Years and Volumes

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Articles from this Volume

Michael Miksa, Dhruv Amin, Rongqian Wu, Weifeng Dong, Thanjavur S Ravikumar, and Ping Wang

Sepsis is a systemic inflammatory response to infection which may lead to multiple organ failure and is associated with increased rates of apoptosis. Clearance of apoptotic cells is crucial to maintaining cellular function under normal and pathological conditions. Administration of exosomes, derived from immature dendritic cells, promotes phagocytosis of apoptotic cells and improves survival in an animal model of sepsis by providing milk fat globule epidermal growth factor-factor VIII (MFG-E8). In this work, Miksa et al. (553-560) investigate whether the CX3CL1-chemokine fractalkine (CX3CL1) plays a role in apoptotic cell clearance. Their results show that CX3CL1 induces MFG-E8 in vitro and in vivo and enhances clearance of apoptotic cells in an MFG-E8 dependent manner. These findings suggest a possible novel treatment for patients with sepsis.

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Posted by Leah Caracappa on Apr 2, 2012 5:05 PM CDT
Chia-Chen Kuo and Shih-Chang Lin

The members of the forkhead box class O (FOXO) transcription factors (FOXO1, FOXO3a, and FOXO4) play an important role in controlling lymphocyte activation and proliferation.  Kuo and Lin (561-566) evaluated the possibility that FOXO transcriptional expression is dysregulated in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA), two autoimmune diseases with tissue damage mediated by overactivation of autoreactive lymphocytes.  Kuo and Lin determined quantities of FOXO forkhead transcription factors in peripheral blood mononuclear cells from control, SLE and RA patients.  Their results show differential regulation of FOXO1 in SLE and RA patients when compared with control subjects. The data suggest transcriptional dysregulation in FOXO1 may be linked with the pathogenesis of autoimmune disease and that FOXO1 transcript levels in peripheral blood may serve as a biomarker for disease activity.

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Posted by Leah Caracappa on Apr 2, 2012 5:04 PM CDT
Rui Wang, Ke Dong, Fang Lin, Xi Wang, Ping Gao, San-Hua Wei, Shi-Yin Cheng, and Hui-Zhong Zhang

Osteosarcomas, the most frequently occurring type of bone tumor, are malignant tumors derived from bone tissues.  Osteosarcomas are characterized by aggressive invasion, early metastasis and resistance to existing chemotherapeutic agents.  Novel diagnostic and treatment approaches are needed to improve the poor prognosis of osteosarcoma.  The stathmin family of proteins is important in signal transduction and is highly expressed in human osteosarcoma.  Here, Wang et al. (567-575) investigate stathmin as a therapeutic target by using osteosarcoma RNA interference to reduce stathmin expression in human osteosarcoma cell lines.  Downregulation of stathmin expression significantly inhibited osteosarcoma cell proliferation in vitro, tumorgenicity in vivo, enhanced apoptosis and enhanced chemosensitivity to taxanes in human osteosarcoma cell lines.  These data indicate that RNA interference-mediated stathmin downregulation exerts potent anti-proliferative and chemosensitizing effects in human osteosarcomas.

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Posted by Leah Caracappa on Apr 2, 2012 5:03 PM CDT
Hidenori Koyama, Hiroshi Yamamoto, and Yoshiki Nishizawa

Receptor for advanced gylcation end-products (RAGE) is associated with macrovascular diabetic complications through regulation of atherogenesis, angiogenic response, vascular injury and inflammatory response.  The significance of RAGE in cardiovascular disease pathogenesis is not confined to diabetic conditions but also plays a role in non-diabetic conditions.  In this review Koyama et al. (625-635) summarize recent findings regarding pathophysiological roles of RAGE and soluble RAGE in cardiovascular disease and discuss their potential usefulness as therapeutic targets and biomarkers for the disease.

