Cupric Ion Research Articles

In Situ Transformable Fibrillar Clusters Disrupt Intracellular Copper Metabolic Homeostasis by Comprehensive Blockage of Cuprous Ions Efflux.

Dysregulation of copper metabolism is intricately associated with the occurrence and therapeutic management of colorectal cancer. Previous studies have attempted to induce cuproptosis by delivering lethal doses of copper ions into tumor cells, often with systemic safety risks. In vivo, transformable peptide is modular and designed for various tumor-related proteins, which can affect protein function and distribution. Here, a fibrillar transformation peptidic (FTP) nanoparticle is synthesized, which can bind ATP7B membrane proteins (cuprous ions transporter) and transform into nanofibrils/ATP7B clusters, inducing "copper-free cuproptosis" in vivo. Without adding exogenous copper ions, the spherical FTP nanoparticles bound the high distribution regions of ATP7B membrane proteins, transforming into fibrillar networks in situ with prolonged retention. The cage-like fibrillar network would further capture unbound or newly generated free ATP7B membrane proteins, thereby significantly and consistently preventing cuprous ions efflux. The FTP nanoparticles would not undergo in situ fibrillar transformation on the low expression region of ATP7B membrane proteins but enter the cell for safe degradation, which exhibited high specificity and safety in vivo. By disrupting intracellular copper homeostasis, the transformable fibrillar clusters displayed a long-term anti-tumor effect on subcutaneous transplantation and liver metastatic CRC models.

Determination of Biological Activity and Biochemical Content of Ethanol Extract from Fruiting Body of Tricholoma bufonium (Pers.) Gillet

The current study investigates the biochemical composition and biological activities of ethanol extract from the fruit body of Tricholoma bufonium, marking the first detailed examination of this species. The primary goal was to assess the antimicrobial, anti-biofilm, and antioxidant properties of ethanol extract from the fruit body of T. bufonium against a range of bacterial strains. Conventional microbiological and biochemical techniques were employed to assess the antimicrobial efficacy of the extract and to determine its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) values. Furthermore, a GC-MS analysis identified bioactive compounds, such as palmitic acid and oleic acid, which are likely contributors to the observed antimicrobial activity. The anti-biofilm activity was tested using glucose monohydrate-modified environments for biofilm formation, while the antioxidant potential was measured using the DPPH radical scavenging assay, CUPRAC (cupric ion reducing antioxidant capacity) assay, and FRAP (ferric ion reducing antioxidant power) assay. The ethanol extract exhibited potent antimicrobial activity, particularly against Enterococcus faecium, Bacillus subtilis, and Staphylococcus aureus MRSA, with MIC values as low as 0.0338 mg/mL for several pathogens. Additionally, the extract exhibited significant anti-biofilm activity against Bacillus cereus and antioxidant activity with an EC50 value of 11.745 mg/mL. These results suggest that ethanol extract from the fruit body of T. bufonium may be a potent candidate for developing novel antimicrobial agents, particularly against resistant strains such as MRSA, while also providing antioxidant benefits.

Antioxidant potential and xanthine oxidase inhibition of flavonol glycosides from Phyllanthus emblica L. leaves

Context: Hyperuricemia is the cause of gout in the inflammatory joint condition. The xanthine oxidase enzyme is a therapeutic target for gout treatment because it plays a role in the generation of uric acid. Allopurinol is used to treat gout. It prevents the xanthine oxidase enzyme from producing as much uric acid. When selecting a medication, one must consider the various adverse effects of allopurinol. Phyllanthus emblica plants are among the medicinal plants that can be used as an alternative treatment for gout. Aims: To evaluate isolated compounds from the Phyllanthus emblica as antihyperuricemia candidates. Methods: The isolated compounds were characterized using High-Performance Liquid Chromatography Analysis and Thin Layer Chromatography-Densitometry. The 2,2-diphenyl-1-picrylhydrazyl (DPPH) and cupric ion (CUPRAC) antioxidant capacity procedures were used to develop the antioxidant activity index. The ability to inhibit xanthine oxidase was determined using a spectrophotometer. Results: Compound 1 was indicated as rutin having antioxidant capacity with an antioxidant activity index (AAI) DPPH value of 7.89 ± 0.03 and AAI CUPRAC value of 15.83 ± 0.04 stronger than compound 2 (quercitrin) with an AAI DPPH value of 3.72 ± 0.01 and AAI CUPRAC 3.24 ± 0.03. The IC50 for quercitrin's inhibition of xanthine oxidase is 23.85 ± 2.04, which was higher than rutin’s IC50 value of 32.77 ± 4.49 µg/mL. Conclusions: Flavonol glycosides present in the ethanol extract of Phyllanthus emblica leaves gave potent xanthine oxidase inhibitory activity stronger than the extract. Quercitrin gave stronger xanthine oxidase inhibitory activity, but this compound has weaker antioxidant capacity compared to rutin.

