RESUMEN
Metal-organic frameworks (MOFs) are porous materials resulting from the coordination of metal clusters or ions with organic ligands, merging macromolecular and coordination chemistry features. Among these, zeolitic imidazolate framework-8 (ZIF-8) stands out as a widely utilized MOF known for its robust stability in aqueous environments owing to the robust interaction between its constituent zinc ions (Zn2+) and 2-methylimidazole (2-MIM). ZIF-8 readily decomposes under acidic conditions, serving as a promising candidate for pH-responsive drug delivery systems. Moreover, biomimetic materials typically possess good biocompatibility, reducing immune reactions. By mimicking natural structures or surface features within the body, they enhance the targeting of nanoparticles, prolong their circulation time, and increase their bioavailability in vivo. This review explores the latest advancements in biomimetic ZIF-8 nanoparticles for drug delivery, elucidating the primary obstacles and future prospects in utilizing ZIF-8 for drug delivery applications.
Asunto(s)
Materiales Biomiméticos , Sistemas de Liberación de Medicamentos , Imidazoles , Estructuras Metalorgánicas , Nanopartículas , Zeolitas , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacocinética , Humanos , Materiales Biomiméticos/química , Materiales Biomiméticos/farmacocinética , Zeolitas/química , Zeolitas/farmacocinética , Nanopartículas/química , Sistemas de Liberación de Medicamentos/métodos , Imidazoles/química , Imidazoles/farmacocinética , Imidazoles/administración & dosificación , Animales , Zinc/química , Zinc/farmacocinética , Zinc/administración & dosificación , Biomimética/métodos , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Concentración de Iones de HidrógenoRESUMEN
BACKGROUND: Eucalyptus spp. are candidates for phytoremediation in heavy metal (HM)-polluted soils as they can adapt to harsh environments, grow rapidly, and have good economic value. Arbuscular mycorrhizal fungi (AMF) are the most widely distributed plant symbiotic fungi in nature, and they play an important role in promoting the phytoremediation of HM-polluted soils. However, few studies have evaluated the HM detoxification mechanism of E. spp. in symbiosis with AMF, and thus, the molecular mechanism remains unclear. RESULTS: The gene transcription and metabolic pathways of E. grandis were studied with and without inoculation with AMF and at different zinc (Zn) concentrations. Here, we focused on the transcript level of six HM-related gene families (ZNT, COPT/Ctr, YSL, ZIFL and CE). Under high-Zn conditions, thirteen genes (ZNT:2, COPT/Ctr:5, YSL:3, ZIFL:1, CE:2) were upregulated, whereas ten genes (ZNT:3, COPT/Ctr:2, YSL:3, ZIFL:1, CE:1) were downregulated. With AMF symbiosis under high-Zn conditions, ten genes (ZNT:4, COPT/Ctr:2, YSL:3, CE:1) were upregulated, whereas nineteen genes (ZNT:9, COPT/Ctr:2, YSL:3, ZIFL:4, CE:1) were downregulated. Under high-Zn conditions, genes of three potassium-related transporters, six phosphate transporters (PHTs), and two nitrate transporters (NRTs) were upregulated, whereas genes of four potassium-related transporters,four PHTs, and four nitrogen-related transporters were downregulated. With AMF symbiosis under high-Zn conditions, genes of two potassium-related transporters, six ammonium transporters (AMTs) and five PHTs were upregulated, whereas genes of six potassium-related transporters, two AMTs and five PHTs were downregulated. CONCLUSIONS: Our results indicates that AMF increases the resistance of E. grandis to high-Zn stress by improving nutrients uptake and regulating Zn uptake at the gene transcription level. Meanwhile, our findings provide a genome-level resource for the functional assignments of key genes regulated by Zn treatment and AM symbiosis in six HM-associated gene families and macromineral nutrient-related gene families of E. grandis. This may contribute to the elucidation of the molecular mechanisms of the response to Zn stress in E. grandis with AM symbiosis at the aspect of the interaction between HM tolerance and nutrient acquisition.
Asunto(s)
Eucalyptus/genética , Eucalyptus/metabolismo , Micorrizas/fisiología , Proteínas de Plantas/genética , Zinc/metabolismo , Transporte Biológico , Citosol/metabolismo , Eucalyptus/efectos de los fármacos , Regulación de la Expresión Génica de las Plantas , Familia de Multigenes , Proteínas de Plantas/metabolismo , Simbiosis , Zinc/farmacocinéticaRESUMEN
In this paper, we reviewed the role of dairy products in dietary zinc absorption. Dairy products can have a reasonable contribution for dietary zinc intake in Western diets, where dairy consumption is high. However, the co-ingestion of dairy products can also improve zinc absorption from other food products. Such improvements have been observed when dairy products (e.g., milk or yoghurt) were ingested together with food such as rice, tortillas or bread products, all of which are considered to be high-phytate foods with low inherent zinc absorption. For foods low in phytate, the co-ingestion of dairy products did not improve zinc absorption. Improved zinc absorption of zinc from high-phytate foods following co-ingestion with dairy products may be related to the beneficial effects of the citrate and phosphopeptides present in dairy products. Considering that the main dietary zinc sources in areas in the world where zinc deficiency is most prevalent are typically high in phytate, the inclusion of dairy products in meals may be a viable dietary strategy to improve zinc absorption.
