Search Results (59)

The metalloid arsenic (As) and the metals lead (Pb) and mercury (Hg), which together we call the “Toxic Triad”, are among the pollutants of greatest global concern, harming the health of millions of people and contributing to biodiversity loss. The widespread distribution of As, Pb and Hg facilitates the exposure of humans and other species to these elements simultaneously, potentially amplifying their individual toxic effects. While As, Pb and Hg are well established as toxic elements, the mechanisms by which they interact with genetic material and impact the health of various species remain incompletely understood. This is particularly true regarding the combined effects of these three elements. In this context, the objective of this work was to perform a toxicogenomic analysis of As, Pb and Hg to highlight multiple aspects of element-gene interactions, in addition to revisiting information on the genotoxicity and carcinogenicity of the Toxic Triad. By using The Comparative Toxicogenomics Database, it was possible to identify that As interacts with 7666 genes across various species, while Pb influences 3525 genes, and Hg affects 692 genes. Removing duplicate gene names, the three elements interact with 9763 genes across multiple species. Considering the top-20 As/Pb/Hg-interacting genes, catalase (CAT), NFE2 like bZIP transcription factor 2 (NFE2L2), caspase 3 (CASP3), heme oxygenase (HMOX1), tumor necrosis factor (TNF), NAD(P)H quinone dehydrogenase 1 (NQO1) and interleukin 6 (IL6) were the most frequently observed. In total, 172 genes have the potential to interact with the three elements. Gene ontology analysis based on those genes evidenced that the Toxic Triad affects several cellular compartments and molecular functions, highlighting its effect on stimulation of toxic stress mechanisms. These 172 genes are also associated with various diseases, especially those of the urogenital tract, as well as being related to biological pathways involved in infectious diseases caused by viruses, bacteria and parasites. Arsenic was the element with the best-substantiated genotoxic and carcinogenic activity. This article details, through a toxicogenomic approach, the genetic bases that underlie the toxic effects of As, Pb and Hg. Full article

: Negative energy balance (NEB) in dairy cows induces excessive lipolysis, leading to elevated levels of β-hydroxybutyric acid (BHBA), which, when accumulated, can cause liver damage. Rutin (RT), a natural flavonoid with antioxidant and anti-inflammatory properties, has demonstrated potential hepatoprotective effects; however, its ability to mitigate BHBA-induced hepatocellular injury in calves remains unclear. This study first assessed the impact of various BHBA concentrations on oxidative stress in calf hepatocytes, then explored the protective effects and underlying mechanisms of RT, and finally employed untargeted metabolomics to further elucidate RT’s mode of action. The results showed that exposure to 1.2 mM BHBA significantly increased malondialdehyde (MDA), nitric oxide (NO) contents, and reactive oxygen species (ROS) levels, while markedly decreasing glutathione (GSH) content and catalase (CAT) activity compared with the blank control. Notably, pretreatment with 100 μg/mL RT resulted in the greatest increase in GSH contents (180%) compared to BHBA treatment alone, while 150 μg/mL RT led to the most pronounced reduction in MDA contents (220%). Furthermore, BHBA treatment significantly upregulated the expression of Kelch-like ECH-associated protein 1 (Keap1) and downregulated nuclear factor erythroid 2-related factor 2 (Nrf2), NAD(P)H quinone dehydrogenase 1 (NQO1), and heme oxygenase-1 (HO-1) at both the mRNA and protein levels. These alterations were effectively reversed by pretreatment with 100 μg/mL RT. Non-targeted metabolomics identified 1525 metabolites in total. Based on OPLS-DA, metabolites with a variable importance in projection (VIP) > 1 and p < 0.05 were considered significantly altered. Compared with the blank control, BHBA treatment upregulated 47 metabolites—including 8-hydroxy-2′-deoxyguanosine, 3-hydroxyisovaleric acid, and N-palmitoyl-sphingosine—and downregulated 58 metabolites, such as betaine, linolenic acid, and arachidonic acid. In contrast, RT pretreatment upregulated 207 metabolites relative to the BHBA treatment, including linolenic acid, taurocholic acid, and 4-hydroxybenzoic acid, and downregulated 126 metabolites, including 3-hydroxyisovaleric acid, 8-hydroxy-2′-deoxyguanosine, and pyruvaldehyde. Pathway enrichment analysis indicated that RT alleviated BHBA-induced hepatocyte injury primarily by modulating the fatty acid degradation pathway. In summary, RT mitigated BHBA-induced oxidative stress in calf hepatocytes by regulating the Keap1/Nrf2 signaling pathway and further exerted protective effects through metabolic reprogramming. Full article

