Propofol Concentrations Research Articles

Propofol enhances the lethality of cisplatin on liver cancer cells by up-regulating miR-195-5p

Literatures have demonstrated that propofol can improve the efficacy of cisplatin, and miR-195 is implicated in the underlying mechanism concerning the anticancer effects of propofol. However, correlation between propofol and miR-195 has been little studied. This study clarified that propofol enhanced the inhibitory effect of cisplatin in liver cancer cells via miR-195-5p. 50 samples of liver cancer and para-cancer tissues in patients were collected and the difference in the expression of miR-195-5p was then analyzed. The liver cancer cells treated with gradient concentrations of cisplatin (3, 6.25, 12.5, 25, 50 μg/mL) and propofol (2, 5, 10 μg/mL) were tested for drug toxicity using CCK-8 assay. Next, following the transfection, the effects of propofol, cisplatin and miR-195-5p on the functions of liver cancer cells and the expressions of related proteins were analyzed by clone formation, flow cytometry and western blot. The downstream target genes of miR-195-5p were predicted by bio-informatics analysis and verified by dual-luciferase reporter assay, and their expressions in cancer cell was also calculated. The changes on the expressions of target genes were further detected by qRT-PCR and western blot. MiR-195-5p was lowly-expressed in liver cancer, and the up-regulation of miR-195-5p enhanced the sensitivity of liver cancer cells to cisplatin. Propofol inhibited the viability of liver cancer cells and stimulated the up-regulation of miR-195-5p. Propofol enhanced the lethality of cisplatin to liver cancer cells and reversed the repressive effects of miR-195-5p inhibitor on the efficacy of cisplatin. CCNE1 was the downstream target gene of miR-195-5p and its expression was up-regulated by miR-195-5p inhibitor in cisplatin-treated liver cancer cells. Collectively, propofol enhances the lethality of cisplatin to liver cancer cells by up-regulating miR-195-5p.

Safe Practice of Total Intravenous Anesthesia With Target-Controlled Infusion in Taiwan: A Recommendation.

There have been immense advances in the safety and variety of intravenous anesthetic delivery systems including drug cost reduction, development of more effective opioids, and improvement in depth of anesthesia monitoring in the last 20 years. Propofol-based total intravenous anesthesia (TIVA) with target-controlled infusion (TCI) is relatively easy to practice. While this technique promotes a higher overall anesthesia quality and patient survival, especially for cancer patients, there are deficiencies in training and education of the technique. Therefore, the Society for Intravenous Anesthesia and the Association of Anesthetists (United Kingdom) have laid out guidelines in an attempt to highlight multiple important TIVA-related safety issues to help clinicians feel more confident. In the present article, we discuss five recommendations and four special clinical situations. Preparation, equipment familiarity, and safe delivery techniques are extremely important for the proper employment of this method. Herein, we emphasize the importance of proper education, and the clinical practice experience of the TIVA technique. Additionally, we suggest a modified connection method to set up a safely administered line. We highlight the advantages of using processed electroencephalogram monitoring (such as bispectral index or Entropy) to prevent awareness during TIVA administration in difficult clinical situations. These situations may include triple low patients (e.g., low blood pressure, low maintained effect-site concentration of propofol, and low body weight ≤ 18), obese patients, and patients with difficult infusion site monitoring or use of neuromuscular blocking agents. Due to a limited consensus among Taiwanese medical professionals, this document is intended to act as a safe practice reference for the use of TIVA with TCI. Additionally, two pithy formula codes, 4321 for propofol with fentanyl/alfentanil and 42222111 for propofol with remifentanil, are provided for the general population and one pithy formula code, 4321 for propofol with fentanyl, is provided for pediatric patients.

The Chronotropic Function of Propofol and the Underlying Mechanism in Rabbits.

