Reactive Oxygen Species Activity Research Articles

Dusp26 phosphatase regulates mitochondrial respiration and oxidative stress and protects neuronal cell death.

The dual specificity protein phosphatases (Dusps) control dephosphorylation of mitogen-activated protein kinases (MAPKs) as well as other substrates. Here, we report that Dusp26, which is highly expressed in neuroblastoma cells and primary neurons is targetedtothe mitochondrial outermembrane via its NH2-terminal mitochondrial targeting sequence. Loss of Dusp26 has asignificant impact on mitochondrial function that is associated with increased levels of reactive oxygen species (ROS), reduction in ATP generation, reduction in mitochondria motility and release of mitochondrial HtrA2 protease into the cytoplasm. The mitochondrial dysregulation in dusp26-deficient neuroblastoma cells leads to the inhibition of cell proliferation and cell death. In vivo, Dusp26 is highly expressed in neurons in different brain regions, including cortex and midbrain (MB). Ablation of Dusp26 in mouse model leads to dopaminergic (DA) neuronal cell loss in the substantia nigra par compacta (SNpc), inflammatory response in MB and striatum, and phenotypes that are normally associated with Neurodegenerative diseases. Consistent with the data fromour mouse model, Dusp26 expressing cells are significantly reduced in the SNpc of Parkinson's Disease patients. The underlying mechanism of DA neuronal death is that loss of Dusp26 in neurons increases mitochondrial ROS and concurrent activation of MAPK/p38 signaling pathway and inflammatory response. Our results suggest that regulation of mitochondrial-associated protein phosphorylation is essential for the maintenance of mitochondrial homeostasis and dysregulation of this process may contribute to the initiation and development of neurodegenerative diseases.

Mechanism of paeoniflorin inhibiting apoptosis of hippocampal neurons of rats induced by lead acetate

Objective: To investigate the effect and underlying mechanism of paeoniflorin on hippocampal neuron apoptosis induced by lead acetate. Methods: In September 2020, primary hippocampal neuronal cells were isolated and cultured from fetal rats, and identified using cellular immunofluorescent. MTT assay was used to measure the cell viability to determine the concentration and time of lead acetate-induced hippocampal neuron apoptosis. MTT was also used to evaluate the effect of paeoniflorin concentration on the apoptosis of hippocampal neurons induced by lead acetate. According to the results, different concentrations of paeoniflorin were selected to intervene hippocampal neuron cells, after 24 h, lead acetate was added to the cells, meanwhile, blank and model groups were set up, the content of reactive oxygen species (ROS) , superoxide dismutase (SOD) , lactate dehydrogenase (LDH) , malondialdehyde (MDA) and Caspase-3 were measured. Extracellular signal regulated kinase (ERK) , phosphorylated ERK (p-ERK) , p38 mitogen -activated protein kinases (p38MAPK) , phosphorylated p38MAPK (p-p38MAPK) , c-Jun N-terminal kinase (JNK) and phosphorylated JNK (p-JNK) protein expression in hippocampal neuronal cells were determined by Western blotting. Results: The isolated and cultured hippocampal neurons were identified by immunofluorescence chemical staining and then treated with lead acetate, MTT results showed that lead acetate had the best toxicity effect when treated for 24 h at a concentration of 25 μmol/L. Paeoniflorin showed no cytotoxic effect on hippocampal neuronal cells when the concentrations below 80 μmol/L. Compared with the model group, the activity of hippocampal neuronal cells was significantly increased after treating with 20, 40 or 80 μmol/L paeoniflorin (P<0.05) . Compared with the blank group, the ROS activity, LDH release level, MDA content and caspase-3 content were significantly increased (P<0.01) , and the SOD activity was significantly decreased (P< 0.01) in the hippocampal neuronal cells of the model group. Compared with the model group, the ROS activity, LDH release level, MDA content and caspase-3 content were obviously decreased (P<0.05) , SOD activity was significantly increased (P <0.01) after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin. Relative to the model group, the ratio of p-ERK/ERK were significantly up-regulated (P<0.01) , while the ratios of p-p38MAPK/p38MAPK and p-JNK/JNK were significantly down-regulated after hippocampal neuronal cells were treated with 40 or 80 μmol/L paeoniflorin (P<0.05) . Conclusion: Paeoniflorin may down-regulate the expression of p-p38MAPK and p-JNK protein, up-regulate the expression of p-ERK protein, and inhibit the apoptosis of hippocampal neurons induced by lead acetate through the MAPK signaling pathway.

