RESUMEN
This study aims to determine the effects of copper, copper oxide nanoparticles, aluminium, and aluminium oxide nanoparticles on the growth rate and expression of ACT-1, CDPK, LIP, NFC, P5CR, P5CS, GR, and SiZIP1 genes in five days old seedling of Setaria italica ssp. maxima, cultivated in hydroponic culture. Depending on their concentration (ranging from 0.1 to 1.8 mg L-1), all tested substances had both stimulating and inhibiting effects on the growth rate of the seedlings. Copper and copper oxide-NPs had generally a stimulating effect whereas aluminium and aluminium oxide-NPs at first had a positive effect but in higher concentrations they inhibited the growth. Treating the seedlings with 0.4 mg L-1 of each tested toxicant was mostly stimulating to the expression of the genes and reduced the differences between the transcript levels of the coleoptiles and roots. Increasing concentrations of the tested substances had both stimulating and inhibiting effects on the expression levels of the genes. The highest expression levels were usually noted at concentrations between 0.4 and 1.0 mg/L of each metal and metal nanoparticle, except for SiZIP1, which had the highest transcript amount at 1.6 mg L-1 of Cu2+ and at 0.1-0.8 mg L-1 of CuO-NPs, and LIP and GR from the seedling treated with Al2O3-NPs at concentrations of 0.1 and 1.6 mg L-1, respectively.
Asunto(s)
Aluminio , Cobre , Regulación de la Expresión Génica de las Plantas , Nanopartículas del Metal , Plantones , Setaria (Planta) , Cobre/farmacología , Plantones/efectos de los fármacos , Plantones/crecimiento & desarrollo , Plantones/genética , Plantones/metabolismo , Aluminio/toxicidad , Aluminio/farmacología , Nanopartículas del Metal/química , Regulación de la Expresión Génica de las Plantas/efectos de los fármacos , Setaria (Planta)/genética , Setaria (Planta)/efectos de los fármacos , Setaria (Planta)/crecimiento & desarrollo , Setaria (Planta)/metabolismo , Óxido de Aluminio/farmacología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Raíces de Plantas/metabolismo , Raíces de Plantas/genéticaRESUMEN
As the main challenge of dental healthcare, oral infectious diseases are highly associated with the colonization of pathogenic microbes. However, current antibacterial treatments in the field of stomatology still lack a facile, safe, and universal approach. Herein, we report the controllable synthesis of copper aluminum-layered double hydroxides (CuAl-LDHs) with high Fenton-like catalytic activity, which can be utilized in the treatment of oral infectious diseases with negligible side effects. Our strategy can efficiently avoid the unwanted doping of other divalent metal ions in the synthesis of Cu-contained LDHs and result in the formation of binary CuAl-LDHs with high crystallinity and purity. Evidenced by experimental and theoretical results, CuAl-LDHs exhibit excellent catalytic ability toward the ·OH generation in the presence of H2O2 and hold strong affinity toward bacteria, endowing them with great catalytic sterilization against both Gram-positive and Gram-negative bacteria. As expected, these CuAl-LDHs provide outstanding treatments for mucosal infection and periodontitis by promoting wound healing and remodeling of the periodontal microenvironment. Moreover, toxicity investigation demonstrates the overall safety. Accordingly, the current study not only provides a convenient and economic strategy for treating oral infectious diseases but also extends the development of novel LDH-based Fenton or Fenton-like antibacterial reagents for further biomedical applications.
Asunto(s)
Aluminio , Antibacterianos , Cobre , Peróxido de Hidrógeno , Cobre/química , Cobre/farmacología , Catálisis , Antibacterianos/farmacología , Antibacterianos/química , Antibacterianos/síntesis química , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/farmacología , Aluminio/química , Aluminio/farmacología , Hidróxidos/química , Hidróxidos/farmacología , Pruebas de Sensibilidad Microbiana , Animales , Hierro/química , Hierro/farmacología , Salud Bucal , Ratones , Humanos , Bacterias Gramnegativas/efectos de los fármacosRESUMEN
Cell senescence is defined as irreversible cell cycle arrest, which can be triggered by telomere shortening or by various types of genotoxic stress. Induction of senescence is emerging as a new strategy for the treatment of cancer, especially when sequentially combined with a second senolytic drug capable of killing the resulting senescent cells, however severely suffering from the undesired off-target side effects from the senolytic drugs. Here, we prepare a bimetalic platinum-aluminum salen complex (Alumiplatin) for cancer therapy-a combination of pro-senesence chemotherapy with inâ situ senotherapy to avoid the side effects. The aluminum salen moiety, as a G-quadruplex stabilizer, enhances the salen's ability to induce cancer cell senescence and this phenotype is in turn sensitive to the cytotoxic activity of the monofunctional platinum moiety. It exhibits an excellent capability for inducing senescence, a potent cytotoxic activity against cancer cells both inâ vitro and inâ vivo, and an improved safety profile compared to cisplatin. Therefore, Alumiplatin may be a good candidate to be further developed into safe and effective anticancer agents. This novel combination of cell senescence inducers with genotoxic drugs revolutionizes the therapy options of designing multi-targeting anticancer agents to improve the efficacy of anticancer therapies.