The report of bradycardia caused by propofol is increasing. In the experiment, we investigated the chronotropic function of propofol and the underlying mechanism. Rabbits of both sexes were randomly divided into 4 groups: propofol 5 mg/kg group, 10 mg/kg group, 15 mg/kg group, and sham group. Heart rate and frequency of vagal efferent discharge were recorded before the injection and 0, 0.5, 1, 2, and 10 min after the injection through intravenous mode. Then, their hearts were removed, and sinoatrial nodes were dissected. The action potentials of the sinus node pacemaker cells were recorded by the intracellular glass microelectrode technique, and the sinoatrial (SA) node was exposed to propofol 1, 3, 5, and 10 µM respectively. The action potentials were recorded after the sinoatrial nodes were exposed to each concentration of propofol for 15 min. Our results show that the heart rate significantly decreased, and the vagal efferent discharge was significantly increased at 0, 0.5, 1, and 2 min after the injection, respectively. Besides, as the dose increases, the magnitude of change shows a dose-dependent manner. Propofol exerts a negative chronotropic action on sinoatrial node pacemaker cells. The drug significantly decreased APA, VDD, RPF, and prolonged APD90 in a concentration-dependent manner. These effects may be the main mechanism of propofol-induced bradycardia in clinical study.

Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia

BackgroundAdministration of propofol, an intravenous anesthetic with antioxidant property, immediately at the onset of post-ischemic reperfusion (propofol postconditioning, P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion injury, while the underlying mechanism remains incompletely understood. The FoxO transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection, however, the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.MethodsRat heart-derived H9c2 cells were exposed to high glucose (HG) for 48 h (h), then subjected to hypoxia/reoxygenation (H/R, composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol (P-PostC) at the onset of reoxygenation. After having identified the optical concentration of propofol, H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.ResultsThe results showed that HG with or without H/R decreased cell viability, increased lactate dehydrogenase (LDH) leakage and the production of reactive oxygen species (ROS) in H9c2 cells, all of which were significantly reversed by propofol (P-PostC), especially at the concentration of 25 µmol/L (P25) (all P < 0.05, NC vs. HG; HG vs. HG + HR; HG + HR + P12.5 or HG + HR + P25 or HG + HR + P50 vs. HG + HR). Moreover, we found that propofol (P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression (all P < 0.05, HG + HR + P25 vs. HG + HR). The protective effects of propofol (P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a (all P < 0.05, HG + HR + P25 vs. HG + HR + P25 + siRNA-1 or HG + HR + P25 + siRNA-5).ConclusionIt is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.

The median effective concentration of propofol with different doses of esketamine during gastrointestinal endoscopy in elderly patients: A randomized controlled trial.

Propofol may result in hypotension, bradycardia and loss of protective reflexes, especially in elderly patients, while esketamine, a N-methyl-D-aspartate receptor antagonist, has analgesic, anaesthetic and sympathomimetic properties and is known to cause less cardiorespiratory depression. We hypothesized that esketamine may reduce the median effective concentration (EC50 ) of propofol and coadministration is less likely to produce hypotension during gastrointestinal endoscopy in elderly patients. Ninety elderly patients, aged 65-89 years, undergoing gastrointestinal endoscopy were randomly assigned into 3 groups: SK0 (control) group (0 mg/kg esketamine); SK0.25 group (0.25 mg/kg esketamine); and SK0.5 group (0.5 mg/kg esketamine). Anaesthesia was achieved by plasma target-controlled infusion of propofol with different bolus doses of esketamine. The EC50 of propofol for gastrointestinal endoscopy was determined by using the up-and-down method of Dixon. The initial plasma target concentration is 2.5 μg/mL and the adjacent concentration gradient is 0.5 μg/mL. Cardiovascular variables were also measured. Propofol EC50 s and its 95% confidence interval for gastrointestinal endoscopy in elderly patients were 3.69 (2.59-4.78), 2.45 (1.85-3.05) and 1.71 (1.15-2.27) μg/mL in the SK0, SK0.25 and SK0.5 groups, respectively (P < .05). The average percent change from baseline mean arterial pressure was -19.7 (7.55), -15.2 (7.14) and -10.1 (6.73), in the SK0, SK0.25 and SK0.5 groups, respectively (P < .001). Combination medication of propofol with esketamine reduced the propofol EC50 during gastrointestinal endoscopy in elderly patients compared with administration of propofol without esketamine. Increasing doses of SK with propofol are less likely to produce hypotension with shorter recovery time.

