Higher Levels Of Lipid Peroxidation Research Articles

Oxidative Stress Biomarkers in Male Infertility: Established Methodologies and Future Perspectives.

Male fertility can be affected by oxidative stress (OS), which occurs when an imbalance between the production of reactive oxygen species (ROS) and the body's ability to neutralize them arises. OS can damage cells and influence sperm production. High levels of lipid peroxidation have been linked to reduced sperm motility and decreased fertilization ability. This literature review discusses the most commonly used biomarkers to measure sperm damage caused by ROS, such as the high level of OS in seminal plasma as an indicator of imbalance in antioxidant activity. The investigated biomarkers include 8-hydroxy-2-deoxyguanosine acid (8-OHdG), a marker of DNA damage caused by ROS, and F2 isoprostanoids (8-isoprostanes) produced by lipid peroxidation. Furthermore, this review focuses on recent methodologies including the NGS polymorphisms and differentially expressed gene (DEG) analysis, as well as the epigenetic mechanisms linked to ROS during spermatogenesis along with new methodologies developed to evaluate OS biomarkers. Finally, this review addresses a valuable insight into the mechanisms of male infertility provided by these advances and how they have led to new treatment possibilities. Overall, the use of biomarkers to evaluate OS in male infertility has supplied innovative diagnostic and therapeutic approaches, enhancing our understanding of male infertility mechanisms.

Role of ferroptosis in Porphyromonas gingivalis-induced impairment of epithelial junction

ABSTRACT Objectives This study aims to clarify the effect of ferroptosis by P. gingivalis on periodontal epithelium impairment and potential mechanisms. Materials and methods The expression of epithelial junction proteins (CDH1, OCLN, ZO-1), FTL and GPX4 in healthy and periodontitis tissues was analyzed using bioinformatics analysis and validated in vivo. An in vitro model was constructed to evaluate ferroptosis by mitochondria morphology, content of iron and GSH, and level of lipid peroxidation, FTL, GPX4 and SLC7A11. The iron concentration was changed with iron chelator DFO and iron supplementation FAC. The epithelial impairment was assessed by protein expression. To investigate the mechanism, si-MYB (a negative transcription factor of SLC7A11) and GPX4 inhibitor RSL3 were employed. Results CDH1, OCLN, ZO-1 and GPX4 expression was decreased, while FTL expression was elevated in periodontitis tissues. Infected cells showed ferroptosis change of the mitochondria with higher level of lipid peroxidation, iron, FTL and lower level of GPX4, GSH, SLC7A11. FAC augmented ferroptosis and weakened epithelial junction, while DFO exhibited a counteractive effect. Silencing MYB rescued SLC7A11, GPX4 and epithelial junction proteins, which was hindered by RSL3. Conclusions Our study demonstrated that P. gingivalis weakened the oral epithelial barrier by causing ferroptosis via inhibiting SLC7A11/GSH/GPX4 axis.

Impacts of sequential salinity and heat stress are recovery time-specific in freshwater crustacean, Daphnia pulicaria

Stressors can interact to affect animal fitness, but we have limited knowledge about how temporal variation in stressors may impact their combined effect. This limits our ability to predict the outcomes of pollutants and future dynamic environmental changes. Elevated salinity in freshwater ecosystems has been observed worldwide. Meanwhile, heatwaves have become more frequent and intensified as an outcome of climate change. These two stressors can jointly affect organisms; however, their interaction has rarely been explored in the context of freshwater ecosystems. We conducted lab experiments using Daphnia pulicaria, a key species in lakes, to investigate how elevated salinity and heatwave conditions collectively affect freshwater organisms. We also monitored the impacts of various recovery times between the two stressors. Daphnia physiological conditions (metabolic rate, Na+-K+-ATPase (NKA) activity, and lipid peroxidation level) and life history traits (survival, fecundity, and growth) in response to salt stress as well as mortality in heat treatment were examined. We found that Daphnia responded to elevated salinity by upregulating NKA activity and increasing metabolic rate, causing a high lipid peroxidation level. Survival, fecundity, and growth were all negatively affected by this stressor. These impacts on physiological conditions and life history traits persisted for a few days after the end of the exposure. Heat treatments caused mortality in Daphnia, which increased with rising temperature. Results also showed that individuals that experienced salt exposure were more susceptible to subsequent heat stress, but this effect decreased with increasing recovery time between stressors. Findings from this work suggest that the legacy effects from a previous stressor can reduce individual resistance to a subsequent stressor, adding great difficulties to the prediction of outcomes of multiple stressors. Our work also demonstrates that cross-tolerance/susceptibility and the associated mechanisms remain unclear, necessitating further investigation.

