Cell Membrane Lipid Peroxidation Research Articles

Recent Advances in the Inhibition of Membrane Lipid Peroxidation by Food-Borne Plant Polyphenols via the Nrf2/GPx4 Pathway.

Lipid peroxidation (LP) leads to changes in the fluidity and permeability of cell membranes, affecting normal cellular function and potentially triggering apoptosis or necrosis. This process is closely correlated with the onset of many diseases. Evidence suggests that the phenolic hydroxyl groups in food-borne plant polyphenols (FPPs) make them effective antioxidants capable of preventing diseases triggered by cell membrane LP. Proper dietary intake of FPPs can attenuate cellular oxidative stress, especially damage to cell membrane phospholipids, by activating the Nrf2/GPx4 pathway. Nuclear factor E2-related factor 2 (Nrf2) is an oxidative stress antagonist. The signaling pathway regulated by Nrf2 is a defense transduction pathway of the organism against external stimuli such as reactive oxygen species and exogenous chemicals. Glutathione peroxidase 4 (GPx4), under the regulation of Nrf2, is the only enzyme that reduces cell membrane lipid peroxides with specificity, thus playing a pivotal role in regulating cellular ferroptosis and counteracting oxidative stress. This study explored the Nrf2/GPx4 pathway mechanism, antioxidant activity of FPPs, and mechanism of LP. It also highlighted the bioprotective properties of FPPs against LP and its associated mechanisms, including (i) activation of the Nrf2/GPx4 pathway, with GPx4 potentially serving as a central target protein, (ii) regulation of antioxidant enzyme activities, leading to a reduction in the production of ROS and other peroxides, and (iii) antioxidant effects on LP and downstream phospholipid structure. In conclusion, FPPs play a crucial role as natural antioxidants in preventing LP. However, further in-depth analysis of FPPs coregulation of multiple signaling pathways is required, and the combined effects of these mechanisms need further evaluation in experimental models. Human trials could provide valuable insights into new directions for research and application.

Copper Poisoning with Emphasis on Its Clinical Manifestations and Treatment of Intoxication

Background. Copper is an essential trace element found in the human body in an oxidized (Cu II) and reduced (Cu I) form. It plays a crucial role in the integrity and function of proteins and enzymes. Short-term and long-term exposure to copper can result in harmful effects and lead to clinical manifestations in multiple bodily systems, including the gastrointestinal tract, liver, kidneys, eyes, respiratory, cardiovascular, central nervous, endocrine, and hematopoietic systems. Objective. The purpose of this study is the importance of early recognition and diagnosis of copper poisoning immediate and necessary measures and the use of chelators. Materials and Methods. In this review article, authors from Pub Med, Scopus, and a toxicologic emergencies reference book from 1996 to 2024 are used. Result. An excessive increase in copper level produces reactive oxygen species that can cause lipid peroxidation in cell membranes, direct oxidation of proteins, and the breakdown of DNA and RNA molecules. All of these can generally be reasons for cell death. Conclusion. Assessing levels of copper in whole blood, free serum copper, 24-hr urine copper, liver biopsy for copper concentration, and ceruloplasmin play a crucial role in the diagnosis. The blood copper concentration is directly related to the severity of poisoning. Treatment for copper poisoning typically involves removing the source of exposure and administering medications to help remove the excess copper from the body. Supportive care for copper intoxication usually includes managing vomiting, correcting fluids and electrolytes, and stabilizing vital signs. Chelators like D-penicillamine, succimer, trientine, tetrathiomolybdate, and PBT-2 have been utilized in treatment.

