Search Results (3,761)

Anticoagulants can complicate the interpretation of routine and specialised coagulation assays. Several methodologies have been developed to minimise or eliminate anticoagulant-associated interferences; however, no ‘universal methodology’ that encompasses different anticoagulant classes is currently available. Ciraparantag is a promising reversal agent that can bind both direct oral anticoagulants (DOACs) and heparin-like anticoagulants. As such, we aimed to investigate whether ciraparantag could be employed as a ‘universal’ anticoagulant chelator in vitro. Human plasma was spiked with ascending concentrations of ciraparantag, with or without DOACs or heparin, and assayed for routine coagulation parameters. Ciraparantag had minimal effects on coagulation testing when added to human plasma at concentrations similar to pharmacokinetic maxima; however, ciraparantag did not remove DOAC- or heparin-associated activities in vitro, which was likely due to the preferential chelation of anionic substances in the coagulation reagents. In contrast, DOAC-Stop™, a commercial activated charcoal-based adsorbent, efficiently removed both DOAC- and ciraparantag-associated interferences. In conclusion, although ciraparantag is not effective as a ‘universal’ anticoagulant chelator in vitro, we report that activated charcoal-based adsorbents may be clinically useful in situations where laboratory investigations are complicated by the presence of DOACs and/or ciraparantag. Full article

2,6-Dipicolinoylbis(N,N-dialkylthioureas) and H₂L^R2 react with uranyl salts and a supporting base (e.g., NEt₃) under formation of monomeric or oligomeric complexes of the compositions [UO₂(L^R2)(solv)] (solv = donor solvents) or [{UO₂(L^R2)(µ₂-OMe)}₂]^2–. In such complexes, the uranyl ions are commonly coordinated by the “hard” O,N,O or N,N,N donor atom sets of the central ligand unit and the lateral sulfur donor atoms remain uncoordinated. Their individual structures, however, depend on the reaction conditions, particularly on the equivalents of NEt₃ used. An unprecedented, selective hydrolysis of the uranium-coordinating bis(thioureato) ligands results in an S/O donor atom exchange at exclusively one thiourea side-arm, when an excess of NEt₃ is used. The resulting trimeric uranyl complexes are isolated in fair yields and have a composition of [(UO₂)₃(L^2Et2)₂(µ₂–OR)(µ₃-O)]^–. H₂L^2Et2 represents the newly formed 2,6-dipicolinoyl(N,N-diethylthiourea)(N,N-diethylurea) and R = H, Me, or Et. {L^2Et2}^2– binds to the uranyl units via the pyridine ring, the dialkylurea arm, and the central carbonyl groups, while the thiourea unit remains uncoordinated. The central cores of the products consist of oxido-centered triangular {(UO₂)₃O}⁴⁺ units. The observed reactivity is metal-driven and corresponds mechanistically most probably to a classical metal-catalyzed hydrodesulfurization. The hydrolytic thiourea/urea conversion is only observed in the presence of uranyl ions. The products were isolated in crystalline form and studied spectroscopically and by X-ray diffraction. The experimental findings are accompanied by DFT calculations, which help to understand the energetic implications in such systems. Full article

In the present study, polysaccharides were isolated from the leaves (WSPRaL) and stems (WSPRaS) of Rhamnus alaternus with yields of 3% and 3.25% for WSPRaS and WSPRaL, respectively. Crude WSPRaL was composed of proteins (260.740 ± 0.98 µg/mg), lipids (53.34 ± 2.38 µg/mg), total sugars (482.716 ± 3.02 µg/mg), and reducing sugars (420.240 ± 1.68 µg/mg). In contrast, WSPRaS contained proteins (269.629 ± 1.48 µg/mg), lipids (13.33 ± 0.28 µg/mg), total sugars (569.135 ± 3.82 µg/mg), and reducing sugars (531.732 ± 2.59 µg/mg). FTIR, TLC, and HPLC analyses revealed that the carbohydrate fraction of WSPRaS consisted mainly of glucuronic acid, glucose, galactose, xylose, mannose, and arabinose, whereas WSPRaL consisted of galacturonic acid, sucrose, glucose, rhamnose, xylose, mannose, and arabinose. Scanning electron microscopy (SEM) analysis was used to determine the microstructure of the water-soluble polysaccharides. The physicochemical properties were evaluated using Fourier transform infrared (FT-IR) spectroscopy and ultraviolet‒visible (UV‒visible) absorption spectroscopy. The total antioxidant activities of the crude polysaccharides were evaluated using various assays: DPPH radical scavenging (IC₅₀ WSPRaL = 615 ± 2.05 µg/mL, IC₅₀ WSPRaS = 628 ± 2.38 µg/mL), ABTS radical scavenging (470 ± 5.78 µg/mL and 559 ± 4.32 µg/mL for WSPRaL and WSPRaS, respectively), reducing power (IC₅₀ WSPRaS = 141.76 ± 3.16 µg/mL, IC₅₀ WSPRaL = 203.89 ± 1.07 µg/mL), and chelating capacity (IC₅₀ WSPRaS = 225 ± 1.75 µg/mL, IC₅₀ WSPRaL = 219 ± 2.51 µg/mL). In addition, the antibacterial and biofilm inhibitory activities of both polysaccharides were tested against pathogenic strains, and the polysaccharides significantly inhibited plant growth. Overall, the results indicate that the crude polysaccharides extracted from R. alaternus are promising for use as functional and bioactive ingredients in the food and nutraceutical industries. These results highlight the potential of both polysaccharides as natural products in various sectors, including food, cosmetics, pharmaceuticals, and medicine, due to their significant biological properties. Full article

