Malondialdehyde Research Articles

Abstract Background Pancreatic cancer, a highly aggressive malignancy of the digestive tract, is characterized by an insidious onset, nonspecific early symptoms, early metastatic propensity, and resistance to conventional radiotherapy and chemotherapy. These features contribute to its poor clinical outcomes and dismal prognosis. Aims This study aimed to elucidate the molecular mechanisms underlying pancreatic cancer progression, identify clinically actionable diagnostic and therapeutic targets, and ultimately improve patient survival rates and treatment efficacy. Methods Using Enhancer Linking by Methylation/Expression Relationships (ELMER), a computational approach, we identified MAFF as a pivotal transcription factor driving pancreatic cancer progression. The oncogenic role of MAFF was validated through in vitro cellular assays and in vivo xenograft models in nude mice. Transcriptome sequencing and functional experiments further delineated the molecular mechanisms by which MAFF promotes tumorigenesis. Results MAFF knockdown significantly suppressed cell proliferation, colony formation, migration, and invasion in AsPC-1 and SUIT-2 cell lines. Bioinformatics analysis and dual-luciferase reporter assays identified AKR1C1 as a downstream effector of MAFF. Mechanistically, MAFF-AKR1C1 axis led to malondialdehyde (MDA) accumulation, elevated lipid reactive oxygen species (ROS), and ferroptosis inhibition, thereby fostering pancreatic cancer progression. Conclusions Our findings demonstrate that MAFF promotes tumorigenesis by suppressing ferroptosis and nominates MAFF as a promising therapeutic target for pancreatic cancer.

Diabetic nephropathy is still a chief reason for morbidity and mortality in persons with renal dysfunction. Thymoquinone, a primary constituent of black seed oil extracted from Nigella sativa, has anti-inflammatory, antioxidant, anticancer, and antimicrobial properties. Glycine, an amino acid and neurotransmitter, participates in diverse physiological mechanisms. This study investigated the nephroprotective role of thymoquinone and glycine against streptozotocin (STZ)-induced diabetic nephropathy. Forty-two adult male Swiss albino rats were segregated into seven groups, each comprising six. These groups consisted of control normal rats; rats administered 60-mg STZ/kg (nephropathy); nephropathy rats treated with oral doses of 20-mg/kg/day thymoquinone (T20) or 30-mg/kg/day thymoquinone (T30); nephropathy rats treated with oral doses of 50-mg/kg/day glycine (G50) or 100-mg/kg/day glycine (G100); (T + G) nephropathy rats receiving combination therapy of 30-mg/kg/day thymoquinone and 100-mg/kg/day glycine. Various biochemical factors, including glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), interleukin-10 (IL-10), total and myocardial creatine kinase (CK), kidney function parameters, blood electrolytes (Na, K, Cl, Ca, and P), and kidney histopathology, were assessed. The combined therapy of thymoquinone and glycine demonstrated enhanced efficacy in improving biochemical profiles, antioxidant levels, anti-inflammatory responses, and renal structure compared to monotherapies employing thymoquinone or glycine. The confluence of thymoquinone and glycine potentially operates through manifold pathways, encompassing the regulation of oxidative stress and modulation of inflammatory cascades. This study elucidates the potential synergistic benefits of integrating thymoquinone and glycine in diabetic nephropathy management, thereby heralding novel avenues for therapeutic interventions.

Root colonization by the endophytic fungus Serendipita indica (Si) effectively inhibited Sclerotium rolfsii (Sr) and controlled peanut stem rot. In vitro and microscopic analyses confirmed the strong antifungal activity of S. indica against S. rolfsii. Pot experiments revealed that Si markedly reduced the disease index to 5.12 ± 0.49% in resistant 'Luhua11' (L) and 8.65 ± 0.53% in susceptible 'Huayu6103' (H), indicating > 90% protection. Furthermore, Si colonization increased the biomass and health of the two peanut cultivars. Antioxidant enzyme activities were significantly increased: peroxidase (POD) activity in roots increased by 39.28-110.8% (24-96h), superoxide dismutase (SOD) activity was increased in 'LSi-Sr' and 'HSi-Sr' at 48-96h, ascorbate peroxidase (APX) activity was increased in 'LSi-Sr' (≥ 48h) and 'HSi-Sr' (≥ 72h), phenylalanine ammonia-lyase (PAL) activity peaked at 72h, and catalase (CAT) activity under 'Si-Sr' exceeded that under 'Sr'. Similarly, hydrogen peroxide (H2O2) was detected within 96h after Sr infection, whereas the malondialdehyde (MDA) content decreased. Si significantly increased jasmonic acid (JA) (500-600 pmol L⁻¹) and salicylic acid (SA) (900-1100 pmol L⁻¹) accumulation in peanut roots, with stronger induction in the Huayu103 cultivar under Si + Sr and Si + Sr treatments, peaking at 72-96h, whereas leaf levels remained comparatively low and less variable. Defense gene expression was activated, with greater induction of AhPAL, AhNPR1, and AhPR10 in the 'Luhua11' cultivar than in 'Huayu6103' at 96h; AhCSD1 increased in 'LSi-Sr' at 24h and 96h and in 'HSi-Sr' at 96h; AhAPX was upregulated in 'LSi-Sr' at 96h; and AhCAT was greater in 'LSi-Sr' (72h) and 'HSi-Sr' (96h). This study highlights S. indica as a potent biocontrol agent for managing peanut stem rot caused by S. rolfsii.

