Reactive Oxygen Species Scavenging Capacity Research Articles

Establishment of Agrobacterium-Mediated Transient Transformation System in Desert Legume Eremosparton songoricum (Litv.) Vass.

Eremosparton songoricum (Litv.) Vass. is a desert legume exhibiting extreme drought tolerance and the ability to withstand various harsh environments, making it a good candidate for investigating stress tolerance mechanisms and exploring valuable stress-resistant genes. However, the absence of a genetic transformation system for E. songoricum poses significant limitations for functionally validating these stress-resistant genes in situ. In this study, we developed an Agrobacterium-mediated transient transformation system for E. songoricum utilizing the β-glucuronidase (GUS) gene as a reporter. We investigated three types of explants (seedlings, assimilated branches and callus) and the effects of different Agrobacterium strains, seedling ages, OD600 values, acetosyringone (AS) concentrations, sucrose concentrations and infection times on the transformation efficiency. The results reveal that the optimal transformation system was infecting one-month-old regenerating assimilated branches with the Agrobacterium strain C58C1. The infection solution comprised 1/2 MS medium with 3% sucrose and 200 μM AS at an OD600 of 0.8, infection for 3 h and then followed by 2 days of dark cultivation, which achieving a maximum transformation rate of 97%. The maximum transformation rates of the seedlings and calluses were 57.17% and 39.51%, respectively. Moreover, we successfully utilized the assimilated branch transient transformation system to confirm the role of the previously reported transcription factor EsDREB2B in E. songoricum. The overexpression of EsDREB2B enhanced drought tolerance by increasing the plant’s reactive oxygen species (ROS) scavenging capacity in situ. This study established the first transient transformation system for a desert legume woody plant, E. songoricum. This efficient system can be readily applied to investigate gene functions in E. songoricum. It will expedite the exploration of genetic resources and stress tolerance mechanisms in this species, offering valuable insights and serving as a reference for the transformation of other desert plants and woody legumes.

Hyaluronic acid methacrylate/Pluronic F127 hydrogel enhanced with spermidine-modified mesoporous polydopamine nanoparticles for efficient synergistic periodontitis treatment

Bacterial infection, reactive oxygen species (ROS) accumulation, and persistent inflammation pose significant challenges in the treatment of periodontitis. However, the current single-modal strategy makes achieving the best treatment effect difficult. Herein, we developed a double-network hydrogel composed of Pluronic F127 (PF-127) and hyaluronic acid methacrylate (HAMA) loaded with spermidine-modified mesoporous polydopamine nanoparticles (M@S NPs). The PF-127/HAMA/M@S (PH/M@S) hydrogel was injectable and exhibited thermosensitivity and photocrosslinking capabilities, which enable it to adapt to the irregular shape of periodontal pockets. In vitro, the PH/M@S displayed multiple therapeutic effects, such as photothermal antibacterial activity, a high ROS scavenging capacity, and anti-inflammatory effects, which are beneficial for the multimodal treatment of periodontitis. The underlying anti-inflammatory mechanism of this hydrogel involves suppression of the extracellular regulated protein kinase 1/2 and nuclear factor kappa-B signalling pathways. Furthermore, in lipopolysaccharide-stimulated macrophage conditioned media, the PH/M@S effectively restored the osteogenic differentiation potential. In a rat model of periodontitis, the PH/M@S effectively reduced the bacterial load, relieved local inflammation and inhibited alveolar bone resorption. Collectively, these findings highlight the versatile functions of the PH/M@S, including photothermal antibacterial activity, ROS scavenging, and anti-inflammatory effects, indicating that this hydrogel is a promising multifunctional filling material for the treatment of periodontitis.

Eugenol-Loaded Lipid Nanoparticles-Derived Hydrogels Ameliorate Psoriasis-like Skin Lesions by Lowering Oxidative Stress and Modulating Inflammation.

