Removal Of Reactive Oxygen Species Research Articles

Modulations of Cardiac Functions and Pathogenesis by Reactive Oxygen Species and Natural Antioxidants

Homeostasis in the level of reactive oxygen species (ROS) in cardiac myocytes plays a critical role in regulating their physiological functions. Disturbance of balance between generation and removal of ROS is a major cause of cardiac myocyte remodeling, dysfunction, and failure. Cardiac myocytes possess several ROS-producing pathways, such as mitochondrial electron transport chain, NADPH oxidases, and nitric oxide synthases, and have endogenous antioxidation mechanisms. Cardiac Ca2+-signaling toolkit proteins, as well as mitochondrial functions, are largely modulated by ROS under physiological and pathological conditions, thereby producing alterations in contraction, membrane conductivity, cell metabolism and cell growth and death. Mechanical stresses under hypertension, post-myocardial infarction, heart failure, and valve diseases are the main causes for stress-induced cardiac remodeling and functional failure, which are associated with ROS-induced pathogenesis. Experimental evidence demonstrates that many cardioprotective natural antioxidants, enriched in foods or herbs, exert beneficial effects on cardiac functions (Ca2+ signal, contractility and rhythm), myocytes remodeling, inflammation and death in pathological hearts. The review may provide knowledge and insight into the modulation of cardiac pathogenesis by ROS and natural antioxidants.

Isoprene: An Antioxidant Itself or a Molecule with Multiple Regulatory Functions in Plants?

Isoprene (C5H8) is a small lipophilic, volatile organic compound (VOC), synthesized in chloroplasts of plants through the photosynthesis-dependent 2-C-methyl-D-erythritol 4-phosphate (MEP) pathway. Isoprene-emitting plants are better protected against thermal and oxidative stresses but only about 20% of the terrestrial plants are able to synthesize isoprene. Many studies have been performed to understand the still elusive isoprene protective mechanism. Isoprene reacts with, and quenches, many harmful reactive oxygen species (ROS) like singlet oxygen (1O2). A role for isoprene as antioxidant, made possible by its reduced state and conjugated double bonds, has been often suggested, and sometimes demonstrated. However, as isoprene is present at very low concentrations compared to other molecules, its antioxidant role is still controversial. Here we review updated evidences on the function(s) of isoprene, and outline contrasting indications on whether isoprene is an antioxidant directly scavenging ROS, or a membrane strengthener, or a modulator of genomic, proteomic and metabolomic profiles (perhaps as a secondary effect of ROS removal) eventually leading to priming of antioxidant plant defenses, or a signal of stress for neighbor plants alike other VOCs, or a hormone-like molecule, controlling the metabolic flux of other hormones made by the MEP pathway, or acting itself as a growth and development hormone.

Chloroplast thylakoid ascorbate peroxidase PtotAPX plays a key role in chloroplast development by decreasing hydrogen peroxide in Populus tomentosa.

Chloroplast development is a complex process that is critical to the growth and development of plants. However, the detailed mechanism of chloroplast development in woody plants remains unclear. In this study, we showed that chloroplasts with elaborate thylakoids could develop from proplastids in the cells of calli derived from leaf tissues of Populus tomentosa upon exposure to light. Chloroplast development was confirmed at the molecular and cellular levels. Transcriptome analysis revealed that genes related to photoreceptors and photosynthesis were significantly up-regulated during chloroplast development in a time-dependent manner. In light-induced chloroplast development, a key process was the removal of hydrogen peroxide, in which thylakoid-localized PtotAPX played a major role; light-induced chloroplast development was enhanced in PtotAPX-overexpressing transgenic P. tomentosa callus with lower levels of hydrogen peroxide, but was suppressed in PtotAPX antisense transgenic callus with higher levels of hydrogen peroxide. Moreover, the suppression of light-induced chloroplast development in PtotAPX antisense transgenic callus was relieved by the exogenous reactive oxygen species scavenging agent N,N'-dimethylthiourea (DMTU). Based on these results, we propose that PtotAPX-mediated removal of reactive oxygen species plays a key role in chloroplast development from proplastids upon exposure to light in P. tomentosa.

