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1.
BMC Vet Res ; 20(1): 137, 2024 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-38575964

RESUMO

OBJECTIVES: Fasciolosis is of significant economic and public health importance worldwide. The lack of a successful vaccine and emerging resistance in flukes to the drug of choice, triclabendazole, has initiated the search for alternative approaches. In recent years, metallic nanoparticles have been extensively investigated for their anthelmintic effects. This study investigates the in vitro anthelmintic activity of copper oxide and zinc oxide nanoparticles against Fasciola hepatica. METHODS: The in vitro study was based on egg hatchability test (EHA), adult motility inhibition tests, DNA damage, ROS levels, as well as several biomarkers of oxidative stress, including glutathione peroxidase (GSH) and glutathione S-transferase (GST), superoxide dismutase (SOD) and malondialdehyde (MDA). For this purpose, different concentrations of copper oxide nanoparticles (CuO-NPs) and Zinc oxide nanoparticles (ZnO-NPs) (1, 4, 8, 12, and 16 ppm) were used to evaluate the anthelmintic effect on different life stages, including egg and adults of Fasciola hepatica, over 24 h. RESULTS: In vitro treatment of F. hepatica worms with both CuO-NPs and ZnO-NPs could significantly increase ROS production and oxidative stress induction (decreased SOD, GST and GSH and increased MDA) compared to control group. CONCLUSIONS: Based on the results, it seems that CuO-NPs and ZnO-NPs may be effective in the control and treatment of F. hepatica infection. Further research is needed to investigate their potential for in vivo use in the treatment of parasitic infections.


Assuntos
Anti-Helmínticos , Fasciola hepatica , Nanopartículas Metálicas , Nanopartículas , Óxido de Zinco , Animais , Óxido de Zinco/farmacologia , Cobre/farmacologia , Espécies Reativas de Oxigênio , Estresse Oxidativo , Anti-Helmínticos/farmacologia , Dano ao DNA , Superóxido Dismutase/metabolismo , Biomarcadores
2.
Nan Fang Yi Ke Da Xue Xue Bao ; 44(3): 447-454, 2024 Mar 20.
Artigo em Chinês | MEDLINE | ID: mdl-38597435

RESUMO

OBJECTIVE: To investigate the neuroprotective effect of Huangpu Tongqiao Capsule (HPTQ) in a rat model of Wilson disease (WD) and explore the underlying mechanisms. METHODS: SD rat models of WD were established by feeding of coppersupplemented chow diet and drinking water for 12 weeks, and starting from the 9th week, the rats were treated with low-, moderate- and high-dose HPTQ, penicillamine, or normal saline by gavage on a daily basis for 3 weeks. Copper levels in the liver and 24-h urine of the rats were detected, and their learning and memory abilities were evaluated using Morris water maze test. HE staining was used to observe morphological changes of CA1 region neurons in the hippocampus, and neuronal apoptosis was detected with TUNEL staining. Hippocampal expressions of endoplasmic reticulum stress (ERS)-mediated apoptosis pathway-related proteins GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 at both the mRNA and protein levels were detected using RT-qPCR, immunofluorescence assay or Western blotting. RESULTS: Compared with normal control rats, the rat models with copper overload-induced WD exhibited significantly increased copper levels in both the liver and 24-h urine, impaired learning and memory abilities, obvious hippocampal neuronal damage in the CA1 region and increased TUNEL-positive neurons (P<0.01), with also lowered mRNA and protein expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the hippocampus (all P<0.01). Treatments with HPTQ and penicillamine significantly lowered copper level in the liver but increased urinary copper level, improved learning and memory ability, alleviated neuronal damage and apoptosis in the hippocampus, and decreased hippocampal expressions of GRP78, CHOP, caspase-12, cleaved caspase-9, and cleaved caspase-3 in the rat models (P<0.01 or 0.05). CONCLUSION: HPTQ Capsule has neuroprotective effects in rat models of WD possibly by inhibiting ERS-mediated apoptosis pathway.


Assuntos
Disfunção Cognitiva , Degeneração Hepatolenticular , Ratos , Animais , Ratos Sprague-Dawley , Degeneração Hepatolenticular/tratamento farmacológico , Caspase 3/metabolismo , Caspase 9/metabolismo , Caspase 12/metabolismo , Cobre/metabolismo , Cobre/farmacologia , Chaperona BiP do Retículo Endoplasmático , Estresse do Retículo Endoplasmático , Apoptose , Hipocampo/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Penicilamina/farmacologia , Disfunção Cognitiva/tratamento farmacológico , RNA Mensageiro
3.
Int J Nanomedicine ; 19: 3217-3232, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38596410

