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1.
Commun Biol ; 7(1): 776, 2024 Jun 27.
Artículo en Inglés | MEDLINE | ID: mdl-38937578

RESUMEN

Aggregation of the human islet amyloid polypeptide (hIAPP) contributes to the development and progression of Type 2 Diabetes (T2D). hIAPP aggregates within a few hours at few micromolar concentration in vitro but exists at millimolar concentrations in vivo. Natively occurring inhibitors of hIAPP aggregation might therefore provide a model for drug design against amyloid formation associated with T2D. Here, we describe the combined ability of low pH, zinc, and insulin to inhibit hIAPP fibrillation. Insulin dose-dependently slows hIAPP aggregation near neutral pH but had less effect on the aggregation kinetics at acidic pH. We determine that insulin alters hIAPP aggregation in two manners. First, insulin diverts the aggregation pathway to large nonfibrillar aggregates with ThT-positive molecular structure, rather than to amyloid fibrils. Second, soluble insulin suppresses hIAPP dimer formation, which is an important early aggregation event. Further, we observe that zinc significantly modulates the inhibition of hIAPP aggregation by insulin. We hypothesize that this effect arose from controlling the oligomeric state of insulin and show that hIAPP interacts more strongly with monomeric than oligomeric insulin.


Asunto(s)
Insulina , Polipéptido Amiloide de los Islotes Pancreáticos , Agregado de Proteínas , Zinc , Polipéptido Amiloide de los Islotes Pancreáticos/química , Polipéptido Amiloide de los Islotes Pancreáticos/metabolismo , Concentración de Iones de Hidrógeno , Humanos , Zinc/farmacología , Zinc/metabolismo , Zinc/química , Insulina/metabolismo , Agregado de Proteínas/efectos de los fármacos , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Cinética , Amiloide/metabolismo , Amiloide/química , Agregación Patológica de Proteínas/metabolismo
2.
ACS Appl Mater Interfaces ; 16(25): 32104-32117, 2024 Jun 26.
Artículo en Inglés | MEDLINE | ID: mdl-38865210

RESUMEN

The repair of infected wounds is a complex physiopathologic process. Current studies on infected wound treatment have predominantly focused on infection treatment, while the factors related to delayed healing caused by vascular damage and immune imbalance are commonly overlooked. In this study, an extracellular matrix (ECM)-like dynamic and multifunctional hyaluronic acid (HA) hydrogel with antimicrobial, immunomodulatory, and angiogenic capabilities was designed as wound dressing for the treatment of infected skin wounds. The dynamic network in the hydrogel dressing was based on reversible metal-ligand coordination formed between sulfhydryl groups and bioactive metal ions. In our design, antibacterial silver and immunomodulatory zinc ions were employed to coordinate with sulfhydrylated HA and a vasculogenic peptide. In addition to the desired bioactivities for infected wounds, the hydrogel could also exhibit self-healing and injectable abilities. Animal experiments with infected skin wound models indicated that the hydrogel dressings enabled minimally invasive injection and seamless skin wound covering and then facilitated wound healing by efficient bacterial killing, continuous inflammation inhibition, and improved blood vessel formation. In conclusion, the metal ion-coordinated hydrogels with wound-infection-desired bioactivities and ECM-like dynamic structures represent a class of tissue bionic wound dressings for the treatment of infected and chronic inflammation wounds.


Asunto(s)
Antibacterianos , Hidrogeles , Cicatrización de Heridas , Cicatrización de Heridas/efectos de los fármacos , Animales , Hidrogeles/química , Hidrogeles/farmacología , Antibacterianos/química , Antibacterianos/farmacología , Ratones , Plata/química , Plata/farmacología , Ácido Hialurónico/química , Ácido Hialurónico/farmacología , Zinc/química , Zinc/farmacología , Factores Inmunológicos/química , Factores Inmunológicos/farmacología , Infección de Heridas/tratamiento farmacológico , Infección de Heridas/patología , Infección de Heridas/microbiología , Vendajes , Humanos , Neovascularización Fisiológica/efectos de los fármacos , Staphylococcus aureus/efectos de los fármacos , Iones/química
3.
Biomed Mater ; 19(5)2024 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-38917820

RESUMEN

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.