Asunto(s)
Productos Lácteos , Ingestión de Alimentos/fisiología , Zinc/farmacocinética , Disponibilidad Biológica , Ácido Cítrico/farmacocinética , Humanos , Absorción Intestinal/fisiología , Comidas/fisiología , Fosfopéptidos/farmacocinética , Ácido Fítico/farmacocinéticaRESUMEN
The increasing incidence of trauma in medicine brings with it new demands on the materials used for the surgical treatment of bone fractures. Titanium, its alloys, and steel are used worldwide in the treatment of skeletal injuries. These metallic materials, although inert, are often removed after the injured bone has healed. The second-stage procedure-the removal of the plates and screws-can overwhelm patients and overload healthcare systems. The development of suitable absorbable metallic materials would help us to overcome these issues. In this experimental study, we analyzed an extruded Zn-0.8Mg-0.2Sr (wt.%) alloy on a rabbit model. From this alloy we developed screws which were implanted into the rabbit tibia. After 120, 240, and 360 days, we tested the toxicity at the site of implantation and also within the vital organs: the liver, kidneys, and brain. The results were compared with a control group, implanted with a Ti-based screw and sacrificed after 360 days. The samples were analyzed using X-ray, micro-CT, and a scanning electron microscope. Chemical analysis revealed only small concentrations of zinc, strontium, and magnesium in the liver, kidneys, and brain. Histologically, the alloy was verified to possess very good biocompatibility after 360 days, without any signs of toxicity at the site of implantation. We did not observe raised levels of Sr, Zn, or Mg in any of the vital organs when compared with the Ti group at 360 days. The material was found to slowly degrade in vivo, forming solid corrosion products on its surface.
Asunto(s)
Implantes Absorbibles , Aleaciones , Ensayo de Materiales , Tibia/metabolismo , Fracturas de la Tibia , Aleaciones/química , Aleaciones/farmacocinética , Aleaciones/farmacología , Animales , Humanos , Magnesio/química , Magnesio/farmacocinética , Magnesio/farmacología , Conejos , Estroncio/química , Estroncio/farmacocinética , Estroncio/farmacología , Tibia/patología , Fracturas de la Tibia/metabolismo , Fracturas de la Tibia/cirugía , Zinc/química , Zinc/farmacocinética , Zinc/farmacologíaRESUMEN
Nano-sized zinc oxide (nano-ZnO) affects lipid deposition, but its absorption patterns and mechanisms affecting lipid metabolism are still unclear. This study was undertaken to investigate the molecular mechanism of nano-ZnO absorption and its effects on lipid metabolism in the intestinal tissues of a widely distributed freshwater teleost yellow catfish Pelteobagrus fulvidraco. We found that 100 mg/kg dietary nano-ZnO (H-Zn group) significantly increased intestinal Zn contents. The zip6 and zip10 mRNA expression levels were higher in the H-Zn group than those in the control (0 mg/kg nano-ZnO), and zip4 mRNA abundances were higher in the control than those in the L-Zn (50 mg/kg nano-ZnO) and H-Zn groups. Eps15, dynamin1, dynamin2, caveolin1, and caveolin2 mRNA expression levels tended to reduce with dietary nano-ZnO addition. Dietary nano-ZnO increased triglyceride (TG) content and the activities of the lipogenic enzymes glucose 6-phosphate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), and isocitrate dehydrogenase (ICDH), upregulated the mRNA abundances of lipogenic genes 6pgd, fatty acid synthase (fas), and sterol regulatory element binding protein 1 (srebp1), and reduced the mRNA expression of farnesoid X receptor (fxr) and small heterodimer partner (shp). The SHP protein level in the H-Zn group was lower than that in the control and the L-Zn group markedly. Our in vitro study indicated that the intestinal epithelial cells (IECs) absorbed nano-ZnO via endocytosis, and nano-Zn-induced TG deposition and lipogenesis were partially attributable to the endocytosis of nano-ZnO in IECs. Mechanistically, nano-ZnO-induced TG deposition was closely related to the metal responsive transcription factor 1 (MTF-1)-SHP pathway. Thus, for the first time, we found that the lipogenesis effects of nano-ZnO probably depended on the key gene shp, which is potentially regulated by MTF1 and/or FXR. This novel signaling pathway of MTF-1 through SHP may be relevant to explain the toxic effects and lipotoxicity ascribed to dietary nano-ZnO addition.
