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1.
Molecules ; 28(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36677708

RESUMO

Dental implants made of titanium (Ti) are used in dentistry, but peri-implantitis is a serious associated problem. Antibacterial and osteoconductive Ti dental implants may decrease the risk of peri-implantitis. In this study, titania (TiO2) co-doped with silver (Ag) at 2.5 at.% and copper (Cu) at 4.9 at.% was formed on Ti substrates via chemical and thermal treatments. The Ag and Cu co-doped TiO2 formed apatite in a simulated body fluid, which suggests osteoconductivity. It also showed antibacterial activity against Escherichia coli, which was enhanced by visible-light irradiation. This enhancement might be caused by the synergistic effect of the release of Ag and Cu and the generation of •OH from the sample. Dental implants with such a Ag and Cu co-doped TiO2 formed on their surface may reduce the risk of peri-implantitis.


Assuntos
Implantes Dentários , Peri-Implantite , Humanos , Titânio/química , Prata/farmacologia , Prata/química , Cobre/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Escherichia coli
2.
Int J Mol Sci ; 24(1)2023 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-36614204

RESUMO

The three Schiff base ligands, derivatives of hesperetin, HHSB (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]isonicotinohydrazide), HIN (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]benzhydrazide) and HTSC (N-[2,3-dihydro-5,7-dihydroxy-2-(3-hydroxy-4-methoxyphenyl)chromen-4-ylidene]thiosemicarbazide) and their copper complexes, CuHHSB, CuHIN, and CuHTSC were designed, synthesized and analyzed in terms of their spectral characterization and the genotoxic activity. Their structures were established using several methods: elemental analysis, FT-IR, UV-Vis, EPR, and ESI-MS. Spectral data showed that in the acetate complexes the tested Schiff bases act as neutral tridentate ligand coordinating to the copper ion through two oxygen (or oxygen and sulphur) donor atoms and a nitrogen donor atom. EPR measurements indicate that in solution the complexes keep their structures with the ligands remaining bound to copper(II) in a tridentate fashion with (O-, N, Oket) or (O-, N, S) donor set. The genotoxic activity of the compounds was tested against model tumour (HeLa and Caco-2) and normal (LLC-PK1) cell lines. In HeLa cells the genotoxicity for all tested compounds was noticed, for HHSB and CuHHSB was the highest, for HTSC and CuHTSC-the lowest. Generally, Cu complexes displayed lower genotoxicity to HeLa cells than ligands. In the case of Caco-2 cell line HHSB and HTSC induced the strongest breaks to DNA. On the other side, CuHHSB and CuHTSC induced the highest DNA damage against LLC-PK1.


Assuntos
Complexos de Coordenação , Cobre , Humanos , Cobre/farmacologia , Cobre/química , Bases de Schiff/farmacologia , Bases de Schiff/química , Espectroscopia de Infravermelho com Transformada de Fourier , Células HeLa , Células CACO-2 , Oxigênio , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Ligantes
3.
Comput Math Methods Med ; 2023: 3311834, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36684691

RESUMO

Objective: The objective of this study was to explore the medicinal properties of herbal medicines that can interfere with the copper death pathway. Methods: The Human Gene Database, Chemical Interactions in Comparative Toxicogenomics Database, Encyclopedia of Traditional Chinese Medicine, China Medical Information Platform, and Cytoscape software were used to find target and chemicals that interfere with copper death targets, as well as herbal medicines containing these chemicals and their four natures and five flavors (basic properties of herbal medicines). Results: 27 copper death-related targets were finally retrieved, as well as 2143 chemicals that could interfere with them, including 180 herbal compounds. The compounds with the highest degree values (number of nodes connected to this node) were folic acid, resveratrol, and quercetin. The 180 compounds were related to 278 herbs; those with the highest degree values (number of nodes connected to this node) were Jujubae Fructus, Ginkgo biloba L, and Acanthopanax senticosus. The 27 copper death targets were indirectly associated with 278 herbs; those with the highest degree values (number of nodes connected to this node) were Achyranthis Bidentatae Radix, Polygonum cuspidatum Sieb. et Zucc, and Mori Folium. Among the 278 herbs, 6 had incomplete information. A pharmacological analysis showed that among the 272 Chinese herbs, the most frequent meridians were the liver (133), lung (104), and spleen (91). Of the four natures, the most frequent were cold (73), warm (68), and flat (45). Of the five flavors, the most frequent were bitter (165), pungent (116), and sweet (99). Conclusion: This study preliminarily discussed the material basis and medicinal properties of herbs that can intervene in copper death, which can provide reference for the theoretical discussion, drug development, and clinical research of Chinese medicine regulating copper death.


