Alleviated Lipid Peroxidation Research Articles

Carnosine Synthase (TsATPGD) Alleviates Lipid Peroxidation Under Transcriptional Control by an Nfe2-like Gene in Tridacna Squamosa

As an important mollusk in reef ecosystems, Tridacna squamosa forms pro-survival symbiotic relationships that hinge on an exquisite redox equilibrium between the host and the photosynthetic symbiont, zooxanthellae. The exact regulatory mechanisms thereof remain poorly understood. In this study, a novel Nfe2-like transcription factor in T. squamosa was identified and characterized with respect to its antioxidant and cytoprotective roles. Gene structure and phylogenetic analysis reveal that T. squamosa possesses a single transcription factor TsNfe2l in contrast to mammalian Nfe2l1 (Nrf1) and Nfe2l2 (Nrf2), belonging to protein members of the bZIP-NFE2 subfamily and functionally resembling the mammalian Nfe2l1. A conserved bZIP domain permits its binding to the antioxidant response element (ARE) in vitro and in HEK293T cells. Further analyses such as promoter prediction suggest that TsNfe2l target genes engage mainly in the regulation of multiple enzymes involved in antioxidation and allied pathways. Notably, TsNfe2l transcriptionally upregulates carnosine synthase (TsATPGD), which subsequently produces L-carnosine abundantly to shield cells from oxidative damage. Moreover, the blockage of TsNfe2l nucleic acid binding reduced the expression of TsATPGD and L-carnosine content in the gill, resulting in elevated lipid peroxidation. Collectively, our findings establish novel molecular insight into TsNfe2l as a critical regulator of redox homeostasis in T. squamosa through carnosine synthesis.

Silencing of lncRNA NEAT1 alleviates acute myocardial infarction by suppressing miR-450–5p/ACSL4-mediated ferroptosis

Ferroptosis is principally initiated by dysregulation of iron metabolism and excessive accumulation of ROS, which exacerbates myocardial injury during acute myocardial infarction (AMI). Previous studies have indeed demonstrated the significant involvement of long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) exerts its pleiotropic effects in the pathophysiology of myocardial infarction, heart failure and atherosclerosis by modulating inflammation, apoptosis, and oxidative stress. However, whether and how NEAT1 mediates myocardial ferroptosis remain unknown. In this study, we found that NEAT1 expression was significantly elevated in hypoxic HL-1 cells and AMI mice, while silencing of NEAT1 alleviated lipid peroxidation and myocardial ferroptosis both in vitro and in vivo. Mechanistically, NEAT1 directly sponged miR-450b-5p and negatively regulated its expression. In addition, miR-450b-5p directly targeted Acyl-CoA synthase long-chain family member 4 (ACSL4). Notably, inhibition of miR-450b-5p reversed the role of NEAT1 in AMI mice. Collectively, these findings newly illustrated that NEAT1 acts as a competitive endogenous RNA (ceRNA) of miR-450–5p in AMI. Especially, silencing of NEAT1 effectively ameliorated myocardium ischemia by suppression of ferroptosis via miR-450–5p/ACSL4 pathway, which providing a brand-new therapeutic strategy for myocardial ischemia injury.

Acteoside alleviates lipid peroxidation by enhancing Nrf2-mediated mitophagy to inhibit ferroptosis for neuroprotection in Parkinson's disease

Increasing evidence underscores the pivotal role of ferroptosis in Parkinson's Disease (PD) pathogenesis. Acteoside (ACT) has been reported to possess neuroprotective properties. However, the effects of ACT on ferroptosis and its molecular mechanisms remain unknown. This study aimed to explore whether ACT can regulate ferroptosis in dopaminergic (DA) neurons within both in vitro and in vivo PD models and to elucidate the underlying regulatory mechanisms. PD models were established and treated with various concentrations of ACT. Cell viability assays, Western blot, lipid peroxidation assessments, immunohistochemistry, and transmission electron microscopy were employed to confirm ACT's inhibition of ferroptosis and its protective effect on DA neurons across PD models. Immunofluorescence staining, MitoSOX staining, and confocal laser scanning microscopy further validated ACT's regulation regulatory effects on ferroptosis via the Nrf2-mitophagy pathway. Four animal behavioral tests were used to assess behavioral improvements in PD animals. ACT inhibited ferroptosis in PD models in vitro, as evidenced by increased cell viability, the upregulation of GPX4 and SLC7A11, reduced lipid peroxides, and attenuation of mitochondrial morphological alterations typical of ferroptosis. By activating the Nrf2-mitophagy axis, ACT enhanced mitochondrial integrity and reduced lipid peroxidation, mitigating ferroptosis. These in vitro results were consistent with in vivo findings, where ACT treatment significantly preserved DA neurons, curbed ferroptosis in these cells, and alleviated cognitive and behavioral deficits. This study is the first demonstration of ACT's capability to inhibit neuronal ferroptosis and protect DA neurons, thus alleviating behavioral and cognitive impairments in both in vitro and in vivo PD models. Furthermore, The suppression of ferroptosis by ACT is achieved through the activation of the Nrf2-mitophagy signaling pathway. Our results show that ACT is beneficial for both treating and preventing PD. They also offer novel therapeutic options for treating PD and molecular targets for regulating ferroptosis.

