RESUMEN
The threat of climate change, which includes shifts in salinity and temperature, has generated a global concern for marine organisms. These changes directly impact them and may alter their susceptibility to contaminants, such as terbium (Tb), found in electronic waste. This study assessed how decreased and increased salinity, as well as increased temperature, modulates Tb effects in Mytilus galloprovincialis mussels. After an exposure period of 28 days, Tb bioaccumulation and biochemical changes were evaluated. Results indicated no significant modulation of salinity and temperature on Tb accumulation, suggesting detoxification mechanisms and adaptations. Further analysis showed that Tb exposure alone caused antioxidant inhibition and neurotoxicity. When exposed to decreased salinity, these Tb-exposed organisms activated defense mechanisms, a response indicative of osmotic stress. Moreover, increased salinity also led to increased oxidative stress and metabolic activity in Tb-exposed organisms. Additionally, Tb-exposed organisms responded to elevated temperature with altered biochemical activities indicative of damage and stress response. Such responses suggested that Tb effects were masked by osmotic and heat stress. This study provides valuable insights into the interactions between temperature, salinity, and contaminants such as Tb, impacting marine organisms. Understanding these relationships is crucial for mitigating climate change and electronic waste effects on marine ecosystems.
Asunto(s)
Mytilus , Contaminantes Químicos del Agua , Animales , Temperatura , Terbio/metabolismo , Terbio/farmacología , Salinidad , Ecosistema , Contaminantes Químicos del Agua/análisis , Estrés Oxidativo , Mytilus/metabolismoRESUMEN
Recovery of rare earth elements (REEs) from wastewater with Bacillus subtilis (B. subtilis) during culture is promising due to its environmental benefits. However, the effects of REEs in the culture media on B. subtilis are poorly understood. This study aims to investigate the effects of the terbium (Tb(III)), a typical rare earth element, on the cell growth, sporulation, and spore properties of B. subtilis. Tb(III) can suppress bacterial growth while enhancing spore tolerance to wet heat. Spore germination and content of dipicolinic acid (DPA) were promoted at low concentrations of Tb(III) while inhibited at a high level, but an inverse effect on initial sporulation appeared. Scanning electron microscope and energy dispersive spectrometer detection indicated that Tb(III) complexed cells or spores and certain media components simultaneously. The germination results of the spores after elution revealed that Tb(III) attached to the spore surface was a key effector of spore germination. In conclusion, Tb(III) directly or indirectly regulated both the nutrient status of the media and certain metabolic events, which in turn affected most of the properties of B. subtilis. Compared to the coat-deficient strain, the wild-type strain grew faster and was more tolerant to Tb(III), DPA, and wet heat, which in turn implied that it was more suitable for the recovery of REEs during cultivation. These findings provide fundamental insights for the recovery of rare earths during the culture process using microorganisms.
Asunto(s)
Bacillus subtilis , Terbio , Bacillus subtilis/metabolismo , Terbio/metabolismo , Terbio/farmacología , Esporas Bacterianas , Calor , Proteínas Bacterianas/metabolismoRESUMEN
Myocardial hypoxia reperfusion (H/R) injury is the paradoxical exacerbation of myocardial damage, caused by the sudden restoration of blood flow to hypoxia affected myocardium. It is a critical contributor of acute myocardial infarction, which can lead to cardiac failure. Despite the current pharmacological advancements, clinical translation of cardioprotective therapies have proven challenging. As a result, researchers are looking for alternative approaches to counter the disease. In this regard, nanotechnology, with its versatile applications in biology and medicine, can confer broad prospects for treatment of myocardial H/R injury. Herein, we attempted to explore whether a well-established pro-angiogenic nanoparticle, terbium hydroxide nanorods (THNR) can ameliorate myocardial H/R injury. For this study, in vitro H/R-injury model was established in rat cardiomyocytes (H9c2 cells). Our investigations demonstrated that THNR enhance cardiomyocyte survival against H/R-induced cell death. This pro-survival effect of THNR is associated with reduction of oxidative stress, lipid peroxidation, calcium overload, restoration of cytoskeletal integrity and mitochondrial membrane potential as well as augmentation of cellular anti-oxidant enzymes such as glutathione-s-transferase (GST) and superoxide dismutase (SOD) to counter H/R injury. Molecular analysis revealed that the above observations are traceable to the predominant activation of PI3K-AKT-mTOR and ERK-MEK signalling pathways by THNR. Concurrently, THNR also exhibit apoptosis inhibitory effects mainly by suppression of pro-apoptotic proteins like Cytochrome C, Caspase 3, Bax and p53 with simultaneous restoration of anti-apoptotic protein, Bcl-2 and Survivin. Thus, considering the above attributes, we firmly believe that THNR have the potential to be developed as an alternative approach for amelioration of H/R injury in cardiomyocytes.
