Catalyst-Free Synthesis of Thiosulfonates and 3-Sulfenylindoles from Sodium Sulfinates in Water.

This paper presents a green and efficient aqueous-phase method for the synthesis of thiosulfonates, which has the benefits of no need for catalysts or redox reagents and a short reaction time, providing a method with great economic value for synthesizing thiosulfonates. Furthermore, 3-Sulfenylindoles can be easily synthesized using this method, which expands the potential applications of this reaction.

Redox Properties of Mn(III)porphyrins in Hyaluronan Oxidative Degradation: Single Electron Transfer Mechanism.

Cationic Mn(III)-meso-tetraarylporphyrin derivatives, substituted in para position with different size alkyl chains, were investigated to function as antioxidants in free-radical degradation of high-molar-mass hyaluronan by the methods of rotational viscometry and oximetry. The results of rotational viscometry showed that MnTM-4-PyP5+, MnTE-4-PyP5+, MnTPr-4-PyP5+, MnTPen-4-PyP5+ and MnTHep-4-PyP5+ showed high efficiency in decomposing H2O2, and reducing of peroxidized hyaluronan. When using oxygen electrode, MnTE-4-PyP5+, MnTPr-4-PyP5+, MnTPen-4-PyP5+, and MnTHep-4-PyP5+ applied to function as protective antioxidants in hyaluronan degradation, the uptake of dissolved oxygen from the reaction milieu was rapid, followed by continual increase in oxygen concentration up to the end of the measurement. However, when especially MnTE-4-PyP5+, MnTPr-4-PyP5+, and MnTPen-4-PyP5+ were examined as hyaluronan chain-breaking antioxidants, after short-term dissolved oxygen uptake, almost no increase in oxygen concentration was shown.

Decreased proteasome function increases oxidative stress in the early stage of pressure ulcer development.

The aging process in the elderly results in heightened skin fragility associated with various disorders, including pressure ulcers (PUs). Despite the high incidence of PUs in the elderly population, there is a limited body of research specifically examining the impact of aging on the development of pressure ulcers. Therefore, investigating age-related physiological abnormalities is essential to elucidate the pathogenesis of PUs. Ischemia-reperfusion (I/R) injury and the subsequent oxidative stress caused by reactive oxygen species (ROS) play essential roles in the early stage of PUs. In this study, we used a mouse model of proteasomal dysfunction with an age-related phenotype to examine the role of proteasome activity in cutaneous I/R injury in vivo. Decreased proteasome function did not affect the expression of inflammatory cytokines and adhesion molecules in the I/R area in transgenic mice; however, proteasome inhibition increased oxidative stress that was not attenuated by activation of the oxidative stress response mediated by NF-E2-related factor 2 (Nrf2). In dermal fibroblasts (FCs) subjected to hypoxia-reoxygenation (H/R), proteasome inhibition induced oxidative stress and ROS production, and Nrf2 activation did not adequately upregulate antioxidant enzyme expression, possibly leading to antioxidant/oxidant imbalance. The free radical scavenger edaravone had protective effects against I/R injury in vivo and decreased oxidative stress in FCs treated with a proteasome inhibitor and subjected to H/R in vitro. The results suggest that the age-related decline in proteasome activity promotes cutaneous I/R injury-induced oxidative stress, and free radical scavengers may exert protective effects by preventing oxidative stress in the early stage of PUs.

Peroxydisulfate-Driven Reductive Dechlorination as Affected by Soil Constituents: Free Radical Formation and Conversion.