Silicon and arbuscular mycorrhizal fungi alleviate chromium toxicity in Brassica rapa by regulating Cr uptake, antioxidant defense expression, the glyoxalase system, and secondary metabolites

The potential contribution of silicon (Si) (300 mg kg−1 potash silica) or arbuscular mycorrhizal fungi (AMF) (Rhizophagus irregularis) to reduce chromium toxicity (Cr; 0 and 300 mg kg−1) in Brassica rapa was examined in this work. Under Cr stress, Si and AMF were used separately and in combination (no Si, or AMF, Si, AMF, and Si + AMF). Brassica rapa growth, colonization, photosynthesis, and physio-biochemical characteristics decreased under Cr stress. Oxidative stress was a side effect of Cr stress and was associated with high levels of methylglyoxal (MG), hydrogen peroxide (H2O2), lipid peroxidation (MDA), and maximum lipoxygenase activity (LOX). On the other hand, quantitative real-time PCR analyses of gene expression showed that under Cr stress, the expression of genes for secondary metabolites and antioxidant enzymes was higher than that under the control. The co-application of Si and AMF activated the plant defense system by improving the antioxidative enzymes activities, the potassium citrate and glutathione pool, the glyoxalase system, metabolites, and genes encoding these enzymes under Cr stress. Under the influence of Cr stress, oxidative stress was reduced by the coordinated control of the antioxidant and glyoxalase systems. However, the restricted Cr uptake and root and shoot accumulation of Si and AMF co-applied to only Cr-stressed plants was more significant. In summary, Si and AMF applied together successfully counteract the deleterious effects of Cr stress and restore growth and physio-biochemical characteristics. As a result, the beneficial effects of the combined Si and AMF application may be attributed to mycorrhizae-mediated enhanced Si absorption and metal resistance.

The infection of Aeromonas hydrophila activated Multiple programmed cell death pathways in red blood cells of Clarias fuscus

In contrast to mammalian red blood cells (RBCs), Osteichthyes RBCs contain a nucleus and organelles, suggesting the involvement of more intricate mechanisms, particularly in the context of ferroptosis. In this study, we utilized RBCs from Clarias fuscus (referred to as Cf-RBCs) as a model system. We conducted RNA-seq analysis to quantify gene expression levels in Cf-RBCs after exposure to both Aeromonas hydrophila and lipopolysaccharides. Our analysis unveiled 1326 differentially expressed genes (DEGs) in Cf-RBCs following 4 h of incubation with A. hydrophila, comprising 715 and 611 genes with upregulated and downregulated expression, respectively. These DEGs were further categorized into functional clusters: 292 related to cellular processes, 241 involved in environmental information processing, 272 associated with genetic information processing, and 399 linked to organismal systems. Additionally, notable changes were observed in genes associated with the autophagy pathway at 4 h, and alterations in the ferroptosis pathway were observed at 8 h following A. hydrophila incubation. To validate these findings, we assessed the expression of cytokines (DMT1, TFR1, LC3, and GSS). All selected genes were significantly upregulated after exposure to A. hydrophila. Using flow cytometry, we evaluated the extent of ferroptosis, and the group incubated with A. hydrophila for 8 h exhibited higher levels of lipid peroxidation compared with the 4-h incubation group, even under baseline conditions. An evaluation of the glutathione redox system through GSSG/GSH ratios indicated an increased ratio in Cf-RBCs after exposure to A. hydrophila. In summary, our data suggest that A. hydrophila may induce ferroptosis in Cf-RBCs, potentially by triggering the cystine/glutamate antiporter system (system XC−), while Cf-RBCs counteract ferroptosis through the regulation of the glutathione redox system. These findings contribute to our understanding of the iron overload mechanism in Osteichthyes RBCs, provide insights into the management of bacterial diseases in Clarias fuscus, and offer potential strategies to mitigate economic losses in aquaculture.