Asunto(s)
Daño por Reperfusión Miocárdica , Nanotubos , Animales , Ratas , Miocitos Cardíacos/metabolismo , Terbio/metabolismo , Terbio/farmacología , Terbio/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Línea Celular , Hipoxia/metabolismo , Daño por Reperfusión Miocárdica/tratamiento farmacológico , Daño por Reperfusión Miocárdica/metabolismoRESUMEN
The increasing demand for electric and electronic equipment has led to a rise in potentially hazardous electronic waste, including rare-earth elements (REEs), such as terbium (Tb), which have been already detected in aquatic systems. This study investigated the biochemical effects of anthropogenic Tb on mussels over a 28-day period. The mussels were exposed to different concentrations of Tb (0, 5, 10, 20, 40 µg/L), and biomarkers related to metabolism, oxidative stress, cellular damage, and neurotoxicity were evaluated. Bioaccumulation of Tb in the mussels' tissue increased with exposure concentrations, but the bioconcentration factor remained similar between treatments. Exposure to Tb enhanced glycogen consumption and decreased metabolic capacity which could be seen as a physiological adaptation to limit Tb accumulation. Antioxidant defenses and glutathione S-transferases showed a more complex dose-response, with enzymatic responses increasing until 10 µg/L but then returning to control levels at 20 µg/L. At 40 µg/L, enzymatic responses were also enhanced but to a lower extent than at 10 µg/L. The presence of Tb had clearly an inhibitory effect on biotransformation enzymes such as carboxylesterases in a dose-dependent manner. Likely, thanks to biochemical and physiological adaptations, no cellular damage or neurotoxicity was observed in any treatments, confirming the mussels' ability to tolerate Tb exposure. Nevertheless, prolonged exposure to these concentrations could lead to harmful consequences when facing other environmental stressors, such as misallocating energy resources for growth, reproduction, and defense mechanisms.
Asunto(s)
Mytilus , Contaminantes Químicos del Agua , Animales , Mytilus/metabolismo , Terbio/metabolismo , Terbio/farmacología , Contaminantes Químicos del Agua/análisis , Estrés Oxidativo , Antioxidantes/metabolismo , Biomarcadores/metabolismoRESUMEN
X-ray-triggered scintillators (Sc) and photosensitizers (Ps) have been developed for X-ray-induced photodynamic therapy (X-PDT) to selectively destruct deep tissue tumors with a low X-ray dose. This study designed terbium (Tb)-rose bengal (RB) coordination nanocrystals (T-RBNs) by a solvothermal treatment, aiming to reduce photon energy dissipation between Tb3+ and RB and thus increase the reactive oxygen species (ROS) production efficiency. T-RBNs synthesized at a molar ratio of [RB]/[Tb] = 3 exhibited a size of 6.8 ± 1.2 nm with a crystalline property. Fourier transform infrared analyses of T-RBNs indicated successful coordination between RB and Tb3+. T-RBNs generated singlet oxygen (1O2) and hydroxyl radicals (â¢OH) under low-dose X-ray irradiation (0.5 Gy) via scintillating and radiosensitizing pathways. T-RBNs produced â¼8-fold higher ROS amounts than bare RB and â¼3.6-fold higher ROS amounts than inorganic nanoparticle-based controls. T-RBNs did not exhibit severe cytotoxicity up to 2 mg/mL concentration in cultured luciferase-expressing murine epithelial breast cancer (4T1-luc) cells. Furthermore, T-RBNs were efficiently internalized into cultured 4T1-luc cells and induced DNA double strand damage, as evidenced by an immunofluorescence staining assay with phosphorylated γ-H2AX. Ultimately, under 0.5 Gy X-ray irradiation, T-RBNs induced >70% 4T1-luc cell death via simultaneous apoptosis/necrosis pathways. Overall, T-RBNs provided a promising Sc/Ps platform under low-dose X-PDT for advanced cancer therapy.
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Neoplasias de la Mama , Nanopartículas , Fotoquimioterapia , Humanos , Animales , Ratones , Femenino , Rosa Bengala/farmacología , Rosa Bengala/química , Terbio/farmacología , Terbio/química , Terbio/uso terapéutico , Especies Reactivas de Oxígeno/metabolismo , Rayos X , Nanopartículas/uso terapéutico , Nanopartículas/químicaRESUMEN
Compact RNA structural motifs control many aspects of gene expression, but we lack methods for finding these structures in the vast expanse of multi-kilobase RNAs. To adopt specific 3-D shapes, many RNA modules must compress their RNA backbones together, bringing negatively charged phosphates into close proximity. This is often accomplished by recruiting multivalent cations (usually Mg2+), which stabilize these sites and neutralize regions of local negative charge. Coordinated lanthanide ions, such as terbium (III) (Tb3+), can also be recruited to these sites, where they induce efficient RNA cleavage, thereby revealing compact RNA 3-D modules. Until now, Tb3+ cleavage sites were monitored via low-throughput biochemical methods only applicable to small RNAs. Here we present Tb-seq, a high-throughput sequencing method for detecting compact tertiary structures in large RNAs. Tb-seq detects sharp backbone turns found in RNA tertiary structures and RNP interfaces, providing a way to scan transcriptomes for stable structural modules and potential riboregulatory motifs.