Propofol mediates pancreatic cancer cell activity through the repression of ADAM8 via SP1.

Propofol is a commonly used anesthetic with controversial effects on cancer cells. A growing number of studies have demonstrated that low concentrations of propofol are associated with tumor suppression and when used as an intravenous anesthesia improved recurrence‑free survival rates for many cancers, but deeper insights into its underlying mechanism are needed. The study detailed herein focused upon the effect of propofol on pancreatic cancer cells and the mechanism by which propofol reduces A disintegrin and metalloproteinase8(ADAM8) expression. The ability of propofol to impact the proliferation, migration and cell cycle of pancreatic cancer cell lines was assessed invitro. This was mechanistically explored following the identification of SP1 binding sites within ADAM8, which enabled the regulatory effects of specificity protein1(SP1) on ADAM8 following propofol treatment to be further explored. Ultimately, this study was able to show that propofol significantly inhibited the proliferation, migration and invasion of pancreatic cancer cells and decreased the percentage of cells in S‑phase. Propofol treatment was also shown to repress ADAM8 and SP1 expression, but was unable to affect ADAM8 expression following knockdown of SP1. Moreover, a direct physical interaction between SP1 and ADAM8 was verified using co‑immunoprecipitation and dual‑luciferase reporter assays. Cumulatively, these results suggest that propofol represses pathological biological behaviors associated with pancreatic cancer cells through the suppression of SP1, which in turn results in lower ADAM8 mRNA expression and protein levels.

Behavioral and histological features of zebrafish following sedation with eugenol or propofol

The use of anesthesia during short or lengthy procedures is scientifically and ethically required when dealing with fish. In this setting, the present study investigated whether a 3 h exposure to eugenol (4 and 8 mg/L) or propofol (0.2 and 0.4 mg/L) at sedative levels, followed by a 1 h wash-out time, would interfere with behavioral and histological characteristics of zebrafish. Anxiety-like phenotypes were assessed in the novel tank test using an automated tracking software, and histological features of the gills were determined through light microscopy. In the eugenol trial, zebrafish showed behavioral signs of complete recovery from sedation, but the novel environment diving response was amplified at both concentrations tested, thus pointing to the production of an anxiogenic phenotype. Furthermore, transitory alterations were implemented to increase the functional surface area of the gill and decrease lamellar epithelium thickness in order to improve gas exchange in the individuals bathed in 8 mg/L eugenol. Differently, the zebrafish submitted to 0.2 and 0.4 mg/L propofol presented an anti-anxiety response, since they dwelled much longer in the upper half of the tank; together with other behavioral endpoints which indicated a certain degree of inactivity, it seems that these fish were still under the effect of the drug, despite the 1 h wash-out, and thus neurological function had not been fully restored. Moreover, both concentrations of propofol induced shrinkage of the gill structure, which may have contributed towards an incomplete recovery; hence the behavioral pattern displayed in the novelty-based tank paradigm. This work reports contrasting behavioral and histological effects produced by eugenol and propofol upon zebrafish, thus demonstrating that standardization is a challenge with psychoactive drugs. Therefore, it is paramount to refine anesthetic protocols for this highly qualified test organism in order to maximize welfare and reduce experimental variability.

Effect of chemotherapy on effect-site concentration of propofol for loss of consciousness in patients with colorectal cancer.

