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1.
Sci Rep ; 14(1): 18144, 2024 08 05.
Artigo em Inglês | MEDLINE | ID: mdl-39103470

RESUMO

The exclusion mechanism of food contaminants such as bisphenol A (BPA), Flavonoids (FLA), and Goitrin (GOI) onto the novel gallium-metal organic framework (MOF) and functionalized MOF with oxalamide group (MOF-OX) is evaluated by utilizing molecular dynamics (MD) and Metadynamics simulations. The atoms in molecules (AIM) analysis detected different types of atomic interactions between contaminant molecules and substrates. To assess this procedure, a range of descriptors including interaction energies, root mean square displacement, radial distribution function (RDF), density, hydrogen bond count (HB), and contact numbers are examined across the simulation trajectories. The most important elements in the stability of the systems under examination are found to be stacking π-π and HB interactions. It was confirmed by a significant value of total interaction energy for BPA/MOF-OX (- 338.21 kJ mol-1) and BPA/MOF (- 389.95 kJ mol-1) complexes. Evaluation of interaction energies reveals that L-J interaction plays an essential role in the adsorption of food contaminants on the substrates. The free energy values for the stability systems of BPA/MOF and BPA/MOF-OX complexes at their global minima reached about BPA/MOF = - 254.29 kJ mol-1 and BPA/MOF-OX = - 187.62 kJ mol-1, respectively. Nevertheless, this work provides a new strategy for the preparation of a new hierarchical tree-dimensional of the Ga-MOF hybrid material for the adsorption and exclusion of food contaminates and their effect on human health.


Assuntos
Contaminação de Alimentos , Gálio , Estruturas Metalorgânicas , Simulação de Dinâmica Molecular , Estruturas Metalorgânicas/química , Gálio/química , Contaminação de Alimentos/análise , Fenóis/química , Fenóis/análise , Compostos Benzidrílicos/química , Compostos Benzidrílicos/análise , Ligação de Hidrogênio , Adsorção , Flavonoides/química , Flavonoides/análise
2.
Inorg Chem ; 63(33): 15409-15420, 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39116415

RESUMO

Microorganisms of the ESKAPE group pose an enormous threat to human well-being, thus requiring a multidisciplinary approach for discovering novel drugs that are not only effective but utilize an innovative mechanism of action in order to decrease fast developing resistance. A promising but still hardly explored implementation in the "Trojan horse" antibacterial strategy has been recognized in gallium, an iron mimicry species with no known function but exerting a bacteriostatic/bactericidal effect against some representatives of the group. The study herewith focuses on the bacterium A. baumannii and its siderophore acinetobactin in its two isomeric forms depending on the acidity of the medium. By applying the powerful tools of the DFT approach, we aim to delineate those physicochemical characteristics that are of great importance for potentiating gallium's ability to compete with the native ferric cation for binding acinetobactin such as pH, solvent exposure (dielectric constant of the environment), different metal/siderophore ratios, and complex composition. Hence, the provided results not only furnish some explanation of the positive effect of three Ga3+-based anti-infectives in terms of metal cation competition but also shed light on reported in vitro and in vivo observations at a molecular level in regard to gallium's antibacterial effect against A. baumannii.


Assuntos
Acinetobacter baumannii , Antibacterianos , Teoria da Densidade Funcional , Gálio , Testes de Sensibilidade Microbiana , Gálio/química , Gálio/farmacologia , Acinetobacter baumannii/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/síntese química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Oxazóis/química , Oxazóis/farmacologia , Estrutura Molecular , Imidazóis/química , Imidazóis/farmacologia
3.
Nat Commun ; 15(1): 7096, 2024 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-39154092

RESUMO

The intratumor microbiome imbalance in pancreatic cancer promotes a tolerogenic immune response and triggers immunotherapy resistance. Here we show that Lactobacillus rhamnosus GG probiotics, outfitted with a gallium-polyphenol network (LGG@Ga-poly), bolster immunotherapy in pancreatic cancer by modulating microbiota-immune interactions. Upon oral administration, LGG@Ga-poly targets pancreatic tumors specifically, and selectively eradicates tumor-promoting Proteobacteria and microbiota-derived lipopolysaccharides through a gallium-facilitated disruption of bacterial iron respiration. This elimination of intratumor microbiota impedes the activation of tumoral Toll-like receptors, thus reducing immunosuppressive PD-L1 and interleukin-1ß expression by tumor cells, diminishing immunotolerant myeloid populations, and improving the infiltration of cytotoxic T lymphocytes in tumors. Moreover, LGG@Ga-poly hampers pancreatic tumor growth in both preventive and therapeutic contexts, and amplifies the antitumor efficacy of immune checkpoint blockade in preclinical cancer models in female mice. Overall, we offer evidence that thoughtfully designed biomaterials targeting intratumor microbiota can efficaciously augment immunotherapy for the challenging pancreatic cancer.


