ROS Scavenging Ability Research Articles

New Horizons in Micro/Nanoplastic-Induced Oxidative Stress: Overlooked Free Radical Contributions and Microbial Metabolic Dysregulations in Anaerobic Digestion.

Excessive production of reactive oxygen species (ROS) induced by micro/nanoplastics (MPs/NPs) is highly toxic to microbes. However, the mechanisms underlying ROS generation and metabolic regulation within anaerobic guilds remain poorly understood. In this study, we investigated the effects of environmentally relevant levels of polypropylene (PP)-MPs/NPs on oxidative stress and microbial ecology during anaerobic digestion (AD). Electron paramagnetic resonance spectroscopy revealed that PP-MPs/NPs elevated the concentrations of environmentally persistent free radicals (EPFRs) and derived hydroxyl radicals (•OH). EPFRs were identified as the primary contributors to •OH generation, as evidenced by a high Spearman correlation coefficient (r = 0.884, p < 0.001) and free radical-quenching studies. The formation of •OH enhanced ROS production by 86.2-100.9%, resulting in decreased cellular viability and methane production (by 37.5-50.5%) at 100 mg/g TS PP-MPs/NPs. Genome-centric metagenomic and metatranscriptomic analyses suggested that PP-MPs/NPs induced the reassembly of community structures, re-evolution of functional traits, and remodeling of interspecies interactions. Specifically, PP-MPs/NPs induced a shift in methanogen consortia from hydrogenotrophic Methanofollis sp. to acetoclastic and hydrogenotrophic Methanothrix soehngenii, primarily because of the latter's diverse ingestion patterns, electron bifurcation complexes, and ROS-scavenging abilities. Downregulation of genes associated with antioxidative defense systems (i.e., sodN, katA, and osmC) and ROS-driven redox signal transduction pathways (c-di-AMP and phosphorylation signaling pathways) provided insights into the mechanisms underlying ROS-induced microbial metabolic dysregulation. Our findings enhance the understanding of microbial ecological and metabolic traits under MPs/NPs stressors, facilitating the control of MPs/NPs toxicity and the stabilization of AD processes.

Comparative analysis of the PAL gene family in nine citruses provides new insights into the stress resistance mechanism of Citrus species

BackgroundThe phenylalanine ammonia-lyase (PAL) gene, a well-studied plant defense gene, is crucial for growth, development, and stress resistance. The PAL gene family has been studied in many plants. Citrus is among the most vital cash crops worldwide. However, the PAL gene family has not been comprehensively studied in most Citrus species, and the biological functions and specific underlying mechanisms are unclear.ResultsWe identified 41 PAL genes from nine Citrus species and revealed different patterns of evolution among the PAL genes in different Citrus species. Gene duplication was found to be a vital mechanism for the expansion of the PAL gene family in citrus. In addition, there was a strong correlation between the ability of PAL genes to respond to stress and their evolutionary duration in citrus. PAL genes with shorter evolutionary times were involved in more multiple stress responses, and these PAL genes with broad-spectrum resistance were all single-copy genes. By further integrating the lignin and flavonoid synthesis pathways in citrus, we observed that PAL genes contribute to the synthesis of lignin and flavonoids, which enhance the physical defense and ROS scavenging ability of citrus plants, thereby helping them withstand stress.ConclusionsThis study provides a comprehensive framework of the PAL gene family in citrus, and we propose a hypothetical model for the stress resistance mechanism in citrus. This study provides a foundation for further investigations into the biological functions of PAL genes in the growth, development, and response to various stresses in citrus.

Comparison and Assessment of Anti-Inflammatory and Antioxidant Capacity Between EGCG and Phosphatidylcholine-Encapsulated EGCG.