Although sepsis-induced acute kidney injury (AKI) is associated with significant morbidity and mortality, its treatment remains unresolved. Oxidative stress and inflammation are key elements in the pathomechanism of AKI. Therefore, in the present study, we investigated the role of DJ-1 protein, known for its antioxidant and anti-inflammatory properties in an animal model of lipopolysaccharide (LPS)-induced AKI. The presence of DJ-1 was detected by immunofluorescence staining in mice kidney samples, human embryonic kidney cells (HEK-293), and peripheral blood mononuclear cells (PBMCs). To investigate DJ-1 functions, Compound-23, a specific DJ-1-binding and preserving compound (CAS: 724737-74-0), was used in vitro and in vivo. Compound-23 reduced the H₂O₂-induced reactive oxygen species (ROS) production of the HEK-293 cells, and their LPS- or H₂O₂-induced death, as well. In accordance, Compound-23 decreased the mRNA expression of the oxidative stress markers NAD(P)H quinone dehydrogenase 1 (NQO1) and glutamate-cysteine ligase (GCLC) in the LPS-treated, and NQO1 in the H₂O₂-treated cells. Moreover, Compound-23 reduced the H₂O₂- and LPS-induced mRNA expression of inflammatory cytokine interleukin 6 (IL6) in both HEK-293 and PBMCs. Using the mice model of LPS-induced AKI, we demonstrated that Compound-23 treatment improved the renal functions of the mice. In addition, Compound-23 decreased the renal mRNA expression of kidney injury molecule 1 (Kim1), neutrophil gelatinase-associated lipocalin (Ngal), Nqo1, Gclc, and Il6 in the LPS-treated mice. Our study revealed that compounds protecting DJ-1 functions may protect the kidney from LPS-induced damage, suggesting that DJ-1 could be a potential drug target for sepsis-induced AKI therapy. Full article

Background: Oxidative stress is a key therapeutic target in neurological disorders. As processing wastes from the peanut industry, peanut skins are great sources of antioxidants and possess potential in neuroprotection. Methods: We prepared a peanut skin extract (PSE) and investigated its protective effects against tert-butyl hydroperoxide (t-BHP)-induced oxidative injury in HT-22 neuronal cells. Results: PSE was rich in phenolic compounds (123.90 ± 0.46 mg GAE/g), comprising flavonoids (75.97 ± 0.23 mg RE/g) and proanthocyanidins (53.34 ± 1.58 mg PE/g), and displayed potent radical scavenging activities in chemical-based assays. In HT-22 cells, PSE pretreatment restored oxidative balance and endogenous antioxidant defense disrupted by t-BHP, as evidenced by significant reductions in ROS generation and lipid peroxidation levels, along with enhanced endogenous antioxidants. Specifically, 25 μg/mL PSE pretreatment reduced ROS levels by 53.03%, decreased MDA content by 78.82%, enhanced superoxide dismutase (SOD) activity by 12.42%, and improved the ratio of glutathione (GSH) to oxidized glutathione (GSSG) by 80.34% compared to the t-BHP group. Furthermore, PSE rescued mitochondrial membrane potential collapse, inhibited cytochrome c (Cyt.c) release, and prevented subsequent apoptotic death. Notably, the neuroprotective efficacy of PSE was comparable to that of edaravone, an approved neuroprotective drug. Mechanistic investigations combining network pharmacology and experimental validation revealed that the PI3K/Akt/Nrf2 signaling pathway played a pivotal role in mediating the neuroprotective effects of PSE. Compared to t-BHP-treated cells, 25 µg/mL PSE pretreatment significantly upregulated PI3K/Akt phosphorylation, the expression of Nrf2, and its downstream antioxidant proteins heme oxygenase-1 (HO-1) and NAD(P)H dehydrogenase quinone 1 (NQO1). Conclusions: Collectively, these findings demonstrate the potential of PSE as a natural protective agent against oxidative-related neurological disorders. Full article

