Search Results (1,823)

Cancer metastasis, characterized by the dissemination of malignant cells from the primary tumor to distant organs, remains the leading cause of cancer-related mortality in solid tumors. In colorectal cancer (CRC), increasing attention has been directed toward therapeutic strategies aimed at suppressing cancer cell migration and invasion rather than solely reducing tumor mass, giving rise to the concept of migrastatic therapies. In the present study, green-synthesized silver nanoparticles (AgNPs), previously obtained using aqueous extracts of Filipendula ulmaria (L.) Maxim. and Salvia verticillata L., were evaluated for their antimigratory and anti-inflammatory potential in human colorectal carcinoma HCT-116 cells. Treatment with AgNPs induced considerable perturbations in cellular redox homeostasis, as evidenced by increased intracellular reactive oxygen species (ROS), lipid peroxidation (LPO), glutathione (GSH), and nitric oxide (NO) levels. These redox alterations were accompanied by a significant inhibition of cancer cell migration, together with reduced expression of matrix metalloproteinases MMP-2 and MMP-9, key mediators of extracellular matrix remodeling associated with tumor progression. AgNP exposure was associated with activation of the cytoprotective transcription factor Nrf-2 and suppression of the pro-inflammatory NF-κB/COX-2 signaling axis, indicating coordinated modulation of redox-sensitive pathways linked to tumor cell motility and inflammatory responses. Collectively, these findings demonstrate that green-synthesized AgNPs derived from F. ulmaria and S. verticillata exert multi-level regulatory effects on redox balance, inflammatory signaling, and migration-associated molecular markers in colorectal cancer cells. This study supports their potential as promising migrastatic nanocarriers for further investigation in colorectal cancer research. Full article

The successful use of Assisted Reproductive Technologies (ARTs) such as artificial insemination (AI) in small ruminants and other mammals depends on many factors, the most important of which is the quality of the semen used. The liquid storage and cryopreservation of spermatozoa at lower temperatures are associated with artificial insemination and rapid genetic improvement programs in the sheep production industry. Several studies have reported increased lipid peroxidation (LPO) and highly reactive oxygen species (ROS) production during liquid storage or cryopreservation of ram semen, leading to oxidative stress (OS), decreased antioxidant defense, and changes in sperm quality parameters like biokinetic and biochemical characteristics, viability, functional membrane and DNA integrity, along with mitochondrial activity. Therefore, supplementing ram semen extenders with exogenous antioxidants before preservation could mitigate this harmful effect. Various in vitro studies have reported improvements in ram sperm quality parameters like motility indexes, vitality, functional membrane/DNA integrity, antioxidant enzyme activity, total antioxidant content, mitochondrial activity, in vivo/in vitro fertility with significant decline in sperm abnormality, free radical production, LPO, ROS, apoptosis rate, and cytochrome C release from the mitochondrial matrix after the addition of various natural and synthetic antioxidant (vitamins, glutathione, taurine, pyruvate, melatonin, cysteine, selenium, zinc, plant extracts, sugars, amino acids, polyphenols) substances during preservation. Therefore, this review summarizes recent findings on oxidative stress-induced damage to sperm quality parameters in various ram breeds during chilling storage and cryopreservation. Moreover, supplementing basic semen extenders with different non-enzymatic antioxidant substances as a method to maintain sperm quality—along with their efficacy in reducing or preventing sperm damage during preservation—was discussed in detail. Full article

Aflatoxin B1 (AFB1) is a highly toxic mycotoxin which can be carried over into animal products and cause deterioration of livestock productivity when fed to livestock and wildlife. This review proposes a biomarker-guided framework for improving the early assessment of AFB1 exposure and toxicological responses in animal models. Oral exposure leads to the absorption of AFB1, which is bioactivated in the liver to the reactive AFB1-exo-8,9-epoxide that causes DNA and protein adduct formation, inflammation, mitochondrial apoptosis, and other effects. Cytochrome P450 activation and glutathione-dependent detoxification are in balance in determining susceptibility species, and this balance is different for poultry, pigs, ruminants, and rodents. In addition to traditional liver enzymes and histopathology, we highlight mechanistically informative biomarkers such as metabolites of aflatoxin, DNA and albumin adduct, lipid peroxidation products, antioxidant indices, cytokines, apoptotic markers, as well as signals involved in the Nrf2/NFκB pathway. AFB1 also damages the integrity of the intestinal barrier, the maintenance of the intestinal gut microbiota, reproductive function, growth performance, and development, thus creating a gut–liver-systemic toxic cascade. Finally, an assessment of stage-targeted interventions such as aluminosilicate binders, adsorbents derived from yeast, probiotics and nano-enabled interventions is conducted as viable tools for the reduction in exposure and injury. This review offers targeted mitigation strategies for early diagnosis of aflatoxicosis in animal production systems based on a biomarker approach. Full article

