Search Results (6,997)

The microstructures and oxidation behavior of the NbSiTiAlHf alloys doped with rare earth elements at 1300 °C were investigated. The nominal compositions of the selected alloys are Nb-13.5Si-23Ti-37Al-5Hf-0.5X (at.%), where X = Y, Dy, and La, respectively. It was shown that the whole scales were mainly composed of the major phases of Al₂O₃ and the minor phases of TiO₂, where the TiO₂ formed on the surface or in the upper layer of scales, for the undoped, Y, and Dy-doped alloy. But, for the 0.5 at.% La-doped alloys, the whole scales were constituted with the major phases of both Al₂O₃ and TiO₂, and contained plenty of large voids. The 0.5 at.% Dy-doped alloys exhibited the lowest scale growth rate with the value of 1.87 × 10⁻¹¹ cm²/s, and the benefits of Y on the oxidation rates were short-term, while 0.5 at.% La-doped alloys had the highest scale growth rate of 4.55 × 10⁻¹⁰ cm²/s compared with those of all the selected alloys. Then, the effects of Y, Dy, and La on the oxidation behavior of the alumina-scale-forming NbSiTiAlHf alloys were discussed. Full article

Downy mildew, caused by Plasmopara halstedii, is a major threat to sunflower production worldwide, leading to severe yield losses. Since resistance in sunflower hybrids can be easily broken by the pathogen, it is important to find alternative and sustainable control methods against this disease. This study investigated the potential use of NeemAzal^®-T/S (a neem-based biopesticide formulation) to induce antioxidant defense responses in sunflower seedlings inoculated with P. halstedii (pathotype 704). Its effects, alone, or in combination with a reduced dose of Mefenoxam, were evaluated under controlled conditions. Plant height, sporulation, antioxidant enzyme activities (SOD, CAT, APX, POX, and PPO), lipid peroxidation (MDA), and hydrogen peroxide (H₂O₂) contents were measured. Our results indicate that the antioxidant responses of seedlings varied according to the treatment. MDA levels decreased even when NeemAzal^®-T/S was applied alone, while H₂O₂ production only decreased when both treatments were applied combined. Overall, NeemAzal^®-T/S can be a valuable alternative strategy to help control sunflower downy mildew, since it reduced sporulation and MDA content, and increased APX, POX, and PPO activities even at a later stage of infection in susceptible seedlings. These findings indicate that NeemAzal^®-T/S can activate defense mechanisms associated with oxidative stress reduction in sunflower, offering a promising strategy to help manage downy mildew in a more sustainable manner. Full article

Background: Cystic echinococcosis (CE) is a globally distributed zoonosis triggered by the larval stage of Echinococcus granulosus (E. granulosus), impacting humans and an extensive array of mammalian intermediate hosts. EGR-01664 is the major egg antigen of E. granulosus, but almost nothing is currently known about the function of EGR-01664 from E. granulosus. Methods: This study aimed to investigate the E. granulosus EGR-01664 gene (GenBank ID: 36337379), and the recombinant EGR-01664 protein was expressed successfully. Next, the transcription of the EGR-01664 gene across various developmental stages of E. granulosus was analyzed. Its spatial expression patterns in adult worms and protoscoleces were characterized using both quantitative PCR (qPCR) and immunofluorescence assays. Furthermore, the immunomodulatory effects of rEGR-01664 on cell proliferation, nitric oxide production, and cytokine secretion were examined by co-culturing the recombinant protein with canine PBMCs. Results: The rEGR-01664 could be recognized by sera from dogs infected with E. granulosus. Immunofluorescence assay (IFA) localization revealed the protein’s presence in the epidermis of protoscoleces, the adult epidermis, and some parenchymal tissues. qPCR revealed that EGR-01664 mRNA levels were significantly higher in protoscoleces compared to adults (p < 0.0001). At a concentration of 20 μg/mL, rEGR-01664 could significantly activate the transcription and expression of IL-10, TGF-β1, IL-17A, and Bax in canine PBMCs. However, with an increase in concentration, it inhibited the expression of IFN-γ, Bcl-2, GSDMD, IL-18, and IL-1β. These results suggest that the EGR-01664 gene plays a crucial role in the development, parasitism, and reproduction of E. granulosus. In vitro studies have shown that rEGR-01664 protein regulates the immune regulation function of canine PBMCs, suggesting its potential as a vaccine adjuvant or immunotherapy target. Conclusions: EGR-01664 may modulate canine PBMC functions to regulate host immune responses, thereby facilitating our understanding of how E. granulosus EGR-01664 contributes to the mechanism of parasitic immune evasion. Full article

