Search Results (970)

Glioblastoma (GBM) remains one of the most therapy-resistant human malignancies, yet the physiological limits of mitochondrial stress adaptation against which its remarkable resilience might be interpreted remain poorly defined. This opinion article proposes the developmental stress boundary framework, a hypothesis-generating model in which insect embryonic cells, particularly those of Drosophila melanogaster, serve as an experimentally tractable, non-malignant reference platform for quantitative mapping of mitochondrial stress tolerance. Within this framework, GBM stress tolerance may be interpreted not as the product of fundamentally novel adaptive mechanisms, but as a pathological displacement and long-term stabilization of conserved mitochondrial programs transiently engaged during normal embryonic development. The framework is intended to complement, rather than replace, existing models of glioblastoma biology. The proposed framework integrates four interconnected dimensions of mitochondrial adaptation—redox homeostasis, lipid metabolism and ferroptosis-like resistance, proteostasis, and metabolic flexibility—into a multidimensional physiological stress boundary that defines the limits of reversible cellular adaptation. Comparative evidence from developmental biology and glioblastoma research is consistent with the possibility that malignant cells expand these conserved adaptive programs beyond their normal physiological constraints, although this relationship has not yet been directly tested. The framework generates four testable predictions: (i) stress–response curves in GBM may be right-shifted relative to embryonic baselines while preserving their overall architecture; (ii) mesenchymal-like GBM states may exhibit the greatest displacement of stress tolerance; (iii) effective therapeutic strategies may require simultaneous compression of multiple adaptive dimensions to prevent compensatory responses; and (iv) pharmacodynamic biomarkers, including lipid peroxidation products and GSSG/GSH ratios, could provide early indicators of declining stress-buffering capacity during treatment. Establishing quantitative developmental baselines using insect embryonic systems, alongside complementary reference points such as tissue regeneration, may provide a conceptual and experimental basis for interpreting mitochondrial stress adaptation in glioblastoma. Rather than proposing a new explanatory model of glioblastoma biology, this framework seeks to provide a quantitative developmental reference against which mitochondrial stress adaptation in glioblastoma can be experimentally interpreted, tested, and, where necessary, revised. Full article

Multiomics is increasingly valued as a strategy for investigating the regulatory mechanisms by which plants respond to adverse stress conditions. Currently, information on the molecular processes underlying plant responses to Pb stress, particularly those observed through an approach that combines proteomics and metabolomics, is lacking. Therefore, in this study, we aimed to explore functional correlations between Pb-responsive proteins and metabolites under Pb stress by performing label-free quantitative proteomics and untargeted metabolomics on the roots of the Pb hyperaccumulator Pogonatherum crinitum (Thunb.) Kunth. The selected Pb stress-responsive proteins were functionally verified using quantitative reverse transcription polymerase chain reaction (RT-qPCR) and parallel reaction monitoring (PRM). Under Pb stress, 397 upregulated and 431 downregulated proteins were identified through proteomic analysis. Metabolomic analysis identified 478 upregulated and 354 downregulated metabolites. Pathway enrichment analysis using the Kyoto Encyclopedia of Genes and Genomes revealed that differentially expressed proteins and metabolites were involved in pathways linked to heavy metal stress, such as starch and sucrose metabolism and plant hormone signal transduction. Through integrated proteomic and metabolomics analyses, we uncovered the coordinated regulatory interplay between glutathione (GSH) metabolism and jasmonic acid signaling. GSH reductase and 12-oxophytodienoate reductase drive the accumulation of GSH and jasmonic acid, respectively. The synergistic enhancement of these components is critical for maintaining cellular redox homeostasis and activating hormone-mediated defense signaling. These downstream metabolites were upregulated under Pb stress. RT-qPCR validation revealed that the transcriptional change trends were consistent with those of the proteomics analysis. Further quantitative validation of the target protein using PRM revealed significant upregulation under Pb stress. In conclusion, the P. crinitum root system upregulated the activity of key enzymes in the antioxidant system and plant hormone synthesis under Pb stress, thereby regulating the accumulation of GSH, glutamate, and metabolites for jasmonic acid synthesis. This integrated regulatory network provides promising candidate targets for breeding Pb-tolerant hyperaccumulators to remediate Pb-contaminated farmland and mining soil. Full article