Targeted radionuclide therapy (TRT) for internal pathway-directed treatment is a game changer for precision medicine. TRT improves tumor control while minimizing damage to healthy tissue and extends the survival for patients with cancer. The application of theranostic-paired TRT along with cellular phenotype and genotype correlative analysis has the potential for malignant disease management. Chelation chemistry is essential for the development of theranostic-paired radiopharmaceuticals for TRT. Among image-guided TRT, ⁶⁸Ga and ^99mTc are the current standards for diagnostic radionuclides, while ¹⁷⁷Lu and ²²⁵Ac have shown great promise for β- and α-TRT, respectively. Their long half-lives, potent radiobiology, favorable decay schemes, and ability to form stable chelation conjugates make them ideal for both manufacturing and clinical use. The current challenges include optimizing radionuclide production processes, coordinating chelation chemistry stability of theranostic-paired isotopes to reduce free daughters [this pertains to ²²⁵Ac daughters ²²¹Fr and ²¹³Bi]-induced tissue toxicity, and improving the modeling of micro dosimetry to refine dose–response evaluation. The empirical approach to TRT delivery is based on standard radionuclide administered activity levels, although clinical trials have revealed inconsistent outcomes and normal-tissue toxicities despite equivalent administered activities. This review presents the latest optimization methods for chelation-based theranostic radiopharmaceuticals, advancements in micro-dosimetry, and SPECT/CT technologies for quantifying whole-body uptake and monitoring therapeutic response as well as cytogenetic correlative analyses. Full article

The use of deep eutectic solvents (DESs) as catalysts presents indisputable advantages, for example, their simplicity of preparation, high biodegradability, and recyclability, as well as zero toxicity and their effectiveness as environmentally friendly reaction media. However, aspects related to their reactivity and catalytic activity are still unclear. In this work, we explore the versatility of ChCl/ZnCl₂ DES in the formation of C-C bonds through the Michael-type addition of pyrrole to maleimide, where ChCl/ZnCl₂ DES leads to catalysis and chelation of the substrates, thus describing a recommended method for the construction of C-C bonds with high atomic economy. We describe experimental and theoretical aspects that explain the ability of ChCl/ZnCl₂ DES in the presence of water to act as a catalyst in the formation of C-C bonds between pyrrole and maleimide. The potential energy surface showed that the ChCl and the zinc-zincate species 2ZnCl₂·3H₂O, formed by the interaction between zinc chloride and water, decrease the relative free Gibbs energy values for all the species involved in the reaction mechanism (TSs, intermediates, product), favoring the kinetics and thermodynamics of the Michael addition. Full article