Psoriasis is a chronic T-cell-mediated autoimmune skin disorder characterized by excessive epidermal thickening, overproliferation of keratinocyte, disruption of epidermal cell differentiation, and increased blood vessel growth in the dermal layer. Despite the common use of corticosteroids in psoriasis treatment, their limited efficacy and numerous side effects pose significant challenges. This research introduces a promising alternative approach by encapsulating eugenol (EU) in soya phosphatidylcholine (SPC) nanoparticles (EUNPs) which showed spherical shape nanoparticles with a hydrodynamic size of approximately 200 nm, polydispersity index 0.23, encapsulation efficiency of 85% having good colloidal stability indicated by ζ-potential of -27 mV. Later on, these EUNPs were formulated into a topical hydrogel system by using Carbopol 974P (EUNPGel), which exhibited superior drug loading, enhanced release kinetics for 48 h, long-term stability, and the ability to scavenge reactive oxygen species (ROS). Furthermore, EUNPs inhibited keratinocyte proliferation, induced apoptosis, and augmented the uptake of IL-6-mediated inflammation in human keratinocyte cells. Application of EUNPs-loaded gels (EUNPGel) to imiquimod-induced psoriatic lesions demonstrated effective dermal penetration, suppressed keratinocyte hyperplasia and restored epidermal growth. This led to a remarkable reduction in the Psoriasis Area and Severity Index (PASI) score from 3.75 to 0.5 within 5 days. This novel approach enhances ROS scavenging capacity, improves cellular uptake, facilitates skin penetration and retention, reduces the activity of hyperactive immune cells, and suggests potential applications for treating other immune-related disorders such as acne and atopic dermatitis.

Selenium-doped carbon dots inhibit ferroptosis by multi-hierarchy iron chelation and mitochondrial homeostasis regulation to control inflammation

Ferroptosis has been identified as a prevalent pathological process in both infectious and non-infectious inflammation. Multiregional iron accumulation within extracellular, cytoplasmic, and subcellular compartments, particularly into mitochondria, can trigger lipid peroxidation and subsequent ferroptosis. Meanwhile, mitochondrial dysfunction, as a hallmark feature of ferroptosis, also exacerbates ferroptosis and inflammation. Here, a strategy of multi-hierarchy iron chelation coupled with mitochondrial homeostasis regulation is proposed to inhibit ferroptosis and relieve inflammation based on selenium-doped carbon dots (SeCDs). SeCDs with reactive oxygen species (ROS) scavenging capacity can be efficiently internalized into cells and enriched in mitochondria. Through the multi-hierarchy chelation for extracellular, cytoplasmic, and mitochondrial iron, iron overload is remarkably inhibited. Meanwhile, promoting glutathione peroxidase 4 (GPX4) expression and activating the AMPK pathway can restrain the metabolism of glycerophospholipids and polyunsaturated fatty acids and lipid peroxidation. Importantly, SeCDs restore mitochondrial homeostasis by chelating mitochondrial iron, scavenging mtROS, and increasing the level of GPX4, thereby enhancing ferroptosis suppression. Further, SeCDs rescue the osteogenic differentiation potential of stem cells, which is generally weakened by ferroptosis. In vivo experiments prove that SeCDs can significantly inhibit ferroptosis and inflammation, and facilitate tissue regeneration. Thus, this multifunctional nanosystem provides a promising therapeutic strategy to inhibit ferroptosis and ease inflammation.

Hybrid hydrogel loaded with natural plant extract accelerates diabetic wound healing via ROS scavenging and immunoregulation

Diabetic wound (DW) is often characterised by reactive oxygen species (ROS) accumulation, disordered inflammation, and macrophage polarisation abnormality. Herein, natural plant extract, Kunzea ericoides leaf extract (KELE), was loaded into Gelatin Methacryloyl (GelMA) to fabricate a hybrid hydrogel (referred to as KELE@Gel) as a multi-functional dressing to treat DW. Using the UHPLC-Q-Exactive Orbitrap MS/MS strategy aided by database analysis, multiple compounds with antioxidative and anti-inflammatory properties were identified in KELE. The optimal concentration of GelMA and KELE was determined based on the mechanical properties and biocompatibility evaluation to obtain an ideal hydrogel for wound application. Further in vitro investigations discovered that the KELE@Gel hydrogel possessed a superior cytocompatibility and ROS scavenging capacity on RAW 264.7 cell lines under hydrogen peroxide (H2O2) or lipopolysaccharides (LPS) stimulation. Meanwhile, the hybrid hydrogel inhibited expressions of several cytokines, such as interleukin (IL)-1β, IL-6, and tumour necrosis factor (TNF)-α and manipulated M1/M2 macrophage polarisation in an inflammatory microenvironment. The immunoregulatory mechanism of the hydrogel was investigated through mRNA-sequencing and transcriptomic bioinformatics analysis. Animal experiments also discovered that the KELE@Gel hydrogel significantly promoted DW healing with preferable re-epithelialisation, angiogenesis and collagen deposition by enhanced antioxidative, anti-inflammatory and immunoregulatory activities. Above all, the KELE@Gel hydrogel released bioactive components sustainably, achieving a moderate antioxidative, anti-inflammatory and immunoregulatory capacity alongside the whole course of DW healing. In conclusion, this naturally derived hybrid hydrogel ameliorated undesirable microenvironments in DW and showed great potential to serve as a multi-functional wound dressing in clinical practice.

