Search Results (119)

Reactive oxygen species (ROS) play a dual role as both essential signaling molecules and harmful mediators of damage. Imbalances in the redox state of the liver can overwhelm antioxidant defenses and promote mitochondrial dysfunction, oxidative damage, and inflammation. Complex feedback loops between ROS and immune signaling pathways are a hallmark of pathological liver conditions, such as hepatic ischemia–reperfusion injury (IRI). This is a major cause of liver transplant failure and is of increasing significance due to the increased use of marginally discarded livers for transplantation. This review outlines the major enzymatic and metabolic sources of ROS in hepatic IRI, including mitochondrial reverse electron transport, NADPH oxidases, cytochrome P450 enzymes, and endoplasmic reticulum stress. Hepatocyte injury activates redox feedback loops that initiate immune cascades through DAMP release, toll-like receptor signaling, and cytokine production. Emerging regulatory mechanisms, such as succinate accumulation and cytosolic calcium–CAMKII signaling, further shape oxidative dynamics. Pharmacological therapies and the use of antioxidant and immunomodulatory approaches, including nanoparticles and redox-sensitive therapeutics, are discussed as protective strategies. A deeper understanding of how redox and immune feedback loops interact is an exciting and active area of research that warrants further clinical investigation. Full article

Chemical endodontic irritants can lead to the demineralization of the inorganic tooth structure, its loss of integrity, microhardness changes, erosion, and an increased risk of fractures. We investigated the action of iron oxide nanomagnet particles (IONPs) as an irrigant solution for improving hardness and identifying the concentration of element ions in the root canal. There were six groups in total: a control group (no treatment) and experimental groups (UN: ultrasound agitation normal saline, UI: ultrasound agitation IONPs, MSI: magnetic field and endodontic needle with syringe agitation IONPs, MUI: magnetic field and ultrasound agitation IONPs, and EDTA: ethylenediaminetetraacetic acid). We hypothesized that IONPs with magnetic agitation would preserve microhardness better than EDTA. Vickers hardness testing was used to evaluate microhardness, which was then analyzed using energy-dispersive X-ray spectroscopy (EDS) to investigate the calcium/phosphorus ratio and the presence of iron. The IONP groups exhibit a higher VHN value than the EDTA group (p < 0.05). These results support our hypothesis, indicating that utilizing an IONP irrigant solution with an external magnetic field does not change microhardness but enhances it compared to the EDTA group, suggesting that employing an external magnetic field to deliver nanoparticles to the root canal wall does not affect the properties of the tooth structure compared to conventional instrumentation techniques, which lead to unnecessary loss of root structure. Full article

Plant callus cultures are a sustainable alternative for producing bioactive secondary metabolites, but their low yields limit industrial applications. Carob (Ceratonia siliqua L.) is rich in medicinally valuable compounds, yet conventional cultivation faces challenges. To address this, we use biofortified calcium phosphate nanoparticles, which refer to CaP-NPs that have been enriched with bioactive compounds via green synthesis using Jania rubens extract, thereby enhancing their functional properties as elicitors in carob callus. CaP-NPs were green-synthesized using Jania rubens extract and applied to 7-week-old callus cultures at 0, 25, 50, and 75 mg/L concentrations. At the optimal concentration (50 mg/L), CaP-NPs increased callus fresh weight by 23.9% and dry weight by 35.1%. At 50 mg/L CaP-NPs, phenolic content increased by 95.7%, flavonoids by 34.4%, tannins by 131.8%, and terpenoids by 211.9% compared to controls. Total antioxidant capacity rose by 76.2%, while oxidative stress markers malondialdehyde (MDA) and hydrogen peroxide (H₂O₂) decreased by 34.8% and 14.1%, respectively. Gene expression analysis revealed upregulation of PAL (4-fold), CHI (3.15-fold), FLS (1.16-fold), MVK (8.3-fold), and TA (3.24-fold) at 50 mg/L CaP-NPs. Higher doses (75 mg/L) induced oxidative damage, demonstrating a hormetic threshold. These findings indicate that CaP-NPs effectively enhance secondary metabolite production in carob callus by modulating biosynthetic pathways and redox balance, offering a scalable, eco-friendly approach for pharmaceutical and nutraceutical applications. Full article

