Free Radical Generation Research Articles

Synergistic effect of curcumin and Piperine loaded Niosomal nanoparticles on acute pulmonary toxicity induced by Paraquat in mice

Abstract Objective Paraquat (PQ), a widely used non-selective herbicide, induces severe lung toxicity by promoting cell death and tissue necrosis through the generation of reactive oxygen species (ROS) and free radicals. This study aimed to develop and evaluate novel niosomal nanoparticles (NPs) encapsulating curcumin and piperine to mitigate PQ-induced acute pulmonary toxicity in Balb/c mice. Methods The NPs were prepared using non-ionic surfactants and cholesterol via the thin film hydration method. Results Characterization revealed high encapsulation efficiency (>85%), proper particle sizes (264–286 nm), narrow polydispersity index (PDI) (0.19 ± 0.04 to 0.23 ± 0.02), and good stability over 90 days. Thermal analysis confirmed successful encapsulation of curcumin and piperine within the niosomal NPs. In vivo studies showed that PQ exposure significantly elevated ROS, lipid peroxidation (LPO), and protein carbonylation (PC) levels, while reducing glutathione (GSH) levels and impairing mitochondrial function (P < 0.001). However, co-treatment with curcumin- and piperine-loaded niosomal NPs effectively reversed these effects (P < 0.001), improving mitochondrial function. Conclusion The combined formulation of curcumin and piperine in niosomal NPs offers a promising therapeutic strategy for treating PQ-induced pulmonary toxicity, likely due to enhanced bioavailability and potent antioxidant activity.

Incretin-Based Therapies: A Promising Approach for Modulating Oxidative Stress and Insulin Resistance in Sarcopenia.

Recent studies have linked sarcopenia development to the hallmarks of diabetes, oxidative stress, and insulin resistance. The anti-oxidant and insulin sensitivityenhancing effects of incretin-based therapies may provide a promising option for the treatment of sarcopenia. This review aimed to unveil the role of oxidative stress and insulin resistance in the pathogenesis of sarcopenia and explore the potential benefits of incretin-based therapies in individuals with sarcopenia. PubMed, the Cochrane Library, and Google Scholar databases were searched by applying keywords relevant to the main topic, to identify articles that met our selection criteria. Incretin-based therapies manifested anti-oxidant effects by increasing the anti-oxidant defense system and decreasing free radical generation or by indirectly minimizing glucotoxicity, which was mainly achieved by improving insulin signaling and glucose homeostasis. Likewise, these drugs exhibit insulin-sensitizing activities by increasing insulin secretion, transduction, and β-cell function or by reducing inflammation and lipotoxicity. Incretin-based therapies, as modulators of oxidation and insulin resistance, may target the main pathophysiological factors of sarcopenia, thus providing a promising strategy for the treatment of this disease.

A mechanistic systems biology model of brain microvascular endothelial cell signaling reveals dynamic pathway-based therapeutic targets for brain ischemia

Ischemic stroke is a significant threat to human health. Currently, there is a lack of effective treatments for stroke, and progress in new neuron-centered drug target development is relatively slow. On the other hand, studies have demonstrated that brain microvascular endothelial cells (BMECs) are crucial components of the neurovascular unit and play pivotal roles in ischemic stroke progression. To better understand the complex multifaceted roles of BMECs in the regulation of ischemic stroke pathophysiology and facilitate BMEC-based drug target discovery, we utilized a transcriptomics-informed systems biology modeling approach and constructed a mechanism-based computational multipathway model to systematically investigate BMEC function and its modulatory potential. Extensive multilevel data regarding complex BMEC pathway signal transduction and biomarker expression under various pathophysiological conditions were used for quantitative model calibration and validation, and we generated dynamic BMEC phenotype maps in response to various stroke-related stimuli to identify potential determinants of BMEC fate under stress conditions. Through high-throughput model sensitivity analyses and virtual target perturbations in model-based single cells, our model predicted that targeting succinate could effectively reverse the detrimental cell phenotype of BMECs under oxygen and glucose deprivation/reoxygenation, a condition that mimics stroke pathogenesis, and we experimentally validated the utility of this new target in terms of regulating inflammatory factor production, free radical generation and tight junction protection in vitro and in vivo. Our work is the first that complementarily couples transcriptomic analysis with mechanistic systems-level pathway modeling in the study of BMEC function and endothelium-based therapeutic targets in ischemic stroke.

