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1.
J Chromatogr A ; 1735: 465308, 2024 Oct 25.
Article in English | MEDLINE | ID: mdl-39244912

ABSTRACT

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.


Subject(s)
Carbon , Hydrogen Bonding , Insecticides , Nitrogen , Solid Phase Extraction , Insecticides/analysis , Insecticides/chemistry , Insecticides/isolation & purification , Solid Phase Extraction/methods , Adsorption , Carbon/chemistry , Nitrogen/chemistry , Metal-Organic Frameworks/chemistry , Porosity , Triazines/chemistry , Triazines/isolation & purification , Limit of Detection , Urea/chemistry , Zeolites/chemistry
2.
BMC Oral Health ; 24(1): 1089, 2024 Sep 14.
Article in English | MEDLINE | ID: mdl-39277736

ABSTRACT

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.


Subject(s)
Carbamide Peroxide , Composite Resins , Dental Amalgam , Dental Materials , Dental Restoration, Permanent , Materials Testing , Peroxides , Tooth Bleaching Agents , Urea , Carbamide Peroxide/pharmacology , Peroxides/chemistry , Composite Resins/chemistry , Tooth Bleaching Agents/chemistry , Dental Amalgam/chemistry , Urea/analogs & derivatives , Urea/chemistry , Dental Restoration, Permanent/methods , Dental Materials/chemistry , Ions , Ceramics/chemistry , Humans , Time Factors
3.
Int J Mol Sci ; 25(17)2024 Aug 29.
Article in English | MEDLINE | ID: mdl-39273310

ABSTRACT

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.


Subject(s)
Aspartic Acid , Glutamic Acid , Protein Denaturation , Aspartic Acid/chemistry , Protein Denaturation/drug effects , Glutamic Acid/chemistry , Ribonuclease, Pancreatic/chemistry , Ribonuclease, Pancreatic/metabolism , Thermodynamics , Calorimetry, Differential Scanning , Entropy , Protein Stability , Guanidine/chemistry , Guanidine/pharmacology , Urea/chemistry , Urea/pharmacology , Protein Conformation
4.
Bioorg Med Chem Lett ; 112: 129932, 2024 Nov 01.
Article in English | MEDLINE | ID: mdl-39182737

ABSTRACT

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.


Subject(s)
Drug Design , Glycogen Synthase Kinase 3 beta , Protein Kinase Inhibitors , Pyrazoles , Urea , Pyrazoles/chemistry , Pyrazoles/pharmacology , Pyrazoles/chemical synthesis , Humans , Glycogen Synthase Kinase 3 beta/antagonists & inhibitors , Glycogen Synthase Kinase 3 beta/metabolism , Urea/pharmacology , Urea/analogs & derivatives , Urea/chemistry , Urea/chemical synthesis , Structure-Activity Relationship , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemical synthesis , Protein Kinase Inhibitors/chemistry , Molecular Structure , Glycogen Synthase Kinase 3/antagonists & inhibitors , Glycogen Synthase Kinase 3/metabolism , Dose-Response Relationship, Drug
5.
Bioorg Chem ; 152: 107724, 2024 Nov.
Article in English | MEDLINE | ID: mdl-39167873

ABSTRACT

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.


Subject(s)
Enzyme Inhibitors , Molecular Docking Simulation , Monophenol Monooxygenase , Pyridines , Monophenol Monooxygenase/antagonists & inhibitors , Monophenol Monooxygenase/metabolism , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Humans , Structure-Activity Relationship , Pyridines/chemistry , Pyridines/pharmacology , Pyridines/chemical synthesis , Molecular Structure , Dose-Response Relationship, Drug , Urea/pharmacology , Urea/analogs & derivatives , Urea/chemistry , Urea/chemical synthesis , Molecular Dynamics Simulation
6.
J Proteome Res ; 23(9): 3890-3903, 2024 Sep 06.
Article in English | MEDLINE | ID: mdl-39115235