Zinc oxide nanoparticles (ZnONPs) are increasingly used in agriculture to stimulate plant growth and development, including under in vitro culture conditions. However, there is limited data on the effects of ZnONPs on the micropropagation of Scutellaria baicalensis Georgi. The pharmacological properties of this species make it a valuable medicinal plant. In Poland, it does not occur naturally but is cultivated for the production of herbal material. In vitro micropropagation is an effective method for obtaining genetically uniform plantlets. The aim of this study was to evaluate the effects of various concentrations of ZnONPs on growth parameters and the content of mineral nutrients, phenolic compounds, antioxidants, and photosynthetic pigments in Scutellaria baicalensis cultured in vitro. Shoot tip explants were cultured on MS medium supplemented with 1.0 mg dm⁻³ BA and 0.1 mg dm⁻³ IBA, together with ZnONPs at concentrations of 0 (control), 10, 20, 30, and 40 mg dm⁻³. The results showed that ZnONPs at concentrations of 10–20 mg dm⁻³ had no statistically significant effect on shoot or root development or on fresh weight gain. However, higher concentrations (30 and 40 mg dm⁻³) had a significantly negative impact on the number and length of shoots and roots, as well as on biomass accumulation. ZnONPs at 10–20 mg dm⁻³ significantly increased the content of potassium, calcium, magnesium, iron, and zinc in regenerated multi-shoot plantlets. A strong positive correlation (r = 0.951) was observed between ZnONP concentration and zinc accumulation in the plantlets. The levels of manganese and copper were not significantly different from the control. Plantlets treated with 30–40 mg dm⁻³ ZnONPs had significantly lower levels of calcium, iron, manganese, and copper. Those grown at 30 mg dm⁻³ had the highest potassium and magnesium levels, while plantlets exposed to 40 mg dm⁻³ had the highest zinc content. The total phenolic content and antioxidant activity (measured using ABTS and DPPH assays) were significantly higher in ZnONP-treated plantlets compared to the control. In contrast, the levels of chlorophyll a, chlorophyll b, total chlorophyll (a + b), and carotenoids were significantly lower in plants treated with ZnONPs. A strong negative correlation was found between ZnONP concentration and photosynthetic pigment content, while the ZnONP concentration was positively correlated with total phenolic content and antioxidant activity (ABTS⁺ and DPPH). Full article

The hypoxic microenvironment is the main challenge for the repair of damaged tissue, and oxygen supply is an effective means of alleviating hypoxia. In this study, a series of core–shell-structured calcium peroxide/poly(ethylene glycol)@silica (CPO@SiO₂) nanoparticles are prepared to generate oxygen steadily. The size of the CPO@SiO₂ nanoparticles ranges from 205 to 302 nm, with a narrow polydispersity index (PDI). In this system, the nano CPO core acts as the oxygen source to improve hypoxia, while the SiO₂ shell layer serves as the physical barrier to control the oxygen-generating rate and improve biocompatibility. The results suggest that the thickness of the SiO₂ shell layer can be modulated by adjusting the amount of tetraethyl orthosilicate (TEOS). The prepared CPO@SiO₂ nanoparticles show a controlled oxygen-generating rate. Moreover, compared with CPO, the CPO@SiO₂ nanoparticles have good biocompatibility. To assess the modulating effects for the hypoxic microenvironment, L929 cells are co-cultured with CPO@ SiO₂ nanoparticles under hypoxia. The results suggest that the CPO@ SiO₂ nanoparticles can support the cell survival under hypoxia. Moreover, they can effectively decrease oxidative stress damage and reduce the levels of expression of hypoxia-induced superoxide dismutase (SOD) and malondialdehyde (MDA). Therefore, the prepared CPO@ SiO₂ nanoparticles with controlled oxygen-generating properties could be a promising candidate for repairing damaged tissue. Full article