A select thiosemicarbazone copper(II) complex induces apoptosis in gastric cancer and targets cancer stem cells reducing pluripotency markers

Copper(II)-based complexes are promising candidates as anti-cancer agents due to their ability to target cancer cells. Here we describe the synthesis and characterization of two copper(II) thiosemicarbazone complexes with the ligands 4-(dimethylamino)benzaldehyde N4-methylthiosemicarbazone (HL1) and 4-(dimethylamino)benzaldehyde N4-(4-(dimethylamino)phenylthiosemicarbazone (HL2) and general formula [Cu(L)2]. The complexes show stability in aqueous solution with 1 % of DMSO that allows to stablish its solution profile in biological buffers. Compound [Cu(L1)₂] lipophilicity was lower than [Cu(L2)₂], however, its solubility in biological buffer was not only better but also its DLS and ζ-potential data. In vitro studies demonstrate a higher cytotoxic effect of [Cu(L1)₂] on gastric cancer cells. The proposed mechanism of action consists in the generation of free radicals that induce DNA lesions, oxidative stress and ultimately autophagy deregulation and apoptosis. Additionally, [Cu(L1)₂] is equally active on gastric cancer stem cells and tumor cells resistant to cisplatin. More importantly, stem cells treated with [Cu(L1)₂] show a downregulation of pluripotency markers such as TWIST, NANOG and OCT4. Overall, our results with [Cu(L1)₂] prompt a significant advancement in the development of rational-designed pharmaceuticals for combating cancer.

Differential Cytoprotective Effect of Resveratrol and Its Derivatives: Focus on Antioxidant and Autophagy-Inducing Effects

Numerous beneficial effects of resveratrol were reported; however, its pharmacological profile is contradictious. Previously, we have demonstrated that resveratrol has a dose-dependent cytoprotective effect and the essential role of autophagy induction was demonstrated. Resveratrol suffers from unfavorable pharmacokinetics, hindering its clinical use. Our aim was to study the cytoprotective effect of resveratrol derivatives to better understand structure–activity relationships that may facilitate the development of compounds with better druglike characteristics. Serum-deprivation-induced caspase activation, free radical generation, mitochondrial membrane depolarization and autophagy were detected in the presence of resveratrol analogs with different oxidation states on mouse embryonal fibroblasts. Distinct cytoprotective mechanisms of the examined compounds were revealed. Monomethyl resveratrol had similar potency to resveratrol (EC50: 85.3 vs. 84.2 μM); however, autophagy induction was not essential for its cytoprotective effect. Oxyresveratrol was found to be a strong antioxidant that can induce direct cytoprotection rather than autophagy. Trimethyl-resveratrol, lacking free hydroxyl groups, induced damage that was too significant and hardly compensated by the activation of cytoprotective machineries, and caspase activation was reduced by only 24.5%. Based on our results, methylation of resveratrol reduces its antioxidant activity, while autophagy induction can still contribute to its cytoprotective effect. The introduction of an additional hydroxyl group, however, augments the antioxidant properties, inducing cytoprotection without autophagy induction.

Exploring the 3,5-Dibromo-4,6-dimethoxychalcones and Their Flavone Derivatives as Dual α-Glucosidase and α-Amylase Inhibitors with Antioxidant and Anticancer Potential.

