Search Results (8,382)

Staphylococcus aureus (S. aureus)-induced mastitis poses a significant threat to animal husbandry. This condition triggers sustained mammary inflammation, oxidative stress, and disrupts mitochondrial homeostasis, ultimately impairing mammary gland function and milk yield. Conjugated linoleic acid (CLA) is a long-chain fatty acid found in meat and dairy products derived from ruminants. It exhibits multiple biological activities, including anti-cancer, anti-inflammatory, and antioxidative stress-alleviating effects. Thus, this study sought to determine whether CLA alleviates S. aureus-induced mastitis in Hu sheep through the PPARG-UCP2 axis. Fifteen lactating Hu sheep were randomly allocated into three groups (n = 5): control group, model group, and CLA group. The CLA group received 1 mg/mammary gland of CLA via intramammary infusion for seven days, followed by S. aureus challenge (5 × 10⁷ cells/mL, 2 mL/mammary gland) in the model and CLA groups, while the control group received saline. Venous blood and mammary tissue samples were collected at two days post-infection. The results demonstrated that S. aureus infection significantly upregulated the expression of inflammatory factors (IL-1β, IL-6, and NF-κB) in the mammary tissue of Hu sheep, p < 0.01. Relative to the control, the model group showed increased ROS and MDA levels, a diminished NAD+/NADH ratio, and downregulated expression of the antioxidant factors SOD, Nrf2, HO-1, and SIRT3, p < 0.01. Furthermore, the expression of p-AMPK and mitophagy-related factors (PARKIN, PINK1, and LC3b) showed a statistically significant increase in the model group than in the control group, p < 0.01. S. aureus infection also suppressed the expression of PPARG and UCP2, p < 0.01. In contrast, the CLA group showed lower levels of inflammatory factors (IL-1β, IL-6, and NF-κB), ROS and MDA, while the NAD+/NADH ratio and the expression of antioxidant factors (SOD, p-Nrf2, HO-1, and SIRT3) were elevated compared with the model group, p < 0.01. Moreover, the expression of p-AMPK and mitophagy-related factors (PARKIN, PINK1, and LC3b) was reduced in the CLA group relative to the model group, p < 0.05. Concurrently, the expression of PPARG and UCP2 was higher in the CLA group than in the model group, p < 0.001. These findings demonstrated that S. aureus infection induced mastitis in Hu sheep mammary tissue, whereas CLA alleviated the infection by upregulating the PPARG-UCP2 pathway, thereby reducing inflammation, oxidative stress, and mitophagy levels. This study offers a novel perspective on mammary tissue repair during mastitis and expands the understanding of UCP2’s biological role. Full article

Pathogenic variants in the PAK1 gene are linked to neurodevelopmental and neurodegenerative disorders by disrupting neuronal signaling and function. Despite increasing recognition, the mechanisms underlying these conditions remain incompletely understood, limiting therapeutic options. Here, we report a novel de novo PAK1 variant, c.396C>A (p.Asn132Lys), in a 5-year-old girl with Intellectual Developmental Disorder with Macrocephaly, Seizures, and Speech Delay (IDDMSSD). The patient presented with mild intellectual disability, delayed speech, macrocephaly, hypotonia, gait ataxia, autism-like behaviors, and focal epileptiform activity. Trio exome sequencing confirmed the variant as likely pathogenic, absent in her parents and population databases. This finding expands the phenotypic spectrum of PAK1-related disorders and underscores the critical role of the autoinhibitory domain in neurodevelopment. In addition, we performed a comprehensive literature review of PAK1 variants affecting both the autoregulatory and kinase domains, summarizing associated clinical features and pathogenic mechanisms. Our study highlights the importance of identifying PAK1 pathogenic variants for accurate diagnosis, refined genotype-phenotype correlations, and the development of potential targeted therapeutic strategies. By integrating novel case data with existing literature, this work advances understanding of PAK1-related neurodevelopmental disorders and supports the application of genetic analysis in rare pediatric NDD cases. Full article