Downy mildew (DM), caused by Plasmopara viticola, is one of the most serious grapevine diseases. Resistant grapevines are a well-known tool for mitigating pathogen-caused damage. We evaluated 29 global grapevine cultivars from 7 species for the sensitivity to P. viticola. Chardonnay belonging to the sensitive species V. vinifera and Qingdahean belonging to the well-known resistant species V. riparia were chosen for further investigation on the resistance mechanism against DM. Unlike Chardonnay, Qingdahean exerted an inhibitory effect on stomatal targeting, suppression of stomatal closure, stomatal penetration of P. viticola, and the development of primary hyphae and haustoria during the early phase of infection, and contained higher levels of malondialdehyde (MDA), which was significantly increased by P. viticola infection, toxic to the pathogen and had an interfering effect on the stomatal targeting. Furthermore, Qingdahean resisted pathogen invasion through the rapid induction of guard cell death and the hypersensitive responses (HR) of other cell types. These findings suggest that resistance to P. viticola in V. riparia consists of layered stomatal immunity in addition to the well-known HR, which is overcome by the pathogen in V. vinifera.

The development and pathogenesis of rheumatoid arthritis (RA) are associated with ferroptosis. This study aims to investigate the regulatory role of ribonucleotide reductase subunit M2 (RRM2) in ferroptosis and the pathogenic phenotype of fibroblast-like synoviocytes (FLSs) in RA. Transcriptomic datasets associated with rheumatoid arthritis were analyzed to identify differentially expressed genes (DEGs), which were then intersected with known ferroptosis-related genes using a Venn diagram to determine overlapping candidates. The receiver operating characteristic (ROC) curve was utilized to evaluate the diagnostic value of key genes. The expression of RRM2 was silenced using short hairpin RNA transfection. Cell viability, motility, and invasive capacity were evaluated through the CCK-8 assay, scratch assay, Transwell, and ELISA assay, respectively. Inflammatory cytokines and ferroptosis-associated indicators were quantified using ELISA and specific biochemical detection kits. Additionally, the transcriptional and protein levels of genes linked to FLS function were analyzed. RRM2 was upregulated in tumor necrosis factor-alpha (TNF-α)-induced MH7A cells. Knockdown of RRM2 significantly inhibited TNF-α-induced cell proliferation, migration, invasiveness, and the release of pro-inflammatory cytokines in MH7A cells. Additionally, RRM2 knockdown induced ferroptosis, as evidenced by increased reactive oxygen species (ROS), ferrous iron (Fe2+), and malondialdehyde (MDA), alongside decreased expression of glutathione peroxidase 4 (GPX4) and solute carrier family 7 member 11 (SLC7A11). Further mechanistic analysis revealed that RRM2 led to nuclear factor-kappa B (NF-κB) signaling activation. RRM2 inhibits ferroptosis and enhances the pathogenic behavior of RA FLSs through activation of the NF-κB pathway, highlighting its pivotal contribution to RA development.

