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Asthma is a prevalent chronic respiratory disease, yet understanding its ecology and pathogenesis remains a challenge. Trim27, a ubiquitination ligase belonging to the TRIM (tripartite motif-containing) family, has been implicated in regulating multiple pathophysiological processes such as inflammation, oxidative stress, apoptosis, and cell proliferation. However, the role of Trim27 in asthma has not been investigated. Our study found that Trim27 expression significantly increases in the airway epithelium of asthmatic mice. Knockdown of Trim27 expression effectively relieved ovalbumin (OVA)-induced airway hyperresponsiveness (AHR) and lung tissue histopathological changes. Moreover, Trim27 knockdown exhibited a significant reduction in airway inflammation and oxidative stress in asthmatic mice, and in vitro analysis confirmed the favorable effect of Trim27 deletion on inflammation and oxidative stress in mouse airway epithelial cells. Furthermore, our study revealed that deletion of Trim27 in MLE12 cells significantly decreased NLRP3 inflammasome activation, as evidenced by reduced expression of NLRP3, ASC, and pro-IL-1β mRNA. This downregulation was reversed when Trim27, but not its mutant lacking ubiquitination ligase activity, was replenished in these cells. Consistent with these findings, protein levels of NLRP3, pro-caspase-1, pro-IL-1β, cleaved-caspase-1, and cleaved-IL-1β were higher in Trim27-replenished cells compared to cells expressing Trim27C/A. Functionally, the downregulation of IL-1β and IL-18 levels induced by Trim27 deletion was rescued by replenishing Trim27. Overall, our findings provide evidence that Trim27 contributes to airway inflammation and oxidative stress in asthmatic mice via NLRP3 inflammasome activation, providing crucial insights into potential therapeutic interventions targeting Trim27 as a way to treat asthma., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Ischemic stroke is a severe and acute neurological disorder with limited therapeutic strategies currently available. Oxidative stress is one of the critical pathological factors in ischemia/reperfusion injury, and high levels of reactive oxygen species (ROS) may drive neuronal apoptosis. Rescuing neurons in the penumbra is a potential way to recover from ischemic stroke. Endogenous levels of the potent ROS quencher glutathione (GSH) decrease significantly after cerebral ischemia. Here, we aimed to investigate the neuroprotective effects of γ -glutamylcysteine ( γ -GC), an immediate precursor of GSH, on neuronal apoptosis and brain injury during ischemic stroke. Middle cerebral artery occlusion (MCAO) and oxygen-glucose deprivation/reoxygenation (OGD/R) were used to mimic cerebral ischemia in mice, neuronal cell lines, and primary neurons. Our data indicated that exogenous γ -GC treatment mitigated oxidative stress, as indicated by upregulated GSH and decreased ROS levels. In addition, γ -GC attenuated ischemia/reperfusion-induced neuronal apoptosis and brain injury in vivo and in vitro. Furthermore, transcriptomics approaches and subsequent validation studies revealed that γ -GC attenuated penumbra neuronal apoptosis by inhibiting the activation of protein kinase R-like endoplasmic reticulum kinase (PERK) and inositol-requiring enzyme 1 α (IRE1 α ) in the endoplasmic reticulum (ER) stress signaling pathway in OGD/R-treated cells and ischemic brain tissues. To the best of our knowledge, this study is the first to report that γ -GC attenuates ischemia-induced neuronal apoptosis by suppressing ROS-mediated ER stress. γ -GC may be a promising therapeutic agent for ischemic stroke., Competing Interests: The authors declare that they have no conflict of interest., (Copyright © 2021 Hui-qin Li et al.)

Fucoxanthin (FX), a natural carotenoid found in seaweed with multiple functional activities, is unstable with a poor water solubility that limits its utilization. This study aimed to improve FX's stability and bioavailability via the nano-encapsulation of FX in polyvinylpyrrolidone (PVP)-coated FX@PVP nanoparticles (NPs). The FX@PVP NPs were evaluated in terms of their morphology, stability, encapsulation efficiency (EE), loading capacity (LC), and in vitro release to optimize the encapsulation parameters, and a 1:8 FX:PVP ratio was found to perform the best with the highest EE (85.50 ± 0.19%) and LC (10.68 ± 0.15%) and improved FX stability. In addition, the FX@PVP NPs were shown to effectively deliver FX into Caco-2 cancer cells, and the accumulation of FX in these cancer cells showed pro-oxidative activities to ameliorate H 2 O 2 -induced damage and cell death. The FX@PVP NPs could potentially become a new therapeutical approach for targeted cancer treatment.