Cardioprotective Potential of Moringa Oleifera Leaf Extract Loaded Niosomes Nanoparticles - Against Doxorubicin Toxicity In Rats.

Doxorubicin (DOX) is one of the most potent anticancer drugs that has ubiquitous usage in oncology; however, its marked adverse effects, such as cardiotoxicity, are still a major clinical issue. Plant extracts have shown cardioprotective effects and reduced the risk of cardiovascular diseases. The current study is intended to explore the cardioprotective effect of ethanolic Moringa oleifera extracts (MOE) leaves loaded into niosomes (MOE-NIO) against DOXinduced cardiotoxicity in rats. MOE niosomes nanoparticles (NIO-NPs) were prepared and characterized by TEM. Seventy male Wistar rats were randomly divided into seven groups: control, NIO, DOX, DOX+MOE, DOX+MOE-NIO, MOE+DOX, and MOE-NIO+DOX. DOX (4 mg/kg, IP) was injected once per week for 4 weeks with daily administration of MOE or MOENIO (250 mg/kg, PO) for 4 weeks; in the sixth and seventh groups, MOE or MOE-NIO (250 mg/kg, PO) was administered one week before DOX injection. Various parameters were assessed in serum and cardiac tissue. Pre and co-treatment with MOE-NIO have mitigated the cardiotoxicity induced by DOX as indicated by serum aspartate aminotransferase (AST), creatine kinase - MB(CK-MB) and lactate dehydrogenase (LDH), cardiac Troponin 1(cTn1) and lipid profile. MOE-NIO also alleviated lipid peroxidation (MDA), nitrosative status (NO), and inflammatory markers levels; myeloperoxidase (MPO) and tumor necrosis factor-alpha (TNF-α) obtained in DOX-treated animals. Additionally, ameliorated effects have been recorded in glutathione content and superoxide dismutase activity. MOE-NIO effectively neutralized the DOXupregulated nuclear factor kappa B (NF-kB) and p38 mitogen-activated protein kinases (p38 MAPK), and DOX-downregulated nuclear factor-erythroid 2-related factor 2 (Nrf2) expressions in the heart. It is concluded that pre and co-treatment with MOE-NIO could protect the heart against DOX-induced cardiotoxicity by suppressing numerous pathways including oxidative stress, inflammation, and apoptosis and by the elevation of tissue antioxidant status. Thus, it may be reasonable to suggest that pre and co-treatment with MOE-NIO can provide a potential cardioprotective effect when doxorubicin is used in the management of carcinoma.

Aristolochic acid induces acute kidney injury through ferroptosis.

Aristolochic acid (AA)-induced acute kidney injury (AKI) presents with progressive decline in renal function and rapid progression to end-stage renal disease. Among the multiple mechanisms identified in AKI, ferroptosis has been shown to be involved in various forms of AKI. But few studies have elucidated the role of ferroptosis in AA-induced AKI. In this study, we investigated the role of ferroptosis in AA-induced acute renal tubular injury in vivo and in vitro. Mice with acute aristolochic acid nephropathy showed increased malondialdehyde levels, aggravated lipid peroxidation, decreased superoxide dismutase activity, and glutathione depletion. The expression of glutathione peroxidase 4 was decreased and the expression of acyl-CoA synthetase long-chain family member 4 was increased. Inhibition of ferroptosis by ferrostatin-1 significantly improved the renal function, reduced histopathological lesions, partially alleviated lipid peroxidation, and restored the antioxidant capacity. In vitro studies also revealed that AA significantly reduced cell viability, induced reactive oxygen species production, increased intracellular iron level and decreased ferroptosis-related protein expression. Inhibition of ferroptosis significantly increased cell viability and attenuated AA-induced renal tubular epithelial cell injury. It is suggested that ferroptosis plays an important role in AA-induced acute tubular injury. And inhibition of ferroptosis may exert renoprotective effects possibly by preventing lipid peroxidation, restoring the antioxidant activity or regulating iron metabolism.