Assuntos
Gálio , Lacticaseibacillus rhamnosus , Microbiota , Neoplasias Pancreáticas , Polifenóis , Probióticos , Neoplasias Pancreáticas/imunologia , Neoplasias Pancreáticas/terapia , Neoplasias Pancreáticas/microbiologia , Animais , Probióticos/administração & dosagem , Camundongos , Feminino , Humanos , Lacticaseibacillus rhamnosus/imunologia , Polifenóis/farmacologia , Microbiota/imunologia , Microbiota/efeitos dos fármacos , Linhagem Celular Tumoral , Imunoterapia/métodos , Camundongos Endogâmicos C57BL , Antígeno B7-H1/metabolismo , Antígeno B7-H1/imunologia , Linfócitos T Citotóxicos/imunologia
4.
ACS Nano ; 18(33): 22257-22274, 2024 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-39121010

RESUMO

Iron metabolism has emerged as a promising target for cancer therapy; however, the innate metabolic compensatory capacity of cancer cells significantly limits the effectiveness of iron metabolism therapy. Herein, bioactive gallium sulfide nanodots (GaSx), with dual functions of "reprogramming" and "interfering" iron metabolic pathways, were successfully developed for tumor iron metabolism therapy. The constructed GaSx nanodots ingeniously harness hydrogen sulfide (H2S) gas, which is released in response to the tumor microenvironment, to reprogram the inherent transferrin receptor 1 (TfR1)-ferroportin 1 (FPN1) iron metabolism axis in cancer cells. Concurrently, the gallium ions (Ga3+) derived from GaSx act as a biochemical "Trojan horse", mimicking the role of iron and displacing it from essential biomolecular binding sites, thereby influencing the fate of cancer cells. By leveraging the dual mechanisms of Ga3+-mediated iron disruption and H2S-facilitated reprogramming of iron metabolic pathways, GaSx prompted the initiation of a paraptosis-apoptosis hybrid pathway in cancer cells, leading to marked suppression of tumor proliferation. Importantly, the dysregulation of iron metabolism induced by GaSx notably increased tumor cell susceptibility to both chemotherapy and immune checkpoint blockade (ICB) therapy. This study underscores the therapeutic promise of gas-based interventions and metal ion interference strategies for the tumor metabolism treatment.


Assuntos
Apoptose , Gálio , Ferro , Humanos , Gálio/química , Gálio/farmacologia , Apoptose/efeitos dos fármacos , Ferro/metabolismo , Ferro/química , Animais , Camundongos , Proliferação de Células/efeitos dos fármacos , Receptores da Transferrina/metabolismo , Antineoplásicos/farmacologia , Antineoplásicos/química , Sulfetos/química , Sulfetos/farmacologia , Microambiente Tumoral/efeitos dos fármacos , Linhagem Celular Tumoral , Sulfeto de Hidrogênio/metabolismo , Sulfeto de Hidrogênio/química , Sulfeto de Hidrogênio/farmacologia , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Neoplasias/patologia , Paraptose , Proteínas de Transporte de Cátions
5.
ACS Nano ; 18(32): 21077-21090, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39088785

RESUMO

Porphyromonas gingivalis has been demonstrated to have the strongest association with periodontitis. Within the host, P. gingivalis relies on acquiring iron and heme through the aggregation and lysis of erythrocytes, which are important factors in the growth and virulence of P. gingivalis. Additionally, the excess obtained heme is deposited on the surface of P. gingivalis, protecting the cells from oxidative damage. Based on these biological properties of the interaction between P. gingivalis and erythrocytes, this study developed an erythrocyte membrane nanovesicle loaded with gallium porphyrins to mimic erythrocytes. The nanovesicle can target and adhere with P. gingivalis precisely, being lysed and utilized by P. gingivalis as erythrocytes. Ingested gallium porphyrin replaces iron porphyrin in P. gingivalis, causing intracellular metabolic disruption. Deposited porphyrin generates a large amount of reactive oxygen species (ROS) under blue light, causing oxidative damage, and its lethality is enhanced by bacterial metabolic disruption, synergistically killing P. gingivalis. Our results demonstrate that this strategy can target and inhibit P. gingivalis, reduce its invasion of epithelial cells, and alleviate the progression of periodontitis.