Intracellular signalling pathways provide a mechanism to connect events at a cell surface to the nucleus and are of fundamental importance to normal cell functioning. Intracellular signalling pathways control many aspects of cell metabolism, including mitochondrial function, oxidative stress, inflammation, and apoptosis/ferroptosis. Randomised controlled clinical trials supplementing coenzyme Q10 (CoQ10) have reported significant clinical improvements in a number of disorders, in turn associated with the action of CoQ10 to promote normal mitochondrial function, reduce oxidative stress and inflammation, and mediate apoptosis and ferroptosis. However, the precise mechanisms by which CoQ10 facilitates beneficial changes in the above factors is not completely understood. In the present article, the evidence we have reviewed provides a supporting rationale that the beneficial role of CoQ10 in the above disorders occurs via mediation of major intracellular signalling pathways, including the Nrf2/NQO1, NF-κB, P13/AKT/mTOR, MAPK, JAK/STAT, WNT/B-catenin, AMPK-YAP-OPA1, and hedgehog (Hh) pathways; the clinical consequences of such mediation are also reviewed. Full article

Background/Objectives: Cardiovascular diseases (CVDs) remain a major cause of mortality globally, driven in part by oxidative stress and inflammation. The present study investigated the polyphenolic composition and cardioprotective potential of polyphenol-rich Citrullus lanatus (PRCL) rind extract against doxorubicin-induced cardiotoxicity in rats; Methods: High-performance liquid chromatography (HPLC) was employed to identify and quantify the major bioactive compounds present in the extract. Total 30 healthy male Wistar Kyoto rats were recruited and divided into 6 groups and various cardiovascular markers and antioxidant were measured in vivo and in vitro methods; Results: Ethanolic extraction of Citrullus lanatus rind yielded 19.58 g extract per 100 g of dry plant material. HPLC analysis identified five phenolic acids, i.e., gallic acid, p-hydroxybenzoic acid (PHBA), chlorogenic acid, caffeic acid, and vanillic acid, and two flavonoids, i.e., catechin and hesperetin, with PHBA (163.66 mg/g of extract) being the most abundant. Total phenolic and flavonoid content was determined to be 35.6 mg GAE/g and 12.8 mg CE/g, respectively. In vitro antioxidant assays showed moderate free radical scavenging, reducing power, and 86.9% inhibition of linoleic acid peroxidation. In vivo, Wistar rats were treated with doxorubicin (10 mg/kg) to induce cardiotoxicity, followed by PRCL extract administration (21 days at 250 and 500 mg/kg/day). The extract significantly improved body weight, serum lipid profile, and reduced cardiovascular risk indices. Antioxidant biomarkers (SOD, CAT, GPx, GSH) were restored, while lipid peroxidation (MDA) and inflammatory cytokines (TNF-α, IL-6) were significantly reduced in treated groups. The 500 mg/kg dose demonstrated superior efficacy, comparable to the standard quercetin group. Histopathological examination revealed notable protection of cardiac tissue architecture in the high-dose PRCL-500 group; Conclusions: These findings suggest that PRCL rind extract contains potent compounds having antioxidant and cardioprotective properties and may be used as a natural therapeutic agent against cardiotoxicity. Full article

The latest exploration developments and discoveries from the eastern Mediterranean documented that Neogene formations can act as source-rocks for hydrocarbon generation and their exploitation delivered large amounts of mostly biogenic gas to the market. Examples of such offshore gas-fields include the Zohr-Egypt, Leviathan/Tamar-Israel, and Aphrodite-Cyprus. Having attracted the oil majors’ attention for hydrocarbons exploration in southern Greece (e.g., Exxon-Mobil, Chevron), by using onshore geologic analogs, we suggest relevant perspectives in the country’s offshore sector. Our study focuses on Miocene marine deposits exploration, from Gavdos Island, southern Greece, evaluating their characteristics as potential source-rocks affected by a paleodepositional framework. By integrating fieldwork, organic (Rock-Eval VI-pyrolysis, CHNS) and inorganic geochemical data (XRF), the current results indicate gas-prone organic matter with variable preservation status, reflecting a few oxidation episodes during deposition under generally dysoxic-to-suboxic conditions. Paleoclimatic weathering indices (CIA, C.I., Sr/Cu, Rb/Sr) suggest predominantly arid to semi-arid regimes punctuated by short-lived humid phases that locally enhance organic accumulation and nutrient supply. Variations in paleosalinity and stratification, particularly within the Messinian section, are interpreted as precursors to the Messinian Salinity Crisis. Our findings highlight the potential for hydrocarbon-prone intervals in the deeper-offshore Eastern Mediterranean basins, where most favorable conditions for organic-carbon preservation and maturation are documented by the discoveries. Full article