Asunto(s)
ARN , Terbio , Conformación de Ácido Nucleico , ARN/metabolismo , Terbio/metabolismo , Terbio/farmacología , Motivos de Nucleótidos , CationesRESUMEN
Soils contaminated with rare earth elements (REEs) can damage agriculture by causing physiological disorders in plants which are evaluated as the main connection of the human food chain. A biphasic dose response with excitatory responses to low concentrations and inhibitory/harmful responses to high concentrations has been defined as hormesis. However, not much is clear about the ecological effects and potential risks of REEs to plants. For this purpose, here we showed the impacts of different concentrations of nano terbium (Tb) applications (5-10-25-50-100-250-500 mg L-1) on the accumulation of endogeneous certain ions and hormones, chlorophyll fluoresence, photochemical reaction capacity and antioxidant activity in duckweed (Lemna minor). Tb concentrations less than 100 mg L-1 increased the contents of nitrogen (N), phosphate (P), potassium (K+), calcium (Ca2+), magnesium (Mg2+), manganese (Mn2+) and iron (Fe2+). Chlorophyll fluorescence (Fv/Fm and Fv/Fo) was suppressed under 250-500 mg L-1 Tb. In addition, Tb toxicity affected the trapped energy adversely by the active reaction center of photosystem II (PSII) and led to accumulation of inactive reaction centers, thus lowering the detected level of electron transport from photosystem II (PSII) to photosystem I (PSI). On the other hand, 5-100 mg L-1 Tb enhanced the activities of superoxide dismutase (SOD), catalase (CAT), peroxidase (POX), NADPH oxidase (NOX), ascorbate peroxidase (APX), glutathione reductase (GR), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR) and glutathione S-transferase (GST). Tb (5-50 mg L-1) supported the maintenance of cellular redox status by promoting antioxidant pathways involved in the ascorbate-glutathione (AsA-GSH) cycle. In addition to the antioxidant system, the contents of some hormones such as indole-3-acetic acid (IAA), gibberellic acid (GA), cytokinin (CK) and salicylic acid (SA) were also induced in the presence of 5-100 mg L-1 Tb. In addition, the levels of hydrogen peroxide (H2O2) and lipid peroxidation (TBARS) were controlled through ascorbate (AsA) regeneration and effective hormonal modulation in L. minor. However, this induction in the antioxidant system and phytohormone contents could not be resumed after applications higher than 250 mg L-1 Tb. TBARS and H2O2, which indicate the level of lipid peroxidation, increased. The results in this study showed that Tb at appropriate concentrations has great potential to confer tolerance of duckweed by supporting the antioxidant system, protecting the biochemical reactions of photosystems and improving hormonal regulation.
Asunto(s)
Antioxidantes , Reguladores del Crecimiento de las Plantas , Humanos , Antioxidantes/metabolismo , Reguladores del Crecimiento de las Plantas/farmacología , Complejo de Proteína del Fotosistema II/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico , Terbio/farmacología , Peróxido de Hidrógeno/metabolismo , Hormesis , Fotoquímica , Clorofila/metabolismo , Hormonas/farmacología , Glutatión/metabolismo , Estrés OxidativoRESUMEN
This work explores in depth the simultaneous self-assembly and mineralization of type I collagen by a base-acid neutralization technique to prepare biomimetic collagen-apatite fibrils with varying mineralization extent and doped with luminescent bactericidal Tb3+ ions. Two variants of the method are tested: base-acid titration, a solution of Ca(OH)2 is added dropwise to a stirred solution containing type I collagen dispersed in H3 PO4 ; and direct mixing, the Ca(OH)2 solution is added by fast dripping onto the acidic solution. Only the direct mixing variant yielded an effective control of calcium phosphate polymorphism. Luminescence spectroscopy reveals the long luminescence lifetime and high relative luminescence intensity of the Tb3+ -doped materials, while two-photon confocal fluorescence microscopy shows the characteristic green fluorescence light when using excitation wavelength of 458 nm, which is not harmful to bone tissue. Cytotoxicity/viability tests reveal that direct mixing samples show higher cell proliferation than titration samples. Additionally, osteogenic differentiation essays show that all mineralized fibrils promote the osteogenic differentiation, but the effect is more pronounced when using samples prepared by direct mixing, and more notably when using the Tb3+ -doped mineralized fibrils. Based on these findings it is concluded that the new nanocomposite is an ideal candidate for bone regenerative therapy.
