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The liver is vitally metabolic for a multitude of biochemical reactions. Consequently, it generates many free radicals and reactive oxygen species, rendering it more susceptible to oxidative stress-induced damage. Oxidative stress represents a pivotal factor in the pathogenesis of liver diseases. We screened some antioxidant peptides previously. Here we investigated whether the peptides could attenuate oxidative damage with APPH in L02 cells. The results showed that one of the peptides, sequence FETLMPLWGNK, could decrease the excessive reactive oxygen species, increase antioxidant enzyme activity and protect mitochondrial function, reduce the ratio of apoptosis and S phase cycle arrest, and improve the survival rate of L02 cells damaged by APPH compared to cells of the control group. Then the peptide was evaluated in mice that CCl 4 injured. We found that CCl 4 -injured mice had significantly increased serum inflammatory factors and liver injury markers, a large number of inflammatory cell infiltration, and local necrosis in the liver. The peptide could reduce inflammation, and improve liver pathological changes. This phenomenon may be associated with the activation of the Nrf2 signaling pathway. Concurrently, the peptide protects the liver by regulating the expression of proteins related to the mitochondrial apoptosis pathway (p53, Bax, Bcl-2, and Caspase3) and mitophagy-related proteins (PINK1, Parkin, and AMPKα). Therefore, the results indicated that the peptide is an active substance with antioxidant activity and anti-inflammatory effects., 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 Elsevier Inc. All rights reserved.)

Perfluorooctane sulfonate (PFOS) and its precursor, perfluorooctane sulfonamide (PFOSA), are widespread in the environment. Evidence suggests a strong link between maternal exposure to PFOS/PFOSA and congenital heart diseases in the offspring, but the underlying mechanisms remain unclear. We hypothesized that PFOS and PFOSA induce cardiac defects through the peroxisome proliferator-activated receptor gamma (PPARγ) and aryl hydrocarbon receptor (AHR) pathways, respectively. In this study, we demonstrated that exposing zebrafish embryos to either PFOSA or PFOS caused cardiac malformations and dysfunction. Both PFOS and PFOSA induced reactive oxygen species (ROS) overproduction, mitochondrial damage, and apoptosis in zebrafish larvae hearts. Blockade of PPARγ through either pharmaceutical inhibition or genetic knockdown only attenuated the changes caused by PFOS, but not those elicited by PFOSA. Conversely, inhibition of AHR alleviated the adverse effects induced by PFOSA but not by PFOS. Both PFOSA and PFOS exhibited similar binding affinities to AHR using molecular docking techniques. The varying ability of PFOS and PFOSA to induce AHR activity in zebrafish embryonic hearts can be attributed to their different capabilities for activating PPARγ. In summary, our findings indicate that PFOS and PFOSA induce excessive ROS production in zebrafish larvae via the PPARγ and AHR pathways, respectively. This oxidative stress in turn causes mitochondrial damage and apoptosis, leading to cardiac defects., 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 Elsevier B.V. All rights reserved.)

Increasing evidence has demonstrated that coenzyme Q10 (CoQ10) exhibits a range of biological properties. Herein, we explored the protective effect and potential molecular mechanism of CoQ10 on lipopolysaccharide (LPS)-induced acute lung injury (ALI). We found that medium (10 mg/kg) and high (50 mg/kg) doses of CoQ10 ameliorated LPS (50 µg/µL)-induced ALI to varying degrees, as demonstrated by reduced lung coefficient, lower wet/dry weight lung tissue ratio, decreased bronchoalveolar lavage fluid protein concentration, less anatomical and histopathological damage to the lung, and increased expression of proteins related to lung epithelial barrier structure. CoQ10 also alleviated LPS-induced oxidative stress and inflammation mediated by NOD-like receptor protein 3 (NLRP3) by reducing the reactive oxygen species (ROS), malondialdehyde, and mitochondrial ROS concentrations, increasing superoxide dismutase, glutathione, and catalase activity, and decreasing NLRP3 expression at the protein and mRNA levels. Moreover, CoQ10 alleviated structural and functional damage to the mitochondria, inhibited mitochondrial fission, and promoted mitochondrial fusion, mainly by inhibiting phosphorylation of dynamin-related protein 1 (Drp1) at Ser616 and Ser637. Correlation analysis revealed that mitochondrial fission (especially Drp1) was positively correlated with oxidative stress, NLRP3-mediated inflammation, and structural damage to the lung epithelial barrier. Molecular docking analysis showed that CoQ10 binds stably to Drp1, with a binding energy of -5.9 kcal/mol. Furthermore, the use of schaftoside (a Drp1 inhibitor) has further elucidated the mechanism of action of CoQ10. Together, these results suggest that CoQ10 alleviates LPS-induced ALI by regulating mitochondrial dynamics, attenuating oxidative stress, and decreasing NLRP3-medated inflammation, thereby promoting lung epithelial barrier structural remodeling., 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. Published by Elsevier B.V.)

N-(1,3-dimethylbutyl)-N '-phenyl-p-phenylenediamine (6PPD) and N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine-quinone (6PPD-Q) are ubiquitous in the environment and can cause toxicity to aquatic animals. However, research on the toxicological effects of 6PPD and 6PPD-Q on aquatic plants remains limited. The present study investigated the physiological, biochemical, and metabolic responses of the floating aquatic plant Eichhornia crassipes (E. crassipes) to environmentally relevant concentrations (0.1, 1, and 10 μg·L -1 ) of 6PPD and 6PPD-Q. We found that 6PPD and 6PPD-Q elicited minimal effects on plant growth, but 6PPD induced a concentration-dependent decrease in the content of photosynthetic pigments. Low doses (0.1 μg·L -1 and 1 μg·L -1 ) of 6PPD-Q significantly elevated Reactive Oxygen Species (ROS) content in E. crassipes roots, indicating oxidative damage. Furthermore, 6PPD-Q induced a more pronounced osmotic stress compared to 6PPD. Metabolic analyses revealed that carbohydrates were significantly altered under 6PPD and 6PPD-Q treatments. The findings of this study enhance the understanding of the environmental risks posed by 6PPD and 6PPD-Q to plants and reveal the potential mechanisms of phytotoxicity., 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 Elsevier B.V. All rights reserved.)

Given their relatively low persistence and mammalian toxicity, neonicotinoid pesticides have been extensively used worldwide and are omnipresent in the environment. Recent studies have shown that neonicotinoids may pose adverse effects on non-target organisms other than the known neurotoxicity, raising emerging concerns that these insecticides might pose human health risk through additional toxicity pathways. In the present study, the mitochondria function, oxidative stress, DNA damages, and genes transcription levels were examined in the human neuroblastoma SH-SY5Y cells after 48-h exposure to imidacloprid at concentrations from 0.05 to 200 μmol/L. Results showed that imidacloprid induced mitochondrial dysfunction with the degradation of adenosine triphosphate (ATP) and mitochondrial membrane potential (MMP) levels. In addition, imidacloprid caused oxidative stress by stimulating the generation of reactive oxygen species (ROS) and hydrogen peroxide (H 2 O 2 ) via the disruption of calcium ion level and mitochondrial function. Ultimately, the oxidative stress continued to produce DNA damage and apoptosis in SH-SY5Y cells at imidacloprid concentrations above 47.6 μmol/L. Among the evaluated endpoints, ATP was the most sensitive, with a median activity concentration of 0.74 μmol/L. The 5 % hazard concentration of imidacloprid was estimated to be 0.69 μmol/L, which can be used as a threshold for human health risk assessment for imidacloprid. Collectively, our results provide an important support for further research on potential toxicity of neonicotinoids related to mitochondrial toxicity in humans., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Huizhen Li reports financial support was provided by the National Natural Science Foundation of China. Fenghua Wei reports financial support was provided by the National Natural Science Foundation of China. Jing You reports financial support was provided by the Department of Education of Guangdong Province. Fenghua Wei reports financial support was provided by the Department of Education of Guangdong Province. If there are other authors, they 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 Elsevier B.V. All rights reserved.)

Chronic myeloid leukemia (CML) treatment with Bcr-Abl tyrosine kinase inhibitors (TKIs) has significantly improved patient outcomes, yet challenges such as drug resistance and persistence of leukemic stem cells persist. This study explores the potential of naringenin, a natural flavonoid, to enhance the efficacy of Bcr-Abl TKIs in CML therapy. We showed that naringenin reduces viability of a panel of CML cell lines regardless of varying cellular origin and genetic mutations, and acts synergistically with dasatinib and ponatinib. Importantly, naringenin is effective in targeting blast crisis CML CD34 + cells by decreasing their colony formation, self-renewal and viability. Compared to CML, naringenin is significantly less effective against normal bone marrow (NBM) counterparts. In addition, naringenin significantly enhances the inhibitory effects of dasatinib in CML but not NBM CD34 + cells. Mechanism studies showed that naringenin's inhibitory effects were associated with the induction of oxidative stress and lipid damage, as evidenced by increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels. Notably, naringenin upregulated genes related to mitochondrial biogenesis while downregulating antioxidant defense genes. Pretreatment with α-tocopherol, which inhibits lipid-mediated ROS production, completely abolished the ROS increase and restored cell viability, indicating that lysosomal lipid peroxidation plays a crucial role in naringenin's mechanism of action. In a CML xenograft mouse model, the combination of naringenin and dasatinib resulted in remarkably more tumor growth suppression compared to single drug alone. Importantly, this combination was well-tolerated, with no adverse effects on body weight observed. These findings suggest that naringenin, by inducing oxidative lipid damage, enhances the anti-leukemic effects of Bcr-Abl TKIs, offering a promising therapeutic strategy for CML., 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 Elsevier Inc. All rights reserved.)