Asunto(s)
Endocitosis/fisiología , Mucosa Intestinal , Lípidos/toxicidad , Lipogénesis/efectos de los fármacos , Óxido de Zinc/farmacocinética , Alimentación Animal/toxicidad , Animales , Bagres , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Dieta , Absorción Intestinal/efectos de los fármacos , Mucosa Intestinal/efectos de los fármacos , Mucosa Intestinal/metabolismo , Intestinos/efectos de los fármacos , Intestinos/metabolismo , Intestinos/patología , Lípidos/farmacocinética , Redes y Vías Metabólicas/genética , Nanopartículas del Metal/toxicidad , Regulación hacia Arriba/efectos de los fármacos , Zinc/metabolismo , Zinc/farmacocinética , Óxido de Zinc/química , Óxido de Zinc/toxicidadRESUMEN
Microgel affords a porous and swollen microstructure for the establishment of pulmonary delivery system with sustained released properties. Here, we report a microgel (with the diameter around 4 µm) prepared with a precipitation method, synthesized by coordinating Zn2+ to the Schiff base cross-linked carboxymethyl chitosan and glycol split hyaluronate. The microgel has shown well swollen and pH sensitive behaviors, high safety and biocompatibility in vitro. Besides, the biomaterial could escape from macrophage phagocytosis, a key factor contribute to quick drug clearance in the lung after co-incubated with RAW 264.7 cells. In consist with this, the bovine serum albumin loaded in the microgel showed sustained release behavior in 24 h in vitro; meanwhile, the drug had a retention time up to 36 h in the lung and followed by clearance in ICR mice through pulmonary administration. Thus, our microgel platform provides a promising candidate for pulmonary drug delivery systems with controlled release rate.
Asunto(s)
Quitosano/análogos & derivados , Portadores de Fármacos , Ácido Hialurónico , Pulmón/metabolismo , Microgeles/química , Zinc , Animales , Quitosano/química , Quitosano/farmacocinética , Quitosano/farmacología , Portadores de Fármacos/síntesis química , Portadores de Fármacos/química , Portadores de Fármacos/farmacocinética , Portadores de Fármacos/farmacología , Ácido Hialurónico/química , Ácido Hialurónico/farmacocinética , Ácido Hialurónico/farmacología , Ratones , Ratones Endogámicos ICR , Células 3T3 NIH , Células RAW 264.7 , Zinc/química , Zinc/farmacocinética , Zinc/farmacologíaRESUMEN
The transmetalation reaction between zinc dithiocarbamates functionalized with organic groups and the cation fac-[99mTc(H2O)3(CO)3]+ has been studied as a new strategy to bind biomolecules to this radionuclide for preparing radiopharmaceuticals with high molar activity. All complexes were obtained in high yields by heating at moderate temperatures and without subsequent purification. The chemical identity was ascertained by HPLC comparison with the homologous rhenium complexes. Stability studies in cysteine solution and serum have shown a good stability of the coordination set fac-[99mTc(CO)3(SS)(P)]. Preliminary biological studies of the radiocomplex functionalized with D-(+)-glucosamine with carcinoma cells have been performed.
Asunto(s)
Complejos de Coordinación/química , Radiofármacos/química , Tecnecio/farmacocinética , Zinc/química , Animales , Complejos de Coordinación/administración & dosificación , Complejos de Coordinación/farmacocinética , Ratones , Radiofármacos/administración & dosificación , Radiofármacos/farmacocinética , Tomografía Computarizada por Tomografía Computarizada de Emisión de Fotón Único , Tecnecio/administración & dosificación , Tecnecio/química , Distribución Tisular , Zinc/administración & dosificación , Zinc/farmacocinéticaRESUMEN
SCOPE: Manganese (Mn) and zinc (Zn) are not only essential trace elements, but also potential exogenous risk factors for various diseases. Since the disturbed homeostasis of single metals can result in detrimental health effects, concerns have emerged regarding the consequences of excessive exposures to multiple metals, either via nutritional supplementation or parenteral nutrition. This study focuses on Mn-Zn-interactions in the nematode Caenorhabditis elegans (C. elegans) model, taking into account aspects related to aging and age-dependent neurodegeneration. METHODS AND RESULTS: Chronic co-exposure of C. elegans to Mn and Zn increases metal uptake, exceeding levels of single metal exposures. Supplementation with Mn and/or Zn also leads to an age-dependent increase in metal content, a decline in overall mRNA expression, and metal co-supplementation induced expression of target genes involved in Mn and Zn homeostasis, in particular metallothionein 1 (mtl-1). Studies in transgenic worms reveal that mtl-1 played a prominent role in mediating age- and diet-dependent alterations in metal homeostasis. Metal dyshomeostasis is further induced in parkin-deficient nematodes (Parkinson's disease (PD) model), but this did not accelerate the age-dependent dopaminergic neurodegeneration. CONCLUSIONS: A nutritive overdose of Mn and Zn can alter interactions between essential metals in an aging organism, and metallothionein 1 acts as a potential protective modulator in regulating homeostasis.
