Search Results (1,270)

Ultraviolet B (UVB) irradiation is a major environmental factor contributing to skin photoaging by inducing oxidative stress, apoptosis, inflammation, and extracellular matrix degradation in dermal fibroblasts. This study investigated the photoprotective effects of Thua Nao, a Thai fermented soybean, against UVB-induced human dermal fibroblast damage, and explores its underlying mechanisms. The dichloromethane fraction of Thua Nao (TN-DC) most effectively mitigated UVB-induced cell death. HPLC analysis identified daidzein and glycitein as the major constituent isoflavones in TN-DC that protect fibroblasts against UVB-induced cellular damage. Mechanistically, they reduced apoptosis by suppressing caspase-9/3 activation and preserving mitochondrial membrane potential. Additionally, they suppressed inflammatory mediators (IL-6, IL-8, iNOS, COX-2) and prevented collagen loss. These protective outcomes correlated with decreased intracellular reactive oxygen species and upregulated endogenous antioxidant enzymes (SOD-1, HO-1). Signaling pathway analysis revealed that TN-DC activated the pro-survival ERK1/2 and Akt pathways in UVB-exposed cells. Conversely, daidzein and glycitein selectively attenuated JNK MAPK activation, downregulating downstream pro-inflammatory cytokines and mediators. Collectively, these findings demonstrate that TN-DC protects human dermal fibroblasts against UVB-induced photoaging primarily by enhancing endogenous antioxidant defense, thereby preserving cellular homeostasis through coordinated regulation of oxidative stress-responsive signaling pathways. Full article

Spinal cord injury is strongly associated with male infertility, traditionally attributed to erectile and ejaculatory dysfunction. However, accumulating evidence demonstrates that infertility in this population extends beyond neurogenic impairment and involves profound biochemical and molecular alterations within the male reproductive system. The objective of this review is to synthesize current evidence on the role of oxidative stress, inflammation, and sperm DNA damage as central mechanisms driving impaired fertility in men with spinal cord injury. A comprehensive evaluation of clinical and experimental studies indicates that seminal plasma in affected individuals is characterized by elevated reactive oxygen species, reduced antioxidant capacity, and a pro-inflammatory cytokine profile, including increased levels of tumor necrosis factor alpha, interleukin 6, and interleukin 1 beta. These alterations are closely linked to leukocytospermia, mitochondrial dysfunction, and disruption of the blood–testis barrier, creating a toxic microenvironment that compromises sperm function. As a consequence, spermatozoa exhibit reduced motility, impaired membrane integrity, and significantly increased DNA fragmentation and chromatin abnormalities. Elevated sperm DNA damage has been consistently associated with poor fertilization outcomes, reduced embryo quality, and increased risk of pregnancy loss in assisted reproductive settings. Importantly, these molecular defects persist even when sperm are retrieved using advanced techniques such as electroejaculation or surgical extraction, highlighting the need for targeted therapeutic strategies. Interventions aimed at reducing oxidative stress and modulating inflammation, including antioxidant supplementation and advanced sperm selection methods, show promise but remain insufficiently standardized. Future research should focus on the development of personalized approaches integrating molecular diagnostics and targeted therapies to improve reproductive outcomes in this population. Collectively, this review reframes spinal cord injury-related infertility as a complex inflammatory and oxidative disorder and underscores the importance of addressing sperm DNA integrity in clinical management. Full article

Chronic stress is increasingly recognized as a major contributor to systemic disease. Prolonged or repeated activation of the hypothalamic–pituitary–adrenal (HPA) axis and sympathoadrenal systems may contribute to glucocorticoid receptor resistance and chronic low-grade inflammation, although stress-related responses vary depending on stressor characteristics, population, age, sex, health status, and study design. Elevated levels of pro-inflammatory cytokines (IL-6, IL-1β, TNF-α), oxidative stress, and NF-κB activation contribute to immune dysfunction, neuroinflammation, metabolic disturbances, reproductive and endocrine imbalance, as well as structural and functional alterations in stress-sensitive brain regions. Prolonged exposure to stress may contribute to the development of neuropsychiatric, cardiovascular, metabolic, neurodegenerative, and malignant diseases, highlighting the need for effective strategies to mitigate the detrimental consequences of chronic stress. Given the limitations and adverse effects associated with conventional pharmacological approaches, increasing attention has been directed toward natural bioactive compounds. Terpenes represent a diverse class of phytochemicals with reported anti-inflammatory, antioxidant, and neuromodulatory properties. Terpenes such as limonene and β-caryophyllene, as well as terpenoids such as linalool, may modulate NF-κB, MAPK, and Nrf2 signaling pathways and interact with the endocannabinoid system, thereby attenuating neuroinflammation, oxidative stress, and stress-induced immune dysregulation. This review summarizes current evidence regarding the mechanisms linking chronic stress, HPA axis dysfunction, and systemic disease, with particular emphasis on endocrine, immune, and nervous system alterations. In addition, it critically evaluates the mechanistic and translational potential of terpenes as possible indirect neuroimmune and redox modulators of stress-related pathophysiology. Full article

