Search Results (2,006)

Background: Alcohol abuse is one of the most common causes of mortality worldwide. This study aimed to investigate the efficacy of a treatment in reducing circulating ethanol and oxidative stress biomarkers. Methods: Twenty wine-drinking subjects were investigated in a randomized controlled, single-blind trial (ClinicalTrials.gov. Identifier: NCT06548503; Ethical Committee of the University of Padova (HEC-DSB/12-2023) to evaluate the effect of the intake of a product containing silymarin, pyrroloquinoline quinone sodium salt, and myricetin (referred to as Si.Pi.Mi. for this project) on blood alcohol, ethyl glucuronide (EtG: marker for alcohol consumption) and markers of oxidative stress levels (Reactive Oxygen Species—ROS, Total Antioxidant Capacity—TAC, CoQ10, thiols redox status, 8-isoprostane, NO metabolites, neopterin, and uric acid). The effects of the treatment versus placebo were evaluated acutely and after 1 week of supplementation in blood and/or saliva and urine samples. Results: Si.Pi.Mi intake reduced circulating ethanol after 120 min (−33%). Changes in oxidative stress biomarkers, particularly a TAC (range +9–12%) increase and an 8-isoprostane (marker of lipidic peroxidation) decrease (range −22–27%), were observed too. Conclusion: After the administration of Si.Pi.Mi, the data seemed to suggest a better alcohol metabolism and oxidative balance in response to wine intake. Further verification is requested. Full article

Hydrogels are widely used in tissue engineering due to their ability to form three-dimensional (3D) structures that support cellular functions and mimic the extracellular matrix (ECM). Despite their advantages, dextran-based hydrogels lack intrinsic biological activity, limiting their use in this field. Here, we present a strategy for developing bioactive hydrogels through sequential thiol–maleimide bio-functionalization and enzyme-catalyzed crosslinking. The hydrogel network is formed through the reaction of tyramine moieties in the presence of horseradish peroxidase (HRP) and hydrogen peroxide (H₂O₂), allowing for tunable gelation time and stiffness by adjusting H₂O₂ concentrations. Maleimide groups on the hydrogel backbone enable the coupling of thiol-containing bioactive molecules, such as arginylglycylaspartic acid (RGD) peptides, to enhance biological activity. We examined the effects of hydrogel stiffness and RGD concentration on human mesenchymal stem cells (hMSCs) during differentiation and found that hMSCs encapsulated within these hydrogels exhibited over 88% cell viability on day 1 across all conditions, with a slight reduction to 60–81% by day 14. Furthermore, the hydrogels facilitated adipogenic differentiation, as evidenced by positive Oil Red O staining. These findings demonstrate that DexTA–Mal hydrogels create a biocompatible environment that is conducive to cell viability and differentiation, offering a versatile platform for future tissue engineering applications. Full article

The principal reactions that maintain redox homeostasis in living systems are the deprotonation of thiols, followed by the oxidative conversion of the produced thiolates into disulfides, which thus reduce the harmful oxidizing agents. The various biological thiols have different molecule-specific propensities to carry on the co-dependent deprotonation and redox processes. This study utilizes the known correlation between thiolate basicities and oxidizabilities, to quantify antioxidant or reducing capacities and pH-dependences of thiol–disulfide antioxidant systems, as a tool to find adequate molecules against oxidative stress. Full article

Superhydrophobic surfaces have been used in various fields of engineering due to their resistance to corrosion and fouling and their ability to control fluid movement. Traditionally, superhydrophobic surfaces are fabricated via chemical methods of changing the surface energy or mechanical methods of controlling the surface topology. Many of the conventional mechanical methods use a top-to-bottom scheme to control the surface topolopy. Here, we develop a novel fabrication method of superhydrophobic substrates using a bottom-to-top scheme via polymer OSTE, which is a prototyping polymer material developed for the fabrication of microchips due to its superior photocuring ability, mechanical properties, and surface modification ability. We fabricate a superhydrophobic substrate by OSTE–OSTE micro mushroom forest via a two-step lithography process. At first, we fabricate an OSTE pillar forest as the mushroom stems; then, we fabricate the mushroom heads via backside lithography with diffused UV light. Such topology and surface properties of OSTE render these structures superhydrophobic, with water droplets reaching a contact angle of 152.9 ± 0.2°, a sliding angle of 4.1°, and a contact angle hysteresis of less than 0.5°. These characteristics indicate the promising potential of this substrate for superhydrophobic applications. Full article