Development of oral pH-sensitive redox nanotherapeutics for gastric ulcer therapy

Gastric ulcer is a common gastrointestinal disorder worldwide. Although its pathogenesis is unclear, the overproduction of reactive oxygen species (ROS), which results in an oxidative imbalance, has been reported as a central driving mechanism. Within the scope of this investigation, we developed two different self-assembling redox nanoparticles (RNPs) with ROS-scavenging features for the oral treatment of gastric ulcers. One of them, referred to as RNPN, disintegrates in response to acidic pH, whereas the other, denoted as RNPO, remains intact regardless of pH variations. Both types of RNPs showed different free radical scavenging activities in vitro. Protonation of the amino linkages in the side chains of RNPN caused the micelle structure to collapse and the nitroxide radicals encapsulated in the core were exposed to the outside, resulting in a significant increase in antioxidant capacity as the pH decreases. In contrast, RNPO maintained its spherical structure and consistent antioxidant reactivity irrespective of pH changes. The in vivo gastric retention of orally administered RNPN was significantly improved compared to that of RNPO which might be explained by the increased exposure of cationic protonating segments in RNPN on the negatively charged gastric mucosal surface. Owing to its improved gastric retention and enhanced ROS scavenging capacity under acidic pH conditions, RNPN exhibited superior protective effects against oxidative stress induced by aspirin in a gastric ulcer mouse model compared to RNPO. In addition, neither RNPN nor RNPO resulted in severe lethal effects or significant changes in the morphology of zebrafish embryos, indicating their biosafety. Our results suggest that the oral administration of RNPs has a high therapeutic potential for gastric ulcer treatment.

Gastrointestinal Self-Adaptive and Nutrient Self-Sufficient Akkermansia muciniphila-Gelatin Porous Microgels for Synergistic Therapy of Ulcerative Colitis.

To realize effective and long-term synergistic therapy of ulcerative colitis (UC) with probiotics, we developed gastrointestinal self-adaptive and nutrient self-sufficient Akkermansia muciniphila (AKK)-gelatin porous microgels (AKK@GPMGs). In AKK@GPMGs, AKK was covered with sequential layers of proanthocyanidins (PAs), mucin (MUC), and phosphatidylcholine (PC) to obtain AKK@PAs-MUC-PC (AKK@PMP), and then encapsulated within the methacrylate-modified gelatin porous microgels. AKK@GPMGs provide sufficient mucus as a nutrition source for AKK and boost resistance to stomach acid by 30.49-fold, and colonization in the intestines is enhanced by 83.46 times. The microgels can be dissociated by matrix metalloproteinase at the inflammatory sites of the intestine, and release AKK@PMP, which acts as "band-aid" that adheres to the inflamed colon for a long time and offers improved synergistic therapy for UC. Compared to uncoated AKK, AKK@GPMGs increase reactive oxygen species scavenging capacity by 26.47 times, improve the intestinal mucus layer thickness by 5.63 times, increase the goblet cells abundance by 3.93 times, reduce intestinal permeability by 5.60 times and significantly enhance beneficial gut microbiota while repressing harmful microbiota. These results indicate that AKK@GPMGs can restore mucus layer and tight junction integrity, reduce inflammation and oxidative stress, and regulate gut microbiota homeostasis to effectively treat intestinal inflammation.

Decreased ability to manage increases in reactive oxygen species may underlie susceptibility to arrhythmias in mice lacking Scn1b.