The rising levels of type 2 diabetes mellitus (T2DM) and the poor medical effects of the commercially available antidiabetic drugs necessitate the development of potent analogs to treat this multifactorial metabolic disorder. It has been demonstrated that targeting two or more biochemical targets associated with the onset and progression of diabetes along with oxidative stress and/or cancer could be a significant strategy for treating complications related to this metabolic disorder. The 3,5-dibromo-4,6-dimethoxychalcones (2a-f) and the corresponding flavone derivatives (3a-f) were synthesized and characterized using spectroscopic (NMR, HR-MS and FT-IR) techniques. The inhibitory effect of both series of compounds against α-glucosidase and α-amylase was evaluated in vitro through enzymatic assays. Selected compounds were also evaluated for potential to activate or inhibit superoxide dismutase. Compound 3c was selected as a representative model for the flavone series and evaluated spectrophotometrically for potential to coordinate Cu(II) and/or Zn(II) ions implicated in the metal-catalyzed free radical generation. A plausible mechanism for metal-chelation of the test compounds is presented. Furthermore, the most active compounds from each series against the test carbohydrate-hydrolyzing enzymes were selected and evaluated for their antigrowth effect on the human breast (MCF-7) and lung (A549) cancer cell lines and for cytotoxicity against the African Green Monkey kidney (Vero) cell line. The parent chalcone 2a and flavone derivatives 3a, 3c and 3e exhibited relatively high inhibitory activity against the MCF-7 cells with IC50 values of 4.12 ± 0.55, 8.50 ± 0.82, 5.10 ± 0.61 and 6.96 ± 0.66 μM, respectively. The chalcones 2a and 2c exhibited significant cytotoxicity against the A549 cells with IC50 values of 7.40 ± 0.67 and 9.68 ± 0.80 μM, respectively. Only flavone 3c exhibited relatively strong and comparable cytotoxicity against the MCF-7 and A549 cell lines with IC50 values of 6.96 ± 0.66 and 6.42 ± 0.79 μM, respectively. Both series of compounds exhibited strong activity against the MCF-7 and A549 cell lines compared to the analogous quercetin (IC50 = 35.40 ± 1.78 and 35.38 ± 1.78 μM, respectively) though moderate compared to nintedanib (IC50 = 0.53 ± 0.11 and 0.74 ± 0.15 μM, respectively). The test compounds generally exhibited reduced cytotoxicity against the Vero cells compared to this anticancer drug. Molecular docking revealed strong alignment of the test compounds with the enzyme backbone to engage in hydrogen bonding interaction/s and hydrophobic contacts with the residues in the active sites of α-glucosidase and α-amylase. The test compounds possess favorable drug-likeness properties, supporting their potential as therapeutic candidates against T2DM.

Exfoliated Porous Carbon Nitride by Simultaneous Oxidation-Corrosion for Photocatalytic H2O2 Production and Organic Degradation.

Graphitic carbon nitride (g-C3N4) is a fascinating material with potential applications in photocatalysis due to its good chemical stability, high thermal stability, and relative ease of synthesis. In this work, ultrathin g-C3N4 is constructed using a hybridized method, which combines the advantages of thermal and liquid-phase stripping methods. This sample can improve performance in degrading organic pollutants several times, and the highest enhancement efficiency occurs in an alkaline environment. In addition, photocatalytic production of hydrogen peroxide can be increased to 2.6 times that of the bulk sample. These improved properties are due to the increase in specific surface area, the generation of free radicals, and adsorption capacity. This work presents a one-step exfoliation method for bulk g-C3N4 for more surface-active sites and strong redox capacity.

Numerical Study on the Explosion Reaction Mechanism of Multicomponent Combustible Gas in Coal Mines

Combustible gases, such as CO, CH4, and H2, are produced during spontaneous coal combustion in goaf, which may cause an explosion under the stimulation of an external fire source. It is of great significance to study the influence of combustible gases, such as CO and H2, on the characteristics of a gas explosion. In this study, CHEMKIN software (Version 17.0) and the GRI-Mech 3.0 reaction mechanism were used to study the influences of different concentration ratios between CO and H2 on the ignition delay time, free radical concentration, and key reaction step of a gas explosion. The results show that the increase in the initial CH4 and CO concentrations prolonged the ignition delay time, while the increase in the H2 concentration shortened the time and accelerated the explosion reaction. The addition of H2 promoted the generation of free radicals (H⸱, O⸱, ⸱OH) and accelerated the occurrence of the gas explosion. CO generated ⸱OH free radicals and dominated the methane consumption through the R119 and R156 reactions. As the concentrations of CO and H2 increased, the R38 reaction gradually became the main driving factor of the gas explosion.

Free radical detection in precision-cut mouse liver slices with diamond-based quantum sensing

Free radical generation plays a key role in many biological processes including cell communication, maturation, and aging. In addition, free radical generation is usually elevated in cells under stress as is the case for many different pathological conditions. In liver tissue, cells produce radicals when exposed to toxic substances but also, for instance, in cancer, alcoholic liver disease and liver cirrhosis. However, free radicals are small, short-lived, and occur in low abundance making them challenging to detect and especially to time resolve, leading to a lack of nanoscale information. Recently, our group has demonstrated that diamond-based quantum sensing offers a solution to measure free radical generation in single living cells. The method is based on defects in diamonds, the so-called nitrogen-vacancy centers, which change their optical properties based on their magnetic surrounding. As a result, this technique reveals magnetic resonance signals by optical means offering high sensitivity. However, compared to cells, there are several challenges that we resolved here: Tissues are more fragile, have a higher background fluorescence, have less particle uptake, and do not adhere to microscopy slides. Here, we overcame those challenges and adapted the method to perform measurements in living tissues. More specifically, we used precision-cut liver slices and were able to detect free radical generation during a stress response to ethanol, as well as the reduction in the radical load after adding an antioxidant.