Asunto(s)
Aluminio , Antineoplásicos , Senescencia Celular , Etilenodiaminas , Platino (Metal) , Humanos , Antineoplásicos/farmacología , Antineoplásicos/química , Etilenodiaminas/química , Etilenodiaminas/farmacología , Senescencia Celular/efectos de los fármacos , Platino (Metal)/química , Platino (Metal)/farmacología , Aluminio/química , Aluminio/farmacología , Animales , Complejos de Coordinación/química , Complejos de Coordinación/farmacología , Complejos de Coordinación/uso terapéutico , Ratones , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ensayos de Selección de Medicamentos Antitumorales , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Compuestos Organoplatinos/farmacología , Compuestos Organoplatinos/químicaRESUMEN
Despite being a weaker metal, zinc has become an increasingly popular candidate for biodegradable implant applications due to its suitable corrosion rate and biocompatibility. Previous studies have experimented with various alloy elements to improve the overall mechanical performance of pure Zn without compromising the corrosion performance and biocompatibility; however, the thermal stability of biodegradable Zn alloys has not been widely studied. In this study, TiC nanoparticles were introduced for the first time to a Zn-Al-Cu system. After hot rolling, TiC nanoparticles were uniformly distributed in the Zn matrix and effectively enabled phase control during solidification. The Zn-Cu phase, which was elongated and sharp in the reference alloy, became globular in the nanocomposite. The strength of the alloy, after introducing TiC nanoparticles, increased by 31% from 259.7 to 340.3 MPa, while its ductility remained high at 49.2% elongation to failure. Fatigue performance also improved greatly by adding TiC nanoparticles, increasing the fatigue limit by 47.6% from 44.7 to 66 MPa. Furthermore, TiC nanoparticles displayed excellent phase control capability during body-temperature aging. Without TiC restriction, Zn-Cu phases evolved into dendritic morphologies, and the Al-rich eutectic grew thicker at grain boundaries. However, both Zn-Cu and Al-rich eutectic phases remained relatively unchanged in shape and size in the nanocomposite. A combination of exceptional tensile properties, improved fatigue performance, better long-term stability with a suitable corrosion rate, and excellent biocompatibility makes this new Zn-Al-Cu-TiC material a promising candidate for biodegradable stents and other biodegradable applications.
Asunto(s)
Implantes Absorbibles , Cobre , Stents , Zinc , Zinc/química , Zinc/farmacología , Cobre/química , Cobre/farmacología , Aleaciones/química , Humanos , Titanio/química , Titanio/farmacología , Aluminio/química , Aluminio/farmacología , Ensayo de Materiales , Corrosión , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Nanopartículas del Metal/química , Nanopartículas del Metal/uso terapéutico , Nanopartículas/química , Nanocompuestos/químicaRESUMEN
To incorporate different concentrations of Al2O9Zr3 (1%, 5%, and 10%) nanoparticles (NP) into the ER adhesive and subsequently assess the impact of this addition on the degree of conversion, µTBS, and antimicrobial efficacy. The current research involved a wide-ranging examination that merged various investigative techniques, including the application of scanning electron microscopy (SEM) for surface characterization of NP coupled with energy-dispersive x-ray spectroscopy (EDX), Fourier-transform infrared (FTIR) spectroscopy, µTBS testing, and microbial analysis. Teeth were divided into four groups based on the application of modified and unmodified three-step ER adhesive primer. Group 1 (0% Al2O9Zr3 NPs) Control, Group 2 (1% Al2O9Zr3 NPs), Group 3 (5% Al2O9Zr3 NPs), and Group 4 (10% Al2O9Zr3 NPs). EDX analysis of Al2O9Zr3 NPs was performed showing elemental distribution in synthesized NPs. Zirconium (Zr), Aluminum (Al), and Oxides (O2). After primer application, an assessment of the survival rate of Streptococcus mutans was completed. The FTIR spectra were analyzed to observe the characteristic peaks indicating the conversion of double bonds, both before and after the curing process, for the adhesive Etch and rinse containing 1,5,10 wt% Al2O9Zr3 NPs. µTBS and failure mode assessment were performed using a Universal Testing Machine (UTM) and stereomicroscope respectively. The µTBS and S.mutans survival rates comparison among