RETRACTED: Ali et al. A Novel Herbal Hydrogel Formulation of Moringa oleifera for Wound Healing. Plants 2021, 10, 25.

The journal retracts the article, "A Novel Herbal Hydrogel Formulation of Moringa oleifera for Wound Healing" [...].

Deoxynivalenol induces cell senescence in RAW264.7 macrophages via HIF-1α-mediated activation of the p53/p21 pathway.

Deoxynivalenol (DON), a potent mycotoxin, exhibits strong immunotoxicity and poses a significant threat to human and animal health. Cell senescence has been implicated in the immunomodulatory effects of DON; however, the potential of DON to induce cell senescence remains inadequately explored. Emerging evidence suggests that hypoxia-inducible factor-1α (HIF-1α) serves as a crucial target of mycotoxins and is closely involved in cell senescence. To investigate this potential, we employed the RAW264.7 macrophage model and treated the cells with varying concentrations of DON (2-8 µM) for 24 h. Transcriptome analysis revealed that 2365 genes were significantly upregulation while 2405 genes were significantly decreased after exposure to DON. KEGG pathway enrichment analysis demonstrated substantial enrichment in pathways associated with cellular senescence and hypoxia. Remarkably, we observed a rapid and sustained increase in HIF-1α expression following DON treatment. DON induced cell senescence through the activation of the p53/p21WAF1/CIP1 (p21) and p16INK4A (p16) pathways, while also upregulating the expression of nuclear factor-κB, leading to the secretion of senescence-associated secretory phenotype (SASP) factors, including IL-6, IL-8, and CCL2. Crucially, HIF-1α positively regulated the expression of p53, p21, and p16, as well as the secretion of SASP factors. Additionally, DON induced cell cycle arrest at the S phase, enhanced the activity of the senescence biomarker senescence-associated ß-galactosidase, and disrupted cell morphology, characterized by mitochondrial damage. Our study elucidates that DON induces cell senescence in RAW264.7 macrophages by modulating the HIF-1α/p53/p21 pathway. These findings provide valuable insights for the accurate prevention of DON-induced immunotoxicity and associated diseases.

Injectable nano-in situ-thermosensitive-hydrogels based on halofuginone and silver for postoperative treatment against triple-negative breast cancer.

Postoperative distant metastasis and high recurrence rate causes a dilemma in treating triple-negative breast cancer (TNBC) owing to its unforeseeable invasion into various organs or tissues. The wealth of nutrition provided by vascular may facilitate the proliferation and angiogenesis of cancer cells, which further enhance the rates of postoperative metastasis and recurrence. Chemotherapy, as a systemic postoperative adjuvant therapy, is generally applied to diminish recurrence and metastasis of TNBC. Herein, an halofuginone-silver nano thermosensitive hydrogel (HTPM&AgNPs-gel) was prepared via a physical swelling method. The in vitro anticancer efficacy of HTPM&AgNPs-gel was analyzed by investigating cell proliferation, migration, invasion, and angiogenesis capacity. Furthermore, the in vivo anti-cancer activity of HTPM&AgNPs-gel was further appraised through the tumor suppression, anti-metastatic, anti-angiogenic, and anti-inflammatory ability. The optimized HTPM&AgNPs-gel, a thermosensitive hydrogel, showed excellent properties, including syringeability, swelling behavior, and a sustained release effect without hemolysis. In addition, HTPM&AgNPs-gel was confirmed to effectively inhibit the proliferation, migration, invasion, and angiogenesis of MDA-MB-231 cells. An evaluation of the in vivo anti-tumor efficacy demonstrated that HTPM&AgNPs-gel showed a stronger tumor inhibition rate (68.17%) than did HTPM-gel or AgNPs-gel used alone and exhibited outstanding biocompatibility. Notably, HTPM&AgNPs-gel also inhibited lung metastasis induced by residual tumor tissue after surgery and further blocked angiogenesis-related inflammatory responses. Taken together, the suppression of inflammation by interdicting the blood vessels adjoining the tumor and inhibiting angiogenesis is a potential strategy to attenuate the recurrence and metastasis of TNBC. HTPM&AgNPs-gel is a promising anticancer agent for TNBC as a local postoperative treatment.