This study evaluated oxidative damage, antioxidant-related, and nitric oxide (NO)-related chemical markers in commercial bee pollen using two extraction systems. For this purpose, a total of 30 bee pollen samples from different brands and/or manufacturers were examined; each sample was subjected to aqueous extraction and ethanol/water (80:20, v/v). The levels of reduced glutathione (GSH), malondialdehyde (MDA), and NO metabolites, comprising nitrite and nitrate and expressed as total NOx, were determined in pollen extracts using spectrophotometric methods. The data were analyzed using descriptive statistics, group comparisons, and Spearman correlation analysis. The findings showed that ethanol/water (80:20, v/v) extraction provided significantly higher measured GSH equivalents and total NOx levels than aqueous extraction. Mean GSH equivalents were 79.12 ± 25.54 µmol/g in the aqueous extracts and 189.77 ± 45.09 µmol/g in the ethanol/water extracts, and the difference was found to be statistically significant (p < 0.001). NO metabolite levels were determined as 5.97 ± 8.34 and 366.70 ± 85.10 µmol/g, respectively, and the difference between the extraction methods was found to be statistically significant (p < 0.001). In contrast, MDA levels did not show a significant difference between the two extraction systems (p = 0.391). A significant positive correlation was observed between GSH and NO metabolites in the combined dataset (r = 0.660, p < 0.001). The findings suggest that 80% ethanolic bee pollen extract may represent a promising source of NO metabolites for future investigation as a natural alternative to synthetic sodium nitrite in processed meat products. However, this hypothesis requires validation through microbiological, technological, sensory, and shelf-life studies. Full article

Background: Danshen–Gegen is a classic herb pair in traditional Chinese medicine, which has been used to treat cardiovascular and cerebrovascular diseases. Ischemic stroke (IS) is a prevalent cerebrovascular condition; ferroptosis is one of the contributing factors driving the progression of IS. This study aims to determine the underlying mechanism and examine if Danshen–Gegen (DG) extract may prevent cerebral ischemia–reperfusion injury by preventing ferroptosis. Methods: The comprehensive compositional characterization of DG was analyzed by ultra-high-performance liquid chromatography coupled with hybrid quadrupole-orbitrap high-resolution mass spectrometry (UPLC-Q-orbitrap MS). The experiments were conducted in middle cerebral artery occlusion/reperfusion (MCAO/R) rats and oxygen-glucose deprivation/re-oxygenation (OGD/R) cells. The neuroprotective effects of DG on IS were assessed by examining rat survival rates, infarct volume, behavioral scores, and cerebral water content. Then, we tested the accumulation of Fe²⁺ and lipid peroxidation products such as reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), myeloperoxidase (MPO), and 4-hydroxynonenal (4-HNE) in rats and cells. The expression of nuclear factor erythroid-derived 2-like 2 (Nrf2), Solute Carrier Family 7 Member 11 (-xCT), Glutathione peroxidase 4 (GPX4), Cyclooxygenase-2 (COX-2), Transferrin Receptor 1 (TFR1), and Long-chain-fatty-acid–CoA ligase 4 (ACSL4) was also assessed in vivo and in vitro. Results: UPLC-Q-orbitrap MS analysis was performed to characterize the chemical profile of DG, and a total of 33 chemical constituents were successfully identified. DG significantly alleviated the ischemic damage to brain tissue, reduced infarct volume, and improved neurological dysfunction. The content of Fe²⁺ and lipid peroxidation products was markedly decreased. Furthermore, DG could restore the expression of Nrf2, -xCT, and GPX4 with the inhibition of COX-2, TFR1, and ACSL4, thus achieving a suppressive effect on ferroptosis. Conclusions: The regulatory influence of DG via the Nrf2/System xc-/GPX4 axis may play a crucial role in alleviating ferroptosis and enhancing recovery from cerebral ischemia injury. Full article