Assuntos
Medicamentos de Ervas Chinesas , Plantas Medicinais , Humanos , Medicamentos de Ervas Chinesas/farmacologia , Cobre/farmacologia , Medicina Tradicional Chinesa , Extratos Vegetais/farmacologia , Computadores
4.
Lett Appl Microbiol ; 76(1)2023 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-36688787

RESUMO

Among the various biotic factors that disrupt crop yield, Xanthomonas oryzae pv oryzae (Xoo) is the most ruinous microbe of rice and causes bacterial leaf blight (BLB) disease. The present study focused on the utilization of copper nanoparticles (Cu-NPs) to control BLB. The copper nanosuspension (259.7 nm) prepared using Na-CMC, CuSO4·7H2O, and NaOH showed effectively inhibited Xoo (65.0 µg/ml). The performance of Cu-NPs in vivo showed enhanced plant attributes (127.9% root length and 53.9% shoot length) compared to the control and CuSO4 treated seedling. Furthermore, Cu-NPs treated seedlings showed 23.01% disease incidence (DI) compared to CuSO4 (85.71%) treated and control plants (91.83%). In addition to enhancing the growth parameters and reducing DI, seed priming with Cu-NPs improved the total chlorophyll content to 36.0% compared to the control. The assessment of antioxidant enzymes such as superoxide dismutase (1.9 U), polyphenol oxidase, peroxidase, and phenylalanine ammonia-lyase (two- to three-fold) in roots and shoots of rice plants revealed significant enhancement in Cu-NPs treated seedlings (P < 0.05). The present study suggests that Cu-NPs can be used to control Xoo and enhance rice growth.


Assuntos
Nanopartículas , Oryza , Xanthomonas , Oryza/microbiologia , Cobre/farmacologia , Plântula/microbiologia , Doenças das Plantas/microbiologia
5.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36674818

RESUMO

In this study, zinc (Zn)- and copper (Cu)-doped 13-93B3 borate mesoporous bioactive glasses (MBGs) were successfully synthesized using nitrate precursors in the presence of Pluronic P123. We benefited from computational approaches for predicting and confirming the experimental findings. The changes in the dynamic surface tension (SFT) of simulated body fluid (SBF) were investigated using the Du Noüy ring method to shed light on the mineralization process of hydroxyapatite (HAp) on the glass surface. The obtained MBGs were in a glassy state before incubation in SBF. The formation of an apatite-like layer on the SBF-incubated borate glasses was investigated by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The incorporation of Zn and Cu into the basic composition of 13-93B3 glass led to changes in the glass transition temperature (Tg) (773 to 556 °C), particle size (373 to 64 nm), zeta potential (-12 to -26 mV), and specific surface area (SBET) (54 to 123 m2/g). Based on the K-means algorithm and chi-square automatic interaction detection (CHAID) tree, we found that the SFT of SBF is an important factor for the prediction and confirmation of the HAp mineralization process on the glasses. Furthermore, we proposed a simple calculation, based on SFT variation, to quantify the bioactivity of MBGs. The doped and dopant-free borate MBGs could enhance the proliferation of mouse fibroblast L929 cells at a concentration of 0.5 mg/mL. These glasses also induced very low hemolysis (<5%), confirming good compatibility with red blood cells. The results of the antibacterial test revealed that all the samples could significantly decrease the viability of Pseudomonas aeruginosa. In summary, we showed that Cu-/Zn-doped borate MBGs can be fabricated using a cost-effective method and also show promise for wound healing/skin tissue engineering applications, as especially supported by the cell test with fibroblasts, good compatibility with blood, and antibacterial properties.


Assuntos
Cobre , Zinco , Animais , Camundongos , Cobre/farmacologia , Zinco/farmacologia , Boratos/farmacologia , Vidro , Antibacterianos/farmacologia , Durapatita/farmacologia , Cicatrização
6.
Int J Mol Sci ; 24(2)2023 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-36675139

RESUMO

A mild and efficient protocol for the synthesis of p-quinols under aqueous conditions was developed. The pivotal role of additives in the copper-catalyzed addition of aryl boronic and heteroaryl boronic acids to benzoquinones was observed. It was found that polyvinylpyrrolidone (PVP) was the most efficient additive used for the studied reaction. The noteworthy advantages of this procedure include its broad substrate scope, high yields up to 91%, atom economy, and usage of readily available starting materials. Another benefit of this method is the reusability of the catalytic system up to four times. Further, the obtained p-quinols were characterized on the basis of their antimicrobial activities against E. coli. Antimicrobial activity was further compared with the corresponding 4-benzoquinones and 4-hydroquinones. Among tested compounds, seven derivatives showed an antimicrobial activity profile similar to that observed for commonly used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained p-quinols constitute a suitable platform for further modifications, allowing for a convenient change in their biological activity profile.


