搜索结果：Antioxidants (Basel, Switzerland)

Bio-based and biodegradable polymer composites based on polylactic acid (PLA) and polybutylene succinate-co-adipate (PBSA) were developed for rigid food packaging applications. Agro-industrial residues consisting of ground leaves and branches derived from tangerine tree cultivation (pruning) were used as fillers at high loading (30 wt%) before (PRE) or after (POST) extraction of bioactive compounds. The influence of blend composition (PLA/PBSA 60/40 and 30/70), filler extraction, and the addition of antioxidants (0.5 wt%) on material properties was systematically investigated. Composites were processed via extrusion and injection molding and characterized through FTIR, SEM, tensile testing and thermal analysis. The results show that polymer blend morphology affects mechanical behavior, with co-continuous structures (60/40) exhibiting improved ductility compared to dispersed systems (30/70). The incorporation of lignocellulosic residues increased stiffness but reduced elongation at break. Extraction treatment significantly modified filler morphology and interfacial interactions, slightly improving dispersion and processability. The effect of the extracted bioactive compounds on the thermal stabilization of biocomposites was also investigated. Overall, the findings demonstrate the potential of combining biodegradable polymer blends with treated agricultural residues to produce sustainable rigid packaging materials while supporting a bio-circular approach. In fact, preliminary extraction of valuable compounds from tangerine pruning waste appears to be a convenient strategy for its efficient cascade valorization.

Cirsium arvense (L.) Scop is a perennial plant of the family Asteraceae that is mainly distributed in the temperate regions of the Northern Hemisphere. Despite being widely recognized as an invasive weed in agriculture, most of the scientific evidence shows its significant phytochemical and pharmacological importance. In the present review article, a comprehensive summary of the available literature on C. arvense's botanical properties, phytochemical composition, biological activities, standardization potential, and future therapeutic prospects has been carefully provided. This plant has been used traditionally for the treatment of inflammation, infections, bleeding disorders, and liver-related disorders. Phytochemical investigations showed the presence of many bioactive compounds such as flavonoids, phenolic acids, triterpenes, sterols, tannins, glycosides, and volatile compounds. Among the reported biological activities, antioxidants and antimicrobial properties are the most studied activities. In addition, anticancer, antidiabetic, neuroprotective, anti-inflammatory, and antiproliferative activities have also been investigated. The environmental adaptability, rapid growth, and extensive root system of C. arvense highlight its potential for development as a sustainable medicinal and industrial crop. However, there are critical research gaps present in phytochemical standardization, toxicity assessment, pharmacokinetics, and clinical validation, warranting further comprehensive studies.

Flavonoids play critical roles in plant adaptation to abiotic stress by acting as potent antioxidants that regulate reactive oxygen species (ROS) homeostasis. In Atriplex canescens (Pursh) Nutt., a halophytic shrub well-adapted to saline and arid environments, transcriptomic analyses revealed that salt stress induces strong upregulation of flavanone 3-hydroxylase (F3H), a key enzyme in the flavonoid biosynthetic pathway. However, the functional role of AcF3H in stress adaptation remains poorly understood. Here, we cloned the AcF3H gene from A. canescens and generated transgenic Arabidopsis thaliana (L.) Heynh. lines constitutively overexpressing this gene. Overexpression of AcF3H significantly enhanced flavonoid accumulation, as confirmed by DPBA staining and total flavonoid quantification, and selectively upregulated the expression of downstream biosynthetic genes AcDFR and AcANS, which encode the dihydroflavonol 4-reductase (DFR) and anthocyanidin synthase (ANS), respectively. Under salt and drought stress, transgenic lines exhibited improved root elongation, increased shoot and root biomass, and higher relative water content compared to wild-type plants. Mechanistic investigations revealed that AcF3H overexpression led to reduced H2O2 accumulation and lower plasma membrane permeability under stress conditions, indicating enhanced antioxidative capacity and cellular membrane stability. These results suggest that AcF3H confers enhanced tolerance to abiotic stresses by promoting flavonoid-mediated ROS homeostasis. Our findings highlight AcF3H as a promising genetic target for engineering salt- and drought-tolerant crops.