Epigenetic modifications in the ferroptosis pathway in cord blood cells from newborns of smoking mothers and their influence on fetal growth

Maternal smoking during pregnancy increases oxidative stress and decreases antioxidant capacity in newborns. Uncontrolled oxidative stress plays a role in fetal development disorders and in adverse perinatal outcomes. In order to identify molecular pathways involved in low fetal growth, epigenetic modifications in newborns of smoking and non-smoking mothers were examined. Low birth weight newborns of mothers who smoked more than 10 cigarettes per day during the first trimester of pregnancy and normal birth weight newborns of mothers who did not smoke during pregnancy were included in the study. DNA was extracted from umbilical cord blood of term newborns. 125 differentially methylated regions were identified by MeDIP-Seq. Functional analysis revealed several pathways, such as ferroptosis, that were enriched in differentially methylated genes after prenatal smoke exposure. GPX4 and PCBP1 were found to be hypermethylated and associated with low fetal growth. These epigenetic modifications in ferroptosis pathway genes in newborns of smoking mothers can potentially contribute to intrauterine growth restriction through the induction of cell death via lipid peroxidation of cell membranes. The identification of epigenetic modifications in the ferroptosis pathway sheds light on the potential mechanisms underlying the pathophysiology of low birth weight in infants born to smoking mothers.

Antifungal Activities of L-Methionine and L-Arginine Treatment In Vitro and In Vivo against Botrytis cinerea.

Gray mold caused by Botrytis cinerea is a common postharvest fungal disease in fruit and vegetables. The prevention and treatment of postharvest gray mold has been one of the hot research issues addressed by researchers. This study aimed to investigate the effect of L-methionine and L-arginine on Botrytis cinerea in vitro and on cherry tomato fruit. The results of the in vitro experiment showed that L-methionine and L-arginine had significant inhibitory effects on the mycelial growth and spore germination of Botrytis cinerea, and the inhibitory effects were enhanced with increasing L-methionine or L-arginine concentration. In addition, L-methionine and L-arginine treatment increased the leakage of Botrytis cinerea electrolytes, proteins and nucleic acids. The experiment involving propidium iodide staining and malondialdehyde content assay also confirmed that L-methionine and L-arginine treatment could lead to cell membrane rupture and lipid peroxidation. The results of scanning electron microscopy further verified that the morphology of hyphae was damaged, deformed, dented and wrinkled after treatment with L-methionine or L-arginine. Fruit inoculation experiments displayed that L-methionine and L-arginine treatments significantly inhibited the occurrence and development of gray mold in postharvest cherry tomato. Therefore, treatment with L-methionine or L-arginine might be an effective means to control postharvest gray mold in fruit and vegetables.

Mitigative Effect of Rare Earth Element Cerium on the Growth of Zinc-stressed Wheat （Triticum aestivum L.）Seedlings

This research aimed to clarify the mitigative effect of exogenously applied rare earth element cerium （Ce） on the growth， zinc （Zn） accumulation， and physiological characteristics of wheat （Triticum aestivum L.） seedlings under Zn stress. The wheat variety studied was Bainong307 （BN307）， and Zn stress was achieved by growing seedlings in a hydroponic culture experiment with 500 μmol·L-1 Zn2 + added to the culture solution. It was found that Zn stress at 500 μmol·L-1 significantly inhibited the chlorophyll content， photosynthesis， and biomass accumulation of wheat seedlings. Seedling roots became shorter and thicker， and the lateral roots decreased under Zn stress. The Zn stress also increased MDA accumulation and the degree of cell membrane lipid peroxidation and reduced soluble protein contents and the activities of antioxidant enzymes such as superoxide dismutase （SOD）， catalase （CAT）， and ascorbate peroxidase （APX）. On the contrary， exogenous Ce decreased the adsorption and transport of Zn by the root system and alleviated the damage of Zn stress to wheat seedlings. Specifically， the increase in chlorophyll content （chlorophyll a， chlorophyll b， and total chlorophyll） and photosynthetic parameters， the enhancement of antioxidant enzymes activities and soluble protein levels， and the reduction in MDA content and the damage of lipid peroxidation to the cell membrane were all driven by exogenous Ce， which ultimately led to the increase in dry matter biomass of the root system and shoot. In summary， these results provide basic data for the application of exogenous Ce to alleviate Zn toxicity to plants.