Assuntos
Cobre , Hidroquinonas , Cobre/farmacologia , Cobre/química , Escherichia coli , Ácidos Borônicos/farmacologia , Ácidos Borônicos/química , Benzoquinonas , Antibacterianos/farmacologia , Catálise
7.
Int J Mol Sci ; 24(2)2023 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-36675172

RESUMO

Mastitis is one of the most common issues for milk producers around the world. Antibiotic therapy is often ineffective, and therefore, scientists must find a new solution. The aim of this paper is to estimate the influence of common and well-known cosmetic substrates and mixtures of nanoparticles (NPs) and cosmetic substrates on the viability of frequently occurring mastitis pathogens, Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The obtained results suggest that only collagen + elastin and glycerine influenced and increased bacteria viability. In case of the rest of the cosmetic substrates, the viability of E. coli and S. aureus was decreased, and the results were statistically significant (p ≤ 0.01). Prepared pre-dipping and dipping mixtures decrease (p ≤ 0.01) the viability of the mentioned pathogens. The obtained results of the in vitro analysis are very promising. In the next step, prepared mixtures should be tested in different herd conditions if they can be used in mastitis prevention or decrease the number of subclinical mastitis cases. Furthermore, these mixtures could become an interesting alternative for organic milk production where conventional preparations and antibiotics are forbidden. However, further analysis, especially on the influence of prepared mixtures on other bacteria species and, algae, fungi, are necessary.


Assuntos
Desinfetantes , Mastite Bovina , Nanopartículas , Infecções Estafilocócicas , Animais , Bovinos , Feminino , Humanos , Leite/microbiologia , Desinfetantes/farmacologia , Staphylococcus aureus , Cobre/farmacologia , Prata/farmacologia , Escherichia coli , Mastite Bovina/tratamento farmacológico , Mastite Bovina/microbiologia , Antibacterianos/farmacologia
8.
BMC Oral Health ; 23(1): 48, 2023 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-36709299

RESUMO

BACKGROUND: To investigate the inhibition mechanism of copper ions on Streptococcus mutans-Veillonella parvula dual biofilm. METHODS: S. mutans-V. parvula dual biofilm was constructed and copper ions were added at different concentrations. After the biofilm was collected, RNA-seq and qRT-PCR were then performed to get gene information. RESULTS: The coculture of S. mutans and V. parvula formed a significantly better dual biofilm of larger biomass than S. mutans mono biofilm. And copper ions showed a more significant inhibitory effect on S. mutans-V. parvula dual biofilm than on S. mutans mono biofilm when copper ions concentration reached 100 µM, and copper ions showed a decreased inhibitory effect on S. gordonii-V. parvula dual biofilm and S. sanguis-V.parvula dual biofilm than on the two mono biofilms as the concentration of copper ions increased. And common trace elements such as iron, magnesium, and zinc showed no inhibitory effect difference on S. mutans-V. parvula dual biofilm. The RNA-seq results showed a significant difference in the expression of a new ABC transporter SMU_651c, SMU_652c, SMU_653c, and S. mutans copper chaperone copYAZ. SMU_651c, SMU_652c, and SMU_653c were predicted to function as nitrite/nitrate transporter-related proteins, which suggested the specific inhibition of copper ions on S. mutans-V. parvula dual biofilm may be caused by the activation of S. mutans reactive nitrogen species. CONCLUSIONS: Streptococcus mutans and Veillonella parvula are symbiotic, forming a dual biofilm of larger biomass to better resist the external antibacterial substances, which may increase the virulence of S. mutans. While common trace elements such as iron, magnesium, and zinc showed no specific inhibitory effect on S. mutans-V. parvula dual biofilm, copper ion had a unique inhibitory effect on S. mutans-V. parvula dual biofilm which may be caused by activating S. mutans RNS when copper ions concentration reached 250 µM.


Assuntos
Streptococcus mutans , Oligoelementos , Humanos , Cobre/farmacologia , Cobre/metabolismo , Oligoelementos/metabolismo , Oligoelementos/farmacologia , Magnésio/metabolismo , Magnésio/farmacologia , Zinco
9.
Mol Neurodegener ; 18(1): 1, 2023 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-36597122