Background: Oscillatory shear stress (OSS) disrupts endothelial homeostasis and promotes oxidative stress, which can lead to atherosclerosis. In atherosclerotic lesions, Toll-like receptor 4 (TLR4) is highly expressed. However, the molecular mechanism by which TLR4 modulates oxidative changes and the cell signaling transudation upon OSS is yet to be determined., Methods and Results: Carotid artery constriction (CAC) surgery and a parallel-plate flow chamber were used to modulate shear stress. The results showed that OSS significantly increased the oxidative burden, and this was partly due to TLR4 activation. OSS activated NOX2 and had no significant influence to NOX1 or NOX4 in endothelial cells (ECs). OSS phosphorylated caveolin-1, promoted its binding with endothelial nitric oxide synthase (eNOS), and resulted in deactivation of eNOS. TLR4 inhibition restored levels of nitric oxide (NO) and superoxide dismutase (SOD) in OSS-exposed cells., Conclusion: TLR4 modulates OSS-induced oxidative stress by activating NOX2 and suppressing eNOS.

Background: Oscillatory shear stress (OSS) occurs in areas where atherosclerosis is prevalent. Toll-like receptor 2 (TLR2) has been associated with mechanical-stress-mediated activation of signalling pathways that may lead to inflammation, apoptosis, and atherosclerosis. Nonetheless, the mechanism underlying the connection between TLR2 and OSS is not fully understood. The purpose of this study was to investigate the link between OSS and TLR2 in human umbilical vein endothelial cell (HUVECs)., Methods: Monolayer endothelial cells were stimulated or not stimulated by OSS. Protein expression was determined by western blotting and immunofluorescent staining. Endothelial function was assessed by using dihydroethidium assay, RT-PCR, immunofluorescent staining and western blotting. The carotid artery of rats was ligated for 1 week, and a section exposed to OSS was excised and analysed., Results: In vitro, the expression of TLR2 in HUVECs was activated by OSS. Additionally, OSS increased apoptosis, inflammatory changes, and oxidative stress in HUVECs, and these effects were reversed by down-regulation the expression of TLR2. We proved that OSS regulates the inflammatory response of endothelial cells through the TLR2-TAK1-IKK2 pathway. In the rats with carotid artery ligation, TLR2, TAK1 and phospho-IKK2 amounts increased at the site of OSS., Significance: According to our results, the OSS-mediated HUVECs injury may be associated with an increase in TLR2 expression. Accordingly, strategies designed to reduce TLR2 expression or inhibit TLR2 activation may be an effective approach to reduce the incidence of atherosclerosis., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Amyloid-β (Aβ) induces a burst of oxidative stress and plays a critical role in the pathogenesis of Alzheimer's disease (AD). Our previous results have shown that histone deacetylase 3 (HDAC3) inhibition ameliorates spatial memory deficits and decreases the Aβ burden in the brains of 9-month-old APPswe/PS1dE9 (APP/PS1) mice. In this study, we investigated the role of HDAC3 inhibition in oxidative stress in vivo and in vitro models of AD. HDAC3 was detected mainly in the neurons, and HDAC3 inhibition significantly decreased reactive oxygen species generation and improved primary cortical neuron viability. In addition, HDAC3 inhibition attenuated spatial memory dysfunction in 6-month-old APP/PS1 mice, and decreased the apoptotic rate in the hippocampi as demonstrated by TUNEL staining. HDAC3 inhibition also reduced markers of lipid peroxidation, protein oxidation, and DNA/RNA oxidation in the hippocampi of APP/PS1 mice. Moreover, HDAC3 inhibition inactivated the c-Abl/MST1/YAP signaling pathway in the hippocampi of APP/PS1 mice. In conclusion, our data show that HDAC3 inhibition can attenuate spatial memory deficits and inhibit oxidative stress in APP/PS1 mice; these results indicate a potential strategy for AD treatment.

