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BMC Neurology Jun 2024Edaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating the...
BACKGROUND
Edaravone dexborneol has been reported as an effective neuroprotective agent in the treatment of acute ischemic stroke (AIS). This study aimed at investigating the impact of edaravone dexborneol on functional outcomes and systematic inflammatory response in AIS patient.
METHODS
All participants were recruited from the AISRNA study (registered 21/11/2019, NCT04175691 [ClinicalTrials.gov]) between January 2022 and December 2022. The AIS patients were divided into two groups based on whether they received the treatment of edaravone dexborneol (37.5 mg/12 hours, IV) within 48 h after stroke onset. Inflammatory response was determined by detecting levels of cytokines (interleukin-2 [IL-2], IL-4, IL-5, IL-8, IL-6, IL-10, IL-12p70, IL-17, tumor necrosis factor-α [TNF-α], interferon-γ [IFN-γ], IFN-α, and IL-1β) within 14 days after stroke onset.
RESULTS
Eighty-five AIS patients were included from the AISRNA study. Patients treated with edaravone dexborneol showed a significantly higher proportion of modified Rankin Scale score < 2 compared to those who did not receive this treatment (70.7% versus 47.8%; P = 0.031). Furthermore, individuals receiving edaravone dexborneol injection exhibited lower expression levels of interleukin (IL)-1β, IL-6, and IL-17, along with higher levels of IL-4 and IL-10 expression during the acute phase of ischemic stroke (P < 0.05). These trends were not observed for IL-2, IL-5, IL-8, IL-12p70, tumor necrosis factor-α, interferon-γ [IFN-γ], and IFN-α (P > 0.05).
CONCLUSIONS
Treatment with edaravone dexborneol resulted in a favorable functional outcome at 90 days post-stroke onset when compared to patients without this intervention; it also suppressed proinflammatory factors expression while increasing anti-inflammatory factors levels.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04175691. Registered November 21, 2019, https://www.
CLINICALTRIALS
gov/ct2/show/NCT04175691 .
Topics: Humans; Edaravone; Male; Ischemic Stroke; Female; Aged; Middle Aged; Cytokines; Neuroprotective Agents; Treatment Outcome; Inflammation
PubMed: 38902691
DOI: 10.1186/s12883-024-03712-1 -
Microbiome Research Reports 2024The gut and its microbiome have a major impact on many aspects of health and are therefore also an attractive target for drug- or food-based therapies. Here, we report...
The gut and its microbiome have a major impact on many aspects of health and are therefore also an attractive target for drug- or food-based therapies. Here, we report on the added value of combining a microbiome screening model, the i-screen, with fresh intestinal tissue explants in a microfluidic gut-on-a-chip model, the Intestinal Explant Barrier Chip (IEBC). Adult human gut microbiome (fecal pool of 6 healthy donors) was cultured anaerobically in the i-screen platform for 24 h, without and with exposure to 4 mg/mL inulin. The i-screen cell-free culture supernatant was subsequently applied to the luminal side of adult human colon tissue explants ( = 3 donors), fixed in the IEBC, for 24 h and effects were evaluated. The supplementation of the media with inulin promoted the growth of , , , and in the i-screen, and triggered an elevated production of butyrate by the microbiota. Human colon tissue exposed to inulin-treated i-screen cell-free culture supernatant or control i-screen cell-free culture supernatant with added short-chain fatty acids (SCFAs) showed improved tissue barrier integrity measured by a 28.2%-34.2% reduction in FITC-dextran 4000 (FD4) leakage and 1.3 times lower transport of antipyrine. Furthermore, the release of pro-inflammatory cytokines IL-1β, IL-6, IL-8, and TNF-α was reduced under these circumstances. Gene expression profiles confirmed these findings, but showed more profound effects for inulin-treated supernatant compared to SCFA-supplemented supernatant. The combination of i-screen and IEBC facilitates the study of complex intestinal processes such as host-microbial metabolite interaction and gut health.
PubMed: 38841408
DOI: 10.20517/mrr.2023.79 -
International Journal of Molecular... May 2024Polyurethanes are among the most significant types of polymers in development; these materials are used to produce construction products intended for work in various... (Review)
Review
Polyurethanes are among the most significant types of polymers in development; these materials are used to produce construction products intended for work in various conditions. Nowadays, it is important to develop methods for fire load reduction by using new kinds of additives or monomers containing elements responsible for materials' fire resistance. Currently, additive antipyrines or reactive flame retardants can be used during polyurethane material processing. The use of additives usually leads to the migration or volatilization of the additive to the surface of the material, which causes the loss of the resistance and aesthetic values of the product. Reactive flame retardants form compounds containing special functional groups that can be chemically bonded with monomers during polymerization, which can prevent volatilization or migration to the surface of the material. In this study, reactive flame retardants are compared. Their impacts on polyurethane flame retardancy, combustion mechanism, and environment are described.