Ineffective Erythropoiesis Negatively Impacts the Erythroblastic Island in Sickle Cell Disease

Sickle cell disease (SCD) is a genetic recessive disorder, characterized by painful episodes of vaso-occlusion, chronic hemolytic anemia, and progressive organ failure. It is one of the most common and severe monogenic diseases worldwide. SCD is caused by a point mutation in the β-globin gene, leading to the expression of an abnormal hemoglobin (HbS) that polymerizes under hypoxic conditions, driving red blood cells (RBC) sickling. Peripheral RBCs are extensively studied in SCD, as hemolysis is the major contributor to anemia, but little is known about erythroid differentiation in this pathology. We recently demonstrated the occurrence of ineffective erythropoiesis in the bone marrow (BM) of SCD patients, characterized by the death of a significant proportion of erythroblasts between the polychromatic and the orthochromatic stages. We hypothesize that this increased cell death could negatively impact the central macrophages of the erythroblastic islands (EBIs) as they would engulf high numbers of hemoglobin-rich apoptotic erythroblasts and undergo ferroptosis because of excess iron. To investigate our hypothesis, we used an in vitro system whereby CD14 + monocytes were isolated from peripheral blood and cultured in media supplemented with M-CSF and dexamethasone. This led them to differentiate towards anti-inflammatory tissue macrophages, with an “EBI-like” phenotype, expressing markers such as CD16, CD163, CD169, CD206. Phagocytosis of high numbers of RBCs by “EBI-like” macrophages led to increased cell death, reactive oxygen species, and lipid peroxidation, and to the upregulation of genes involved in ferroptosis pathways such as HO-1 and SLC7A11. This was circumvented by the ferroptosis inhibitors ferrostatin-1 and liproxtatin-1. Furthermore, phagocytosis of apoptotic in vitro-generated SCD erythroblasts also induced ferroptosis in EBI-like macrophages, with increased cell death and lipid peroxidation in a time-dependent manner. Interestingly, while this was the case with hemoglobin-rich, terminally differentiating erythroblasts, phagocytosis of cells without hemoglobin, such as K562 or GPA - progenitor cells did not affect cell viability, indicating that the observed ferroptosis was due to the iron content of the internalized cells. We investigated the effect of increased RBC phagocytosis on the phenotype of surviving macrophages and found an M2 to M1 shift indicating a switch to a pro-inflammatory phenotype under the condition of elevated levels of intracellular iron and oxidative stress. We challenged these findings in vivo using the Townes humanized SCD mouse model. Data on 4-month-old mice showed the expected switch in erythroid production from steady-state erythropoiesis in the BM to a stress erythropoiesis in the spleen. This was associated with a decrease in the number of EBI macrophages (F4/80 HighVCAM+CD169+Ly6G-) in the BM of SS mice when compared to AS and AA mice, and an expansion of red pulp macrophages (RPMs) F4/80 HighCD169+VCAM+. Using a flow cytometry-based assay we found high lipid peroxidation levels in BM EBI macrophages of SS mice as compared to AA, suggesting occurrence of ferroptosis in these cells. Our study suggests that IE in SCD may contribute to anemia, directly by cell death of differentiating erythroblasts, and indirectly by disrupting the erythroblastic island or by inducing its collapse following ferroptosis of the central macrophage. Our work with the Townes mouse model and BM samples from SCD patients will help to elucidate this hypothesis.

Differential response of phenylpropanoid pathway as linked to hormonal change in two Brassica napus cultivars contrasting drought tolerance.

Oilseed rape (Brassica napus L.) is a significant agro-economic crop with a wide range of uses. Drought is the most frequent unfavourable environmental stressor restraining its growth and development worldwide. This study was conducted to characterize the drought-responsive phenylpropanoid pathway and its link to hormonal changes in two cultivars, drought-resistant "Saturnin" and drought-susceptible "Mosa." Drought susceptibility in cv. Mosa was confirmed by its lower water use efficiency and higher lipid peroxidation levels with reactive oxygen species (ROS) accumulation. In cv. Saturnin, higher salicylic acid (SA) levels and expression of dehydration-responsive element binding 2 (DREB2) and non-expressor of pathogenesis-related gene 1 (NPR1) led to an upregulation of production of anthocyanin pigment 1 (PAP1) and phenylpropanoid pathway-related gene (CHS, F5H and COMT1) expression, increasing hydroxycinnamic acid and flavonoid compound concentrations. However, in cv. Mosa, higher increases in the activity of lignifying enzymes (polyphenol oxidase, coniferyl alcohol peroxidase, syringaldazine peroxidase, guaiacol peroxidase) and expression of the lignin synthesis-related gene cinnamyl alcohol dehydrogenase 2 (CAD2) were found along with greater increases in abscisic acid (ABA) levels and upregulation of ABA-responsive element binding 2 (AREB2) and basic helix-loop-helix transcription factor MYC2. These results indicate that drought-induced SA-mediated activation of the hydroxycinnamic acid and flavonoid pathways contributes to drought resistance, whereas ABA-mediated lignification contributes to drought susceptibility.