Asunto(s)
Envejecimiento/efectos de los fármacos , Proteínas de Caenorhabditis elegans/metabolismo , Caenorhabditis elegans/efectos de los fármacos , Manganeso/efectos adversos , Metalotioneína/metabolismo , Zinc/efectos adversos , Envejecimiento/fisiología , Animales , Animales Modificados Genéticamente , Disponibilidad Biológica , Caenorhabditis elegans/fisiología , Proteínas de Caenorhabditis elegans/genética , Neuronas Dopaminérgicas/efectos de los fármacos , Neuronas Dopaminérgicas/patología , Sobredosis de Droga/metabolismo , Homeostasis/efectos de los fármacos , Homeostasis/genética , Manganeso/administración & dosificación , Manganeso/farmacocinética , Metalotioneína/genética , Mutación , Pruebas de Toxicidad Crónica , Ubiquitina-Proteína Ligasas/genética , Zinc/administración & dosificación , Zinc/farmacocinéticaRESUMEN
This work presents new findings on the nutritional quality of recently introduced biofortified and non-biofortified cowpea cultivars as well as some common beans. ICP-MS was used for the measurements. Biofortified cowpea cultivars showed high levels of Fe and Zn, greater than 60 and 40 mg kg-1 dry weight, respectively. The in vitro digestion protocol enabled simultaneous evaluation of bioaccessibility and bioavailability. Fe levels in cowpea cultivars were ca. 2.5-fold higher than in common beans. Cowpea seeds also had higher Zn levels, reaching 50.1% bioaccessibility and 44.2% bioavailability. Cooking improved the availability of micronutrients in bean seeds. The cooked biofortified Aracê cowpea showed a high Zn bioavailability above 60%. Consumption of 50 g of Aracê would contribute 27% and 48% of the Fe and Zn DRI for 1-3-year-old children. The new cowpea cultivars biofortified are a potential vehicle for improving the Fe and Zn status in groups in which the micronutrient deficiency is prevalent.
Asunto(s)
Hierro/farmacocinética , Semillas/química , Vigna/química , Zinc/farmacocinética , Disponibilidad Biológica , Preescolar , Culinaria , Humanos , LactanteRESUMEN
Tiller number is one of the most important agronomic traits that determine rice (Oryza sativa) yield. Active growth of tiller bud (TB) requires high amount of mineral nutrients; however, the mechanism underlying the distribution of mineral nutrients to TB with low transpiration is unknown. Here, we found that the distribution of Zn to TB is mediated by OsZIP4, one of the ZIP (ZRT, IRT-like protein) family members. The expression of OsZIP4 was highly detected in TB and nodes, and was induced by Zn deficiency. Immunostaining analysis revealed that OsZIP4 was mainly expressed in phloem of diffuse vascular bundles in the nodes and the axillary meristem. The mutation of OsZIP4 did not affect the total Zn uptake, but altered Zn distribution; less Zn was delivered to TB and new leaf, but more Zn was retained in the basal stems at the vegetative growth stage. Bioimaging analysis showed that the mutant aberrantly accumulated Zn in enlarged and transit vascular bundles of the basal node, whereas in wild-type high accumulation of Zn was observed in the meristem part. At the reproductive stage, mutation of OsZIP4 resulted in delayed panicle development, which is associated with decreased Zn distribution to the panicles. Collectively, OsZIP4 is involved in transporting Zn to the phloem of diffuse vascular bundles in the nodes for subsequent distribution to TBs and other developing tissues. It also plays a role in transporting Zn to meristem cells in the TBs.
Asunto(s)
Proteínas de Transporte de Catión/metabolismo , Oryza/metabolismo , Proteínas de Plantas/metabolismo , Zinc/metabolismo , Transporte Biológico , Proteínas de Transporte de Catión/genética , Regulación de la Expresión Génica de las Plantas , Mutación , Oryza/crecimiento & desarrollo , Fenotipo , Floema/metabolismo , Hojas de la Planta/metabolismo , Proteínas de Plantas/genética , Plantas Modificadas Genéticamente , Plantones/genética , Plantones/crecimiento & desarrollo , Distribución Tisular , Zinc/farmacocinética , Isótopos de Zinc/farmacocinéticaRESUMEN
To improve our understanding of underlying toxic mechanisms, it is important to evaluate differences in effects that a variety of metals exert at concentrations representing the same toxic level to the organism. Therefore, the main goal of the present study was to compare the effects of waterborne copper (Cu(II)), zinc (Zn(II)) and cadmium (Cd (II)) on a freshwater fish, the common carp (Cyprinus carpio), at concentrations being 0%, 25%, 50% and 100% of the 96 h LC50 (the concentration which is lethal to 50% of the population in 96 h). All the exposures were performed for a period of 1 week at 20°C. Our results show a rapid increase in the amount of copper and cadmium accumulated in the gills, while zinc only started to increase by the end of the experiment. All three metal ions increased metallothionein gene expression in both gills and liver. However, clear adverse effects were mainly observed for the Cu exposed group. Cu caused a decrease in Na level in gill tissue; it altered the expression of genes involved in ionoregulation such as Na+ /K+ -ATPase and H+ -ATPase as well as the expression of oxidative stress-related genes, such as catalase, glutathione reductase and glutathione S-transferase. Zinc and cadmium exposure did not alter the ion levels in the gills. In addition, no obvious effect of oxidative stress was observed, except for a transient increase in glutathione reductase at the highest cadmium concentration.
