Search Results (19,645)

As an important bioactive signaling molecule, nitric oxide (NO) participates in the responses of plants to various environmental stresses. The aim of this study was to investigate the influence of exogenous NO on the growth and cadmium (Cd) accumulation of alfalfa (Medicago sativa) during early growth. The results showed that Cd significantly inhibited alfalfa seedling growth and induced membrane lipid peroxidation. Addition of sodium nitroprusside (SNP, as an NO donor) significantly promoted seedling growth and induced the mobilization of seed photosynthate reserves, leading to an increase in total soluble sugar (SS) and reducing sugar (RS) contents. Application of SNP mitigated membrane peroxidation damage caused by Cd stress by enhancing catalase (CAT), ascorbate peroxidase (APX), superoxide dismutase (SOD) and peroxidase (POD) activities in order to eliminate reactive oxygen species (ROS), thereby improving Cd resistance and increasing Cd accumulation in alfalfa. This promoting effect of SNP depended on its concentration; the most optimal SNP concentration to promote the growth and Cd absorption of alfalfa under Cd stress was found to be 200 µM. The fresh weight (FW), dry weight (DW) and Cd accumulation of seedlings treated with 200 µM SNP increased significantly by 23.10%, 30.32% and 82.50%, respectively, on the fifth day, compared with the Cd-only treatment. Full article

Background: Neuroblastoma (NB) presents significant challenges in pediatric oncology, particularly in high-risk cases where local recurrence occurs in ~35% of patients. Cold Atmospheric Plasma (CAP) has emerged as a promising treatment due to its selective cytotoxicity toward cancer cells while sparing normal cells. Methods: This study assessed CAP efficacy using in vitro NB cell lines (SK-N-AS and LAN-5) and in vivo xenograft murine models. In vitro, CAP was applied via a helium jet, and cellular responses were evaluated for viability, reactive oxygen species (ROS), lipid peroxidation, DNA damage, and cell cycle, while apoptosis was measured by Annexin V/PI flow cytometry. In vivo, CAP was applied to unresected tumors and residual tumors after incomplete resection. Tumor regrowth was monitored, and histological analysis was performed. Results: CAP reduced NB cell viability in a dose- and time-dependent manner by increasing intracellular ROS and lipid peroxidation. CAP-treated NB cells showed a 50% rise in oxidative DNA damage, a two-fold increase in apoptosis, and alterations in cell-cycle progression, while normal fibroblasts showed modest effects. CAP predominantly induced apoptosis, though secondary necrosis appeared with prolonged exposures, consistent with caspase-3 and PARP pathways. In xenografts, CAP reduced tumor diameter by 60% and increased caspase-3-positive cells, with minimal effects on normal tissue. Conclusions: CAP demonstrates strong therapeutic potential as a targeted, non-invasive NB treatment, particularly for residual tumors near vascular structures with consistent exposure times (60–300 s). Full article

Laser-assisted hatching (LAH) is used during in vitro fertilization (IVF) to improve the chances of embryo implantation into the uterine wall by creating a small, precise opening in its outer shell (zona pellucida). The primary objective of this study was to evaluate the safety profile of LAH performed using an infrared femtosecond laser system (λ = 1028 nm, E = 155 nJ, and I = 6.5 TW/cm²). We aimed to identify and quantify the potential biological effects of the laser and compare them with results from previous studies that used visible wavelength laser pulses (λ = 514 nm, E = 49 nJ, and I = 2.5 TW/cm²). To achieve this, we designed a controlled experiment using a mouse model. A critical component of our safety assessment involved quantifying the levels of reactive oxygen species (ROS) and analyzing the expression of heat-shock proteins (HSPs). Robust analyses revealed no statistically significant differences in either ROS production or HSP expression—assessed at both the protein and mRNA levels—between embryos in the negative control group and those subjected to the femtosecond LAH procedure. This key finding indicates that neither infrared nor visible femtosecond laser microsurgery of the zona pellucida induced a detectable oxidative or thermal stress response within the tested parameters. Full article