BackgroundThe depth of anesthesia is an essential factor in surgical prognosis. The neurotoxic effect of chemotherapeutic drugs affects the sensitivity to anesthetics. This study was conducted to determine whether the effect-site concentration (Ce) of propofol for loss of consciousness (LOC) differs in patients undergoing preoperative chemotherapy. MethodsA total of 60 patients scheduled for surgery for colorectal cancer under general anesthesia were included in this study. Patients who had received chemotherapy comprised the experimental (C) group, and those without a previous history of chemotherapy comprised the control (N) group. Propofol was administered as an effect-site target-controlled infusion, and the Modified Observer’s Assessment of Alertness/Sedation (MOAA/S) scores were evaluated. When the plasma concentration and Ce were similar, and if the MOAA/S score did not change, the target Ce was increased by 0.2 μg/ml; otherwise, the Ce was maintained for 2 min and then increased. ResultsThe Ce values of propofol for loss of verbal contact (LVC) in groups C and N were 2.40 ± 0.39 and 2.29 ± 0.39 μg/ml (P = 0.286), respectively, and those for LOC in groups C and N were 2.69 ± 0.43 and 2.50 ± 0.36 μg/ml (P = 0.069), respectively. No significant difference was observed in Ce values between the two groups.ConclusionsChemotherapy had no effect on the Ce of propofol for LVC and LOC in patients with colorectal cancer. We do not recommend reducing the dose of propofol for the induction of LOC in patients with colorectal cancer undergoing chemotherapy.

The relationship between the effect-site concentration of propofol and sedation scale in children: a pharmacodynamic modeling study

BackgroundContinuous infusion of propofol has been used to achieve sedation in children. However, the relationship between the effect-site concentration (Ce) of propofol and sedation scale has not been previously examined. The objective of this study was to investigate the relationship between the Ce of propofol and the University of Michigan Sedation Scale (UMSS) score in children with population pharmacodynamic modeling.MethodsA total of 30 patients (aged 3 to 6 years) who underwent surgery under general anesthesia with propofol and remifentanil lasting more than 1 h were enrolled in this study. Sedation levels were evaluated using the UMSS score every 20 s by a 1 μg/mL stepwise increase in the Ce of propofol during the induction of anesthesia. The pharmacodynamic relationship between the Ce of propofol and UMSS score was analyzed by logistic regression with nonlinear mixed-effect modeling.ResultsThe estimated Ce50 (95% confidence interval) of propofol to yield UMSS scores equal to or greater than n were 1.84 (1.54–2.14), 2.64 (2.20–3.08), 3.98 (3.66–4.30), and 4.78 (4.53–5.03) μg/mL for n = 1, 2, 3, and 4, respectively. The slope steepness for the relationship of the Ce versus sedative response to propofol (95% confidence interval) was 5.76 (4.00–7.52).ConclusionsWe quantified the pharmacodynamic relationship between the Ce of propofol and UMSS score, and this finding may be helpful to predict the sedation score at the target Ce of propofol in children.Trial registrationhttp://www.clinicaltrials.gov (No.: NCT03195686, Date of registration: 22/06/2017).

Propofol induces the ferroptosis of colorectal cancer cells by downregulating STAT3 expression.

Propofol is a commonly used intravenous anesthetic agent that can also suppress the proliferation of various human cancer types, including colorectal cancer (CRC). The present study aimed to investigate whether propofol could induce the ferroptosis of CRC cells by regulating signal transducer and activator of transcription 3 (STAT3). STAT3 expression in normal and CRC tissues was measured. Human normal colonic epithelial NCM460 cells and human CRC SW480 cells were exposed to different concentrations of propofol and then cell viability was detected. SW480 cells were transfected with a vector overexpressing STAT3 and treated with propofol, and the cell viability, colony formation, cell proliferation, iron level, ROS production and ferroptosis of these cells and control cells were evaluated. Overall, the results showed that STAT3 was highly expressed in CRC tissues. Propofol exerted no marked effect on NCM460 cell viability, but inhibited SW480 cell viability in a concentration-dependent manner. Meanwhile, STAT3 was downregulated by propofol in a concentration-dependent manner. Propofol also inhibited CRC cell proliferation and colony formation, and enhanced cellular iron and ROS levels. Additionally, the expression of proteins involved in ferroptosis was also altered by propofol, including the upregulation of CHAC1 and PTGS2 expression in CRC cells, and the inhibition of GPX4 expression. However, STAT3 overexpression blocked the effect of propofol on CRC cells. In conclusion, propofol may trigger the ferroptosis of CRC cells by downregulating STAT3 expression.