Asunto(s)
Cadmio/toxicidad , Carpas , Cobre/toxicidad , Zinc/toxicidad , Animales , Cadmio/farmacocinética , Cobre/farmacocinética , Branquias/metabolismo , Dosificación Letal Mediana , Hígado/efectos de los fármacos , Hígado/metabolismo , Metalotioneína/biosíntesis , Metalotioneína/genética , Estrés Oxidativo/efectos de los fármacos , ATPasas de Translocación de Protón/metabolismo , Sodio/metabolismo , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Contaminantes Químicos del Agua/toxicidad , Zinc/farmacocinéticaRESUMEN
Zinc is an essential trace element and participates in a variety of biological processes. ZnT (SLC30) family members are generally responsible for zinc efflux across the membrane regulating zinc homeostasis. In mammals, the only predominantly plasma membrane resident ZnT has been reported to be ZnT1, and ZnT1-/ZnT1- mice die at the embryonic stage. In Drosophila, knock down of ZnT1 homologue (dZnT1//ZnT63C/CG17723) results in growth arrest under zinc-limiting conditions. To investigate the essentiality of dZnT1 for zinc homeostasis, as well as its role in dietary zinc uptake especially under normal physiological conditions, we generated dZnT1 mutants by the CRISPER/Cas9 method. Homozygous mutant dZnT1 is lethal, with substantial zinc accumulation in the iron cell region, posterior midgut as well as gastric caeca. Expression of human ZnT1 (hZnT1), in the whole body or in the entire midgut, fully rescued the dZnT1 mutant lethality, whereas tissue-specific expression of hZnT1 in the iron cell region and posterior midgut partially rescued the developmental defect of the dZnT1 mutant. Supplementation of zinc together with clioquinol or hinokitiol conferred a limited but observable rescue upon dZnT1 loss. Our work demonstrated the absolute requirement of dZnT1 in Drosophila survival and indicated that the most essential role of dZnT1 is in the gut.
Asunto(s)
Proteínas de Transporte de Catión/metabolismo , Proteínas de Drosophila/metabolismo , Drosophila melanogaster/metabolismo , Zinc/metabolismo , Animales , Animales Modificados Genéticamente , Sistemas CRISPR-Cas , Proteínas de Transporte de Catión/antagonistas & inhibidores , Proteínas de Transporte de Catión/genética , Dieta , Proteínas de Drosophila/antagonistas & inhibidores , Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crecimiento & desarrollo , Femenino , Técnicas de Silenciamiento del Gen , Genes de Insecto , Humanos , Absorción Intestinal/genética , Absorción Intestinal/fisiología , Masculino , Mutación , Filogenia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Oligoelementos/administración & dosificación , Oligoelementos/metabolismo , Oligoelementos/farmacocinética , Zinc/administración & dosificación , Zinc/farmacocinéticaRESUMEN
In urban set up, increasing combustion and processing activities have contaminated the air with toxic heavy metals which are generally enriched on atmospheric particulate matter. Vegetation around urban area act as a sink where such metal enriched particles generally deposit on the foliar surfaces, however, role of vegetation in uptake of metals adhered on the atmospheric particulate matter is yet not explored properly and is important to study to evaluate their role as bio-remediator. The undertaken work examines the foliar surface of Morus alba for its potential to deposit and accumulate atmospheric heavy metals. Further, to understand foliar uptake mechanism and translocation of atmospheric metal enriched on particulate matter a simulated experiment was conducted by labeling the known particle size (45 µm and 120 µm) with radio labeled 65Zn, applied on the tagged leaf with two particle loads, 25â¯mg and 50â¯mg. The study showed that owing to its rough foliar surface with trichomes and grooves, Morus alba efficiently trap heavy metal enriched particles and was capable of accumulating metals from particulate matter into different plant parts. It was recorded that 65Zn adhered on different size particles was taken up by tagged leaf of mulberry and majorly translocated to the lower stem and roots. It was also inferred from the study that both particle size and particle load significantly affect the foliar uptake and translocation of atmospheric heavy metal. The study focuses on the fact that urban avenue trees are capable of taking up atmospheric heavy metals and can play a crucial role in improving air quality.