Osteosarcoma is the third most common malignancy among children and adolescents, necessitating the development of effective therapeutic strategies. This study investigated the anticancer activity of green-synthesized zinc oxide nanoparticles (ZnO-NPs) fabricated using bark extract of Ficus benghalensis against the human osteosarcoma Saos-2 cell line. The synthesized ZnO-NPs were characterized using UV–Vis spectroscopy, Fourier Transform Infrared (FTIR), and X-ray Diffraction (XRD), confirming nanoparticle formation and a hexagonal wurtzite crystalline structure. Cytotoxicity evaluation revealed significant dosage-dependent inhibition of Saos-2 cell proliferation, with an IC₅₀ value of 75 μg mL⁻¹. Morphological alterations and 4′,6-diamidino-2-phenylindole (DAPI) staining confirmed apoptotic cell death following ZnO-NPs treatment. Furthermore, ZnO-NPs induced oxidative stress by increasing nitric oxide (NO) and lipid peroxidation (LPO) levels while significantly reducing antioxidant markers, including catalase (CAT), superoxide dismutase (SOD), and glutathione (GSH). Flow cytometry analysis demonstrated G0/G1cell cycle arrest, accompanied by elevated caspase-8 activity. Gene expression analysis showed upregulation of Bax and p53 and downregulation of Bcl-2, indicating activation of the mitochondrial apoptotic pathway. Collectively, these findings demonstrate that phytochemical-mediated ZnO-NPs exert potent anticancer effects against Saos-2 cells through oxidative stress-induced apoptosis and cell-cycle arrest, highlighting their potential for osteosarcoma therapy. Full article

Copper sulfate (CuSO₄) is one of the most widely used chemotherapeutic agents in aquaculture and aquatic veterinary medicine because of its broad-spectrum antiparasitic, antifungal, and antimicrobial activities. However, repeated exposure may induce oxidative stress and impair hematological and immune functions, thereby compromising fish health. This study evaluated the effects of pre-exposure and post-exposure dietary ellagic acid (EA) supplementation on CuSO₄-induced hematological, immunological, and oxidative stress alterations in common carp (Cyprinus carpio). A total of 150 fish were randomly allocated to five experimental groups: Control, EA, CuSO₄, pre-exposure EA + CuSO₄, and post-exposure CuSO₄ + EA. Fish were fed a diet supplemented with 100 mg EA kg⁻¹ feed for 14 days either before or after repeated CuSO₄ exposure (1 mg L⁻¹, 30 min day⁻¹ for seven consecutive days). Hematological variables, innate immune responses, and oxidative stress biomarkers were subsequently evaluated. CuSO₄ exposure significantly decreased red blood cell (RBC) count, hemoglobin (Hb), hematocrit (Ht), phagocytic activity (PA), phagocytic index (PI), total plasma protein (TP), immunoglobulin M (IgM), bactericidal activity (BA), lysozyme (LYZ), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione S-transferase (GST), and reduced glutathione (GSH), while significantly increasing mean corpuscular hemoglobin concentration (MCHC), white blood cell (WBC) count, respiratory burst activity (NBT), myeloperoxidase (MPO), and malondialdehyde (MDA) (p < 0.05). Dietary EA supplementation markedly alleviated these alterations by restoring hematological homeostasis, improving innate immune responses, reducing lipid peroxidation, and reinforcing antioxidant defense systems in the liver, kidney, spleen, and gill. Both pre-exposure and post-exposure EA supplementation were associated with improvements in the evaluated biomarkers under the experimental conditions of the present study. However, because the two supplementation strategies were not evaluated against a time-matched CuSO₄ recovery control group, the present study does not permit a direct comparison of their relative efficacy. These findings demonstrate that dietary EA was associated with improvements in hematological, immunological, and oxidative stress biomarkers following experimental CuSO₄ exposure, potentially through antioxidant and immunomodulatory mechanisms. Therefore, dietary EA may serve as a promising functional feed additive to support antioxidant and immune status during experimental CuSO₄ exposure in common carp. Further studies including pathogen challenge models are required before its use as an adjunct to CuSO₄ treatments can be recommended. Full article