Clinically relevant concentration of propofol and benzodiazepines did not affect in vitro angiogenesis.

Angiogenesis, one of regenerative medicine, is essential in the process of wound healing. The detailed effects of intravenous anesthetics and sedatives used during perioperative period have not yet been clarified. We investigated the effects of benzodiazepines and propofol on in vitro capillary tube formation. The effects of midazolam, diazepam and propofol (1, 10, 50µM each) on proliferation of human umbilical vein endothelial cells (HUVEC) and normal human diploid fibroblasts (NHDF) were determined. Quantitation of migration was achieved by measuring the fluorescence of migrating HUVEC using angiogenesis system. The effects of midazolam, diazepam and propofol on in vitro angiogenesis were investigated in co-cultured HUVEC and NHDF incubated. The effects of midazolam on activation of p38 mitogen-activated protein kinase (MAPK) and extracellular signal-regulated kinases were examined by Western blot analysis using phospho-specific antibodies. Parametric data were analyzed with one-way repeated measures analysis of variance followed by the Scheffé test. A value of P < 0.05 was considered statistically significant. Fifty µM of midazolam significantly impaired endothelial cell proliferation, migration, and in vitro capillary tube formation. Propofol, diazepam or lower dose midazolam did not show any enhancing or suppressive effects on in vitro angiogenesis. Fifty µM of midazolam remarkably activated ERK, but not p38 MAPK in HUVEC. Propofol and benzodiazepines except high-dose midazolam did not affect in vitro angiogenesis. High-dose midazolam may impair in vitro capillary tube formation due to by suppressing proliferation and migration of endothelial cells via activation of ERK.

Obesity and anesthetic pharmacology: simulation of target-controlled infusion models of propofol and remifentanil.

The prevalence of obesity is increasing, resulting in an increase in the number of surgeries performed to treat obesity and diseases induced by obesity. The associated comorbidities as well as the pharmacokinetic and pharmacodynamic changes that occur in obese patients make it difficult to control the appropriate dose of anesthetic agents. Factors that affect pharmacokinetic changes include the increase in adipose tissue, lean body weight, extracellular fluid, and cardiac output associated with obesity. These physiological and body compositional changes cause changes in the pharmacokinetic and pharmacodynamic parameters. The increased central volume of distribution and alterations in the clearance of drugs affect the plasma concentration of propofol and remifentanil in the obese population. Additionally, obesity can affect pharmacodynamic properties, such as the 50% of maximal effective concentration and the effect-site equilibration rate constant (ke0). Conducting a simulation of target-controlled infusions based on pharmacokinetic and pharmacodynamic models that include patients that are obese can help clinicians better understand the pharmacokinetic and pharmacodynamic changes of anesthetic drugs associated with this population.

Potency of propofol for inducing loss of consciousness in end-stage kidney disease patients