Propolis alleviates 4‐aminobiphenyl‐induced oxidative DNA damage by inhibition of CYP2E1 expression in human liver cells

4-Aminobiphenyl (4-ABP) may cause DNA damage in human liver cells (HepG2 and L-02). Propolis exhibits antioxidant properties through reactive oxygen species (ROS) scavenging. We determined the effects of propolis in alleviating 4-ABP -induced DNA damage using the comet assay. Results revealed that propolis could significantly alleviated oxidative damaged DNA by 4-ABP. Furthermore, we proved that inhibition of cytochrome P450 2E1 (CYP2E1) expression by propolis could contribute to the decreased oxidative DNA damage in the treated cells, as the conversion of 4-ABP into its metabolite, N-hydroxy-ABP (HOABP), was blocked; after all, HOABP showed more genotoxic than its parent chemical, 4-ABP. With the homologous recombination assay, propolis failed to induce DNA repair enzymes. Furthermore, the expression of RAD51, Ku70/Ku80, and OGG1 in treated cells were determined with the western blot, revealing that the expression of these protein were unchanged in comparison with those in nontreated cells. However, propolis could protect the treated cells from DNA damage. In conclusion, propolis could antagonize 4-ABP-induced oxidative DNA damage though the removal of ROS and inhibition of CYP2E1 expression in the treated cells.

Grafting Enhances Pepper Water Stress Tolerance by Improving Photosynthesis and Antioxidant Defense Systems.

Currently, limited water supply is a major problem in many parts of the world. Grafting peppers onto adequate rootstocks is a sustainable technique used to cope with water scarcity in plants. For 1 month, this work compared grafted peppers by employing two rootstocks (H92 and H90), with different sensitivities to water stress, and ungrafted plants in biomass, photosynthesis, and antioxidant response terms to identify physiological–antioxidant pathways of water stress tolerance. Water stress significantly stunted growth in all the plant types, although tolerant grafted plants (variety grafted onto H92, Var/H92) had higher leaf area and fresh weight values. Var/H92 showed photosynthesis and stomata conductance maintenance, compared to sensitive grafted plants (Var/H90) and ungrafted plants under water stress, linked with greater instantaneous water use efficiency. The antioxidant system was effective in removing reactive oxygen species (ROS) that could damage photosynthesis; a significant positive and negative linear correlation was observed between the rate of CO2 uptake and ascorbic acid (AsA)/total AsA (AsAt) and proline, respectively. Moreover, in Var/H92 under water stress, both higher proline and ascorbate concentration were observed. Consequently, less membrane lipid peroxidation was quantified in Var/H92.

Oxidative stress induced in rice suspension cells exposed to microcystin-LR at environmentally relevant concentrations.

Microcystins (MCs) are cyclic heptapeptide hepatotoxins that are highly soluble in water and can be transferred to farmland through irrigation with potentially substantial effects on crops, especially rice. In order to investigate the possible negative effects of microcystin-LR (MC-LR) on rice, the oxidative stress induced in rice suspension cells exposed to MC-LR at environmentally relevant concentrations (0.05, 0.5, 5.0, and 50.0 μg·L-1) was investigated. Results showed that the exposure to MC-LR at 0.5-50.0 μg·L-1 resulted in a significant decline in viability of rice suspension cells and an increase in malondialdehyde (MDA) contents. In the 50.0-μg·L-1 MC-LR treatment group, the content of MDA was as much as 5.39 times that of the control group after 6 days of exposure. The excess MDA production indicated that MC-LR exposure has caused lipid peroxidation damage in rice cells, whereas these negative effects could be recovered over time when suspension cells were exposed to low concentration of MC-LR (0.05 μg·L-1). When exposed to MC-LR for 3 days, the O2- content in all treatment groups increased significantly compared with the control group. Additionally, the antioxidant system of rice suspension cells initiated a positive stress response to MC-LR exposure. Indeed, peroxidase (POD) played an active role in the removal of reactive oxygen species (ROS) in rice suspension cells during the early period of exposure, while total superoxide dismutase (T-SOD) was induced after 6 days. Similarly, after 6 days of exposure, the anti-superoxide anion free radical activity (ASAFR), glutathione (GSH), and glutathione-S transferase (GST) in rice suspension cells were higher than that in the control group. These results provided a comprehensive understanding of the exposure time- and dose-dependent oxidative stress induced by the environmentally relevant concentrations of MC-LR in rice suspension cells.