TCF3 fusion partner (TFPT) remains insufficiently characterized in hepatocellular carcinoma (HCC), particularly in relation to tumor growth and cellular features linked to lipid peroxidation defense. We integrated public transcriptomic and clinical datasets and established stable TFPT-knockdown and TFPT-overexpression models in MHCC97-H and Huh-7 cells. TFPT expression was higher in HCC tissues and selected HCC cell lines. In TCGA-LIHC, higher TFPT expression was associated with shorter overall survival after multivariable adjustment (HR, 1.37; 95% CI, 1.06–1.77), although this association was not reproduced in GSE14520. TFPT-high tumors were enriched for E2F Targets, MYC Targets, G2/M Checkpoint, and metabolic and cellular-stress-related programs. Internally constructed descriptive scores related to lipid peroxidation defense were higher in TFPT-high tumors but showed limited external reproducibility. In vitro, shTFPT cells showed lower CCK-8 signals, colony formation, monolayer closure, GSH levels, total glutathione peroxidase activity, and relative GPX4, SLC7A11, and FSP1 protein abundance, together with higher Fe²⁺ and MDA levels and higher BODIPY-C11 green-to-red fluorescence ratios; oeTFPT cells showed opposite patterns. These findings support an association between TFPT abundance and growth-related phenotypes and cellular features linked to lipid peroxidation defense in HCC, without establishing direct molecular regulation, ferroptotic cell death, causality, or independently validated prognostic utility. Full article

Previous studies have indicated that polyethylene terephthalate (PET) micro/nanoplastics (MNPs) may coexist with antibiotics in environmental and biological matrices; however, their combined behavior in blood remains insufficiently characterized. This study examined PET MNPs prepared from water bottles at 0.5, 2.5, and 7.5 mg/mL together with tetracycline (2–50 µg/mL) in defibrinated horse blood. After 24 h exposure and particle removal, UV–visible absorbance, intrinsic fluorescence, redox indicators, and subsequent Escherichia coli responses were evaluated. The blood biochemical results showed condition-dependent changes in hemoglobin-associated absorbance, tryptophan-dominated fluorescence, reactive oxygen species, reduced glutathione, superoxide dismutase, and lipid peroxidation. When treated blood supernatants were applied to Escherichia coli, tetracycline alone reduced bacterial OD600, whereas selected PET MNP–tetracycline co-exposures partially restored bacterial proliferation and modified oxidative-stress responses. ATR–FTIR analysis of Escherichia coli pellets showed dose-dependent modulation of phosphate-, lipid-, and protein-associated bands, indicating changes in bacterial biochemical fingerprints under specific exposure combinations. Overall, the findings suggest that PET MNPs can modify tetracycline-associated spectral, redox, and bacterial response patterns in a blood matrix. Future studies incorporating adsorption assays, free tetracycline quantification, protein-corona profiling, time-course exposure designs, and antibiotic susceptibility testing would further clarify the mechanistic basis and biological relevance of these matrix-dependent interaction effects. Full article

