Metabolic syndrome: definitions and controversies

Metabolic syndrome (MetS) is a complex disorder defined by a cluster of interconnected factors that increase the risk of cardiovascular atherosclerotic diseases and diabetes mellitus type 2. Currently, several different definitions of MetS exist, causing substantial confusion as to whether they identify the same individuals or represent a surrogate of risk factors. Recently, a number of other factors besides those traditionally used to define MetS that are also linked to the syndrome have been identified. In this review, we critically consider existing definitions and evolving information, and conclude that there is still a need to develop uniform criteria to define MetS, so as to enable comparisons between different studies and to better identify patients at risk. As the application of the MetS model has not been fully validated in children and adolescents as yet, and because of its alarmingly increasing prevalence in this population, we suggest that diagnosis, prevention and treatment in this age group should better focus on established risk factors rather than the diagnosis of MetS

Anti-septic effects of pelargonidin on HMGB1-induced responses in vitro and in vivo

A certain nucleosomal protein-high mobility group box-1 (HMGB1)-has recently been established as a late mediator of sepsis, with a relatively wide therapeutic window for pharmacological intervention. Pelargonidin (PEL) is a well-known red pigment found in plants; it has important biological activities that are potentially beneficial for human health. In the present study, we investigated whether PEL can modulate HMGB1-mediated inflammatory responses in human umbilical vein endothelial cells (HUVECs) and in mice. The anti-inflammatory activities of PEL were determined by measuring permeability, leukocyte adhesion and migration, and activation of pro-inflammatory proteins in HMGB1-activated HUVECs and mice, as well as the beneficial effects of PEL on survival rate in the mouse sepsis model. The data showed that PEL had effectively inhibited lipopolysaccharide (LPS)-induced release of HMGB1 and suppressed HMGB1-mediated septic responses, such as hyperpermeability, adhesion and migration of leukocytes, and expression of cell adhesion molecules. Furthermore, PEL inhibited the HMGB1-mediated production of tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6), as well as the activation of nuclear factor-kappa B (NF-kappa B) and extracellular signal-regulated kinases 1 and 2 (ERK1/2). Collectively, these results indicate that PEL could be used to treat various severe vascular inflammatory diseases via the inhibition of the HMGB1 signaling pathway.close

Bornyl caffeate induces apoptosis in human breast cancer MCF-7 cells via the ROS- and JNK-mediated pathways

AIM: The purpose of the present study was to investigate the anticancer activity of bornyl caffeate in the human breast cancer cell line MCF-7. METHODS: The cell viability was determined using the MTT assay, and apoptosis was initially defined by monitoring the morphology of the cell nuclei and staining an early apoptotic biomarker with Annexin V-FITC. The mitochondrial membrane potential was visualized by JC-1 under fluorescence microscopy, whereas intracellular reactive oxygen species (ROS) were assessed by flow cytometry. The expression of apoptosis-associated proteins was determined by Western blotting analysis. RESULTS: Bornyl caffeate induced apoptosis in MCF-7 cells in a dose- and time-dependent manner. Consistently, bornyl caffeate increased Bax and decreased Bcl-xl, resulting in the disruption of MMP and subsequent activation of caspase-3. Moreover, bornyl caffeate triggered the formation of ROS and the activation of the mitogen-activated protein (MAP) kinases p38 and c-Jun N-terminal kinase (JNK). Antioxidants attenuated the activation of MAP kinase p38 but barely affected the activation of JNK. Importantly, the cytotoxicity of bornyl caffeate was partially attenuated by scavenging ROS and inhibited by MAP kinases and caspases. CONCLUSION: The present study demonstrated that bornyl caffeate induced apoptosis in the cancer cell line MCF-7 via activating the ROS- and JNK-mediated pathways. Thus, bornyl caffeate may be a potential anticancer lead compound