To compare and evaluate the differences between EGCG and phosphatidylcholine-encapsulated EGCG in terms of their anti-inflammatory and antioxidant capacities. In this study, transdermal absorption experiments were conducted to compare the absorption capacity of EGCG and phosphatidylcholine-encapsulated EGCG. Subsequently, the disparity in anti-inflammatory and antioxidant efficacy between EGCG and phosphatidylcholine-encapsulated EGCG were evaluated through cytotoxicity experiments, as well as the determination of cellular inflammatory factors and the measurement of ROS content under different treatment conditions. The concentration of EGCG, encapsulated in phosphatidylcholine, in porcine skin is 40.76 ± 1.29 μg/cm2, which is significantly higher than the concentration of EGCG alone (31.62 ± 2.01 μg/cm2). Also, the ability of phosphatidylcholine-encapsulated EGCG to suppress inflammatory factors such as tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), and prostaglandin E2 (PGE2) was notably superior to that of EGCG alone. Both phosphatidylcholine-encapsulated EGCG and EGCG showed excellent ROS scavenging ability in terms of antioxidant capacity. The percutaneous absorption and anti-inflammatory impact of EGCG encapsulated within phosphatidylcholine were substantially enhanced when compared to EGCG by itself. Additionally, both formulations exhibited enhanced ROS scavenging capacities, albeit the variance between them was not pronounced. These insights furnish a vital theoretical underpinning for the utilization of phosphatidylcholine-encapsulated EGCG in cosmetic applications, specifically for fostering products with anti-inflammatory and antioxidant benefits.

The transcription factor MfbHLH104 from Myrothamnus flabellifolia promotes drought tolerance of Arabidopsis thaliana by enhancing stability of the photosynthesis system

The resurrection plant Myrothamnus flabellifolia can survive extreme drought and desiccation conditions, and quickly recover after rewatering. However, little is known about the mechanism underlying the drought tolerance of M. flabellifolia. In this study, MfbHLH104 was cloned and introduced into Arabidopsis thaliana due to the lack of a transgenic system for M. flabellifolia. MfbHLH104 is localized in the nucleus. Its N-terminal region has transactivation ability in yeast, and the C-terminal region may inhibit the transactivation ability. Overexpressing MfbHLH104 significantly increased drought and salt tolerance of A. thaliana at both seedling and adult stages. It enhanced leaf water retention capacity by decreasing water loss rate and increasing drought- and abscisic acid (ABA) -induced stomatal closure. Additionally, it boosted osmolyte accumulation and ROS scavenging ability by up-regulating genes associated with osmolyte biosynthesis and antioxidant enzymes, and enhancing antioxidant enzyme activities. The expression of ABA-responsive genes were also promoted by MfbHLH104. Remarkably, RNA-seq analysis indicated that MfbHLH104 significantly up-regulated 32 genes (FDR < 0.05 and fold change ≥1.5) involved in photosynthesis related pathways (KEGG pathway No: ko00195, ko00196) under drought, which account for 18.7 % of the total up-regulated genes and the most enriched KEGG pathways. This result suggested that it may help to maintain the stability of the photosynthesis system under drought conditions.

Drug-Loaded Mesoporous Polydopamine Nanoparticles in Chitosan Hydrogels Enable Myocardial Infarction Repair through ROS Scavenging and Inhibition of Apoptosis.

In this study, we synthesized mesoporous polydopamine nanoparticles (MPDA NPs) using an emulsion-induced interface assembly strategy and loaded epigallocatechin gallate (EGCG) into MPDA NPs via electrostatic attraction to form EGCG@MPDA NPs. In the post myocardial infarction (MI) environment, these interventions specifically aimed to eliminate reactive oxygen species (ROS) and facilitate the repair of MI. We further combined them with a thermosensitive chitosan (CS) hydrogel to construct an injectable composite hydrogel (EGCG@MPDA/CS hydrogel). Utilizing in vitro experiments, the EGCG@MPDA/CS hydrogel exhibited excellent ROS-scavenging ability of H9C2 cells under the oxidative stress environment and also could inhibit their apoptosis. The EGCG@MPDA/CS hydrogel significantly promoted left ventricular ejection fraction (LVEF) in infarcted rat models post injection for 28 days compared to the PBS group (51.25 ± 1.73% vs 29.31 ± 0.78%, P < 0.05). In comparison to the PBS group, histological analysis revealed a substantial increase in left ventricular (LV) wall thickness in the EGCG@MPDA/CS hydrogel group (from 0.58 ± 0.03 to 1.39 ± 1.11 mm, P < 0.05). This work presents a novel approach to enhance MI repair by employing the EGCG@MPDA/CS hydrogel. This hydrogel effectively reduces local oxidative stress by ROS and stimulates the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) pathway.