Background/Objectives: Polyendocrine metabolic ovarian syndrome (PMOS) is a complex endocrine–metabolic disorder of multifactorial etiology, driven by interactions among hyperandrogenism, metabolic dysfunction, oxidative stress, and chronic low-grade inflammation that interact to promote reproductive dysfunction and increase risk of cardiometabolic complications. Although the combination of letrozole and high-fat diet (LET + HFD) represents a widely used experimental approach for inducing a PMOS-like phenotype in rats, its multisystem pathophysiological features remain incompletely characterized. The present study aimed to characterize reproductive, cardiometabolic, hormonal, inflammatory, oxidative, and morphometric alterations associated with a LET + HFD-induced PMOS-like phenotype in rats. Methods: PMOS-like model was induced in rats over a 21-day period of orally administered letrozole combined with a high-fat diet. Results: Body weight gain was higher, while uterine weight was lower in the PMOS group compared with controls. Metabolic parameters suggested insulin resistance, while hormonal profiling revealed increased total testosterone and LH levels, accompanied by reduced FSH, estradiol, and progesterone levels. Elevated triglycerides and reduced HDL levels were also observed in the PMOS group. Morphometric analysis revealed numerous atretic and large thin-walled cystic follicles in the ovaries, accompanied by thinning of the uterine luminal and glandular epithelium, stromal layer, and hypoplasia of endometrial glands. Both the longitudinal diameter and cross-sectional area of cardiomyocytes were increased in the PMOS group, together with nuclear hypertrophy and enhanced myocardial collagen deposition. In addition, altered oxidative stress markers, including increased lipid peroxidation and reduced glutathione levels, were observed, whereas IL-6, IL-1β, and IL-23 were not significantly altered. Conclusions: The LET + HFD model reproduces key reproductive and cardiometabolic features of PMOS, extending beyond reproductive dysfunction to involve oxidative and structural alterations in multiple organs. These findings support its use for investigating PMOS pathophysiology and evaluating potential preventive and therapeutic strategies. Full article

Sarcopenia is an age-related pathological syndrome characterized by progressive and generalized loss of skeletal muscle mass and function, with muscle atrophy representing its cardinal pathological hallmark. Ferroptosis, an iron-dependent regulated cell death, has been implicated in the pathogenesis of muscle atrophy; however, the precise role of iron dysregulation in sarcopenia remains incompletely understood. In the present study, we identified ferroptosis in D-galactose (D-gal)-induced senescent myoblasts, as evidenced by elevated intracellular iron levels and lipid peroxidation, increased malondialdehyde (MDA) content, and upregulated expression of prostaglandin endoperoxide synthase 2 (PTGS2), 4-hydroxynonenal (4-HNE), and long-chain acyl-CoA synthetase 4 (ACSL4), accompanied by diminished glutathione peroxidase 4 (GPX4), SLC7A11 (xCT), and glutathione (GSH) levels, as well as pronounced mitochondrial damage. Notably, treatment with the iron chelator deferoxamine (DFO) significantly attenuated senescence-associated ferroptosis. Moreover, D-gal-induced senescence in myoblasts was accompanied by reduced ferritin expression and elevated nuclear receptor coactivator 4 (NCOA4) levels, both of which were reversed by autophagy inhibition with 3-methyladenine (3-MA) or NCOA4 knockdown, suggesting that NCOA4-mediated ferritinophagy is involved in senescence-induced iron overload and ferroptosis. Furthermore, senescent myoblasts exhibited increased reactive oxygen species (ROS) generation and mitochondrial impairment, which were attributed to cytosolic iron overload-mediated upregulation of mitoferrin 2 (Mfrn2), thereby promoting mitochondria iron import. Finally, pharmacological inhibition of iron overload or ferroptosis by DFO or ferrostatin-1 (Ferr-1) effectively ameliorated skeletal muscle atrophy and functional decline in aged sarcopenia mice. Collectively, these findings elucidate the mechanistic basis of sarcopenia and highlight potential therapeutic avenues targeting iron dysregulation and ferroptosis. Full article

Ulcerative colitis is characterized by inflammation, oxidative stress, and excessive free radical production. This study investigated the antioxidant, anti-inflammatory, and protective effects of N-acetylcysteine (NAC), Tiron, and their fixed-ratio combination in acetic acid-induced colitis. An integrated approach was used, combining ligand–ligand docking, acellular antioxidant and protein-denaturation assays, and an in vivo model in male Wistar rats. Colitis was induced by intrarectal administration of 3% acetic acid after 14 days of intraperitoneal pretreatment with NAC, Tiron, or NAC–Tiron. Docking analysis suggested physicochemical compatibility through non-covalent interactions. In vitro, NAC, Tiron, and their combination showed antioxidant and anti-denaturation activities. NAC–Tiron displayed greater activity than the individual compounds in selected endpoints, particularly 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging, but did not consistently outperform them across the other assays. In vivo, NAC, Tiron, and NAC–Tiron attenuated macroscopic and histological colonic damage, reduced inflammatory cell infiltration and edema, decreased lipid peroxidation and protein carbonylation, and helped preserve superoxide dismutase (SOD) activity, reduced glutathione (GSH), and total thiols. The treatments also attenuated increases in C-reactive protein (CRP) and free iron without evident worsening of the measured systemic biochemical parameters. Overall, these findings provide an exploratory proof of concept for fixed-ratio NAC–Tiron co-administration but do not establish pharmacological synergy or superiority over standard therapies. Full article

