system (RAS) activation is associated with arrhythmias. We investigated the effects of RAS inhibition in cardiac-specific angiotensin-converting enzyme (ACE) overexpression (ACE 8/8) mice, which exhibit proclivity to ventricular tachycardia (VT) and sudden death because of reduced connexin43 (Cx43). ACE 8/8 mice were treated with an ACE inhibitor (captopril) or an angiotensin receptor type-1 blocker (losartan). Subsequently, electrophysiological studies were performed, and the hearts were extracted for Cx43 quantification using immunoblotting, immunohistochemistry, fluorescent dye spread method, and sodium current quantification using whole cell patch clamping. VT was induced in 12.5% of captopril-treated ACE 8/8 and in 28.6% of losartan-treated mi... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4811944 Fri, 06 May 2011 16:15:09 +0100 4811944 http://www.medworm.com/index.php?rid=4752926&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fx266wu073x2g6771%2F Abstract  While G-protein-coupled receptors (GPCRs) have received considerable attention for their biological activity in a diversity of physiological functions and have become targets for therapeutic intervention in many diseases, the function of the cell adhesion subfamily of GPCRs remains poorly understood. Within this group, the family of brain angiogenesis inhibitor molecules (BAI1-3) has become increasingly appreciated for their diverse roles in biology and disease. In particular, recent findings suggest emerging roles for BAI1 in the regulation of phenomena including phagocytosis, synaptogenesis, and the inhibition of tumor growth and angiogenesis via the processing of its extracellular domain into secreted vasculostatins. Here we summarize the known biological featu... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4752926 Thu, 21 Apr 2011 06:12:41 +0100 4752926 http://www.medworm.com/index.php?rid=4744636&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7804683h867134v8%2F Abstract  Lafora disease is a fatal autosomal recessive form of progressive myoclonus epilepsy. Patients manifest myoclonus and tonic–clonic seizures, visual hallucinations, intellectual, and progressive neurologic deterioration beginning in adolescence. The two genes known to be involved in Lafora disease are EPM2A and NHLRC1 (EPM2B). The EPM2A gene encodes laforin, a dual-specificity protein phosphatase, and the NHLRC1 gene encodes malin, an E3-ubiquitin ligase. The two proteins interact with each other and, as a complex, are thought to regulate glycogen synthesis. Here, we report three Lafora families with two novel pathogenic mutations (C46Y and L261P) and two recurrent mutations (P69A and D146N) in NHLRC1. Investigation of their functional consequences in cultured mamm... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4744636 Wed, 20 Apr 2011 06:05:44 +0100 4744636 http://www.medworm.com/index.php?rid=4722951&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fnvn81406tr4628x6%2F Abstract  Nanotechnology offers enormous potential in drug delivery and in vivo imaging. Nanoparticles (NPs), for example, are being extensively tested as scaffolds to deliver anti-cancer therapeutics or imaging tags. Our recent work, discussed herein, indicates that an opportunity exists to use NPs to deliver ligands for, and trigger, cognate receptors on T lymphocytes as a way to induce therapeutic immune responses in vivo. Specifically, systemic delivery of NPs coated with Type 1 diabetes (T1D)-relevant peptide-major histocompatibility complex molecules triggered the expansion of cognate memory autoregulatory (disease-suppressing) T cells, suppressed the progression of autoimmune attack against insulin-producing beta cells, and restored glucose homeostasis. This therapeu... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4722951 Fri, 15 Apr 2011 15:47:14 +0100 4722951 http://www.medworm.com/index.php?rid=4722950&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fxl15845408268911%2F Abstract  The hallucinogenic compound, salvinorin A, is a potent κ-opioid receptor (KOR) agonist. However, other target(s) than the KOR, such as the cannabinoid CB1 receptor, have been proposed to explain its multiple pharmacological actions. Here, we have evaluated the effect of salvinorin A in lipopolysaccharide (LPS)-stimulated macrophages as well as in models of inflammation in vivo. Salvinorin A (0.1–10 pM) reduced LPS-stimulated nitrite, TNF-α and IL-10 (but not IL-1β) levels as well as iNOS (but not COX-2) LPS-induced hyperexpression. The effect of salvinorin A on nitrite levels was reverted by the opioid antagonist naloxone, the KOR antagonist nor-binaltorphimine and by the CB1 antagonist rimonabant Salvinorin A also prevented KOR and CB1 hyperexpression i... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4722950 Fri, 15 Apr 2011 15:47:14 +0100 4722950 http://www.medworm.com/index.php?rid=4722953&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fm74l060884175055%2F Abstract  Bone marrow (BM)-derived fibrocytes are a population of CD45+ and collagen Type I-expressing cells that migrate to the spleen and to target injured organs, such as skin, lungs, kidneys, and liver. While CD45+Col+ fibrocytes contribute to collagen deposition at the site of injury, the role of CD45+Col+ cells in spleen has not been elucidated. Here, we demonstrate that hepatotoxic injury (CCl4), TGF-β1, lipopolysaccharide, or infection with Listeria monocytogenes induce rapid recruitment of CD45+Col+ fibrocyte-like cells to the spleen. These cells have a gene expression pattern that includes antimicrobial factors (myleoperoxidase, cathelicidin, and defensins) and MHC II at higher levels than found on quiescent or activated macrophages. The immune functions of these sp... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4722953 Fri, 15 Apr 2011 15:47:11 +0100 4722953 http://www.medworm.com/index.php?rid=4722952&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmq10778w06037776%2F Abstract  Impaired wound healing in the elderly represents a major clinical problem. Delineating the cellular and molecular mechanisms by which aging impairs wound healing may lead to the development of improved treatment strategies for elderly patients with non-healing wounds. Neovascularization is an essential step in wound healing, and bone marrow-derived angiogenic cells (BMDACs) play an important role in vascularization. Using a mouse full-thickness burn wound model, we demonstrate that perfusion and vascularization of burn wounds were impaired by aging and were associated with dramatically reduced mobilization of BMDACs bearing the cell surface molecules CXCR4 and Sca1. Expression of stromal-derived factor 1 (SDF-1), the cytokine ligand for CXCR4, was significantly de... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4722952 Fri, 15 Apr 2011 15:47:11 +0100 4722952 http://www.medworm.com/index.php?rid=4722954&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv1k617mv30532107%2F Abstract  Although nitric oxide (NO) and oxidative stress both contribute to proinflammatory cytokine toxicity in pancreatic β-cells during type 1 diabetes mellitus (T1DM) development, the interactions between NO and reactive oxygen species (ROS) in cytokine-mediated β-cell death have not been clarified. Exposure of insulin-producing RINm5F cells to IL-1β generated NO, while exposure to a combination of IL-1β, TNF-α, and IFN-γ, which simulates T1DM conditions, generated both NO and ROS. In theory, two reactions between NO and ROS are possible, one with the superoxide radical yielding peroxynitrite, and the other with hydrogen peroxide (H2O2) yielding hydroxyl radicals. Results of the present work exclude peroxynitrite involvement in cytokine toxicity to β-cells becau... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4722954 Tue, 12 Apr 2011 21:30:14 +0100 4722954 http://www.medworm.com/index.php?rid=4722955&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl632683g44817130%2F Abstract  It is very well established that purinergic signaling plays a relevant role in vascular physiology and pathophysiology. Recently, a new purinoceptor agonist uridine adenosine tetraphosphate (Up4A) has been identified as a highly potent endothelial-derived contracting factor (EDCF). The purpose of the study was to investigate Up4A's influence on pro-inflammatory mechanisms. An early component of the inflammatory response in atherogenesis is the oxidative stress-induced formation of monocyte chemoattractant protein-1 (MCP-1). Here, we investigated the influence of Up4A on MCP-1 formation and characterized the underlying signaling transduction mechanisms in rat vascular smooth muscle cells (VSMCs). Up4A induced MCP-1 expression and secretion in VSMCs via the activation... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4722955 Tue, 12 Apr 2011 21:30:13 +0100 4722955 http://www.medworm.com/index.php?rid=4696040&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fxv0g057368uk0564%2F In this study, highly purified plasma membrane proteins from clinical tissue samples were obtained using a strategy combining sucrose density gradient centrifugation and subsequent phase partition. Using a two-dimensional gel electrophoresis and MALDI-Q-TOF MS/MS-based proteomics approach, we identified 13 plasma membrane-associated proteins that were differentially expressed in HCC and normal liver tissues. Of those, RhoA was one of the most significantly upregulated proteins in HCC, and its overexpression was confirmed using Western blotting. Immunohistochemistry suggested a link between RhoA expression and poor differentiation and clinicopathologic stage. Suppression of RhoA expression in HepG2 and Hep3B cells by RNA interference led to significant inhibition of cell growth, indu... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4696040 Thu, 07 Apr 2011 17:09:25 +0100 4696040 http://www.medworm.com/index.php?rid=4696041&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn39277p8x634563w%2F Abstract  Congenital dyserythropoietic anaemias (CDAs) are heterogeneous, hereditary disorders hallmarked by ineffective erythropoiesis and tissue iron overload. Growth differentiation factor 15 (GDF15) was suggested to mediate iron overload in iron-loading anaemias, such as the thalassaemias and CDAI by suppressing hepcidin, the key regulator of iron absorption. Here, we show that serum GDF15 concentrations are elevated in subjects with CDAI and CDAII. Despite similar disease characteristics, CDAI patients present with significantly higher GDF15 concentrations compared to CDAII patients. Hepcidin concentrations are inappropriately low in CDAII patients considering the severe hepatic iron overload associated with this disorder. GDF15 significantly correlates with the degree... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4696041 Thu, 07 Apr 2011 17:09:24 +0100 4696041 http://www.medworm.com/index.php?rid=4696042&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv4766883585005j7%2F Content Type Journal ArticlePages 1-3DOI 10.1007/s00109-011-0755-1Authors Friedrich Luft, Experimental and Clinical Research Center, Charité Medical Faculty and Max-Delbrück Center for Molecular Medicine, Robert-Rössle Strasse 10, 13125 Berlin, Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4696042 Thu, 07 Apr 2011 17:09:23 +0100 4696042 http://www.medworm.com/index.php?rid=4692509&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcn67x7j7l54l0451%2F In this study, we investigated the effect of ursolic acid (UA) on NF-κB and STAT3 signaling pathways in both androgen-independent (DU145) and androgen-dependent (LNCaP) prostate cancer cell lines and also prospectively tested the hypothesis of NF-κB and STAT3 inhibition using a virtual predictive functional proteomics tumor pathway technology platform. We found that UA inhibited constitutive and TNF-α-induced activation of NF-κB in DU145 and LNCaP cells in a dose-dependent manner. The suppression was mediated through the inhibition of constitutive and TNF-α-induced IκB kinase (IKK) activation, phosphorylation of IκBα and p65 and NF-κB-dependent reporter activity. Furthermore, UA suppressed both constitutive and inducible STAT3 activation in prostate cancer cells concomitant ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4692509 Tue, 05 Apr 2011 09:58:29 +0100 4692509 http://www.medworm.com/index.php?rid=4663232&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0703h7u611074684%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s00109-011-0745-3Authors Oliver D. K. Maddocks, The Beatson Institute for Cancer Research, Switchback Road, Glasgow, G61 1BD UKKaren H. Vousden, The Beatson Institute for Cancer Research, Switchback Road, Glasgow, G61 1BD UK Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4663232 Tue, 29 Mar 2011 17:34:59 +0100 4663232 http://www.medworm.com/index.php?rid=4663233&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fr53v6v889060v750%2F Abstract  Receptor-activator of NF-κB ligand (TNFSF11, also known as RANKL, OPGL, TRANCE, and ODF) and its tumor necrosis factor (TNF)-family receptor RANK are essential regulators of bone remodeling, lymph node formation, establishment of the thymic microenvironment, mammary gland development during pregnancy, and bone metastasis in cancer. We have recently also reported that the RANKL/RANK system controls the incidence and onset of sex hormone, progestin-driven breast cancer. RANKL and RANK are also expressed in the central nervous systems where they play an essential role in body temperature regulation. RANKL activates brain regions involved in thermoregulation and induces fever via the COX2-PGE2/EP3R pathway. Moreover, female mice with a RANK gene deleted in neurons and... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4663233 Tue, 29 Mar 2011 06:03:00 +0100 4663233 http://www.medworm.com/index.php?rid=4635886&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F8x4253501jm82823%2F Abstract  The coxsackie adenovirus receptor (CAR) is a component of the tight junction complex and involved in cell adhesion. Loss of CAR expression can affect cell adhesion which in the context of carcinogenesis may influence both invasion and metastatic spread. Functional inactivation of CAR may also result from the interaction with its soluble isoforms. To relate alterations of CAR expression to tumor progression, we aimed to establish a highly specific real-time PCR protocol for quantification of all splice variants. In the process of cloning, we identified a novel splice variant termed CAR4/6 that lacked exon 5 but retained exon 6 encoding the transmembrane domain. Localization of CAR4/6 in the cell membrane was confirmed by ectopic expression in HT1080 cells. Expressi... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4635886 Tue, 22 Mar 2011 18:09:49 +0100 4635886 http://www.medworm.com/index.php?rid=4635887&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fyn0770q85vk50v48%2F Abstract  Adenosine monophosphate-activated protein kinase (AMPK) is a crucial regulator of energy metabolic homeostasis and thus a major survival factor in a variety of metabolic stresses and also in the aging process. Metabolic syndrome is associated with a low-grade, chronic inflammation, primarily in adipose tissue. A low-level of inflammation is also present in the aging process. There are emerging results indicating that AMPK signaling can inhibit the inflammatory responses induced by the nuclear factor-κB (NF-κB) system. The NF-κB subunits are not direct phosphorylation targets of AMPK, but the inhibition of NF-κB signaling is mediated by several downstream targets of AMPK, e.g., SIRT1, PGC-1α, p53, and Forkhead box O (FoxO) factors. AMPK signaling seems to enha... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4635887 Tue, 22 Mar 2011 18:09:48 +0100 4635887 http://www.medworm.com/index.php?rid=4577743&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F0366x23048670733%2F Abstract  As aging is a significant risk factor for the development of left ventricular hypertrophy and cardiovascular disease, we hypothesized that hearts from middle-aged mice may be more sensitive to the effects of a high fat (HF) diet than hearts from young mice. To investigate this, young (10–12 week old) and middle-aged (40–44 week old) male mice were fed a low fat (LF) or HF diet (10 or 60 kcal% fat, respectively) for 12 weeks. Following this 12-week period, we show that CD36 protein expression was not changed in hearts from young mice yet was increased 1.5-fold in the middle-aged HF group compared with LF-fed age-matched counterparts. Correlated with increased CD36 expression, middle-aged mice displayed a greater degree of cardiac hypertrophy ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4577743 Wed, 09 Mar 2011 07:01:02 +0100 4577743 http://www.medworm.com/index.php?rid=4577742&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F840415pp8t487126%2F Abstract  Maternal stress can cause loss of both histocompatible (syngeneic) and histoincompatible (semiallogeneic) embryos in pregnant mice. Stress increases abortogenic Th1 cytokines and reduces levels of anti-abortogenic Th2 cytokines, progesterone levels, and T regulatory cell activity. While physiological levels of interferon-γ promote vascular remodeling at the feto-maternal interface, an overshooting Th1 cytokine response requires a Toll-like receptor (TLR)-mediated “danger signal” such as lipopolysaccharide (LPS). Interestingly, stress can enhance permeability of mucosal membranes to entry of bacterial products and promote transmucosal migration of commensal bacteria. We hypothesized that bacterial component such as LPS may provide the danger signal through whi... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4577742 Wed, 09 Mar 2011 07:01:02 +0100 4577742 http://www.medworm.com/index.php?rid=4565262&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe2px5181q887hk34%2F This study suggests that the dTBP2 binding to dTCTP modulates the release of inflammatory mediators of dTCTP. This result may provide a rational strategy for the treatment of allergic diseases. Content Type Journal ArticlePages 1-8DOI 10.1007/s00109-011-0740-8Authors Miyoung Kim, College of Pharmacy, Center for Cell Signalling & Drug Discovery Research, Ewha Womans University, Seoul, 120–750 South KoreaJunho Chung, College of Medicine and Cancer Research Institute, Seoul National University, Seoul, 110–799 South KoreaChulhee Lee, Department of Otorhinolaryngology–Head and Neck Surgery, Seoul National University College of Medicine, Seoul, 110–799 South KoreaJaehoon Jung, College of Pharmacy, Center for Cell Signalling & Drug Discovery Research, Ewha Womans University, Seou... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4565262 Mon, 07 Mar 2011 17:02:36 +0100 4565262 http://www.medworm.com/index.php?rid=4549322&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk64pt41m2816t126%2F Abstract  Vascular endothelial growth factor (VEGF) is best known as an angiogenic factor essential for embryonic vasculogenesis and postnatal angiogenesis. Considerable evidence has accumulated that VEGF also has non-angiogenic functions. Early studies demonstrated that VEGF transcripts are ubiquitously expressed, and the phosphorylation of VEGF receptor is detectable in adult organs that have no feature of angiogenesis. Recent clinical studies showed that the inhibition of VEGF signaling results in diverse angiogenesis-irrelevant side effects involving the dysfunctions of many organs, suggesting non-angiogenic roles of VEGF in the regulation of organ homeostasis. On the other hand, VEGF stimulates endothelial cells (ECs) to express intercellular adhesion molecules that med... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4549322 Wed, 02 Mar 2011 06:57:35 +0100 4549322 http://www.medworm.com/index.php?rid=4549323&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F36231445583qpp58%2F Abstract  A disintegrin and metalloprotease with thrombospondin domains (ADAMTS)-4 (aggrecanase-1) and ADAMTS-5 (aggrecanase-2) are metalloproteases involved in articular cartilage degradation and represent potential therapeutic targets in arthritis treatment. We explore herein the ability of different natural compounds to specifically block the destructive action of these enzymes. Following a preliminary screening using carboxymethylated transferrin as substrate, we focused our interest on luteolin due to its inhibitory effect on ADAMTS-4 and ADAMTS-5 activities using aggrecan and fluorogenic peptides as substrates. However, matrix metalloproteinases (MMPs) activities on these substrates result less affected by this flavonoid. Moreover, incubation of mouse chondrogenic ATD... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4549323 Wed, 02 Mar 2011 06:57:33 +0100 4549323 http://www.medworm.com/index.php?rid=4540025&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fk24m037mj5x8v56g%2F Abstract  Multiple acyl-CoA dehydrogenation deficiency (MADD) is an autosomal recessive disease affecting amino acid, fatty acid, and choline metabolisms and is a common genetic defect responsible for lipid storage myopathy. Most forms of MADD are caused by a deficiency of electron transfer flavoprotein (ETF) or ETF dehydrogenase (ETFDH). However, its molecular feature has not been found uniformly in previous reports of Chinese patients. A large cohort of 56 late-onset MADD patients from 51 unrelated pedigrees in southern China was recruited to investigate a clear correlation between clinical phenotype and molecular genetic basis. All exons of ETFA, ETFB, and ETFDH, including the intron–exon boundaries, and 5′ and 3′ untranslated regions were directly sequenced. ETFDH ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4540025 Wed, 23 Feb 2011 23:14:26 +0100 4540025 http://www.medworm.com/index.php?rid=4574671&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj2002p1057h97587%2F Content Type Journal ArticlePages 423-423DOI 10.1007/s00109-011-0738-2Authors Johannes Lemke, Division of Molecular Oncology, Institute of Experimental Cancer Research, Comprehensive Cancer Center North, UK S-H, Arnold-Heller Str. 3, Haus 17, 24 105 Kiel, GermanyAndreas Noack, Division of Molecular Oncology, Institute of Experimental Cancer Research, Comprehensive Cancer Center North, UK S-H, Arnold-Heller Str. 3, Haus 17, 24 105 Kiel, GermanyDieter Adam, Institute of Immunology, UK S-H, Kiel, GermanyVladimir Tchikov, Institute of Immunology, UK S-H, Kiel, GermanyUwe Bertsch, Institute of Immunology, UK S-H, Kiel, GermanyChristian Röder, Division of Molecular Oncology, Institute of Experimental Cancer Research, Comprehensive Cancer Center North, UK S-H, Arnold-Heller Str. 3, Haus 17, ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4574671 Wed, 23 Feb 2011 23:14:24 +0100 4574671 http://www.medworm.com/index.php?rid=4540026&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fj2002p1057h97587%2F Content Type Journal ArticlePages 1-1DOI 10.1007/s00109-011-0738-2Authors Johannes Lemke, Division of Molecular Oncology, Institute of Experimental Cancer Research, Comprehensive Cancer Center North, UK S-H, Arnold-Heller Str. 3, Haus 17, 24 105 Kiel, GermanyAndreas Noack, Division of Molecular Oncology, Institute of Experimental Cancer Research, Comprehensive Cancer Center North, UK S-H, Arnold-Heller Str. 3, Haus 17, 24 105 Kiel, GermanyDieter Adam, Institute of Immunology, UK S-H, Kiel, GermanyVladimir Tchikov, Institute of Immunology, UK S-H, Kiel, GermanyUwe Bertsch, Institute of Immunology, UK S-H, Kiel, GermanyChristian Röder, Division of Molecular Oncology, Institute of Experimental Cancer Research, Comprehensive Cancer Center North, UK S-H, Arnold-Heller Str. 3, Haus 17, 24 1... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4540026 Wed, 23 Feb 2011 23:14:24 +0100 4540026 http://www.medworm.com/index.php?rid=4511653&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F288gk16372k7u024%2F Content Type Journal ArticlePages 1-4DOI 10.1007/s00109-011-0736-4Authors Sreedhar Bodiga, Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta T6G 2S2, CanadaWang Wang, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, CanadaGavin Y. Oudit, Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta T6G 2S2, Canada Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4511653 Mon, 21 Feb 2011 17:06:58 +0100 4511653 http://www.medworm.com/index.php?rid=4511654&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F447u5117k5jx4264%2F Abstract  Hypoxia is a condition of low oxygen tension that characterizes virtually every site of inflammation, tissue damage, and neoplasia. Hypoxic environment attracts infiltrating immune cells that move against oxygen gradients and respond to these demanding conditions by switching to anaerobic metabolism to maintain their energy requirements. Several lines of evidence suggest that oxygen deprivation causes opposite effects on the innate or adaptive immune responses. We will review the evidence that the hypoxic environment promotes the recruitment, activation, and survival of innate immune cells while inhibiting the adaptive immunity through downregulation of effector lymphocyte functions. This divergent regulation of the innate and adaptive immunity appears to reflect ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4511654 Sat, 19 Feb 2011 07:05:30 +0100 4511654 http://www.medworm.com/index.php?rid=4511655&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fb7xg55747730m365%2F Abstract  Heterozygous trinucleotide in frame duplications, leading to expansions of variable lengths of a 20-alanine stretch (polyAla), is the most frequent PHOX2B variant associated with congenital central hypoventilation syndrome (CCHS), a rare neurocristopathy characterized by defective response of the autonomic nervous system to hypoxia and hypercapnia. Sequencing analysis has shown that the vast majority of polyAla expansions arise de novo; while in about 10% of cases, mutations are inherited by one parent who carries either constitutive or somatic mutations. To investigate transmission of PHOX2B mutant alleles from asymptomatic individuals, we have reassessed 44 parental pairs, previously resulted not to carry any mutation, by coupling amplification with FAM-tagged pr... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4511655 Sat, 19 Feb 2011 07:05:27 +0100 4511655 http://www.medworm.com/index.php?rid=4501099&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F01r7444282g78746%2F This study was performed to investigate whether epigallocatechin-3-gallate (EGCG), the major constituent of green tea, interacted with sunitinib. The interaction between EGCG and sunitinib was examined in vitro and in vivo. 1H nuclear magnetic resonance (1H-NMR) spectroscopy and mass spectrometry (MS) were used to analyze the interaction between these two molecules and whether a new compound was formed. Solutions of sunitinib and EGCG were intragastrically administered to rats to investigate whether the plasma concentrations of sunitinib were affected by EGCG. In this study, we noticed that a precipitate was formed when the solutions of sunitinib and EGCG were mixed under both neutral and acidic conditions. 1H-NMR spectra indicated an interaction between EGCG and sunitinib, but no new... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4501099 Thu, 17 Feb 2011 17:02:54 +0100 4501099 http://www.medworm.com/index.php?rid=4494431&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl381472784k85903%2F Abstract  Ginsenoside-Rg1 (Rg1) has been used in the traditional Chinese medicine for over 2,000 years. The present study was performed to test our hypothesis that Rg1 provides pro-angiogenic and anti-fibrotic benefits in the ischemic myocardium in a rat model of myocardial infarction. The expression of vascular endothelial growth factor (VEGF) and phosphorylation/activation of PI3K, Akt, and p38 MAPK signaling pathways were examined in human umbilical vein endothelial cells and in the myocardial samples of rats. In addition, the expression levels of TNF-α and collagen I level, the number of newly formed blood vessels, the extent of myocardial fibrosis, and left ventricular function were measured in vivo. Our results demonstrated that administration of Rg1 increased V... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4494431 Wed, 16 Feb 2011 06:58:17 +0100 4494431 http://www.medworm.com/index.php?rid=4488782&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fh3077753lw797wk1%2F Abstract  The environmental, genetic, and/or age-related changes in proteostasis induce inflammation, oxidative stress, and apoptosis. We quantified the correlation of protein expression of critical proteostasis mediators to severity of chronic lung disease using lung tissue samples from control and chronic obstructive pulmonary disease (COPD) subjects (GOLD stage 0–IV) and cigarette smoke (CS)-induced murine model. The human bronchial epithelial cells, HEK-293, and Beas2B cells were used for in vitro experiments to verify the mechanisms. Our data verifies the correlation of higher expression of valosin-containing protein (VCP) retrograde translocation complex (VCP-Rma1-gp78) with severity of emphysema in COPD lung tissues and over-expression of inflammatory, ER stress an... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4488782 Fri, 11 Feb 2011 11:49:41 +0100 4488782 http://www.medworm.com/index.php?rid=4459229&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fym378q658153136j%2F Content Type Journal ArticlePages 1-2DOI 10.1007/s00109-011-0733-7Authors Gregg L. Semenza, Vascular Program, Institute for Cell Engineering; Departments of Pediatrics, Medicine, Oncology, Radiation Oncology, Biological Chemistry, and the McKusick-Nathans Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD USA Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4459229 Mon, 07 Feb 2011 22:41:20 +0100 4459229 http://www.medworm.com/index.php?rid=4459230&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F7261p31264508t41%2F Abstract  In 1927, Otto Warburg and coworkers reported the increased uptake of glucose and production of lactate by tumors in vivo as compared with normal tissues. This phenomenon, now known as the Warburg effect, was recapitulated in vitro with cancer tissue slices exhibiting excessive lactate production even with adequate oxygen. Warburg's in vivo studies of tumors further suggest that the dependency of tumors in vivo on glucose could be exploited for therapy, because reduction of arterial glucose by half resulted in a four-fold reduction in tumor fermentation. Recent work in cancer metabolism indicates that the Warburg effect or aerobic glycolysis contributes to redox balance and lipid synthesis, but glycolysis is insufficient to sustain a growing and dividing cancer cel... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4459230 Mon, 07 Feb 2011 22:41:15 +0100 4459230 http://www.medworm.com/index.php?rid=4459231&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fn66t30458j48h276%2F Content Type Journal ArticlePages 1-4DOI 10.1007/s00109-011-0734-6Authors Friedrich C. Luft, Experimental and Clinical Research Center, Max-Delbrück Center and Charité Medical Faculty, Lindenbergerweg 80, 13125 Berlin, Germany Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4459231 Mon, 07 Feb 2011 22:41:14 +0100 4459231 http://www.medworm.com/index.php?rid=4459232&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fe56405735x463443%2F Abstract  Tumors and tumor cell lines rapidly consume the amino acid glutamine (Gln) and use it to supply metabolic pathways that support cell growth and proliferation. Much of the research regarding the relationship between glutamine metabolism and cancer is based on the premise that this abundant nutrient represents an important driver of tumor cell anabolism. However, Gln's influence in cell biology and cancer extends far beyond its use as a carbon and nitrogen source for the structural components of dividing cells. Gln is truly a multipurpose nutrient, feeding many additional pathways that boost the ability of cells to communicate with each other and to cope with stress by oncogenic signaling and by the tumor microenvironment. A number of recent reports have highlighted... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4459232 Mon, 07 Feb 2011 22:41:13 +0100 4459232 http://www.medworm.com/index.php?rid=4459233&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fw88268847v361212%2F Abstract  Granzyme B plays a key role in cell-mediated programmed cell death. We previously demonstrated that p53 is a functional determinant in the granzyme B-induced cytotoxic T-lymphocyte response. However, the pathways leading to activation of p53 by granzyme B remain incompletely understood. We now demonstrate that granzyme B-induced DNA damage signaling as revealed by histone H2AX phosphorylation and subsequent activation of the stress kinase CHK2. Confocal microscopy analysis indicates that granzyme B treatment of tumor cells induced an early translocation of endonuclease caspase-activated DNase. DNA microarray-based global transcriptional profiling and RT-PCR indeed revealed genes related to DNA damage. Among these genes, hSMG-1, a genotoxic stress-activated protein... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4459233 Mon, 07 Feb 2011 22:41:10 +0100 4459233 http://www.medworm.com/index.php?rid=4459234&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fmj340350lr89jp52%2F Abstract  As a key regulator of cell growth and proliferation, the mammalian target of rapamycin (mTOR) complex 1 (mTORC1) has been the subject of intense investigation for its role in tumor development and progression. This research has revealed a signaling network of oncogenes and tumor suppressors lying upstream of mTORC1, and oncogenic perturbations to this network result in the aberrant activation of this kinase complex in the majority of human cancers. However, the molecular events downstream of mTORC1 contributing to tumor cell growth and proliferation are just coming to light. In addition to its better-known functions in promoting protein synthesis and suppressing autophagy, mTORC1 has emerged as a key regulator of cellular metabolism. Recent studies have found that... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4459234 Mon, 07 Feb 2011 22:41:07 +0100 4459234 http://www.medworm.com/index.php?rid=4459236&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv82937t57m551836%2F We describe here the development of a minimally sized S/MAR vector, which is devoid of extraneous bacterial sequences. This minicircle vector comprises an expression cassette and an S/MAR moiety, providing higher and more sustained transgene expression for several months in the absence of selection, both in vitro and in vivo. In contrast to the expression of our original S/MAR plasmid vector, the novel S/MAR minicircle vectors mediate increased transgene expression, which becomes sustained at about twice the levels observed immediately after administration. These promising results demonstrate the utility of minimally sized S/MAR vectors for persistent, atoxic gene expression. Content Type Journal ArticlePages 1-15DOI 10.1007/s00109-010-0713-3Authors Orestis Argyros, Gene Thera... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4459236 Mon, 07 Feb 2011 22:41:04 +0100 4459236 http://www.medworm.com/index.php?rid=4459235&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fv694624h31648477%2F Abstract  The observation that altered metabolism is the fundamental cause of cancer was made by Otto Warburg nearly a century ago. However, the subsequent identification of oncogenes and tumor suppressor genes has displaced Warburg's theory pointing towards genetic aberrations as the underlining cause of cancer. Nevertheless, in the last decade, cancer-associated mutations have been identified in genes coding for tricarboxylic acid cycle (TCA cycle, also known as Krebs cycle) and closely related enzymes that have essential roles in cellular metabolism. These observations have revived interest in Warburg's hypothesis and prompted a flurry of functional studies in the hope of gaining mechanistic insight into the links between mitochondrial dysfunction, metabolic alterations,... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4459235 Mon, 07 Feb 2011 22:41:04 +0100 4459235 http://www.medworm.com/index.php?rid=4428431&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc3g85001517r4q40%2F Abstract  Myocardial infarction is a major cause of morbidity and mortality in the developing and developed world. Although current interventions have been successful in prolonging life, they are inadequate because mortality is still high among MI patients. The multifunctional Ca2+/calmodulin-dependent protein kinase (CaMKII) plays a key role in the structure and contractility of the myocardium. CaMKII activity is increased in MI hearts and CaMKII promotes cardiac hypertrophy and inflammation, processes consistently activated by myocardial injury. Hypertrophy and inflammation are also related to neurohumoral and redox signaling which uncouple CaMKII activation from Ca2+/calmodulin dependence. Thus, CaMKII may act as a nodal point for integrating hypertrophic and inflammatory... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4428431 Fri, 28 Jan 2011 20:28:25 +0100 4428431 http://www.medworm.com/index.php?rid=4428430&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fc762245804p86041%2F This article reviews recent developments in DES. Content Type Journal ArticlePages 1-9DOI 10.1007/s00109-011-0729-3Authors Yue Li, Centre for Vascular Research, University of New South Wales, Sydney, NSW 2052 AustraliaRavinay Bhindi, Department of Cardiology, Royal North Shore Hospital, St Leonards, NSW 2065 Sydney, AustraliaLevon M. Khachigian, Centre for Vascular Research, University of New South Wales, Sydney, NSW 2052 Australia Journal Journal of Molecular MedicineOnline ISSN 1432-1440Print ISSN 0946-2716 (Source: Journal of Molecular Medicine) Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4428430 Fri, 28 Jan 2011 20:28:25 +0100 4428430 http://www.medworm.com/index.php?rid=4404915&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fcq546211p713631v%2F In conclusion, drastic lipid lowering induced by a powerful gene transfer strategy leads to pronounced regression and stabilization of advanced murine atherosclerosis. Content Type Journal ArticlePages 1-13DOI 10.1007/s00109-011-0722-xAuthors Eline Van Craeyveld, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, BelgiumStephanie C. Gordts, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, BelgiumElena Nefyodova, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven, BelgiumFrank Jacobs, Center for Molecular and Vascular Biology, University of Leuven, Campus Gasthuisberg, Herestraat 49, 3000 Leuven,... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4404915 Thu, 20 Jan 2011 07:06:59 +0100 4404915 http://www.medworm.com/index.php?rid=4355301&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2Fl7w178680kr0r010%2F Abstract  The management of tumor cell invasion and metastasis is instrumental in cancer therapy, since metastases are the prime reason for cancer patient mortality. Various cellular mechanisms and underlying molecular pathways relevant for metastasis have been identified so far, providing a basis for antimetastatic drugs. MicroRNAs (miRNAs) are highly conserved, small noncoding RNA molecules that have been shown to regulate various cellular processes by interfering with protein expression through posttranscriptional repression or mRNA degradation. More importantly, beyond their roles in physiological processes, many miRNAs are aberrantly expressed in various pathologies including cancer and regulate tumor- and metastasis-associated genes. Their pivotal role in metastasis h... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4355301 Fri, 14 Jan 2011 16:41:49 +0100 4355301 http://www.medworm.com/index.php?rid=4355302&cid=s_33358_67_f&fid=33358&url=http%3A%2F%2Fwww.springerlink.com%2Fcontent%2F32qwm067nt64651n%2F Abstract  Temperature-sensitive (TS) viruses have been used for decades as vaccines capable of limited replication in their hosts. Although attenuated bacteria, such as the Bacille Calmette–Guérin anti-tuberculosis vaccine, have been used for almost a century, it is only recently that there has been progress in using TS bacterial strains as live vaccines. Decades of work on essential bacterial genes and the recent explosion in the number of available bacterial genomic sequences set the groundwork for the identification of essential genes from diverse bacteria. This knowledge has allowed for the substitution of essential genes from cold-loving bacteria into the chromosomes of pathogenic bacteria. Many of these gene substitutions generated TS pathogenic bacterial strains, ... Journal of Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4355302 Wed, 12 Jan 2011 17:04:55 +0100 4355302