Topics: Flame Retardants; Polyurethanes; Green Chemistry Technology
PubMed: 38791552
DOI: 10.3390/ijms25105512 -
Neuropharmacology Sep 2024Currently, there are no effective therapeutic agents available to treat Alzheimer's disease (AD). However, edaravone dexborneol (EDB), a novel composite agent used to...
Currently, there are no effective therapeutic agents available to treat Alzheimer's disease (AD). However, edaravone dexborneol (EDB), a novel composite agent used to treat acute ischemic stroke, has recently been shown to exert efficacious neuroprotective effects. However, whether EDB can ameliorate cognitive deficits in AD currently remains unclear. To this end, we explored the effects of EDB on AD and its potential mechanisms using an AD animal model (male APP/PS1 mice) treated with EDB for 10 weeks starting at 6 months of age. Subsequent analyses revealed that EDB-treated APP/PS1 mice exhibited improved cognitive abilities compared to untreated APP/PS1 mice. Administration of EDB in APP/PS1 mice further alleviated neuropathological alterations of the hippocampus, including Aβ deposition, pyramidal cell karyopyknosis, and oxidative damage, and significantly decreased the levels of inflammatory cytokines (IL-1β, IL-6 and TNF-α) and COX-2 in the hippocampus of APP/PS1 mice. Transcriptome sequencing analysis demonstrated the critical role of the inflammatory reaction in EDB treatment in APP/PS1 mice, indicating that the alleviation of the inflammatory reaction by EDB in the hippocampus of APP/PS1 mice was linked to the action of the TREM2/TLR4/MAPK signaling pathway. Further in vitro investigations showed that EDB suppressed neuroinflammation in LPS-stimulated BV2 cells by inhibiting the TLR4/MAPK signaling pathway and upregulating TREM2 expression. Thus, the findings of the present study demonstrate that EDB is a promising therapeutic agent for AD-related cognitive dysfunction.
Topics: Animals; Toll-Like Receptor 4; Mice; Male; Cognitive Dysfunction; Receptors, Immunologic; Membrane Glycoproteins; Edaravone; Up-Regulation; Mice, Transgenic; Neuroprotective Agents; MAP Kinase Signaling System; Hippocampus; Amyloid beta-Protein Precursor; Mice, Inbred C57BL; Alzheimer Disease; Disease Models, Animal; Presenilin-1
PubMed: 38763325
DOI: 10.1016/j.neuropharm.2024.110006 -
Biomolecules Apr 2024A considerable effort has been spent in the past decades to develop targeted therapies for the treatment of demyelinating diseases, such as multiple sclerosis (MS)....
A considerable effort has been spent in the past decades to develop targeted therapies for the treatment of demyelinating diseases, such as multiple sclerosis (MS). Among drugs with free radical scavenging activity and oligodendrocyte protecting effects, Edaravone (Radicava) has recently received increasing attention because of being able to enhance remyelination in experimental in vitro and in vivo disease models. While its beneficial effects are greatly supported by experimental evidence, there is a current paucity of information regarding its mechanism of action and main molecular targets. By using high-throughput RNA-seq and biochemical experiments in murine oligodendrocyte progenitors and SH-SY5Y neuroblastoma cells combined with molecular docking and molecular dynamics simulation, we here provide evidence that Edaravone triggers the activation of aryl hydrocarbon receptor (AHR) signaling by eliciting AHR nuclear translocation and the transcriptional-mediated induction of key cytoprotective gene expression. We also show that an Edaravone-dependent AHR signaling transduction occurs in the zebrafish experimental model, associated with a downstream upregulation of the NRF2 signaling pathway. We finally demonstrate that its rapid cytoprotective and antioxidant actions boost increased expression of the promyelinating Olig2 protein as well as of an Olig2:GFP transgene in vivo. We therefore shed light on a still undescribed potential mechanism of action for this drug, providing further support to its therapeutic potential in the context of debilitating demyelinating conditions.
