RESUMEN
Potatoes (Solanum tuberosum L.) are a significant food crop cultivated around the world. Caffeic acid (CA) can enhance plant growth by promoting antioxidant activity and stimulating root development, contributing to overall plant health and vigor. Cobalt sulfate (CoSO4) boosts plant growth by promoting nitrogen (N) fixation, healthier root development, and chlorophyll synthesis, enhancing photosynthesis and overall plant health. Nanoparticle-coated urea (NPCU) improves nutrient uptake, promoting plant growth efficiency and reducing environmental impact. This study investigates the effects of combining CA, CoSO4, and NPCU as amendments on potatoes with and without NPCU. Four treatments, control, 20 µM CA, 0.15 mg/L CoSO4, and 20 µM CA + 0.15 mg/L CoSO4 with and without NPCU, were applied in four replications using a completely randomized design. Results demonstrate that the combination of CA + CoSO4 with NPCU led to an increase in potato stem length (~ 6%), shoot dry weight (~ 15%), root dry weight (~ 9%), and leaf dry weight (~ 49%) compared to the control in nutrient stress. There was a significant rise in chlorophyll a (~ 27%), chlorophyll b (~ 37%), and total chlorophyll (~ 28%) over the control under nutrient stress also showed the potential of CA + CoSO4 with NPCU. In conclusion, the findings suggest that applying CA + CoSO4 with NPCU is a strategy for alleviating potato nutrient stress.
Asunto(s)
Ácidos Cafeicos , Nanopartículas , Solanum tuberosum , Urea , Solanum tuberosum/efectos de los fármacos , Solanum tuberosum/crecimiento & desarrollo , Ácidos Cafeicos/farmacología , Ácidos Cafeicos/química , Urea/farmacología , Nanopartículas/química , Cobalto/farmacología , Cobalto/química , Fotosíntesis/efectos de los fármacos , Clorofila/metabolismo , Raíces de Plantas/efectos de los fármacos , Raíces de Plantas/crecimiento & desarrollo , Hojas de la Planta/efectos de los fármacosRESUMEN
Nitrite-oxidizing bacteria (NOB), which perform the second step of aerobic nitrification, play an important role in soil. In the present study, we report a novel isolate from agricultural soil affiliated with the genus Nitrobacter and its physiological characteristics. We sampled the surface soil of a vegetable field and obtained mixed culture A31 using the most probable number (MPN) method with inorganic medium containing 0.75| |mM urea (pH 5.5). The dilution-extinction procedure on culture A31 led to the isolation of a strain that was designated as Nitrobacter sp. A67. The nxrB1 gene sequence of Nitrobacter sp. A67 (302 bp) was classified into Cluster 5, and the highest sequence identity was 96.10% with Nitrobacter sp. BS5/19. The NO2- oxidation activity of Nitrobacter sp. A67 was investigated at various pH. The optimum pH for NO2- oxidation was 5.8-6.4. This result indicates that Nitrobacter sp. A67 is a moderately acidophilic nitrite-oxidizing bacterium.
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Nitrificación , Nitritos , Nitrobacter , Oxidación-Reducción , Filogenia , ARN Ribosómico 16S , Microbiología del Suelo , Urea , Nitrobacter/metabolismo , Nitrobacter/genética , Nitritos/metabolismo , Urea/metabolismo , Concentración de Iones de Hidrógeno , ARN Ribosómico 16S/genética , ADN Bacteriano/genética , Análisis de Secuencia de ADNRESUMEN
BACKGROUND: To predict the long-term performance of restorative materials in the oral environment, it is important to evaluate their resistance to chemical and mechanical degradation and to know the toxic potential of the type and amount of ions eluted from the filling material. In this study, home bleaching was applied to dental materials with different contents and it was aimed to determine the type and amount of ions released from these materials. METHODS: In this study, amalgam, posterior composite resin, anterior composite resin, bulk fill composite resin, indirect composite resin, hybrid ceramic and all-ceramic were used as restorative materials. 10 specimens of each material were prepared according to the manufacturer's instructions. Each material group was divided into two subgroups as the bleached group and the control group. After bleaching, all specimens were stored in 1 ml of 75% ethanol/water solution. Solutions were renewed after 1, 14 and 28 days. The type and amount of ions released from the materials were determined using Inductively Coupled Plasma-Mass Spectrometer (ICP-MS). Data were analyzed using the Friedman, Wilcoxon Signed Ranks, and Mann-Whitney U tests (α = 0.05). RESULTS: It was determined that the amount of ions release from the restorative materials decreased over time (p < 0.05). According to the results of the Mann-Whitney U test, there was no difference between the bleaching and control groups in most of the restorative materials (p > 0.05). CONCLUSION: Within the limits of this study, home bleaching system does not have a significant effect on ion release from restorative materials.