Acute lung injury is a common and fatal inflammatory condition in critically ill patients. Tetrahedral framework nucleic acids (TFNAs) have good potential for treating inflammatory diseases. The aim of this study was to use TFNAs in the treatment of acute lung injury (ALI) in mice to investigate the effect and possible mechanism. The characteristics of the TFNAs, including particle size and cellular uptake, were detected. TFNAs were subsequently used to treat an ALI mouse lung epithelial cells (MLE12) model with or without an autophagy inhibitor. Flow cytometry and Western blotting (WB) were performed to detect apoptosis and autophagy. The oxidative stress level was assessed by measuring the malondialdehyde (MDA) content, superoxide dismutase (SOD) activity and reactive oxygen species (ROS) content. A survival curve of the ALI model mice treated with TFNAs was constructed, and the lung injury score was assessed through pathological staining. The lung wet/dry weight ratio and inflammatory cytokine content in bronchoalveolar lavage fluid were measured and recorded. Transcription sequencing was performed to elucidate the biological processes associated with TFNA treatment. Finally, the regulatory effect of the cGAS-STING signalling pathway on TFNA-induced autophagy was explored. The synthesized TFNAs are typical nanomaterials. TFNAs significantly reduced the apoptosis rate according to flow cytometry and decreased the BAX/BCL2 ratio in MLE12 cells. Meanwhile, the autophagy level increased, as indicated by the increased expression of the ATG5, ATG7 and LC3II proteins when the cells were incubated with TFNAs. TFNAs could also inhibit the accumulation of ROS, increasing SOD activity and reducing the MDA content. Autophagy inhibitors can significantly inhibit the autophagy and antiapoptotic effects of TFNAs. In the ALI mouse model, TFNAs effectively reduced mortality, BALF inflammatory factor levels, pulmonary oedema, lung injury scores and neutrophil infiltration. The protective effect was significantly reduced with the use of autophagy inhibitors. In addition to autophagy, antigen processing and presentation, antiviral biological processes, and cytoplasmic membrane signal receptor complex functions were significantly upregulated, indicating that TFNAs might activate the cGAS-STING signalling pathway. Inhibition of the cGAS-STING signalling pathway effectively suppressed TFNA-induced autophagy. This study is the first to demonstrate that TFNAs protect MLE-12 cells against LPS-induced oxidative stress injury via autophagy activated by the nonclassical cGAS-STING signalling pathway. Therefore, TFNAs can attenuate ALI and improve patient prognosis in mice. These findings indicate that the cGAS-STING signalling pathway may be a basic mechanism contributing to various therapeutic immunologic effects. This study demonstrated the value of TFNAs in the treatment of ALI, with potential clinical translational value.

Wheat sharp eyespot, mainly caused by Rhizoctonia cerealis, is a destructive soil-borne disease that significantly threatens global wheat production, necessitating the development of sustainable control strategies. In this study, we isolated and identified an endophytic fungus, Penicillium oxalicum G11, from the roots of healthy wheat plants and comprehensively evaluated its antagonistic mechanisms and biocontrol potential against R. cerealis. In vitro assays demonstrated that G11 effectively inhibited R. cerealis growth through multiple mechanisms, including competition, antibiosis, and mycoparasitism. G11 exhibited strong antifungal activity, achieving average inhibition rates of 42.42% in confrontation culture, 45.96% via volatile metabolites, and up to 50.28% with fermentation filtrates. Microscopic analysis revealed that G11 hyphae coiled around R. cerealis hyphae, resulting in cellular degradation and further confirming its mycoparasitic behavior. Greenhouse experiments confirmed that G11 significantly reduced average disease incidence by 53.45% (solid fermentation product) and 49.07% (spore suspension), while promoting wheat growth and enhancing antioxidant enzyme activities. G11 inoculation increased catalase (CAT) activity by 1398.52 U·g⁻¹·min⁻¹ FW and peroxidase (POD) activity by 27456.89 U·g⁻¹·min⁻¹ FW, while significantly reducing malondialdehyde (MDA) content by 18.47 μmol·g⁻¹ FW, indicating improved cell membrane stability and stress resistance. Field trials further confirmed the biocontrol efficacy of G11, demonstrating a reduction in disease severity of 66.29% and an average wheat yield increase of 7.06% compared to nontreated controls. Additionally, G11 successfully colonized wheat roots, as verified by microscopic observation and molecular detection, highlighting its potential for long-term persistence and interaction within the wheat rhizosphere. This study represents the first report of P. oxalicum as a biocontrol agent against wheat sharp eyespot, providing a detailed mechanistic analysis of its antifungal properties. By integrating multiple suppression strategies-competition, antibiosis, and mycoparasitism-G11 demonstrates strong potential as a biocontrol alternative to conventional fungicides. Its effectiveness, combined with its environmentally friendly nature, suggests that G11 could serve as a promising microbial resource for sustainable disease management in wheat production, contributing to the reduction of chemical fungicide dependence and the advancement of eco-friendly agricultural practices.

Baicalein ameliorates high-altitude hypoxic lung injury via macrophage polarization remodeling by downregulating ALOX15 pathway in ferroptosis.