THE IMPACT OF SUCCINATE DERIVATIVE PHENSUCCINAL ON MITOCHONDRIAL FUNCTION AND REDOX STATUS IN THE HEART OF RATS WITH TYPE 2 DIABETES

Dysfunction of cardiac mitochondria appears to play a substantial role in cardiomyopathy and is a promising therapeutic target for many cardiovascular diseases. Persistent hyperglycaemia and hyperlipidemia are believed to be the main causes of increased oxidative stress, mitochondrial dysfunctions, fibrosis and apoptosis of cardiomyocytes in diabetes. We have previously shown that the low-toxic succinate derivative – Phensuccinal (beta-phenylethylamide-2 hydroxy-succinanylic acid, Phe) possesses antioxidant and anti-inflammatory properties. The aim of this study was to assess the effects of Phe on the mitochondrial function and oxidative status in the heart of rats with T2DM. Materials and Methods. T2DM was induced in Wistar rats by a high-caloric diet during 14 weeks combined with intraperitoneal injections of 25 mg/kg streptozotocin twice per week. All diabetic animals were divided into two groups: treated with vehicle or with Phe (in dose 50 mg/kg/day) for four weeks after diabetes induction. Redox status of rats’ heart mitochondria was estimated by determination of reactive oxygen species (ROS) production, GSH level and activity of antioxidant enzymes (Mn-superoxide dismutase, glutathione peroxidase and glutathione reductase). Mitochondrial function was determined by activity of aconitase, succinate dehydrogenase and cytochrome C oxidase in rats’ cardiomyocytes. Results. It was established that Phe inhibited oxidative stress in isolated heart mitochondria of rats with T2DM, which was confirmed by decreasing ROS production and increasing GSH level compared to diabetic rats. The use of Phe led to a normalization of antioxidant enzymes (Mn-superoxide dismutase and glutathione peroxidase) activity in the heart of diabetic rats. In addition, Phe improved metabolic activity of the heart mitochondria activating aconitase and succinate dehydrogenase in cardiomyocytes. We can suggest that Phe ameliorate mitochondrial dysfunction decreasing oxidative stress and preventing deficiency in complex II of ETC in the heart of rats with type 2 diabetes. Conclusion. The data of the present study confirmed the positive effect of Phe on redox homeostasis and functional state of the heart mitochondria in diabetic rats. We suggest that the use of Phe may contribute to the amelioration of cardiovascular risk in type 2 diabetes

Ginsenoside-Rb1 prevents bone cartilage destruction through down-regulation of p-Akt, p-P38, and p-P65 signaling in rabbit

BackgroundOsteoarthritis (OA) is the most common joint complaint resulting in pain, disability, and loss of quality of life. On the other hand, ginsenoside-Rb1 is a plant product derived from ginseng that possesses immune-regulation and anti-inflammatory activities. However, it has been reported that different rout of administration but hydrogel-based Ginsenoside-Rb1 in an OA rabbit model has not been investigated. PurposeThe aim of this study was to investigate the potential effects of ginsenoside-Rb1 such as anti-arthritic activity in a rabbit knee OA model via NF- κB, PI3K/Akt, and P38/(MAPK) pathways. Study DesignIn the current study, rabbit osteoarthritis was induced by hollow trephine on the femur trochlea and the hydrogel-based Ginsenoside-Rb1 sheets were inserted on the rabbit knee to assess the anti-arthritis activity of ginsenoside-Rb1 which is sustained release. MethodsAfter the hydrogel-based Rb1 sheet insert on the rabbit knee, macroscopic and micro CT was performed for investigation of chondroprotective effect. Matrix metalloproteinases (MMPs) and apoptotic expression were assessed through Immunohistochemistry and RT-PCR assay. In addition, the flow cytometry technique was used for the investigation of intracellular reactive oxygen species (ROS) production and histological changes were examined by HE, safranin O, and Masson trichrome staining method. Furthermore, the NF- κB, PI3K/Akt, and P38/(MAPK) pathways were investigated using Western blot analysis. ResultsMacroscopic and micro CT investigation of hydrogel-Rb1 treatment showed a dose-dependent chondroprotective effect. Immunohistochemistry and RT-PCR revealed that expression of matrix metalloproteinases (MMPs) and apoptotic markers TNF-α, caspase-3, and bax are down-regulated in a dose-dependent fashion following implantation of hydrogel-Rb. Higher levels of intracellular reactive oxygen species (ROS) were observed in the OA group. In histopathological investigation of hydrogel-Rb1 exhibited larger amounts of chondro cells, glycosaminoglycan's, and collagen compared to the defect group. Furthermore, the NF- κB, PI3K/Akt, and P38/(MAPK) pathways were downregulated by hydrogel-Rb1 while the disease model showed upstream. In the meantime, MMP expression level was considerably down-regulated. ConclusionsOur results indicate the protective effect of ginsenoside-Rb1 against OA pathogenesis through prevention of apoptosis with suppression of ROS production and activation of NF-κB signaling through downregulation of the MAPK and PI3K/Akt signaling pathways.

