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 'Current Molecular Medicine' source. Thu, 09 Feb 2012 16:56:40 +0100 http://www.medworm.com/index.php?rid=5673920&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300136%26dopt%3DAbstract Authors: Pang JJ, Lei L, Dai X, Shi W, Liu X, Dinculescu A, McDowell JH Abstract In recent years, more and more mutant genes that cause retinal diseases have been detected. At the same time, many naturally occurring mouse models of retinal degeneration have also been found, which show similar changes to human retinal diseases. These, together with improved viral vector quality allow more and more traditionally incurable inherited retinal disorders to become potential candidates for gene therapy. Currently, the most common vehicle to deliver the therapeutic gene into target retinal cells is the adeno-associated viral vector (AAV). Following delivery to the immuno-priviledged subretinal space, AAV-vectors can efficiently target both retinal pigment epithelium and photoreceptor cells,... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673920 Thu, 09 Feb 2012 21:12:49 +0100 5673920 http://www.medworm.com/index.php?rid=5673916&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22303842%26dopt%3DAbstract Authors: Georgakilas AG, Panayiotidis M PMID: 22303842 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673916 Fri, 03 Feb 2012 05:00:00 +0100 5673916 http://www.medworm.com/index.php?rid=5673922&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300134%26dopt%3DAbstract Authors: Chiarella P, Summa V, De Santis S, Signori E, Picardi E, Pesole G, Saglio G, Fazio VM Abstract Philadelphia (Ph+) positive leukaemias are an example of haematological malignant diseases where different chromosomal rearrangements involving both BCR and ABL1 genes generate a variety of chimeric proteins (BCR/ABL1 p210, p190 and p230) which are considered pathological "biomarkers". In addition to these three, there is a variety of fusion transcripts whose origin may depend either on diverse genetic rearrangement or on alternative/atypical splicing of the main mRNAs or on the occurrence of single-point mutations. Although the therapy of Philadelphia+ leukaemias based on Imatinib represents a triumph of medicine, not all patients benefit from such drug and may show resistance a... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673922 Wed, 01 Feb 2012 05:00:00 +0100 5673922 http://www.medworm.com/index.php?rid=5673921&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300135%26dopt%3DAbstract Authors: Izzi B, Van Geet C, Freson K Abstract Endocrinopathies in patients with hypocalcemia and hyperphosphatemia that share resistance to parathyroid hormone (PTH) are grouped under the term pseudohypoparathyroidism (PHP). Patients with PHP type Ia (PHP-Ia) often present with additional hormonal resistance and show characteristic physical features that are jointly termed as having an Albright's hereditary osteodystrophy (AHO) phenotype. Alternatively, PHP-Ib patients predominantly have PTH and sometimes TSH resistance but don't present with AHO features. Most of these PHP forms are caused by defects in GNAS, an imprinted gene locus consisting of maternal, paternal and biallelic transcripts. PHP-Ia is caused by heterozygous inactivating mutations in those exons of GNAS encoding t... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673921 Wed, 01 Feb 2012 05:00:00 +0100 5673921 http://www.medworm.com/index.php?rid=5673919&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300137%26dopt%3DAbstract Authors: Saresella M, Rainone V, Al-Daghri NM, Clerici M, Trabattoni D Abstract T-cell activation is dependent on signals delivered through the antigen-specific T-cell receptor and accessory receptors on T-cells. Integration of signals through this family of costimulatory and inhibitory receptors and their ligands regulates the balance between T-cell activation, tolerance, and immunopathology. Programmed death 1 (PD-1) and its ligands, PD-L1 and PD-L2, deliver inhibitory signals and exert a vital and diverse range of immunoregulatory roles in T-cell activation, tolerance, and immune-mediated tissue damage. In this review, we revisit current understanding of the immunoregulatory functions of PD-1 and its ligands and their involvement in immune-mediated diseases. PMID: 22300137 ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673919 Wed, 01 Feb 2012 05:00:00 +0100 5673919 http://www.medworm.com/index.php?rid=5673918&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300138%26dopt%3DAbstract Authors: Xiong J Abstract MicroRNAs (miRNAs) are an abundant class of small noncoding RNAs that have critical regulatory functions in various biological processes. MicroRNA-22 (miR-22) is a highly-conserved 22-nt miRNA, whose roles in human diseases and normal physiology are just beginning to emerge. Recently, miR-22 has been connected to a great number of activities that encompass tumorigenesis, epigenetic modification, embryonic development, skeletal metabolism, panic disorder, and cardiomyocyte hypertrophy. Aberrant expression of miR-22 has been identified in multiple human diseases. Here, we describe our current understanding of the roles of miR-22 and its signaling circuitry in pathology and physiology, and discuss important advances that set the scene for applying miR-22 to t... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673918 Wed, 01 Feb 2012 05:00:00 +0100 5673918 http://www.medworm.com/index.php?rid=5673917&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22300139%26dopt%3DAbstract Authors: Janssens V, Rebollo A Abstract A block in apoptotic cell death is a likely requirement for cancer maintenance. Likewise, drug resistance, one of the key clinical problems in oncology, can often be explained by apoptotic resistance following drug administration. Several signalling pathways can commit cells to death, including intrinsic mitochondrial pathways controlled by the Bcl-2-like proteins, extrinsic Death Receptor-triggered pathways, and Dependence Receptor-initiated pathways. In addition, depending on the cell type, external stimulus and context, various other pro- or anti-survival signalling pathways may become repressed or activated. Proper coordination and conversion into a common cellular response is ensured by various ways of inter-pathway crosstalk. As for mos... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5673917 Wed, 01 Feb 2012 05:00:00 +0100 5673917 http://www.medworm.com/index.php?rid=5637706&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280353%26dopt%3DAbstract Authors: Das M, Lu J, Joseph M, Aggarwal R, Kanji S, McMichael BK, Lee BS, Agarwal S, Ray-Chaudhury A, Iwenofu OH, Kuppusamy P, Pompili VJ, Jain MK, Das H Abstract Kruppel-like factor 2 (KLF2) plays an important role in the regulation of a variety of immune cells, including monocytes. We have previously shown that KLF2 inhibits proinflammatory activation of monocytes. However, the role of KLF2 in arthritis is yet to be investigated. In the current study, we show that recruitment of significantly greater numbers of inflammatory subset of CD11b+F4/80+Ly6C+ monocytes to the inflammatory sites in KLF2 hemizygous mice compared to the wild type littermate controls. In parallel, inflammatory mediators, MCP-1, Cox-2 and PAI-1 were significantly up-regulated in bone marrow-derived monocytes... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5637706 Sun, 29 Jan 2012 03:19:02 +0100 5637706 http://www.medworm.com/index.php?rid=5637705&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280354%26dopt%3DAbstract Authors: Shen YX, Sun AM, Fang S, Feng LJ, Li Q, Hou HL, Liu C, Wang HP, Shen JL, Luo J, Zhou JN Abstract Intraneuronal accumulation of abnormal phosphorylated tau (p-tau) is a molecular pathology in many neurodegenerative tauopathies, including Alzheimer's disease (AD) and frontotemporal dementia with parkinsonism-linked to chromosome 17 (FTDP-17). However, the underlying mechanism remains unclear. Here, we showed an inverse relationship between endoplasmic reticulum membrane ubiquitin ligase (E3) Hrd1 expression and p-tau accumulation in the hippocampal neurons of AD, and proposed that Hrd1 may be a negative regulator of p-tau. This notion was further supported by in vitro study demonstrating that Hrd1 interacted with tau and promoted the degradation of total tau and p-tau as wel... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5637705 Sun, 29 Jan 2012 03:18:53 +0100 5637705 http://www.medworm.com/index.php?rid=5637704&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280355%26dopt%3DAbstract Authors: Zhang G, Wang Y, Zhang Y, Wan X, Li J, Liu K, Wang F, Liu Q, Yang C, Yu P, Huang Y, Wang S, Jiang P, Qu Z, Luan J, Duan H, Zhang L, Hou A, Jin S, Hsieh TC, Wu E Abstract The purpose of this study was to test the hypothesis that administration of epigallocatechin-3-gallate (EGCG), a polyphenol present in abundance in widely consumed tea, inhibits cell proliferation, invasion, and angiogenesis in breast cancer patients. EGCG in 400 mg capsules was orally administered three times daily to breast cancer patients undergoing treatment with radiotherapy. Parameters related to cell proliferation, invasion, and angiogenesis were analyzed while blood samples were collected at different time points to determine efficacy of the EGCG treatment. Compared to patients who received radioth... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5637704 Sun, 29 Jan 2012 03:18:43 +0100 5637704 http://www.medworm.com/index.php?rid=5637703&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280356%26dopt%3DAbstract Authors: Hu WF, Gong L, Cao Z, Ma H, Ji W, Deng M, Liu M, Hu XH, Chen P, Yan Q, Chen HG, Liu J, Sun S, Zhang L, Liu JP, Wawrousek E, Li DW Abstract The small heat shock protein, α-crystallin, exists in two isoforms, αA and αB, and displays strong ability against stress-induced apoptosis. Regarding their functional mechanisms, we and others have demonstrated that they are able to regulate members in both caspase and Bcl-2 families. In addition, we have also shown that αA and αB may display differential anti-apoptotic mechanisms under certain stress conditions. While αA-crystallin regulates activation of the AKT signaling pathway, αB negatively regulates the MAPK pathway to suppress apoptosis induced by UV and oxidative stress. Although previous studies revealed that αA and �... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5637703 Sun, 29 Jan 2012 03:18:32 +0100 5637703 http://www.medworm.com/index.php?rid=5637702&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280357%26dopt%3DAbstract Authors: Tagariello A, Breuer C, Birkner Y, Schmidt S, Koch AM, Cesnjevar R, Ruffer A, Dittrich S, Schneider H, Winterpacht A, Sticht H, Dotsch J, Toka O Abstract In patients with congenital heart defects, chromosomal anomalies are 100 times more frequent than in control subjects. Coarctation of the aorta can be detected in 15-20% of patients with Ullrich-Turner syndrome. By extensively reviewing literature involving breakpoint analysis of gonosomal deletions in Ullrich- Turner syndrome patients with and without coarctation of the aorta, we identified several gonosomal homolgous gene pairs of interest. Four of these homologous gene pairs were investigated by standard DNA sequencing in a cohort of 83 patients with non-syndromic coarctation of the aorta. Subsequently stability of mut... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5637702 Sun, 29 Jan 2012 03:18:21 +0100 5637702 http://www.medworm.com/index.php?rid=5637701&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22280358%26dopt%3DAbstract In conclusion, early therapy with delapril after MI preserved the normal contraction/relaxation cycle of surviving cardiomyocytes with multiple direct effects on key intracellular mechanisms contributing to preserve cardiac function. PMID: 22280358 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5637701 Sun, 29 Jan 2012 03:18:11 +0100 5637701 http://www.medworm.com/index.php?rid=5637708&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22272725%26dopt%3DAbstract Authors: Erkan M, Reiser-Erkan C, Michalski CW, Kong B, Esposito I, Friess H, Kleeff J Abstract Around 95% of patients diagnosed with pancreatic cancer will die of their disease within 5 years, three quarters within a year. The major hurdle in improving prognosis is the lack of a therapeutic time window. Early cancerous lesions are far beneath our threshold of detection. Therefore, at the time of diagnosis even early (T1) tumors can be metastatic and resistant to conventional treatments. Several therapies targeting epithelial tumor cells-all showing impressive results in vitro and in animal experiments-have failed to show relevant effects in clinical trials. This discrepancy between experimental data and clinical reality results mostly from the inefficiency of our current experimen... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5637708 Thu, 19 Jan 2012 05:00:00 +0100 5637708 http://www.medworm.com/index.php?rid=5637707&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22272726%26dopt%3DAbstract Authors: Guillot-Sestier MV, Checler F Abstract During the last thirty years, part of the scientific community focused on the mechanisms by which a naturally occurring protein called cellular prion (PrPc) converts into a protease-resistant isoform (PrPsc) responsible for fatal Transmissible Spongiform Encephalopathies (TSE). Concomitantly, the physiology of PrPc has also been studied. PrPc undergoes proteolytic attacks leading to both membrane-attached and secreted fragments, the nature of which differs in normal and TSE-affected human brains. Does proteolysis of PrPc correspond to an inactivating mechanism impairing the biological function of the protein, or alternatively, does it represent a maturation process allowing the produced fragments to trigger their own physiological fun... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5637707 Thu, 19 Jan 2012 05:00:00 +0100 5637707 http://www.medworm.com/index.php?rid=5596584&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22229477%26dopt%3DAbstract Authors: Feng D, Cao Z, Li C, Zhang L, Zhou Y, Ma J, Liu R, Zhou H, Zhao W, Wei H, Ling B Abstract Epigenetic silencing of the tumor suppressor gene, RARβ2, through histone deacetylation has been established as an important process of cervical carcinogenesis. This pivotal role has led to the suggestion that a combination of retinoids selective for RARβ2 with histone deacetylase (HDAC) inhibitors may have therapeutic potential. Valproic acid (VPA), a HDAC inhibitor, has a critical role in the regulation of gene expression through histone acetylation and causes transformed cells to undergo growth arrest, differentiation, and apoptosis. Therefore, we hypothesized that the combination of VPA and ATRA could restore RARβ2 expression, thus resulting in enhanced anti-neoplastic activity... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5596584 Tue, 10 Jan 2012 05:00:00 +0100 5596584 http://www.medworm.com/index.php?rid=5558815&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22208613%26dopt%3DAbstract Authors: Wang Y, Zhang Y, Yang J, Ni X, Liu S, Li Z, Hodges SG, Fisher WE, Fisher FC, Gibbs RA, Gingras MC, Li M Abstract Pancreatic cancer is a multiple genetic disorder with many mutations identified during the progression. Two mouse pancreatic cancer cell lines were established which showed different phenotype in vivo: a non-metastatic cell line, Panc02, and a highly metastatic cell line, Panc02-H7, a derivative of Panc02. In order to investigate whether the genetic mutations of key genes in pancreatic cancer such as KRAS, TP53 (p53), CDKN2A (p16), SMAD4, ZIP4, and PDX-1 contribute to the phenotypic difference of these two mouse pancreatic cancer cells, we sequenced the exonic regions of these key genes in both cell lines and in the normal syngeneic mouse pancreas and compared t... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5558815 Mon, 02 Jan 2012 05:00:00 +0100 5558815 http://www.medworm.com/index.php?rid=5527686&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D22126792%26dopt%3DAbstract Authors: Malhotra SV PMID: 22126792 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5527686 Thu, 01 Dec 2011 05:00:00 +0100 5527686 http://www.medworm.com/index.php?rid=5324819&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21999146%26dopt%3DAbstract Authors: Trapani L, Segatto M, Incerpi S, Pallottini V Abstract Oxidative stress has recently been implicated in the pathogenesis of various diseases such as diabetes and coronary artery disease whose main modifiable risk factor is the abnormal level of lipids and/or lipoproteins in the blood. Thus, the maintenance of cholesterol homeostasis together with the reduction of intracellular reactive oxygen species content could partially prevent the occurrence of atherosclerotic phenomena. Owing to the ability exerted by some antioxidants to modulate the activity and/or the protein levels of 3-hydroxy-3-methylglutaryl coenzyme A reductase (the rate-limiting enzyme of cholesterol biosynthetic pathway), their use as additional approach to the management of hypercholesterolemia should be t... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5324819 Tue, 18 Oct 2011 13:01:15 +0100 5324819 http://www.medworm.com/index.php?rid=5324818&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21999147%26dopt%3DAbstract Authors: Gupta M, Kaur H, Jajodia A, Jain S, Satyamoorthy K, Mukerji M, Thirthalli J, Consortium IG, Kukreti R Abstract Dopaminergic system in the prefrontal cortex (PFC) is known to regulate the cognitive functions. Catechol-O-methyl transferase (COMT), one of the major modulators of prefrontal dopamine function, has emerged as an important determinant of schizophrenia associated cognitive dysfunction and response to antipsychotics. A common Val->Met polymorphism (rs4680) in the COMT gene, associated with increased prefrontal dopamine catabolism, impairs prefrontal cognition and might increase risk for schizophrenia. Further, the degree of cognitive improvement observed with antipsychotics in schizophrenia patients is influenced by the COMT activity, and Val/Met has been propos... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5324818 Tue, 18 Oct 2011 13:01:04 +0100 5324818 http://www.medworm.com/index.php?rid=5324817&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21999148%26dopt%3DAbstract Authors: A S, J C, A S, F C Abstract Many plant antioxidants, intaken through the daily diet or plant-derived dietary supplements, have been shown able to prevent free radical-related diseases by counteracting cell oxidative stress. However, it is now considered that the in vivo beneficial effects of these phytochemicals are unlikely to be explained just by their antioxidant capability. Several plant antioxidants exhibit hormetic properties, by acting as 'low-dose stressors' that may prepare cells to resist more severe stress. In fact low doses of these phytochemicals activate cell signaling pathways (being the most prominent examples the modulation of the Nrf2/Keap1 pathway, the NF-κB pathway and the Sirtuin-FOXO pathway) but high doses are cytotoxic. Herein we review the adaptiv... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5324817 Tue, 18 Oct 2011 13:00:54 +0100 5324817 http://www.medworm.com/index.php?rid=5324816&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21999149%26dopt%3DAbstract Authors: Mariani M, Shahabi S, Sieber S, Scambia G, Ferlini C Abstract Class III β-tubulin (TUBB3) is a prominent mechanism of drug resistance expressed in a variety of solid tumors and particularly in lung and ovarian cancer. In the classical view, TUBB3 expression and drug resistance have been linked, and together they have been associated with a perturbation in microtubule dynamics. In keeping with this observation, TUBB3 was associated with drug resistance only when chemotherapy included a taxane in its chemical composition. In this review, we demonstrate that the classical supposition about TUBB3 is not correct, and that instead TUBB3 expression is linked to drug resistance as a complex survival mechanism activated by microenvironmental conditions such as poor nutrient supply... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5324816 Tue, 18 Oct 2011 13:00:44 +0100 5324816 http://www.medworm.com/index.php?rid=5324815&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21999150%26dopt%3DAbstract Authors: Kaushik M, Kaushik S, Bansal A, Saxena S, Kukreti S Abstract Structural multitude of nucleic acids serves basis for its multiple merits and applications. During structural transitions, significant to perform respective cellular functions, these DNA forms can vary from the single stranded to multi-stranded species. Hence, beyond the image of a monotonous DNA double-helix, there is now increasing interest in other polymorphic/ multi-stranded forms, the roles they may play in vivo and their potential use in therapeutics. Distinct guanine-rich nucleic acid sequences readily form a structurally diverse four-stranded architecture called G-quadruplexes. In addition to their presence at physical ends of chromosomes called telomeres, occurrence of these structural motifs in the ups... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5324815 Tue, 18 Oct 2011 13:00:33 +0100 5324815 http://www.medworm.com/index.php?rid=5324814&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21999151%26dopt%3DAbstract Authors: Buttari B, Profumo E, Capozzi A, Sorice M, Riganò R Abstract Beta2-glycoprotein I (β 2-GPI), an abundant 50 kDa plasma glycoprotein, is the most common target for antiphospholipid antibodies (aPLs). These autoantibodies are associated with thrombotic events in patients with anti-phospholipid antibody syndrome (APS) and systemic lupus erythematosus (SLE) and are proatherogenic. β2-GPI can also stimulate a vigorous adaptive cellular immune response in these patients. Although much is known about β2-GPI as a cofactor in autoimmune diseases, crucial information is still lacking to clarify why this abundant self plasma protein is the target of autoimmune responses. Throughout the years, a remarkable number of theories have been proposed to explain how the immune system reco... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5324814 Tue, 18 Oct 2011 13:00:22 +0100 5324814 http://www.medworm.com/index.php?rid=5324813&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21999152%26dopt%3DAbstract Authors: Chakrabarty SP, Balaram H, Chandrasekaran S Abstract Sirtuin (Sir2) proteins being key regulators of numerous cellular processes have been, over the recent past, the subject of intense study. Sirs have been implicated in diverse physiological processes ranging from aging and cancer to neurological dysfunctions. Studies on Sir2s using tools of genetics, molecular biology, biochemistry and structural biology have provided significant insight into the diverse functions of this class of deacetylases. This apart, medicinal chemistry approaches have enabled the discovery of modulators (both activators and inhibitors) of Sir2 activity of diverse chemical structures and properties. The availability of these small molecule modulators of Sir2 activity not only has pharmacological si... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5324813 Tue, 18 Oct 2011 13:00:12 +0100 5324813 http://www.medworm.com/index.php?rid=5216247&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902648%26dopt%3DAbstract Authors: Nagoshi H, Horiike S, Kuroda J, Taniwaki M Abstract Myelodysplastic syndrome (MDS) is a heterogeneous group of clonal hematological disorders characterized by ineffective hematopoiesis which causes peripheral cytopenias and a risk of progression to acute myeloid leukemia. Although various forms of chromosomal abnormalities have been detected in approximately 50-60% of patients with de novo MDS and in up to 80% of patients with therapy-related MDS, their molecular significance for pathogenesis and disease progression is not yet fully understood. Recent technical advances in molecular biology have disclosed more accurately details of pathological chromosomal and molecular aberrations in MDS. Such details could not be identified with conventional cytogenetical techniques, inc... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5216247 Fri, 09 Sep 2011 04:00:00 +0100 5216247 http://www.medworm.com/index.php?rid=5216246&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902649%26dopt%3DAbstract Authors: Deretzi G, Kountouras J, Polyzos SA, Zavos C, Giartza-Taxidou E, Gavalas E, Tsiptsios I Abstract A common characteristic of the central nervous system (CNS) neurodegenerative disorders is neuroinflammation, marked by augmented numbers of activated and primed microglia, increased inflammatory cytokines and decreased anti-inflammatory molecules. CNS neuroinflammation is a critical component in the progression of several neurodegenerative diseases which sensitize the brain to produce an exaggerated response to immune stimuli in the periphery. Neuroinflammation might initiate from the periphery and peripheral conditions through disrupted blood-brain barrier powerfully influence various brain pathologies. Gastrointestinal tract (GIT) represents a vulnerable area through which p... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5216246 Fri, 09 Sep 2011 04:00:00 +0100 5216246 http://www.medworm.com/index.php?rid=5216245&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902650%26dopt%3DAbstract Authors: Doherty KJ, McKay C, Chan KK, El-Tanani MK Abstract The identification of a relevant effector of Ran GTPase (Ran) signaling and its pathways could provide a novel approach to cancer therapeutics. With recent research highlighting the significant relationship between Ran expression and the occurrence and progression of cancer, the development of a small molecule compound that would decrease the endogenous levels of Ran in the cell would have anti-mitotic effects and could lead to the development of new types of cancer therapeutics. In the absence of Ran binding domains, Ran is expected to remain locked up in non-productive complexes with importins and is effectively removed from the system. Thus, Ran binding proteins present as a logical molecular target for the inhibition ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5216245 Fri, 09 Sep 2011 04:00:00 +0100 5216245 http://www.medworm.com/index.php?rid=5216244&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902651%26dopt%3DAbstract Authors: Shan T, Ma Q, Guo K, Liu J, Li W, Wang F, Wu E Abstract Despite decades of research, the treatment and management of malignant tumors still remain a formidable challenge for public health. New strategies for cancer treatment are being developed, and one of the most promising treatment strategies involves the application of chemopreventive agents. The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds. Xanthones, from the pericarp, whole fruit, heartwood, and leaf of mangosteen (Garcinia mangostana Linn., GML), are known to possess a wide spectrum of pharmacologic properties, including anti-oxidant, anti-tumor, anti-allergic, anti-inflammatory, anti-bacterial, anti-fungal, and anti-viral activi... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5216244 Fri, 09 Sep 2011 04:00:00 +0100 5216244 http://www.medworm.com/index.php?rid=5216243&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902652%26dopt%3DAbstract Authors: Drew AP, Blair IP, Nicholson GA Abstract The distal hereditary motor neuropathies (dHMNs) are a clinically and genetically heterogeneous group of disorders that primarily affect motor neurons, without significant sensory involvement. New dHMN genes continue to be identified. There are now 11 causative genes described for dHMN, and an additional five genetic loci with unidentified genes. This genetic heterogeneity has further delineated the classification of dHMN, which was previously classified according to mode of inheritance, age at onset, and additional complicating features. Some overlap between phenotypically distinct forms of dHMN is also apparent. The mutated genes identified to-date in dHMN include HSPB1, HSPB8, HSPB3, DCTN1, GARS, PLEKHG5, BSCL2, SETX, IGHMBP2, AT... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5216243 Fri, 09 Sep 2011 04:00:00 +0100 5216243 http://www.medworm.com/index.php?rid=5216242&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902653%26dopt%3DAbstract Authors: Smolewski P, Robak T Abstract Apoptosis, a programmed cell death, plays a key role in the regulation of tissue homeostasis. However, impairment of its regulation may promote formation and progression of malignancy. An important part of the apoptotic machinery are the inhibitor of apoptosis protein (IAP) family, regulating caspase activity, cell division or cell survival pathways through binding to their baculovirus AIP repeat (BIR) domains and/or by their ubiquitin-ligase RING zinc finger (RZF) activity. The following IAPs have been described so far: NAIP (neuronal apoptosis inhibitory protein; BIRC1), cIAP1 and cIAP2 (cellular inhibitor of apoptosis 1 and 2; BIRC2 and BIRC3, respectively), XIAP (X-chromosome binding IAP; BIRC4), survivin (BIRC5), BRUCE (Apollon; BIRC6), l... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5216242 Fri, 09 Sep 2011 04:00:00 +0100 5216242 http://www.medworm.com/index.php?rid=5216241&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21902654%26dopt%3DAbstract This article reviews the molecular pathogenesis of NMIBCs, discusses recently completed and ongoing clinical trials and anticipates the future direction of molecular targeted agents in this disease. PMID: 21902654 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=5216241 Fri, 09 Sep 2011 04:00:00 +0100 5216241 http://www.medworm.com/index.php?rid=4998553&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707512%26dopt%3DAbstract Authors: Ramana KV, Yadav UC, Calhoun WJ, Srivastava SK The prevalence of asthma and costs of its care have been continuously increasing, but novel therapeutic options to treat this inflammatory disease have not been brought to the US market. Current therapies such as inhaled steroids, long-acting beta-agonist bronchodilators, antihistamines and immunomodulators may control the symptoms of allergic asthma but fail to modify the underlying disease. Excessive use of steroids and other immunosuppresents alter the patient's quality of life, produce undesirable toxicities, and increase the risk of other pathologies such as diabetes. Hence novel therapeutic options to manage asthma are desirable. In the present review, we have discussed the role of the polyol pathway enzyme aldose reductase ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4998553 Sun, 26 Jun 2011 23:00:00 +0100 4998553 http://www.medworm.com/index.php?rid=4998552&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707513%26dopt%3DAbstract Authors: Ventura S Many cellular processes depend on the establishment of selective stable or transient interactions between proteins. Therefore, the ability to identify and characterize these contacts in physiologically relevant environments is crucial to understanding the networks of contacts that allow the transmission and integration of biological information in living cells. Protein-fragment complementation assays (PCA) have emerged as approaches that report on the proximity of two given proteins in the cell at a given location and time. In particular, bimolecular fluorescence complementation (BIFC) allows noninvasive imaging of protein binding in living cells at high spatial resolution and without the requirement for exogenous substrates. In the present review, we discuss PCA and... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4998552 Sun, 26 Jun 2011 23:00:00 +0100 4998552 http://www.medworm.com/index.php?rid=4998551&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707514%26dopt%3DAbstract Authors: Bei R, Mizejewski GJ Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide, with a poor prognosis and limited therapeutic options. Due to its overexpression in the majority of HCCs, alpha-fetoprotein (AFP) represents one of the most useful markers for hepatocarcinomas and for monitoring patients' response to therapy. Although it was earlier reported that AFP has immunosuppressive properties, it has been recently demonstrated that AFP induces spontaneous T and B cells responses in HCC patients. The characterization of AFP-immunogenic epitopes gives the opportunity to design AFP-based cancer vaccines for human HCC. The activity of AFP-based vaccines has been investigated in HCC mouse models in order to develop novel strategies to treat patients with HCC. This ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4998551 Sun, 26 Jun 2011 23:00:00 +0100 4998551 http://www.medworm.com/index.php?rid=4998550&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707515%26dopt%3DAbstract Authors: Wu S, Singh RK Metastatic melanoma is one of the most intractable tumors, with all current regimens showing limited survival impact. Failure of most agents is attributed to development of therapy resistance. Accumulated evidence points to the apoptotic defect of melanoma cells and the surge of survival signals stimulated by cytotoxic drugs, as a way that tumors circumvent cytotoxic chemotherapy. An overview of inhibitors developed against these growth/survival factors, which are potential partners to be combined with systemic chemotherapy, will be discussed. The escape mechanism from molecular inhibitors also suggests a "vertical" or "horizontal" combination of molecularly targeted therapies. A better understanding of the interactions between simultaneously used regimens and o... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4998550 Sun, 26 Jun 2011 23:00:00 +0100 4998550 http://www.medworm.com/index.php?rid=4998549&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707516%26dopt%3DAbstract Authors: Babizhayev MA, Yegorov YE Glaucoma is a major cause of irreversible blindness, affecting more than 70 million individuals worldwide. Elevated intraocular pressure (IOP) is a major risk factor in the development of glaucoma and in the progression of glaucomatous damage. High IOP usually occurs as a result of an increase in aqueous humor outflow resistance in trabecular meshwork (TM). Primary open angle glaucoma (POAG) is characterized by quantifiable parameters including the IOP, the aqueous outflow facility, and geometric measurements of the optic disc and visual defects. Morphological and biochemical analyses of the TM of POAG patients revealed loss of cells, increased accumulation of extracellular matrix (ECM), changes in the cytoskeleton, cellular senescence and the process... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4998549 Sun, 26 Jun 2011 23:00:00 +0100 4998549 http://www.medworm.com/index.php?rid=4998548&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707517%26dopt%3DAbstract Authors: Midgett C, Stitham J, Martin KA, Hwa J The prostacyclin receptor (IP - International Union of Pharmacology nomenclature) is a member of the seven transmembrane G-protein coupled receptor (GPCR) superfamily. Recent concerns with selective and non-selective COX-1/COX-2 inhibition have exposed an important cardioprotective role for IP in preventing atherothrombosis. Receptor dysfunction (genetic variants) or reduced signaling (COX-2 inhibition) in high cardiovascular risk patients leads to increased cardiovascular events. These clinical observations have also been confirmed genetically by mouse knockout studies. Thus, receptor regulation is paramount in ensuring correct function in the prevention of atherothrombosis. This review summarizes recent literature on how this important ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4998548 Sun, 26 Jun 2011 23:00:00 +0100 4998548 http://www.medworm.com/index.php?rid=4998547&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21707518%26dopt%3DAbstract Authors: Rucci N, Sanită P, Angelucci A Metalloproteinases (MMPs) are a cluster of at least 23 enzymes belonging to the more wide family of endopeptidases called Metzincins, whose structure is characterized by the presence of a zinc ion at the catalytic site. Although the general view of MMPs as physiologic scissor involved in extracellular matrix (ECM) degradation and tissue remodeling is still valid, additional functions have recently emerged, including the ability to cleave non ECM molecules such as growth factors, cytokines and chemokines from their membrane-anchored proforms. These functions are utilized by tumor cells and are fundamental in the determination of tumor progression and invasion. The effect of MMPs activity in cancer progression has been traditionally associated wit... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4998547 Sun, 26 Jun 2011 23:00:00 +0100 4998547 http://www.medworm.com/index.php?rid=4950003&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21663586%26dopt%3DAbstract Authors: Jankun J, Skrzypczak-Jankun E Plasminogen activator inhibitor (PAI-1) is a fast acting inhibitor of tissue and urokinase plasminogen activators (tPA and uPA). In that way PAI-1 regulates proteolytic activity of many physiological and pathological processes [1-3]. PAI-1 plays an important role in blood coagulation controlling clot lysis which is triggered by tPA activated plasminogen [4]. Only two types of mutations are reported to be associated with PAI-1; one is the frame-shift mutation in exon 4 of PAI-1 gene resulting in a truncated nonfunctional protein and in complete PAI-1 deficiency. The other SNP causes Ala15Thr mutation in the signal peptide. A literature search revealed five variants of polymorphisms during a study of over one thousand individuals. Two are associated... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4950003 Sun, 12 Jun 2011 23:00:00 +0100 4950003 http://www.medworm.com/index.php?rid=4950002&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21663587%26dopt%3DAbstract In this study, we investigated whether DHA, a nutritionally important n-3 unsaturated fatty acid, modulated the sensitivity of brain tumor cells to the anticancer drug, etoposide (VP16). Medulloblastoma (MB) cell lines, Daoy and D283, and glioblastoma (GBM) cell lines, U138 and U87, were exposed to DHA or VP16 alone or in combination. The effects on cell proliferation and the induction of apoptosis were determined by using MTS and Hoechest 33342/PI double staining. U87 and U138 cells were found to be insensitive to the addition of DHA and VP16, whereas the two MB cell lines showed high sensitivity. DHA or VP16 alone showed little effect on cell proliferation or death in either the MB or GBM cell lines, but pretreatment with DHA enhanced the responsiveness to VP16 in the MB cell lines. To u... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4950002 Sun, 12 Jun 2011 23:00:00 +0100 4950002 http://www.medworm.com/index.php?rid=4950001&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21663588%26dopt%3DAbstract Authors: Zhang H, Lu W, Zhao Y, Rong P, Cao R, Gu W, Xiao J, Miao D, Lappe J, Recker R, Xiao GG The infiltration of adipocytes in osteoporotic patients' bone marrow suggests an important regulatory function of bone marrow fat on the development of aged bone. Therefore, we have examined the effects of adipocytes derived from bone mesenchymal stem cell (MSC) on osteoblast differentiation using two different co-culture modes (direct mode and indirect mode). Alkaline phosphatase (ALP)-positive areas and mineralized areas of MSC-derived osteoblasts decrease similarly in the two co-culture modes as the amount of MSC-derived adipocytes increases, suggesting that the crosstalk between adipocytes and osteoblasts may be mainly through secretory factors in the medium. To further understand the mo... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4950001 Sun, 12 Jun 2011 23:00:00 +0100 4950001 http://www.medworm.com/index.php?rid=4950000&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21663589%26dopt%3DAbstract Authors: Mo X, Xu L, Yang Q, Feng H, Peng J, Zhang Y, Yuan W, Wang Y, Li Y, Deng Y, Wan Y, Chen Z, Li F, Wu X To study the common molecular mechanisms of various viruses infections that might result in congential cardiovascular diseases in perinatal period, changes in mRNA expression levels of ECV304 cells infected by rubella virus (RUBV), human cytomegalovirus (HCMV), and herpes simplex virus type 2 (HSV-2) were analyzed using a microarray system representing 18,716 human genes. 99 genes were found to exhibit differential expression (80 up-regulated and 19 down-regulated). Biological process analysis showed that 33 signaling pathways including 22 genes were relevant significantly to RV, HCMV and HSV-II infections. Of these 33 biological processes, 28 belong to one-gene biological proc... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4950000 Sun, 12 Jun 2011 23:00:00 +0100 4950000 http://www.medworm.com/index.php?rid=4949999&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21663590%26dopt%3DAbstract Authors: Tang X, O'Reilly A, Asano M, Merrill JC, Yokoyama KK, Amar S Abnormal and prolonged inflammatory reaction is seen in a wide variety of disorders, and high level of Tumor Necrosis Factor alpha (TNF-α) has been linked to these disorders. Therefore, modulation of TNF-α expression is important in the regulation of inflammatory disorders. In our previous study, we have shown that a transcription factor LPS-induced TNF factor (LITAF) significantly induces TNF-α production. Furthermore, we found that p53 and its synthetic peptide 162-motif specifically downregulate LITAF/TNF-α gene expression in human cells in vitro. Thus, in the present study, the role of p53 in regulating TNF-α-mediated inflammation was investigated. Our data showed that a synthetic peptide, named 162-motif, c... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4949999 Sun, 12 Jun 2011 23:00:00 +0100 4949999 http://www.medworm.com/index.php?rid=4949998&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21663591%26dopt%3DAbstract Authors: Rull A, García R, Fernández-Sender L, Beltrán-Debón R, Aragonès G, Alegret JM, Alonso-Villaverde C, Mackness B, Mackness M, Camps J, Martin-Paredero V, Joven J Atherosclerosis in symptomatic peripheral arterial disease affects wide portions of numerous arteries in lower extremities. The resulting active inflammation in a considerable amount of arterial tissue facilitates systemic detection via measurement of inflammation-related variables. We reasoned that the combined assessment of defense against oxidative stress, in the form of paraoxonase-1 (PON1), and monocyte migration measured as circulating (C-C motif) ligand 2 (CCL2), may play a role in the evaluation of these patients. Plasma CCL2 and serum PON1-related variables, assessed by their interaction with functional ge... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4949998 Sun, 12 Jun 2011 23:00:00 +0100 4949998 http://www.medworm.com/index.php?rid=4949997&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21663592%26dopt%3DAbstract Authors: Mitchell DC, Bryan BA, Liu L, Hu XH, Huang XQ, Ji WK, Chen PC, Hu WF, Liu JP, Zhang J, Liu M, Li DW The Rho-family of small GTPase specific guanine nucleotide exchange factor, GEFT, is expressed at high levels in adult human excitable tissues including the brain, heart, and skeletal muscle. Previously, we demonstrated that GEFT is specifically expressed in the adult mouse hippocampus and cerebellum, and that overexpression of this protein can result in neurite and dendrite remodeling. This finding prompted us to explore the expression of GEFT in other tissues, which share common developmental ancestry to the nervous system, specifically the ocular system. Using immunohistochemical analysis specific for GEFT protein expression, we observed the highest ocular expression of GEFT ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4949997 Sun, 12 Jun 2011 23:00:00 +0100 4949997 http://www.medworm.com/index.php?rid=4949996&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21663593%26dopt%3DAbstract Authors: Li DW PMID: 21663593 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4949996 Sun, 12 Jun 2011 23:00:00 +0100 4949996 http://www.medworm.com/index.php?rid=4853475&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568930%26dopt%3DAbstract In conclusion, BG is a cornucopia of health and it deserves in-depth investigations for clinical application in the future. PMID: 21568930 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4853475 Sun, 15 May 2011 23:00:00 +0100 4853475 http://www.medworm.com/index.php?rid=4853474&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568931%26dopt%3DAbstract Authors: Blázquez-Medela AM, López-Novoa JM, Martínez-Salgado C Osteoprotegerin (OPG) is a member of the tumour necrosis factor receptor superfamily of cytokines which, in spite of being initially described as a strong anti-resorptive factor, has lately been considered as a possible link between bone and vascular disease. In the last few years, several studies have evidenced its close relationship with the development of diabetes. In this review, we analyse the role of OPG in diabetic patients and its links with the most relevant associated diseases such as atherosclerosis, hypertension, endothelial dysfunction and diabetic nephropathy, as well as its connection with related pathologies as fibrosis, obesity and metabolic syndrome. PMID: 21568931 [PubMed - as supplied by publishe... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4853474 Sun, 15 May 2011 23:00:00 +0100 4853474 http://www.medworm.com/index.php?rid=4853473&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568932%26dopt%3DAbstract Authors: Luoma PV Atherosclerotic vascular disease, diabetes mellitus (DM) and dementia are major global health problems. Both endogenous and exogenous factors activate genes functioning in biological processes. This review article focuses on gene-activation mechanisms that regress atherosclerosis, eliminate DM type 2 (DM2), and prevent cognitive decline and dementia. Gene-activating compounds upregulating functions of liver endoplasmic reticulum (ER) and affecting lipid and protein metabolism, increase ER size through membrane synthesis, and produce an antiatherogenic plasma lipoprotein profile. Numerous gene-activators regress atherosclerosis and reduce the occurrence of atherosclerotic disease. The gene-activators increase glucose disposal rate and insulin sensitivity and, by restor... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4853473 Sun, 15 May 2011 23:00:00 +0100 4853473 http://www.medworm.com/index.php?rid=4853472&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568933%26dopt%3DAbstract Authors: González-Gallego J, García-Mediavilla MV, Sánchez-Campos S Reactive oxygen and nitrogen species (ROS/RNS), whether produced endogenously as a consequence of normal cell functions or derived from external sources, pose a constant threat to cells living in an aerobic environment. When the production of ROS/RNS overrides the antioxidant capability of the target cells, oxidative damage may occur as a consequence of the interaction with DNA, protein, and lipids. Hepatitis C virus (HCV) is a major cause of viral hepatitis. Although the molecular mechanisms of HCV pathogenesis remain unclear, oxidative stress is emerging as a key step and a major initiator in the development and the progression of liver damage, and the evaluation of oxidative stress may be useful for a better unde... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4853472 Sun, 15 May 2011 23:00:00 +0100 4853472 http://www.medworm.com/index.php?rid=4853471&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568934%26dopt%3DAbstract Authors: Apetoh L, Végran F, Ladoire S, Ghiringhelli F Accumulating evidence suggests that the success of some anticancer therapies not only relies on their direct cytotoxicity on tumor cells but also on their ability to promote anticancer immune responses. However, immunosuppressive cells such as Myeloid Derived Suppressor Cells (MDSC) that are generated during tumor progression blunt antitumor immune responses and thus represent a major obstacle to the clinical implementation of immunotherapy protocols. We have recently identified 5-Fluorouracil (5-FU) as an anticancer agent that selectively induced MDSC apoptotic cell death in vitro and in vivo. The elimination of MDSC by 5-FU increased IFNγ secretion by tumor specific CD8(+) T cells infiltrating the tumor and promoted T-cell depe... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4853471 Sun, 15 May 2011 23:00:00 +0100 4853471 http://www.medworm.com/index.php?rid=4853470&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21568935%26dopt%3DAbstract Authors: Pietsch J, Bauer J, Egli M, Infanger M, Wise P, Ulbrich C, Grimm D It has always been a desire of mankind to conquest Space. A major step in realizing this dream was the completion of the International Space Station (ISS). Living there for several months confirmed early observations of short-term spaceflights that a loss of gravity affects the health of astronauts. Space medicine tries to understand the mechanism of microgravity-induced health problems and to conceive potent countermeasures. There are four different aspects which make space medicine appealing: i) finding better strategies for adapting astronauts to weightlessness; ii) identification of microgravity-induced diseases (e.g. osteoporosis, muscle atrophy, cardiac problems and others); iii) defining new therapies to... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4853470 Sun, 15 May 2011 23:00:00 +0100 4853470 http://www.medworm.com/index.php?rid=4798835&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21506919%26dopt%3DAbstract Authors: Lourenço AS, Baldeiras I, Grãos M, Duarte CB Multiple Sclerosis is the most common non-traumatic disorder of the central nervous system and is generally regarded as an immune-mediated disorder that occurs in young adults. Since cerebrospinal fluid is in close contact with the extracellular surface of the brain, it is of great interest to examine possible biomarkers for multiple sclerosis. Proteomic studies of cerebrospinal fluid samples represent an important step towards a better understanding of the disease and may lead to the identification of clinically useful markers. Methodological advances in proteomics allowed the comparison of the protein content in different cerebrospinal fluid samples, using gel or liquid-based approaches coupled with mass spectrometry. In this pa... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4798835 Wed, 20 Apr 2011 23:00:00 +0100 4798835 http://www.medworm.com/index.php?rid=4798834&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21506920%26dopt%3DAbstract Authors: Dotta L, Tassone L, Badolato R WHIM syndrome is a dominantly inherited primary immunodeficiency disorder representing the first identified example of human disease caused by mutations in the gene encoding for the chemokine receptor CXCR4. Pathogenesis is mediated by CXCR4 hyperfunction, leading to increased responsiveness to its unique ligand CXCL12 (also known as SDF-1). The altered CXCR4/CXCL12 interaction likely impairs cellular homeostasis and trafficking, resulting in immunological dysfunctions. The acronym WHIM resumes the main features of the syndrome: Warts, Hypogammaglobulinemia, Infections and Myelokathexis, which is abnormal retention of mature neutrophils in the bone marrow. WHIM patients suffer from recurrent bacterial infections since childhood and manifest a spe... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4798834 Wed, 20 Apr 2011 23:00:00 +0100 4798834 http://www.medworm.com/index.php?rid=4798833&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21506921%26dopt%3DAbstract Authors: McGregor RA, Choi MS Worldwide obesity is a growing health problem, associated with increased risk of chronic disease. Understanding the molecular basis of adipogenesis and fat cell development in obesity is essential to identify newbiomarkers and therapeutic targets for the development of anti-obesity drugs. MicroRNAs (miRNAs) appear to play regulatory roles in many biological processesassociated with obesity, includingadipocyte differentiation, insulin action and fat metabolism. Recent studies show miRNAs are dysregulated in obese adipose tissue. During adipogenesis miRNAs can accelerate or inhibit adipocyte differentiation and hence regulate fat cell development.In addition miRNAs may regulate adipogenic lineage commitment in multipotent stem cells and hence govern fat cell... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4798833 Wed, 20 Apr 2011 23:00:00 +0100 4798833 http://www.medworm.com/index.php?rid=4798832&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21506922%26dopt%3DAbstract Authors: Piskareva O, Lackington W, Lemass D, Hendrick C, Doolan P, Barron N The discovery of new biomarkers is a rapidly advancing area in cancer biology. The challenge of biomarker development for broad clinical use requires the translation of lab-based knowledge into clinical practice. The Long Interspersed Nuclear Elements-1 (LINE-1s or L1 elements) are active members of an autonomous family of non-LTR retrotransposons and occupy nearly 17% of the human genome. There is strong experimental evidence that the global hypomethylation of genomic DNA in cancer cells results in the activation of L1s and their expression is detectable at genome, transcriptome and proteome levels in human cancer cells. Thus, human L1s constitute a potential marker for cancer cells. In this review we have at... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4798832 Wed, 20 Apr 2011 23:00:00 +0100 4798832 http://www.medworm.com/index.php?rid=4798831&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21506923%26dopt%3DAbstract Authors: Ercan C, van Diest PJ, Vooijs M The mammary gland is a highly regenerative organ that can undergo multiple cycles of proliferation, lactation and involution, a process controlled by stem cells. The last decade much progress has been made in the identification of signaling pathways that function in these stem cells to control self-renewal, lineage commitment and epithelial differentiation in the normal mammary gland. The same signaling pathways that control physiological mammary development and homeostasis are also often found deregulated in breast cancer. Here we provide an overview on the functional and molecular identification of mammary stem cells in the context of both normal breast development and breast cancer. We discuss the contribution of some key signaling pathways w... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4798831 Wed, 20 Apr 2011 23:00:00 +0100 4798831 http://www.medworm.com/index.php?rid=4798830&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21506924%26dopt%3DAbstract Proteolytic Cleavage of Notch: "HIT and RUN" Curr Mol Med. 2011 Apr 21; Authors: van Tetering G, Vooijs M The Notch pathway is a highly conserved signaling pathway in multicellular eukaryotes essential in controlling spatial patterning, morphogenesis and homeostasis in embryonic and adult tissues. Notch proteins coordinate cell-cell communication through receptor-ligand interactions between adjacent cells. Notch signaling is frequently deregulated by oncogenic mutation or overexpression in many cancer types. Notch activity is controlled by three sequential cleavage steps leading to ectodomain shedding and transcriptional activation. Here we review the key regulatory steps in the activation of Notch, from receptor maturation to receptor activation (HIT) via a rate-limiting prote... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4798830 Wed, 20 Apr 2011 23:00:00 +0100 4798830 http://www.medworm.com/index.php?rid=4695962&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21470186%26dopt%3DAbstract Authors: Li DW PMID: 21470186 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4695962 Thu, 31 Mar 2011 23:00:00 +0100 4695962 http://www.medworm.com/index.php?rid=4575422&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375489%26dopt%3DAbstract Authors: McCombe PA, Henderson RD Amyotrophic lateral sclerosis (ALS) is a severe progressive neurodegenerative disease. The cause is unknown, but genetic abnormalities have been identified in subjects with familial ALS and also in subjects with sporadic ALS. Environmental factors such as occupational exposure have been shown to be risk factors for the development of ALS. Patients differ in their clinical features and differ in the clinical course of disease. Immune abnormalities have been found in the central nervous system by pathological studies and also in the blood and CSF of subjects with ALS. Inflammation and immune abnormalities are also found in animals with a model of ALS due to mutations in the SOD1 gene. Previously it has been considered that immune abnormalities might cont... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4575422 Fri, 04 Mar 2011 00:00:00 +0100 4575422 http://www.medworm.com/index.php?rid=4575421&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375490%26dopt%3DAbstract Authors: Schwarzer R, Jundt F Classical Hodgkin lymphoma (cHL) is now recognized as a B-cell-derived lymphoma which is characterized by only about 1% malignant pathognomonic Hodgkin and Reed-Sternberg (HRS) cells and an abundant infiltrate of reactive bystander cells. HRS cells are unique with respect to their lost B-cell-specific gene expression pattern and recurrent genetic lesions. Aberrant activity of Notch signaling, a highly conserved developmental pathway, acts as a negative regulator of the B cell program in HRS cells and thereby contributes to their reprogramming. Another striking feature and the major pathogenetic mechanism in HRS cells is constitutive NF-κB activation. A number of aberrations that contribute to canonical NF-κB activity in HRS cells have been described such... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4575421 Fri, 04 Mar 2011 00:00:00 +0100 4575421 http://www.medworm.com/index.php?rid=4575420&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375491%26dopt%3DAbstract Authors: Andrikopoulou E, Zhang X, Sebastian R, Marti G, Liu L, Milner SM, Harmon JW Hypoxia Inducible Factor-1 (HIF-1) is considered the major coordinator of the cellular adaptive response to hypoxia. Over recent years, its activity in the context of wound healing has been the object of increasing investigation. On the molecular level, HIF-1 transcriptional target products have been shown to regulate the process of endothelial cell survival, migration and proliferation (VEGF, ANGPT-1, ANGPT-2, ANGPT-4, FGF-2, PlGF, PDGF-B, RGC-32), vascular smooth muscle cell migration and proliferation (FGF-2, EGF, PDGF, thrombospondin) and mobilization of Circulating Angiogenic Cells to the periphery (SFD-1/CXCR4). Studies on the effect of HIF-1 on the expression and activity of extracellular cell m... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4575420 Fri, 04 Mar 2011 00:00:00 +0100 4575420 http://www.medworm.com/index.php?rid=4575419&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375492%26dopt%3DAbstract Authors: Volders K, Nuytens K, Creemers JW Autism is a developmental disorder of the central nervous system characterized by impairments in social interaction, communication and restricted repetitive and stereotyped behavior. It is generally assumed that in most cases autism has a polygenic cause, but the pathogenesis is still unknown. Neurobeachin (NBEA) has recently been identified as a candidate gene for autism in a patient with a de novo chromosomal translocation and three patients with a monoallelic deletion. This multidomain scaffolding protein has been suggested to be involved in neuronal post-Golgi membrane traffic. Knockout of Nbea in two independent mouse models has demonstrated a role in neurotransmitter release and synaptic functioning. Knockdown in a cell line has shown a ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4575419 Fri, 04 Mar 2011 00:00:00 +0100 4575419 http://www.medworm.com/index.php?rid=4575418&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375493%26dopt%3DAbstract Authors: Militello RD, Colombo MI Autophagy is one of the major catabolic processes present in eukaryotic cells, conserved through evolution, by which damaged or superfluous organelles are degraded in response to different stimuli. A hallmark of the autophagic pathway is the formation of double or multiple layered membranes that engulf the material to be finally degraded in the lysosomes. Despite enormous advances in the last few years to understand the autophagic process at the molecular level, the origin of the sequestering membrane has remained elusive for more than forty years and it is still a matter of debate. In this review we have summarized recent experimental evidence indicating that more than one membrane source may exist. Even though de novo formation or assembly of the iso... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4575418 Fri, 04 Mar 2011 00:00:00 +0100 4575418 http://www.medworm.com/index.php?rid=4575417&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21375494%26dopt%3DAbstract Authors: De Keersmaecker B, Thielemans K, Aerts JL HIV infection is characterized by a number of abnormalities in several components of the immune system. For example, during HIV infection, a massive decrease of CD4(+) T cells is observed, as well as a progressive depletion of naïve CD8(+) T cells. Furthermore, elevated numbers of apoptotic B and T cells are present in HIV-infected patients, and a systemic immune activation results in T-cell exhaustion. Finally, HIV infection is characterized by the presence of functionally impaired dendritic cells, with decreased expression of maturation markers, decreased secretion of cytokines and defects in antigen processing and presentation. All these characteristics result in the occurrence of non-functional cytotoxic T lymphocytes, that fail t... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4575417 Fri, 04 Mar 2011 00:00:00 +0100 4575417 http://www.medworm.com/index.php?rid=4522362&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21342128%26dopt%3DAbstract Authors: Ramaekers CH, Wouters BG In recent years there has been intense investigation and rapid progress in our understanding of the cellular responses to various types of endogenous and exogenous DNA damage that ensure genetic stability. These studies have identified numerous roles for ubiquitylation, the post-translational modification of proteins with single ubiquitin or poly-ubiquitin chains. Initially discovered for its role in targeting proteins for degradation in the proteasome, ubiquitylation functions in a variety of regulatory roles to co-ordinate the recruitment and activity of a large number of protein complexes required for recovery from DNA damage. This includes the identification of essential DNA damage response genes that encode proteins directly involved in the ubiqui... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4522362 Tue, 22 Feb 2011 00:00:00 +0100 4522362 http://www.medworm.com/index.php?rid=4522361&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21342129%26dopt%3DAbstract This article reviews on the importance of this clinical issue, current understanding of the underlying mechanisms for the skeletal defects and potential preventative strategies. Both clinical and basic studies that appeared from 1990 to 2010 were reviewed for bone defects (growth arrest, bone loss, osteonecrosis, and/or fractures) caused by paediatric cancer chemotherapy. As chemotherapy has become more intensive and achieved greater success in treating paediatric malignancies, skeletal complications such as bone growth arrest, low bone mass, osteonecrosis, and fractures during and/or after chemotherapy have become a problem for some cancer patients and survivors particularly those that have received high dose glucocorticoids and methotrexate. While chemotherapy-induced skeletal defects ar... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4522361 Tue, 22 Feb 2011 00:00:00 +0100 4522361 http://www.medworm.com/index.php?rid=4522360&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21342130%26dopt%3DAbstract Authors: Vasieva O Glutathione transferase Pi (GST-pi, GSTP) is known to strongly affect human susceptibility to several cancers, asthma and neurodegenerative disorders. As with other glutathione transferases, it catalyses the addition of reduced glutathione to electrophilic species, and it is important in metabolite detoxification. It also was shown to bind proteins and compounds containing iron and nitric oxide. Some of these interactions have developed in the course of evolution into regulatory pathways that back up the GST's most ancient catalytic functions and provide precise and diverse responses to chemical and redox stresses. An aim of this review is to summarise recent knowledge on GSTP's complementary functions in crosstalking pathways of conventional glutathione transfer, ni... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4522360 Tue, 22 Feb 2011 00:00:00 +0100 4522360 http://www.medworm.com/index.php?rid=4522359&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21342131%26dopt%3DAbstract Authors: Mohan RR, Tovey JC, Gupta R, Sharma A, Tandon A Decorin is a small leucine-rich proteoglycan (SLRP) that plays a vital role in many important cellular processes in several tissues including the cornea. A normal constituent of the corneal stroma, decorin is also found in the majority of connective tissues and is related structurally to other small proteoglycans. It interacts with various growth factors such as epidermal growth factor (EGF) and transforming growth factor beta (TGFβ) to regulate processes like collagen fibrillogenesis, extracellular matrix (ECM) compilation, and cell-cycle progression. Studies have linked decorin dysregulation to delayed tissue healing in patients with various diseases including cancer. In the cornea, decorin is involved in the regulation of tra... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4522359 Tue, 22 Feb 2011 00:00:00 +0100 4522359 http://www.medworm.com/index.php?rid=4522358&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21342132%26dopt%3DAbstract Authors: Witkos TM, Koscianska E, Krzyzosia WJ microRNAs (miRNAs) are endogenous non-coding RNAs that control gene expression at the posttranscriptional level. These small regulatory molecules play a key role in the majority of biological processes and their expression is also tightly regulated. Both the deregulation of genes controlled by miRNAs and the altered miRNA expression have been linked to many disorders, including cancer, cardiovascular, metabolic and neurodegenerative diseases. Therefore, it is of particular interest to reliably predict potential miRNA targets which might be involved in these diseases. However, interactions between miRNAs and their targets are complex and very often there are numerous putative miRNA recognition sites in mRNAs. Many miRNA targets have been co... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4522358 Tue, 22 Feb 2011 00:00:00 +0100 4522358 http://www.medworm.com/index.php?rid=4522357&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21342133%26dopt%3DAbstract Authors: Tan JR, Koo YX, Kaur P, Liu F, Armugam A, Wong PT, Jeyaseelan K Stroke is one of the leading causes of death and disability worldwide. There are two major types of stroke: cerebral ischemia caused by obstruction of blood vessels in the brain and haemorrhagic stroke that is triggered by the disruption of blood vessels. Thrombolytic therapy involving recombinant tissue plasminogen activator (rtPA) has been shown to be beneficial only when used within 4.5 hours of onset of acute ischemic stroke. rtPA treatment beyond this time window has been found to be unsuitable and usually resulting in haemorrhagic transformation. Stroke is a multifactorial disease that forms a possible end state for majority of patients suffering from diabetes, atherosclerosis and hypertension which are know... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4522357 Tue, 22 Feb 2011 00:00:00 +0100 4522357 http://www.medworm.com/index.php?rid=4324882&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21189116%26dopt%3DAbstract Authors: Ping YF, Bian XW Recent studies on cancer stem cells (CSCs), a special subpopulation of tumor cells, promote our understanding of tumorigenesis, neovascularization, invasion, drug resistance and tumor recurrence, which establishes new concepts for cancer diagnosis and treatment. Therefore, the biological features and behaviors of CSCs have become an exciting frontier of cancer research. CSCs initiate tumor neovascularization and promote invasion with yet to be defined mechanisms. In this review, we provide evidence for the role of CSCs in tumor vascularization and discuss the potential mechanisms and therapeutic significance based on the interaction between CSCs and their vascular niches. PMID: 21189116 [PubMed - as supplied by publisher] (Source: Current Molecular Medicin... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4324882 Tue, 28 Dec 2010 00:00:00 +0100 4324882 http://www.medworm.com/index.php?rid=4324881&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21189117%26dopt%3DAbstract Authors: Yaakob N, Malone DT, Exintaris B, Irving HR The serotonin 3 (5-HT(3)) receptor is a ligand gated ion channel unlike the other 5-HT receptors which are G protein coupled receptors. The functional 5-HT(3) receptor forms a pentamer of five symmetrically arranged subunits surrounding a central pore. The 5-HT(3A) subunit was first identified at a molecular level and can form functional homomers or heteromers with the 5-HT(3B) subunit. Recently, three new 5-HT(3) subunits have been discovered and these can also form functional heteromers with the 5-HT(3A) subunit. In addition, splice variants of the 5-HT(3) subunits have also been reported. These findings have markedly increased the complexity of the 5-HT(3) receptor and may form part of the explanation of unresolved differences bet... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4324881 Tue, 28 Dec 2010 00:00:00 +0100 4324881 http://www.medworm.com/index.php?rid=4324880&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21189118%26dopt%3DAbstract Authors: Katsuno M, Adachi H, Banno H, Suzuki K, Tanaka F, Sobue G Transforming growth factor β (TGF-β), a pleiotropic cytokine, regulates a diverse range of cellular responses, such as proliferation, differentiation, migration, and apoptosis. The TGF-β1, -β2, and -β3 isoforms are expressed by neurons and glial cells, and their receptors are expressed throughout the central nervous system. Several lines of evidence demonstrate that TGF-β signaling protects neurons from glutamate-mediated excitotoxicity, a putative mechanism underlying the pathogenesis of various neurodegenerative disorders such as amyotrophic lateral sclerosis (ALS). Recent studies indicate that the TGF-β-Smad2/3 pathway restores motor function in a mouse model of ALS, and that disruption of TGF-β signaling due... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4324880 Tue, 28 Dec 2010 00:00:00 +0100 4324880 http://www.medworm.com/index.php?rid=4324879&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21189119%26dopt%3DAbstract Authors: Hellwig CT, Passante E, Rehm M The regulation of apoptotic cell death, a terminal and fatal cell fate decision, has been intensely investigated and, due to its paramount implications for human health and disease, has sparked one of the most prolific and competitive research fields in biological and biomedical sciences of the past decades. Many key components of the molecular machinery processing and transducing apoptotic cell death signals have been described in great detail by now, dramatically advancing our understanding of how the network of apoptosis signaling proteins integrates and regulates cell death signals, and ultimately executes apoptosis. Building on the latest significant advances in deciphering apoptosis signal transduction as well as on the central original gro... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4324879 Tue, 28 Dec 2010 00:00:00 +0100 4324879 http://www.medworm.com/index.php?rid=4324878&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21189120%26dopt%3DAbstract Authors: Caruso R, Stolfi C, De Nitto D, Pallone F, Monteleone G Interleukin-25 (IL-25) plays a key role in the initiation and expansion of T helper (Th) 2 cell-mediated immune responses, thereby contributing to allergic diseases and host defense against helminthic parasites. More recent studies have however shown that IL-25 can also control the function of non-T cells, such as antigen presenting cells and endothelial cells, and reduces Th1/Th17-mediated pathologies. These new and exciting observations reveal a broader role for IL-25 than previously anticipated, and delineate various scenarios where therapeutic interventions around IL-25 activity can be imagined. PMID: 21189120 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4324878 Tue, 28 Dec 2010 00:00:00 +0100 4324878 http://www.medworm.com/index.php?rid=4324877&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21189121%26dopt%3DAbstract Authors: Szefel J, Piotrowska M, Kruszewski WJ, Jankun J, Lysiak-Szydłowska W, Skrzypczak-Jankun E Eicosanoids, which originate from polyunsaturated fatty acids (PUFAs), have a major impact on homeostasis maintenance as secondary signal transducers. Signal cascade, which includes reception, processing and signal transduction coming from the environment into the cell, determines the type of response evoked. Signal distortion may take place on every level of this cascade and this in consequence could lead to the development of many diseases. Any intervention into PUFAs metabolism leads to quantitative and qualitative changes of synthesized eicosanoids. Some of them promote, whereas others inhibit carcinogenesis, some are pro- or anti-inflammatory and the overall result depends on the ou... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4324877 Tue, 28 Dec 2010 00:00:00 +0100 4324877 http://www.medworm.com/index.php?rid=4324876&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21189122%26dopt%3DAbstract Authors: Vidal R, Caballero B, Couve A, Hetz C A variety of neurological diseases including Huntington's disease (HD), Alzheimer's disease and Parkinson's disease share common neuropathology, primarily featuring the presence of abnormal protein inclusions containing specific misfolded proteins. Mutations leading to expansion of a poly-glutamine track in Huntingtin cause HD, and trigger its misfolding and aggregation. Recent evidence indicates that alterations in the secretory pathway, in particular the endoplasmic reticulum (ER), are emerging features of HD. Although it is not clear how cytoplasmic/nuclear located mutant Huntingtin alters the function of the ER, several reports indicate that mutant Huntingtin affects many essential processes related to the secretory pathway, including ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4324876 Tue, 28 Dec 2010 00:00:00 +0100 4324876 http://www.medworm.com/index.php?rid=4272962&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21143103%26dopt%3DAbstract Authors: Li DW PMID: 21143103 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4272962 Wed, 01 Dec 2010 00:00:00 +0100 4272962 http://www.medworm.com/index.php?rid=4215859&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21091420%26dopt%3DAbstract Authors: Zhang L, Yan Q, Liu JP, Zou LJ, Liu J, Sun S, Deng M, Gong L, Ji WK, Li DW The ocular lens is a non-vascular and non-innervated transparent organ that plays an important role in vision processing. This unique organ is derived from the embryonic ectoderm of the brain region through a complicated differentiation process in which apoptosis plays a key role. First, when the committed ectoderm becomes thickened and invaginated, the defined number of cells required to form the lens vesicle is partially determined by apoptosis. Second, separation of lens vesicle from the above corneal ectoderm is executed through apoptosis of the lens stalk cells. Finally, differentiation of the lens epithelial cells is controlled by the regulators, most of which are involved in control of apoptosis ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4215859 Tue, 23 Nov 2010 00:00:00 +0100 4215859 http://www.medworm.com/index.php?rid=4215858&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21091421%26dopt%3DAbstract Authors: Jiang JX In the last decade or so, increasing evidences suggest that the mutations of two connexin genes, GJA3 and GJA8, are directly linked to human congenital cataracts in North and Central America, Europe and Asia. GIA3 and GIA8 genes encode gap junction-forming proteins, connexin (Cx) 46 and Cx50, respectively. These two connexins are predominantly expressed in lens fiber cells. Majority of identified mutations are missense, and the mutated sites are scattered across various domains of connexin molecules. Genetic deletion of either of these two genes leads to the development of cataracts; however, the types of cataracts developed are distinctive. More interestingly, microphthalmia is only developed in Cx50, but not Cx46 deficient mice, suggesting the unique role of Cx50 in... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4215858 Tue, 23 Nov 2010 00:00:00 +0100 4215858 http://www.medworm.com/index.php?rid=4215857&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21091422%26dopt%3DAbstract Authors: Tseng SC, Chen SY, Shen YC, Chen WL, Hu FR The stem cells (SCs) of the corneal epithelium located in the limbal basal layer are the ultimate source to maintain corneal epithelial homeostasis. Like other adult tissue-specfic SCs, self renewal and fate decision of limbal SCs are regulated by a specialized in vivo microenvironment, termed "niche". Loss of limbal SCs or dysfunction of the limbal niche renders corneas with a unique clinical disease labeled limbal stem cell deficiency (LSCD). Besides transplantation of autologous or allogeneic limbal SCs or amniotic membrane, a new strategy of treating LSCD is to transplant a bio-engineered graft by expanding limbal SCs ex vivo. Herein, we conduct a critical appraisal of six protocols that have successfully been practiced in treatin... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4215857 Tue, 23 Nov 2010 00:00:00 +0100 4215857 http://www.medworm.com/index.php?rid=4215856&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21091423%26dopt%3DAbstract Authors: Toris CB Glaucoma is a group of progressive optic neuropathies in which the axons in the optic nerve are injured, retinal ganglion cell numbers are reduced and vision is gradually and permanently lost. The only approved and effective way to treat glaucoma is to reduce the intraocular pressure (IOP). This is usually accomplished by surgical and/or pharmacological means. Drugs designed to reduce IOP target one or more of the parameters that maintain it. These parameters (collectively known as aqueous humor dynamics) are the production rate of aqueous humor, the pressure in the episcleral veins and the drainage of aqueous humor through the trabecular or uveoscleral outflow pathways. Intraocular pressure lowering drugs can be classified as inflow or outflow depending on whether th... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4215856 Tue, 23 Nov 2010 00:00:00 +0100 4215856 http://www.medworm.com/index.php?rid=4215852&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21091424%26dopt%3DAbstract Authors: Sparrrow JR, Hicks D, Hamel CP Retinal pigment epithelial cells (RPE) constitute a simple layer of cuboidal cells that are strategically situated behind the photoreceptor (PR) cells. The inconspicuousness of this monolayer contrasts sharply with its importance [1]. The relationship between the RPE and PR cells is crucial to sight; this is evident from basic and clinical studies demonstrating that primary dysfunctioning of the RPE can result in visual cell death and blindness. RPE cells carry out many functions including the conversion and storage of retinoid, the phagocytosis of shed PR outer segment membrane, the absorption of scattered light, ion and fluid transport and RPE-PR apposition. The magnitude of the demands imposed on this single layer of cells in order to execute ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4215852 Tue, 23 Nov 2010 00:00:00 +0100 4215852 http://www.medworm.com/index.php?rid=4215850&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21091425%26dopt%3DAbstract Authors: Gong L, Li DW SUMOylation, a posttranslational modification process in which SUMO, the small ubiquitin-related modifier or small ubiquitin-like modifier, is added to the target proteins, plays an important role in regulating a variety of cellular processes including protein-protein interactions, subcellular localization, protein-DNA interactions and enzyme activity. This process adds another layer of control in eukaryote gene expression, and it regulates both transcriptional activation and repression. In the present review, we summarized the currently emerging information regarding the function of SUMOylation in ocular development and pathology. PMID: 21091425 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4215850 Tue, 23 Nov 2010 00:00:00 +0100 4215850 http://www.medworm.com/index.php?rid=4215849&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D21091426%26dopt%3DAbstract Authors: Arrigo AP, Simon S Heat shock proteins (Hsps) are expressed in mammalian embryonic, adult and aging lens, cornea and retina. These proteins, particularly those belonging to the family of small Hsps, such as αA-crystallin (HspB4) and αB-crystallin (HspB5), play important roles in the differentiation of lens cells and are essential for the maintenance and protection of the supraorganization of proteins in differentiated corneal and lens fiber cells. Hsps are molecular chaperones characterized by their protective activity against different types of stress. They also have anti-apoptotic and anti-oxidant functions that help lens and corneal cells to better cope with the oxidative conditions that result from light induced injuries. They are also effective to protect the retina aga... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4215849 Tue, 23 Nov 2010 00:00:00 +0100 4215849 http://www.medworm.com/index.php?rid=4061329&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20937019%26dopt%3DAbstract Authors: Micaroni M The molecular mechanism of membrane fusion essential to vital cellular activities such as intracellular transport, hormone secretion, enzyme release, or neurotransmission, involve the assembly and disassembly of a specialized set of proteins in opposing bilayers. Recent evidences shed new light on the role Ca(2+) has in the regulation of this mechanism in which the Golgi apparatus works as a central station; from here, Ca(2+) ions are released into and recovered from the cytosol during the different steps of the cargo progression. In fact, transient cytosolic Ca(2+) fluctuations take a crucial role to recruit proteins and enzymes Ca(2+)-sensitive on Golgi membranes where they are involved in membranes remodelling which is fundamental process for the fusion events th... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4061329 Wed, 13 Oct 2010 12:15:28 +0100 4061329 http://www.medworm.com/index.php?rid=4061328&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20937020%26dopt%3DAbstract Authors: Chakraborty C, Shah KD, Cao WG, Hsu CH, Wen ZH, Lin CS Induced pluripotent stem (iPS) cell research has been growing a new height throughout the world due to its potentialities in medical applications. We can explore several therapeutic applications through the iPS cell research. In this review, we have first discussed the development of iPS cells, reprogramming factors, and effectiveness of iPS cells. Then we have emphasized the potential applications of iPS cells in pharmaceutical and medical sectors, such as, study of cellular mechanisms for spectrum of disease entities, disease-specific iPS cell lines for drugs discovery and development, toxicological studies of drugs development, personalized medicine, and regenerative medicine. PMID: 20937020 [PubMed - as supplied by... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4061328 Wed, 13 Oct 2010 12:15:25 +0100 4061328 http://www.medworm.com/index.php?rid=4061327&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20937021%26dopt%3DAbstract Authors: Cabarcas SM, Hurt EM, Farrar WL The metabolic syndrome is characterized by a state of metabolic dysfunction resulting in the development of several chronic diseases that are potentially deadly. These metabolic deregulations are complex and intertwined and it has been observed that many of the mechanisms and pathways responsible for diseases characterizing the metabolic syndrome such as type 2 diabetes and cardiovascular disease are linked with cancer development as well. Identification of molecular pathways common to these diverse diseases may prove to be a critical factor in disease prevention and development of potential targets for therapeutic treatments. This review focuses on several molecular pathways, including AMPK, PPARs and FASN that interconnect cancer development, ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4061327 Wed, 13 Oct 2010 12:15:22 +0100 4061327 http://www.medworm.com/index.php?rid=4061326&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20937022%26dopt%3DAbstract Authors: Collini P, Noursadeghi M, Sabroe I, Miller RF, Dockrell DH HIV-1 can establish both long lived and productive infection of macrophages (Mϕ) but circulating monocytes are less permissive to infection. Multiple studies have identified extensive changes to monocyte and Mϕ phenotype, differentiation or function. These include alterations in Toll-like receptor signaling and resultant changes to cytokine responses, specific defects in phagocytosis and microbial killing and modulation of apoptotic responses, all of which may perturb the important role of these cells in innate immunity. Interpretation of contradictory data however, is complicated by the use of different experimental models and many of the reported effects may be an indirect consequence of HIV 1 infection that result... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4061326 Wed, 13 Oct 2010 12:15:19 +0100 4061326 http://www.medworm.com/index.php?rid=4061325&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20937023%26dopt%3DAbstract Authors: Meraviglia S, Caccamo N, Guggino G, Tolomeo M, Siragusa S, Stassi G, Dieli F Monoclonal antibodies (mAbs) constitute the most rapidly growing class of human therapeutics and the second largest class of drugs after vaccines. The treatment of B-cell malignancies and HER2/Neu(+) breast cancer has benefited considerably from the use of therapeutic mAbs, either alone or in combination with standard chemotherapy. Frequent relapses, however, demonstrate that the bioactivity of these mAbs is still suboptimal. The concept of improving the anti-tumor activity of mAbs is well established and potentiating the cytotoxicity induced by anticancer mAbs can be achieved by strategies that target the downstream cytolytic effector cells. The recruitment of Fcγ receptor-dependent functions appear... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4061325 Wed, 13 Oct 2010 12:15:15 +0100 4061325 http://www.medworm.com/index.php?rid=4061324&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20937024%26dopt%3DAbstract In conclusion, new chemopreventive compounds which are effective in animal models are likely to be tested soon in clinical trials, with the final goal of reducing prostate cancer incidence in men. PMID: 20937024 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4061324 Wed, 13 Oct 2010 12:15:12 +0100 4061324 http://www.medworm.com/index.php?rid=4061323&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20937025%26dopt%3DAbstract Authors: Santos-Rebouças CB, Pimentel MM MicroRNAS (miRNAs) are a class of endogenously single-stranded non-coding RNA molecules that can negatively modulate the expression of target messenger RNAs by 3' UTR base pairing. During the processing of a miRNA, a network of orchestrated molecular events provides a dynamic manner to posttranscriptionally modulate gene expression. Recent research has demonstrated that although these molecules are small, they are involved in several crucial biological functions, as well as, in a broad spectrum of human diseases. In this review, we highlighted the current knowledge on the miRNA pathway field, focusing on how the disruption of the miRNA-mediated silencing pathways could lead to the pathogenesis of neurological disorders. The potential use of miR... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=4061323 Wed, 13 Oct 2010 12:15:09 +0100 4061323 http://www.medworm.com/index.php?rid=3882156&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20712585%26dopt%3DAbstract Authors: Vazquez-Martin A, Oliveras-Ferraros C, Cufí S, Martin-Castillo B, Menendez JA A whole new area of investigation has emerged recently with regards to the anti-diabetic drug metformin and breast cancer. Metformin's anti-breast cancer actions, observed in population studies, in rodents and in cultured tumour cells, are especially encouraging because they attack not only the most common bulk of the tumour cells but also the more rare tumour-initiating stem cells. Here, we illustrate the multifaceted and redundant mechanisms through which metformin-reprogrammed energy metabolism at both the organismal and cellular levels constitutes a novel and valuable strategy to prevent and treat breast cancer disease. PMID: 20712585 [PubMed - as supplied by publisher] (Source: Current Mo... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3882156 Sun, 15 Aug 2010 23:00:00 +0100 3882156 http://www.medworm.com/index.php?rid=3882155&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20712586%26dopt%3DAbstract Authors: Pot I, Ikeuchi Y, Bonni A, Bonni S The transcriptional regulator SnoN has been the subject of growing interest due to its diverse functions in normal and pathological settings. A large body of evidence has established a fundamental role for SnoN as a modulator of signaling and responses by the transforming growth beta (TGFb) family of cytokines, though how SnoN regulates TGFb responses remains incompletely understood. In accordance with the critical and complex roles of TGFb in tumorigenesis and metastasis, SnoN may act as a tumor promoter or suppressor depending on the stage and type of cancer. Beyond its role in cancer, SnoN has also been implicated in the control of axon morphogenesis in postmitotic neurons in the mammalian brain. Remarkably, signaling pathways that control... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3882155 Sun, 15 Aug 2010 23:00:00 +0100 3882155 http://www.medworm.com/index.php?rid=3882154&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20712587%26dopt%3DAbstract Authors: Patterson AJ, Zhang L Fetal hearts show a remarkable ability to develop under hypoxic conditions. The metabolic flexibility of fetal hearts allows sustained development under low oxygen conditions. In fact, hypoxia is critical for proper myocardial formation. Particularly, hypoxia inducible factor 1 (HIF-1) and vascular endothelial growth factor play central roles in hypoxia-dependent signaling in fetal heart formation, impacting embryonic outflow track remodeling and coronary vessel growth. Although HIF is not the only gene involved in adaptation to hypoxia, its role places it as a central figure in orchestrating events needed for adaptation to hypoxic stress. Although "normal" hypoxia (lower oxygen tension in the fetus as compared with the adult) is essential in heart format... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3882154 Sun, 15 Aug 2010 23:00:00 +0100 3882154 http://www.medworm.com/index.php?rid=3882153&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20712588%26dopt%3DAbstract Authors: Seigneuric R, Markey L, Nuyten DS, Dubernet C, Evelo CT, Finot E, Garrido C Scientific advances have significantly improved the practice of medicine by providing objective and quantitative means for exploring the human body and disease states. These innovative technologies have already profoundly improved disease detection, imaging, treatment and patient follow-up. Today's analytical limits are at the nanoscale level (one-billionth of a meter) enabling a detailed exploration at the level of DNA, RNA, proteins and metabolites which are in fact nano-objects. This translational review aims at integrating some recent advances from micro- and nano-technologies with high potential for improving daily oncology practice. PMID: 20712588 [PubMed - as supplied by publisher] (Source: ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3882153 Sun, 15 Aug 2010 23:00:00 +0100 3882153 http://www.medworm.com/index.php?rid=3882152&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20712589%26dopt%3DAbstract Authors: Aziz K, Nowsheen S, Georgakilas AG Cancer therapy has been changing over the decades as we move away from the administration of broad spectrum cytotoxic drugs and towards the use of therapy targeted for each tumor type. After the induction of DNA damage through chemotherapeutic agents, tumor cells can survive due to their proficient DNA repair pathways, some of which are dysregulated in cancer. Latest improvements in nanotechnology and drug discovery has led to the discovery of some very unique, highly specific and innovative drugs as inhibitors of various DNA repair pathways like base excision repair and double strand break repair. In this review we look at the efficacy and potency of these small chemical molecules to target the processing of DNA damage induced by standard th... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3882152 Sun, 15 Aug 2010 23:00:00 +0100 3882152 http://www.medworm.com/index.php?rid=3882151&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20712590%26dopt%3DAbstract Authors: Torino F, Paragliola RM, Barnabei A, Corsello SM In recent years, the clinical validation of molecular targeted therapies inhibiting the action of pathogenic tyrosine kinase (TK) has been one of the most exciting developments in cancer research. In this context, medullary thyroid carcinoma (MTC) represents a promising model. It is well known that in MTC, the RET receptor TK and its signal transduction pathways, lead to subsequent neoplastic transformation. Several strategies aimed at blocking the activation and signaling of RET have been preclinically tested. The most advanced results have been obtained by competitive inhibition of RET-TK activity by tyrosine kinases inhibitors (TKI). However, although the inhibition of the RET pathway is actually one of the most studied for t... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3882151 Sun, 15 Aug 2010 23:00:00 +0100 3882151 http://www.medworm.com/index.php?rid=3777130&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20642437%26dopt%3DAbstract In conclusion, the recent advances in mRNA and microRNA profiling and the identification of gene expression-based PD biomarkers may aid investigators to drive drug development through the establishment of quantitative PD effects. PMID: 20642437 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3777130 Mon, 19 Jul 2010 23:00:00 +0100 3777130 http://www.medworm.com/index.php?rid=3777129&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20642438%26dopt%3DAbstract Authors: Fiorucci S, Cipriani S, Mencarelli A, Renga B, Distrutti E, Baldelli F In addition to their role in dietary lipid absorption bile acids are signaling modules activating nuclear receptors and at least one G-protein coupled receptors named the TGR5. With a different rank of potency primary and secondary bile acids activates a subset of nuclear receptors including the farnesoid-X-receptor (FXR, NR1H4); the constitutive androstane receptor (CAR, NR1H3), the pregnane-x- receptor (PXR, NR1H2), the vitamin D receptor (VDR, NR1H1). Originally, these receptors were characterized for their role as bile acid and xenobiotic sensors, emerging evidence, however, indicates that FXR, PXR and VDR and their ligands are important for the modulation of immune and inflammatory reactions in entero-... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3777129 Mon, 19 Jul 2010 23:00:00 +0100 3777129 http://www.medworm.com/index.php?rid=3777128&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20642439%26dopt%3DAbstract Authors: Tandon A, Tovey JC, Sharma A, Gupta And R Transforming growth factor-beta (TGFbeta) is a pleiotropic multifunctional cytokine that regulates several essential cellular processes in many parts of the body including the cornea. Three isoforms of TGFbeta are known in mammals and the human cornea expresses all of them. TGFbeta1 has been shown to play a central role in scar formation in adult corneas whereas TGFbeta2 and TGFbeta3 have been implicated to play a critical role in corneal development and scarless wound healing during embryogenesis. The biological effects of TGFbeta in the cornea have been shown to follow SMAD dependent as well as SMAD-independent signaling pathways depending upon cellular responses and microenvironment. Corneal TGFbeta expression is necessary for maint... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3777128 Mon, 19 Jul 2010 23:00:00 +0100 3777128 http://www.medworm.com/index.php?rid=3777127&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20642440%26dopt%3DAbstract Authors: Schönhofer-Merl S, Wessely R Enteroviruses are common human pathogens involved in a wide spectrum of clinical outcomes ranging from mild or non-symptomatic illness to severe diseases with neurological and/or cardiac manifestation. Despite being responsible for significant morbidity and mortality especially in immunocompromised patients and infants, to date no effective vaccines or specific antiviral treatment modalities are available to prevent or treat non-polio enteroviral infections. The discovery of the endogenous RNA interference pathway as an innate defence mechanism conferring intracellular immunity against foreign genetic elements has provided exciting possibilities in the fight against so far intractable, enteroviral diseases. We and others have shown the encouragi... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3777127 Mon, 19 Jul 2010 23:00:00 +0100 3777127 http://www.medworm.com/index.php?rid=3777126&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20642441%26dopt%3DAbstract Authors: Yadav UC, Srivastava SK, Ramana KV Aldose reductase, although identified initially as a glucose-reducing enzyme via polyol pathway, is believed to be an important component of antioxidant defense system as well as a key mediator of oxidative stress-induced molecular signaling. The dual role played by AR has made it a very important enzyme for the regulation of not only the cellular redox state by detoxifying the reactive lipid-aldehydes generated by lipid peroxidation which is crucial in the cellular homeostasis, but also in the regulation of molecular signaling cascade that may regulate oxidative stress-induced cytotoxic events. Search for the new molecular targets to restrain the oxidative stress-induced inflammation has resulted in the identification of AR as an unanticipat... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3777126 Mon, 19 Jul 2010 23:00:00 +0100 3777126 http://www.medworm.com/index.php?rid=3777125&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20642442%26dopt%3DAbstract Authors: Probst-Kepper M, Balling R, Buer J FOXP3 is essential for the development and function of regulatory CD4(+)CD25(hi) T (T(reg)) cells. However, recent evidence suggests that FOXP3 alone is not sufficient to completely explain the regulatory phenotype of these key players in autoimmunity and inflammation: after being activated, conventional human CD4(+) T cells transiently up-regulate FOXP3 without acquiring a regulatory function. Researchers have recently found that glycoprotein A repetitions predominant (GARP, or LRRC32) is a T(reg)-specific receptor that binds latent TGF-beta and dominantly controls FOXP3 and the regulatory phenotype via a positive feedback loop. This finding provides a missing link in our molecular understanding of FOXP3 in T(reg) cells. This viewpoint focus... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3777125 Mon, 19 Jul 2010 23:00:00 +0100 3777125 http://www.medworm.com/index.php?rid=3777124&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20642443%26dopt%3DAbstract Authors: Magni P, Dozio E, Galliera E, Ruscica M, Corsi MM Adipose tissue is an endocrine organ able to produce a wide series of pleiotropic molecules, defined "adipokines". In addition to the regulation of food intake and energy metabolism, adipokines are also implicated in the complex control of bone biology and specifically of bone remodeling. Leptin, the most studied adipokine, promotes satiety and energy expenditure and its circulating levels are proportional to fat mass. Some paradoxical findings originally suggested the involvement of leptin in controlling bone mass. For example, obese postmenopausal women, with elevated circulating leptin and leptin resistance, appear protected against the development of osteoporosis. Moreover, genetically leptin-deficient mice, which are hypog... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3777124 Mon, 19 Jul 2010 23:00:00 +0100 3777124 http://www.medworm.com/index.php?rid=3673082&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20540701%26dopt%3DAbstract Authors: Montoya-Durango DE, Ramos KS Long interspersed nuclear elements (LINEs) are mobile sequences shown to play a fundamental role in eukaryotic genome evolution. Recently, increasing interest has been directed at unveiling molecular mechanisms by which LINE-1 (L1), a ubiquitous member of this family, regulates gene expression and mammalian cell development, differentiation, and cancer. This mini review summarizes recent studies conducted to examine stress-induced L1 reactivation, with special attention given to the role of E2F/Rb transcription factors in epigenetic silencing of L1 and its potential role as a global modifier of chromatin structure and function. The last section focuses on the impact of histone deacetylase inhibitors in the regulation of gene function, chromatin str... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3673082 Sun, 13 Jun 2010 23:00:00 +0100 3673082 http://www.medworm.com/index.php?rid=3673081&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20540702%26dopt%3DAbstract Authors: Nagpal JK, Rani R, Trink B, Saini KS The discovery of miRNAs and the establishment of it's clinical links with multiple diseases has led to a paradigm shift in the drug development pipeline of major pharmaceutical companies and has given birth to several biotechnology enterprises revolving around these magic molecules. The miRNA profiling studies over the last few years have indicated implicit involvement of miRNAs in the pathobiology of cancer, diabetes, infectious diseases as well as cardiovascular, neurological and immune system disorders. This information is currently being translated into tools for diagnosis, prognosis and predicting response to treatment. In addition, active and vigorous investigations are ongoing in several laboratories across academia and industry to d... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3673081 Sun, 13 Jun 2010 23:00:00 +0100 3673081 http://www.medworm.com/index.php?rid=3673080&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20540703%26dopt%3DAbstract Authors: Brest P, Corcelle EA, Cesaro A, Chargui A, Belaïd A, Klionsky DJ, Vouret-Craviari V, Hebuterne X, Hofman P, Mograbi B Inflammatory bowel diseases (IBD) are common inflammatory disorders of the gastrointestinal tract that include ulcerative colitis (UC) and Crohn's disease (CD). The incidences of IBD are high in North America and Europe, affecting as many as one in 500 people. These diseases are associated with high morbidity and mortality. Colorectal cancer risk is also increased in IBD, correlating with inflammation severity and duration. IBD are now recognized as complex multigenetic disorders involving at least 32 different risk loci. In 2007, two different autophagy-related genes, ATG16L1 (autophagy-related gene 16-like 1) and IRGM (immunity-related GTPase M) were shown... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3673080 Sun, 13 Jun 2010 23:00:00 +0100 3673080 http://www.medworm.com/index.php?rid=3673079&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20540704%26dopt%3DAbstract Authors: Marin JJ, Castaño B, Blazquez AG, Rosales R, Efferth T, Monte MJ When considered together, enterohepatic tumours, i.e., those affecting the liver, the biliary tree and gallbladder and the intestine, constitute the first cause of death due to cancer. Although in many cases surgery and radiotherapy are efficacious, these therapeutic strategies cannot always be implemented. Moreover, even when the removal of tumours is possible, pre- and post-operative pharmacological adjuvant regimens are often needed. However, one important limitation to the use of cytostatic drugs to treat enterohepatic tumours is that they generally exhibit marked refractivity to currently available pharmacological approaches. In addition, most of them increase their chemoresistance during treatment. In vi... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3673079 Sun, 13 Jun 2010 23:00:00 +0100 3673079 http://www.medworm.com/index.php?rid=3673078&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20540705%26dopt%3DAbstract Authors: Zeidan YH, Hannun YA One of the most intriguing enzymes of sphingolipid biology is acid sphingomyelinase (ASMase). In a phospholipase C reaction, ASMase catalyzes the cleavage of the phosphocholine head group of sphingomyelin to generate ceramide. Cumulative efforts of various laboratories over the past 40 years have placed ASMase and its product ceramide at the forefront of lipid research. Activation of the ASMase/ceramide pathway is a shared response to an ever-growing list of receptor and non-receptor mediated forms of cellular stress including: death ligands (TNFalpha, TRAIL, Fas ligand), cytokines (IL-1, IFNgamma), radiation, pathogenic infections, cytotoxic agents and others. The strategic role of ASMase in lipid metabolism and cellular stress response has sparked intere... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3673078 Sun, 13 Jun 2010 23:00:00 +0100 3673078 http://www.medworm.com/index.php?rid=3673077&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20540706%26dopt%3DAbstract Authors: Georgiou KR, Foster BK, Xian CJ The bone marrow microenvironment houses haematopoietic stem cells (HSC), mesenchymal stem cells (MSC) and their progeny, supports haematopoiesis, osteogenesis, osteoclastogenesis, and adipogenesis. It plays a key role in maintaining homeostatic production of erythroid, myeloid or lymphoid cells, appropriate bone mass and bone health throughout life. Through cell-cell adhesion and chemotactic axes, a reciprocal inter-dependent relationship exists between these two cell lineages. Following chemotherapy-induced myelosuppression observed in cancer patients, HSCs are induced to enter into the cell cycle in order to re-establish the damaged microenvironment. These cells not only have the capacity to mobilize to the peripheral blood, but the ability to... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3673077 Sun, 13 Jun 2010 23:00:00 +0100 3673077 http://www.medworm.com/index.php?rid=3580650&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20477748%26dopt%3DAbstract Authors: Zaenker KS PMID: 20477748 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3580650 Thu, 20 May 2010 14:45:06 +0100 3580650 http://www.medworm.com/index.php?rid=3564441&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20459375%26dopt%3DAbstract Authors: Savaraj N, You M, Wu C, Wangpaichitr M, Kuo MT, Feun LG The majority of melanoma cells do not express argininosuccinate synthetase(ASS), and hence cannot synthesize arginine from citrulline. Their growth and proliferation depend on exogenous supply of arginine. Arginine degradation using arginine deiminase (ADI) leads to growth inhibition and eventually cell death while normal cell which express ASS can survive. This notion has been translated into clinical trial. Pegylated ADI (ADI-PEG20) has shown antitumor activity in melanoma. . However, the sensitivity to ADI is different among ASS(-) melanoma cells. We have investigated and reviewed the signaling pathways which are affected by arginine deprivation and their consequences which lead to cell death. We have found that argini... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3564441 Mon, 10 May 2010 23:00:00 +0100 3564441 http://www.medworm.com/index.php?rid=3556537&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455850%26dopt%3DAbstract Authors: Matthes H, Friedel WE, Bock PR, Zänker KS Mistletoe is often used as complementary therapy in oncology. The anti-tumor effects of mistletoe (Iscador(R)) are well documented in-vitro in respect to inhibition of cell proliferation, induction of apoptosis, segmental activation of immune competent cells and trapping of chemotherapeutic drugs within cancer cells by modulating the inhibitory potential of P-glycoprotein (P-gp)-mediated transport of cell toxifying substances (cytotoxic drugs). However, the clinical activity of mistletoe treatment remains still controversial. Implementation of mistletoe therapy as supportive care into anti-cancer programs should be based on the best evidence and must continually be evaluated to ensure safety, effficacy, collection of new data, and c... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3556537 Mon, 10 May 2010 23:00:00 +0100 3556537 http://www.medworm.com/index.php?rid=3556536&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455851%26dopt%3DAbstract Authors: Sarasin A, Dessen P Melanoma causes a considerable public health burden because of its dramatic rise in incidence worldwide since the mid-1960s and because the metastatic disease remains incurable, has a short median survival and is characterized by resistance to almost all classes of cytotoxic agents. DNA repair pathways are multiple and are able to repair, usually in an error-free manner, all kinds of DNA damage induced by exogenous and endogenous genotoxic agents. This review describes the role of DNA repair process in protecting us from cancer and particularly nucleotide excision deficiencies that are associated with melanoma development. Resistance of tumoral cells to antitumoral regimen can be caused by overexpression of DNA repair processes. We showed that melanoma meta... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3556536 Mon, 10 May 2010 23:00:00 +0100 3556536 http://www.medworm.com/index.php?rid=3556535&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455852%26dopt%3DAbstract Authors: Thévenod F, Chakraborty PK Wnt/beta-catenin signaling plays a crucial role during embryogenesis. However, this signaling pathway also plays a role in normal adult tissues and in carcinogenesis, including cadmium (Cd2+) nephrocarcinogenesis, which is the topic of this review. Wnt/beta-catenin signaling is tightly regulated in mature epithelia to balance cell proliferation, differentiation and death. This is accomplished by modulating phosphorylation of the multifunctional protein beta-catenin which in turn determines its preference for a particular fate, i.e. cell-cell adhesion by binding to E-cadherin, proteasomal degradation, or co-activation of the transcription factor Tcf/Lef. The pivotal role of beta-catenin is not limited to Wnt signaling, but can be challenged by othe... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3556535 Mon, 10 May 2010 23:00:00 +0100 3556535 http://www.medworm.com/index.php?rid=3556534&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455853%26dopt%3DAbstract Authors: Voss MJ, Niggemann B, Zänker KS, Entschladen F Fast growing solid tumors generally lack an inner organisation, which causes the problem of a sufficient nutrient of each part of the tumor that then happens only by diffusion. The low oxygen supply leads to the activation of hypoxia-inducible factors, which regulate a plethora of genes. The reaction of tumor cells to hypoxia can be divided into two parts: On the one hand, there are signal substances, predominantly growth factors and cytokines, which provoke the vascularisation (angiogenesis), lymph vessel development (lymphangiogenesis), and the innervation (neoneurogenesis) of tumors and thus connect the tumor to structures of the environment. On the other hand, genes for intracellular proteins and receptors are regulated, wh... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3556534 Mon, 10 May 2010 23:00:00 +0100 3556534 http://www.medworm.com/index.php?rid=3556533&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455854%26dopt%3DAbstract Authors: Yang L Alterations in TGFbeta signaling are common in human cancers. TGFbeta has significant impact on tumor initiation and progression. Therapeutic strategies including neutralizing antibodies and small molecular inhibitors have been developed to target TGFbeta signaling. However, TGFbeta can work as both a tumor suppressor and a tumor promoter. A significant challenge to the development of successful TGFbeta antagonism treatment is understanding how and when TGFbeta switches its function from a tumor suppressor to a tumor promoter. Recent studies demonstrate that TGFbeta regulates the infiltration of inflammatory cells and cancer associated fibroblasts into the tumor microenvironment, resulting in changes in signaling cascade in tumor cells. Additionally, TGFbeta exerts syst... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3556533 Mon, 10 May 2010 23:00:00 +0100 3556533 http://www.medworm.com/index.php?rid=3556532&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455855%26dopt%3DAbstract Authors: Mantovani A Inflammatory conditions in selected organs increase the risk of cancer. An inflammatory component is present also in the microenvironment of tumours that are not epidemiologically related to inflammation. Compounds of the inflammatory tumor microenvironment include leukocytes, cytokines, complement components, and is orchestrated by transcription factors, such as NFkB and Stat3. Recent studies have begun to unravel molecular pathways linking inflammation and cancer. An intrinsic (driven by genetic events that cause neoplasia) and an extrinsic (driven by inflammatory conditions which predispose to cancer) pathway link inflammation and cancer. Smouldering inflammation in the tumour microenvironment promotes proliferation and survival of malignant cells, angiogenesis,... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3556532 Mon, 10 May 2010 23:00:00 +0100 3556532 http://www.medworm.com/index.php?rid=3556531&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455856%26dopt%3DAbstract This article will focus on the current progress in drug discovery using the miRNA strategy. PMID: 20455856 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3556531 Mon, 10 May 2010 23:00:00 +0100 3556531 http://www.medworm.com/index.php?rid=3556530&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455857%26dopt%3DAbstract Authors: Cicardi M, Zanichelli A Acquired deficiency of C1 inhibitor (C1-INH) with angioedema symptoms (acquired angioedema, AAE) is characterized by local increase in vascular permeability (agioedema) of the skin and the gastrointestinal and oro-pharyngo-laryngeal mucosa. The mediator of symptoms is bradykinin, a potent vasoactive peptide, released from high molecular weight kininogen when it is cleaved by plasma kallikrein a serine protease controlled by C1-INH. Autoantibodies inactivating C1-INH are detected in the majority of patients and account for the deficiency. Irrespectively to the presence of anti-C1-INH autoantibodies lymphoproliferative diseases, ranging from benign monoclonal gammopathies to malignant lymphoma, are frequently associated with AAE. Demonstration that monocl... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3556530 Mon, 10 May 2010 23:00:00 +0100 3556530 http://www.medworm.com/index.php?rid=3556529&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20455858%26dopt%3DAbstract Authors: Wang X, Wang Y, Yu L, Sakakura K, Visus C, Schwab JH, Ferrone CR, Favoino E, Koya Y, Campoli MR, McCarthy JB, Deleo AB, Ferrone S Chondroitin sulfate proteoglycan 4 (CSPG4), also known as High Molecular Weight- Melanoma Associated Antigen, is a cell surface proteoglycan which has been recently shown to be expressed not only by melanoma cells, but also by various types of human carcinoma and sarcoma. Furthermore, at least in squamous cell carcinoma of head and neck and in basal breast carcinoma, CSPG4 is expressed by cancer stem cells. CSPG4 plays an important role in tumor cell growth and survival. These CSPG4-associated functional properties of tumor cells are inhibited by CSPG4-specific monoclonal antibodies (mAb) in vitro. Moreover, CSPG4-specific mAb can also inhibit tumor... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3556529 Mon, 10 May 2010 23:00:00 +0100 3556529 http://www.medworm.com/index.php?rid=3457006&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20374193%26dopt%3DAbstract Authors: Sho-Ichi Y PMID: 20374193 [PubMed - in process] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3457006 Wed, 31 Mar 2010 23:00:00 +0100 3457006 http://www.medworm.com/index.php?rid=3408829&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20331433%26dopt%3DAbstract Authors: Pradel G, Schlitzer M The impact of selected antibiotics on combating malaria infections was discovered in the mid of last century. Only recently, studies on their modes of action in malaria parasites have been initiated, prompted by the discovery of a prokaryotic organelle, the apicoplast. This plastid-derived structure, which originates from a secondary endosymbiotic event, possesses important metabolic as well as housekeeping functions, including fatty acid and heme biosynthesis. Due to its indispensability for parasite survival it represents a promising target for the use of antibiotics in malaria therapy. Most antibiotics cause a delayed death phenotype, which manifests in the late onset of antimalarial activity during the second replication cycle of the pathogen. This re... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3408829 Wed, 24 Mar 2010 00:00:00 +0100 3408829 http://www.medworm.com/index.php?rid=3408828&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20334625%26dopt%3DAbstract Authors: Erol A Damaged DNA can lead to aneuploidy and/or chromosomal instability, which is believed to be major contributor to tumor progression. DNA damage in response to genotoxic and oncogenic stresses activate the tumor suppressor pathways initiating DNA damage response (DDR). One of the cellular fates in response to DDR is permanent growth arrest in mitotically active cells, including stem cells, leading to senescence. On the other hand, DDR reasons in adaptive changes in postmitotic cells. These cellular alterations happen through complex interactions and function to disrupt the existing cellular homeostasis. Significant metabolic changes occurred by the influence of the major tumor suppressor protein p53 and other related factors such as FOXO, AMPK, PARP, NF-kappaB and PGC-1 ar... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3408828 Wed, 24 Mar 2010 00:00:00 +0100 3408828 http://www.medworm.com/index.php?rid=3386104&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236050%26dopt%3DAbstract Authors: Fukami K, Yamagishi SI, Okuda S Pigment epithelium-derived factor (PEDF) is reported to play a protective role against diabetic vascular complications through its anti-oxidative properties. However, since a commercially available kit is not suitable for measurement of serum PEDF in humans, kinetics and regulation of serum PEDF are not known in these devastating disorders. Therefore, we developed a simple, specific and reliable method for measurement of serum PEDF in humans using a competitive enzyme-linked immunosorbent assay (ELISA) system. Assay linearity was shown intact with 50~300-fold dilution of urea-pretreated serum by phosphate-buffered saline. The recovery ratio of added recombinant human PEDF in serum was 94.2 +/- 1.7 %. Inter- and intra-assay coefficient of variati... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386104 Thu, 18 Mar 2010 00:00:00 +0100 3386104 http://www.medworm.com/index.php?rid=3386103&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236051%26dopt%3DAbstract Authors: Nakamura T, Yamagishi SI Septic shock is one of the leading causes of morbidity and mortality. Endotoxin plays an important role in the pathogenesis of septic shock. Lack of clinical success with anti-endotoxin or anti-cytokine therapies has shifted interest to extracorporeal therapies to reduce circulating levels of various mediators for septic shock patients. Polymyxin B -immobilized polystyrene fiber (PMX-F) is a medical device that aims to remove circulating endotoxin by adsorption. Since 1994, PMX-F column has been available in Japan, and many investigators have reported that PMX-F treatment is safe and effective in patients with septic shock. Pigment epithelium-derived factor (PEDF) is a glycoprotein that belongs to the superfamily of serine protease inhibitors. PEDF ind... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386103 Thu, 18 Mar 2010 00:00:00 +0100 3386103 http://www.medworm.com/index.php?rid=3386102&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236052%26dopt%3DAbstract Authors: Kawaguchi T, Yamagishi SI, Sata M Pigment epithelial-derived factor (PEDF) is a 50-kDa secreted glycoprotein that belongs to the noninhibitory serpin. It has an alpha/beta core serine-protease inhibitor domain, 3 major beta-sheets, and 10 alpha-helices. Although PEDF does not inhibit either serine or cysteine proteinases, PEDF exerts diverse physiological activities including anti-angiogenesis, anti-vasopermeability, anti-tumor, and neurotrophic activities. Recent studies have shown that a variety of peptides derived from PEDF possess activities similar to those of the parent molecule through interactions with the extracellular matrix, binding to PEDF receptors, nuclear localization and phosphorylation. Thus, peptides derived from PEDF have therapeutic potential for various di... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386102 Thu, 18 Mar 2010 00:00:00 +0100 3386102 http://www.medworm.com/index.php?rid=3386101&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236053%26dopt%3DAbstract Authors: Broadhead ML, Akiyama T, Choong PF, Dass CR First discovered in 1991 as a factor secreted by retinal pigment epithelial cells, the potency of pigment epithelium derived factor (PEDF) as an anti-angiogenic has led to examination of its role in active bone growth, repair and remodelling. In the musculoskeletal system, PEDF expression occurs particularly at sites of active bone formation. Expression has been noted in osteoblasts and to a lesser degree osteoclasts, the major classes of bone cells. In fact, PEDF is capable of inducing differentiation of precursor cells into mature osteoblasts. Expression and localisation are closely linked with that of vascular endothelial growth factor (VEGF). Studies at the epiphyseal plate have revealed that PEDF expression plays a key role in e... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386101 Thu, 18 Mar 2010 00:00:00 +0100 3386101 http://www.medworm.com/index.php?rid=3386100&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236054%26dopt%3DAbstract Authors: Hoshina D, Abe R, Yamagishi SI, Shimizu H Pigment epithelium-derived factor (PEDF), one of the non-inhibitory serpines, is widely expressed throughout the body. Although PEDF was initially identified as a neuronal differentiation factor, more attention has been paid to its anti-angiogenic activity. Additionally, recent researches have demonstrated that PEDF has an anti-tumor effect against several human neoplasms. This review focuses on the pathological role of PEDF in tumors, especially tumor growth and metastasis. PEDF is an endogenous anti-tumor factor and its clinical application seems quite promising, although there is much to be further investigated. PMID: 20236054 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386100 Thu, 18 Mar 2010 00:00:00 +0100 3386100 http://www.medworm.com/index.php?rid=3386099&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236055%26dopt%3DAbstract This article summarizes the pathophysiological role of PEDF in atherothrombosis and its potential therapeutic implication in CVD. We also discuss here the kinetics and regulation of PEDF in high-risk patients for atherothrombosis. PMID: 20236055 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386099 Thu, 18 Mar 2010 00:00:00 +0100 3386099 http://www.medworm.com/index.php?rid=3386098&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236056%26dopt%3DAbstract Authors: Ueda S, Yamagishi SI, Okuda S The vascular system has an important function of supplying tissues with oxygen and nutrients and clearing waste products. Therefore, the microvasculature must be sufficiently permeable to allow the free, bidirectional passage of small molecules and gases and, to a lesser extent, of plasma proteins. It is well recognized that vascular endothelial growth factor (VEGF) can increase vascular permeability, thus playing important roles in variety of disorders, including diabetic retinopathy, nephrotic syndrome, brain edema, acute respiratory distress syndrome, and sepsis-associated hypotension. However, how vascular permeability is controlled by anti-permeable factors is not fully understood. We have recently found that pigment epitheliumderived factor ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386098 Thu, 18 Mar 2010 00:00:00 +0100 3386098 http://www.medworm.com/index.php?rid=3386097&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236057%26dopt%3DAbstract Authors: Tombran-Tink J Most diseases that cause blindness do so as a result of neovascularization. Angiogenesis is a complex process regulated in adult tissues by a large interacting network of molecules. In pathological conditions the checks and balances of the angiogenesis system go awry and endothelial cells of the microvasculature, proliferate, migrate, and form new but leaky vessels that invade the tissue. Hemorrhaging vessels cause edema and damage to surrounding tissues, particularly the retina. Microvascular lesions often cause severe retinal detachment and loss of vision. In this review, the value of an important endogenous anti angiogenic molecule, PEDF, is discussed in relationship to its ability to prevent retinal cell death and counter the abnormal vessel growth induced b... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386097 Thu, 18 Mar 2010 00:00:00 +0100 3386097 http://www.medworm.com/index.php?rid=3386096&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20236058%26dopt%3DAbstract Authors: Yabe T, Sanagi T, Yamada H Neuronal degeneration is closely associated with cognitive, motor and visual dysfunctions. Neuroprotective strategies have been investigated with the view to being employed as potential therapy for patients with these disabilities. Pigment epithelium-derived factor (PEDF) is a 50-kDa secreted glycoprotein and a non-inhibitory member of the serine protease inhibitor (SERPIN) gene family. PEDF is detected in a broad range of human tissues, including almost all brain areas, and has been shown to have strong neuroprotective properties for various types of neurons including cerebellar granule neurons, hippocampal neurons, striatal neurons, retinal neurons and spinal cord motor neurons. These observations raise the possibility that application of PEDF may ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3386096 Thu, 18 Mar 2010 00:00:00 +0100 3386096 http://www.medworm.com/index.php?rid=3336092&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196723%26dopt%3DAbstract Tumor Markers: The Potential of "Omics" Approach. Curr Mol Med. 2010 Mar 3; Authors: Sikaroodi M, Galachiantz Y, Baranova A Tumor markers are the molecules that indicate the presence or prognosis of malignancy. Most often, tumor markers are produced by the cancer tissue itself. Many of them could be secreted into the body fluids in small quantities. Thus, tumor markers could be useful for early diagnostics of primary tumors and relapsed disease, as well as for determining tumor prognosis and predicting likely response of the tumor to therapy. Tumor markers are part of the clinical routine. Nevertheless, lack of sensitivity and specificity precludes routine usage of single tumor markers in population-based screening. Shortcomings of single tumor markers could be solved by parall... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336092 Wed, 03 Mar 2010 00:00:00 +0100 3336092 http://www.medworm.com/index.php?rid=3336091&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196724%26dopt%3DAbstract Authors: Claus RA, Bockmeyer CL, Sossdorf M, Lösche W Purpose: This review investigates and highlights the activity of Willebrand factor (VWF) and its cleaving protease as biomarkers of the development of multiple organ dysfunction in infectious and noninfectious systemic inflammatory response syndrome. State of the Art: Ultra-large VWF (ULVWF) multimers activate platelets resulting in a prothrombotic situation. Systemic inflammation is associated with increased ULVWF plasma level and a decreased ADAMTS13 activity. The potential role of ADAMTS13 as a diagnostic and prognostic marker of disseminated intravascular coagulopathy is largely underestimated. Summary: VWF is an acute phase protein and its plasma level increases in systemic inflammation. When released from endothelial cell... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336091 Wed, 03 Mar 2010 00:00:00 +0100 3336091 http://www.medworm.com/index.php?rid=3336090&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196725%26dopt%3DAbstract In conclusion, there is an unmet medical need for identification and validation of reliable biomarkers of sepsis; the clinical information obtained from the use of novel biomarkers might contribute to transform sepsis from a physiologic syndrome to a group of distinct biochemical disorders, to improve diagnosis and therapeutic decision making for high-risk patients, to monitor the response to therapy and to ensure the enrollment of seriously characterized patients in clinical studies. PMID: 20196725 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336090 Wed, 03 Mar 2010 00:00:00 +0100 3336090 http://www.medworm.com/index.php?rid=3336089&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196726%26dopt%3DAbstract Authors: Koal T, Deigner HP The gap of the post-genomic era is increasingly being filled by the metabolomics approach, comprising a technology for analyzing small molecule endogenous metabolites (<1500 Dalton) in complex biological samples. This new analytical science has progressed within the last years particularly with regard to improvements in mass spectrometry based detection, now allowing highly robust, reproducible, selective and sensitive qualitative or quantitative analysis of endogenous metabolites. The precise and accurate quantitation of these metabolites via targeted metabolomics, now critically contributes to the quantitative analysis of endogenous compounds in biomarker discovery and validation thus to future personalized therapy. The analytical methods of choice in (... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336089 Wed, 03 Mar 2010 00:00:00 +0100 3336089 http://www.medworm.com/index.php?rid=3336088&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196727%26dopt%3DAbstract Authors: Aydiner F, Yetkin CE, Seli E A key step in assisted reproduction is the assessment of embryo viability in order to identify the embryo(s) most likely to result in pregnancy. Currently used embryo assessment systems are largely based on morphology and cleavage rate. While these systems have been pivotal in improving implantation and pregnancy rates and reducing multiple gestations, their precision is still insufficient. The limitations of strategies based on morphology have led to the investigation of adjunctive technologies for non-invasive assessment of embryo viability in assisted reproduction. These include the measurement of glucose, pyruvate, or amino acid levels in the embryo culture media, assessment of oxygen consumption by the embryo, genomic and proteomic profiling, ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336088 Wed, 03 Mar 2010 00:00:00 +0100 3336088 http://www.medworm.com/index.php?rid=3336087&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196728%26dopt%3DAbstract Authors: Bonaterra GA, Zügel S, Kinscherf R Motivated by the challenge of risk assessment in a heterogeneous population and guided by advances in our knowledge of the pathobiology of cardiovascular diseases (CVD), basic and clinical scientists have maintained substantial interest in the development and application of novel biomarkers for risk stratification of CVD. In particular, strategies to identify and combine multiple biomarkers, which may reflect diverse pathobiological contributors to the onset and complications of CVD, have been arising as an approach to improve more effectively the risk assessment and target therapy. Moreover, comparative evaluations of novel markers are necessary to estimate these candidates for integration into present and future strategies. In this rev... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336087 Wed, 03 Mar 2010 00:00:00 +0100 3336087 http://www.medworm.com/index.php?rid=3336086&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196729%26dopt%3DAbstract We describe the necessary development and validation steps including recent results of the second phase of the MAQC project (MAQC-II) and emphasise on potential pitfalls. PMID: 20196729 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336086 Wed, 03 Mar 2010 00:00:00 +0100 3336086 http://www.medworm.com/index.php?rid=3336085&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196730%26dopt%3DAbstract Authors: Estep JM, Birerdinc A, Younossi Z Non-alcoholic fatty liver disease (NAFLD) is a clinico-pathologic spectrum of conditions ranging from simple steatosis to nonalcoholic steatohepatitis (NASH). Although simple or bland steatosis follows a relatively benign clinical course, NASH can potentially progress to cirrhosis (approximately 10 to 15 percent) and hepatocellular carcinoma. NAFLD occurs in an estimated 25 to 30 percent of the US general population, while NASH is reported in 2 to 3 percent of the population. Even though common explanation for the increased prevalence of NAFLD is the increased rate of obesity, the risk of developing NAFLD and NASH is not limited to overweight and obese individuals. Currently, the only way to diagnose NASH or to assess the stage of fibrosis is ... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336085 Wed, 03 Mar 2010 00:00:00 +0100 3336085 http://www.medworm.com/index.php?rid=3336084&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196731%26dopt%3DAbstract Authors: Vlassov VV, Laktionov PP, Rykova EY Since the association of circulating DNA level changes with tumor growth was discovered many attempts have been made to develop the sensitive and robust blood-based tests for early tumor diagnostics. Both genomic as well as mitochondrial DNA quantification in the circulation have been extensively evaluated as a diagnostic and prognostic tool to monitor cancer therapy. Cell-free DNA bearing the same genetic and epigenetic changes as the tumor tissues were shown to be detectable in plasma / serum of cancer patients indicating the principal possibility to create the minimally invasive diagnostic tests based on tumor-specific DNA markers. Apart from circulating DNA, tumor-derived RNA in plasma / serum was found to be a promising approach for the... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336084 Wed, 03 Mar 2010 00:00:00 +0100 3336084 http://www.medworm.com/index.php?rid=3336083&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196732%26dopt%3DAbstract Authors: Luchini A, Fredolini C, Espina BH, Meani F, Reeder A, Rucker S, Petricoin EF, Liotta LA Clinically relevant biomarkers exist in blood and body fluids in extremely low concentrations, are masked by high abundance high molecular weight proteins, and often undergo degradation during collection and transport due to endogenous and exogenous proteinases. Nanoparticles composed of a Nisopropylacrylamide hydrogel core shell functionalized with internal affinity baits are a new technology that can address all of these critical analytical challenges for disease biomarker discovery and measurement. Coreshell, bait containing, nanoparticles can perform four functions in one step, in solution, in complex biologic fluids (e.g. blood or urine): a) molecular size sieving, b) complete exclusio... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336083 Wed, 03 Mar 2010 00:00:00 +0100 3336083 http://www.medworm.com/index.php?rid=3336082&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196733%26dopt%3DAbstract Authors: Shivapurkar N, Gazdar AF DNA methylation plays a critical role in the regulation of gene expression, differentiation and in the development of cancer and other diseases. Hypermethylation of CpG islands located in the promoter regions of tumor suppressor genes is now firmly established as the most frequent mechanism for gene inactivation in cancers. Feasibility of using DNA methylation based biomarkers for early detection of cancer has been shown. Potential of using DNA methylation for prediction of therapeutic outcome and patient survival has also been shown. DNA originated from cancer cells has been routinely detected in clinical specimens (ex. Plasma/serum, sputum, urine etc.) from cancer patients. Presence of methylated DNA sequences in clinical specimens and potential of u... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336082 Wed, 03 Mar 2010 00:00:00 +0100 3336082 http://www.medworm.com/index.php?rid=3336081&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D20196734%26dopt%3DAbstract Authors: Belousov PV, Kuprash DV, Nedospasov SA, Shebzukhov YV Malignant tumors induce humoral immune response in cancer patients, although the incidence of such autoantibody responses against individual tumor-associated antigens (TAA) is rather low. To increase predictive value of TAA-recognizing autoantibodies as potential cancer biomarkers, TAAs should be combined into protein arrays. Here we review recent advances in the application of such arrays and summarize data concerning most promising antigens. We also review the methods of cloning TAA-recognizing autoantibodies, generation of human hybridomas and screening of recombinant human immunoglobulin libraries. PMID: 20196734 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3336081 Wed, 03 Mar 2010 00:00:00 +0100 3336081 http://www.medworm.com/index.php?rid=3032489&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19938317%26dopt%3DAbstract Authors: Shinohara ET, Maity A Sensitivity to radiation and chemotherapy can be influenced by factors extrinsic to the cancer cell. For example, severely hypoxic cells require 2-3 times the radiation dose as do well-oxygenated cells to achieve similar cell killing. Apart from the tumor cells, neighboring cells such as endothelial cells may influence radiosensitivity. Irradiation can lead to expression of molecules that may increase radio/chemoresistance, for example vascular endothelial growth factor (VEGF), a secreted protein that regulates angiogenesis, or hypoxia inducible factor-1 alpha (HIF-1 alpha), a master transcription factor that regulates gene expression in hypoxia. Hence, response to cytotoxic therapy may be improved by modulating the tumor microenvironment (TME). Several a... Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3032489 Fri, 27 Nov 2009 15:02:06 +0100 3032489 http://www.medworm.com/index.php?rid=3015731&cid=s_37012_67_f&fid=37012&url=http%3A%2F%2Fwww.ncbi.nlm.nih.gov%2Fentrez%2Fquery.fcgi%3Ftmpl%3DNoSidebarfile%26db%3DPubMed%26cmd%3DRetrieve%26list_uids%3D19925404%26dopt%3DAbstract Authors: Cao Y PMID: 19925404 [PubMed - as supplied by publisher] (Source: Current Molecular Medicine) Current Molecular Medicine journals http://www.medworm.com/rss/comments.php?id=3015731 Sun, 01 Nov 2009 00:00:00 +0100 3015731