Antioxidative and Antimicrobial Activity of 2-Amino Substituted Halochalcone N-Glycoside Derivative Compounds

Introduction: The aim of this study was to specify the antioxidant and antimicrobial activity synthesized 2-amino substituted halochalcone N-glycoside derivative compounds. Methods: The antioxidant capacity of synthesized compounds (1-4) was determined by cupric ion reducing antioxidant capacity (CUPRAC), and ferric reducing antioxidant power (FRAP). Antimicrobial activity was determined on 9 microorganism by agar well diffusion method.Results: According to the study results, compound 3 showed the highest antioxidant activity. The compound 3 showed antimicrobial activity against Yersinia pseudotuberculosis, Pseudomonas aeruginosa, Candida albicans while compound 4 showed antimicrobial activity against Escherichia coli, Yersinia pseudotuberculosis, Pseudomonas aeruginosa, Enterococcus faecalis, Bacillus cereus, Staphylococcus aureus.Conclusion: 2-amino substituted halochalcone N-glycoside derivative compounds could be evaluated in the pharmaceutical and cosmetic fields due to their antioxidant and antimicrobial potential.

Revealing the complexation of 3-N,N-dimethylaminodithiocarbamoyl-1-propanesulfonic acid (DPS) with cuprous ion and its contribution to Cu electrodeposition

An accelerator is an organic additive used in Cu electrodeposition, crucial for achieving superfilling during the fabrication of Cu interconnects in microelectronics. 3-N,N-dimethylaminodithiocarbamoyl-1-propanesulfonic acid (DPS) has been proposed and investigated as a substitute for SPS. However, its acceleration mechanism associated with its interaction with Cu ions has not been intensively investigated. In this study, the interaction between DPS and Cu+ was investigated using various spectroscopic analyses, including ultraviolet–visible–near-infrared absorption (UV–VIS–NIR), electron paramagnetic resonance (EPR), and nuclear magnetic resonance (NMR) spectroscopy. UV–VIS–NIR and EPR spectroscopy revealed that DPS forms a complex with Cu+, namely Cu(I)(DPS)2. The kinetic study on the complexation of DPS with Cu+ indicated second-order reaction characteristics. The structure of the complex was suggested using 1H and 13C NMR spectroscopy. Furthermore, electrochemical analyses, including cyclic voltammetry (CV) and linear sweep voltammetry (LSV), were conducted to investigate the electrochemical behaviors of the Cu(I)(DPS)2 complex, demonstrating its acceleration effect on Cu electrodeposition. These results will provide valuable insights for understanding the acceleration mechanism of DPS in Cu electrodeposition.

Hamamelitannin’s Antioxidant Effect and Its Inhibition Capability on α-Glycosidase, Carbonic Anhydrase, Acetylcholinesterase, and Butyrylcholinesterase Enzymes