There is a rapidly rising demand for cosmeceutical solutions for skin lightening/brightening due to the growing need for dermatologic applications and consumers’ preference to enhance the brightness of skin. Traditionally, the main ingredients for developing dermatological products were the potentially harmful and controversial hydroquinone compounds; however, in recent years, the research field experienced a transition towards safer antioxidant-based agents. The present review analyzes the application and use of antioxidants in modern cosmetics as an innovative approach, and the chemical and biological mechanisms of their functions that could revolutionize the industrial applications. The most effective ones include competitive inhibition of tyrosinase enzyme, pheomelanin switch through the help of glutathione, protection from reactive oxygen species (ROS) in order to inhibit ultraviolet (UV)-stimulated production of melanin, as well as prevention of the migration of melanosomes using niacinamide. The review identifies and analyzes several components used as ingredients, such as vitamins C, Niacinamide, vitamin E, licorice root, epigallocatechin-3-gallate (EGCG), or resveratrol, among many more. In spite of their high efficiency, there are numerous problems associated with the instability, dermal irritation, and absorption of pure antioxidants. Finally, the legal framework developed by the Food and Drug Administration (FDA) and European Union (EU), potential risks like pro-oxidation damage, and future perspectives such as personalized skincare via machine learning and artificial intelligence (AI) are discussed. Full article

Nonylphenol (NP), a typical emerging pollutant, is widely detected in water bodies, yet its hepatotoxic mechanisms and mitigation strategies remain underexplored. This study evaluated the protective effects of a mixed probiotic (Lactobacillus acidophilus and Bacillus subtilis) against NP-induced hepatotoxicity in Silurus meridionalis by integrating transcriptomic and metabolomic analyses, with validation by RT-qPCR and ELISA. The results showed that NP exposure disrupted the arachidonic acid (AA) pathway (activating pro-inflammatory COX and LOX pathways while the suppressing anti-inflammatory CYP450 branch), promoted ferroptosis via iron dyshomeostasis and oxidative damage, and impaired triglyceride (TG) synthesis. Probiotic pretreatment reversed these toxic effects by modulating AA metabolism, suppressing COX (ptgs2a↓ → PGE₂↓) and LOX (alox12↓ → MDA↓) pathways, while upregulating the CYP450 pathway (cyp2j↑ → 11,12-EET↑). Probiotics also enhanced Fe³⁺ sequestration (steap4↑) and antioxidant defense (CAT↑, gpx4a↑), limiting Fenton reaction-mediated oxidative injury, and restored hepatic TG synthesis through upregulation of the DHAP-to-TG cascade (DHAP—(gpd1b↑) → G3P↑—(gpat3↑) → LPA—(agpat6↑) → PA—(plpp7↑) → DAG↑—(dgat2↑) → TG↑). These findings suggest that NP induces hepatotoxicity in S. meridionalis, involving ferroptosis, AA metabolism disruption and impaired TG synthesis as interconnected pathological events. Probiotics likely counteract this toxicity through systemic metabolic reprogramming. Collectively, these findings elucidate the hepatotoxic mechanisms of NP in S. meridionalis and offer toxicological data for its risk assessment, supporting the potential of probiotic-based strategies to mitigate emerging pollutant impacts in aquatic organisms. Full article