Scn1b plays essential roles in the heart, where it encodes β1-subunits that serve as modifiers of gene expression, cell surface channel activity, and cardiac conductivity. Reduced β1 function is linked to electrical instability in various diseases with cardiac manifestations and increased susceptibility to arrhythmias. Recently, we demonstrated that loss of Scn1b in mice leads to compromised mitochondria energetics and reactive oxygen species (ROS) production. In this study, we examined the link between increased ROS and arrhythmia susceptibility in Scn1b-/- mice. In addition, ROS-scavenging capacity can be overwhelmed during prolonged oxidative stress, increasing arrhythmia susceptibility. Therefore, we isolated whole hearts and cardiomyocytes from Scn1b-/- and Scn1b+/+ mice and subjected them to an oxidative challenge with diamide, a glutathione oxidant. Next, we analyzed gene expression and activity of antioxidant enzymes in Scn1b-/- hearts. Cells isolated from Scn1b-/- hearts died faster and displayed higher rates of ROS accumulation preceding cell death compared with those from Scn1b+/+. Furthermore, Scn1b-/- hearts showed higher arrhythmia scores and spent less time free of arrhythmia. Lastly, we found that protein expression and enzymatic activity of glutathione peroxidase is increased in Scn1b-/- hearts compared with wild type. Our results indicate that Scn1b-/- mice have decreased capability to manage ROS during prolonged oxidative stress. ROS accumulation is elevated and appears to overwhelm ROS scavenging through the glutathione system. This imbalance creates the potential for altered cell energetics that may underlie increased susceptibility to arrhythmias or other adverse cardiac outcomes.NEW & NOTEWORTHY Using an oxidative challenge, we demonstrated that isolated cells from Scn1b-/- mice are more susceptible to cell death and surges in reactive oxygen species accumulation. At the whole organ level, they were also more susceptible to the formation of cardiac arrhythmias. This may in part be due to changes to the glutathione antioxidant system.

2D MXene Nanosheets with ROS Scavenging Ability Effectively Delay Osteoarthritis Progression.

MXenes nanosheets with high conductivity, hydrophilicity, and excellent reactive oxygen species (ROS) scavenging ability have shown promise in treating various degenerative diseases correlated with abnormal ROS accumulation. Herein, the therapeutic potential of Ti3C2Tx nanosheets, which is the most widely investigated MXene material, in delaying osteoarthritis (OA) progression is demonstrated. In vitro experiments indicate the strong ROS scavenging capacity of Ti3C2Tx nanosheets and their acceptable biocompatibility. Ti3C2Tx nanosheets effectively protect chondrocytes from cell death induced by oxidative stress. In addition, Ti3C2Tx nanosheets demonstrate a prominent anti-inflammatory effect and the ability to restore homeostasis between anabolic activities and catabolic activities in chondrocytes. Furthermore, RNA sequencing reveals the potential mechanism underlying the Ti3C2Tx nanosheet-mediated therapeutic effect. Finally, the in vivo curative effect of Ti3C2Tx nanosheets is verified using a rat OA model. Histological staining and immunohistochemical analyses indicate that Ti3C2Tx nanosheets effectively ameliorate OA progression. Conclusively, the in vitro and in vivo experiments suggest that Ti3C2Tx nanosheets could be a promising and effective option for OA treatment.

MnO2 nanozyme boosts synergistic photodynamic/photothermal therapy of bacterial biofilm infections

As a near-infrared (NIR) adsorbing dye approved by the FDA, indocyanine green (ICG) can serve as an attractive therapeutic agent to combat biofilm infections through synergistic photodynamic therapy (PDT) and photothermal therapy (PTT) due to its deep-tissue penetration ability. However, ICG usually suffers from photo/thermal instability. Herein, to tackle the issues, bovine serum albumin (BSA) stabilized nanozyme MnO2 (BSA/MnO2) was synthesized by reducing manganese permanganate (KMnO4) with BSA, which was further loaded with ICG and coated with the positively charged hydroxypropyltrimethyl ammonium chloride chitosan (HACC) as the bacterial targeting moiety through noncovalent interactions. The constructed ICG@BSA/MnO2@HACC (IBMH) displays good photodynamic/thermal effects and bacterial targetability, enabling a synergistic PDT/PTT therapy against biofilm-associated infections. Compared with free ICG, IBMH exhibits enhanced photo/thermal stability owing to the O2-generating and photothermal capacities of MnO2, which significantly promotes biofilm phototherapy. Meanwhile, IBMH can effectively achieve anti-inflammatory effect due to the reactive oxygen species (ROS) scavenging capacity of nanozyme MnO2, thereby greatly accelerating wound healing after synergistic PDT/PTT. Both in vitro and in vivo assays solidly demonstrate its satisfactory anti-biofilm and anti-inflammatory effects. Therefore, our research proposes a promising and convenient strategy for developing multifunctional nanozyme for synergistic PDT/PTT of biofilm infection.

