Arterial spin labeling hyperperfusion in Rasmussen's encephalitis: Is it due to focal brain inflammation or a postictal phenomenon?

Background and purpose

The study evaluated the utility of arterial spin labeling (ASL) perfusion imaging in Rasmussen's encephalitis (RE).

Proteomic characterization of human early pro-angiogenic cells

Early pro-angiogenic cells (EPCs) have been shown to be involved in neovascularization, angiogenesis and re-endothelialization and cathepsin L inhibition blunted their pro-angiogenic effect. In the present study, we have analysed and mapped the proteome and secretome of human EPCs, utilizing a combination of difference in-gel electrophoresis (DIGE) and shotgun proteomics. A population of 206 protein spots were analysed, with 171 being identified in the cellular proteome of EPCs. 82 proteins were identified in their conditioned medium, including the alternative macrophage markers C-C motif chemokine 18 (CCL18) and the hemoglobin scavenger receptor CD163 as well as platelet factor 4 (CXCL4) and platelet basic protein (CXCL7) with “platelet alpha granule” being returned as the top category according to the Gene Ontology Annotation. Apart from cathepsin L, the cathepsin L inhibitor also attenuated the release of a wide range of other cathepsins and lysosomal proteins such as legumain, but stimulated the secretion of members of the S100 protein family. The data presented here are the most comprehensive characterization of protein expression and secretion in human EPCs to date and highlight the potential importance of cysteine proteases in the processing of platelet factors for their pro-angiogenic potential. This article is part of a special issue entitled, "Cardiovascular Stem Cells Revisited".     

CD133 cells from human umbilical cord blood reduce cortical damage and promote axonal growth in neonatal rat organ co-cultures exposed to hypoxia

To evaluate the effect of CD133⁺ cells (endothelial progenitor cells) on the hypoxia-induced suppression of axonal growth of cortical neurons and the destruction of blood vessels (endothelial cells), we used anterograde axonal tracing and immunofluorescence in organ co-cultures of the cortex and the spinal cord from 3-day-old neonatal rats. CD133⁺ cells prepared from human umbilical cord blood were added to the organ co-cultures after hypoxic insult, and axonal growth, vascular damage and apoptosis were evaluated. Anterograde axonal tracing with 1,1′-dioctadecyl-3,3,3′,3′-tetramethylindocarbocyanine perchlorate was used to analyze axonal projections from the cortex to the spinal cord. Immunolabeling co-cultured tissues of the cortex and the spinal cord were used to investigate the effect of CD133⁺ cells on the survival of blood vessels and apoptosis in the brain cortex. Hypoxia remarkably suppressed axonal growth in organ co-cultures of the cortex and the spinal cord, and this suppression was significantly restored by the addition of CD133⁺ cells. CD133⁺ cells also reduced the hypoxia-induced destruction of the cortical blood vessels and apoptosis. CD133⁺ cells had protective effects on hypoxia-induced injury of neurons and blood vessels of the brain cortex in vitro. These results suggest that CD133⁺ cell transplantation may be a possible therapeutic intervention for perinatal hypoxia-induced brain injury.     

Dynamic maternal and fetal Notch activity and expression in placentation

IntroductionMurine placentation requires trophoblast Notch2, while the Notch ligand, JAGGED1, is reduced in invasive trophoblasts from women with preeclampsia. However, the placental cells with active Notch signaling and expression of other Notch proteins and ligands in placentation have yet to be defined. We sought to identify endothelial cell and trophoblast subtypes with canonical Notch signaling in the decidua and placenta and correlate this to expression of Notch proteins and ligands.MethodsNotch reporter transgenic mice were used to define canonical Notch activity and immunofluorescence staining performed to characterize expression of Notch1, 2, 3, 4 and ligands, Delta-like 4 (Dll4) and Jagged1 (Jag1) during early placentation and in the mature placenta.ResultsNotch signaling is active in maternal and fetal endothelial cells and trophoblasts during early placentation and in the mature placenta. Dll4, Jag1, Notch1, and Notch4 are expressed in maternal vasculature in the decidua. Dll4, Jag1 and Notch1 are expressed in fetal vasculature in the labyrinth. Dll4, Notch2 and Notch4 are co-expressed in the ectoplacental cone. Notch2 and Notch4 are expressed in parietal-trophoblast giant cells and junctional zone trophoblasts with active canonical Notch signaling and in labyrinthine syncytiotrophoblasts and sinusoidal-trophoblast giant cells.DiscussionCanonical Notch activity and distinct expression patterns for Notch proteins and ligands was evident in endothelium and trophoblasts, suggesting Notch1, Notch2, Notch4, Dll4, and Jag1 have distinct and overlapping functions in placentation. Characterization of Notch signaling defects in existing mouse models of preeclampsia may shed light on the role of Notch in developing the preeclampsia phenotype.     