Reactive Oxygen Species and Their Consequences on the Structure and Function of Mammalian Spermatozoa.

Significance: Among the 200 or so cell types that comprise mammals, spermatozoa have an ambiguous relationship with the reactive oxygen species (ROS) inherent in the consumption of oxygen that supports aerobic metabolism. Recent Advances: In this review, we shall see that spermatozoa need the action of ROS to reach their structural and functional maturity, but that due to intrinsic unique characteristics, they are, perhaps more than any other cell type, susceptible to oxidative damage. Recent studies have improved our knowledge of how oxidative damage affects sperm structures and functions. The focus of this review will be on how genetic and epigenetic oxidative alterations to spermatozoa can have dramatic unintended consequences in terms of both the support and the suppression of sperm function. Critical Issues: Oxidative stress can have dramatic consequences not only for the spermatozoon itself, but also, and above all, on its primary objective, which is to carry out fertilization and to ensure, in part, that the embryonic development program should lead to a healthy progeny. Future Directions: Sperm oxidative DNA damage largely affects the integrity of the paternal genetic material to such an extent that the oocyte may have difficulties in correcting it. Diagnostic and therapeutic actions should be considered more systematically, especially in men with difficulties to conceive. Research is underway to determine whether the epigenetic information carried by spermatozoa is also subject to changes mediated by pro-oxidative situations. Antioxid. Redox Signal. 37, 481-500.

Iron overload and impaired iron handling contribute to the dystrophic pathology in models of Duchenne muscular dystrophy.

BackgroundOxidative stress is implicated in the pathophysiology of Duchenne muscular dystrophy (DMD, caused by mutations in the dystrophin gene), which is the most common and severe of the muscular dystrophies. To our knowledge, the distribution of iron, an important modulator of oxidative stress, has not been assessed in DMD. We tested the hypotheses that iron accumulation occurs in mouse models of DMD and that modulation of iron through the diet or chelation could modify disease severity.MethodsWe assessed iron distribution and total elemental iron using LA‐ICP‐MS on skeletal muscle cross‐sections of 8‐week‐old Bl10 control mice and dystrophic mdx mice (with moderate dystrophy) and dystrophin/utrophin‐null mice (dko, with severe dystrophy). In addition, mdx mice (4 weeks) were treated with either an iron chelator (deferiprone 150 mg/kg/day) or iron‐enriched feed (containing 1% added iron as carbonyl iron). Immunoblotting was used to determine the abundance of iron‐ and mitochondria‐related proteins. (Immuno)histochemical and mRNA assessments of fibrosis and inflammation were also performed.ResultsWe observed a significant increase in total elemental iron in hindlimb muscles of dko mice (+50%, P < 0.05) and in the diaphragm of mdx mice (+80%, P < 0.05), with both tissues exhibiting severe pathology. Iron dyshomeostasis was further evidenced by an increase in the storage protein ferritin (dko: +39%, P < 0.05) and ferroportin compared with Bl10 control mice (mdx: +152% and dko: +175%, P < 0.05). Despite having features of iron overload, dystrophic muscles had lower protein expression of ALAS‐1, the rate‐limiting enzyme for haem synthesis (dko −44%, P < 0.05), and the haem‐containing protein myoglobin (dko −54%, P < 0.05). Deferiprone treatment tended to decrease muscle iron levels in mdx mice (−30%, P < 0.1), which was associated with lower oxidative stress and fibrosis, but suppressed haem‐containing proteins and mitochondrial content. Increasing iron via dietary intervention elevated total muscle iron (+25%, P < 0.05) but did not aggravate the pathology.ConclusionsMuscles from dystrophic mice have increased iron levels and dysregulated iron‐related proteins that are associated with dystrophic pathology. Muscle iron levels were manipulated by iron chelation and iron enriched feed. Iron chelation reduced fibrosis and reactive oxygen species (ROS) but also suppressed haem‐containing proteins and mitochondrial activity. Conversely, iron supplementation increased ferritin and haem‐containing proteins but did not alter ROS, fibrosis, or mitochondrial activity. Further studies are required to investigate the contribution of impaired ferritin breakdown in the dysregulation of iron homeostasis in DMD.