The tripeptide glutathione (GSH) is the most abundant cellular non-enzymatic antioxidant. The GSH system plays a crucial role in antioxidant defense against oxidative stress and in supporting cellular redox homeostasis, regulating the reduction of lipid peroxides, and protecting cells from ferroptosis depending on the GSH level, which is maintained in a state of dynamic equilibrium not only by the activities of GSH synthesis enzymes, transporters of GSH precursor amino acids, and GSH transporters, but also by the actions of GSH-related enzymes. Some GSH-related enzymes are key enzymes with antioxidant functions such as glutathione peroxidases (GPxs), especially GPx4, and glutathione S-transferases (GSTs), which use GSH as a co-substrate for the reduction of hydroperoxides to alcohols, whereas glutathione-specific gamma-glutamyl cyclotransferase 1 (ChaC1) degrades intracellular GSH, so they can correspondingly lead to suppression or induction of ferroptosis. Ferroptosis is characterized by a buildup of lipid peroxides due to excessive lipid peroxidation and iron accumulation, which results from redox imbalance between ferroptosis’s drivers and defense systems, including impaired cellular antioxidant systems, particularly disruptions of GSH metabolism. It appears pertinent to assess the influence on ferroptosis regulation by GSH-dependent enzymes that utilize the GSH pool in diverse ways. This review offers an updated exploration of the roles of GPx4, ChaC1, and GSTs in redox regulation of ferroptosis in cancer cells, with a focus on both the regulation of each enzyme’s activity and their possible interactions, considering the impact on the risk of ferroptosis induction. Full article

Radiation-induced bystander effect (RIBE) contributes to oxidative and nitrosative stress in non-irradiated tissues following ionizing radiation (IR). This study investigated the protective effects of propolis and caffeic acid phenethyl ester (CAPE) against RIBE-mediated renal injury after total cranial irradiation in rats. Forty-eight male Sprague–Dawley rats were assigned to six groups: IR, IR + propolis, IR + CAPE, propolis control, CAPE control, and sham. A single 5 Gy cranial gamma irradiation was administered. Propolis (80 mg/kg/day, orally) and CAPE (10 μmol/kg/day, intraperitoneally) were given for 10 days. Renal antioxidant (SOD, GSH-Px, GST), oxidative (XO, MDA), and nitrosative (NOS, NO) parameters were evaluated. Multivariate analyses, including principal component analysis (PCA) and partial least squares-discriminant analysis (PLS-DA), were performed. IR significantly decreased SOD activity and increased XO, MDA, NOS, and NO levels. Both propolis and CAPE effectively reversed these alterations, with propolis showing a more pronounced effect on oxidative stress markers. GSH-Px and GST activities remained unchanged. The findings suggest that propolis and CAPE attenuated oxidative/nitrosative changes in kidney tissue, consistent with a possible bystander-associated systemic response. Full article

Ciprofloxacin (CPX) has been associated with neuropsychiatric adverse effects; however, its contribution to depression-like behaviors and the underlying neurobiological mechanisms remain insufficiently characterized. Previous studies have indicated that cinnamic acid (CA) may exert protective actions in the nervous system by modulating oxidative and inflammatory pathways. Nevertheless, its effectiveness in preventing CPX-induced neurobehavioral impairments remains largely unknown. The present study aimed to investigate whether CA attenuates CPX-induced depression-like behaviors through modulation of neuroinflammation and oxidative stress. This study included 60 male Swiss albino mice distributed among six experimental groups (n = 10). Animals were assigned to receive a vehicle, CPX administered at 80 mg/kg, CPX combined with CA at doses of 50, 100, or 200 mg/kg, or CPX together with FLX (20 mg/kg) throughout the 14-day treatment period. Behavioral alterations were assessed using social interaction, forced swimming, tail suspension, and sucrose preference paradigms. In addition, hippocampal and prefrontal cortex tissues were examined for oxidative stress markers (MDA, GSH, and CAT), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), and neurotransmitters (serotonin, dopamine, and GABA) using ELISA-based assays. CPX administration induced significant depression-like behaviors, evidenced by reduced social interaction, increased immobility, and anhedonia (p < 0.05). These behavioral alterations were associated with increased lipid peroxidation, impaired antioxidant defense, elevated pro-inflammatory cytokine levels, and decreased monoaminergic and GABAergic neurotransmission in both HIP and PFC regions. CA treatment significantly improved CPX-induced behavioral and neurochemical alterations. Among the tested doses, the 100 mg/kg regimen produced the most consistent response, accompanied by reduced neuroinflammatory activity and restoration of neurotransmitter levels, particularly in the hippocampus. In conclusion, CA mitigated CPX-induced behavioral deficits and neurochemical alterations, an effect that may be attributed to its regulatory influence on oxidative stress, neuroinflammatory processes, and neurotransmitter balance within the HIP–PFC pathway. Collectively, the findings indicate that CA may have therapeutic relevance in reducing the neuropsychiatric consequences associated with CPX exposure. Full article