Tris(2-chloroethyl) phosphate (TCEP), as an organophosphate contaminant, poses a significant threat to the growth and development of plants, especially roots. This study aimed to clarify the mechanisms of TCEP’s toxicity and damage to root systems, as well as the mechanisms of its damage to the respiration and energy metabolism of alfalfa root cells. The results showed that TCEP obviously affected the root length, root surface area, root volume, and root diameter of alfalfa. With increasing stress intensity, the total mitochondrial respiration rate and Cytochrome C Oxidase (COX) pathway respiration rate progressively declined, while the Alternative Oxidase (AOX) pathway respiration rate and its proportion of total respiration gradually rose. In addition, adenosine triphosphate (ATP) content and root vigor were significantly reduced. Moreover, with an increase in TCEP concentration, root superoxide anion radical content in alfalfa root cells was significantly elevated, while superoxide dismutase (SOD) and catalase (CAT) activities were significantly lowered, and ascorbate peroxidase (APX) and peroxidase (POD) activities were significantly enhanced. The present study indicated that respiration was disrupted, causing a lack of ATP in root cells under TCEP. Both the overproduction of reactive oxygen species (ROS) from the mitochondrial respiratory electron transport chain (mECT) and the deficiency of ROS-scavenging enzymes caused ROS accumulation, which led to the destruction of the cell membrane structure and exacerbated the disruption of the respiratory metabolism. The disruption of the conversion and reuse of energy by TCEP affected root growth and development. Full article

Genipin, a natural compound derived from Gardenia jasminoides, is widely used as an inhibitor of uncoupling protein 2 (UCP2), a protein located in the inner mitochondrial membrane (IMM) that plays a crucial role in regulating oxidative stress and cellular metabolism. Pharmacological inhibition of UCP2 has been explored as a strategy to modulate reactive oxygen species (ROS) and inflammatory responses. However, the utility of genipin is limited by its relatively low bioavailability and dose-dependent toxicity. To address these limitations, we developed mito-genipin, a mitochondria-targeted genipin derivative incorporating a triphenylphosphonium (TPP⁺) moiety, designed to enhance mitochondrial accumulation and thereby increase efficacy. In macrophages, mito-genipin induced mitochondrial hyperpolarization, elevated ROS production, and amplified pro-inflammatory cytokine expression compared with control or genipin treatment. In cells lacking UCP2, mito-genipin did not enhance ROS production. Our data identify mito-genipin as an effective modulator of oxidative stress and inflammation, supporting a putative link to UCP2 inhibition and highlighting potential implications in redox biology and immunomodulation. Full article

Background: Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) such as erlotinib are widely used in non-small-cell lung cancer treatment, and accumulating evidence indicates they can markedly increase ocular toxicity. Nonetheless, whether erlotinib causes optic nerve injury has not been investigated before and remains a subject worth investigating. This study aimed to examine the impact of erlotinib on oxidative stress, inflammation, and histopathological changes in rat optic nerve tissue and evaluate the potential neuroprotective role of thiamine pyrophosphate (TPP). Methods: Twenty-four male Wistar rats were randomly assigned to four groups: healthy control, TPP alone, erlotinib alone, and erlotinib + TPP. Erlotinib (10 mg/kg, orally, on alternate days) and TPP (20 mg/kg, intraperitoneally, daily) were administered for two consecutive weeks. Optic nerve samples were analyzed for malondialdehyde (MDA), total glutathione (tGSH), superoxide dismutase (SOD), catalase (CAT), interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α), followed by histopathological examination. Results: Erlotinib treatment significantly increased MDA, IL-1β, and TNF-α levels while reducing tGSH, SOD, and CAT activity, demonstrating oxidative stress and an inflammatory response. Co-administration of TPP ameliorated these changes by lowering reactive oxygen species, restoring antioxidant capacity, and attenuating inflammation. Histopathological alterations, including astrocyte degeneration, edema, and vascular congestion, were evident after erlotinib exposure but were significantly alleviated when TPP was administered concurrently. Conclusions: Erlotinib induces oxidative and inflammatory optic nerve injury, while TPP co-treatment offers significant neuroprotection. These findings support TPP as a potential adjunct to reduce EGFR-TKI-related ocular toxicity and highlight importance of redox modulation in limiting treatment-associated side effects. Full article