Postovulatory aging of oocytes involves a series of deleterious molecular and cellular changes, which adversely affect oocyte maturation, fertilization, and early embryonic development. Petunidin-3-O-(6-O-pcoumaroyl)-rutinoside-5-O-glucoside (PrG), the main active ingredient of anthocyanin, exerts antioxidant effects. This study investigated whether PrG supplementation could delay postovulatory oocyte aging by alleviating oxidative stress. Our results showed that PrG supplementation decreased the number of abnormal morphology oocytes and improved the oxidative stress of aged oocytes by facilitating the reduction of the reactive oxygen species, the increase in glutathione content, and the recovery of expression of antioxidant-related gene expression. In addition, PrG treatment recovered mitochondrial dysfunction, including mitochondrial distribution, mitochondrial membrane potential and adenosine triphosphate in aged oocytes. PrG-treated oocytes returned to normal levels of cytoplasmic and mitochondrial calcium. Notably, PrG inhibited early apoptosis in aged oocytes. RNA-seq and qRT-PCR results revealed that PrG ameliorated oxidative stress injury in postovulatory aging oocytes of mice via the putrescine pathway. In conclusion, in vitro PrG supplementation is a potential therapy for delaying postovulatory oocyte aging., Competing Interests: Declaration of competing interest All the authors affirm that the research was carried out without any commercial or financial affiliations that could create a conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Inhibiting secondary cell death and promoting neuronal regeneration are critical for nerve repair after spinal cord injury (SCI). The excessive accumulation of reactive oxygen species (ROS) after SCI causes cell death and induces apoptosis. These reactions further increase the level of ROS production, leading to a vicious cycle of spinal cord tissue damage. Therefore, intervention targeting ROS is a potential therapeutic approach to improve the recovery of locomotor function after SCI. In this study, we designed and synthesized a nanozyme hydrogel delivery system loaded with multiple drugs, LA/Me/Se NPs-h. LA/Me/Se NPs-h exhibited a satisfactory size distribution and excellent stability, enhancing the bioavailability of therapeutic drugs. Moreover, we explored the antioxidant and protective effects of LA/Me/Se NPs-h against oxidative stress-induced cell damage caused by ROS production after SCI in vitro. In the mice SCI model, the Basso mouse scale and gait analysis showed that LA/Me/Se NPs-h significantly promoted the recovery of locomotor function after SCI. The histological and immunofluorescence results of the injury site revealed that LA/Me/Se NPs-h upregulated the expression of GFAP, NF-200, and superoxide dismutase in spinal cord lesion, reduced caspase-3 expression, improved spinal cord continuity, reduced lesion cavity, and inhibited the axonal demyelination. Consequently, LA/Me/Se NPs-h increased the activity of antioxidant enzymes and reduced neuronal apoptosis by reducing oxidative stress and ultimately promoted nerve regeneration. Taken together, this study demonstrated promising nanozyme hydrogels and provided an effective therapeutic strategy for SCI and other ROS-related diseases.

Reactive oxygen species (ROS) are physiological byproducts of neuronal metabolism. However, an imbalance between ROS generation and antioxidant capacity, often driven by dysregulated pro-oxidant enzymes like nicotinamide adenine dinucleotide phosphate oxidases (NOX), can result in deleterious oxidative stress. This oxidative stress is a critical factor in the pathogenesis of neurodegenerative diseases. While interventions with broad-spectrum antioxidants have demonstrated limited efficacy, the modulation of endogenous antioxidant mechanisms presents a promising therapeutic avenue. Here, we investigated the potential of the neuroprotective hormone prolactin to mitigate oxidative stress and subsequent neuronal cell death. Prolactin protected primary mouse hippocampal neurons from hydrogen peroxide (H2O2)-induced oxidative damage. Prolactin reduced ROS levels, lipid peroxidation, and apoptosis, and its effects were occluded by a specific prolactin receptor antagonist (G129R-hPRL). Mechanistically, prolactin suppressed H2O2-induced mRNA upregulation of pro-oxidative Nox4 and pro-apoptotic Bax. Moreover, prolactin induced nuclear factor kappa B (NF-κB) nuclear translocation, and the inhibition of the NF-κB signaling pathway abolished the neuroprotective and transcriptional effects of prolactin, indicating its central role in prolactin-mediated protection. Our findings indicate that prolactin exerts potent antioxidant and neuroprotective effects by modulating the expression of Nox4 and Bax, thereby reducing ROS generation and neuronal apoptosis. This study underscores the therapeutic potential of prolactin in attenuating oxidative stress and suggests a possible role in the treatment of neurodegenerative diseases., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Macías et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

The epigenetic reader SntB was identified as an important transcriptional regulator of growth, development, and secondary metabolite synthesis in Aspergillus flavus . However, the underlying molecular mechanism is still unclear. In this study, by gene deletion and complementation, we found SntB is essential for mycelia growth, conidial production, sclerotia formation, aflatoxin synthesis, and host colonization. Chromatin immunoprecipitation sequencing (ChIP-seq) and RNA sequencing (RNA-seq) analysis revealed that SntB played key roles in oxidative stress response of A. flavus , influencing related gene activity, especially catC encoding catalase. SntB regulated the expression activity of catC with or without oxidative stress, and was related to the expression level of the secretory lipase (G4B84_008359). The deletion of catC showed that CatC participated in the regulation of fungal morphogenesis, reactive oxygen species (ROS) level, and aflatoxin production, and that CatC significantly regulated fungal sensitive reaction and AFB1 yield under oxidative stress. Our study revealed the potential machinery that SntB regulated fungal morphogenesis, mycotoxin anabolism, and fungal virulence through the axle of from H3K36me3 modification to fungal virulence and mycotoxin biosynthesis. The results of this study shed light into the SntB-mediated transcript regulation pathways of fungal mycotoxin anabolism and virulence, which provided potential strategy to control the contamination of A. flavus and its aflatoxins., Competing Interests: DW, CY, YY, DM, HL, LH, WX, KY, MS, YH, YY, ZZ No competing interests declared, (© 2024, Wu, Yang et al.)

Perfluorooctanoic acid (PFOA), an emerging pollutant, has been frequently detected in organic solid waste. It becomes a major concern for compost application, but studies on its toxic effects during composting are rare. This study evaluated the impact of PFOA presence at the environmentally relevant level on the humification process and microbiology during composting. The results showed that the PFOA presence (15.5 μg/kg dry) caused 45.5 % and 40.5 % decreases in the total organic carbon and humic acid-like substances, respectively. PFOA negatively affected microbial activity during the thermophilic period, as evidenced by the increases in reactive oxygen species and lactate dehydrogenase concentration. It altered the microbial community with an enrichment of Bacteroidota, conducive to resisting press. Unexpectedly, the PFOA presence induced hormesis at the maturity period, consistent with stimulated carbon metabolism (i.e., glycolysis and oxidative phosphorylation). The modulated microbial metabolism stimulated the catabolic metabolism of small-molecule humus precursors and reduced intracellular quinone availability. Furthermore, the secretion of auxiliary activities for crude fiber degradation was suppressed, which decreased the generation of extracellular quinone, and thereby impeded the humification process. These findings deciphered the metabolic response of composting to PFOA presence and highlighted the potential carbon loss of PFOA-containing composting., 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 Elsevier B.V. All rights reserved.)

Bisphenol S (BPS) is widely used in plastic products, food packaging, electronic products, and other applications. In recent years, BPS emissions have increasingly impacted aquatic ecosystems. The effects of BPS exposure on aquatic animal health have been documented; however, our understanding of its toxicology remains limited. This study aimed to explore the mechanisms of lipid metabolism disorders, oxidative stress, and autophagy dysfunction induced in freshwater crayfish (Procambarus clarkii) by exposure to different concentrations of BPS (0 µg/L, 1 µg/L, 10 µg/L, and 100 µg/L) over 14 d. The results indicated that BPS exposure led to oxidative stress by inducing elevated levels of reactive oxygen species (ROS) and inhibiting the activity of antioxidant-related enzymes. Additionally, BPS exposure led to increased lipid content in the serum and hepatopancreas, which was associated with elevated lipid-related enzyme activity and increased expression of related genes. Furthermore, BPS exposure decreased levels of phosphatidylcholine (PC) and phosphatidylinositol (PI), disrupted glycerophospholipid (GPI) metabolism, and caused lipid deposition in the hepatopancreatic. These phenomena may have occurred because BPS exposure reduced the transport of fatty acids and led to hepatopancreatic lipid deposition by inhibiting the transport and synthesis of PC and PI in the hepatopancreas, thereby inhibiting the PI3K-AMPK pathway. In conclusion, BPS exposure induced oxidative stress, promoted lipid accumulation, and led to autophagy dysfunction in the hepatopancreas of freshwater crayfish. Collectively, our findings provide the first evidence that environmentally relevant levels of BPS exposure can induce hepatopancreatic lipid deposition through multiple pathways, raising concerns about the potential population-level harm of BPS and other bisphenol analogues., 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 Elsevier B.V. All rights reserved.)