It can be difficult for anesthesiologists to determine the optimal dose of propofol for end-stage kidney disease (ESKD) patients due to changes in drug disposition. The purpose of this study was to evaluate the potency of propofol for inducing loss of consciousness in ESKD patients. Patients with normal kidney function (Control group, n = 15), those with ESKD (ESKD group, n = 15), and those with ESKD undergoing cervical epidural anesthesia (ESKD-CEB group, n = 15) were administered propofol by target-controlled infusion (TCI) using the Schneider model. The effect-site concentration (Ce) of propofol started at 0.5 μg/ml and increased in increments of 0.5 μg/ml until the patient did not respond to verbal commands. The relationship between the probability (P) of loss of consciousness and the Ce of propofol was analyzed in each group using logistic regression. The Ce values of propofol at the time of loss of consciousness were 4.3 ± 0.9, 3.7 ± 0.9, and 3.3 ± 1.0 μg/ml for the Control, ESKD, and ESKD-CEB* groups, respectively (*significant difference vs. control, P < 0.05). The estimated Ce50 values for lost ability to respond to verbal command were 4.56, 3.75, and 3.21 μg/ml for the Control, ESKD, and ESKD-CEB groups, respectively. In conclusion, when inducing anesthesia in ESKD patients, we recommend using an initial dose similar to that of patients with normal kidney function, or rather starting with a lower dose.

Propofol Inhibits Lung Cancer Invasion and Metastasis by Attenuating Icam-1/ Mmp-9 Axis

Objective: To investigate the effect of propofol on invasion and metastasis of A549 cells and the expression of intercellular adhesion molecule 1 (ICAM-1) / matrix metalloproteinase-9 (MMP-9) axis.Methods: A549 cells were treated with gradient doses of propofol (25, 50, 100 ng/ml) and different times (12, 24 h). The influences of propofol on ICAM-1 mRNA of A549 cells were observed by qRT-PCR, and the roles of different concentrations of propofol on ICAM-1 and MMP-9 protein and invasion ability were detected by Western Blot and Transwell assay, respectively.Results: The maximum inhibitory influence of propofol was achieved in group 100μg/ml for 24 h. ICAM-1 and MMP-9 protein in the treatment group with 25, 50 and 100μg/ml propofol for 24 h were significantly lower than those in the control group. The number of migrated and invaded cells in the 25, 50 and 100 ng/ml propofol treatment group for 24 h was significantly lower than that in the blank group.Condusion: ICAM-1 protein and MMP-9 protein in human lung cancer A549 cells could be down-regulated after treatment with 50 and 100μg/ml propofol, and the invasion and metastasis ability of A549 cells could be attenuated through ICAM-1/MMP-9 axis.

Efficacy of parasternal block to decrease intraoperative opioid use in coronary artery bypass surgery via sternotomy: a randomized controlled trial

ObjectiveThis study aims to assess the effect of a preoperative parasternal plane block (PSB) on opioid consumption required to maintain hemodynamic stability during sternotomy for coronary artery bypass graft surgery.MethodsThis...

Protective effect of propofol via the regulation of ovarian granulosa cell proliferation and apoptosis.

Propofol is an anesthetic frequently used in surgery. Accumulating evidence suggests that propofol exhibits an effect on cell viability, apoptosis and invasion in several types of cancer cells. MicroRNAs (miRNAs) have been reported to play pivotal roles in the development of polycystic ovary syndrome (PCOS). However, the diagnostic applications of miR-451a in PCOS remain unknown. The present study aimed to elucidate the effects of propofol on ovarian granulosa cell proliferation and apoptosis and illustrate the specific mechanisms associated with this process. Human ovarian granulosa cell-like KGN cells, which were used as a representative of granulosa cells in the present study, were treated with different concentrations (0, 1, 5 and 10 µg/ml) of propofol for 48 h and cell proliferation and apoptosis were assessed using MTT and flow cytometry assays, respectively. Propofol treatment resulted in significant inhibition of cell viability and induction of apoptosis in KGN cells, which was accompanied with increased cleaved caspase 3 and suppressed pro-caspase 3 expression levels. Furthermore, propofol reduced Wnt3a and β-catenin protein and mRNA expression levels. miR-451a expression in KGN cells was evaluated by reverse transcription-quantitative PCR (RT-qPCR). miR-451a expression was upregulated in propofol-stimulated KGN cells. The data further demonstrated that miR-451a mimics suppressed cell proliferation and increased apoptosis of KGN cells compared with cells transfected with control mimics. Furthermore, the association between miR-451a and propofol was investigated. Rescue experiments were performed to investigate the anti-proliferative mechanism of propofol in ovarian granulosa cells. KGN cells were transfected with miR-451a inhibitor or inhibitor control sequences for 6 h and treated with 10 µg/ml propofol for an additional 48 h. The results from the MTT, RT-qPCR and western blot assays indicated that 10 µg/ml propofol inhibited cell viability, induced apoptosis, enhanced cleaved caspase 3 expression, reduced pro-caspase 3 levels and inhibited the protein and mRNA expression of Wnt3a and β-catenin. However, inhibition of miR-451a demonstrated the opposite effects. In conclusion, the results of the present study revealed that propofol exerted an anti-proliferative and apoptosis-inducing role in ovarian granulosa cells through mediation of miR-451a expression. In addition, the data indicated that miR-451a may be used as an effective therapeutic target for PCOS treatment.