Background: Oxidative stress contributes significantly to premature skin aging and inflammatory dermatological conditions. While plant-derived antioxidants have demonstrated considerable promise in topical applications, Bougainvillea glabra Choisy remains underexplored in standardized pharmaceutical dosage form development despite its documented phytochemical richness. Objective: This study aimed to develop, standardize, and characterize topical cold cream formulations incorporating B. glabra ethanolic leaf extract, with HPTLC-based quantification of marker compounds, validated antioxidant assessment, and preliminary dermal safety evaluation. Methods: The ethanolic leaf extract was prepared by maceration and characterized by preliminary phytochemical screening and HPTLC fingerprinting with quantitative densitometric analysis of quercetin and pinitol. Three cold cream formulations were developed at 10% (F1), 20% (F2), and 30% (w/w) (F3) extract loading. Formulations were evaluated for organoleptic properties, pH, homogeneity, spreadability, and viscosity. Antioxidant activity was assessed using a validated methanol extraction procedure followed by DPPH radical scavenging and potassium permanganate reduction assays. Ex vivo skin permeation was evaluated using Franz diffusion cells with freshly excised goat skin. Accelerated stability was conducted at 40 ± 2 °C/75 ± 5% RH for 90 days with HPTLC-based marker retention monitoring. Primary dermal safety was assessed in Wistar albino rats (n = 6) following OECD Test Guideline 404. Results: Quantitative HPTLC confirmed quercetin (4.82 ± 0.14 mg/g dry extract) and pinitol (2.31 ± 0.09 mg/g) as marker compounds, with linearly increasing content across F1-F3. All formulations demonstrated acceptable physicochemical properties (pH 5.7-5.9, viscosity 440,000-460,000 cP, spreadability 11.8 ± 0.3 cm·g/s). F3 exhibited the highest DPPH scavenging activity (56.68 ± 1.05%) with IC50 of 1.3 ± 0.1% w/v, demonstrating a 3.2-fold improvement over F1. Extraction recovery from the cream matrix was 96.4-97.1%, validating the antioxidant data. Ex vivo quercetin permeation through goat skin reached 51.3 ± 2.8 μg/cm2 at 24 h for F3, following Higuchi diffusion kinetics (R2 > 0.99). No dermal irritation was observed (Primary Irritation Index = 0). Accelerated stability confirmed ≥98.3% retention of both marker compounds and antioxidant activity after 90 days. Conclusions:B. glabra leaf extract was successfully incorporated into a physicochemically stable, non-irritating cold cream with demonstrated dose-dependent antioxidant efficacy and cutaneous delivery capability. The study establishes preliminary dermal safety and in vitro antioxidant efficacy warranting further controlled clinical evaluation.

Anemia in aging is multifaceted and may be in part caused by increased inflammation and oxidative stress. Almonds contain nutrients that may improve inflammation or antioxidant activity, which can improve red blood cell (RBC) integrity and mitigate anemia. The aim of this study is to investigate the effects of almond consumption on hematologic markers in a mouse model of aging. Forty-eight 18-month-old male and female C57BL/6 mice were randomized to receive a control diet or an almond-supplemented diet (15% calories from almond meal) for 12 or 21 weeks (four groups, n = 12/group). Blood and tissues were collected after respective intervention periods for analyses of hematologic markers (complete blood count analysis) and antioxidant status (RBC alpha-tocopherol concentration and superoxide dismutase activity). Mice consuming the almond-supplemented diet had significantly lower red cell distribution width at 12 weeks (p = 0.05) and significantly higher RBC count at 21 weeks (p = 0.04). Regression analyses indicated that almond intake resulted in higher RBC count (β = 0.82, p = 0.026) and lower odds of anemia (OR = 0.20, p = 0.046) after adjusting for sex of mice and length of intervention. These findings suggest that almond intake in aging mice improved selected hematologic markers and reduced anemia risk.