Asunto(s)
Supervivencia Celular , Galio , Osteogénesis , Galio/química , Animales , Humanos , Línea Celular Tumoral , Osteogénesis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Ratones , Zinc/química , Ratas , Cementos de Ionómero Vítreo/química , Antineoplásicos/química , Antineoplásicos/farmacología , Ensayo de Materiales , Neoplasias Óseas/tratamiento farmacológico , Osteoblastos/efectos de los fármacos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología
4.
Int J Nanomedicine ; 19: 5059-5070, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38836007

RESUMEN

Purpose: The purpose of this study is to address the need for efficient drug delivery with high drug encapsulation efficiency and sustained drug release. We aim to create nanoparticle-loaded microgels for potential applications in treatment development. Methods: We adopted the process of ionic gelation to generate microgels from sodium alginate and carboxymethyl cellulose. These microgels were loaded with doxorubicin-conjugated amine-functionalized zinc ferrite nanoparticles (AZnFe-NPs). The systems were characterized using various techniques. Toxicity was evaluated in MCF-7 cells. In vitro release studies were conducted at different pH levels at 37 oC, with the drug release kinetics being analyzed using various models. Results: The drug encapsulation efficiency of the created carriers was as high as 70%. The nanoparticle-loaded microgels exhibited pH-responsive behavior and sustained drug release. Drug release from them was mediated via a non-Fickian type of diffusion. Conclusion: Given their high drug encapsulation efficiency, sustained drug release and pH-responsiveness, our nanoparticle-loaded microgels show promise as smart carriers for future treatment applications. Further development and research can significantly benefit the field of drug delivery and treatment development.


Asunto(s)
Preparaciones de Acción Retardada , Doxorrubicina , Portadores de Fármacos , Liberación de Fármacos , Compuestos Férricos , Microgeles , Doxorrubicina/química , Doxorrubicina/farmacocinética , Doxorrubicina/farmacología , Doxorrubicina/administración & dosificación , Humanos , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacocinética , Preparaciones de Acción Retardada/farmacología , Células MCF-7 , Compuestos Férricos/química , Concentración de Iones de Hidrógeno , Microgeles/química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Alginatos/química , Aminas/química , Carboximetilcelulosa de Sodio/química , Nanopartículas/química , Zinc/química , Compuestos de Zinc/química , Supervivencia Celular/efectos de los fármacos
5.
J Chem Phys ; 160(23)2024 Jun 21.
Artículo en Inglés | MEDLINE | ID: mdl-38884404

RESUMEN

Zinc tungstate is a semiconductor known for its favorable photocatalytic, photoluminescence, and scintillation properties, coupled with its relatively low cost, reduced toxicity, and high stability in biological and catalytic environments. In particular, zinc tungstate evinces scintillation properties, namely the ability to emit visible light upon absorption of energetic radiation such as x rays, which has led to applications not only as radiation detectors but also for biomedical applications involving the delivery of optical light to deep tissue, such as photodynamic therapy and optogenetics. Here, we report on the synthesis of zinc tungstate nanorods generated via an optimized but facile method, which allows for synthetic control over the aspect ratio of the as-synthesized anisotropic motifs via rational variation of the solution pH. We investigate the effect of aspect ratio on their resulting photoluminescent and radioluminescent properties. We further demonstrate the potential of these zinc tungstate nanorods for biomedical applications, such as photodynamic therapy for cancer treatment, by analyzing their toxicological profile within cell lines and neurons.


Asunto(s)
Nanotubos , Compuestos de Tungsteno , Compuestos de Tungsteno/química , Compuestos de Tungsteno/toxicidad , Nanotubos/química , Humanos , Animales , Fotoquimioterapia , Supervivencia Celular/efectos de los fármacos , Compuestos de Zinc/química , Ratones , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Zinc/química
6.
ACS Appl Mater Interfaces ; 16(24): 31489-31499, 2024 Jun 19.
Artículo en Inglés | MEDLINE | ID: mdl-38833169

RESUMEN

Currently, photodynamic therapy (PDT) is restricted by the laser penetration depth. Except for PDT at 1064 nm wavelength excitation, the development of other NIR-II-activated nanomaterials with a higher response depth is still hindered and rarely reported in the literature. To overcome these problems, we fabricated a nanoplatform with heterostructures that generate reactive oxygen species (ROS) and ferrite nanoparticles under a high concentration of zinc doping (ZnxFe3-xO4 NPs), which can achieve oxidative damage of tumor cells under near-infrared (NIR) illumination. The recombination of photoelectrons and holes has been markedly inhibited due to the formation of heterostructures in the interfaces, thus greatly enhancing the capability for ROS and oxygen production by modulating the single-component doping content. The efficiency of PDT was verified by in vivo and in vitro assays under NIR light. Our results revealed that NIR-II (1208 nm) light irradiation of ZnxFe3-xO4 NPs exerted a remarkable antitumor activity, superior to NIR-I light (808 nm). More importantly, the reported ZnxFe3-xO4 NPs strategy provides an opportunity for the success of comparison with light in the first and second near-infrared regions.


