Search Results (8,983)

Metabolic syndrome (MeS) is a multifactorial disorder characterized by insulin resistance, dyslipidemia, hypertension, and obesity, and oxidative stress plays a key role in tissue damage in this syndrome. This study aimed to investigate this role in Na⁺/K⁺-ATPase (NKA) expression in skeletal muscle and to evaluate the effects of quercetin. A high-sucrose-diet-induced MeS model was established in Wistar albino rats (n = 32), and skeletal muscle tissues were analyzed. Biochemical parameters were measured, including aspartate aminotransferase (AST), lactate dehydrogenase (LDH), total antioxidant status (TAS), total oxidant status (TOS), superoxide dismutase (SOD), and malondialdehyde (MDA). In addition, thioredoxin-1 (TRX1) and NKA protein expression levels were evaluated using Western blot analysis. In the MeS group, AST, TAS, TRX1, and NKA expression significantly decreased, while LDH, TOS, SOD, and MDA levels increased, indicating disrupted redox balance, elevated oxidative stress, and impaired antioxidant defense. Increased MDA and TOS levels reflected enhanced lipid peroxidation, whereas decreased TAS and TRX1 suggested reduced antioxidant capacity. Elevated SOD activity may indicate a compensatory response to excessive reactive oxygen species (ROS). The reduction in NKA expression may contribute to impaired ion transport and potential skeletal muscle dysfunction. Quercetin administration improved oxidative stress markers and partially restored NKA expression. These findings suggest that oxidative stress contributes to NKA dysfunction in MeS, and quercetin may have therapeutic potential by modulating oxidative stress and preserving enzyme function. Full article

Oxidative stress is an important component of cancer biology and is characterized by an imbalance between the production of reactive oxygen species (ROS) and antioxidant defense systems. Excess ROS can cause molecular damage and genomic instability; at the same time, ROS signaling remains necessary for normal cellular function. Redox homeostasis is of particular importance in this balance. The aim of this structured narrative review was to summarize and critically discuss current evidence on how dietary antioxidants influence redox-sensitive pathways involved in cancer prevention, with particular attention to metabolic inflammation, mitochondrial quality control, and gut microbiota-related mechanisms. We performed a structured literature search of Scopus, Web of Science, and PubMed, focusing on articles published between 2021 and 2026. The evidence covered major redox-sensitive pathways, including Nrf2-Keap1-ARE signaling, AMPK-mTOR regulation, NF-κB-mediated inflammation, mitochondrial quality control (autophagy and mitophagy), and inflammasome activation. These pathways, which are involved in tumor initiation and progression, link oxidative stress to metabolic and inflammatory processes. Current evidence suggests that dietary antioxidants act primarily by supporting endogenous defense systems. This may help explain the “antioxidant paradox”, in which antioxidant-rich dietary patterns are associated with a lower risk of cancer. In some studies, high-dose supplementation with isolated antioxidants has produced inconsistent or sometimes adverse results. These effects depend on dose, chemical form, metabolic context, and baseline redox state. The gut microbiota is also an important mediator of antioxidant bioactivity; by converting dietary polyphenols into bioactive metabolites, it can influence systemic redox balance and metabolic signaling. This microbiota-dependent modulation may partially explain inter-individual variability in responses to dietary interventions. In conclusion, dietary antioxidants should be considered as modulators of redox-sensitive signaling networks, not merely as simple radical scavengers. Personalized modulation of redox homeostasis is a future strategy for cancer prevention, with a greater emphasis on whole-diet and biomarker-guided approaches. Full article

Background: Muscle function determines overall health and is often impaired in metabolic syndrome and cancer, largely due to oxidative stress and inflammation. Olive mill wastewater (OMWW) is rich in bioactive polyphenols (e.g., hydroxytyrosol and verbascoside) that may hinder these potential pro-sarcopenic mechanisms, representing a potential nutraceutical to limit muscle health decline. Objective: To evaluate the effects of short-term supplementation with an OMWW-derived polyphenol extract (Oliphenolia^®, OMWW-OL) on muscle-related parameters and antioxidant biomarkers in adults at metabolic risk while maintaining dietary habits. Methods: This exploratory, hypothesis-driven secondary analysis was based on a single-arm longitudinal pilot study assessing patients at baseline (T0), after 30 days of supplementation (T1), and 30 days post-discontinuation (T2). Anthropometry, bioelectrical impedance, and biochemical assessments were performed. Results: Supplementation was associated with modest increases in skeletal muscle mass, muscle mass percentage, and wrist, arm, and calf circumferences. Fat mass decreased progressively, while total body water percentage and hydration status improved. Ferritin levels rose at T2, alongside increases in protein thiols (PSH) and Trolox equivalent antioxidant capacity (TEAC), suggesting improved iron status and reduced oxidative stress. Body weight and BMI decreased, as expected in a dietary intervention for metabolic syndrome, while muscle health showed a tendency toward improvement. Conclusions: Although the findings require cautious interpretation, short-term OMWW-OL supplementation was associated with modest but consistent directional changes in muscle-related and metabolic indicators in adults at metabolic risk. The results support hypothesis generation and highlight the need for larger studies to further explore the potential role of OMWW-OL in the context of cancer-associated sarcopenia. Full article