Background: Alzheimer’s disease (AD) is a progressive neurodegenerative disorder with unclear pathogenic mechanisms. Dysregulated zinc metabolism contributes to AD pathology. This study aimed to identify zinc metabolism-related hub genes to provide potential biomarkers and therapeutic targets for AD. Methods: We performed an integrative analysis of multiple transcriptomic datasets from AD patients and normal controls. Differentially expressed genes and weighted gene co-expression network analysis (WGCNA) were combined to identify hub genes. We then conducted Gene Set Enrichment Analysis (GSEA), immune cell infiltration analysis (CIBERSORT), and receiver operating characteristic (ROC) curve analysis to assess the hub gene’s biological function, immune context, and diagnostic performance. Drug-gene interactions were predicted using the DrugBank database. Results: We identified a single key zinc transporter–related hub gene, SLC30A3, which was significantly downregulated in AD and demonstrated potential diagnostic value (AUC 0.70–0.80). Lower SLC30A3 expression was strongly associated with impaired synaptic plasticity (long-term potentiation, long-term depression, calcium signaling pathway, and axon guidance), mitochondrial dysfunction (the citrate cycle and oxidative phosphorylation), and pathways common to major neurodegenerative diseases (Parkinson’s disease, AD, Huntington’s disease, and amyotrophic lateral sclerosis). Furthermore, SLC30A3 expression correlated with specific immune infiltrates, particularly the microglia-related chemokine CX3CL1. Zinc chloride and zinc sulfate were identified as potential pharmacological modulators. Conclusions: Our study systematically identifies SLC30A3 as a novel biomarker in AD, linking zinc dyshomeostasis to synaptic failure, metabolic impairment, and neuroimmune dysregulation. These findings offer a new basis for developing targeted diagnostic and therapeutic strategies for AD. Full article

Statins are the drugs most commonly used for lowering plasma low-density lipoprotein (LDL) cholesterol levels and reducing cardiovascular disease risk. Although generally well-tolerated, statins can induce myopathy, a major cause of non-adherence to treatment. Impaired mitochondrial function has been implicated in the development of statin-induced myopathy, but the underlying mechanism remains unclear. We have shown that simvastatin downregulates the transcription of TOMM40 and TOMM22, genes that encode major subunits of the translocase of the outer mitochondrial membrane (TOM) complex. Mitochondrial effects of knockdown of TOMM40 and TOMM22 in mouse C2C12 and primary human skeletal cell myotubes include impaired oxidative function, increased superoxide production, reduced cholesterol and CoQ levels, and disrupted markers of mitochondrial dynamics and morphology as well as increased mitophagy, with similar effects resulting from simvastatin exposure. Overexpression of TOMM40 and TOMM22 in simvastatin-treated mouse and human skeletal muscle cells rescued effects on markers of mitochondrial dynamics and morphology, but not oxidative function or cholesterol and CoQ levels. These results show that TOMM40 and TOMM22 have key roles in maintaining both mitochondrial dynamics and function and indicate that their downregulation by statin treatment results in mitochondrial effects that may contribute to statin-induced myopathy. Full article

Solar lentigo is a significant dermatological concern affecting individuals of different genders and ethnicities. Its pathogenesis is primarily attributed to chronic ultraviolet (UV) exposure, increased melanogenesis, and disrupted epidermal turnover, leading to the development of hyperpigmented lesions. A major challenge in solar lentigo research is acquiring viable skin tissue, which is crucial for understanding the dynamics of the cellular microenvironment. In the present study, we sought to establish a non-invasive in vivo measurement technique to visualize cellular dynamics associated with solar lentigo. Utilizing fluorescence lifetime imaging microscopy (FLIM), we quantified the decay of NAD(P)H fluorescence lifetime and observed a reduction in oxidative phosphorylation (OXPHOS) activity in solar lentigo lesions compared to adjacent non-lesional skin. To determine whether the observed reduction in OXPHOS activity was due to excessive melanin accumulation in keratinocytes, we developed a melanin deposition model and examined the pleiotropic alterations occurring in keratinocytes following the phagocytosis of excessive melanin. Our findings indicate that excessive melanin deposition downregulates OXPHOS in differentiating keratinocytes and induces senescence-associated phenotypes characterized by perturbed cell cycle progression, increased cell size and aneuploidy, and the secretion of inflammatory mediators in proliferating keratinocytes. Collectively, our results implicate a solar lentigo-specific senescence mechanism driven by excessive melanin accumulation in keratinocytes, providing new insights about the intrinsic modulators of the pathological condition. Full article