Lung cancer remains a leading cause of cancer-related mortality worldwide, underscoring the need for safer and more effective therapeutic strategies. In this study, zinc oxide nanoparticles (ZnO NPs) were synthesized via a green, biogenic approach using Lantana camara L. flower aqueous extract and evaluated for their anticancer potential against human non-small cell lung cancer (NSCLC) NCI-H460 cells. The biosynthesized ZnO NPs were characterized using UV-visible spectroscopy, Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), Transmission electron microscopy (TEM), energy-dispersive X-ray analysis (EDX), X-ray diffraction (XRD) and particle size analysis, confirming the formation of nanocrystalline ZnO. LC-MS profiling of the Lantana camara flower extract revealed the presence of several bioactive phytochemicals, including phenolic compounds, terpenoids, fatty acids, and alkaloids, which may contribute to the reduction and stabilization of ZnO NPs during green synthesis. Cytotoxicity assessment of ZnO NPs using MTT and trypan blue exclusion assays revealed a dose-dependent reduction in cell viability, with an IC₅₀ value of 50 µg/mL. Mechanistic investigations demonstrated that ZnO NP exposure induced significant oxidative stress, evidenced by increased nitric oxide, lipid peroxidation, and reactive oxygen species levels, along with depletion of intracellular glutathione. Apoptotic cell death was further confirmed by nuclear DNA fragmentation, mitochondrial membrane depolarization, and G0/G1 phase cell cycle arrest. Quantitative real-time PCR analysis revealed upregulation of the pro-apoptotic genes Bax and p53, accompanied by downregulation of the anti-apoptotic gene Bcl-2, indicating activation of a mitochondrial-dependent intrinsic apoptotic pathway. Collectively, these findings suggest that Lantana camara L. flower-mediated ZnO nanoparticles induced apoptotic responses associated with oxidative stress in NSCLC cells, highlighting their ability as an eco-friendly nanoplatform for further anticancer investigations. Full article

Arsenic (As) is a highly toxic metalloid that can be absorbed by plants, inducing stress that disrupts vital physiological processes. In response, plants activate defense mechanisms that allow them to cope with As-induced stress. This review provides a comprehensive overview of the metabolic pathways involved in plant responses to As stress, focusing on the mechanisms of As uptake and transport, metabolic and antioxidant responses, molecular regulation, and mitigation strategies that contribute to plant adaptation and tolerance. As exposure disrupts primary metabolism by impairing photosynthesis, the Calvin cycle, and carbon and energy metabolism, while also altering aquaporin-mediated transport and phosphate homeostasis. In addition, As induces oxidative stress, leading to increased lipid peroxidation and enhanced activities of antioxidant enzymes, including superoxide dismutase (SOD), ascorbate peroxidase (APX), and glutathione reductase (GR). It also affects secondary metabolism by modifying the biosynthesis and accumulation of specialized metabolites involved in stress tolerance. Overall, the evidence reviewed indicates that As can induce changes in both primary and secondary metabolic pathways. Although primary metabolic alterations are relatively well documented, information regarding changes in secondary metabolites, including phenolics and flavonoids, remains limited. Therefore, future research should integrate genomics, transcriptomics, proteomics, and metabolomics to elucidate the molecular basis of As tolerance and support modern crop breeding programs aimed at developing arsenic-tolerant cultivars. Moreover, this knowledge is fundamental for mitigating the impact of As on major food crops such as rice, wheat, maize, and vegetables, where arsenic contamination can reduce productivity, compromise crop quality, and increase the risk of As entry into the food chain. Furthermore, the mechanistic insights gained from these crops may serve as a basis for developing mitigation strategies applicable to other agriculturally important species. Full article