RESUMO

BACKGROUND: APOE variants are strongly associated with abnormal amyloid aggregation and additional direct effects of APOE on tau aggregation are reported in animal and human cell models. The degree to which these effects are present in humans when individuals are clinically unimpaired (CU) but have abnormal amyloid (Aß+) remains unclear. METHODS: We analyzed data from CU individuals in the Anti-Amyloid Treatment in Asymptomatic AD (A4) and Longitudinal Evaluation of Amyloid Risk and Neurodegeneration (LEARN) studies. Amyloid PET data were available for 4486 participants (3163 Aß-, 1323 Aß+) and tau PET data were available for a subset of 447 participants (55 Aß-, 392 Aß+). Linear models examined APOE (number of e2 and e4 alleles) associations with global amyloid and regional tau burden in medial temporal lobe (entorhinal, amygdala) and early neocortical regions (inferior temporal, inferior parietal, precuneus). Consistency of APOE4 effects on regional tau were examined in 220 Aß + CU and mild cognitive impairment (MCI) participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI). RESULTS: APOE2 and APOE4 were associated with lower and higher amyloid positivity rates, respectively. Among Aß+ CU, e2 and e4 were associated with reduced (-12 centiloids per allele) and greater (+15 centiloids per allele) continuous amyloid burden, respectively. APOE2 was associated with reduced regional tau in all regions (-0.05 to -0.09 SUVR per allele), whereas APOE4 was associated with greater regional tau (+0.02 to +0.07 SUVR per allele). APOE differences were confirmed by contrasting e3/e3 with e2/e3 and e3/e4. Mediation analyses among Aß+ s showed that direct effects of e2 on regional tau were present in medial temporal lobe and early neocortical regions, beyond an indirect pathway mediated by continuous amyloid burden. For e4, direct effects on regional tau were only significant in medial temporal lobe. The magnitude of protective e2 effects on regional tau was consistent across brain regions, whereas detrimental e4 effects were greatest in medial temporal lobe. APOE4 patterns were confirmed in Aß+ ADNI participants. CONCLUSIONS: APOE influences early regional tau PET burden, above and beyond effects related to cross-sectional amyloid PET burden. Therapeutic strategies targeting underlying mechanisms related to APOE may modify tau accumulation among Aß+ individuals.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Animais , Humanos , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Apolipoproteína E4/genética , Apolipoproteína E4/metabolismo , Apolipoproteína E2 , Estudos Transversais , Cobre/metabolismo , Cobre/farmacologia , Disfunção Cognitiva/metabolismo , Encéfalo/metabolismo , Amiloide/metabolismo , Proteínas Amiloidogênicas/metabolismo , Proteínas tau/metabolismo , Peptídeos beta-Amiloides/metabolismo , Tomografia por Emissão de Pósitrons
10.
Bioresour Technol ; 371: 128610, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36640818

RESUMO

There is limited information on the phosphorus availability under copper and tetracycline-amended composting: Insights into microbial communities and genes. Thus, this work investigated the phosphorus redistribution and transformation, illustrated the variation in microbial communities and genes, and ascertained the multiple action-patterns among which within copper and tetracycline-amended composting. Phosphorus bioavailability reduced by 8.96 % âˆ¼ 13.10 % due to the conservation of Ex-P to Ca-P. Copper and tetracycline showed a significant effect on fungal succession, but not to bacteria, as well as inhibited the phosphorus functional genes in fungal communities, while accelerated it in bacterial communities. Under the copper/tetracycline-stressed conditions, bacterial Firmicutes could promote the mineralization of organic phosphorus, and bacterial Proteobacteria might facilitate the dissolution of inorganic phosphorus. These findings could provide theoretical guidance for the further research on phosphorus bioavailability ascribed to microbial communities and genes.


Assuntos
Compostagem , Fósforo , Cobre/farmacologia , Disponibilidade Biológica , Antibacterianos/farmacologia , Tetraciclina , Bactérias/genética , Solo , Esterco/microbiologia
11.
ACS Appl Mater Interfaces ; 15(2): 3253-3265, 2023 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-36598330

RESUMO

Phototheranostics has attracted considerable attention in the fields of cancer diagnosis and treatment. However, the complete eradication of solid tumors using traditional phototheranostics is difficult because of the limited depth and range of laser irradiation. New phototheranostics enabling precise phototherapy and post-treatment imaging-guided programmed therapy for residual tumors is urgently required. Accordingly, this study developed a novel transformable phototheranostics by assembling hyaluronic acid (HA) with copper-nitrogen-coordinated carbon dots (CDs). In this transformable nanoplatform, named copper-nitrogen-CDs@HA, the HA component enables the specific targeting of cluster determinant (CD) 44-overexpressing tumor cells. In the tumor cells, redox glutathione converts Cu(II) (cupric ions) into Cu(I) (cuprous ions), which confers the novel transformable functionality to phototheranostics. Both in vitro and in vivo results reveal that the near-infrared-light-photoactivated CuII-N-CDs@HA could target CD44-overexpressing tumor cells for precise synergistic photothermal therapy and photodynamic therapy. This study is the first to observe that CuII-N-CDs@HA could escape from lysosomes and be transformed in situ into CuI-N-CDs@HA in tumor cells, with the d9 electronic configuration of Cu(II) changing to the d10 electronic configuration of Cu(I), which turns on their fluorescence and turns off their photothermal properties. This transformable phototheranostics could be used for post-treatment imaging-guided photodynamic therapy on residual tumor cells. Thus, the rationally designed copper-nitrogen-coordinated CDs offer a simple in situ transformation strategy for using multiple-stimulus-responsive precise phototheranostics in post-treatment monitoring of residual tumor cells and imaging-guided programmed therapy.