Epidemiological studies show that particulate matter (PM) with an aerodynamic diameter ≤ 2.5 μm (PM2.5) is associated with cardiorespiratory diseases via the induction of excessive oxidative stress. However, the precise mechanism underlying PM2.5-mediated oxidative stress injury has not been fully elucidated. Accumulating evidence has indicated the microRNA let-7 family might play a role in PM-mediated pathological processes. In this study, we investigated the role of let-7a in oxidative stress and cell injury in human bronchial epithelial BEAS2B (B2B) cells after PM2.5 exposure. The let-7a level was the most significantly decreased in B2B cells after PM2.5 exposure. The overexpression of let-7a suppressed intracellular reactive oxygen species levels and the percentage of apoptotic cells after PM2.5 exposure, while the let-7a level decreased arginase 2 (ARG2) mRNA and protein levels in B2B cells by directly targeting the ARG2 3'-untranslated region. ARG2 expression was upregulated in B2B cells during PM2.5 treatment, and ARG2 knockdown could remarkably reduce oxidative stress and cellular injury. Moreover, its restoration could abrogate the protective effects of let-7a against PM2.5-induced injury. In conclusion, let-7a decreases and ARG2 increases resulting from PM2.5 exposure may exacerbate oxidative stress, cell injury and apoptosis of B2B cells. The let-7a/ARG2 axis is a likely therapeutic target for PM2.5-induced airway epithelial injury. Copyright © 2016 John Wiley & Sons, Ltd., (Copyright © 2016 John Wiley & Sons, Ltd.)

Background: Previous studies have suggested that exogenous hydrogen sulfide can alleviate the development of diabetic cardiomyopathy (DCM) by inhibiting oxidative stress, inflammation, and apoptosis. However, the underlying mechanism is not fully understood. Nuclear expression and function of the transcription factor Forkhead box protein O (FoxO1) have been associated with cardiovascular diseases, and thus, the importance of FoxO1 in DCM has gained increasing attention. This study was designed to investigate the interactions between hydrogen sulfide (H2S) and nuclear FoxO1 in DCM. Methods: Diabetes was induced in adult male C57BL/6J mice by intraperitoneal injection of streptozotocin and was treated with H2S donor sodium hydrosulfide for 12 weeks. The H9C2 cardiomyoblast cell line and neonatal rat cardiomyocytes (NRCMs) were treated with the slow‐releasing H2S donor GYY4137 before high‐glucose (HG) exposure with or without pretreatment with the Akt inhibitor MK‐2206 2HCl. Changes in FoxO1 protein phosphorylation and subcellular localization were determined in H9C2 cells, NRCMs, and cardiac tissues from normal and diabetic mice. Cardiac structure and function in the diabetic mice were evaluated by echocardiography and histological analysis and compared with those in control animals. Results: The echocardiographic and histopathological data indicated that exogenous H2S improved cardiac function and attenuated cardiac hypertrophy and myocardial fibrosis in diabetic mice. H2S also improved HG‐induced oxidative stress and apoptosis in cardiac tissue and NRCMs. In addition, H2S induced FoxO1 phosphorylation and nuclear exclusion in vitro and in vivo, and this function was not inhibited by MK‐2206 2HCl. Alanine substitution mutation of three sites in FoxO1‐enhanced FoxO1 transcriptional activity, and subsequent treatment with exogenous H2S could not prevent HG‐induced nuclear retention. Conclusions: Our data indicate that H2S is a novel regulator of FoxO1 in cardiac cells and provide evidence supporting the potential of H2S in inhibiting the progression of DCM. Our data indicate that hydrogen sulfide (H2S) is a novel regulator of Forkhead box protein O in cardiac cells and provide evidence supporting the potential of H2S in inhibiting the progression of diabetic cardiomyopathy. [ABSTRACT FROM AUTHOR]

