Search Results (903)

(1) Background: The goal of the present study was to evaluate whether the supplementation with a multi-species probiotic in the diet of laying hens can change the microbiota and health status of the oviduct. (2) Methods: A total of 60 cages housing lightweight laying hens (36 weeks old) were randomly assigned to the following two different treatments: a control group fed a diet without probiotic, and a treatment group receiving diets supplemented with 50 g/ton of probiotics. The trial lasted for 26 weeks, after which five layers were slaughtered per treatment for oviduct (magnum) assessment, focusing on microbiome composition, oxidant and antioxidant status, and morphological analyses. Additionally, intestinal (jejunum) samples were collected to determine oxidant and antioxidant status. (3) Results: Probiotic supplementation resulted in lower counts of organisms from the RB41 order (p = 0.039) and Burkholderia genus (p = 0.017), and a total reduction in Bacillus and Corynebacterium (p = 0.050) compared to the control treatment. Genera Burkholderia (p = 0.017), Corynebacterium (p = 0.050), and Bacillus (p = 0.050) were also lower with the probiotic supplementation in relation to the control. Genera Epulopiscium (p = 0.089), Flavobacterium (p = 0.100), Ruminococcus (p = 0.089), and Staphylococcus (p = 0.100) tended to be lower in the probiotic group compared to the control. No significant differences were found between treatments for oviduct lesions. Probiotic treatment resulted in a higher protein thiol level in the intestine compared to the control (p < 0.001). However, the use of probiotics tended to reduce glutathione S-transferase levels in the oviduct compared to the control (p = 0.068). (4) Conclusions: These results suggest that dietary supplementation with probiotics can modulate the oviduct microbiota and improve the antioxidant status of laying hens, without causing tissue damage. Further research is warranted to explore the long-term implications of these changes on reproductive performance and egg quality. Full article

Oxidative stress significantly contributes to the exacerbation of brain damage during cerebral ischemia-reperfusion injury (CIR/I). In our previous study, purified cornel iridoid glycoside (PCIG), consisting of morroniside (MOR) and loganin (LOG), showed neuroprotective effects against CIR/I. To further explore the antioxidative effects and underlying molecular mechanisms, we applied PCIG, MOR, and LOG to rats injured by middle cerebral artery occlusion/reperfusion (MCAO/R) as well as H₂O₂-stimulated PC12 cells. Additionally, the molecular docking analysis was performed to assess the interaction between the PCIG constituents and Kelch-like ECH-associated protein 1 (Keap1). The results showed that the treated rats experienced fewer neurological deficits, reduced lesion volumes, and lower cell death accompanied by decreased levels of malondialdehyde (MDA) and protein carbonyl, as well as increased activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px). In H₂O₂-stimulated PC12 cells, the treatments decreased reactive oxygen species (ROS) production, mitigated mitochondrial dysfunction, and inhibited mitochondrial-dependent apoptosis. Moreover, the treatments facilitated Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) translocation into the nucleus and selectively increased the expression of NAD(P)H quinone oxidoreductase 1 (NQO-1) and heme oxygenase 1 (HO-1) through MOR and LOG, respectively. Both MOR and LOG demonstrated strong binding affinity to Keap1. These findings suggested that PCIG, rather than any individual components, might serve as a valuable treatment for ischemic stroke by activating the Nrf2/NQO-1 and Nrf2/HO-1 signaling pathway. Full article

The impact of Oedema Disease produced by Shiga toxigenic Escherichia coli (STEC) in swine is increasing in some production countries due to increasing limitations on treatment with antimicrobials and zinc oxide, either because of the increased prevalence of multi-resistant strains or because of legal restrictions. The main pathological effect of Shiga toxin 2e is represented by damage to the endothelial cells of the blood vessel walls, leading to liquid extravasation and oedema formation in multiple tissues. These oedemas are generally easily identifiable in acute clinical cases. However, disease caused by Shiga toxin can occur without any externally visible oedema in the pigs, as observed in the subclinical presentation of Oedema Disease. It also causes productive losses, so it is important to identify and/or diagnose cases to set up control measures in order to optimize production and health. This article includes a comprehensive review of lesions and signs caused by Shiga toxin toxicosis in pigs, as well as other insights about the aetiology and epidemiology of STEC in pigs, and the effect of Shiga toxin recombinant toxoid vaccines in reducing these clinical and subclinical signs under field conditions. Full article