Maintaining the nutritional and functional quality of blueberries during cold storage remains a postharvest challenge. This study evaluated the effects of short-term high-CO₂ treatments on phenylpropanoid-related metabolism in two commercially important blueberry cultivar–season combinations: Duke (Vaccinium corymbosum L., highbush; early-season, June harvest) and Ochlockonee (V. virgatum Aiton, rabbiteye; late-season, September harvest). Fruits were exposed to 15% or 20% CO₂ for 3 days at 1 °C and subsequently stored for up to 29 days at 1 °C. Phenolic compounds, antioxidant capacity, and the expression of selected phenylpropanoid-related genes, including flavonoid biosynthetic enzymes and R2R3-MYB transcription factors, were analyzed. Short-term CO₂ treatments were associated with transient transcriptional responses, particularly in anthocyanin-related pathways, together with genotype-associated differences in phenolic composition and antioxidant capacity during storage. Overall, the results indicate associations between CO₂ exposure and secondary metabolism under cold storage conditions and should be interpreted as correlative rather than mechanistic evidence of priming. Full article

Background/Objectives: Goji berry (Lycium barbarum L.), renowned as a typical medicinal and edible plant, is mainly cultivated across four agroclimatic zones in China, including semi-arid, arid, monsoon, and high-altitude regions. Ningxia has long been recognized as the daodi production area for goji berries. However, the metabolic diversity of goji berries from other core cultivation regions and how these differences are shaped by local environments remain poorly understood. Methods: In this study, untargeted metabolomics was employed to comprehensively investigate the metabolic difference in goji across seven production regions. By integrating multivariate analysis with KEGG pathway enrichment (p < 0.05), 49 discriminative markers enriched in 10 key pathways were putatively identified, and their roles in plant stress tolerance were elucidated. In addition, we conducted targeted quantification of key bioactive components and antioxidant capacity. Results: Significant regional differences were revealed. Redundancy analysis further identified rainfall, temperature, and UV radiation as the key climatic drivers of this variation. Conclusions: These findings provide insights into the metabolic adaptation of goji to local environments and serve as a basis for further functional studies. Full article

The bactericidal mechanisms of fluoroquinolones extend beyond their canonical inhibition of DNA topoisomerases, yet the associated metabolic perturbations remain incompletely understood. In this study, we systematically investigated the metabolic responses of Escherichia coli to three representative FQs—ofloxacin, enrofloxacin, and ciprofloxacin—using untargeted UPLC–Q Exactive Orbitrap–MS-based metabolomics. Bacterial cells were exposed to bactericidal concentrations (2 × MIC) for a single-time point (1 h), followed by comprehensive metabolomic profiling with six biological replicates per group. Our findings demonstrate that FQ-induced metabolic reprogramming serves as a primary driver of oxidative stress and nucleic acid damage, rather than a mere secondary effect. All three FQs induced substantial metabolic reprogramming characterized by disruptions in nucleotide biosynthesis, central carbon metabolism, and redox-related pathways, with notable drug-specific differences. Ciprofloxacin exhibited the most pronounced suppression of energy metabolism and antioxidant systems, whereas ofloxacin and enrofloxacin showed partial compensatory metabolic responses. Consistently, intracellular ROS levels were significantly elevated in all treatment groups, and this effect was attenuated by antioxidant supplementation. Furthermore, increased accumulation of 8-hydroxydeoxyguanosine and 8-hydroxyguanosine confirmed the occurrence of oxidative DNA and RNA damage. Collectively, these findings indicate that FQs induce distinct metabolic perturbations that are closely associated with oxidative stress and nucleic acid damage, providing a metabolic perspective on their bactericidal activity and suggesting potential targets for metabolic adjuvant strategies. Full article

