01月 2, 2008 at 4:06 pm | 综述
- Posted by qixinming |
Published Online: 31 Dec 2007
Blood circulating from the intestines to the liver is rich in bacterial products, environmental toxins, and food antigens. To effectively and quickly defend against potentially toxic agents without launching harmful immune responses, the liver relies on its strong innate immune system. This comprises enrichment of innate immune cells (such as macrophages, natural killer, natural killer T, and gamma delta T cells) and removal of waste molecules and immunologic elimination of microorganisms by liver endothelial cells and Kupffer cells. In addition, the liver also plays an important role in controlling systemic innate immunity through the biosynthesis of numerous soluble pathogen-recognition receptors and complement components. Conclusion: The liver is an organ with predominant innate immunity, playing an important role not only in host defenses against invading microorganisms and tumor transformation but also in liver injury and repair. Recent evidence suggests that innate immunity is also involved in the pathogenesis of liver fibrosis, providing novel therapeutic targets to treat such a liver disorder. (HEPATOLOGY 2007.)
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12月 21, 2007 at 3:35 pm | 综述
- Posted by qixinming |
The BCL-2 protein family: opposing activities that mediate cell death
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| Nature Reviews Molecular Cell Biology 9, 47-59 (January 2008) | doi:10.1038/nrm2308 |
| have either pro- or anti-apoptotic activities, have been studied intensively for the past decade owing to their importance in the regulation of apoptosis, tumorigenesis and cellular responses to anti-cancer therapy. They control the point of no return for clonogenic cell survival and thereby affect tumorigenesis and host–pathogen interactions and regulate animal development. Recent structural, phylogenetic and biological analyses, however, suggest the need for some reconsideration of the accepted organizational principles of the family and how the family members interact with one another during programmed cell death. Although these insights into interactions among BCL-2 family proteins reveal how these proteins are regulated, a unifying hypothesis for the mechanisms they use to activate caspases remains elusive |
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12月 20, 2007 at 4:15 pm | 综述
- Posted by qixinming |
| Cell, Vol 131, 966-979, 30 November 2007 |
| A Nonapoptotic Cell Death Process, Entosis, that Occurs by Cell-in-Cell Invasion |
| we describe a nonapoptotic cell death program in matrix-detached cells that is initiated by a previously unrecognized and unusual process involving the invasion of one cell into another, leading to a transient state in which a live cell is contained within a neighboring host cell. Live internalized cells are either degraded by lysosomal enzymes or released. We term this cell internalization process entosis and present evidence for entosis as a mechanism underlying the commonly observed “cell-in-cell” cytological feature in human cancers. Further we propose that entosis is driven by compaction force associated with adherens junction formation in the absence of integrin engagement and may represent an intrinsic tumor suppression mechanism for cells that are detached from ECM. |
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12月 20, 2007 at 9:22 am | 综述
- Posted by qixinming |
| Nature Reviews Genetics 9, 4-5 (January 2008) | doi:10.1038/nrg2287 |
Gene expression: One allele or two?
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| The above survey, supported by RNA fluorescence in situ hybridization and allele-specific RT-PCR, revealed that monogenic allele expression can be clonally stable. As the authors point out, this stability — together with clonal expansion during development — might lead to functional differences among individuals. So, in the future, epigenetic inter-individual variation might also have to be taken into consideration when assessing population-level variation in human disease susceptibility. |
| Apart from some notable exceptions, diploid organisms are expected to express both alleles at a given locus. Recent work shows that monoallelic expression is much more widespread than previously thought, implying that variation of an epigenetic nature might have important consequences for studies of human disease susceptibility. |
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12月 19, 2007 at 12:55 pm | 综述
- Posted by qixinming |
12月 19, 2007 at 12:50 pm | 综述
- Posted by qixinming |
12月 7, 2007 at 4:21 pm | 综述
- Posted by qixinming |
DNA Mismanagement Leads to Immune System Oversight |
| Trex1, a major 3′ DNA exonuclease in mammalian cells, has been thought to act primarily in DNA replication or repair. Surprisingly, the major phenotype resulting from Trex1 deficiency in humans and mice is a chronic inflammatory disease. In this issue, Yang et al. (2007) report that Trex1 deficiency causes chronic activation of the ATM-dependent DNA-damage checkpoint and accumulation of a discrete single-stranded DNA species in the cytoplasm, either of which could contribute to chronic inflammation. |
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12月 6, 2007 at 4:49 pm | 综述
- Posted by qixinming |
Drug-induced mitochondrial toxicity.
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| Mitochondria play a critical role in generating most of the cell’s energy as ATP. They are also involved in other metabolic processes such as urea generation, haem synthesis and fatty acid beta-oxidation. Disruption of mitochondrial function by drugs can result in cell death by necrosis or can signal cell death by apoptosis (e.g., following cytochrome c release). Drugs that injure mitochondria usually do so by inhibiting respiratory complexes of the electron chain; inhibiting or uncoupling oxidative phosphorylation; inducing mitochondrial oxidative stress; or inhibiting DNA replication, transcription or translation. It is important to test for mitochondrial toxicity early in drug development as impairment of mitochondrial function can induce various pathological conditions that are life threatening or can increase the progression of existing mitochondrial diseases. |
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11月 30, 2007 at 10:36 am | 综述
- Posted by qixinming |
Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges
Nature Reviews Drug Discovery 6, 904 (2007). doi:10.1038/nrd2423
Authors: Russell A. Wilke, Debbie W. Lin, Dan M. Roden, Paul B. Watkins, David Flockhart, Issam Zineh, Kathleen M. Giacomini
& Ronald M. Krauss
Serious adverse drug reactions (SADRs) are a major cause of morbidity and mortality worldwide. Some SADRs may be predictable, based upon a drug’s pharmacodynamic and pharmacokinetic properties. Many, however, appear to be idiosyncratic. Genetic factors may underlie susceptibility to SADRs and the identification of predisposing |
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-TNFR1 as the model system, specifically addressing the involvement of intracellular ROS in TNF
B and JNK and their crosstalk.—Shen, H-M., Pervaiz, S. TNF receptor superfamily-induced cell death: redox-dependent execution. 