Red-flowered strawberry possesses both ornamental and edible value, but its short single-flower lifespan severely limits its ornamental potential. In this study, petals of the red-flowered strawberry cultivar ‘140’ were collected at five developmental stages (large bud, half-bloom, full-bloom, initial withering, and withered) to systematically analyze the senescence process from morphological characteristics, physiological, and ethylene-related gene expression perspectives. The results showed that the epidermal cell breakage rate increased continuously during petal senescence, with lower epidermal cells consistently exhibiting higher breakage rates than the upper epidermal cells. Moisture content decreased progressively, while relative electrolyte leakage, malondialdehyde, hydrogen peroxide, and superoxide anion contents increased continuously. Superoxide dismutase, peroxidase, and catalase activities, as well as glutathione content, exhibited unimodal responses, peaking at different stages. Both ethylene and abscisic acid contents increased and then decreased, with ethylene showing greater amplitude and faster rate of change. The ethylene biosynthesis gene FaACO1 and signaling genes FaETR1, FaETR2, FaEIN2, FaEIN7, FaERF13, and FaERF118 were significantly upregulated at full-bloom or initial withering stages, with FaERF118 showing the highest and continuously increasing expression. These findings indicate that water loss, membrane lipid peroxidation, and reactive oxygen species accumulation synergistically drive petal senescence, with the ethylene signaling pathway playing a key regulatory role. Full article

Resistance to apoptosis, metabolic plasticity, and redox adaptation are major contributors to cancer progression and treatment failure. Ferroptosis and cuproptosis have therefore emerged as metal-dependent forms of regulated cell-death programs with potential relevance for tumours that survive conventional therapy. Ferroptosis is driven by iron-dependent phospholipid peroxidation when glutathione peroxidase 4 (GPX4)-dependent and parallel antioxidant systems fail, whereas cuproptosis depends on mitochondrial copper engagement of lipoylated tricarboxylic-acid-cycle proteins, lipoylated-protein aggregation, iron–sulfur protein destabilization, and proteotoxic stress. This review integrates the molecular basis, genetic architecture, long non-coding RNA (lncRNA)-mediated regulation, mechanistic crosstalk, and therapeutic implications of ferroptosis and cuproptosis in cancer. It emphasizes a critical evidence hierarchy: expression association, computational signature construction, metal accumulation, reactive oxygen species (ROS) generation, or reduced viability should not be interpreted as pathway dependency without pathway-defining biochemical endpoints and rescue experiments. The most credible translational opportunities will depend on functional stratification, tumour-selective delivery, and pharmacodynamic confirmation that distinguishes pathway-defined ferroptosis or cuproptosis from nonspecific metal-induced and oxidative cytotoxicity. Full article

Lotus corniculatus L. can spontaneously colonize metal-contaminated areas like the old Zn-Pb calamine tailings. This study compared two L. corniculatus ecotypes collected from metal-contaminated (HM) and non-contaminated (NM) sites to identify physiological adaptations to long-term metal exposure. The results indicated that HM ecotype accumulates Zn, Pb, and Cd in shoots without showing any toxic symptoms at the ultrastructural level. The HM ecotype exhibited a different composition of photosynthetic pigments, lower lipid peroxidation, and oxidative stress levels and increased the efficiency of the antioxidant defense system and antioxidant activity compared to the NM ecotype. Leaf antioxidant enzymes such as SOD, CAT, POX, and GPX were more active in the shoots of the HM ecotype, while GR and APX showed lower activity compared to the NM ecotype. In addition, the HM ecotype was characterized by higher glutathione and total phenolics content (mainly catechin, rutin, ferulic, and salicylic acids); however, these non-enzymatic metabolites primarily function in metal chelation alongside their role in oxidative stress mitigation. The results showed that calamine Lotus plants exhibit effective adaptation to long-term metal exposure by keeping metals away from metabolically active compartments and strengthening antioxidant defenses. These coordinated mechanisms reduce oxidative stress and contribute to the enhanced metal tolerance of calamine plants. Full article