DNA is continuously exposed to endogenous and exogenous factors that induce oxidative modifications leading to mutations and genomic instability. Oxidative DNA damage plays a dual role, contributing to physiological signaling at low levels while promoting mutagenesis, carcinogenesis and degenerative diseases when unpaired. Among various lesions, an oxidized base, such as 8-oxo-2′-deoxyguanosine (8-oxodG), is one of the major biomarkers of oxidative stress and genomic damage. Cells have evolved sophisticated repair processes, including base excision repair (BER), nucleotide excision repair (NER), and mismatch repair (MMR), to maintain genomic integrity. Dysregulation or polymorphism of these repair genes has been linked with cancer, neurologic, and cardiovascular disorders. This review discusses an overview of what is presently known concerning oxidative DNA damage and repair mechanisms, particularly emphasizing their molecular players, signaling routes, and human disease implications. It further refers to the latest advances in CRISPR-based technologies and multi-omics approaches that are redefining our understanding of DNA damage response (DDR) networks and creating new frontiers for therapeutic interventions. Full article

This study addresses the environmental challenge of end-of-life tire accumulation, a major source of toxic metals such as lead and cadmium in marine ecosystems. As a sustainable solution, multicomponent metal-oxide nanoparticles (Fe₃O₄, ZnO, CaO, MgO, and minor CaCO₃) were green-synthesized from sugarcane bagasse and stabilized with blackberry (Rubus glaucus) extract. Structural characterization (XRD, SEM, TEM, and EDS) confirmed their crystalline inorganic composition. Pb²⁺ was almost completely removed (95–99%) within 15–30 min using 50–100 mg of nanoparticles, with ~80–90% efficiency at 75 mg. Cd²⁺ removal showed dose-dependent kinetics: ~90% removal occurred within 10 min at 75 mg, while 50 and 100 mg reached ~60–70% after 60 min. Equilibrium, kinetic, and thermodynamic analyses revealed that Pb²⁺ adsorption followed the Langmuir model (R² = 0.982) with monolayer chemisorption, whereas Cd²⁺ obeyed the Freundlich model (R² = 0.945), indicating heterogeneous multilayer adsorption. Pb²⁺ removal fitted a pseudo-second-order model (R² = 0.991), while Cd²⁺ followed a pseudo-first-order behavior (R² = 0.958). Thermodynamic parameters (ΔG° < 0, ΔH° > 0, ΔS° > 0) confirmed a spontaneous and endothermic process. Sugarcane-bagasse-derived Fe₃O₄–ZnO–CaO–MgO nanomaterials act as sustainable and effective adsorbents for marine heavy metal removal. Full article

Acute kidney injury (AKI) occurs commonly in hospitalized patients, especially patients in intensive care units (ICUs). Medications are among the major causative factors of AKI. This narrative review addressed and updated different aspects of anti-infective-associated AKI, including amphotericin B, cidofovir, foscarnet, polymyxins, vancomycin, and aminoglycosides. There is no standard definition or operational criteria to describe anti-infective-associated AKI. Characteristically, it usually occurs during the first two weeks of treatment and is typically dose dependent. Functional resolution occurs, but kidney injury can affect renal functional reserve and increase susceptibility to future AKI events. A variety of pathophysiological mechanisms impacting glomerular, tubular, and interstitial components of the kidney are usually responsible for the development of AKI from anti-infective medications. Oxidative stress and inflammation play a pivotal role in the pathogenesis of antibiotic-related AKI. Numerous patient-related, medication-related, and co-administered-related scenarios have been demonstrated as risk factors for anti-infective-induced AKI. Apart from traditional indexes of kidney function (serum creatinine and urine output), novel biomarkers of kidney function (e.g., serum cystatin C) and damage (e.g., urinary kidney-injury molecule-1 and neutrophil gelatinase-associated lipocalin) have been noticed in recent clinical studies with promising findings. The efficiency of preventive strategies against anti-infective-associated AKI in most cases appears to be variable, relative, and modest. Close and regular monitoring of kidney function parameters is crucial during treatment with nephrotoxic antibiotics. Currently, there is no definitive treatment modalities for the management of AKI with anti-infectives. Therefore, supportive care is the mainstay of treatment. Full article