Mitochondrial dysfunction is a pivotal driver in the pathogenesis of acute kidney injury (AKI), chronic kidney disease (CKD), and congenital anomalies of the kidney and urinary tract (CAKUT). The kidneys, second only to the heart in mitochondrial density, rely on oxidative phosphorylation to meet the high ATP demands of solute reabsorption and filtration. Disrupted mitochondrial dynamics, such as excessive fission mediated by Drp1, exacerbate tubular apoptosis and inflammation in AKI models like ischemia–reperfusion injury. In CKD, persistent mitochondrial dysfunction drives oxidative stress, fibrosis, and metabolic reprogramming, with epigenetic mechanisms (DNA methylation, histone modifications, non-coding RNAs) regulating genes critical for mitochondrial homeostasis, such as PMPCB and TFAM. Epigenetic dysregulation also impacts mitochondrial–ER crosstalk, influencing calcium signaling and autophagy in renal pathology. Mitophagy, the selective clearance of damaged mitochondria, plays a dual role in kidney disease. While PINK1/Parkin-mediated mitophagy protects against cisplatin-induced AKI by preventing mitochondrial fragmentation and apoptosis, its dysregulation contributes to fibrosis and CKD progression. For instance, macrophage-specific loss of mitophagy regulators like MFN2 amplifies ROS production and fibrotic responses. Conversely, BNIP3/NIX-dependent mitophagy attenuates contrast-induced AKI by suppressing NLRP3 inflammasome activation. In diabetic nephropathy, impaired mitophagy correlates with declining eGFR and interstitial fibrosis, highlighting its diagnostic and therapeutic potential. Emerging therapeutic strategies target mitochondrial dysfunction through antioxidants (e.g., MitoQ, SS-31), mitophagy inducers (e.g., COPT nanoparticles), and mitochondrial transplantation, which mitigates AKI by restoring bioenergetics and modulating inflammatory pathways. Nanotechnology-enhanced drug delivery systems, such as curcumin-loaded nanoparticles, improve renal targeting and reduce oxidative stress. Epigenetic interventions, including PPAR-α agonists and KLF4 modulators, show promise in reversing metabolic reprogramming and fibrosis. These advances underscore mitochondria as central hubs in renal pathophysiology. Tailored interventions—ranging from Drp1 inhibition to mitochondrial transplantation—hold transformative potential to mitigate kidney injury and improve clinical outcomes. Additionally, dietary interventions and novel regulators such as adenogens are emerging as promising strategies to modulate mitochondrial function and attenuate kidney disease progression. Future research should address the gaps in understanding the role of mitophagy in CAKUT and optimize targeted delivery systems for precision therapies. Full article

Background/Objectives: Periodontitis and diabetes mellitus share a well-established bidirectional relationship, where hyperglycemia exacerbates periodontal inflammation, and periodontal disease further impairs glycemic control. Within the diabetic periodontal microenvironment, an imbalance between pro-inflammatory (M1) and anti-inflammatory (M2) macrophages promotes chronic inflammation, oxidative stress, delayed healing, and alveolar bone resorption. Resveratrol (RSV), a polyphenol with antioxidant, anti-inflammatory, and pro-osteogenic properties, holds potential to restore macrophage balance. However, its clinical application is limited by poor bioavailability and instability. This study aimed to develop and evaluate a novel RSV delivery system to overcome these limitations and promote periodontal tissue regeneration under diabetic conditions. Methods: A drug delivery system comprising RSV-loaded solid lipid nanoparticles embedded within a cross-linked hyaluronic acid hydrogel (RSV@CLgel) was formulated. The system was tested under hyperglycemic and inflammatory conditions for its effects on macrophage polarization, cytokine expression, oxidative stress, mitochondrial function, and osteoblast differentiation. Results: RSV@CLgel effectively suppressed pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) while upregulating anti-inflammatory markers (IL-10, TGF-β). It significantly reduced oxidative stress by decreasing ROS and lipid peroxidation levels and improved mitochondrial function and antioxidant enzyme activity. Furthermore, RSV@CLgel enhanced osteoblast differentiation, as evidenced by increased ALP activity, calcium nodule formation, and upregulation of osteogenic genes (COL-I, RUNX2, OCN, OPN). It also inhibited RANKL-induced osteoclastogenesis, contributing to alveolar bone preservation. Conclusions: The RSV@CLgel delivery system presents a promising multifunctional strategy for the management of diabetic periodontitis. By modulating immune responses, reducing oxidative stress, and promoting periodontal tissue regeneration, RSV@CLgel addresses key pathological aspects of diabetes-associated periodontal disease. Full article