different groups was performed using one-way ANOVA and Tukey post hoc (p = .05). Group 4 (10 wt% Al2O9Zr3 NPs + ER adhesive) specimens exhibited the minimum survival of S.mutans (0.11 ± 0.02 CFU/mL). Nonetheless, Group 1 (0 wt% Al2O9Zr3 NPs + ER adhesive) displayed the maximum surviving S.mutans (0.52 ± 0.08 CFU/mL). Moreover, Group 2 (1 wt% Al2O9Zr3 NPs + ER adhesive) (21.22 ± 0.73 MPa) samples displayed highest µTBS. However, the bond strength was weakest in Group 1 (0 wt% Al2O9Zr3 NPs + ER adhesive) (14.13 ± 0.32 MPa) study samples. The etch-and-rinse adhesive exhibited enhanced antibacterial activity and micro-tensile bond strength (µTBS) when 1% Al2O9Zr3 NPs was incorporated, as opposed to the control group. Nevertheless, the incorporation of Al2O9Zr3 NPs led to a decrease in DC. RESEARCH HIGHLIGHTS: 10 wt% Al2O9Zr3 NPs + ER adhesive specimens exhibited the minimum survival of S.mutans. 1 wt% Al2O9Zr3 NPs + ER adhesive samples displayed the most strong composite/CAD bond. The highest DC was observed in Group 1: 0 wt% Al2O9Zr3 NPs + ER adhesive.
Asunto(s)
Aluminio , Antibacterianos , Dentina , Microscopía Electrónica de Rastreo , Streptococcus mutans , Resistencia a la Tracción , Circonio , Circonio/química , Streptococcus mutans/efectos de los fármacos , Aluminio/química , Aluminio/análisis , Aluminio/farmacología , Antibacterianos/farmacología , Humanos , Dentina/química , Dentina/efectos de los fármacos , Dentina/microbiología , Caries Dental/microbiología , Nanopartículas/química , Espectroscopía Infrarroja por Transformada de Fourier/métodos , Cementos Dentales/química , Cementos Dentales/farmacología , Espectrometría por Rayos X/métodos , Recubrimiento Dental Adhesivo , Propiedades de Superficie , Adhesivos/químicaRESUMEN
Pyroptosis is an effective anti-tumor strategy. However, monometallic pyroptosis biotuners have not been explored until now. Here, we discover for the first time that biodegradable monometallic Al can act as a pyroptosis biotuner for tumor therapy. pH-sensitive Al nanoparticles (Al@P) are obtained by equipping polyethylene glycol-b-(poly(methyl methacrylate)-co-poly(4-vinylpyridine), which can exert their effect at the tumor site without affecting normal cells. The H2 and Al3+ release by Al@P in the acidic environment of tumors disrupts the redox balance and ionic homeostasis in tumor cells, thus generating large amounts of reactive oxygen species (ROS), leading to caspase-1 activation, gasdermin D cleavage, and IL-1ß/LDH release, which induces canonical pyroptotic death. Meanwhile, the prodrug Doxorubicin (Pro-DOX) is successfully loaded onto Al@P (Al@P-P) and can be activated by ROS to release DOX in the tumor cells, thus further improving the tumor-killing efficiency. Ultimately, Al@P-P is degradable and exhibits efficient tumor inhibition.
Asunto(s)
Metacrilatos , Neoplasias , Polietilenglicoles , Piroptosis , Humanos , Aluminio/farmacología , Especies Reactivas de Oxígeno , Neoplasias/tratamiento farmacológico , Doxorrubicina/farmacología , Doxorrubicina/uso terapéuticoRESUMEN
Sucralfate, which is a sucrose octasulfate aluminum complex, is an active pharmaceutical ingredient (API) falling in the category of cytoprotective agents which are very effective for gastric and duodenal ulcers. On interaction with stomach acid, it ionizes into aluminum and sucrose octasulfate ions to form a protective layer over the ulcerated region inhibiting further attack from acid. The mechanism of action of sucralfate in the context of its structure is not well understood. Considering that at least two forms of this API are available in the market, there are no reports on the various forms of sucralfate and differences in their pharmacological action. We characterized the two forms of sucralfate using multinuclear, multidimensional solid-state NMR, and the results show significant structural differences between them arising from variation in the aluminum environment and the level of hydration. The impact of structural differences on pharmacological action was examined by studying acid-induced Al release by 27Al liquid-state NMR. The sucralfate, European pharmaceutical standard, Form I, undergoes faster disruption in acid compared to Form II. The difference is explained on the basis of structural differences in the two forms which gives significant insights into the action of sucralfate in relation to its structure.