Effects of dietary carbohydrate/lipid ratios on growth, body composition, amylase activity, oxidative status, and mTOR/autophagy pathway in juvenile clam, Sinonovacula constricta

The nutritional requirements and metabolism of bivalves remain largely unknown. In this study, we investigated the effects of dietary carbohydrate/lipid ratios on growth performance, body composition, digestive enzyme activities, oxidative status, and transcriptome profile in juvenile razor clam Sinonovacula constricta. Five microcapsule diets with varying levels of carbohydrate (30–45%) and lipid (2–15%) were prepared and designated as C45L2 (45% carbohydrate and 2% lipid), C41L5, C36L8, C33L11, and C30L15 groups. Juvenile S. constricta with an initial shell length of 4.9 mm were fed with these microcapsule diets for 2 weeks. The results showed that the clam in the C33L11 group exhibited the fastest growth rate. The body protein content decreased with the decreasing dietary carbohydrate/lipid ratio. The clam in the C33L11 group showed significantly higher glycogen content compared to the C45L2, C41L5, or C30L5 group. The amylase activity of the clam in the C45L2 and C41L5 group was significantly higher than that in the C36L8, C33L11, and C30L15 group. The clam in the C33L11 group showed significantly higher catalase and superoxide dismutase activities compared to other microcapsule groups. The malondialdehyde level of the clam in the C30L15 group was significantly higher than that in the C45L2, C41L5, and C33L11 group. Transcriptome analysis showed that the autophagy pathway in the clam fed C41L5 was upregulated compared with those fed C33L11. Meanwhile, the protein levels of microtubule-associated protein 1 A/1B-light chain 3 membrane type (LC3-II) in the C41L5 group were also significantly higher than those in the C33L11 group. Moreover, the clam in the C41L5 group exhibited increased phosphorylation levels of the eukaryotic translation initiation factor 4E-binding protein (4E-BP) and decreased phosphorylation levels of the ribosomal protein S6 kinase beta-1 (S6K). Our results revealed that the optimal dietary carbohydrate/lipid ratio for juvenile S. constricta was approximately 3.01. The high-carbohydrate/low-lipid diet may repress the growth of clam by inhibiting mammalian target of rapamycin complex 1 (mTORC1) and subsequently activating autophagy, while the poor growth performance in the low-carbohydrate/high-lipid diet group may be associated with high lipid peroxidation levels in juvenile S. constricta.

Chemical alterations of grain surface by cold plasma technology: Comparison of buckwheat and wheat grain responses to oxygen low-pressure plasma

Cold plasma (CP) has a great potential for decontamination or improvement of grain germination. However, disputing results have been reported, as plasma treatment can affect species and varieties of grains in different ways. The differences may be due to the chemical composition of grain pericarps, the structure of the grains and metabolic response mechanisms. CP treatment decreased grain germination rate, speed and activity of α-amylase of buckwheat grains. Such effects on both varieties of wheat grains were present after longer exposure to plasma. Lipid peroxidation was highest in buckwheat grains, whereas wheat grains were less affected. Plasma-treated Gorolka variety exhibited a low level of lipid peroxidation, no different to untreated grains, compared to Primorka grains, where longer treatment triggered higher levels of lipid peroxidation. The response of grains to CP treatment depends on the chemical and structural properties of grains pericarp, as well as plant tolerance to certain abiotic conditions.

Extracellular mechanical forces and ferroptosis in triple negative breast cancer (TNBC): Targeting of aurora kinase A (AURKA).

