Figure - available from: Functional & Integrative Genomics
This content is subject to copyright. Terms and conditions apply.
Nrf2 participated in the neuroprotection of ciprofol in MCAO/R mice model. Western blot showed A Nrf2 and B xCT level ascending to the peak after 24 h since cerebral ischemia injury. N = 6 mice per group. C cerebral blood flow in MCAO mice under ciprofol intervention. In the context of similar baseline blood flow, ciprofol treatment led to the cerebral rejuvenation in bloodstream profiling after reperfusion in MCAO mice, whereas deletion of Nrf2 failed to rescue cerebra from ischemia relative to the control group. Quantification of D water content and E neurological deficit scores in sham, stroke, stroke + ciprofol, and stroke + ciprofol + Nrf2 KO groups. F Infarct volume with ciprofol treatment was significantly diminished in contrast to the stroke group. Knockout of Nrf2 could eliminate the neuroprotective effect of ciprofol. All data represent the mean ± SD. ****p < 0.0001
Source publication
Neuroinflammation and oxidative stress damage are involved in the pathogenesis of cerebral ischemia–reperfusion injury (CIRI). Ferroptosis emerged as a new player in the regulation of lipid peroxidation processes. This study aimed at exploring the potential involvement of ciprofol on ferroptosis-associated CIRI and subsequent neurological deficits...
Citations
... What's more, Another study also found that the expression of Nrf2 in laryngeal squamous cell carcinoma patients is related to the pathologic stage [85]. Meanwhile, a considerable number of experiments have now clarified that Nrf2 is a signaling molecule upstream of the xCT/GPX4 axis and that ferroptosis can be effectively regulated by modulating the Nrf2/ xCT/GPX4 axis [86][87][88]. The underlying mechanism is that Nfr2 upregulates SLC7A11 expression by upregulating SLC7A11 promoter activity, which in turn affects ferroptosis. ...
Background
Laryngeal cancer (LC) is among the most prevalent tumors of the respiratory tract. In recent years, the implementation of non-surgical treatments like radiotherapy and chemotherapy has significantly enhanced the therapeutic outcomes for LC. Nevertheless, the underlying therapeutic mechanisms remain unclear, posing a hindrance to the progression of subsequent treatment strategies.
Objectives
To explore the potential mechanisms from existing effective treatments for LC and identify relevant targets, thereby providing guidance for subsequent therapeutic research on LC.
Methods
This study focuses on ferroptosis, a common type of non-apoptotic cell death that is closely linked to various malignancies. It examines the relationship between ferroptosis and LC by analyzing how regulating ferroptosis-related targets in LC cells can influence the development of the cancer.
Results
There is a strong association between ferroptosis and LC. Regulating the targets related to ferroptosis in LC cells can effectively counteract the progression of LC.
Conclusions
Taking ferroptosis as an entry point, analyzing its potential mechanism in inhibiting LC can provide a direction for the treatment of laryngeal cancer, which may contribute to the improvement of therapeutic strategies for this disease.
... Endogenous Nrf2 is activated after ischemic stroke, resulting in an initial increase in the expression of overall Nrf2 protein and a subsequent decrease in the ischemic zone (Tian et al., 2020;Yang et al., 2009). Oxygen-glucose deprivation/reperfusion (OGD/R)-induced ferroptosis can be reversed by accelerating the transcription of GPX4 via the Nrf2-SLC7A11 signaling pathway (Liu et al., 2023b), which may be associated with disulfidptosis. After transient middle cerebral artery occlusion in Nrf2 gene knockout mice, the induction and activation of antioxidant enzymes are inhibited, resulting in a larger stroke area . ...
Disulfidptosis is a pathologic process that occurs under conditions of NADPH deficiency and excess disulfide bonds in cells that express high levels of SLC7A11. This process is caused by glucose deprivation-induced disulfide stress and was first described by cancer researchers. Oxidative stress is a hypothesized mechanism underlying diseases of the central nervous system (CNS), and disulfide stress is a specific type of oxidative stress. Proteins linked to disulfidptosis and metabolic pathways involved in disulfidptosis are significantly associated with diseases of the CNS (neurodegenerative disease, neurogliomas and ischemic stroke). However, the specific mechanism responsible for this correlation remains unknown. This review provides a comprehensive overview of the current knowledge regarding the origin elements, genetic factors, and signaling proteins involved in the pathogenesis of disulfidptosis. It demonstrates that the disruption of thiometabolism and disulfide stress play critical roles in CNS diseases, which are associated with the potential role of disulfidptosis. We also summarize disulfidptosis-related drugs and highlight potential therapeutic strategies for treating CNS diseases. Additionally, this paper suggests a testable hypothesis that might be a promising target for treating CNS diseases.