Accumulating evidence suggests that manganese oxide nanoparticles (NPs) show multiple enzyme-mimicking antioxidant activities, which supports their potential in redox-targeting therapeutic strategies for diseases with impaired redox signaling. However, the systemic administration of any NP requires thorough hemocompatibility testing. In this study, we assessed the hemocompatibility of synthesized Mn₃O₄ NPs, identifying their ability to induce spontaneous hemolysis and eryptosis or impair osmotic fragility. Concentrations of up to 20 mg/L were found to be safe for erythrocytes. Eryptosis assays were shown to be more sensitive than hemolysis and osmotic fragility as markers of hemocompatibility for Mn₃O₄ NP testing. Flow cytometry- and confocal microscopy-based studies revealed that eryptosis induced by Mn₃O₄ NPs was accompanied by Ca²⁺ overload, altered redox homeostasis verified by enhanced intracellular reactive oxygen species (ROS) and reactive nitrogen species (RNS), and a decrease in the lipid order of cell membranes. Furthermore, Mn₃O₄ NP-induced eryptosis was calpain- and caspase-dependent. Full article

Nucleic acid (NA)-based drugs are promising therapeutics agents. Beyond efficacy, addressing safety concerns—particularly those specific to this class of drugs—is crucial. Here, we propose an in vitro approach to screen for potential adverse off-target effects of NA-based drugs. Human peripheral blood mononuclear cells (PBMCs), purified from buffy coats of healthy donors, were used to investigate the ability of NA-drugs to trigger toxicity pathways and inappropriate immune stimulation. PBMCs were selected for their ability to represent potential human responses, given their likelihood of interacting with administered drugs. As proof of concept, a small interfering RNA (siRNA) targeting Ryanodine Receptor mRNA (RyR2) identified by the Italian National Center for Gene Therapy and Drugs based on RNA Technology as a potential therapeutic target for dominant catecholaminergic polymorphic ventricular tachycardia, was selected. This compound and its scramble were formulated within a calcium phosphate nanoparticle-based delivery system. Positive controls for four toxicity pathways were identified through literature review, each associated with a specific type of cellular stress: oxidative stress (tert-butyl hydroperoxide), mitochondrial stress (rotenone), endoplasmic reticulum stress (thapsigargin), and autophagy (rapamycin). These controls were used to define specific mRNA signatures triggered in PBMCs, which were subsequently used as indicators of off-target effects. To assess immune activation, the release of pro-inflammatory cytokines (interleukin-6, interleukin-8, tumor necrosis factor-α, and interferon-γ) was measured 24 h after exposure. The proposed approach provides a rapid and effective screening method for identifying potential unintended effects in a relevant human model, which also allows to address gender effects and variability in responses. Full article