Research on the antibacterial mechanism of medical nanosilver latex composite materials

Objective: This study investigates the antibacterial mechanisms of medical nanosilver latex materials by conducting antibacterial experiments on nanosilver latex, observing the morphological changes in Escherichia coli after co-cultivation with nanosilver, and detecting variations in nitric oxide, malondialdehyde, protein, and DNA fragment content. The aim is to provide a theoretical foundation for the application of antibacterial materials in medical settings.Methods: To prepare the composite latex film, nanosilver was combined with natural latex. The antibacterial efficacy of nanosilver latex were assessed using co-cultivation and colony counting methods. Electron microscopy facilitated the observation of Escherichia coli post co-cultivation with nanosilver, and subsequent changes in nitric oxide, malondialdehyde, protein, and DNA fragment content were measured.Results: The composite film of nanosilver latex demonstrated antibacterial properties, which were proportional to its concentration and inversely proportional to the particle size. Exposure to nanosilver resulted in bacterial cell membranes, leading to increased levels of nitric oxide, malondialdehyde, protein, and DNA content within bacteria.Conclusion: Nanosilver particles, especially those of 10 nm, were found to be most effective in antibacterial activity. The antibacterial effects were primarily due to the disruption of bacterial cell membranes and walls, altering intra and extracellular osmotic pressure, inducing lipid peroxidation of bacterial cell membranes, triggering of oxidative stress, and damage to DNA.

Lipid Peroxidation Drives Liquid-Liquid Phase Separation and Disrupts Raft Protein Partitioning in Biological Membranes.

The peroxidation of membrane lipids by free radicals contributes to aging, numerous diseases, and ferroptosis, an iron-dependent form of cell death. Peroxidation changes the structure and physicochemical properties of lipids, leading to bilayer thinning, altered fluidity, and increased permeability of membranes in model systems. Whether and how lipid peroxidation impacts the lateral organization of proteins and lipids in biological membranes, however, remains poorly understood. Here, we employ cell-derived giant plasma membrane vesicles (GPMVs) as a model to investigate the impact of lipid peroxidation on ordered membrane domains, often termed membrane rafts. We show that lipid peroxidation induced by the Fenton reaction dramatically enhances the phase separation propensity of GPMVs into coexisting liquid-ordered (Lo) and liquid-disordered (Ld) domains and increases the relative abundance of the disordered phase. Peroxidation also leads to preferential accumulation of peroxidized lipids and 4-hydroxynonenal (4-HNE) adducts in the disordered phase, decreased lipid packing in both Lo and Ld domains, and translocation of multiple classes of raft proteins out of ordered domains. These findings indicate that the peroxidation of plasma membrane lipids disturbs many aspects of membrane rafts, including their stability, abundance, packing, and protein and lipid composition. We propose that these disruptions contribute to the pathological consequences of lipid peroxidation during aging and disease and thus serve as potential targets for therapeutic intervention.

Comprehensive biochemical approach forunderstanding the interaction between host "common bean" and pathogen "Colletotrichum lindemuthianum" causing bean anthracnose.

Anthracnose (ANT) caused by Colletotrichum lindemuthianum is the most devastating seed-borne fungal disease of common bean. In response to fungal infections, it is hypothesized that pathogen-plant interactions typically cause hypersensitive reactions by producing reactive oxygen species, hydrogen peroxide and lipid peroxidation of cell membranes. esent study was conducted by inoculating susceptible bean genotype "SB174" and resistant bean genotype "E10" with pathogen "C. lindemuthianum". Defense-related enzymes (ascorbate peroxidase, peroxidase, lipid peroxidase, and catalase) and C-based compounds (total phenols and flavonoids) were studied using the detached bean leaf method. Comparative defense response was studied in different plant tissues (pod, stem, and seed) in susceptible and resistant bean genotypes under uninoculated and pathogen-inoculated conditions. The host‒pathogen interaction was studied at mock inoculation, 2, 4 and 6 days after inoculation (dai). Comparing the pathogen-inoculated bean leaves to water-treated bean leaves, defense enzymes as well as total phenols and flavonoids exhibited differential expression. In a comparative study, the enzyme activity also displayed differential biochemical responses in pods, stems and seeds in both contrasting genotypes. For example, 5.1-fold (pod), 1.5-fold (stem) and 1.06-fold (seed) increases in ascorbate peroxidase activity were observed in the susceptible genotype at 6 dai compared to mock inoculation. Similarly, catalase activity in pods was upregulated (1.47-fold) in the resistant genotype and downregulated (1.30-fold) in the susceptible genotype at 6 dai. The study revealed that defense-related antioxidative enzymes, phenols and flavonoids are fine-tuned to detoxify important reactive oxygen species (ROS) molecules, induce systemic resistance and are successfully controlled in common bean plants against pathogen invasion.