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Antiulcerosos , Úlcera Duodenal , Humanos , Sucralfato/uso terapéutico , Sucralfato/química , Sucralfato/farmacología , Aluminio/farmacología , Úlcera Duodenal/tratamiento farmacológico , Espectroscopía de Resonancia Magnética , Imagen por Resonancia Magnética , Antiulcerosos/uso terapéuticoRESUMEN
The assessment of amphibian responses as bioindicators of exposure to chemical pollutants is an important tool for conservation of native species. This study aimed to investigate the effects of chronic aluminum (Al) and zinc (Zn) exposure on survival, body size, morphology (malformations), and immune system (leukocyte profile) in P. cuvieri tadpoles. Ecotoxicological analyses were performed utilizing chronic toxicity tests in which 210 tadpoles at the 25th Gosner developmental stage were exposed to Al and Zn. Individuals of P. cuvieri were maintained in glass containers containing various concentrations of aluminum sulfate (0.1, 0.2, or 0.3 mg/L) and zinc sulfate (0.18, 0.27 or 0.35 mg/L), and tests were performed in triplicate. After 14 days, amphibians were weighed, measured and survival rate, malformations in the oral and intestine apparatus, leukocyte profile, and ratio between neutrophils and lymphocytes determined. The differing concentrations of Al and Zn did not produce lethality in P. cuvieri where 95% of the animals survived 326 hr following metal exposure. Individuals exposed to Zn achieved greater body growth and weight gain compared to controls. Aluminum increased weight gain compared controls. These metals also produced malformations of the oral and intestine apparatus and enhanced occurrence of hemorrhages, especially at the highest doses. Lymphocytes were the predominant cells among leukocytes, with lymphopenia and neutrophilia observed following Al and Zn treatment, as evidenced by elevated neutrophil/lymphocyte ratio, an important indicator of stress in animals. Data suggest that further studies need to be carried out, even with metal concentrations higher than those prescribed by CONAMA, to ensure the conservation of this species.
Asunto(s)
Contaminantes Químicos del Agua , Zinc , Humanos , Animales , Zinc/farmacología , Zinc/toxicidad , Aluminio/farmacología , Larva , Anuros/fisiología , Metales , Sistema Inmunológico/química , Tamaño Corporal , Aumento de Peso , Contaminantes Químicos del Agua/toxicidadRESUMEN
BACKGROUND: Aluminum-based adjuvants (ABAs) enhance the immune response following vaccine injection. Their mechanisms of action are not fully understood, and their bio-persistency have been described associated with long-term adverse effects. METHODS: We evaluated and compared the cellular effects of the two main ABAs and whole vaccines on ATP production, ROS generation and cytokines production (IL-6 and IL-10), using THP-1 cells. RESULTS: ABAs altered the cell energy metabolism by increasing ROS production after 24 h and reducing ATP production after 48 h. In addition, both ABAs and whole vaccines induced different kinetics of IL-6 production, whereas only ABAs induced IL-10 secretion. CONCLUSION: This study showed clearly, for a first time, a difference in cellular response to the ABAs and whole vaccines which should be taken into consideration in future studies focusing on the effect of ABA in vaccines. Future studies on ABAs should also pay attention to mitochondrial function alterations following exposure to ABA-containing vaccines.