As some previously reported studies have proven that amodiaquine, in addition to its primary antimalarial activity, also has potential for new applications such as the inhibition of cholinesterases, in our study we focused on the evaluation of the influence of different substituents in the aminoquinoline part of the amodiaquine structure on the inhibition of human acetylcholinesterase and butyrylcholinesterase to investigate the possibility for their use as drugs for the treatment of AD. We synthesized a series of amodiaquine derivatives bearing H-, F-, CF₃-, NO₂-, CN-, CO₂H- or CH₃O- groups on the aminoquinoline ring, and determined that all of the tested derivatives were very potent inhibitors of both cholinesterases, with inhibition constants (K_i) in the nM and low μM range and with prominent selectivity (up to 300 times) for the inhibition of acetylcholinesterase. All compounds displayed an ability to chelate biometal ions Fe²⁺, Zn²⁺ and Cu²⁺ and an antioxidant power comparable to that of standard antioxidants. Most of the compounds were estimated to be able to cross the blood–brain barrier by passive transport and were nontoxic toward cells that represent the models of individual organs. Considering all these beneficial features, our study has singled out compound 5, the most potent AChE inhibitor with a CH₃O- on C(7) position, followed by 6 and 14, compounds without substituent or hydroxyl groups in the C(17) position, respectively, as the most promising compounds from the series which could be considered as potential multi-target drugs for the treatment of AD. Full article

Methicillin-resistant Staphylococcus aureus (MRSA) is associated with the acquisition of nosocomial infections, community-acquired infections, and infections related to livestock animals. In the pursuit of molecular targets in the development process of antibacterial drugs, enzymes within the shikimate pathway, such as 3-dehydroquinate dehydratase (DHQD), are regarded as promising targets. Therefore, through biochemical and biophysical techniques, in the present work, the characterization of DHQD from MRSA (SaDHQD) was performed. The kinetic results showed that the enzyme had a V_max of 107 μmol/min/mg, a K_m of 54 μM, a k_cat of 48 s⁻¹, and a catalytic efficiency of 0.9 μM⁻¹ s⁻¹. Within the biochemical parameters, the enzyme presented an optimal temperature of 55 °C and was thermostable at temperatures from 10 to 20 °C, being completely inactivated at 60 °C in 10 min. Furthermore, SaDHQD showed an optimal pH of 8.0 and was inactivated at pH 4.0 and 12.0. Moreover, the activity of the enzyme was affected by the presence of ions, surfactants, and chelating agents. The thermodynamic data showed that the rate of inactivation of the enzyme was a temperature-dependent process. Furthermore, the enthalpy change, entropy change, and Gibbs free energy change of inactivation were positive and practically constant, which suggested that the inactivation of SaDHQD by temperature was driven principally by enthalpic contributions. These results provide, for the first time, valuable information that contributes to the knowledge of this enzyme and will be useful in the search of SaDHQD inhibitors that can serve as leads to design a new drug against MRSA to combat antibiotic resistance. Full article

Background/Objectives: Hypertension and its associated complications, such as cardiac remodeling and dysfunction, continue to impose a significant burden on global healthcare. Nutritional interventions have been recognized as playing a crucial role in addressing this devastating condition termed a ‘silent killer’. Plant-based proteins could potentially be utilized as a non-pharmacological strategy to combat hypertension and its related risk factors. In this study, we investigated the efficacy of an oat protein diet in managing hypertension and cardiac abnormalities. Methods: Four-week-old male spontaneously hypertensive rats (SHRs) and Wistar–Kyoto (WKY) rats were fed a regular diet with casein as a protein source or an oat-protein-based diet for 16 weeks. Twenty-week-old male SHRs showed high blood pressure (BP), cardiac remodeling, cardiac dysfunction, higher levels of markers of oxidative stress [malondialdehyde (MDA)] and inflammation [tumor necrosis factor-α (TNF-α)], as well as lower levels of a marker of vascular function (nitric oxide). Results: The oat protein diet was able to significantly lower high BP, prevent cardiac remodeling and dysfunction, improve the levels of nitric oxide, and reduce the levels of TNF-α. Oat protein, after in vitro gastrointestinal digestion, also exhibited angiotensin-converting enzyme inhibition and significantly higher antioxidant activity than casein when assessed with the 2,2-diphenyl-1-picrylhydrazyl and the iron-chelating assays in vitro. Conclusions: oat protein lowers BP and prevents cardiac remodeling and dysfunction partly via improving the levels of nitric oxide and TNF-αin SHRs. Its high antioxidant potential could contribute to the observed cardiovascular effects. Full article