Melanoma is a highly aggressive and invasive form of skin cancer that arises from the uncontrolled growth of melanocytes. It is characterized by early spread through the lymphatic system and metastasis. The success of metastasis is linked to the ability of melanoma and other cancer cells to resist anoikis, a type of cell death that occurs when cells lose their adhesion to the extracellular matrix. Redox signaling plays an essential role in anoikis resistance. The balance between intracellular levels of nitric oxide (NO) and the reactive oxygen species (ROS) O2- and H2O2 stimulate signaling pathways related to proliferation and survival or cell death. A375 and SK-MEL-28 human melanomas cell lines, representing primary melanoma and lymph node metastatic melanoma cells, respectively, under suspension and adherent culture conditions were used to investigate the redox regulation of anoikis resistance. Both cell lines express the three isoforms of nitric oxide synthases (NOS) and NADPH oxidase 4 (NOX4) as endogenous sources of NO and ROS, respectively. When A375 cells in suspension were treated with the pan-NOS inhibitor L-NAME, their viability decreased. The treatment resulted in a decrease in FAK phosphorylation at Tyr397 and in ERK 1/2 phosphorylation. The expression of FAK, ERK 1/2, β-actin, and α-tubulin were significantly reduced. Treatment with L-NAME led to an increase in the expression of the metalloprotease MMP-9. SK-MEL-28 cells in suspension and treated with the NOX4 inhibitor, GKT36901, exhibited reduced viability. This was accompanied by the inhibition of FAK phosphorylation at Tyr397, ERK 1/2 phosphorylation, and a reduction in the expression of FAK, ERK 1/2, β-actin, and α-tubulin, with a slight elevation in the expression of MMP-9. Migration and invasion were strongly inhibited in A375 cells upon treatment with L-NAME, while treatment with GKT36901 had a marginal effect on the migration and invasion capacities of SK-MEL-28 cells. In summary, melanoma cells employ nitrosative and oxidative stress to shield themselves from anoikis. Nitric oxide was essential for melanoma cells at the primary site for resisting anoikis, while H2O2 contributed to anoikis resistance in metastatic melanoma cells.

Diabetic wounds remain a major clinical challenge due to impaired healing associated with persistent inflammation, oxidative stress, and microvascular dysfunction. Plasma-based therapies have emerged as promising approaches for promoting tissue repair; however, comparative evidence regarding different plasma modalities remains limited. In this study, we evaluated and compared the effects of atmospheric pressure cold plasma (APCP) and plasma-activated water (PAW) on wound healing in a streptozotocin-induced diabetic rat model. Forty Wistar albino rats were randomly assigned to five groups: isotonic wet dressing, hydrocolloid dressing, APCP treatment, PAW application, and a non-diabetic control group. Wound healing was assessed using macroscopic evaluation, histopathological analysis, and biochemical measurements of systemic oxidative status. PAW treatment significantly accelerated wound closure during the early healing phase compared with conventional dressing methods (p < 0.05). Histological findings demonstrated enhanced re-epithelialization, increased collagen deposition, and improved follicular regeneration in the PAW group. Although total oxidant status (TOS) did not differ significantly among groups (p = 0.996), total antioxidant status (TAS) was significantly increased following PAW treatment (p < 0.05), indicating a more favorable systemic antioxidant profile. These findings suggest an association between improved wound healing and a more favorable systemic antioxidant profile following PAW treatment. However, because local wound-level redox parameters and molecular markers were not assessed, the contribution of redox-related mechanisms remains to be clarified. Moreover, PAW demonstrated superior therapeutic efficacy compared with direct plasma application, highlighting its potential as a non-invasive approach for diabetic wound management.