Background/Objectives: Using a well-established model of streptozotocin-induced diabetic retinopathy (DR), this study sought to evaluate the neuroprotective effect of intravitreal Forskolin (FSK) on retinal ganglion cell survival and glial activation and explore the association of circulating miR-200b with metabolic and oxidative stress in DR. Methods: A total of 18 male Wistar rats were divided into a control group (n = 6) and a streptozotocin-induced diabetic group (n = 12), which were further divided into diabetic control and FSK-treated groups (n = 6 each). Total antioxidant capacity (TAC), total peroxide (TP), triglycerides (TGs), total cholesterol, and high-density lipoprotein cholesterol (HDL-C) were measured. qRT-PCR analysis for miRNA-200b and immunohistochemistry were performed. Results: Diabetic rats showed oxidative stress and hyperlipidemia associated with increased circulating miR-200b levels. The retina showed reduced neuron numbers (Caspase-3), altered glial and astrocyte staining (IBA1, GFAP), and changes in microglia/macrophage morphology and distribution. Intravitreal FSK improved retinal ganglion cell survival and reduced glial activation, while systemic lipid profile and oxidative stress markers remained largely unchanged. Circulating miR-200b levels showed a positive correlation with oxidative stress markers across groups. Conclusions: Intravitreal FSK was able to limit the disease exacerbation via improved neuronal survival through inhibition of apoptosis. FSK did not produce observable qualitative changes in GFAP expression or IBA1+ cell morphology under the conditions tested. Full article

This study presents the first tissue-resolved targeted metabolomic analysis of artificially cultivated Termitomyces upsilocystidiatus fruiting bodies using LC-MS/MS. We identified pronounced metabolic divergence between the pileus and stipe. The pileus was enriched in a nitrogen-recycling and antioxidant module, exemplified by L-citrulline (~13.5-fold higher than stipe, p < 0.01) and urea, while the stipe accumulates sulfur-derived and oxidized metabolites such as L-homocystine (~3.5-fold higher, p < 0.01) and methionine sulfoxide. Lipid profiles further distinguished the two tissues: the pileus featured high levels of linoleic acid-derived oxylipins, including 13(S)-HODE and 12(13)-DiHOME (~9.7-fold and ~303-fold enrichment, respectively, p < 0.01), suggesting a role in signaling and redox buffering. In contrast, the stipe preferentially accumulated oxidized eicosanoids (e.g., 5-oxoETE) and thromboxane B1, indicative of a stress-responsive lipid network. Together, these metabolite-level observations support a tentative “pileus-synthesis/stipe-defense” dual-hub model. This work provides a quantitative metabolic framework for understanding tissue specialization in a symbiotic fungus and offers practical entry points for cultivation optimization and quality control of Termitomyces. Full article

Background: Pulmonary fibrosis (PF) is a chronic, progressive lung disease with limited treatment options. Liuweidihuang pill (LDP), a classical formula for kidney-yin deficiency, has been reported to have anti-inflammatory and anti-oxidative activities, suggesting potential relevance to PF. Purpose: This study evaluated whether LDP attenuates bleomycin-induced PF in mice and whether gut microbiota remodeling may contribute to its protective effects. Methods: Mice received intratracheal bleomycin followed by LDP gavage. Lung pathology was assessed by hematoxylin–eosin (HE) and Masson staining. Inflammatory cytokines, hydroxyproline (HYP), and α-SMA were measured. LDP and LDP-containing serum were profiled by UPLC-MS. The gut microbiota was analyzed using 16S rDNA sequencing. To further explore whether microbiota-related changes were associated with the protective phenotype, fecal microbiota transplantation (FMT) and probiotic VSL#3 intervention were performed. In addition, LDP-containing serum was tested in a TGF-β1-induced EMT model in A549 cells. Results: LDP reduced lung index, inflammatory infiltration, interstitial fibrosis, α-SMA expression, HYP content, and pro-inflammatory cytokine levels in bleomycin-treated mice. These effects were accompanied by gut microbiota remodeling and transcriptomic changes related to inflammation, metabolism, and fibrosis. VSL#3 partially reproduced the protective phenotype, whereas FMT showed limited efficacy. LDP-containing serum had a limited inhibitory effect on EMT inhibited EMT in vitro, suggesting that systemic host responses may contribute to the in vivo effect. Conclusions: LDP attenuated early bleomycin-induced PF and was associated with reduced inflammation and gut microbiota remodeling. These findings suggest a possible role for microbiota–host interactions in LDP-associated protection; however, causal directionality, key active effectors, and protein-level pathway validation remain unresolved. Full article