Molecular and Supramolecular Structure of the Mitochondrial Oxidative Phosphorylation System: Implications for Pathology.

Under aerobic conditions, mitochondrial oxidative phosphorylation (OXPHOS) converts the energy released by nutrient oxidation into ATP, the currency of living organisms. The whole biochemical machinery is hosted by the inner mitochondrial membrane (mtIM) where the protonmotive force built by respiratory complexes, dynamically assembled as super-complexes, allows the F1FO-ATP synthase to make ATP from ADP + Pi. Recently mitochondria emerged not only as cell powerhouses, but also as signaling hubs by way of reactive oxygen species (ROS) production. However, when ROS removal systems and/or OXPHOS constituents are defective, the physiological ROS generation can cause ROS imbalance and oxidative stress, which in turn damages cell components. Moreover, the morphology of mitochondria rules cell fate and the formation of the mitochondrial permeability transition pore in the mtIM, which, most likely with the F1FO-ATP synthase contribution, permeabilizes mitochondria and leads to cell death. As the multiple mitochondrial functions are mutually interconnected, changes in protein composition by mutations or in supercomplex assembly and/or in membrane structures often generate a dysfunctional cascade and lead to life-incompatible diseases or severe syndromes. The known structural/functional changes in mitochondrial proteins and structures, which impact mitochondrial bioenergetics because of an impaired or defective energy transduction system, here reviewed, constitute the main biochemical damage in a variety of genetic and age-related diseases.

Oral delivery of antioxidant enzymes for effective treatment of inflammatory disease

Oral administration of protein is very challenging for therapeutic applications due to its instability and easy degradation in the gastrointestinal tract. Herein, we reported an approach to encapsulate native anti-inflammatory proteins in wind chimes like cyclodextrin (WCC) for efficient oral protein delivery. The amphiphilic WCC can self-assemble into nanoparticles in aqueous solution and achieve superior encapsulation of two antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) by simply mixing with protein solution, avoiding any extra cumbersome steps that might inactivate protein. WCC nanovehicles can effectively protect enzyme activity and enhance their intracellular delivery. SOD and CAT co-loaded WCC nanoparticles (SC/WCC) can integrate the synergistic effect of SOD and CAT for enhancing the removal of reactive oxygen species (ROS), effectively inhibit the inflammatory response by reducing the secretion of proinflammatory factors and protect cells from ROS-induced oxidative damage. In the mouse colitis model, SC/WCC administered orally was able to efficiently accumulate in the inflamed colon, significantly inhibited the expression of proinflammatory mediators and notably alleviated the symptoms related to colitis. Therefore, we believe that the strategies we described here may provide a convenient and powerful platform for the treatment of other inflammatory diseases.

Combined Transcriptomic and Metabolomic Analysis Reveals the Role of Phenylpropanoid Biosynthesis Pathway in the Salt Tolerance Process of Sophora alopecuroides.

Salt stress is the main abiotic stress that limits crop yield and agricultural development. Therefore, it is imperative to study the effects of salt stress on plants and the mechanisms through which plants respond to salt stress. In this study, we used transcriptomics and metabolomics to explore the effects of salt stress on Sophora alopecuroides. We found that salt stress incurred significant gene expression and metabolite changes at 0, 4, 24, 48, and 72 h. The integrated transcriptomic and metabolomic analysis revealed that the differentially expressed genes (DEGs) and differential metabolites (DMs) obtained in the phenylpropanoid biosynthesis pathway were significantly correlated under salt stress. Of these, 28 DEGs and seven DMs were involved in lignin synthesis and 23 DEGs and seven DMs were involved in flavonoid synthesis. Under salt stress, the expression of genes and metabolites related to lignin and flavonoid synthesis changed significantly. Lignin and flavonoids may participate in the removal of reactive oxygen species (ROS) in the root tissue of S. alopecuroides and reduced the damage caused under salt stress. Our research provides new ideas and genetic resources to study the mechanism of plant responses to salt stress and further improve the salt tolerance of plants.