Bioorthogonal Regulated Metabolic Balance for Promotion of Ferroptosis and Mild Photothermal Therapy.

The nanozyme with NADPH oxidase (NOX)-like activity can promote the consumption of NADPH and the generation of free radicals. In consideration of that the upregulation of glucose-6-phosphate dehydrogenase (G6PD) would accelerate the compensation production of NADPH, for inhibition of G6PD activity, our designed bioorthogonal nanozyme can in situ catalyze pro-DHEA to produce G6PD inhibitor and dehydroepiandrosterone (DHEA) drugs to inhibit G6PD activity. Therefore, the well-defined platform can disrupt NADPH homeostasis, leading to the collapse of the antioxidant defense system in the tumor cells. The enzyme-like activity of PdCuFe is further enhanced when irradiated by NIR-II light. The destruction of NADPH homeostasis can promote ferroptosis and, in turn, facilitate mild photothermal therapy. Our design can realize NADPH depletion and greatly improve the therapeutic effect through metabolic regulation, which may provide inspiration for the design of bioorthogonal catalysis.

Enhanced activation of peroxymonosulfate by nanomagnetic CoFe2O4-CeO2/g-C3N4 composites as a heterogeneous catalyst for metronidazole degradation

Antibiotic-induced catastrophic pollution has the potential to migrate over vast distances through water, thereby posing a detrimental effect on both humans and the environment. The construction of a highly robust catalyst to activate peroxymonosulfate (PMS) has become a fascinating approach for treating such types of wastewaters. In this study, we have developed CoFe2O4-CeO2/CN catalysts using an impregnation-hydrothermal and ultrasonication method to efficiently degrade metronidazole (MNZ). The synthesized catalyst materials were analyzed through multiple characterization techniques in order to correlate the material properties and the degradation performance. The degradation trials exhibited that MNZ underwent complete degradation within 40 min in the CoFe2O4-CeO2/CN-2/PMS system, with a rate constant of 0.1354 min−1, nearly 5.29 times faster than the CoFe2O4-CeO2/PMS (0.0235 min−1) under optimal conditions ([catalyst] = 0.5 g/L, [PMS] = 0.5 mM, [MNZ] = 20 mg/L, pH = 6.72). The increased abatement of MNZ in CoFe2O4-CeO2/CN-2/PMS system could be attributed to the higher surface area of the CoFe2O4-CeO2/CN-2 (75.96 m2/g) catalyst in comparison to the CoFe2O4-CeO2 (53.98 m2/g), which enhances the catalytically active sites and improves the PMS activation reaction. Besides, the impact of several operational variables and influencing anions on MNZ degradation was researched as well. The generation of free radicals was confirmed by radical scavenging analysis and authenticated using electron paramagnetic resonance analysis. The mechanistic analysis established that the activation of PMS was initiated by the transformations of Co3+/Co2+, Fe3+/Fe2+, and Ce4+/Ce3+. Briefly, this research provides valuable perspective for future research regarding heterogeneous catalysis leveraging PMS activation to alleviate toxic contaminants.

Square-wave pulsed potential driven electrocatalytic degradation of 4-chlorophenol using Fe-Ni/rGO/PPy@NF three dimensional electrode

To develop an energy-efficient system for the removal of chlorinated organic pollutants, Fe-Ni/reduced graphite oxide/polymerized polypyrrole@nickel foam was constructed as a catalytic cathode for pulsed electrocatalytic degradation, where cathode-catalyzed production of hydrogen radicals (H*) and hydroxyl radical (·OH) generated at the anode led to dechlorination of 4-chlorophenol (4-CP), and dechlorination products were mineralized and degraded under the action of·OH. When energy was continuously supplied to the reaction system in the constant potential mode, the 4-CP concentration near the electrode was insufficient, limiting the reaction rate. Conversely, in the square-wave pulsed potential mode, mass transfer limitations were mitigated, significantly enhancing reaction efficiency and reducing energy consumption. At −1.2 V (vs. Ag/AgCl), the 4-CP removal efficiency reached 93.79 % in the pulsed potential mode, surpassing the constant potential mode's performance of 81.40 %. The synergistic periodic oscillation of the potential, direct electron transfer, and catalytic generation of active free radicals in the pulsed potential mode reduced intermediate concentrations and increased 4-CP mineralization, while the degradation pathway remained unchanged. This research presents a method for the efficient treatment of chlorinated organic pollutants in water using pulsed electrocatalytic degradation.

