CNS Neuroscience & Therapeutics
·
2022
·Vol. 29
·期 1
·306-316
·
IF 7.035
Ayang Zhao,Hongjiang Jin,Guibo Fan,Yan Li,Chenglong Li,Qi Li,Xiaofei Ma,Tianyang Zhao,Siqi Sun,Shuai Liu,Yueyue Gao,Sihua Qi
Background Exposure to anesthesia leads to extensive neurodegeneration and long-term cognitive deficits in the developing brain. Caenorhabditis elegans also shows persistent behavioral changes during development after exposure to anesthetics. Clinical and rodent studies have confirmed that altered expression of the regulators of G protein signaling (RGS) in the nervous system is a factor contributing to neurodegenerative and psychological diseases. Evidence from preclinical studies has suggested that RGS controls drug-induced plasticity, including morphine tolerance and addiction. This study aimed to observe the effect of propofol exposure in the neurodevelopmental stage on learning and memory in the L4 stage and to study whether this effect is related to changes in rgs-3 expression. Methods Caenorhabditis elegans were exposed to propofol at the L1 stage, and learning and memory abilities were observed at the L4 stage. The expression of rgs-3 and the nuclear distribution of EGL-4 were determined to study the relevant mechanisms. Finally, RNA interference was performed on rgs-3 -expressing cells after propofol exposure. Then, we observed their learning and memory abilities. Results Propofol time- and dose-dependently impaired the learning capacity. Propofol induced a decline in non-associative and associative long-term memory, rgs-3 upregulation, and a failure of nuclear accumulation of EGL-4/PKG in AWC neurons. Inhibition of rgs-3 could alleviate the propofol-induced changes. Conclusion Inhibition of the expression of rgs-3 alleviated propofol-induced learning and memory deficits in Caenorhabditis elegans .
研究领域:
神经科学
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药理学
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分子生物学
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DOI
PubMed
高影响因子
EPILEPSIA
·
2021
·Vol. 62
·期 1
·238-249
·
IF 5.866
Yi Zhao,Long An,Shupan Guo,Xiaoxing Huang,Huajie Tian,Li Liu,Tao Chen,Xun Sun,Qibing Mei,Rutao Wang
Objective LMR-101 is a bisphenol derivative of propofol, a short-acting general anesthetic, which is also used to manage status epilepticus (SE). We evaluated the sedative and anticonvulsant effects of LMR-101 to discover its potential to manage epilepsy and SE in the clinic. Methods Comparative studies between LMR-101 and propofol were performed in mice to elucidate an appropriate dose range for LMR-101 that produced anticonvulsant effects without significant sedation. Then, the anticonvulsive efficacy for LMR-101 was evaluated using seizure models induced by pentylenetetrazol and (+)-bicuculline. The ability of LMR-101 to inhibit SE was assessed using a rat model of SE induced by pilocarpine. Radioligand binding assay profiles for LMR-101 were performed to evaluate the potential mechanisms of action underlying its anticonvulsant properties. Results In the mouse study, LMR-101 exhibited greater anticonvulsant and lesser sedative effect compared with propofol. LMR-101 completely inhibited pentylenetetrazol-induced seizures at a dose of 50 mg/kg and exhibited heavy sedation at 300 mg/kg. Propofol anesthetized all mice and only decreased the seizure rate at 25 mg/kg. LMR-101 also suppressed seizure behaviors evoked by (+)-bicuculline in mice in a dose-dependent manner. In the pilocarpine-induced SE model, LMR-101 significantly decreased the maximum seizure score and seizure duration in a dose-dependent manner. The median effective dose for LMR-101 was 14.30 mg/kg and 121.87 mg/kg to prevent and inhibit sustained SE, respectively. In binding assays, LMR-101 primarily inhibited tert -[ 35 S] butylbicyclophosphorothionate binding to γ-aminobutyric acid type A (GABA A ) receptors (half-maximal inhibitory concentration = 2.06 μmol·L –1 ), but it did not affect [ 3 H] flunitrazepam or [ 3 H] muscimol binding. Significance It is anticipated that LMR-101 might play an essential role in the clinical management of epilepsy and SE. LMR-101 also might bind to a novel target site on the GABA A receptor that is different from existing antiepileptic drugs. Further study of the mechanisms of action of LMR-101 would be of considerable value in the search for new active drug sites on GABA A receptors.