Asunto(s)
Rayos Infrarrojos , Fotoquimioterapia , Zinc , Humanos , Zinc/química , Zinc/farmacología , Animales , Ratones , Especies Reactivas de Oxígeno/metabolismo , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Compuestos Férricos/química , Compuestos Férricos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Ratones Endogámicos BALB C
7.
Mikrochim Acta ; 191(7): 366, 2024 06 04.
Artículo en Inglés | MEDLINE | ID: mdl-38833071

RESUMEN

Aristolochic acids (AAs), which are a group of nitrophenanthrene carboxylic acids formed by Aristolochia plant, have become an increasing serious threat to humans due to their nephrotoxicity and carcinogenicity. Fast and accurate approaches capable of simultaneous sensing of aristolochic acids (I-IV) are vital to avoid intake of such compounds. In this research, the novel ratiometric fluorescence zinc metal-organic framework and its nanowire have been prepared. The two different coordination modes (tetrahedral configuration and twisted triangular bipyramidal configuration) within zinc metal-organic framework lead to the significant double emissions. The ratiometric fluorescence approach based on nanowire provides a broader concentration range (3.00 × 10-7~1.00 × 10-4 M) and lower limit of detection (3.70 × 10-8 M) than that based on zinc metal-organic framework (1.00 × 10-6~1.00 × 10-4 M, 5.91 × 10-7 M). The RSDs of the results are in the range 1.4-3.5% (nanowire). The density functional theory calculations and UV-Vis absorption verify that the sensing mechanism is due to charge transfer and energy transfer. Excellent spiked recoveries for AAs(I-IV) in soil and water support that nanowire is competent to simultaneously detect these targets in real samples, and the proposed approach has potential as a fluorescence sensing platform for the simultaneous detection of AAs (I-IV) in complex systems.


Asunto(s)
Ácidos Aristolóquicos , Límite de Detección , Estructuras Metalorgánicas , Nanocables , Ácidos Aristolóquicos/análisis , Ácidos Aristolóquicos/química , Estructuras Metalorgánicas/química , Nanocables/química , Zinc/química , Espectrometría de Fluorescencia/métodos , Contaminantes Químicos del Agua/análisis , Contaminantes Químicos del Agua/química , Mediciones Luminiscentes/métodos , Colorantes Fluorescentes/química
8.
J Mater Sci Mater Med ; 35(1): 33, 2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38900208

RESUMEN

Phosphate bioactive glass has been studied for its advanced biodegradability and active ion release capability. Our previous research found that phosphate glass containing (P2O5)-(Na2O)-(TiO2)-(CaO)-(SrO) or (ZnO) showed good biocompatibility with MG63 and hMSCs. This study further investigated the application of 5 mol% zinc oxide or 17.5 mol% strontium oxide in titanium-doped phosphate glass for bone tissue engineering. Ti-Ca-Na-Phosphate glasses, incorporating 5% zinc oxide or 17.5% strontium oxide, were made with melting quenching technology. The pre-osteoblast cell line MC3T3-E1 was cultured for indirect contact tests with graded diluted phosphate glass extractions and for direct contact tests by seeding cells on glass disks. The cell viability and cytotoxicity were analysed in vitro over 7 days. In vivo studies utilized the tibial defect model with or without glass implants. The micro-CT analysis was performed after surgery and then at 2, 6, and 12 weeks. Extractions from both zinc and strontium phosphate glasses showed no negative impact on MC3T3-E1 cell viability. Notably, non-diluted Zn-Ti-Ca-Na-phosphate glass extracts significantly increased cell viability by 116.8% (P < 0.01). Furthermore, MC3T3-E1 cells cultured with phosphate glass disks exhibited no increase in LDH release compared with the control group. Micro-CT images revealed that, over 12 weeks, both zinc-doped and strontium-doped phosphate glasses demonstrated good bone incorporation and longevity compared to the no-implant control. Titanium-doped phosphate glasses containing 5 mol% zinc oxide, or 17.5 mol% strontium oxide have promising application potential for bone regeneration research.


