Search Results (319)

Ant venoms are rich sources of bioactive molecules, including peptide toxins with potent and selective activity on ion channels, which makes them valuable for pharmacological research and therapeutic development. Voltage-dependent potassium (Kv) channels, critical for regulating cellular excitability or cell cycle progression control, are targeted by a diverse array of venom-derived peptides. This study focuses on MYRTX_A4-Tb11a, a peptide from Tetramorium bicarinatum venom, which was previously shown to have a strong paralytic effect on dipteran species without cytotoxicity on insect cells. In the present study, we show that Tb11a exhibited no or low cytotoxicity toward mammalian cells either, even at high concentrations, while electrophysiological studies revealed a blockade of hKv1.3 activity. Additionally, Ta11a, an analog of Tb11a from the ant Tetramorium africanum, demonstrated similar Kv1.3 inhibitory properties. Structural analysis supports that the peptide acts on Kv1.3 channels through the functional dyad Y21-K25 and that the disulfide bridge is essential for biological activity, as reduction seems to disrupt the peptide conformation and impair the dyad. These findings highlight the importance of three-dimensional structure in channel modulation and establish Tb11a and Ta11a as promising Kv1.3 inhibitors. Future research should investigate their selectivity across additional ion channels and employ structure-function studies to further enhance their pharmacological potential. Full article

Background/Objectives: Colorectal cancer (CRC) is among the most prevalent malignant neoplasms globally. Chemotherapeutic treatment strategies have demonstrated minimal improvement over the past decade. Combination therapies, including those with nutraceuticals, are currently being investigated as promising alternatives to enhance therapeutic efficacy. The organosulfur garlic extract diallyl disulfide (DADS) has demonstrated anti-tumoral activity in several types of cancer. This study aimed to investigate the effects of DADS and 5-fluorouracil (5-FU), both individually and in combination, on the human CRC cell lines Caco-2 and HT-29. Methods: Caco-2, HT-29, and non-tumoral human umbilical vein endothelial cells (HUVEC) were exposed to DADS (25–600 µM) and 5-FU (5–100 µM), either individually or in simultaneous combination (DADS 100 µM + 5-FU 100 µM), for 24 h. Cytotoxicity was evaluated in all three cell lines. In addition, the effects of these treatments on oxidative stress, cell migration, genotoxicity, cell death, global DNA methylation, and gene–nutraceutical interactions were assessed in both tumor cell lines. Results: DADS demonstrated cytotoxic effects at high concentrations in Caco-2, HT-29, and HUVECs and induced DNA damage in both colorectal cancer cell lines. The combination of DADS and 5-FU significantly promoted apoptotic cell death, increased genotoxicity, elevated global DNA methylation, and inhibited cell migration, with these effects being particularly pronounced in HT-29 cells. Conclusions: We provide evidence that DADS combined with 5-FU is potentially useful in the therapy of CRC. However the combination of nutraceuticals and chemotherapy must consider the distinct molecular and phenotypic characteristics of each tumor cell line. Full article

This study investigates the effect of the surface functionalization of tungsten disulfide (WS₂) nanoparticles with aminoacetic acid (glycine) on the structure, curing behavior, and mechanical performance of epoxy nanocomposites. Aminoacetic acid, as a non-toxic, bio-based modifier, enables a sustainable approach to producing more efficient nanofillers. Functionalization, as confirmed by FTIR, EDS, and XRD analyses, led to elevated surface polarity and greater chemical affinity between WS₂ and the epoxy matrix, thereby promoting uniform nanoparticle dispersion. The strengthened interfacial bonding resulted in a notable decrease in the curing onset temperature—from 51 °C (for pristine WS₂) to 43 °C—accompanied by an increase in polymerization enthalpy from 566 J/g to 639 J/g, which reflects more extensive crosslinking. The SEM examination of fracture surfaces revealed tortuous crack paths and localized plastic deformation zones, indicating superior fracture resistance. Mechanical testing showed marked improvements in flexural and tensile strength, modulus, and impact toughness at the optimal WS₂ loading of 0.5 phr and a 7.5 wt% aminoacetic acid concentration. The surface-modified WS₂ nanoparticles, which perform dual functions, not only reinforce interfacial adhesion and structural uniformity but also accelerate the curing process through chemical interaction with epoxy groups. These findings support the development of high-performance, environmentally sustainable epoxy nanocomposites utilizing amino acid-modified 2D nanofillers. Full article