Daidzein is a naturally occurring isoflavone phytoestrogen, mainly found in leguminous plants. This component exerts anti-inflammatory effects by regulating inflammatory cells via multiple targets, blocking core inflammatory pathways, and inhibiting the release of inflammatory factors. It also scavenges reactive oxygen species, activates the antioxidant enzyme system, and regulates antioxidant signaling pathways to achieve antioxidant effects. By regulating these two core pathological processes, it exerts protective effects in diseases such as cancer, cardiovascular disease, and acute kidney injury, based on preclinical evidence. The development of nanodelivery systems has effectively improved the physicochemical properties of daidzein, enhanced its bioavailability, and enabled disease-targeted delivery. Most previous reviews have either focused exclusively on daidzein or broadly covered the pharmacological activities of isoflavones, yet have largely overlooked the dual anti-inflammatory and antioxidant mechanisms specific to daidzein. This review summarizes these mechanisms and their preclinical effects on various diseases, including cancer, cardiovascular diseases, and acute kidney injury. It also reviews the pharmacokinetic limitations of daidzein and recent progress in nanodelivery strategies aimed at enhancing its bioavailability and bioactivity. Overall, this review serves as a reference for the future standardized comparison of nanocarriers, targeted therapies, and clinical applications.

Intervertebral disk degeneration (IVDD) is widely recognized as a major contributor to discogenic low back pain (LBP), imposing a substantial burden on global public health and socioeconomic systems. Growing evidence confirms that disrupted redox homeostasis, excessive reactive oxygen species (ROS) accumulation, and oxidative stress act as major convergent mechanisms that propagate inflammatory cascades, nucleus pulposus cell dysfunction, and extracellular matrix degradation. Although conventional conservative therapies and surgical interventions are clinically effective in relieving macrostructural compression, they remain limited in resolving localized molecular dysregulation. In recent years, nanotechnology has emerged as a promising strategy for overcoming the limitations of traditional therapy for IVDD. This review provides an analysis of four categories of antioxidant nanotherapies for IVDD, including inorganic functional nanozymes, bioactive nanomaterials, stimuli-responsive nanosystems, and nanocomposite scaffolds. We elaborate on their mechanisms in scavenging excessive ROS, restoring redox equilibrium, protecting mitochondrial function, and ameliorating oxidative stress-induced degeneration. Integrating structural biomimicry with microenvironmental responsiveness enables the engineering of composite nanosystems with multi-pathway ROS-scavenging capabilities. Therefore, these platforms emerge as promising therapeutic strategies for arresting IVDD progression. Finally, we discuss the key obstacles to clinical translation. Overall, this review provides insights into the development of redox-targeted therapies.

Background/Objectives: Dioscorea batatas Decne (yam), which contains various bioactive compounds, has been utilized in the cosmetics industry, while most of the peel of D. batatas (DBP) is discarded without further use. Recent studies have shown that DBP contains higher levels of bioactive substances than the rhizome flesh. The aim of this study was to evaluate the skin biological activities of DBP extracts obtained using 70% ethanol (70% EtOH DBP), 95% ethanol (95% EtOH DBP), and ethyl acetate (EA DBP), with particular attention to their antioxidant-associated protective effects. Methods: Skin-related bioactivities of DBP extracts prepared using ultrasonic extraction were evaluated using in vitro tyrosinase and matrix metalloproteinase-1 (MMP-1) assays, alpha-melanocyte-stimulating hormone (&#x3b1;-MSH)-induced melanogenesis in B16F10 cells, ultraviolet B (UVB)-irradiated HaCaT viability assays, and Western blot analysis of pro-collagen type I alpha 1(Pro-COL1A1) and MMP-1 in HDF cells. In addition, the ABTS and DPPH radical scavenging activities of DBP extracts and representative DBP derivatives were assessed. Results: DBP extracts inhibited tyrosinase activity in vitro and reduced melanogenesis in B16F10 cells. DBP extracts also protected skin cells from UVB by increasing the viability of UVB-irradiated HaCaT cells. In UVB-irradiated HDF cells, DBP extracts restored Pro-COL1A1 expression and suppressed MMP-1 levels. Additionally, DBP extracts inhibited MMP-1 activity in a concentration-dependent manner. The DBP extracts themselves exhibited ABTS and DPPH radical scavenging activities, with EA DBP showing the highest vitamin C equivalent antioxidant capacity among the tested extracts. Representative DBP-derived phenanthrene compounds also showed radical scavenging activities, supporting the antioxidant potential of peel-derived phytochemicals. Conclusions: These findings indicate that DBP extracts possess skin-whitening and anti-photoaging effects and suggest that these protective activities may be associated with the antioxidant potential of both DBP extracts and DBP derivatives.