Background/Objectives: Liposomes and niosomes are established drug delivery systems, some of which have received FDA approval and demonstrated therapeutic efficacy. This study investigates a novel niosome formulation, utilizing two natural food-derived components, as a cost-effective alternative to traditional nanocarriers. The active pharmaceutical ingredient, calcium fructoborate (CF), possesses notable anti-inflammatory properties. The study aims to evaluate the efficacy of this novel natural niosome (NN) system, in comparison to existing nanocarrier formulations, in an ischemia–reperfusion (I/R) pain model. Methods: An acute ischemia/reperfusion injury model was employed to induce pain in 36 rats. The efficacy of the following treatments was assessed: standard CF, liposomal CF, niosomal CF, and natural niosomal CF. Efficacy was determined by quantifying the treatments’ ability to mitigate inflammation and oxidative stress in the kidneys, lungs, heart, and liver, and by evaluating potential organ damage through histopathological analysis. Results: The NN treatment significantly reduced malondialdehyde (MDA) and tumor necrosis factor-alpha (TNF-α) levels in the kidneys and liver compared to the other treatments (p < 0.05). In the kidney, NN treatment also significantly decreased creatinine levels relative to the other treatments (p < 0.01). The histopathological analysis of kidney tissue revealed that NN treatment attenuated tubular dilation, interstitial inflammation, and epithelial thinning. In the heart, liposomal treatment significantly increased MDA levels (p < 0.05) and decreased sialic acid levels (p < 0.05); however, no significant differences were observed in troponin levels (p > 0.05). In the lung, no significant differences in MDA, lactate, TNF-α, or sialic acid levels were detected among the treatment groups (p > 0.05). Conclusions: The natural niosome drug delivery system demonstrates potential as a therapeutic intervention for protecting and improving kidney and liver health. While liposomal treatment exhibited some adverse effects, it effectively suppressed inflammation. This study provides a foundation for future research and positions the NN drug delivery system as a promising, cost-effective alternative for inflammation-associated pathologies.

Intervertebral disc degeneration (IVDD) is a complex and multifactorial condition characterized by the progressive deterioration of the intervertebral discs. Ginsenoside Rg1, a bioactive compound isolated from Panax ginseng C.A.Mey., that has demonstrated promising therapeutic potential in the treatment of IVDD. This study employed a multi-faceted approach to investigate the therapeutic effects of ginsenoside Rg1 on IVDD. Initially, histopathology, magnetic resonance imaging (MRI) were performed in clinical IVDD patients. Subsequently, histopathology, safranin green staining, X-ray, and MRI were utilized to evaluate the efficacy of ginsenoside Rg1 in alleviating in a rat model in vivo. Transcriptomics and gene set enrichment analysis (GESA) were conducted, and a network pharmacology visualization of ginsenoside Rg1-ferroptosis key targets-pathways-IVDD was constructed, along with molecular docking of ginsenoside Rg1 and targets, to identify the signaling pathways and proteins associated with the therapeutic effects of ginsenoside Rg1 on alleviating IVDD. Additionally, an Hydrogen peroxide (H2O2)-induced degeneration model of nucleus pulposus cells (NP cells) was used to evaluate the efficacy of ginsenoside Rg1 in alleviating IVDD in vitro. Methods including lipid-reactive oxygen species (ROS) detection, enzyme-linked immunosorbent assay (ELISA), FerroOrange staining, and transmission electron microscopy were employed to validate the effect and mechanism of ginsenoside Rg1 on alleviating IVDD in vivo and in vitro. ML385, a nuclear factor erythroid 2-related factor 2 (NRF2) inhibitor, was used to reverse the effect of ginsenoside Rg1 in mitophagy and ferroptosis, respectively. The expression of proteins was assessed on immunochemical, immunofluorescence, and western blotting techniques. Significant ferroptosis was observed in the NP tissue of IVDD patients, with more effects in patients with higher imaging grades. Ginsenoside Rg1 significantly mitigated IVDD in rats and promoted intervertebral disc repair. Network pharmacology and transcriptomics analyses indicated the key targets of ginsenoside Rg1 for the treatment of IVDD, including NRF2, glutathione peroxidase 4 (GPX4), solute carrier family 7a member 11 (SLC7A11), and ferritin light chain 1 (FTL1). Molecular docking exhibited that ginsenoside Rg1 had good binding ability between ginsenoside Rg1 and these ferroptosis key targets. Ginsenoside Rg1 reduced the expression of ROS and malondialdehyde (MDA), decreased Fe2+ content, increased the expression of glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), and upregulated the expression of ferroptosis key proteins NRF2, GPX4, FTL1, and SLC7A11 in intervertebral disc tissues and NP cells. Treatment with ML385 attenuated the ginsenoside Rg1-induced upregulation of these proteins in NP cells, thereby promoting ferroptosis and reversing the protective effects of ginsenoside Rg1. Ginsenoside Rg1 can mitigate IVDD by inhibiting ferroptosis in NP cells. The NRF2/GPX4 pathway was validated as the key ferroptosis pathway through which ginsenoside Rg1 exerts its therapeutic effects on IVDD.