The rapid detection of contaminants in water resources is vital for safeguarding the environment, where the use of eco-friendly materials for water monitoring technologies has become increasingly prioritized. In this context, the role of biocomposites in the development of a SERS sensor is reported in this study. Grafted chitosan was employed as a matrix support for Ag nanoparticles (NPs) for the surface-enhanced Raman spectroscopy (SERS). Chitosan (CS) was decorated with thiol and carboxylic acid groups by incorporating S-acetyl mercaptosuccinic anhydride (SAMSA) to yield CS-SAMSA. Then, Ag NPs were immobilized onto the CS-SAMSA (Ag@CS-SAMSA) and characterized by spectral methods (IR, Raman, NIR, solid state ¹³C NMR with CP-MAS, XPS, and TEM). Ag@CS-SAMSA was evaluated as a substrate for SERS, where methylene blue (MB) was used as a model dye adsorbate. The Ag@CS-SAMSA sensor demonstrated a high sensitivity (with an enhancement factor ca. 10⁸) and reusability over three cycles, with acceptable reproducibility and storage stability. The Raman imaging revealed a large SERS effect, whereas the MB detection varied from 1–100 μM. The limits of detection (LOD) and quantitation (LOQ) of the biocomposite sensor were characterized, revealing properties that rival current state-of-the-art systems. The dye adsorption profiles were studied via SERS by fitting the isotherm results with the Hill model to yield the ΔG°_ads for the adsorption process. This research demonstrates a sustainable dual-function biocomposite with tailored adsorption and sensing properties suitable for potential utility in advanced water treatment technology and environmental monitoring applications. Full article

Leishmania infantum is the vector-borne trypanosomatid parasite causing visceral leishmaniasis in the Mediterranean basin. This neglected tropical disease is treated with a limited number of obsolete drugs that are not exempt from adverse effects and whose overuse has promoted the emergence of resistant pathogens. In the search for novel antitrypanosomatid molecules that help overcome these drawbacks, drug repurposing has emerged as a good strategy. Nitroaromatic compounds have been found in drug discovery campaigns as promising antileishmanial molecules. Fexinidazole (recently introduced for the treatment of stages 1 and 2 of African trypanosomiasis), and pretomanid, which share the nitroimidazole nitroaromatic structure, have provided antileishmanial activity in different studies. In this work, we have tested the in vitro efficacy of these two nitroimidazoles to validate our 384-well high-throughput screening (HTS) platform consisting of L. infantum parasites emitting the near-infrared fluorescent protein (iRFP) as a biomarker of cell viability. These molecules showed good efficacy in both axenic and intramacrophage amastigotes and were poorly cytotoxic in RAW 264.7 and HepG2 cultures. Fexinidazole and pretomanid induced the production of ROS in axenic amastigotes but were not able to inhibit trypanothione reductase (TryR), thus suggesting that these compounds may target thiol metabolism through a different mechanism of action. Full article

The present study aimed to investigate the effects of the Gypsophila paniculata ethanol extract (GPEE) on oxidative stress, inflammation, and metabolic markers in a rat model of streptozotocin-induced diabetes mellitus (DM). Phytochemical analysis using high-performance liquid chromatography coupled with mass spectrometry was performed to measure the total phenolic and flavonoid contents. In vitro antioxidant activity was evaluated through DPPH, FRAP, H₂O₂, and NO scavenging tests, and the in vivo effects of the GPEE were assessed in streptozotocin-induced DM rats. Treatments with the GPEE, metformin, and Trolox were administrated by gavage for 10 days. On day 11, blood was collected, and serum oxidative stress (total oxidative status, oxidative stress index, malondialdehyde, advanced oxidation protein products, 8-hydroxydeoxyguanosine, nitric oxide, 3-nitrotyrosine, advanced glycation end-products, total antioxidant reactivity, total thiols), inflammatory (IL-1β, NF-κB, IL-18, and gasdermin D), metabolic (fasting glucose, total cholesterol, triglycerides, and triglyceride–glucose index), and liver injury (AST, ALT, and AST:ALT ratio) markers were measured. The GPEE was found to have a significant polyphenols content and a moderate in vitro antioxidant effect. In vivo, the GPEE lowered oxidants and increased antioxidants, decreased inflammatory markers and blood glucose, and improved lipid profiles and transaminases in a dose-dependent manner, with higher doses having a better effect, being comparable to those of metformin and Trolox. Full article