RESUMO

Background: Skin wounds are a prevalent issue that can have severe health consequences if not treated correctly. Nanozymes offer a promising therapeutic approach for the treatment of skin wounds, owing to their advantages in regulating redox homeostasis to reduce oxidative damage and kill bacteria. These properties make them an effective treatment option for skin wounds. However, most of current nanozymes lack the capability to simultaneously address inflammation, oxidative stress, and bacterial infection during the wound healing process. There is still great potential for nanozymes to increase their therapeutic functional diversity and efficacy. Methods: Herein, copper-doped hollow mesopores cerium oxide (Cu-HMCe) nanozymes with multifunctional of antioxidant, antimicrobial and pro-vascularity is successfully prepared. Cu-HMCe can be efficiently prepared through a simple and rapid solution method and displays sound physiological stability. The biocompatibility, pro-angiogenic, antimicrobial, and antioxidant properties of Cu-HMCe were assessed. Moreover, a full-thickness skin defect infection model was utilized to investigate the wound healing capacity, as well as anti-inflammatory and pro-angiogenic properties of nanozymes in vivo. Results: Both in vitro and in vivo experiments have substantiated Cu-HMCe's remarkable biocompatibility. Moreover, Cu-HMCe possesses potent antioxidant enzyme-like catalytic activity, effectively clearing DPPH radicals (with a scavenging rate of 80%), hydroxyl radicals, and reactive oxygen species. Additionally, Cu-HMCe exhibits excellent antimicrobial and pro-angiogenic properties, with over 70% inhibition of both E. coli and S. aureus. These properties collectively promote wound healing, and the wound treated with Cu-HMCe achieved a closure rate of over 90% on the 14th day. Conclusion: The results indicate that multifunctional Cu-HMCe with antioxidant, antimicrobial, and pro-angiogenic properties was successfully prepared and exhibited remarkable efficacy in promoting wound healing. This nanozymes providing a promising strategy for skin repair.


Assuntos
Anti-Infecciosos , Antioxidantes , Antioxidantes/farmacologia , Cobre/farmacologia , Escherichia coli , Staphylococcus aureus , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Hidrogéis
4.
Carbohydr Polym ; 332: 121923, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38431418

RESUMO

Bacterial cellulose (BC) produced by Acetobacter xylinum has great advantages in wound dressing. However, the structural limitation under static culture, and lack of antibacterial properties restrict its application, especially for infectious wound healing. The present study reported an original wound dressing, which was composed of a Janus BC membrane with antibacterial nano-sized copper oxide (CuO) through polydopamine (PDA) conjugation to promote wound healing under infectious condition. The finished product (CuO/PDA/BC membrane) exhibited favorable air permeability, high hydrophilicity and good mechanical properties, as well as strong antibacterial effects by the sustained release of CuO and photothermal effect of CuO/PDA. Furthermore, CuO/PDA/BC membrane inhibited inflammatory response and promoted wound healing in an infectious wound model in vivo. These results suggested that our CuO/PDA/BC membrane had great potential as wound dressing for infectious wound healing.


Assuntos
Celulose , Indóis , Polímeros , Infecção dos Ferimentos , Humanos , Celulose/farmacologia , Celulose/química , Cobre/farmacologia , Cobre/química , Cicatrização , Antibacterianos/farmacologia , Antibacterianos/química , Óxidos/farmacologia
5.
Int J Nanomedicine ; 19: 1985-2004, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38435754

RESUMO

Introduction: The anti-cancer potency of copper-doped carbon quantum dots (Cu-CDs) against breast cancer progression needs more detailed investigations. Methods: With urea and ethylene glycol applied as carbon sources and copper sulfate used as a reactive dopant, Cu-CDs were synthesized in the current study by a one-step hydrothermal synthesis method, followed by the characterization and biocompatibility evaluations of Cu-CDs. Subsequently, the anti-cancer potency of Cu-CDs against breast cancer progression was confirmed by these biochemical, molecular, and transcriptomic assessments, including viability, proliferation, migration, invasion, adhesion, clonogenicity, cell cycle distribution, apoptosis, redox homeostasis, and transcriptomic assays of MDA-MB-231 cells. Results: The biocompatibility of Cu-CDs was confirmed based on the non-significant changes in the pathological and physiological parameters in the Cu-CDs treated mice, as well as the noncytotoxic effect of Cu-CDs on normal cells. Moreover, the Cu-CDs treatments not only decreased the viability, proliferation, migration, invasion, adhesion, and clonogenicity of MDA-MB-231 cells but also induced the redox imbalance, cell cycle arrest, and apoptosis of MDA-MB-231 cells via ameliorating the mitochondrial dysfunctions and regulating the MAPK signaling pathway. Conclusion: Our findings confirmed the biosafety and excellent anti-cancer potency of Cu-CDs against breast cancer progression by tapping into mechanisms that disrupt malignant behaviors and oxidative homeostasis of breast cancer cells.


Assuntos
Neoplasias , Pontos Quânticos , Animais , Camundongos , Cobre/farmacologia , Apoptose , Carbono/farmacologia
6.
BMC Biotechnol ; 24(1): 11, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443850