Asunto(s)
Aluminio , Vacunas , Humanos , Aluminio/farmacología , Interleucina-10 , Monocitos , Células THP-1 , Interleucina-6 , Especies Reactivas de Oxígeno , Adyuvantes Inmunológicos/efectos adversos , Adenosina TrifosfatoRESUMEN
Effective loading and delivering the wound healing-based materials to the wound site and area with an optimum concentration and limited cytotoxicity are essential for a complete and fast healing process. Here, we have designed Zn/Al-LDH nanoparticles-loaded CMC films for encapsulation and delivery of gallic acid (GA) in order to develop an effective and efficient wound-healing scaffold. The physicochemical properties of the prepared Zn/Al-LDH nanohybrids were thoroughly characterized by several characterization techniques, such as FESEM, Hi-TEM, FTIR, and XRD techniques. The thermal properties of the scaffolds were evaluated by DSC and TGA analysis. The release profiles of GA from fabricated films were studied over 8 h by UV-vis spectroscopy. In vitro drug release studies in PBS solutions with pH 7.4 showed a mono-phasic profile in which the liberation of the drug mainly occurred by scaffold erosion and increased by increasing the experiment period. The in vitro antibacterial activity of Zn/Al-LDH-GA-loaded CMC films was assessed by disk diffusion and cell viability contact tests. The results showed the desired antibacterial activity against Staphylococcus aureus and Escherichia coli bacteria. Incorporating GA within CMC and CMC-Zn/Al-LDH films rereleased good cytocompatibility at the studied incubation time and different concentrations toward human normal HFF cell line than the free drug. The results of the present study indicated that the Zn/Al-LDH and Zn/Al-LDH-GA-loaded CMC have promising wound healing features to further develop a better future for clinical remedy of the different non-healing and hard-to-heal wounds.
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Nanocompuestos , Compuestos de Zinc , Zinc , Humanos , Zinc/farmacología , Carboximetilcelulosa de Sodio/química , Aluminio/farmacología , Hidróxido de Aluminio , Antibacterianos/farmacología , Antibacterianos/química , Hidróxidos/química , Nanocompuestos/química , Cicatrización de HeridasRESUMEN
MAIN CONCLUSION: Auxin acts upstream of NO through NOA and XXT5 pathways to regulate the binding capacity of the root cell wall to Al. In our previous study, we identified an unknown mechanism by which 1-naphthaleneacetic acid (NAA) decreased the fixation of aluminum (Al) in the cell wall. Here, we observed that external application of the nitric oxide (NO) donor S-nitrosoglutathion (GSNO) increased the inhibition of Al on root elongation. Further analysis indicated that GSNO could induce Al accumulation in the roots and root cell walls, which is consistent with lower xyloglucan content. In comparison to the Columbia-0 (Col-0) wild type (WT), endogenous NO-reduced mutants noa1 (NOA pathway) and nia1nia2 (NR pathway) were more resistant to Al, with lower root Al content, higher xyloglucan content, and more Al accumulation in the root cell walls. By contrast, the xxt5 mutant with reduced xyloglucan content exhibited an Al-sensitive phenotype. Interestingly, Al treatment increased the endogenous auxin and NO levels, and the auxin levels induced under Al stress further stimulated NO production. Auxin application reduced Al retention in hemicellulose and decreased the xyloglucan content, similar to the effects observed with GSNO. In yucca and aux1-7 mutants, exogenous application of NO resulted in responses similar to those of the WT, whereas exogenous auxin had little effect on the noa1 mutant under Al stress. In addition, as auxin had similar effects on the nia1nia2 mutant and the WT, exogenous auxin and NO had little effect on the xxt5 mutant under Al stress, further confirming that auxin acts upstream of NO through NOA and XXT5 pathways to regulate the binding capacity of the root cell wall to Al.
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Arabidopsis , Glucanos , Óxido Nítrico , Xilanos , Arabidopsis/genética , Aluminio/farmacología , Pared Celular , Ácidos IndolacéticosRESUMEN
The plasticity and growth of plant cell walls (CWs) remain poorly understood at the molecular level. In this work, we used atomic force microscopy (AFM) to observe elastic responses of the root transition zone of 4-day-old Arabidopsis thaliana wild-type and almt1-mutant seedlings grown under Fe or Al stresses. Elastic parameters were deduced from force-distance curve measurements using the trimechanic-3PCS framework. The presence of single metal species Fe2+ or Al3+ at 10 µM exerts no noticeable effect on the root growth compared with the control conditions. On the contrary, a mix of both the metal ions produced a strong root-extension arrest concomitant with significant increase of CW stiffness. Raising the concentration of either Fe2+ or Al3+ to 20 µM, no root-extension arrest was observed; nevertheless, an increase in root stiffness occurred. In the presence of both the metal ions at 10 µM, root-extension arrest was not observed in the almt1 mutant, which substantially abolishes the ability to exude malate. Our results indicate that the combination of Fe2+ and Al3+ with exuded malate is crucial for both CW stiffening and root-extension arrest. However, stiffness increase induced by single Fe2+ or Al3+ is not sufficient for arresting root growth in our experimental conditions.