Assuntos
Eritrócitos , Periodontite , Porfirinas , Porphyromonas gingivalis , Porphyromonas gingivalis/efeitos dos fármacos , Porphyromonas gingivalis/metabolismo , Porphyromonas gingivalis/química , Periodontite/microbiologia , Periodontite/tratamento farmacológico , Periodontite/patologia , Eritrócitos/efeitos dos fármacos , Eritrócitos/metabolismo , Humanos , Porfirinas/química , Porfirinas/farmacologia , Animais , Espécies Reativas de Oxigênio/metabolismo , Gálio/química , Gálio/farmacologia , Camundongos , Antibacterianos/farmacologia , Antibacterianos/química , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia
6.
PLoS One ; 19(8): e0306738, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39141686

RESUMO

In order to implement the fifth generation (5G) communication system for a large number of users, the governments of many countries nominated the low 5G frequency band between 3.3 and 4.3 GHz. This paper proposes a wideband RFPA by designing the input matching network (MN) and output MN of the device using the simplified real frequency technique (SRFT) and the harmonic tuning network. The load-pull and source-pull is applied at multiple points for 100 MHz intervals over the bandwidth to obtain the optimum impedances at the output and input of the 10W Gallium Nitride (GaN) Cree CGH40010F device. To verify the design, the RFPA is simulated, and the performance is measured between 3.3 and 4.3 GHz. According to experimental findings, the measured drain efficiency (DE) throughout the whole bandwidth ranged from 57.5 to 67.5% at the output power of 40 dBm. Moreover, at the 1 dB compression point between 39.2 and 42.2 dBm output power, the drain efficiency (DE) achieves a high value of 81.2% with an output power of 42.2 dBm at a frequency of 3.3 GHz. The RFPA can obtain a maximum gain of 12.4 dB at 3.5 GHz. The linearity of the RFPA with a two-tone signal is measured and the value is less than -22 dBc all over the band.


Assuntos
Gálio , Gálio/química , Desenho de Equipamento , Amplificadores Eletrônicos , Tecnologia sem Fio/instrumentação
7.
Sci Rep ; 14(1): 16313, 2024 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-39009630

RESUMO

In 67Ga-citrate scintigraphy (Ga-S), visual assessment is used by evaluating renal-uptake comparison with liver and spine and is simple and objective. We adopted the standardized uptake value (SUV) for 67Ga-citrate and proposed two quantitative indices, active nephritis volume (ANV) and total nephritis uptake (TNU). This study clarified the utility of new Ga-S-based quantitative indices in nephritis management. Before SUV measurement, the Becquerel calibration factor of 67Ga-citrate was obtained using a phantom experiment. Seventy patients who underwent SPECT/CT imaging were studied. SUV, ANV, and TNU were calculated using a quantitative analysis software for bone SPECT. SUVmean, ANV, and TNU were analyzed using the (1) threshold method (set 40%) and constant-value method for (2) vertebral SUVmax, and (3) vertebral SUVmean. ROC analysis was used to evaluate SUV, ANV, and TNU diagnostic abilities to distinguish nephritis presence and absence as well as interstitial nephritis (IN) and non-IN. The area under the curve (AUC) for nephritis presence or absence had a good value (0.80) for SUVmean (1), ANV (3), and TNU (3). The AUC for differentiation between IN and non-IN groups had a good value (0.80) for SUVmean (1). Thus, the new Ga-S-based quantitative indices were useful to evaluate nephritis and distinguish IN and non-IN.


Assuntos
Radioisótopos de Gálio , Gálio , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Nefrite/diagnóstico por imagem , Citratos , Curva ROC , Idoso de 80 Anos ou mais , Compostos Radiofarmacêuticos , Tomografia Computadorizada com Tomografia Computadorizada de Emissão de Fóton Único/métodos
8.
Biomed Phys Eng Express ; 10(5)2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-38968931

RESUMO

Quantitative contrast-enhanced breast computed tomography (CT) has the potential to improve the diagnosis and management of breast cancer. Traditional CT methods using energy-integrated detectors and dual-exposure images with different incident spectra for material discrimination can increase patient radiation dose and be susceptible to motion artifacts and spectral resolution loss. Photon Counting Detectors (PCDs) offer a promising alternative approach, enabling acquisition of multiple energy levels in a single exposure and potentially better energy resolution. Gallium arsenide (GaAs) is particularly promising for breast PCD-CT due to its high quantum efficiency and reduction of fluorescence x-rays escaping the pixel within the breast imaging energy range. In this study, the spectral performance of a GaAs PCD for quantitative iodine contrast-enhanced breast CT was evaluated. A GaAs detector with a pixel size of 100µm, a thickness of 500µm was simulated. Simulations were performed using cylindrical phantoms of varying diameters (10 cm, 12 cm, and 16 cm) with different concentrations and locations of iodine inserts, using incident spectra of 50, 55, and 60 kVp with 2 mm of added aluminum filtration and and a mean glandular dose of 10 mGy. We accounted for the effects of beam hardening and energy detector response using TIGRE CT open-source software and the publicly available Photon Counting Toolkit (PcTK). Material-specific images of the breast phantom were produced using both projection and image-based material decomposition methods, and iodine component images were used to estimate iodine intake. Accuracy and precision of the proposed methods for estimating iodine concentration in breast CT images were assessed for different material decomposition methods, incident spectra, and breast phantom thicknesses. The results showed that both the beam hardening effect and imperfection in the detector response had a significant impact on performance in terms of Root Mean Squared Error (RMSE), precision, and accuracy of estimating iodine intake in the breast. Furthermore, the study demonstrated the effectiveness of both material decomposition methods in making accurate and precise iodine concentration predictions using a GaAs-based photon counting breast CT system, with better performance when applying the projection-based material decomposition approach. The study highlights the potential of GaAs-based photon counting breast CT systems as viable alternatives to traditional imaging methods in terms of material decomposition and iodine concentration estimation, and proposes phantoms and figures of merit to assess their performance.