Cellular senescence plays a crucial role in skin aging, with senescent dermal fibroblasts contributing to reduced skin elasticity and increased inflammation. This study investigated the potential of Ganoderma lucidum (Reishi) ethanol extract to modulate the senescent phenotype of human dermal fibroblasts. Reishi powder of two different vendors was used. The extract was produced by extracting the Reishi powder for at least three weeks in 40% ethanol at room temperature. Etoposide-induced senescent fibroblasts were treated with Reishi extracts from two commercial sources for 14 days. Gene expression analysis was performed using qPCR to assess senescence makers, antioxidant defense, and extracellular matrix remodeling. Results showed that Reishi extracts significantly upregulated antioxidant and cytoprotective genes, including Heme oxygenase 1 (HO-1), γ-Glutamylcysteine synthetase (γGCS-L), and NAD(P)H dehydrogenase [quinone] 1 (NQO1), compared to untreated controls. Importantly, Reishi treatment suppressed the expression of p16^INK4a, a key marker of cellular senescence, while transiently upregulating p21^Cip1. The extracts also demonstrated potential senolytic properties, reducing the percentage of senescent cells as measured by senescence-associated β-galactosidase staining. However, Reishi treatment did not mitigate the upregulation of MMP1 and IL-8 in one Reishi treatment group, indicating differences in the preparations of different vendors. These findings suggest that Ganoderma lucidum extract may help alleviate some aspects of cellular senescence in dermal fibroblasts, primarily through enhanced antioxidant defense and cytoprotection, potentially offering a novel approach to combat skin aging. Full article

Backgrounds/Objectives: Following previous findings on high-salt (HS)-intake-related increase of oxidative stress, this study explored whether carnosine (CAR; β-alanyl-L-histidine), a reactive oxygen species (ROS) scavenger, enhanced antioxidative defence and vascular function following HS, potentially via the NRF2 or HIF-1α signalling pathway. Methods: Sprague Dawley rats (64, 8–10 weeks old, both sexes) were divided into four groups (n = 6/group): CTRL (0.4% NaCl), HS (4% NaCl for 7 days), CTRL + CAR (0.4% NaCl and 150 mg/kg/day oral CAR supplementation), and HS + CAR (4% NaCl and CAR). Acetylcholine-induced relaxation (AChIR) and hypoxia-induced relaxation (HIR) were evaluated in norepinephrine-precontracted (NE, 10⁻⁷ M) aortic rings. HIR was also tested with NRF2 (ML-385, 5 × 10⁻⁶ M) and HIF-1α (LW6, 10⁻⁴ M) inhibitors. Gene expression of superoxide dismutases 1, 2, and 3 (SOD1, 2 and 3), glutathione peroxidases (GPx1 and 4), catalase (CAT), NRF2, and NAD(P)H dehydrogenase (quinone 1) (NQO1) in aortic tissue was measured by RT-qPCR. Ferric reducing antioxidant power (FRAP) and advanced oxidation protein products (AOPPs) assays were performed on serum samples. All experimental procedures conformed to the European Guidelines (directive 86/609) and were approved by the local and national Ethical Committees (#2158-61-46-23-36, EP355/2022). Results: HS impaired AChIR and HIR, both preserved by CAR. NRF2 and HIF-1α inhibitors suppressed HIR in the HS and HS + CAR groups. CAR significantly increased SOD1 and 2, NRF2, and NQO1 expression and SOD activity compared to the CTRL and HS groups. GPx1 and GPx4 were upregulated in HS + CAR compared to HS. CAR prevented an increase in AOPPs, which were elevated in HS, while FRAP was highest in HS + CAR. Conclusions: Carnosine enhances antioxidative defence by upregulating antioxidant enzymes and activities and preserves vascular relaxation, likely via NRF2 signalling. Full article