Nitrogen-modified atmosphere technology, due to its effectiveness in pest control, is widely used in grain storage as an eco-friendly preservation method. This study compared the quality changes in unhulled rough rice (paddy) stored under nitrogen-modified atmosphere and conventional conditions. Fatty acid value (FAV), reactive oxygen species (ROS) content, coenzyme levels, antioxidant enzyme activities, and concentrations of central carbon metabolism-related metabolites of paddy were monitored during storage under different storage conditions. The results revealed that compared to conventional storage, nitrogen-modified atmosphere resulted in lower FAV and ROS levels, as well as higher pyridine nucleotides contents and antioxidant enzyme activities, including superoxide dismutase (SOD), peroxidase (POD), catalase (CAT), and glutathione reductase (GR). Metabolomic profiling demonstrated that N₂-MAS induced metabolic changes characterized by the down-regulation of 2-hydroxyglutaric acid and the up-regulation of fructose 6-phosphate, glucose 1-phosphate, glycerol 3-phosphate, gluconic acid, fumaric acid, and malic acid, which collectively contribute to reduced oxidative damage and enhanced preservation quality. These findings elucidated the mechanism of N₂-MAS-delayed quality deterioration and revealed the regulatory role of the antioxidant system and central carbon metabolism. Full article

Background: Dry Eye Disease (DED) is a multifactorial ocular disorder characterized by tear film instability, inflammation, oxidative stress, and ocular surface damage. Current therapeutic options often provide only temporary relief and are limited by poor patient compliance and inadequate drug retention at the ocular surface. Aim: This review aims to critically analyze the therapeutic potential of polyphenols and their nanoencapsulated formulations for the management of DED, focusing on pharmacological mechanisms, formulation strategies, and translational implications. Methods: A comprehensive literature search was conducted in PubMed, Scopus, and Web of Science databases using combinations of the following keywords: “dry eye disease,” “polyphenols,” “antioxidants,” “nanocarriers,” “ocular delivery,” and “bioavailability.” Studies published in English from 2000 to 2024 were considered. Inclusion criteria encompassed experimental, preclinical, and clinical studies evaluating polyphenol-based formulations for ocular application, while reviews without original data or studies unrelated to DED were excluded. Results: The analysis identified EGCG, curcumin, resveratrol, and quercetin as the most extensively investigated polyphenols, exhibiting antioxidant, anti-inflammatory, and cytoprotective activities through modulation of cytokines, reactive oxygen species, and immune signaling pathways. Nanoformulations such as lipid nanoparticles, micelles, and cyclodextrin complexes improved solubility, stability, ocular retention, and bioavailability, leading to enhanced therapeutic efficacy in preclinical DED models. Conclusions and Future Perspectives: Polyphenol-loaded nanocarriers represent a promising approach for improving the management of DED by enhancing local drug delivery and sustained release. However, further clinical studies are needed to assess long-term safety, scalability, and regulatory feasibility. Future research should focus on optimizing formulation reproducibility and exploring personalized nanotherapeutic strategies to overcome interindividual variability in treatment response. Full article

