GLUTATHIONE

Diazinon is extensively used as an insecticide or pesticide in agriculture. This insecticide can be absorbed by the human body through inhalation, oral ingestion, and skin, leading to human poisoning. The liver is the first organ affected by diazinon. The present study focused on the recovery of antioxidant biomarkers, including malondialdehyde (MDA), catalase (CAT), superoxide dismutase (SOD), and reduced glutathione (GSH), in addition to the acetylcholinesterase activity (AChE), using two flavonoids, namely rutin and quercetin, in the rat liver. The antioxidant properties of these two compounds are well-established. The results show that both rutin and quercetin at a dosage of 200 mg/kg can reduce the malondialdehyde and improve the other markers and acetylcholinesterase, with quercetin being more effective. Quercetin, owing to its superior antioxidant activity and higher bioavailability compared to rutin, effectively restored antioxidant enzyme activities (SOD, CAT, and GSH) and AChE levels in the liver of diazinon-poisoned rats to near control values. The current study suggests that quercetin is a more effective therapeutic agent than rutin for mitigating diazinon-induced hepatic oxidative stress and toxicity by scavenging ROS, inhibiting lipid peroxidation, and restoring redox homeostasis. Accordingly, quercetin can be considered as a potential treatment for diazinon poisoning. However, more animal, cellular, and clinical studies are necessary for prescribing and final approval for use in humans.

An acute bout of high intensity exercise can transiently increase circulating extracellular vesicles (EVs) that possess beneficial molecular cargo. However, no studies to date have comprehensively evaluated plasma quantity, protein content, and function of EVs collected from blood after multiple bouts of endurance exercise. Here we demonstrate that 4 weeks of voluntary wheel running increases plasma EV quantity when collected immediately after the last bout of training in mice. These EVs (ExerVs) are enriched in oxidoreductases, including the antioxidant glutathione peroxidase 1 (GPX1). Repeated, systemic injections of ExerVs into sedentary recipient mice twice per week for 4 weeks did not alter mitochondrial content or function, fiber size, or fiber type, but increased capillary density and perfusion in skeletal muscle. ExerVs also stimulated tube formation and branch lengthening in vitro and improved the recovery of capillary content after a period of disuse in vivo. ExerVs isolated from GPX1 -/- mice lacked the ability to stimulate vessel formation, whereas GPX1-encapsulated liposomes robustly increased capillary growth, both in vitro and in vivo. The results from this study suggest that circulating ExerVs positively impact vascular structure and function in skeletal muscle in a manner that may be dependent on GPX1.

Breast cancer remains one of the most prevalent malignancies among women worldwide. Current therapeutic strategies comprising surgery, radiation therapy, immunotherapy, and postoperative chemotherapy have significantly improved patient outcomes. However, the emergence of multidrug resistance (MDR) continues to impede treatment efficacy. Several factors contribute to MDR, including drug inactivation, enhanced metabolism, transporter protein-mediated drug efflux, and epigenetic alterations. Among these, the overexpression of drug-metabolizing enzymes such as glutathione S -transferases (GSTs), alongside transporter proteins like the breast cancer resistance protein (BRCA), plays a pivotal role. Numerous studies have demonstrated that GSTs not only accumulate on the cell surface but also interact with proteins involved in critical signaling pathways, thereby enhancing mRNA translation, promoting cell proliferation, and inhibiting apoptosis. These interactions highlight an essential link between GST activity and breast cancer progression. To counter GST-mediated resistance, various GST inhibitors and prodrugs specifically targeting cancer cells with elevated GST expression have been developed, showing considerable therapeutic promise. Nevertheless, the precise molecular mechanisms underlying GST-induced drug resistance remain incompletely understood. A comprehensive understanding of these mechanisms is vital for the rational design of effective therapeutic interventions. Given that breast cancer continues to be the leading cause of cancer-related mortality in women, in-depth exploration of GST's role in altering the tumor microenvironment (TME), regulating metastasis, and modulating apoptotic pathways is imperative. This review consolidates previous findings and integrates recent experimental evidence, providing a foundational framework for identifying novel GST-related targets in drug design and delivery.