Assuntos
Nanopartículas , Fotoquimioterapia , Humanos , Fotoquimioterapia/métodos , Carbono , Neoplasia Residual , Cobre/farmacologia , Fototerapia , Linhagem Celular Tumoral , Nanopartículas/uso terapêutico
12.
J Colloid Interface Sci ; 634: 852-863, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36565626

RESUMO

Limited by the effective radius of metal ion release, higher concentrations of antibacterial agents are usually required to achieve satisfactory efficacy. Unfortunately, the potential cytotoxicity of metal ions limits the administered dose, which greatly hinders the widespread use of metal antibacterial agents. In this work, we used a convenient electrochemical method to prepare electropositive copper selenide (CuSe) nanosheets gathered from the cathode. Under physiological conditions, trace amounts of electrolytic CuSe (E-CuSe, 1 µg mL-1) could electrostatically bind to bacterial membranes and almost completely kill three resistant bacteria models (106 colony forming unit (CFU) mL-1). The extremely low effective dose of E-CuSe reaches a new benchmark in comparison with copper-based nanomaterials in other related studies. In addition, due to the reasonable coupling of selenium and copper, the as-prepared E-CuSe nanosheets exhibit lower cytotoxicity compared to copper oxide. As expected, the E-CuSe performed well in resistant bacteria-infected wound healing in rats, rapidly promoting wound tissue with a diameter of about 1 cm recovery within 7 days. Transcriptome analysis revealed the E-CuSe mainly acted on the membrane transport and DNA synthesis systems of bacterial cells. This work presents an efficient and in-depth paradigm for the scientific design and inactivation mechanism of metal antibacterial agents.


Assuntos
Cobre , Nanoestruturas , Ratos , Animais , Cobre/farmacologia , Cobre/metabolismo , Bactérias/metabolismo , Cicatrização , Antibacterianos/farmacologia
13.
Biomed Pharmacother ; 158: 114107, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36502753

RESUMO

BACKGROUND AND OBJECTIVE: There are considerable evidence of reproductive impairment in male organisms with Wilson disease (WD). The purpose of this study was to observe spermatogenesis, mitochondrial damage, apoptosis, and the level of oxidative stress in the testes of Wilson disease model TX mice, and to observe the effect and mechanism of glutathione on testicular spermatogenesis. METHODS: Mice were divided into a normal control group (control group), Wilson disease model TX mice group (WD group), penicillamine-treated TX mice group (penicillamine group) and glutathione-treated TX mice group (glutathione group). Testicular coefficient, histomorphology of testis and epididymis, number of spermatozoa, apoptosis of spermatogenic cells and expression of apoptosis-related proteins were observed. Ultrastructural analysis of mitochondria and mitochondrial membrane potential (MMP) monitored using JC-1 dye were used to detect mitochondrial damage. The levels of malondialdehyde (MDA), glutathione (GSH), catalase (CAT), and reactive oxygen species (ROS) in testicular cells were measured to assess oxidative stress. RESULTS: Testicular coefficient did not change in mice with Wilson disease. However, the tissue structure of the testicular seminiferous tubules was damaged, and the number of spermatozoa in the epididymal lumen was significantly reduced in WD group. The apoptosis rate in the testes was significantly increased. The protein expression of the pro-apoptotic proteins Bax and Caspase-3 significantly increased, and the expressions of the anti-apoptotic protein Bcl-2 significantly decreased. The levels of ROS and MDA significantly increased, and the levels of CAT and GSH significantly decreased. Mitochondria with abnormal ultrastructure and the rate of JC-1 positive cells were significantly increased in the WD group. After copper chelation by penicillamine, the structure of the testicular seminiferous tubules and the number of spermatozoa in the epididymal lumen were significantly improved. The number of apoptotic cells was significantly reduced. The levels of Bax and Caspase-3 decreased, and the expression of Bcl-2 increased. The contents of CAT and GSH increased, and the levels of ROS and MDA decreased significantly. The abnormal mitochondria and JC-1 positive cells was significantly decreased. The histomorphology of seminiferous tubules, spermatogenic function, apoptosis rate, apoptosis-related proteins, mitochondrial damage, and oxidative stress in Wilson disease TX mice significantly improved after glutathione treatment. CONCLUSION: Copper deposition in Wilson disease can lead to oxidative stress injury, mitochondrial damage, and apoptosis in the testis, leading to the impairment of spermatogenesis. Glutathione may improve testicular spermatogenesis in male Wilson disease TX mice by inhibiting copper deposition-induced oxidative stress, mitochondrial damage, and apoptosis.