ABSTRACT

Archaeological textiles represent precious remains from ancient culture; this is because of the historical and cultural importance of the information that can be obtained by such relics. However, the extremely complicated state of preservation of these textiles, which can be charred, partially or totally mineralized, with heavy soil or biological contamination, requires highly specialized and sensitive analytical tools to perform a comprehensive study. Starting from these considerations, the paper presents a combined workflow that provides the extraction of dyes and keratins and keratin-associated proteins in a single step, minimizing sampling while maximizing the amount of information gained. In the first phase, different approaches were tested and two different protocols were found suitable for the purpose of the unique workflow for dyes/keratin-proteins: a slightly modified urea protocol and a recently proposed new TCEP/CAA procedure. In the second step, after the extraction, different methods of cleanup and workflow for proteins and dyes were investigated to develop protocols that did not result in a loss of aliquots of the analytes of interest and to maximize the recovery of both components from the extracting solution. These protocols investigated the application of two types of paramagnetic beads, unmodified and carboxylate-coated hydrophilic magnetic beads, and dialysis and stage-tip protocols. The newly designed protocols have been applied to cochineal, weld, orchil, kermes, and indigo keratin-based dyed samples to evaluate the effectiveness of the protocols on several dye sources. These protocols, based on a single extraction step, show the possibility of investigating dyes and keratins from a unique sample of 1 mg or lesser, with respect to the thresholds of sensitivity and accuracy required in the study of textile artifacts of historical and artistic values.


Subject(s)
Coloring Agents , Keratins , Textiles , Keratins/chemistry , Keratins/isolation & purification , Textiles/analysis , Coloring Agents/chemistry , Coloring Agents/analysis , Urea/chemistry
7.
Mikrochim Acta ; 191(8): 505, 2024 08 04.
Article in English | MEDLINE | ID: mdl-39097544

ABSTRACT

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.


Subject(s)
Carbon , Copper , Fluorescent Dyes , Limit of Detection , Quantum Dots , Spectrometry, Fluorescence , Urea , Urease , Urea/analysis , Urea/chemistry , Urease/chemistry , Copper/chemistry , Carbon/chemistry , Hydrogen-Ion Concentration , Quantum Dots/chemistry , Fluorescent Dyes/chemistry , Spectrometry, Fluorescence/methods , Animals , Milk/chemistry , Azo Compounds/chemistry , Food Contamination/analysis
8.
Int J Mol Sci ; 25(15)2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39126049

ABSTRACT

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.


Subject(s)
Cryoelectron Microscopy , DNA, Viral , Urea , DNA, Viral/genetics , Urea/pharmacology , Urea/chemistry , Models, Molecular , Viral Proteins/chemistry , Viral Proteins/metabolism
9.
Int J Biol Macromol ; 277(Pt 2): 134118, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39098460

ABSTRACT

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.


Subject(s)
Bentonite , Delayed-Action Preparations , Fertilizers , Pectins , Soil , Water , Pectins/chemistry , Water/chemistry , Soil/chemistry , Bentonite/chemistry , Delayed-Action Preparations/chemistry , Biodegradation, Environmental , Triticum/chemistry , Urea/chemistry
10.
ACS Appl Mater Interfaces ; 16(33): 43180-43188, 2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39110843

ABSTRACT

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.


Subject(s)
Polyurethanes , Polyurethanes/chemistry , Polyurethanes/pharmacology , Animals , Swine , Humans , Temperature , Urea/chemistry , Urea/pharmacology , Urea/analogs & derivatives , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemical synthesis , Tissue Adhesives/chemistry , Tissue Adhesives/pharmacology , Tissue Adhesives/chemical synthesis , Cell Adhesion/drug effects , Mice , Adhesives/chemistry , Adhesives/pharmacology
11.
Molecules ; 29(16)2024 Aug 21.
Article in English | MEDLINE | ID: mdl-39203016

ABSTRACT

Herein, we report a new strategy for the design of antibiotic agents based on the electrostatic interaction and hydrogen bonding, highlighting the significance of hydrogen bonding and the increased recognition sites in facilitating the interaction with bacterial cell membranes and DNA. A series of quaternary ammonium functionalized urea-based anion receptors were studied. While the monodentate mono-urea M1, bisurea M2, and trisurea M3 failed to break through the cell membrane barrier and thus could not kill bacteria, the extended bidentate dimers D1-D3 presented gradually increased membrane penetrating capabilities, DNA conformation perturbation abilities, and broad-spectrum antibacterial activities against E. coli, P. aeruginosa, S. aureus, E. faecalis, and S. epidermidis.


Subject(s)
Anti-Bacterial Agents , Cell Membrane , Hydrogen Bonding , Urea , Urea/chemistry , Urea/pharmacology , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Cell Membrane/metabolism , Cell Membrane/drug effects , Microbial Sensitivity Tests , DNA, Bacterial/metabolism , Bacteria/drug effects , Bacteria/metabolism , Quaternary Ammonium Compounds/chemistry , Quaternary Ammonium Compounds/pharmacology , Escherichia coli/drug effects
12.
J Contam Hydrol ; 266: 104414, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39154557