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Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Malatos , Raíces de Plantas , Aluminio/farmacología , Pared Celular , IonesRESUMEN
Microorganisms can play a significant role in material corrosion, with bacterial biofilms as major participants in microbially influenced corrosion (MIC). The exact mechanisms by which this takes place are poorly understood, resulting in a scarcity of information regarding MIC detection and prevention. In this work, a consortium of moderately thermophilic bacteria isolated from a biofilm growing over aluminum alloy 7075 was characterized. Its effect over the alloy was evaluated on a 40-day period using Electron Microscopy, demonstrating acceleration of corrosion in comparison to the abiotic control. The bacterial consortium was biochemically and microbiologically characterized as an attempt to elucidate factors contributing to corrosion. Molecular analysis revealed that the consortium consisted mainly of members of the Bacillus genus, with lower abundance of other genera such as Thermoanaerobacterium, Anoxybacillus and Paenibacillus. The EPS polysaccharide presented mainly mannose, galactose, rhamnose and ribose. Our observations suggest that the acidification of the culture media resulting from bacterial metabolism acted as the main contributor to corrosion, hinting at an unspecific mechanism. The consortium was not sulfate-reducing, but it was found to produce hydrogen, which could also be a compounding factor for corrosion.
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Aleaciones , Aluminio , Humanos , Aleaciones/química , Aluminio/química , Aluminio/metabolismo , Aluminio/farmacología , Corrosión , Bacterias/metabolismo , Biopelículas , Acero/químicaRESUMEN
The utilization of guided tissue regeneration membranes is a significant approach for enhancing bone tissue growth in areas with bone defects. Biodegradable magnesium alloys are increasingly being used as guided tissue regeneration membranes due to their outstanding osteogenic properties. However, the degradation rates of magnesium alloy bone implants documented in the literature tend to be rapid. Moreover, many studies focus only on the initial 3-month period post-implantation, limiting their applicability and impeding clinical adoption. Furthermore, scant attention has been given to the interplay between the degradation of magnesium alloy implants and the adjacent tissues. To address these gaps, this study employs a well-studied magnesium-aluminum (Mg-Al) alloy membrane with a slow degradation rate. This membrane is implanted into rat skull bone defects and monitored over an extended period of up to 48 weeks. Observations are conducted at various intervals (2, 4, 8, 12, 24, and 48 weeks) following the implantation. Assessment of degradation behavior and tissue regeneration response is carried out using histological sections, micro-CT scans, and scanning electron microscopy (SEM). The findings reveal that the magnesium alloy membranes demonstrate remarkable biocompatibility and osteogenic capability over the entire observation duration. Specifically, the Mg-Al alloy membranes sustain their structural integrity for 8 weeks. Notably, their osteogenic ability is further enhanced as a corrosion product layer forms during the later stages of implantation. Additionally, our in vitro experiments employing extracts from the magnesium alloy display a significant osteogenic effect, accompanied by a notable increase in the expression of osteogenic-related genes. Collectively, these results strongly indicate the substantial potential of Mg-Al alloy membranes in the context of guided tissue regeneration.
Asunto(s)
Aleaciones , Magnesio , Ratas , Animales , Aleaciones/farmacología , Aleaciones/química , Magnesio/farmacología , Magnesio/química , Aluminio/farmacología , Regeneración Ósea , OsteogénesisRESUMEN
BACKGROUND: Studies have shown that aluminum (Al) is one of the environmental risk factors leading to Alzheimer's disease (AD), and Al exposure can cause elevated levels of BACE1mRNA, ß-secretase (BACE1), and amyloid beta (Aß) in vivo and in vitro. Previous studies by our research group have shown that this is partly caused by the negative regulation of BACE1 by miRNA29a/b1 (miR29a/b1). Despite the observed the role of nuclear factor kappa B (NF-κB) on many miRNAs, the upstream regulation of NF-κB protein on miR29 remains poorly understood. The purpose of this study was to better define the relationship between NF-κB and miR29a/b1 and the potentially relevant signaling pathways. METHODS: On the one hand, we constructed the animal model of Al exposure by the intraperitoneal injection of aluminum-maltolate (Al(mal)3) in rats. Conversely, NF- κB inhibitors were added to adrenal phaeochromocytoma (PC12) cells exposed to Al(mal)3. RESULTS: We verified that NF-κB shows an increasing trend with Al accumulation in the brain of rats, which is accompanied by a downward trend of miR29a/b1. Notably, the suppression of NF-κB significantly increased miR29a/b1 and affected the expression of BACE1mRNA and downstream proteins. CONCLUSION: Al-induced NF-κB can negatively regulate the expression of miR29a/b1, which then significantly enhances the expression of BACE1 and Aß plaques.