Asunto(s)
Peróxido de Carbamida , Resinas Compuestas , Amalgama Dental , Materiales Dentales , Restauración Dental Permanente , Ensayo de Materiales , Peróxidos , Blanqueadores Dentales , Urea , Peróxido de Carbamida/farmacología , Peróxidos/química , Resinas Compuestas/química , Blanqueadores Dentales/química , Amalgama Dental/química , Urea/análogos & derivados , Urea/química , Restauración Dental Permanente/métodos , Materiales Dentales/química , Iones , Cerámica/química , Humanos , Factores de TiempoRESUMEN
By performing differential scanning calorimetry(DSC) measurements on RNase A, we studied the stabilization provided by the addition of potassium aspartate(KAsp) or potassium glutamate (KGlu) and found that it leads to a significant increase in the denaturation temperature of the protein. The stabilization proves to be mainly entropic in origin. A counteraction of the stabilization provided by KAsp or KGlu is obtained by adding common denaturants such as urea, guanidinium chloride, or guanidinium thiocyanate. A rationalization of the experimental data is devised on the basis of a theoretical approach developed by one of the authors. The main contribution to the conformational stability of globular proteins comes from the gain in translational entropy of water and co-solute ions and/or molecules for the decrease in solvent-excluded volume associated with polypeptide folding (i.e., there is a large decrease in solvent-accessible surface area). The magnitude of this entropic contribution increases with the number density and volume packing density of the solution. The two destabilizing contributions come from the conformational entropy of the chain, which should not depend significantly on the presence of co-solutes, and from the direct energetic interactions between co-solutes and the protein surface in both the native and denatured states. It is the magnitude of the latter that discriminates between stabilizing and destabilizing agents.
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Ácido Aspártico , Ácido Glutámico , Desnaturalización Proteica , Ácido Aspártico/química , Desnaturalización Proteica/efectos de los fármacos , Ácido Glutámico/química , Ribonucleasa Pancreática/química , Ribonucleasa Pancreática/metabolismo , Termodinámica , Rastreo Diferencial de Calorimetría , Entropía , Estabilidad Proteica , Guanidina/química , Guanidina/farmacología , Urea/química , Urea/farmacología , Conformación ProteicaRESUMEN
The high speed enrichment of benzoylurea insecticides (BUs) in complex matrices is an essential and challenging step. The present study focuses on the synthesis of a hierarchical pore nitrogen-doped carbon material for magnetic solid phase extraction (MSPE) of BUs. This material was prepared through the carbonization of a composite material ZIF-67@MCA which assembly with hydrogen-bonded organic frameworks (melamine-cyanurate, MCA) and zeolitic imidazolate framework (ZIF-67) at room temperature. The optimal adsorption effect is achieved when the mass ratio of ZIF-67 to MCA is 1/3, and the carbonization was performed at 600 °C, the such obtained carbon material was denoted as 1/3ZIF-67@MCA-DCs-600. The material was characterized with various physical methods including X-ray diffractometry (XRD), Fourier transform infrared spectrometry (FTIR), X-ray photoelectron spectroscopy (XPS), scanning electron microscope (SEM), Brunauer-Emmett-Teller (BET), vibrating sample magnetometer (VSM), water contact angle measurement, Raman spectrometry. 1/3ZIF-67@MCA-DCs-600 exhibits a macro-mesoporous 3D structure with a high degree of nitrogen doping and relatively large specific surface area, making it suitable for magnetic solid phase extraction (MSPE). The adsorption of BUs with concentration of 100 ng mL-1 can reach equilibrium within 5 s. The interaction between BUs and the adsorbent, facilitated by π-π stacking, hydrophobic interactions, hydrogen bonding forces, as well as the material's porosity, enables efficient extraction recoveries ranging from 45 % to 92 %. The enrichment of BUs was achieved through the establishment of an MSPE method under optimized conditions, which was further coupled with high performance liquid chromatography (HPLC) for the determination of the four BUs. The linear range spans from 5 ng ml-1 to 1000 ng ml-1 with the correlation coefficient (R2) of ≥ 0.99, Meanwhile, the detection limit for these four BUs falls within the range of 0.01 to 0.10 ng ml-1. The material exhibits good reusability and can be reused for at least 5 cycles. Inter day and intra-day precision ranges from 2.1-7.9 % and 1.0-5.4 %, respectively. The method demonstrates a high level of reliability in practical applications for the determination of BUs.