Cocoa-based foods are increasingly recognized as complex plant-derived matrices with potential relevance for metabolic health, driven by interactions among multiple bioactive components. Metabolic disorders, including insulin resistance and type 2 diabetes, are characterized by disturbances in glucose homeostasis, oxidative stress, and endothelial dysfunction. This narrative review critically examines the antidiabetic potential of cocoa-based plant matrices, integrating evidence from nutritional biochemistry and metabolic physiology. We analyze the specific role of cocoa flavanols in redox-sensitive signaling pathways related to nitric oxide bioavailability and insulin signaling. Furthermore, we evaluate how complementary matrix components, such as non-glycemic sweeteners, prebiotic and viscous fibers, oleic-rich lipids, and micronutrients, modulate postprandial glycemic responses, gut microbiota activity, and overall metabolic regulation. Current evidence indicates that the metabolic effects of cocoa cannot be attributed to isolated compounds but emerge from coordinated interactions within the food matrix. Understanding these multi-component dynamics is essential for the rational design of cocoa-based functional foods aimed at improving glycemic control and supporting metabolic resilience.

The valorization of agri-food by-products generated during juice extraction represents a key strategy within circular economy frameworks, as it reduces the environmental impact of waste disposal while creating added value and improving the food supply chain. In this work, five betaine-based natural deep eutectic solvents (NaDES) differing in their hydrogen-bond donors, namely citric acid, lactic acid, acetic acid, glycerol, and ethylene glycol, were used for the green extraction of blueberry pomace, a largely underutilized by-product that is nevertheless rich in bioactive compounds. The extracts were characterized by liquid chromatography coupled with diode-array and tandem mass spectrometric detection, allowing targeted profiling of anthocyanins and non-anthocyanin phenolics, including phenolic acids, flavonoids, and phenolic aldehydes. The extraction performance of NaDES was benchmarked against conventional solvents (water and ethanol) to evaluate differences in selectivity and efficiency toward distinct phenolic classes. Antioxidant capacity was determined using DPPH and ABTS radical scavenging assays. Among the NaDES systems, the betaine-citric acid NaDES extract exhibited notable phenolic recovery together with marked radical scavenging activity. After evaluating its inhibitory activity against elastase and tyrosinase, enzymes involved in the skin aging process, the selected NaDES extract was incorporated into a natural-based antiaging cosmetic formulation, and its main physicochemical properties were assessed to verify suitability for topical application. This study demonstrated that the use of NaDES represents an environmentally friendly and sustainable approach to transform blueberry by-products into high-value, safe, and ready-to-use cosmetic functional ingredients without the need for solvent removal.