Albumin-based nanoparticles are promising drug delivery systems due to their biocompatibility, biodegradability, and ability to improve targeted drug release. Among various preparation methods, radiation-induced cross-linking in the presence of ethanol has been proposed in the literature as an effective method for producing protein nanoparticles with preserved bioactivity and controlled size. However, the mechanisms by which ethanol radicals contribute to protein aggregation remain insufficiently understood. In this study, we investigate the role of ethanol in the aggregation of albumins to determine whether its presence is necessary or beneficial for nanoparticle formation. Using pulse radiolysis, spectroscopy methods, resonance light scattering (RLS), and near-infrared (NIR) spectroscopy, we examined aqueous ethanol solutions of albumins before and after irradiation. Our results show that ethanol concentrations above 40% (v/v) significantly promote both radiation-induced and spontaneous protein aggregation. Mechanistic analysis indicates that ethanol radicals react with albumin similarly to hydrated electrons, mainly targeting disulfide bridges. This reaction leads to the formation of sulfur-centered radicals and the formation of intermolecular disulfide bonds that stabilize protein nanostructures by excluding the formation of dityrosine bridges, as described in the literature. In contrast, ethanol concentration below 40% does not favor the radiation-induced aggregation compared to the solution containing t-BuOH. These results provide novel insights into the role of organic cosolvents in protein aggregation and contribute to a broader understanding of the mechanisms of formation of albumin-based nanoparticles using ionizing radiation. Full article

Urine, which has a high concentration of urea, can be used as a sustainable resource for nutrient recovery and sustainable energy. However, urea undergoes hydrolysis, catalyzed by urease, generating ammonia and carbon dioxide. As ammonia is released during hydrolysis in stored urine, the pH rises progressively until the pK_a of ammonium is reached (i.e., 9.3). At elevated pH levels, struvite and other related precipitates are formed. These reactions lower the efficiency of ammonia and urea nitrogen recovery and often cause scaling, pipe blockage, and odors. Herein, we explore an approach to stabilize urea, using pharmaceuticals and their metabolites that are commonly present in human urine. Based on a survey of the urease inhibitory effects of twenty-three pharmaceuticals and metabolites, we determined that the polyphenolic and disulfide-containing compounds had the highest urease inhibition efficiency. Specifically, outstanding inhibitors include catechol (CAT), hydroquinone (HYD), and disulfiram (DSF). Furthermore, when added to urine, these compounds resulted in the retardation of urease-catalyzed hydrolysis, leading to longer-term urine stabilization upon storage. Reaction mechanisms for urease inhibition by polyphenolics and disulfiram are proposed. Evidence is provided that pharmaceutical metabolites can stabilize urea and thus could lead to a sustainable method for nitrogen nutrient recovery from stored urine. Full article

Minced lamb remains one of the most produced meat products in the meat industry, across both the food service and retail sectors. Tea polyphenols (TPs), renowned for their diverse biological activities, are increasingly being employed as natural food additives in research and development. Tea polyphenols at concentrations of 0.00% (CG), 0.01% (TP1), 0.10% (TP2), and 0.30% (TP3) were added to lamb which had undergone a series of freeze–thaw cycles. The presence of tea polyphenols led to a significant decrease in the number of disulfide bonds, resulting in a slower oxidation rate. In addition, the surface hydrophobicity and juice loss of the minced lamb supplemented with tea polyphenols were 91.23 ± 0.22 and 20.00 ± 0.46, respectively, representing a reduction of 1.5% and 7.59% compared to the group without the addition of tea polyphenols. However, the addition of high-dose tea polyphenols also led to a reduction in emulsification stability, alterations in protein conformation, and changes in water migration. Furthermore, the incorporation of a minimal quantity of tea polyphenols (0.01%) resulted in enhanced emulsification stability, water retention, textural properties, and microstructures in minced lamb. This suggests that tea polyphenols have the potential to improve the quality of minced lamb following freezing and thawing processes. Full article