Asunto(s)
Carbono , Enlace de Hidrógeno , Insecticidas , Nitrógeno , Extracción en Fase Sólida , Insecticidas/análisis , Insecticidas/química , Insecticidas/aislamiento & purificación , Extracción en Fase Sólida/métodos , Adsorción , Carbono/química , Nitrógeno/química , Estructuras Metalorgánicas/química , Porosidad , Triazinas/química , Triazinas/aislamiento & purificación , Límite de Detección , Urea/química , Zeolitas/químicaRESUMEN
Inhibition of soluble epoxide hydrolase (sEH) is a promising therapeutic strategy for treating neuropathic pain. These inhibitors effectively reduce diabetic neuropathic pain and inflammation induced by Freund's adjuvant which makes them a suitable alternative to traditional opioids. This study showcased the notable analgesic effects of compound AMHDU (1,1'-(hexane-1,6-diyl)bis(3-((adamantan-1-yl)methyl)urea)) in both inflammatory and diabetic neuropathy models. While lacking anti-inflammatory properties in a paw edema model, AMHDU is comparable to celecoxib as an analgesic in 30 mg/kg dose administrated by intraperitoneal injection. In a diabetic tactile allodynia model, AMHDU showed a prominent analgesic activity in 10 mg/kg intraperitoneal dose (p < 0.05). The effect is comparable to that of gabapentin, but without the risk of dependence due to a different mechanism of action. Low acute oral toxicity (>2000 mg/kg) and a high therapeutic index makes AMHDU a promising candidate for further structure optimization and preclinical evaluation.
Asunto(s)
Analgésicos , Epóxido Hidrolasas , Neuralgia , Epóxido Hidrolasas/antagonistas & inhibidores , Epóxido Hidrolasas/metabolismo , Animales , Neuralgia/tratamiento farmacológico , Masculino , Ratones , Analgésicos/farmacología , Analgésicos/uso terapéutico , Hiperalgesia/tratamiento farmacológico , Modelos Animales de Enfermedad , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/uso terapéutico , Neuropatías Diabéticas/tratamiento farmacológico , Urea/análogos & derivados , Urea/farmacología , Evaluación Preclínica de Medicamentos , Edema/tratamiento farmacológico , Ratas , Adamantano/análogos & derivados , Adamantano/farmacología , Adamantano/uso terapéuticoRESUMEN
T5 is a siphophage that has been extensively studied by structural and biochemical methods. However, the complete in situ structures of T5 before and after DNA ejection remain unknown. In this study, we used cryo-electron microscopy (cryo-EM) to determine the structures of mature T5 (a laboratory-adapted, fiberless T5 mutant) and urea-treated empty T5 (lacking the tip complex) at near-atomic resolutions. Atomic models of the head, connector complex, tail tube, and tail tip were built for mature T5, and atomic models of the connector complex, comprising the portal protein pb7, adaptor protein p144, and tail terminator protein p142, were built for urea-treated empty T5. Our findings revealed that the aforementioned proteins did not undergo global conformational changes before and after DNA ejection, indicating that these structural features were conserved among most myophages and siphophages. The present study elucidates the underlying mechanisms of siphophage infection and DNA ejection.
Asunto(s)
Microscopía por Crioelectrón , ADN Viral , Urea , ADN Viral/genética , Urea/farmacología , Urea/química , Modelos Moleculares , Proteínas Virales/química , Proteínas Virales/metabolismoRESUMEN
We performed a comprehensive study of protein (total protein, medium-molecular-weight peptides, creatinine, and urea), purine (uric acid), and lipid (cholesterol, triglycerides) metabolism, activity of AST, ALT, and acid phosphatase in blood plasma of white male rats under conditions of restriction of motor activity up to 28 days. Patterns of changes in metabolic profile during hypokinesia were established: prevalence of catabolic processes and atherogenic shifts in the lipid spectrum with maximum manifestation on 14-21 days of the experiment.