This study investigated the influence of photoaging on a nanoscale metal-organic framework (MOF), truncated rhombic dodecahedron nano-zeolitic imidazolate framework-8 (nZIF-8), focusing on its oxidative stress, inflammation, and implications for pulmonary diseases. We observed significant photodegradation-induced transformations in nZIF-8, characterized by a reduction in particle size from 200.5 to 101.4 nm and notable structural disintegration after prolonged exposure to simulated solar radiation. This alteration resulted in a marked decrease in oxidative cytotoxicity in BEAS-2B cells, which was attributed to changes in surface properties and reduced reactive oxygen species (ROS) production. Gene expression analysis further revealed a decrease in cytotoxic and inflammatory responses, which potentially lowers the risk of chronic obstructive pulmonary disease (COPD). Aged nZIF-8 also showed diminished capacity to induce pro-inflammatory cytokines and influence COPD-related gene expression, reducing its potential to exacerbate COPD pathogenesis. Our findings highlight the critical need for comprehensive safety evaluations of these materials, while considering their long-term environmental and biological impacts. The diminished cytotoxicity and inflammatory potential of aged nZIF-8 highlighted its enhanced suitability for broader applications, indicating that photoaging may lead to safer and more sustainable material utilization., 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 Elsevier B.V. All rights reserved.)

The endoplasmic reticulum (ER) responds to cellular stress by initiating an unfolded protein response (UPR) that mitigates misfolded protein accumulation by promoting protein degradation pathways. Chronic ER stress leads to UPR-mediated apoptosis and is a common underlying feature of various diseases, highlighting the modulators of the UPR as attractive targets for therapeutic intervention. Ataxia-telangiectasia mutated protein kinase (ATM) is a stress-responsive kinase that initiates autophagy in response to reactive oxygen species (ROS), and ATM deficiency is associated with increased ER stress markers in vitro. However, whether ATM participates in the UPR remains unclear. In this in vitro study, a novel role for ATM in the ER stress response is described using the well-characterized HEK293 cells treated with the common ER stress-inducing agent, tunicamycin, with and without the potent ATM inhibitor, KU-60019. We show for the first time that ATM is activated in a time-dependent manner downstream of UPR initiation in response to tunicamycin treatment. Furthermore, we demonstrate that ATM is required for p62-bound protein cargo degradation through the autophagy pathway in response to ER stress. Lastly, our data suggest a protective role for ATM in ER stress-mediated oxidative stress and mitochondrial apoptosis. Taken together, we highlight ATM as a potential novel drug target in ER stress-related diseases., 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 Inc. All rights reserved.)

Purpose: Aging alters the function of the lacrimal gland and disrupts the balance of the microenvironment on the ocular surface, eventually leading to aqueous-tear-deficient dry eye. Mitophagy has been reported to play an important role in aging, but the underlying mechanism remains unclear., Methods: The young (6 weeks) and middle-aged (12 months) male C57BL/6J mice were used in this study, and mitophagy agonist rapamycin and inhibitor Mdivi-1 were used in in vivo experiments. Hematoxylin and eosin, Masson, Oil Red O, and reactive oxygen species (ROS) staining were used to detect histological changes and lipids in lacrimal gland. Changes in the expression of proteins were identified by Western blotting of lacrimal gland lysates. Transmission electron microscopy and immunofluorescence staining were used to assess mitophagy. The single-cell RNA sequencing (scRNA-seq) and bioinformatics analyses were used to detect transcription signature changes during aging., Results: In this study, we discovered that aging increased oxidative stress, which increased apoptosis, and generated ROS in acinar epithelial cells. Furthermore, activation of PINK1/Parkin-mediated mitophagy by rapamycin reduced lacrimal gland ROS concentrations and prevented aging-induced apoptosis of acinar cells, thereby causing histological alterations, microstructural degradation, and increasing tear secretion associated with ROS accumulation. By contrast, Mdivi-1 aggregates mitochondrial function and thereafter leads to lacrimal gland function impairment by inhibiting mitochondrial fission and giving rise to mitophagy., Conclusions: Overall, our findings suggested that aging could impair mitochondrial function of acinar cells, and age-related alterations may be treated with therapeutic approaches that enhance mitophagy while maintaining mitochondrial function.

Background: Excitotoxicity is a process in which NADPH oxidase-2 (NOX-2) plays a pivotal role in the generation of reactive oxygen species (ROS). Oxidative stress influences the expression of Aquaporin 4 (AQP4), a water channel implicated in blood-brain barrier (BBB) permeability and edema formation. The endocannabinoid system is widely distributed in the brain, particularly through the cannabinoid receptor type 1 (CB1) and type 2 (CB2), which have been shown to have a neuroprotective function in brain injury. Given the significant involvement of NOX-2 in ROS production during excitotoxicity, our research aims to assess the participation of NOX-2 in the neuroprotective effect of the cannabinoid receptor agonist WIN55,212-2 against glutamate-induced excitotoxicity damage in the striatum using in vivo model., Methods: Wild-type mice (C57BL/6) and NOX-2 KO (gp91 Cybbtm1Din/J ) were stereotactically injected in the striatum with monosodium glutamate or vehicle. Subsequently, a group of mice was administered an intraperitoneal dose of WIN55,212-2, AM251, or AM251/WIN55,212-2 following the intracerebral injection. Motor activity was assessed, and the lesion was examined through histological sections stained with cresyl violet. Additionally, brain water content and Evans blue assay were conducted. The activity of NOX was quantified, and the protein expression of CB1, gp91 phox , AQP4, Iba-1, TNF-α, and NF-κB was analyzed using Western blot. Furthermore, ROS formation was measured through the DHE assay., Results: The activation of the endocannabinoid receptors demonstrated a neuroprotective response during excitotoxicity, meditated by NOX-2. The reduction in ROS production led to a decrease in neuroinflammation, and AQP4 expression, resulting in reduced edema formation, and BBB permeability., Conclusions: During excitotoxic damage, WIN55,212-2 inhibits NOX-2-induced ROS production, reducing brain injury., (© 2024 The Author(s). CNS Neuroscience & Therapeutics published by John Wiley & Sons Ltd.)

Kidney stones result from abnormal biomineralization, although the mechanism behind their formation remains unclear. Annexin A6 (AnxA6), a calcium-dependent lipid-binding protein, is associated with several mineralization-related diseases, but its role in kidney stones is unknown. This study aimed to explore the role and mechanism of AnxA6 in calcium oxalate (CaOx) kidney stones. An in vitro model in which renal tubular epithelial cells (RTECs) were treated with 1 mmol/L oxalate was established, and AnxA6 protein and mRNA expression were examined. Genetic engineering, drug intervention, and biochemical assays were used to investigate the role of AnxA6. The results revealed that AnxA6 was significantly overexpressed in the CaOx model. AnxA6 knockdown in RTECs reduced oxalate-induced oxidative stress, ROS accumulation, and mitochondrial damage, whereas AnxA6 overexpression exacerbated these effects. Blocking ryanodine receptor-mediated calcium release reversed AnxA6-induced oxidative damage. Additionally, AnxA6 increased oxalate adhesion to RTECs by binding to oxalate. In conclusion, AnxA6 contributes to CaOx kidney stone formation by promoting both oxidative stress via calcium release and crystal-cell adhesion by binding to oxalate. This study offers new insight into CaOx kidney stone formation., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Redox reactions, involving electron transfer, are critical to human physiology. However, progress in understanding redox metabolism is hindered by flawed analytical methods. This review highlights emerging techniques that promise to revolutionize redox research, enhancing our comprehension of human health and disease. Oxygen, vital for aerobic metabolism, also produces reactive oxygen species (ROS), such as superoxide and hydrogen peroxide. While historically seen as harmful, ROS at low concentrations are now recognized as key regulators of cell signaling. A balance between ROS and antioxidants, known as redox balance, is crucial, and deviations can lead to oxidative stress. Recent studies have distinguished beneficial "oxidative eustress" from harmful "oxidative distress." New techniques, such as advanced mass spectrometry and high-throughput immunoassays, offer improved accuracy in measuring redox states and oxidative damage. These advancements are pivotal for understanding redox signaling, cysteine oxidation, and their implications for disease. Looking ahead, the development of precision redox medicine could lead to better treatments for oxidative stress-related diseases and foster interventions promoting health., (© 2024 The Author(s). Physiological Reports published by Wiley Periodicals LLC on behalf of The Physiological Society and the American Physiological Society.)