Cerebral ischemia/reperfusion (I/R) injury triggers oxidative stress, neuroinflammation, neuronal degeneration, and white matter damage not only in directly affected cerebral regions but also in remote brain areas such as the cerebellum. Skimmianine, a naturally occurring furoquinoline alkaloid, has been reported to possess antioxidant and anti-inflammatory properties. This study investigated the protective effects of skimmianine pretreatment against secondary cerebellar injury following experimental cerebral I/R. Thirty-two female Wistar rats were randomly assigned to sham, Skimmianine, I/R, and I/R + Skimmianine groups (n = 8/group). Cerebral I/R was induced by transient middle cerebral artery occlusion for 60 min followed by 23 h reperfusion. Skimmianine (40 mg/kg/day, intraperitoneally) was administered for 14 days before ischemia induction. Oxidative stress markers, neuroinflammatory mediators, histopathological alterations, behavioral outcomes, and ultrastructural changes were evaluated. In addition, network pharmacology and molecular docking analyses were performed to explore potential molecular mechanisms. Cerebral I/R significantly decreased TAS levels compared with sham (0.89 &#xb1; 0.15 vs. 1.52 &#xb1; 0.18 mmol Trolox Eq/L) and increased TOS (15.60 &#xb1; 3.03 vs. 6.80 &#xb1; 1.41 &#xb5;mol H2O2 Eq/L), OSI (17.48 &#xb1; 0.50 vs. 4.43 &#xb1; 0.47), TNF-&#x3b1; (68.4 &#xb1; 10.2 vs. 18.6 &#xb1; 4.4 pg/mL), Iba1 (41.3 &#xb1; 9.7 vs. 11.7 &#xb1; 1.6 pg/mL), and GFAP levels (334.5 &#xb1; 12.5 vs. 87.7 &#xb1; 9.5 ng/mL; all p < 0.001). I/R also impaired motor performance, as shown by increased beam crossing time (11.7 &#xb1; 2.2 vs. 4.8 &#xb1; 0.7 s) and grid foot fault rate (18.6 &#xb1; 4.0% vs. 3.4 &#xb1; 1.1%). Skimmianine pretreatment significantly improved these alterations, increasing TAS to 1.29 &#xb1; 0.20 mmol Trolox Eq/L and reducing TOS, OSI, TNF-&#x3b1;, Iba1, and GFAP levels to 9.20 &#xb1; 2.04, 7.07 &#xb1; 0.47, 34.9 &#xb1; 7.4, 24.2 &#xb1; 6.9, and 237.0 &#xb1; 7.9, respectively, compared with the untreated I/R group. Histopathological scores for Purkinje cell loss, edema, vascular congestion, and TNF-&#x3b1; expression were also significantly reduced by skimmianine. Quantitative TEM analysis showed that I/R reduced myelin thickness (0.29 &#xb1; 0.05 vs. 0.53 &#xb1; 0.07 &#xb5;m), increased G-ratio values (0.75 &#xb1; 0.05 vs. 0.63 &#xb1; 0.04), and increased vacuolized fibers (24.70 &#xb1; 4.20% vs. 3.20 &#xb1; 1.10%), whereas skimmianine partially restored myelin thickness (0.42 &#xb1; 0.07 &#xb5;m), reduced the G-ratio (0.68 &#xb1; 0.05), and decreased vacuolized fibers (11.20 &#xb1; 2.80%; p < 0.05 vs. I/R). Molecular docking demonstrated favorable binding between skimmianine and TNF-&#x3b1;, with a predicted binding energy of -6.953 kcal/mol. These findings indicate that skimmianine exerts neuroprotective effects against secondary cerebellar injury following cerebral I/R through coordinated modulation of oxidative stress, systemic neuroinflammatory responses, astroglial injury-associated pathways, and inflammation-related mechanisms.

SQSTM1/p62 is a multifunctional scaffold protein that plays important roles in selective autophagy and cellular redox homeostasis. While phosphorylation-dependent regulation of p62 has been extensively studied, the functional significance of oxidative modification remains incompletely understood. Our previous studies showed that the natural small compound Alternol induces cancer cell-specific killing via a xanthine oxidase-mediated strong oxidative stress. In this study, we investigated p62-associated oxidative responses under Alternol-induced oxidative stress conditions in prostate cancer cells. Using biochemical assays and cell-based models, we found that Alternol treatment was associated with the accumulation of oxidized and high-molecular-weight p62 species, accompanied by altered KEAP1 association and increased Nrf2-associated signaling. Furthermore, Alternol-induced p62 oxidative modification was associated with autophagy-related responses and adaptive cellular survival under oxidative stress conditions. Disruption of the Cys105/113-dependent oxidative modification response attenuated Nrf2-associated transcriptional activity and increased cellular sensitivity to Alternol treatment. Collectively, our findings support an association between p62 oxidative modification and redox-responsive autophagy- and antioxidant-associated signaling pathways under Alternol-induced oxidative stress conditions, providing new insight into adaptive stress responses in prostate cancer cells.