Assuntos
Arsenicais , Neoplasias da Mama , Mama , Meios de Contraste , Gálio , Iodo , Mamografia , Imagens de Fantasmas , Fótons , Tomografia Computadorizada por Raios X , Gálio/química , Humanos , Feminino , Tomografia Computadorizada por Raios X/métodos , Meios de Contraste/química , Mamografia/métodos , Neoplasias da Mama/diagnóstico por imagem , Mama/diagnóstico por imagem , Simulação por Computador , Método de Monte Carlo , Processamento de Imagem Assistida por Computador/métodos , Doses de Radiação
9.
Carbohydr Polym ; 342: 122357, 2024 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-39048189

RESUMO

In this study, we address the challenge of developing highly conductive hydrogels with enhanced stretchability for use in wearable sensors, which are critical for the precise detection of human motion and subtle physiological strains. Our novel approach utilizes amylopectin, a biopolymer, for the uniform integration of liquid metal gallium into the hydrogel matrix. This integration results in a conductive hydrogel characterized by remarkable elasticity (up to 7100 % extensibility) and superior electrical conductance (Gauge Factor = 31.4), coupled with a minimal detection limit of less than 0.1 % and exceptional durability over 5000 cycles. The hydrogel demonstrates significant antibacterial activity, inhibiting microbial growth in moist environments, thus enhancing its applicability in medical settings. Employing a synthesis process that involves ambient condition polymerization of acrylic acid, facilitated by a hydrophobic associative framework, this hydrogel stands out for its rapid gelation and robust mechanical properties. The potential applications of this hydrogel extend beyond wearable sensors, promising advancements in human-computer interaction through technologies like wireless actuation of robotic systems. This study not only introduces a viable material for current wearable technologies but also sets a foundation for future innovations in bio-compatible sensors and interactive devices.


Assuntos
Amilopectina , Antibacterianos , Condutividade Elétrica , Gálio , Hidrogéis , Dispositivos Eletrônicos Vestíveis , Hidrogéis/química , Hidrogéis/farmacologia , Antibacterianos/farmacologia , Antibacterianos/química , Amilopectina/química , Gálio/química , Humanos , Staphylococcus aureus/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Elasticidade
10.
Sci Adv ; 10(28): eadn1745, 2024 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-38996026

RESUMO

Rapid drug clearance and off-target effects of therapeutic drugs can induce low bioavailability and systemic side effects and gravely restrict the therapeutic effects of inflammatory bowel diseases (IBDs). Here, we propose an amplifying targeting strategy based on orally administered gallium (Ga)-based liquid metal (LM) nano-agents to efficiently eliminate reactive oxygen and nitrogen species (RONS) and modulate the dysregulated microbiome for remission of IBDs. Taking advantage of the favorable adhesive activity and coordination ability of polyphenol structure, epigallocatechin gallate (EGCG) is applied to encapsulate LM to construct the formulations (LM-EGCG). After adhering to the inflamed tissue, EGCG not only eliminates RONS but also captures the dissociated Ga to form EGCG-Ga complexes for enhancive accumulation. The detained composites protect the intestinal barrier and modulate gut microbiota for restoring the disordered enteral microenvironment, thereby relieving IBDs. Unexpectedly, LM-EGCG markedly decreases the Escherichia_Shigella populations while augmenting the abundance of Akkermansia and Bifidobacterium, resulting in favorable therapeutic effects against the dextran sulfate sodium-induced colitis.


Assuntos
Microbioma Gastrointestinal , Doenças Inflamatórias Intestinais , Animais , Doenças Inflamatórias Intestinais/tratamento farmacológico , Administração Oral , Microbioma Gastrointestinal/efeitos dos fármacos , Camundongos , Catequina/análogos & derivados , Catequina/química , Catequina/administração & dosagem , Catequina/farmacologia , Gálio/química , Gálio/farmacologia , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Espécies Reativas de Oxigênio/metabolismo , Colite/tratamento farmacológico , Humanos , Espécies Reativas de Nitrogênio/metabolismo
11.
J Inorg Biochem ; 259: 112663, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39024775