ABSTRACT Cadmium chloride (CdCl₂), a widespread environmental contaminant, poses serious risks to food safety and human health by disrupting endocrine balance, impairing hematological parameters, and damaging reproductive organs. This study assessed the protective efficacy of silver nanoparticles (Ag NPs) synthesized using Helianthemum lippii phytochemicals against CdCl₂-induced toxicity in male Wistar rats. Animals were divided into four groups: control, CdCl₂-exposed, Ag NPs-treated, and CdCl₂-exposed followed by Ag NPs post-treatment. CdCl₂ significantly reduced free triiodothyronine (FT3: 3.95 ± 0.01 pmol/L) and free thyroxine (FT4: 18.99 ± 0.21 pmol/L), while elevating thyroid-stimulating hormone (TSH: 0.0055 ± 0.00087 µU/mL). It also induced anemia, lowering red blood cell count (RBC: 6.37 ± 0.14 × 106/µL) and hemoglobin (Hb: 12.27 ± 0.37 g/dL). Post-treatment with phytochemical-loaded Ag NPs restored FT3 and FT4 by 140% and 160%, respectively, and normalized TSH. Oxidative stress was alleviated, with malondialdehyde (MDA) reduced by 55% (0.33 ± 0.03 nmol/mg protein). Histopathological analysis confirmed testicular regeneration with a 30% decrease in inflammation and structural injury. These findings demonstrate that H. lippii-derived Ag NPs possess strong antioxidants, endocrine-protective, and cytoprotective potential against cadmium toxicity.

Citral is an active compound of lemongrass oil which has been reported to have anti-inflammatory effects. This study investigates, for the first time, the simultaneous protective effects of citral on both liver and kidney in a rat model of lipopolysaccharide (LPS)-induced oxidative stress and metabolic dysfunction, a condition relevant to sepsis-associated multi-organ injury. Male rats were divided into six groups of six animals each pretreated orally with citral (10, 20, and 40 mg kg-1, body weight (b.w.)) for 7 days before LPS intoxication (8 mg kg-1, intraperitoneal (i.p.)). Citral significantly prevented oxidative damage induced by LPS. This was evidenced by the decrease in elevated levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2), restoration of the enzymatic antioxidant (catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx)), and non-enzymatic defenses (glutathione (GSH) and thiol groups). In addition, citral improved liver and kidney function markers, as shown by decrease levels of aspartate transaminase (AST), alanine transaminase (ALT), bilirubin, urea, creatinine, and uric acid levels, and also stabilized lipid profiles. Inflammatory markers such as C-reactive protein (CRP) and alkaline phosphatase (ALP) were similarly mitigated. Citral gives strong protection against LPS-induced hepatorenal injuries, likely mediated through its antioxidant, lipid regulatory and anti-inflammatory actions. These results highlight citral's translational potential as a natural therapeutic agent for preventing or treating endotoxin-mediated organ damage, suggesting promise for future clinical applications in sepsis or systemic inflammatory disorders. © 2025 Society of Chemical Industry.

The immune system is essential for human health. Traditional chemical immunomodulators often have toxic side effects; for example, long-term use of cyclophosphamide (CTX) can lead to severe adverse consequences. Stropharia rugosoannulata, a flavorful edible mushroom native to China, exhibits antioxidant, immunomodulatory, and antibacterial activity, with its polysaccharides being the key active components responsible for its immunomodulatory effects. Polysaccharides were extracted from S. rugosoannulata using a three-phase method to investigate their immunomodulatory activity and hepatoprotective effects in cyclophosphamide-induced mice. In vivo experiments showed that these polysaccharides significantly increased body weight, spleen index, and phagocytic index, regulated the CD4+/CD8+ ratio, and promoted secretion of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), immunoglobulin A (IgA), and immunoglobulin G (IgG). The mechanism involved activation of the TLR4/MyD88/NF-κB signaling pathway, effectively enhancing immune function. Regarding hepatic protection, S. rugosoannulata polysaccharides (SRP) increased serum malondialdehyde (MDA) and decreased superoxide dismutase (SOD), alanine aminotransferase (ALT), and aspartate aminotransferase (AST) levels in immunosuppressed mice, reversing CTX-induced liver injury. Histopathological analysis confirmed that SRP ameliorated CTX-induced pathological changes, including single-cell necrosis in the jejunal mucosa and insufficient hematopoietic compensation, and reduced lymphocytes in splenic white pulp. This study provides a theoretical basis for developing and applying SRP as an immunomodulator or hepatoprotective agent, with potential value in functional food and pharmaceutical applications. © 2025 Society of Chemical Industry.