Reactive oxygen species-responsive nanodrug of natural crocin-i with prolonged circulation for effective radioprotection

With the progress of nuclear technology including radiotherapy and radiodiagnosis, radiation has been widely used in many fields as a powerful diagnostic and therapeutic tool in the medical area. Unfortunately, acute radiation disease will occur if the human body is accidentally exposed to a large dosage of ionizing radiation. However, clinical radioprotective agents are being challenged by the short half-life and several side effects. In this work, a reactive oxygen species-responsive nanodrug is developed for efficient radioprotection. The nanodrug was prepared by modifying Crocin-I with 4-pentylphenylboronic acid (PBA) and exhibited effective responsiveness and scavenging activity of reactive oxygen species. PBA-Crocin nanodrug displayed good biocompatibility and radioprotection effect compared to Crocin-I in vitro. The survival rate of cells treated with PBA-Crocin (10 μg mL−1) is comparable to that treated with amifostine (12.5 μg mL−1, the only radioprotector approved by the United States Food and Drug Administration clinically) after 6 Gy irradiation. Importantly, PBA-Crocin resulted in markedly prevention of radiation-induced damage in peripheral blood cells and a 1.6-fold longer retention time of Crocin-I in plasma in comparison with Crocin-I. The finding suggests a new design for natural medicine in effective radioprotection.

Ecophysiological Responses of Five Mangrove Species (Bruguiera gymnorrhiza, Rhizophora stylosa, Aegiceras corniculatum, Avicennia marina, and Kandelia obovata) to Chilling Stress

Although the low temperature is a critical growth constraint on plants, the physiological mechanism remains unclear, especially in mangrove plants. Hence, the morphological characteristics of five mangrove plants (Bruguiera gymnorrhiza, Rhizophora stylosa, Aegiceras corniculatum, Avicennia marina, and Kandelia obovata) were compared under chilling stress. The contents of hydrogen peroxide (H2O2), malondialdehyde (MDA), and proline were tested. Activities of reactive oxygen species (ROS)-scavenging enzyme [superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT)] were also measured after chilling stress. It was concluded that K. obovata can well tolerate chilling stress, and B. gymnorrhiza suffered the most severe chilling damage. Leaf-morphology observation exhibited that K. obovata and A. corniculatum can sustain chilling stress, while B. gymnorrhiza wilted and A. marina turned brown. The content of H2O2 increased at first and subsequently decreased in all plants. MDA increased instantaneously in B. gymnorrhiza and R. stylosa but changed slowly in K. obovata and A. corniculatum. The high content of proline accumulated in B. gymnorrhiza and K. obovata. The activities of the SOD, POD, and CAT increased at first and then decreased in all mangrove species. The antioxidants maintained high activity in K. obovata while decreasing earliest in A. marina exposed to the long-term chilling stress. Principal component analysis (PCA) indicated that high antioxidant enzyme activities play key roles in chilling tolerance for mangrove plants. The longer-term chilling tolerance of K. obovata may be related to the high antioxidant enzyme activities and proline accumulation. Lower H2O2 and MDA contents strengthen the anti-chilling ability of A. corniculatum. Further investigation on the molecular mechanisms will facilitate the understanding of the anti-chilling ability of mangrove plants.