The development of marine-derived bioactive natural products has long been constrained by the dual bottlenecks of low extraction efficiency and unclear target mechanisms. In this study, single-factor experiments integrated with response surface methodology were employed to systematically establish an ultrasound-assisted high-efficiency extraction system for Sargassum fusiforme polyphenols (SP). The optimal extraction was achieved under the following conditions: ethanol concentration of 50%, liquid-to-solid ratio of 40 mL/g, ultrasonic power of 150 W, temperature of 50 °C, and extraction time of 60 min. Under these conditions, the experimentally obtained SP yield reached 38.91 ± 0.82 mg/g, showing no significant deviation from the model-predicted value (p > 0.05), thereby validating the reliability of the established process. In functional assessments, SP exhibited a mitigating effect on oxidative stress and inflammatory injury in cultured RAW 264.7 macrophages. In cellular assays, SP treatment was associated with elevated activities of endogenous antioxidant enzymes (SOD, GSH-Px and CAT), alongside reduced levels of pro-inflammatory mediators (NO, TNF-α, IL-1β, PGE₂ and IL-6) and an increased level of IL-10 in LPS-stimulated macrophages. Collectively, this study establishes an efficient laboratory-scale extraction protocol for SP and presents in vitro evidence for its cytoprotective effects. These findings provide an empirical basis for future investigations into the bioactive potential of this marine polyphenol. Full article

Heat stress (HS) impairs boar reproductive capacity via damaging Sertoli cells (SCs) and disrupting the integrity of the blood–testis barrier (BTB). This present study investigated the protective effects and underlying molecular mechanisms of PTD-FNK against HS-induced injury in porcine SCs. A HS model (43 °C, 1 h) was established, and 0.1 nM was determined as the optimal working concentration of PTD-FNK. Results showed that PTD-FNK effectively reversed HS-induced BTB disruption by restoring the expression levels of tight junction proteins (Claudin-1, Occludin, ZO-1, and Cx43) to baseline levels (p < 0.05). Concurrently, PTD-FNK alleviated HS-induced oxidative stress by enhancing total antioxidant capacity (T-AOC) and superoxide dismutase (SOD) activity, while reducing malondialdehyde (MDA) content (p < 0.05). It also suppressed HS-triggered apoptosis by downregulating the expression of pro-apoptotic proteins (Caspase-3/8/9 and Bax) and upregulating the anti-apoptotic protein Bcl-2 (p < 0.05). Furthermore, PTD-FNK maintained cellular homeostasis by regulating mitochondrial dynamics—restoring mitochondrial membrane potential (MMP) and balancing the expression of fusion-related protein Mfn1 and fission-related protein Drp1.Transcriptomic and LY294002 experiments confirmed PTD-FNK exerted effects via the PI3K/AKT pathway, modulating ID3, H2AX, DDIT3, CDKN1C, RAD51, and TP53. Thus, PTD-FNK protects SCs from HS through multi-target regulation dependent on PI3K/AKT, providing a novel strategy for boar reproductive health under HS. Full article

Mannheimia haemolytica (Mh) is a major bovine respiratory pathogen that can trigger marked inflammatory and barrier injuries. This study evaluated the protective effect of oral curcumin pretreatment in a proof-of-concept mouse model of early Mh-induced acute pulmonary injury. Mice received curcumin at 50 or 150 mg/kg/day for seven days before an intranasal Mh challenge and were evaluated 12 h after infection. Curcumin pretreatment was associated with lower lung wet-to-dry ratios, bronchoalveolar lavage fluid protein concentrations, histological injury scores, and serum pro-inflammatory cytokine levels. It was also associated with reduced abundance or phosphorylation of NF-κB/NLRP3-related proteins, increased expression of Nrf2-associated antioxidant proteins, reduced apoptosis, and preservation of the tight-junction protein ZO-1. In addition, curcumin pretreatment was associated with changes in fecal microbial composition and intestinal short-chain fatty acid profiles, including partial recovery of propionic acid. Because this study did not include a curcumin-only group, post-infection treatment, bacterial-burden measurements, pathway-perturbation experiments, or microbiota-causality experiments, the findings support prophylactic host-protective associations in an early mouse model rather than antibacterial activity, therapeutic efficacy after established infection, or causal gut–lung mechanisms. Validation in bovine models is required before veterinary application. Full article

