Effects of regional anesthesia aided sedation on patients’ psychological stress and postoperative recovery
Ontology highlight
ABSTRACT:
DISEASE(S): Colorectal Cancer
PROVIDER: 2665415 | ecrin-mdr-crc |
REPOSITORIES: ECRIN MDR
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Project description:General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 + T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 + T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation.
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Project description:Ciprofol is a new anesthetic, which combines with γ- Aminobutyric acid-a (GABAA) receptor. Ciprofol has shown equivalent anesthetic efficacy of propofol at 1/4 to 1/5 of the dosage. Ciprofol has the pharmacodynamic characteristics of rapid onset, stable and rapid recovery. Phase III clinical results showed that the incidence of injection pain and respiratory and circulatory depression of ciprofol was lower than that of propofol. Therefore, ciprofol has a good application prospect in sedation for gastrointestinal endoscopy, especially for obese patients. In the current study, we would explore the proper dose of Ciprofol in sedated gastrointestinal endoscopy in obese patients.
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Project description:1H Nuclear Magnetic Resonance (NMR) spectroscopy was used to investigate the metabolic consequences of general anesthesia in the plasma of two groups of patients with diagnosis for non-metastatic colorectal cancer and metastatic colorectal cancer with liver-metastasis, respectively. Patients were treated with Etomidate or Propofol, two frequently used sedation agents. Plasma samples were obtained via Ficoll separation. Here, we demonstrated that this procedure introduces a number of limitations for NMR-based metabolomics studies, due to the appearance of spurious signals. Nevertheless, the comparison of the 1H NMR metabolomic profiles of patients treated with Etomidate or Propofol at equipotent dose ranges was still feasible and proved that both agents significantly decrease the plasma levels of several NMR-detectable metabolites. Consequently, samples collected during anesthesia are not suitable for metabolic profiling studies aimed at patient stratification, because interpersonal variability are reduced by the overall depression of metabolites levels. On the other hand, this study showed that plasma metabolomics could represent a valuable tool to monitor the effect of different sedation agents and/or the individual metabolic response to anesthesia, providing hints for an appropriate tuning of personalized sedation procedures. In our reference groups, the metabolomic signatures were slightly different in patients anesthetized with Etomidate versus Propofol. The importance of standardized collection procedures and availability of exhaustive metadata of the experimental design for the accurate evaluation of the significance of the observed changes in metabolites levels are critically discussed.
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Project description:Chloride intracellular channels (CLICs) are a unique family of evolutionarily conserved metamorphic proteins, switching between stable conformations based on redox conditions. CLICs have been implicated in a wide variety biological processes including ion channel activity, apoptosis, membrane trafficking, and enzymatic oxidoreductase activity. Understanding the molecular mechanisms by which CLICs engage in these activities is an area of active research. Here, the sole Drosophila melanogaster ortholog, Clic, was targeted for RNAi knockdown to identify genes and biological processes associated with Clic expression. Clic knockdown had a substantial impact on global transcription, altering expression of over 9% of transcribed Drosophila genes. Overrepresentation analysis of differentially expressed genes identified enrichment of 23 Gene Ontology terms including Cytoplasmic Translation, Oxidation-Reduction Process, Heme Binding, Membrane, Cell Junction, and Nucleolus. The top term, Cytoplasmic Translation, was enriched almost exclusively with downregulated genes. Drosophila Clic and vertebrate ortholog Clic4 have previously been tied to ethanol sensitivity and ethanol-regulated expression. Clic knockdown-responsive genes from the present study were found to overlap significantly with gene sets from 4 independently published studies related to ethanol exposure and sensitivity in Drosophila. Bioinformatic analysis of genes shared between these studies revealed an enrichment of genes related to amino acid metabolism, protein processing, oxidation-reduction processes, and lipid particles among others. To determine whether the modulation of ethanol sensitivity by Clic may be related to co-regulated oxidation-reduction processes, we evaluated the effect of hyperoxia on ethanol sedation in Clic knockdown flies. Consistent with previous findings, Clic knockdown reduced acute ethanol sedation sensitivity in flies housed under nomoxia. However, this effect was reversed by exposure to hyperoxia, suggesting a common set of molecular-genetic mechanism may modulate each of these processes. This study suggests that Drosophila Clic has a major influence on regulation of oxidative stress signaling and that this function overlaps with the molecular mechanisms of acute ethanol sensitivity in the fly.
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Project description:We sequenced microRNA from heads of two D. melanogaster populations: an ethanol treated group (30 minutes after sedation with ethanol saturated vapor), and an age-matched untreated control group; and calculated differential microRNA expression between the two groups.
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Project description:Propofol is an intravenous anesthetic that has been widely used in the clinical setting. Besides its anesthetic effects, propofol has been reported to influence the regulation of autonomic system. Controversies exist with regards to whether propofol exposure is safe for pregnant women and young children. The recent emergence of human induced pluripotent stem cells (hiPSCs) has provided a promising and theoretically inexhaustible source of neural progenitor cells (NPCs) for drug testing, which could be extended to in vitro experiments for anesthetics such as propofol. NPCs derived from three hiPSC lines, NES-GFP (a NESTIN-GFP reporter), USCK7 (iPSCs derived from urine derived cells), and ND2-0 (NIH), were treated with propofol at different concentrations (20, 50, 100 and 300 µM) for 6 h or 24 h. Early and late cell injury, cell proliferation and apoptosis were evaluated. Comparison of genome-wide gene expression profiles was performed for propofol-treated and untreated control iPSC-NPCs. Propofol treatment of NPCs for 6 h at the clinically relevant concentration (20 or 50 µM) did not affect cell viability, apoptosis, or proliferation, while propofol at higher concentration (100 or 300 µM) decreased NPC viability and induced apoptosis. Prolonged treatment of propofol for 24 h significantly decreased cell viability. In addition, 20 µM propofol treatment for 6 h did not alter global gene expression. Higher concentration of propofol exerted potential cytotoxicity via multiple cellular mechanisms. In summary, propofol treatment at commonly practiced clinical doses for 6 h did not have adverse effects on hiPSC-derived NPCs. In contrast, longer exposure and/or higher concentration of propofol treatment could decrease NPC viability and induce apoptosis.
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