Exposure to urban air pollution particulate matter: neurobehavioral alteration and hippocampal inflammation.

Air pollution is associated with many neurodevelopmental and neurological disorders in human populations. Rodent models show similar neurotoxic effects of urban air pollution ultrafine particulate matter (UFPs < 100nm (PM0.1)), collected by different methods or from various sources. Exposure to ultrafine particulate matter (UFPs < 100nm (PM0.1)) can be adversely impacting the central nervous system (CNS) by the activation of proinflammatory pathways and reactive oxygen species associated with air pollution particulate matter. We investigated hippocampal inflammatory cytokines, neurobehavioral alteration, and neuronal morphology following exposure to diesel exhaust particles (DEPs) in mice. Male mice were DEPs exposed for 14weeks. Mice exposed to DEPs showed more disorders in spatial memory and learning and depressive-like responses than control mice. Expression of hippocampal pro-inflammatory cytokine was increased among DEPs exposure mice. The density of neurons in hippocampus CA1, CA3, and dentate gyrus (DG) regions decreased in DEPs mice. Overall, these findings show that prolonged exposure to DEPs in the world's major cities can alter neurobehavioral and impair cognition.

Resveratrol exhibits neuroprotection against paraquat-induced PC12 cells via heme oxygenase 1 upregulation by decreasing MiR-136-5p expression

ABSTRACT Resveratrol (Res) is a flavonoid with an antioxidant effect and has been utilized to treat oxidative stress-related illnesses; however, its mechanism remains ambiguous. This research aims to explore whether Res inhibits miR-136-5p expression, increases heme oxygenase 1 (HMOX1) expression, and mitigates oxidative stress and PC12 cell apoptosis triggered by paraquat (PQ). Results showed that PQ dose-dependently increased the expression of miR-136-5p, the apoptosis of PC12 cells, the activities of reactive oxygen species (ROS), and the levels of lactate dehydrogenase (LDH), malondialdehyde (MDA), caspase-3, and pro-apoptotic protein Bax. In addition, PQ reduced the expression of anti-apoptotic protein Bcl-2, HMOX1 mRNA and protein, and nuclear factor-erythroid factor 2-related factor 2 (Nrf2) protein and the activity of superoxide dismutase 1 (SOD1) and PC12 cells. After the PQ-treated PC12 cells were administered with different Res concentrations for 24 h, the miR-136-5p expression was dose-dependently decreased. An increase was observed in the activity and survival rate of PC12 cells, the protein and mRNA levels of HMOX1 and Nrf2, and the content of anti-apoptotic protein B-cell lymphoma/leukemia gene-2 (Bcl-2). By contrast, the activities of ROS, LDH, and MDA and the apoptosis of PC12 cells decreased. These findings illustrated that Res could reduce the oxidative stress and apoptosis triggered by PQ and enhance the activity and survival rate of PC12 cells. The underlying mechanism might be correlated with the reduced miR-136-5p expression and the elevated activity of the HMOX1/Nrf2 pathway.

Vascular Dysfunction and Its Cardiovascular Consequences During and After COVID-19 Infection: A Narrative Review.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory coronavirus 2 (SARS-CoV2) has brought out changes in our daily life and has caused severe morbidity and mortality across the globe. Especially, post covid complications may remain a threat to the patient’s life. It may also increase the burden on existing health infrastructure and the country’s economy. This disease affects the respiratory system and other organ systems of the body, such as the cardiovascular system. The aim of the present narrative review is to understand how COVID-19 infection deranges vascular homeostasis, leading to endothelial dysfunction and arterial stiffness in the acute phase and following infection. To this effect, definite keywords were employed to obtain relevant information using PubMed database and Google Scholar search engines. It was documented that preexisting cardiovascular disease enhances morbidity in COVID-19 patients. Moreover, an elevated risk of development of new onset cardiovascular events has also been reported. Even a small amount of myocardial injury was significantly associated with death. The presence of virus in myocardial cells has also been documented. Furthermore, endothelial dysfunction and arterial stiffness were documented in the acute phase and 3–4 weeks to 4 months after COVID infection. The virus enters endothelial cells by binding with ACE2 “receptor” on its surface and deranges cellular machinery. It results in reduced conversion of Ang II to Ang (1–7). Accumulated Ang II then activates PI3K-Akt signaling pathway and regulates endothelial activation and production of IL-6 and reactive oxygen species (ROS). An imbalance between renin angiotensin aldosterone system (RAAS) and kallikrein kinin system (KKS) also occurs, which may cause endothelial dysfunction. It is understandable that the underlying pathophysiology of this altered arterial stiffness is multifactorial, involving various cellular and immunological biomolecules.