Neurodegenerative diseases represent a significant clinical challenge. Understanding the pathogenic mechanisms is essential for developing more effective therapies, and mitochondria appear to play a key role in these processes. Since current treatments are limited to symptom management, natural strategies capable of preserving mitochondrial function could represent a promising preventive and therapeutic approach in neurodegeneration. This study aims at investigating the molecular mechanisms underlying the neuroprotective potential of an anthocyanin-rich extract from Callistemon citrinus flower (Cce) in differentiated SH-SY5Y cells exposed to 6-hydroxydopamine (6-OHDA). Exposure of cells to 6-OHDA inhibited cell viability and caused cell death, events hindered by the pre-treatment with Cce. Furthermore, it restored normal cell cycle distribution, as well as hampered 6-OHDA-induced apoptosis. Given the pro-oxidant effect of 6-OHDA, we observed that Cce reduced reactive oxygen species in stressed SH-SY5Y cells, along with recovering their antioxidant protection system. Focusing on mitochondria, Cce was able to protect their membranes from 6-OHDA, as suggested by the restoration of mitochondrial membrane potential. This led to a reduction in release of cytochrome c and the consequent activation of caspases 9 and 3, characteristic of the intrinsic apoptotic pathway, supporting our initial findings. Our results indicate that Cce prevents SH-SY5Y cell death induced by 6-OHDA via the preservation of mitochondrial integrity mainly through to its antioxidant properties, encouraging further studies to support its exploitation in the management of neurodegeneration. Full article

Ovarian ischemia/reperfusion (I/R) injury is a major cause of tissue damage following the surgical detorsion of ovarian torsion and is characterized by excessive oxidative stress, inflammation, and progressive cellular injury. Although ranolazine has been reported to exert antioxidant and anti-inflammatory effects in various experimental models, its potential protective effects against ovarian I/R injury have not yet been investigated. This study aimed to evaluate whether pretreatment with ranolazine protects ovarian tissue against experimental I/R injury in rats. Twenty-four female Wistar albino rats were randomly assigned to four groups: a healthy group (HG), sham-operated group (SOG), ovarian ischemia/reperfusion (OIR) group, and ranolazine-treated ovarian ischemia/reperfusion (ROIR) group. Ovarian ischemia was induced by 1 h of torsion followed by 6 h of reperfusion. Ranolazine (50 mg/kg) was administered 1 h before the induction of ischemia as a preventive pretreatment. Oxidative stress markers (MDA, tGSH, SOD, and CAT), pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6), histopathological alterations, and the expression of COX-1, COX-2, IL-1β, and IL-6 were evaluated by double immunofluorescence staining. Ovarian I/R significantly increased MDA and pro-inflammatory cytokine levels while markedly decreasing tGSH levels and SOD and CAT activities (p < 0.001). These biochemical alterations were accompanied by severe follicular degeneration, mononuclear cell infiltration, interstitial edema, decreased COX-1 immunoreactivity, and increased expression of COX-2, IL-1β, and IL-6. Ranolazine treatment significantly attenuated oxidative stress and inflammatory responses, preserved the antioxidant defense system, ameliorated histopathological damage, restored COX-1 immunoreactivity, and inhibited the expression of COX-2, IL-1β, and IL-6. This is the first experimental study evaluating ranolazine in ovarian I/R injury. These findings suggest that preventive pretreatment with ranolazine attenuates experimental ovarian I/R injury through antioxidant and anti-inflammatory mechanisms. Future studies are needed to determine whether similar protective effects can be achieved when ranolazine is administered after ovarian torsion or following surgical detorsion. Full article