RESUMO

BACKGROUND: One of the current challenges is to secure wheat crop production to meet the increasing global food demand and to face the increase in its purchasing power. Therefore, the current study aimed to exploit a new synthesized nanocomposite to enhance wheat growth under both normal and drought regime. The effectiveness of this nanocomposite in improving the microbiological quality of irrigation water and inhibiting the snail's growth was also assessed. RESULTS: Upon the employed one-step synthesis process, a spherical Fe/Cu/P nanocomposite was obtained with a mean particle size of 4.35 ± 1.524 nm. Cu2+, Fe2+, and P4+ were detected in the dried nanocomposite at 14.533 ± 0.176, 5.200 ± 0.208, and 34.167 ± 0.203 mg/ml concentration, respectively. This nanocomposite was found to exert antibacterial activity against Escherichia coli and Salmonella typhi. It caused good inhibition percent against Fusarium oxysporum (43.5 ± 1.47%) and reduced both its germination rate and germination efficiency. The lethal concentration 50 (LC50) of this nanocomposite against Lanistes carinatus snails was 76 ppm. The treated snails showed disturbance in their feeding habit and reached the prevention state. Significant histological changes were observed in snail digestive tract and male and female gonads. Drought stress on wheat's growth was mitigated in response to 100 and 300 ppm treatments. An increase in all assessed growth parameters was reported, mainly in the case of 100 ppm treatment under both standard and drought regimes. Compared to control plants, this stimulative effect was accompanied by a 2.12-fold rise in mitotic index and a 3.2-fold increase in total chromosomal abnormalities. CONCLUSION: The finding of the current study could be employed to mitigate the effect of drought stress on wheat growth and to enhance the microbiological quality of irrigation water. This is due to the increased efficacy of the newly synthesized Fe/Cu/P nanocomposite against bacteria, fungi, and snails. This methodology exhibits potential for promoting sustainable wheat growth and water resource conservation.


Assuntos
Anti-Infecciosos , Triticum , Cobre/farmacologia , Escherichia coli , Água , Fosfatos , Ferro
7.
Spectrochim Acta A Mol Biomol Spectrosc ; 313: 124117, 2024 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-38461559

RESUMO

Cancer's global impact necessitates innovative and less toxic treatments. Thiosemicarbazones (TSCs), adaptable metal chelators, offer such potential. In this study, we have synthesized N (4)-substituted heterocyclic TSCs from syringaldehyde (TSL1, TSL2), and also report the unexpected copper-mediated cyclization of the TSCs to form thiadiazoles (TSL3, TSL4), expanding research avenues. This work includes extensive characterization and studies such as DNA/protein binding, molecular docking, and theoretical analyses to demonstrate the potential of the as-prepared TSCs and thiadiazoles against different cancer cells. The DFT results depict that the thiadiazoles exhibit greater structural stability and reduced reactivity compared to the corresponding TSCs. The docking results suggest superior EGFR inhibition for TSL3 with a binding constant value of - 6.99 Kcal/mol. According to molecular dynamics studies, the TSL3-EGFR complex exhibits a lower average RMSD (1.39 nm) as compared to the TSL1-EGFR complex (3.29 nm) suggesting that both the thiadiazole and thiosemicarbazone examined here can be good inhibitors of EGFR protein, also that TSL3 can inhibit EGFR better than TSL1. ADME analysis indicates drug-likeness and oral availability of the thiadiazole-based drugs. The DNA binding experiment through absorption and emission spectroscopy discovered that TSL3 is more active towards DNA which is quantitatively calculated with a Kb value of 4.74 × 106 M-1, Kq value of 4.04 × 104 M-1and Kapp value of 5 × 106 M-1. Furthermore, the BSA binding studies carried out with fluorescence spectroscopy showed that TSL3 shows better binding capacity (1.64 × 105 M-1) with BSA protein. All the compounds show significant cytotoxicity against A459-lung, MCF-7-breast, and HepG2-liver cancer cell lines; TSL3 exhibits the best cytotoxicity, albeit less effective than cisplatin. Thiadiazoles demonstrate greater cytotoxicity than the TSCs. Overall, the promise of TSCs and thiadiazoles in cancer research is highlighted by this study. Furthermore, it unveils unexpected copper-mediated cyclization of the TSCs to thiadiazoles.


Assuntos
Antineoplásicos , Tiadiazóis , Tiossemicarbazonas , Simulação de Acoplamento Molecular , Teoria da Densidade Funcional , Cobre/farmacologia , Cobre/química , Tiossemicarbazonas/farmacologia , Tiossemicarbazonas/química , Ciclização , Tiadiazóis/farmacologia , Tiadiazóis/química , Espectrometria de Fluorescência , DNA/química , Receptores ErbB/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química
8.
Curr Microbiol ; 81(5): 118, 2024 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-38492019