Background: Ulva lactuca (sea lettuce) is a green macroalgae rich in sulfated polysaccharides (ulvans), polyphenols, and pigments with documented antioxidant and anti-inflammatory activity in preclinical models. Translational human data remain limited. Methods: Twenty healthy adults (20–35 years; BMI 18.5–30 kg/m²) were enrolled in a single-center, randomized, double-blind, placebo-controlled, parallel-group trial (CTRI/2025/11/097278) and assigned 1:1 to receive 300 mg of an U. lactuca extract or matched placebo once daily for 28 days. Antioxidant biomarkers (GSH, MDA, catalase, GPx-1, thioredoxin) and inflammatory biomarkers (CRP, IL-6, IL-1β, IL-11, PPAR-γ) were measured at Day 0 and Day 28. Safety was assessed throughout. Results: Eighteen of 20 participants completed the study. Compared with placebo, U. lactuca produced significant within-group improvements at Day 28 in GSH (+4.04 ng/mL), GPx-1 (+67.8 µU/mL), and catalase (+32.4 kU/L) and reductions in MDA (−6.08 nmol/mL) and thioredoxin (−1.48 ng/mL); inflammatory markers CRP (−0.91 mg/L), IL-6 (−2.97 pg/mL), IL-11 (−4.28 ± 1.88 ng/mL) and IL-1β (−8.87 pg/mL) decreased and PPAR-γ increased. Conclusions: In this short-duration pilot trial, daily supplementation with 300 mg of an U. lactuca extract was well tolerated and modulated systemic oxidative-stress and low-grade inflammatory biomarkers in healthy adults. Larger and longer studies in populations with elevated oxidative stress are warranted. Full article

Background/Objectives: The aim of this study is to evaluate the relationship between adherence to the Mediterranean diet and intestinal microbiota metabolite trimethylamine N-oxide (TMAO) levels, systemic inflammation markers, and oxidative stress parameters in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Methods: MASLD patients whose fatty liver and fibrosis severity were determined with FibroScan and a healthy control group were included in the study. In addition to the routine biochemical parameters, serum TMAO levels, inflammatory cytokines (IL-6, IL-10, TNF-α), and oxidative stress indicators (malondialdehyde, glutathione, and MDA/GSH ratio) of all participants were measured. In comparing these parameters between fibrosis groups, adjustment for potential confounding variables (age, BMI, sex, comorbidity, relevant medication use, MEDAS score, and physical activity) was performed. Following anthropometric evaluations, the adherence levels of the participants to the Mediterranean diet were determined by the Mediterranean Diet Adherence Screening Scale (MEDAS), and their physical activity levels were determined through the International Physical Activity Questionnaire-Short Form (IPAQ-SF). Results: Individuals diagnosed with MASLD had significantly lower adherence to the Mediterranean diet and lower physical activity levels compared with healthy controls. Among the inflammatory parameters, IL-6 levels were significantly higher in the advanced fibrosis group than in the early-stage and significant fibrosis groups, while TNF-α levels were significantly higher in the advanced fibrosis group than in the early fibrosis group. No significant differences were observed among the groups in TMAO, IL-10, GSH levels, or the MDA/GSH ratio; however, among the oxidative stress markers, MDA levels were significantly higher in the early fibrosis group than in the significant fibrosis group. Conclusions: In MASLD patients, fibrosis severity was associated with alterations in TMAO, inflammatory, and oxidative stress markers, with increased TNF-α and IL-6 levels reflecting a high inflammatory burden as fibrosis progressed. Lower TMAO levels in fibrosis groups likely reflect reduced hepatic FMO3 activity, lower fish intake, and medication use, while elevated MDA levels in early-stage fibrosis suggest that lipid peroxidation may be more prominent in the initial phases of disease. Mediterranean diet adherence and physical activity were inversely associated with pro-inflammatory markers and MASLD severity, being highest in the control group, suggesting a potential protective role for these lifestyle factors in MASLD progression. Full article