Background/aim: The administration of contrast agents can adversely affect kidney function. Nevertheless, the nephrotoxicity of iopromide in human renal cells, potential therapeutic agents, and the underlying molecular mechanisms have not been thoroughly investigated., Materials and Methods: The proliferation of HEK-293 kidney cells was assessed using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazoliumbromide (MTT) assay. Apoptotic cell death was examined using the TUNEL assay and caspase-3 activity measurements. The impacts and potential pathways of epigallocatechin-3-gallate (EGCG) on iopromide-induced renal damage were analyzed through whole transcriptome sequencing. The redox state was assessed by measuring reactive oxygen species (ROS) production and 2,2-Diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity., Results: Iopromide-induced inhibition of cell proliferation and apoptosis in HEK-293 cells was counteracted by EGCG co-treatment. Pathway analysis revealed that molecules related to antioxidant and anti-inflammatory responses, such as ERK1/2, STAT1, and NF-[Formula: see text]B, were pivotal in the action of EGCG., Conclusion: Iopromide-induced ROS production, decreased DPPH scavenging ability, DNA strand breaks, elevated caspase-3 activity, and reduced cell proliferation were all reversed by EGCG co-treatment in HEK-293 cells. The mechanisms likely involve the attenuation of oxidative stress, inflammatory responses, and apoptosis, with regulation through the ERK1/2, STAT1, and NF-[Formula: see text]B pathways. Further research is necessary to confirm the protective effects of EGCG on renal function, particularly against damage induced by contrast agents like iopromide., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

In clinical practice, the limited efficacy of standard comprehensive therapy for advanced bladder cancer and the lack of targeted treatment options are well recognized. Targeting abnormal epigenetic modifications in tumors has shown considerable potential in cancer therapy. Through drug screening in tumor organoids, we identified that ML324, a histone lysine demethylase 4A (KDM4A) inhibitor, exhibits potent antitumor effects in both in vitro and in vivo cancer models. Mechanistically, Kdm4a demethylates H3K9me3, leading to chromatin opening and increased accessibility of Gabpa to the squalene epoxidase (Sqle) gene promoter, resulting in transcriptional activation. Inhibition of Kdm4a downregulates Sqle transcription, blocking cholesterol synthesis and causing squalene (SQA) accumulation. This process induces reactive oxygen species (ROS) clearance and suppresses JNK/c-Jun phosphorylation, ultimately inducing apoptosis. Furthermore, ML324 treatment significantly inhibited tumor growth in bladder cancer patient-derived xenograft (PDX) models. Our findings reveal the presence of a Kdm4a-Sqle-ROS-JNK/c-Jun signaling axis that regulates oxidative stress balance, offering a novel strategy for targeted therapy in bladder cancer., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Alda-1 functions as an agonist of aldehyde dehydrogenase (ALDH2) within the mitochondria, contributing to the preservation of mitochondrial structure and function. This study aimed to determine whether Alda-1 inhibited the accumulation of mitochondrial reactive oxygen species (mtROS) and improved cardiomyocyte damage under oxidative stress. Cardiomyocytes derived from human induced pluripotent embryonic stem cells (iPSC-CMs) and human AC16 cardiomyocytes were chosen for the experiments. Oxidative stress was induced in both cardiomyocyte types using hydrogen peroxide (H 2 O 2 ), a commonly employed agent. The mtROS accumulation and mitochondrial functional status were assessed by measuring the ROS content, mitochondrial membrane potential, and mitochondrial respiratory chain function. Co-IP experiments were used to analyze whether mtROS promoted protein interactions between TXNIP and NLRP3 and induced NLRP3 inflammasome activation. The results showed that Alda-1 mitigated damage to mitochondrial structure and function under oxidative stress, concurrently reducing the accumulation of mtROS. Co-IP experiments revealed that elevated mtROS levels attenuated the protein interaction between TXNIP and TRX while intensifying the interaction between TXNIP and NLRP3. Consequently, this triggers activation of the NLRP3 inflammasome, leading to cardiomyocyte damage. In contrast, TXNIP knockdown inhibited H 2 O 2 -induced myocardial injury and enhanced the therapeutic effects of Alda-1. Collectively, the results show that, in an H 2 O 2 environment, Alda-1 increased the production of ALDH2 activity in cardiomyocytes, hindered the production of mtROS, disrupted the interaction between TXNIP and NLRP3, and alleviated myocardial damage during oxidative stress., (© 2024 Wiley Periodicals LLC.)

H 2 O 2 is a significant reactive oxygen species (ROS) that hinders redox-mediated processes and contributes to oxidative stress and neurodegenerative disorders. Oxidative stress causes impairment of cell macromolecules, which results in cell dysfunction and neurodegeneration. Alzheimer's disease and other neurodegenerative diseases are serious conditions linked to oxidative stress. Antioxidant treatment approaches are a novel and successful strategy for decreasing neurodegeneration and reducing oxidative stress. This study explored the antioxidant and neuroprotective characteristics of KK14 peptide synthesized from LEAP 2B (liver-expressed antimicrobial peptide-2B) derived from Cyprinus carpio L. Molecular docking studies were used to assess the antioxidant properties of KK14. The peptide at concentrations 5-45 μM was examined by using in vitro and in vivo assessment. Analysis was done on the developmental and neuroprotective potential of KK14 peptide treatment in H 2 O 2 -exposed zebrafish larvae which showed Nonlethal deformities. KK14 improves antioxidant enzyme activity like catalase and superoxide dismutase. Furthermore, it reduces neuronal damage by lowering lipid peroxidation and nitric oxide generation while increasing acetylcholinesterase activity. It improved the changes in swimming behavior and the cognitive damage produced by exposure to H 2 O 2 . To further substantiate the neuroprotective potential of KK14, intracellular ROS levels in zebrafish larvae were assessed. This led to a reduction in ROS levels and diminished lipid peroxidation. The KK14 has upregulated the antioxidant genes against oxidative stress. Overall, this study proved the strong antioxidant activity of KK14, suggesting its potential as a strong therapeutic option for neurological disorders caused by oxidative stress., (© 2024 Wiley Periodicals LLC.)

Healthy cells have developed a sophisticated network of antioxidant molecules to prevent the toxic accumulation of reactive oxygen species (ROS) generated by diverse environmental stresses. On the opposite, cancer cells often exhibit high levels of ROS and an altered levels of antioxidant molecules compared to normal cells. Among them, the antioxidant enzyme catalase plays an essential role in cell defense against oxidative stress through the dismutation of hydrogen peroxide into water and molecular oxygen, and its expression is often decreased in cancer cells. The elevation of ROS in cancer cells provides them proliferative advantages, and leads to metabolic reprogramming, immune escape and metastasis. In this context, catalase is of critical importance to control these cellular processes in cancer through various mechanisms. In this review, we will discuss the major progresses and challenges in understanding the role of catalase in cancer for this last decade. This review also aims to provide important updates regarding the regulation of catalase expression, subcellular localization and discuss about the potential role of microbial catalases in tumor environment. Finally, we will describe the different catalase-based therapies and address the advantages, disadvantages, and limitations associated with modulating catalase therapeutically in cancer treatment., Competing Interests: Declaration of competing interest All authors declare that there are no conflicts of interest to be disclosed., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose: Lycium barbarum polysaccharides (LBPs) have been proven to protect the eyes by inhibiting apoptosis. This study was designed to investigate the effect of LBPs on DNA damage and oxidative stress induced by ultraviolet B (UVB) radiation in human corneal epithelial cells (HCECs)., Methods: HCECs were divided into a control group, UVB group and UVB + LBP group and treated with varying concentrations of LBP (0, 0.05, 0.1, 0.2, 0.4, 0.8, 1.6 and 3.2 mg/mL). Then, the effects of LBP on the viability and apoptosis of HCECs were detected via MTT assay and flow cytometry. Additionally, the contents of superoxide dismutase (SOD), malondialdehyde (MDA), and reactive oxygen species (ROS) in the cells of each group were measured to evaluate the level of oxidative stress., Results: LBP at a concentration of 0.4 mg/mL showed the best effect on promoting the viability and inhibiting the apoptosis of HCECs. Compared with the control group, the UVB and UVB + LBP groups exhibited significantly decreased levels of cell viability and SOD and notably increased apoptosis, MDA, ROS, tail DNA percentage, olive tail moment, p-CHK2, and gamma histone (γH2AX). In contrast to the UVB group, the UVB + LBP group presented notably upregulated levels of cell viability and SOD and downregulated apoptosis, MDA, ROS, tail DNA percentage, olive tail moment, p-CHK2, and γH2AX., Conclusions: The optimal concentration of LBP to promote the viability and reduce the apoptosis of HCECs is 0.4 mg/mL. Moreover, LBP can alleviate DNA damage and oxidative stress induced by UVB in HCECs.

Oxidative stress is a crucial concept in redox biology, and significant progress has been made in recent years. Excessive levels of reactive oxygen species (ROS) can lead to oxidative damage, heightening vulnerability to various diseases. By contrast, ROS maintained within a moderate range plays a role in regulating normal physiological metabolism. Choosing suitable animal models in a complex research context is critical for enhancing research efficacy. While rodents are frequently utilized in medical experiments, they pose challenges such as high costs and ethical considerations. Alternatively, non-rodent model organisms like zebrafish, Drosophila, and C. elegans offer promising avenues into oxidative stress research. These organisms boast advantages such as their small size, high reproduction rate, availability for live imaging, and ease of gene manipulation. This review highlights advancements in the detection of oxidative stress using non-rodent models. The oxidative homeostasis regulatory pathway, Kelch-like ECH-associated protein 1-Nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2), is systematically reviewed alongside multiple regulation of Nrf2-centered pathways in different organisms. Ultimately, this review conducts a comprehensive comparative analysis of different model organisms and further explores the combination of novel techniques with non-rodents. This review aims to summarize state-of-the-art findings in oxidative stress research using non-rodents and to delineate future directions., 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.)