Asunto(s)
Regeneración Ósea , Supervivencia Celular , Vidrio , Fosfatos , Estroncio , Titanio , Estroncio/química , Estroncio/farmacología , Regeneración Ósea/efectos de los fármacos , Animales , Ratones , Fosfatos/química , Fosfatos/farmacología , Vidrio/química , Titanio/química , Supervivencia Celular/efectos de los fármacos , Ensayo de Materiales , Zinc/química , Línea Celular , Osteoblastos/efectos de los fármacos , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Ingeniería de Tejidos/métodos , Sustitutos de Huesos/química , Sustitutos de Huesos/farmacología , Microtomografía por Rayos X
9.
Environ Sci Pollut Res Int ; 31(27): 39533-39548, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38822960

RESUMEN

The present study evaluated a solvo-metallurgical technique for metal extraction from industrial solid waste (jarosite) using ionic liquids (ILs) and waste-derived solvents. The jarosite contains a considerable amount of metal ions, namely iron, zinc, and lead. The jarosite was characterized by XRF, XRD, SEM, and FTIR techniques. The parameters affecting metal extraction, such as stirring time, acid molarity, and temperature, have been examined. Aliquat 336 was used to extract metals from fresh and roasted jarosite after equilibration with HCl. The response surface methodology (RSM) was used to optimize the parameters for the maximum metal extraction using [A336] [Cl]. Maximum extraction of iron (86.75%), zinc (51.96%), and lead (94.38%) from roasted jarosite was achieved at optimum conditions (125-min stirring time, 5 M acid molarity, and 20 ml/g liquid-to-solid ratio). Furthermore, the metal extraction was investigated using waste-derived solvents. The results show that waste-derived solvents, such as biomass and plastic pyrolysis oil, can effectively extract metals from fresh and roasted jarosite. Biomass pyrolysis oil achieved the highest extraction at 50 °C for 90 min, while plastic pyrolysis oil achieved the highest extraction at 50 °C for 60 min from roasted jarosite. These solvents are also cost-effective because they are made from waste plastic and biomass.


Asunto(s)
Líquidos Iónicos , Solventes , Zinc , Líquidos Iónicos/química , Solventes/química , Zinc/química , Metales/química , Plomo , Hierro/química , Compuestos Férricos , Sulfatos
10.
Int J Biol Macromol ; 271(Pt 2): 132766, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38823742

RESUMEN

The efficient development and utilization of green biomass-based macromolecule engineering materials are essential for the sustainable development of human civilization. In this study, lignin-based ethylene-propylene-diene-monomer (EPDM) composites with excellent mechanical performance were fabricated using a simple method. The effects of water-insoluble enzymatically hydrolyzed lignin (EL) and alkali lignin (KL) on the mechanical performance of the composites were investigated separately. The results showed that the tensile strength of EPDM reinforced with KL and EL increased to 24.5 MPa and 22.1 MPa, respectively, surpassing that of the carbon black (CB)-reinforced EPDM. After 72 h of thermo-oxidative aging, the retention rates of the tensile strength and elongation at break in the lignin-reinforced EPDM were much better than those formed with pure CB, indicating that lignin significantly improved the thermo-oxidative aging resistance of the composites. In summary, the Zn2+ coordination bonds formed between the interface of EPDM and lignin in lignin/CB/EPDM ternary composites effectively improved the mechanical performance and aging resistance of the composites. This study has significant implications for enhancing the utilization of lignin and green functional polymer materials.


Asunto(s)
Lignina , Lignina/química , Resistencia a la Tracción , Etilenos/química , Relación Estructura-Actividad , Zinc/química , Oxidación-Reducción , Reactivos de Enlaces Cruzados/química , Elastómeros
11.
Angew Chem Int Ed Engl ; 63(27): e202401003, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38808693

RESUMEN

The gasotransmitter hydrogen sulfide (H2S) is thought to be involved in the post-translational modification of cysteine residues to produce reactive persulfides. A persulfide-specific chemoselective proteomics approach with mammalian cells has identified a broad range of zinc finger (ZF) proteins as targets of persulfidation. Parallel studies with isolated ZFs show that persulfidation is mediated by ZnII, O2, and H2S, with intermediates involving oxygen- and sulfur-based radicals detected by mass spectrometry and optical spectroscopies. A small molecule ZnII complex exhibits analogous reactivity with H2S and O2, giving a persulfidated product. These data show that ZnII is not just a biological structural element, but also plays a critical role in mediating H2S-dependent persulfidation. ZF persulfidation appears to be a general post-translational modification and a possible conduit for H2S signaling. This work has implications for our understanding of H2S-mediated signaling and the regulation of ZFs in cellular physiology and development.