The increasing incidence of colorectal cancer and inflammatory diseases poses a major health concern, with oxidative stress playing a significant role in the onset of these pathologies. Factors such as excessive consumption of sugar-rich and fatty foods, synthetic food additives, pesticides, alcohol, and tobacco contribute to oxidative stress and disrupt intestinal homeostasis. Functional foods arise as a potential tool to regulate redox balance in the intestinal tract. Herbs (such as Thymus spp.) have long been screened for their antioxidant properties, but their use as antioxidants for medicinal purposes requires validation in biological models. In this study, we addressed the potential antioxidant protection and preventive effects of extracts from two thyme species at the intestinal level, as well as their molecular mechanisms of action. Caco-2 cells were pre-exposed (4 h) to aqueous (AD) and hydroethanolic (HE) extracts of Thymus carnosus and Thymus capitellatus, followed by a recovery period in culture medium (16 h), and then treated with tert-butyl-hydroperoxide (TBHP; 4 h), before analyzing cell viability. The effect of the extracts’ main components was also analysed. Cellular oxidative stress, cell-death markers, and the expression of antioxidant-related proteins were evaluated using flow cytometry on cells pre-exposed to the AD extracts and salvianolic acid A (SAA). Results showed that pre-exposure to AD extracts or SAA reduced TBHP-induced oxidative stress and cell death, mediated by increased levels of nuclear factor erythroid 2-related factor 2 (Nrf2) protein. The protective activity of T. capitellatus AD extract was shown to be dependent on NAD(P)H quinone dehydrogenase 1 (NQO1) protein expression and on increased glutathione (GSH) content. Furthermore, ursolic acid induced cytotoxicity and low cellular antioxidant activity, and thus the presence of this triterpenoid impaired the antioxidant effect of HE extracts. Thus, AD extracts show high potential as prophylactic dietary agents, while HE extracts arise as a source of nutraceuticals with antioxidant potential. Full article

Oxidative stress frequently contributes to intestinal barrier injury in animals and humans. It was reported that both Selenomethionine (SeMet) and allicin exhibit protective effects against a range of diseases caused by oxidative stress. This study aimed to investigate the synergistic antioxidant effects and underlying mechanisms of SeMet and allicin on a H₂O₂-induced intestinal barrier injury model using IPEC-J2 cells and mice. The results showed that H₂O₂ induced severe oxidative stress, including a decrease in cell viability, antioxidant level, migration capacity, and cell integrity. SeMet and allicin exhibited significant synergistic anti-oxidative effects on intestinal epithelial cells. The combined use of SeMet and allicin increased SOD activity, GSH content, and GSH/GSSG ratio while decreasing MDA, NO, and ROS content levels. Furthermore, we found that SeMet and allicin synergistically activated the nuclear factor erythroid-related factor 2 (Nrf2)-NAD(P)H dehydrogenase [quinone] 1 (NQO1) signaling pathway and down-regulated endoplasmic reticulum stress (ER stress)-related proteins. However, the synergistic antioxidative and intestinal barrier protective effects of SeMet and allicin were abolished by Nrf2 inhibitor ML385 in vitro and in vivo. In conclusion, SeMet and allicin synergistically attenuate intestinal barrier injury induced by excessively oxidative stress through the activation of the Nrf2 signaling pathway and inhibition ER stress. These findings support that the combined use of SeMet and allicin could enhance antioxidative properties and alleviate intestinal injury in further clinical practice. Full article