We report a previously unrecognized but efficient reductive degradation pathway in peroxydisulfate (PDS)-driven soil remediation. With supplements of naturally occurring low-molecular-weight organic acids (LMWOAs) in anaerobic biochar-activated PDS systems, degradation rates of 12 γ-hexachlorocyclohexanes (HCH)-spiked soils boosted from 40% without LMWOAs to a maximum of 99% with 1 mM malic acid. Structural analysis revealed that an increase in α-hydroxyl groups and a diminution in pKa1 values of LMWOAs facilitated the formation of reductive carboxyl anion radicals (COO•-) via electrophilic attack by SO4•-/•OH. Furthermore, degradation kinetics were strongly correlated with soil organic matter (SOM) contents than iron minerals. Combining a newly developed in situ fluorescence detector of reductive radicals with quenching experiments, we showed that for soils with high, medium, and low SOM contents, dominant reactive species switched from singlet oxygen/semiquinone radicals to SO4•-/•OH and then to COO•- (contribution increased from 30.8 to 66.7%), yielding superior HCH degradation. Validation experiments using SOM model compounds highlighted critical roles of redox-active moieties, such as phenolic - OH and quinones, in radical formation and conversion. Our study provides insights into environmental behaviors related to radical activation of persulfate in a broader soil horizon and inspiration for more advanced reduction technologies.

Low-Migration Compounds with Amine Functionality as Coinitiators of Radical Polymerization.

The utilization of two-component systems comprising camphorquinone (CQ) and aromatic amines has become prevalent in the photopolymerization. However, there are still concerns about the safety of this CQ/amine system, mainly because of the toxicity associated with the leaching of aromatic amines. In light of these concerns, this study aims to develop novel coinitiator combinations featuring CQ and amines which cannot be leached out of materials, enabling free radical polymerization of representative dentalmethacrylate resins under blue light irradiation. This approach involves the initial design and analysis of hydrogen donors with low C─H bond dissociation energy through molecular modeling. Subsequently, copolymerizable methacrylate functional groups are incorporated via chemical modification, allowing it to act as both coinitiator and copolymerization monomer to achieve low migrationand leachability properties. This work presents, for the first time, the synthesis of the innovative coinitiator and compares its performance with the benchmark CQ/ethyl-4-dimethylaminobenzoate (EDB)-based photoinitiation system (PIS). The results demonstrate the effectiveness of the newly proposed PIS. Finally, an in-depth investigation is conducted into the reaction mechanism associated with this PIS through molecular orbital calculations and electron spin resonance studies.

Polyhedral Vinyl Polymer Particles Synthesized Via Solvent-Free Radical Polymerization.

Liquid marbles (LMs) with a cubic shape are created by using various vinyl monomers as an inner liquid and polymer plates with mm size as a stabilizer. The relationship between the surface tension of the vinyl monomers and formability of the LMs is investigated. LMs can be fabricated using vinyl monomers with surface tensions of 42.7-40.3 mN m-1. The cubic polymer particles are successively synthesized via free-radical polymerizations by irradiation of the cubic LMs with UV light in a solvent-free manner. In addition, controlling the number of polymer plates per one LM, the shape of the plate or the coalescence of the LMs can lead to production of polymer particles with desired forms (e.g., Platonic and rectangular solids) that correspond to the shapes of the original LMs.

DMF-DMA catalyzed Synthesis, molecular docking, in-vitro, in-silico design, and binding free energy studies of novel thiohydantoin derivatives as antioxidant and antiproliferative agents targeting EGFR tyrosine kinase and aromatase cytochrome P450 enzyme.

A set of novels 2-thiohydantoin derivatives were synthesized and enaminone function was discussed at position 5 using DMFDMA catalyst which result in formation of pyrazole, isoxazole, benzoxazepine by using reagents such as hydrazine, hydroxylamine and 2-aminothiophenol. These newly synthesized compounds were evaluated for their antioxidant and antiproliferative activity. In vitro studies on the effect of 2-thiohydantoin on scavenging 2,2-diphenyl-1-picrylhydrazyl radical (DPPH•) confirmed the free radical scavenging and antioxidant activity of 2-thiohydantoin. The synthesized compounds show significant antioxidant activity. The in vitro antitumor activity of 2-thiohydantoin on MCF7 (breast) and PC3 cells (prostate) was evaluated using MTT assay. Some of the synthesized compounds show significant to moderate antiproliferative properties compared to reference drug erlotinib. Among all, compound 4a exhibit potent antitumor properties against MCF7 and PC3 cancer cell lines with IC50 = 2.53 ± 0.09 /ml & with IC50 = 3.25 ± 0.12 µg/ml respectively and has potent antioxidant activity with IC50 = 10.04 ± 0.49 µg/ml.