RESUMO

Synthesizing nanoparticles through a green synthesis approach is common nowadays. Cyanobacteria have attained great importance in the field of biosynthesis of nanoparticles as there is no use of toxic chemicals as reducing or capping agents for the synthesis of metal oxide nanoparticles. Micronutrient-based nano-formulations have become a topic of great interest in recent times due to their various advantageous properties and applications in agriculture. The current study aims to exploit the potential cyanobacterial strains isolated from different locations such as freshwater and soil ecosystems. The potential cyanobacterial isolates were screened based on their multiple plant growth promoting (PGP) attributes such as Indol acetic acid (IAA) production, siderophores, and phosphate solubilization. After the screening of cyanobacteria based on multiple PGP activities, the cyanobacterial strain was identified at the species level as Pseudanabaena foetida RJ1, based on microscopy and molecular characterization using 16S rRNA gene sequencing. The cyanobacterial biomass extract and cell-free extracts are utilized for the synthesis of CuO micronutrient Nanoparticles (NPs). The cyanobacterial strain Pseudanabaena foetida RJ1 possesses plant growth-promoting (PGP) attributes that provide reduction and capping for CuO NPs. The synthesized NPs were characterized and subjected to make a nano-formulation, utilizing the cyanobacteria-mediated CuO NPs along with low-cost zeolite as an adsorbent. The application of cyanobacterial biomass extract and cell-free extract provided an excellent comparative aspect in terms of micronutrient NP synthesis. The NPs in the form of formulations were applied to germinated paddy seeds (Pusa Basmati -1509) with varying concentrations (5, 10, 15 mg/l). Effects of cyanobacteria based CuO NPs on hydroponically grown paddy crops were analyzed. The application of nano-formulations has shown a significant increase in plant growth promotion in rice plants under hydroponics conditions. There is no such type of comparative investigation reported earlier, and NPs of micronutrients can be utilized as a new economic nanofertilizer and can be applied to plants for their growth promotion.


Assuntos
Cianobactérias , Nanopartículas Metálicas , Nanopartículas , Oryza , Cobre/farmacologia , Hidroponia , RNA Ribossômico 16S/genética , Ecossistema , Nanopartículas Metálicas/química , Micronutrientes , Extratos Vegetais
9.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38430558

RESUMO

To investigate effects of inorganic or complexed trace mineral source (zinc, copper, manganese, and cobalt) on receiving period performance and morbidity, crossbred beef heifer calves (n = 287) arriving on three delivery dates were used in a 42-d receiving trial. Heifers were processed after arrival, stratified by day -1 body weights (BW) and allocated randomly to eight pens (11 to 13 heifers/pen, 24 pens total). Within truckload, pens were assigned randomly to dietary treatment (n = 12 pens/treatment). Heifers were housed on 0.42-ha grass paddocks, provided ad libitum bermudagrass hay and provided dietary treatments in grain supplements fed daily. Treatments consisted of supplemental zinc (360 mg/d), copper (125 mg/d), manganese (200 mg/d), and cobalt (12 mg/d) from complexed (Zinpro Availa 4, Zinpro Corp. Eden Prairie, MN) or inorganic sources (sulfates). Heifers were observed daily for clinical bovine respiratory disease (BRD). If presenting BRD symptoms and rectal temperature ≥ 40 °C, heifers were deemed morbid and treated with antibiotics. Six heifers/pen were bled to determine serum haptoglobin concentrations on days 0, 14, and 28. Liver biopsies were taken on day 5 ±â€…2 and 43 ±â€…1 from three calves selected randomly from each pen for mineral status comparisons. Statistical analyses were performed using the MIXED, GLIMMIX, and repeated measures procedures of SAS 9.4 with truckload as a random effect and pen within truckload specified as subject. There tended to be a treatment by day interaction for BW (P = 0.07). Heifer BW did not differ on day 0 (P = 0.82) and day 14 (P = 0.36), but heifers fed complexed trace minerals had greater BW on day 28 (P = 0.04) and day 42 (P = 0.05). Overall average daily gains were greater for heifers fed complexed trace minerals (P = 0.05; 0.78 vs. 0.70 kg, SE = 0.03). Heifers supplemented with inorganic trace minerals had greater BRD incidence (P = 0.03; 58 vs. 46%, SE = 3.6). Haptoglobin concentrations decreased throughout the trial (P < 0.001), and heifers fed complexed trace minerals tended to have a decrease in haptoglobin concentrations (P = 0.07). The source of trace mineral supplementation had no effect (P ≥ 0.20) on liver mineral concentrations and there were no treatment × day interactions (P ≥ 0.35). In conclusion, supplementing diets for the first 42 d after arrival with complexed trace mineral sources improved heifer performance as compared to heifers supplemented with inorganic trace minerals.


Issues associated with health and management of newly received cattle continue to pose significant animal welfare and economic challenges for the beef industry. Diagnosis of bovine respiratory disease, accompanied with poor growth performance, can be addressed by nutritional intervention in receiving cattle. Trace mineral inclusion in receiving rations is vital to calf performance. There are numerous sources of trace mineral supplements that exist commercially for cattle and their effects on immune function, growth, and performance measures were evaluated. Organic trace mineral supplements are being used in replacement of inorganic salts due to potentially greater bioavailability and functionality. An organic source that is commonly used are amino acid complexes. Replacing inorganic sources with complexed sources of trace minerals (zinc, copper, manganese, and cobalt) improved growth performance and decreased sickness during the 42-d receiving study.


