STAT3 is a ubiquitous transcription factor that is indispensable during early embryogenesis. To study the functions of STAT3 postnatally, we generated conditional STAT3-deficient mice. To that end, STAT3 lox/lox mice were crossed with mice expressing Cre under the control of rat insulin II gene promoter (RIP-Cre mice). Immunohistochemical and Western blot analyses showed that STAT3 is deleted from ␤ cells in the islets of Langerhans. Genomic DNA PCR revealed that STAT3 deletion also occurred in the hypothalamus. lox/lox mice also failed to decrease adiposity or to correct other abnormalities in these mice. These data thus suggest that loss of STAT3 in the hypothalamus caused by RIP-Cre action likely interferes with normal body weight homeostasis and glucose metabolism. Signal transducers and activators of transcription (STAT)proteins are a family of latent cytoplasmic transcription factors that are produced in many cell types and that are activated by tyrosine phosphorylation and dimerization in response to a wide variety of extracellular ligands, such as cytokines and growth factors (12,36). One member of this family, STAT3, is expressed ubiquitously and is transiently activated by a large number of ligands, including epidermal growth factor, plateletderived growth factor, interleukin 6 (IL-6), ciliary neurotrophic factor (CNTF), oncostatin M, leukemia inhibitory factor, leptin, growth hormone, and prolactin, as well as a number of oncogenic receptor and nonreceptor (Src-like) tyrosine kinases (12). While gene disruption approaches have been used extensively to define the functions of members of the STAT family of transcription factors (18), the knockout of STAT3 results in early embryonic lethality (42). At the cellular level, STAT3 is required in order to maintain the pluripotency of embryonic stem cells, as demonstrated by the reduced ability of cells to undergo undifferentiated clonal growth when the level of STAT3 is reduced (33).The early embryonic lethality of STAT3 knockout mice prevents any type of physiological study (42). To overcome this limitation, many laboratories have employed tissue-specific conditional gene targeting to study STAT3 function in adult mice (2,3,24,39). These efforts have led to the elucidation of the roles played by STAT3 in various aspects of cytokine and growth factor signaling in different tissues and cell types. For instance, in T cells, STAT3 functions to transduce the antiapoptotic function of IL-6 independently from that of Bcl-2 (41); in macrophages and neutrophils, STAT3 is required to suppress the overshooting of inflammatory stimulus-induced proinflammatory response (40); in keratinocytes, loss of STAT3 results in compromised wound healing (19,34,35); in the mammary gland, loss of STAT3 causes delayed mammary gland involution after weaning (9); in the liver, STAT3 is required to mediate the ability of both IL-6-and lipopolysaccharide-induced acute-phase gene expressions (4); in sensory neurons, loss of STAT3 is associated with their enhanced death, which is normally p...

Ischaemic stroke is becoming the most common cerebral disease in aging populations, but the underlying molecular mechanism of the disease has not yet been fully elucidated. Increasing evidence has indicated that an excess of iron contributes to brain damage in cerebral ischaemia/reperfusion (I/R) injury. Although mitochondrial ferritin (FtMt) plays a critical role in iron homeostasis, the molecular function of FtMt in I/R remains unknown. We herein report that FtMt levels are upregulated in the ischaemic brains of mice. Mice lacking FtMt experience more severe brain damage and neurological deficits, accompanied by typical molecular features of ferroptosis, including increased lipid peroxidation and disturbed glutathione (GSH) after cerebral I/R. Conversely, FtMt overexpression reverses these changes. Further investigation shows that Ftmt ablation promotes I/R-induced inflammation and hepcidin-mediated decreases in ferroportin1, thus markedly increasing total and chelatable iron. The elevated iron consequently facilitates ferroptosis in the brain of I/R. In brief, our results provide evidence that FtMt plays a critical role in protecting against cerebral I/R-induced ferroptosis and subsequent brain damage, thus providing a new potential target for the treatment/prevention of ischaemic stroke.

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Species of the genus Iris (Iridaceae) have a long history of traditional medicinal use in many places of the world, and they have been previously recognized as rich sources of secondary metabolites, in which flavonoids are found predominantly. During the last decade (1999-2008) over 90 flavonoid constituents have been discovered and characterized, including 38 new compounds, from 15 species of Iris. This review elucidates the structural features of these flavonoid constituents, and gives the details of their source, identification, biological activity and chemotaxonomy significance. At last, a checklist of the flavonoid compounds in Iris by species is given.

Salt stress is one of the major abiotic factors that affect the metabolism, growth and development of plants, and soybean [Glycine max (L.) Merr.] germination is sensitive to salt stress. Thus, to ensure the successful establishment and productivity of soybeans in saline soil, the genetic mechanisms of salt tolerance at the soybean germination stage need to be explored. In this study, a population of 184 recombinant inbred lines (RILs) was utilized to map quantitative trait loci (QTLs) related to salt tolerance. A major QTL related to salt tolerance at the soybean germination stage named qST-8 was closely linked with the marker Sat_162 and detected on chromosome 8. Interestingly, a genome-wide association study (GWAS) identified several single nucleotide polymorphisms (SNPs) significantly associated with salt tolerance in the same genetic region on chromosome 8. Resequencing, bioinformatics and gene expression analyses were implemented to identify the candidate gene Glyma.08g102000, which belongs to the cation diffusion facilitator (CDF) family and was named GmCDF1. Overexpression and RNA interference of GmCDF1 in soybean hairy roots resulted in increased sensitivity and tolerance to salt stress, respectively. This report provides the first demonstration that GmCDF1 negatively regulates salt tolerance by maintaining K+-Na+ homeostasis in soybean. In addition, GmCDF1 affected the expression of two ion homeostasis-associated genes, salt overly sensitive 1 (GmSOS1) and Na+/H+ exchanger 1 (GmNHX1), in transgenic hairy roots. Moreover, a haplotype analysis detected ten haplotypes of GmCDF1 in 31 soybean genotypes. A candidate-gene association analysis showed that two SNPs in GmCDF1 were significantly associated with salt tolerance and that Hap1 was more sensitive to salt stress than Hap2. The results demonstrated that the expression level of GmCDF1 was negatively correlated with salt tolerance in the 31 soybean accessions (r = -0.56, P < 0.01). Taken together, these results not only indicate that GmCDF1 plays a negative role in soybean salt tolerance but also help elucidate the molecular mechanisms of salt tolerance and accelerate the breeding of salt-tolerant soybean.