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Chemical topology refers to the three-dimensional arrangement (i.e., connectivity and spatial relationship) of a molecule's constituent atoms and bonds. The molecular mechanism for translation defines the linear configuration of all nascent proteins. Nontrivial protein topology arises only upon post-translational processing events and often imparts functional benefits such as enhanced stability, making topology a unique dimension for protein engineering. Utilizing the assembly-reaction synergy, our group has developed several methods for the effective and convenient cellular synthesis of a variety of topological proteins, such as lasso proteins, protein rotaxanes, and protein catenanes. The work opens the access to new protein classes and paves the road toward illustrating the topological effects on structure-function relationship of proteins, which lays solid foundation for exploring topological proteins' practical application. [ABSTRACT FROM AUTHOR]

Background: Simulation-based training (SBT) has become a standard for medical education. However, the efficacy of simulation based training in airway management education remains unclear. Methods: The aim of this study was to evaluate all published evidence comparing the effectiveness of SBT for airway management versus non-simulation based training (NSBT) on learner and patient outcomes. Systematic review with meta-analyses were used. Data were derived from PubMed, EMBASE, CINAHL, Scopus, the Cochrane Controlled Trials Register and Cochrane Database of Systematic Reviews from inception to May 2016. Published comparative trials that evaluated the effect of SBT on airway management training in compared with NSBT were considered. The effect sizes with 95% confidence intervals (CI) were calculated for outcomes measures. Results: Seventeen eligible studies were included. SBT was associated with improved behavior performance [standardized mean difference (SMD):0.30, 95% CI: 0.06 to 0.54] in comparison with NSBT. However, the benefits of SBT were not seen in time-skill (SMD:-0.13, 95% CI: -0.82 to 0.52), written examination score (SMD: 0.39, 95% CI: -0.09 to 0.86) and success rate of procedure completion on patients [relative risk (RR): 1.26, 95% CI: 0.96 to 1.66]. Conclusion: SBT may be not superior to NSBT on airway management training. [ABSTRACT FROM AUTHOR]

Background: It has been demonstrated that κ-opioid receptor agonists can reduce hypoxia-ischemia brain injury in animal models. However, it is unclear how the κ-opioid receptor responds to hypoxia-ischemia. In the current study, the authors used an in vitro model of oxygen-glucose deprivation and reoxygenation to explore how κ-opioid receptors respond to hypoxia and reoxygenation.Methods: Mouse neuroblastoma Neuro2A cells were stably transfected with mouse κ-opioid receptor-tdTomato fusion protein or Flag-tagged mouse κ-opioid receptor, divided into several groups (n = 6 to 12), and used to investigate the κ-opioid receptor movement. Observations were performed under normal oxygen, at 30 min to 1 h after oxygen-glucose deprivation and at 1 h after reoxygenation using high-resolution imaging techniques including immunoelectronmicroscopy in the presence and absence of κ-opioid receptor antagonist, dynamin inhibitors, potassium channel blockers, and dopamine receptor inhibitor.Results: Hypoxic conditions caused the κ-opioid receptor to be internalized into the cells. Inhibition of dynamin by Dyngo-4a prevented the receptor internalization. Interestingly, a specific κ-opioid receptor antagonist norbinaltorphimine blocked internalization, suggesting the involvement of activation of a specific κ-opioid receptor. κ-Opioid receptor internalization appears to be reversed by reoxygenation. Quantities of intracellular κ-opioid receptor-associated gold particles as demonstrated by immunoelectron microscopy were increased from 37 to 85% (P < 0.01) after oxygen-glucose deprivation. Potassium channel blockers and dopamine receptor inhibitor failed to block hypoxia-induced κ-opioid receptor internalization.Conclusions: Hypoxia induces reversible κ-opioid receptor internalization, which was inhibited by selective κ-opioid receptor antagonists or dynamin inhibitor, and can be reversed by reoxygenation in neuroblastoma cells, indicating the modulating effects between κ-opioid receptor and hypoxia via κ-opioid receptor activation and the dynamin-dependent mechanism. [ABSTRACT FROM AUTHOR]