Asunto(s)
Colesterol , Triglicéridos , Animales , Masculino , Ratas , Triglicéridos/sangre , Triglicéridos/metabolismo , Colesterol/sangre , Colesterol/metabolismo , Ácido Úrico/sangre , Ácido Úrico/metabolismo , Actividad Motora/fisiología , Metaboloma/fisiología , Metabolismo de los Lípidos/fisiología , Aspartato Aminotransferasas/sangre , Aspartato Aminotransferasas/metabolismo , Alanina Transaminasa/sangre , Alanina Transaminasa/metabolismo , Creatinina/sangre , Fosfatasa Ácida/metabolismo , Fosfatasa Ácida/sangre , Urea/sangre , Hipocinesia/metabolismo , Hipocinesia/fisiopatologíaRESUMEN
Purpose: The purpose of this study was to assess, in vitro, the color stability and bleaching response of three bulk-fill composite resins-Activa™, Tetric®-N-Ceram Bulk-Fill, and Filtek™ One Bulk-Fill???and one conventional composite resin, Filtek™ Z250, after immersion in commonly consumed carbonated beverages and subsequent home bleaching with 15 percent carbamide peroxide. Methods: Ninety-six samples (two- and four-mm thick) of the materials were immersed in malt drink, energy drink, cola, or distilled water for one day, one week, and two months. After two months, samples underwent home bleaching with 15 percent carbamide peroxide gel. Spectrophotometric analysis measured color and whiteness changes pre-immersion, post-immersion, and post-bleaching. Statistical significance was determined using factorial mixed analysis of variance (ANOVA), three-way ANOVA, and Bonferroni post hoc tests (P<0.05). Results: All tested composite resins exhibited unacceptable discoloration (color change greater than 3.3) after two months in carbonated beverages. Filtek™ One Bulk-Fill and Filtek™ Z250 displayed the most significant discoloration, particularly when immersed in the malt drink (P<0.05). In contrast, Activa™ samples reached unacceptable discoloration within just one week in malt and cola drinks. Home bleaching yielded limited whiteness recovery, with Activa™ presenting acceptable whiteness post-bleaching after staining with cola and energy drinks. Conclusions: This study highlights the aesthetic risks of prolonged carbonated beverage consumption and the limitations of the assessed home bleaching technique using 15 percent carbamide peroxide. Enhanced dental education on the dietary effects of some beverages on restorative materials is indicated by these findings.
Asunto(s)
Peróxido de Carbamida , Bebidas Gaseosas , Color , Resinas Compuestas , Blanqueamiento de Dientes , Blanqueamiento de Dientes/métodos , Blanqueadores Dentales , Humanos , Peróxidos/efectos adversos , Urea/análogos & derivados , Urea/efectos adversos , Ensayo de Materiales , Espectrofotometría , Bebidas EnergéticasRESUMEN
A novel and sensitive fluorescence ratiometric method is developed for urea detection based on the pH-sensitive response of two fluorescent carbon dot (CD) systems: R-CDs/methyl red (MR) and NIR-CDs/Cu2+. The sensing mechanism involves breaking down urea using the enzyme urease, releasing ammonia and increasing pH. At higher pH, the fluorescence of NIR-CDs is quenched due to the enhanced interaction with Cu2+, while the fluorescence of R-CDs is restored as the acidic MR converts to its basic form, removing the inner filter effect. The ratiometric signal (F608/F750) of the R-CDs/MR and NIR-CDs/Cu2+ intensities changed in response to the pH induced by urea hydrolysis, enabling selective and sensitive urea detection. Detailed spectroscopic and morphological investigations confirmed the fluorescence probe design and elucidated the sensing mechanism. The method exhibited excellent sensitivity (0.00028 mM LOD) and linearity range (0.001 - 8.0 mM) for urea detection, with successful application in milk samples for monitoring adulteration, demonstrating negligible interference and high recovery levels (96.5% to 101.0%). This ratiometric fluorescence approach offers a robust strategy for selective urea sensing in complicated matrices.