Involvement of the Metallothionein gene OsMT2b in Drought and Cadmium Ions Stress in Rice

Abiotic stress is one of the major factors restricting the production of rice (Oryza sativa L.). Developing rice varieties with dual abiotic stress tolerance is essential to ensure sustained rice production, which is necessary to illustrate the regulation mechanisms underlying dual stress tolerance. At present, only a few genes that regulate dual abiotic stress tolerance have been reported. In this study, we determined that the expression of OsMT2b was induced by both drought and Cd2+ stress. After stress treatment, OsMT2b-overexpression lines exhibited enhanced drought tolerance and better physiological performance in terms of relative water content and electrolyte leakage compared with wild-type (WT). Further analysis indicated that ROS levels were lower in OsMT2b-overexpression lines than in WT following stress treatment, suggesting that OsMT2b-overexpression lines had a stronger ability to scavenge ROS under stress. Reverse transcription-quantitative PCR (RT-qPCR) results demonstrated that under drought stress, OsMT2b influenced the expression of genes involved in ROS scavenging to enhance drought tolerance in rice. In addition, OsMT2b-overexpression plants displayed increased tolerance to Cd2+ stress, and physiological assessment results were consistent with the observed phenotypic improvements. Thus, enhancing ROS scavenging ability through OsMT2b overexpression is a novel strategy to boost rice tolerance to both drought and Cd2+ stress, offering a promising approach for developing rice germplasm with enhanced resistance to the abiotic stressors.

Improvement of Saccharomyces cerevisiae strain tolerance to vanillin through heavy ion radiation combined with adaptive laboratory evolution

Vanillin is an inhibitor of lignocellulose hydrolysate, which can reduce the ability of Saccharomyces cerevisiae to utilize lignocellulose, which is an important factor limiting the development of the ethanol fermentation industry. In this study, mutants of vanillin-tolerant yeast named H6, H7, X3, and X8 were bred by heavy ion irradiation (HIR) combined with adaptive laboratory evolution (ALE). Phenotypic tests revealed that the mutants outperformed the original strain WT in tolerance, growth rate, genetic stability and fermentation ability. At 1.6 g/L vanillin concentration, the average OD600 value obtained for mutant strains was 0.95 and thus about 3.4-fold higher than for the wild-type. When the concentration of vanillin was 2.0 g/L, the glucose utilization rate of the mutant was 86.3 % within 96 h, while that of the original strain was only 70.0 %. At this concentration of vanillin, the mitochondrial membrane potential of the mutant strain recovered faster than that of the original strain, and the ROS scavenging ability was stronger. We analyzed the whole transcriptome sequencing map and the whole genome resequencing of the mutant, and found that DEGs such as FLO9, GRC3, PSP2 and SWF1, which have large differential expression multiples and obvious mutation characteristics, play an important role in cell flocculation, rDNA transcription, inhibition of DNA polymerase mutation and protein palmitoylation. These functions can help cells resist vanillin stress. The results show that combining HIR with ALE is an effective mutagenesis strategy. This approach can efficiently obtain Saccharomyces cerevisiae mutants with improved vanillin tolerance, and provide reference for obtaining robust yeast strains with lignocellulose inhibitor tolerance.

Nanominerals Packaged in pH‐Responsive Alginate Microcapsules Exhibit Selective Delivery in Small Intestine and Enhanced Absorption and Bioavailability