MCL1 inhibition: a promising approach to augment the efficacy of sorafenib in NSCLC through ferroptosis induction

Ferroptosis, an iron-dependent form of regulated cell death, plays a crucial role in modulating the therapeutic response in non-small cell lung cancer (NSCLC) patients. Studies have identified the signal transducer and activator of transcription 3 (STAT3) and myeloid cell leukemia-1 (MCL1) as potential targets for sorafenib, which exhibits activities in inducing ferroptosis. However, the role of STAT3-MCL1 axis in sorafenib-induced ferroptosis in NSCLC is still unclear. This study provided evidence that ferroptosis is a critical driver of sorafenib-induced cell death in NSCLC, supported by the accumulation of lipid peroxidation products, indicative of oxidative stress-induced cell death. Additionally, both in vitro and in vivo experiments showed that ferroptosis contributed to a significant portion of the anti-cancer effects elicited by sorafenib in NSCLC. The noticeable accumulation of lipid peroxidation products in sorafenib-treated mice underscored the significance of ferroptosis as a contributing factor to the therapeutic response of sorafenib in NSCLC. Furthermore, we identified the involvement of the STAT3/MCL1 axis in sorafenib-induced antitumor activity in NSCLC. Mechanistically, sorafenib inhibited endogenous STAT3 activation and downregulated MCL1 protein expression, consequently unleashing the ferroptosis driver BECN1 from the BECN1-MCL1 complex. Conversely, there is an augmented association of BECN1 with the catalytic subunit of system Xc−, SLC7A11, whose activity to import cystine and alleviate lipid peroxidation is hindered upon its binding with BECN1. Notably, we found that MCL1 upregulation correlated with ferroptosis resistance in NSCLC upon sorafenib treatment. Our findings highlight the importance of sorafenib-triggered ferroptosis in NSCLC and offer a novel strategy to treat advanced NSCLC patients: by downregulating MCL1 and, in turn, predispose NSCLC cells to ferroptosis.

Nuclear mutagenesis and adaptive evolution improved photoautotrophic growth of Euglena gracilis with flue-gas CO2 fixation

To effectively improve biomass growth and flue-gas CO2 fixation of microalgae, acid-tolerant Euglena gracilis was modified with cobalt-60 γ-ray irradiation and polyethylene glycol (PEG) adaptive screening to obtain the mutant strain M800. The biomass dry weight and maximum CO2 fixation rate of M800 were both 1.47 times higher than that of wild strain, which was attributed to a substantial increase in key carbon fixation enzyme RuBisCO activity and photosynthetic pigment content. The high charge separation quantum efficiency in PSII reaction center, efficient light utilization and energy regulation that favors light conversion, were the underlying drivers of efficient photosynthetic carbon fixation in M800. M800 had stronger antioxidant capacity in sufficient high-carbon environment, alleviating lipid peroxidation damage. After adding 1 mM PEG, biomass dry weight of M800 reached 2.31 g/L, which was 79.1 % higher than that of wild strain. Cell proliferation of M800 was promoted, the apoptosis and necrosis rates decreased.

Silibinin Inhibits Cell Ferroptosis and Ferroptosis-Related Tissue Injuries.

Ferroptosis is involved in various tissue injuries including neurodegeneration, ischemia-reperfusion injury, and acute liver injury. Ferroptosis inhibitors exhibit promising clinical potential in the treatment of various diseases. As a traditional chemical, silymarin has been widely used in healthcare and clinical applications to treat liver injuries in which ferroptosis is involved. Silibinin is the main active ingredient of silymarin. However, the effect of silibinin on ferroptosis and ferroptosis-related diseases remains unclear. Here, we found that silibinin inhibited death in different kinds of cells caused by ferroptosis inducers including RSL3 and erastin. Moreover, silibinin alleviated lipid peroxidation induced by RSL3 without affecting the labile iron pool. Next, the antioxidant activity of silibinin was demonstrated by the DPPH assay. In vivo, silibinin strikingly relieved tissue injuries and ferroptosis in the liver and kidney of glutathione peroxidase 4 (GPX4) knockout C57 BL/6J mice. Moreover, silibinin effectively rescued renal ischemia-reperfusion, a well-known ferroptosis-related disease. In conclusion, our study revealed that silibinin effectively inhibits cell ferroptosis and ferroptosis-related tissue injuries, implicating silibinin as a potential chemical to treat ferroptosis-related diseases.

Upregulation of UHRF1 Promotes PINK1-mediated Mitophagy to Alleviates Ferroptosis in Diabetic Nephropathy.