Background Eimeria infection in pigeons induces severe oxidative stress in intestinal tissues, disrupting the balance between oxidant and antioxidant systems and leading to cellular and physiological damage. The resin of Commiphora myrrha has long been recognized in traditional medicine for its therapeutic potential. Purpose This study evaluated the protective effect of methanolic C. myrrha resin extract (MYE) against oxidative stress and cellular injury induced by Eimeria labbeana -like infection in pigeons. Methods Twenty-five pigeons (300–380 g) were divided into five groups (G1–G5). Following infection, birds were treated daily with MYE. On day 8 post-infection, intestinal tissues were collected to assess oxidative stress markers, antioxidant enzyme activities, and inducible nitric oxide synthase (iNOS) expression via immunohistochemistry. Results Infection with E. labbeana -like markedly elevated intestinal levels of nitric oxide (NO), malondialdehyde (MDA), and hydrogen peroxide (H 2 O 2 ), indicating enhanced oxidative stress. MYE administration significantly reduced these markers compared to infected controls. Concurrently, MYE enhanced antioxidant defense by increasing catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH) activities. Moreover, MYE modulated iNOS expression, suggesting regulation of inflammation-associated oxidative pathways. Conclusion Methanolic extract of C. myrrha resin effectively mitigated oxidative and related intestinal issues induced by E. labbeana -like infection in pigeon intestines. These findings highlight its potential as a natural source of antioxidant and anticoccidial agents for managing avian coccidiosis.

ABSTRACT Background Osteonecrosis of the femoral head (ONFH) is a debilitating condition characterized by bone tissue necrosis due to vascular insufficiency, often triggered by corticosteroid use. Steroids are commonly employed in the management of autoimmune diseases, organ transplantation, and COVID-19. Early detection is crucial, as ONFH primarily affects young and middle-aged individuals and often progresses to femoral head collapse if untreated. Objective To evaluate the protective effects of Apelin-13 (Ap-13) on steroid-induced ONFH (SONFH) in a rat model. Methods Thirty-two female Sprague-Dawley rats were randomized into four groups: Control, Ap-13 only, ONFH, and ONFH + Ap-13. SONFH was induced using lipopolysaccharide (LPS) and methylprednisolone (MPS). The treatment group received daily intraperitoneal Ap-13 injections. At the fourth week, radiological, histopathological, immunohistochemical, and biochemical analyses were conducted on femoral heads. Results Micro-CT showed no significant differences in bone mineral density or trabecular parameters. Histopathology revealed increased osteonecrosis, empty lacunae, and vascular thrombosis in the ONFH group, which were significantly reduced in the ONFH + Ap-13 group (p < 0.05). Ap-13 decreased serum malondialdehyde (MDA) levels (p = 0.0002), reduced caspase-3 expression (p < 0.05), and elevated VEGF expression (p = 0.046), indicating reduced oxidative stress, apoptosis, and enhanced vascularization. Additionally, LDL and triglyceride levels were significantly lower in the Ap-13 treated group (p < 0.05). Conclusion Apelin-13 demonstrates protective effects against SONFH by reducing oxidative stress, apoptosis, and improving vascularization. It may represent a promising noninvasive therapeutic strategy for early-stage ONFH.