Hamamelitannin (2′,5-di-O-galloyl-hamamelose) bears two-gallate moieties in its structure, and is a natural phenolic product in the leaves and the bark of Hamamelis virginiana. The antioxidant capacity of hamamelitannin was evaluated by a range of methods, with the following findings: the ability to reduce potassium ferric cyanide; the scavenging of N,N-dimethyl-p-phenylenediamine dihydrochloride radical (DMPD•+); the scavenging of 2,2′-azinobis-(3-ethylbenzothiazoline-6-sulphonate) radical (ABTS•+); the scavenging of 1,1-diphenyl-2-picrylhydrazyl radical (DPPH•); and the ability to reduce cupric ions (Cu2+). Additionally, reference antioxidants of α-Tocopherol, butylated hydroxyanisole (BHA), Trolox, and butylated hydroxytoluene (BHT) were used for comparison. For DPPH radical scavenging, hamamelitannin had an IC50 value of 19.31 μg/mL, while the IC50 values for BHA, BHT, Trolox, and α-Tocopherol were 10.10, 25.95, 7.05, and 11.31 μg/mL, respectively. The study found that hamamelitannin functioned similarly to BHA, α-tocopherol, and Trolox in terms of DPPH• scavenging, but better than BHT. Additionally, as a polyphenolic secondary metabolite, the hamamelitannin inhibition capability of several metabolic enzymes was demonstrated, including acetylcholinesterase (AChE), butyrylcholinesterase (BChE), carbonic anhydrase I (CA I), carbonic anhydrase II (CA II) and α-glycosidase. The Ki values of hamamelitannin exhibited 7.40, 1.99, 10.18, 18.26, and 25.79 nM toward AChE, BChE, hCA I, hCA II, and α-glycosidase, respectively.

Effect of Anions on Deformation of Gallium-Based Liquid Metal in Solution.

In this study, deformation behaviors of gallium-based liquid metals in acidified cupric sulfate or cupric chloride solutions with varying concentrations of chloride anion or sulfate anion were investigated to explore their potential applications in soft machines and electronics. Gallium-based liquid metals are known for their unique deformability, making them promising materials for various fields. Previous research has shown that deformation of the liquid metal can be achieved in the presence of acidified cupric or ferric salts. However, the specific influence of different anions on the deformation process remains unclear. Our findings indicate that the deformation rate of the liquid metal increases with higher concentrations of chloride ions and decreases with higher concentrations of sulfate ions in the solution. UV-vis absorbance spectra of the solutions were analyzed to identify the formation of hydrated cupric cations. It was observed that increasing the concentration of Cl- ions promotes the formation of cupric-chloro complexes, thereby reducing the concentration of hydrated cupric ions in the solution. Furthermore, the addition of sulfate ions to the solution enhances the ionic strength of the medium, leading to the dissociation of cupric-chloro complexes. Additionally, sulfate ions can form insoluble layers with gallium ions, which impede the deformation of the liquid metal. The deformation rate of the liquid metal was found to be inversely correlated with the concentration of cupric ions in the solution. These results provide valuable insights into the deformable behavior of gallium-based liquid metals and their potential applications in liquid metal-based soft robots. This study highlights the importance of understanding the role of different anions in the deformation process of liquid metals, shedding light on the design and optimization of soft machines and electronics utilizing these materials.

Enhancement of cold-adapted heterotrophic nitrification and denitrification in Pseudomonas sp. NY1 by cupric ions: Performance and mechanism

Cupric ions can restrain biological nitrogen removal processes, which comprise nitrite reductase and nitric oxide reductase. Here, Pseudomonas sp. NY1 can efficiently perform heterotrophic nitrification and aerobic denitrification with cupric ions at 15 °C. At optimal culturing conditions, low cupric ion levels accelerated nitrogen degradation, and ammonium and nitrite removal efficiencies increased by 2.33%–4.85% and 6.76%–12.30%, respectively. Moreover, the maximum elimination rates for ammonium and nitrite increased from 9.48 to 10.26 mg/L/h and 6.20 to 6.80 mg/L/h upon adding 0.05 mg/L cupric ions. Additionally, low cupric ion concentrations promoted electron transport system activity (ETSA), especially for nitrite reduction. However, high concentrations of cupric ions decreased the ETSA during nitrogen conversion processes. The crucial enzymes ammonia monooxygenase, nitrate reductase, and nitrite reductase possessed similarly trends as ETSA upon exposure to cupric ion. These findings deepen the understanding for the effect of cupric ions on nitrogen consumption and bioremediation in nitrogen-polluted waters.