Estrogen is a steroid hormone that plays a key role in regulating many physiological processes, such as follicle activation and development and oocyte maturation in mammals. Ca²⁺ is crucial in oogenesis, oocyte maturation, ovulation, and fertilization. However, the mechanism by which estrogen regulates Ca²⁺ during oocyte maturation in mice has not been reported. This study revealed that Ca²⁺ levels in oocytes significantly increase during the 4–12 h period in vitro. Oocytes treated with 0.1 µM estrogen and 1 µM G1, a G-protein-coupled estrogen receptor (GPER) agonist, showed significantly increased Ca²⁺ levels, while treatment with 1 µM G15, an antagonist of GPER, significantly decreased Ca²⁺ levels. Notably, estrogen regulates Ca²⁺ in oocytes through the GPER pathway and promotes the expression of the Ca²⁺-producing protein EPAC1. In addition, estrogen alleviates the inhibitory effect of the Ca²⁺ chelator BAPTA-AM during oocyte maturation by promoting Ca²⁺ production. Furthermore, estrogen can promote the expression of the mitochondrial generation-associated protein SIRT1 through the GPER pathway, alleviate mitochondrial oxidative damage caused by BAPTA-AM, and restore the mitochondrial membrane potential level. Collectively, this study demonstrates that estrogen can regulate Ca²⁺ through the GPER-EPAC1 pathway and promote the expression of SIRT1, which promotes oocyte mitochondrial function during oocyte maturation. Full article

A simple and innovative method was introduced for the production of green and recoverable flame-retardant cotton fabrics, where sulfonated cotton fabric (COT-SC) was synthesized by oxidizing cotton fabric with sodium periodate, followed by a sulfonation step with sodium bisulfite to provide active sites, which further chelated barium ions (Ba²⁺) to achieve flame retardancy. The morphological and structural characterizations of the fabricated cotton fabrics (COT-SC-Ba) demonstrated that the cleavage of C₂-C₃ free hydroxy groups within the cellulose macromolecule was chemically modified for grafting a considerable number of sulfonic acid groups, and Ba²⁺ ions were effectively immobilized on the macromolecule of the cotton fabric through a chelation effect. Results from cone calorimeter tests (CCTs) revealed that COT-SC-Ba became nonflammable, displayed a delayed ignition time, and decreased the values of the heat release rate (HRR), total smoke release (TSR), effective heat of combustion (EHC), and CO/CO₂ ratio. TG/DTG analysis demonstrated that COT-SC-Ba possessed greater thermal stability, fewer flammable volatiles, and more of a char layer during burning than that of the original cotton fabric. Its residual mass was increased from 0.02% to 26.9% in air and from 8.05% to 26.76% in N₂, respectively. The COT-SC-Ba not only possessed a limiting oxygen index (LOI) of up to 34.4% but could also undergo vertical burning tests evidenced by results such as the non-afterflame, non-afterglow, and a mere 75 mm char length. Those results demonstrated that the combination of SO₃⁻ and Ba²⁺ promoted the formation of a char layer. Moreover, cotton fabric regained its superior flame retardancy after being washed and re-chelated with Ba²⁺. Additional characteristics of the cotton fabric, such as the rupture strength, white degree, and hygroscopicity, were maintained at an acceptable level. In conclusion, this research can offer a fresh perspective on the design and development of straightforward, efficient, eco-friendly, and recoverable fire-retardant fabrics. Full article

The delicate balance of trace mineral supplementation is critical for optimizing rumen function and overall ruminant health. This study evaluated the solubility of an advanced chelate technology-based supplement and assessed its impact on rumen degradability and apparent total tract digestibility (ATTD) when replacing inorganic sources. The solubility of the advanced trace minerals supplement (ACTM) was assessed at pH 5 and pH 2. In situ ruminal degradability of dry matter (DM), organic matter (OM), and fiber fractions was evaluated using two fistulated rams fed diets supplemented with either ACTM or inorganic trace minerals. ATTD was determined in 6 lambs fed diets supplemented with 100% ACTM, 50% ACTM, and 50% inorganic (50% ACTM), or 100% inorganic sources in a Latin square design. Results showed solubilities ranging from 6.75% to 11.81% at pH 5, increasing to 69.24% to 80.47% at pH 2. ACTM supplementation significantly enhanced the rumen degradability of neutral detergent fiber (NDF) and acid detergent fiber (ADF) at 6 h of incubation (p ≤ 0.05). The 100% ACTM treatment significantly decreased rumen pH (p = 0.051) and improved DM, OM, NDF, and ADF digestibility, as well as trace mineral absorbability compared to 100% inorganic (p ≤ 0.05). These findings highlight the potential of ACTM supplementation to enhance ruminal degradability, promote better trace mineral absorption, and improve the ATTD of nutrients compared to inorganic sources. Full article