Asunto(s)
Carbono , Cobre , Colorantes Fluorescentes , Límite de Detección , Puntos Cuánticos , Espectrometría de Fluorescencia , Urea , Ureasa , Urea/análisis , Urea/química , Ureasa/química , Cobre/química , Carbono/química , Concentración de Iones de Hidrógeno , Puntos Cuánticos/química , Colorantes Fluorescentes/química , Espectrometría de Fluorescencia/métodos , Animales , Leche/química , Compuestos Azo/química , Contaminación de Alimentos/análisisRESUMEN
The transient receptor potential melastatin 7 channel (TRPM7) is a nonselective cation channel highly expressed in some human cancer tissues. TRPM7 is involved in the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of cancer cells. Modulation of TRPM7 could be a promising therapeutic strategy for treating cancer; however, efficient and selective pharmacological TRPM7 modulators are lacking. In this study we investigated N- [4- (4, 6-dimethyl- 2-pyrimidinyloxy) - 3- methylphenyl] -N' - [2 -(dimethylamino)] benzoylurea (SUD), a newly synthesized benzoylurea derivative, for its effects on cancer cell migration and EMT and on functional expression of TRPM7. Our previous studies showed that SUD induces cell cycle arrest and apoptosis of MCF-7 and BGC-823 cells (human breast cancer and gastric cancer cell lines, respectively). Here, we show that SUD significantly decreased the migration of both types of cancer cells. Moreover, SUD decreased vimentin expression and increased E-cadherin expression in both cell types, indicating that EMT is also decreased by SUD. Importantly, SUD potentially reduced the TRPM7-like current in a concentration-dependent manner and decreased TRPM7 expression through the PI3K/Akt signaling pathway. Finally, molecular docking simulations were used to investigate potential SUD binding sites on TRPM7. In summary, our research demonstrated that SUD is an effective TRPM7 inhibitor and a potential agent to suppress the metastasis of breast and gastric cancer by inhibiting TRPM7 expression and function.
Asunto(s)
Movimiento Celular , Transición Epitelial-Mesenquimal , Proteínas Serina-Treonina Quinasas , Canales Catiónicos TRPM , Urea , Humanos , Canales Catiónicos TRPM/metabolismo , Canales Catiónicos TRPM/genética , Canales Catiónicos TRPM/antagonistas & inhibidores , Movimiento Celular/efectos de los fármacos , Transición Epitelial-Mesenquimal/efectos de los fármacos , Urea/análogos & derivados , Urea/farmacología , Urea/química , Línea Celular Tumoral , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Antineoplásicos/farmacología , Antineoplásicos/química , Simulación del Acoplamiento Molecular , Células MCF-7RESUMEN
We evaluated the incidence and potential etiology of tracheobronchial uptake in patients being evaluated by 18F-DCFPyL PET/CT for prostate cancer (PCa). Methods: The study included a consecutive 100 PCa patients referred for 18F-DCFPyL PET/CT. The PET/CT scans were retrospectively reviewed. The presence or absence of physiologic tracheobronchial uptake on PET/CT was recorded. To further evaluate tracheal prostate-specific membrane antigen (PSMA) expression, immunohistochemistry was performed on tracheal samples taken from 2 men who had surgical resection of lung cancer. Results: Tracheal uptake was present in 31 of 100 patients (31%). When tracheal uptake was present, the SUVmax was significantly higher in the left main bronchus (mean, 2.7) than in the right (mean, 2.3) (P < 0.001). Histopathologic testing of tracheobronchial samples showed PSMA expression in bronchial submucosal glands. Conclusion: In PCa patients undergoing 18F-DCFPyL PET/CT, tracheobronchial uptake occurred in 31% of patients. This is attributed to normal physiologic PSMA expression in bronchial submucosal glands.
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Bronquios , Glutamato Carboxipeptidasa II , Lisina , Tomografía Computarizada por Tomografía de Emisión de Positrones , Neoplasias de la Próstata , Tráquea , Urea , Humanos , Masculino , Neoplasias de la Próstata/diagnóstico por imagen , Neoplasias de la Próstata/metabolismo , Tráquea/diagnóstico por imagen , Tráquea/metabolismo , Anciano , Glutamato Carboxipeptidasa II/metabolismo , Bronquios/diagnóstico por imagen , Bronquios/metabolismo , Persona de Mediana Edad , Lisina/análogos & derivados , Lisina/metabolismo , Estudios Retrospectivos , Urea/análogos & derivados , Urea/metabolismo , Antígenos de Superficie/metabolismo , Anciano de 80 o más Años , Transporte Biológico , RadiofármacosRESUMEN
Urea cycle impairment and its relationship to obesity and inflammation remained elusive, partly due to the dramatic clinical presentation of classical urea cycle defects. We generated mice with hepatocyte-specific arginase 2 deletion (Arg2LKO) and revealed a mild compensated urea cycle defect. Stable isotope tracing and respirometry revealed hepatocyte urea and TCA cycle flux defects, impaired mitochondrial oxidative metabolism, and glutamine anaplerosis despite normal energy and glucose homeostasis during early adulthood. Yet during middle adulthood, chow- and diet-induced obese Arg2LKO mice develop exaggerated glucose and lipid derangements, which are reversible by replacing the TCA cycle oxidative substrate nicotinamide adenine dinucleotide. Moreover, serum-based hallmarks of urea, TCA cycle, and mitochondrial derangements predict incident fibroinflammatory liver disease in 106,606 patients nearly a decade in advance. The data reveal hierarchical urea-TCA cycle control via ARG2 to drive oxidative metabolism. Moreover, perturbations in this circuit may causally link urea cycle compromise to fibroinflammatory liver disease.