Asunto(s)
Sulfuro de Hidrógeno , Proteómica , Sulfuros , Dedos de Zinc , Zinc , Sulfuro de Hidrógeno/química , Sulfuro de Hidrógeno/metabolismo , Zinc/química , Humanos , Sulfuros/química , Procesamiento Proteico-Postraduccional
12.
Molecules ; 29(10)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38792033

RESUMEN

Copper(II), nickel(II) and zinc(II) complexes of various peptide fragments of tau protein were studied by potentiometric and spectroscopic techniques. All peptides contained one histidyl residue and represented the sequences of tau(91-97) (Ac-AQPHTEI-NH2), tau(385-390) (Ac-KTDHGA-NH2) and tau(404-409) (Ac-SPRHLS-NH2). Imidazole-N donors of histidine were the primary metal binding sites for all peptides and all metal ions, but in the case of copper(II) and nickel(II), the deprotonated amide groups were also involved in metal binding by increasing pH. The most stable complexes were formed with copper(II) ions, but the presence of prolyl residues resulted in significant changes in the thermodynamic stability and speciation of the systems. It was also demonstrated that nickel(II) and especially zinc(II) complexes have relatively low thermodynamic stability with these peptides. The copper(II)-catalyzed oxidation of the peptides was also studied. In the presence of H2O2, the fragmentation of peptides was detected in all cases. In the simultaneous presence of H2O2 and ascorbic acid, the fragmentation of the peptide is less preferred, and the formation of 2-oxo-histidine also occurs.


Asunto(s)
Complejos de Coordinación , Cobre , Níquel , Fragmentos de Péptidos , Zinc , Proteínas tau , Níquel/química , Cobre/química , Zinc/química , Proteínas tau/química , Complejos de Coordinación/química , Fragmentos de Péptidos/química , Oxidación-Reducción , Histidina/química , Concentración de Iones de Hidrógeno , Peróxido de Hidrógeno/química , Termodinámica
13.
Biosens Bioelectron ; 259: 116387, 2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-38754194

RESUMEN

The incidence of esophageal cancer is positively associated with fumonisin contamination. It is necessary to develop methods for the rapid detection of fumonisins. In this work, a self-powered photoelectrochemical aptamer sensor based on ZnIn2S4/WO3 photoanode and Au@W-Co3O4 photocathode is proposed for the sensitive detection of fumonisin B1 (FB1). Among them, under visible light irradiation, the Z-type heterostructure of ZnIn2S4/WO3 acts as a photoanode to improve the electron transfer rate, which contributes to the enhancement of the photocathode signal and lays the foundation for a wider detection range. The Au@W-Co3O4 photocathode as a sensing interface reduces the probability of false positives (comparison of anode sensing platforms). The PEC sensor has a good working performance in the detection range (10 pg/mL-1000 ng/mL) with a detection limit of 2.7 pg/mL (S/N = 3). In addition, the sensor offers good selectivity, stability and excellent recoveries in real sample analysis. This work is expected to play a role in the field of analyzing environmental toxins.


Asunto(s)
Aptámeros de Nucleótidos , Técnicas Biosensibles , Técnicas Electroquímicas , Fumonisinas , Límite de Detección , Fumonisinas/análisis , Fumonisinas/química , Aptámeros de Nucleótidos/química , Tungsteno/química , Electrodos , Óxidos/química , Oro/química , Humanos , Luz , Zinc/química
14.
J Inorg Biochem ; 257: 112598, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38763101

RESUMEN

In this work, we report on the synthesis of a novel zinc(II) coordination compound [ZnL2] (1), which was readily obtained from the reaction of Zn(OAc)·2H2O and N'-(pyridin-2-ylmethylene)nicotinohydrazide (HL) in methanol. Recrystallization of 1 from dimethylformamide under ambient conditions allowed to produce yellow block-like crystals of 1·H2O. Complex 1·H2O was characterized by FT-IR and 1H NMR spectroscopy, while its optical properties were studied by UV-vis and spectrofluorimetry in methanol. The crystal structure of the title complex was revealed by single crystal X-ray diffraction and further explored in detail by the Hirshfeld surface analysis. Theoretical investigations based on the DFT calculations have also been applied to show the electronic properties of complex 1. The antitumor activities of the parent ligand HL and complex 1 were studied using Dalton's lymphoma malignant cancer model. Both compounds were found to induce concentration-dependent cytotoxicity and apoptotic cell death, leading to a decrease in cell viability, body weight, and tumor volume in mice with the superior activity of complex 1 over HL. Mice treated with complex 1 demonstrated an increase in life span with a survival period of 23 days. Finally, using a molecular docking approach, we have probed complex 1 to inhibit the recombinant mouse tumor-necrosis factor alpha (mTNF).