The betel nut is one of the most widely consumed addictive substances in the world after nicotine, ethanol, and caffeine. Arecoline is an active ingredient from the areca nut. It has many pharmacological effects and can affect the central nervous system. In this study, we found that arecoline can relieve fatigue behavior. Objective: This research aims to estimate the anti-fatigue effects of arecoline and explore its underlying mechanisms using a murine model of central fatigue precipitated by sleep deprivation (SD). Methods: Seventy-two male C57BL/6 mice were randomly assigned to six groups: a control group, an SD-induced fatigue model group, a group that received Rhodiola Rosea capsules (2.5 mg/kg), and three arecoline groups, which were administered at low, medium, and high doses (10, 20, and 40 mg/kg, respectively). Following 28 days of continuous administrations, the effects of arecoline on mouse fatigue-related behaviors were assessed by behavioral tests, including grip strength, rotarod performance, and weight-bearing swimming endurance. The release levels of the related biochemical markers were measured by enzyme-linked immunosorbent assays (ELISAs). Western blotting was employed to quantify the expression levels of nuclear factor erythroid 2-related factor (Nrf2), Kelch-like ECH-associated protein 1 (Keap1), heme oxygenase 1 (HO-1), sequestosome-1 (p62), and NADPH quinone oxidoreductase 1 (NQO1) in the gastrocnemius muscle. Results: Arecoline administration notably enhanced grip strength, delayed the onset of fatigue as evidenced by extended latencies in rotarod tests, and increased the duration of weight-bearing swimming in mice. In the elevated plus maze, arecoline obviously decreased both the number of entries and the total distance traveled in the open arms. Arecoline markedly decreased the contents of creatine kinase, blood urea nitrogen, lactate dehydrogenase, triglycerides, and cholesterol in the serum, while it elevated the levels of total testosterone, lactate dehydrogenase, and immunoglobulin G. Furthermore, it significantly increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase in the gastrocnemius muscle, reduced malondialdehyde levels, augmented hippocampal SOD and CAT activity, and elevated glycogen stores in both liver and muscle tissues. Neurotransmitter levels showed significant increases, cytokine levels were markedly reduced, and the expressions of Nrf2, Keap1, NQO1, p62, and HO-1 in brain tissues were significantly upregulated. Conclusions: This study demonstrates that arecoline has anti-fatigue activity, and the specific mechanisms are associated with elevating glucose and lipid metabolism levels, relieving oxidative stress damage, inhibiting neuroinflammatory response, and regulating neurotransmitter levels and the Keap1/Nrf2/HO-1 signaling pathway. The research provides a new direction for arecoline’s potential in preventing and improving fatigue. Full article

Limosilactobacillus fermentum (L. fermentum) is widely used in industrial food fermentations, and its probiotic and health-promoting roles attracted much attention in the past decades. In this work, the probiotic potential of L. fermentum 664 isolated from Chinese fermented pickles was assessed. In addition, the anti-inflammatory properties and mechanisms were investigated using lipopolysaccharide (LPS)-stimulated RAW264.7 cells. Results indicated that L. fermentum 664 demonstrated excellent acid and bile salt tolerance, adhesion capability, antimicrobial activity, and safety profile. L. fermentum 664 downregulated the release of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β), and cyclooxygenase-2 (COX-2) stimulated with LPS. Moreover, L fermentum 664 inhibited the nuclear translocation of the nuclear factor κB (NF-κB) and the activation of mitogen-activated protein kinases (MAPKs) induced by LPS. This action was associated with a reduction in reactive oxygen species (ROS) levels and an enhanced expression of heme oxygenase-1 (HO-1) protein. Additionally, whole genome sequencing indicated that L. fermentum 664 contained genes that encode proteins with antioxidant and anti-inflammatory functions, including Cytochrome bd ubiquinol oxidase subunit I (CydA), Cytochrome bd ubiquinol oxidase subunit II (CydB), and NAD(P)H dehydrogenase quinone 1 (NQO1). In conclusion, our study suggested that L. fermentum 664 has the potential to become a probiotic and might be a promising strategy for the prevention of inflammation. Full article