Topics: Animals; Humans; Mice; Antioxidants; Basic Helix-Loop-Helix Transcription Factors; Cell Line, Tumor; Edaravone; Molecular Docking Simulation; Molecular Dynamics Simulation; NF-E2-Related Factor 2; Receptors, Aryl Hydrocarbon; Signal Transduction; Zebrafish
PubMed: 38672460
DOI: 10.3390/biom14040443 -
Medicine Apr 2024To explore the value of thromboelastography (TEG) in evaluating the efficacy of Xueshuantong combined with edaravone for the treatment of acute cerebral infarction... (Observational Study)
Observational Study
To explore the value of thromboelastography (TEG) in evaluating the efficacy of Xueshuantong combined with edaravone for the treatment of acute cerebral infarction (ACI). We retrospectively analyzed the clinical data of 96 patients with ACI treated with Xueshuantong combined with edaravone and monitored by TEG. The correlation between the results of TEG examination and treatment outcomes in patients after treatment was analyzed. After treatment, 65 of 96 patients showed good efficacy and 31 had poor efficacy. kinetic time (KT), reaction time (RT), and the percentage of clot lysis at 30 minutes after Ma value (LY30) of patients with good therapeutic effects were significantly higher than those with poor therapeutic effects; However, maximum amplitude (MA) and coagulation index (CI) were significantly lower than those with poor efficacy (P < .05). There was a significant positive correlation between KT, RT, and LY30 and the therapeutic effect of ACI, and a significant negative correlation between the therapeutic effects of MA, CI, and ACI (P < .05). Logistic analysis confirmed that KT, RT, and LY30 were protective factors for the therapeutic effect of ACI; MA and CI were risk factors for the therapeutic effect of ACI (P < .05). TEG has a high value in evaluating the efficacy of Xueshuantong combined with edaravone in the treatment of ACI. It can clarify changes in the coagulation function of patients, thereby guiding clinical follow-up treatment.
Topics: Humans; Thrombelastography; Edaravone; Male; Female; Cerebral Infarction; Retrospective Studies; Middle Aged; Aged; Drugs, Chinese Herbal; Treatment Outcome; Drug Therapy, Combination; Acute Disease; Aged, 80 and over
PubMed: 38669396
DOI: 10.1097/MD.0000000000037954 -
Applied Microbiology and Biotechnology Apr 2024Water bodies are increasingly contaminated with a diversity of organic micropollutants (OMPs). This impacts the quality of ecosystems due to their recalcitrant nature....
Water bodies are increasingly contaminated with a diversity of organic micropollutants (OMPs). This impacts the quality of ecosystems due to their recalcitrant nature. In this study, we assessed the removal of OMPs by spent mushroom substrate (SMS) of the white button mushroom (Agaricus bisporus) and by its aqueous tea extract. Removal of acesulfame K, antipyrine, bentazon, caffeine, carbamazepine, chloridazon, clofibric acid, and N, N-diethyl-meta-toluamide (DEET) by SMS and its tea was between 10 and 90% and 0-26%, respectively, in a 7-day period. Sorption to SMS particles was between 0 and 29%, which can thus not explain the removal difference between SMS and its tea, the latter lacking these particles. Carbamazepine was removed most efficiently by both SMS and its tea. Removal of OMPs (except caffeine) by SMS tea was not affected by heat treatment. By contrast, heat-treatment of SMS reduced OMP removal to < 10% except for carbamazepine with a removal of 90%. These results indicate that OMP removal by SMS and its tea is mediated by both enzymatic and non-enzymatic activities. The presence of copper, manganese, and iron (0.03, 0.88, and 0.33 µg L, respectively) as well as HO (1.5 µM) in SMS tea indicated that the Fenton reaction represents (part of) the non-enzymatic activity. Indeed, the in vitro reconstituted Fenton reaction removed OMPs > 50% better than the teas. From these data it is concluded that spent mushroom substrate of the white button mushroom, which is widely available as a waste-stream, can be used to purify water from OMPs.
Topics: Ecosystem; Caffeine; Hydrogen Peroxide; Agaricus; Water; Tea; Carbamazepine
PubMed: 38639797
DOI: 10.1007/s00253-024-13132-3 -
Scientific Reports Apr 2024The etiopathogenesis of severe acute pancreatitis (SAP) remains poorly understood. We aim to investigate the role of immune cells Infiltration Characteristics during SAP...
The etiopathogenesis of severe acute pancreatitis (SAP) remains poorly understood. We aim to investigate the role of immune cells Infiltration Characteristics during SAP progression. Gene expression profiles of the GSE194331 dataset were retrieved from the GEO. Lasso regression and random forest algorithms were employed to select feature genes from genes related to SAP progression and immune responses. CIBERSORT was utilized to estimate differences in immune cell types and proportions and the relationship between immune cells and gene expression. We performed pathway enrichment analysis using GSEA to examine disparities in KEGG signaling pathways when comparing the two groups. Additionally, CMap analysis was executed to identify prospective small molecular compounds. The three hub genes (CBLB, JADE2, RNF144A) were identified that can predict SAP progression. Analysis of CIBERSORT and TISIDB databases has shown that there are significant differences in immune cell expression levels between the normal and SAP groups, and three hub genes (CBLB, JADE2, RNF144A) were highly correlated with multiple immune cells, regulating the characteristics of immune cell infiltration in the microenvironment. Finally, drug prediction through the Connectivity Map database suggested that compounds such as Entecavir, KU-0063794, Y-27632, and Antipyrine have certain effects as potential targeted drugs for the treatment of SAP. CBLB, JADE2, and RNF144A are hub genes in SAP, potentially playing important roles in SAP progression. This finding further broadens the understanding of the etiopathogenesis of SAP and provides a feasible basis for future research on diagnostic and immunotherapeutic targets for SAP.