RESUMO

Given the recognized major problem of microbial drug resistance for human health, new metal-based drugs have been currently explored for their antimicrobial properties, including gallium-based compounds as potential metallophores that could perturb Fe's interactions with proteins. Herein we have designed and synthesized two bis-kojate ligands (named L4 and L6) and studied their Ga(III) complexes for their physico-chemical and biological properties. In particular a detailed study of their complexation properties in aqueous solution, showed equilibrium models with formation of quite stable dinuclear 2:3 metal:ligand complexes, though with different stability. Solid state complexes were also prepared and characterized and complementary DFT studies indicated that [Ga2(L4)3] complex, with higher stability, seems to adopt a three-ligand bridging conformation, while that for L6 adopt a one ligand bridging conformation. Preliminary investigation of the antibacterial activity of these gallium complexes showed antipseudomonal activity, which appeared higher for the complex with L4, a feature of potential interest for the scientific community.


Assuntos
Antibacterianos , Complexos de Coordenação , Gálio , Testes de Sensibilidade Microbiana , Gálio/química , Gálio/farmacologia , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Complexos de Coordenação/farmacologia , Complexos de Coordenação/síntese química , Complexos de Coordenação/química , Ligantes
12.
Biomater Sci ; 12(16): 4194-4210, 2024 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-38980095

RESUMO

Effective treatment of infected bone defects resulting from multi-drug resistant bacteria (MDR) has emerged as a significant clinical challenge, highlighting the pressing demand for potent antibacterial bone graft substitutes. Mesoporous nanoparticles have been introduced as a promising class of biomaterials offering significant properties for treating bone infections. Herein, we synthesize antibacterial mesoporous hydroxyapatite substituted with zinc and gallium (Zn-Ga:mHA) nanoparticles using a facile sol-gel method. The resulting mesoporous nanoparticles are applied for the controlled release of melatonin (Mel). Zn-Ga:mHA nanoparticles with an average particle size of 36 ± 3 nm and pore size of 10.6 ± 0.4 nm reveal a Mel loading efficiency of 58 ± 1%. Results show that 50% of Mel is released within 20 h and its long-term release is recorded up to 50 h. The Zn-Ga:mHA nanoparticles exhibit highly effective antibacterial performance as reflected by a 19 ± 1% and 8 ± 2% viability reduction in Escherichia coli and Staphylococcus bacteria, respectively. Noticeably, Mel-loaded Zn-Ga:mHA nanoparticles are also cytocompatible and stimulate in vitro osteogenic differentiation of human mesenchymal stem cells (hMSCs) without any osteoinductive factor. In vivo studies in a rabbit skull also show significant regeneration of bone during 14 days. In summary, Mel-loaded Zn-Ga:mHA nanoparticles provide great potential as an antibacterial and osteogenic component in bone substitutes like hydrogels, scaffolds, and coatings.


Assuntos
Antibacterianos , Regeneração Óssea , Durapatita , Gálio , Melatonina , Células-Tronco Mesenquimais , Nanopartículas , Zinco , Gálio/química , Gálio/farmacologia , Gálio/administração & dosagem , Melatonina/farmacologia , Melatonina/administração & dosagem , Melatonina/química , Durapatita/química , Durapatita/farmacologia , Animais , Zinco/química , Zinco/farmacologia , Zinco/administração & dosagem , Antibacterianos/farmacologia , Antibacterianos/química , Antibacterianos/administração & dosagem , Coelhos , Humanos , Nanopartículas/química , Nanopartículas/administração & dosagem , Células-Tronco Mesenquimais/efeitos dos fármacos , Regeneração Óssea/efeitos dos fármacos , Porosidade , Escherichia coli/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
13.
Radiat Prot Dosimetry ; 200(11-12): 1173-1177, 2024 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-39016480

RESUMO

The effect of 60Co gamma irradiation on gallium oxide and titanium oxide (Ga2O3-TiO2) nanocomposites are investigated in the present study. The Ga2O3-TiO2 nanocomposite was synthesized by hydrothermal method at 120°C. The precursors for the synthesis consist of gallium nitrate anhydrous and titanium trichloride along with sodium hydroxide to achieve the pH of 9. The synthesized Ga2O3-TiO2 was subjected to 60Co gamma irradiation for different doses such as 25, 50 and 75 kGy. The morphological, optical and microstructural characteristics were studied using scanning electron microscopy, UV-Visible spectroscopy, X-ray diffraction and Fourier transform infrared spectroscopy, respectively. The results shows that the gamma irradiation induces significant changes in the Ga2O3-TiO2 microstructure and there is increase in the grain size and bandgap of the nanocomposites.