Piezoelectric-mediated two-dimensional copper-based metal–organic framework for synergistic sonodynamic and cuproptosis-driven tumor therapy

Sonodynamic therapy (SDT) is a minimally invasive therapeutic approach that utilizes sonosensitizers to catalyze substrates and generate reactive oxygen species (ROS) under ultrasound stimulation, ultimately inducing tumor cell death. Enhancing the piezoelectric properties of nanomaterials and modulating the semiconductor energy band are effective strategies to improve the catalytic efficiency of sonosensitizers. In this study, we developed a two-dimensional (2D) copper-based piezoelectric metal–organic framework (MOF) sonosensitizer, denoted as CM, through the coordination of copper and dimethylimidazole. The unique 2D MOF structure imparts CM with piezoelectric characteristics, enabling it to enhance SDT efficacy by modulating the semiconductor bandgap and carrier mobility. Upon ultrasound irradiation, CM catalyzes oxygen to undergo a cascade reaction, producing highly toxic singlet oxygen. Additionally, cupric ions in CM can be reduced by glutathione, facilitating the spontaneous catalysis of hydrogen peroxide in tumors to generate hydroxyl radicals and deplete glutathione, thereby inducing oxidative damage. Moreover, cupric ions in CM can trigger tumor cell cuproptosis, which, in combination with the generated ROS, accelerates cell death. Thus, this study establishes a MOF-based system for controllably inducing multi-pathway cancer cell death and provides a foundation for enhancing ultrasound-catalyzed tumor therapy through the optimization of piezoelectric properties.

HPAL of a lateritic nickel ore: An investigation on the relationship between nickel and cobalt extraction and acid consumption

Nickel and cobalt raw materials have become essential in industries like batteries such as robotics, and drones, which are considered as future technologies due to their expanding applications and diversity. Research towards the development of environmentally friendly and relatively low-cost alternative methods for extracting nickel, particularly from low-grade deposits, is becoming increasingly crucial. Laterite ores processing is plagued by high reagent consumption and scale formation. This study focused on investigating the relationship between Ni and Co extraction and acid consumption in the high-pressure acid leaching of lateritic ore, as well as the characterization of leach residue. Analysis has shown that the lateritic ore contains 1.05 % Ni, 0.05 % Co and 21.94 % Fe. In the acid leaching tests based upon a Box-Behnken Design, the initial acid concentration and leach time have a beneficial effect on the Ni extraction (70–94 %). Cobalt extractions ranged between 93 % and 96 %. To facilitate Fe dissolution and increase Ni extraction, cuprous ions were added into the leach solution. Moderate level copper addition (0.025 M) resulted in a significant improvement in Ni extraction, whereas high levels of cuprous addition (0.050 M) did not have further benefit. It has been noted that adding cuprous ions significantly reduces the amount of scale that forms in the autoclave. The lowest Ni extraction was obtained under two different test conditions that did not include copper ions. Increased acid addition was correlated with the increase in Ni leaching and decreased Fe content in residue. There will exist an optimal situation where the acid addition is enough to enhance Ni dissolution and the Eh condition, leading to minimal dissolved Fe.

Design, Synthesis, and Quantum Chemical Calculations of Triazole-Based Aroylhydrazone Molecules: Dual Assessment of Antioxidant Properties via in vitro and in silico Approaches

In this study, five novel Triazole-Based Aroylhydrazone compounds (6a-e) were synthesized in high yields (87-79%), starting from deferasirox which has known iron chelator, and characterized with NMR, FTIR, Mass, and UV-vis spectroscopic methods. Quantum chemical calculations of all synthesized molecules were performed at the DFT/B3LYP/6,311G(d,p) level. It was observed that both theoretical and experimental spectral values were compatible. Optimized molecular geometries were acquired from DFT calculations and used in molecular docking studies. Tyrosinase (PDB ID: 3NM8) protein, which is a related antioxidant, was utilized in molecular docking studies. 6d-3NM8 complex had the highest docking score with the -10.1 kcal/mol. Stabilization of the 6d-3NM8 complex during 100 ns was determined via molecular dynamics simulations. Intramolecular interactions of all molecules were also analyzed by NCI-RDG analysis. The frequently used cupric ion reducing antioxidant capacity method (CUPRAC) was used to determine the antioxidant activity of synthesized compounds and Trolox which is unknown in the literature on its activity in DMSO. The highest TEAC value was 1.76 (6d) while the lowest one was 1.34 (6e). It is possible to say that the synthesized substance 6d has the potential to be an antioxidant reagent based on the results of in vitro and in silico antioxidant activity. An explanation of the reason for using the CUPRAC method was added to the manuscript.