e13086 Background: The mechanics of tumor microenvironment, primarily induced by extracellular matrix (ECM), function to regulate cell biological behaviors. However, it is unclear if and how triple negative breast cancer (TNBC) cells adapt their biological characteristics to variable extracellular mechanical forces. Methods: TNBC tissues of different stiffness from patients were harvested for untargeted metabolomics to investigate the potential effects of mechanical forces on metabolism. TNBC cells were cultured within gels of different type I collagen (Col-I) densities, which were the major component of ECM, to simulate the effects of extracellular mechanical forces on cells. The metabolic changes of TNBC cells were also examined by using untargeted metabolomics. TNBC cells bathed in different Col-I densities were injected subcutaneously into the breast pad of nude mice. Ferroptosis indicators were evaluated between different groups of mechanical force both in vitro and in vivo. Real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were carried out to examine the expression of ferroptosis-related genes and proteins between different groups of mechanical force. Results: Untargeted metabolomics studies showed significant differences in ferroptosis-related metabolites between TNBC tissues with different stiffness, which were also verified in TNBC cells subjected to different extracellular mechanical forces. In vitro experiment suggested that TNBC cells cultured within high Col-I density (strong extracellular forces) exhibited higher levels of lipid peroxidation, reactive oxygen accumulation, mitochondria membrane potential and iron concentration, and lower levels of total glutathione and reduced glutathione concentration, compared with low Col-I density (weak extracellular forces). In addition, mitochondria in high Col-I density group appeared to have volume decrease, fracture and fuzzy cristae. The above results indicated that extracellular mechanical force significantly induced ferroptosis in TNBC. RT-qPCR and western blot of ferroptosis-related genes and protein showed that both mRNA and protein levels of aurora kinase A (AURKA) were significantly decreased in TNBC cells with strong extracellular mechanical force. In addition, overexpression of AURKA inhibited ferroptosis caused by mechanical forces. Furthermore, this cause and effect among mechanical force, AURKA and ferroptosis was also evident in vivo experiments. Conclusions: Our data clarified the role of extracellular mechanical forces in TNBC and showed that the extracellular mechanical forces induced ferroptosis through decreasing the expression of AURKA.

Analysis of genetic variants related to oxidative stress in patients with Alzheimer’s disease

AbstractBackgroundAlzheimer’s disease (AD) is one of the common neurodegenerative diseases with an incompletely understood pathomechanism. In AD, generation of oxidative stress is observed as a result of dysfunction of the mitochondrial respiratory chain. The effect of this disturbance is the production of reactive oxygen species (ROS). The SOD2 gene is involved in the elimination of ROS. Glutathione S‐transferases (GST) are a group of enzymes with antioxidant properties that protect cells from ROS damage. GSTP1 gene variants may impair the activity of these enzymes. APOE gene, is also related to the regulation of oxidative stress. In AD patients with APOE E4, higher levels of lipid peroxidation are found. The precise nature of the association between oxidative stress and hallmarks of AD pathology is unknown.The aim of the study was to analyze of genetic variants of SOD2 c.47T>C (exon 2) and GSTP1 c.341C>T (exon 6) genes in AD patients, control subjects related to AD cases (CR), and controls subjects without family history of AD (CU). The APOE E4 allele was included in the studies.MethodThe studies were conducted on 156 individuals (AD and controls). The APOE genotype was determined by real‐time PCR. The SOD2 and GSTP1 genetic variants were determined by HRM and sequencing. The apoE concentration was determined by the ELISA method.ResultVariant CC c.47T>C SOD2 was more frequent in CR, while CT in CU. The TT variant of this gene tended to occur more frequently in patients with AD. In AD, the TT variant was more common in the subject without E4 allele (p<0.05). The CC and CT variants of the c.341C>T GSTP1 gene occurred with equal frequency in AD and CR. The TT variant of this gene was not found in the examined subjects. Regardless of the genetic variant of APOE, SOD2, GSTP1, a significantly higher level of apoE was found in CR.ConclusionGenes involved in the regulation of oxidative stress may play an important role in the pathogenesis of AD.

Aflatoxin B1 Degradation by Ery4 Laccase: From In Vitro to Contaminated Corn.

Aflatoxins (AFs) are toxic secondary metabolites produced by Aspergillus spp. and are found in food and feed as contaminants worldwide. Due to climate change, AFs occurrence is expected to increase also in western Europe. Therefore, to ensure food and feed safety, it is mandatory to develop green technologies for AFs reduction in contaminated matrices. With this regard, enzymatic degradation is an effective and environmentally friendly approach under mild operational conditions and with minor impact on the food and feed matrix. In this work, Ery4 laccase, acetosyringone, ascorbic acid, and dehydroascorbic acid were investigated in vitro, then applied in artificially contaminated corn for AFB1 reduction. AFB1 (0.1 µg/mL) was completely removed in vitro and reduced by 26% in corn. Several degradation products were detected in vitro by UHPLC-HRMS and likely corresponded to AFQ1, epi-AFQ1, AFB1-diol, or AFB1dialehyde, AFB2a, and AFM1. Protein content was not altered by the enzymatic treatment, while slightly higher levels of lipid peroxidation and H2O2 were detected. Although further studies are needed to improve AFB1 reduction and reduce the impact of this treatment in corn, the results of this study are promising and suggest that Ery4 laccase can be effectively applied for the reduction in AFB1 in corn.