Pain remains a major clinical challenge due to its complex physiopathology and limited treatment options. In this context, several supplements based on palmitoylethanolamide (PEA) and alpha-lipoic acid (ALA) are known for their neuroprotective properties. ALA-based supplements have shown potential, but concerns about adverse effects persist. This study examines the formulations of two commercial products based on ALA and PEA, IperALA^® and IperALA^® Forte, in which ALA and vitamin D3 are replaced with Coriandrum sativum extract (C. sativum e.s.), N-acetylcysteine (NAC) and glutathione (GSH), assessing improvement of neuroprotective, anti-inflammatory and analgesic properties of the new formulation. Intestinal, blood–brain barrier (BBB), and central nervous system (CNS) models were sequentially stimulated with the test compounds. Both formulations were assessed for cytotoxicity, barrier integrity, permeability, oxidative stress, inflammation, and neuroprotection-related biomarkers. IperALA^® Forte demonstrated superior performance compared to IperALA^® and individual agents. It enhanced cell viability, preserved intestinal and BBB integrity, and improved compound permeability. Notably, it reduced ROS and pro-inflammatory cytokines (TNFα, IL-1), while increasing analgesic markers (CB2R, GABA) in the central system. The replacement of ALA and vitamin D3 with C. sativum, NAC, and GSH in IperALA^® Forte significantly improved the neuroprotective, antioxidant, and anti-inflammatory profile of the supplement. These results indicate a possible connection between the observed neuroprotective properties and the pathways involved in nociception and pain regulation, stating the hypothetical potential relevance of this approach for the treatment of pain-related conditions. Full article

Background: Fusarium solani (Fs), a drug-resistant phytopathogenic fungus, is a major cause of severe infections in both plants and humans. Artemisia annua and its derivatives exhibit antimicrobial, antiviral and anticholesterolemic activities, yet their clinical use has been dominated by potent antimalarial and anticancer effects. Artemisinin (ART), a sesquiterpene lactone isolated from A. annua, is well recognized for its antimalarial efficacy but remains underexplored as an antifungal agent. Methods: Conidia of Fs were treated with increasing concentrations of ART (75–500 μM) for 0 and 24 h. Fungal viability was assessed using viability assays. Membrane permeability was examined using confocal laser scanning microscopy with propidium iodide (PI) staining. Protein carbonylation assays were performed to quantify oxidative damage induced by ART. Results: A 24 h, ART exposure reduced Fs viability in a dose-dependent manner, with an IC₅₀ of 147.5 μM. At 500 μM, ART achieved fungicidal activity with 99% growth inhibition. Confocal microscopy confirmed extensive membrane disruption in ART-treated conidia, while carbonylation assays demonstrated marked protein oxidation, supporting a mechanism involving free radical generation from the peroxide bridge of ART. ART exhibits potent antifungal activity against Fs, mediated by oxidative stress, membrane disruption and protein carbonylation. Conclusions: These findings highlight ART as a promising candidate for antifungal drug development against resistant Fusarium species. Full article

Salt stress is a major form of abiotic stress that disrupts soybean germination and early seedling establishment. In this study, physiological, biochemical, and transcriptomic analyses—including germination index, antioxidant enzyme activity, and RNA-seq profiling—were conducted during soybean germination to elucidate early responses to salt stress and biostimulant treatment. A preliminary screening of six biostimulants (nanoparticle zinc oxide (NP-ZnO), nanoparticle silicon dioxide (NP-SiO₂), silicon dioxide (SiO₂), glucose, humic acid, and fulvic acid) revealed NP-SiO₂ as the most effective in promoting germination under salt stress. Under 150 mM NaCl, NP-SiO₂ increased the germination rate and length of the radicle compared with the control, also enhancing peroxidase and ascorbate peroxidase activities while reducing malondialdehyde accumulation, suggesting alleviation of oxidative stress. RNA sequencing revealed extensive transcriptional reprogramming under salt stress, identifying 4579 differentially expressed genes (DEGs) compared with non-stress conditions, while NP-SiO₂ treatment reduced this number to 2734, indicating that NP-SiO₂ mitigated the transcriptional disturbance caused by salt stress and stabilized gene expression networks. Cluster analysis showed that growth- and hormone-related genes suppressed by salt stress were restored under NP-SiO₂ treatment, whereas stress-responsive genes that were induced by salt were attenuated. Hormone-related DEG analysis revealed that NP-SiO₂ down-regulated the overactivation in the abscisic acid, jasmonic acid, and salicylic acid pathways while partially restoring gibberellin, auxin, cytokinin, and brassinosteroid signaling. Overall, NP-SiO₂ at 100 mg/L mitigated salt-induced oxidative stress and promoted early soybean growth by fine-tuning physiological and transcriptional responses, representing a promising nano-based biostimulant for enhancing salt tolerance in plants. Full article