Introduction Phytohormone abscisic acid (ABA) plays a pivotal regulatory role in crop responses to abiotic stress. However, the specificities of the coordinated transcriptional and metabolic regulatory network in wheat under ABA signaling remain to be fully elucidated. Methods This study systematically investigated the regulatory effects of exogenous ABA on wheat germinating seeds through integrated physiological, transcriptomic, and metabolomic analyses. Results Physiological results demonstrated that low-concentration ABA (2 mg·L -1 ) promoted primary root elongation (12% increase vs. 0 mg·L -1 (CK)), whereas high concentrations (≥4 mg·L -1 ) significantly inhibited growth (40% root length reduction under 6 mg·L -1 ABA). Concurrently, electrolyte leakage, malondialdehyde (MDA) content, and catalase (CAT) activity markedly increased with ABA concentration ( P &amp;lt; 0.05), indicating aggravated oxidative stress. Transcriptomic profiling (CK vs. 6 mg·L -1 ABA) identified 854 differentially expressed genes (DEGs; 470 up-regulated/384 down-regulated). Gene Ontology (GO) enrichment revealed DEGs predominantly involved in “Cellular process”, “Metabolic process”, “Catalytic activity”, and “Transporter activity”. KEGG analysis highlighted activation of “Linoleic acid metabolism”, “Alpha-Linolenic acid metabolism”, “Glycolysis/Gluconeogenesis”, and “Biosynthesis of amino acids” pathways. Metabolomics detected 665 differentially accumulated metabolites (DAMs), with “Lipids”, “Organic acids”, and “Amino acids” exhibiting significant alterations. KEGG enrichment emphasized “benzoxazinoid biosynthesis” and “Nicotinate/nicotinamide metabolism”. Integrative multi-omics analysis uncovered 10 core pathways, such as “Glycolysis/Gluconeogenesis”, “Biosynthesis of amino acids”, and “Cysteine and methionine metabolism”, that orchestrating ABA stress responses. Notably, L-serine and the genes TraesCS3A02G276100 and TraesCS5A02G398300 were recurrently implicated in multiple pathways, indicating their function as key network nodes. Discussion This study elucidates the molecular mechanisms by which wheat adapts to ABA stress through dynamic reprogramming of its metabolic and gene expression networks, thereby laying a theoretical foundation for developing future ABA-based seed treatment technologies or stress-resistant breeding strategies.

Background Cardioprotection is an important aspect of preventive medicine. Quercetin, a plant-derived flavonoid with antioxidant and anti-inflammatory properties, has been linked to reduced cardiovascular risk. Objective To investigate the cardioprotective effects of quercetin in rats with traumatic cardiac injury (TCI). Methods Fifty-two Wistar Albino rats were randomly divided into six groups: control ( n = 7); TCI only ( n = 9); TCI + DMSO ( n = 6); and TCI + quercetin at 10, 20, or 40 mg/kg ( n = 9 each). Quercetin or DMSO was given intraperitoneally at 0.5, 12, and 24 h after trauma. Cardiac trauma was induced by dropping a standardized weight on the chest. Serum biochemical parameters (GPx, SOD, IL-1, IL-33, sST2, MDA) were measured by ELISA, and histopathological damage was scored semiquantitatively. Data were analyzed using ANOVA or Kruskal–Wallis tests with p &amp;lt; 0.05 as significant. Results GPx elevation was detected only at 10 and 20 mg/kg (vs. TCI; p &amp;lt; 0.05); 40 mg/kg was non-significant ( p &amp;gt; 0.05). Overall, IL-1 differed among groups ( p = 0.008), with no pairwise comparisons significant after correction (all p &amp;gt; 0.05). For IL-33, an overall group effect was observed ( p = 0.025), while adjusted pairwise tests did not show a consistent between-group pattern ( p &amp;gt; 0.05). In contrast, malondialdehyde (MDA) levels were significantly reduced, particularly at the highest dose of 40 mg/kg ( p &amp;lt; 0.05). Superoxide dismutase (SOD) and soluble suppression of tumorigenicity-2 (sST2) levels showed no significant differences among groups ( p &amp;gt; 0.05). Histopathological evaluation demonstrated that quercetin mitigated myocardial degeneration, inflammatory infiltration, edema, vascular congestion, hemorrhage, and necrosis in a dose-dependent manner, with the most pronounced protective effects observed at 40 mg/kg ( p &amp;lt; 0.05). Conclusions Quercetin, especially at 40 mg/kg, may help prevent secondary cardiac injury after trauma by reducing oxidative stress and limiting histopathological damage. These results support quercetin's cardioprotective potential and warrant confirmation in larger preclinical models with broader designs.

Emerging evidence suggests that TBI triggers ferroptosis, and dexmedetomidine (Dex) has a neuroprotective effect. This study aimed to explore the underlying mechanism of function of Dex in ferroptosisi after TBI. TBI model was established using the modified Feeney's weight drop injury method. Our experiment included the assessment of lesion volume by hematoxylin and eosin (HE) staining, the evaluation of the expression levels of ferroptosis-related proteins NRF2, HO-1, GPX4, FPN1, and TRFC by Western blotting (WB), the morphological changes via transmission electron microscopy (TEM), the increase in reactive oxygen species (ROS) through the measurement of malondialdehyde (MDA), the expression of HO-1 and GPX4 in the hippocampal tissues by immunofluorescence staining (IF), the behavioral assay by the Morris water maze (MWM) test and the open field test (OFT). Dex could alleviate the cognitive impairment in TBI mice and reduce ferroptosis after TBI. Dex could promote the nuclear translocation of NRF2 and enhance the expression of downstream HO-1, xCT, and GPX4, thereby inhibiting ferroptosis of neuronal cells. In addition, ML385 inhibited the expression of NRF2 and then reversed the neuroprotective effect of Dex. Dex alleviates ferroptosis and oxidative stress responses after TBI in mice through the NRF2/HO-1/GPX4 pathway, thus relieving the cognitive impairment in mice after TBI.