ABSTRACT

Composite with a high specific surface area of 224.62 m2 g-1 was prepared by adding urea as a nitrogen source to hazelnut shell biochar (HSB). Nitrogen doping significantly enhanced the ability of biochar for Cr(VI) elimination, achieving twice the removal efficiency of unmodified biochar. The impacts of varying the pH and initial concentrations on Cr(VI) removal by urea-modified biochar (N-HSB) were investigated. The Cr(VI) removal by N-HSB was better described by intra particle diffusion model and pseudo-second order kinetic model under optimal conditions. Furthermore, XPS, FTIR, SEM, and BET analyses were used to verify the pivotal roles of oxygen- and nitrogen-containing functional groups. Electrostatic attraction, redox reaction, and complexation constituted the principal mechanisms facilitating Cr(VI) elimination by N-HSB. This study demonstrated that the modification of biochar with urea as a nitrogen source represented a promising strategy for enhancing the removal capacity of biochar for Cr(VI) in aqueous environments.


Subject(s)
Charcoal , Chromium , Corylus , Urea , Water Pollutants, Chemical , Charcoal/chemistry , Corylus/chemistry , Chromium/chemistry , Urea/chemistry , Water Pollutants, Chemical/chemistry , Adsorption , Kinetics , Water Purification/methods , Hydrogen-Ion Concentration
13.
Anal Methods ; 16(33): 5676-5683, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39118596

ABSTRACT

In this study, we describe a rapid and high-throughput smartphone-based digital colorimetric method for determining urea in milk. A compact and cost-effective 3D-printed image box microplate-based system was designed to measure multiple samples simultaneously, using minimal sample and reagent volumes. The apparatus was applied for the quantification of urea in milk based on its reaction with p-dimethylaminobenzaldehyde (DMAB). The predictive performance of calibration was evaluated using RGB and different colour models (CMYK, HSV, and CIELAB), with the average blue (B) values of the RGB selected as the analytical signal for urea quantification. Under optimized conditions, a urea concentration linear range from 50 to 400 mg L-1 was observed, with a limit of detection (LOD) of 15 mg L-1. The values found with the smartphone-based DIC procedure are in good agreement with spectrophotometric (spectrophotometer and microplate treader) and reference method (mid-infrared spectroscopy) values. This proposed approach offers an accessible and efficient solution for digital image colorimetry, with potential applications for various target analytes in milk and other fields requiring high-throughput colorimetric analysis.


Subject(s)
Colorimetry , Milk , Printing, Three-Dimensional , Smartphone , Urea , Milk/chemistry , Colorimetry/methods , Colorimetry/instrumentation , Animals , Urea/analysis , Urea/chemistry , Limit of Detection , Benzaldehydes/chemistry , Benzaldehydes/analysis
14.
Channels (Austin) ; 18(1): 2396339, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39212541

ABSTRACT

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.


Subject(s)
Cell Movement , Epithelial-Mesenchymal Transition , Protein Serine-Threonine Kinases , TRPM Cation Channels , Urea , Humans , TRPM Cation Channels/metabolism , TRPM Cation Channels/genetics , TRPM Cation Channels/antagonists & inhibitors , Cell Movement/drug effects , Epithelial-Mesenchymal Transition/drug effects , Urea/analogs & derivatives , Urea/pharmacology , Urea/chemistry , Cell Line, Tumor , Protein Serine-Threonine Kinases/metabolism , Protein Serine-Threonine Kinases/genetics , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Molecular Docking Simulation , MCF-7 Cells
15.
Lab Chip ; 24(15): 3728-3737, 2024 07 23.
Article in English | MEDLINE | ID: mdl-38953748

ABSTRACT

We present the development and validation of an impedance-based urine osmometer for accurate and portable measurement of urine osmolality. The urine osmolality of a urine sample can be estimated by determining the concentrations of the conductive solutes and urea, which make up approximately 94% of the urine composition. Our method utilizes impedance measurements to determine the conductive solutes and urea after hydrolysis with urease enzyme. We built an impedance model using sodium chloride (NaCl) and urea at various known concentrations. In this work, we validated the accuracy of the impedance-based urine osmometer by developing a proof-of-concept first prototype and an integrated urine dipstick second prototype, where both prototypes exhibit an average accuracy of 95.5 ± 2.4% and 89.9 ± 9.1%, respectively in comparison to a clinical freezing point osmometer in the hospital laboratory. While the integrated dipstick design exhibited a slightly lower accuracy than the first prototype, it eliminated the need for pre-mixing or manual pipetting. Impedance calibration curves for conductive and non-conductive solutes consistently yielded results for NaCl but underscored challenges in achieving uniform urease enzyme coating on the dipstick. We also investigated the impact of storing urine at room temperature for 24 hours, demonstrating negligible differences in osmolality values. Overall, our impedance-based urine osmometer presents a promising tool for point-of-care urine osmolality measurements, addressing the demand for a portable, accurate, and user-friendly device with potential applications in clinical and home settings.