Valorization of Strawberry Tree Berries and Beeswax from Montesinho Natural Park for Cosmetic Industry-A Case Study Formulation.

Consumers are increasingly concerned about cosmetic ingredients' origin, looking more than ever to sustainable and greener formulations. The Natural Park of Montesinho, located in Portugal, is characterized by an enormous fauna and flora diversity. Among them, beeswax and strawberry trees (Arbutus unedo) have attracted the cosmetic researchers' interest due to their bioactive compounds' richness, particularly fatty acids and phenolic compounds. The main goal of this study was to develop an innovative cosmetic product with antioxidant properties composed by both matrices. Briefly, samples were obtained in the Natural Park of Montesinho in October 2022. Beeswax was analysed for lipid profile and contaminants, while extracts were obtained from fruits by ultrasound-assisted extraction (UAE) using water as a solvent. The effect of extraction time (15-90 min) was studied on the total phenolic content (TPC), in vitro antioxidant/antiradical activity, and reactive oxygen species (ROS) scavenging capacity. The beeswax lipid profile presented a high incidence of palmitic, oleic, and linoleic acids. The extract obtained at 60 min presented the highest TPC (30.27 mg GAE/g dw) and antioxidant/antiradical activities (ABTS = 30.36 mg AAE/g dw; DPPH = 43.83 mg TE/g dw; FRAP = 415.61 µmol FSE/g dw). An IC50 of 19.78 µg/mL was achieved for the hypochlorous acid, while for superoxide radical and peroxyl radical the IC50 were, respectively, 90.51 µg/mL and 0.19 µmol TE/mg dw. The phytochemical profile revealed a high content of gallic acid, and catechin and its derivatives. The hydrophilic cream developed revealed ideal technological parameters, particularly its stability.

Can Rice Growth Substrate Substitute Rapeseed Growth Substrate in Rapeseed Blanket Seedling Technology? Lesson from Reactive Oxygen Species Production and Scavenging Analysis.

Rapeseed (Brassica napus L.) seedlings suffering from inappropriate growth substrate stress will present poor seedling quality. However, the regulatory mechanism for the production and scavenging of reactive oxygen species (ROS) caused by this type of stress remains unclear. In the current study, a split plot experiment design was implemented with two crop growth substrates-a rice growth substrate (RIS) and rapeseed growth substrate (RAS)-as the main plot and two genotypes-a hybrid and an open-pollinated variety (Zheyouza 1510 and Zheyou 51, respectively)-as the sub-plot. The seedling quality was assessed, and the ROS production/scavenging capacity was evaluated. Enzymatic and non-enzymatic systems, including ascorbic acid and glutathione metabolism, and RNA-seq data were analyzed under the two growth substrate treatments. The results revealed that rapeseed seedling quality decreased under RIS, with the plant height, maximum leaf length and width, and aboveground dry matter being reduced by 187.7%, 64.6%, 73.2%, and 63.8% on average, respectively, as compared to RAS. The main type of ROS accumulated in rapeseed plants was hydrogen peroxide, which was 47.8% and 14.1% higher under RIS than under RAS in the two genotypes, respectively. The scavenging of hydrogen peroxide in Zheyouza 1510 was the result of a combination of enzymatic systems, with significantly higher peroxidase (POD) and catalase (CAT) activity as well as glutathione metabolism, with significantly higher reduced glutathione (GSH) content, under RAS, while higher oxidized glutathione (GSSH) was observed under RIS. However, the scavenging of hydrogen peroxide in Zheyou 51 was the result of a combination of elevated oxidized ascorbic acid (DHA) under RIS and higher GSH content under RAS. The identified gene expression levels were in accordance with the observed enzyme expression levels. The results suggest that the cost of substituting RAS with RIS is a reduction in rapeseed seedling quality contributing to excessive ROS production and a reduction in ROS scavenging capacity.