Abstract Daphnetin, one of the major bioactive components isolated from Daphne odora , has been reported to have anti-inflammatory and anti-oxidative effects. Inflammation and oxidative stress have been known to play critical roles in cisplatin-induced nephrotoxicity. The purpose of this study was to investigate the protective effects of daphnetin on cisplatin-induced nephrotoxicity. The levels of blood urea nitrogen (BUN) and creatinine, as well as the kidney reactive oxygen species (ROS), and malondialdehyde (MDA) activity were measured in this study. The expression of inflammatory cytokines TNF-α and IL-1β were measured by ELISA. The results showed that daphnetin protected against cisplatin-induced nephrotoxicity by attenuating kidney histological changes, serum BUN and creatinine. Furthermore, the expression of TNF-α and IL-1β, as well as ROS and MDA in kidney tissues were decreased by daphnetin. In addition, daphnetin dose-dependently inhibited cisplatin-induced NF-κB activation and up-regulated the expression of Nrf2 and HO-1. In conclusion, the results of this study suggested that daphnetin inhibited cisplatin-induced nephrotoxicity by inhibiting NF-κB and activating Nrf2 signaling pathways. Daphnetin might be a promising agent in the treatment of kidney injury. Highlights • Daphnetin protected against cisplatin-induced nephrotoxicity by attenuating kidney histological changes, serum BUN and creatinine. • The production of TNF-α, IL-1ß, ROS, and MDA were inhibited by daphnetin. • Daphnetin inhibited cisplatin-induced NF-κB activation and up-regulated Nrf2 and HO-1. [ABSTRACT FROM AUTHOR]

Amyloid-β (Aβ) induces a burst of oxidative stress and plays a critical role in the pathogenesis of Alzheimer's disease (AD). Our previous results have shown that histone deacetylase 3 (HDAC3) inhibition ameliorates spatial memory deficits and decreases the Aβ burden in the brains of 9-month-old APPswe/PS1dE9 (APP/PS1) mice. In this study, we investigated the role of HDAC3 inhibition in oxidative stress in vivo and in vitro models of AD. HDAC3 was detected mainly in the neurons, and HDAC3 inhibition significantly decreased reactive oxygen species generation and improved primary cortical neuron viability. In addition, HDAC3 inhibition attenuated spatial memory dysfunction in 6-month-old APP/PS1 mice, and decreased the apoptotic rate in the hippocampi as demonstrated by TUNEL staining. HDAC3 inhibition also reduced markers of lipid peroxidation, protein oxidation, and DNA/RNA oxidation in the hippocampi of APP/PS1 mice. Moreover, HDAC3 inhibition inactivated the c-Abl/MST1/YAP signaling pathway in the hippocampi of APP/PS1 mice. In conclusion, our data show that HDAC3 inhibition can attenuate spatial memory deficits and inhibit oxidative stress in APP/PS1 mice; these results indicate a potential strategy for AD treatment. [ABSTRACT FROM AUTHOR]

Globally, microplastics (MPs) are highly prevalent, especially in coastal areas. Unfortunately, golden pompano as a major marine fish in China is typically raised in floating marine cages near coasts, facing these MPs sources. However, toxicological studies on Golden Pompano which farm in coastal areas and face actual microplastic exposure are rare. Therefore, golden pompano were exposed to 10.0 μg/L, 100.0 μg/L, and 1000.0 μg/L polystyrene MPs (PS-MPs) for 14 days to study the potential impact of the microplastics on the Golden Pompano. Fish show slowed growth after 14 days of exposure. Histopathology shows irregular shaped nuclei and nuclear and cytoplasmic vacuolation traits in liver. Oxidative stress-related enzyme activity and gene expression data show that oxidative damage occurs in the high-concentrations (100.0 μg/L and 1000.0 μg/L) of PS-MPs exposures. Up-regulation of Grp78 , Xbp-1 , Eif-2α and chop gene expression indicates the occurrence of endoplasmic reticulum stress, and the western blot results also confirmed this. Severe oxidative stress also caused ERS, which ultimately increased BAX/Bcl-2 ratios and induces apoptosis. Furthermore, up-regulated anaerobic respiration, altered lipid metabolism, and immune disturbance were exhibited during PS-MPs stress. Therefore, oxidative stress appeared to be the main toxicity issue caused by MPs, while ERS-mediated apoptosis, metabolic alterations, and immune responses were induced by this stress. Notably, endoplasmic reticulum stress and apoptosis are a self-protective mechanism, which may be an intermediate link in the toxicity of microplastics. This study highlights the role of endoplasmic reticulum stress in MPs toxicology and assesses the adverse effects of microplastics on Golden Pompano. • Microplastics will affect the physiological status of large cultured fishes. • Microplastics alter liver structure and function in golden pompano. • Oxidative stress induced by microplastics mediates endoplasmic reticulum stress leading to apoptosis of liver. [ABSTRACT FROM AUTHOR]