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Péptidos beta-Amiloides , FN-kappa B , Ratas , Animales , FN-kappa B/metabolismo , Péptidos beta-Amiloides/metabolismo , Secretasas de la Proteína Precursora del Amiloide/genética , Secretasas de la Proteína Precursora del Amiloide/metabolismo , Aluminio/farmacología , Aluminio/metabolismo , Regulación hacia Abajo , Ácido Aspártico Endopeptidasas/genética , Ácido Aspártico Endopeptidasas/metabolismoRESUMEN
The present study is aimed at investigating the long-term effects of the aluminum hydroxide administration in the small intestine, lung, liver, and kidney of male BALB/c mice. The mice received via orogastric gavage phosphate buffered or 10 mg/kg aluminum hydroxide 3 times a week for 6 months. Administration of aluminum hydroxide decreased hemoglobin, hematocrit, and erythrocyte. In the blood, kidney and liver function markers were evaluated, and long-term administration of aluminum hydroxide led to an increase in AST levels and a decrease in urea levels. The animals exposed to aluminum showed higher lipid and protein oxidation in all the organs analyzed. In relation to the enzymes involved in antioxidant defense, the lungs showed lower superoxide dismutase (SOD) and catalase activity and a lower reduced and oxidized glutathione (GSH/GSSG) ratio. In the liver, aluminum administration led to a decrease in catalase activity and the GSH/GSSG ratio. Lower catalase activity was observed in the small intestine, as well as in the lungs and liver. In addition to alterations in antioxidant defense, increased levels of the chemokine CCL-2 were observed in the lungs, lower levels of IL-10 in the liver and small intestine, and decreased levels of IL-6 in the intestine of the animals that received aluminum hydroxide for 6 months. Long-term exposure to aluminum promoted steatosis in the liver. In the kidneys, mice treated with aluminum presented a decreased glomerular density than in the naive control group. In the small intestine, exposure caused villi shortening. Our results indicate that long-term oral administration of aluminum hydroxide provokes systemic histological damage, inflammation, and redox imbalance.
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Antioxidantes , Glutatión , Ratones , Masculino , Animales , Antioxidantes/farmacología , Disulfuro de Glutatión/metabolismo , Glutatión/metabolismo , Catalasa/metabolismo , Hidróxido de Aluminio/farmacología , Ratones Endogámicos BALB C , Aluminio/farmacología , Oxidación-Reducción , Superóxido Dismutasa/metabolismo , Hígado/metabolismo , Inflamación/inducido químicamente , Inflamación/metabolismo , Estrés OxidativoRESUMEN
Aim: Here, we report the synthesis and evaluation of fullerene C60 nanoparticles' (FC60 NPs) therapeutic efficacy in animals with aluminum-induced oxidative stress. Materials & methods: Effects of FC60 NPs on the altered activity levels of neurobiochemical enzymes and oxidative parameters in brain and liver tissues have been evaluated. Aluminum was injected for 3 weeks and from the beginning of the third week, FC60 NPs were injected for 1 week. Results: Administration of FC60 NPs showed a significant improvement in the altered activity level of the selected markers. Conclusion: Results suggest synthesized FC60 NPs as a therapeutic option for the treatment of neurodegenerative diseases.
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Fulerenos , Animales , Fulerenos/farmacología , Fulerenos/uso terapéutico , Neuroprotección , Aluminio/farmacología , Estrés Oxidativo , CogniciónRESUMEN
At present, the most widely used aluminum adjuvants have poor ability to induce effective Th1 type immune responses. Existing evidence suggests that manganese is a potential metal adjuvant by activating cyclic guanosine phospho-adenosine synthase (cGAS)-interferon gene stimulator protein (STING) signaling pathway to enhance humoral and cellular immune response. Hence, the effective modulation of metal components is expected to be a new strategy to improve the efficiency of vaccine immunization. Here, we constructed a manganese and aluminum dual-adjuvant antigen co-delivery system (MnO2-Al-OVA) to enhance the immune responses of subunit vaccines. Namely, the aluminum hydroxide was first fused on the surface of the pre-prepared MnO2 nanoparticles, which were synthesized by a simple redox reaction with potassium permanganate (KMnO4) and oleic acid (OA). The engineered MnO2-Al-OVA could remarkably promote cellular internalization and maturation of dendritic cells. After subcutaneous vaccination, MnO2-Al-OVA rapidly migrated into the lymph nodes (LNs) and efficiently activate the cGAS-STING pathway, greatly induced humoral and cellular immune responses. Of note, our findings underscore the importance of coordination manganese adjuvants in vaccine design by promoting the activation of the cGAS-STING-IFN-I pathway. With a good safety profile and facile preparation process, this dual-adjuvant antigen co-delivery nanovaccine has great potential for clinical translation prospects.