Physiological responses and algae inhibition of Pontederiacordata to simulated eutrophication and acid rain co-pollution

BackgroundEutrophication and acid rain are two threats that many water bodies must contend with. Eutrophication and climate change have accelerated widespread outbreaks of cyanobacterial blooms as both have become more severe. Pontederiacordata, a garden ornamental plant, can inhibit some algae growth and remove total nitrogen (TN) and total phosphorus (TP) from the water. In this study, we investigated how simulated acid rain and eutrophication co-pollution affected P.cordata's growth physiology and ability to inhibit algae growth.ResultsUnder mild eutrophication (2 mg·L−1 TN, 0.4 mg·L−1 TP, and 15 mg·L−1 CODMn) or weak acid rain (pH = 5.0), P.cordata alleviated the degree of cell membrane lipid peroxidation by stabilizing superoxide dismutase (SOD) and catalase (CAT) activities in the leaves, allowing for normal plant growth. Under mild eutrophication and acid rain conditions, cultured P.cordata water samples maintained strong algae inhibition by reducing the Chl a content and SOD activity of Microcystisaeruginosa cells. Compound stress where acid rain was the primary inhibitory factor along with moderate or severe eutrophication inhibited P.cordata growth, which probably reduced the input of algae-inhibiting allelochemicals, thus reducing its ability to inhibit algae.ConclusionsIn summary, P. cordata has application potential in mild eutrophic water and acid rain (pH ≥ 4). These findings provide guidance for further research on phytoremediation and algae control in scenarios of compound pollution.

Silicon alleviates autotoxicity by regulating membrane lipid peroxidation and improving photosynthetic efficiency in cucumber seedlings (Cucumis sativus L.)

Autotoxicity is one of the main causes of cucumber continuous cropping obstacles. Cinnamic acid (CA), a phenolic acid derivative, acts as an autotoxin found in cucumber root exudates. The autotoxicity mimicked by CA significantly increases membrane lipid peroxidation in root and leaf cells, resulting in damage to the structure and function of root tip cells and leaf cells. It also injures the activity of photosystem PSII, reducing the photosynthetic rate and inhibiting the growth of cucumber plants. Supplementing Si alleviates CA-mimicked autotoxicity by increasing the thickness and smoothness of root tip cell walls, inhibiting the absorption and accumulation of CA, as well as relieving osmotic stress and membrane lipid peroxidation caused by CA in cucumber roots and leaves. Additionally, Si promotes grana lamella (GL) stacking and increases thylakoid numbers in chloroplasts. It also enhances the chlorophyll content in cucumber leaves and improves the energy conversion efficiency of photosystem PSII. These effects lead to an improvement in both photosynthetic efficiency and dry matter accumulation, as well as increased the resistance to CA-induced autotoxicity in cucumber plants. The same concentration of Si had no significant effect on the growth of cucumber seedlings, indicating that Si plays an important role in improving the tolerance to autotoxicity in cucumbers. These findings provide an effective theoretical basis and methods for research regarding the alleviation of continuous cropping obstacles.