AbstractMineral supplementation is crucial for human nutrition to facilitate appropriate growth, disease prevention, and improved reproductive health. The conventional forms of mineral supplementation involve an ionic form of elements mixed with biomolecules; however, suffer from unfavorable reactions under an acidic environment of stomach, ROS generation, and poor absorption in the small intestine. To address this, nanominerals (NMs) of six essential mineral elements are synthesized and packed in pH‐responsive microcapsule. Each NMs is coated with biomolecules that are known to rapidly absorb through the intestinal epithelium. Microcapsules are found intact at acidic pH (pH: 2.0–6.5); however, selectively release NMs at pH ≥7.0. The in vitro study demonstrates that the mixture of NMs and microcapsules is biocompatible and exhibits excellent ROS scavenging ability at physiological pH. Oral administration of NMs‐loaded microcapsules to rats shows enhanced levels of minerals, vitamin B12, hemoglobin, and total antioxidant activity in blood. The liver, kidneys, and spleen show enhanced expression of Cu/Zn‐SOD and Mn‐SOD enzymes due to high absorption and bioavailability of ZnO, Cu2O, and MnO2 NMs through the intestine. Thus, the pH‐responsive microcapsules hold promise to effectively stealth the encapsulated nutrient materials from the acidic environment of stomach and precisely deliver them to small intestine.

Integrating network pharmacology and experimental verification to explore the pharmacological mechanisms of phlorizin against osteoarthritis.

To study the pharmacological effects and mechanisms of phlorizin in the treatment of osteoarthritis (OA) through network pharmacological analysis, molecular docking, and experimental validation. First, we screened out the relevant targets related to phlorizin and OA from the public database. The key targets, biological processes, and signaling pathways of phlorizin against OA were identified by protein-protein interaction (PPI) network, Gene Ontology (GO), and Encyclopedia of Kyoto Genes and Genomes (KEGG) pathway enrichment analysis. Subsequently, molecular docking was performed to predict the binding activity between phlorizin and key targets. Finally, we evaluated the effects of phlorizin on hydrogen peroxide-induced OA in rats and validated its possible mechanism of action based on the findings of the network pharmacology analysis. Network pharmacology revealed a total of 235 cross-targets involved in the treatment of OA. Phlorizin's anti-OA effect was found to be primarily mediated through oxidoreductase activity, with JAK-STAT and NF-κB signaling pathways playing a regulating role, according to pathway enrichment analysis. Phlorizin demonstrated a strong affinity for NF-κB1 targets through molecular docking. Moreover, in vitro experiments demonstrated that phlorizin could enhance intracellular antioxidant enzyme activities with good ROS scavenging ability and significantly reduce the expression of NF-κB1 and inflammatory cytokines. Phlorizin can inhibit the progression of OA. The potential underlying mechanism involves inhibiting the NF-κB pathway to reduce inflammation and promote intracellular antioxidant action.

Georgian Medicinal Plants as Rich Natural Sources of Antioxidant Derivatives: A Review on the Current Knowledge and Future Perspectives.

The study of antioxidants is of pivotal importance in biomedicine as these molecules could be involved in biological pathways associated with disease. The identification of new antioxidants together with the acquisition of a deeper knowledge on their biology, could lead to the use of these compounds as drugs for innovative treatments. Plants are an important reservoir of phytodrugs that in many cases can be isolated with good extraction yields directly from the vegetal source and are often endowed with a low toxicity profile. Georgia, a country situated on the Black Sea coast in the Caucasus region at the intersection of Western Asia and Eastern Europe, is renowned for its unique woodland habitats and immense biological diversity due to the great variety of climate zones and landscapes. Many wild plants in the area are used as remedies for a number of illnesses in the local traditional medicine. However, the scientific knowledge of these sources of natural drugs and of their molecular components is still far from exhaustive. Therefore, with the present work we reviewed the scientific literature on some of the main Georgian medicinal plants and found that several species are a valuable source of hydrophilic and hydrophobic antioxidants, endowed in some cases with a high ROS-scavenging ability. The analysis of the literature also demonstrated that most of the medicinal extracts and compounds isolated from these plants are beneficial in suppressing multiple diseases in vitro. This review will provide information for scientists looking to develop secure plant-based pharmaceuticals as well as a rationale for using Georgian medicinal plants for the treatment of a range of diseases.

Multifunctional Glycopeptide-Based Hydrogel via Dual-Modulation for the Prevention and Repair of Radiation-Induced Skin Injury.