Dry eye disease (DED) is a chronic inflammatory disorder of the ocular surface, characterized by tear film homeostasis imbalance, with aging being identified as a crucial independent risk factor. Oxidative stress, which refers to the excessive production of reactive oxygen species (ROS) and reactive nitrogen substances during mitochondrial metabolism and the weakened protective effect of antioxidants, plays a central role in this process. With aging, the mitochondrial function of ocular surface tissues, such as the corneal epithelium, meibomian glands, and lacrimal glands, declines. Concurrently, the activity of endogenous antioxidant enzymes (such as superoxide dismutase and glutathione peroxidase) decreases, and the levels of tear antioxidants such as lactoferrin also decrease. These age-related changes collectively lead to excessive accumulation of ROS, triggering oxidative stress that directly damages biomacromolecules in ocular surface cells and impairs the stability of the tear film. Furthermore, we have summarized the current therapeutic strategies for oxidative stress in DED, including both conventional antioxidants and emerging approaches such as eye drops based on nanoenzymes, thermosensitive hydrogels, intense pulsed light therapy, and drug-eluting contact lenses. By combining the new progress in the delivery systems of biomaterials-based drugs with mechanism-guided interventions, this review systematically establishes the intimate functional linkages between mitochondrial dysfunction, oxidative stress, and the pathogenesis of DED and focuses on elaborating the translational potential of advanced biomaterials-based antioxidant regimens, aiming to provide novel foundations and insights theoretical for the development of more effective and precise therapeutic strategies for DED. Full article

Background: Plants of the genus Nepeta are widely used in ethnomedicine for treating inflammatory disorders due to their rich content of bioactive compounds. This study investigated how extraction temperature specifically affects the bioactive potential of aqueous extracts from wild-grown Nepeta nuda L. Methods: The previously used maceration approach for this plant was applied at 30–60 °C to flowers, leaves, and stems. Phytochemical profiling included spectrophotometric assays, metabolite identification, and quantification. Biological activities reported for this plant were assessed, including antioxidant, anti-inflammatory, antiviral, antiproliferative, and antibacterial capacities. Results: Extraction yield was highest in flowers and leaves, where it increased significantly with rising temperature, while stems were less productive. All plant organs exhibited notable bioactivity falling into two groups: lower temperatures (30 and 40 °C) were optimal for antiviral and anti-inflammatory effects, whereas and higher temperatures (50 and 60 °C) enhanced antioxidant potential. The phytochemical composition, evaluated at representative extraction temperatures, revealed differential accumulation of p-coumaric acid and luteolin in all organs at 40 °C, while extraction at 60 °C corresponded to elevated levels of phenolic compounds. Flower extracts were confirmed to have the richest metabolic composition and were therefore subjected to further investigation. Extracts obtained at 40 °C influenced C1q binding, supporting their anti-inflammatory activity, whereas extraction at 60 °C resulted in stronger antiproliferative activity in colon cancer cell line. Antibacterial effects were similar at both temperatures. Conclusions: These findings highlight the importance of optimizing extraction conditions for future pharmacological applications of N. nuda. Full article

Background: Diabetic peripheral neuropathy (DPN) affects up to 50% of diabetes patients and is driven by hyperglycemia-induced oxidative stress, mitochondrial dysfunction, polyol pathway activation, advanced glycation end-product formation, and inflammation. Current management is largely symptomatic, prompting interest in metabolic/nutritional therapies. This review critically evaluates the mechanistic rationale and clinical evidence for alpha-lipoic acid (ALA) and benfotiamine as adjunctive treatments for DPN. Methods: A structured narrative review of PubMed/MEDLINE was conducted using predefined keywords for DPN, oxidative stress, metabolic therapy, and thiamine derivatives. Randomized controlled trials, clinical studies, systematic reviews, and relevant experimental studies were included. Evidence was synthesized qualitatively with emphasis on mechanistic plausibility, clinical efficacy, intervention duration, and methodological rigor. Results: ALA consistently improves short-term symptoms across multiple randomized trials. The long-term NATHAN 1 trial reported a marginal, borderline significant effect on the primary composite endpoint (NIS-LL, p = 0.05) without significant improvements in nerve conduction studies; therefore, evidence for functional stabilization is very limited and inconclusive. ALA’s effects are attributed to antioxidant activity, mitochondrial protection, and improved microvascular function. Benfotiamine has a strong biochemical rationale (transketolase activation, diversion of glycolytic intermediates from damaging pathways), but clinical evidence remains limited to short-duration, symptom-based studies, with no large-scale, long-term trials published. Conclusions: Both agents target key pathways in DPN pathogenesis. ALA is the most established adjunctive metabolic therapy for symptomatic DPN, although no study has demonstrated structural nerve regeneration or a definitive disease-modifying effect. Benfotiamine is biologically plausible but requires further validation in long-term randomized trials with structural and biomarker-based endpoints. Outside of documented thiamine deficiency, its routine use cannot be recommended based on current evidence. Full article