Photodynamic Therapy Combined with Ferroptosis Is a Synergistic Antitumor Therapy Strategy.

Ferroptosis is a programmed death mode that regulates redox homeostasis in cells, and recent studies suggest that it is a promising mode of tumor cell death. Ferroptosis is regulated by iron metabolism, lipid metabolism, and intracellular reducing substances, which is the mechanism basis of its combination with photodynamic therapy (PDT). PDT generates reactive oxygen species (ROS) and 1O2 through type I and type II photochemical reactions, and subsequently induces ferroptosis through the Fenton reaction and the peroxidation of cell membrane lipids. PDT kills tumor cells by generating excessive cytotoxic ROS. Due to the limited laser depth and photosensitizer enrichment, the systemic treatment effect of PDT is not good. Combining PDT with ferroptosis can compensate for these shortcomings. Nanoparticles constructed by photosensitizers and ferroptosis agonists are widely used in the field of combination therapy, and their targeting and biological safety can be improved through modification. These nanoparticles not only directly kill tumor cells but also further exert the synergistic effect of PDT and ferroptosis by activating antitumor immunity, improving the hypoxia microenvironment, and inhibiting the tumor angiogenesis. Ferroptosis-agonist-induced chemotherapy and PDT-induced ablation also have good clinical application prospects. In this review, we summarize the current research progress on PDT and ferroptosis and how PDT and ferroptosis promote each other.

Synthesis, properties and mechanism of carbon dots-based nano-antibacterial materials.

Antibiotics play an important role in the treatment of diseases, but bacterial resistance caused by their widespread and unreasonable use has become an urgent problem in clinical treatment. With the rapid advancement of nanoscience and nanotechnology, the development of nanomedicine has been transformed into a new approach to the problem of bacterial resistance. As a new type of carbon-based nanomaterial, carbon dots (CDs) have attracted the interest of antibacterial researchers due to their ease of preparation, amphiphilicity, facile surface functionalization, and excellent optical properties, among other properties. This article reviewed the synthesis methods and properties of various CDs and their composites in order to highlight the advancements in the field of CDs-based antibacterial agents. Then we focused on the relationship between the principal properties of CDs and the antibacterial mechanism, including the following: (1) the physical damage caused by the small size, amphiphilicity, and surface charge of CDs. (2) Photogenerated electron transfer characteristics of CDs that produce reactive oxygen species (ROS) in themselves or in other compounds. The ability of ROS to oxidize can lead to the lipid peroxidation of cell membranes, as well as damage proteins and DNA. (3) The nano-enzyme properties of CDs can catalyze reactions that generate ROS. (4) Synergistic antibacterial effect of CDs and antibiotics or other nanocomposites. Finally, we look forward to the challenges that CDs-based nanocomposites face in practical antibacterial applications and propose corresponding solutions to further expand the application potential of nanomaterials in the treatment of infectious diseases, particularly drug-resistant bacterial infections.

Low-Dose Exposure of WS2 Nanosheets Induces Differential Apoptosis in Lung Epithelial Cells.

Escalating the production and application of tungsten disulfide (WS2) nanosheets inevitably increases environmental human exposure and warrants the necessity of studies to elucidate their biological impacts. Herein, we assessed the toxicity of WS2 nanosheets and focused on the impacts of low doses (≤10 μg/mL) on normal (BEAS-2B) and tumorigenic (A549) lung epithelial cells. The low doses, which approximate real-world exposures, were found to induce cell apoptosis, while doses ≥ 50 μg/mL cause necrosis. Focused studies on low-dose exposure to WS2 nanosheets revealed more details of the impacts on both cell lines, including reduction of cell metabolic activity, induction of lipid peroxidation in cell membranes, and uncoupling of mitochondrial oxidative phosphorylation that led to the loss of ATP production. These phenomena, along with the expression situations of a few key proteins involved in apoptosis, point toward the occurrence of mitochondria-dependent apoptotic signaling in exposed cells. Substantial differences in responses to WS2 exposure between normal and tumorigenic lung epithelial cells were noticed as well. Specifically, BEAS-2B cells experienced more adverse effects and took up more nanosheets than A549 cells. Our results highlight the importance of dose and cell model selection in the assessment of nanotoxicity. By using doses consistent with real-world exposures and comparing normal and diseased cells, we can gain knowledge to guide the development of safety precautions for mitigating the adverse impacts of nanomaterial exposure on human health.

