ß-Elemene Inhibits the Proliferation and Migration of Human Glioblastoma Cell Lines via Suppressing Ring Finger Protein 135.

ß-Elemene is commonly used as an anti-cancer agent in different types of cancers and its effects on glioblastoma have been studied through different pathways. However, its effect through ring finger protein 135 (RNF135, OMIM 611358) (RNF135), which is upregulated in glioblastomas, has not yet been explored. The current study is focused on the effects of ß-elemene on human glioblastoma cell lines U251, U118, A172 and U87 through RNF13 5. A cell counting kit-8 assay and wound healing assay have been utilized to test the proliferation and migration of the cells. Western blot and quantitative real-time-polymerase chain reaction (qRT-PCR) were used to evaluate the level of expression of RNF135. A model of nude mice was used to explore progression of the tumor in vivo. It was observed that increasing treatment time or dose of ß-elemene remarkably decreased viability of the cells. The cells that were treated with ß-elemene had a much lower speed of moving toward the gap in comparison to untreated cell lines. ß-Elemene-treated cells showed a much lower level of expression of RNF135 mRNA than control groups (p <0.05) and the levels of RNF135 protein were lower in the cells treated with ß-elemene than in control groups (p <0.05). Moreover, tumor progression in subcutaneous xenograft nude mice was delayed with the injection of ß-elemene. Altogether, our findings suggest that ß-elemene inhibits proliferation, migration and tumorigenicity of human glioblastoma cells through suppressing RNF135.

Plasma-derived human C1-esterase inhibitor does not prevent mechanical ventilation-induced pulmonary complement activation in a rat model of Streptococcus pneumoniae pneumonia.

Mechanical ventilation has the potential to cause lung injury, and the role of complement activation herein is uncertain. We hypothesized that inhibition of the complement cascade by administration of plasma-derived human C1-esterase inhibitor (C1-INH) prevents ventilation-induced pulmonary complement activation, and as such attenuates lung inflammation and lung injury in a rat model of Streptococcus pneumoniae pneumonia. Forty hours after intratracheal challenge with S. pneumoniae causing pneumonia rats were subjected to ventilation with lower tidal volumes and positive end-expiratory pressure (PEEP) or high tidal volumes without PEEP, after an intravenous bolus of C1-INH (200 U/kg) or placebo (saline). After 4 h of ventilation blood, broncho-alveolar lavage fluid and lung tissue were collected. Non-ventilated rats with S. pneumoniae pneumonia served as controls. While ventilation with lower tidal volumes and PEEP slightly amplified pneumonia-induced complement activation in the lungs, ventilation with higher tidal volumes without PEEP augmented local complement activation more strongly. Systemic pre-treatment with C1-INH, however, failed to alter ventilation-induced complement activation with both ventilation strategies. In accordance, lung inflammation and lung injury were not affected by pre-treatment with C1-INH, neither in rats ventilated with lower tidal volumes and PEEP, nor rats ventilated with high tidal volumes without PEEP. Ventilation augments pulmonary complement activation in a rat model of S. pneumoniae pneumonia. Systemic administration of C1-INH, however, does not attenuate ventilation-induced complement activation, lung inflammation, and lung injury.

Plasma-derived human antithrombin attenuates ventilator-induced coagulopathy but not inflammation in a Streptococcus pneumoniae pneumonia model in rats.

BACKGROUND: Mechanical ventilation exaggerates pneumonia-associated pulmonary coagulopathy and inflammation. We hypothesized that the administration of plasma-derived human antithrombin (AT), one of the natural inhibitors of coagulation, prevents ventilator-induced pulmonary coagulopathy, inflammation and bacterial outgrowth in a Streptococcus pneumoniae pneumonia model in rats. METHODS: Forty-eight hours after induction of S. pneumoniae pneumonia rats were subjected to mechanical ventilation (tidal volume 12 mL kg(-1), positive end-expiratory pressure 0 cmH(2)O and inspired oxygen fraction 40%). Rats were randomized to systemic treatment with AT (250 IU administered intravenously (i.v.) before the start of mechanical ventilation) or placebo (saline). Non-ventilated, non-infected rats and non-ventilated rats with pneumonia served as controls. The primary endpoints were pulmonary coagulation and inflammation in bronchoalveolar lavage fluid (BALF). RESULTS: Pneumonia was characterized by local activation of coagulation and inhibition of fibrinolysis, resulting in increased levels of fibrin degradation products and fibrin deposition in the lung. Mechanical ventilation exaggerated pulmonary coagulopathy and inflammation. Systemic administration of AT led to supra-normal BALF levels of AT and decreased ventilator-associated activation of coagulation. AT neither affected pulmonary inflammation nor bacterial outgrowth from the lungs or blood. CONCLUSIONS: Plasma-derived human AT attenuates ventilator-induced coagulopathy, but not inflammation and bacterial outgrowth in a S. pneumoniae pneumonia model in rats.

Induction of a hypometabolic state during critical illness - a new concept in the ICU?

Induced hypothermia after cardiopulmonary resuscitation provides organ protection and is currently considered standard of care in clinical practice. An increasing number of reports indicate that induced hypothermia is also beneficial in other conditions of hypoxia-induced organ injury, including brain injury, intestinal ischaemia-reperfusion injury and acute lung injury. The mechanism of the protective effect is thought to be caused by a reduction in metabolism. A hibernation-like state, characterised by hypothermia, bradypnoea and a reduction in metabolic rate, was induced in animals that normally do not hibernate, after inhalation of hydrogen sulphide. This state was termed a 'suspended animation-like state'. In critically ill patients, an exaggerated systemic inflammatory response is common, which often results in multiple organ injury. Inducing a hypometabolic state during critical illness may limit organ injury by reducing oxygen consumption, constituting a fascinating new therapeutic perspective for the treatment of critically ill patients. In this manuscript, we describe mitochondrial dysfunction during critical illness and preclinical data that suggest a potential therapeutic possibility of lowering metabolism. In addition, we discuss issues that warrant further research before clinical applicability.