6-PPD quinone (6-PPDQ) is extensively existed in various environments. In Caenorhabditis elegans, exposure to 6-PPDQ could cause multiple toxic effects. In the current study, we further used C. elegans to investigate the effect of paeoniflorin (PF) treatment on 6-PPDQ toxicity and accumulation and the underlying mechanism. Treatment with PF (25-100 mg/L) inhibited 6-PPDQ toxicity on reproduction capacity and locomotion behavior and in inducing reactive oxygen species (ROS) production. Additionally, PF (25-100 mg/L) alleviated the dysregulation in expression of genes governing oxidative stress caused by 6-PPDQ exposure. Moreover, PF (25-100 mg/L) inhibited the enhancement in intestinal permeability caused by 6-PPDQ exposure and the accumulation of 6-PPDQ in the body of nematodes. In 6-PPDQ exposed nematodes, PF (25-100 mg/L) increased expression of acs-22 encoding a fatty acid transporter. RNAi of acs-22 could inhibit the beneficial effect of PF against 6-PPDQ toxicity in decreasing reproductive capacity and locomotion behavior, in inducing intestinal ROS production, and in enhancing intestinal permeability. RNAi of acs-22 could also suppress the PF beneficial effect against 6-PPDQ accumulation in the body of nematodes. Therefore, our results demonstrate the function of PF treatment against 6-PPDQ toxicity and accumulation in nematodes by activating the ACS-22., 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 Inc. All rights reserved.)

Cancer cells maintain high levels of reactive oxygen species (ROS) to drive their growth, but ROS can trigger cell death through oxidative stress and DNA damage. To survive enhanced ROS levels, cancer cells activate their antioxidant defenses. One such defense is MTH1, an enzyme that prevents the incorporation of oxidized nucleotides into DNA, thus preventing DNA damage and allowing cancer to proliferate. MTH1 levels are often elevated in many cancers, and thus, inhibiting MTH1 is an attractive strategy for suppressing tumor growth and metastasis. Targeted MTH1 inhibition can induce DNA damage in cancer cells, exploiting their vulnerability to oxidative stress and selectively targeting them for destruction. Targeting MTH1 is promising for cancer treatment because normal cells have lower ROS levels and are less dependent on these pathways, making the approach both effective and specific to cancer. This review aims to investigate the potential of MTH1 as a therapeutic target, especially in cancer treatment, offering detailed insights into its structure, function, and role in disease progression. We also discussed various MTH1 inhibitors that have been developed to selectively induce oxidative damage in cancer cells, though their effectiveness varies. In addition, this review provide deeper mechanistic insights into the role of MTH1 in cancer prevention and oxidative stress management in various diseases., 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.)

Delaying or preventing the loss of retinal ganglion cells (RGCs) in glaucoma is needed for vision preservation. Glutamate-mediated neurotoxicity arises from the excessive stimulation of N-methyl-D-aspartate membrane receptors by glutamate. This overstimulation, occurring specifically in RGCs, triggers a progressive deterioration of the optic nerve that ultimately leads to the vision loss in glaucoma. Our previous investigation demonstrated that nicotinamide riboside (NR) effectively preserved RGCs in multiple mouse models of glaucoma. To investigate the precise role of NR concerning RGCs which remains uncertain, a glutamate-induced excitotoxicity RGCs damage model was established using R28 cells in this study. Results showed that NR treatment could not only prevent the decrease in cell viability but also effectively inhibit the apoptosis of R28 cells induced by glutamate, as proven by flow cytometry and expression of key pro-apoptotic proteins. Additionally, it significantly attenuated oxidative stress induced by glutamate, as evaluated by the production of inflammatory factors, reactive oxygen species (ROS) and mitochondrial ROS (mtROS). Furthermore, NR elevated the intracellular nicotinamide adenine dinucleotide (NAD+) levels in R28 cells. Lastly, we used RNA-seq to reveal the underlying mechanism of NR protection. Combining the results of RNA-seq and Western blot, we found that NR also restored the decreased protein expression of sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-gamma coactivator (PGC1α) induced by glutamate. These findings strongly indicated that NR exhibits a protective effect against R28 cell apoptosis in a glutamate-induced excitotoxicity RGCs damage model. This protective effect is likely mediated through the activation of the SIRT1/PGC1α pathway, achieved by increasing intracellular NAD + levels., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Insulin participates in glucose homeostasis in the body and regulates glucose, protein, and lipid metabolism. Chronic hyperglycemia triggers oxidative stress and the generation of reactive oxygen species (ROS), leading to oxidized insulin variants. Oxidative protein modifications can cause functional changes or altered immunogenicity as known from the context of autoimmune disorders. However, studies on the biological function of native and oxidized insulin on glucose homeostasis and cellular function are lacking. Native insulin showed heterogenous effects on metabolic activity, proliferation, glucose carrier transporter (GLUT) 4, and insulin receptor (INSR) expression, as well as glucose uptake in cell lines of five different human tissues. Diverse ROS compositions produced by different gas plasma approaches enabled the investigations of variously modified insulin (oxIns) with individual oxidative post-translational modification (oxPTM) patterns as identified using high-resolution mass spectrometric analysis. Specific oxIns variants promoted cellular metabolism and proliferation in several cell lines investigated, and nitrogen plasma emission lines could be linked to insulin nitration and elevated glucose uptake. In addition, insulin oxidation modified blood glucose levels in the chicken embryos (in ovo), underlining the importance of assessing protein oxidation and function in health and disease., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Histone deacetylases (HDACs) play critical roles in cardiovascular diseases (CVDs). In addition, reactive oxygen species (ROS) produced by NADPH oxidases (NOXs) exert damaging effects due to oxidative stress on heart and blood vessels. Although NOX-dependent ROS production is implicated in pathogenesis, the relationship between HDACs and NOXs in CVDs remains to be elucidated. Here, we present an overview of the regulatory effects and interconnected signaling pathways of HDACs and NOXs in CVDs. Improved insights into these relationships will facilitate the discovery of novel therapeutic agents that target HDACs, oxidase stress pathways, and the interactions between these systems which may be highly effective in the prevention and treatment of cardiovascular disorders., 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.)

Chronic obstructive pulmonary disease (COPD) is strongly linked to cigarette smoke, which contains toxins that induce oxidative stress and airway inflammation, ultimately leading to premature airway epithelial cell senescence and exacerbating COPD progression. Current treatments for COPD are symptomatic and hampered by limited efficacy and severe side effects. This highlights the need to search for an optimal therapeutic candidate to address the root causes of these conditions. This study investigates the possible potential of poly (lactic-co-glycolic acid) (PLGA)-based nanoparticles encapsulating the plant-based bioactive compound 18-β-glycyrrhetinic acid (18βGA) as a strategy to intervene in cigarette smoke extract (CSE)-induced oxidative stress, inflammation, and senescence, in vitro. We prepared 18βGA-PLGA nanoparticles, and assessed their effects on cell viability, reactive oxygen species (ROS) production, anti-senescence properties (expression of senescence-associated β galactosidase and p21 mRNA), and expression of pro-inflammatory genes (CXCL-1, IL-6, TNF-α) and inflammation-related proteins (IL-8, IL-15, RANTES, MIF). The highest non-toxic concentration of 18βGA-PLGA nanoparticles to healthy human broncho epithelial cell line BCiNS1.1 was identified as 5 µM. These nanoparticles effectively mitigated cigarette smoke-induced inflammation, reduced ROS production, protected against cellular aging, and counteracted the effects of CSE on the expression of the inflammation-related genes and proteins. This study underscores the potential of 18βGA encapsulated in PLGA nanoparticles as a promising therapeutic approach to alleviate cigarette smoke-induced oxidative stress, inflammation, and senescence. Further research is needed to explore the translational potential of these findings in clinical and in vivo settings., 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 GmbH.. All rights reserved.)

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice. Though the pathogenesis of AF is complex and is not completely understood, many studies suggest that oxidative stress is a major mechanism in pathophysiology of AF. Through multiple mechanisms, reactive oxygen species (ROS) lead to the formation of an AF substrate that facilitates the development and maintenance of AF. In this review article, we provide an update on the different mechanisms by which oxidative stress promotes atrial remodeling. We then discuss several therapeutic strategies targeting oxidative stress for the prevention or treatment of AF. Considering the complex biology of ROS induced remodeling, and the evolution of ROS sources and compartmentalization during AF progression, there is a definite need for improvement in timing, targeting and reduction of off-target effects of therapeutic strategies targeting oxidative injury in AF., Competing Interests: Declaration of competing interest RA: Ownership interest, Inomagen Therapeutics, Inc. Other authors have no disclosures to report., (Copyright © 2024. Published by Elsevier Ltd.)