This study investigates the bio-physiological responses occurring under extreme stress conditions and the characterization of the oxy-inflammatory profile of Finishers (FRs) and NoFinishers (NFRs) athletes during the time course and following the Transpyrénéa, an 866 km extreme ultra-race across the French Pyrenees with an altitude difference of 52,900+ m ascent. Thirty-nine experienced ultra-marathon runners (age 43.5 ± 9.1 years; weight 72.1 ± 11.1 kg; BMI 23.3 ± 2.6 kg/m²) were studied using minimally invasive methods on capillary blood and urine samples obtained at baseline (T0), during (T1, 2, 3) and at the end (T4) of the race. Reactive Oxygen Species (ROS) production, total antioxidant capacity (TAC), oxidative damage (8-hydroxy-2-deoxy Guanosine: 8-OH-dG and 8-isoprostane: 8-isoPGF2α), inflammatory (IL-6), nitric oxide pathway (NOx and 3-NT), neopterin, and hematologic (lactate, and hematocrit) biomarkers were assessed. In both FR and NFR athletes a marked systemic increase in ROS, oxidative and nitrosative damage, inflammation, transient immune-renal dysfunction and lactate release were detected throughout the race. Compared to FRs, NFRs displayed significant differences concerning ROS production at T0, 8-isoPGF2-α at T0, T1 and T2, and perceived exertion (RPE score) at T2. These data potentially reflect enhanced adaptative responses to training and metabolic efficacy in FRs, allowing them to better tolerate extreme physiological stress. Full article

Dark septate endophytes (DSE) and ericoid mycorrhizal fungi (ERMF) are employed to augment the abiotic stress resistance of fruits. However, their potential functions in enhancing the drought resistance of blueberry, an economically important fruit, remain unclear. Thus, this study aims to identify optimal inoculation combinations to enhance the drought resistance of blueberry seedlings. Specifically, the effects of single and dual inoculations with DSE (Cladosporium cladosporioides, D79) and ERMF (Oidiodendron citrinum, N12) on seedling physiology and metabolism were explored under varying drought conditions. The results showed that dual inoculation significantly improved leaf physiological characteristics. Under severe drought stress, the 1:2 DSE:ERMF ratio (D1N2) notably increased leaf relative water content (RWC) and reduced electrolyte leakage by up to 42.1% compared with the non-inoculated control. Dual inoculation also significantly decreased malondialdehyde (MDA) content, with the smallest increase observed in D1N2. Regarding antioxidant enzymes, dual inoculation sustained higher superoxide dismutase (SOD) activity under moderate drought and minimized the decline in SOD activity under severe drought (the lowest decrease was 36.4% in D1N2 versus 56.7% in CK). Moreover, the antioxidant losses under drought stress were reduced by upregulating various metabolic processes, especially the biosynthesis of phenylalanine, tyrosine, and tryptophan. A comprehensive evaluation suggested that inoculation with a 1:2 mixture of DSE and ERMF most effectively improved blueberry drought resistance, primarily by enhancing water and metabolite supply and stimulating the antioxidant defenses. Full article

Glycolysis and the pentose phosphate pathway (PPP) are two metabolic pathways that play crucial roles in brain energy metabolism. The glycolytic pathway is differentially regulated in neurons compared to astrocytes. In neurons, the flux directly through the glycolytic pathway is reduced due to compromised ability to activate the key glycolytic enzyme 6-phosphofructo-1-kinase (PFK1). Consequently, potential increases in neuronal glucose metabolic flux can occur through the PPP, leading to the generation of NADPH, which is essential for the antioxidant defense system in these cells. Additionally, the PPP can supply glycolysis with intermediates downstream of PFK1, resulting in the production of pyruvate, which is used by mitochondria for oxidative phosphorylation and ATP production. In this review, we propose that during increased activity, neurons will preferentially metabolize glucose through the PPP. This allows them to support their antioxidant defense mechanisms and maintain bioenergetic metabolism by bypassing the limiting PFK1 enzyme and still forming pyruvate for mitochondrial oxidation. Full article