Gelatin capsule waste (GCW), a protein-rich by-product, represents a promising substrate for the generation of potential bioactive substances, including free amino acids and other soluble substances generated during enzymatic hydrolysis. In this study, gelatin hydrolysates with degrees of hydrolysis (DH) ranging from 10% to 40% were produced using the commercial enzymes NS AC0106 (endopeptidase) and NS AC0107 (aminopeptidase) to enhance their functional properties. Increasing DH significantly improved antioxidant activity, surface hydrophobicity, and emulsifying capacity (p < 0.05), while sterilization further enhanced antioxidant capacity. Structural analyses confirmed extensive protein degradation and conformational modifications, as evidenced by SDS-PAGE (formation of low-molecular-weight substances), FTIR (shifts in the amide I region), and NMR (release of free amino acids). Electronic tongue analysis indicated that enzymatic hydrolysis enhanced umami and salty taste attributes. Notably, hydrolysis using NS AC0107 at 40% DH resulted in the highest antioxidant activity, together with pronounced umami taste and low bitterness. Overall, GCW-derived hydrolysates show considerable potential as functional ingredients and provide a sustainable strategy for the valorization of protein-rich industrial by-products.

Oxidative stress is a major contributor to the development of age-related macular degeneration (AMD), and excessive oxidative stress can induce retinal pigment epithelium (RPE) dysfunction, apoptosis, and retinal degeneration. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 (NOX2) is a major enzymatic source of reactive oxygen species (ROS); however, its mechanistic role in sodium iodate (NaIO3)-induced oxidative injury remains unclear. Tetrahydrocurcumin (THC), the major metabolite of curcumin, exhibits potent antioxidant and cytoprotective activities, but its protective effects against AMD-associated retinal degeneration have not been fully elucidated. In the present study, we investigated whether THC protects against NaIO3-induced ROS-mediated apoptosis in RPE cells through regulation of NOX2 signaling. In vitro, THC significantly attenuated NaIO3-induced cytotoxicity and prevented apoptosis by suppressing hydrogen peroxide (H2O2) production and intracellular ROS accumulation in ARPE-19 cells. THC also preserved mitochondrial membrane potential by inhibiting the Src/p47phox/NOX2 signaling pathway and subsequently attenuated mitochondria-mediated apoptotic signaling. Furthermore, THC markedly reduced the expression of apoptotic proteins, including Bax, cleaved caspase-3, and cleaved PARP, concomitantly with suppression of Ras/Raf/MEK/ERK signaling. Mechanistically, treatment with the selective NOX2 inhibitor GSK2795039 significantly attenuated NaIO3-induced ROS accumulation and mitochondrial depolarization, while co-treatment with THC further enhanced these protective effects. In vivo, THC ameliorated NaIO3-induced retinal structural abnormalities by preserving the outer nuclear layer (ONL), reducing caspase-3 expression, and improving pupillary light responses in mice. Collectively, these findings demonstrate that THC protects against NaIO3-induced retinal degeneration through suppressing NOX2-dependent oxidative stress and downstream Ras/Raf/MEK/ERK-mediated apoptotic signaling, highlighting its potential as a therapeutic candidate for AMD and other oxidative stress-related retinal disorders.