Diabetes mellitus (DM) is one of the leading causes of death and disability worldwide and its prevalence continues to rise. Chronic hyperglycemia exposes patients to severe complications. Among these, diabetic vascular lesions are the most destructive. Their primary driver is the synergistic interaction between hyperglycemia-induced oxidative stress and chronic inflammation. This review systematically elucidates how multiple pathological pathways—namely, metabolic dysregulation, mitochondrial dysfunction, endoplasmic reticulum stress, and epigenetic reprogramming—cooperate to drive oxidative stress and inflammatory cascades. Confronting this complex pathological network, natural products, unlike conventional single-target synthetic drugs, exert multi-target synergistic effects, simultaneously modulating several key pathogenic networks. This enables the restoration of redox homeostasis and the suppression of inflammatory responses, thereby improving vascular function and delaying both microvascular and macrovascular disease progression. However, the clinical translation of natural products still faces multiple challenges and requires comprehensive mechanistic studies and rigorous validation to fully realize their therapeutic potential. Full article

Among the new strategies for managing diseases in agricultural crops is the application of metallic nanoparticles due to their ability to inhibit the development of phytopathogenic microorganisms and to induce plant defense responses. Therefore, this research evaluated the effects of silver (AgNPs), zinc oxide (ZnONPs), and silicon dioxide (SiO₂NPs) nanoparticles on symptom progression and physiological parameters in two pathosystems: Pseudomonas syringae pv. tomato (Psto) in tomato (pathosystem one, culturable pathogen) and Candidatus Liberibacter solanacearum (CaLso) in pepper plants (pathosystem two, non-culturable pathogen). For in vitro pathosystem one assays, SiO₂NPs did not inhibit Psto growth. The minimum inhibitory concentration (MIC) was 31.67 ppm for AgNPs and 194.3 ppm for ZnONPs. Furthermore, the minimum lethal concentration (MLC) for AgNPs was 100 ppm, while for ZnONPs, it was 1000 ppm. For in planta assays, ZnONPs, AgNPs, and SiO₂NPs reduced the number of lesions per leaf, but only ZnONPs significantly decreased the severity. Regarding pathosystem two, AgNPs, ZnONPs, and SiO₂NPs application delayed symptom progression. However, only AgNPs significantly reduced severity percentage. Moreover, treatments with AgNPs and SiO₂NPs increased the plant height and dry weight compared to the results for the control. Full article

Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. Our goal was to explore the protective effects of Prist against APAP-induced acute liver damage. Method: Mice were divided into six groups: control, Prist control, N-acetylcysteine (NAC) + APAP, APAP, and two Prist + APAP groups. Prist (0.4 and 0.8 mg/kg) was given for five days and APAP on day 5. Liver and blood samples were taken 24 h after APAP administration and submitted for different biochemical and molecular assessments. Results: Prist counteracted APAP-induced acute liver damage, as it decreased general liver dysfunction biomarkers, and attenuated APAP-induced histopathological lesions. Prist decreased oxidative stress and enforced hepatic antioxidants. Notably, Prist significantly reduced the genetic and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-II), p-phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (p-AKT), and the inflammatory cytokines: nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins-(IL-6 and IL-1β) in hepatic tissues. Additionally, the m-RNA and protein levels of the apoptotic Bcl2-associated X protein (BAX) and caspase-3 were lowered and the anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) was increased upon Prist administration. Conclusion: Prist ameliorated APAP-induced liver injury in mice via its potent anti-inflammatory/antioxidative and anti-apoptotic activities. These effects were mediated through modulation of NF-κB/iNOS/COX-II/cytokines, PI3K/AKT, and BAX/BCL-2/caspase-3 signaling pathways. Full article

Recent findings highlight that Reelin, a glycoprotein involved in neural development, synaptic plasticity, and neuroinflammation, plays some specific roles in neurodegenerative disorders associated with aging, such as age-related macular degeneration (AMD) and Alzheimer’s disease (AD). Reelin modulates synaptic function and guarantees homeostasis in neuronal-associated organs/tissues (brain and retina). The expression of Reelin is dysregulated in these neurological disorders, showing common pathways depending on chronic neurogenic inflammation and/or dysregulation of the extracellular matrix in which Reelin plays outstanding roles. Recently, the relationship between AMD and AD has gained increasing attention as they share many common risk factors (aging, genetic/epigenetic background, smoking, and malnutrition) and histopathological lesions, supporting certain pathophysiological crosstalk between these two diseases, especially regarding neuroinflammation, oxidative stress, and vascular complications. Outside the nervous system, Reelin is largely produced at the gastrointestinal epithelial level, in close association with innervated regions. The expression of Reelin receptors inside the gut suggests interesting aspects in the field of the gut–brain–eye axis, as dysregulation of the intestinal microbiota has been frequently described in neurodegenerative and behavioral disorders (AD, autism, and anxiety and/or depression), most probably linked to inflammatory, neurogenic mediators, including Reelin. Herein we examined previous and recent findings on Reelin and neurodegenerative disorders, offering findings on Reelin’s potential relation with the gut–brain and gut–brain–eye axes and providing novel attractive hypotheses on the gut–brain–eye link through neuromodulator and microbiota interplay. Neurodegenerative disorders will represent the ground for a future starting point for linking the common neurodegenerative biomarkers (β-amyloid and tau) and the new proteins probably engaged in counteracting neurodegeneration and synaptic loss. Full article