A new eco-friendly method for the synthesis of mono- and multifunctional organosulfur compounds, based on the process between ynals and thiols, catalyzed by bulky N-heterocyclic carbene (NHC), was designed and optimized. The proposed organocatalytic approach allows the straightforward formation of a broad range of thioesters and sulfenyl-substituted aldehydes in yields above 86%, in mild and metal-free conditions. In this study, thirty-six sulfur-based derivatives were obtained and characterized by spectroscopic methods. Full article

l-Homocysteine, formed from S-adenosyl methionine following demethylation and adenosine release, accumulates when the methionine recycling pathway and other pathways become impaired, thus leading to hyperhomocysteinemia, a biomarker in cardiovascular diseases, neurological/psychiatric disorders, and cancer. The partial oxidation of the l-homocysteine thiol group and its decarboxylation on C-alpha lead to the formation of l-homocysteinesulfinic acid (l-HCSA) and homohypotaurine (HHT), respectively. Both compounds are not readily available from commercial suppliers, which hinders the investigation of their biological activities. Herein, the chemical synthesis of l-HCSA, from l-homocystine, was the starting point for establishing the bio-based synthesis of HHT using recombinant Escherichia coli glutamate decarboxylase (EcGadB), an enzyme already successfully employed for the bio-based synthesis of GABA and its phosphinic analog. Prior to HHT synthesis, k_cat (33.92 ± 1.07) and K_M (38.24 ± 3.45 mM) kinetic constants were determined for l-HCSA on EcGadB. The results of our study show that the EcGadB-mediated synthesis of HHT can be achieved with good yields (i.e., 40% following enzymatic synthesis and column chromatography). Purified HHT was tested in vitro on primary human umbilical vein endothelial cells and rat cardiomyoblasts and compared to the fully oxidized analog, homotaurine (OT, also known as tramiprosate), in widespread pharmaceutical use. The results show that both cell lines display statistically significant recovery from the cytotoxic effects induced by H₂O₂ in the presence of HHT. Full article

Currently, antimicrobial resistance (AMR) is a serious health problem in the world, mainly because of the rapid spread of multidrug-resistant (MDR) bacteria. These include bacteria that produce β-lactamases, which confer resistance to β-lactams, the antibiotics with the most prescriptions in the world. Carbapenems are particularly noteworthy because they are considered the ultimate therapeutic option for MDR bacteria. However, this group of antibiotics can also be hydrolyzed by β-lactamases, including metallo-β-lactamases (MBLs), which have one or two zinc ions (Zn²⁺) on the active site and are resistant to common inhibitors of serine β-lactamases, such as clavulanic acid, sulbactam, tazobactam, and avibactam. Therefore, the design of inhibitors against MBLs has been directed toward various compounds, with groups such as nitrogen, thiols, and metal-binding carboxylates, or compounds such as bicyclic boronates that mimic hydrolysis intermediates. Other compounds, such as dipicolinic acid and aspergillomarasmin A, have also been shown to inhibit MBLs by chelating Zn^2+. In fact, recent inhibitors are based on Zn²⁺ chelation, which is an important factor in the mechanism of action of most MBL inhibitors. Therefore, in this review, we analyzed the current strategies for the design and mechanism of action of metal-ion-binding inhibitors that combat MDR bacteria. Full article

This study aimed to investigate the antioxidant and anti-inflammatory activities mechanism of Artemisia dracunculus (A. dracunculus) and Artemisia abrotanum (A. abrotanum) ethanol extracts in acute rat inflammation induced in Wistar male rats with turpentine oil. The characterization of the polyphenolic compounds in the extracts was conducted using UV–Vis and Fourier-transform infrared spectroscopy and high-performance liquid chromatography coupled with mass spectrometry techniques. The antioxidant activity of the extracts was evaluated in vitro by DPPH, FRAP, H₂O₂, and NO scavenging tests and in vivo by measuring the total oxidative status (TOS), total antioxidant capacity (TAC), oxidative stress index (OSI), 8-hydroxy-deoxyguanosine (8-Oxo-dG), advanced oxidation protein products (AOPP), malondialdehyde (MDA), nitric oxide (NO), 3-nitrotyrosine (3NT), and total thiols (SH). Inflammation was evaluated by measuring nuclear factor-kB-p65 (NfkB-p65) and NLRP3 inflammasome activation with IL-1β, IL-18, and gasdermin D. Liver and renal toxicity was determined following transaminases (ALT and AST), creatinine, and urea. The experimental results indicated that A. dracunculus and A. abrotanum ethanol extracts have moderate in vitro antioxidant activity and had in vivo antioxidant activity and an anti-inflammatory effect by NfkB-p65, IL-1b, IL-18, and gasdermin D serum level reduction. The antioxidant activity correlated with the chemical composition of the extracts. These results bring evidence-based use of A. dracunculus and A. abrotanum’s in traditional and contemporary medicine. Full article

A precise understanding of the self-assembly kinetics of small molecules on nanoparticles (NPs) can give greater control over the size and architecture of the functionalized NPs. Herein, a single-nanoparticle electrochemical collision (SNEC)-based method was developed to monitor the self-assembly processes of 6-mercapto-1-hexanol (6-MCH) and 1-hexanethiol (MCH) on Au NPs at the single-particle level, and to investigate the self-assembly kinetics exactly. Results showed that the self-assembly processes of both consisted of rapid adsorption and slow recombination. However, the adsorption rate of MCH was significantly lower than that of 6-MCH due to the poorer polarity. Also noteworthy is that the rapid adsorption of 6-MCH on Au NPs conformed to the Langmuir model of diffusion control. Hence, the proposed SNEC-based method could serve as a complementary method to research the self-assembly mechanism of functionalized NPs. Full article