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Aluminio , Nanopartículas , Aluminio/farmacología , Manganeso , Compuestos de Manganeso/farmacología , Óxidos , Adyuvantes Inmunológicos , Inmunidad Celular , Antígenos , Vacunas de Subunidad , Nucleotidiltransferasas/farmacología , Células Dendríticas , Inmunidad HumoralRESUMEN
Chinese yam polysaccharides (CYPs) have received wide attention for their immunomodulatory activity. Our previous studies had discovered that the Chinese yam polysaccharide PLGA-stabilized Pickering emulsion (CYP-PPAS) can serve as an efficient adjuvant to trigger powerful humoral and cellular immunity. Recently, positively charged nano-adjuvants are easily taken up by antigen-presenting cells, potentially resulting in lysosomal escape, the promotion of antigen cross-presentation, and the induction of CD8 T-cell response. However, reports on the practical application of cationic Pickering emulsions as adjuvants are very limited. Considering the economic damage and public-health risks caused by the H9N2 influenza virus, it is urgent to develop an effective adjuvant for boosting humoral and cellular immunity against influenza virus infection. Here, we applied polyethyleneimine-modified Chinese yam polysaccharide PLGA nanoparticles as particle stabilizers and squalene as the oil core to fabricate a positively charged nanoparticle-stabilized Pickering emulsion adjuvant system (PEI-CYP-PPAS). The cationic Pickering emulsion of PEI-CYP-PPAS was utilized as an adjuvant for the H9N2 Avian influenza vaccine, and the adjuvant activity was compared with the Pickering emulsion of CYP-PPAS and the commercial adjuvant (aluminum adjuvant). The PEI-CYP-PPAS, with a size of about 1164.66 nm and a ζ potential of 33.23 mV, could increase the H9N2 antigen loading efficiency by 83.99%. After vaccination with Pickering emulsions based on H9N2 vaccines, PEI-CYP-PPAS generated higher HI titers and stronger IgG antibodies than CYP-PPAS and Alum and increased the immune organ index of the spleen and bursa of Fabricius without immune organ injury. Moreover, treatment with PEI-CYP-PPAS/H9N2 induced CD4+ and CD8+ T-cell activation, a high lymphocyte proliferation index, and increased cytokine expression of IL-4, IL-6, and IFN-γ. Thus, compared with the CYP-PPAS and aluminum adjuvant, the cationic nanoparticle-stabilized vaccine delivery system of PEI-CYP-PPAS was an effective adjuvant for H9N2 vaccination to elicit powerful humoral and cellular immune responses.
Asunto(s)
Subtipo H9N2 del Virus de la Influenza A , Vacunas contra la Influenza , Nanopartículas , Animales , Pollos , Aluminio/farmacología , Emulsiones/farmacología , Antígenos , Inmunidad Celular , Copolímero de Ácido Poliláctico-Ácido Poliglicólico/farmacología , Adyuvantes Inmunológicos , Polisacáridos/farmacologíaRESUMEN
In this article, we describe the antimicrobial properties of pristine anodised aluminium oxide matrices-the material many consider biologically inert. During a typical anodisation process, chromium and chlorine compounds are used for electropolishing and the removal of the first-step aluminium oxide. Matrices without the use of those harmful compounds were also fabricated and tested for comparison. The antibacterial tests were conducted on four strains of Escherichia coli: K12, R2, R3 and R4. The properties of the matrices were also compared to the three types of antibiotics: ciprofloxacin, bleomycin and cloxacillin using the Minimal Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. Moreover, DNA was isolated from the analysed bacteria which was additionally digested with formamidopyrimidine-DNA glycosylase (Fpg) protein from the group of repair glycosases. These enzymes are markers of modified oxidised bases in nucleic acids produced during oxidative stress in cells. Preliminary cellular studies, MIC and MBC tests and digestion with Fpg protein after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than the aforementioned antibiotics. The described composites are highly specific for the analysed model Escherichia coli strains and may be used in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the progressing pandemic era. The results show much stronger antibacterial properties of the functionalised membranes on the action of bacterial membranes in comparison to the antibiotics in the Fpg digestion experiment. This is most likely due to the strong induction of oxidative stress in the cell through the breakdown of the analysed bacterial DNA.