Polypropylene/Poly(butylene adipate-co-terephthalate) Breathing Film for Inhibiting Pseudomonas and Maintaining Microbial Communities and Postharvest Quality of Allium mongolicum Regel during Storage.

Allium mongolicum Regel (A. mongolicum) is a healthy edible plant but highly perishable with a short shelf life of 1-2 d. Modified atmosphere packaging (MAP) could inhibit the postharvest senescence and decay of the vegetables. Thus, the aim of this study was to apply MAP with different gas permeabilities to the storage of A. mongolicum and evaluate its effects on maintaining microbial communities and the postharvest quality of A. mongolicum. The results showed that polypropylene/poly(butylene adipate-co-terephthalate) (PP/PBAT, abbreviated as PAT) MAP was suitable for the storage of A. mongolicum by establishing an optimal atmosphere of 0.5-0.6% O2 and 6.2-7.1% CO2 in the bag. It could delay the postharvest senescence of A. mongolicum and maintain its quality by slowing down its respiration rate and weight loss, reducing cell membrane permeability and lipid peroxidation, maintaining the cell wall, and reducing infection and the growth of microorganisms. However, A. mongolicum in HPT was more perishable than that in PAT during storage. Pseudomonas was found to be the main spoilage bacteria, and they could also be effectively inhibited by PAT-MAP. The next-generation sequencing results also showed the growth of Escherichia-Shigella, Clostridium sensu stricto 1, Streptococcus, Aureobasidium, Didymella, and Fusarium, responsible for A. mongolicum decay or human disease, was well inhibited by PAT-MAP. The results suggested that PAT-MAP could be used to maintain microbial diversity and the postharvest quality of A. mongolicum under cold storage conditions. It provided a feasible solution for the preservation, food quality, and safety control of A. mongolicum.

Is There an Association Between Dietary Antioxidant Levels and Sperm Parameters in Male Infertility?

Oxidative stress is known as a mechanism underlying male infertility; it is defined as an imbalance between pro-oxidants and antioxidants leading to DNA damage, peroxidation of plasma membrane lipids, and protein oxidation.This study was conducted to investigate the relationship between total antioxidant capacity and sperm parameters in male infertility. A total of 187 men with infertility (asthenospermia group (n=51), oligospermia group (n=40), and control group (n=96) were included in the current study. The following risk factors were recorded: age, sperm volume, sperm motility, hormone levels, and dietary antioxidant content. Demographic parameters and hormone levels of cases showed no statistically significant difference between groups (p > 0.05). Semen volume, motility, vitamin A, retinol, vitamin D, and vitamin C levels were statistically significantly lower in the asthenospermia and oligospermia groups (p < 0.05). According to the logistic regression model, lower vitamin A, retinol, vitamin D, and vitamin C levels were risk factors for poor sperm outcomes (p < 0.001). Conclusıon: Male infertility with poor sperm outcomes should have an assessment of antioxidant capacity and nutritional specialization including food high in antioxidants could improve sperm parameters in asthenospermia and oligospermia and it could be used for therapeutic opportunities.

Biomacromolecular and Toxicity Responses of Bacteria upon the Nano-Bio Interfacial Interactions with Ti3C2Tx Nanosheets.