Diabetic nephropathy (DN) is a common diabetic complication. Studies show that mitophagy inhibition induced-ferroptosis plays a crucial role in DN progression. UHRF1 is associated with mitophagy and is highly expression in DN patients, however, the effect of UHRF1 on DN is still unclear. Thus, in this study, we aimed to investigate whether UHRF1 involves DN development by the mitophagy/ferroptosis pathway. We overexpressed UHRF1 using an adeno-associated virus 9 (AAV9) system in high-fat diet/streptozotocin-induced diabetic mice. Renal function index, pathological changes, mitophagy factors, and ferroptosis factors were detected in vivo. High-glucose cultured human renal proximal tubular (HK-2) cells were used as in vitro models to investigate the mechanism of UHRF1 in DN. We found that diabetic mice exhibited kidney damage, which was alleviated by UHRF1 overexpression. UHRF1 overexpression promoted PINK1-mediated mitophagy and inhibited the expression of thioredoxin interacting protein (TXNIP), a factor associated with mitochondrial dysfunction. Additionally, UHRF1 overexpression alleviated lipid peroxidation and free iron accumulation, and upregulated the expression of GPX4 and Slc7a11, indicating the inhibition effect of UHRF1 overexpression on ferroptosis. We further investigated the mechanism of UHRF1 in the mitophagy/ferroptosis pathway in DN. We found that UHRF1 overexpression promoted PINK1-mediated mitophagy via inhibiting TXNIP expression, thus suppressing ferroptosis. These findings confirmed that upregulation of UHRF1 expression alleviates DN, indicating that UHRF1 has a reno-protective effect against DN.

Valproic Acid Treatment Improves Organ Function, Survival Rate, and Lipid Peroxidation in Fatally Scalded Rats

Background After hypovolemic shock caused by severe burns, lipid peroxidation is an important factor in tissue edema and multiorgan dysfunction syndrome (MODS). Many studies have shown that valproic acid (VPA) inhibits lipid peroxidation and reduces tissue and organ injury. Objectives This study investigated whether the VPA treatment of scalded rats reduced tissue edema by inhibiting lipid peroxidation, thereby improving organ function and survival rate. Materials and Methods A total of 60 male Sprague-Dawley rats (weighing: 280–300 g) with a 50% total body surface area (TBSA) full-thickness dermal burn were randomly assigned to the following 3 groups (with 20 rats per group): (I) the no infusion resuscitation (NR) group; (II) the sodium lactate Ringer’s solution (LR) group; and (III) the sodium valproate Ringer’s solution (VR) group. After scalding, the following hemodynamic parameters were measured: Copper2+-Zinc2+-superoxide dismutase (Cu2+-Zn2+-SOD) activity, thiobarbituric acid reactive substances (TBARSs), oxidized glutathione (GSSG), reduced glutathione (GSH), and antioxidant enzyme activities. Organ function parameters and water content were also measured. Another 60 male Sprague-Dawley rats were used to observe the 24-h survival rate of the rats using the same scald model and fluid resuscitation. Results VPA significantly increased the mean arterial pressure (MAP) and cardiac output (CO), and significantly decreased the pulmonary vascular permeability index (PVPI) and extravascular lung water index (ELWI). VPA also increased plasma Cu2+-Zn2+-SOD activity and decreased the plasma TBARS level. VPA reduced the TBARS level and GSSG in various tissues and increased the concentration of GSH. VPA decreased glutathione peroxidase (GPx) and catalase (CAT) activity, but significantly increased glutathione reductase (GR) activity in various tissues. VPA significantly improved organ functions and decreased water content. VPA significantly improved the survival rate, and the 24-h survival rate of the VR group was double that of the LR group. Conclusion Resuscitation with VPA reduced tissue edema, protected visceral functions, and improved the survival rate of rats with severe burn shock (BS) by alleviating lipid peroxidation.

Punicalagin relieves lipotoxic injuries on pancreatic β-cells via regulating the oxidative stress and endoplasmic reticulum stress-mediated apoptosis.