In silico assessment of antioxidant activity and toxicity profiling of bioactive molecules from Murraya koenigii

The antioxidant activity of curry leaves is of interest because oxidative stress is implicated in a variety of diseases, including cancer, heart disease, and neurodegenerative disorders. By scavenging free radicals and inhibiting lipid peroxidation, antioxidants can help protect cells from damage and reduce the risk of these diseases. Overall, in-silico studies suggest that curry leaves and their bioactive compounds have potent antioxidant activity. The objective of the study was to assess the antioxidant activity of the bioactive molecules from Murraya koenigii and anticipate the toxicity by in-silico research. iGEMDOCK software was used to assess the antioxidant activity. ProTox II software was used to conduct the toxicity investigations. Osthol (− 81.4863, − 81.9046 kcal/mol), mukoenineA (− 81.0417, − 78.9941 kcal/mol), murrayone(− 80.0731, − 78.9453 kcal/mol), kaempferol (− 97.0774, − 89.3534 kcal/mol), and apigenin (− 89.5291, − 108.704 kcal/mol) were found to have the highest binding energies with SOD and GPx proteins, respectively, when compared with standard (ascorbic acid; − 81.132, − 98.917 kcal/mol). All the mentioned compounds have low levels of hepatotoxicity, carcinogenicity, immunotoxicity, mutagenicity, and cytotoxicity. The bioactive molecules of Murraya koenigii have a potent antioxidant effect and low level of toxicity that gives valuable insight for optimizing lead molecules to combat free radical generation or oxidation.

Cu‐Doped 0D Bi2WO6 Nanoparticles for Efficient Visible‐Light‐Driven Photocatalytic Tetracycline Degradation

AbstractBismuth‐based photocatalysts have been widely employed in the photocatalytic degradation of organic pollutants in wastewater. However, the lack of rational structural design and the slow generation of active free radicals have hindered its efficiency. Here, we stabilized Bi2WO6 nanoparticles by wrapping them with hydroxyl groups, introduced metal Cu doping, and underwent an annealing process to construct Cu‐BiNP nanocatalysts with exposed active sites. Under visible light irradiation, 0.03Cu‐BiNP achieved a 94.5% TC degradation efficiency, which is 15.8 times higher than the rate of bulk BiWO. The 0D structure endows Cu‐BiNP with ample opportunities for O2 adsorption and activation, and Cu atomic doping reduces the bandgap and increases the oxygen vacancy, promoting the generation of active oxygen species. This work demonstrates the rapid charge separation and activation of O2 to generate active oxygen species by 0D bismuth‐based nanocatalysts in photocatalytic oxidation reactions, providing a scalable nanocatalyst platform for TC photocatalytic degradation.

High performance of heterogeneous catalytic ozonation for tetracycline removal by a N-doped biochar derived from co-pyrolysis of sludge and water hyacinth

Enhancing the performance of heterogeneous catalytic ozonation (HCO) for contaminant removal using biochar that is both cost-effective and stable is of great significance. In this research, a novel nitrogen-doped biochar (HSBC) was synthesized through the co-pyrolysis of sludge and water hyacinth. The presence of pyrrolic N, pyridinic N and graphitic N in HSBC as well as the high-temperature co-pyrolysis process, conferred a high degree of graphitization to the biochar. The graphitic N species facilitated the generation of free radicals, while the graphitic structure enhanced electron transfer between the catalyst and tetracycline (TC). HSBC demonstrated exceptional efficiency in TC removal via HCO, achieving a 93% removal rate within just 130 minutes. Moreover, the biodegradability of actual printing and dyeing wastewater with a chemical oxygen demand (COD) of (9900 mg/L) was increased sevenfold after HCO treatment. This study offers new perspectives on the preparation of N-doped biochar and its practical application in the treatment of industrial wastewater through HCO processes.