Identifying eleven new ferroptosis inhibitors as neuroprotective agents from FDA-approved drugs.

With increasing evidence that ferroptosis is associated with diverse neurological disorders, targeting ferroptosis offers a promising avenue for developing effective pharmaceutical agents for neuroprotection. In this study, we identified ferroptosis inhibitors as neuroprotective agents from US Food and Drug Administration (FDA)-approved drugs. 1176 drugs have been screened against erastin-induced ferroptosis in HT22 cells, resulting in 89 ferroptosis inhibitors. Among them, 26 drugs showed significant activity with EC50 below10 µM. The most active ferroptosis inhibitor is lumateperone tosylate at nanomolar level. 11 drugs as ferroptosis inhibitors were not reported previously. Further mechanistic studies revealed that their mechanisms of actions involve free radical scavenging, Fe2+ chelation, and 15-lipoxygenase inhibition. Notably, the active properties of some drugs were firstly revealed here. These ferroptosis inhibitors increase the chemical diversity of ferroptosis inhibitors, and offer new therapeutic possibilities for the treatments of related neurological diseases.

Removal of tetracycline by ultraviolet/sodium percarbonate (UV/SPC)advanced oxidation process in water.

Tetracycline (TC) was widely used and frequently detected in various water bodies, where the presence of TC posed a significant threat to the health of aquatic organisms. Furthermore, antibiotics were hardly degraded by biological treatment. Thus, in order to enhance the removal of TC, we proposed the use of a novel ultraviolet/sodium percarbonate (UV/SPC) advanced oxidation process and initiated an in-depth study. The study investigated the influence of oxidant dosage, initial pH, UV intensity, and TC concentration on the removal of TC. The results demonstrated that the UV/SPC system efficiently removed TC, with removal efficiency increasing as the SPC concentration increased. Within the pH range of 3-11, TC degradation exhibited minimal variation, indicating the UV/SPC system's strong adaptability to pH variations. The research on the impact of the water matrix on TC removal revealed that HCO3- had an inhibitory effect on TC degradation, while NO3- promoted TC degradation. Additionally, the presence of free radical species (·OH, ·CO3-, ·O2-) were detected and rate constants for the secondary reactions (k·OH,TC = 6.3 × 109 L mol-1·s-1, k·CO3-,TC = 3.4 × 108 L mol-1·s-1) were calculated, indicating that ·OH exhibited a stronger oxidative performance compared to ·CO3-. This study did not only present a novel strategy via UV/SPC to remove TC but also uncovered the unique role of ·CO3- for contaminant removal.

Structure-dependent degradation of phthalate esters with persulfate oxidation activated by thermal in soil.

Phthalate esters (PAEs) have become one of the most concerned emerging organic pollutants in the world, due to the toxicity to human health, and hard to remove it efficiently. In this study, the degradation performance of DBP and DEHP in the soil by water bath heating activated sodium persulfate (PS) method under different factors were studied, in which the degradation rate of DBP and DEHP were improved with the increasing of temperature, PS concentration and water/soil ratio, and higher diffusion efficiency treatments methods, due to the improved mass transfer from organic phase to aqueous media. However, the degradation rate of DEHP was much lower than that of DBP, because DEHP in the soil was more difficult to contact with SO4•- for reaction on soil surface, and the degradation rate of PAEs in soil was significantly lower than that in water. Redundancy analysis of degradation rate of DBP and DEHP in water demonstrated that the key factors that determine the degradation rate is time for DBP, and cosolvent dosage for DEHP, indicating that the solubility and diffusion rate of PAEs from soil to aqueous are predominance function. This study provides comprehensive scenes in PAEs degradation with persulfate oxidation activated by thermal in soil, reveal the difference of degradation between DBP and DEHP is structure-dependent. So that we provide fundamental understanding and theoretical operation for subsequent filed treatment of various structural emerging pollutants PAEs contaminated soil with thermal activated persulfate.

Receptor-Mediated and Receptor-Independent Actions of Melatonin in Vertebrates.

Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine that is synthesized from tryptophan in the pineal glands of vertebrates through four enzymatic reactions. Melatonin is a quite unique bioactive substance, characterized by a combination of both receptor-mediated and receptor-independent actions, which promote the diverse effects of melatonin. One of the main functions of melatonin, via its membrane receptors, is to regulate the circadian or seasonal rhythm. In mammals, light information, which controls melatonin synthesis, is received in the eye, and transmitted to the pineal gland, via the suprachiasmatic nucleus, where the central clock is located. Alternatively, in many vertebrates other than mammals, the pineal gland cells, which are involved in melatonin synthesis and secretion and in the circadian clock, directly receive light. Recently, it has been reported that melatonin possesses several metabolic functions, which involve bone and glucose, in addition to regulating the circadian rhythm. Melatonin improves bone strength by inhibiting osteoclast activity. It is also known to maintain brain activity during sleep by increasing glucose uptake at night, in an insulin-independent manner. Moreover, as a non-receptor-mediated action, melatonin has antioxidant properties. Melatonin has been proven to be a potent free radical scavenger and a broad-spectrum antioxidant, even protecting organisms against radiation from space. Melatonin is a ubiquitously distributed molecule and is found in bacteria, unicellular organisms, fungi, and plants. It is hypothesized that melatonin initially functioned as an antioxidant, then, in vertebrates, it combined this role with the ability to regulate rhythm and metabolism, via its receptors.

Tea polyphenol-derived nanomedicine for targeted photothermal thrombolysis and inflammation suppression.

Thrombotic diseases impose a significant global health burden, and conventional drug-based thrombolytic therapies are encumbered by the risk of bleeding complications. In this study, we introduce a novel drug-free nanomedicine founded on tea polyphenols nanoparticles (TPNs), which exhibits multifaceted capabilities for localized photothermal thrombolysis. TPNs were synthesized through a one-pot process under mild conditions, deriving from the monomeric epigallocatechin-3-gallate (EGCG). Within this process, indocyanine green (ICG) was effectively encapsulated, exploiting multiple intermolecular interactions between EGCG and ICG. While both TPNs and ICG inherently possessed photothermal potential, their synergy significantly enhanced photothermal conversion and stability. Furthermore, the nanomedicine was functionalized with cRGD for targeted delivery to activated platelets within thrombus sites, eliciting robust thrombolysis upon laser irradiation across diverse thrombus types. Importantly, the nanomedicine's potent free radical scavenging abilities concurrently mitigated vascular inflammation, thus diminishing the risk of disease recurrence. In summary, this highly biocompatible multifunctional nanomaterial holds promise as a comprehensive approach that combines thrombolysis with anti-inflammatory actions, offering precision in thrombosis treatment.

Mitochondrial DNA Mutations and Ageing.

Mitochondria are subcellular organelles present in most eukaryotic cells which play a significant role in numerous aspects of cell biology. These include carbohydrate and fatty acid metabolism to generate cellular energy through oxidative phosphorylation, apoptosis, cell signalling, haem biosynthesis and reactive oxygen species production. Mitochondrial dysfunction is a feature of many human ageing tissues, and since the discovery that mitochondrial DNA mutations were a major underlying cause of changes in oxidative phosphorylation capacity, it has been proposed that they have a role in human ageing. However, there is still much debate on whether mitochondrial DNA mutations play a causal role in ageing or are simply a consequence of the ageing process. This chapter describes the structure of mammalian mitochondria, and the unique features of mitochondrial genetics, and reviews the current evidence surrounding the role of mitochondrial DNA mutations in the ageing process. It then focusses on more recent discoveries regarding the role of mitochondrial dysfunction in stem cell ageing and age-related inflammation.

Cytoglobin has potent superoxide dismutase function.