Long-term exposure to a hypomagnetic field attenuates adult hippocampal neurogenesis and cognition

Adult hippocampal neurogenesis contributes to learning and memory, and is sensitive to a variety of environmental stimuli. Exposure to a hypomagnetic field (HMF) influences the cognitive processes of various animals, from insects to human beings. However, whether HMF exposure affect adult hippocampal neurogenesis and hippocampus-dependent cognitions is still an enigma. Here, we showed that male C57BL/6 J mice exposed to HMF by means of near elimination of the geomagnetic field (GMF) exhibit significant impairments of adult hippocampal neurogenesis and hippocampus-dependent learning, which is strongly correlated with a reduction in the content of reactive oxygen species (ROS). However, these deficits seen in HMF-exposed mice could be rescued either by elevating ROS levels through pharmacological inhibition of ROS removal or by returning them back to GMF. Therefore, our results suggest that GMF plays an important role in adult hippocampal neurogenesis through maintaining appropriate endogenous ROS levels.

Temperature rise and copper exposure reduce heart mitochondrial reactive oxygen species scavenging capacity

Mitochondria produce and scavenge reactive oxygen species (ROS); however, whether oxidative distress due to exogenous stress arises from excessive production or impaired scavenging remains unclear. We assessed the effect of copper (Cu) and thermal stress on kinetics of ROS (H2O2) consumption in mitochondria isolated from fish heart. Mitochondria were energized with succinate, glutamate-malate or palmitoylcarnitine (PC) and incubated with 1–25 μM Cu at 11 (control) and 23 °C. We found that H2O2 consumption capacity of heart mitochondria varies with substrate and is additively reduced by temperature rise and Cu. While Cu is a potent inhibitor of H2O2 consumption in mitochondria oxidizing glutamate-malate and succinate, mitochondria oxidizing PC are resistant to the inhibitory effect of the metal. Moreover, the sensitivity of H2O2 consumption pathways to Cu depend on the substrate and are greatly impaired during oxidation of glutamate-malate. Pharmacological manipulation of mitochondrial antioxidant systems revealed that NADPH-dependent peroxidase systems are the centerpieces of ROS scavenging in heart mitochondria, with the glutathione-dependent pathway being the most prominent while catalase played a minimal role. Surprisingly, Cu is as efficacious in inhibiting thioredoxin-dependent peroxidase pathway as auranofin, a selective inhibitor of thioredoxin reductase. Taken together, our study uncovered unique mechanisms by which Cu alters mitochondrial H2O2 homeostasis including its ability to inhibit specific mitochondrial ROS scavenging pathways on a par with conventional inhibitors. Importantly, because of additive inhibitory effect on mitochondrial ROS removal mechanisms, hearts of organisms jointly exposed to Cu and thermal stress are likely at increased risk of oxidative distress.

Propolis from the Monte Region in Argentina: A Potential Phytotherapic and Food Functional Ingredient.

The aim of this review is to provide overall information on Argentine propolis and to shed light on its potential, especially the one from the Monte region so as to support future research in the field. Around 1999, the Argentine propolis began to be chemically and functionally characterized to give it greater added value. Because Argentina has a wide plant biodiversity, it is expected that its propolis will have various botanical origins, and consequently, a different chemical composition. To date, five types have been defined. Based on their functionality, several products have been developed for use in human and veterinary medicine and in animal and human food. Because the Argentine propolis with the greatest potential is that of the Monte eco-region, this review will describe the findings of the last 20 years on this propolis, its botanical source (Zuccagnia punctata Cav.), its chemical composition, and a description of markers of chemical quality (chalcones) and functionality. Propolis can regulate the activity of various pro-inflammatory enzymes and carbohydrate and lipid metabolism enzymes, as well as remove reactive oxygen and nitrogen species. Consequently, it can modulate metabolic syndrome and could be used as a functional ingredient in food. Furthermore, hydroalcoholic extracts can act against human and animal pathogenic bacteria and human yeast, and mycelial pathogenic fungi. The ability to stop the growth of post-harvest pathogenic bacteria and fungi was also demonstrated. For this reason, Argentine propolis are natural products capable of protecting crops and increasing the lifespan of harvested fruit and vegetables. Several reports indicate the potential of Argentine propolis to be used in innovative products to improve health, food preservation, and packaging. However, there is still much to learn about these natural products to make a wholesome use of them.