Subject(s)
Electric Impedance , Urea , Urease , Urea/urine , Urea/chemistry , Osmolar Concentration , Hydrolysis , Humans , Urease/metabolism , Urease/chemistry , Urinalysis/instrumentation , Equipment Design
16.
Comput Biol Chem ; 112: 108131, 2024 Oct.
Article in English | MEDLINE | ID: mdl-38968781

ABSTRACT

Human glutaminyl cyclase (hQC) inhibitors have great potential to be used as anti- Alzheimer's disease (AD) agents by reducing the toxic pyroform of ß-amyloid in the brains of AD patients. The four-dimensional quantitative structure activity relationship (4D-QSAR) model of N-substituted urea/thioureas was established with satisfying predictive ability and statistical reliability (Q2 = 0.521, R2 = 0.933, R2prep = 0.619). By utilizing the developed 4D-QSAR model, a set of new N-substituted urea/thioureas was designed and evaluated for their Absorption Distribution Metabolism Excretion and Toxicity (ADMET) properties. The results of molecular dynamics (MD) simulations, Principal component analysis (PCA), free energy landscape (FEL), dynamic cross-correlation matrix (DCCM) and molecular mechanics generalized Born Poisson-Boltzmann surface area (MM-PBSA) free energy calculations, revealed that the designed compounds were remained stable in protein binding pocket and compounds b ∼ f (-35.1 to -44.55 kcal/mol) showed higher binding free energy than that of compound 14 (-33.51 kcal/mol). The findings of this work will be a theoretical foundation for further research and experimental validation of urea/thiourea derivatives as hQC inhibitors.


Subject(s)
Aminoacyltransferases , Enzyme Inhibitors , Molecular Dynamics Simulation , Quantitative Structure-Activity Relationship , Thiourea , Urea , Humans , Thiourea/chemistry , Thiourea/pharmacology , Thiourea/analogs & derivatives , Urea/chemistry , Urea/analogs & derivatives , Urea/pharmacology , Aminoacyltransferases/antagonists & inhibitors , Aminoacyltransferases/metabolism , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/pharmacology , Molecular Structure , Drug Design
17.
Molecules ; 29(13)2024 Jun 26.
Article in English | MEDLINE | ID: mdl-38998987

ABSTRACT

The inhibition of soluble epoxide hydrolase (sEH) can reduce the level of dihydroxyeicosatrienoic acids (DHETs) effectively maintaining endogenous epoxyeicosatrienoic acids (EETs) levels, resulting in the amelioration of inflammation and pain. Consequently, the development of sEH inhibitors has been a prominent research area for over two decades. In the present study, we synthesized and evaluated sulfonyl urea derivatives for their potential to inhibit sEH. These compounds underwent extensive in vitro investigation, revealing their potency against human and mouse sEH, with 4f showing the most promising sEH inhibitory potential. When subjected to lipopolysaccharide (LPS)-induced acute lung injury (ALI) in studies in mice, compound 4f manifested promising anti-inflammatory efficacy. We investigated the analgesic efficacy of sEH inhibitor 4f in a murine pain model of tail-flick reflex. These results validate the role of sEH inhibition in inflammatory diseases and pave the way for the rational design and optimization of sEH inhibitors based on a sulfonyl urea template.


Subject(s)
Enzyme Inhibitors , Epoxide Hydrolases , Urea , Epoxide Hydrolases/antagonists & inhibitors , Epoxide Hydrolases/metabolism , Animals , Mice , Humans , Urea/pharmacology , Urea/analogs & derivatives , Urea/chemistry , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/chemical synthesis , Anti-Inflammatory Agents/therapeutic use , Lipopolysaccharides , Structure-Activity Relationship , Solubility , Disease Models, Animal , Pain/drug therapy
18.
Langmuir ; 40(31): 16502-16510, 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39039728