Cellular toxicity of hyperlipidemia has been long considered a major cause of various intractable disease such as diabetes. Discovering lipotoxicity antagonist with high efficiency and low side effects is of importance to develop therapeutics for relevant diseases. In the current study, we evaluate the anti-lipotoxic potential of punicalagin (PU) on pancreatic cells and investigate its underpinning mechanism involved. The administration of PU effectively improved cell viability, quenched intracellular reactive oxygen species, alleviated lipid peroxidation, and enhanced cellular antioxidative capacity in RINm5F cells stimulated by sodium palmitate. Besides that, PU treatment significantly inhibited the overload of mitochondrial calcium ions; alleviated the activation of endoplasmic reticulum (ER) stress mediators including glucose-regulated protein 78, protein kinase RNA-like ER kinase, eukaryotic initiation factor 2α, activating transcription factor 6, caspase 12, and C/EBP homologous protein (CHOP); and attenuated the expression of cleaved caspase 3 and poly ADP-ribose polymerase in test cells. Further RNA interference experiment results and miR211-5p expression analysis revealed that PU may directly mitigate CHOP expression and upregulate the expression of miR211-5p to reduce ER stress-induced pancreatic cell death. The efficacy of PU in maintaining redox equilibrium and diminishing ER stress on pancreatic cells stressed by hyperlipidemia suggests that PU can be used as a promising dietary natural product to safeguard the pancreatic health against lipotoxicity.

MP34-15 THE ROLE OF FERROPTOSIS IN NEUTROPHILS-MEDIATED INNATE IMMUNE DEFENSE AGAINST URINARY TRACT INFECTION

You have accessJournal of UrologyCME1 Apr 2023MP34-15 THE ROLE OF FERROPTOSIS IN NEUTROPHILS-MEDIATED INNATE IMMUNE DEFENSE AGAINST URINARY TRACT INFECTION Yan Liu, Hongying Huang, Herbert Lepor, Xue-Ru Wu, and Ellen Shapiro Yan LiuYan Liu More articles by this author , Hongying HuangHongying Huang More articles by this author , Herbert LeporHerbert Lepor More articles by this author , Xue-Ru WuXue-Ru Wu More articles by this author , and Ellen ShapiroEllen Shapiro More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003268.15AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Ferroptosis is a recently discovered programmed cell death involved in disorders including infectious disease, autoimmune disease, and cancer. It is characterized by iron accumulation and reactive oxygen species (ROS)-induced lipid peroxidation. Neutrophils are the first line of innate defense against urinary tract infection (UTI), and their interaction with uropathogenic E.coli (UPEC) triggers generation of ROS and leads to cell death. However, whether UPECs induce ferroptosis in neutrophils remains elusive. This study aims to elucidate the role of ferroptosis in neutrophils-mediated host defense against UTI. METHODS: Human myeloblastic cells HL-60 were induced to terminally differentiated neutrophils by 1.5% DMSO for 72 hours. The differentiated cells were challenged by type 1 piliated UPEC strains (UTI89, NU14), isogenic FimH adhesin deletion strain (NU14-1), or non-fimbriated laboratory strain (HB101) at a multiplicity of infection of 40. ROS level was examined by H2DCFDA cellular ROS assay. Iron level was measured by Phen Green FL diacetate assay. Cell membrane integrity was checked by DiO cell labeling. Lipid peroxidation was detected by cell-based lipid peroxidation assay. The cells were exposed to UPEC virulent factors lipopolysaccharide (LPS) and flagellin. HL-60 cells pretreated with or without the ferroptosis inhibitor ferrostatin-1 were infected, and cell suspensions were lysed, diluted, and plated to assess viable UPECs. RESULTS: Type 1 piliated UPEC strains UTI89 and NU14 induced a rapid elevation in ROS and iron accumulation in differentiated HL-60 cells in a dose- and time-dependent manner and accompanied by lipid peroxidation with multiple perforations on the membrane, all of which are hallmarks of ferroptosis. On the contrary, pretreatment of HL-60 cells with ferroptosis inhibitor ferrostatin-1 reduced 20% of UPEC-induced ROS production, alleviated lipid peroxidation, and led to a 36% higher number of viable UPECs compared to the controls. Furthermore, FimH deletion isogenic strain NU14-1 and non-fimbriated laboratory strain HB101 did not elicit activation of ferroptosis in HL-60 cells, indicating FimH-mediated adherence is required for inducing ferroptosis. Lastly, UPEC virulent factors LPS or flagellin alone did not evoke ferroptosis. CONCLUSIONS: Our data demonstrate for the first time that UPECs induce ferroptosis in neutrophils, and the induction depends on the adhesion of UPECs to the cell surface. The results also suggest that enhancing ferroptosis holds the therapeutic potential for improved clearance of UPECs. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e464 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Yan Liu More articles by this author Hongying Huang More articles by this author Herbert Lepor More articles by this author Xue-Ru Wu More articles by this author Ellen Shapiro More articles by this author Expand All Advertisement PDF downloadLoading ...

Physiological Toxicity and Antioxidant Mechanism of Photoaging Microplastics on Pisum sativum L. Seedlings.