Assuntos
Oligoelementos , Bovinos , Animais , Feminino , Oligoelementos/farmacologia , Manganês/farmacologia , Cobre/farmacologia , Haptoglobinas/análise , Suplementos Nutricionais , Minerais/farmacologia , Zinco/farmacologia , Cobalto/farmacologia , Dieta/veterinária , Peso Corporal , Ração Animal/análise
10.
ACS Appl Mater Interfaces ; 16(13): 16653-16668, 2024 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-38520338

RESUMO

Cancer metastasis and recurrence are closely associated with immunosuppression and a hypoxic tumor microenvironment. Chemodynamic therapy (CDT) and photothermodynamic therapy (PTT) have been shown to induce immunogenic cell death (ICD), effectively inhibiting cancer metastasis and recurrence when combined with immune adjuvants. However, the limited efficacy of Fenton's reaction and suboptimal photothermal effect present significant challenges for successfully inducing ICD through CDT and PTT. This paper described the synthesis and immunoantitumor activity of the novel iron-copper-doped folic acid carbon dots (CFCFB). Copper-doped folic acid carbon dots (Cu-FACDs) were initially synthesized via a hydrothermal method, using folic acid and copper gluconate as precursors. Subsequently, the nanoparticles CFCFB were obtained through cross-linking and self-assembly of Cu-FACDs with ferrocene dicarboxylic acid (FeDA) and 3-bromopyruvic acid (3BP). The catalytic effect of carbon dots in CFCFB enhanced the activity of the Fenton reaction, thereby promoting CDT-induced ICD and increasing the intracellular oxygen concentration. Additionally, 3BP inhibited cellular respiration, further amplifying the oxygen concentration. The photothermal conversion efficiency of CFCFB reached 55.8%, which significantly enhanced its antitumor efficacy through photothermal therapy. Immunofluorescence assay revealed that treatment with CFCFB led to an increased expression of ICD markers, including calreticulin (CRT) and ATP, as well as extracellular release of HMGB-1, indicating the induction of ICD by CFCFB. Moreover, the observed downregulation of ARG1 expression indicates a transition in the tumor microenvironment from an immunosuppressive state to an antitumor state following treatment with CFCFB. The upregulation of IL-2 and CD8 expression facilitated the differentiation of effector T cells, resulting in an augmented population of CD8+ T cells, thereby indicating the activation of systemic immune response.


Assuntos
Nanopartículas , Neoplasias , Humanos , Cobre/farmacologia , Linfócitos T CD8-Positivos , Ferro/farmacologia , Carbono/farmacologia , Ácido Fólico/farmacologia , Neoplasias/tratamento farmacológico , Oxigênio/farmacologia , Linhagem Celular Tumoral , Microambiente Tumoral , Peróxido de Hidrogênio
11.
Mol Pharm ; 21(4): 1987-1997, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-38507593

RESUMO

The misuse and overdose of antimicrobial medicines are fostering the emergence of novel drug-resistant pathogens, providing negative repercussions not only on the global healthcare system due to the rise of long-term or chronic patients and inefficient therapies but also on the world trade, productivity, and, in short, to the global economic growth. In view of these scenarios, novel action plans to constrain this antibacterial resistance are needed. Thus, given the proven antiproliferative tumoral and microbial features of thiosemicarbazone (TSCN) ligands, we have here synthesized a novel effective antibacterial copper-thiosemicarbazone complex, demonstrating both its solubility profile and complex stability under physiological conditions, along with their safety and antibacterial activity in contact with human cellular nature and two most predominant bacterial strains, respectively. A significant growth inhibition (17% after 20 h) is evidenced over time, paving the way toward an effective antibacterial therapy based on these copper-TSCN complexes.


Assuntos
Anti-Infecciosos , Complexos de Coordenação , Compostos Organometálicos , Tiossemicarbazonas , Humanos , Cobre/farmacologia , Tiossemicarbazonas/farmacologia , Anti-Infecciosos/farmacologia , Antibacterianos/farmacologia , Complexos de Coordenação/farmacologia
12.
ACS Appl Bio Mater ; 7(3): 1588-1599, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38437727

RESUMO

The synthesis of copper nanoparticles (CuNPs) was accomplished by using a rapid, green, and versatile argon plasma reduction method that involves solvent extraction. With this method, a plasma-solid state interaction forms and CuNPs can be synthesized from copper(II) sulfate using a low-pressure, low-temperature argon plasma. Characterization studies of the CuNPs revealed that when a metal precursor is treated under optimal experimental conditions of 80 W of argon plasma for 300 s, brown CuNPs are synthesized. However, when those same brown CuNPs are placed in Milli-Q water for a period of 10 days, oxidation occurs and green CuNPs are formed. Confirmation of the chemical identity of the CuNPs was performed by using X-ray photoelectron spectroscopy. The results reveal that the brown CuNPs are predominantly Cu0 or what we refer to as CuNPs, while the green CuNPs are a mixture of Cu0 and Cu(OH)2 NPs. Upon further characterization of both brown and green CuNPs with scanning electron microscopy (SEM), the results depict brown CuNPs with a rod-like shape and approximate dimensions of 40 nm × 160 nm, while the green CuNPs were smaller in size, with dimensions of 40-80 nm, and more of a round shape. When testing the antibacterial activity of both brown and green CuNPs, our findings demonstrate the effectiveness of both CuNPs against Escherichia coli and Staphylococcus aureus bacteria at a concentration of 17 µg/mL. The inactivation of S. aureus and E. coli 7-day-old biofilms required CuNP concentrations of 99 µg/mL. SEM images of treated 7-day-old S. aureus and E. coli biofilms depict cell membranes that are completely damaged, suggesting a physical killing mechanism. In addition, when the same concentration of CuNPs used to inactivate biofilms were tested with human fibroblasts, both brown and green CuNPs were found to be biocompatible.