Inhaled tea polyphenol-loaded nanoparticles coated with platelet membranes largely attenuate asthmatic inflammation

BackgroundTea polyphenols (TPs), prominent constituents of green tea, possess remarkable antioxidant and anti-inflammatory properties. However, their therapeutic potential is limited due to low absorption and poor bioavailability. To address this limitation and enhance their efficacy, we developed a biomimetic nanoplatform by coating platelet membrane (PM) onto poly-lactic-co-glycolic acid (PLGA) nanoparticles (NPs) to create targeted delivery vehicles for TPs (PM@TP/NPs) to the inflamed tissues in asthma.MethodsAfter synthesizing and characterizing PM@TP/NPs, we assessed their biocompatibility and biosafety through cell viability assays, hemolysis tests, and inflammation analysis in vivo and in vitro. The therapeutic effect of PM@TP/NPs on asthma was then evaluated using a mouse model of HDM-induced asthma. Additionally, PM@TP/NPs-mediated reactive oxygen species (ROS) scavenging capacity, as well as the activation of signaling pathways, were analyzed in HBE cells and asthmatic mice via flow cytometry, RT-qPCR, and western blotting.ResultsCompared with free TPs, PM@TP/NPs demonstrated excellent biocompatibility and safety profiles in both in vitro and in vivo, as well as enhanced retention in inflamed lungs. In HDM-induced mouse asthma model, inhaled PM@TP/NPs largely attenuated lung inflammation and reduced the secretion of type 2 pro-inflammatory cytokines in the lungs compared to free TPs. The therapeutic effects of PM@TP/NPs on asthma might be associated with an enhanced ROS scavenging capacity, increased activation of the Nrf2/HO-1 pathway, and decreased activation of the CCL2/MAPK and TLR4/NF-κB pathway in the lungs.ConclusionsOur findings demonstrate that inhalation of PM@TP/NPs largely attenuated lung inflammation in HDM-induced asthmatic mice. These results suggest that PM@TP/NPs might be a novel therapeutic strategy for asthma.

CRISPR/Cas9-mediated genome editing of OsCS511 enhances cold tolerance in Oryza sativa L.

The frequency of climate change is increasing globally, which makes predictions challenging. Cold spells during the rice seedling stage can significantly reduce yield, prompting a constant need for cold-tolerant cultivars, which is a major breeding goal. However, the traditional crossbreeding of rice cultivars requires substantial time and effort. Recently, the application of CRISPR/Cas9 to reduce defects in elite cultivars has become a more cost-effective and time-efficient method for breeding cultivars than cross-breeding methods and can alleviate food insecurity. In the present study, CRISPR/Cas9-mediated genome editing was performed for OsCS511 a gene involved in cold susceptibility, identified using quantitative trait loci (QTL) mapping in Ilmi (Oryza sativa L. spp. Japonica cv. Ilmi). In Ilmi, CRISPR/Cas9 tool-edited OsCS511 homozygous lines were used in T0 and advanced generations in the field. CRISPR/Cas9 induced variations in the DNA sequence and plants with insertions or deletions compared to OsCS511 of Ilmi were selected as genome-edited lines. Agricultural traits, reactive oxygen species scavenging capacity, and stress-tolerance-related gene expression levels were evaluated under normal and cold stress conditions. Under normal conditions, all traits evaluated in the Ilmi and OsCS511 genome-edited lines exhibited similar results; however, when subjected to cold stress, the cold tolerance of OsCS511 genome-edited lines improved or reached the same level as that of Ilmi. OsCS511 genome-edited lines recovered and survived. From a breeding perspective, we suggest that CRISPR/Cas9 technology can precisely reduce defects in existing superior rice cultivars with high efficiency and speed.

Synthesis and Anticancer Evaluation of Disubstituted Benzimidazoles via One-Pot Telescopic Grinding Approach.

Benzimidazole compounds are known for their broad spectrum therapeutic potentials. A small library of benzimidazole derivatives were designed and synthesized via a one-pot telescopic grinding approach. The ability of these molecules as proposed anticancer agents were evaluated by their potential to bind to two important cancer pathway protein targets, human estrogen receptors and cyclin dependant kinases, 3ERT and 5FGK respectively. Further nucleic acid binding and reactive oxygen species (ROS) scavenging capacity being in the scope for anticancer potential evaluations, the ability of these molecules have been evaluated for the same. Further, to support the experimental and computational results, AI-assisted tools were employed to predict the anticancer activity (PASS) as well as to identify false positives (PAINS). Also, the druggability of the proposed compounds was evaluated by following their pharmacokinetic parameters - ADME.