Quantitative proteomic analysis of Xanthoceras sorbifolium Bunge seedlings in response to drought and heat stress

Yellowhorn (Xanthoceras sorbifolium Bunge) is a woody oil species that is widely distributed in northwestern China. To investigate the molecular mechanisms underlying the drought and heat tolerance response of yellowhorn seedlings, changes in protein abundance were analyzed via comparative proteomics. Drought and heat treatment of seedlings was applied in growth chamber, and the leaves were harvested after 7 days of treatment. The total protein was extracted, and comparative proteomic analysis was performed via isobaric tag for relative and absolute quantitation (iTRAQ). The abundance of most of the proteins associated with oxidative phosphorylation, NADH dehydrogenase and superoxide dismutase (SOD) was reduced. The differential proteins associated with photosynthesis enzymes indicated that stress had different effects on photosystem I (PSI) and photosystem II (PSII). After comprehensively analyzing the results, we speculated that drought and heat stress could hinder the synthesis of riboflavin, reducing NADH dehydrogenase content, which might further have an impact on energy utilization. Yellowhorn seedlings relied on Fe–Mn SOD enzymes rather than Cu/Zn SOD enzymes to remove reactive oxygen species (ROS). In addition, heat-shock proteins (HSPs) had significant increase and played a key role in stress response, which could be divided into two categories according to their transcription and translation efficiency. Over all, the results can provide a basis for understanding the molecular mechanism underlying resistance to drought and heat stress in yellowhorn and for subsequent research of posttranslational modification-related omics of key proteins.

Phenotype, Physiology, and Gene Expression of Barley Seedlings in Response to Nano Zinc Oxide Stress

In recent years, zinc oxide nanoparticles (ZnO NPs) have been widely used as zinc fertilizers and pesticides. The use of ZnO NPs in this way can provide benefits to humans, but also has potential risks. ZnO NPs inevitably enter the environment during their production and use, which affects the ecological environment and crop growth. In order to investigate the phenotype, physiology, and gene expression of barley (Hordeum vulgare L.) seedlings under ZnO NPs stress, the barely cultivars ZJU3 (P21), Golden Promise (GP) and L23 were chosen for study. Different ZnO NPs concentrations were applied to compare the physiological and biochemical indexes of the barley seedlings and the responses of six stress-related genes, when seedlings were cultured to the two-leaf stage through hydroponics. The results showed that the density of brown spots on the leaf surface increased with increasing ZnO NPs concentration. ZnO NPs stress inhibited the root growth of barley seedlings, and P21 was the most sensitive. Furthermore, ZnO NPs stress could stimulate plants to produce a large number of reactive oxygen species (ROS), resulting in an imbalance between the production and removal of ROS and membrane lipid peroxidation in plants. This imbalance inhibited the growth and development of the barley seedlings. With increasing ZnO NPs concentration, the activity of superoxide dismutase was gradually increased, the activity of catalase was progressively decreased, and the contents of malondialdehyde and proline were increased. Compared with the control, among six stress-related genes, the expression levels of five genes were downregulated and one gene was upregulated in the experimental group. This study preliminarily revealed the toxic effect of ZnO NPs on seedlings and the effect on the expression of stress-related resistance genes in different barley varieties.