The radiation-induced skin injury (RISI) remains a great challenge for clinical wound management and care after radiotherapy, as patients will suffer from the acute radiation injury and long-term chronic inflammatory damage during the treatment. The excessive ROS in the early acute stage and prolonged inflammatory response in the late healing process always hinder therapeutic efficiency. Herein, we developed an extracellular matrix (ECM)-mimetic multifunctional glycopeptide hydrogel (oCP@As) to promote and accelerate RISI repair via a dual-modulation strategy in different healing stages. The oCP@As hydrogel not only can form an ECM-like nanofiber structure through the Schiff base reaction but also exhibits ROS scavenging and DNA double-strand break repair abilities, which can effectively reduce the acute radiation damage. Meanwhile, the introduction of oxidized chondroitin sulfate, which is the ECM polysaccharide-like component, enables regulation of the inflammatory response by adsorption of inflammatory factors, accelerating the repair of chronic inflammatory injury. The animal experiments demonstrated that oCP@As can significantly weaken RISI symptoms, promote epidermal tissue regeneration and angiogenesis, and reduce pro-inflammatory cytokine expression. Therefore, this multifunctional glycopeptide hydrogel dressing can effectively attenuate RISI symptoms and promote RISI healing, showing great potential for clinical applications in radiotherapy protection and repair.

Multibiofunctional Self-healing Adhesive Injectable Nanocomposite Polysaccharide Hydrogel.

Injectable hydrogels with good antimicrobial and antioxidant properties, self-healing characteristics, suitable mechanical properties, and therapeutic effects have great practical significance for developing treatments for pressing healthcare challenges. Herein, we have designed a novel, self-healing injectable hydrogel composite incorporating cross-linked biofunctional nanomaterials by mixing alginate aldehyde (Ox-Alg), quaternized chitosan (QCS), adipic acid dihydrazide (ADH), and copper oxide nanosheets surface functionalized with folic acid as the bioligand (F-CuO). Gelation was achieved under physiological conditions via the dynamic Schiff base cross-linking mechanism. The developed nanocomposite injectable hydrogel demonstrated the fast self-healing ability essential to bear deformation and outstanding antibacterial properties along with ROS scavenging ability. Furthermore, the optimized formulation of our F-CuO-embedded injectable hydrogel exhibited excellent cytocompatibility, blood compatibility, and in vitro wound healing performance. Taken together, the F-CuO nanosheet cross-linked injectable hydrogel composite presented herein offers a promising candidate biomaterial with multifunctional properties to develop solutions for addressing clinical challenges.

P-587 Salidroside improves the reproductive capacity of aged mice via improving oocyte mitochondrial function

Abstract Study question The potential application value of salidroside as a reproductive anti-aging drug. Summary answer After old mice were intraperitoneally injected with salidroside, the reproductive function was significantly improved. This improvement is due to salidroside’s enhancement of mitochondrial function. What is known already The main cause of fecundity decline with maternal age is ovarian aging, which is characterized by decreases in follicle number and oocyte quality, However, there are currently no approved drugs for the treatment of ovarian aging. Salidroside has been regarded as an effective medicine to prevent and treat high-altitude illnesses. Emerging studies found that it also has a variety of pharmacological properties, such as anti-aging, antioxidation, anti-inflammatory and antivirus. In terms of anti-aging, salidroside supplements can extend the lifespan of fish Nothobranchius guentheri, reverse the premature senescence of human skin fibroblasts and ameliorate age-related disease. Study design, size, duration In this study, salidroside was used in two ways: First, we injected salidroside into naturally aging mice via intraperitoneal injection for 14 consecutive days and observed the fertility and ovarian reserve function of mice. Subsequently, we added salidroside to the oocyte IVM culture medium to observe changes in oocyte and mitochondrial function. Participants/materials, setting, methods Experiments were conducted in vivo and in vitro. In vivo, naturally, 10-month-old C57/B6 mice were used as treatment models. The mice were injected with 50 mg/kg salidroside every day for a total of 14 days. Then, the corresponding reproductive function. In vitro, We added 25uM salidroside to the IVM solution and conducted IVM experiments on 10-month-old GV oocytes. CGS and spindle staining observed the oocyte maturation. Main results and the role of chance We found that salidroside can increase the number of MII oocytes excreted in 10-month-old female mice, and at the same time, increase the number of pups per litter and the total number of pups. Follicle statistics showed that the addition of salidroside could increase the follicle reserve of 10-month-old female mice. Collection of GV stage oocytes. In the in vitro IVM treatment group, salidroside can delay oocyte GVBD. Improve the GVBD condition and polar body excretion of aged oocytes, At the same time, parthenogenetic activation showed that the salidroside treatment group could significantly improve the developmental ability of old parthenogenetic embryos. After 14 days of in vivo treatment, GV oocytes were collected to detect mitochondrial function. It was found that salidroside could increase the mitochondria distribution, enhance changes in mitochondrial membrane potential, and improve ROS scavenging ability. The same results were also obtained in the in vitro IVM treatment group. Limitations, reasons for caution This study found that salidroside treatment can improve ovarian aging, but the specific molecular mechanism is not clear, which is not conducive to the use of salidroside as a clinical medication. Wider implications of the findings In this study, we discovered the potential therapeutic effect of salidroside in ovarian aging and made a preliminary exploration of the therapeutic mechanism, which provides important insights into salidroside as a drug for ovarian aging. Trial registration number not applicable