Recent studies have confirmed that changes in the physical properties of microplastics (MPs) trigger toxicological effects and ecological risks. To explore the toxicity of different types of MPs on plants, and the influence of MP photoaging, this study investigated the toxicity mechanisms of pristine, 7 and 14 d photoaged polystyrene (PS), polyamide (PA), polyethylene (PE), and polyethylene terephthalate (PET) MPs on seed germination, root growth, nutrient fraction, oxidative stress, and antioxidant systems of Pisum sativum L. (pea) seedlings. The results showed that pristine PS and 14 d photoaged PET inhibited seed germination. Compared to the pristine MPs, photoaged MPs had negative effects on root elongation. Moreover, photoaged PA and PE impeded the nutrient transport of soluble sugars from roots to stems. Notably, the production of superoxide anion radicals (•O2-) and hydroxyl radicals (•OH) through the photoaging of MPs exacerbated oxidative stress and reactive oxygen species formation in roots. Antioxidant enzyme data revealed that the activities of superoxide dismutase and catalase were significantly activated in photoaged PS and PE, respectively, in order to scavenge •O2- and hydrogen peroxide (H2O2) accumulation and alleviate lipid peroxidation levels in cells. These findings provide a new research perspective on the phytotoxicity and ecological risk of photoaged MPs.

Toxicity and tolerance mechanism of binary zinc oxide nanoparticles and tetrabromobisphenol A regulated by humic acid in Chlorella vulgaris.

Recent studies have reported that nanoparticles (NPs) released into the aquatic environment may interact with persistent organic pollutants such as brominated flame retardants, whereas the environmental processes and toxicological impacts induced by such binary NPs require further specification. This study investigated the ultrastructural damage of Chlorella vulgaris triggered by exposure to zinc oxide (ZnO) NPs, tetrabromobisphenol A (TBBPA), ZnO-TBBPA, and ZnO-TBBPA-humic acid (HA), clarified the uptake and distribution of ZnO NPs in cells, and explored the physiological toxicity and tolerance mechanism. The results demonstrated that ZnO NPs induced irregular morphology in algal cells, and the disruption of the cellular ultrastructure by binary ZnO-TBBPA was also extremely severe due to the excessive uptake of ZnO NPs, which resulted in strong oxidative stress responses. In particular, the accumulation of reactive oxygen species further exacerbated the reduction of total chlorophyll content and algal density. Moreover, the cluster heat map and correlation analysis revealed that superoxide dismutase activity played a critical role in alleviating lipid peroxidation damage and enhancing the tolerance of algal cells to the stress of binary ZnO NPs. More notably, the existence of HA intensified the dispersion stability of NP suspensions and significantly mitigated the synergistic toxicity of binary ZnO-TBBPA. This study provides new insights into the environmental behavior and biological impacts of binary NPs in the natural environment.

SS31 Confers Cerebral Protection by Reversing Mitochondrial Dysfunction in Early Brain Injury Following Subarachnoid Hemorrhage, via the Nrf2- and PGC-1α-Dependent Pathways.

In early brain injury (EBI), oxidative stress occurs following subarachnoid hemorrhage (SAH), and mitochondria are intricately linked to this process. SS31, a mitochondria-targeting antioxidative peptide, has been demonstrated to be beneficial for multiple diseases because of its powerful antioxidant and neuroprotective properties. Although our previous study revealed that SS31 was involved in the powerful antioxidant effect following SAH, the underlying molecular mechanisms remained unclear. Thus, our study aimed to investigate the neuroprotective effects of SS31 by reversing mitochondrial dysfunction in EBI following SAH, via activating the Nrf2 signaling and PGC-1α pathways. Our findings confirmed that SS31 ameliorated SAH-triggered oxidative insult. SS31 administration decreased redundant reactive oxygen species, alleviated lipid peroxidation, and elevated the activities of antioxidant enzymes. Concomitant with the inhibited oxidative insult, SS31 dramatically attenuated neurological deficits, cerebral edema, neural apoptosis, and blood-brain barrier disruption following SAH. Moreover, SS31 remarkably promoted nuclear factor-erythroid 2 related factor 2 (Nrf2) nuclear shuttle and upregulated the expression levels of heme oxygenase-1 and NADPH: quinine oxidoreductase1. Additionally, SS31 enhanced the expression levels of PGC-1α and its target genes, and increased the mtDNA copy number, promoting mitochondrial function. However, PGC-1α-specific inhibitor SR-18292 pretreatment dramatically suppressed SS31-induced Nrf2 expression and PGC-1α activation. Furthermore, pretreatment with SR-18292 reversed the neuroprotective and antioxidant roles of SS31. These significant beneficial effects were associated with the activation of the Nrf2 signaling and PGC-1α pathways and were antagonized by SR-18292 administration. Our findings reveal that SS31 exhibits its neuroprotective activity by reversing mitochondrial dysfunction via activating the Nrf2 signaling pathway, which could be mediated through PGC-1α activation.