122 Colour-Doppler ultrasonography as a tool for oocyte donor selection

Colour-Doppler ultrasonography (CDU) has been applied for a more detailed examination of the ovary and uterus, mainly local blood flow in ovarian follicles and the corpus luteum (CL). The main use of CDU is for the diagnosis of early pregnancy or the selection of recipients for embryo transfer in cattle; however, this tool can also be used to select oocyte donors according to blood flow to the ovary. The concept is that more blood flow in the ovary is conducive to a healthier intraovarian environment (e.g. higher progesterone levels and removal of reactive oxygen species), yielding higher quality oocytes. The objective of this research was to evaluate invitro embryo production (IVP) after selection of oocyte donors, considering ovary irrigation before ovum pickup (OPU). The research was carried out in the reproduction laboratory at the Palominos Ranch (Jalisco, México). The oocyte donors (n=15) were synchronized before each round of OPU using an intravaginal device (1.9g of progesterone) with oestradiol benzoate (2mg) and cloprostenol sodium (500µg) on Day 0, to avoid the presence of a corpus luteum and to synchronize the follicular wave. On Day 6, the intravaginal device was removed and OPU was performed. All Angus breed donors between 3 and 5 years old with a body condition score between 5–6 (scale 1–9, where 1 is extremely thin and 9 is very obese) and were evaluated with transrectal CDU (Sonoscape S2™) with a linear-array probe (7.5MHz) before the first OPU session only. The oocyte donors were classified subjectively into three categories: low blood flow (LBF, ∼30% ovarian area), median blood flow (MBF, ∼50% ovarian area), and high blood flow (HBF, ∼70% ovarian area) and were submitted to 3 cycles of IVP each (45 total cycles). Semen from a proven bull for IVF was used during all IVP cycles. All oocytes collected from each donor were used in IVF with the same semen in all IVP cycles. The total oocytes collected, and percentages of viable oocytes, cleavage, and blastocysts on Day 7 of culture were evaluated. Statistical analysis was carried out using the GLM procedure of SAS software (version 9.3; SAS Institute Inc.) to evaluate the results of LBF, MBF, and HBF (P-value=0.05). Total oocyte recovery was 11.28±1.92, 10.06±1.31, and 15.52±1.05 for HBF, MBF, and LBF, respectively, being significantly higher for LBF (P<0.05). There were no differences in viable oocytes among groups. Cleavage rates were 53.04%±3.43 for HBF, 43.18%±2.34 for MBF, and 43.69%±1.89 for LBF, being significantly higher for HBF (P<0.05). Percentage of blastocysts on Day 7 was 38.16%±3.80 for HBF, 30.11%±2.60 for MBF, and 17.78%±2.10 for LBF. This value tended to be significantly higher for HBF than MBF, and both were significantly superior to LBF (P<0.05). In conclusion, under the conditions of this research, although LBF donors had more total recovered oocytes, blastocyst rates were increased in HBF and MBF donors. Therefore, based on the results of the present study, CDU can be a useful tool for the selection of oocyte donors.

IRGM/Irgm1 facilitates macrophage apoptosis through ROS generation and MAPK signal transduction: Irgm1+/- mice display increases atherosclerotic plaque stability.

Rationale: Atherosclerosis plaque rupture (PR) is the pathological basis and chief culprit of most acute cardiovascular events and death. Given the complex and important role of macrophage apoptosis and autophagy in affecting plaque stability, an important unanswered question include is whether, and how, immunity-related GTPase family M protein (IRGM) and its mouse orthologue IRGM1 affect macrophage survival and atherosclerotic plaque stability.Methods: To investigate whether serum IRGM of ST-segment elevation myocardial infarction (STEMI) patients is related to plaque morphology, we divided 85 STEMI patients into those with and without plaque rupture (PR and non-PR, respectively) based on OCT image analysis, and quantified the patients' serum IRGM levels. Next, we engineered Irgm1 deficient mice (Irgm1+/-) and chimera mice with Irgm1 deficiency in the bone marrow on an ApoE-/- background, which were then fed a high-fat diet for 16 weeks. Pathological staining was used to detect necrotic plaque cores, ratios of neutral lipids and cholesterol crystal, as well as collagen fiber contents in these mice to characterize plaque stability. In addition, immunofluorescence, immunohistochemical staining and western blot were used to detect the apoptosis of macrophages in the plaques. In vitro, THP-1 and RAW264.7 cells were stimulated with ox-LDL to mimic the in vivo environment, and IRGM/IRGM1 expression were modified by specific siRNA (knockdown) or IRGM plasmid (knocked-in). The effect of IRGM/Irgm1 on autophagy and apoptosis of macrophages induced by ox-LDL was then evaluated. In addition, we introduced inhibitors of the JNK/p38/ERK signaling pathway to verify the specific mechanism by which Irgm1 regulates RAW264.7 cell apoptosis.Results: The serum IRGM levels of PR patients is significantly higher than that of non-PR patients and healthy volunteers, which may be an effective predictor of PR. On a high-fat diet, Irgm1-deficient mice exhibit reduced necrotic plaque cores, as well as neutral lipid and cholesterol crystal ratios, with increased collagen fiber content. Additionally, macrophage apoptosis is inhibited in the plaques of Irgm1-deficient mice. In vitro, IRGM/Irgm1 deficiency rapidly inhibits ox-LDL-induced macrophage autophagy while inhibiting ox-LDL-induced macrophage apoptosis in late stages. Additionally, IRGM/Irgm1 deficiency suppresses reactive oxygen species (ROS) production in macrophages, while removal of ROS effectively inhibits macrophage apoptosis induced by IRGM overexpression. We further show that Irgm1 can affect macrophage apoptosis by regulating JNK/p38/ERK phosphorylation in the MAPK signaling pathway.Conclusions: Serum IRGM may be related to the process of PR in STEMI patients, and IRGM/Irgm1 deficiency increases plaque stability. In addition, IRGM/Irgm1 deficiency suppresses macrophage apoptosis by inhibiting ROS generation and MAPK signaling transduction. Cumulatively, these results suggest that targeting IRGM may represent a new treatment strategy for the prevention and treatment of acute cardiovascular deaths caused by PR.