H. pylori infection induces oxidative stress and inflammatory responses in gastric epithelial cells, which are key factors in the pathogenesis of gastritis and ulcers. Given the increasing threat of antibiotic resistance, non-antibiotic approaches that target host cell injury mechanisms are gaining considerable interest. While peptides derived from corn protein are known for their antioxidant and anti-inflammatory activities, whether they can alleviate H. pylori-induced gastric epithelial injury remains unclear. In this study, we evaluated the preventive effects of corn protein-derived bioactive peptides (CPDP-N), prepared by neutral protease hydrolysis, against H. pylori-triggered injury in human GES-1 cells. CPDP-N exhibited no cytotoxic effects, reduced H. pylori-induced intracellular ROS accumulation in a dose-dependent manner, and markedly increased the activities of intracellular antioxidant enzymes. Flow cytometry and fluorescence imaging demonstrated that CPDP-N attenuated the loss of mitochondrial membrane potential and relieved G0/G1 cell cycle arrest. CPDP-N markedly suppressed the secretion of the pro-inflammatory cytokines TNF-α, IL-1β, and IL-8, attenuated LDH release, and upregulated the anti-inflammatory cytokine IL-10. Moreover, CPDP-N markedly lowered the H. pylori-induced elevation of nuclear factor kappa-B (NF-κB) p65 protein, a key regulator of inflammatory signaling. These protective effects were accompanied by reduced intracellular ROS levels and lower NF-κB p65 abundance, suggesting the involvement of oxidative stress and NF-κB pathways. Collectively, these findings demonstrate that corn protein-derived peptides can protect gastric epithelial cells from H. pylori-induced oxidative and inflammatory injury, highlighting their potential as a dietary intervention for H. pylori-associated gastric diseases. Full article

This review examines the structural variety, distribution, and physicochemical properties of chlorogenic acids (CGAs), identifying coffee and green coffee as the leading dietary sources of these compounds. Preclinical studies indicate that plant-derived phenolic compounds exhibit strong antioxidant, anti-inflammatory, neuroprotective, cardioprotective, and antidiabetic effects across various disease models. The biological effectiveness of CGAs is attributed to their modulation of cellular signaling pathways, particularly by activating the erythroid 2-related factor 2 antioxidant defense mechanism and inhibiting the pro-inflammatory nuclear factor kappa B pathway. The regulation of the energy-sensing Sirtuin 1 and AMP-activated protein kinase pathways further enhances these therapeutic effects. In the gastrointestinal tract, CGAs serve as key modulators of the microbiota–gut–brain axis by exerting prebiotic-like effects, lowering the Firmicutes/Bacteroidetes ratio, promoting the production of short-chain fatty acids, and preserving gut barrier integrity. Some preclinical studies with coffee, Ilex paraguariensis, Eugenia uniflora, and other CGAs-rich extracts are also discussed. However, despite strong preclinical evidence, translating these findings into human clinical settings remains inconsistent due to significant individual differences in gut microbiota metabolism and the confounding effects of other components in dietary supplements, such as caffeine. Considering this, the review will first explore the molecular mechanisms supporting the potential development of CGAs as preventive interventions, while also discussing current human trials demonstrating selective improvements in neurological, cardiovascular, and metabolic functions. It will also highlight a historical limitation: the lack of studies on the bioavailability, bioactivity, and efficacy of isolated CGAs. The review will conclude by addressing the constraints of clinical studies, emphasizing the urgent need for future precision nutrition frameworks that employ standardized CGAs formulations to enhance potential therapeutic outcomes. Full article

Gastric cancer (GC) remains a major global health challenge, ranking among the most lethal malignancies due to late diagnosis, high tumor heterogeneity, and limited treatment efficacy. The search for safer, nutritionally based adjuncts to conventional therapies is therefore a research priority. Donkey milk (DM), traditionally used as a hypoallergenic substitute for infants, is emerging as a functional food with remarkable bioactivity. Its composition closely resembles human milk, with high levels of bioactive proteins, a favorable polyunsaturated lipid profile, antioxidant vitamins, and immune-supportive minerals. Despite its growing nutraceutical appeal, the anticancer potential of DM in GC has not yet been explored. This study represents the first investigation of DM in human gastric adenocarcinoma (AGS) cells. Using increasing concentrations of whole DM (25–100%), a dose-dependent inhibition of cell viability and migration was observed. Mechanistic insights reveal that DM induces mitochondrial oxidative stress, disrupts cell cycle progression (S/G2 accumulation at 75%, G2 arrest at 100%), and unexpectedly triggers a pro-inflammatory gene signature suggesting stress-driven immunostimulation rather than canonical apoptosis. These findings highlight a non-classical, context-dependent cytotoxic mechanism that distinguishes DM from conventional pro-apoptotic agents. DM may represent a promising nutraceutical candidate for GC management, bridging traditional food resources with modern oncology. By inhibiting hallmark cancer traits while engaging unique immunological pathways, DM offers a sustainable, low-toxicity approach with translational potential. Future studies will focus on the characterization of active components, validation in organoid and animal models, and exploring clinical applications of DM-derived bioactive components in cancer prevention and therapy. Full article