Pink lotus ( Nelumbo nucifera Gaertn.) contains bioactive flavonoids and alkaloids that exert anti-inflammatory and antioxidant activities, and inhibit TNF-α, IL-1β, IL-6 and NF-κB signaling pathways implicated in the pathogenesis of psoriasis. However, the effects of pink lotus flower oil (PLO) on psoriasis-like skin inflammation remain unexplored. Therefore, the present study aimed to evaluate the effects of PLO treatment on imiquimod (IMQ)-induced psoriasis-like skin inflammation in a mouse model. Briefly, BALB/c mice with IMQ-induced psoriasis were administered PLO (100 and 200 mg/kg), and the psoriasis area and severity index were measured. Histopathology, proinflammatory cytokine levels, antioxidant gene expression, oxidative stress and antioxidant marker levels, and immunoreactivity were also assessed. PLO treatment markedly reduced erythema, scaling and epidermal thickening, and suppressed keratinocyte proliferation, as evidenced by decreased proliferating cell nuclear antigen immunoreactivity, and downregulated mRNA levels of keratin-encoding genes keratin 6 ( K6 ), K16 and K17 . Moreover, PLO significantly downregulated the levels of proinflammatory cytokines, including TNF-α, IL-17A, IL-23 and IL-6 , and reduced the infiltration of CD4 + and mast cells. Mechanistically, PLO treatment decreased phosphorylated (p)-JAK2, p-JAK3 and p-STAT3 immunoreactivity by inhibiting JAK2/JAK3/STAT3 signaling. Oxidative stress was attenuated, as evidenced by reduced malondialdehyde levels, and increased nuclear factor erythroid 2-related factor 2, Cu/Zn-superoxide dismutase ( Cu/Zn-SOD ), Mn-SOD , catalase and glutathione peroxidase mRNA expression levels. PLO treatment also mitigated IMQ-induced splenomegaly, and suppressed IL-1b and IL-6 expression in the spleen, and reduced IL-6 expression in the axillary lymph nodes. In conclusion, PLO treatment ameliorated IMQ-induced psoriasis by enhancing antioxidant defenses, and by inhibiting JAK2 and JAK3/STAT3 signaling, supporting its potential as a therapeutic candidate for psoriasis.

The control of the fall armyworm (FAW), Spodoptera frugiperda, relies heavily on insecticides, which has accelerated the evolution of resistance; thus it is urgent to monitor the insecticide resistance status of this pest. In this study, insecticide bioassays were conducted using the topical application method on 16 field populations collected in China in 2023. The results showed that FAW in China is susceptible to emamectin benzoate, chlorantraniliprole, tetrachlorantraniliprole and lambda-cyhalothrin, whereas some populations exhibited low-level resistance to indoxacarb, spinetoram, broflanilide, chlorfenapyr and acephate. No mutations were detected in the target genes GluCl, nAChR, RyR, GABAR and VGSC; however, 67.7% individuals displayed mutations at locus F290V of ace-1. Detoxification enzyme activity and synergistic assays suggest that cytochrome P450 enzymes (P450s), glutathione S-transferases (GSTs) and esterases (ESTs) are implicated in the low-level resistance to indoxacarb, spinetoram and acephate. GSTs and ESTs also contributed to broflanilide resistance, whereas only GSTs played a role in chlorfenapyr resistance. Our study offers substantial insights for monitoring and managing the development of insecticide resistance in S. frugiperda populations in China. Future research will be needed to further investigate the metabolic mechanisms of related detoxifying enzymes and the resistance mechanisms mediated by ace-1 mutations. © 2026 Society of Chemical Industry.