Gingival inflammation compromises the integrity of the gingival epithelium and the underlying tissues, highlighting the need for adjuvant therapies with immunomodulatory and healing properties. Casearia sylvestris, a medicinal plant known as guaçatonga, is traditionally used to treat inflammatory lesions. This study aimed to investigate the effects of C. sylvestris on the synthesis of pro- and anti-inflammatory, proteolytic, and antioxidant molecules and on wound healing in epithelial cells. A human telomerase-immortalized gingival keratinocyte cell line (TIGKs) was used, and cells were exposed to Escherichia coli lipopolysaccharide (LPS) in the presence and absence of C. sylvestris extract, its diterpene-concentrated fraction, and its clerodane diterpene casearin J for 24 h and 48 h. Gene expression and protein synthesis were analyzed by RT-qPCR and ELISA, respectively. Nitric oxide (NO) and NF-κB activation were analyzed by Griess reaction and immunofluorescence, respectively. Additionally, cell viability was evaluated by alamarBlue^® assay, and an automated scratch assay was used for wound healing. LPS significantly increased the expression of cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10, IL-17), proteases (MMP-1 and MMP-13), iNOS as well as NO synthesis, and triggered NF-κB nuclear translocation. It also reduced IL-4 expression, cell viability, and cellular wound repopulation. Treatment with C. sylvestris derivatives significantly abrogated all aforementioned LPS-induced effects by 80–100%. Furthermore, even at higher concentrations, C. sylvestris did not affect cell viability, thus proving the safety of its derivatives. C. sylvestris exerts anti-inflammatory, antiproteolytic, and antioxidant effects on gingival keratinocytes, highlighting its potential as a valuable adjunct in the prevention and treatment of periodontal diseases. Full article

Inflammatory bowel disease (IBD) is characterized by oxidative stress imbalance and intestinal barrier disruption. Reducing excessive ROS has become a promising therapeutic strategy. Compared with conventional polyphenols, nanomaterials offer greater stability and bioavailability for ROS scavenging. Here, ellagic acid (EA) was converted into uniform nanoparticles (EAs) with reactive oxygen scavenging capacity through horseradish peroxidase (HRP)-mediated oxidative polymerization and subsequently encapsulated in the anti-gastric acid hydrogel F-DP to obtain the hybrid system F-DP@EAs. EAs reduced ROS, MDA, NO, IL-1β, and TNF-α levels in vitro, while increasing IL-4 and IL-10 expression, thus alleviating inflammation. Herein, F-DP@EAs prolonged intestinal retention time and exerted superior protective effects in the DSS-induced colitis model. Oral F-DP@EAs lowered DAI, preserved colon length, increased glutathione (GSH) and superoxide dismutase (SOD), decreased NO and MDA, restored zonula occludens-1 (ZO-1), and reduced mucosal lesions. These findings demonstrate that combining nanoparticle and hydrogel technologies markedly enhances the preventive and protective efficacy of EA, highlighting F-DP@EAs as a promising candidate for future IBD therapy. Full article