Ferroptosis is a novel kind of regulated cell death that occurs when redox equilibrium is disrupted, leading to iron-dependent lipid peroxidation. Ferroptosis is defined by the buildup of deleterious lipid hydroperoxides, the inactivation of glutathione peroxidase 4 (GPX4), and mitochondrial shrinkage, setting it apart from apoptosis and necrosis. The relevance of this route to human reproduction remains unknown, despite its thorough investigation in neurodegeneration and cancer. Recent studies demonstrate that the ovarian follicular milieu is especially susceptible to ferroptosis owing to its high content of polyunsaturated fatty acids, iron-dependent metabolism, and the generation of reactive oxygen species. Dysregulation of ferroptosis may result in infertility by affecting granulosa cell survival, oocyte maturation, and embryonic competence. Ferroptotic activity correlates with oxidative stress indicators identified in clinical diseases including polycystic ovary syndrome, reduced ovarian reserve, and insufficient responsiveness to ovarian stimulation. Potential indicators include GPX4 expression, decreased glutathione levels, and the accumulation of lipid reactive oxygen species in granulosa cells and follicular fluid. Melatonin, which boosts antioxidant defences, and ferrostatin-1, a prototype inhibitor of ferroptosis that lowers lipid peroxidation, are two early candidates for treatment. For future evaluations, these agents should be used with standardised FF biomarker panels. Significantly, vitamin E, coenzyme Q10, and small-molecule ferroptosis inhibitors have shown efficacy in halting ferroptosis in experimental settings. These approaches have shown protective benefits in alternative systems and may signify viable treatment options for assisted reproduction. This narrative review encapsulates ferroptosis inside the ovarian follicle, its influence on oocyte quality, and the implications for in vitro fertilization results. Full article

Dysregulated redox signaling, mitochondrial dysfunction and impaired autophagy form an interconnected network that drives inflammatory and immune responses in cardiovascular disease. Among these, disturbances in redox balance, largely mediated by reactive oxygen species (ROS), serve as key drivers linking inflammatory signaling to adverse cardiovascular outcomes. Mitochondria are essential for energy production and cellular homeostasis, but their dysfunction leads to the accumulation of excessive ROS, which triggers inflammation. This pro-oxidative milieu disrupts immune regulation by activating inflammasomes, promoting cytokine secretion, triggering immune cell infiltration and ultimately contributing to cardiovascular injury. Conversely, intracellular degradation processes such as mitophagy alleviate these effects by selectively eliminating dysfunctional mitochondria, thereby decreasing ROS levels and maintaining immune homoeostasis. These interconnected processes influence myeloid cell function, including mitochondrial reprogramming, macrophage polarization and autophagic activity. The modulation of these immune responses is crucial for determining the severity and resolution of cardiac and vascular inflammation, and consequently the extent of cellular injury. This review examines the latest developments and understanding of the intricate relationships between redox signaling, mitochondrial dysfunction, autophagy and oxidative stress in modulating inflammation and immune responses in cardiovascular diseases. Understanding these interrelationships will inform future studies and therapeutic solutions for the prevention and treatment of cardiovascular diseases. Full article

The reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) is a primary electron donor for both antioxidant enzymes, such as glutathione reductase, and pro-oxidant enzymes, such as NADPH oxidases that produce reactive oxygen species (ROS) and nitric oxide synthases that generate nitric oxide which act as signaling molecules. Monitoring NADPH levels, NADPH/NADP⁺ ratio, and especially distinguishing from NADH, provides vital information about cellular redox status, energy generation, survival, lineage specification, and death pathway selection. NADPH detection is key to understanding metabolic reprogramming in cancer, aging, and cardiovascular, hormonal, neurodegenerative, and autoimmune diseases. Liquid chromatography combined with mass spectrometry (LC-MS) is crucial for NADPH detection in redox signaling because it offers the high sensitivity, specificity, and comprehensive profiling needed to quantify this vital but labile redox cofactor in complex biological samples. Using hepatoma cell lines, liver tissues, and primary hepatocytes from mice lacking transaldolase or nicotinamide nucleotide transhydrogenase, or having lupus, this study demonstrates that accurate measurement of NADPH depends on its preservation in reduced form which can be optimally achieved by extraction of metabolites in alkaline solution, such as 0.1 M potassium hydroxide (KOH) in comparison to 80% methanol (MeOH) alone or 40:40:20 methanol/acetonitrile/formic acid solution. While KOH extraction coupled with hydrophilic interaction liquid chromatography (HILIC) and mass spectrometry most reliably detects NADPH, NADP, NADH, NAD, polyamines, and polyols, MeOH extraction is best suited for detection of glutathione and overall discrimination between complex metabolite extracts. This study therefore supports performing parallel KOH and MeOH extractions to enable comprehensive metabolomic analysis of redox signaling. Full article