... In painless gastrointestinal endoscopy, propofol is a commonly used anesthetic drug, which has a significant sedative effect but also shows some side effects during use, such as respiratory depression, decreased blood pressure, and slowed heart rate [40]. In order to find safer and more effective anesthesia drugs, researchers developed ciprofol [41] based on the activity of propofol. ...
Background
The role of ciprofol as a novel anesthetic in gastrointestinal endoscopic surgery is unclear. We conducted a systematic review and meta-analysis to evaluate the efficacy and safety of ciprofol for gastrointestinal endoscopy in patients aged over 65 years and under 65 years, aiming to provide evidence-based information for clinical decision-making.
Methods
We conducted a search for RCTs(randomized controlled trials) comparing ciprofol and propofol in gastrointestinal endoscopy on databases including PubMed, Embase, Cochrane Library, Web of Science, (China National Knowledge Infrastructure)CNKI, Wanfang, and Vipro Chinese Journal Service up to September 15, 2024. The required information was screened and extracted, and the quality of the included research literatures was assessed using the Cochrane Collaboration risk of bias assessment tool, and Meta-analysis of outcome metrics was performed using Revman 5.4 and Stata software.
Results
A total of 17 RCTs involving 2800 patients were included, with 1,450 patients in the ciprofol group and 1350 patients in the propofol group. The results of the meta-analysis indicated that there was no statistically significant difference in the sedation success rate or recovery time between the two groups across all age categories. In patients under 65 years old, the induction time of the ciprofol group (MD = 0.41 min, 95%CI: 0.04 min ∼ 0.78 min, P = 0.03) was longer than that in the propofol group. The incidences of hypotension (OR = 0.48, 95%CI: 0.32 ∼ 0.72, P = 0.004), bradycardia (OR = 0.66, 95%CI: 0.49 ∼ 0.87, P = 0.004), injection pain (OR = 0.08, 95%CI: 0.05 ∼ 0.15, P<0.0001), respiratory depression (OR = 0.21, 95%CI: 0.15 ∼ 0.30, P<0.0001), and hypoxemia (OR = 0.29, 95%CI: 0.20 ∼ 0.43, P<0.0001), in the ciprofol group were much lower than those in the propofol group.
Conclusion
Meta-analysis results indicate that, across various age groups, ciprofol demonstrates a higher safety profile and effectively reduces the incidence of postoperative (ADRs)adverse reactions compared to propofol. However, there is no significant difference in the sedative effects of the two agents. This study categorized elderly patients into subgroups, thereby providing a foundation for the application of ciprofol in gastrointestinal examinations of elderly patients. Consequently, we propose that ciprofol may serve as a safer alternative to intravenous anesthesia compared to propofol; However, this conclusion requires further validation through high-quality studies.
... 33,34 Dose adjustment was not required for the administration of ciprofol in patients with mild to moderate renal function impairment. 35 Regarding its effects on organ function, ciprofol has been shown to exert neuroprotection against cerebral I/R injury in mice; 36 another study suggested that ciprofol could mitigate myocardial damage but did not explore underlying mechanisms. 37 We found that ciprofol reduced CK-MB and cTnI levels and improved cardiac function in mice with myocardial I/R injury. ...
Purpose
Ciprofol is a novel intravenous anesthetic that has been increasingly used in clinical anesthesia and sedation. Studies suggested that ciprofol reduced oxidative stress and inflammatory responses to alleviate cerebral ischemia/reperfusion (I/R) injury, but whether ciprofol protects the heart against I/R injury and the mechanisms are unknown. Herein, we assessed the effects of ciprofol on ferroptosis during myocardial I/R injury.
Methods
Experimental models of myocardial I/R injury in mice (ischemia for 30 min and reperfusion for 24 h) and hypoxia/reoxygenation (H/R) injury in H9c2 cardiomyocytes (hypoxia for 6 h followed by 6 h of reoxygenation) were established. Ciprofol was used prior to ischemia or hypoxia. Echocardiography, myocardial TTC staining, HE staining, DAB-enhanced Perl’s staining, transmission electron microscopy, FerroOrange staining, Liperfluo staining, JC-1 staining, Rhodamine-123 staining, DCFH-DA staining, and Western blot were performed. Cell viability, serum cardiac enzymes, and oxidative- and ferroptosis-related biomarkers were measured. HIF-1α siRNA transfection and the specific inhibitor BAY87-2243 were utilized for mechanistic investigation.