Assuntos
Anti-Infecciosos , Nanopartículas , Gases em Plasma , Humanos , Cobre/farmacologia , Gases em Plasma/farmacologia , Escherichia coli , Staphylococcus aureus , Anti-Infecciosos/farmacologia
13.
Inorg Chem ; 63(11): 4925-4938, 2024 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-38442008

RESUMO

Osteosarcoma cancers are becoming more common in children and young adults, and existing treatments have low efficacy and a very high mortality rate, making it pressing to search for new chemotherapies with high efficacy and high selectivity index. Copper complexes have shown promise in the treatment of osteosarcoma. Here, we report the synthesis, characterization, and anticancer activity of [Cu(N-N-Fur)(NO3)(H2O)] complex where N-N-Fur is (E)-N'-(2-hydroxy-3-methoxybenzylidene)furan-2-carbohydrazide. The [Cu(N-N-Fur)(NO3)(H2O)] complex was characterized via X-ray diffraction and electron spin resonance (ESR), displaying a copper center in a nearly squared pyramid environment with the nitrate ligand acting as a fifth ligand in the coordination sphere. We observed that [Cu(N-N-Fur)(NO3)(H2O)] binds to DNA in an intercalative manner. Anticancer activity on the MG-63 cell line was evaluated in osteosarcoma monolayer (IC50 2D: 1.1 ± 0.1 µM) and spheroids (IC50 3D: 16.3 ± 3.1 µM). Selectivity assays using nontumoral fibroblast (L929 cell line) showed that [Cu(N-N-Fur)(NO3)(H2O)] has selectivity index value of 2.3 compared to cis-diamminedichloroplatinum(II) (CDDP) (SI = 0.3). Additionally, flow cytometry studies demonstrated that [Cu(N-N-Fur)(NO3)(H2O)] inhibits cell proliferation and conveys cells to apoptosis. Cell viability studies of MG-63 spheroids (IC50 = 16.3 ± 3.1 µM) showed that its IC50 value is 4 times lower than for CDDP (IC50 = 65 ± 6 µM). Besides, we found that cell death events mainly occurred in the center region of the spheroids, indicating efficient transport to the microtumor. Lastly, the complex showed dose-dependent reductions in spheroid cell migration from 7.5 to 20 µM, indicating both anticancer and antimetastatic effects.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Criança , Adulto Jovem , Humanos , Cobre/farmacologia , Ligantes , Osteossarcoma/tratamento farmacológico , Cisplatino
14.
BMC Microbiol ; 24(1): 81, 2024 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-38461228

RESUMO

BACKGROUND: Copper-induced gene expression in Xanthomonas campestris pv. campestris (Xcc) is typically evaluated using targeted approaches involving qPCR. The global response to copper stress in Xcc and resistance to metal induced damage is not well understood. However, homologs of heavy metal efflux genes from the related Stenotrophomonas genus are found in Xanthomonas which suggests that metal related efflux may also be present. METHODS AND RESULTS: Gene expression in Xcc strain BrA1 exposed to 0.8 mM CuSO4.5H2O for 15 minutes was captured using RNA-seq analysis. Changes in expression was noted for genes related to general stress responses and oxidoreductases, biofilm formation, protein folding chaperones, heat-shock proteins, membrane lipid profile, multiple drug and efflux (MDR) transporters, and DNA repair were documented. At this timepoint only the cohL (copper homeostasis/tolerance) gene was upregulated as well as a chromosomal czcCBA efflux operon. An additional screen up to 4 hrs using qPCR was conducted using a wider range of heavy metals. Target genes included a cop-containing heavy metal resistance island and putative metal efflux genes. Several efflux pumps, including a copper resistance associated homolog from S. maltophilia, were upregulated under toxic copper stress. However, these pumps were also upregulated in response to other toxic heavy metals. Additionally, the temporal expression of the coh and cop operons was also observed, demonstrating co-expression of tolerance responses and later activation of part of the cop operon. CONCLUSIONS: Overall, initial transcriptional responses focused on combating oxidative stress, mitigating protein damage and potentially increasing resistance to heavy metals and other biocides. A putative copper responsive efflux gene and others which might play a role in broader heavy metal resistance were also identified. Furthermore, the expression patterns of the cop operon in conjunction with other copper responsive genes allowed for a better understanding of the fate of copper ions in Xanthomonas. This work provides useful evidence for further evaluating MDR and other efflux pumps in metal-specific homeostasis and tolerance phenotypes in the Xanthomonas genus. Furthermore, non-canonical copper tolerance and resistance efflux pumps were potentially identified. These findings have implications for interpreting MIC differences among strains with homologous copLAB resistance genes, understanding survival under copper stress, and resistance in disease management.