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Posted by Leah Caracappa on Dec 5, 2007 12:00 AM CST
Silvia Bertuglia, Hideo Ichimura, Gianluca Fossati, Kaushik Parthasarathi, Flavio Leoni, Daniela Modena, Piero Cremonesi, Jahar Bhattacharya, and Paolo Mascagni

The ability to inhibit functions of activated endothelial cells represents a promising strategy for pathologies involving abnormal microcirculation activation such as re-occulsion after angioplasty and acute rejection in allo- and zenotransplantation.  Small peptides containing the Lys-Pro motif at the core of their sequence have been shown to stimulate phagocytosis and exhibit antiinflammatory properties.  However, efficacy is uncertain due to limited metabolic stability.  Bertuglia et al. (615-624) synthesized ITF1697, a chemically modified form of these peptides with increased resistance to proteolysis.  Data indicate that ITF1697 can maintain normal arteriolar responses and capillary perfusion during post-ischemic reperfusion by inhibiting calcium-dependent exocytosis of Weibel Palade bodies from endothelial cells, an early hallmark of inflammation.  These results indicate that ITF1697 may be a pharmacological tool for the treatment of pathologies involving abnormal microcirculation activation.

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Posted by Leah Caracappa on Dec 4, 2007 12:00 AM CST
Susanne Rohrbach, Stefan Engelhardt, Martin J Lohse, Karl Werdan, Juergen Holtz, and Ursula Muller-Werdan

Acute activation of a proinflammatory cytokine stress response initially provides the heart with adaptive and protective mechanisms. However, prolonged cytokine activity can lead to overt cardiac decompensation, edema and failure. While several mechanisms of cardiac induction of proinflammatory cytokines have been investigated, the effects of sympathetic overactivity on the proinflammatory stress response are less clear. Beta-adrenoceptor activation contributes to proinflammatory stress responses and in this work, Rohrback et al. (605-614) analyze myocardial cytokine expression under various conditions of B-adrenoceptor activation. Results show that B-adrenoceptor-mediated activation of cAMP-responseive element and activating protein-1 directly contribute to interleukin 6 induction in healthy and failing myocardium. These results advance our understanding of sympathetic activity during cardiac proinflammatory stress.

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Posted by Leah Caracappa on Dec 3, 2007 12:00 AM CST
Tiffany Frey and Antonio De Maio

Sepsis is a systemic response to infection and a major health problem with approximately 750,000 cases per year in the United States.  Adequate therapies do not exist and patient care is mainly supportive.  Statins, which are widely used for the treatment of hypercholesterolemia, also have antiinflammatory effects via mechanisms that are not well understood.  Lipopolysaccharide (LPS) induces an inflammatory response and interacts with CD14, a major LPS binding site on macrophages. Here Frey and De Maio (592-604) investigate the effect of statins on CD14 expression. Their results suggest that statin treatment may modulate macrophage function and have an impact on inflammation and the outcome of sepsis.

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Posted by Leah Caracappa on Dec 2, 2007 12:00 AM CST
Bárbara Macedo, Ana Rita Batista, José Barbas do Amaral, and Maria João Saraiva

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant hereditary disease characterized by the extracellular deposition of amyloid fibrils in connective tissue.  FAP affects the peripheral nervous system with progressive and severe sensory and autonomic neuropathy.  Early lesion detection using biomarkers may aid in the clinical management of patients.  In order to better define biomarkers for future assessment of prophylactic and therapeutic drugs in the treatment of FAP, Macedo et al. (584-591) extended the search for oxidative stress and apoptotic biomarkers in clincical simples and in animal models.  A robust biomarker profile was identified and may improve future assessment of selected markers in experimental animal studies and in clinical trials.

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Posted by Leah Caracappa on Dec 1, 2007 12:00 AM CST
Oonagh Dowling, Burton Rochelson, Kathleen Way, Yousef Al-Abed, and Christine N Metz

Pregnancy-induced hypertension (PIH), also known as preeclampsia, is one of the major causes of maternal and fetal death.  While the precise cause of PIH is not known, aberrant cytokine production and placenta participation are considered to be important factors.  Gestational cigarette smoking, which is widely accepted to be harmful to both the mother and fetus, is protective against the development of PIH.  Based on the anti-inflammatory activity of nicotine, the major component of cigarettes, Dowling et al. (576-583) examined the effect of nicotine and other cholinergic agonists on placenta inflammatory responses ex vivo. Nicotine and other cholinergic agonists significantly suppress placenta cytokine production following stimulation through the NFkB pathway.  These data suggest that cholinergic agonists, including nicotine, may protect against PIH.

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Posted by Leah Caracappa on Nov 4, 2007 12:00 AM CDT