γHerkinorin is an opiate analgesic with limited adverse effects, functioning as a primary selective atypical opioid μ agonist. The present study aimed to identify whether herkinorin has a positive effect on ischemic/reperfusion (I/R) injury. Adult male C57BL/6 mice were randomly divided into five groups: i) Naïve, ii) sham, iii) I/R, iv) I/R with dimethyl sulfoxide (I/R+D) and v) I/R with herkinorin (I/R+H). The I/R injury model was induced by occluding the middle cerebral artery for 1 h followed by 24 h or 7 days of reperfusion. Neurobehavioral scores and sensorimotor functions were examined 24 h and 7 days following reperfusion. In addition, infarct volumes were examined at these time points using a 2,3,5‑triphenyltetrazolium chloride assay. Herkinorin treatment improved neurobehavioral and sensorimotor functional recovery from I/R‑induced brain injury. There was a significant decrease in infarct volume in the I/R+H group at 24 h or 7 days following reperfusion compared with the I/R and I/R+D groups. Western blotting suggested that the decrease in conventional protein kinase C γ (cPKCγ) membrane translocation in the peri‑infarct region may be attenuated by herkinorin pretreatment. These results indicated that herkinorin may be beneficial in I/R‑induced mouse brain injury, and this may be attributed to the membrane translocation of cPKCγ following activation. [ABSTRACT FROM AUTHOR]

The inhalation anesthetic isoflurane has been reported to induce caspase activation and apoptosis, which may lead to learning and memory impairment. However, the underlying mechanisms of these effects are largely unknown. Isoflurane has been shown to induce elevation of cytosol calcium levels, accumulation of reactive oxygen species (ROS), opening of the mitochondrial permeability transition pore, reduction in mitochondria membrane potential, and release of cytochrome c. The time course of these effects, however, remains to be determined. Therefore, we performed a pilot study to determine the effects of treatment with isoflurane for various times on ROS levels in HEK-293 cells. The cells were treated with 2% isoflurane plus 21% O2 and 5% CO2 for 15, 30, 60, or 90 min. We then used fluorescence imaging and microplate fluorometer to detect ROS levels. We show that 2% isoflurane for 60 or 90 min, but not 15 or 30 min, induced ROS accumulation in the cells. These data illustrated that isoflurane could cause time-dependent effects on ROS levels. These findings have established a system to further determine the time course effects of isoflurane on cellular and mitochondria function. Ultimately, the studies would elucidate, at least partially, the underlying mechanisms of isoflurane-induced cellular toxicity. [ABSTRACT FROM AUTHOR]

Background: Accumulation of β-amyloid protein (Aβ) and tau protein is the main feature of Alzheimer disease neuro-pathogenesis. Anesthetic isoflurane, but not desflurane, may increase Aβ levels in vitro and in animals. Therefore, we set out to determine the effects of isoflurane and desflurane on cerebrospinal fluid (CSF) levels of Aβ and tau in humans. Methods: The participants were assigned into spinal anesthesia (N = 35), spinal plus desflurane anesthesia (N = 33), or spinal plus isoflurane anesthesia (N = 38) group by randomization using computer-generated lists. Pre- and postoperative human CSF samples were obtained through an inserted spinal catheter. The levels of Aβ (Aβ40 and Aβ42) and total tau in the CSF were determined. Results: Here, we show that isoflurane, but not desflurane, was associated with an increase in human CSF Aβ40 levels (from 10.90 to 12.41 ng/ml) 24h after the surgery under anesthesia compared to spinal anesthesia (from 11.59 to 11.08 ng/ml), P = 0.022. Desflurane, but not isoflurane, was associated with a decrease in Aβ42 levels 2h after the surgery under anesthesia (from 0.39 to 0.35 ng/ml) compared to spinal anesthesia (from 0.43 to 0.44ng/ml), P = 0.006. Isoflurane and desflurane did not significantly affect the tau levels in human CSF. Conclusions: These studies have established a system to study the effects of anesthetics on human biomarkers associated with Alzheimer disease and cognitive dysfunction. These findings have suggested that isoflurane and desflurane may have different effects on human CSF Aβ levels. [ABSTRACT FROM AUTHOR]