The bidirectional association between diabetes mellitus (DM) and periodontitis remains a major focus in oral and systemic health research. DM is a key risk factor influencing the onset, progression, and severity of periodontitis, yet the molecular mechanisms underlying this relationship are not fully understood. Periodontitis is characterized by bacterial biofilm formation and a destructive host immune-inflammatory response. In this study, we explored the therapeutic potential of Ti 3 C 2 T x MXene, a two-dimensional nanomaterial, for enhancing gingival wound healing under diabetic conditions. Ti 3 C 2 T x MXene treatment of fibroblast cells derived from diabetic rat gingival tissue modulated oxidative stress and restored glutathione balance. The material exhibited significant biocompatibility, preserved mitochondrial membrane potential, and reduced intracellular reactive oxygen species (ROS) levels. Moreover, Ti 3 C 2 T x MXene influenced lipid peroxidation and cytochrome c release, contributing to controlled caspase activation and balanced apoptotic responses. These results suggest that Ti 3 C 2 T x MXene supports cellular and mitochondrial homeostasis, promoting improved wound repair in diabetic gingiva. Collectively, this study presents the first evidence of Ti 3 C 2 T x MXene as a promising nanotherapeutic platform for managing diabetic oral wounds and potentially other chronic wounds, paving the way for future applications in nano-enabled topical formulations and interdisciplinary oral healthcare strategies.

Owing to advancements in implantable bioelectronic devices, there has been an increase in demand for biocompatible energy sources with long-term electrochemical and mechanical stability. In this study, we present the fabrication of a flexible asymmetric supercapacitor (MXene//AC) based on two-dimensional Ti 3 C 2 T x MXene nanosheets. The supercapacitor demonstrates excellent electrochemical performance with an areal capacitance of 66.43 mF cm -2 , energy density of 13.2 Wh kg -1 , and a high power density of 2300 W kg -1 . The supercapacitor retained 95% capacitance after 5000 charge-discharge cycles and displayed negligible performance degradation under various bending angles, highlighting its mechanical suitability for wearable electronics. Density functional theory (DFT) analysis revealed that the metallic Ti-C backbone of Ti3C2T x MXene and its O/F terminations work synergistically to enable rapid electron transport and reversible proton-coupled surface redox, supporting predominantly surface-controlled charge storage with a significant pseudocapacitive contribution. To complement device-level studies, we assessed the in vivo safety profile and antioxidant potential of Ti 3 C 2 T x MXene nanosheets in Sprague-Dawley (SD) rats through acute dermal, subchronic oral, and subchronic intraperitoneal toxicity evaluations. Acute dermal exposure up to 100 mg kg -1 caused mild skin responses without necrosis, while subchronic administration for 28 days revealed no considerable abnormalities in biochemical parameters (alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine), inflammatory markers (IL-1β, IL-6), or oxidative stress biomarkers (malondialdehyde, glutathione). Histopathological evaluations confirmed the absence of structural damage or inflammation in vital organs. Additionally, MXene nanosheets demonstrated antioxidant activity by scavenging 2,2-azino-bis(3-ethyl)benzothiazoline-6-sulfonic acid free radicals in a dose-dependent manner, highlighting their potential to reduce oxidative stress in biomedical applications. Overall, this dual-focused study demonstrates that MXene nanosheets are not only highly effective for developing flexible, stable asymmetric supercapacitors but also exhibit favorable in vivo biocompatibility and antioxidant properties at the tested doses. These findings emphasize the potential of MXene-based materials as next-generation, fully biocompatible energy storage devices for advanced implantable bioelectronic systems.

Zinc oxide nanoparticles (N-ZnO) represent a promising alternative for zinc (Zn) supplementation, since their reduced size provides greater bioavailability and better integration into the body. Furthermore, this characteristic becomes particularly relevant during periods of increased metabolic stress, such as the transition phase. Thus, the objective was to evaluate the effects of N-ZnO supplementation in Santa Inês sheep during the peripartum period. Thirty-three ewes with an average body weight of 43.3 ± 2.05 kg were, distributed into three experimental groups: control group (CON), without supplementation, receiving only Cynodon spp. hay; and groups supplemented with 300 mg/animal/day of N-ZnO (40 nm) and zinc oxide microparticles (M-ZnO). The supplementation was administered orally in capsules daily from late pregnancy until weaning. The results showed no significant differences (P > 0.05) in body weight, egg count per gram of feces (EPG), and in most of the hematological, biochemical, and immunological parameters evaluated. However, differences (P < 0.05) were observed in monocyte counts and albumin levels, with higher means in the N-ZnO group, showing differences compared with the M-ZnO group, while the CON group maintained intermediate values. The N-ZnO group showed differences compared to the M-ZnO group, while the CON group maintained intermediate values. Regarding antioxidant activity, a significant effect (P < 0.05) was observed on the enzymes Superoxidase dismutase (SOD), Glutathione peroxidase (GPx), Catalase (Cat), and on the total antioxidant status (ORAC) of the sheep supplemented with N-ZnO. It is concluded that N-ZnO supplementation improved the antioxidant response, with no signs of intoxication, using a dose of 300 mg during the period of greatest oxidative stress.