Bidirectionally Regulating Viral and Cellular Ferroptosis with Metastable Iron Sulfide Against Influenza Virus.

Influenza virus with numerous subtypes and frequent variation limits the development of high-efficacy and broad-spectrum antiviral strategy. Here, a novel multi-antiviral metastable iron sulfides (mFeS) against various influenza A/B subtype viruses is developed. This work finds that mFeS induces high levels of lipid peroxidation and •OH free radicals in the conservative viral envelope, which depends on Fe2+ . This phenomenon, termed as a viral ferroptosis, results in the loss of viral infectibility and pathogenicity in vitro and in vivo, respectively. Furthermore, the decoction of mFeS (Dc(mFeS)) inhibits cellular ferroptosis-dependent intracellular viral replication by correcting the virus-induced reprogrammed sulfur metabolism, a conserved cellular metabolism. Notably, personal protective equipment (PPE) that is loaded with mFeS provides good antiviral protection. Aerosol administration of mFeS combined with the decoction (mFeS&Dc) has a potential therapeutic effect against H1N1 lethal infection in mice. Collectively, mFeS represents an antiviral alternative with broad-spectrum activity against intracellular and extracellular influenza virus.

High-Dose Ionizing Radiation Accelerates Atherosclerotic Plaque Progression by Regulating P38/NCOA4-Mediated Ferritinophagy/Ferroptosis of Endothelial Cells

Radiation therapy (RT) significantly increased the incidence of coronary artery diseases, especially atherosclerosis. Endothelial dysfunction has been the major side effect of RT among tumor patients who received RT. However, the involvement between endothelial dysfunction and radiation-induced atherosclerosis (RIA) remains unclear. Here, we constructed a murine model of RIA, aiming to uncover its underlying mechanisms and identify novel strategies for RIA prevention and treatment. Eight-week-old ApoE-/- mice that were fed a Western diet were subjected to partial carotid ligation (PCL). Four weeks later, ionizing radiation (IR) of 10 Gy was performed to verify the detrimental role of IR on atherogenesis. Ultrasound imaging, RT quantitative polymerase chain reaction, histopathology and immunofluorescence, and biochemical analysis were performed 4 weeks after IR. To study the involvement of endothelial ferroptosis induced by IR in RIA, mice after IR were administrated with ferroptosis agonist (cisplatin) or antagonist (ferrostatin-1) intraperitoneally. Western blotting, autophagic flux measurement, reactive oxygen species level detection, and coimmunoprecipitation assay were carried out in vitro. Furthermore, to determine the effect of ferritinophagy inhibition on RIA, in vivo knockdown of NCOA4 was carried out by pluronic gel. We verified that accelerated plaque progression was concomitant with endothelial cell (EC) ferroptosis after IR induction, as suggested by a higher level of lipid peroxidation and changes in ferroptosis-associated genes in the PCL+IR group than in the PCL group within vasculature. In vitro experiments further validated the devastating effects of IR on oxidative stress and ferritinophagy in ECs. Mechanistic experiments revealed that IR induced EC ferritinophagy and subsequent ferroptosis in a P38/NCOA4-dependent manner. Both in vitro and in vivo experiments confirmed the therapeutic effect of NCOA4 knockdown in alleviating IR-induced ferritinophagy/ferroptosis of EC and RIA. Our findings provide novel insights into the regulatory mechanisms of RIA and first prove that IR accelerates atherosclerotic plaque progression by regulating ferritinophagy/ferroptosis of ECs in a P38/NCOA4-dependent manner.

Mechanism of ferroptosis in a rat model of premature ovarian insufficiency induced by cisplatin