Cytoglobin (Cygb) was discovered as a novel type of globin that is expressed in mammals; however, its functions remain uncertain. While Cygb protects against oxidant stress, the basis for this is unclear, and the effect of Cygb on superoxide metabolism is unknown. From dose-dependent studies of the effect of Cygb on superoxide catabolism, we identify that Cygb has potent superoxide dismutase (SOD) function. Initial assays using cytochrome c showed that Cygb exhibits a high rate of superoxide dismutation on the order of 108 M-1 ⋅ s-1 Spin-trapping studies also demonstrated that the rate of Cygb-mediated superoxide dismutation (1.6 × 108 M-1 ⋅ s-1) was only ∼10-fold less than Cu,Zn-SOD. Stopped-flow experiments confirmed that Cygb rapidly dismutates superoxide with rates within an order of magnitude of Cu,Zn-SOD or Mn-SOD. The SOD function of Cygb was inhibited by cyanide and CO that coordinate to Fe3+-Cygb and Fe2+-Cygb, respectively, suggesting that dismutation involves iron redox cycling, and this was confirmed by spectrophotometric titrations. In control smooth-muscle cells and cells with siRNA-mediated Cygb knockdown subjected to extracellular superoxide stress from xanthine/xanthine oxidase or intracellular superoxide stress triggered by the uncoupler, menadione, Cygb had a prominent role in superoxide metabolism and protected against superoxide-mediated death. Similar experiments in vessels showed higher levels of superoxide in Cygb-/- mice than wild type. Thus, Cygb has potent SOD function and can rapidly dismutate superoxide in cells, conferring protection against oxidant injury. In view of its ubiquitous cellular expression at micromolar concentrations in smooth-muscle and other cells, Cygb can play an important role in cellular superoxide metabolism.

Investigation of the inhibition of bacteria and endotoxin influx by back filtration through dialyzer membranes.

We investigated the usefulness of assays using human neutrophils for radical production as well as endotoxin (ET) measurement and bacterial culture for endotoxin and bacterial influx by back filtration using dialyzers with different membrane pore diameters. Three types of dialyzers made of cellulose triacetate membrane material with different pore size FB-110EG eco, FB-110U eco, and FB-150UHß eco were used. A circuit to generate back filtration was created. Back filtrate generated by hydraulic head pressure operation was collected. ET and bacteria were examined. Human neutrophils were exposed to back filtrate (experiments using three different membranes) and contaminated solution, and free radical production was measured using LBP-953 (Berthold) to see if there were differences in production. No bacteria were detected and the concentration of endotoxin was below the detection limit in the back filtrate from the three types of membranes and purified water. Free radical production from neutrophils in the contaminated water was highest at 4,405,750 ± 61,244 cpm (counts per minute) (mean ± SD) (P < 0.01 vs FB-150UHß eco, FB-110U-eco, and FB-110EG eco) followed by that in back filtrate via FB-150UHß eco, FB-110U-eco, FB-110EG eco. Radical production from neutrophils was thereby higher in the back filtrate of dialyzers with larger pore-size membranes. No bacteria were observed and the concentration of ET was below the detection limit in back filtrate from any of the membranes. However, when the reverse filtrate was exposed to neutrophils, radical production increased along with pore size, suggesting the influx of small pyrogens and other pyrogenic substances.

Theoretical insights into the mechanism underlying aflatoxin B1 transformation by the BsCotA-methyl syringate system.

Global concern exists regarding the contamination of food and animal feed with aflatoxin B1 (AFB1), which poses a threat to the health of both humans and animals. Previously, we found that a laccase from Bacillus subtilis (BsCotA) effectively detoxified AFB1 in a reaction mediated by methyl syringate (MS), although the underlying mechanism has not been determined. Therefore, our primary objective of this study was to explore the detoxification mechanism employed by BsCotA. First, the enzyme and mediator dependence of AFB1 transformation were studied using the BsCotA-MS system, which revealed the importance of MS radical formation during the oxidation process. Aflatoxin Q1 (AFQ1) resulting from the direct oxidation of AFB1 by BsCotA, was identified using ultra-high-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The results of UPLC-MS/MS and density functional theory calculations indicated that the products included AFQ1, AFB1-, and AFD1-MS-coupled products in the BsCotA-MS system. The toxicity evaluations revealed that the substances derived from the transformation of AFB1 through the BsCotA-MS mechanism exhibited markedly reduced toxicity compared to AFB1. Finally, we proposed a set of different AFB1-transformation pathways generated by the BsCotA-MS system based on the identified products. These findings greatly enhance the understanding of the AFB1-transformation mechanism of the laccase-mediator system.