The skin is a complex immunological organ in which reactive oxygen species (ROS)-related pathways and host-microbe interactions synergically maintain immune homeostasis. Dysregulation of several oxidative mechanisms, including lipid peroxidation, mitochondrial dysfunction, ferroptosis, and impaired antioxidant defenses, alongside gut microbiome imbalance, is increasingly recognized as a key modulator of the immune response involved in disease onset and progression. However, their role in immune-mediated dermatoses remains incompletely defined. This narrative review aims to provide a comprehensive overview of the contribution of these altered pathways to the pathogenesis and prognosis of the major immune-mediated skin diseases. Across all conditions examined, elevated oxidative biomarkers, such as malondialdehyde (MDA), advanced glycation end-products (AGEs), advanced oxidation protein products (AOPPs), 8-hydroxydeoxyguanosine (8-OHdG), and reduced antioxidant capacity are consistently reported. Ferroptosis, driven by iron-dependent lipid peroxidation and dysfunction of Glutathione peroxidase 4 (GPX4), emerges as a relevant cell death pathway, particularly in psoriasis and atopic dermatitis (AD). In parallel, dysbiosis of the gut and skin microbiomes, characterized by depletion of short-chain fatty acid (SCFA)-producing taxa such as Faecalibacterium prausnitzii , Bifidobacterium , and Akkermansia muciniphila , has been reported across multiple diseases. Particular attention is given to shared molecular axes, such as the disruption of epithelial barrier integrity, activation of innate and adaptive immune responses, and the role of microbial-derived metabolites in modulating redox signaling, unraveling a bidirectional crosstalk. Emerging therapeutic strategies targeting these bidirectional crosstalks show biological plausibility and promising preliminary results. Integrating redox and microbial profiling into clinical practice may improve patient stratification and foster the development of more personalized therapeutic approaches beyond conventional immunological treatments.

Algae have shown an effective defense system that enables their survival in environments exposed to radiation stress, especially from ultraviolet (UV) light and ionizing radiation. Their protective system comprises specific photoprotective chemicals along with a multilayered antioxidant strategy that encompasses both non-enzymatic and enzymatic approaches. In this defence system, scytonemin and mycosporin-like amino acids play a crucial role in photoprotection by functioning as natural sunscreen with high photostability and strong UV-absorbing capacity. These chemical compounds also possess antioxidant properties that help minimize indirect damage produced by reactive oxygen species formed after radiation exposure. Scytonemin becomes significant due to its capability to block 90% of UV-radiation, effectively absorbing all types of UV (A, B and C) wavelengths. In the process of quenching photosensitization products and scavenging free radicals, carotenoids act as a stress reliever by preventing oxidative damage and lipid peroxidation. The internally generated ROS gets neutralized by algae, which utilize an enzymatic antioxidant system. In the enzymatic defence system of algae, ascorbate peroxidase, catalase, superoxide dismutase and glutathione reductase play important roles in ROS elimination. Additionally, α-tocopherol and ascorbic acid which are non-enzymatic antioxidants, complement the enzymatic reaction described above. The biochemical properties of these photoprotective and antioxidant compounds have significant biotechnological implications, applications in pharmaceuticals, cosmetics, anticancer treatments, nutraceuticals and antimicrobials. Interestingly, exposure to low-dose radiation has been shown to enhance algae growth, stimulate the production of valuable metabolites for biofuels and biomaterials and strengthen the resilience of cultivated strains against stressors.