ABSTRACT

An oral sorbent with high capacity for NH4+ is desirable in lowering the blood urea level and mitigating the dialysis burden for end-stage kidney disease (ESKD) patients. Zirconium phosphate (ZrP) is an amorphous cation ion exchanger with high NH4+ binding capacity as a sorbent material, but its selectivity to remove NH4+ is limited in the presence of other competing ions in water solution. We previously have developed a gas-permeable and hydrophobic perfluorocarbon coating on ZrP, which improves ZrP's NH4+ selectivity. However, the coating preparation procedure, a wet chemistry approach, is complicated and time-consuming, and more importantly, the large amount of usage of acetone poses a concern for the application of ZrP as an oral sorbent. In this study, we developed a solventless coating protocol that effectively coats ZrP with tetraethyl orthosilicate (TEOS) and 1H,1H,2H,2H-perfluorooctyltriethoxysilane (FOTS) via thermal vapor deposition (TVD) in a simplified manner. X-ray photoelectron spectroscopy (XPS) and contact angle measurements verify the two coatings are successfully deposited on the ZrP surface, and the coating condition was optimized based on an in vitro static binding study. The dynamic binding study of competing ions on Na-loaded ZrP with TVD coatings yields a maximum NH4+ removal (∼3.2 mequiv/g), which can be improved to ∼4.7 mequiv/g if H-loaded ZrP under the same coating condition is used in basic stock solutions. More importantly, both materials barely remove Ca2+ and show excellent acid resistance. The significant improvement in the NH4+ binding capacity and selectivity reported here establishes a highly promising surface modification approach to optimize oral sorbents for ESKD patients.


Subject(s)
Hydrophobic and Hydrophilic Interactions , Urea , Zirconium , Zirconium/chemistry , Urea/chemistry , Membranes, Artificial , Humans , Adsorption , Renal Insufficiency/therapy
19.
Biomacromolecules ; 25(8): 4843-4855, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-38985577

ABSTRACT

Tannin, after lignin, is one of the most abundant sources of natural aromatic biomolecules. It has been used and chemically modified during the past few decades to create novel biobased materials. This work intended to functionalize for the first time quebracho Tannin (T) through a simple phosphorylation process in a urea system. The phosphorylation of tannin was studied by Fourier transform infrared spectroscopy (FTIR), NMR, inductively coupled plasma optical emission spectroscopy (ICP-OES), and X-ray fluorescence spectrometry (XRF), while further characterization was performed by scanning electron microscopy/energy dispersive X-ray spectroscopy (SEM/EDX) and thermogravimetric analysis (TGA) to investigate the morphology, composition, structure, and thermal degradation of the phosphorylated material. Results indicated the occurrence of phosphorylation, suggesting the insertion of phosphate-containing groups into the tannin structure, revealing a high content of phosphate for modified tannin (PT). This elevated phosphorus content serves as evidence for the successful incorporation of phosphate groups through the functionalization process. The corresponding PT and T were employed as adsorbents for methylene blue (MB) removal from aqueous solutions. The results revealed that the Langmuir isotherm model effectively represents the adsorption isotherms. Additionally, the pseudo-second-order model indicates that chemisorption predominantly controls the adsorption mechanism. This finding also supports the fact that the introduced phosphate groups via the phosphorylation process significantly contributed to the improved adsorption capacity. Under neutral pH conditions and at room temperature, the material achieved an impressive adsorption capacity of 339.26 mg·g-1 in about 2 h.


Subject(s)
Methylene Blue , Tannins , Urea , Methylene Blue/chemistry , Methylene Blue/isolation & purification , Tannins/chemistry , Urea/chemistry , Phosphorylation , Adsorption , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification
20.
Int J Biol Macromol ; 277(Pt 2): 134190, 2024 Oct.
Article in English | MEDLINE | ID: mdl-39069036

ABSTRACT

Plants require essential nutrients to grow, which soil alone cannot provide. Chemical fertilizers like urea supply the necessary nutrients, including nitrogen. They quickly dissolve in water and can contaminate it with nitrate and nitrite, which can cause diseases. Slow-release fertilizers are a better option to reduce environmental risks. Researchers are exploring cheap and biodegradable alternatives, such as lignin. A critical discussion in the coated urea fertilizer is modeling the nitrogen diffusion process in the coating, which predicts the system's behavior. This article uses lignin sulfonate to coat urea fertilizer, which should first be acetylated with decanoyl chloride. One of the critical parameters is the diffusion coefficient (D). D is determined using the mass transfer flux and the completion time of the effective substance, and with its help, the graph of the total mass transferred from the membrane in a specific time (Mt) is determined. D equals 6.298813 × 10-8 cm2/s using the time lag method. Also, with the fixed-point convergence method, 5.8849 × 10-8 cm2/s was obtained, which has about 0.80 % error with the D obtained by the time lag method. The Mt obtained from the analytical method and the experimental data coincides with a minimal error, which indicates high accuracy.


Subject(s)
Fertilizers , Lignin , Urea , Fertilizers/analysis , Lignin/chemistry , Urea/chemistry , Diffusion , Acetylation , Delayed-Action Preparations/chemistry
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