Plasma coupled with ultrasonic for degradation of organic pollutants in water: Revealing the generation of free radicals and the dominant degradation pathways

This study explores the synergistic effects of dielectric barrier discharge (DBD) plasma coupled with ultrasound (US) in the degradation of organic pollutants in water. The optimal degradation conditions were determined to be 100W ultrasonic power, 190V DBD plasma voltage, and neutral pH. The combination of DBD plasma and US significantly enhances the generation of reactive species (·OH, ·O2-, and 1O2), leading to a 97.3% degradation efficiency of methyl orange (MO), which is 17.3% higher than DBD plasma alone. Electron spin resonance (ESR) identified ·OH, ·O2-, and 1O2 in DBD/US system, and radical scavengers were employed to elucidate their roles. The degradation process was assessed through changes in pH, conductivity, TOC and COD, with characterization and analysis via UV-Vis and LC-MS. By combining LC-MS with density functional theory (DFT) calculations, nine intermediates were identified and three degradation pathways dominated by free radicals were established. Additionally, the DBD/US system treated wastewater containing sulfamethoxazole (SMX), sulfadiazine (SDZ), tetracycline (TC), and ciprofloxacin (CIP), achieving degradation rates exceeding 80%. These findings suggest that the DBD/US coupled system holds promising potential for treating organic pollutant wastewater.

Mitigating Oxidative Stress and Lung Fibrosis with Low Dose Radiation Therapy in Paraquat Poisoning: A Case Series

Paraquat poisoning, a frequent cause of fatalities in India, has become a significant public health issue, particularly among farmers. This herbicide, known for its high toxicity, results in severe pulmonary damage, with no specific antidote available. Ingestion of even small amounts of paraquat can lead to rapid multiorgan failure and death, largely due to its accumulation in the lungs, triggering oxidative stress and alveolar fibrosis. The toxicological mechanism involves the generation of free radicals that damage cellular membranes, eventually causing extensive lung fibrosis and alveolitis. Mortality rates remain high, with no definitive treatment. Recent advancements in low-dose radiotherapy (LDRT) have shown promise in treating lung injury caused by paraquat. LDRT’s anti-inflammatory properties have been previously explored in non-cancerous conditions like musculoskeletal disorders. Its ability to modulate inflammatory responses in lung tissue suggests potential benefits in mitigating paraquat-induced lung fibrosis. While preliminary evidence from small-scale studies has shown some improvement in patients treated with LDRT, the efficacy remains uncertain. At our center, we have treated five patients using LDRT, with mixed outcomes. Some patients showed improvement, while others succumbed to early pulmonary fibrosis. Further research is needed to establish the role of LDRT in managing paraquat poisoning. Larger studies are required to assess its ability to prevent lung fibrosis and improve long-term survival in patients with severe poisoning.

Malignant Pleural Mesothelioma: A Comprehensive Review.

Mesotheliomas are hyperplastic tumors that envelop the serosal membranes that safeguard the body's external surfaces. Although certain instances may exhibit indolent characteristics, a significant number of tumors demonstrate rapid progression and a poor prognosis. Mesotheliomas are typically categorized as benign or malignant, with malignant mesothelioma being more frequently linked to asbestos exposure. Malignant pleural mesothelioma (MPM) predominantly impacts males and often emerges in the late 50 s or beyond, characterized by a median age of early 70 s among patients exposed to asbestos lasting from 2 to 4 decades. Respiratory exposure to asbestos particles leads to the development of malignant mesothelioma, characterized by recurrent inflammation, disruption of cell division, activation of proto-oncogenes, and generation of free radicals. In pleural mesothelioma, BAP1, CDKN2A, and NF are the most often mutated genes. Accurate diagnosis and assessment usually require the use of chest computed tomography (CT) scans, magnetic resonance imaging (MRI), and positron emission tomography (PET). Radiation therapy, immunotherapy, chemotherapy, and surgery are some of the treatment options that are currently available. This systematic review provides a comprehensive analysis of the latest research, biomarkers, evaluation, and management strategies for malignant pleural mesothelioma.