The mechanism of arbuscular mycorrhizal fungi-alleviated manganese toxicity in plants: A review.

The development of the mining industry and the overuse of inorganic fertilizers have led to an excess of manganese (Mn) in the soil, thereby, contaminating the soil environment and people's health. On heavy metal-contaminated soils, the combined arbuscular mycorrhizal fungi (AMF)-phytoremediation technique becomes a hotspot because of its environmentally friendly, in situ remediation. AMF inoculation often leads to a decrease in host Mn acquisition, which provides a basis for its application in phytoremediation of contaminated soils. Moreover, the utilization value of native AMF is greater than that of exotic AMF, because native AMF can adapt better to Mn-contaminated soils. In addition to the fact that AMF enhance plant Mn tolerance responses such as regionalization, organic matter chelation, limiting uptake and efflux, and so on, AMF also develop plant-independent fungal pathways such as direct biosorption of Mn by mycorrhizal hyphae, fungal Mn transporter genes, and sequestration of Mn by mycorrhizal hyphae, glomalin, and arbuscule-containing root cortical cells, which together mitigate excessive Mn toxicity to plants. Clarifying AMF-plant interactions under Mn stress will provide support for utilizing AMF as a phytoremediation in Mn-contaminated soils. The review reveals in detail how AMF develop its own mechanisms for responding to excess Mn and how AMF enhance plant Mn tolerance, accompanied by perspectives for future research.

Value addition of mango kernel for development and characterization of starch with starch nanoparticles for packaging applications.

The present research was conducted to explore the potential of mango kernel starch from the Chaunsa variety to develop starch and starch nanoparticles (SNPs) based films. The investigation included starch isolation from mango kernel followed by the preparation of SNPs by acid hydrolysis and a thorough examination of various physicochemical properties for film formation. The properties of SNPs were found to be distinctly different from those of native starch. SNPs exhibited an aggregated form with an irregular surface, whereas native starch had an oval and elongated shape with a smooth surface. X-ray diffraction (XRD) analysis confirmed that the starch type in SNPs was of the A-type. Additionally, the pasting properties of SNPs were minimal due to the acid hydrolysis process. SNP-based composite film was developed with (5 %) SNP concentration added. This successful incorporation of SNPs enhanced biodegradability, with complete degradation occurring within three weeks. Moreover, the composite films displayed increased burst strength, measuring 1303.51 ±â€¯73.7 g, and lower water vapor transmission rates (WVTR) at (7.40 ±â€¯0.50) × 10-3 g per square meter per second and reduced water solubility at 35.32 ±â€¯3.0 %. This development represents a significant advancement in the field of eco-friendly packaging materials.

Biodiversity conservation in the context of climate change: Facing challenges and management strategies.

Biodiversity conservation amidst the uncertainty of climate change presents unique challenges that necessitate precise management strategies. The study reported here was aimed at refining understanding of these challenges and to propose specific, actionable management strategies. Employing a quantitative literature analysis, we meticulously examined 1268 research articles from the Web of Science database between 2005 and 2023. Through Cite Spaces and VOS viewer software, we conducted a bibliometric analysis and thematic synthesis to pinpoint emerging trends, key themes, and the geographical distribution of research efforts. Our methodology involved identifying patterns within the data, such as frequency of keywords, co-authorship networks, and citation analysis, to discern the primary focus areas within the field. This approach allowed us to distinguish between research concentration areas, specifically highlighting a predominant interest in Environmental Sciences Ecology (67.59 %) and Biodiversity Conservation (22.63 %). The identification of adaptive management practices and ecosystem services maintenance are central themes in the research from 2005 to 2023. Moreover, challenges such as understanding phenological shifts, invasive species dynamics, and anthropogenic pressures critically impact biodiversity conservation efforts. Our findings underscore the urgent need for precise, data-driven decision-making processes in the face of these challenges. Addressing the gaps identified, our study proposes targeted solutions, including the establishment of germplasm banks for at-risk species, the development of advanced genomic and microclimate models, and scenario analysis to predict and mitigate future conservation challenges. These strategies are aimed at enhancing the resilience of biodiversity against the backdrop of climate change through integrated, evidence-based approaches. By leveraging the compiled and analyzed data, this study offers a foundational framework for future research and practical action in biodiversity conservation strategies, demonstrating a path forward through detailed analysis and specified solutions.