Asunto(s)
Contaminantes Atmosféricos/metabolismo , Morus/metabolismo , Material Particulado/farmacocinética , Zinc/farmacocinética , Contaminantes Atmosféricos/farmacocinética , Contaminación del Aire , Biodegradación Ambiental , Tamaño de la Partícula , Material Particulado/análisis , Material Particulado/química , Hojas de la Planta/metabolismo , Raíces de Plantas/metabolismo , Trazadores Radiactivos , Radioisótopos de Zinc/farmacocinéticaRESUMEN
Disulfiram (DSF) is an FDA-approved anti-alcoholic drug that has recently proven to be effective in cancer treatment. However, the short half-life in the bloodstream and the metal ion-dependent antitumor activity significantly limited the further application of DSF in the clinical field. To this end, we constructed a silk fibroin modified disulfiram/zinc oxide nanocomposites (SF/DSF@ZnO) to solubilize and stabilize DSF, and, more importantly, achieve pH triggered Zn2+ release and subsequent synergistic antitumor activity. The prepared SF/DSF@ZnO nanocomposites were spherical and had a high drug loading. Triggered by the lysosomal pH, SF/DSF@ZnO could induce the rapid release of Zn2+ under the acidic conditions and caused nanoparticulate disassembly along with DSF release. In vitro experiments showed that cytotoxicity of DSF could be enhanced by the presence of Zn2+, and further amplified when encapsulated into SF/DSF@ZnO nanocomposites. It was confirmed that the significantly amplified cytotoxicity of SF/DSF@ZnO was resulted from pH-triggered Zn2+ release, inhibited cell migration, and increased ROS production. In vivo study showed that SF/DSF@ZnO nanocomposites significantly increased the tumor accumulation and prolonged the retention time. In vivo antitumor experiments in the xenograft model showed that SF/DSF@ZnO exerted the highest tumor-inhibition rate among all the drug treatments. Therefore, this exquisite study established silk fibroin-modified disulfiram/zinc oxide nanocomposites, SF/DSF@ZnO, where ZnO not only acted as a delivery carrier but also served as a metal ion reservoir to achieve synergistic antitumor efficacy. The established DSF nanoformulation displayed excellent therapeutic potential in future cancer treatment.
Asunto(s)
Antineoplásicos/farmacocinética , Nanocompuestos/administración & dosificación , Neoplasias/tratamiento farmacológico , Zinc/farmacocinética , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/química , Bombyx/química , Cationes Bivalentes/farmacocinética , Línea Celular Tumoral/trasplante , Modelos Animales de Enfermedad , Disulfiram/administración & dosificación , Disulfiram/química , Disulfiram/farmacocinética , Composición de Medicamentos/métodos , Liberación de Fármacos , Ensayos de Selección de Medicamentos Antitumorales , Sinergismo Farmacológico , Femenino , Fibroínas/química , Semivida , Humanos , Concentración de Iones de Hidrógeno , Ratones , Neoplasias/patología , Óxido de Zinc/administración & dosificación , Óxido de Zinc/química , Óxido de Zinc/farmacocinéticaRESUMEN
A greenhouse pot experiment was conducted to evaluate the effect of biochar on the growth and uptake of Pb and Zn by tomato plants (Solanum lycopersicum, L.) cultivated in two highly contaminated Kosovo soils, A and B. Plants were cultivated in the biochar amended and unamended soils. As expected, the biochar addition to the two polluted soils has contributed to significantly improve the crop yields, in terms of both fresh and dry weight. Further, results indicated that the effect of biochar on metal mobility is closely related, besides its properties, to soil's native characteristics. In fact, the addition of biochar to soil B had also beneficial effects on the uptake of both metals, halving in some cases the values of the biological accumulation and transfer coefficients, while it did not show the same efficacy on soil A.