Assuntos
Xanthomonas campestris , Xanthomonas , Cobre/farmacologia , Cobre/metabolismo , Xanthomonas campestris/genética , Xanthomonas campestris/metabolismo , Xanthomonas/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo
15.
Colloids Surf B Biointerfaces ; 236: 113804, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38428209

RESUMO

In this study, a double network (DN) hydrogel was synthesized using poly(ethylene glycol) diacrylate (PEGDA) and sodium alginate (SA), incorporating copper-doped mesoporous silica nanospheres (Cu-MSNs) and zinc oxide nanoparticles (ZnO NPs). The blending of PEGDA and SA (PS) facilitates the double network and improves the less porous microstructure of pure PEGDA hydrogel. Furthermore, the incorporation of ZnO NPs and Cu-MSNs into the hydrogel network (PS@ZnO/Cu-MSNs) improved the mechanical properties of the hydrogel (Compressive strength = ⁓153 kPa and Young's modulus = ⁓ 1.66 kPa) when compared to PS hydrogel alone (Compressive strength = ⁓ 103 kPa and Young's modulus = ⁓ 0.95 kPa). In addition, the PS@ZnO/Cu-MSNs composite hydrogel showed antibacterial activities against Staphylococcus aureus and Escherichia coli. Importantly, the PS@ZnO/Cu-MSNs hydrogel demonstrated excellent biocompatibility, enhanced MC3T3-E1 cell adhesion, proliferation, and significant early-stage osteoblastic differentiation, as evidenced by increased alkaline phosphatase (ALP), and improved calcium mineralization, as evidenced by increased alizarin red staining (ARS) activities. These findings point to the possible use of the PS@ZnO/Cu-MSNs composite hydrogel in bone tissue regeneration.


Assuntos
Nanopartículas , Nanosferas , Óxido de Zinco , Nanosferas/química , Cobre/farmacologia , Óxido de Zinco/farmacologia , Osteogênese , Engenharia Tecidual , Hidrogéis/farmacologia , Hidrogéis/química , Dióxido de Silício/química , Alginatos/farmacologia , Alginatos/química , Nanopartículas/química , Polietilenoglicóis/química
16.
Artigo em Inglês | MEDLINE | ID: mdl-38464913

RESUMO

Background: The wing-beating tremor, characteristic of Wilson's disease (WD), is a disabling symptom that can be resistant to anti-copper and anti-tremor medications. Phenomenology Shown: This video illustrates severe bilateral wing-beating tremor, moderate head and lower limb tremors, mild cervical dystonia, and subtle cerebellar ataxia, with nearly resolution after penicillamine treatment. Educational Value: This case highlights a typical aspect of WD, emphasizing the importance of early detection and treatment, and its correlation with MRI findings. Highlights: This case highlights the typical wing-beating tremor in Wilson's disease and its correlation with the involvement of the dentato-rubro-thalamic pathway. The early diagnosis and initiation of treatment with penicillamine resulted in an excellent clinical and radiological response.


Assuntos
Degeneração Hepatolenticular , Penicilamina , Humanos , Cobre/farmacologia , Degeneração Hepatolenticular/diagnóstico por imagem , Degeneração Hepatolenticular/tratamento farmacológico , Imageamento por Ressonância Magnética , Penicilamina/uso terapêutico , Tremor/diagnóstico por imagem , Tremor/tratamento farmacológico , Tremor/etiologia
17.
ACS Nano ; 18(9): 6975-6989, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38377439

RESUMO

Regarded as one of the hallmarks of tumorigenesis and tumor progression, the evasion of apoptotic cell death would also account for treatment resistance or failure during cancer therapy. In this study, a Ca2+/Cu2+ dual-ion "nano trap" to effectively avoid cell apoptosis evasion by synchronously inducing paraptosis together with apoptosis was successfully designed and fabricated for breast cancer treatment. In brief, disulfiram (DSF)-loaded amorphous calcium carbonate nanoparticles (NPs) were fabricated via a gas diffusion method. Further on, the Cu2+-tannic acid metal phenolic network was embedded onto the NPs surface by self-assembling, followed by mDSPE-PEG/lipid capping to form the DSF-loaded Ca2+/Cu2+ dual-ions "nano trap". The as-prepared nanotrap would undergo acid-triggered biodegradation upon being endocytosed by tumor cells within the lysosome for Ca2+, Cu2+, and DSF releasing simultaneously. The released Ca2+ could cause mitochondrial calcium overload and lead to hydrogen peroxide (H2O2) overexpression. Meanwhile, Ca2+/reactive oxygen species-associated mitochondrial dysfunction would lead to paraptosis cell death. Most importantly, cell paraptosis could be further induced and strengthened by the toxic dithiocarbamate (DTC)-copper complexes formed by the Cu2+ combined with the DTC, the metabolic products of DSF. Additionally, the released Cu2+ will be reduced by intracellular glutathione to generate Cu+, which can catalyze the H2O2 to produce a toxic hydroxyl radical by a Cu+-mediated Fenton-like reaction for inducing cell apoptosis. Both in vitro cellular assays and in vivo antitumor evaluations confirmed the cancer therapeutic efficiency by the dual ion nano trap. This study can broaden the cognition scope of dual-ion-mediated paraptosis together with apoptosis via a multifunctional nanoplatform.