Background: Dithiolopyrrolones (DTPs), such as holomycin and thiolutin, exhibit potent antibacterial activities. DTPs contain a disulfide within a unique bicyclic scaffold, which may chelate metal ions and disrupt metal-dependent cellular processes once the disulfide is reductively transformed to thiols. However, the contribution of the intrinsic redox mechanism of DTPs to their antibacterial activity remains unclear. Herein we used pyrroloformamide (Pyf) A, a DTP with a unique formyl substituent, as a prototype to study the antibacterial potential and mechanism against ESKAPE pathogens, in particular carbapenem-resistant Klebsiella pneumoniae (CRKP). Methods: The antibacterial and anti-biofilm activities of Pyf A were mainly assessed against clinical CRKP isolates. Propidium iodide staining, scanning electron microscopy, glutathione (GSH) quantification, and reactive oxygen species (ROS) analysis were utilized to infer its anti-CRKP mechanism. The synergistic antibacterial effects of Pyf A and AgNO₃ were evaluated through checkerboard and time-kill assays, as well as in vivo murine wound and catheter biofilm infection models. Results: Pyf A exhibited broad-spectrum antibacterial activity against ESKAPE pathogens with minimum inhibitory concentrations ranging from 0.25 to 4 μg/mL. It also showed potent anti-biofilm effects against CRKP. Pyf A disrupted the cell membranes of CRKP and markedly depleted intracellular GSH without triggering ROS accumulation. Pyf A and AgNO₃ showed synergistic anti-CRKP activities in vitro and in vivo, by disrupting both GSH- and thioredoxin-mediated redox homeostasis. Conclusions: Pyf A acts as a GSH-depleting agent and, when combined with AgNO₃, achieves dual-targeted disruption of bacterial thiol redox systems. This dual-targeting strategy enhances antibacterial efficacy of Pyf A and represents a promising therapeutic approach to combat CRKP infections. Full article

This article presents the single-crystal structure of the complex salt sodium dithiocuprate(I) dodecahydrate Na₃CuS₂·12(H₂O), i.e., [Na₃(H₂O)₁₂][CuS₂], which forms in the high-sulfide concentrations of the alkaline solutions used for arsenic separation from copper concentrates. It features a linear hydrogen-bonded dithiocuprate(I) anion, a novelty in crystallographically characterized thiocuprates. During the study of the alkaline sulfide leaching of Chilean copper concentrates, an analytical investigation of the solution led to the detection of this complex. This study aimed to understand the chemical behavior of the leaching solution by identifying existing ions, which facilitated the discovery of the complex using single-crystal analysis. The newly discovered complex was also synthesized from a modeling solution based on the leaching solution recipe for arsenic removal, allowing for further crystal characterization through Raman and XRD analysis. By estimating the sodium sulfide threshold concentration that enhanced the formation of the copper disulfide complex, this study defined the upper technical threshold limit of sulfide concentration for the economic development of alkaline sulfide leaching to remove arsenic. Full article

Background/Objectives: In the past 50 years, human reproductive capacity has steadily declined with elusive and idiopathic origins. Amongst theorized causes, oxidative stress has been proposed to directly contribute to male infertility. The glutathione (GSH) and glutathione disulfide (GSSG) molecular couple reflect cellular redox environments and are thus reflective of oxidative stress in most cells. Shifting GSH/GSSG redox states to abnormal, more oxidizing conditions can disrupt normal cellular activities. This study explores the correlation between the GSH/GSSG redox system and factors involved in male infertility, including sperm quality, specifically sperm motility and total count. Methods: Semen samples from 98 patients underwent high-performance liquid chromatography (HPLC) for GSH/GSSG analysis. A protein assay determined the protein concentration for normalization, and GSH/GSSG redox potentials (E_h) were calculated using the Nernst equation. Results: A significant inverse correlation between GSH/GSSG E_h and sperm count was identified (p = 0.0046 and R² = 0.071). Analysis also found that cellular GSH concentrations (p < 0.001 and R² = 0.11) and total GSH (GSH + (GSSG × 2); p = 0.0039 and R² = 0.074) were significantly and positively correlated with total sperm count, whereas GSSG concentrations were not. The correlation between redox potential and motility was not significantly different (p = 0.11 and R² = 0.02). Conclusions: This study shows that total sperm count decreases with increasing redox potential, indicating that more oxidized systems, such as the GSH/GSSG system, are associated with lower sperm counts in ejaculated sperm samples. These findings support a potential link between oxidative stress and sperm parameters. As understanding of the relationship between GSH/GSSG E_h and sperm quality improves, this may inform future potential therapies and approaches aimed at supporting male reproductive health. Full article