Assuntos
Degeneração Hepatolenticular , Testículo , Camundongos , Masculino , Animais , Cobre/farmacologia , Caspase 3/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Degeneração Hepatolenticular/metabolismo , Proteína X Associada a bcl-2/metabolismo , Espermatogênese , Estresse Oxidativo , Apoptose , Glutationa/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Penicilamina/metabolismo , Penicilamina/farmacologia
14.
J Inorg Biochem ; 240: 112093, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36525715

RESUMO

Three new synthetic terpyridine copper(II) complexes were characterized. The copper(II) complexes induced apoptosis of three cancer cell lines and arrested T-24 cell cycle in G1 phase. The complexes were accumulated in mitochondria of T-24 cells and caused significant reduction of the mitochondrial membrane potential. The complexes increased both intracellular ROS and Ca2+ levels and activated the caspase-3/9 expression. The apoptosis was further confirmed by Western Blotting analysis. Bcl-2 was down-regulated and Bax was upregulated after treatment with complexes 1-3. The in vivo studies showed that complexes 1-3 obviously inhibited the growth of tumor without significant toxicity to other organs.


Assuntos
Antineoplásicos , Complexos de Coordenação , Neoplasias , Humanos , Cobre/farmacologia , Cobre/uso terapêutico , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Ligantes , Linhagem Celular , Neoplasias/tratamento farmacológico , Apoptose , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Linhagem Celular Tumoral
15.
Brain Res ; 1802: 148226, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36586663

RESUMO

Glycogen synthase kinase-3 (GSK-3), a key role in the pathogenesis of Alzheimer's disease (AD), has been linked with the formation of ß-amyloid (Aß), tubulin-associated unit (tau) protein phosphorylation and apoptosis. Moreover, the excessive presence of elements such as copper (Cu) can promote Aß aggregation and increase the risk of AD. Combined with the role of GSK-3 and metal elements in AD, a metal-chelating imine GSK-3 inhibitor N-(4-{[(2-amino-5-phenylpyridin-3-ylidene)imino]methyl}pyridin-2-yl)cyclopropanecarboxamide (PIMPC) was designed and synthesized. In our study, Aß/Cu2+-induced AD rat model was established and treated with PIMPC. The results indicated that PIMPC can not only down-regulate the high expression levels of Aß, tau and p-tau proteins of the AD rats, but also chelate Cu and aluminum (Al) elements in the brain. In addition, PIMPC may play an anti-apoptotic effect by down-regulating the high expression of cleaved Caspase-3 protein, and it can modulate ATPase and nitric oxide synthase (NOS) levels, oxidative stress and neurotransmitter disturbance. In summary, PIMPC acts on multiple targets to relieve the learning and memory impairment of AD rats induced by Aß/Cu2+.


Assuntos
Doença de Alzheimer , Animais , Ratos , Doença de Alzheimer/metabolismo , Peptídeos beta-Amiloides/metabolismo , Encéfalo/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta/metabolismo , Fosforilação , Proteínas tau/metabolismo , Cobre/farmacologia
16.
Lasers Med Sci ; 38(1): 15, 2022 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-36550257

RESUMO

The cancer treatment by laser-conjugated nanomaterial has become a new developing trend due of their unique physicochemical performance. The previous few studies reported the preparation of undoped CuS nanoprisms. The current research was concerned with the Mn doping effect on the CuS nanoprisms and its activity in tumor toxicity of M.D. Anderson-Metastatic Breast 231 (MDA-MB-231) cell line with laser treatment. To prepare a novel CuS and Mn-doped CuS nanoprisms with high surface area by two-phase colloidal method, copper nitrate and sulfur powder were used as sources of copper and sulfur respectively. The prepared nanoprisms were investigated as antibacterial and photothermal agents in MDA-MB-231 cancer treatment using near-infrared (NIR) laser. The Mn-CuS nanoprisms were modified with glutathione (GSH) to decrease the cytotoxicity and increase the biocompatibility. The characterization of synthesized nanoprisms involved the structural, compositional, surface charges, optical, and morphological property analyses. X-ray diffraction (XRD) showed the peaks of hexagonal covellite copper sulfide nanoparticles and additional diffraction peaks at Mn-CuS which are assigned to orthorhombic chalcocite CuS. The transmission electron microscopy (TEM) images showed that the CuS and Mn-CuS nanoparticles have nanoprism morphology. The antibacterial activity test revealed that the activity enhances by doping and the prepared Mn-CuS nanostructures were more effective against the Staphylococcus aureus and Escherichia coli bacteria. The results of photothermal treatment indicated that the cancer cells were effectively killed and the GSH@Mn-CuS nanoprisms are able to be used as an efficient theranostic agent for tumor photothermal therapy in the future.