Ferroptosis is widely present in fibrosis-related diseases. The basic pathology of premature ovarian insufficiency (POI) involves ovarian tissue fibrosis, and there are currently fewer relevant studies addressing the association between ferroptosis and POI. This study aimed to demonstrate that ferroptosis induced by cisplatin (CDDP) caused ovarian tissue fibrosis, leading to POI. Vitamin E (VE), a ferroptosis inhibitor, could repair damaged ovarian function. CDDP was used to establish a rat model of POI, and VE was administered to reverse the reproductive toxicity of CDDP. Ovarian function was assessed by histological section staining, follicle counts, sex hormone levels, as well as fertility assays. The extent of ferroptosis was assessed by transmission electron microscopy (TEM), malondialdehyde (MDA), Perls staining. CCK-8, Ethynyl-2-Deoxyuridine (EdU), and scratch assays were used to determine the effect of CDDP and VE on ovarian granulosa cell (GC) viability. Western blot, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry were performed to evaluate ferroptosis-related molecular changes. Our results showed that CDDP caused follicle development disorders and ovarian tissue fibrosis, the levels of sex hormones suggested impaired ovarian function, and VE could reverse the reproductive toxicity of CDDP. The results of TEM, MDA and Perls staining suggested that the typical mitochondrial signature of ferroptosis was altered in ovarian GCs from the CDDP group, with significantly higher levels of lipid peroxidation and significant iron deposition in ovarian tissue, whereas VE mitigated the extent of ferroptosis. Molecular experiments then confirmed that the ferroptosis-related molecules acetyl CoA synthetase long chain family member 4 (ACSl4), 15-lipoxygenase-1 (ALOX15), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were differentially expressed in each group. In summary, our study preliminarily demonstrated that CDDP may promote GCs to undergo ferroptosis, cause follicle development disorders, ovarian tissue fibrosis, and induce POI by regulating the expression of ACSl4, ALOX15, SLC7A11, and GPX4, while VE improved impaired ovarian function.

Physiological and Biochemical Changes in the Seeds of Naturally Aged Wenling Medic (Medicago polymorpha) with Its Recovery of Viability

Wenling Medic (Medicago polymorpha) is common in southern China and has long been utilized as a vegetable in eastern China, as well as a significant raw ingredient for livestock and pickled meals. As a legume, there is still a research vacuum, and the first problem Wenling Medic faces in production is the problem of seed germination. The germination percentage of Wenling Medic was low, according to production practice and laboratory tests performed in this work. Furthermore, after more than two years of storage, the germination percentage of Wenling Medic dropped sharply, and it lacked a long enough seed life. An attempt was made to restore the viability of the seeds using the polyethylene glycol (PEG) osmoregulation-mediated priming method, after the physiological and biochemical characteristics of the seeds were assessed using the anthrone method, Bradford assay, 3,5-dinitrosalicylic acid (DNS) method, and thiobarbituric acid (TBA) method. The findings showed that it has a relatively short storage age and, with a useable life of only two years under normal aging circumstances, is not deactivated soon after harvesting. In addition, whereas protein content and α-amylase concentration did not significantly correlate (p > 0.05) with storage life, the conductivity of exudate, malondialdehyde content, and carbohydrate content did (p < 0.05). The seed viability was not considerably increased by the saturation initiation mediated by osmoregulation, utilizing PEG. In conclusion, the decrease in Wenling Medic seeds’ germination ability was substantially connected with higher levels of lipid peroxidation and decreased carbohydrate levels, but not with protein concentrations or α-amylase activity. The timing of dehydration may need to be carefully controlled when using PEG osmoregulation to prime Wenling Medic seeds.

Effects of overwintering on proximate composition, fatty acid composition, serum parameters, antioxidant status, and lipid metabolism in Onychostoma macrolepis

AbstractTo investigate the metabolic adaptation and lipid utilization to overwintering in Onychostoma macrolepis (27.05 ± 1.79 g), fish were sampled at 0, 75, and 150 days, respectively. Fish were randomly reared into three outdoor tanks (water temperature range:0–10°C). After overwintering, body weight, viscera index, hepatopancreas index, and intraperitoneal fat index were significantly lower than before (p < 0.05). In liver, the contents of monounsaturated fatty acid and polyunsaturated fatty acid (PUFA) were observed to be the lowest and the highest after 150 days of overwintering, respectively (p < 0.05). In serum, the concentrations of triglyceride (TG) and total cholesterol significantly decreased while the activities of alanine aminotransferase and aspartate aminotransferase significantly increased at Day 75 (p < 0.05). Hepatic antioxidant activities were significantly lower whereas malondialdehyde content was significantly higher at Day 150 (p < 0.05). Serum antioxidant indexes were similar to those in liver. During overwintering, the decrease of TG contents in tissues was influenced by the upregulation of lipidolysis genes. These results indicate that lipids were continuously mobilized as physiological fuels throughout overwintering. Overwintering could result in poor antioxidant status and higher lipid peroxidation level in O. macrolepis.