Hepatoprotective effects of fruits pulp, seed, and peel against chemical-induced toxicity: Insights from in vivo studies.

The liver is a vital organ in human physiology positioned in the upper right quadrant of the peritoneal cavity, which plats a critical role in metabolic processes, detoxification of various substances and overall homeostasis. Along with these critical functions, hepatic diseases impose as significant global health threat. Liver illness is the cause of two million fatalities every year, or 4% of all deaths. Traditionally, healthcare providers have prescribed antibacterial and antiviral medications to address liver illness. Nephrotoxicity is a frequently observed negative reaction to drugs, with the majority of such events happening in individuals who have advanced cirrhosis. Thus, recognizing this gap, there is a dire need of exploration of pharmaceutical alterative for hepatic diseases, with special focus on their efficacy and reduced toxicity. Fruits have long been known to therapeutic impact on human health, thus exploration of fruits components namely pulp, seeds and peels containing phytochemicals have emerged as a promising avenue for hepatoprotective interventions. Thus, review comprehends the information about worldwide burden of chemical induced toxicity and injuries as well as highlight the on-going challenges in hepatic disease management. It also shed light on the valuable contributions fruit parts and their phytocompounds obtained from different components of fruits. Fruit pulp, especially when rich in flavonoids, has demonstrated significant potential in animal model studies. It has been observed to enhance the activity of antioxidant enzymes and reduce the expression of pro-inflammatory markers. The methanolic and ethanolic extracts have demonstrated the most favorable outcomes. Further, this review also discusses about the safety assessments of fruits extracts for their utilization as hepatoprotective agents.

The role of cellular senescence in neurodegenerative diseases.

Increasing evidence has revealed that cellular senescence drives NDs, including Alzheimer's disease (AD) and Parkinson's disease. Different senescent cell populations secrete senescence-associated secretory phenotypes (SASP), including matrix metalloproteinase-3, interleukin (IL)-1α, IL-6, and IL-8, which can harm adjacent microglia. Moreover, these cells possess high expression levels of senescence hallmarks (p16 and p21) and elevated senescence-associated ß-galactosidase activity in in vitro and in vivo ND models. These senescence phenotypes contribute to the deposition of ß-amyloid and tau-protein tangles. Selective clearance of senescent cells and SASP regulation by inhibiting p38/mitogen-activated protein kinase and nuclear factor kappa B signaling attenuate ß-amyloid load and prevent tau-protein tangle deposition, thereby improving cognitive performance in AD mouse models. In addition, telomere shortening, a cellular senescence biomarker, is associated with increased ND risks. Telomere dysfunction causes cellular senescence, stimulating IL-6, tumor necrosis factor-α, and IL-1ß secretions. The forced expression of telomerase activators prevents cellular senescence, yielding considerable neuroprotective effects. This review elucidates the mechanism of cellular senescence in ND pathogenesis, suggesting strategies to eliminate or restore senescent cells to a normal phenotype for treating such diseases.

Neutrophils in Cancer immunotherapy: friends or foes?