Metal-coordinated hydrogels offer a strategy to integrate local drug retention, responsive release, and multimodal therapy, but assigning structural and therapeutic roles to a single metal complex remains challenging. Here, we report an injectable polypyridyl Ru(II)-scaffolded hydrogel, Ru(fmb) 3 HADH-PDA@IR780, formed by dynamic Schiff-base crosslinking and loaded with polydopamine nanoparticles carrying IR780. In this platform, PDA@IR780 enables 808 nm near-infrared-activated photothermal and photodynamic outputs whereas the Ru(II) complex functions as both a hydrogel crosslinking unit and a redox-active therapeutic component. This formulation demonstrates dual pH/photo-responsiveness: acidic tumor microenvironment (TME) promoted formulation release, and NIR irradiation triggered rapid local heating and reactive oxygen species (ROS) generation. In vitro, the hydrogel produced enhanced tumor-cell killing through combined photothermal, photodynamic, and Ru-associated oxidative and chemodynamic therapy (CDT), accompanied by glutathione depletion and lipid-peroxidation-related stress. In vivo, local administration followed by short NIR irradiation markedly suppressed tumor growth, increased tumor-cell apoptosis, prolonged tumor-site retention, and showed no obvious short-term systemic toxicity under the tested regimen. Transcriptomic and histological analyses further suggested treatment-associated redox disruption and favorable modulation of the local immune microenvironment. This Ru(II)-scaffolded hydrogel provides a component-defined, single-wavelength-activated platform for locally retained multimodal tumor therapy. Notably, this work represents the first report of a polypyridyl Ru(II)-scaffolded hydrogel that unifies Ru(II)'s structural coordination with intrinsic therapeutic action, offering a translational strategy for synergistic, site-selective tumor therapy.

Psoriasis is skin inflammation caused by an immune system dysfunction, involving a complex interaction between immune cells and keratinocytes. The aim of this study was to develop nanoemulsion (NE) based hydrogel containing ferulic acid, a poorly water-soluble compound and evaluate its effect on imiquimod induced psoriasis like skin inflammation. Ferulic acid nanoemulsion (FA-NE) was prepared by ultra-sonication method. Castor oil, Tween-80 and propylene glycol were selected for NE preparation as oil phase surfactant and cosurfactant respectively based on solubility. The NE particle size (29.8 ± 0.49 nm) was within colloidal range, polydispersity index (0.21 ± 0.02) showed homogenous NE, zeta potential (28.5 ± 0.57 mV) indicated stable NE. Entrapment efficiency (96.26 ± 0.33%) and pH (6.8 ± 0.15) was also in suitable range. The rheological study results of FA-NE hydrogel indicated pseudoplastic behavior. The pH and spreadibility were 6.2 ± 0.15 and 8.2 ± 0.89 respectively, suitable for topical application. The optimized FA-NE hydrogel was tested on male Wistar rats (100-150 g) divided into five groups (n = 5). Psoriasis like disease was induced by applying 5% imiquimod (IMQ) cream for 7 days on the shaved dorsal skin of four groups (except normal group) and psoriasis area severity index (PASI) scoring were calculated. The application of optimized FA-NE hydrogel dramatically reduced TNF-α, IL-6, IL-17 A, IL-23, superoxide dismutase, glutathione peroxidase, malondialdehyde and catalase biomarkers when compared to the disease group. These results were consistent with the in-silico docking studies with highest docking score observed with TNF-α. The treatment group's spleen index reduced significantly. Histopathological findings showed increased capillaries, skin thinning, small dermal projections, and inflammatory cells around blood vessels with 5% IMQ cream application and FA-NE hydrogel greatly reduced these psoriatic changes. Immunohistochemical Ki-67 analysis demonstrated that disease control rats expressed more protein than normal, treatment, and standard animals. The FA-NE hydrogel effectively reduced inflammation and oxidative stress in a rat model of psoriasis, suggesting its potential as a topical treatment.