研究领域:
神经科学
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药理学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ACS ES&T Water
·
2024
·
IF 4.8
Nan Jiang,Xianxu Li,Guangcai Zhang,Zhuran Hu,Xiaoteng Fan,Mingsheng Li,Huimin Sun,Xianqiang Yin,Jun Wang
Propofol is increasingly perceived as an emerging threat to aquatic ecosystems, although the ecotoxicity and underlying mechanisms of propofol on aquatic life have not yet been clearly established. In this study, zebrafish (Danio rerio) was exposed to different concentrations of propofol (0.008, 0.04, and 0.2 mg·L–1) to probe the effect of propofol on functional metabolism and the ecological response mechanism in aquatic organisms. Propofol induced severe hepatic damage, including increased interstitial spaces and nuclear malformations at the tissue level. Reactive oxygen species (ROS) production and lipid peroxidation in zebrafish were induced after 28 days of exposure, while the activities of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) were substantially increased, suggesting that propofol may influence hepatic tissue injury through exacerbating oxidative damage. Exacerbated levels of triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) were indicative of dysregulated lipid metabolism. Comprehensive transcriptomics and metabolomics analyses showed that propofol mainly changed the glycerophospholipid metabolism, citric acid cycle, and purine metabolism, and the disorders of these pathways can aggravate lipid accumulation and oxidative damage. Overall, this study revealed the mechanisms of hepatotoxicity and metabolic dysfunction of propofol on zebrafish, providing constructive insights for a comprehensive assessment of the toxicity risk posed by propofol to aquatic environmental health.
研究领域:
环境科学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
高影响因子
Analytical Methods
·
2017
·Vol. 9
·期 35
·5101-5107
·
IF 1.9
Rongwei Yan,Leilei Zhao,Yanfei Li,Yong Zou,Xinjun Xu
As a novel injection preparation, propofol liposomes have extensive application prospects in clinical practice, and lipid components in them need to be quantified for quality control. In this study, a simple and accurate GC-FID method coupled with a methyl esterification pretreatment was developed for simultaneous determination of three main excipients (tricaprylin, TA; dipalmitoyl phosphatidylglycerol, DPPG; 2-dierucoyl-sn-glycero-3-phosphocholine, DEPC) in propofol liposomes with stearic acid used as the internal standard (IS). Response surface methodology was utilized for optimizing three factors of the methyl esterification reaction (the temperature, BF3 concentration and reaction time were optimized to be 75.0 °C, 14.5% and 6.5 min, respectively). Under optimum conditions, the average methyl esterification rate of the three analytes reached 96.43 ± 0.16% (n = 3). Moreover, multiple sample solutions could be simultaneously prepared, which would promote the efficiency and accuracy of quantitative analysis. Three calibration curves had good linear regression (r > 0.9999) within the tested ranges, the average recoveries ranged from 98.64% to 102.44% and the RSDs of the precision, repeatability, stability and recoveries were all below 1.53%. Finally, the validated method was successfully applied to the quantitative analysis of the three analytes in six batches of propofol liposomes.
研究领域:
药学
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分析化学
✓ 已验证
产品关联
DOI
高影响因子
TOXICOLOGY MECHANISMS AND METHODS
·
2025
·
IF 2.7
Dan Wang,Hui Sun,Kerong Hai,Ningkang Li,Yang Gu,Zengrui Ma
Traumatic brain injury (TBI), a prevalent neurological disorder in clinical practice, is primarily induced by external trauma. Propofol has been reported to alleviate the symptoms associated with TBI. In this study, a TBI model was established in mice using the controlled cortical impact (CCI) method. After treatment with propofol and BML-275, neuronal damage in the TBI model was assessed through the modified Neurological Severity Score (mNSS), Hematoxylin and Eosin (HE) staining, and Nissl staining. To investigate the role of the AMPK/SIRT1 pathway in propofol-regulated TBI, AMPKα-silenced vectors and overexpressed SIRT1 vectors were transfected. Western blot was performed to evaluate the expression of proteins involved in the AMPK/SIRT1 pathway and pyroptosis markers. The regulatory impact of Th17/Treg balance was examined by detecting the key transcription factors RORγt and FOXP3 through immunofluorescent staining and RT-qPCR. Enzyme-linked immunosorbent assay (ELISA) was used to measure IL-17 and IL-10 concentrations. Results showed that propofol significantly reduced neuronal injury in the TBI model, an effect that was reversed by BML-275. Moreover, propofol mitigated pyroptosis by downregulating Caspase-1 and GSDMD-N expression post-TBI. Propofol inhibited Th17 differentiation while promoting Treg differentiation by modulating RORγt/FOXP3 and IL-17/IL-10 levels. Silencing AMPKα markedly diminished propofol’s effects on Th17 and Treg differentiation, with these effects being reversed upon SIRT1 overexpression. Propofol suppressed neuronal pyroptosis through the regulation of Th17/Treg balance via activation of the AMPK/SIRT1 pathway. These findings suggest propofol exerts a protective effect against neuronal damage following TBI, potentially through the modulation of the Th17/Treg balance and AMPK/SIRT1 signaling pathway.