Asunto(s)
Antineoplásicos , Complejos de Coordinación , Zinc , Zinc/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/síntesis química , Antineoplásicos/química , Humanos , Cristalografía por Rayos X , Línea Celular Tumoral , Apoptosis/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos
15.
J Biomater Appl ; 39(2): 129-138, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38782577

RESUMEN

Zn-Ag-In-S (ZAIS) quantum dots (QDs) were synthesized with various Ag-to-In ratios and used as novel photosensitizers for photodynamic therapy (PDT) on cancer cell inhibition and bacterial sterilization, and their structural, optical, and photodynamic properties were investigated. The alloyed QDs displayed a photoluminescence quantum yield of 72% with a long fluorescence lifetime of 5.3 µs when the Ag-to-In ratio was 1:3, suggesting a good opportunity as a dual functional platform for fluorescence imaging and PDT. The ZAIS QDs were then coated with amphiphilic brush copolymer poly(maleic anhydride-alt-1-octadecene) (PMAO) before application. The 1O2 quantum yield of the ZAIS/PMAO was measured to be 8%, which was higher than previously reported CdSe QDs and comparable to some organic photosensitizers. Moreover, the ZAIS QDs showed excellent stability in aqueous and biological media, unlike organic photosensitizers that tend to degrade over time. The in vitro PDT against human melanoma cell line (A2058) and Staphylococcus aureus shows about 30% inhibition rate upon 20 min light irradiation. Cell staining images clearly demonstrated that co-treatment with ZAIS QDs and light irradiation effectively killed A2058 cells, demonstrating the potential of ZAIS QDs as novel and versatile photosensitizers for PDT in cancer and bacterial treatment, and provides useful information for future designing of QD-based photosensitizers.


Asunto(s)
Fotoquimioterapia , Fármacos Fotosensibilizantes , Puntos Cuánticos , Oxígeno Singlete , Staphylococcus aureus , Puntos Cuánticos/química , Humanos , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/química , Oxígeno Singlete/metabolismo , Oxígeno Singlete/química , Staphylococcus aureus/efectos de los fármacos , Línea Celular Tumoral , Plata/química , Plata/farmacología , Zinc/química , Zinc/farmacología , Indio/química , Indio/farmacología , Antibacterianos/farmacología , Antibacterianos/química , Supervivencia Celular/efectos de los fármacos
16.
Acta Biomater ; 182: 245-259, 2024 07 01.
Artículo en Inglés | MEDLINE | ID: mdl-38729545

RESUMEN

Diabetic wound healing is a great clinical challenge due to the microenvironment of hyperglycemia and high pH value, bacterial infection and persistent inflammation. Here, we develop a cascade nanoreactor hydrogel (Arg@Zn-MOF-GOx Gel, AZG-Gel) with arginine (Arg) loaded Zinc metal organic framework (Zn-MOF) and glucose oxidase (GOx) based on chondroitin sulfate (CS) and Pluronic (F127) to accelerate diabetic infected wound healing. GOx in AZG-Gel was triggered by hyperglycemic environment to reduce local glucose and pH, and simultaneously produced hydrogen peroxide (H2O2) to enable Arg-to release nitric oxide (NO) for inflammation regulation, providing a suitable microenvironment for wound healing. Zinc ions (Zn2+) released from acid-responsive Zn-MOF significantly inhibited the proliferation and biofilm formation of S.aureus and E.coli. AZG-Gel significantly accelerated diabetic infected wound healing by down-regulating pro-inflammatory tumor necrosis factor (TNF)-α and interleukin (IL)-6, up-regulating anti-inflammatory factor IL-4, promoting angiogenesis and collagen deposition in vivo. Collectively, our nanoreactor cascade strategy combining "endogenous improvement (reducing glucose and pH)" with "exogenous resistance (anti-bacterial and anti-inflammatory)" provides a new idea for promoting diabetic infected wound healing by addressing both symptoms and root causes. STATEMENT OF SIGNIFICANCE: A cascade nanoreactor (AZG-Gel) is constructed to solve three key problems in diabetic wound healing, namely, hyperglycemia and high pH microenvironment, bacterial infection and persistent inflammation. Local glucose and pH levels are reduced by GOx to provide a suitable microenvironment for wound healing. The release of Zn2+ significantly inhibits bacterial proliferation and biofilm formation, and NO reduces wound inflammation and promotes angiogenesis. The pH change when AZG-Gel is applied to wounds is expected to enable the visualization of wound healing to guide the treatment of diabetic wound. Our strategy of "endogenous improvement (reducing glucose and pH)" combined with "exogenous resistance (anti-bacterial and anti-inflammatory)" provides a new way for promoting diabetic wound healing.