Lignin-Based Antioxidant Hydrogel Patch for the Management of Atopic Dermatitis by Mitigating Oxidative Stress in the Skin.

Atopic dermatitis (AD), a chronic skin condition characterized by itching, redness, and inflammation, is closely associated with heightened levels of endogenous reactive oxygen species (ROS) in the skin. ROS can contribute to the onset and progression of AD through oxidative stress, which leads to the release of proinflammatory cytokines, T-cell differentiation, and the exacerbation of skin symptoms. In this study, we aim to develop a therapeutic antioxidant hydrogel patch for the potential treatment of AD using lignin, a biomass waste material. Lignin contains polyphenol groups that enable it to scavenge ROS and exhibit antioxidant properties. The lignin hydrogel patches, possessing optimized mechanical properties through the control of the lignin and cross-linker ratio, demonstrated high ROS-scavenging capabilities. Furthermore, the lignin hydrogel demonstrated excellent biocompatibility with the skin, exhibiting beneficial properties in protecting human keratinocytes under high oxidative conditions. When applied to an AD mouse model, the hydrogel patch effectively reduced epidermal thickness in inflamed regions, decreased mast cell infiltration, and regulated inflammatory cytokine levels. These findings collectively suggest that lignin serves as a therapeutic hydrogel patch for managing AD by modulating oxidative stress through its ROS-scavenging ability.

Hot Water Treatment Preserves Chinese Chestnut (Castanea mollissima Blume) Quality during Storage by Increasing Its Sugar Accumulation and ROS-Scavenging Ability

Heat treatment is a widely used physical technology for postharvest fruit and crops. The Chinese chestnut cultivar “Kuili” has high sugar and amylose contents, and is popular among people. However, the chestnut quality decreases quickly after harvest. In order to maintain the chestnuts’ quality during storage, this study explores five hot water treatments for chestnuts: T1 (control, no treatment), T2 (50 °C), T3 (65 °C), T4 (75 °C), and T5 (90 °C) for 45 min. T1 was dried at ambient temperature, while the other heat treatments were dried at 30 °C for 30 min. After treatment, chestnuts were placed in plastic trays, covered with a 15 μm thick PVC film, and stored at 4 °C with 70% relative humidity; they remained in the same air for 120 days. Results indicated that T3 and T4 showed slight color changes while maintaining shell and kernel firmness, and their weight loss was reduced (+5–8%), as well as their decay rate (limited to within 20%). The T3, T4, and T5 treatments (from days 60 to 120) decreased their pest survival rates to &lt;2%. Additionally, heat treatments facilitated the accumulation of total soluble sugar and increased the expression of sugar biosynthesis-related genes. Meanwhile, T3 and T4 delayed starch reduction (they maintained relatively higher contents, from 288 to ~320 mg g−1 DW) and altered some starch biosynthesis genes. Furthermore, T2, T3, and T4 exhibited higher antioxidant activity and lower hydrogen peroxide (H2O2) and superoxide anions (O2−) contents than T1. At the end of storage, the scores of T3 and T4 treatments were 55.1 and 52.3, and they ranked first and second among the five treatments, respectively. Therefore, these findings provide valuable insights for controlling postharvest losses in chestnuts.