Scaffolds for regenerative therapy can be made from natural or synthetic polymers, each offering distinct benefits. Natural biopolymers like chitosan (CS) are biocompatible and biodegradable, supporting cell interactions, but lack mechanical strength. Synthetic polymers like polyvinyl alcohol (PVA) provide superior mechanical strength and cost efficiency but are not biodegradable or supportive of cell adhesion. Combining these polymers optimizes their advantages while adding metal oxide nanoparticles like calcium oxide (CaO NPs) enhances antimicrobial properties by damaging bacterial membranes. In this study, we obtained the formation of CaO NPs by calcinating eggshells, which were mixed in a polymeric network of CS and PVA to obtain four different membrane formulations for subdermal tissue regeneration. The spherical nanoparticles measured 13.43 ± 0.46 nm in size. Their incorporation into the membranes broadened the hydroxyl bands in the Fourier transform infrared (FTIR) analysis at 3331 cm⁻¹. X-ray diffraction (XRD) analysis showed changes in the crystalline structure, with new diffraction peaks at 2θ values of 7.2° for formulations F2, F3, and F4, likely due to the increased amorphous nature and concentration of CaO NPs. Additionally, higher CaO NPs concentrations led to a reduction in thermal properties and crystallinity. Scanning electron microscopy (SEM) revealed a heterogeneous morphology with needle-like structures on the surface, resulting from the uniform dispersion of CaO NPs among the polymer chains and the solvent evaporation process. A histological examination of the implanted membranes after 60 days indicated their biocompatibility and biodegradability, facilitated by incorporating CaO NPs. During the degradation process, the material fragmented and was absorbed by inflammatory cells, which promoted the proliferation of collagen fibers and blood vessels. These findings highlight the potential of incorporating CaO NPs in soft tissue regeneration scaffolds. Full article

The key role of calcium in various physiological and pathological processes includes its involvement in various forms of regulated cell death (RCD). The concept of ‘calcicoptosis’ has been introduced as a calcium-induced phenomenon associated with oxidative stress and cellular damage. However, its definition remains controversial within the research community, with some considering it a general form of calcium overload stress, while others view it as a tumor-specific calcium-induced cell death. This review examines ‘calcicoptosis’ in the context of established RCD mechanisms such as apoptosis, necroptosis, ferroptosis, and others. It further analyzes the intricate relationship between calcium dysregulation and oxidative stress, emphasizing that while calcium overload often triggers cell death, it may not represent an entirely new type of RCD but rather an extension of known pathways. The purpose of this paper is to discuss the implications of this perspective for cancer therapy focusing on calcium-based nanoparticles. By investigating the connections between calcium dynamics and cell death pathways, this review contributes to the advancement of our understanding of calcicoptosis and its possible therapeutic uses. Full article

This study introduces a novel paper coating approach using modified zinc oxide (ZnO), providing a comparison with conventional materials used in the paper industry. The research focused on determining the concentration for effective microbial growth inhibition and evaluates the impact of different ZnO types on coated-paper properties, including antimicrobial activity, surface morphology, tensile strength, and water absorption. Specifically, ZnO microparticles (ZnO_ws), ZnO nanoparticles (ZnO_np), and modified ZnO_np (ZnO_np-CaCO₃, with a core–shell structure composed of calcium carbonate [CaCO₃] and nano-zinc oxide) were incorporated into coating formulations at varying concentrations (0 × MIC, 1 × MIC, 2 × MIC, and 3 × MIC, based on minimum inhibitory concentrations [MICs]). The results demonstrated that among all tested microorganisms, ZnO_np-CaCO₃ showed the lowest MIC values. ZnO_np-CaCO₃-coated paper exhibited superior antimicrobial activity against both Gram-positive and Gram-negative bacteria, as well as fungi, outperforming ZnO_ws and ZnO_np. At 1 × MIC, %inhibition for E. coli, S. aureus, and A. niger were 98.3%, 99.1%, and 90.8%, respectively. Additionally, ZnO_np-CaCO₃ coatings caused minimal color change in the paper compared to the other ZnO variants. The coating did not negatively impact the mechanical properties of the paper across all ZnO types and concentrations. Water absorption tests showed increased hydrophobicity with higher ZnO content, with ZnO_np and ZnO_np-CaCO₃ exhibiting greater reductions in water absorption than ZnO_ws. Overall, ZnO_np-CaCO₃ showed strong potential as an antimicrobial agent for paper surfaces, making it ideal for packaging and hygiene products. By partially replacing ZnO_np with inexpensive CaCO₃ core particles, ZnO_np-CaCO₃ delivers enhanced performance, reduced costs, and greater sustainability for large-scale applications. Full article