The biomolecular responses of bacteria to 2D nanosheets that result from nano-bio interfacial interactions remain to be thoroughly examined. Herein, Fourier transform infrared (FTIR) multivariate and 2D correlation analyses were performed to assess the composition and conformational changes in bacterial biomacromolecules (lipids, polysaccharides, and carbohydrates) upon exposure to Ti3C2Tx nanosheets. General toxicity assays, 3D excitation-emission matrix fluorescence analyses, extended Derjaguin-Landau-Verwey-Overbeek theory interaction calculations, and isothermal titration calorimetry were also performed. Our results demonstrate that Ti3C2Tx nanosheets considerably impact Gram-positive bacteria (Bacillus subtilis), causing oxidative damage and inactivation by preferentially interacting with and disrupting the cell walls. The bilayer membrane structure of Gram-negative bacteria (Escherichia coli) endows them with increased resistance to Ti3C2Tx nanosheets. The unmodified nanosheets had a higher affinity to bacterial protein components with lower toxicity due to their susceptibility to oxidation. Surface modification with KOH or hydrazine (HMH), particularly HMH, induced stronger dispersion, antioxidation, and affinity to bacterial phospholipids, which resulted in severe cell membrane lipid peroxidation and bacterial inactivation. These findings provide valuable insight into nano-bio interfacial interactions, which can facilitate the development of antimicrobial and antifouling surfaces and contribute to the evaluation of the environmental risks of nanomaterials.

Abstract P1156: Potential Role Of Ferroptosis In Duchenne Muscular Dystrophy-associated Cardiomyopathy

Background and Aims: Duchenne muscular dystrophy (DMD) is the most common and fatal form of muscular dystrophy. DMD-associated cardiomyopathy (DMD-CM) is a major cause of morbidity and mortality in patients with DMD. Ferroptosis, a new type of regulated cell death characterized by iron-dependence and the accumulation of cell membrane lipid peroxidation, has been manifested in various cardiovascular disease conditions. However, ferroptosis has not been studied in DMD-CM. Here, we aim to determine whether ferroptosis play a potential role in DMD-CM. Methods and Results: We used a dystrophin/utrophin double knockout (mdx:utr -/- ) mouse model that displays clinical signs of DMD and DMD-CM. We performed RNA isolation from the ventricles of 3-month-old wild type (WT) and mdx:utr -/- mice (n=3) and performed RNA-Seq analysis. We found alterations of ferroptosis-related pathways such as GTP cyclohydrolase 1, transferrin receptor, glutamine transporter SLC38A1, heme oxygenase-1 (HMOX-1), and arachidonate 5-lipoxygenase (ALOX5) pathways in mdx:utr -/- hearts compared to WT hearts. Western blots confirmed the upregulation of ALOX5 and downregulation of HMOX-1, ferroptosis suppressor protein 1, and NADPH oxidase 4 in mdx:utr -/- hearts, while there was no change in glutathione peroxidase 4 (GPX4) levels. We also observed an increased level of lipid peroxidation in mdx:utr -/- hearts compared to WT as estimated by the level of malondialdehyde. Live/dead viability assays demonstrated a higher cell death rate in cardiomyocytes from mdx:utr -/- mice (53.7±7.2%, n=24) compared to those from WT mice (11.7±1.1%, n=17, p&lt; 0.01) under control conditions. The observed cell death in mdx:utr -/- cardiomyocytes was efficiently prevented by the selective ferroptosis inhibitor ferrostatin-1 (10 μM) (7.4±1.5%, n=9, p&lt;0.01), but not by the apoptosis inhibitor emricasan (20 μM) (56.0±1.6%, n=3, NS). Similarly, higher death rates were also observed in mdx:utr -/- than in WT cardiomyocytes when they were treated with various ferroptosis inducers such as iron overload and the GPX4 inhibitor RSL3. Conclusion: We have deciphered the link between ferroptosis and DMD-CM for the first time. Our data suggest novel targets for the treatment of DMD-CM by inhibiting ferroptosis.