A phased small interfering RNA-derived pathway mediates lead stress tolerance in maize.

Phased small interfering RNAs (phasiRNAs) are a distinct class of endogenous small interfering RNAs, which regulate plant growth, development and environmental stress response. To determine the effect of phasiRNAs on maize (Zea mays L.) tolerance to lead (Pb) stress, the roots of 305 maize lines under Pb treatment were subjected to generation of individual databases of small RNAs. We identified 55 high-confidence phasiRNAs derived from 13 PHAS genes (genes producing phasiRNAs) in this maize panel, of which 41 derived from nine PHAS loci were negatively correlated with Pb content in the roots. The potential targets of the 41 phasiRNAs were enriched in ion transport and import. Only the expression of PHAS_1 (ZmTAS3j, Trans-Acting Short Interference RNA3) was regulated by its cis-expression quantitative trait locus and thus affected the Pb content in the roots. Using the Nicotiana benthamiana (N. benthamiana) transient expression system, 5'-rapid amplification of cDNA ends, and Arabidopsis heterologously expressed, we verified that ZmTAS3j was cleaved by zma-miR390 and thus generated tasiRNA targeting ARF genes (tasiARFs), and that the 5' and 3' zma-miR390 target sites of ZmTAS3j were both necessary for efficient biosynthesis and functional integrity of tasiARFs. We validated the involvement of the zma-miR390-ZmTAS3j-tasiARF-ZmARF3-ZmHMA3 pathway in Pb accumulation in maize seedlings using genetic, molecular, and cytological methods. Moreover, the increased Pb tolerance in ZmTAS3j-overexpressed lines was likely attributed to the zma-miR390-ZmTAS3j-tasiARF-ZmARF3-SAURs pathway, which elevated indole acetic acid levels and thus reactive oxygen species scavenging capacity in maize roots. Our study reveals the importance of the TAS3-derived tasiRNA pathway in plant adaptation to Pb stress.

Responsive mechanism of Hemerocallis citrina Baroni to complex saline-alkali stress revealed by photosynthetic characteristics and antioxidant regulation.

Saline-alkali stress induces oxidative damage and photosynthesis inhibition in H. citrina, with a significant downregulation of the expression of photosynthesis- and antioxidant-related genes at high concentration. Soil salinization is a severe abiotic stress that impacts the growth and development of plants. In this study, Hemerocallis citrina Baroni was used to investigate its responsive mechanism to complex saline-alkali stress (NaCl:Na2SO4:NaHCO3:Na2CO3 = 1:9:9:1) for the first time. The growth phenotype, photoprotective mechanism, and antioxidant system of H. citrina were studied combining physiological and transcriptomic techniques. KEGG enrichment and GO analyses revealed significant enrichments of genes related to photosynthesis, chlorophyll degradation and antioxidant enzyme activities, respectively. Moreover, weighted gene co-expression network analysis (WGCNA) found that saline-alkali stress remarkably affected the photosynthetic characteristics and antioxidant system. A total of 29 key genes related to photosynthesis and 29 key genes related to antioxidant enzymes were discovered. High-concentration (250mmolL-1) stress notably inhibited the expression levels of genes related to light-harvesting complex proteins, photosystem reaction center activity, electron transfer, chlorophyll synthesis, and Calvin cycle in H. citrina leaves. However, most of them were insignificantly changed under low-concentration (100mmolL-1) stress. In addition, H. citrina leaves under saline-alkali stress exhibited yellow-brown necrotic spots, increased cell membrane permeability and accumulation of reactive oxygen species (ROS) as well as osmolytes. Under 100mmolL-1 stress, ROS was eliminate by enhancing the activities of antioxidant enzymes. Nevertheless, 250mmolL-1 stress down-regulated the expression levels of genes encoding antioxidant enzymes, and key enzymes in ascorbate-glutathione (AsA-GSH) cycle as well as thioredoxin-peroxiredoxin (Trx-Prx) pathway, thus inhibiting the activities of these enzymes. In conclusion, 250mmolL-1 saline-alkali stress caused severe damage to H. citrina mainly by inhibiting photosynthesis and ROS scavenging capacity.