Selected phytocannabinoids inhibit SN-38- and cytokine-evoked increases in epithelial permeability and improve intestinal barrier function in vitro

Irinotecan use is linked to the development of gastrointestinal toxicity and inflammation, or gastrointestinal mucositis. Selected phytocannabinoids have been ascribed anti-inflammatory effects in models of gastrointestinal inflammation, associated with maintaining epithelial barrier function. We characterised the mucoprotective capacity of the phytocannabinoids: cannabidiol, cannabigerol, cannabichromene and cannabidivarin in a cell-based model of intestinal epithelial stress occurring in mucositis.Transepithelial electrical resistance (TEER) was measured to determine changes in epithelial permeability in the presence of SN-38 (5 μM) or the pro-inflammatory cytokines TNFα and IL-1β (each at 100 ng/mL), alone or with concomitant treatment with each of the phytocannabinoids (1 μM). The DCFDA assay was used to determine the ROS-scavenging ability of each phytocannabinoid following treatment with the lipid peroxidant tbhp (200 μM).Each phytocannabinoid provided significant protection against cytokine-evoked increases in epithelial permeability. Cannabidiol, cannabidivarin and cannabigerol were also able to significantly inhibit SN-38-evoked increases in permeability. None of the tested phytocannabinoids inhibited tbhp-induced ROS generation.These results highlight a novel role for cannabidiol, cannabidivarin and cannabigerol as inhibitors of SN-38-evoked increases in epithelial permeability and support the rationale for the further development of novel phytocannabinoids as supportive therapeutics in the management of irinotecan-associated mucositis.

Physiological Studies and Transcriptomic Analysis Reveal the Mechanism of Saline-Alkali Stress Resistance of Malus sieversii f. niedzwetzkyan

Malus sieversii f. niedzwetzkyan, a wild species capable of growing on saline-alkali soil in Xinjiang, is the most promising horticultural crop for improving the saline-alkali wasteland. However, the tolerance of M. niedzwetzkyan to saline-alkali stress and the underlying molecular mechanisms remains largely unknown. Here, we conducted a hydroponic experiment in which M. niedzwetzkyana and M. domestica “Royal Gala” seedlings were subjected to 150 mM saline-alkali stress. Physiological data showed that M. niedzwetzkyana had a strong ROS scavenging ability and ion transport ability, and its saline-alkali resistance was higher than that of M. “Royal Gala”. Saline-alkali stress also promoted the synthesis of anthocyanins in M. niedzwetzkyana. Transcriptome analysis was conducted on the leaves and roots of M. niedzwetzkyana at different time points under saline-alkali stress (0 h, 6 h, and 12 h). Transcriptome analysis revealed that saline stress down-regulated most genes involved in the anthocyanin flavonoid synthesis pathway. Transcription levels of genes involved in antioxidant enzyme activity and ion transport were altered. We identified hub genes related to superoxide dismutase as well as Na+ and K+ transport using weighted gene co-expression network analysis. This study elucidated, for the first time at the molecular level, the saline-alkali tolerance of M. niedzwetzkyana, including the complex changes in pathways that regulate reactive oxygen species homeostasis, ion uptake, and anthocyanoside synthesis under saline-alkali stress conditions. This research provides an important genetic resource for identifying genes involved in responses to saline-alkali stress.

Synergistic Effect of Flavonoids and Metformin on Protection of the Methylglyoxal-Induced Damage in PC-12 Neuroblastoma Cells: Structure-Activity Relationship and Potential Target.