A hydrophilic porous graphene aerogel electrode with a large specific surface area for high-performance all-aqueous thermally regenerative batteries

All-aqueous thermally regenerative batteries (ATRBs) have shown great potential in harvesting low-grade waste heat. In this study, a hydrophilic porous graphene aerogel (GA) electrode developed by an ice template was developed for ATRBs to enhance electricity generation. The physicochemical property of GA was analyzed by traditional characterization. The main functional group of GA was N–H, which offered ATRBs a high hydrophilic surface. As a result of the ice templates, the diameter of pores in GA was almost lower than 4 nm, which provided a high specific area and good wettability. In addition, density functional theory calculations were carried out to verify the superiority of good electrical conductivity and strong adsorption on the cupric ions. Therefore, ATRB with GA achieved a competitive performance (a peak power density of 432 W/m2), illustrating great potential in the future thermoelectricity conversion application.

Antioxidant capacity and phenolic profile of defatted seed powder derived from organically grown vine crops

Grape seeds derived from winemaking pomace represent a significant waste stream with potential for valorization due to their rich phenolic content. The present study aimed to assess the phenolic composition and antioxidant potency of defatted grape seeds powder (DP) resulting after oil extraction through three different methods (i.e., cold stirring (ST), ultrasound-assisted extraction (US), and microwave-assisted extraction (MW)) from two grape varieties (i.e., Fetească Regală and Merlot) grown under organic farming conditions. The phenolic profile was determined using High-performance liquid chromatography with diode array detection and mass spectrometry operating in electrospray ionization positive mode, while the total phenolic content was determined using an adapted Folin-Ciocalteu technique, The samples' antioxidant properties were determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) radical scavenging ability assessments, as well as Cupric ion reducing antioxidant capacity and Ferric reducing antioxidant power assays. The phenolic qualitative profile differed between the two varieties and was unaffected by the defatting method. Instead, at the level of each variety, significant variations (p<0.05) were observed in the quantity of phenolic compounds, depending on the defatting method. Moreover, the total phenolic content was significantly higher in the MW-DP compared to ST-DP and US-DP (p<0.05), particularly from Fetească Regală grape seeds. The DPPH assay demonstrated the highest antioxidant activity in MW-DP from Fetească Regală. The study underscores the importance of the extraction methods and grape variety on the phenolic profile and antioxidant potency of DP. These findings suggest potential applications in pharmaceuticals, functional foods, and cosmetics, offering sustainable solutions for grape pomace utilization.

Cupric ion coordination-mediated molecularly imprinted electrochemical sensor for the recognition and ratiometric detection of lidocaine

Molecularly imprinted polymers (MIPs) have been widely used as artificial recognition elements in sensing applications. However, their electrochemical sensing performance is generally hampered by limited affinity and uncontrolled condition change. In this work, a novel MIP electrochemical sensor based on metal coordination interaction was prepared and used for the recognition and ratiometric detection of lidocaine (LC). The sensor was constructed by electrodepositing Cu-coordinated MIP on biomass carbon modified glassy carbon electrode. Herein, Cu2+ ions acted as anchor for the immobilization of LC during the synthesis process, enabling the orderly formation of molecular recognition sites. Reversely, the metal coordination between Cu2+ ions and LC molecules facilitated the recognition of LC. Moreover, the doped cupric ions in the polymer film could provide a reference signal for subsequent ratiometric strategy. Thus the resulting sensor exhibited high selectivity, sensitivity, satisfactory reproducibility, and anti-interference ability. Under the selected conditions, the peak current ratio of LC and cupric ion was linear to LC concentration in the range of 0.008–2.5 μmol L−1 (R2 = 0.9951), and the limit of detection was 1.9 nmol L−1 (S/N = 3). The practical feasibility of the sensor was evaluated by detecting human serum and pharmaceutical samples, and satisfactory outcomes were obtained.

Synthesis of novel polyethyleneimine-capped silver nanoclusters exhibiting ultraviolet-A fluorescence and their application in multiple sensing.