Background: Elevated lipoprotein(a) (Lp(a)) levels are causally and independently associated with increased cardiovascular (CV) risk. EPA administered as icosapent ethyl (IPE) reduced CV events in high-risk, statin-treated patients (REDUCE-IT), including those with elevated Lp(a) levels. The mechanism of action may be related to reduced lipoprotein oxidation, including Lp(a), resulting in endothelial cell (EC) stress reduction. Hypothesis: We hypothesized that EPA attenuates Lp(a) oxidation – possibly by scavenging free radicals – leading to reduced EC stress response and related protein expression. Methods: Lp(a) was enriched to &gt;50% of total ApoB-containing (LDL) particles in plasma from patients with elevated levels following isopycnic centrifugation. Lp(a)-enriched fractions were incubated with EPA (Lp(a) + EPA, 50 µM) or equivolume vehicle (Lp(a) + veh) at 37°C for 30 min followed by oxidation with CuSO 4 (20 µM). After 2 h, human umbilical vein ECs (HUVECs) were incubated with Lp(a) + EPA or Lp(a) + veh for 8 h. Cell lysate samples were then analyzed by global LC/MS-based proteomics. Between group protein changes &gt;1-fold and a false discover rate (FDR)-adjusted p &lt;0.05 were considered significant. Lp(a) oxidation levels were characterized by both lipid hydroperoxide (LOOH) formation and malondialdehyde (MDA) using colorimetric assays. Results: EPA significantly attenuated Lp(a)-enriched oxidation through 2 h compared with vehicle-treated control, including 8% and 61% reduction of LOOH and MDA, respectively, both p &lt;0.001. A total of 20 proteins were significantly modulated by Lp(a) + veh relative to control. Among these, Lp(a) + veh induced increased expression of heat shock protein (HSP) 70 kDa (3.8-fold) along with its co-chaperones HSP 105/110 kDa (1.5-fold) and Bcl-2-associated athanogene 3 (BAG3, 1.5-fold). Lp(a) + veh also increased expression of matrix metalloproteinase-1 (MMP-1, 1.6-fold) and antioxidant response proteins heme oxygenase-1 (HO-1, 2.6-fold) and p62 (1.7-fold). EPA treatment of Lp(a) prior to oxidation limited these protein changes as none were significantly modulated relative to control. Conclusions: EPA attenuated Lp(a)-enriched oxidation over time, which resulted in differential expression of proteins involved in HUVEC inflammatory responses. Inhibition of Lp(a) oxidation by EPA, administered as IPE, may reduce vascular dysfunction and inflammation, thereby contributing to lower CV risk in patients with elevated Lp(a) levels.

Background Our goal was to assess if febuxostat (FEB) could prevent ovarian damage caused by cyclophosphamide (CP). Material and methods Four sets were created: control group, FEB group: received FEB 10 mg/kg orally for 14 days, CPgroup: a single ip dose of CP (200 mg/kg) at 8th day and CP + FEB group. Serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), anti-mullerian hormone (AMH), malondialdehyde (MDA), total antioxidant capacity (TAC), interluken-6 (IL-6), tumor necrosis factor alpha (TNF-α), Nod-like receptor protein 3 (NLRP3) were estimated. Apoptotic Bcl-2-associated protein x (Bax) and anti-apoptotic B-cell leukemia/lymphoma 2 protein (Bcl2) gene expression were measured. Histological alterations and immuno-expression of nuclear factor-kappa B (NF-κB) and toll like receptor4 (TLR4) were assessed. Results FSH, LH, MDA, IL-6, TNF-α, NLRP3 levels, Bax and Bax/Bcl-2 ratio gene expression, NF-κB and TLR4 immuno-expression were all significantly elevated in the CP group. AMH, TAC levels and Bcl-2 gene expression have significantly decreased. Every metric indicated a notable improvement with FEB. Conclusion: By controlling the TLR4/NF-Κb/NLRP3 signaling pathway, FEB has strong mitigating effects against oxidative stress, inflammatory processes, and apoptosis that result from CP-induced ovarian toxicity.