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Arginasa , Ciclo del Ácido Cítrico , Hepatocitos , Urea , Animales , Arginasa/metabolismo , Hepatocitos/metabolismo , Ratones , Urea/metabolismo , Ratones Noqueados , Masculino , Humanos , Ratones Endogámicos C57BL , Oxidación-Reducción , Mitocondrias/metabolismo , FemeninoRESUMEN
Coated fertilizers have been widely used to improve fertility in barren land. However, improving soil structure and water-retention capacity is also essential for arid and semi-arid areas with sandy soils to promote crop growth. Most currently available coated fertilizers rarely meet these requirements, limiting their application scope. Therefore, this study "tailored" pectin-montmorillonite (PM) multifunctional coatings for arid areas, featuring intercalation reactions and nanoscale entanglement between pectin and montmorillonite via hydrogen bonding and electrostatic and van der Waals forces. Notably, PM coatings have demonstrated an effective "relay" model of action. First, the PM-50 coating could act as a "shield" to protect urea pills, increasing the mechanical strength (82.12 %). Second, this coating prolonged the release longevity of urea (<0.5 h to 15 days). Further, the remaining coating performed a water-retention function. Subsequently, the degraded coating improved the soil properties. Thus, this coating facilitated the growth of wheat seedlings in a simulated arid environment. Moreover, the cytotoxicity test, life cycle assessment, and soil biodegradation experiment showed that the PM coating exhibited minimal environmental impact. Overall, the "relay" model of PM coating overcomes the application limitations of traditional coated fertilizers and provides a sustainable strategy for developing coating materials in soil degradation areas.
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Bentonita , Preparaciones de Acción Retardada , Fertilizantes , Pectinas , Suelo , Agua , Pectinas/química , Agua/química , Suelo/química , Bentonita/química , Preparaciones de Acción Retardada/química , Biodegradación Ambiental , Triticum/química , Urea/químicaRESUMEN
The development of bioadhesives with strong adhesion and on-demand adhesion-detachment behavior is still critically important and challenging for facilitating painless and damage-free removal in clinical applications. In this work, for the first time, we report the easy fabrication of novel polyurethane-urea (PUU)-based bioadhesives with thermoresponsive on-demand adhesion and detachment behavior. The PUU copolymer was synthesized by a simple copolymerization of low-molecular-weight, hydrophilic, and biocompatible poly(ethylene glycol), glyceryl monolaurate (GML, a special chain extender with a long side hydrophobic alkyl group), and isophorone diisocyanate (IPDI). Here, GML was expected to not only adjust the temperature-dependent adhesion behavior but also act as an internal plasticizer. By simple adjustment of the water content, the adhesion strength of the 15 wt % water-containing PUU film toward porcine skin is as high as 55 kPa with an adhesion energy of 128 J/m2 at 37 °C. The adhesion strength dramatically decreases to only 3 kPa at 10 °C, exhibiting switching efficiency as high as 0.95. Furthermore, the present PUU-based adhesive also shows good on-demand underwater adhesion and detachment with a cell viability close to 100%. We propose that biomaterial research fields, especially novel PUU/polyurethane (PU)-based functional materials and bioadhesives, could benefit from such a novel thermoresponsive copolymer with outstanding mechanical and functional performances and an easy synthesis and scaled-up process as described in this article.