Extract from the Macroalgae Ulva rigida Induces Table Grapes Resistance to Botrytis cinerea.

Fungal pathogens are a central cause of the high wastage rates of harvested fruit and vegetables. Seaweeds from the genus Ulva are fast-growing edible green macroalgae whose species can be found on the shore of every continent, and therefore present a resource that can be utilized on a global scale. In this study, we found that the application of ulvan extract, a sulfated polysaccharide extracted from Ulva rigida (1000 mg/L), elicited table grapes defense and reduced the incidence and decay area of Botrytis cinerea by 43% and 41%, respectively. In addition, compared to the control group at two days post-treatment, ulvan extract elicited a variety of defense-related biomarkers such as a 43% increase in the activity of reactive oxygen species, 4-fold increase in the activity of catalase, 2-fold increase in the activity of superoxide dismutase and 1.4-fold increase in the activity of chitinase. No increase was observed in phenylalanine ammonia-lyase activity, and the treatment did not affect fruit quality parameters such as the pH levels, sugar levels, and titratable acidity of grapes. These results illustrate the potential of ulvan extract to naturally induce the plant defense response and to reduce postharvest decay.

MicroRNA miR-34a-5p inhibition restrains oxidative stress injury of macrophages by targeting MDM4.

Atherosclerosis is a chronic cardiovascular disease associated with oxidative stress damage, which is caused by excessive oxidation of low-density lipoprotein (ox-LDL). The role of microRNA miR-34a-5p on oxidative stress in ox-LDL-treated macrophages was investigated in this study. Flow cytometry was prepared for assessing THP1-derived macrophage apoptosis. The protein and expression levels of miR-34a-5p and MDM4 were examined by Western blot and RT-qPCR, respectively. We also measured the levels of total cholesterol (TC) and triglyceride to determine the lipid accumulation. Subsequently, the activities of superoxide dismutase, malondialdehyde, and reactive oxygen species revealed the level of oxidative stress injury after miR-34a-5p and MDM4 knockdown. After ox-LDL treatment, cell apoptosis of macrophages increased in a dose-dependent and time-dependent manner. With the increase of ox-LDL treatment and the prolongation of treatment time, the expression level of miR-34a-5p was upregulated. Next, interfering with miR-34a-5p inhibited lipid accumulation and oxidative stress injury in ox-LDL-stimulated macrophages. MDM4 was a target gene of miR-34a-5p and was upregulated in ox-LDL-stimulated macrophages. With the increase of ox-LDL treatment and the prolongation of treatment time, the expression level of MDM4 was downregulated. Importantly, MDM4 knockdown partially counteracted the inhibitory effect of miR-34a-5p on oxidative stress injury. MicroRNA miR-34a-5p knockdown suppressed oxidative stress injury via MDM4 in ox-LDL-treated macrophages.

Role of Reactive Oxygen Species against Pathogens in Relation to Postharvest Disease of Papaya Fruit

Reactive oxygen species (ROS) play an active role in plant defense. Polyphenol oxidase (PPO) and peroxidase (POD) participate in the synthesis of phytoalexins. The comparative activities of ROS, including hydrogen peroxide (H2O2), superoxide anions (O2−), and hydroxyl radicals (·OH), against the fungal pathogen Colletotrichum gloeosporioides from papaya fruit were evaluated. The effects of ROS on PPO and POD activities in papaya fruit inoculated with C. gloeosporioides and the development of natural decay in intact fruit were also investigated. ·OH was the most effective in inhibiting conidial germination and mycelial growth of C. gloeosporioides in vitro. However, 20 or 30 mM H2O2 exhibited the best control of the three ROS treatments at ameliorating the disease symptoms associated with the highest levels of PPO and POD activities in papaya fruit. Furthermore, the activities of PPO and POD negatively correlated with the disease index. Overall, H2O2 treatments can induce the resistance of papaya fruit against C. gloeosporioides owing to the enhanced activities of PPO and POD. Treatment with 20 mM H2O2 also significantly reduced the incidence of decay in intact papaya fruit in semi-commercial experiment, which could make it a potential alternative manner to control postharvest disease in papaya fruit.