Background/Objectives: Burn injuries in children represent a significant clinical challenge, as current standard-of-care agents such as silver sulfadiazine (SSD) present limitations, including delayed re-epithelialization. This study aimed to evaluate the therapeutic potential of Castanea sativa (sweet chestnut) flower extract—rich in polyphenols and flavonoids with documented antioxidant, anti-inflammatory, and antimicrobial properties but previously uncharacterized in burn wound healing—applied topically on second-degree burn wounds in a juvenile rat model, comparing its efficacy to SSD and their combination. Methods: Forty five-week-old female Wistar albino juvenile rats were randomly allocated into five groups (n = 8): burn control (Group C), SSD monotherapy (Group BS), vaseline vehicle/sham (Group Sham), 5% chestnut flower extract (Group BCs), and SSD combined with extract (Group BSCs). All topical treatments were applied once daily for 14 days. Healing outcomes were assessed by macroscopic wound closure analysis, systemic organ stress markers (ALT, AST, BUN), oxidative stress indices (MDA, SOD, CAT, GPx, GSH), inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-10), and histopathological/immunohistochemical analyses (Ki-67, VEGF). Results: All active treatment groups demonstrated significant reductions in organ damage markers, oxidative stress burden, and pro-inflammatory cytokine levels, alongside enhanced antioxidant enzyme activity, compared to Group C (p < 0.001). Extract-treated groups exhibited more pronounced suppression of oxidative and inflammatory parameters than SSD monotherapy. The combination group (BSCs) achieved optimal wound healing outcomes, including near-complete re-epithelialization, superior collagen organization, and prominent angiogenesis, corroborated by the highest Ki-67 proliferation index and VEGF expression scores (p < 0.001). Conclusions:C. sativa flower extract significantly accelerates burn wound healing via antioxidant and anti-inflammatory mechanisms. When combined with SSD, a synergistic effect is observed that overcomes the re-epithelialization delays associated with SSD monotherapy. These findings support C. sativa flower extract as a promising candidate for further preclinical and clinical investigation in pediatric burn management, supporting the ethnopharmacological relevance of this plant in traditional wound care practices; further safety and efficacy validation is required before clinical translation. Full article