Parkinson's disease (PD) is the second most common neurodegenerative disease, and it has affected the living quality of elderly people significantly. PD is characterised by the accumulation of α-Synuclein and progressive loss of dopaminergic neurons at the substantia nigra pars compacta. In the pathogenesis of Parkinson's disease, α-Synuclein, oxidative stress, and electron transport chain (ETC) are the three main factors that contribute to the production of reactive oxygen species (ROS). Currently, there is no commercial disease-modifying agent available for PD; the first-line treatment, Levodopa (l-DOPA), could only relieve the symptoms of PD, with many side effects. Carotenoids, which encompass red, orange, and yellow pigments found in nature and contribute to the colouration of plants, have been associated with various health benefits, including anti-cancer and neuroprotective effects due to their antioxidant properties. This scoping review delves into the impact and underlying mechanisms of carotenoids on cell-based models of neurodegenerative diseases., Competing Interests: Declaration of competing interest We wish to declare that we have no conflicts of interest regarding our submission entitled " Carotenoids Modulate Protective Pathways in In vitro Models of Parkinson's Disease: A Comprehensive Scoping Review" to the Neurochemistry International., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Oxidative stress mediated by reactive oxygen species (ROS) contributes to apoptosis of tubular epithelial cells (TECs) and renal inflammation during acute kidney injury (AKI). Copper metabolism MURR1 domain-containing 5 [COMMD5/hypertension-related, calcium-regulated gene (HCaRG)] shows strong cytoprotective properties. COMMD5 is highly expressed in proximal tubules (PTs), where it controls cell differentiation. We assessed its role in cisplatin-induced AKI using transgenic mice in which COMMD5 is overexpressed in the PTs. Cisplatin caused the accumulation of damaged mitochondria and cellular waste in PTs, thus increasing the apoptosis of TECs. COMMD5 overexpression effectively protected TECs from cisplatin nephrotoxicity by decreasing intracellular ROS levels, mitochondrial dysfunction, and apoptosis through the preservation of tubular epithelial integrity, thus alleviating morphological and functional kidney damage. Excessive ROS production by hydrogen peroxide led to long-term autophagy activation through an increased burden on the autophagy/lysosome degradation system in TECs, and autophagic elimination of damaged mitochondria and cellular waste was compromised. COMMD5 attenuated oxidative injury by increasing autophagy flux, possibly due to a reduction of intracellular ROS levels through maintained tubular epithelial integrity, which decreased JNK/caspase-3-dependent apoptosis. Meanwhile, COMMD5 inhibition by siRNA reduced the resistance of TECs to cisplatin cytotoxicity, as shown by disrupted tubular epithelial integrity and cell viability. These data indicated that COMMD5 protects TECs from drug-induced oxidative stress and toxicity by maintaining tubular epithelial integrity and autophagy flux and ultimately decreases mitochondrial dysfunction and apoptosis. Increasing COMMD5 content in PTs is proposed as a new protective and therapeutic strategy against AKI. NEW & NOTEWORTHY Oxidative stress overload by drug treatment causes the accumulation of damaged mitochondria that could contribute to tubulopathy. However, effective preventive treatment for drug-induced acute kidney injury remains incompletely understood. Our study showed that copper metabolism MURR1 domain-containing 5 (COMMD5) reduced mitochondrial dysfunction and increased autophagy flux by alleviating reactive oxygen species production through maintaining tubular epithelial integrity when tubular epithelial cells were under oxidative stress, thus ameliorating renal function in cisplatin-treated mice. These results uncover a novel renoprotective mechanism underlying tubular epithelial integrity and autophagy flux.

Keratoconus (KC) is a progressive, multifactorial and ectatic corneal disorder that characterized by steepening thinning of the cornea. It was previously demonstrated that oxidative stress has a strong link with KC progression. However, the molecular mechanism underlying oxidative stress response in KC remains unclear. Hence, the present study analyzed the heterogeneity of response of corneal stromal cells (CSCs) to oxidative stress in order to further illustrate how oxidative shape the pathophysiology of KC. Single-cell transcriptomics analysis revealed that CSCs demonstrated significant higher oxidative stress score in the KC group compared to the Ctrl group. The expression of oxidative markers verified by experiments illustrated elevated oxidative stress levels and insufficient antioxidant levels in CSCs of KC. In further single-cell transcriptomics analysis, we identified CYR61 to distinguish different subgroups of CSCs responding to oxidative stress. The cornea stroma cells in KC could be differentiated into CYR61 high cells and CYR61 low cells. Of note, the CYR61 high cells showed lower score in collagen production process and higher score in collagen catabolic process. Further experiments illustrated that CYR61 was elevated in KC and associated with collagen production., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Reactive oxygen species (ROS) play a significant role in toxicity to the retina in a variety of diseases. N-acetylcysteine (NAC), N-acetylcysteine amide (NACA) and the dimeric di-N-acetylcysteine amide (diNACA) were evaluated in terms of protecting retinal cells, in vitro, in a variety of stress models. Three types of rat retinal cell cultures were utilized in the study: macroglial-only cell cultures, neuron-only retinal ganglion cell (RGC) cultures, and mixed cultures containing retinal glia and neurons. Ability of test agents to attenuate oxidative stress in all cultures was ascertained. In addition, capability of agents to protect against a variety of alternate clinically-relevant stressors, including excitotoxins and mitochondrial electron transport chain inhibitors, was also evaluated. Capacity of test agents to elevate cellular levels of reduced glutathione under normal and compromised conditions was also determined. NAC, NACA and diNACA demonstrated concentration-dependent cytoprotection against oxidative stress in all cultures. These three compounds, however, had differing effects against a variety of alternate insults to retinal cells. The most protective agent was NACA, which was most potent against the most stressors (including oxidative stress, mitochondrial impairment by antimycin A and azide, and glutamate-induced excitotoxicity). Similar to NAC, NACA increased glutathione levels in non-injured cells, although diNACA did not, suggesting a different, unknown mechanism of antioxidant activity for the latter. In support of this, diNACA was the only agent to attenuate rotenone-induced toxicity in mitochondria. NAC, NACA and diNACA exhibited varying degrees of antioxidant activity, i.e., protected cultured rat retinal cells from a variety of stressors which were designed to mimic aspects of the pathology of different retinal diseases. A general rank order of activity was observed: NACA ≥ diNACA > NAC. These results warrant further exploration of NACA and diNACA as antioxidant therapeutics for the treatment of retinal diseases, particularly those involving oxidative stress. Furthermore, we have defined the battery of tests carried out as the "Wood, Chidlow, Wall and Casson (WCWC) Retinal Antioxidant Indices"; we believe that these are of great value for screening molecules for potential to reduce retinal oxidative stress in a range of retinal diseases., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Chinese dragon's blood, the red resin of Dracaena cochinchinensis (Lour.) S. C. Chen., is widely used to treat cardiovascular and cerebrovascular diseases in China. Longxuetongluo Capsule (LTC) is a total phenolic compound extracted from Chinese dragon's blood, currently used in treating ischemic stroke. Myocardial injury can be aggravated after reperfusion of ischemic myocardium, which is called myocardial ischemia-reperfusion injury (MIRI), and the mechanism of MIRI is complex. However, the exact effect and mechanism of LTC on MIRI are still unclear. We explore the effect of LTC on alleviating MIRI based on mitochondrial dysfunction and oxidative stress., Aim of the Study: To explore the cardioprotective mechanism of LTC against MIRI., Materials and Methods: A rat MIRI model was constructed through ligation of the left anterior descending coronary artery, and LTC was given continuously for 28 days before surgery. The H9c2 cardiomyocyte injury model was induced by oxygen-glucose deprivation/reperfusion (OGD/R), and LTC was given 24 h before OGD. Myocardial ischemia areas were detected with 2,3,5-triphenyltetrazolium chloride (TTC) staining. Cardiac histopathological changes were detected with hematoxylin-eosin (HE) staining. And biochemical indexes were detected with serum biochemical kit. Terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining and flow cytometry were used to detect apoptosis. Fluorescent probes were used to observe reactive oxygen species (ROS), mitochondrial membrane potential (ΔΨm), Ca 2+ and other indexes. MitoTracker staining and immunofluorescence were used to observe the morphology of mitochondria and translocation of dynamin-related protein 1 (Drp1). Finally, immunohistochemistry and Western blotting were used to examine the expression of proteins related to apoptosis, mitochondrial fission and fusion and oxidative stress., Results: LTC could ameliorate cardiac pathological changes, decrease myocardial infarct area and the content or level of relevant serum cardiac enzymes, indicating that LTC could alleviate MIRI. Meanwhile, LTC could inhibit cardiomyocyte apoptosis via regulating apoptosis-related protein expression, and it could restore mitochondrial morphology, maintain ΔΨm, inhibit mitochondrial ROS generation and Ca 2+ accumulation, increase the expression of mitochondrial fusion protein 2 (Mfn2), decrease the level of phosphorylation dynamin-related protein 1 (p-Drp1), and regulate ATP synthesis, thereby significantly ameliorating mitochondrial dysfunction. Moreover, LTC significantly reduced the expression of NADPH oxidase 2 (NOX2), NADPH oxidase 4 (NOX4) and neutrophil cytosolic factor 2 (NOXA2/p67 phox ), and reduced ROS production., Conclusion: The study demonstrated that LTC could inhibit MIRI induced cardiomyocyte apoptosis by inhibiting ROS generation and mitochondrial dysfunction, and these fundings suggested that LTC can be used to alleviate MIRI, which provides a potential therapeutic approach for future treatment of MIRI., 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 Elsevier GmbH. All rights reserved.)