Propofol regulates miR-1-3p/IGF1 axis to inhibit the proliferation and accelerates apoptosis of colorectal cancer cells.

This study aimed to clarify the mechanism of propofol on proliferation and apoptosis of colorectal cancer (CRC) cell. SW620 and HCT15 cells were exposed to different concentrations of propofol, the proliferation and apoptotic rate, were measured by MTT, colony formation and flow cytometry assays, respectively. The expressions of miR-1-3p and insulin-like growth factors 1 (IGF1) were examined by real-time polymerase chain reaction (RT-qPCR). Western bolt was employed to quantify the protein levels of IGF1 and apoptotic proteins. The molecular interaction between miR-1-3p and IGF1 was validated using dual-luciferase reporter assay. A xenograft tumor model was established to further assess the effects of propofol on CRC in vivo. Propofol dramatically decreased the proliferation and elevated apoptotic rate of CRC cells. RT-qPCR assay demonstrated that miR-1-3p was downregulated in CRC cells, and could be strikingly increased by propofol. Importantly, miR-1-3p inhibited IGF-1 expression through interacting with its 3'-UTR region, thus inactivating AKT/mTOR signals. Gain or loss of functional study revealed that miR-1-3p downregulation remarkedly diminished the anti-tumor roles of propofol by directly inhibiting IGF1. In vivo study showed that propofol inhibited tumor growth by regulating miR-1-3p/IGF1 axis. Our data eventually elucidated that propofol suppressed CRC progression by promoting miR-1-3p which targeted IGF1. These results might provide a scientific basis for the application of propofol on the clinical surgery and the prognosis of patients with CRC.

Brain activity complexity has a nonlinear relation to the level of propofol sedation

BackgroundBrain activity complexity is a promising correlate of states of consciousness. Previous studies have shown higher complexity for awake compared with deep anaesthesia states. However, little attention has been paid to complexity in intermediate states of sedation. MethodsWe analysed the Lempel–Ziv complexity of EEG signals from subjects undergoing moderate propofol sedation, from an open access database, and related it to behavioural performance as a continuous marker of the level of sedation and to plasma propofol concentrations. We explored its relation to spectral properties, to propofol susceptibility, and its topographical distribution. ResultsSubjects who retained behavioural performance despite propofol sedation showed increased brain activity complexity compared with baseline (M=13.9%, 95% confidence interval=7.5–20.3). This was not the case for subjects who lost behavioural performance. The increase was most prominent in frontal electrodes, and correlated with behavioural performance and propofol susceptibility. This effect was positively correlated with high-frequency activity. However, abolishing specific frequency ranges (e.g. alpha or gamma) did not reduce the propofol-induced increase in Lempel–Ziv complexity. ConclusionsBrain activity complexity can increase in response to propofol, particularly during low-dose sedation. Propofol-mediated Lempel–Ziv complexity increase was independent of frequency-specific spectral power manipulations, and most prominent in frontal areas. Taken together, these results advance our understanding of brain activity complexity and anaesthetics. They do not support models of consciousness that propose a direct relation between brain activity complexity and states of consciousness.

