Years and Volumes

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Articles from this Volume

Michael Bacher, Oliver Deuster, Bayan Aljabari, Rupert Egensperger, Frauke Neff, Frank Jessen, Julius Popp, Carmen Noelker, Jens Peter Reese, Yousef Al-Abed, and Richard Dodel

Inflammatory processes have been implicated in the pathophysiology of Alzheimer’s disease (AD), but the role of macrophage migration inhibitory factor (MIF) had not been thoroughly investigated. MIF is associated with β-amyloid (Aβ) peptide, the main constituent of Alzheimer plaques, demonstrating a proinflammatory etiology in AD. Bacher et al. examined MIF expression and function in vivo and in vitro, confirmed its association with plaques and demonstrated that Aβ-induced toxicity could be mitigated by small molecule inhibition of MIF. Additionally, the authors measured MIF levels in cerebrospinal fluid (CSF) of AD patients, and found an increase of MIF levels as compared with healthy, age-matched controls. These results may implicate MIF in the pathogenesis of AD, and suggest that inhibition of MIF may be a therapeutic strategy in prevention of Alzheimer’s disease onset and progression.

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Posted by MolMed Editor on Mar 4, 2010 12:00 AM CST
Daniela Spano, Roberta Russo, Vittorio Di Maso, Natalia Rosso, Luigi M Terracciano, Massimo Roncalli, Luigi Tornillo, Mario Capasso, Claudio Tiribelli, and Achille Iolascon

Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and ranks third among causes of cancer-related deaths. The severity of the disease, compounded with a lack of good diagnostic markers and treatment strategies, render HCC a major clinical challenge. To garner a better understanding of HCC, Spano et al. performed a systematic functional genomic analysis of human HuH-7 and JHH-6 HCC cells. Of the 11 genes identified, LGALS1 was selected and characterized in the context of HCC patient samples. LGALS1 codes for Galectin-1, a protein involved in various aspects of tumorigenesis. The authors show that Galectin-1 overexpression leads to increased carcinoma cell migration and invasion in vitro. They also show a positive association between increased expression of Galectin-1 and the presence of metastasis, an indicator of cancer aggression. This study clears the way for future investigations to identify markers for the prediction, diagnosis and prognosis of HCC.

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Supplementery Data A1.CEL      B1 .CEL      C1 .CEL      A2 .CEL      B2 .CEL      C2 .CEL 
Posted by MolMed Editor on Mar 3, 2010 12:00 AM CST
Irena Pastar, Olivera Stojadinovic, Agata Krzyzanowska, Stephan Barrientos, Christina Stuelten, Karen Zimmerman, Miroslav Blumenberg, Harold Brem, and Marjana Tomic-Canic

Each year, more than eight million patients develop chronic nonhealing wounds, including venous ulcers (VUs). In normal wound healing, the pleiotropic cytokine TGFβ and its receptors are highly expressed, but not in chronic wounds. Pastar et al. investigated the pathogenesis of VUs by examining TGFβ regulation and found that TGFβ signaling is blocked via the downregulation of its receptors and the attenuation of Smad signaling. This results in the deregulation of TGFβ target genes and consequently a loss of homeostasis and hyperproliferation. The authors suggest that, although exogenously-applied TGFβ may be beneficial for acute wound healing, the disruption of the TGFβ signaling cascade in VUs likely limits the efficacy of this specific treatment strategy.

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Posted by MolMed Editor on Mar 2, 2010 12:00 AM CST
Silvia Deaglio, Semra Aydin, Maurizia Mello Grand, Tiziana Vaisitti, Luciana Bergui, Giovanni D’Arena, Giovanna Chiorino, and Fabio Malavasi

Chronic lymphocytic leukemia (CLL) is the most common type of leukemia, and usually affects the adult population. Like all cancers, an understanding of the specific mechanisms of cell proliferation is crucial for the development of effective CLL treatments. Human CD38, a glycoprotein involved in the catabolism of extracellular nucleotides, is a negative prognostic marker for CLL patients. Malavasi and colleagues characterize the long-term interactions between CD38-positive CLL cells and CD31-positive cells, and thus confirm the role of this protein complex in proliferation, cell migration and homing. These results suggest that the CD31/CD38 axis is part of a network of accessory signals that modify the cellular microenvironment, favoring localization of leukemic cells to growth-permissive sites. Improved understanding of cell–cell interactions could lead to new diagnoses and treatments for CLL.

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Posted by MolMed Editor on Mar 1, 2010 12:00 AM CST
Review Article

Meng Xiang and Jie Fan

Acute respiratory distress syndrome (ARDS), a central cause of morbidity and mortality in intensive care units, is caused by an uncontrolled systemic inflammatory response to such conditions as sepsis, major surgery, and trauma. Innate immunity can be triggered through pattern recognition receptors (PRRs), which recognize conserved microbial motifs or pathogen associated molecular patterns (PAMPs) and endogenous danger signals. The activation of PRRs initiates extracellular as well as intracellular signaling cascades that ultimately promote inflammatory responses. Drs. Xiang and Fan focus on recent advances on the role of PRRs in the mechanisms of ARDS. A greater understanding of these complex pathways is necessary to explore new treatment options for ARDS patients.