Asunto(s)
Apatitas/farmacología , Calcificación Fisiológica , Diferenciación Celular , Colágeno Tipo I/farmacología , Luminiscencia , Células Madre Mesenquimatosas/citología , Osteogénesis , Terbio/farmacología , Calcificación Fisiológica/efectos de los fármacos , Muerte Celular/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Colágeno Tipo I/ultraestructura , Humanos , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Espectroscopía Infrarroja por Transformada de Fourier , Difracción de Rayos XRESUMEN
A novel folic acid functionalized terbium-doped dendritic fibrous nanoparticle (Tb@KCC-1-NH2 -FA) with high surface area was synthesized using a novel hydrothermal protocol. In the present work, we report the fluorescent Tb-doted nanomaterial with emission wavelength at 497 nm which confirms the formation of Tb@KCC-1-NH2 -FA. Synthesized nanoparticles were investigated through transmission electron microscope, field emission scanning electron Microscopy, Fourier transform infrared spectra, Brunauer-Emmett-Teller, energy dispersive X-ray, Zeta potential and particle size distribution values and AFM (Atomic force microscopy) techniques. Specially, our desired nanomaterial which has FA moieties on the surface of Tb@KCC-1-NH2-FA where interact with folate receptor (FR) which there is on the surface of the various cancer cells. For this purpose, fluorescence microscopy images were used to prove the uptake of FA based nanomaterial with FR-positive MDA breast cancer and HT 29 colon cancer cells. Also HEK 293 normal cells as FR-negative cells verified the specificity of our desired nanomaterial toward the FR-positive cells. The cytotoxicity survey of Tb@KCC-1-NH2 -FA was examined by MTT assays against MDA breast cancer, HT 29 colon cancer and HEK 293 Normal cell lines which confirmed their biocompatible nature with any significant cytotoxic effects even for concentration higher than 900 µg/mL which could be used as a non-toxic catalyst or carrier in biological ambient. Hence, Tb@KCC-1-NH2 -FA were synthesized using green and hydrothermal method; the process was simple with good productivity and desired nanocomposite was non-toxic.
Asunto(s)
Técnicas Biosensibles , Ácido Fólico/farmacología , Nanopartículas/química , Terbio/farmacología , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Neoplasias de la Mama/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Neoplasias del Colon/tratamiento farmacológico , Femenino , Receptor 1 de Folato/genética , Ácido Fólico/química , Células HEK293 , Células HT29 , Humanos , Microscopía Fluorescente , Dióxido de Silicio/química , Dióxido de Silicio/farmacología , Terbio/químicaRESUMEN
Iron is a class of essential elements involved in the metabolic process in all living organisms. However, excessive or deficient iron levels from normal ranges can lead to severe diseases. In this study, a fluorescent Tb(III)-based metal-organic framework with the chemical formula of [Tb(cptpy)3]n (1, Hcptpy = 4'-(4-carboxyphenyl)-2,2':6',2''-terpyridine) has been prepared under the hydrothermal condition successfully and its properties were determined by X-ray single-crystal diffraction, IR spectra, powder X-ray diffraction (PXRD) thermogravimetric analyses (TGA) and elemental analyses. Luminescent and sensing properties of complex 1 were examined closely, and it is shown that the Tb-MOF has the distinct ability to efficiently and selectively detect the Fe3+ ion and acetone. Furthermore, the RT-PCR was employed to determine the effect of compound on the ß-receptor and mmp-9 genes expression in cardiomyocytes. And the ELISA assay was used for the measurement of D-Dimer in the serum after compound treatment.
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Compuestos Férricos/análisis , Colorantes Fluorescentes/farmacología , Metaloproteinasa 9 de la Matriz/metabolismo , Estructuras Metalorgánicas/farmacología , Receptores Adrenérgicos beta/metabolismo , Terbio/farmacología , Dimerización , Colorantes Fluorescentes/química , Humanos , Iones/análisis , Metaloproteinasa 9 de la Matriz/genética , Estructuras Metalorgánicas/química , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Receptores Adrenérgicos beta/genética , Terbio/químicaRESUMEN
A luminescent coordination polymer based on Tb(III) has been synthesized with the tripodal carboxylic acid ligand containing N,O codonors (H2PBA = 5-[4-pyridin-3-yl-benzoylamino]-isophthalic acid) as ligand under solvothermal conditions. The chemical formula of this polymer is {[Tb2(PBA)3(H2O)3]·DMF·3H2O}n (1). Complex 1 has good sensitivity and selectivity to picric acid (PA). At 0-30 µmol/L, 1's quenching constant is 4.5 × 104 L/mol. In the biological function study, the motor function of spinal cord-injured animals after different treatments was evaluated using the blood-brain barrier (BBB) method. The trka expression level on the neural stem cells after treatment was measured to reveal the underlying mechanism.