Nonsteroidal anti-inflammatory drug-based therapies are the cause of 20–30% cases of gastric lesions in chronic users worldwide. Co-medication with omeprazole (OMP) is the most commonly used option to prevent these lesions, although this carries risks of its own; thus, alternatives are being explored, such as dietary antioxidant therapies. The objective of this study was to evaluate the gastroprotective activity of quinoa (Chenopodium quinoa Willd.) on ibuprofen (IBP)-induced gastric ulcers in a rat model. Quinoa cookies were formulated with heat-treated quinoa using microwave radiation. The intestinal bioaccessibility of phenols and flavonoids, and the antioxidant activity of microwaved quinoa cookies (MQCs) were notably higher than quinoa cookies without thermal treatment (RQCs): 132% TPC, 52% TFC, 1564% TEAC vs. 67% TPC, 24% TFC, and 958% TEAC, respectively. Basal diets were supplemented with MQCs (20%) and quercetin (Q, 0.20%) as a reference flavonoid and administered for 30 days. Gastric lesions were induced by intragastric IBP doses, with OMP treatment as a positive control. Gastric damage index (macroscopic study), histological score (microscopic study), and plasma antioxidant enzyme activity (SOD and CAT) were evaluated. Macroscopic results showed that the addition of MQCs, Q, and OMP decreased the gastric damage index (GDI) by 50%, 40%, and 3%, respectively, as compared to IBP (GDI 100%). Histological analyses showed neutrophil infiltration and congested blood vessels in IBP-treated tissues; in contrast, the experimental diet groups showed lower infiltration for MQC > OMP > Q, respectively. A significant increase in SOD and CAT enzyme activity was observed in the MQC and Q groups as compared to the IBP group. We conclude that a reduction in the GDI and histological score was observed in IBP-induced murine models fed diets containing 20% MQC and 0.20% Q, demonstrating a preventive gastroprotective effect. Full article

Background: Vitiligo, a chronic depigmentation disorder driven by oxidative stress and immune dysregulation, remains poorly understood mechanistically. The Keap1/NRF2/ARE pathway is critical for melanocyte protection against oxidative damage; however, the role of Cullin-3 (CUL3), a scaffold for E3 ubiquitin ligases that regulate NRF2 degradation, and its interplay with inflammatory mediators in vitiligo pathogenesis are underexplored. This study investigates CUL3, NRF2, and the associated regulatory networks in vitiligo, integrating clinical profiling and computational docking to identify therapeutic targets. Methods: A case-control study compared non-segmental vitiligo patients with age-/sex-matched controls. Lesional skin biopsies were analyzed by qRT-PCR for the expression of CUL3, NRF2, miRNA-146a, FOXP3, NF-κB, IL-6, TNF-α, and P53. Molecular docking was used to evaluate vitexin’s binding affinity to Keap1, validated by root mean square deviation (RMSD) calculations. Results: Patients with vitiligo exhibited significant downregulation of CUL3 (0.27 ± 0.03 vs. 1 ± 0.58; p = 0.013), NRF2 (0.37 ± 0.26 vs. 1 ± 0.8; p = 0.001), and FOXP3 (0.09 ± 0.2 vs. 1 ± 0.3; p = 0.001), alongside the upregulation of miRNA-146a (4.7 ± 1.9 vs. 1 ± 0.8; p = 0.001), NF-κB (4.7 ± 1.9 vs. 1 ± 0.5; p = 0.001), IL-6 (2.8 ± 1.5 vs. 1 ± 0.4; p = 0.001), and TNF-α (2.2 ± 1.1 vs. 1 ± 0.3; p = 0.001). P53 showed no differential expression (p > 0.05). Docking revealed a strong binding of vitexin to Keap1 (RMSD: 0.23 Å), mirroring the binding of the control ligand CDDO-Im. Conclusions: Dysregulation of the CUL3/Keap1/NRF2 axis and elevated miRNA-146a levels correlate with vitiligo progression, suggesting a role for oxidative stress and immune imbalance. Vitexin’s high-affinity docking to Keap1 positions it as a potential modulator of the NRF2 pathway, offering novel therapeutic avenues. This study highlights the translational potential of targeting the ubiquitin–proteasome and antioxidant pathways in the management of vitiligo. Full article

Metastases are the leading cause of cancer-related deaths. The spread of neoplasms involves multiple mechanisms, with metastatic tumors exhibiting molecular behaviors distinct from their primary counterparts. The key hallmarks of metastatic lesions include chromosomal instability, copy number alterations (CNAs), and a reduced degree of subclonality. Furthermore, metabolic adaptations such as enhanced glycogen synthesis and storage, as well as increased fatty acid oxidation (FAO), play a critical role in sustaining energy supply in metastases and contributing to chemoresistance. FAO promotes the infiltration of macrophages into the tumor, where they polarize to the M2 phenotype, which is associated with immune suppression and tissue remodeling. Additionally, the tumor microbiome and the action of cytotoxic drugs trigger neutrophil extravasation through inflammatory pathways. Chemoresistant neutrophils in the tumor microenvironment can suppress effector lymphocyte activation and facilitate the formation of neutrophil extracellular traps (NETs), which are linked to drug resistance. This article examines the genomic features of metastatic tumors, along with the metabolic and immunological dynamics within the metastatic tumor microenvironment, and their contribution to drug resistance. It also discusses the molecular mechanisms underlying resistance to chemotherapeutic agents commonly used in the treatment of metastatic cancer. Full article