Cupric ions (Cu2+), pyrophosphate (PPi), and alkaline phosphatase (ALP) are involved in a variety of biochemical processes such as DNA replication, cellular metabolism and play an important role in human growth and development. It is of great significance to establish a method for the sensitive detection of Cu2+, PPi and ALP. In this work, polyethyleneimine-capped silver nanoclusters (PEI-AgNCs) were successfully synthesized by a one-pot method using hydrazine sulfate as reductant, exhibiting a unique strong fluorescence emission in the near-ultraviolet region at ∼339nm. Since the fluorescence of PEI-AgNCs can be quenched by Cu2+ through inner filtering effect (IFE), then recovered by competitive binding of pyrophosphate and Cu2+, and later weakened again by catalytic hydrolysis of alkaline phosphatase, a sensitive and selective strategy based on the changes of fluorescence "ON" or "OFF" was established to detect Cu2+, PPi and ALP. The LODs of these three analyteswere 36nM, 0.2μM, and 0.14 U L-1 at a S/N ratio of 3, respectively. A series of logic gate circuits for sensing cupric ions, pyrophosphate, and alkaline phosphatase were successfully constructed. The established methods have the potential for biosensing and environmental analysis and the specific UV-A fluorescence property of PEI-AgNCs may be helpful in photonic and optical areas.

Phytochemical Profiling and Biological Activity of the Methanolic Extracts of Cirsium Monspessulanum (L.) Hill.

The study of new plant species and the identification of their chemical composition may contribute to the discovery of a new breakthrough substances for pharmacotherapeutical applications. For the first time, we examined antioxidant and antimicrobial activity of 70 % v/v methanolic extracts from inflorescences and roots of Cirsium monspessulanum (L.) Hill. obtained by the ASE method. In the (2,2-diphenyl-1-picrylhydrazyl) DPPH analysis, tested extract of inflorescences showed antioxidant activity with an EC50=0.223±0.0479 mg/mL, and (Cupric Ion Reducting Antioxidant Capacity) CUPRAC test assessed the antiradical activity on 14.95±0.13 mgTE/g and for roots the values were EC50=0.307±0.0554 mg/mL and 11.18±0.49 mgTE/g, respectively. Furthermore, extract from the inflorescences possessed the highest antimicrobial activity against Staphylococcus aureus, Staphylococcus epidermidis and Micrococcus luteus with MIC=1.25 mg/mL for each. HPLC/ESI-QTOF-MS/MS method identified 7 phenolic acids and 14 flavonoids in inflorescences extract and only 7 phenolic acids in roots extract. To the best of our knowledge, this is the first qualitative analysis of Cirsium monspessulanum (L.) Hill. and all substances were described for the first time.

Electrically polarized nanoscale surfaces generate reactive oxygenated and chlorinated species for deactivation of microorganisms.

Because of the decreasing supply of new antibiotics, recent outbreaks of infectious diseases, and the emergence of antibiotic-resistant microorganisms, it is imperative to develop new effective strategies for deactivating a broad spectrum of microorganisms and viruses. We have implemented electrically polarized nanoscale metallic (ENM) coatings that deactivate a wide range of microorganisms including Gram-negative and Gram-positive bacteria with greater than 6-log reduction in less than 10 minutes of treatment. The electrically polarized devices were also effective in deactivating lentivirus and Candida albicans. The key to the high deactivation effectiveness of ENM devices is electrochemical production of micromolar cuprous ions, which mediated reduction of oxygen to hydrogen peroxide. Formation of highly damaging species, hydroxyl radicals and hypochlorous acid, from hydrogen peroxide contributed to antimicrobial properties of the ENM devices. The electric polarization of nanoscale coatings represents an unconventional tool for deactivating a broad spectrum of microorganisms through in situ production of reactive oxygenated and chlorinated species.

Exploring the In Vitro and In Vivo Therapeutic Efficacy of Juniperus oxycedrus Cade Oil: Antioxidant, Anti-inflammatory, and Anti-asthmatic Effects in an Allergic Asthma Model.