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Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Modelos Animales de Enfermedad , Picratos/análisis , Receptor trkA/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Animales , Complejos de Coordinación/síntesis química , Luminiscencia , Células-Madre Neurales/metabolismo , Polímeros/química , Polímeros/farmacología , Ratas , Ratas Sprague-Dawley , Receptor trkA/genética , Traumatismos de la Médula Espinal/metabolismo , Terbio/química , Terbio/farmacología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
BACKGROUND: Nanomaterials that exhibit intrinsic enzyme-like characteristics have shown great promise as potential antibacterial agents. However, many of them exhibit inefficient antibacterial activity and biosafety problems that limit their usefulness. The development of new nanomaterials with good biocompatibility and rapid bactericidal effects is therefore highly desirable. Here, we show a new type of terbium oxide nanoparticles (Tb4O7 NPs) with intrinsic oxidase-like activity for in vitro and in vivo antibacterial application. RESULTS: We find that Tb4O7 NPs can quickly oxidize a series of organic substrates in the absence of hydrogen peroxide. The oxidase-like capacity of Tb4O7 NPs allows these NPs to consume antioxidant biomolecules and generate reactive oxygen species to disable bacteria in vitro. Moreover, the in vivo experiments showed that Tb4O7 NPs are efficacious in wound-healing and are protective of normal tissues. CONCLUSIONS: Our results reveal that Tb4O7 NPs have intrinsic oxidase-like activity and show effective antibacterial ability both in vitro and in vivo. These findings demonstrate that Tb4O7 NPs are effective antibacterial agents and may have a potential application in wound healing.
Asunto(s)
Antibacterianos/química , Escherichia coli , Nanopartículas del Metal/química , Óxidos/química , Oxidorreductasas/química , Staphylococcus aureus , Terbio/química , Cicatrización de Heridas , Animales , Antibacterianos/farmacología , Materiales Biocompatibles/química , Supervivencia Celular , Escherichia coli/efectos de los fármacos , Hemólisis , Células Endoteliales de la Vena Umbilical Humana , Humanos , Ratones Endogámicos BALB C , Óxidos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Staphylococcus aureus/efectos de los fármacos , Terbio/farmacologíaRESUMEN
The adoptive transfer of immune effector cells, such as CD8+ killer αß T cells, γδ T cells, NK (natural killer) cells, and genetically-modified T cells, has been receiving increasing attention. It is essential to determine cellular cytotoxicity so as to monitor the function and quality of ex vivo-expanded immune effector cells before infusion. The most common method is the [51Cr]-sodium chromate release assay. It is, however, preferable to avoid the use of radioactive materials in clinical laboratories. In order to establish a non-radioactive alternative to the standard radioactive assay, we previously synthesized a chelate-forming prodrug (BM-HT) and demonstrated that a combination of BM-HT and europium (Eu3+) was useful to determine NK cell-mediated cytotoxicity. In the present study, we examined whether or not this improved assay system could be used to determine the cellular cytotoxicity exhibited by Vγ2Vδ2+ γδ T cells. In addition, we compared Eu3+ and terbium (Tb3+) in the measurement of cellular cytotoxicity. Our assay system using BM-HT could be used successfully for the analysis of both γδ T cell receptor (TCR)- and CD16-mediated cytotoxicity. When the intensity of fluorescence was compared between Eu3+ and Tb3+, Tb3+ chelate was more sensitive than Eu3+ chelate, suggesting that the detection system using Tb3+ is superior to Eu3+ when tumor cells are not efficiently labeled with BM-HT. The method established herein is expected to promote the development of novel adoptive cell therapies for cancer.
Asunto(s)
Citotoxicidad Inmunológica/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/análisis , Linfocitos T CD8-positivos/efectos de los fármacos , Linfocitos T CD8-positivos/inmunología , Línea Celular Tumoral , Citotoxicidad Inmunológica/efectos de los fármacos , Europio/farmacología , Humanos , Células Asesinas Naturales/efectos de los fármacos , Células Asesinas Naturales/inmunología , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Terbio/farmacologíaRESUMEN
An antibacterial hydrogel shows promise for treating infected chronic wounds, but it is commonly difficult to disrupt bacterial biofilms, and incorporation of antibiotics in the hydrogel may lead to antibiotic resistance. To overcome these limitations, reduced graphene oxide (rGO) and rare earth terbium ions (Tb3+) were incorporated in a poly(vinyl alcohol) (PVA)-alginate (SA) hydrogel. Compared with the PVA-SA hydrogel, the PVA-SA hydrogel containing Tb3+ (PVA-SA-Tb) reduced the number of Gram-positive Staphylococcus aureus and Gram-negative Pseudomonas aeruginosa in biofilms by 1.5 and 1 orders of magnitude, respectively. Further incorporation of rGO that did not exhibit antibacterial properties alone in the PVA-SA-Tb hydrogel (PVA-SA-rGO-Tb) raised the killing efficacy of Staphylococcus aureus and Pseudomonas aeruginosa in biofilms by 1.5 and 2 orders of magnitude, respectively. We found that such a synergistic antibacterial effect between Tb3+ and rGO resulted from the increased loading and release of Tb3+ owing to rGO-induced loosening of the hydrogel network. The in vivo assay further shows that the PVA-SA-rGO-Tb hydrogel can effectively promote the healing of infected wounds in diabetic rats. These results demonstrated that the PVA-SA-rGO-Tb hydrogel which contains no antibiotics shows promise for treating infected chronic wounds.
