BackgroundSplenic artery embolization (SAE) has been an effective adjunct to the Non-operative management (NOM) for blunt splenic injury (BSI). However, the optimal embolization techniques are still inconclusive. To further understand the roles of different embolization locations and embolic materials in SAE, we conducted this system review and meta-analyses.MethodsClinical studies related to SAE for adult patients were researched in electronic databases, included PubMed, Embase, ScienceDirect and Google Scholar Search (between October 1991 and March 2013), and relevant information was extracted. To eliminate the heterogeneity, a sensitivity analysis was conducted on two reduced study sets. Then, the pooled outcomes were compared and the quality assessments were performed using Newcastle-Ottawa Scale (NOS). The SAE success rate, incidences of life-threatening complications of different embolization techniques were compared by χ 2 test in 1st study set. Associations between different embolization techniques and clinical outcomes were evaluated by fixed-effects model in 2nd study set.ResultsTwenty-three studies were included in 1st study set. And then, 13 of them were excluded, because lack of the necessary details of SAE. The remaining 10 studies comprised 2nd study set, and quality assessments were performed using NOS. In 1st set, the primary success rate is 90.1% and the incidence of life-threatening complications is 20.4%, though the cases which required surgical intervention are very few (6.4%). For different embolization locations, there was no obvious association between primary success rate and embolization location in both 1st and 2nd study sets (P > 0.05). But in 2nd study set, it indicated that proximal embolization reduced severe complications and complications needed surgical management. As for the embolic materials, the success rate between coil and gelfoam is not significant. However, coil is associated with a lower risk of life-threatening complications, as well as less complications requiring surgical management.ConclusionsDifferent embolization techniques affect the clinical outcomes of SAE. The proximal embolization is the best option due to the less life-threatening complications. For commonly embolic material, coil is superior to gelfoam for fewer severe complications and less further surgery management.

CREG protects heart against MI/R injury-induced cardiomyocytes apoptosis by activating lysosomal autophagy. This article is part of a Special Issue entitled: Genetic and epigenetic control of heart failure - edited by Jun Ren and Megan Yingmei Zhang.

Talin is a cytoskeletal protein that binds to integrin ␤ cytoplasmic tails and regulates integrin activation. Talin1 ablation in mice disrupts gastrulation and causes embryonic lethality. However, the role of talin in mammalian epithelial morphogenesis is poorly understood. Here we demonstrate that embryoid bodies (EBs) differentiated from talin1-null embryonic stem cells are defective in integrin adhesion complex assembly, epiblast elongation, and lineage differentiation. These defects are accompanied by a significant reduction in integrin ␤1 protein levels due to accelerated degradation through an MG-132-sensitive proteasomal pathway. Overexpression of integrin ␤1 or MG-132 treatment in mutant EBs largely rescues the phenotype. In addition, epiblast cells isolated from talin1-null EBs exhibit impaired cell spreading and focal adhesion formation. Transfection of the mutant cells with green fluorescent protein (GFP)-tagged wild-type but not mutant talin1 that is defective in integrin binding normalizes integrin ␤1 protein levels and restores focal adhesion formation. Significantly, cell adhesion and spreading are also improved by overexpression of integrin ␤1. All together, these results suggest that talin1 binding to integrin promotes epiblast adhesion and morphogenesis in part by preventing integrin ␤1 degradation.Talin is a 270-kDa adaptor protein that is localized predominantly in macromolecular complexes formed at the junctions between cells and the extracellular matrix (ECM) where it has been shown to connect the integrin family of cell adhesion molecules to the actin cytoskeleton (4,9,20,43,50). In addition, talin is thought to be a key regulator of integrin activation (1, 45), and small interfering RNA (siRNA)-mediated knockdown of talin in various cell lines reduced the affinity of ␤1 and ␤3 integrins for their ligands (47). In vivo, conditional deletion of the talin1 gene in mouse platelet precursors inhibited ligand-induced ␣IIb␤3 integrin activation and platelet aggregation, leading to impaired hemostasis in the whole animal (13,36,40). Similarly, in B-lymphocytes, talin1 is required for ␣4␤1 (VLA-4) and ␣ L ␤2 (LFA-1) integrin activation and thereby for homing to lymph nodes and bone marrow (31).At the organismal level, talin is required for embryonic development and tissue morphogenesis. In Caenorhabditis elegans, RNA interference-induced talin suppression impaired distal tip cell migration and disrupted the muscle actin cytoskeleton, leading to gonad malformation and paralysis (8). In Drosophila melanogaster, talin is concentrated at the muscle attachment site in an integrin-dependent manner. Talin-null mutants die during embryogenesis, displaying a muscle detachment phenotype similar to that conferred by integrin-null mutations (3). In these invertebrates, talin functions mainly to link ECM-bound integrins to the actin cytoskeleton during tissue morphogenesis and maintenance (15). The mutant phenotype is evident when the actin cytoskeleton is under stress conditions, such as muscle contraction an...

The tumor suppressor phosphatase and tensin homolog (PTEN) dephosphorylates PIP3 and antagonizes the prosurvival PI3K-Akt pathway. Targeted deletion of PTEN in mice led to early embryonic lethality. To elucidate its role in embryonic epithelial morphogenesis and the underlying mechanisms, we used embryonic stem cell-derived embryoid body (EB), an epithelial cyst structurally similar to the periimplantation embryo. PTEN is upregulated during EB morphogenesis in parallel with apoptosis of core cells, which mediates EB cavitation. Genetic ablation of PTEN causes Akt overactivation, apoptosis resistance and cavitation blockade. However, rescue experiments using mutant PTEN and pharmacological inhibition of Akt suggest that the phosphatase activity of PTEN and Akt are not involved in apoptosis-mediated cavitation. Instead, hypoxia-induced upregulation of Bnip3, a proapoptotic BH3-only protein, mediates PTEN-dependent apoptosis and cavitation. PTEN inactivation inhibits hypoxia-and reactive oxygen species-induced Bnip3 elevation. Overexpression of Bnip3 in PTEN-null EBs rescues apoptosis of the core cells. Mechanistically, suppression of Bnip3 following PTEN loss is likely due to reduction of hypoxia-inducible factor-2α (HIF-2α) because forced expression of an oxygen-stable HIF-2α mutant rescues Bnip3 expression and apoptosis. Lastly, we show that HIF-2α is upregulated by PTEN at both transcriptional and posttranscriptional levels. Ablation of prolyl hydroxylase domain-containing protein 2 (PHD2) in normal EBs or inhibition of PHD activities in PTEN-null EBs stabilizes HIF-2α and induces Bnip3 and caspase-3 activation. Altogether, these results suggest that PTEN is required for apoptosis-mediated cavitation during epithelial morphogenesis by regulating the expression of HIF-2α and Bnip3.

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