Shedding a New Light on Skin Aging, Iron- and Redox-Homeostasis and Emerging Natural Antioxidants.

Reactive oxygen species (ROS) are necessary for normal cell signaling and the antimicrobial defense of the skin. However excess production of ROS can disrupt the cellular redox balance and overwhelm the cellular antioxidant (AO) capacity, leading to oxidative stress. In the skin, oxidative stress plays a key role in driving both extrinsic and intrinsic aging. Sunlight exposure has also been a major contributor to extrinsic photoaging of the skin as its oxidising components disrupt both redox- and iron-homeostasis, promoting oxidative damage to skin cells and tissue constituents. Upon oxidative insults, the interplay between excess accumulation of ROS and redox-active labile iron (LI) and its detrimental consequences to the skin are often overlooked. In this review we have revisited the oxidative mechanisms underlying skin damage and aging by focussing on the concerted action of ROS and redox-active LI in the initiation and progression of intrinsic and extrinsic skin aging processes. Based on these, we propose to redefine the selection criteria for skin antiaging and photoprotective ingredients to include natural antioxidants (AOs) exhibiting robust redox–balancing and/or iron-chelating properties. This would promote the concept of natural-based or bio-inspired bifunctional anti-aging and photoprotective ingredients for skincare and sunscreen formulations with both AO and iron-chelating properties.

Immune-responsive gene 1 protects against liver injury caused by concanavalin A via the activation Nrf2/HO-1 pathway and inhibition of ROS activation pathways

Itaconate is produced by an enzyme encoded by the immune-responsive gene 1 (IRG1) and exerts antibacterial, anti-inflammatory, and antioxidant effects via multiple mechanisms. However, the role of IRG1/itaconate in liver injury caused by Concanavalin A (Con A) is not fully understood. In this study, we explored the therapeutic effect of IRG1/four-octyl itaconate (4-OI), a derivative of itaconate, on liver injury caused by Con A and its possible underlying mechanisms. In vivo experiments, we found that Con A promoted IRG1 expression in the liver tissue. Deletion of IRG1 in mice aggravated Con A-induced liver injury. Compared to wild-type (WT) mice, the inflammatory response, hepatocyte apoptosis, and serum cytokine levels were significantly increased, while the antioxidant capacity was significantly attenuated in IRG1−/− mice. In addition, we found that Con A promoted the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 inflammasome, caspase-1, and gasdermin D activation, and pyroptosis was more obvious in IRG1−/− mice, while 4-OI inhibited pyroptosis. In vivo experiments showed that Con A promoted hepatocyte apoptosis by promoting reactive oxygen species (ROS) expression, and 4-OI reduced ROS-mediate apoptosis in NCTC 1469 cells. In RAW264.7 cells, we demonstrated that 4-OI inhibited the inflammatory response by promoting the nuclear factor erythroid 2 [NF-E2]-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway and inhibiting the nuclear factor-kappa B (NF-κB)/mitogen-activated protein kinases signaling pathway. To further confirm that Nrf2 is the target of itaconate, we pretreated WT mice with ML385, an Nrf2 inhibitor, and found that ML385 could weaken the protection of 4-OI in Con A-induced liver injury mouse model. Furthermore, when we knocked down the Nrf2 gene in NCTC 1469 and RAW264.7 cells, the effect of 4-OI in inhibiting inflammation and apoptosis also decreased. In conclusion, our study shows the importance of IRG1 in inflammation and oxidative stress, and suggests that it plays a vital protective role in Con A-induced liver injury. These findings indicate IRG1/itaconate is a potential therapeutic strategy for immune liver injury, which requires further clinical exploration.

Doxycycline Decreases Atherosclerotic Lesions in the Aorta of ApoE-⁄- and Ovariectomized Mice with Correlation to Reduced MMP-2 Activity.