Conventional gelatin-based hydrogels lack responsiveness to the tumor microenvironment and exhibit low drug-loading efficiency for hydrophobic drugs, which limits their application in targeted cancer therapy. In this study, a reduction-responsive gelatin hydrogel was developed by grafting hydrophobic tert-butoxycarbonyl (Boc) groups onto gelatin chains, followed by EDC/NHS-mediated chemical cross-linking with L-cysteine dimethyl ester dihydrochloride, which contains disulfide bonds. The success of Boc grafting was confirmed by ¹H NMR, and free amine quantitative analysis. Rheological characterization confirmed the formation of a stable elastic network with controllable gelation times (5–12 min), demonstrating excellent injectability. Reduction-triggered degradation was observed in the presence of DTT or GSH, with the cleavage of disulfide bonds further evidenced by the detection of free sulfhydryl (-SH) groups via X-ray Photoelectron Spectroscopy. Microscale thermophoresis (MST) demonstrated measurable binding between Boc-modified gelatin and hydrophobic drugs, with dissociation constants (K_d) of 0.46 ± 0.37 μM for curcumin and 0.14 ± 0.14 μM for camptothecin. Drug loading assays show dramatically enhanced encapsulation efficiency for hydrophobic drugs (62.7% for curcumin, 66.6% for camptothecin) compared to unmodified hydrogels (7.2% and 16.8%, respectively). In vitro release kinetics follow the Korsmeyer–Peppas model, indicating a non-Fickian diffusion–erosion mechanism, and can be precisely tuned by gelatin concentration and reducing agent levels. Complete drug release occurs within approximately 325 min in 15 mM GSH. MTT and hemolysis assays confirm high biocompatibility. Collectively, this reduction-responsive system offers a promising platform for controlled, site-specific delivery of hydrophobic anticancer agents. Full article

A novel carbohydrazide-based ligand (L) and its binuclear Cu(II) complex were successfully synthesized and characterized. Structural analysis confirmed that the Cu(II) complex adopted a monoclinic crystal system with a distorted coordination configuration, in which the multidentate Schiff base ligand chelated and bridged two Cu(II) centers. The in vitro anti-tumor results revealed that the Cu(II) complex exhibited prominent cytotoxicity against five human cancer cell lines with much lower IC₅₀ values than the free ligand, copper chloride and cisplatin. Mechanistic studies demonstrated that the Cu(II) complex significantly increased intracellular ROS and MDA levels, decreased the GSH/GSSG ratio, and reduced ATP content, thereby disrupting cellular redox balance and bioenergetic metabolism. In addition, flow cytometry analysis verified that the complex effectively triggered tumor cell apoptosis. In contrast, free CuCl₂ showed almost no anticancer activity, indicating that the synergistic effect between the Schiff base ligand and copper ions contributed to the excellent anti-tumor performance. This work suggests that the prepared binuclear Cu(II) complex can serve as a promising candidate for developing metal-based anticancer agents. Full article

Alterations in the redox status and the DNA damage response (DDR) parameters are early, mechanistically interconnected drivers of carcinogenesis. Herein, we investigated whether such alterations, arising during the progression of Multiple Myeloma (MM), are systemically reflected in peripheral blood mononuclear cells (PBMCs). Redox status, expressed as the GSH/GSSG ratio, and DDR-related parameters, including baseline DNA damage, efficiency of key DNA repair pathways, namely nucleotide excision repair (NER) and double-strand break repair (DSB/R), as well as apoptotic sensitivity, were evaluated in PBMCs from 17 patients with Monoclonal Gammopathy of Undetermined Significance (MGUS), 20 with smoldering MM (SMM), and 19 with MM. PBMCs from 20 healthy controls (HCs) were analyzed in parallel. Baseline DNA damage levels and DNA repair capacities across all examined pathways increased progressively in the following order: HC < MGUS < SMM < MM (p < 0.001). This progression was accompanied by a gradual increase in chromatin relaxation. Conversely, the GSH/GSSG ratio and apoptotic sensitivity declined during disease progression (p < 0.001). Collectively, malignant transformation in MM is associated with progressive dysregulation of DDR pathways and redox status in PBMCs. The identification of these molecular perturbations in an easily accessible tissue, such as peripheral blood, underscores their potential utility for early detection and prognostic assessment of MM. Full article