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Biopelículas/efectos de los fármacos , Hidrogeles/farmacología , Infecciones Estafilocócicas/tratamiento farmacológico , Cicatrización de Heridas/efectos de los fármacos , Infección de Heridas/tratamiento farmacológico , Alginatos/farmacología , Animales , Antibacterianos/farmacología , Diabetes Mellitus Experimental , Masculino , Alcohol Polivinílico/farmacología , Pseudomonas aeruginosa/efectos de los fármacos , Ratas , Ratas Sprague-Dawley , Staphylococcus aureus/efectos de los fármacos , Terbio/farmacologíaRESUMEN
PURPOSE: Radionuclide therapy is increasingly seen as a promising option to target minimal residual disease. Copper-67, scandium-47 and terbium-161 have a medium-energy ß(-) emission which is similar to that of lutetium-177, but offer the advantage of having diagnostic partner isotopes suitable for pretreatment imaging. The aim of this study was to compare the efficacy of (67)Cu, (47)Sc and (161)Tb to irradiate small tumors. METHODS: The absorbed dose deriving from a homogeneous distribution of (67)Cu, (47)Sc or (161)Tb in water-density spheres was calculated with the Monte Carlo code CELLDOSE. The diameters of the spheres ranged from 5 mm to 10 µm, thus simulating micrometastases or single tumor cells. All electron emissions, including ß(-) spectra, Auger and conversion electrons were taken into account. Because these radionuclides differ in electron energy per decay, the simulations were run assuming that 1 MeV was released per µm(3), which would result in a dose of 160 Gy if totally absorbed. RESULTS: The absorbed dose was similar for the three radionuclides in the 5-mm sphere (146-149 Gy), but decreased differently in smaller spheres. In particular, (161)Tb delivered higher doses compared to the other radionuclides. For instance, in the 100-µm sphere, the absorbed dose was 24.1 Gy with (67)Cu, 14.8 Gy with (47)Sc and 44.5 Gy with (161)Tb. Auger and conversion electrons accounted for 71% of (161)Tb dose. The largest dose differences were found in cell-sized spheres. In the 10-µm sphere, the dose delivered by (161)Tb was 4.1 times higher than that from (67)Cu and 8.1 times that from (47)Sc. CONCLUSION: (161)Tb can effectively irradiate small tumors thanks to its decay spectrum that combines medium-energy ß(-) emission and low-energy conversion and Auger electrons. Therefore (161)Tb might be a better candidate than (67)Cu and (47)Sc for treating minimal residual disease in a clinical setting.
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Neoplasia Residual/radioterapia , Neoplasias/radioterapia , Radioisótopos/farmacología , Simulación por Computador , Radioisótopos de Cobre/farmacología , Escandio/farmacología , Terbio/farmacologíaRESUMEN
The synthesis of inner transition metal nanoparticles via an ecofriendly route is quite difficult. This study, for the first time, reports synthesis of terbium oxide nanoparticles using fungus, Fusarium oxysporum. The biocompatible terbium oxide nanoparticles (Tb2O3 NPs) were synthesized by incubating Tb4O7 with the biomass of fungus F. oxysporum. Multiple physical characterization techniques, such as UV-visible and photoluminescence spectroscopy, TEM, SAED, and zeta-potential were used to confirm the synthesis, purity, optical and surface characteristics, crystallinity, size, shape, distribution, and stability of the nanoemulsion of Tb2O3 NPs. The Tb2O3 NPs were found to inhibit the propagation of MG-63 and Saos-2 cell-lines (IC50 value of 0.102µg/mL) and remained non-toxic up to a concentration of 0.373µg/mL toward primary osteoblasts. Cell viability decreased in a concentration-dependent manner upon exposure to 10nm Tb2O3 NPs in the concentration range 0.023-0.373µg/mL. Cell toxicity was evaluated by observing changes in cell morphology, cell viability, oxidative stress parameters, and FACS analysis. Morphological examinations of cells revealed cell shrinkage, nuclear condensation, and formation of apoptotic bodies. The level of ROS within the cells-an indicator of oxidative stress was significantly increased. The induction of apoptosis at concentrations ≤IC50 was corroborated by 4',6-diamidino-2-phenylindole dihydrochloride (DAPI) staining (DNA damage and nuclear fragmentation). Flow-cytometric studies indicated that the response was dose dependent with a threshold effect.
Asunto(s)
Neoplasias Óseas/tratamiento farmacológico , Nanopartículas , Osteosarcoma/tratamiento farmacológico , Óxidos/farmacología , Terbio/farmacología , Neoplasias Óseas/metabolismo , Neoplasias Óseas/patología , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Fusarium/química , Humanos , Nanopartículas/química , Nanopartículas/ultraestructura , Nanotecnología , Osteosarcoma/metabolismo , Osteosarcoma/patología , Estrés Oxidativo/efectos de los fármacos , Óxidos/química , Especies Reactivas de Oxígeno/metabolismo , Terbio/químicaRESUMEN
Agarose gel electrophoresis, absorption, fluorescence, viscosity, and circular dichroism (CD) have been used in exploring the interaction of terbium(III) complex, [Tb(bpy)2Cl3(OH2)] where bipy is 2,2'-bipyridine, with Fish salmon DNA. Agarose gel electrophoresis assay, along with absorption and fluorescence studies, reveal interaction between the corresponding complex and FS-DNA. Also, the binding constants (Kb) and the Stern-Volmer quenching constants (Ksv) of Tb(III) complex with FS-DNA were determined. The calculated thermodynamic parameters suggested that the binding of mentioned complex to FS-DNA was driven mainly by hydrophobic interactions. A comparative study of this complex with respect to the effect of iodide-induced quenching, ionic strength effect, and ethidium bromide exclusion assay reflects binding of explicit to the FS-DNA primarily in a groove fashion. CD and viscosity data also support the groove binding mode. Furthermore, Tb(III) complex have been simultaneously screened for their antibacterial and antifungal activities.