Atherogenic events promote changes in vessel walls, with alteration of the redox state, and increased activity of matrix metalloproteinases (MMPs). Thus, this study aims to evaluate aortic remodeling, MMP activity, and reactive oxygen species (ROS) levels after treatment with doxycycline in ApoE-⁄- and ovariectomized mice (OVX). Female ApoE-⁄--knockout mice (5 weeks) were submitted to ovariectomy surgery to induce experimental menopause. They then received chow enriched with 1% cholesterol to induce hypercholesterolemia. The animals were divided into two experimental groups: ApoE-⁄-/OVX vehicle and ApoE-⁄-/OVX doxycycline (30 mg/kg) administered by gavage once a day for 28 days (15th to the 18th week of life). Blood samples were collected to measure total cholesterol and fractions. The aorta was used for morphometry and to measure the activity and expression of MMP-2 and ROS levels. The ApoE-⁄-/OVX doxycycline group showed no change in total and fraction cholesterol levels. However, there was a reduction in ROS levels, MMP-2 expression, and activity that correlated with a decrease in atherosclerotic lesions relative to the ApoE-⁄-/OVX vehicle (p > 0.05). Therefore, we conclude that doxycycline in ApoE-⁄-/OVX animals promotes a reduction in atherosclerotic lesions by reducing ROS and MMP-2 activity and expression.

Transcriptional landscapes of de novo root regeneration from detached Arabidopsis leaves revealed by time-lapse and single-cell RNA sequencing analyses

Detached Arabidopsis thaliana leaves can regenerate adventitious roots, providing a platform for studying de novo root regeneration (DNRR). However, the comprehensive transcriptional framework of DNRR remains elusive. Here, we provide a high-resolution landscape of transcriptome reprogramming from wound response to root organogenesis in DNRR and show key factors involved in DNRR. Time-lapse RNA sequencing (RNA-seq) of the entire leaf within 12 h of leaf detachment revealed rapid activation of jasmonate, ethylene, and reactive oxygen species (ROS) pathways in response to wounding. Genetic analyses confirmed that ethylene and ROS may serve as wound signals to promote DNRR. Next, time-lapse RNA-seq within 5 d of leaf detachment revealed the activation of genes involved in organogenesis, wound-induced regeneration, and resource allocation in the wounded region of detached leaves during adventitious rooting. Genetic studies showed that BLADE-ON-PETIOLE1/2, which control aboveground organs, PLETHORA3/5/7, which control root organogenesis, and ETHYLENE RESPONSE FACTOR115, which controls wound-induced regeneration, are involved in DNRR. Furthermore, single-cell RNA-seq data revealed gene expression patterns in the wounded region of detached leaves during adventitious rooting. Overall, our study not only provides transcriptome tools but also reveals key factors involved in DNRR from detached Arabidopsis leaves.

Tumor-Selective Cascade-Amplified Dual-Prodrugs Activation for Synergistic Oxidation-Chemotherapy

Tumor-Selective Cascade-Amplified Dual-Prodrugs Activation for Synergistic Oxidation-Chemotherapy

Effects of IrO2 nanoparticle sizes on Ir/Al2O3 catalysts for the selective catalytic oxidation of ammonia

Gaseous ammonia (NH3), especially that emitted from selective catalytic reduction with NH3 (NH3–SCR) units in the atmosphere is potentially harmful to both human health and the environment. The noble metal catalytic oxidation technology placed behind the SCR unit has been considered to be a promising method for decreasing NH3 slip. In this study, we prepared Ir/Al2O3 catalysts using two different crystal structures of Al2O3 (α–Al2O3 or γ–Al2O3) as supported by an impregnation method and evaluated the performance of the selective catalytic oxidation of NH3 (NH3–SCO). We found that the Ir/γ–Al2O3 catalyst performed better than the Ir/α–Al2O3 catalysts, with 99% of NH3 converted at 260 °C. The X–ray absorption fine structure revealed that the active species on the Ir/Al2O3 catalysts are mainly oxidized IrO2. High–angle annular dark–field images of aberration–corrected scanning transmission electron microscopy revealed that IrO2 species over 1 nm in diameter are beneficial for activity. In situ diffuse reflectance for infrared Fourier transform spectroscopy studies suggested that the differences in NH3–SCO activity were caused by the activity of reactive oxygen species, and the formation of –NH2 may be the decisive step of the NH3 oxidation reaction.