LCS-1, a putative selective inhibitor of SOD1, is a substituted pyridazinone with rudimentary similarity to quinones and naphthoquinones. As quinones catalytically oxidize H₂S to biologically active reactive sulfur species (RSS), we hypothesized LCS-1 might have similar attributes. Here, we examine LCS-1 reactions with H₂S and SOD1 using thiol-specific fluorophores, liquid chromatography–mass spectrometry, electron paramagnetic resonance (EPR), UV–vis spectrometry, and oxygen consumption. We show that LCS-1 catalytically oxidizes H₂S in buffer solutions to form RSS, namely per- and polyhydrosulfides (H₂S_n, n = 2–6). These reactions consume oxygen and produce hydrogen peroxide, but they do not have an EPR signature, nor do they affect the UV–vis spectrum. Surprisingly, LCS-1 synergizes with SOD1, but not SOD2, to oxidize H₂S to H₂S_3-6. LCS-1 forms monothiol adducts with H₂S, glutathione (GSH), and cysteine (Cys), but not with oxidized glutathione or cystine; both thiol adducts inhibit LCS-1-SOD1 synergism. We propose that LCS-1 forms an adduct with SOD1 that disrupts the intramolecular Cys⁵⁷-Cys¹⁴⁶ disulfide bond and transforms SOD1 from a dismutase to an oxidase. This would increase cellular ROS and polysulfides, the latter potentially affecting cellular signaling and/or cytoprotection. Full article

Amid the rapid development of modern society, the widespread use of plastic products has led to significant environmental issues, including the accumulation of non-degradable waste and extensive consumption of non-renewable resources. Developing healable, recyclable, bio-based materials from abundant renewable resources using diverse dynamic interactions attracts increasing global attention. However, achieving a good balance between the self-healing capacity and mechanical performance, such as strength and toughness, remains challenging. In our study, we address this challenge by developing a new type of dynamic network from epoxidized soybean oil (ESO) and poly(butylene adipate-co-terephthalate) (PBAT) with good strength and toughness. For the synthetic strategy, a thiol–epoxy click reaction was conducted to functionalize ESO with thiol and hydroxyl groups. Subsequently, a curing reaction with isocyanates generated dynamic thiourethane and urethane bonds with different bonding energies in the dynamic networks to reach a trade-off between dynamic features and mechanical properties; amongst these, the thiourethane bonds with a lower bonding energy provide good dynamic features, while the urethane bonds with a higher bonding energy ensure good mechanical properties. The incorporation of flexible PBAT segments to form the rational multi-phase structure with crystalline domains further enhanced the products. A typical sample, OTSO₁₀₀-PBAT₁₀₀, exhibited a tensile strength of 33.2 MPa and an elongation at break of 1238%, demonstrating good healing capacity and desirable mechanical performance. This study provides a promising solution to contemporary environmental and energy challenges by developing materials that combine mechanical and repair properties. It addresses the specific gap of achieving a trade-off between tensile strength and elongation at break in bio-based self-healing materials, promising a wide range of applications. Full article

Ribosomal protein S6 kinases belong to a family of highly conserved enzymes in eukaryotes that regulate cell growth, proliferation, survival, and the stress response. It is well established that the activation and downstream signalling of p70S6Ks involve multiple phosphorylation events by key regulators of cell growth, survival, and energy metabolism. Here, we report for the first time the covalent modification of p70S6K1 by coenzyme A (CoA) in response to oxidative stress, which regulates its kinase activity. The site of CoA binding (CoAlation) was mapped by mass spectrometry to cysteine 217 (Cys217), located in the kinase activation loop and only one amino acid away from the tripeptide DFG motif, which facilitates ATP-binding. The CoAlation of recombinant p70S6K1 was demonstrated in vitro and was shown to inhibit its kinase activity. Our molecular docking and dynamics analysis revealed the most likely mode for CoA binding to p70S6K1. This mechanism involves the non-covalent binding of the CoA ADP moiety to the p70S6K1 nucleotide-binding pocket, positioning the CoA thiol group in close proximity to form a covalent bond with the surface-exposed Cys217 residue. These findings support a “dual anchor” mechanism for protein kinase inhibition by CoAlation in cellular response to oxidative stress. Furthermore, the inhibition of S6K1 by CoAlation may open new avenues for developing novel inhibitors. Full article