Asunto(s)
Carbón Orgánico , Plomo/farmacocinética , Contaminantes del Suelo/farmacocinética , Solanum lycopersicum/efectos de los fármacos , Zinc/farmacocinética , Kosovo , Plomo/análisis , Solanum lycopersicum/crecimiento & desarrollo , Solanum lycopersicum/metabolismo , Contaminantes del Suelo/análisis , Zinc/análisisRESUMEN
Trace elements such as selenium (Se) and zinc (Zn) are essential elements in the human body, while cadmium (Cd) has no physiological function. A high proportion of people consume dietary supplements to enhance the performance of the body or alter the nutrient contents within the body. Therefore, this study was conducted to evaluate the interaction effects of several popular dietary supplements on the bioaccessibility of Se, Zn and Cd in rice with the hope of identifying dietary supplements that can increase rice Se and Zn bioaccessibility but decrease rice Cd bioaccessibility. The results from in vitro gastrointestinal simulation tests showed that the bioaccessibility of these elements in rice was in the order of Cd (52.07%) > Zn (36.63%) > Se (10.19%) during the gastric phase and Zn (26.82%) > Cd (18.72%) > Se (14.70%) during the intestinal phase. The bioaccessibility of Se during the intestinal phase was greater than that during the gastric phase, and the bioaccessibility of Zn and Cd were the opposite. The bioaccessibility of Se significantly increased in response to vitamin C (VC), vitamin E (VE), vitamin B6 (VB6) and vitamin B9 (VB9), especially VC, which also increased the bioaccessibility of Zn and decreased that of Cd. Procyanidins (OPC), methionine (Met) and coenzyme Q10 (Q10) significantly reduced the bioaccessibility of Se. These results suggest that the reasonable use of dietary supplements can effectively regulate the in vivo contents of trace elements, which provide valuable information for developing health interventions to address problems for specific people, especially selenium-deficient people.
Asunto(s)
Cadmio , Suplementos Dietéticos , Oryza , Selenio , Zinc , Disponibilidad Biológica , Cadmio/farmacocinética , Humanos , Oryza/química , Selenio/farmacocinética , Zinc/farmacocinéticaRESUMEN
The role of metal speciation on metal bioavailability, bio-reactivity and toxicity at the fish intestine is poorly understood. To investigate these processes, we used an in vitro model of the rainbow trout (Oncorhynchus mykiss) intestine, the RTgutGC cell line. Cells were exposed to two essential metals (copper and zinc) and two non-essential metals (cadmium and silver) in a medium of well-defined composition, which allowed the determination of metal speciation in solution. Concentrations resulting in a 50% cell viability reduction (EC50) were measured using a viability assay based on two endpoints: metabolic activity and membrane integrity. Metal bioavailability and bio-reactivity was studied at non-toxic (300 nM all metals) and toxic (EC10; Ag-0.6, Cu-0.9, Cd-3, and Zn-9 µM) concentrations. Bioavailability (i.e. intracellular metal accumulation) was determined by ICP-MS, while bio-reactivity (i.e. induction of a metal specific transcriptional response) was determined by measuring the mRNA levels of a known biomarker of metal exposure (i.e. metallothionein) and of copper and zinc transporters (i.e. ATP7A and ZnT1). Dominant metal species in the exposure medium were Zn2+, CuHPO4, CdCl+, and AgCl2- respectively for Zn, Cu, Cd, and Ag. The EC50s showed the metal toxicity hierarchy: Ag > Cu > Cd > Zn. In RTgutGC cells, essential metal homeostasis was tightly regulated while non-essential metals accumulated more readily. Non-essential metals were also more bio-reactive inducing higher MT and ZnT1 mRNA levels. Taken together these findings indicate that metal toxicity in RTgutGC cannot solely be explained by extracellular metal speciation but requires the evaluation of metal bioavailability and bio-reactivity.
Asunto(s)
Cadmio/toxicidad , Cobre/toxicidad , Oncorhynchus mykiss/fisiología , Plata/toxicidad , Zinc/toxicidad , Animales , Disponibilidad Biológica , Cadmio/farmacocinética , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Células Cultivadas , Cobre/farmacocinética , ATPasas Transportadoras de Cobre/genética , ATPasas Transportadoras de Cobre/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Metalotioneína/genética , Metalotioneína/metabolismo , Plata/metabolismo , Zinc/farmacocinéticaRESUMEN
Two new Schiff base ligands (TE and TF) were prepared from conjugation of testosterone with 4-(4-ethylphenyl)-3-thiosemicarbazide and 4-(4-fluorophenyl)-3-thiosemicarbazide, respectively. Their nickel (NE and NF) and zinc (ZE and ZF) complexes were reported. X-ray crystallography revealed a distorted square planar geometry was adopted by NE. The compounds demonstrated excellent selectivity towards the colorectal carcinoma cell line HCT 116 despite their weak preferences towards the prostate cancer cell lines (PC-3 and LNCaP). Against HCT 116, all these compounds were able to arrest cell cycle at G0/G1 phase and induce apoptosis via mitochondria-dependent (TE, NE, and TF) and extrinsic apoptotic pathway (ZE, NF, and ZF). Moreover, only ZE was able to act as topoisomease I poison and halt its enzymatic reactions although all compounds presented excellent affinity towards DNA.