Antioxidant and Anti-inflammatory Activities Mediate the Radioprotective Effect of Trianthema portulacastrum L. Extracts

Background: Ionizing radiation (IR) generates reactive oxygen species (ROS), which leads to oxidative stress that often leads to inflammatory responses in organisms. Objective: Trianthema portulacastrum L., a plant commonly growing in India, is rich in antioxidant phytochemicals. This is responsible for scavenging free radicals and may provide radioprotective and anti-inflammatory effects in response to ionizing radiation. Methods: The effect of T. portulacastrum extracts was studied in hepatic cells, which are susceptible to radiation-induced damage and in macrophages, which are the primary inflammatory cells of the body. Results: T. portulacastrum stem extracts showed efficient free radical scavenging activity in hepatocytes and decreased radiation-induced lipid peroxidation in cell and mitochondrial membranes. Treatment of irradiated cells with T. portulacastrum stem extracts enhanced cell viability at lower concentration and reduced cell viability at higher concentration. Treatment with low concentration of T. portulacastrum stem extract also reduced cellular ROS generation and increased the concentration of cellular anti-oxidant, glutathione. T. portulacastrum extracts also showed remarkable anti-inflammatory properties in macrophages activated by the inflammatory agonist bacterial lipopolysaccharide (LPS). The extract reduced nitric oxide (NO) production and suppressed the expression of inflammatory genes. Conclusion: Together, these observations demonstrated a potential radioprotective role of T. portulacastrum extract mediated by both its antioxidant activity on hepatic epithelial cells and its anti-inflammatory activity on immune cells.

Melatonin Preserves Fluidity in Cell and Mitochondrial Membranes against Hepatic Ischemia-Reperfusion.

We evaluated the in vivo effects of melatonin treatment on oxidative damage in the liver in an experimental model of ischemia-reperfusion. A total of 37 male Sprague-Dawley rats were randomly divided into four groups: control, ischemia, ischemia + reperfusion, and ischemia + reperfusion + melatonin. Hepatic ischemia was maintained for 20 min, and the clamp was removed to initiate vascular reperfusion for 30 min. Melatonin (50 mg/kg body weight) was intraperitoneally administered. Fluidity was measured by polarization changes in 1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene-p-toluene sulfonate). After 20 min of ischemia, no significant changes were observed in cell and mitochondrial membrane fluidity levels, lipid peroxidation, and protein carbonylation. However, after 30 min of reperfusion, membrane fluidity decreased compared to controls. Increases in lipid and protein oxidation were also seen in hepatic homogenates of animals exposed to reperfusion. Melatonin injected 30 min before ischemia and reperfusion fully prevented membrane rigidity and both lipid and protein oxidation. Livers from ischemia-reperfusion showed histopathological alterations and positive labeling with antibodies to oxidized lipids and proteins. Melatonin reduced the severity of these morphological changes and protected against in vivo ischemia-reperfusion-induced toxicity in the liver. Therefore, melatonin might be a candidate for co-treatment for patients with hepatic vascular occlusion followed by reperfusion.

Inactivation of Salmonella using ultrasound in combination with Litsea cubeba essential oil nanoemulsion and its bactericidal application on cherry tomatoes

The presence of Salmonella in nature poses a significant and unacceptable threat to the human public health domain. In this study, the antibacterial effect and mechanism of ultrasound (US) combined with Litsea cubeba essential oil nanoemulsion (LEON) on Salmonella. LEON + US treatment has a significant bactericidal effect on Salmonella. Reactive oxygen species (ROS), malondialdehyde (MDA) detection, N-phenyl-l-naphthylamine (NPN) uptake and nucleic acid release assays showed that LEON + US exacerbated cell membrane lipid peroxidation and increased the permeability of the cell membrane. The results of field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM) showed that LEON + US treatment was able to alter cell morphology. It can be observed by flow cytometry (FCM) that LEON + US treatment can cause cell apoptosis. In addition, bacterial counts of cherry tomatoes treated with LEON (0.08 μL/mL) + US (345 W/cm2) for 9 min were reduced by 6.50 ± 0.20 log CFU/mL. This study demonstrates that LEON + US treatment can be an effective way to improve the safety of fruits and vegetables in the food industry.