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Poliuretanos , Poliuretanos/química , Poliuretanos/farmacología , Animales , Porcinos , Humanos , Temperatura , Urea/química , Urea/farmacología , Urea/análogos & derivados , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Materiales Biocompatibles/síntesis química , Adhesivos Tisulares/química , Adhesivos Tisulares/farmacología , Adhesivos Tisulares/síntesis química , Adhesión Celular/efectos de los fármacos , Ratones , Adhesivos/química , Adhesivos/farmacologíaRESUMEN
Psychosis is a distressing symptom commonly occurring in people with dementia. To treat Parkinson's disease psychosis, pimavanserin (1), a 5-HT2A receptor inverse agonist having minimal 5-HT2C receptor affinity and no dopamine D2 receptor affinity, was approved in the United States, but not for dementia-related psychosis due to limited efficacy issues. Herein, we report on the identification of a potent and dual 5-HT2A and 5-HT2C receptor inverse agonist 8 having minimal hERG inhibition, after having demonstrated the involvement of both 5-HT2A and 5-HT2C receptors to deliver antipsychotic efficacy in an MK-801-induced locomotor model and having conducted 5-HT2A and 5-HT2C occupancy studies including a surrogate method. The introduction of a spirocyclopropyl group boosting 5-HT2C affinity in 1 followed by further optimization to control lipophilicity resulted in balanced dual potency and metabolic stability, and mitigating hERG inhibition led to 8 that showed significant antipsychotic efficacy due to the involvement of both receptors.
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Antipsicóticos , Demencia , Trastornos Psicóticos , Receptor de Serotonina 5-HT2A , Receptor de Serotonina 5-HT2C , Agonistas del Receptor de Serotonina 5-HT2 , Antipsicóticos/farmacología , Antipsicóticos/uso terapéutico , Antipsicóticos/química , Antipsicóticos/síntesis química , Animales , Receptor de Serotonina 5-HT2A/metabolismo , Humanos , Trastornos Psicóticos/tratamiento farmacológico , Agonistas del Receptor de Serotonina 5-HT2/farmacología , Agonistas del Receptor de Serotonina 5-HT2/uso terapéutico , Agonistas del Receptor de Serotonina 5-HT2/química , Receptor de Serotonina 5-HT2C/metabolismo , Demencia/tratamiento farmacológico , Relación Estructura-Actividad , Masculino , Agonismo Inverso de Drogas , Canal de Potasio ERG1/metabolismo , Canal de Potasio ERG1/antagonistas & inhibidores , Ratas , Ratones , Piperidinas/farmacología , Piperidinas/uso terapéutico , Piperidinas/química , Ratas Sprague-Dawley , Canales de Potasio Éter-A-Go-Go/antagonistas & inhibidores , Canales de Potasio Éter-A-Go-Go/metabolismo , Urea/análogos & derivadosRESUMEN
The exploration of environmentally friendly slow-release fertilizer (SRF) based on natural bio-polymers is of great importance in the development of modern agriculture and horticulture. Herein, a novel starch carbamate (SC) modified sodium alginate (SA) hydrogel (SC/SAH) was prepared utilizing as-synthesized SC and natural SA through the cationic ions crosslinking method and ultimately the corresponding slow-release fertilizer (SC/SAH-SRF) was successfully developed by immersing the dried SC/SAH matrix into saturated urea solution. Due to the low gelation temperature and high viscosity of the synthesized SC, the formed SC/SAH exhibits significantly enhanced properties including excellent water absorbency up to 8.02 g/g with considerable repeatability, abundant pore structure and high hydrophilicity compared with the neat SAH and natural starch based hydrogel (NS/SAH). Accordingly, the SC/SAH leads to higher urea loading amount â¼ 1.28 g/g. Importantly, the resultant SC/SAH-SRF also shows superior slow-release performance, yielding a cumulative urea release of only 61.6 % within 10 h and almost completely release >16 h in water, what's more, only 58.5 % of the urea releases within 25 days and exceeding 50 days for complete release in soil column assays. The slow-release of urea from SC/SAH-SRF well complies for the first-order kinetics and accomplishes via a non-Fickian diffusion process. Moreover, the pot experiment demonstrates that the SC/SAH-SRF has higher growth promotion role for the maize seedlings than those of others. Consequently, this work provides a novel strategy for preparing environmentally friendly SRF by blending modified starch and hydrogel.
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Alginatos , Carbamatos , Preparaciones de Acción Retardada , Fertilizantes , Hidrogeles , Almidón , Alginatos/química , Almidón/química , Hidrogeles/química , Carbamatos/química , Preparaciones de Acción Retardada/química , Zea mays/química , Agua/química , Urea/química , ViscosidadRESUMEN
Glycogen synthase kinase 3ß (GSK-3ß) is a potential therapeutic target for the treatment of a variety of human diseases. Here, we report the design and synthesis of a series of thieno[3,2-c]pyrazol-urea derivatives and evaluation of their GSK-3ß inhibitory activity. Among these analogues, the compound without substitution on terminal phenyl ring (3a) was found to be the most potent GSK-3ß inhibitor with an IC50 of 74.4 nM, while substitution on the terminal phenyl (3b-3p) led to decreased potency, independent of the position, size, or electronic properties of the substituents. Kinase selectivity assay revealed that 3a showed good selectivity over a panel of kinases, but was less selective over CDK1, CDK2 and CDK5. Additionally, the pharmacological properties of the synthesized compounds were investigated computationally by the SwissADME and the results showed that most of the compounds have good ADME profiles.