Elevated brain iron levels are characteristic of many neurodegenerative diseases. As an iron chelator with short biological half-life, deferiprone leads to agranulocytosis and neutropenia with a prolonged therapeutic course. Its inclusion in sustained-release dosage forms may reduce the frequency of administration. On the other hand, when administered by an alternative route of administration, such as the nasal route, systemic exposure to deferiprone will be reduced, thereby reducing the occurrence of adverse effects. Direct nose-to-brain delivery has been raised as a non-invasive strategy to deliver drugs to the brain, bypassing the blood–brain barrier. The aim of the study was to develop and characterize nanocomposite microspheres suitable for intranasal administration by combining nano- and microparticle-based approaches. Nanoparticles with an average particle size of 213 ± 56 nm based on the biodegradable polymer poly-ε-caprolactone were developed using the solvent evaporation method. To ensure the deposition of the particles in the nasal cavity and avoid exhalation or deposition into the small airways, the nanoparticles were incorporated into composite structures of sodium alginate obtained by spray drying. Deferiprone demonstrated sustained release from the nanocomposite microspheres and high iron-chelating activity. Full article

Background: Invasive aspergillosis (IA) is a deadly fungal lung infection. Antifungal resistance and treatment side effects are major concerns. Iron chelators are vital for IA management, but systemic use can cause side effects. We developed nanoparticles (NPs) to selectively deliver the iron chelator deferasirox (DFX) for IA treatment. Methods: DFX was encapsulated in poly(lactic-co-glycolic acid) (PLGA) NPs using a single emulsion solvent evaporation method. The NPs were characterized by light scattering and electron microscopy. DFX loading efficiency and release were assessed spectrophotometrically. Toxicity was evaluated using SRB, luciferase, and XTT assays. Therapeutic efficacy was tested in an IA mouse model, assessing fungal burden by qPCR and biodistribution via imaging. Results: DFX-NPs had a size of ~50 nm and a charge of ~−30 mV, with a loading efficiency of ~80%. Release kinetics showed DFX release via diffusion and bioerosion. The EC50 of DFX-NPs was significantly lower (p < 0.001) than the free drug, and they were significantly less toxic (p < 0.0001) in mammalian cell cultures. In vivo, NP treatment significantly reduced Af burden (p < 0.05). Conclusion: The designed DFX-NPs effectively target and kill Af with minimal toxicity to mammalian cells. The significant in vivo therapeutic efficacy suggests these NPs could be a safe and effective treatment for IA. Full article

Calcium-chelated polysaccharides have been increasingly considered as promising calcium supplements. In this study, degraded fucoidans (DFs) with different molecular weights (Mws) were prepared after UV/H₂O₂ treatment; their calcium-chelating capacities and intestinal absorption properties were also investigated. The results showed that the calcium-chelating capacities of DFs were improved with a decrease in Mw. This was mainly ascribed to the increased carboxyl content, which was caused by free-radical-mediated degradation. Meanwhile, the conformation of DF changed from a rod-like chain to a shorter and softer chain. The thermodynamic analysis demonstrated that DF binding to calcium was spontaneously driven by electrostatic interactions. Additionally, DF-Ca chelates with lower Mw showed favorable transport properties across a Caco-2 cell monolayer and could effectively accelerate the calcium influx through intestinal enterocytes. Furthermore, these chelates also exhibited a protective effect on the epithelial barrier by alleviating damage to tight junction proteins. These findings provide an effective free-radical-related approach for the development of polysaccharide-based calcium supplements with improved intestinal calcium transport ability. Full article

Advancements in membrane separation techniques will expand the applications and requirements for highly specialized, inventive, efficient, and resistant separation materials. The selective separation of rare earth elements (REEs) is one of the expanding applications of membrane-based techniques, as their use is becoming more widespread. Membrane techniques are becoming increasingly desired as environmentally friendly, straightforward methods for treating wastewater and separating metals. For the separation of REEs, an innovative impregnated mixed-matrix membrane (IMMM) technique was developed in this study. It provides a selective, efficient, and reusable method that is suitable for industrial applications. Terbium was selectively adsorbed from other REEs using organophosphorus IMMM with a loading capacity of 113.2 mg/g in 3 h and was reused three times without destroying the initial membrane. Solvent impregnation is thought to offer specific chelation sites that are selective for terbium separation. Full article