Assuntos
Neoplasias da Mama , Dissulfiram , Polifenóis , Humanos , Feminino , Dissulfiram/farmacologia , Cobre/farmacologia , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Peróxido de Hidrogênio/metabolismo , Linhagem Celular Tumoral , Apoptose
18.
ACS Nano ; 18(9): 7024-7036, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38394383

RESUMO

Chronic wounds frequently arise as a complication in diabetic patients, and their management remains a significant clinical hurdle due to their nonhealing nature featured by heightened oxidative stress and impaired healing cells at the wound site. Herein, we present a 2D copper antioxidant nanozyme induced by phenolic ligand-metal charge transfer (LMCT) to eliminate reactive oxygen species (ROS) and facilitate the healing of chronic diabetic wounds. We found that polyphenol ligands coordinated on the Cu3(PO4)2 nanosheets led to a strong charge transfer at the interface and regulated the valence states of Cu. The obtained Cu nanozyme exhibited efficient scavenging ability toward different oxidative species and protected human cells from oxidative damage. The nanozyme enhanced the healing of diabetic wounds by promoting re-epithelialization, collagen deposition, angiogenesis, and immunoregulation. This work demonstrates the LMCT-induced ROS scavenging ability on a nanointerface, providing an alternative strategy of constructing metal-based nanozymes for the treatment of diabetic wounds as well as other diseases.


Assuntos
Cobre , Diabetes Mellitus , Humanos , Espécies Reativas de Oxigênio , Cobre/farmacologia , Ligantes , Cicatrização , Hidrogéis
19.
BMC Genomics ; 25(1): 220, 2024 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-38413895

RESUMO

BACKGROUND: The appropriate mineral nutrients are essential for sheep growth and reproduction. However, traditional grazing sheep often experience mineral nutrient deficiencies, especially copper (Cu), due to inadequate mineral nutrients from natural pastures. RESULTS: The results indicated that dietary Cu deficiency and supplementation significantly reduced and elevated liver concentration of Cu, respectively (p < 0.05). FOXO3, PLIN1, ACTN2, and GHRHR were identified as critical genes using the weighted gene co-expression network analysis (WGCNA), quantitative real-time polymerase chain reaction (qRT-PCR), and receiver operating characteristic curve (ROC) validation as potential biomarkers for evaluating Cu status in grazing sheep. Combining these critical genes with gene functional enrichment analysis, it was observed that dietary Cu deficiency may impair liver regeneration and compromise ribosomal function. Conversely, dietary Cu supplementation may enhance ribosomal function, promote lipid accumulation, and stimulate growth and metabolism in grazing sheep. Metabolomics analysis indicated that dietary Cu deficiency significantly decreased the abundance of metabolites such as cholic acid (p < 0.05). On the other hand, dietary Cu supplementation significantly increased the abundance of metabolites such as palmitic acid (p < 0.05). Integrative analysis of the transcriptome and metabolome revealed that dietary Cu deficiency may reduce liver lipid metabolism while Cu supplementation may elevate it in grazing sheep. CONCLUSIONS: The Cu content in diets may have an impact on hepatic lipid metabolism in grazing sheep. These findings provide new insights into the consequences of dietary Cu deficiency and supplementation on sheep liver and can provide valuable guidance for herders to rationalize the use of mineral supplements.


Assuntos
Cobre , Fígado , Ovinos , Animais , Cobre/farmacologia , Fígado/metabolismo , Suplementos Nutricionais , Minerais/metabolismo , Perfilação da Expressão Gênica , Expressão Gênica
20.
J Colloid Interface Sci ; 661: 802-814, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38330653

RESUMO

The strong antimicrobial resistance (AMR) of multidrug-resistant (MDR) bacteria and biofilm, especially the biofilm with extracellular polymeric substance (EPS) protection and persister cells, not only renders antibiotics ineffective but also causes chronic infections and makes the infectious tissue difficult to repair. Considering the acidic properties of bacterial infection microenvironment and biofilm, herein, a binary graphene oxide and copper iron sulfide nanocomposite (GO/CuFeSx NC) is synthesized by a surfactant free strategy and utilized as an alternative smart nanozyme to fight against the MDR bacteria and biofilm. For the GO/CuFeSx NC, the iron decoration facilitates the well distribution of bimetallic CuFeSx NPs on the GO surfaces compared to monometallic CuS NPs, providing synergistically enhanced peroxidase (POD)-like activity in acidic medium (pH 4 âˆ¼ 5) and intrinsic strong near infrared (NIR) light responsive photothermal activity, while the ultrathin and sharp structure of 2D GO nanosheet allows the GO/CuFeSx NC to strongly interact with the bacteria and biofilm, facilitating the catalytic and photothermal attacks on the bacterial surfaces. In addition, the GO in GO/CuFeSx NC exhibits a "Pseudo-Photo-Fenton" effect to promote the ROS generation. Therefore, the GO/CuFeSx NC can effectively kill bacteria and biofilm both in vitro and in vivo, finally eliminating the infections and accelerating the tissue repair when treating the biofilm-infected wound. This work paves a new way to the design of novel nanozyme for smart antibacterial therapy against antimicrobial resistance.


Assuntos
Antibacterianos , Compostos Ferrosos , Grafite , Nanocompostos , Antibacterianos/farmacologia , Antibacterianos/química , Cobre/farmacologia , Cobre/química , Ferro/farmacologia , Matriz Extracelular de Substâncias Poliméricas , Farmacorresistência Bacteriana , Nanocompostos/química , Bactérias
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