The enhancement of gel properties in chicken myofibrillar proteins (MPs) is a crucial objective in meat processing. In this experiment, we systematically investigated the effects of lentinan (LNT) on MP gel formation ability and three-dimensional network structure features through multi-scale structural characterization and molecular interactions analysis and elucidated the molecular pathways of their molecular actions in regulating gel properties. The addition of LNT (0–2%, w/v) significantly enhanced the water-holding capacity (WHC), textural, and rheological properties of LNT-MPs. As the concentration of LNT increased, the hydrophobic and electrostatic interactions became more pronounced. Conversely, the contribution from disulfide bonds exhibited an inverse relationship, with hydrogen bonds demonstrating the least impact. Subsequently, the α-helix content decreased from 23.75% to 22.64%, and the β-fold content increased from 28.03% to 29.22%, suggesting that the protein aggregates reorganized to form larger aggregates, which contributed to forming a more stable network structure of gels. This investigation establishes LNT’s capacity to modify the gelation mechanisms of MPs. These outcomes offer crucial insights for implementing fungal polysaccharides in processed meat product development. Full article

Thiol-containing drugs may interact with a region of tropomyosin receptor kinase A (TrkA), potentially inhibiting its activation by nerve growth factor (NGF). This action has been linked to potential analgesic activities. Here, we describe the ability of erdosteine, a thiolic compound classified as a mucolytic agent, to bind to the TrkA receptor sequence in silico and its in vitro effects on TrkA activation induced by NGF in cultured human neuroblastoma cells. Our results show that erdosteine and its metabolite, Met-1, bind to the TrkA receptor pocket, involving the primary TrkA residues Glu331, Arg347, His298, and His297. Furthermore, Met-1 has the ability to reduce the disulfide bridge between Cys300 and Cys345 of TrkA. In vitro measurement of TrkA autophosphorylation following NGF activation confirmed that erdosteine and Met-1 interfere with NGF-induced TrkA activation, leading to a consequent loss of the molecular recognition and spatial reorganization necessary for the induction of the autophosphorylation process. This effect was inhibited by low millimolar concentrations of the two compounds, reaching a maximal inhibition (around 40%) after 24 h of exposure to 1 mM erdosteine, and then plateauing. These findings suggest that erdosteine can act as a TrkA antagonist, thus indicating that this drug may have potential as an analgesic via a novel non-opioid mechanism of action operating through NGF signaling inhibition at the level of TrkA. Full article

This study successfully prepared MIL-101(Fe)@MoS₂ composite photocatalysts via hydrothermal methods to address the efficient removal of refractory organic dyes in dye wastewater. Characterization using X-ray diffraction (XRD), Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), and energy-dispersive X-ray spectroscopy (EDS) confirmed that molybdenum disulfide (MoS₂) was uniformly loaded onto the surface of MIL-101(Fe), forming a heterojunction that significantly enhanced light absorption capacity and charge separation efficiency. In a visible-light-driven photo-Fenton system, this material exhibited excellent degradation performance for Congo red (CR). At an initial CR concentration of 50 mg/L, a catalyst dosage of 0.2 g/L, 4 mL of added H₂O₂, and pH 7, CR was completely degraded within 30 min, with the total organic carbon (TOC) removal reaching 72.5%. The material maintained high degradation efficiency (>90%) across a pH range of 3–9, overcoming the traditional Fenton system’s dependency on acidic media. Radical-trapping experiments indicated that superoxide radicals (·O₂⁻) and photogenerated holes (·h⁺) were the primary active species responsible for degradation, revealing a synergistic catalytic mechanism at the heterojunction interface. Recyclability tests showed that the material retained 90.8% degradation efficiency after five cycles, and an X-ray photoelectron spectroscopy (XPS) analysis demonstrated the stable binding of Fe and Mo, preventing secondary pollution. This study provides a scientific basis for developing efficient, stable, and wide-pH adaptable photo-Fenton catalytic systems, contributing significantly to the advancement of green water treatment technologies. Full article