This investigation aimed to explore the antioxidant, anti-inflammatory effects of Cade oil and its efficacy within a Wistar allergic asthma model. The antioxidant activity was assessed through various in vitro tests using chain-breaking antioxidant effects (radical scavenging and reducing abilities assays). In vivo experiments involved Wistar rats categorized into four groups: negative control group, Ovalbumin-sensitised/challenged group, Cade oil-treated group, and Ovalbumin-sensitised/challenged Cade oil-treated group. These experiments aimed to evaluate oxidative stress parameters in the lungs and erythrocytes. The results indicated that the Cade oil exhibited significant antioxidant capabilities, evidenced by its radical scavenging activity against DPPH, ABTS, and Galvinoxyl radicals, with IC50 values ranging from 21.92 to 24.44 µg/mL. Besides, the reducing abilities methods showed A0,5 value ranging from 11.51 to 30.40 µg/mL for reducing power, Cupric ion reducing antioxidant capacity, and O-phenanthroline assays. Additionally, the IC50 value for β-carotene scavenging was found to be (8.2 ± 0.25 µg/ml). Analysis revealed high levels of polyphenols and flavonoids in Cade oil, indicating rich polyphenol (275.21 ± 3.14 mg GAE/g DW) and flavonoid (28.23 ± 1.91 µg QE/mg) content. In vivo findings highlighted Cade oil's efficacy in reducing inflammatory cell recruitment, enhancing antioxidant status, reducing lipid peroxidation, and improving histopathological alterations within the allergic asthma model. These results demonstrated that Cade oil has a potent antioxidant, anti-inflammatory, and anti-asthmatic properties, suggesting its potential therapeutic application in asthma treatment.

Nano-photosensitizers with gallic acid-involved Fe–O–Cu “electronic storage station” bridging ligand-to-metal charge transfer for efficient catalytic theranostics

NH2-MIL-88B (Fe) (MOF) is a promising photocatalytic material for antitumor therapy because of its distinctive electronic structure. However, inadequate separation of photo-generated electrons and slow reaction rate in low/high-valence iron (Fe) cycles limit their clinical application. In the present study, “electronic storage station” as a ligand-to-metal charge transfer bridge bond was constructed to inhibit recombination of electron/hole under 650 nm laser irradiation. Cupric (Cu) ions and gallic acid (GA) were self-assembled into a MOF (denoted as CGMOF) to create an FeO(GA)Cu bridge bond. GA, characterized by robust electron delocalization and abundant electron-donating groups, significantly enhances electron transfer efficiency for photodynamic therapy (PDT). CGMOF can respond to endogenous glutathione and release cuprous ions, accelerating the iron ion/ferrous ion cycles for chemodynamic therapy (CDT). The released Fe species can serve as T2-weighted magnetic resonance imaging contrast. Extended X-ray absorption fine structure spectra confirmed the presence of GA-containing FeOCu bonds in CGMOF. Furthermore, a series of photo-electrochemical tests confirmed that the formation of FeO(GA)Cu bond prominently elevated the redox capacity and increased the carrier density of CGMOF by 2.74-fold compared to that of MOF. In addition, cinnamaldehyde was grafted onto CGMOF for tumor-responsive hydrogen peroxide self-supply. Concurrently, hyaluronic acid was surface-modified to achieve the targeted delivery of nano-photosensitizers. In summary, this study presents an innovative approach for engineering Fe-based metal–organic frameworks for synergetic PDT/CDT applications.

Regenerating Chemotherapeutics through Copper-Based Nanomedicine: Disrupting Protein Homeostasis for Enhanced Tumor Therapy.

The bis-(diethyldithiocarbamate)-copper (CuET), the disulfiram (DSF)-Cu complex, has exhibited noteworthy anti-tumor property. However, its efficacy is compromised due to the inadequate oxidative conditions and the limitation of bioavailable copper. Because CuET can inactivate valosin-containing protein (VCP), a bioinformatic pan-cancer analysis of VCP is first conducted in this study to identify CuET as a promising anticancer drug for diverse cancer types. Then, based on the drug action mechanism, a nanocomposite of CuET and copper oxide (CuO) is designed and fabricated utilizing bovine serum albumin (BSA) as the template (denoted as CuET-CuO@BSA, CCB). CCB manifests peroxidase (POD)-mimicking activity to oxidize the tumor endogenous H2O2 to generate reactive oxygen species (ROS), enhancing the chemotherapy effect of CuET. Furthermore, the cupric ions released after enzymatic reaction can regenerate CuET, which markedly perturbs intracellular protein homeostasis and induces apoptosis of tumor cells. Meanwhile, CCB triggers cuproptosis by inducing the aggregation of lipoylated proteins. The multifaceted action of CCB effectively inhibits tumor progression. Therefore, this study presents an innovative CuET therapeutic strategy that creates an oxidative microenvironment in situ and simultaneously self-supply copper source for CuET regeneration through the combination of CuO nanozyme with CuET, which holds promise for application of CuET for effective tumor therapy.