Effect of photobiomodulation therapy on the morphology, intracellular calcium concentration, free radical generation, apoptosis and necrosis of human mesenchymal stem cells-an in vitro study.

The aim of the study was to investigate the impact of multiwave locked system (MLS M1) emitting synchronized laser radiation at 2 wavelength simultaneous (λ = 808 nm, λ = 905 nm) on the mesenchymal stem cells (MSCs). Human MSCs were exposed to MLS M1 system laser radiation with the power density 195-318 mW/cm2 and doses of energy 3-20 J, in continuous wave emission (CW) or pulsed emission (PE). After irradiation exposure in doses of energy 3 J, 10 J (CW, ƒ = 1000 Hz), and 20 J (ƒ = 2000 Hz), increased proliferation of MSCs was observed. Significant reduction of Fluo-4 Direct™ Ca2+ indicator fluorescence over controls after CW and PE with 3 J, 10 J, and 20 J was noticed. A decrease in fluorescence intensity after the application of radiation with a frequency of 2000 Hz in doses of 3 J, 10 J, and 20 J was observed. In contrary, an increase in DCF fluorescence intensity after irradiation with laser radiation of 3 J, 10 J, and 20 J (CW, ƒ = 1000 Hz and ƒ = 2000 Hz) was also shown. Laser irradiation at a dose of 20 J, emitted at 1000 Hz and 2000 Hz, and 3 J emitted at a frequency of 2000 Hz caused a statistically significant loss of MSC viability. The applied photobiomodulation therapy induced a strong pro-apoptotic effect dependent on the laser irradiation exposure time, while the application of a sufficiently high-energy dose and frequency with a sufficiently long exposure time significantly increased intracellular calcium ion concentration and free radical production by MSCs.

Update on Antioxidant Therapy with Edaravone: Expanding Applications in Neurodegenerative Diseases.

The brain is susceptible to oxidative stress, which is associated with various neurological diseases. Edaravone (MCI-186, 3-methyl-1 pheny-2-pyrazolin-5-one), a free radical scavenger, has promising effects by quenching hydroxyl radicals (∙OH) and inhibiting both ∙OH-dependent and ∙OH-independent lipid peroxidation. Edaravone was initially developed in Japan as a neuroprotective agent for acute cerebral infarction and was later applied clinically to treat amyotrophic lateral sclerosis (ALS), a neurodegenerative disease. There is accumulating evidence for the therapeutic effects of edaravone in a wide range of diseases related to oxidative stress, including ischemic stroke, ALS, Alzheimer's disease, and placental ischemia. These neuroprotective effects have expanded the potential applications of edaravone. Data from experimental animal models support its safety for long-term use, implying broader applications in various neurodegenerative diseases. In this review, we explain the unique characteristics of edaravone, summarize recent findings for specific diseases, and discuss its prospects for future therapeutic applications.

The Triumph of the Spin Chemistry of Fullerene C60 in the Light of Its Free Radical Copolymerization with Vinyl Monomers.

The spin theory of fullerenes is taken as a basis concept to virtually exhibit a peculiar role of C60 fullerene in the free radical polymerization of vinyl monomers. Virtual reaction solutions are filled with the initial ingredients (monomers, free radicals, and C60 fullerene) as well as with the final products of a set of elementary reactions, which occurred in the course of the polymerization. The above objects, converted to the rank of digital twins, are considered simultaneously under the same conditions and at the same level of the theory. In terms of the polymerization passports of the reaction solutions, a complete virtual picture of the processes considered is presented.

Intracellular Protective Functions and Therapeutical Potential of Trehalose.

Trehalose is a naturally occurring, non-reducing saccharide widely distributed in nature. Over the years, research on trehalose has revealed that this initially thought simple storage molecule is a multifunctional and multitasking compound protecting cells against various stress factors. This review presents data on the role of trehalose in maintaining cellular homeostasis under stress conditions and in the virulence of bacteria and fungi. Numerous studies have demonstrated that trehalose acts in the cell as an osmoprotectant, chemical chaperone, free radical scavenger, carbon source, virulence factor, and metabolic regulator. The increasingly researched medical and therapeutic applications of trehalose are also discussed.