Neutrophils play a Janus-faced role in the complex landscape of cancer pathogenesis and immunotherapy. As immune defense cells, neutrophils release toxic substances, including reactive oxygen species and matrix metalloproteinase 9, within the tumor microenvironment. They also modulate the expression of tumor necrosis factor-related apoptosis-inducing ligand and Fas ligand, augmenting their capacity to induce tumor cell apoptosis. Their involvement in antitumor immune regulation synergistically activates a network of immune cells, bolstering anticancer effects. Paradoxically, neutrophils can succumb to the influence of tumors, triggering signaling cascades such as JAK/STAT, which deactivate the immune system network, thereby promoting immune evasion by malignant cells. Additionally, neutrophil granular constituents, such as neutrophil elastase and vascular endothelial growth factor, intricately fuel tumor cell proliferation, metastasis, and angiogenesis. Understanding the mechanisms that guide neutrophils to collaborate with other immune cells for comprehensive tumor eradication is crucial to enhancing the efficacy of cancer therapeutics. In this review, we illuminate the underlying mechanisms governing neutrophil-mediated support or inhibition of tumor progression, with a particular focus on elucidating the internal and external factors that influence neutrophil polarization. We provide an overview of recent advances in clinical research regarding the involvement of neutrophils in cancer therapy. Moreover, the future prospects and limitations of neutrophil research are discussed, aiming to provide fresh insights for the development of innovative cancer treatment strategies targeting neutrophils.

Nonpharmacological intervention therapies for dementia: potential break-even intervention price and savings for selected risk factors in the European healthcare system.

BACKGROUND: New effective treatments for dementia are lacking, and early prevention focusing on risk factors of dementia is important. Non-pharmacological intervention therapies aimed at these factors may provide a valuable tool for reducing the incidence of dementia. This study focused on the development of a mathematical model to predict the number of individuals with neurodegenerative diseases, specifically Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis. Scenarios for non-pharmacological intervention therapies based on risk factor reduction were also assessed. The estimated total costs and potential cost savings from societal were included. METHODS: Based on demographic and financial data from the EU, a mathematical model was developed to predict the prevalence and resulting care costs of neurodegenerative diseases in the population. Each disease (Alzheimer's disease, Parkinson's disease, vascular dementia, and amyotrophic lateral sclerosis) used parameters that included prevalence, incidence, and death risk ratio, and the simulation is related to the age of the cohort and the disease stage. RESULTS: A replicable simulation for predicting the prevalence and resulting cost of care for neurodegenerative diseases in the population exhibited an increase in treatment costs from 267 billion EUR in 2021 to 528 billion EUR by 2050 in the EU alone. Scenarios related to the reduction of the prevalence of dementia by up to 20% per decade led to total discounted treatment cost savings of up to 558 billion EUR. CONCLUSION: The model indicates the magnitude of the financial burden placed on EU healthcare systems due to the growth in the population prevalence of neurodegenerative diseases in the coming decades. Lifestyle interventions based on reducing the most common risk factors could serve as a prevention strategy to reduce the incidence of dementia with substantial cost-savings potential. These findings could support the implementation of public health approaches throughout life to ultimately prevent premature mortality and promote a healthier and more active lifestyle in older individuals.

Leprosy: Comprehensive insights into pathology, immunology, and cutting-edge treatment strategies, integrating nanoparticles and ethnomedicinal plants.

Mycobacterium leprae is the causative agent responsible for the chronic disease known as leprosy. This condition is characterized by dermal involvement, often leading to peripheral nerve damage, sensory-motor loss, and related abnormalities. Both innate and acquired immunological responses play a role in the disease, and even in individuals with lepromatous leprosy, there can be a transient increase in T cell immunity during lepromatous reactions. Diagnosing of early-stage leprosy poses significant challenges. In this context, nanoparticles have emerged as a promising avenue for addressing various crucial issues related to leprosy. These include combatting drug resistance, mitigating adverse effects of conventional medications, and enhancing targeted drug delivery. This review serves as a comprehensive compilation, encompassing aspects of pathology, immunology, and adverse effects of multidrug delivery systems in the context of leprosy treatment. Furthermore, the review underscores the significance of ethnomedicinal plants, bioactive secondary metabolites, and nanotherapeutics in the management of leprosy. It emphasizes the potential to bridge the gap between existing literature and ongoing research efforts, with a profound scope for validating traditional claims, developing herbal medicines, and formulating nanoscale drug delivery systems that are safe, effective, and widely accepted.