Methylglyoxal-induced ROS elevation is the primary cause of neuronal damage. Metformin is a traditional hypoglycemic drug that has been reported to be beneficial to the nervous system. In this study, flavonoids were found to enhance the protective effect of metformin when added at a molar concentration of 0.5%. The structure-activity relationship (SAR) analysis indicated that ortho- substitution in the B ring, and the absence of double bonds between the 2 and 3 position combined with the gallate substitution with R configuration at the 3 position in the C ring played crucial roles in the synergistic effects, which could be beneficial for designing a combination of the compounds. Additionally, the mechanism study revealed that a typical flavonoid, EGCG, enhanced ROS scavenging and anti-apoptotic ability via the BCL2/Bax/Cyto C/Caspase-3 pathway, and synergistically inhibited the expression of GSK-3β, BACE-1, and APP in PC-12 cells when used in combination with metformin. The dose of metformin used in the combination was only 1/4 of the conventional dose when used alone. These results suggested that ROS-mediated apoptosis and the pathways related to amyloid plaques (Aβ) formation can be the targets for the synergistic neuroprotective effects of flavonoids and metformin.

Chitosan catechol-tannic acid composite hydrogel and cryogel with antimicrobial and hemostatic properties

Hydrogels containing catechol group have received attention in the biomedical field due to their robust adhesive/cohesive capabilities, biocompatibility, and hemostatic abilities. Catechol-functionalized chitosan holds promise for preparing self-assembly hydrogels. However, issues of inefficient gelation and instability still persist in these hydrogels. In the current study, we synthesized chitosan catechol (CC) of high catechol substitution (∼28 %) and combined CC with tannic acid (TA, which also contains catechol) to form self-healing CC-TA hydrogels. The catechol-enriched CC-TA composite hydrogels showed rapid gelation and mechanical reinforcement (shear modulus ∼110 Pa). In situ coherent small-angle X-ray scattering (SAXS) coupled with rheometry revealed a morphological feature of mesoscale clusters (∼20 nm) within CC-TA hydrogel. The clusters underwent dynamic destruction under large-amplitude oscillatory shear, corresponding with the strain-dependent and self-healing behavior of the CC-TA hydrogel. The composite hydrogel had osmotic-responsive and notable adhesive properties. Meanwhile, CC-TA composite cryogel prepared simply through freeze-thawing procedures exhibited distinctive macroporous structure (∼200 μm), high water swelling ratio (∼7000 %), and favorable compressive modulus (∼8 kPa). The sponge-like cryogel was fabricated into swabs, demonstrating hemostatic capacity. The CC-TA composites, in both hydrogel and cryogel forms, possessed ROS scavenging ability, antimicrobial activity, and cell compatibility with potentials in biological applications.

Ruthenium(II) Polypyridyl Complexes with Benzoxazole Derivatives and Non-Innocent Ligands as Effective Antioxidants in Human Neuroblasts.

Ruthenium(II) polypyridyl complexes continue to raise increasing interest for the encouraging results in several biomedical areas. Considering their vast chemical-physical repertoire, in particular the possibility to switch from the sensitization of reactive oxygen species (ROS) to ROS-scavenging abilities by tuning the nature of their ligands, it is therefore surprising that their potential as antioxidants has not been largely investigated so far. Herein, we explored the antioxidant behaviour of the novel ruthenium compound [Ru(dbpy)(2,3-DAN)Cl]PF6 (Ru1), featuring a benzoxazole derivative (dpby=2,6-bis(4-methyl-2-benzoxazolyl)pyridine) and the non-innocent 2,3-diamminonaftalene (2,3-DAN) ligand, along with the reference tpy-containing analogue [Ru(tpy)(2,3-DAN)Cl]PF6 (Ru2) (tpy=2,2':6',2''-terpyridine). Following the synthesis and the electrochemical characterization, chemical antioxidant assays highlighted the beneficial role of dpby for the ROS-scavenging properties of Ru1. These data have been corroborated by the highest protective effect of Ru1 against the oxidative stress induced in SH-SY5Y human neuroblastoma, which exerts pro-survival and anti-inflammatory actions. The results herein reported highlight the potential of Ru1 as pharmacological tool in neurodegenerative diseases and specially prove that the antioxidant properties of such compounds are likely the result of a non-trivial synergetic action involving the bioactive ligands in their chemical architectures.