研究领域:
神经科学
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免疫学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF GENE MEDICINE
·
2021
·Vol. 23
·期 8
·e3349
·
IF 4.565
Xuyang Li,Zhan Zhang,Aipeng Li,Yubo Hu
Background Propofol (PPF) plays a protective role in ischemia–reperfusion (I/R) in multiple organs, including renal ischemia–reperfusion injury (RIRI). The present study aimed to investigate the underlying mechanisms by which PPF exerts its protective functions in RIRI. Methods BALB/c mice were employed for the construction of RIRI animal model. PPF pre-treatment was carried out before I/R. An in vitro I/R model was established with HK-2 cells after hypoxia/reoxygenation (H/R) culture, and PPF was utilized to treat the cells before H/R. A quantitative-polymerase chain reaction (qPCR) was conducted to detect long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and miR-126-5p expression levels. Flow cytometry was adopted to detect the apoptosis of HK-2 cells. Bioinformatics analysis, qPCR, a luciferase reporter gene experiment and a RNA immunoprecipitation experiment were used to determine the regulatory relationship between MALAT1 and miR-126-5p. The expression level of vascular endothelial growth factor A (VEGFA) was examined by western blotting. Results MALAT1 expression was augmented and miR-126-5p was decreased in RIRI models. PPF pre-treatment remarkably reduced creatinine and urea nitrogen levels in the serum of BALB/c mice with RIRI, and diminished the apoptosis of HK-2 cells treated with H/R. In addition, PPF pre-treatment markedly restrained the expression of MALAT1 in both in vivo and in vitro models and up-regulated miR-126-5p expression. MALAT1 could adsorb miR-126-5p to repress it and up-regulate VEGFA. MALAT1 overexpression reversed the protective effects of PPF on RIRI. Conclusions PPF protects the kidney against RIRI by inhibiting MALAT1 and up-regulating miR-126-5p expression, as well as indirectly inhibiting the expression of VEGFA.
研究领域:
药理学
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分子生物学
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肾脏病学
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产品关联
DOI
PubMed
高影响因子
METABOLIC BRAIN DISEASE
·
2022
·Vol. 38
·期 1
·233-244
·
IF 3.655
Xiao Gaopeng,Yu Liuqiong,Tan Wenmin,Yang Hao,Li Wensen,Xia Rongzhou,Li Yujin
Propofol has a tumor-suppressive role in glioma, but the mechanism by which propofol is involved in glioma progression is largely unknown. This study aims to explore a potential circular RNAs (circRNAs)/microRNAs (miRNAs)/mRNA network in response to Propofol in glioma. Human glioma cell lines (U251 and LN229) were suffered from Propofol treatment (5 μg/mL for 24 h) and transfection. circRNA mitogen-activated protein kinase 4 (circMAPK4), miR-622, homeobox A9 (HOXA9) abundances were determined by quantitative reverse transcription polymerase chain reaction and western blot. Migration and invasion were analyzed via transwell analysis. Cell proliferation was evaluated using Cell Counting Kit-8 and colony formation analysis. Cell apoptosis and related protein expression were determined via flow cytometry and western blot. Target relationship was assessed via dual-luciferase reporter analysis, RNA pull-down and RNA immunoprecipitation. Propofol reduced circMAPK4 expression. Propofol inhibited cell proliferation, migration and invasion, while increased apoptosis via decreasing circMAPK4 in glioma cells. miR-622 was targeted via circMAPK4. circMAPK4 knockdown decreased glioma cell growth, migration and invasion by up-regulating miR-622. miR-622 knockdown reversed the effect of Propofol on glioma progression. HOXA9 was targeted by miR-622, and its expression was decreased by Propofol treatment. miR-622 overexpression restrained glioma progression via decreasing HOXA9. Propofol regulated circMAPK4/miR-622/HOXA9 axis in glioma cells. Propofol constrains glioma progression by regulating circMAPK4/miR-622/HOXA9 axis in vitro. Propofol restrains glioma cell growth, migration and invasion. circMAPK4 can regulate HOXA9 by sponging miR-622 in glioma cells. Propofol represses glioma progression via a circMAPK4/miR-622/HOXA9 axis.