AP-1 and SP1 trans-activate the expression of hepatic CYP1A1 and CYP2A6 in the bioactivation of AFB1 in chicken.

Dietary exposure to aflatoxin B1 (AFB1) is harmful to the health and performance of domestic animals. The hepatic cytochrome P450s (CYPs), CYP1A1 and CYP2A6, are the primary enzymes responsible for the bioactivation of AFB1 to the highly toxic exo-AFB1-8,9-epoxide (AFBO) in chicks. However, the transcriptional regulation mechanism of these CYP genes in the liver of chicks in AFB1 metabolism remains unknown. Dual-luciferase reporter assay, bioinformatics and site-directed mutation results indicated that specificity protein 1 (SP1) and activator protein-1 (AP-1) motifs were located in the core region -1,063/-948, -606/-541 of the CYP1A1 promoter as well as -636/-595, -503/-462, -147/-1 of the CYP2A6 promoter. Furthermore, overexpression and decoy oligodeoxynucleotide technologies demonstrated that SP1 and AP-1 were pivotal transcriptional activators regulating the promoter activity of CYP1A1 and CYP2A6. Moreover, bioactivation of AFB1 to AFBO could be increased by upregulation of CYP1A1 and CYP2A6 expression, which was trans-activated owing to the upregulalion of AP-1, rather than SP1, stimulated by AFB1-induced reactive oxygen species. Additionally, nano-selenium could reduce ROS, downregulate AP-1 expression and then decrease the expression of CYP1A1 and CYP2A6, thus alleviating the toxicity of AFB1. In conclusion, AP-1 and SP1 played important roles in the transactivation of CYP1A1 and CYP2A6 expression and further bioactivated AFB1 to AFBO in chicken liver, which could provide novel targets for the remediation of aflatoxicosis in chicks.

Comprehensive analysis of prohibited substances and methods in sports: Unveiling trends, pharmacokinetics, and WADA evolution.

This review systematically compiles sports-related drugs, substances, and methodologies based on the most frequently detected findings from prohibited lists published annually by the World Anti-Doping Agency (WADA) between 2003 and 2021. Aligned with structure of the 2023 prohibited list, it covers all proscribed items and details the pharmacokinetics and pharmacodynamics of five representatives from each section. Notably, it explores significant metabolites and metabolic pathways associated with these substances. Adverse analytical findings are summarized in tables for clarity, and the prevalence is visually represented through charts. The review includes a concise historical overview of doping and WADA's role, examining modifications in the prohibited list for an understanding of evolving anti-doping measures.

New insight into mycotoxins and bacterial toxins: Toxicity assessment, molecular mechanism and food safety (preface to the special issue of food and chemical toxicology on the outcomes of Myco & bacterial toxin).

The special issue "New Insight into Mycotoxins and Bacterial Toxins: Toxicity Assessment, Molecular Mechanism and Food Safety" in Food and Chemical Toxicology contains 19 articles on current hot topics in mycotoxins and bacterial toxins. Dietary exposure to mycotoxins and risk assessments are reported in this issue. Molecular mechanisms of multiple mycotoxins and emerging mechanisms of toxicity are especially concerned by researchers. Moreover, mycotoxin-detoxifying substances and antimicrobial agents are also fully investigated in the context. This special issue will help to further understand the mycotoxins and bacterial toxins, casting new light for the control of food safety.

Fentanyl and its derivatives: Pain-killers or man-killers?