Asunto(s)
Neoplasias Colorrectales , Complejos de Coordinación , Níquel , Testosterona , Tiosemicarbazonas , Zinc , Muerte Celular/efectos de los fármacos , Neoplasias Colorrectales/tratamiento farmacológico , Neoplasias Colorrectales/metabolismo , Neoplasias Colorrectales/patología , Complejos de Coordinación/síntesis química , Complejos de Coordinación/química , Complejos de Coordinación/farmacocinética , Complejos de Coordinación/farmacología , Células HCT116 , Humanos , Níquel/química , Níquel/farmacocinética , Níquel/farmacología , Testosterona/química , Testosterona/farmacocinética , Testosterona/farmacología , Tiosemicarbazonas/química , Tiosemicarbazonas/farmacocinética , Tiosemicarbazonas/farmacología , Zinc/química , Zinc/farmacocinética , Zinc/farmacologíaRESUMEN
PURPOSE: Zinc (Zn), an essential trace element in the body, has stable chemical properties, excellent osteogenic ability and moderate immunomodulatory property. In the present study, a Zn-incorporated TiO2 nanotube (TNT) was fabricated on titanium (Ti) implant material. We aimed to evaluate the influence of nano-scale topography and Zn on behaviors of murine RAW 264.7 macrophages. Moreover, the effects of Zn-incorporated TNT surface-regulated macrophages on the behaviors and osteogenic differentiation of murine MC3T3-E1 osteoblasts were also investigated. METHODS: TNT coatings were firstly fabricated on a pure Ti surface using anodic oxidation, and then nano-scale Zn particles were incorporated onto TNTs by the hydrothermal method. Surface topography, chemical composition, roughness, hydrophilicity, Zn release pattern and protein adsorption ability of the Zn-incorporated TiO2 nanotube surface were characterized by scanning electron microscopy (SEM), X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS), surface profiler, contact angle test, Zn release test and protein adsorption test. The cell behaviors and both pro-inflammatory (M1) and pro-regenerative (M2) marker gene and protein levels in macrophages cultured on Zn-incorporated TNTs surfaces with different TNT diameters were detected. The supernatants of macrophages were extracted and preserved as conditioned medium (CM). Furthermore, the behaviors and osteogenic properties of osteoblasts cultured in CM on various surfaces were evaluated. RESULTS: The release profile of Zn on Zn-incorporated TNT surfaces revealed a controlled release pattern. Macrophages cultured on Zn-incorporated TNT surfaces displayed enhanced gene and protein expression of M2 markers, and M1 markers were moderately inhibited, compared with the LPS group (the inflammation model). When cultured in CM, osteoblasts cultured on Zn-incorporated TNTs showed strengthened cell proliferation, adhesion, osteogenesis-related gene expression, alkaline phosphatase activity and extracellular mineralization, compared with their TNT counterparts and the Ti group. CONCLUSION: This study suggests that the application of Zn-incorporated TNT surfaces may establish an osteogenic microenvironment and accelerate bone formation. It provided a promising strategy of Ti surface modification for a better applicable prospect.
Asunto(s)
Factores Inmunológicos/farmacología , Macrófagos/efectos de los fármacos , Nanotubos , Osteoblastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Zinc/farmacocinética , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Medios de Cultivo Condicionados/farmacología , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos/inmunología , Ratones , Microscopía Electrónica de Rastreo , Nanotubos/química , Osteoblastos/citología , Osteogénesis/genética , Espectroscopía de Fotoelectrones , Células RAW 264.7 , Propiedades de Superficie , Titanio/química , Difracción de Rayos X , Zinc/químicaRESUMEN
Sodium sulfide (Na2S) is usually used as an amendment in industrial sewage treatment. To evaluate the effects of Na2S on the growth of Robinia pseudoacacia (black locust), heavy metal immobilization, and soil microbial activity, the R. pseudoacacia biomass and nutrient content and the soil heavy metal bioavailability, enzyme activity, and arbuscular mycorrhizal (AM) fungal community were measured by a single-factor pot experiment. The Pb-Zn-contaminated soil was collected from a Pb-Zn mine that had been remediated by R. pseudoacacia for five years. Three pollution levels (unpolluted, mildly polluted, and severely polluted) were evaluated by the pollution load index. Na2S application increased the shoot biomass under severe and mild contamination. In soil, Na2S application decreased the bioavailable Pb and Zn contents under severe and mild contamination, which resulted in a decrease in the Pb and Zn content in R. pseudoacacia. However, Na2S application did not affect the total Pb content per plant and enhanced the total Zn content per plant because of the higher biomass of the plants under Na2S application. Increased phosphatase activity and increased available phosphorous content may promote the uptake of phosphorus in R. pseudoacacia. Moreover, Na2S application is beneficial to the diversity of AM fungi under mild and severe pollution. Overall, Na2S application has great potential for enhancing soil heavy metal immobilization, enhancing soil microbial activity, and improving the growth of R. pseudoacacia in polluted soils. Therefore, Na2S is suitable for use in Pb-Zn remediation to ameliorate environmental heavy metal pollution.