Impaired development and dysfunction of endothelial progenitor cells in type 2 diabetic mice

AimDysfunction of circulating endothelial progenitor cells (EPCs) has been shown to affect the development of microvascular diseases in diabetes patients. The aim of this study was to elucidate the development and mechanical dysfunction of EPCs in type 2 diabetes (T2D).MethodsThe colony-forming capacity of EPCs and differentiation potential of bone marrow (BM) c-Kit(+)/Sca-I(+) lineage-negative mononuclear cells (KSL) were examined in T2D mice, db/db mice and KKA^y mice, using EPC colony-forming assay (EPC-CFA).ResultsT2D mice had fewer BM stem/progenitor cells, and proliferation of KSL was lowest in the BM of db/db mice. In T2D mice, the frequency of large colony-forming units (CFUs) derived from BM-KSL was highly reduced, indicating dysfunction of differentiation into mature EPCs. Only a small number of BM-derived progenitors [CD34(+) KSL cells], which contribute to the supply of EPCs for postnatal neovascularization, was also found. Furthermore, in terms of their plasticity to transdifferentiate into various cell types, BM-KSL exhibited a greater potential to differentiate into granulocyte macrophages (GMs) than into other cell types.ConclusionT2D affected EPC colony formation and differentiation of stem cells to mature EPCs or haematopoietic cells. These data suggest opposing regulatory mechanisms for differentiation into mature EPCs and GMs in T2D mice.     

Differential Effects of Fondaparinux and Bemiparin on Angiogenic and Vasculogenesis-like processes

Introduction

Conventional therapy for venous thromboembolism or acute coronary syndrome involves the administration of glycoanticoagulants (heparins) or oligosaccharides (fondaparinux). We evaluated the effects of such drugs on angiogenesis and vasculogenesis-like models.

Materials and Methods

Human umbilical vein endothelial cells or human endothelial progenitor cells were treated with bemiparin, fondaparinux or unfractionated heparin, at concentrations reflecting the doses used in clinical practice. After 24 h, cell viability, proliferation, tubule formation and angiogenic molecular mechanisms, such as activation of the serine/threonine kinase AKT, were assessed. In vivo angiogenesis was studied using a Matrigel sponge assay in mice.

Results

Bemiparin gave a significant decrease of in vitro angiogenesis as shown by the reduction of endothelial cell tubule network, while both fondaparinux and unfractionated heparin did not show any significant effect. In assays of Matrigel sponge invasion in mice, unfractionated heparin was able to stimulate angiogenesis and, conversely, bemiparin inhibited angiogenesis. Furthermore, both bemiparin and fondaparinux caused a significant reduction in an in vitro vasculogenesis-like model, as demonstrated by the decrease of tubule network after co-seeding of endothelial progenitor cells and human umbilical vein endothelial cells. In addition, unfractionated heparin but not bemiparin was able to increase AKT phosphorylation.

Conclusions

In in vitro experiments, bemiparin was the only drug to show an anti-angiogenic and vasculogenic-like effect, unfractionated heparin showed only a trend to increase in angiogenesis assay and fondaparinux affected only the vasculogenesis-like model. Notably, the in vivo experiments corroborated these data. Such results are important for the choice of a patient-tailored therapy.     

乳腺包被性乳头状癌的临床病理分析

目的 探讨乳腺包被性乳头状癌（encapsulated papillary carcinoma, EPC）的临床病理学特征、诊断、治疗及预后。方法 回顾性分析新疆医科大学附属肿瘤医院病理科2010年1月-2013年12月间,诊断为囊内乳头状癌或包被性/包裹性乳头状癌35例及48例对照组导管内乳头状癌的临床病理资料及免疫表型。结果 EPC患者均为女性,年龄29~83岁,平均61岁,肿块大小平均2.4 cm (范围0.6~4 cm)。35例EPC中,22例为单纯性EPC、7例伴导管原位癌、4例伴微小浸润癌、2例伴非特殊类型浸润癌。35例EPC与48例导管内乳头状癌病变内部均未见肌上皮细胞,CK5/6及p63肌上皮染色结果显示,EPC病变周围肌上皮数量较导管内乳头状癌导管壁肌上皮数量明显减少,差异具有统计学意义（P<0.05）;35例EPC中80%激素受体阳性,5.71%HER2表达阳性。8例（22.86%）EPC患者行肿块切除,27例（77.14%）患者行乳房切除术,3例（8.57%）发生淋巴结转移。术后经随访2~48月,患者均存活。结论 乳腺包被性乳头状癌是一种好发于老年女性的恶性肿瘤,病变周缘肌上皮明显减少甚至缺如,单纯性EPC也可发生淋巴结转移,被认为是一种惰性的浸润癌,生物学行为介于原位癌与浸润癌之间。若单独发生或伴随原位癌及微小浸润癌时,应参照原位癌治疗, EPC伴随浸润癌时,应参照浸润癌的治疗标准进行。     

Experimental and clinical basis for the use of statins in patients with ischemic and nonischemic cardiomyopathy

Over the past 2 decades our understanding of the pathologic mechanisms that lead to heart failure (HF) has evolved from simplistic hemodynamic models to more complex models that have implicated neurohormonal activation and adverse cardiac remodeling as important mechanisms of disease progression. 3-Hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) have become a standard part of the armamentarium in the prevention and treatment of coronary artery disease. Apart from their lipid-lowering capabilities, statins seem to have non-lipid-lowering effects that impact neurohormonal activation and cardiac remodeling. This review will examine the potential benefits of statins in HF patients with ischemic and nonischemic cardiomyopathy as well as potential concerns regarding the use of statins in these patients.