Background: Aging-induced decline in ciliary muscle function is an important factor in visual accommodative deficits in elderly adults. With this study, we provide an innovative investigation of the interaction between ciliary muscle aging and oxidative stress., Methods: Tricolor guinea pigs were used for the experiments in vivo and primary guinea pig ciliary smooth muscle cells were used for the experiments in vitro., Results: We enriched for genes associated with muscle-aging-lutein relationship using bioinformatics, including Nuclear factor-erythroid 2-related factor-2 (Nrf2), Glutathione Peroxidase (GPx) gene family, Superoxide Dismutase (SOD) gene family, NAD(P)H: Quinone Oxidoreductase 1 (NQO1) and Heme Oxygenase-1 (HO-1). After gavage to aged guinea pigs, lutein reduced Reactive Oxygen Species (ROS) and P21 levels in senescent ciliary muscle; lutein decreased refractive error and restored accommodation of the eye. In addition, lutein increased GPx, SOD, and Catalase (CAT) levels in serum; lutein increased GPx and CAT levels in ciliary bodies. Lutein regulated the expression of proteins such as Nrf2, Kelch-like ECH-associated protein 1 (Keap1), and downstream proteins in senescent ciliary bodies. Similarly, guinea pig ciliary muscle cell senescence was associated with oxidative stress. In vitro, 100 μM lutein reversed the damage caused by 800 μM H 2 O 2 ; it reduced Senescence-Associated β-galactosidase (SA-β-Gal) and ROS activites, cell apoptosis and cell migration. Also, lutein increased the expression of smooth muscle contractile proteins. Lutein also increased the expression of Nrf2, GPx2, NQO1 and HO-1, decreased the expression of Keap1. A reduction in Nrf2 activity led to a reduction in the ability of lutein to activate antioxidant enzymes in the cells, thus reducing its inhibitory effect on cell senescence., Conclusion: lutein improved resistance to oxidative stress in senescent ciliary muscle in vivo and in vitro by regulating the Keap1/Nrf2/Antioxidant Response Element pathway. We have innovatively demonstrated the molecular pharmacological mechanism by which lutein reverse age-related ciliary muscle systolic and diastolic deficits., 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 Elsevier GmbH. All rights reserved.)

Carbon monoxide (CO) poisoning presents a substantial public health challenge that necessitates the identification of its pathological mechanisms and therapeutic targets. CO toxicity arises from tissue hypoxia-ischemia secondary to carboxyhemoglobin formation, and cellular damage mediated by CO at the cellular level. The mitochondria are the major targets of neuronal damage caused by CO. Under normal physiological conditions, mitochondria produce reactive oxygen species (ROS), which are byproducts of aerobic metabolism. While low ROS levels are crucial for essential cellular functions, including signal transduction, differentiation, responses to hypoxia and immunity, transcriptional regulation, and autophagy, excess ROS become pathological and exacerbate CO poisoning. This review presents the evidence of elevated ROS being associated with the progression of CO poisoning. Antioxidant treatments targeting ROS removal have been proven effective in mitigating CO poisoning, underscoring their therapeutic potential. In this review, we highlight the latest advances in the understanding of the role and the clinical implications of ROS in CO poisoning. We focus on cellular sources of ROS, the molecular mechanisms underlying mitochondrial oxidative stress, and potential therapeutic strategies for targeting ROS in CO poisoning., 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 Elsevier B.V. All rights reserved.)

25-hydroxycholesterol (25HC) is an oxysterol derived from cholesterol and plays a role in various cellular processes, such as lipid metabolism, inflammatory responses, and cell survival. Extravillous trophoblasts (EVTs) are a major cell type found in the placenta, which are highly energetic cells with proliferative and invasive properties. EVT dysfunction can lead to pregnancy complications, including preeclampsia and intrauterine growth restriction. This study investigated the effects and underlying mechanisms of action of 25HC on EVT proliferation. Swan 71 cells, an EVT cell line, were treated with different concentrations of 25HC. Next, cell proliferation was assessed. The mitochondrial reactive oxygen species (mtROS), mitochondrial membrane potentials (MMPs), lipid peroxidation (LPO), and glutathione (GSH) levels were measured. Apoptosis, ferroptosis, and autophagy were evaluated by western blotting and flow cytometry. The results revealed that 25HC significantly inhibited proliferation and decreased the metabolic activity of EVTs. Moreover, 25HC caused oxidative stress by altering mtROS, LPO, MMPs, and GSH levels. Additionally, 25HC induces apoptosis, ferroptosis, and autophagy through the modulation of relevant protein levels. Interestingly, pretreatment with Z-VAD-FMK, an apoptosis inhibitor, and ferrostatin-1, a ferroptosis inhibitor, partially restored the effects of 25HC on cell proliferation, oxidative stress, and cell death. In summary, our findings suggest that 25HC treatment inhibits EVT proliferation and triggers apoptosis, ferroptosis, and autophagy, which are attributable to oxidative stress., 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. Published by Elsevier B.V.)

Calcium ions (Ca 2+ ) regulate cell proliferation and differentiation and participate in various physiological activities of cells. The calcium transfer protein inositol 1,4,5-triphosphate receptor (IP 3 R), located between the endoplasmic reticulum (ER) and mitochondria, plays an important role in regulating Ca 2+ levels. However, the mechanism by which IP 3 R1 affects porcine meiotic progression and embryonic development remains unclear. We established a model in porcine oocytes using siRNA-mediated knockdown of IP 3 R1 to investigate the effects of IP 3 R1 on porcine oocyte meiotic progression and embryonic development. The results indicated that a decrease in IP 3 R1 expression significantly enhanced the interaction between the ER and mitochondria. Additionally, the interaction between the ER and the mitochondrial Ca 2+ ([Ca 2+ ] m ) transport network protein IP 3 R1-GRP75-VDAC1 was disrupted. The results of the Duolink II in situ proximity ligation assay (PLA) revealed a weakened pairwise interaction between IP 3 R1-GRP75 and VDAC1 and a significantly increased interaction between GRP75 and VDAC1 after IP 3 R1 interference, resulting in the accumulation of large amounts of [Ca 2+ ] m . These changes led to mitochondrial oxidative stress, increased the levels of reactive oxygen species (ROS) and reduced ATP production, which hindered the maturation and late development of porcine oocytes and induced apoptosis. Nevertheless, after treat with [Ca 2+ ] m chelating agent ruthenium red (RR) or ROS scavenger N-acetylcysteine (NAC), the oocytes developmental abnormalities, oxidative stress and apoptosis caused by Ca 2+ overload were improved. In conclusion, our results indicated IP 3 R1 is required for meiotic progression and embryonic development by regulating mitochondrial calcium and oxidative damage., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Rice bran oil is a type of rice oil made by leaching or pressing during rice processing and has a high absorption rate after consumption. When oxidative rancidity occurs, it may cause oxidative stress (OS) and affect intestinal function. Meanwhile, the toxic effects of oxidised rice bran oil have been less well studied in pigs. Therefore, the IPEC-J2 cells model was chosen to explore the regulatory mechanisms of oxidised rice bran oil on OS and apoptosis. Oxidised rice bran oil extract treatment (OR) significantly decreased the viability of IPEC-J2 cells. The results showed that OR significantly elevated apoptosis and reactive oxygen species levels and promoted the expression of pro-apoptotic gene Caspase-3 messenger RNA levels. The activation of Nrf2 signalling pathway by OR decreased the cellular antioxidant capacity. This was further evidenced by the expression of kelch-like ECH-associated protein 1, heme oxygenase 1, NADH: quinone oxidoreductase 1, superoxide dismutase 2 and heat shock 70 kDa protein genes and proteins were all downregulated. In conclusion, our results suggested that oxidised rice bran oil induced damage in IPEC-J2 cells through the Nrf2 signalling pathway., (© 2024 Wiley‐VCH GmbH. Published by John Wiley & Sons Ltd.)

Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Nickel phytotoxicity has been attributed, among others, to oxidative stress. However, little is known about Ni-induced phospholipid modifications, including the oxidative ones. Accumulation of reactive oxygen species (ROS), antioxidative enzyme activities, malondialdehyde and the early lipid oxidation products contents, membrane permeability, phospholipid profile as well as phospholipid unsaturation degree were studied in the 1st and the 2nd leaves of hydroponically grown cucumber seedlings subjected to Ni stress. Compared to the 2nd leaf the 1st one showed stronger visual Ni toxicity symptoms, higher Ni, O 2 .- and H 2 O 2 accumulation as well as greater enhancement in membrane permeability. Enzyme activities were differently influenced by Ni stress, however most pronounced changes were generally found in the 1st leaf. Ni treatment resulted in oxidation of leaf lipids, which was evidenced by appearance of increased contents of MDA and the early produced oxylipins. Among the latter 9-hydroxyoctadecatrienoic acid (9-HOTrE) and 13-hydroxyoctadecatrienoic acid (13-HOTrE) contents showed the most pronounced increase in response to Ni treatment. Exposure to the metal led to the changes in the leaf phospholipid profile and increased degree of phospholipid unsaturation. The obtained results have been discussed in relation to the difference in Ni stress severity between the 1st and the 2nd leaves., 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.)