The production of pro-inflammatory cytokines and the state of cellular immunity in patients with pulmonary tuberculosis with and without relapse

The purpose of the study was to conduct a comparative study of the synthesis of pro-inflammatory cytokines, the state of cellular immunity, free radical oxidation reactions and antioxidant protection in patients with pulmonary tuberculosis with and without relapse. Material and methods. The study was carried out on two groups of patients: the first group basic which included 39 patients with relapsed pulmonary tuberculosis (TBR); 2nd control group 39 patients with non-relapsed pulmonary tuberculosis (TB). Pro-inflammatory cytokines (TNF-α, IL-2 IL-6), CD-3 lymphocyte content, lymphocyte blast transformation response to phytohemagglutinin and tuberculin, NBT-test, AOPP, SOD, and catalase were determined in patients of both groups and healthy people. Results. In patients with tuberculosis with relapses, compared with patients without relapses, complaints of cough and dyspnea were more often presented, a longer duration of hospitalization, late abacillation. In patients with relapses, a pronounced suppression of the functional and specific activity of lymphocytes and neutrophils was noted, which is confirmed by high levels of lipid peroxidation (Advanced Oxidation Protein Products AORP) and low levels of the antioxidant system (SOD and catalase). The high content of pro-inflammatory cytokines in patients with relapses indicates a higher activity of the inflammatory process in these patients and corresponds to a low blast formation rate for both phytohemagglutinin and tuberculin. Conclusion. Сhanges in the content of pro-inflammatory cytokines, the state of cellular immunity and the characteristics of reactions of free radical oxidation and antioxidant protection indicate a higher activity of the inflammatory process in patients with pulmonary tuberculosis with relapses compared to patients without relapses, which led to a longer duration of hospitalization, late abacillation.

ACSL4 and the lipoxygenases 15/15B are pivotal for ferroptosis induced by iron and PUFA dyshomeostasis in dopaminergic neurons.

Ferroptosis, an iron-dependent regulated cell death triggered by high lipid peroxide levels, has been implicated in several neurodegenerative diseases, including Parkinson's disease (PD). Brain regions such as the striatum are highly rich in both peroxidation susceptible PUFAs and iron, which accumulate at a greater rate than age in PD. The exact molecular pathways and patho-physiological conditions promoting cell death in the dopaminergic neurons that are particularly susceptible in PD remain elusive. In the current work, we show that modifying the PUFA composition in membranes of dopaminergic neurons using arachidonic acid (AA) can determine ferroptosis susceptibility. Furthermore, cotreatment with iron (Fe), increases AA-containing phospholipid association and synergistically promotes high lipid peroxidation to facilitate ferroptosis. Ex vivo analysis with organotypic brain slices, confirm that AA+Fe induces cell death in the nigrostriatal pathway and can be rescued by the anti-ferroptotic drug Ferrostatin-1. Prevention of ferroptotic AA+Fe induced cell death through inhibition of ACSL4, ALOX15 or ALOX15B provides mechanistic support of this lipid peroxidation pathway being involved in dopaminergic neuronal death and novel potential pharmacological targets for neuroprotective strategies in PD.

Interaction effect of fungicide and chitosan on non-target lichenized fungi

Excessive use of plant growth stimulants and pesticides is currently a considerable problem, especially in agriculture, horticulture, and arboriculture. Understanding the impacts of these compounds and their combinations on non-target organisms is crucial to minimize unintended consequences, while maintaining their use in plant protection. The aim of this study was to test how long-term spraying with different solutions of natural biostimulator chitosan, synthetic fungicide Switch 62.5 WG, and their combinations affects the physiology of epiphytic lichen Xanthoria parietina naturally occurring in fruit orchards and farmlands. We showed that fungicides composed of fludioxionil and cypronidil, as well as the combined use of such fungicides together with chitosan, can cause the considerable impairment of lichen physiology, and these disturbances relate to both algal and fungal partners of the symbiotic association. This negative effect was especially visible in the loss of cell membrane integrity, the high level of membrane lipid peroxidation, and changes in chlorophyll fluorescence parameters on the last day of the experiment. The combined use of these agents also leads to clear disturbances in the functioning of the mitochondrial respiratory chain, which was manifested by increased NADH dehydrogenase activity, while the use of these compounds separately led to a decrease in the activity of this enzyme. We concluded that the regular use of these agents in fruit tree cultivation may cause serious ecological consequences for epiphytic lichen communities as a result of the death of lichen thalli. This study suggests that the impact of some plant protection agents, both individually and in combinations, merits further attention in terms of their impact on non-target fungi.