Propofol induces apoptosis of hepatocellular carcinoma cells by upregulating miR-134 expression.

BackgroundPropofol is an anesthetic used in clinical surgery. Many studies have shown that propofol has the potential to kill cancer cells; however, the mechanism by which it kills hepatocellular carcinoma (HCC) cells remains unclear.MethodsTo examine this issue, the apoptosis change of HepG2 and Huh-7 cell lines treated with propofol were observed. Additionally, a quantitative reverse-transcriptase polymerase chain reaction was used to measure the expression level of hsa-miR-134 (miR-134), and a Cell Counting Kit-8 assay and flow cytometry assay were used to observe cell apoptosis. A dual-luciferase assay was used to confirm the binding effect of miR-134 and BCL-2 (B cell lymphoma-2), and a western blot assay was used to detect expression level changes of BCL-2 and cleaved caspase-3.ResultsThe results showed that propofol significantly promoted HepG2 and Huh-7 cell apoptosis, and that miR-134 expression level is related to the concentration of propofol. The dual-luciferase assay showed that miR-134 significantly reduced the luciferase activity of BCL-2-wt, but had no notable effect on BCL-2-mut. In rescue experiments, miR-134 deficiency resulted in a high apoptosis rate, a low BCL-2 expression level, and a high cleaved caspase-3 expression level induced by propofol in HepG2.ConclusionsIn summary, propofol appears to upregulate the expression level of miR-134, decrease the BCL-2 level, and induce HCC cell apoptosis by promoting the cleaved caspase-3 expression level.Trial registrationChinese Clinical Trial Registry ChiCTR18000199

Correlation of exhaled propofol with Narcotrend index and calculated propofol plasma levels in children undergoing surgery under total intravenous anesthesia -\xa0an observational study

BackgroundExhaled propofol concentrations correlate with propofol concentrations in adult human blood and the brain tissue of rats, as well as with electroencephalography (EEG) based indices of anesthetic depth. The pharmacokinetics of propofol are however different in children compared to adults. The value of exhaled propofol measurements in pediatric anesthesia has not yet been investigated. Breathing system filters and breathing circuits can also interfere with the measurements. In this study, we investigated correlations between exhaled propofol (exP) concentrations and the Narkotrend Index (NI) as well as calculated propofol plasma concentrations.MethodsA multi-capillary-column (MCC) combined with ion mobility spectrometry (IMS) was used to determine exP. Optimal positioning of breathing system filters (near-patient or patient-distant) and sample line (proximal or distal to filter) were investigated. Measurements were taken during induction (I), maintenance (M) and emergence (E) of children under total intravenous anesthesia (TIVA). Correlations between ExP concentrations and NI and predicted plasma propofol concentrations (using pediatric pharmacokinetic models Kataria and Paedfusor) were assessed using Pearson correlation and regression analysis.ResultsNear-patient positioning of breathing system filters led to continuously rising exP values when exP was measured proximal to the filters, and lower concentrations when exP was measured distal to the filters. The breathing system filters were therefore subsequently attached between the breathing system tubes and the inspiratory and expiratory limbs of the anesthetic machine. ExP concentrations significantly correlated with NI and propofol concentrations predicted by pharmacokinetic models during induction and maintenance of anesthesia. During emergence, exP significantly correlated with predicted propofol concentrations, but not with NI.ConclusionIn this study, we demonstrated that exP correlates with calculated propofol concentrations and NI during induction and maintenance in pediatric patients. However, the correlations are highly variable and there are substantial obstacles: Without patient proximal placement of filters, the breathing circuit tubing must be changed after each patient, and furthermore, during ventilation, a considerable additional loss of heat and moisture can occur. Adhesion of propofol to plastic parts (endotracheal tube, breathing circle) may especially be problematic during emergence.Trial RegistrationThe study was registered in the German registry of clinical studies (DRKS-ID: DRKS00015795).