Asunto(s)
Glucosa Oxidasa , Estructuras Metalorgánicas , Óxido Nítrico , Cicatrización de Heridas , Zinc , Cicatrización de Heridas/efectos de los fármacos , Animales , Zinc/química , Zinc/farmacología , Óxido Nítrico/metabolismo , Estructuras Metalorgánicas/farmacología , Estructuras Metalorgánicas/química , Glucosa Oxidasa/farmacología , Glucosa Oxidasa/metabolismo , Diabetes Mellitus Experimental/patología , Microambiente Celular/efectos de los fármacos , Ratones , Hidrogeles/química , Hidrogeles/farmacología , Masculino , Staphylococcus aureus/efectos de los fármacos , Biopelículas/efectos de los fármacos , Escherichia coli/efectos de los fármacos , Antibacterianos/farmacología , Antibacterianos/química , Arginina/farmacología , Arginina/química
17.
J Mech Behav Biomed Mater ; 156: 106581, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38776740

RESUMEN

Patient-specific fabrication of scaffold/implant requires an engineering approach to manufacture the ideal scaffold. Herein, we design and 3D print scaffolds comprised of polyether-ether-ketone (PEEK) and sodium-carboxymethyl cellulose (Na-CMC). The fabricated scaffold was dip coated with Zn and Mn doped bioactive glass nanoparticles (Zn-Mn MBGNs). The synthesized ink exhibit suitable shear-thinning behavior for direct ink write (DIW) 3D printing. The scaffolds were crafted with precision, featuring 85% porosity, 0.3 mm layer height, and 1.5 mm/s printing speed at room temperature. Scanning electron microscopy images reveal a well-defined scaffold with an average pore size of 600 ± 30 µm. The energy dispersive X-ray spectroscopy analysis confirmed a well dispersed/uniform coating of Zn-Mn MBGNs on the PEEK/Na-CMC scaffold. Fourier transform infrared spectroscopy approved the presence of PEEK, CMC, and Zn-Mn MBGNs. The tensile test revealed a Young's modulus of 2.05 GPa. Antibacterial assays demonstrate inhibition zone against Staphylococcus aureus and Escherichia Coli strains. Chick Chorioallantoic Membrane assays also present significant angiogenesis potential, owing to the antigenic nature of Zn-Mn MBGNs. WST-8 cell viability assays depicted cell proliferation, with a 103% viability after 7 days of culture. This study suggests that the PEEK/Na-CMC scaffolds coated with Zn-Mn MBGNs are an excellent candidate for osteoporotic fracture treatment. Thus, the fabricated scaffold can offer multifaceted properties for enhanced patient outcomes in the bone tissue regeneration.


Asunto(s)
Benzofenonas , Carboximetilcelulosa de Sodio , Vidrio , Cetonas , Manganeso , Nanopartículas , Polietilenglicoles , Polímeros , Impresión Tridimensional , Staphylococcus aureus , Andamios del Tejido , Zinc , Porosidad , Benzofenonas/química , Vidrio/química , Cetonas/química , Cetonas/farmacología , Andamios del Tejido/química , Staphylococcus aureus/efectos de los fármacos , Carboximetilcelulosa de Sodio/química , Nanopartículas/química , Zinc/química , Zinc/farmacología , Polímeros/química , Manganeso/química , Polietilenglicoles/química , Antibacterianos/química , Antibacterianos/farmacología , Animales , Escherichia coli/efectos de los fármacos , Ensayo de Materiales , Humanos
18.
J Med Chem ; 67(11): 9686-9708, 2024 Jun 13.
Artículo en Inglés | MEDLINE | ID: mdl-38809692

RESUMEN

High extracellular concentrations of adenosine triphosphate (ATP) in the tumor microenvironment generate adenosine by sequential dephosphorylation of CD39 and CD73, resulting in potent immunosuppression to inhibit T cell and natural killer (NK) cell function. CD73, as the determining enzyme for adenosine production, has been shown to correlate with poor clinical tumor prognosis. Conventional inhibitors as analogues of adenosine 5'-monophosphate (AMP) may have a risk of further metabolism to adenosine analogues. Here, we report a new series of malonic acid non-nucleoside inhibitors coordinating with zinc ions of CD73. Compound 12f was found to be a superior CD73 inhibitor (IC50 = 60 nM) by structural optimization, and its pharmacokinetic properties were investigated. In mouse tumor models, compound 12f showed excellent efficacy and reversal of immunosuppression in combination with chemotherapeutic agents or checkpoint inhibitors, suggesting that it deserves further development as a novel CD73 inhibitor.