Japanese encephalitis virus (JEV) is a zoonotic pathogen. Infection in breeding boars triggers severe testicular inflammatory storms, resulting in testicular swelling, asthenospermia, oligozoospermia and even irreversible loss of reproductive capacity. Magnolol, a natural extract, exhibits remarkable anti-inflammatory and antioxidant activities. This study utilized swine testicular (ST) cells as an in vitro model to explore magnolol’s protective effects against JEV-mediated inflammation and its underlying mechanism. ST cells were infected with JEV at an MOI of 1 and treated with magnolol at 8, 12 and 16 μg/mL. We detected pro-inflammatory cytokine expression, performed 4D-FastDIA quantitative proteomics to screen differentially expressed proteins, verified key RIG-I and NF-κB cascade molecules at mRNA and protein levels, and tracked p65 nuclear translocation through immunofluorescence. The data showed that JEV significantly elevated TNF-α, IL-1β, IL-6, IL-8 and CCL5, while magnolol reduced these cytokines in a dose-dependent manner. JEV reshaped the proteome of innate immunity and inflammation, and excessively activated the RIG-I/NF-κB axis to increase IKKβ, TRAF2, TRAF6 transcription and p65 phosphorylation and nuclear import; 24 h treatment with 16 μg/mL magnolol greatly restrained this overactivation. In summary, magnolol alleviates JEV-triggered inflammatory injury by inhibiting the RIG-I/NF-κB pathway, offering experimental evidence for its use as a natural agent to mitigate JEV-induced cellular inflammatory response in boars. Full article

The RING-type E3 ubiquitin ligase plays a significant role in plant responses and adaptations to abiotic stresses such as drought. However, few studies have explored the role of E3 ubiquitin ligases in potato drought stress, especially DRIP1. In this study, 172 StHCa genes were identified across the potato genome. These genes were unevenly distributed on twelve chromosomes and divided into six subclades (group I–VI). The molecular weight of potato HCa proteins ranges from 5445.38 to 143,293.69 Da. More than half of them are acidic proteins and most are unstable. There are 161 hydrophilic proteins, and the subcellular localization analysis indicated that they were mainly located in the nucleus. The co-linearity analysis of StHCa genes showed that 172 genes underwent 40 tandem duplications and 28 segmental duplication events. Potato and tomato share a recent common ancestor and exhibit highly similar evolutionary trajectories. Promoter sequence analysis of the StHCa family identified abundant cis-acting elements associated with light signal transduction, hormone responses, plant growth and development, and abiotic stress responses. These results suggest that the StHCa genes may play important regulatory roles in different environmental signals and developmental stages. Expression profiling revealed that StDRIP1 exhibited higher transcript levels in potato roots than in stems and leaves, and its expression was significantly induced by drought stress. Physiological phenotyping demonstrated that StDRIP1-overexpressing (OE) plants displayed reduced root growth compared with wild-type (WT) plants, with decreases in root length, total root area, total root volume, and root vitality. Under 20% PEG-6000-simulated drought stress, the root expression level of StDRIP1 was higher in OE lines than in WT plants. Furthermore, StDRIP1 overexpression suppressed the activities of antioxidant enzymes (POD, CAT, and SOD) and weakened their osmotic adjustment ability by reducing proline (Pro) accumulation. At the late stage of stress treatment (9 h), the SOD, POD, and CAT activities of OE plants were 5.0%, 19.9%, and 25.1% lower than those of WT plants, respectively. These physiological alterations exacerbated oxidative damage, as evidenced by increased malondialdehyde (MDA) content and elevated electrolyte leakage in OE plants. In summary, this study comprehensively characterized the StHCa gene family in potato, providing a valuable theoretical basis for elucidating the functional mechanism of StDRIP1 in modulating drought stress responses. Collectively, StDRIP1 acts as a negative regulator of potato drought tolerance through two primary mechanisms: (1) repressing root growth and weakening root vitality, thereby reducing the water absorption capacity of roots; and (2) diminishing antioxidant enzyme activities and impairing osmotic homeostasis, which further exacerbates oxidative damage under drought stress. Full article