Results
Ciprofol treatment reduced myocardial infarct area and myocardium damage, alleviated oxidative stress and mitochondrial injury, suppressed Fe²⁺ accumulation and ferroptosis, and improved cardiac function in mice with myocardial I/R injury. Ciprofol also increased cell viability, attenuated mitochondrial damage, and reduced intracellular Fe²⁺ and lipid peroxidation in cardiomyocytes with H/R injury. Ciprofol enhanced the protein expression of HIF-1α and GPX4 and reduced the expression of ACSL4. Specifically, the protective effects of ciprofol against I/R or H/R injury were abolished by downregulating the expression of HIF-1α using siRNA transfection or the inhibitor BAY87-2243.
Conclusion
Ciprofol ameliorated myocardial I/R injury in mice and H/R injury in cardiomyocytes by inhibiting ferroptosis via the upregulation of HIF-1α expression.
... Additionally, ciprofol also protects the heart from ISO insults by suppressing oxidative stress and excessive inflammatory responses [17]. Another study indicated that ciprofol exhibited a protective effect against cerebral ischemia-reperfusion injury through attenuating lipid preoxidation and oxidative stress [36]. ...
Background
Patients who suffered from sepsis-induced acute lung injury (ALI) always need sedation for mechanical ventilation in intensive care unit (ICU). Ciprofol(Cip), a novel intravenous anesthetic, was revealed to have anti-inflammatory and antioxidative properties. Ferroptosis, categorized as a type of newly non-apoptotic cell death, participates in the development of lung injury. This study aimed to identify the effect of ciprofol on sepsis-induced ALI and to determine whether ferroptosis is involved.
Methods and results
To create ALI models, MLE12 alveolar epithelial. Cells and lipopolysaccharide (LPS)-stimulated C57BL/6J mice were used. Our results displyed that Cip reduced lung injury and ferroptosis. In the LPS-induced sepsis mice model, Cip pretreatment partially reduced respiratory system damage, as evaluated by HE, TUNEL and inflammatory factors. By raising GSH levels, ciprofol activated the Nrf2 antioxidative pathway, blocked ferroptosis, increased ferroptosis-related protein (GPX4 and SLC7A11) expressions, and reduced Fe²⁺ content, as well as MDA and 4-HNE levels. However, the protective effects of Cip on lung injury and ferroptosis diminished in Nrf2-KO mice. Additionally, Cip activated the Nrf2 pathway and reduced cell death by preventing detrimental lipid peroxidation and ferroptosis in vitro. However, these effects were not observed in siNrf2-treated cells.
Conclusion
Our study demonstrated that Cip may prevent septic lung injury by suppressing ferroptosis through the Nrf2 pathway.
... It has been reported that excessive production of ROS is associated with neuronal disorders of apoptosis signaling [20][21][22][23] and that mitogen-activated protein kinase (MAPK) is involved in cell survival and apoptosis [24][25][26]. Therefore, studies of the modulation of ROS and MAPK signaling pathways that aim to protect neuronal cells against damage need to be elucidated. ...
... To [47] and that oxidative stress induced by ROS also plays a key role in neuronal damage in the hippocampus [21,48,49]. ...
Background: The peptidyl-prolyl isomerase (PIN1) plays a vital role in cellular processes, including intracellular signaling and apoptosis. While oxidative stress is considered one of the primary mechanisms of pathogenesis in brain ischemic injury, the precise function of PIN1 in this disease remains to be elucidated. Objective: We constructed a cell-permeable PEP-1–PIN1 fusion protein and investigated PIN1’s function in HT-22 hippocampal cells as well as in a brain ischemic injury gerbil model. Methods: Transduction of PEP-1–PIN1 into HT-22 cells and signaling pathways were determined by Western blot analysis. Intracellular reactive oxygen species (ROS) production and DNA damage was confirmed by DCF-DA and TUNEL staining. Cell viability was determined by MTT assay. Protective effects of PEP-1-PIN1 against ischemic injury were examined using immunohistochemistry. Results: PEP-1–PIN1, when transduced into HT-22 hippocampal cells, inhibited cell death in H2O2-treated cells and markedly reduced DNA fragmentation and ROS production. This fusion protein also reduced phosphorylation of mitogen-activated protein kinase (MAPK) and modulated expression levels of apoptosis-signaling proteins in HT-22 cells. Furthermore, PEP-1–PIN1 was distributed in gerbil hippocampus neuronal cells after passing through the blood–brain barrier (BBB) and significantly protected against neuronal cell death and also decreased activation of microglia and astrocytes in an ischemic injury gerbil model. Conclusions: These results indicate that PEP-1–PIN1 can inhibit ischemic brain injury by reducing cellular ROS levels and regulating MAPK and apoptosis-signaling pathways, suggesting that PIN1 plays a protective role in H2O2-treated HT-22 cells and ischemic injury gerbil model.