Assuntos
Radioisótopos de Cobalto , Gálio , Raios gama , Nanocompostos , Titânio , Titânio/química , Nanocompostos/química , Nanocompostos/efeitos da radiação , Radioisótopos de Cobalto/química , Gálio/química , Difração de Raios X , Espectroscopia de Infravermelho com Transformada de Fourier , Microscopia Eletrônica de Varredura
14.
ACS Biomater Sci Eng ; 10(7): 4452-4462, 2024 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-38875708

RESUMO

Mg-based biodegradable metallic implants are gaining increased attraction for applications in orthopedics and dentistry. However, their current applications are hampered by their high rate of corrosion, degradation, and rapid release of ions and gas bubbles into the physiological medium. The aim of the present study is to investigate the osteogenic and angiogenic potential of coated Mg-based implants in a sheep cranial defect model. Although their osteogenic potential was studied to some extent, their potential to regenerate vascularized bone formation was not studied in detail. We have studied the potential of magnesium-calcium (MgCa)-based alloys modified with zinc (Zn)- or gallium (Ga)-doped calcium phosphate (CaP) coatings as a strategy to control their degradation rate while enhancing bone regeneration capacity. MgCa and its implants with CaP coatings (MgCa/CaP) as undoped or as doped with Zn or Ga (MgCa/CaP + Zn and MgCa/CaP + Ga, respectively) were implanted in bone defects created in the sheep cranium. MgCa implants degraded faster than the others at 4 weeks postop and the weight loss was ca. 50%, while it was ca. 15% for MgCa/CaP and <10% in the presence of Zn and Ga with CaP coating. Scanning electron microscopy (SEM) analysis of the implant surfaces also revealed that the MgCa implants had the largest degree of structural breakdown of all the groups. Radiological evaluation revealed that surface modification with CaP to the MgCa implants induced better bone regeneration within the defects as well as the enhancement of bone-implant surface integration. Bone volume (%) within the defect was ca. 25% in the case of MgCa/CaP + Ga, while it was around 15% for undoped MgCa group upon micro-CT evaluation. This >1.5-fold increase in bone regeneration for MgCa/CaP + Ga implant was also observed in the histopathological examination of the H&E- and Masson's trichrome-stained sections. Immunohistochemical analysis of the bone regeneration (antiosteopontin) and neovascularization (anti-CD31) at the defect sites revealed >2-fold increase in the expression of the markers in both Ga- and Zn-doped, CaP-coated implants. Zn-doped implants further presented low inflammatory reaction, notable bone regeneration, and neovascularization among all the implant groups. These findings indicated that Ga- and Zn-doped CaP coating is an important strategy to control the degradation rate as well as to achieve enhanced bone regeneration capacity of the implants made of Mg-based alloys.


Assuntos
Ligas , Fosfatos de Cálcio , Materiais Revestidos Biocompatíveis , Gálio , Magnésio , Osteogênese , Crânio , Zinco , Animais , Zinco/química , Zinco/farmacologia , Ovinos , Crânio/efeitos dos fármacos , Crânio/patologia , Crânio/lesões , Osteogênese/efeitos dos fármacos , Magnésio/farmacologia , Gálio/química , Gálio/farmacologia , Ligas/química , Ligas/farmacologia , Materiais Revestidos Biocompatíveis/química , Materiais Revestidos Biocompatíveis/farmacologia , Fosfatos de Cálcio/química , Fosfatos de Cálcio/farmacologia , Regeneração Óssea/efeitos dos fármacos , Cálcio/metabolismo , Implantes Absorvíveis
15.
Arch Microbiol ; 206(7): 304, 2024 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-38878097

RESUMO

The extension of multidrug-resistant strains of Staphylococcus aureus (S. aureus) is one of the main health challenges in the world, which requires serious solutions to deal with it. Combination therapies using conventional antibiotics and new antibacterial compounds that target different bacterial pathways are effective methods against resistant bacterial infections. Gallium is an iron-like metal that competes with iron for uptake into bacteria and has the potential to disrupt iron-dependent vital processes in bacteria. In this study, we explored the antibacterial effects of gallium nitrate (Ga(NO3)3) and vancomycin alone and in combination with each other on methicillin-sensitive S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA) using microdilution assay and checkerboard test, respectively. Then, their effect on the formation and destruction of biofilms was investigated. Finally, the amount of ROS production in the presence of these two compounds in bacteria was evaluated. The results indicated that the vancomycin/ Ga(NO3)3 combination reduced the MIC of vancomycin in the MRSA strain and had an additive effect on it. Vancomycin plus Ga(NO3)3 reduced the formation of biofilms and increased the destruction of biofilms formed in both strains, especially in the MRSA strain. ROS production was also higher in the combination of vancomycin with Ga(NO3)3 compared to vancomycin alone, especially in MRSA. Therefore, our results showed that Ga(NO3)3 enhances the antibacterial activity of vancomycin and this combination therapy can be considered as a new strategy for the treatment of MRSA infections.