Asunto(s)
2,2'-Dipiridil/farmacología , ADN/metabolismo , Terbio/farmacología , Absorción de Radiación , Animales , Antiinfecciosos/farmacología , Bacterias/efectos de los fármacos , Sitios de Unión , Dicroismo Circular , División del ADN , Electroforesis en Gel de Agar , Etidio/química , Etidio/metabolismo , Hongos/efectos de los fármacos , Cinética , Ligandos , Luminiscencia , Pruebas de Sensibilidad Microbiana , Concentración Osmolar , Salmón , Espectrometría de Fluorescencia , Temperatura , ViscosidadRESUMEN
The ternary terbium(III) complexes [Tb(HDAP)3â biq], [Tb(HDAP)3â dmph] and [Tb(HDAP)3â bathophen] were prepared by using methoxy substituted hydroxyketone ligand HDAP (2-hydroxy-4,6-dimethoxyacetophenone) and an ancillary ligand 2,2-biquinoline or 5,6-dimethyl-1,10-phenanthroline or bathophenanthroline respectively. The ligand and synthesized complexes were characterised based on elemental analysis, FT-IR and (1)H NMR. Thermal behaviour of the synthesized complexes illustrates the general decomposition patterns of the complexes by thermogravimetric analysis. Photophysical properties such as excitation spectra, emission spectra and luminescence decay curves of the complexes were investigated in detail. The main green emitting peak at 548nm can be attributed to (5)D4â(7)F5 of Tb(3+) ion. Thus, these complexes might be used to make a bright green light-emitting diode for display purpose. In addition the in vitro antibacterial activities of HDAP and its Tb(III) complexes against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and antifungal activities against Candida albicans and Aspergillus niger are reported. The Tb(3+) complexes were found to be more potent antimicrobial agent as compared to the ligand. Among all these complexes, [Tb(HDAP)3â bathophen] exhibited excellent antimicrobial activity which proves its potential usefulness as an antimicrobial agent. Furthermore, in vitro antioxidant activity tests were carried out by using DPPH method which indicates that the complexes have considerable antioxidant activity when compared with the standard ascorbic acid.
Asunto(s)
Acetofenonas/química , Antiinfecciosos/química , Complejos de Coordinación/química , Fenantrolinas/química , Quinolinas/química , Terbio/química , Acetofenonas/síntesis química , Acetofenonas/farmacología , Antibacterianos/síntesis química , Antibacterianos/química , Antibacterianos/farmacología , Antiinfecciosos/síntesis química , Antiinfecciosos/farmacología , Antifúngicos/síntesis química , Antifúngicos/química , Antifúngicos/farmacología , Antioxidantes/síntesis química , Antioxidantes/química , Antioxidantes/farmacología , Bacterias/efectos de los fármacos , Infecciones Bacterianas/tratamiento farmacológico , Complejos de Coordinación/síntesis química , Complejos de Coordinación/farmacología , Hongos/efectos de los fármacos , Humanos , Ligandos , Micosis/tratamiento farmacológico , Nitrógeno/química , Nitrógeno/farmacología , Fenantrolinas/síntesis química , Fenantrolinas/farmacología , Quinolinas/síntesis química , Quinolinas/farmacología , Terbio/farmacologíaRESUMEN
Herein, we report the fabrication of a multifunctional nanoprobe based on highly monodispersed, optically and magnetically active, biocompatible, PEI-functionalized, highly crystalline ß-NaYF4:Gd(3+)/Tb(3+) nanorods as an excellent multi-modal optical/magnetic imaging tool and a pH-triggered intracellular drug delivery nanovehicle. The static and dynamic photoluminescence spectroscopy showed the presence of sharp emission peaks, with long lifetimes (â¼3.5 milliseconds), suitable for optical imaging. The static magnetic susceptibility measurements at room temperature showed a strong paramagnetic signal (χâ¼ 3.8 × 10(-5) emu g(-1) Oe(-1)). The nuclear magnetic resonance (NMR) measurements showed fair T1 relaxivity (r1 = 1.14 s(-1) mM(-1)) and magnetic resonance imaging gave enhanced T1-weighted MRI images with increased concentrations of ß-NaYF4:Gd(3+)/Tb(3+) making them suitable for simultaneous magnetic resonance imaging. In addition, an anticancer drug, doxorubicin (DOX) was conjugated to the amine-functionalized ß-NaYF4:Gd(3+)/Tb(3+) nanorods via pH-sensitive hydrazone bond linkages enabling them as a pH-triggered, site-specific drug delivery nanovehicle for DOX release inside tumor cells. A comparison between in vitro DOX release studies undertaken in normal physiological (pH 7.4) and acidic (pH 5.0) environments showed an enhanced DOX dissociation (â¼80%) at pH 5.0. The multifunctional material was also applied as an optical probe to confirm the conjugation of DOX and to monitor DOX release via a fluorescence resonance energy transfer (FRET) mechanism. The DOX-conjugated ß-NaYF4:Gd(3+)/Tb(3+) nanorods exhibited a cytotoxic effect on MCF-7 breast cancer cells and their uptake by MCF-7 cells was demonstrated using confocal laser scanning microscopy and flow cytometry. The comparative cellular uptakes of free DOX and DOX-conjugated ß-NaYF4:Gd(3+)/Tb(3+) nanorods were studied in tumor microenvironment conditions (pH 6.5) using confocal imaging, which showed an increased uptake of DOX-conjugated ß-NaYF4:Gd(3+)/Tb(3+) nanorods. Thus, DOX-conjugated ß-NaYF4:Gd(3+)/Tb(3+) nanorods combining pH-triggered drug delivery, efficient luminescence and paramagnetic properties are promising for a potential multifunctional platform for cancer therapy, biodetection, and optical and magnetic resonance imaging.