Asunto(s)
Diseño de Fármacos , Glucógeno Sintasa Quinasa 3 beta , Inhibidores de Proteínas Quinasas , Pirazoles , Urea , Pirazoles/química , Pirazoles/farmacología , Pirazoles/síntesis química , Humanos , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Urea/farmacología , Urea/análogos & derivados , Urea/química , Urea/síntesis química , Relación Estructura-Actividad , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/síntesis química , Inhibidores de Proteínas Quinasas/química , Estructura Molecular , Glucógeno Sintasa Quinasa 3/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3/metabolismo , Relación Dosis-Respuesta a DrogaRESUMEN
Tyrosinase inhibitors are studied in the cosmetics and pharmaceutical sectors as tyrosinase enzyme is involved in the biosynthesis and regulation of melanin, hence these inhibitors are beneficial for the management of melanogenesis and hyperpigmentation-related disorders. In the current work, a novel series of diphenyl urea derivatives containing a halo-pyridine moiety (5a-t) was synthesized via a multi-step synthesis. In vitro, tyrosinase inhibitory assay results showed that, except for two compounds, the derivatives were excellent inhibitors of human tyrosinase. The average IC50 value of the inhibitors (15.78 µM) is lower than that of kojic acid (17.3 µM) used as the reference compound, indicating that, on average, these molecules are more potent than the reference. Derivative 5a was identified as the most potent human tyrosinase inhibitor of the series, with an IC50 value of 3.5 ± 1.2 µM, approximately 5 times more potent than kojic acid. To get further insights into the nature of binding site interactions, molecular docking and molecular dynamics simulation studies were carried out. Moreover, the evaluation of in silico ADME properties showed a highly favorable profile for the synthesized compounds. These findings suggested that the further development of this class of compounds could be useful to get potent drug-like compounds that can target hyperpigmentation-related disorders.
Asunto(s)
Inhibidores Enzimáticos , Simulación del Acoplamiento Molecular , Monofenol Monooxigenasa , Piridinas , Monofenol Monooxigenasa/antagonistas & inhibidores , Monofenol Monooxigenasa/metabolismo , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/síntesis química , Inhibidores Enzimáticos/química , Humanos , Relación Estructura-Actividad , Piridinas/química , Piridinas/farmacología , Piridinas/síntesis química , Estructura Molecular , Relación Dosis-Respuesta a Droga , Urea/farmacología , Urea/análogos & derivados , Urea/química , Urea/síntesis química , Simulación de Dinámica MolecularRESUMEN
Studies have indicated that stress-related symptoms can lead to hormonal and neural changes, affecting the pain threshold and nociceptive behaviors. The precise role of orexin receptors (OX1r and OX2r) in stress-induced analgesia (SIA) remains an inquiry yet to be comprehensively elucidated. The current investigation aimed to assess the impact of acute immobilization restraint stress on pain-related behavioral responses after administering antagonists targeting OX1r and OX2r in a rat model using the tail-flick test. After a period of five to seven days post-stereotaxic surgery in CA1, the baseline tail-flick latency (TFL) was recorded for each animal. Subsequently, rats were unilaterally administered varying doses of the OX1r antagonist (SB334867; 1, 3, 10, and 30 nmol), the OX2r antagonist (TCS OX2 29; 1, 3, 10, and 30 nmol), or a vehicle (0.5 µl solution containing 12% DMSO) through an implanted cannula. Following a 5-min interval, the animals were subjected to a restraint stress (RS) lasting for 3 h. The tail-flick test was conducted after the stress exposure, and the TFLs were assessed at 60-min intervals. The findings of this study revealed that RS elicits antinociceptive responses in the tail-flick test. Microinjection of OX1r and OX2r antagonists into the CA1 attenuated RS-induced analgesia during the tail-flick test. Furthermore, the results underscored the preeminent role of OX2 receptors in modulating SIA. In conclusion, the orexin system localized within the hippocampal CA1 region may, in part, contribute to the manifestation of SIA in the context of acute pain.