Intracanal medicaments are an important adjunct to the effective disinfection of the root canal system. However, conventional intracanal medicaments do not provide adequate protection against Enterococcus faecalis, which is the organism of interest in many cases of root canal failures. This study aimed to evaluate the influence of biosynthesized calcium oxide nanoparticles (CaO NPs) on the antibacterial activity, pH, microleakage and cytotoxicity of intracanal medicaments. CaO NPs were biosynthesized by the direct thermal decomposition of eggshells (EGS) and the reduction of calcium nitrate with papaya leaf extract (PLE). These nanoparticles were mixed with a proprietary calcium hydroxide powder in 10% and 25% (w/w) concentrations and blended in analytical-grade coconut oil to formulate the experimental medicaments. These were then evaluated for antibacterial activity, pH, microleakage and cytotoxicity at 1 day, 7 days and 15 days. A proprietary calcium hydroxide paste formulation (MX) was used as the control. Means and standard deviations were calculated and analyzed using repeated-measures ANOVA for pH and three-way ANOVA for the antibacterial effect, microleakage and cytotoxicity, followed by LSD post hoc analysis. Significant antibacterial activity was noted against Enterococcus faecalis at all times, with zones of inhibition (ZOI) up to 19.60 ± 2.30 mm. pH levels up to 13.13 ± 0.35 were observed for the experimental groups. Microleakage remained comparable to the control, while cytotoxicity was not observed in any of the groups at any time. Intracanal medicaments formulated with 10% and 25% (w/w) of biosynthesized CaO NPs could be promising candidates for the disinfection of the root canal system compared to conventional counterparts. Full article

The continuous development of biomedical materials necessitates exploring new solutions to enhance implant performance. This study investigates the impact of titanium dioxide nanoparticles on calcium phosphate coatings applied to VT1-0 titanium substrates using micro-arc oxidation. Titanium, widely recognized for its excellent mechanical properties and compatibility, serves as an ideal substrate for implants. The coatings were synthesized in an electrolyte with varying titanium dioxide concentrations to examine their influence on surface morphology, wettability, roughness, hardness, and tribological characteristics. Characterization techniques, such as scanning electron microscopy, X-ray diffraction, and profilometry, were employed to analyze the coatings’ structural and mechanical properties. The results demonstrate that increasing titanium dioxide concentrations leads to enhanced uniformity, reduced pore sizes, and higher hardness. Furthermore, the coatings showed improved wear resistance and reductions in friction coefficients at optimal nanoparticle levels. The inclusion of titanium dioxide significantly enhances the mechanical and tribological performance of the calcium phosphate coatings, making them suitable for biomedical applications, especially in implants requiring long-term durability and enhanced compatibility. Full article

Amongst the many types of food waste, eggshells contain various minerals and bioactive materials, and they can become hazardous if not properly disposed of. However, they can be made useful for the environment and people by being converted to environmentally friendly catalytic materials or environmental purification agents. Simple calcination can enhance their properties and thereby render them suitable for catalytic and environmental applications. This work aimed to prepare CaO from waste eggshells and examine its effectiveness in photocatalytic pollution remediation, electrocatalytic activity, optical sensing, and antibacterial activities. As opposed to other techniques, this calcination process does not require any chemical reagents due to the high purity of CaCO₃ in eggshells. Calcium oxide nanoparticles were prepared by subjecting waste eggshells (ES) to high-temperature calcination, and the synthesized CaO nanoparticles were characterized for their structural, morphological, chemical, optical, and other properties. Furthermore, their photocatalytic degradation of methylene blue dye and antibacterial efficiency against Escherichia coli and Staphylococcus aureus were investigated. It was found that the green-converted CaO can be efficiently used in environmental applications, showing good catalytic properties. Full article