Porphyromonas gingivalis (Pg), a Gram-negative oral pathogen, promotes and accelerates periodontitis-associated gut disorders. Intestinal epithelial barrier dysfunction is crucial in the pathogenesis of intestinal and systemic diseases. In this study, we sought to elucidate the protective role of cinnamaldehyde (CNM, an activator of Nrf2) against P. gingivalis (W83) and Pg-derived lipopolysaccharide (Pg-LPS) induced intestinal epithelial barrier dysfunction via antioxidative mechanisms in IEC-6 cells. IEC-6 (ATCC, CRL-1592) cells were pretreated with or without CNM (100 µM), in the presence or absence of P. gingivalis (strain W83, 10⁹ MOI) or Pg-LPS (1, 10, and 100 µg/mL), respectively, between 0–72 h time points by adopting a co-culture method. Intestinal barrier function, cytokine secretion, and intestinal oxidative stress protein markers were analyzed. P. gingivalis or Pg-LPS significantly (p < 0.05) increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels expressing oxidative stress damage. Pg-LPS, as well as Pg alone, induces inflammatory cytokines via TLR-4 signaling. Furthermore, infection reduced Nrf2 and NAD(P)H quinone dehydrogenase 1 (NQO1). Interestingly, inducible nitric oxide synthase (iNOS) protein expression significantly (p < 0.05) increased with Pg-LPS or Pg infection, with elevated levels of nitric oxide (NO). CNM treatment suppressed both Pg- and Pg-LPS-induced intestinal oxidative stress damage by reducing ROS, MDA, and NO production. Furthermore, CNM treatment significantly upregulated the expression of tight junction proteins via increasing the phosphorylation levels of PI3K/Akt/Nrf2 suppressing inflammatory cytokines. CNM protected against Pg infection-induced intestinal epithelial barrier dysfunction by activating the PI3K/Akt-mediated Nrf2 signaling pathway in IEC-6 cells. Full article

Neutrophils are innate immune cells that play a key role in pathogen clearance. They contribute to inflammatory diseases, including diabetes, by releasing pro-inflammatory cytokines, reactive oxygen species, and extracellular traps (NETs). NETs contain a DNA backbone and catalytically active myeloperoxidase (MPO), which produces hypochlorous acid (HOCl). Chlorination of the DNA nucleoside 8-chloro-deoxyguanosine has been reported as an early marker of inflammation in diabetes. In this study, we examined the reactivity of different chlorinated nucleosides, including 5-chloro-(deoxy)cytidine (5ClC, 5CldC), 8-chloro-(deoxy)adenosine (8ClA, 8CldA) and 8-chloro-(deoxy)guanosine (8ClG, 8CldG), with the INS-1E β-cell line. Exposure of INS-1E cells to 5CldC, 8CldA, 8ClA, and 8CldG decreased metabolic activity and intracellular ATP, and, together with 8ClG, induced apoptotic cell death. Exposure to 8ClA, but not the other nucleosides, resulted in sustained endoplasmic reticulum stress, activation of the unfolded protein response, and increased expression of thioredoxin-interacting protein (TXNIP) and heme oxygenase 1 (HO-1). Exposure of INS-1E cells to 5CldC also increased TXNIP and NAD(P)H dehydrogenase quinone 1 (NQO1) expression. In addition, a significant increase in the mRNA expression of NQO1 and GPx4 was seen in INS-1E cells exposed to 8ClG and 8CldA, respectively. However, a significant decrease in intracellular thiols was only observed in INS-1E cells exposed to 8ClG and 8CldG. Finally, a significant decrease in the insulin stimulation index was observed in experiments with all the chlorinated nucleosides, except for 8ClA and 8ClG. Together, these results suggest that increased formation of chlorinated nucleosides during inflammation in diabetes could influence β-cell function and may contribute to disease progression. Full article

Triple-negative breast cancer (TNBC) has been clearly recognized as a heterogeneous tumor with the worst prognosis among the subtypes of breast cancer (BC). The advent and application of current small-molecule drugs for treating TNBC, as well as other novel inhibitors, among others, have made treatment options for TNBC more selective. However, there are still problems, such as poor patient tolerance, large administration doses, high dosing frequency, and toxic side effects, necessitating the development of more efficient and less toxic treatment strategies. High expression of Nrf2, a vital antioxidant transcription factor, often promotes tumor progression, and it is also one of the most effective targets in BC therapy. We found that in MDA-MB-231 cells and SUM159 cells, brusatol (BRU) combined with polydatin (PD) could significantly inhibit cell proliferation in vitro, significantly downregulate the expression of Nrf2 protein as well as the expression of downstream related target genes Heme Oxygenase-1 (HO-1) and NAD(P)H dehydrogenase, quinone 1 (NQO1), and promote reactive oxygen species (ROS) levels to further strengthen the anti-tumor effect. Furthermore, we discovered in our in vivo experiments that by reducing the drug dosage three times, we could significantly reduce tumor cell growth while avoiding toxic side effects, providing a treatment method with greater clinical application value for TNBC treatment. Full article