SPY1 inhibits neuronal ferroptosis in amyotrophic lateral sclerosis by reducing lipid peroxidation through regulation of GCH1 and TFR1

Ferroptosis is an iron-dependent cell death with the accumulation of lipid peroxidation and dysfunction of antioxidant systems. As the critical regulator, glutathione peroxidase 4 (GPX4) has been demonstrated to be down-regulated in amyotrophic lateral sclerosis (ALS). However, the mechanism of ferroptosis in ALS remains unclear. In this research, bioinformatics analysis revealed a high correlation between ALS, ferroptosis, and Speedy/RINGO cell cycle regulator family member A (SPY1). Lipid peroxidation of ferroptosis in hSOD1G93A cells and mice was generated by TFR1-imported excess free iron, decreased GSH, mitochondrial membrane dysfunction, upregulated ALOX15, and inactivation of GCH1, GPX4. SPY1 is a “cyclin-like” protein that has been proved to enhance the viability of hSOD1G93A cells by inhibiting DNA damage. In our study, the decreased expression of SPY1 in ALS was resulted from unprecedented ubiquitination degradation mediated by MDM2 (a nuclear-localized E3 ubiquitin ligase). Further, SPY1 was identified as a novel ferroptosis suppressor via alleviating lipid peroxidation produced by dysregulated GCH1/BH4 axis (a resistance axis of ferroptosis) and transferrin receptor protein 1 (TFR1)-induced iron. Additionally, neuron-specific overexpression of SPY1 significantly delayed the occurrence and prolonged the survival in ALS transgenic mice through the above two pathways. These results suggest that SPY1 is a novel target for both ferroptosis and ALS.

Sucrose + 8-HQC improves the postharvest quality of lily and rose cut flowers by regulating ROS-scavenging systems and ethylene release

The objective of the present investigation was to study the effects of sucrose + 8-hydroxyquinoline citrate (8-HQC) on the reactive oxygen species (ROS)-scavenging systems and ethylene release during the vase life of cut lilies (ethylene-insensitive type) and roses (ethylene-sensitive type). ROS production and the degree of lipid peroxidation increased with the senescence of cut lily and rose flowers. The treatment with sucrose + 8-HQC enhanced ROS-scavenging abilities, decreased Superoxide radical (O2.−) release and mitigated the oxidative damage marked by lower malondialdehyde (MDA) level, although the up-regulated extent of each antioxidant enzyme was not exactly the same in both cut flower species. The treatment of sucrose + 8-HQC decreased the level of proline in cut rose, which suggested water stress of cut rose was alleviated. On the other hand, the increase of proline in cut lily due to sucrose + 8-HQC was elaborated. The preservation effect induced by sucrose + 8-HQC was involved in the regulation of ethylene production in ethylene-sensitive cut flowers, not in ethylene-insensitive cut flowers. From the results of ethylene and proline analysis, it can be found that there are differences in the regulation mechanism of sucrose on the fresh-keeping of the two cut flowers, but the treatment with sucrose and 8-HQC can improve the postharvest quality of cut flowers with different sensitivity to ethylene by enhancing ROS-scavenging activities and alleviating lipid peroxidation.

Integrating Broussonetia papyrifera and Two Bacillus Species to Repair Soil Antimony Pollutions.

Heavy metal resistant bacteria play an important role in the metal biogeochemical cycle in soil, but the benefits of microbial oxidation for plants and soil have not been well-documented. The purpose of this study was to explore the contribution of two Bacillus spp. to alleviate the antimony (Sb) toxicity in plants, and, then, to propose a bioremediation method for Sb contaminated soil, which is characterized by environmental protection, high efficiency, and low cost. This study explored the effects of Bacillus cereus HM5 and Bacillus thuringiensis HM7 inoculation on Broussonetia papyrifera and soil were evaluated under controlled Sb stressed conditions (0 and 100 mmol/L, antimony slag) through a pot experiment. The results show that the total root length, root volume, tips, forks, crossings, and root activities of B. papyrifera with inoculation are higher than those of the control group, and the strains promote the plant absorption of Sb from the soil environment. Especially in the antimony slag treatment group, B. cereus HM5 had the most significant effect on root promotion and promoting the absorption of Sb by B. papyrifera. Compared with the control group, the total root length, root volume, tips, forks, crossings, and root activities increased by 64.54, 70.06, 70.04, 78.15, 97.73, and 12.95%, respectively. The absorption of Sb by root, stem, and leaf increased by 265.12, 250.00, and 211.54%, compared with the control group, respectively. Besides, both B. cereus HM5 and B. thuringiensis HM7 reduce the content of malondialdehyde, proline, and soluble sugars in plant leaves, keeping the antioxidant enzyme activity of B. papyrifera at a low level, and alleviating lipid peroxidation. Principal component analysis (PCA) shows that both B. cereus HM5 and B. thuringiensis HM7 are beneficial to the maintenance of plant root functions and the improvement of the soil environment, thereby alleviating the toxicity of Sb. Therefore, B. cereus HM5 and B. thuringiensis HM7 in phytoremediation with B. papyrifera is a promising inoculant used for bacteria-assisted phytoremediation on Sb contaminated sites.

