2007医学十大进展

       这一期的Nature Medicine(Dec 12, 2007)的“2007 in review”评选出了今年十大“Notable advances”，内容涉及到成骨细胞的内分泌、干细胞的reprogramming、吸烟的致病机理、维生素在感染中作用、糖尿病肥胖感染、MiRNA与心脏病、MiRNA与心脏发育、血小板生理活动、MiRNA与HIV感染、多发性硬化致病基因等。CMBI特将与此十大进展相关的全文文献收集如下，供大家参考。

• Bone is often the target of hormones, but it also acts as an endocrine organ, releasing a hormone that enhances sugar and fat metabolism. Bone-forming cells secrete the protein osteocalcin, which acts as a hormone, increasing the mass of insulin-producing pancreatic cells, serum insulin levels and fat cell sensitivity to insulin.
• Endocrine Regulation of Energy Metabolism by the Skeleton (Cell 130, 456–469)
• Attempts to derive stem cells that can be used for regenerative therapy without destroying embryos continued unabated this year. In January, researchers showed that cells present in amniotic fluid can differentiate into a wide variety of cell types. In June, two independent groups reported that mouse fibroblasts can be reprogrammed into cells that closely resemble embryonic stem cells, and in September, another group identified a new marker for multipotent stem cells in the testes that may enable the use of these cells for therapy.
• Isolation of amniotic stem cell lines with potential for therapy (Nat. Biotechnol. 25, 100–106)
• Generation of germline-competent induced pluripotent stem cells (Nature 448, 313–317)
• In vitro reprogramming of fibroblasts into a pluripotent ES-cell-like state (Nature 448, 318–324)
• Generation of functional multipotent adult stem cells from GPR125+ germline progenitors (Nature 449, 346–350)
• Lung cancers, including the poorly understood tumors associated with smoking, may be triggered by the fusion of two genes, Japanese researchers reported in August. Formed by a small chromosomal inversion, the transforming gene fusion generates an activated kinase, and is found in seven percent of tumors from smokers and nonsmokers. Small compounds already known to inhibit the kinase may be able to treat the disease.
• Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer (Nature 448, 561–566)
• Remember the old wives' tale that carrots can help you see in the dark? A cluster of papers provided a sounder reason to get your daily dose of vitamin A: it may help ward off inflammatory bowel disease by promoting the generation of regulatory T cells, which dampen inflammation. Dendritic cells in the gut are particularly adept at synthesizing the vitamin A metabolite retinoic acid, which, along with TGF-beta, skews T cells toward becoming regulatory T cells.
• Reciprocal TH17 and Regulatory T Cell Differentiation Mediated by Retinoic Acid (Science 317, 256–260)
• A functionally specialized population of mucosal CD103+ DCs induces Foxp3+ regulatory T cells via a TGF-β– and retinoic acid–dependent mechanism (J. Exp. Med. 204, 1757–1764)
• All-trans retinoic acid mediates enhanced T reg cell growth, differentiation, and gut homing in the face of high levels of co-stimulation (J. Exp. Med. 204, 1765–1774)
• Small intestine lamina propria dendritic cells promote de novo generation of Foxp3 T reg cells via retinoic acid (J. Exp. Med. 204, 1775–1785)
• Eating too much can lead to increased inflammation in fat tissue and, over time, trigger diabetes. In May, researchers showed that STAMP2, a protein in fat cells, controls proper nutrient storage while keeping inflammation at bay. Feeding increases the levels of STAMP2, reducing the expression of key cytokines that promote inflammation and stimulating the cell's insulin signaling pathway, which regulates the storage of excess nutrients.
• Coordinated Regulation of Nutrient and Inflammatory Responses by STAMP2 Is Essential for Metabolic Homeostasis (Cell 129, 537–548)
• A flurry of papers this year unveiled the importance of microRNAs (miRNAs) in heart development, function and disease. The studies delineated the mechanisms by which specific miRNAs act to regulate heart morphogenesis, contractility, electrical conduction and remodeling. Hearts from patients with cardiomyopathy or coronary artery disease have abnormal levels of some of these miRNAs, suggesting that they could be new therapeutic targets for heart disease.
• The muscle-specific microRNA miR-1 regulates cardiac arrhythmogenic potential by targeting GJA1 and KCNJ2 (Nat. Med. 13, 486–491)
• MicroRNA-133 controls cardiac hypertrophy (Nat. Med. 13, 613–618)
• Dysregulation of Cardiogenesis, Cardiac Conduction, and Cell Cycle in Mice Lacking miRNA-1-2 (Cell 129, 303–317)
• Control of Stress-Dependent Cardiac Growth and Gene Expression by a MicroRNA (Science 316, 575–579)
• How the heart is put together during embryonic development has been extensively studied, but scientists reported a new twist to this story late last year. Three groups isolated mouse multipotent progenitor cells that can give rise to three major heart cell types—cardiac muscle, smooth muscle and endothelial cells. The findings may help researchers devise treatments for congenital and adult heart disease.
• Multipotent Flk-1+ Cardiovascular Progenitor Cells Give Rise to the Cardiomyocyte, Endothelial, and Vascular Smooth Muscle Lineages (Dev. Cell 11, 723–732)
• Developmental Origin of a Bipotential Myocardial and Smooth Muscle Cell Precursor in the Mammalian Heart (Cell 127, 1137–1150)
• Multipotent Embryonic Isl1+ Progenitor Cells Lead to Cardiac, Smooth Muscle, and Endothelial Cell Diversification (Cell 127, 1151–1165)
• Platelets live for only ten days before they are removed from the bloodstream. In March, an Australian team revealed that anuclear apoptosis is the secret to this platelet lifespan. Antagonism between the proapoptotic protein Bak and the antiapoptotic Bcl-xL protein sets up the ticking clock, and targeting this interaction could extend or limit the life of platelets to maintain healthy platelet counts.
• Programmed Anuclear Cell Death Delimits Platelet Life Span (Cell 128, 1173–1186)
• MiRNAs are key in the battle between viruses and their host cells, as revealed by four papers this year. Host cells produce a battery of miRNAs that shut off HIV gene expression, suppressing replication of the virus and contributing to latent infection. But other viruses can make their own miRNAs to hit back: human cytomegalovirus expresses miRNAs that promote the survival of infected cells.
• Suppression of MicroRNA-Silencing Pathway by HIV-1 During Virus Replication (Science 315, 1579–1582)
• Host Immune System Gene Targeting by a Viral miRNA (Science 317, 376–381)
• Complex I Binding by a Virally Encoded RNA Regulates Mitochondria-Induced Cell Death (Science 316, 1345–1348)
• Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes (Nat. Med. 13, 1241–1247)
• The decades-long search for genes associated with multiple sclerosis finally bore fruit this year, as three groups reported a link between polymorphisms in the interleukin-7 receptor gene and the disorder. The polymorphisms may dampen the signaling pathways downstream of interleukin-7, potentially affecting the survival of some inflammatory cells.
• Interleukin 7 receptor alpha chain (IL7R) shows allelic and functional association with multiple sclerosis (Nat. Genet. 39, 1083–1091)
• Variation in interleukin 7 receptor alpha chain (IL7R) influences risk of multiple sclerosis (Nat. Genet. 39, 1108–1113)
• Risk Alleles for Multiple Sclerosis Identified by a Genomewide Study (N. Engl. J. Med. 357, 851–862)