In the modern poultry industry, the application of novel phytogenic bioactive compounds with antioxidant potential aims to enhance productivity and quality and to minimize the stress of associated diseases. Herein, myricetin, a natural flavonoid, was evaluated for the first time on broiler chickens’ performance, antioxidants and immune modulating functions, and tackling avian coccidiosis. A total of 500 one-day-old chicks were divided into five groups. The negative (NC) and infected control (IC) groups were fed a control diet without additives, and the latter was infected with Eimeria spp. Groups supplemented with myricetin (Myc) were fed a control diet of Myc (200, 400 and 600 mg/kg diet each). On d 14, all chicks except those in NC were challenged with oocysts of mixed Eimeria spp. Significant improvements in the overall growth rate and feed conversion ratio were detected in the group that was fed 600 mg/kg, unlike the IC group. Notably, groups that were fed 400 and 600 mg/kg showed higher total meat antioxidant capacity with an inverse reduction in oxidative and lipid peroxidation biomarkers (hydrogen peroxide: H₂O₂; reactive oxygen species: ROS; Malondialdehyde: MDA). Of note, the upregulation of glutathione peroxidase; GSH-Px, catalase; CAT, superoxide dismutase; SOD, heme oxygenase-1; HO-1 and NAD(P)H dehydrogenase quinone 1 NQO1 genes in jejunum and muscle were prominently observed with increasing levels of supplemental Myc. At 21 dpi, the severity of coccoidal lesions (p < 0.05) induced by mixed Eimeria spp. and oocyst excretion were greatly reduced in the group that was fed 600 mg/kg of Myc. In the IC group, higher serum levels of C-reactive protein; CRP and nitric oxide; and NO and the upregulated expression of inflammatory biomarkers (interleukin-1β; IL-1β, interleukin-6; IL-6, tumor necrosis factor-α; TNF-α, chemotactic cytokines; CCL20, stromal cell-derived factor-1; CXCL13, and avian defensins; AvBD612) were subsided in higher levels in the Myc-fed groups. Taken together, these findings indicate the promising antioxidant role of Myc in modulating immune responses and reducing growth depression associated with coccidia challenges. Full article

Red blood cells are found within the abdominal aortic aneurysm (AAA), in the intraluminal thrombus (ILT), and in neovessels. Hemolysis promotes aortic degeneration, e.g., by heme-induced reactive oxygen species formation. To reduce its toxicity, hemoglobin is endocytosed by the CD163 receptor and heme is degraded by heme oxygenase-1 (HO-1). A soluble form (sCD163) is discussed as an inflammatory biomarker representing the activation of monocytes and macrophages. HO-1 and NAD(P)H quinone dehydrogenase 1 (NQO1) are antioxidant genes that are induced by the Nrf2 transcription factor, but their regulation in AAA is only poorly understood. The aim of the present study was to analyze linkages between CD163, Nrf2, HO-1, and NQO1 and to clarify if plasma sCD163 has diagnostic and risk stratification potential. Soluble CD163 was 1.3-fold (p = 0.015) higher in AAA compared to patients without arterial disease. The difference remained significant after adjusting for age and sex. sCD163 correlated with the thickness of the ILT (r_s = 0.26; p = 0.02) but not with the AAA diameter or volume. A high aneurysmal CD163 mRNA was connected to increases in NQO1, HMOX1, and Nrf2 mRNA. Further studies are needed to analyze the modulation of the CD163/HO-1/NQO1 pathway with the overall goal of minimizing the detrimental effects of hemolysis. Full article