Magnetic particles with perpendicular anisotropy for mechanical cancer cell destruction

We demonstrate the effectiveness of out-of-plane magnetized magnetic microdiscs for cancer treatment through mechanical cell disruption under an applied rotating magnetic field. The magnetic particles are synthetic antiferromagnets formed from a repeated motif of ultrathin CoFeB/Pt layers. In-vitro studies on glioma cells are used to compare the efficiency of the CoFeB/Pt microdiscs with Py vortex microdiscs. It is found that the CoFeB/Pt microdiscs are able to damage 62 ± 3% of cancer cells compared with 12 ± 2% after applying a 10 kOe rotating field for one minute. The torques applied by each type of particle are measured and are shown to match values predicted by a simple Stoner-Wohlfarth anisotropy model, giving maximum values of 20 fNm for the CoFeB/Pt and 75 fNm for the Py vortex particles. The symmetry of the anisotropy is argued to be more important than the magnitude of the torque in causing effective cell destruction in these experiments. This work shows how future magnetic particles can be successfully designed for applications requiring control of applied torques.This research was funded by NIH grant R01NS077388 ‘Magnetic Vortex Mixrodiscs for Glioma therapy’, the European Community under the Seventh Framework Program ERC contract No. 247368: 3SPIN, and the EPSRC Cambridge NanoDTC, EP/G037221/1

Soluble CD200 Correlates With Interleukin-6 Levels in Sera of COPD Patients: Potential Implication of the CD200/CD200R Axis in the Disease Course

BACKGROUND: COPD represents a multifactorial lung disorder with high morbidity and mortality. Despite intensive research concerning the underlying disease mechanisms, the involvement of the CD200/CD200R axis in supporting or preventing the onset of COPD has not yet been addressed. Since the CD200/CD200R axis is crucially implicated in the maintenance of pulmonary immune homeostasis, we hypothesized that it might be involved in controlling the onset of COPD.METHODS: To address this, we analyzed the serum samples from COPD patients and normal controls for soluble (s) CD200 and correlated the data to COPD-relevant clinical parameters. In addition, basic studies were conducted in CD200-deficient and wild-type mice in which COPD-like inflammation was induced with elastase/LPS followed by lung and serum component analysis.RESULTS: We observed a positive correlation between serum sCD200 and IL-6 levels as well as a trend toward a negative correlation of sCD200 with vitamin D3 in COPD patients. Further investigations in mice revealed that despite elevated serum concentration of MMP-9 in CD200KO mice, the early onset of COPD-like lung inflammation was similar in CD200-deficient and wild-type animals in terms of immune cell infiltration, emphysematous changes, and mucus overproduction.CONCLUSIONS: While our murine studies suggest that the co-inhibitory molecule CD200 does not appear to play a prominent role in the early onset of COPD-like features, correlation of sCD200 serum levels with COPD-related parameters in humans with established disease revealed that the CD200/CD200R axis may be mechanistically linked to the disease course in COPD patients.</p

Matrix metalloproteinase 9 expression: new regulatory elements

Retinal ganglion cells apoptosis is linked to matrix metalloproteinase 9 (MMP-9) controlled changes of extracellular matrix. Abnormal expression of MMP-9 is associated with glaucomatous alterations. Thus, the knowledge of MMP-9 regulation is important for the understanding the pathogenesis of glaucoma. Here, we investigated the role of 3′-untranslated regions (3′-UTR) and microRNAs in MMP-9 regulation. We used in vitro mutagenesis and Luc reporter system to identify regulatory elements in the 3′-UTR of MMP-9. microRNAs were analyzed by qRT-PCR, and their role was investigated with inhibitors and mimics. We identified targets for miRNAs in 3′-UTR of MMP-9 involved in the regulation of MMP-9 expression. We then isolated miRNAs from the optic nerve A7 astrocytes and 293 T cells and confirmed the role of mi340 in the regulation using specific inhibitors and mimics. The results obtained show a new miRNA-mediated mechanism of MMP-9 expression regulation