Dithiolethiones D3T and ACDT Protect Against Ferroptosis Induced by Erastin and RSL3

Ferroptosis is an iron‐dependent and non‐apoptotic form of cell death characterized by increased lipid peroxidation. It is morphologically, biochemically, and genetically different from other types of cell death. Erastin and RSL3 are the canonical inducers of ferroptosis. While erastin inhibits the cystine/glutamate antiporter (xCT) leading to intracellular glutathione (GSH) depletion, RSL3 directly inhibits the glutathione peroxidase‐4 (GPX4) enzyme, resulting in increased lipid peroxidation and ferroptosis. Dithiolethiones 3H‐1,2‐dithiole‐3‐thione (D3T) and 5‐amino‐3‐thioxo‐3H‐(1,2) dithiole‐4‐carboxylic acid ethyl ester (ACDT) are lipophilic, organosulfur compounds that are known to activate the Nrf2 transcription factor and induce the cellular antioxidant machinery. They have previously been shown to be cytoprotective against various oxidative stressors both in vitro and in vivo. Furthermore, as lipophilic antioxidants are known to oppose ferroptosis and the activation of Nrf2 has been reported to inhibit this form of cell death, the present study was aimed to evaluate the protective effect of dithiolethiones against erastin‐ and RSL3‐induced ferroptosis in U‐87 MG human astrocytoma cells. Ferrostatin‐1, a known ferroptosis inhibitor was used as a standard comparator. Cells were pretreated with either 50 µM D3T, ACDT, or 10 µM ferrostatin‐1 for 24 hours followed by another 24 hour exposure to either 20 µM erastin or 10 µM RSL3. Pretreatment with dithiolethiones reversed erastin‐induced cell death measured by MTS cell viability assay and upregulated xCT transporter expression indicated by western blotting. Dithiolethiones increased intracellular GSH (GSH‐Glo luminescence assay) and alleviated lipid peroxidation (TBARS assay) against erastin. RSL3‐induced ferroptosis and lipid peroxidation were also counteracted by both the dithiolethiones, however no effect was observed on GPX4 enzyme levels. These effects of dithiolethiones were comparable to those of the standard ferroptosis inhibitor ferrostatin‐1. Collectively, our data indicate a strong ability of dithiolethiones to counteract ferroptosis, and is the first such study in astrocytes. D3T and ACDT can therefore be potential therapeutic candidates in the treatment of ferroptosis‐related brain disorders.

Ginger and curcumin can inhibit heterocyclic amines and advanced glycation end products in roast beef patties by quenching free radicals as revealed by electron paramagnetic resonance

This study investigated the inhibitory effects of ginger and curcumin on the formation of free and bound heterocyclic amines (HAs)1 and advanced glycation end products (AGEs) in roast beef patties. The underlying mechanism related to quenching free radical, alleviating lipid peroxidation and scavenging carbonyl intermediates was explored by electron paramagnetic resonance (EPR) and UPLC-MS/MS. Ginger (0.5%, 1.0%, 1.5%) and curcumin (0.005%, 0.010%, 0.015%) dose-dependently inhibited free and bound HAs and AGEs simultaneously. The maximum inhibition rates for free and bound HAs were 59.97% (0.015% curcumin) and 27.42% (1.5% ginger), and those for free and bound AGEs were 71.57% and 35.64% (1.5% ginger). EPR result indicated alkyl free radical and 1O2 were the pivotal free radicals for HAs and AGEs, and ginger and curcumin also dose-dependently reduced these radicals. Lipid peroxidation, active carbonyl intermediates-phenylacetaldehyde, glyoxal, and methylglyoxal were also inhibited by ginger and curcumin in a dose-dependent manner, probably due to quenching of free radical.