The enzyme ABH2, one of nine human DNA dioxygenases of the AlkB family, belongs to the superfamily of Fe(II)/α-ketoglutarate-dependent dioxygenases and plays a crucial role in the direct reversal repair of nonbulky alkyl lesions in DNA nucleobases. ABH2 has broad substrate specificity, directly oxidizing DNA damages such as N¹-methyladenine, N³-methylcytosine, 1,N⁶-ethenoadenine, 3,N⁴-ethenocytosine, and a number of others. In our investigation, we sought to uncover the subtleties of the mechanisms governing substrate specificity in ABH2 by focusing on several critical amino acid residues situated in its active site. To gain insight into the function of this enzyme, we performed a functional mapping of its active site region, concentrating on pivotal residues, participating in forming a damaged binding pocket of the enzyme (Val99 and Ser125), as well as the residues directly involved in interactions with damaged bases, namely Arg110, Phe124, Arg172, and Glu175. To support our experimental data, we conducted a series of molecular dynamics simulations, exploring the interactions between the ABH2 mutant forms, bearing corresponding substitutions and DNA substrates, and harboring various types of methylated bases, specifically N¹-methyladenine or N³-methylcytosine. The comparative studies revealed compelling data indicating that alterations in most of the studied amino acid residues significantly influence both the binding affinity of the enzyme for DNA and its catalytic efficiency. Intriguingly, the findings suggest that the mutations impact the catalytic activity of ABH2 to a greater extent than its ability to associate with DNA strands. Collectively, these results show how changes to the active site affect molecular dynamics and reaction kinetics, improving our understanding of the substrate recognition process in this pivotal enzyme. Full article

PrimPol is a human DNA primase and DNA polymerase involved in DNA damage tolerance in both nuclei and mitochondria. PrimPol restarts stalled replication forks by synthesizing DNA primers de novo and also possesses DNA translesion activity (TLS activity). PrimPol efficiently and relatively accurately bypasses several DNA lesions including 8-oxoguanine, thymine glycol and 5-formyluracil. In this work, we showed that PrimPol possesses efficient and accurate TLS activity across 8-oxoadenine, another common DNA lesion caused by oxidative stress. The accuracy of PrimPol on DNA with 8-oxoA was significantly higher compared to DNA containing 8-oxoG. Replacement of Mg²⁺ ions with Mn²⁺ stimulated activity of PrimPol on DNA with 8-oxoA and 8-oxoG as well as undamaged A in a sequence-dependent manner by the lesion skipping (or template scrunching) mechanism. Altogether, our data support the idea that PrimPol possesses efficient TLS activity across a wide range of DNA lesions caused by oxidative stress. Full article

Atherosclerosis, a chronic inflammatory disease, remains a leading cause of cardiovascular mortality worldwide. Despite standard treatments like statins and percutaneous coronary intervention (PCI), significant residual risk and therapeutic limitations underscore the need for innovative strategies. This review summarizes recent advances in nanoparticle-based therapies for atherosclerosis, focusing on key developments from the last five years. We discuss various nanoplatforms designed to selectively target key cellular players in plaque pathogenesis, including macrophages, endothelial cells, and vascular smooth muscle cells (VSMCs), to inhibit inflammation, modulate cellular phenotypes, and stabilize plaques. A significant focus is placed on the emerging field of biomimetic nanoparticles, where therapeutic cores are camouflaged with cell membranes derived from macrophages, platelets, neutrophils, or erythrocytes. This approach leverages the natural biological functions of the source cells to achieve enhanced immune evasion, prolonged circulation, and precise targeting of atherosclerotic lesions. Furthermore, the review covers nanoparticles engineered for specific functional interventions, such as lowering LDL levels and exerting direct anti-inflammatory and anti-oxidative effects. Finally, we address the critical challenges hindering clinical translation, including nanotoxicity, biodistribution, and manufacturing scalability. In conclusion, nanotechnology offers a versatile and powerful platform for atherosclerosis therapy, with targeted and biomimetic strategies holding immense promise to revolutionize future cardiovascular medicine. Full article