Assuntos
Antibacterianos , Biofilmes , Gálio , Staphylococcus aureus Resistente à Meticilina , Testes de Sensibilidade Microbiana , Staphylococcus aureus , Vancomicina , Gálio/farmacologia , Vancomicina/farmacologia , Antibacterianos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Biofilmes/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos , Sinergismo Farmacológico , Espécies Reativas de Oxigênio/metabolismo , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Humanos
16.
Analyst ; 149(16): 4267-4275, 2024 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-38904993

RESUMO

Vertical flow assay (VFA) is an effective point-of-care (POC) diagnostic tool for widespread application. Nevertheless, the lack of multi-target detection and multi-signal readout capability still remains a challenge. Herein, a brand new VFA scheme for multi-target saliva detection based on electronic tags was proposed, where AlGaN/GaN HEMT sensors modified with different bio-receptors as electronic tags endowed the VFA with multi-target detection capability. In addition, the use of electronic tags instead of optical tags allowed the VFA to simultaneously carry out direct multi-target readouts, which ensure effective POC diagnostics for saliva analysis. Moreover, by integrating a hydrophilically optimized micro-sieve, impurities like sticky filaments, epidermal cells and other large-scale charged particles in saliva were effectively screened, which enabled the direct detection of saliva using AlGaN/GaN HEMT sensors. Glucose, urea, and cortisol were selected to verify the feasibility of the multi-target e-VFA scheme, and the results showed that the limit of detection (LOD) was as low as 100 aM. The linear response was demonstrated in the dynamic range of 100 aM to 100 µM, and the specificity, long-term stability and validity of the actual saliva test were also verified. These results demonstrated that the as-proposed e-VFA has potential for application in saliva detection for simultaneous multi-target detection, and it is expected to achieve the real-time detection of more biological targets in saliva.


Assuntos
Gálio , Hidrocortisona , Limite de Detecção , Saliva , Saliva/química , Gálio/química , Humanos , Hidrocortisona/análise , Glucose/análise , Ureia/análise , Ureia/química , Técnicas Biossensoriais/métodos , Técnicas Biossensoriais/instrumentação , Sistemas Automatizados de Assistência Junto ao Leito , Compostos de Alumínio/química
17.
Int J Biol Macromol ; 274(Pt 2): 133438, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38936583

RESUMO

The increasing threat of spoilage bacterial infections, driven by the resistance of bacteria to many antimicrobial treatments, is a significant worldwide public health problem, especially concerning food preservation. To tackle these difficulties, this research investigates the possibility of using packaging sheets that include antimicrobial agents and increasing the prolonged storage time by preventing the bioburden of foodborne pathogens. This approach uses metal nanoparticles' ability to prevent harmful bacteria that cause food spoiling. Gallium nanoparticles (GaNPs) were created using a water-based extract from Andrographis paniculata leaves as a bioreducing agent. The GaNPs were added to a film made of sodium alginate (SA) and polyvinylpyrrolidone (PVP). The study showed that incorporating GaNPs into polymer films resulted in films with a desirable contact angle and decreased water vapor permeability. Significantly, the developed films demonstrated increased efficiency against E.coli O157 compared to other species. Also, it exhibited increased vulnerability to bacterial strains at the biofilm stage, surpassing PVP-SA/GaNPs-0. Remarkably, the toxicity tests showed that the films exhibited no cytotoxicity. Overall, the films indicated their potential for avoiding bacterial bioburden, prolonging the shelf life of perishable products, and contributing to diverse antimicrobial applications in the food industry.


Assuntos
Alginatos , Antibacterianos , Gálio , Nanopartículas Metálicas , Povidona , Alginatos/química , Alginatos/farmacologia , Povidona/química , Antibacterianos/farmacologia , Antibacterianos/química , Nanopartículas Metálicas/química , Gálio/química , Gálio/farmacologia , Embalagem de Alimentos/métodos , Microbiologia de Alimentos , Testes de Sensibilidade Microbiana , Conservação de Alimentos/métodos , Biofilmes/efeitos dos fármacos , Permeabilidade
18.
Int J Biol Macromol ; 274(Pt 2): 133420, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38925194

RESUMO

The treatment of diabetic wounds possessed significant challenges in clinical practice, which was accompanied with continuous infection, inflammation, and limited angiogenesis. Current wound dressings used for diabetic wound healing struggle to address these issues simultaneously. Therefore, Ga3+ was added to the chitosan/silk solution to confer potent antibacterial properties. Subsequently, umbilical cord mesenchymal stem cell exosomes (UCSC-Exo) were integrated into the gallium/chitosan/silk solution to enhance its angiogenesis-inducing activity. The mixture was lyophilized to prepare gallium/chitosan/silk/exosome sponge scaffolds (Ga/CSSF-Exo sponge scaffolds). The experiments of In vitro and in vivo demonstrated that Ga/CSSF-Exo sponge scaffolds exhibited sustained release of Ga3+ and bioactive exosomes, which effectively exerted continuous antibacterial effects and promoted angiogenesis. In diabetic rat wound models, Ga/CSSF-Exo sponge scaffolds facilitated angiogenesis, suppressed bacterial growth and inflammation, as well as promoted collagen deposition and re-epithelialization of wounds. Collectively, our findings suggested that Ga/CSSF-Exo held excellent potential for diabetic wound healing.