Oxidative stress has long been known as a pathogenic factor of ulcerative colitis. Superoxide dismutase (SOD) has been demonstrated to mitigate gut mucosal injury via combating oxidative stress. Herein, we developed SOD-loaded multivesicular liposomes (S-MVLs) as sustained-release depot for ulcerative colitis treatment. S-MVLs were spherical honeycomb-like particles with average particle size of 27.3 ± 5.4 μm and encapsulating efficiency of 78.7 ± 2.6 %. Moreover, the two-phase release profiles of SOD from S-MVLs were exhibited, that was, the burst release phase within 4 h and the sustained-release phase within 96 h. After intraperitoneally injecting S-MVLs, in situ retention time of SOD at bowel cavity extended by 4-fold in comparison with SOD solution. In vitro cells experiment showed that S-MVLs had the protective effect on LPS-treated RAW 264.7 cells via scavenging ROS and inhibiting pro-inflammatory cytokines production. S-MVLs ameliorated the body weight loss, DAI score and the colon shortening of colitis mice. Meanwhile, the colonic morphology and the epithelial barrier of colitis mice were effectively recovered after S-MVLs treatment. The therapeutic mechanism might be associated with polymerizing M1 macrophages to M2 phenotypes and alleviating oxidative stress. Collectively, multivesicular liposomes might be a promising sustained-release depot of SOD for ulcerative colitis treatments., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests. Helin Xu reports financial support was provided by Wenzhou Medical University. If there are other authors, they 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 Elsevier B.V. All rights reserved.)

Pesticides are a group of extensively used man-made chemicals with high toxicity and strong residues, which are closely related to hearing health. Pesticide metabolite 3, 5, 6-Trichloro-2-pyridinol (TCP) exposure leads to neurotoxicity and auditory cell toxicity. However, whether TCP causes damage to hearing in adult mice is not clear. In this study, adult male C57BL/6 mice continuously exposed to TCP for 21 days showed a dose-dependent elevation of hearing threshold. Outer hair cells and spiral neuron cells were lost in a dose-dependent manner. Type I and V of spiral ligament were severely shrunk and stria vascularis were thinned in mice after 50 and 150 mg/kg TCP exposure. Similarly, ROS levels in the cochlea were significantly increased whereas the activities of anti-oxidation enzymes were decreased after TCP exposure. The expression level of Na + /K + ATPase was decreased, resulting in cochlear potential disruption. Levels of inflammatory factors (TNF-α and IL-1β), γ-H2AX, and pro-apoptotic-related factors (Bax and cleaved-Caspase 3) were elevated, respectively. These results suggest that TCP can cause oxidative stress, inflammation, and imbalance of cochlear potential in the cochlea, induce cochlear DNA damage and apoptosis, and cause cochlear morphological changes, eventually leading to impaired hearing function., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Rong Chen reports financial support was provided by Zhejiang Provincial Natural Science Foundation of China. If there are other authors, they 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 Elsevier Ltd. All rights reserved.)

Tributyltin (TBT) is an organotin compound that has several adverse health effects, including the development of obesity. Although obesity is strongly associated with adipose redox imbalance, there is a lack of information on whether TBT promotes a pro-oxidative environment in WAT. Thus, adult male Wistar rats were randomly exposed to either vehicle (ethanol 0.4%) or TBT (1000 ng/kg) for 30 days. Body and fat pad masses, visceral fat morphology, lipid peroxidation, protein carbonylation, redox status markers, and catalase activity were evaluated. TBT promoted increased adiposity and visceral fat, with hypertrophic adipocytes, but did not alter body mass and subcutaneous fat. ROS production and lipid peroxidation were elevated in TBT group, as well as catalase protein expression and activity, although protein oxidation and glutathione peroxidase protein expression remained unchanged. In conclusion, this is the first study to demonstrate that subacute TBT administration leads to visceral adipose redox imbalance, with increased oxidative stress. This enlights the understanding of the metabolic toxic outcomes of continuous exposure to TBT in mammals., 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 Elsevier B.V. All rights reserved.)

Objective: An imbalance between the generation of reactive oxygen species (ROS) and the body's antioxidant defense mechanisms is believed to be a critical factor in the development of schizophrenia (SCZ) like neurological illnesses. Understanding the roles of ROS in the development of SCZ and the potential activity of natural antioxidants against SCZ could lead to more effective therapeutic options for the prevention and treatment of the illness., Methods: SCZ is a mental disorder characterised by progressive impairments in working memory, attention, and executive functioning. In present investigation, we summarized the experimental findings for understanding the role of oxidative stress (OS) in the development of SCZ and the potential neuroprotective effects of natural antioxidants in the treatment of SCZ., Results: Current study supports the use of the mentioned antioxidant natural compounds as a potential therapeutic candidates for the treatment of OS mediated neurodegeneration in SCZ., Discussion: Elevated levels of harmful ROS and reduced antioxidant defense mechanisms are indicative of increased oxidative stress (OS), which is associated with SCZ. Previous research has shown that individuals with SCZ, including non-medicated, medicated, first-episode, and chronic patients, exhibit decreased levels of total antioxidants and GSH. Additionally, they have reduced antioxidant enzyme levels such as catalase (CAT), glutathione (GPx), and, superoxide dismutase (SOD) and lower serum levels of brain-derived neurotrophic factor (BDNF) in their brain tissue. The mentioned natural antioxidants may assist in reducing oxidative damage in individuals with SCZ and increasing BDNF expression in the brain, potentially improving cognitive function and learning ability.

Bisphenol P (BPP) has been detected in human biological samples; however studies on its nephrotoxicity are scarce. Given the susceptibility of kidneys to endocrine-disrupting chemicals, there is an urgent need to investigate the renal toxicity of BPP. This study aimed to evaluate the effects of different concentrations of BPPs on the kidneys of C57BL/6 mice and elucidate the underlying mechanisms of renal damage using a combination of mouse renal transcriptomic data and human renal proximal tubular epithelial cells (HK-2). Mice were exposed to BPP (0, 0.3, 30, 3000 μg/kg bw/d) via gavage for 5 weeks. Renal injury was assessed based on changes in body and kidney weights, serum renal function indices, and histopathological examination. Transcriptomic analysis identified differentially expressed genes and pathways, whereas cellular assays were used to measure cell viability, reactive oxygen species (ROS), apoptosis, and the expression of key genes and proteins. The results show that BPP exposure induces renal injury, as evidenced by increased body weight, abnormal renal function indices, and renal tissue damage. Transcriptomic analysis revealed alterations in genes and pathways related to oxidative stress, p53 signaling, autophagy, and apoptosis. Cellular experiments confirmed that BPP induces oxidative stress and apoptosis. Furthermore, BPP exposure significantly inhibits autophagy, potentially exacerbating apoptosis and contributing to kidney injury. Treatment with a ROS inhibitor (N-Acetylcysteine, NAC) mitigated BPP-induced autophagy inhibition and apoptosis, implicating oxidative stress as a key factor. BPP exposure may lead to renal injury through excessive ROS accumulation, oxidative stress, inflammatory responses, autophagy inhibition, and increased apoptosis. The effects of NAC highlight the role of oxidative stress in BPP-induced nephrotoxicity. These findings enhance our understanding of BPP-induced nephrotoxicity and underscore the need to control BPP exposure to prevent renal disease. This study emphasized the importance of evaluating the safety of new Bisphenol A analogs, including BPP, in environmental toxicology., 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.)

Abstract: The high level of oxidative stress induced by angiotensin II (AngII) is the main pathophysiological process that promotes the proliferation and migration of vascular smooth muscle cells (VSMCs) and induces vascular remodeling. LncRNA metastasis-related lung adenocarcinoma transcript 1 (MALAT1) has been determined to play an important role in the modulation of oxidative stress and the development of cardiovascular diseases. Nevertheless, the function and underlying mechanism of MALAT1 in restenosis induced by hypertensive angioplasty remain unclear. AngII increased the expression of MALAT1 in VSMCs. We found that antisense oligonucleotide lncRNA MALAT1 (ASO-MALAT1) could inhibit AngII-induced reactive oxygen species production and VSMCs proliferation and migration by inducing the expression of glutathione peroxidase 4 (GPX4), which can be reversed by siRNA-GPX4. GPX4 overexpression can inhibit the proliferation and migration of VSMCs induced by AngII. In addition, we found that the process by which MALAT1 knockdown induces GPX4 expression involves nuclear factor erythrocyte 2-related factor 2 (Nrf2). Overexpression of Nrf2 can increase the expression of GPX4, and downregulation of GPX4 by ML385 (Nrf2 inhibitor) blocked the protective effect of ASO-MALAT1 on AngII-induced proliferation and migration of VSMCs. Ferrostatin-1 (Fer-1, ip 5 mg/kg per day for 2 weeks), a GPX4 agonist, significantly inhibited neointimal formation in spontaneously hypertensive rat by the inhibition of oxidative stress. In conclusion, these data imply that ASO-MALAT1 suppresses the AngII-induced oxidative stress, proliferation, and migration of VSMCs by activating Nrf2/GPX4 antioxidant signaling. GPX4 may be a potential target for the therapeutic intervention of hypertensive vascular restenosis., Competing Interests: The authors report no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)