研究领域:
肿瘤学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF INTERNATIONAL MEDICAL RESEARCH
·
2023
·
IF 1.6
Xuena Zhang,Jie Li
ObjectivesTo observe changes in actin and dendritic spines in the hippocampus after propofol anesthesia, and to evaluate the role of these changes in subsequent learning impairment in both young (3-month-old) and aged (20-month-old) male rats.MethodsThe shuttle box test was used to evaluate learning from 1, 3, 7, or 14 days after anesthesia. Both F-actin content and dendritic spines in the hippocampal CA1 region were observed using immunofluorescent staining and western blot assays.ResultsThe latency of the escape response was significantly prolonged until 7 days after anesthesia in the aged rats, and their learning curves were shifted. Dendritic spines were also decreased in the aged rats within 7 days after anesthesia, and F-actin content was significantly increased until 14 days after anesthesia.ConclusionsLearning was inhibited after propofol anesthesia, especially in aged rats. The over-polymerization of actin and subsequent reorganization of dendritic spines in the hippocampus may be responsible for this learning impairment. Our findings suggest that synaptic plasticity may be an underlying mechanism of perioperative neurocognitive disorders.
研究领域:
神经科学
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药理学
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认知科学
✓ 已验证
产品关联
DOI
高影响因子
JOURNAL OF CHROMATOGRAPHIC SCIENCE
·
2024
·
IF 1.5
Liang Shan-Yan,Xu Xiao-Min,Wang Peng,Ye Ming-Li,Zhang Shui-Feng,Zhao Yong-Gang
Novel C18-functionalized magnetic nanomaterials; i.e., C18@poly-styrene-divinylbenzene-glycidyl methacrylate-Fe3O4 (C18@PS-DVB-GMA-Fe3O4) have been synthesized by using N, N-dimethyloctadecylamine as modifying agent, which could be beneficial to remove the blood phospholipids. The C18@PS-DVB-GMA-Fe3O4 nanoparticles have been used and evaluated in the Quick, Easy, Cheap, Effective, Rugged and Safe (QuEChERS) procedure for human plasma prior to the analysis of propofol by supercritical fluid chromatography (SFC). In the QuEChERS procedure, human plasma samples are directly mixed with extraction solvent and C18@PS-DVB-GMA-Fe3O4 nanoparticles, and the extraction and cleanup procedures have been accomplished simultaneously. The SFC separation was performed with a C18 column (Thermo Scientific™ Acclaim™ 120, 250 × 4. 6 mm, 5 μm) within 5 min, using thymol as the internal standard. Supercritical carbon dioxide was used as the mobile phase with methanol as the cosolvent at the flow rate of 1.0 mL/min. The column temperature was 38°C, and detection wavelength was 275 nm. A good linearity was obtained among the propofol concentration range of 0.5–10 mg/L (R2 = 0.9997) with the limit of detection of 0.17 mg/L. Recoveries were in the range of 76.5–91.9%, with RSD less than 7.9%. These results suggested that method is convenient, rapid with high accuracy and little matrix effect, and suitable for rapid determination of propofol plasma concentration.