Di(2-ethylhexyl) phthalate (DEHP) has been well acknowledged for its endocrine disruption and associated metabolic diseases, leading to the search for safer industrial alternatives including di-isononyl phthalate (DINP). However, safety data for the latter chemical has been relatively scarce particularly regarding potential damage to the kidney at low doses. Five-week-old ICR male mice were exposed to vehicle, DEHP or DINP (0.05 and 4.8 mg/kg bw) daily via gavage for 5 weeks. We observed increased levels of reactive oxygen species and malondialdehyde, decreased levels of reduced glutathione, in the kidney at higher dose for both chemicals suggestive of oxidative damage. Elevated levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 of the kidney further suggested inflammatory status as a result of phthalate exposure in both high dose groups. Targeted lipidomics demonstrated greatest changes in the kidney induced by high dose of DEHP, although DINP also induced significant changes in phospholipids diacylglycerides that are associated with lipid accumulation in glomerular podocytes and inflammatory responses. Our data suggest that oxidative stress may be involved in both DEHP- and DINP-induced renal lipidomic disruption and continue to question the suitability of DINP as proper DEHP substitute. • Both DEHP and DINP induced renal oxidative stress at higher exposure levels. • Low levels of DEHP and DINP induced obesogenic effect. • DEHP and DINP caused significant disruptions in renal lipidome. • Oxidative stress may be involved in phthalate-induced renal lipidomic disruption. [ABSTRACT FROM AUTHOR]

Doxorubicin (Dox) is a potent antineoplastic agent, but its use is curtailed by severe cardiotoxicity, known as Dox-induced cardiomyopathy (DIC). The molecular mechanism underlying this cardiotoxicity remains unclear. Our current study investigates the role of Ubiquitin-Specific Protease 36 (USP36), a nucleolar deubiquitinating enzyme (DUB), in the progression of DIC and its mechanism. We found increased USP36 expression in neonatal rat cardiomyocytes and H9C2 cells exposed to Dox. Silencing USP36 significantly mitigated Dox-induced oxidative stress injury and apoptosis in vitro. Mechanistically, USP36 upregulation positively correlated with Poly (ADP-ribose) polymerase 1 (PARP1) expression, and its knockdown led to a reduction in PARP1 levels. Further investigation revealed that USP36 could bind to and mediate the deubiquitination of PARP1, thereby increasing its protein stability in cardiomyocytes upon Dox exposure. Moreover, overexpression of wild-type (WT) USP36 plasmid, but not its catalytically inactive mutant (C131A), stabilized PARP1 in HEK293T cells. We also established a DIC model in mice and observed significant upregulation of USP36 in the heart. Cardiac knockdown of USP36 in mice using a type 9 recombinant adeno-associated virus (rAAV9)-shUSP36 significantly preserved cardiac function after Dox treatment and protected against Dox-induced structural changes within the myocardium. In conclusion, these findings suggest that Dox promotes DIC progression by activating USP36-mediated PARP1 deubiquitination. This novel USP36/PARP1 axis may play a significant regulatory role in the pathogenesis of DIC. • Deficiency in USP36 provides a protective effect against cardiac oxidative stress injury and apoptosis induced by Dox. • USP36 interacts with PARP1, and it is through this interaction that USP36 influences the regulation of cardiac injury. • This research broadens our understanding of the USP family's role in cardiovascular diseases. [ABSTRACT FROM AUTHOR]