Fentanyl is a synthetic µ-opioid receptor agonist approved to treat severe to moderate pain with faster onset of action and about 100 times more potent than morphine. Over last two decades, abuse of fentanyl and its derivatives has an increased trend, globally. Currently, the United States (US) faces the most serious situation related to fentanyl overdose, commonly referred to as the opioid epidemic. Nowadays, fentanyl is considered as the number one cause of death for adults aged 18-45 in the US. Synthesis and derivatization of fentanyl is inexpensive to manufacture and easily achievable. Indeed, more than 1400 fentanyl derivatives have been described in the scientific literature and patents. In addition, accessibility and efficacy of fentanyl and its derivatives can play a potential role in misuse of these compounds as a chemical weapon. In this review, the properties, general pharmacology, and overdose death cases associated with fentanyl and selected derivatives are presented. Moreover, current opioid epidemic in the US, Moscow theatre hostage crisis, and potential misuse of fentanyl and its derivatives as a chemical weapon are disclosed.

Cloning of CAT genes in Satsuma mandarin and their expression characteristics in response to environmental stress and arbuscular mycorrhizal fungi.

KEY MESSAGE: CitCAT1 and CitCAT2 were cloned and highly expressed in mature leaves. High temperatures up-regulated CitCAT1 expression, while low temperatures and Diversispora versiformis up-regulated CitCAT2 expression, maintaining a low oxidative damage. Catalase (CAT), a tetrameric heme-containing enzyme, removes hydrogen peroxide (H2O2) to maintain low oxidative damage in plants exposed to environmental stress. This study aimed to clone CAT genes from Citrus sinensis cv. "Oita 4" and analyze their expression patterns in response to environmental stress, exogenous abscisic acid (ABA), and arbuscular mycorrhizal fungal inoculation. Two CAT genes, CitCAT1 (NCBI accession: PP067858) and CitCAT2 (NCBI accession: PP061394) were cloned, and the open reading frames of their proteins were 1479 bp and 1539 bp, respectively, each encoding 492 and 512 amino acids predicted to be localized in the peroxisome, with CitCAT1 being a stable hydrophilic protein and CitCAT2 being an unstable hydrophilic protein. The similarity of their amino acid sequences reached 83.24%, and the two genes were distantly related. Both genes were expressed in stems, leaves, flowers, and fruits, accompanied by the highest expression in mature leaves. In addition, CitCAT1 expression was mainly up-regulated by high temperatures (37 °C), exogenous ABA, and PEG stress within a short period of time, whereas CitCAT2 expression was up-regulated by exogenous ABA and low-temperature (4 °C) stress. Low temperatures (0 °C) for 12 h just up-regulated CitCAT2 expression in Diversispora versiformis-inoculated plants, and D. versiformis inoculation up-regulated CitCAT2 expression, along with lower hydrogen peroxide and malondialdehyde levels in mycorrhizal plants at low temperatures. It is concluded that CitCAT2 has an important role in resistance to low temperatures as well as mycorrhizal enhancement of host resistance to low temperatures.

Prominent Perspective on Existing Biological Hallmarks of Alzheimer's Disease.

Biomarkers are the most significant diagnosis tools tending towards unique approaches and solutions for the prevention and cure of Alzheimer's Disease (AD). The current report provides a clear perception of the concept of various biomarkers and their prominent features through analysis to provide a possible solution for the inhibition of events in AD. Scientists around the world truly believe that crucial hallmarks can serve as critical tools in the early diagnosis, cure, and prevention, as well as the future of medicine. The awareness and understanding of such biomarkers would provide solutions to the puzzled mechanism of this neuronal disorder. Some of the argued biomarkers in the present article are still in an experimental phase as they need to undergo specific clinical trials before they can be considered for treatment.

Revisiting the ethnomedicinal, ethnopharmacological, phytoconstituents and phytoremediation of the plant Solanum viarum Dunal.