In the present work, we designed a straightforward and disposable voltammetric sensor utilizing a molybdenum disulfide/multi-walled carbon nanotube nanostructure-modified screen-printed carbon electrode (MoS₂/MWCNTs/SPCE) for 4-nitrophenol (4-NP) determination. The successful synthesis of the MoS₂/MWCNT nanostructure was characterized using Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and energy-dispersive X-ray spectroscopy (EXD) mapping. The electrochemical behavior of 4-NP at the MoS₂/MWCNTs/SPCE was examined using differential pulse voltammetry (DPV), cyclic voltammetry (CV), and chronoamperometry techniques. The MoS₂/MWCNTs/SPCE exhibited outstanding electro-catalytic activity for the voltammetric detection of 4-NP. Under optimized conditions, the reduction peak current showed a linear dependence with the concentration of 4-NP in the range of 0.05 to 800.0 µM, and a detection limit (LOD) of 0.01 µM was determined. In addition, the MoS₂/MWCNTs/SPCE sensor has advantages including repeatability, reproducibility, stability, inexpensiveness, and practical application. The MoS₂/MWCNTs/SPCE-based sensor was also utilized for the determination of 4-NP in real water specimens. Full article

Background: Liver cancer, especially hepatocellular carcinoma, a prevalent malignant tumor of the digestive system, poses significant therapeutic challenges. While traditional chemotherapy can inhibit tumor progression, its clinical application is limited by insufficient efficacy. Hydrophobic therapeutic agents further encounter challenges including low tumor specificity, poor bioavailability, and severe systemic toxicity. This study aimed to develop a liver-targeted, glutathione (GSH)-responsive micellar system to synergistically enhance drug delivery and antitumor efficacy. Methods: A GSH-responsive disulfide bond was chemically synthesized to conjugate glycyrrhetinic acid (GA) with curcumin (Cur) at a molar ratio of 1:1, forming a prodrug Cur-GA (CGA). This prodrug was co-assembled with glycyrrhizic acid (GL) at a 300% w/w loading ratio into micelles. The system was characterized for physicochemical properties, in vitro drug release in PBS (7.4) without GSH and in PBS (5.0) with 0, 5, or 10 mM GSH, cellular uptake in HepG2 cells, and in vivo efficacy in H22 hepatoma-bearing BALB/c mice. Results: The optimized micelles exhibited a hydrodynamic diameter of 157.67 ± 2.14 nm (PDI: 0.20 ± 0.02) and spherical morphology under TEM. The concentration of CUR in micelles can reach 1.04 mg/mL. In vitro release profiles confirmed GSH-dependent drug release, with 67.5% vs. <40% cumulative Cur release observed at 24 h with/without 10 mM GSH. Flow cytometry and high-content imaging revealed 1.8-fold higher cellular uptake of CGA-GL micelles compared to free drug (p < 0.001). In vivo, CGA-GL micelles achieving 3.6-fold higher tumor accumulation than non-targeted controls (p < 0.001), leading to 58.7% tumor volume reduction (p < 0.001). Conclusions: The GA/GL-based micellar system synergistically enhanced efficacy through active targeting and stimuli-responsive release, providing a promising approach to overcome current limitations in hydrophobic drug delivery for hepatocellular carcinoma therapy. Full article

Different materials are studied for environmental gas sensors as well as photodetection prototypes. A ZnO/MoS₂ p-n junction was synthetized to act as a multifunctional sensor prototype. After the ZnO was prepared on a silicon substrate by using DC sputtering at room temperature, molybdenum disulfide layers were spin-coated on a nanostructured zinc oxide flake-shaped surface to form an active layer. The heterostructure’s composite surface was examined using scanning electron microscopy, energy-dispersed X-ray, and Raman spectroscopy. Responses to light frequencies, light intensities, and gas chemical tracing were characterized, revealing an enhanced multifunctional performance of the prototype. Characterizations of light-induced photocurrents indicted that the obtained response strength (photocurrent/illumination light power) was up to 0.01 A/W, and the response time was less than 5 ms. In contrast, the gas-sensing measurements showed that its response strength (variation in resistance/original resistance) was up to 3.7% and the response time was down to 150 s when the prototype was exposed to ammonia gas, with the concentration down to 168 ppm. The fabricated prototype appears to have high stability and reproducibility, quick response and recovery times, as well as a high signal-to-noise ratio. Full article