Therapeutic potential of monoterpene molecules acts against 7KCh-mediated oxidative stress and neuroinflammatory amyloidogenic signalling pathways

Alzheimer’s disease (AD) is a degenerative disorder characterised by amyloid-beta aggregates activated by the accumulation of lipid molecules and their derivatives, especially 7-ketocholesterol (7KCh), an oxidised lipid that plays a great part in the progression of AD. The current therapeutics need bio-potential molecules and their biomedical application preventing 7KCh-induced cytotoxicity. In this study, bornyl acetate (BA) and menthol (ME), the natural monoterpenes were investigated for their neuroprotective effects against 7KCh-induced SH-SY5Y cells and their effects were compared to the standard drug galantamine (GA). 7KCh-induced changes like lipid accumulation, amyloid generation, free radical generation, acetylcholinesterase levels, calcium accumulation and mitochondrial membrane integrity were analysed in SH-SY5Y cells with or without BA and ME treatment. Furthermore, various mediators involved in the amyloidogenic, inflammatory and apoptotic pathways were studied. In our results, the cells induced with 7KCh upon co-treatment with BA and ME significantly reduced lipid accumulation and amyloid generation through toll-like receptor (TLR) 4 suppression and enhanced ATP binding cassette (ABCA) 1-mediated clearance. Co-treatment with BA and ME concurrently regulated oxidative stress, acetylcholinesterase activity, mitochondrial membrane potential and intracellular calcification altered by 7KCh-induced SH-SY5Y cells. Moreover, 7KCh-induced cells showed elevated mRNA levels of misfolded protein markers and apoptotic mediators which were significantly downregulated by BA and ME co-treatment. In addition, the protein expression of amyloidogenic, proinflammatory as well as pro-apoptotic markers was decreased by BA and ME co-treatment in 7KCh-induced cells. Overall, BA and ME mediated inhibition of amyloidogenic activation and cell survival against 7KCh-induced inflammation, thereby preventing the onset and progression of AD in comparison to GA.

High performance long-afterglow phosphor-based ZnIn2S4/Sr2MgSi2O7:Eu2+,Dy3+ photocatalyst capable of dark state long-term application for photocatalytic sterilization

Eco-friendly photocatalytic sterilization utilizing solar energy via the generation of reactive radicals excited by light irradiation devastating bacterial cells and mineralizing organic pollutants effectively exhibits vast application potential in marine biofouling prevention due to the abundant solar energy available in the ocean. Focusing on the issue of the cessation of photocatalytic processes in the absence of light, in this study, we selected the long afterglow material Sr2MgSi2O7:Eu2+,Dy3+ (SMSO), which exhibits persistent sky-blue luminescence after brief illumination, as the substrate for in situ compositing with the visible-light-responsive ZnIn2S4 (ZIS). The emission spectrum of SMSO partially overlaps with the absorption spectrum of ZIS, and their energy bands were well-matched. Consequently, the ZIS/SMSO=1:0.5 (mass ratio) exhibited the synergistic degradation and bactericidal performance under both light and dark conditions. ZIS/SMSO=1:0.5 exhibited the degradation rate of methyl orange (MO) of 72.4 % when exposed to 5 minutes of simulated sunlight, 2.6-fold increase compared to ZIS, and especially, it exhibited the sustained degradation rate of 38.7 % after 5 h in darkness. Besides, ZIS/SMSO=1:0.5 exhibited the bactericidal rate of 28.9 % under simulated visible light of 1 h, which was 2.9 and 2.5 times the bactericidal rate of ZIS and SMSO, respectively; and especially, after 6 h in darkness, it reached 64.4 %, which was 2.8 and 1.9 times the bactericidal rate of ZIS and SMSO, respectively. The Electron Spin Resonance (ESR) test validated the notably higher ·OH and ·O2- signals of the ZIS/SMSO=1:0.5 complex than those of individual components when exposed to light, and the sustained existence of ·OH signal even in darkness, revealing that the continuously generation of active free radicals even in the absence of light due to that the SMSO can continuously excite the ZIS. Combining with the in situ XPS analysis and the density functional theory calculations, an S-scheme heterojunction between ZIS and SMSO is formed which contribute to the higher yield of ·OH for ZIS/SMSO=1:0.5 under both light and dark conditions. And the calculation of the adsorption energies of ZIS and SMSO for O2 and OH- in the composite revealed that the ZIS component is more favorable for adsorbing O2, while the SMSO component is more favorable for adsorbing OH-. These analyses manifested the S-scheme electron transfer of the system. Finally, the ZIS/SMSO=1:0.5 composite of environmentally friendly broad-spectral-responsive ternary metal sulfides with the long afterglow materials is capable of a sustained degradation and bactericidal effect, not only under light irradiation but also in the subsequent darkness. It offers valuable insights into photocatalytic materials that overcome light availability limitations for preventing marine biofouling.