Solanum viarum, a perennial shrub, belongs to the family Solanaceae known for its therapeutic value worldwide. As a beneficial remedial plant, it is used for treating several disorders like dysentery, diabetes, inflammation, and respiratory disorders. Phytochemistry studies of this plant have shown the presence of steroidal glycoside alkaloids, including solasonine, solasodine, and solamargine. It also has flavonoids, saponins, minerals, and other substances. S. viarum extracts and compounds possess a variety of pharmacological effects, including antipyretic, antioxidant, antibacterial, insecticidal, analgesic, and anticancer activity. Most of the heavy metals accumulate in the aerial sections of the plant which is considered a potential phytoremediation, a highly effective method for the treatment of metal-polluted soils. We emphasize the forgoing outline of S. viarum, as well as its ethnomedicinal and ethnopharmacological applications, the chemistry of its secondary metabolites, and heavy metal toxicity. In addition to describing the antitumor activity of compounds and their mechanisms of action isolated from S. viarum, liabilities are also explained and illustrated, including any significant chemical or metabolic stability and toxicity risks. A comprehensive list of information was compiled from Science Direct, PubMed, Google Scholar, and Web of Science using different key phrases (traditional use, ethnomedicinal plants, western Himalaya, Himachal Pradesh, S viarum, and biological activity). According to the findings of this study, we hope that this review will inspire further studies along the drug discovery pathway of the chemicals extracted from the plant of S. viarum. Further, this review shows that ethnopharmacological information from ethnomedicinal plants can be a promising approach to drug discovery for cancer and diabetes.

Several lines of antioxidant defense against oxidative stress: antioxidant enzymes, nanomaterials with multiple enzyme-mimicking activities, and low-molecular-weight antioxidants.

Reactive oxygen species (ROS) and reactive nitrogen species (RNS) are well recognized for playing a dual role, since they can be either deleterious or beneficial to biological systems. An imbalance between ROS production and elimination is termed oxidative stress, a critical factor and common denominator of many chronic diseases such as cancer, cardiovascular diseases, metabolic diseases, neurological disorders (Alzheimer's and Parkinson's diseases), and other disorders. To counteract the harmful effects of ROS, organisms have evolved a complex, three-line antioxidant defense system. The first-line defense mechanism is the most efficient and involves antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx). This line of defense plays an irreplaceable role in the dismutation of superoxide radicals (O2•-) and hydrogen peroxide (H2O2). The removal of superoxide radicals by SOD prevents the formation of the much more damaging peroxynitrite ONOO- (O2•- + NO• → ONOO-) and maintains the physiologically relevant level of nitric oxide (NO•), an important molecule in neurotransmission, inflammation, and vasodilation. The second-line antioxidant defense pathway involves exogenous diet-derived small-molecule antioxidants. The third-line antioxidant defense is ensured by the repair or removal of oxidized proteins and other biomolecules by a variety of enzyme systems. This review briefly discusses the endogenous (mitochondria, NADPH, xanthine oxidase (XO), Fenton reaction) and exogenous (e.g., smoking, radiation, drugs, pollution) sources of ROS (superoxide radical, hydrogen peroxide, hydroxyl radical, peroxyl radical, hypochlorous acid, peroxynitrite). Attention has been given to the first-line antioxidant defense system provided by SOD, CAT, and GPx. The chemical and molecular mechanisms of antioxidant enzymes, enzyme-related diseases (cancer, cardiovascular, lung, metabolic, and neurological diseases), and the role of enzymes (e.g., GPx4) in cellular processes such as ferroptosis are discussed. Potential therapeutic applications of enzyme mimics and recent progress in metal-based (copper, iron, cobalt, molybdenum, cerium) and nonmetal (carbon)-based nanomaterials with enzyme-like activities (nanozymes) are also discussed. Moreover, attention has been given to the mechanisms of action of low-molecular-weight antioxidants (vitamin C (ascorbate), vitamin E (alpha-tocopherol), carotenoids (e.g., ß-carotene, lycopene, lutein), flavonoids (e.g., quercetin, anthocyanins, epicatechin), and glutathione (GSH)), the activation of transcription factors such as Nrf2, and the protection against chronic diseases. Given that there is a discrepancy between preclinical and clinical studies, approaches that may result in greater pharmacological and clinical success of low-molecular-weight antioxidant therapies are also subject to discussion.