Diabetic nephropathy (DN) remains the leading cause of end-stage renal disease worldwide, with proximal tubular epithelial cells (PTECs) playing a central role in its pathogenesis. Under hyperglycemic conditions, PTECs drive a pathological triad of inflammation, apoptosis, and fibrosis. Recent advances reveal that these processes interact synergistically to form a self-perpetuating vicious cycle, rather than operating in isolation. This review systematically elucidates the molecular mechanisms underlying this crosstalk in PTECs. Hyperglycemia induces reactive oxygen species (ROS) overproduction, advanced glycation end products (AGEs) accumulation, and endoplasmic reticulum stress (ERS), which collectively activate key inflammatory pathways (NF-κB, NLRP3, cGAS-STING). The resulting inflammatory milieu triggers apoptosis via death receptor and mitochondrial pathways, while apoptotic cells release damage-associated molecular patterns (DAMPs) that further amplify inflammation. Concurrently, fibrogenic signaling (TGF-β1/Smad, Hippo-YAP/TAZ) promotes epithelial–mesenchymal transition (EMT) and extracellular matrix (ECM) deposition. Crucially, the resulting fibrotic microenvironment reciprocally exacerbates inflammation and apoptosis through mechanical stress and hypoxia. Quantitative data from preclinical and clinical studies are integrated to underscore the magnitude of these effects. Current therapeutic strategies are evolving toward multi-target interventions against this pathological network. We contrast the paradigm of monotargeted agents (e.g., Finerenone, SGLT2 inhibitors), which offer high specificity, with that of multi-targeted natural product-based formulations (e.g., Huangkui capsule, Astragaloside IV), which provide synergistic multi-pathway modulation. Emerging approaches (metabolic reprogramming, epigenetic regulation, mechanobiological signaling) hold promise for reversing fibrosis. Future directions include leveraging single-cell technologies to decipher PTEC heterogeneity and developing kidney-targeted drug delivery systems. We conclude that disrupting the inflammation–apoptosis–fibrosis vicious cycle in PTECs is central to developing next-generation therapies for DN. Full article

Natural killer (NK) cells are the main cytotoxic lymphocytes of the natural immune system, which play an important role in tumor immune surveillance and anti-viral response. The surface receptor NKG2D can recognize NKG2D ligands on the surface of tumor or metabolism-stressed cells, thereby activating immune responses and mediating cytotoxicity and anti-tumor activity of NK cells. However, NKG2D-positive NK cells are regulated by metabolites, and play a negative role in metabolic diseases. Various metabolites, including lipids, reactive oxygen species (ROS), glucose and amino acids, regulate NKG2D expression and NK cell activity and decide the immune microenvironment of pathological tissue. Thus, targeted therapies based on NKG2D-positive NK cell have entirely different strategies in the treatment of tumor or metabolic diseases. This article focuses on the metabolic regulation of NKG2D-positive NK cells and their opposite roles in disease progression, including of cancer and metabolic disease. In the future, in-depth studies of the regulatory mechanisms of the NKG2D signaling pathway by metabolites and the optimization of the safety and efficacy of targeted therapeutic strategies will lead to new breakthroughs in the treatment of tumors and metabolic diseases, providing patients with more effective treatment options. Full article