Assuntos
Nanopartículas , Neoplasias , Humanos , Cobre/farmacologia , Cobre/química , Nanopartículas/química , Fototerapia , Neoplasias/terapia , Neoplasias/patologia , Antibacterianos
17.
Mar Drugs ; 20(12)2022 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-36547934

RESUMO

Metal-polysaccharides have recently raised significant interest due to their multifunctional bioactivities. The antimicrobial activity of a complex of Cu2O with the sulfated polysaccharide (PS) of the marine red microalga Porphyridium sp. was previously attributed to spikes formed on the complex surface (roughness). This hypothesis was further examined here using other Cu-PS complexes (i.e., monovalent-Cu2O, CuCl and divalent-CuO, CuCl2). The nanostructure parameters of the monovalent complexes, namely, longer spikes (1000 nm) and greater density (2000-5000 spikes/µm2) were found to be related to the superior inhibition of microbial growth and viability and biofilm formation. When Escherichia coli TV1061, used as a bioluminescent test organism, was exposed to the monovalent Cu-PS complexes, enhanced bioluminescence accumulation was observed, probably due to membrane perforation by the spikes on the surface of the complexes and consequent cytoplasmic leakage. In addition, differences were found in the surface chemistry of the monovalent and divalent Cu-PS complexes, with the monovalent Cu-PS complexes exhibiting greater stability (ζ-potential, FTIR spectra, and leaching out), which could be related to spike formation. This study thus supports our hypothesis that the spikes protruding from the monovalent Cu-PS surfaces, as characterized by their aspect ratio, are responsible for the antimicrobial and antibiofilm activities of the complexes.


Assuntos
Anti-Infecciosos , Microalgas , Porphyridium , Microalgas/química , Metais , Anti-Infecciosos/farmacologia , Polissacarídeos/farmacologia , Polissacarídeos/química , Cobre/farmacologia , Cobre/química
18.
Int J Nanomedicine ; 17: 6095-6112, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36514376

RESUMO

Introduction: Metal nanoparticle synthesis using plant has emerged as an eco-friendly, clean, and viable strategy alternative to chemical and physical approaches. Methods: The fruit extract of Salvadora persica (SP) was utilized as a reducing and stabilizing agent in the synthesis of gold (AuNPs) and copper (CuNPs) nanoparticles. Results: UV-Vis spectra of the AuNPs and CuNPs showed peaks at the wavelengths of 530 nm and 440 nm, respectively. Transmission electron microscopy showed that nanoparticles exhibited a mainly spherical form, with a distribution range of 100 to 113 nm in diameter for AuNPs and of 130 to 135 nm in diameter for CuNPs. While energy-dispersive X-ray spectroscopy was able to confirm the existence of AuNPs and CuNPs. The alcoholic extract of the fruit SP was analyzed by GC-MS in order to identify whether or not it contained any active phytochemicals. Fourier-transform infrared spectra confirmed the presence capping functional biomolecules of SP on the surface of nanoparticles that acts as stabilizers. Analysis of the zeta potential revealed that NPs with high degree of stability, as demonstrated by a strong negative potential value in the range of 25.2 to 28.7 mV. Results showed that both green AuNPs and CuNPs have potential antimicrobial activity against human pathogens such gram-negative bacteria and gram-positive bacteria, with CuNPs having antimicrobial activity higher than AuNPs. In addition, AuNPs and CuNPs have promising antioxidant and anticancer properties when applied to MCF-7 and MDA-MB-231 breast cancer cells. Studies of molecular docking of SP bioactive compounds were conducted against methenyl tetrahydrofolate synthetase. Among all of them, Beta - Sitosterol was the most prominent. Conclusion: These AuNPs and CuNPs are particularly appealing in a variety of applications in the pharmaceutical and medicinal industries due to their economical and environmentally friendly production.