Saline–alkaline aquaculture is a promising strategy to alleviate freshwater shortages; however, such environments severely impair fish growth and physiological homeostasis. Nutritional regulation has been proposed to improve stress tolerance, yet the benefits of single additives are often limited under the multifactorial challenges imposed by saline–alkaline conditions. Therefore, a compound feed additive (CFA) consisting of glutamate, cholesterol, β-glucan, myo-inositol, zinc methionine, and curcumin was developed and evaluated in Nile tilapia (Oreochromis niloticus). To assess the robustness and practical applicability of this nutritional strategy, three independent feeding trials were conducted using different commercial basal diets as validation systems. Within each dietary system, fish were reared under freshwater (FW), saline–alkaline water (SAW), or saline–alkaline water supplemented with CFA (SAW+CFA). Saline–alkaline stress significantly reduced WG and SR, increased FCR, and elevated VSI and HSI, indicating impaired growth performance and metabolic burden. These changes were accompanied by increased serum glucose and ion concentrations (Na⁺, K⁺, Cl⁻), elevated ammonia levels, and reduced crude protein content. Dietary CFA improved growth and feed utilization under saline–alkaline conditions. It enhanced hepatic glycogen content and reduced serum glucose levels. Meanwhile, it downregulated glycolysis-related genes (hk, pfk1, pk) and upregulated genes involved in gluconeogenesis and the pentose phosphate pathway (g6pase, pc, g6pdh), indicating altered glucose metabolism and improved energy homeostasis. Saline–alkaline stress induced oxidative stress, apoptosis, and histological damage in the liver, whereas CFA alleviated these alterations by reducing MDA levels, enhancing antioxidant enzyme activities (CAT, GSH-Px, T-SOD) and suppressing apoptosis-related genes (caspases, p53, c-myc). In addition, CFA alleviated saline–alkaline stress-induced gill structural damage and reduced serum ion concentrations while modulating ion transport-related gene expression, suggesting improved osmoregulatory capacity. It also enhanced ammonia metabolism and transport, as reflected by reduced serum ammonia levels and altered expression of related genes. Furthermore, Saline–alkaline stress impaired intestinal structure and function, whereas CFA improved intestinal villus structure, increased digestive enzyme activities (amylase, trypsin, lipase), and suppressed pro-inflammatory genes (il-1β, il-8). Importantly, similar beneficial response patterns were observed across the three independently analyzed dietary systems. Overall, CFA improved saline–alkaline adaptability of Nile tilapia and was associated with improvements in energy metabolism, oxidative homeostasis, osmoregulation, ammonia detoxification, and intestinal function, providing a practical nutritional strategy for saline–alkaline aquaculture. Full article

Usnic acid (UA) is a secondary metabolite produced by lichens that has attracted interest because of its antimicrobial, photoprotective, and antioxidant properties, suggesting its potential use as a biostimulant in agriculture. However, its evaluation in agricultural crops is limited. In the present study, we evaluated the effect of applying (+) UA on enzymatic and non-enzymatic antioxidant systems, photosynthetic pigments, photosynthetic enzyme activity, and markers of oxidative stress in “Albion” strawberry plants. The plants were grown in a peat moss:perlite substrate (1:1, v/v) and cultivated under tunnel greenhouse conditions using a nutrient solution applied via fertigation. (+) UA was applied at 400 µg/mL via three routes (foliar, drench, and a combination of foliar and drench) on three occasions. Leaf tissue was collected 117 days after transplantation, and the biochemical parameters were quantified. (+) UA increased the activity of glutathione peroxidase (GPX) (53% via foliar-drench) and catalase (CAT) by 73.5% (via drench), and reduced glutathione (GSH) content by 58% (via foliar). β-carbonic anhydrase (βCA) activity increased by 415% and 384% (foliar and foliar-drench, respectively). Likewise, Ribulose 1,5-bisphosphate carboxylase-oxygenase (RuBisCO) activity increased by 58.23% (drench) and phosphoenolpyruvate carboxylase (PEPC) by 25% and 46% (foliar and drench), suggesting positive effects on the processes associated with CO₂ assimilation and transport. In contrast, no significant changes were observed in the levels of hydrogen peroxide (H₂O₂), malondialdehyde (MDA), or proline, indicating the absence of oxidative stress. These findings suggest that (+) UA modulates the enzymatic antioxidant system, promoting favorable physilogical responses without inducing oxidative stress. The use of (+) UA has been proposed as a potential promoter of metabolism in agricultural crops. In addition, new avenues of research are being explored to investigate the role in modulating antioxidant responses under biotic and abiotic stress conditions. Full article