研究领域:
分析化学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ACS Chemical Neuroscience
·
2021
·
IF 4.418
Bei Sun,Hao Ou,Fei Ren,Yujiao Guan,Ye Huan,Hongwei Cai
Cerebral ischemia-reperfusion (CI/R) injury is a serious central nervous system disease. Propofol (PPF) exerts a neuroprotective effect in CI/R injury; the underlying cause is still unclear. Here, we cultured mouse hippocampal neuron (HT22 cells) in oxygen-glucose deprivation/reoxygenation (OGD/R) conditions to mimic CI/R injury in vitro. PPF treatment promoted cell viability and reduced apoptotic cells in the OGD/R-treated HT22 cells, which was effectively abrogated by SNHG14 overexpression. Moreover, we constructed a CI/R injury mouse model on C57BL/6J mice by middle cerebral artery occlusion/reperfusion (MCAO/R), followed by administration of PPF. PPF reduced neuronal damage and loss, enhanced glial cell hyperplasia, and ameliorated cerebral cortex tissue damage and brain infarct in MCAO/R-induced mice. SNHG14 overexpression aggravated MCAO/R-induced CI/R injury in mice. Furthermore, SNHG14 promoted the expression of Atg5 and Beclin 1 via competitively binding miR-30b-5p, which contributed to activate autophagy and apoptosis in HT22 cells. In addition, the levels of p-p38 and p-SP1 were reduced in the OGD/R-treated HT22 cells in the presence of PPF. SP1 interacted with the promoter of SNHG14 and elevated the expression of SNHG14. PPF treatment inhibited the SP1-mediated up-regulation of SNHG14. In conclusion, this work demonstrates that PPF inhibits SNHG14 expression though the p38 MAPK signaling pathway. SNHG14 promotes Atg5 and Beclin 1 expression by sponging miR-30b-5p and thus activates autophagy and aggravates CI/R injury.
研究领域:
神经科学
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药理学
·
分子生物学
·
细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
·
2018
·
IF 2.831
Zhuoling Zheng,Shuyu Zhang,Wudi Ma,Lingyi Zhang,Ling Huang,Wenqi Huang,Min Huang,Zhongxing Wang,Jiali Li
The combination of dexmedetomidine (DEX) and propofol (PPF) is extensively used in the field of anaesthesiology. This study aimed to develop and validate a rapid, simple and sensitive ultra high-performance liquid chromatography-tandem mass spectrometry (UHPLC–MS/MS) method for the determination of DEX in human plasma. The method was applied to evaluate the effect of DEX concentration on the target-controlled infusion (TCI) concentration of PPF. Analytes were separated on a Waters XTERRA ® MS C18 column with a mobile phase of acetonitrile-methanol-water containing 0.1% formic acid and 5 mM ammonium acetate (70:10:20, v/v/v ) at a flow-rate of 0.3 mL/min. Mass spectrometry was performed in the positive selection reaction monitoring mode. The 201.12 → 95.12 and 515.29 → 275.68 mass transitions of DEX and IS (telmisartan), respectively, were monitored. The calibration curve of DEX was linear over the concentrations of 0.1–10 ng/mL. The intra-batch and inter-batch precisions of quality control samples were less than 10.05% and had accuracies of less than 6.25%. The newly developed method was successfully applied to quantify the DEX concentrations of plasma samples from 34 patients who were co-medicated with DEX prior to receiving anaesthesia by PPF. Results showed that comedication with DEX could reduce the requirements of PPF. Specifically, it was firstly found that the concentration of DEX is negatively correlated with the TCI concentration of PPF at the time of loss of consciousness.
研究领域:
药理学
·
麻醉学
·
临床医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
RSC Advances
·
2021
·Vol. 11
·期 34
·20983-20991
·
IF 3.361
Yujie Tang,Shiyin Zhao,Zemin Peng,Zhen Li,Liang Chen,Pei Gan
Anesthetic drug wastage has increasingly become the main resource of operating room sewage, which poses a great risk to the safety of humans and other organisms. Propofol is the most widely used anesthetic drug in the world, and also occupies the largest proportion of the total anesthetic wastage in the operating room. In this work, a 2D Cu2O anchored carbon catalyst (Cu2O@NC) was prepared by the assembly-pyrolysis process and successfully applied to peroxymonosulfate (PMS) activation. We took propofol as a typical example and investigated the removal activity through heterostructure-enhanced advanced oxidation processes (AOPs). Through the degradation process, propofol can be removed from 20 ppm to ultralow levels within 5 min using the PMS/Cu2O@NC system. The degradation pathway of propofol was deduced through quantum chemical calculation and LC/GC-MS results. The final products were verified as CO2 and H2O. Moreover, sulfate radicals (SO4˙−) proved to be the dominant reactive oxidation species by radical scavenger experiments and ESR results. In addition, it has great universality for various pharmaceuticals such as tetracycline (TC), amoxicillin (AMX), cephalexin (CPX), and norfloxacin (NFX). Our work provided the possibility to treat operation room sewage in a rapid, high-efficiency, and feasible way.
研究领域:
环境科学
·
材料科学
·
医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）