NIR triggered polydopamine coated cerium dioxide nanozyme for ameliorating acute lung injury via enhanced ROS scavenging

Acute lung injury (ALI) is a life threatening disease in critically ill patients, and characterized by excessive reactive oxygen species (ROS) and inflammatory factors levels in the lung. Multiple evidences suggest that nanozyme with diversified catalytic capabilities plays a vital role in this fatal lung injury. At present, we developed a novel class of polydopamine (PDA) coated cerium dioxide (CeO2) nanozyme (Ce@P) that acts as the potent ROS scavenger for scavenging intracellular ROS and suppressing inflammatory responses against ALI. Herein, we aimed to identify that Ce@P combining with NIR irradiation could further strengthen its ROS scavenging capacity. Specifically, NIR triggered Ce@P exhibited the most potent antioxidant and anti-inflammatory behaviors in lipopolysaccharide (LPS) induced macrophages through decreasing the intracellular ROS levels, down-regulating the levels of TNF-α, IL-1β and IL-6, up-regulating the level of antioxidant cytokine (SOD-2), inducing M2 directional polarization (CD206 up-regulation), and increasing the expression level of HSP70. Besides, we performed intravenous (IV) injection of Ce@P in LPS induced ALI rat model, and found that it significantly accumulated in the lung tissue for 6 h after injection. It was also observed that Ce@P + NIR presented the superior behaviors of decreasing lung inflammation, alleviating diffuse alveolar damage, as well as promoting lung tissue repair. All in all, it has developed the strategy of using Ce@P combining with NIR irradiation for the synergistic enhanced treatment of ALI, which can serve as a promising therapeutic strategy for the clinical treatment of ROS derived diseases as well.

Mesoporous MOFs with ROS scavenging capacity for the alleviation of inflammation through inhibiting stimulator of interferon genes to promote diabetic wound healing

Excessive production of reactive oxygen species (ROS) and inflammation are the key problems that impede diabetic wound healing. In particular, dressings with ROS scavenging capacity play a crucial role in the process of chronic wound healing. Herein, Zr-based large-pore mesoporous metal–organic frameworks (mesoMOFs) were successfully developed for the construction of spatially organized cascade bioreactors. Natural superoxide dismutase (SOD) and an artificial enzyme were spatially organized in these hierarchical mesoMOFs, forming a cascade antioxidant defense system, and presenting efficient intracellular and extracellular ROS scavenging performance. In vivo experiments demonstrated that the SOD@HMUiO-MnTCPP nanoparticles (S@M@H NPs) significantly accelerated diabetic wound healing. Transcriptomic and western blot results further indicated that the nanocomposite could inhibit fibroblast senescence and ferroptosis as well as the stimulator of interferon genes (STING) signaling pathway activation in macrophages mediated by mitochondrial oxidative stress through ROS elimination. Thus, the biomimetic multi-enzyme cascade catalytic system with spatial ordering demonstrated a high potential for diabetic wound healing, where senescence, ferroptosis, and STING signaling pathways may be potential targets.Graphical Schematic diagram showing the proposed mechanism that S@M@H NPs promoted diabetic wound healing

PagWOX11/12a from hybrid poplar enhances drought tolerance by modulating reactive oxygen species

WOX11/12 is a homeobox gene of WOX11 and WOX12 in Arabidopsis that plays important roles in crown root development and growth. It has been reported that WOX11/12 participates in adventitious root (AR) formation and different abiotic stress responses, but the downstream regulatory network of WOX11/12 in poplar remains to be further investigated. In this study, we found that PagWOX11/12a is strongly induced by PEG-simulated drought stress. PagWOX11/12a-overexpressing poplar plantlets showed lower oxidative damage levels, greater antioxidant enzyme activities and reactive oxygen species (ROS) scavenging capacity than non-transgenic poplar plants, whereas PagWOX11/12a dominant repression weakened root biomass accumulation and drought tolerance in poplar. RNA-seq analysis revealed that several differentially expressed genes (DEGs) regulated by PagWOX11/12a are involved in redox metabolism and drought stress response. We used RT-qPCR and yeast one-hybrid (Y1H) assays to validate the downstream target genes of PagWOX11/12a. These results provide new insights into the biological function and molecular regulatory mechanism of WOX11/12 in the abiotic resistance processes of poplar.