Background: Diabetic wound healing has always been a clinical challenge with minimal response or efficacy to standard treatment. This study aims to assess the therapeutic potential of hypoxia-induced extracellular vesicles (hy-EVs) produced by human umbilical cord mesenchymal stem cells (HUCMSCs) to treat diabetic wounds. Methods: HUCMSCs were isolated from umbilical cord tissue, cultured under hypoxic conditions to induce the release of extracellular vesicles (EVs) and compared with normoxia-induced extracellular vesicles (n-EVs). We assessed the functions of hy-EVs on human skin fibroblasts (HSFs) and human umbilical vein endothelial cells (HUVECs) in vitro. Simultaneously, we analyzed the pro-angiogenic effects of hy-EVs, their effects on macrophage polarization, and their ability to scavenge endogenous reactive oxygen species (ROS). In addition, a diabetic wound model was established to assess the curative effect of hy-EVs in diabetic wound healing. Results: We found by in vitro study that hy-EVs markedly improved the functional activities of HSFs, thus significantly promoting wound repair. Remarkably, it was determined that hy-EVs greatly enhanced the proliferation and migration ability as well as the angiogenic ability of HUVECs, while promoting the expression of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial-generation-associated factor A (VEGFA), and platelet endothelial adhesion molecule (CD31), which suggested that hy-EVs can effectively activate the HIF-1α pathway to promote angiogenesis. Above all, we found that hy-EVs promoted the expression of CD206 while decreasing the expression of CD86, suggesting that hy-EVs could induce macrophages to shift from M1-type (pro-inflammatory) to M2-type (anti-inflammatory), thereby modulating the inflammatory response. Additionally, hy-EVs inhibited ROS production in both HSFs and HUVECs to reduce oxidative stress. In vivo results showed that hy-EVs enhanced collagen deposition and angiogenesis, modulated macrophage polarization, and inhibited immune response at the wound spot, which significantly enhanced diabetic wound healing. Conclusions: Our study shows that hy-EVs significantly promote angiogenesis through activation of the HIF-1α pathway, modulate macrophage polarization and attenuate cellular oxidative stress, possibly through delivery of specific miRNAs and proteins. Our discoveries offer a key theoretical basis and potential application to develop novel therapeutic strategies against diabetes-related tissue injury. Full article

One way to counteract the effects of environmental stresses, including drought, is to use products with growth-promoting properties for plants. Such agents include quercetin, which is known for its antioxidant and photosynthesis-enhancing properties. In the conducted experiment, the influence of the quercetin–copper complex (Q-Cu (II)) treatment, characterized by strong high solubility in water and strong antioxidant properties, was investigated. The pot experiment demonstrated the effect of spraying with Q-Cu (II) solutions (0.01, 0.05 and 0.1%) on wheat plants growing under drought stress conditions. Two treatments of Q-Cu (II) solutions were applied, and chlorophyll content and chlorophyll fluorescence (the maximum quantum yield of photosystem II (PSII) photochemistry (F_v/F_m), the efficiency of the water-splitting complex on the donor side of PSII (F_v/F_o), and the photosynthetic efficiency index (PI)), as well as gas exchange (photosynthetic network intensity (P_N), transpiration rate (E), stomatal conductance (g_s) and intercellular CO₂ concentration (C_i)), were measured 1 and 7 days after each treatment. In addition, antioxidant enzyme activity (catalase (CAT), peroxidase (SOD) and guaiacol peroxidase (GPOX)) and reactive oxygen species (ROS) levels were determined. Drought stress caused a decrease in chlorophyll content, and values of parameters F_v/F_m, F_v/F_o, PI and P_N, E, g_s, C_i, as well as an increase in ROS levels and antioxidant enzyme activity. Exogenous Q-Cu (II) improved photosynthetic indices and modulated redox status in a dose-dependent manner: 0.01–0.05% reduced ROS, whereas 0.1% increased ROS while concomitantly enhancing antioxidant enzyme activities and photosynthetic performance, consistent with ROS-mediated priming. The conducted research indicates the possibility of using Q-Cu (II) as a product to enhance the efficiency of the photosynthetic process under drought stress. Full article