Glycosaminoglycans and their synthetic mimetics inhibit RANTES-induced migration and invasion of human hepatoma cells

The CC-chemokine regulated on activation, normal T-cell expressed, and presumably secreted (RANTES)/CCL5 mediates its biological activities through activation of G protein-coupled receptors, CCR1, CCR3, or CCR5, and binds to glycosaminoglycans. This study was undertaken to investigate whether this chemokine is involved in hepatoma cell migration or invasion and to modulate these effects in vitro by the use of glycosaminoglycan mimetics. We show that the human hepatoma Huh7 and Hep3B cells express RANTES/CCL5 G protein-coupled receptor CCR1 but not CCR3 nor CCR5. RANTES/CCL5 binding to these cells depends on CCR1 and glycosaminoglycans. Moreover, RANTES/CCL5 strongly stimulates the migration and the invasion of Huh7 cells and to a lesser extent that of Hep3B cells. RANTES/CCL5 also stimulates the tyrosine phosphorylation of focal adhesion kinase and activates matrix metalloproteinase-9 in Huh7 hepatoma cells, resulting in increased invasion of these cells. The fact that RANTES/CCL5-induced migration and invasion of Huh7 cells are both strongly inhibited by anti-CCR1 antibodies and heparin, as well as by beta-d-xyloside treatment of the cells, suggests that CCR1 and glycosaminoglycans are involved in these events. We then show by surface plasmon resonance that synthetic glycosaminoglycan mimetics, OTR4120 or OTR4131, directly bind to RANTES/CCL5. The preincubation of the chemokine with each of these mimetics strongly inhibited RANTES-induced migration and invasion of Huh7 cells. Therefore, targeting the RANTES-glycosaminoglycan interaction could be a new therapeutic approach for human hepatocellular carcinoma.     

Risk factors for metabolic syndrome after liver transplantation: A systematic review and meta-analysis

Introduction

Metabolic syndrome is associated with increased risk of cardiovascular events, which contributes to the elevated mortality rate among liver transplant recipients. The objective of this systematic review and meta-analysis was to assess the prevalence and risk factors for metabolic syndrome after liver transplantation.

RP-HPLC法测定克霉唑乳膏的含量和有关物质

目的 建立反相高效液相色谱法测定克霉唑乳膏含量及其有关物质.方法.色谱柱为Waters C1g(150cmX4.6mm,5pm),流动相为0.05mol/L磷酸二氢钾-甲醇(3:7)用稀磷酸调pH值至5.7~5.8,测定波长为215nm,流速为1.5mL/min,柱温为300C.结果 克霉唑在10.62-106.2gg/mL浓度范围内线性关系良好(r=0.9999),平均回收率为100.11%,RSD=0.89%(n=9).有关物质含量少于1%.结论 该方法准确、简便、快速、可靠,能有效控制克霉唑乳膏的质量.     

In vivo MR tracking of therapeutic microglia to a human glioma model

A knowledge of the spatial localization of cell vehicles used in gene therapy against glioma is necessary before launching therapy. For this purpose, MRI cell tracking is performed by labeling the cell vehicles with contrast agents. In this context, the goal of this study was to follow noninvasively the chemoattraction of therapeutic microglial cells to a human glioma model before triggering therapy. Silica nanoparticles grafted with gadolinium were used to label microglia. These vehicles, expressing constitutively the thymidine kinase suicide gene fused to the green fluorescent protein gene, were injected intravenously into human glioma-bearing nude mice. MRI was performed at 4.7 T to track noninvasively microglial accumulation in the tumor. This was followed by microscopy on brain slices to assess the presence in the glioma of the contrast agents, microglia and fusion gene through the detection of silica nanoparticles grafted with tetramethyl rhodamine iso-thiocyanate, 3,3'-dioctadecyloxacarbocyanine perchlorate and green fluorescent protein fluorescence, respectively. Finally, gancyclovir was administered systemically to mice. Human microglia were detectable in living mice, with strong negative contrast on T(2) *-weighted MR images, at the periphery of the glioma only 24 h after systemic injection. The location of the dark dots was identical in MR microscopy images of the extracted brains at 9.4 T. Fluorescence microscopy confirmed the presence of the contrast agents, exogenous microglia and suicide gene in the intracranial tumor. In addition, gancyclovir treatment allowed an increase in mice survival time. This study validates the MR tracking of microglia to a glioma after systemic injection and their use in a therapeutic strategy against glioma.     

Cortical responses to the mirror box illusion: a high-resolution EEG study

The mirror box illusion has proven a helpful therapy in pathologies such as phantom limb pain, and although the effect has been suggested to be a result of the interaction between pain, vision, touch, and proprioception, the mechanisms are still unknown. Multichannel (124) brain responses were investigated in healthy men (N = 11) and women (N = 14) during the mirror box illusion. Tactile somatosensory evoked potentials were recorded from the right thumb during two control conditions and two illusions: (control 1) no mirror: looking at the physical right thumb during stimulation, (control 2) no mirror: looking at the physical left thumb during stimulation, (illusion 1) mirror: the illusion that both thumbs were stimulated, and (illusion 2) mirror: the illusion that none of the thumbs were stimulated. In men, a significant medial shift in the y coordinate of the N70 dipole in illusion 2 (P = 0.021) was found when compared with illusion 1. No dipole shift was found for women. Additionally, men showed higher prevalence of P180 cingulate cortex activation during illusion 2 when compared with control 1 and 2 (P = 0.002). During illusion 2, the degree of conformity with the statement "The hand in the mirror feels like my other hand" was negatively correlated with the N70 x coordinate for men and positively correlated with the N70 z coordinate for women. In conclusion, short-term cortical plasticity can be induced by a mismatch between visual input and location of tactile stimulation in men. The present study suggests that gender differences exist in the perception of the mirror box illusion.     

Species identification of clinical isolates of anaerobic bacteria: a comparison of two matrix-assisted laser desorption ionization-time of flight mass spectrometry systems

We compared two matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) systems (Shimadzu/SARAMIS and Bruker) on a collection of consecutive clinically important anaerobic bacteria (n = 290). The Bruker system had more correct identifications to the species level (67.2% versus 49.0%), but also more incorrect identifications (7.9% versus 1.4%). The system databases need to be optimized to increase identification levels. However, MALDI-TOF MS in its present version seems to be a fast and inexpensive method for identification of most clinically important anaerobic bacteria.     

EULID Project: European Living Donation and Public Health

The choice of transplantation from a living donor offers advantages over a deceased donor. However, it also carries disadvantages related to donor risks in terms of health and safety. Furthermore, there are several controversial ethical aspects to be taken into account. Several national and international institutions and the scientific community have stated standards that have great influence on professional codes and legislations. Living organ donation and transplantation are to some extent regulated by parliamentary acts in most European countries. It is necessary to take a step forward to develop a legal framework to regulate all of these processes to guarantee the quality and to prevent illegal and nonethical practices. It is also necessary to develop and implement living donor protection practices not only in terms of physical health, but also to minimize potential impacts on the psychological, social, and economic spheres. Finally, an additional effort should be made to create a database model with recommendations for registration practices as part of the standardized follow-up care for the living donor. The European Living Donation (EULID) project's (http://www.eulivingdonor.eu/) main objective was to contribute to a European consensus to set standards and recommendations about legal, ethical, and living donor protection practices to guarantee the health and safety of living donors.