A Marine Terpenoid, Heteronemin, Induces Both the Apoptosis and Ferroptosis of Hepatocellular Carcinoma Cells and Involves the ROS and MAPK Pathways.

Hepatocellular carcinoma (HCC) is a leading cause of death, resulting in over 700 thousand deaths annually worldwide. Chemotherapy is the primary therapeutic strategy for patients with late-stage HCC. Heteronemin is a marine natural product isolated from Hippospongia sp. that has been found to protect against carcinogenesis in cholangiocarcinoma, prostate cancer, and acute myeloid leukemia. In this study, heteronemin was found to inhibit the proliferation of the HCC cell lines HA22T and HA59T and induce apoptosis via the caspase pathway. Heteronemin treatment also induced the formation of reactive oxygen species (ROS), which are associated with heteronemin-induced cell death, and to trigger ROS removal by mitochondrial SOD2 rather than cytosolic SOD1. The mitogen-activated protein kinase (MAPK) signaling pathway was associated with ROS-induced cell death, and heteronemin downregulated the expression of ERK, a MAPK that is associated with cell proliferation. Inhibitors of JNK and p38, which are MAPKs associated with apoptosis, restored heteronemin-induced cell death. In addition, heteronemin treatment reduced the expression of GPX4, a protein that inhibits ferroptosis, which is a novel form of nonapoptotic programmed cell death. Ferroptosis inhibitor treatment also restored heteronemin-induced cell death. Thus, with appropriate structural modification, heteronemin can act as a potent therapeutic against HCC.

Physiological Mechanisms of Improved Smut Resistance in Sugarcane Through Application of Silicon.

Sugarcane smut caused by Sporisorium scitamineum is a severe, global sugarcane disease with severe economic losses and is difficult to prevent. To explore more effective control techniques for smut, the effects and physiological mechanism of silicon (Si) on smut resistance in two smut-susceptible cultivars, ROC22 and Badila, were investigated. The results show that Si application significantly enhances smut resistance in ROC22 and Badila, and the incidence of sugarcane smut decreased by 11.57–22.58% (ROC22) and 27.75–46.67% (Badila). The incidence of smut is negatively correlated with the amount of Si applied and the Si content in sugarcane leaves, stems, and roots (highly significantly negatively correlated with stem Si content). Under S. scitamineum stress, the activities of pathogenesis-related enzymes, chitinase and β-1,3-glucanase, secondary metabolism-related enzymes such as polyphenoloxidase (PPO) and phenylalanine-ammonia-lyase (PAL), and the contents of secondary metabolites, total soluble phenol, and lignin in sugarcane leaves treated with Si were significantly higher than those without Si (CK). The results also demonstrated that the content of malondialdehyde (MDA) and hydrogen peroxide (H2O2), the superoxide dismutase (SOD) activity of sugarcane leaves treated with Si increased in the seedling and tillering stages, and the peroxidase (POD) activity decreased in the seedling stage, which caused the accumulation of reactive oxygen species (ROS) that in turn triggered defense responses. Moreover, MDA and H2O2 levels decreased, and the activities of SOD and POD increased at the jointing stage, which was beneficial to the removal of excessive ROS. Collectively, these results suggest that Si modulates pathogenesis-related protein activity, secondary metabolism, and active oxygen metabolism of sugarcane that positively regulate resistance to smut. This study is the first to reveal the physiological mechanism of Si in improving smut resistance in sugarcane, and the results provide a theoretical basis for the development of Si fertilizers to control sugarcane smut.