Many rhizobia use quorum sensing (QS) systems to detect their population density and modify their symbiotic behavior with the legume host. There are three LuxRI-type QS systems in Rhizobium etli CFN42, and CinR plays a key role in symbiotic performance. However, the details of how CinR regulates the symbiotic process remain unknown. In this study, we employed the RNA-Seq method to screen differentially expressed genes between the wild-type strain and the &#x394;cinR mutant of R. etli CFN42. We found that most of the genes related to reactive oxygen species (ROS) were expressed at lower levels in the &#x394;cinR mutant than in CFN42. We also found that the &#x394;cinR mutant was more sensitive to H2O2 than to CFN42. We then showed that CinR positively regulated katG expression and possessed an affinity to bind the katG promoter in the absence of the AHL ligand. The addition of AHLs promoted CinR binding to the katG promoter and enhanced katG expression. Accumulation of H2O2 and O2&#x2022;- was observed in root nodules formed by the &#x394;cinR mutant. Crucially, katG overexpression rescued the H2O2-sensitive phenotype in vitro and partially restored defective symbiotic performance in nodules formed by the &#x394;cinR mutant on the common bean. These results suggest that CinR globally regulates ROS scavenging gene expression in order to balance oxidative stress within root nodules, promoting nitrogenase activity of R. etli CFN42.

Plants of the genus Astragalus are recognized as rich sources of bioactive compounds with antioxidant and therapeutic potential; however, European species remain less explored than the well-known Astragalus membranaceus (Fisch.) Bunge. The aim of this study was to compare the phytochemical composition and in vitro biological activity of selected Astragalus species occurring in Poland (A. cicer L., A. glycyphyllos L., A. membranaceus). Phenolic compounds in methanolic extracts obtained from the roots and aerial parts were analyzed using spectrophotometric methods and UHPLC-DAD-ESI/TOF-MS. Antioxidant activity was evaluated using DPPH, ABTS, FRAP, CUPRAC, metal chelation, superoxide radical scavenging, and lipid peroxidation (TBARS) assays. Additionally, enzyme inhibition toward &#x3b1;-amylase, lipase, hyaluronidase, tyrosinase, and butyrylcholinesterase was assessed. The root of A. membranaceus exhibited the highest total phenolic content (199.84 &#xb1; 3.64 mg GAE/g extract) and the strongest antioxidant activity (DPPH IC50 = 36.53 &#xb1; 1.22 &#xb5;g/mL; ABTS IC50 = 26.31 &#xb1; 0.03 &#xb5;g/mL), as well as the most pronounced &#x3b1;-amylase inhibition (IC50 = 17.78 &#xb1; 1.16 &#xb5;g/mL). It also demonstrated moderate protective effects against AAPH-induced lipid peroxidation. The herb of A. cicer showed moderate radical scavenging capacity and the most effective inhibition of lipid peroxidation at higher concentrations. Extracts of A. glycyphyllos displayed weaker radical scavenging but notable metal-chelating properties. Selected extracts also exhibited moderate inhibitory activity against tyrosinase and butyrylcholinesterase. A. membranaceus remains the most potent source of phenolic compounds and antioxidant activity; European species such as A. cicer and A. glycyphyllos represent promising, locally available alternatives and may be used in phytotherapy and functional products.

FLASH RT, which employs ultra-high dose rates (UHDR), has shown potential in reducing irradiation-induced damage to normal tissue while maintaining effective tumor targeting. For successful clinical translation, mechanistic explanation behind the so-called FLASH effect has yet to be deciphered and new in vivo model systems for mechanistic studies are therefore of high demand. We investigated the differential effects of UHDR (3000-7000 Gy/s) and conventional (CONV) (0.5 Gy/s) irradiation in D. melanogaster by irradiating adult female flies with 16 MeV and 9 MeV electron beams using an adapted clinical linear accelerator. Substantial lifespan prolongations were observed in single high-dose UHDR-irradiated groups compared to CONV irradiation groups with increasing doses (1000-1500 Gy). Split-dose UHDR irradiation further increased the lifespan compared to single high-dose UHDR irradiation. In addition, climbing deficits were induced by 300 Gy of CONV irradiation, but not by single high-dose UHDR irradiation. Additionally, we identified increased levels of lipid peroxidation in D. melanogaster brains indicating ferroptosis following CONV irradiation, which was not observed after single high-dose UHDR irradiation. Using relevant biological endpoints, we here demonstrate D. melanogaster with its advantageous characteristics to be a highly practical preclinical model organism to mechanistically investigate differential responses to UHDR and CONV irradiation.