Asunto(s)
5'-Nucleotidasa , 5'-Nucleotidasa/antagonistas & inhibidores , 5'-Nucleotidasa/metabolismo , Animales , Humanos , Ratones , Malonatos/farmacología , Malonatos/química , Malonatos/síntesis química , Zinc/química , Zinc/metabolismo , Relación Estructura-Actividad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Inhibidores Enzimáticos/farmacocinética , Proteínas Ligadas a GPI/antagonistas & inhibidores , Proteínas Ligadas a GPI/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/farmacocinética , Descubrimiento de Drogas , Línea Celular Tumoral
19.
ACS Appl Bio Mater ; 7(5): 3316-3329, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38691017

RESUMEN

Basic fibroblast growth factor (bFGF) plays an important role in active wound repair. However, the existing dosage forms in clinical applications are mainly sprays and freeze-dried powders, which are prone to inactivation and cannot achieve a controlled release. In this study, a bioactive wound dressing named bFGF-ATP-Zn/polycaprolactone (PCL) nanodressing with a "core-shell" structure was fabricated by emulsion electrospinning, enabling the sustained release of bFGF. Based on the coordination and electrostatic interactions among bFGF, ATP, and Zn2+, as well as their synergistic effect on promoting wound healing, a bFGF-ATP-Zn ternary combination system was prepared with higher cell proliferation activity and used as the water phase for emulsion electrospinning. The bFGF-ATP-Zn/PCL nanodressing demonstrated improved mechanical properties, sustained release of bFGF, cytocompatibility, and hemocompatibility. It increased the proliferation activity of human dermal fibroblasts (HDFs) and enhanced collagen secretion by 1.39 and 3.45 times, respectively, while reducing the hemolysis rate to 3.13%. The application of the bFGF-ATP-Zn/PCL nanodressing in mouse full-thickness skin defect repair showed its ability to accelerate wound healing and reduce wound scarring within 14 days. These results provide a research basis for the development and application of this bioactive wound dressing product.


Asunto(s)
Adenosina Trifosfato , Materiales Biocompatibles , Proliferación Celular , Emulsiones , Factor 2 de Crecimiento de Fibroblastos , Ensayo de Materiales , Cicatrización de Heridas , Zinc , Cicatrización de Heridas/efectos de los fármacos , Emulsiones/química , Animales , Zinc/química , Zinc/farmacología , Humanos , Factor 2 de Crecimiento de Fibroblastos/química , Factor 2 de Crecimiento de Fibroblastos/farmacología , Ratones , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Proliferación Celular/efectos de los fármacos , Adenosina Trifosfato/metabolismo , Tamaño de la Partícula , Fibroblastos/efectos de los fármacos , Poliésteres/química , Poliésteres/farmacología , Vendajes
20.
Talanta ; 276: 126214, 2024 Aug 15.
Artículo en Inglés | MEDLINE | ID: mdl-38718647

RESUMEN

In this work, miRNA-10b in the glioblastoma (GBM) tumor tissues has been detected by a novel electrochemiluminescence (ECL) biosensor. Firstly, a new kind of bright luminescent Zn2GeO4:Mn NPs were prepared as ECL nanoprobe, which possessed high fluorescence quantum yield and ECL quantum efficiency. Secondly, Ti3C2 MXene hydrogel (MXG) have been developed as the sensing interface. The MXG retained the inherent biocompatibility and mechanical features of hydrogel. Furthermore, the uniform distribution of metallic Ti3C2 MXene in the hydrogel microstructure provided the good conductivity and multiple binding sites for biomolecules. MXene also can promote the separation of the electrons and holes to accelerate the electron-transfer rate and improve ECL efficiency. Due to these synergistic effects, the screen printed electrode was successfully modified with MXG as sensing platform to enhance the ECL intensity of Zn2GeO4:Mn NP, which greatly improved the detection efficiency and facilitated the high-throughput analysis. Finally, the toehold mediated strand displacement (TMSD) strategy was employed with then biosensor to detect miRNA-10b with the range of 10 fM to 1 nM. The limit of detection was 5 fM. This ECL biosensor has been used to analyze miRNA-10b expression in GBM tumor tissues, which possessed the great potential value for clinical diagnosis.


Asunto(s)
Técnicas Biosensibles , Glioblastoma , Hidrogeles , Mediciones Luminiscentes , MicroARNs , Glioblastoma/diagnóstico , Humanos , Técnicas Biosensibles/métodos , MicroARNs/análisis , Hidrogeles/química , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Zinc/química , Nanopartículas del Metal/química , Neoplasias Encefálicas/diagnóstico , Titanio
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