The effect of selenium and vitamin E supplementation on anti-Mullerian hormone and antral follicle count in infertile women with occult premature ovarian insufficiency: A randomized controlled clinical trial

ObjectiveIncreased accumulation of reactive oxygen species (ROS) in the process of oogenesis is one of the most well known causes of ovarian insufficiency and decreased ovarian reserve. Selenium and vitamin E as cofactors of glutathione peroxidase plays an important role in the removal of ROS in the ovary. We evaluated the effects of selenium and vitamin E supplementation on anti-Mullerian hormone (AMH) index and antral follicle count (AFC) (primary outcomes) and mean ovarian volume (MOV) and side effects of these supplements (secondary outcome) in infertile women with occult premature ovarian insufficiency (OPOI). Methods70 patients were allocated into the control and treatment groups through block randomization method. 35 women in the treatment group received 200 ng selenium and 400IU vitamin E and 35 women in the control group received placebo for a total of 90 days. AMH index, AFC and mean ovarian volume (MOV) were investigated in both groups after 12 months of study. ResultThere was no significant difference between groups before intervention in AMH (Mean difference: −0.08; 95% CI: −0.20 to.08; p=0.33), AFC (−0.71; 95%CI: −1.44 to −0.01; p=0.05) and MOV (−0.55; 95% CI: −0.85 to −0.24; p=0.001). There was a significant increase in AMH (mean difference: 0.59; 95% CI: 0.48 to 0.71; p<0.001), AFC (5.08; 95% CI: 4.36 to 5.08; p<0.001) and MOV (2.17; 95% CI: 1.87 to 2.47; p<0.001) in selenium + vitamin E group compared to placebo group 12 months after intervention. These supplements had no side effects. ConclusionSupplementation with selenium and vitamin E can increase AMH, AFC and MOV in women with OPOI.

Mitochondrial TXN2 attenuates amyloidogenesis via selective inhibition of BACE1 expression.

Thioredoxin-2 (TXN2) is a mitochondrial protein and represents one of the intrinsic antioxidant enzymes. It has long been recognized that mitochondrial dysfunction and oxidative stress contribute to the pathogenesis of Alzheimer's disease (AD). We hypothesized that mitochondrial TXN2 might play a role in AD-like pathology. In this study, we found that in SH-SY5Y and HEK cells stably express full-length human amyloid-β precursor protein (HEK-APP), TXN2 silencing or over-expression selectively increased or decreased the transcription of beta-site amyloid precursor protein cleaving enzyme 1 (BACE1), respectively, without altering the protein levels of others enzymes involved in the catalytic processing of APP. As a result, β-amyloid protein (Aβ) levels were significantly decreased by TXN2. In addition, in cells treated with 3-nitropropionic acid (3-NP) that is known to increase reactive oxygen species (ROS) and promote mitochondrial dysfunction, TXN2 silencing resulted in further enhancement of BACE1 protein levels, suggesting a role of TXN2 in ROS removal. The downstream signaling might involve NFκB, as TXN2 reduced the phosphorylation of p65 and IκBα; and p65 knockdown significantly attenuated TXN2-mediated regulation of BACE1. Concomitantly, the levels of cellular ROS, apoptosis-related proteins and cell viability were altered by TXN2 silencing or over-expression. In APPswe/PS1E9 mice, an animal model of AD, the cortical and hippocampal TXN2 protein levels were decreased at 12months but not at 6months, suggesting an age-dependent decline. Collectively, TXN2 regulated BACE1 expression and amyloidogenesis via cellular ROS and NFκB signaling. TXN2 might serve as a potential target especially for early intervention of AD.