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Posted by MolMed Admin on Feb 4, 2010 12:00 AM CST
Review Article

Karen CM Moraes 

Understanding RNA processing and surveillance mechanisms is essential to advancing clinical diagnosis and therapeutic procedures. Numerous diseases are caused by errors and mutations of significant RNA sequences leading to the expression of pathological proteins. Recent studies have elucidated our understanding of molecular mechanisms of mRNA processing and the complex series of events that lead to loss or gain of both functional and deleterious proteins. In this review, Dr. Moraes discusses mRNA quality control mechanisms and their clinical relevance to developing therapeutic strategies.

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Posted by MolMed Admin on Feb 3, 2010 12:00 AM CST
Akhil Hegde, Mahesh Uttamchandani, Shabbir M Moochhala, and Madhav Bhatia

Understanding gene expression of immune regulators such as cytokines is essential to developing better prognostic tools and therapeutic strategies for treating sepsis. Hegde et al. investigated circulating cytokine profiles in preproptachykinin-A  knockout (PPTA-/-) mice, a gene found to induce expression of immunoregulatory proteins that protect against microbial sepsis. A range of both pro- and anti- inflammatory cytokines was analyzed using multiplexed bead–suspension arrays. Deletion of the PPTA  gene resulted in an increase of both pro- and antiinflammatory cytokines in septic mice and improved survival. This study reveals that multiple factors controlled by PPTA are involved in the response to microbial sepsis, some of which may be detrimental to survival from sepsis. This work provides insight into the molecular mechanisms underlying the immune response to sepsis and identifies a technique for rapid and cost-effective biomarker identification, which has implications for improved clinical diagnostic tools for septic patients.

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Posted by MolMed Admin on Feb 2, 2010 12:00 AM CST
Aviad Levin, Joseph Rosenbluh, Zvi Hayouka, Assaf Friedler, and Abraham Loyter

Human immunodeficiency virus (HIV) integration into the host cell DNA is the central event in the life cycle of the retrovirus. For this to occur, a combination of the viral integrase (IN) and host LEDGF/p75 proteins are required. In their latest efforts, Levin et al. examined the early viral integration pathway and demonstrate that the viral Rev protein, an inhibitor of viral integration, associates with LEDGF/p75. Furthermore, they demonstrate a role for Rev in the dissociation of the IN-LEDGF/p75 complex. The authors propose a model whereby viral integration is regulated by the interplay between LEDGF/p75, Rev and IN, with the LEDGF/p75-Rev and IN-Rev complexes leading to inhibition of viral integration. This work could ultimately lead to new strategies for preventing and treating HIV infection.

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Supplementary Data PDF
Posted by MolMed Admin on Feb 1, 2010 12:00 AM CST
Hayder A Giha, Amre Nasr, Mattias Ekström, Elisabeth Israelsson, Gishanthi Arambepola, David Arnot, Thor G Theander, Marita Troye-Blomberg, Klavs Berzins, Per Tornvall, and Gehad ElGhazali

Every year there are between 300 and 500 million new cases of malaria worldwide, making malaria a major cause of morbidity and mortality in equatorial regions of the globe. Inflammation in malaria pathogenesis is induced by non-specific acute phase proteins, such as C-reactive protein (CRP). The CRP gene is highly polymorphic, and single nucleotide polymorphisms (SNPs) have been identified at several loci. Of these, the triallelic –286 (C > T > A) SNP was strongly associated with plasma CRP concentration. Giha et al. examined the CRP –286 SNP in a population of Sudanese donors and found the CRP –286 A-allele was associated with an increase in malaria susceptibility. This study identifies a genetic marker for malaria susceptibility and elucidates the role of inflammation in malaria infection.

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Posted by MolMed Admin on Jan 4, 2010 12:00 AM CST
John G Routsias, Nikolaos Kyriakidis, Michael Latreille, and Athanasios G Tzioufas

Autoimmune diseases such as systemic lupus erythematosus (SLE) are caused by the diminution of self-tolerance, which results in numerous health complications involving the skin, joints, kidneys, lungs, nervous system and serous membranes. SLE is caused by diversification and augmentation of the immune response via epitope spreading, whereby the immune response “jumps” from one antigen to another. Routsias et al. demonstrated the ability of autoantigens to induce antibodies to cross-recognize components of protein particles corresponding to RRMs (RNA recognition motifs) of different nuclear autoanitgens via molecular mimicry. The investigators discovered that the RRM region of La/SSB can trigger interparticle B cell diversification to U1-RNP. This confirms the importance of the RRM region pathway, resulting in autoimmunity in lupus. Understanding the molecular mechanisms involved in the initial events of the autoimmune process could lead to the development of therapeutic strategies that block the cascade of events resulting in the development of SLE.

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Posted by MolMed Admin on Jan 3, 2010 12:00 AM CST
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