Topics: Humans; Acute Disease; Prospective Studies; Pancreatitis; Drug Delivery Systems; Computational Biology
PubMed: 38622245
DOI: 10.1038/s41598-024-59205-1 -
Environmental Research Jul 2024In this study, the removal of two emerging pollutants (EPs), antipyrine and acetanilide, through adsorption on activated carbons (ACs) prepared by chemical activation of...
In this study, the removal of two emerging pollutants (EPs), antipyrine and acetanilide, through adsorption on activated carbons (ACs) prepared by chemical activation of Organosolv lignin with HPO were evaluated. ACs with different pore size distribution were obtained at different impregnation ratios (HPO/lignin, 0.5-3.0 w/w) and activating temperatures (500-900 °C). The porosity and surface chemistry of the ACs were determined, and a bimodal size distribution of micropores and narrow mesopores was observed for the different ACs. These ACs were tested for antipyrine and acetanilide adsorption in aqueous solutions in a batch system at 20 °C and low concentration levels (0.5-10 ppm). In general, the ACs exhibited higher adsorption affinity to acetanilide than to antipyrine due to its smaller molecular size. Langmuir adsorption isotherm was able to describe the adsorption equilibrium data. A new Linear Driving Force (2-LDF) kinetic model, based on the bimodal size distribution of micropores and narrow mesopores observed for the ACs has been developed. The new model provided a more accurate description of the batch adsorption rates than that obtained from conventional kinetic models, and also enabled to relate the pore size distribution of the adsorbent with the adsorption kinetics. The validity of this model was checked in small-scale column fixed bed adsorption for the AC showing the highest affinity for both EP. The kinetic model and equilibrium adsorption isotherm obtained from the batch experiments were successfully used to provide an accurate description of the bed service time and the full breakthrough profile of acetanilide and antipyrine.
Topics: Adsorption; Lignin; Antipyrine; Acetanilides; Charcoal; Water Pollutants, Chemical
PubMed: 38614198
DOI: 10.1016/j.envres.2024.118918 -
Brain Research Jun 2024Exploring the intricate pathogenesis of Vascular Dementia (VD), there is a noted absence of potent treatments available in the current medical landscape. A new...
Edaravone dexborneol attenuates cognitive impairment in a rat model of vascular dementia by inhibiting hippocampal oxidative stress and inflammatory responses and modulating the NMDA receptor signaling pathway.
Exploring the intricate pathogenesis of Vascular Dementia (VD), there is a noted absence of potent treatments available in the current medical landscape. A new brain-protective medication developed in China, Edaravone dexboeol (EDB), has shown promise due to its antioxidant and anti-inflammatory properties, albeit with a need for additional research to elucidate its role and mechanisms in VD contexts. In a research setup, a VD model was established utilizing Sprague-Dawley (SD) rats, subjected to permanent bilateral typical carotid artery occlusion (2VO). Behavioral assessment of the rats was conducted using the Bederson test and pole climbing test, while cognitive abilities, particularly learning and memory, were evaluated via the novel object recognition test and the Morris water maze test. Ensuing, the levels of malondialdehyde (MDA), superoxide dismutase (SOD), IL-1β, IL-6, IL-4, and tumor necrosis factor-α (TNF-α) were determined through Enzyme-Linked Immunosorbent Assay (ELISA). Synaptic plasticity-related proteins, synaptophysin (SYP), post-synaptic density protein 95 (PSD-95), and N-methyl-D-aspartate (NMDA) receptor proteins (NR1, NR2A, NR2B) were investigated via Western blotting technique. The findings imply that EDB has the potential to ameliorate cognitive deficiencies, attributed to VD, by mitigating oxidative stress, dampening inflammatory responses, and modulating the NMDA receptor signaling pathway, furnishing new perspectives into EDB's mechanism and proposing potential avenues for therapeutic strategies in managing VD.
Topics: Animals; Dementia, Vascular; Oxidative Stress; Rats, Sprague-Dawley; Edaravone; Cognitive Dysfunction; Rats; Hippocampus; Receptors, N-Methyl-D-Aspartate; Male; Signal Transduction; Disease Models, Animal; Neuroprotective Agents; Inflammation
PubMed: 38582415
DOI: 10.1016/j.brainres.2024.148917