Assuntos
Diabetes Mellitus Experimental , Células-Tronco Mesenquimais , Neovascularização Fisiológica , Alicerces Teciduais , Cordão Umbilical , Cicatrização , Animais , Humanos , Masculino , Ratos , Angiogênese , Antibacterianos/farmacologia , Antibacterianos/química , Quitosana/química , Quitosana/farmacologia , Diabetes Mellitus Experimental/complicações , Exossomos/metabolismo , Gálio/química , Gálio/farmacologia , Células-Tronco Mesenquimais/citologia , Neovascularização Fisiológica/efeitos dos fármacos , Ratos Sprague-Dawley , Alicerces Teciduais/química , Cordão Umbilical/citologia , Cicatrização/efeitos dos fármacos
19.
Biomed Mater ; 19(5)2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38917820

RESUMO

Metastatic bone lesions are often osteolytic, which causes advanced-stage cancer sufferers to experience severe pain and an increased risk of developing a pathological fracture. Gallium (Ga) ion possesses antineoplastic and anti-bone resorption properties, suggesting the potential for its local administration to impede the growth of metastatic bone lesions. This study investigated the chemotherapeutic potential, cytotoxicity, and osteogenic effects of a Ga-doped glass polyalkenoate cement (GPC) (C-TA2) compared to its non-gallium (C-TA0) counterpart. Ion release profiles revealed a biphasic pattern characterized by an initial burst followed by a gradually declining release of ions. C-TA2 continued to release Ga steadily throughout the experimentation period (7 d) and exhibited prolonged zinc (Zn) release compared to C-TA0. Interestingly, the Zn release from both GPCs appeared to cause a chemotherapeutic effect against H1092 lung cancer cellsin vitro, with the prolonged Zn release from C-TA2 extending this effect. Unfortunately, both GPCs enhanced the viability of HCC2218 breast cancer cells, suggesting that the chemotherapeutic effects of Zn could be tied to cellular differences in preferred Zn concentrations. The utilization of SAOS-2 and MC3T3 cell lines as bone cell models yielded conflicting results, with the substantial decline in MC3T3 viability closely associated with silicon (Si) release, indicating cellular variations in Si toxicity. Despite this ambiguity, both GPCs exhibited harmful effects on the osteogenesis of primary rat osteoblasts, raising concerns about excessive burst Zn release. While Ga/Zn-doped GPCs hold promise for treating metastatic bone lesions caused by lung cancers, further optimization is required to mitigate cytotoxicity on healthy bone.


Assuntos
Sobrevivência Celular , Gálio , Osteogênese , Gálio/química , Animais , Humanos , Linhagem Celular Tumoral , Osteogênese/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Camundongos , Zinco/química , Ratos , Cimentos de Ionômeros de Vidro/química , Antineoplásicos/química , Antineoplásicos/farmacologia , Teste de Materiais , Neoplasias Ósseas/tratamento farmacológico , Osteoblastos/efeitos dos fármacos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Materiais Biocompatíveis/química , Materiais Biocompatíveis/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/patologia
20.
Int Wound J ; 21(6): e14940, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38888416

RESUMO

Bacterial infection is the most common complication in wound healing, highlighting an urgent need for the development of innovative antibacterial technologies and treatments to address the growing threats posed by bacterial infections. Black phosphorus nanosheets (BPNSs), as a promising two-dimensional nanomaterial, have been utilized in treating infected wounds. However, BP's limited stability restricts its application. In this study, we enhance BP's stability and its antibacterial properties by anchoring gallium ions (Ga3+) onto BP's surface, creating a novel antibacterial platform. This modification reduces BP's electron density and enhances its antibacterial capabilities through a synergistic effect. Under near-infrared (NIR) irradiation, the BP/Ga3+ combination exerts antibacterial effects via photothermal therapy (PTT) and photodynamic therapy (PDT), while also releasing Ga3+. The Ga3+ employ a 'Trojan horse strategy' to disrupt iron metabolism, significantly boosting the antibacterial efficacy of the complex. This innovative material offers a viable alternative to antibiotics and holds significant promise for treating infected wounds and aiding skin reconstruction.


Assuntos
Antibacterianos , Gálio , Fósforo , Cicatrização , Gálio/farmacologia , Gálio/uso terapêutico , Cicatrização/efeitos dos fármacos , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Humanos , Animais , Nanoestruturas/uso terapêutico , Infecção dos Ferimentos/tratamento farmacológico , Fotoquimioterapia/métodos , Infecções Bacterianas/tratamento farmacológico , Camundongos , Terapia Fototérmica/métodos
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