Asunto(s)
Doxorrubicina , Fluoruros , Gadolinio , Mediciones Luminiscentes/métodos , Imagen por Resonancia Magnética/métodos , Imagen Óptica/métodos , Terbio , Itrio , Animales , Preparaciones de Acción Retardada/química , Preparaciones de Acción Retardada/farmacología , Doxorrubicina/química , Doxorrubicina/farmacología , Femenino , Fluoruros/química , Fluoruros/farmacología , Gadolinio/química , Gadolinio/farmacología , Humanos , Concentración de Iones de Hidrógeno , Células MCF-7 , Ratones , Células 3T3 NIH , Terbio/química , Terbio/farmacología , Itrio/química , Itrio/farmacologíaRESUMEN
The europium(III) and terbium(III) complexes, namely [Eu(dpq)(DMF)2(NO3)3] (1), [Eu(dppz)2(NO3)3] (2), [Tb(dpq)(DMF)2Cl3] (3), and [Tb(dppz)(DMF)2Cl3] (4), where dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 1 and 3), dipyrido[3,2-a:2',3'-c]phenazine (dppz in 2 and 4) and N,N'-dimethylformamide (DMF) have been isolated, characterized from their physicochemical data, luminescence studies and their interaction with DNA, serum albumin protein and photo-induced DNA cleavage activity are studied. The X-ray crystal structures of complexes 1-4 show discrete mononuclear Ln(3+)-based structures. The Eu(3+) in [Eu(dpq)(DMF)2(NO3)3] (1) and [Eu(dppz)2(NO3)3] (2) as [Eu(dppz)2(NO3)3]·dppz (2a) adopts a ten-coordinated bicapped dodecahedron structure with a bidentate N,N-donor dpq ligand, two DMF and three NO3(-) anions in 1 and two bidentate N,N-donor dppz ligands and three NO3(-) anions in 2. Complexes 3 and 4 show a seven-coordinated mono-capped octahedron structure where Tb(3+) contains bidentate dpq/dppz ligands, two DMF and three Cl(-) anions. The complexes are highly luminescent in nature indicating efficient photo-excited energy transfer from the dpq/dppz antenna to Ln(3+) to generate long-lived emissive excited states for characteristic f â f transitions. The time-resolved luminescence spectra of complexes 1-4 show typical narrow emission bands attributed to the (5)D0 â (7)F(J) and (5)D4 â (7)F(J) f-f transitions of Eu(3+) and Tb(3+) ions respectively. The number of inner-sphere water molecules (q) was determined from luminescence lifetime measurements in H2O and D2O confirming ligand-exchange reactions with water in solution. The complexes display significant binding propensity to the CT-DNA giving binding constant values in the range of 1.0 × 10(4)-6.1 × 10(4) M(-1) in the order 2, 4 (dppz) > 1, 3 (dpq). DNA binding data suggest DNA groove binding with the partial intercalation nature of the complexes. All the complexes also show binding propensity (K(BSA) â¼ 10(5) M(-1)) to the bovine serum albumin (BSA) protein. The intensity of the time-gated luminescence spectral bands enhances significantly with the increasing DNA concentration in aqueous buffer medium due to displacement of bound water upon interaction with DNA, thus reducing non-radiative quenching through the O-H oscillator. Complexes 1-4 efficiently cleave supercoiled (SC) ds-DNA to its nicked circular (NC) form on exposure to UV-A light of 365 nm via formation of singlet oxygen ((1)O2) and hydroxyl radicals (HOË) as the reactive oxygen species at micromolar concentrations under physiological conditions.