Assuntos
Nanopartículas Metálicas , Salvadoraceae , Humanos , Ouro/farmacologia , Ouro/química , Nanopartículas Metálicas/química , Cobre/farmacologia , Cobre/química , Frutas , Simulação de Acoplamento Molecular , Testes de Sensibilidade Microbiana , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Antibacterianos/química , Química Verde , Espectroscopia de Infravermelho com Transformada de Fourier
19.
Malar J ; 21(1): 386, 2022 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-36528584

RESUMO

BACKGROUND: Malaria remains one of the most virulent and deadliest parasitic disease in the world, particularly in Africa and Southeast Asia. Widespread occurrence of artemisinin-resistant Plasmodium falciparum strains from the Greater Mekong Subregion is alarming. This hinders the national economies, as well as being a major drawback in the effective control and elimination of malaria worldwide. Clearly, an effective anti-malarial drug is urgently needed. METHODS: The dinuclear and mononuclear copper(II) and zinc(II) complexes were synthesized in ethanolic solution and characterized by various physical measurements (FTIR, CHN elemental analysis, solubility, ESI-MS, UV-Visible, conductivity and magnetic moment, and NMR). X-ray crystal structure of the dicopper(II) complex was determined. The in vitro haemolytic activities of these metal complexes were evaluated spectroscopically on B+ blood while the anti-malarial potency was performed in vitro on blood stage drug-sensitive Plasmodium falciparum 3D7 (Pf3D7) and artemisinin-resistant Plasmodium falciparum IPC5202 (Pf5202) with fluorescence dye. Mode of action of metal complexes were conducted to determine the formation of reactive oxygen species using PNDA and DCFH-DA dyes, JC-1 depolarization of mitochondrial membrane potential, malarial 20S proteasome inhibition with parasite lysate, and morphological studies using Giemsa and Hoechst stains. RESULTS: Copper(II) complexes showed anti-malarial potency against both Pf3D7 and Pf5202 in sub-micromolar to micromolar range. The zinc(II) complexes were effective against Pf3D7 with excellent therapeutic index but encountered total resistance against Pf5202. Among the four, the dinuclear copper(II) complex was the most potent against both strains. The zinc(II) complexes caused no haemolysis of RBC while copper(II) complexes induced increased haemolysis with increasing concentration. Further mechanistic studies of both copper(II) complexes on both Pf3D7 and Pf5202 strains showed induction of ROS, 20S malarial proteasome inhibition, loss of mitochondrial membrane potential and morphological features indicative of apoptosis. CONCLUSION: The dinuclear [Cu(phen)-4,4'-bipy-Cu(phen)](NO3)4 is highly potent and can overcome the total drug-resistance of Pf5202 towards chloroquine and artemisinin. The other three copper(II) and zinc(II) complexes were only effective towards the drug-sensitive Pf3D7, with the latter causing no haemolysis of RBC. Their mode of action involves multiple targets.


Assuntos
Antimaláricos , Artemisininas , Complexos de Coordenação , Malária Falciparum , Malária , Humanos , Plasmodium falciparum , Antimaláricos/uso terapêutico , Complexos de Coordenação/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/uso terapêutico , Cobre/farmacologia , Cobre/uso terapêutico , Artemisininas/uso terapêutico , Resistência a Medicamentos , Malária/tratamento farmacológico , Metais , Zinco/farmacologia , Zinco/uso terapêutico , Malária Falciparum/tratamento farmacológico
20.
Molecules ; 27(24)2022 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-36557987

RESUMO

Glioblastoma multiforme (GBM) is a fast-growing and aggressive type of brain cancer. Unlike normal brain cells, GBM cells exhibit epithelial-mesenchymal transition (EMT), which is a crucial biological process in embryonic development and cell metastasis, and are highly invasive. Copper reportedly plays a critical role in the progression of a variety of cancers, including brain, breast, and lung cancers. However, excessive copper is toxic to cells. D-penicillamine (DPA) and triethylenetetramine (TETA) are well-known copper chelators and are the mainstay of treatment for copper-associated diseases. Following treatment with copper sulfate and DPA, GBM cells showed inhibition of proliferation and suppression of EMT properties, including reduced expression levels of N-cadherin, E-cadherin, and Zeb, which are cell markers associated with EMT. In contrast, treatment with copper sulfate and TETA yielded the opposite effects in GBM. Genes, including TGF-ß, are associated with an increase in copper levels, implying their role in EMT. To analyze the invasion and spread of GBM, we used zebrafish embryos xenografted with the GBM cell line U87. The invasion of GBM cells into zebrafish embryos was markedly inhibited by copper treatment with DPA. Our findings suggest that treatment with copper and DPA inhibits proliferation and EMT through a mechanism involving TGF-ß/Smad signaling in GBM. Therefore, DPA, but not TETA, could be used as adjuvant therapy for GBM with high copper concentrations.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Animais , Glioblastoma/metabolismo , Cobre/farmacologia , Peixe-Zebra , Linhagem Celular Tumoral , Sulfato de Cobre/farmacologia , Neoplasias Encefálicas/metabolismo , Transdução de Sinais , Fator de Crescimento Transformador beta/farmacologia , Quelantes/farmacologia , Transição Epitelial-Mesenquimal , Movimento Celular
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