Cadmium (Cd) is a typical pollutant with strong toxicity even at low concentrations. In the marine environment, Cd is a problem of magnitude and ecological significance due to its high toxicity and accumulation in living organisms. The clam Meretrix meretrix is a useful bioindicator species for evaluating heavy-metal stress. This study investigated the extent of recovery from Cd²⁺-induced oxidative and immune impairments in M. meretrix gills achieved by short-term depuration. Clams were exposed to 3 mg/L Cd²⁺ for six days or three days followed by three days of depuration, and the Cd contents, morphological structure, osmoregulation, oxidative stress, and immune responses in the gills were evaluated. The results showed that gill Cd contents increased with exposure, reaching 9.857 ± 0.074 mg·kg⁻¹ on day 3 but decreased slightly to 8.294 ± 0.056 mg·kg⁻¹ after depuration, while reaching 18.665 ± 0.040 mg·kg⁻¹ on day 6 after continuous exposure. Histological lesions, including lamellar fusion, hemolymphatic sinus dilation, and ciliary degeneration, partially recovered after depuration. Reactive oxygen species (ROS) and malondialdehyde (MDA) levels decreased significantly, while DNA-protein crosslinking rate (DPC) and protein carbonyl (PCO) showed minor reductions. Total antioxidant capacity (T-AOC) and the activities of Ca²⁺/Mg²⁺-ATPase (CMA), cytochrome c oxidase (COX), succinate dehydrogenase (SDH), and lactate dehydrogenase (LDH) increased by over 10% during depuration, though these changes were not statistically significant. Lysozyme (LZM) activity and MT transcript levels increased progressively with Cd exposure, indicating their suitability as biomarkers of Cd stress. Acid and alkaline phosphatase (ACP, AKP) activities and Hsp70 and Nrf2 mRNA transcripts exhibited inverted U-shaped response consistent with hormetic response. ACP and AKP activity levels rose by more than 20% after depuration, suggesting partial restoration of immune capacity. Overall, Cd exposure induced oxidative damage, metabolic disruption, and immune suppression in M. meretrix gills, yet short-term depuration allowed partial recovery. These findings enhance understanding of Cd toxicity and reversibility in marine bivalves and reinforce the usage of biochemical and molecular markers for monitoring Cd contamination and assessing depuration efficiency in aquaculture environments. Full article

Oxidative stress is a defining feature of stroke pathology, but the magnitude, timing and impact of redox imbalance are not static. Emerging evidence indicates that physiological contexts, such as aging, metabolic stress, and circadian disruption, continuously reshape oxidative status and determine the brain’s vulnerability to ischemic and reperfusion injury. This review integrates recent insights into how these intrinsic modulators govern the transition from adaptive physiological redox signaling to pathological oxidative stress during stroke. Aging compromises mitochondrial quality control and blunts NRF2-driven antioxidant responses, heightening susceptibility to ROS-driven damage. Metabolic dysfunction, as seen in obesity and diabetes, amplifies oxidative burden through NADPH oxidase activation, lipid peroxidation, and impaired glutathione recycling, further aggravating post-ischemic inflammation. Circadian misalignment, meanwhile, disrupts the rhythmic expression of antioxidant enzymes and metabolic regulators such as BMAL1, REV-ERBα, and SIRT1, constricting the brain’s temporal window of resilience. We highlight convergent signaling hubs, NRF2/KEAP1, SIRT–PGC1α, and AMPK pathways, as integrators of these physiological inputs that collectively calibrate redox homeostasis. Recognizing oxidative stress as a dynamic, context-dependent process reframes it from a static pathological state to a dynamic outcome of systemic and temporal imbalance, offering new opportunities for time-sensitive and metabolism-informed redox interventions in stroke. Full article

The antimicrobial resistance crisis necessitates novel therapeutics. Selenium nanoparticles (SeNPs) offer promise, but their precise bactericidal mechanism remains poorly defined. This study aimed to define the antibacterial action of SeNPs synthesized via a green method with ascorbic acid and sodium citrate. The resulting SeNPs were monodisperse (17.8 ± 0.66 nm), crystalline, and highly stable (zeta potential: −69.9 ± 4.3 mV), exhibiting potent bactericidal activity against multidrug-resistant E. coli. To generate a mechanistic hypothesis, we integrated phenotypic analyses with a preliminary, single-replicate proteomic profiling. Recognizing this as an exploratory step, we focused our analysis on proteins with the most substantial changes. This revealed a coherent pattern of a targeted dual assault on core cellular processes. The data indicate that SeNPs simultaneously induce oxidative stress while severely depleting key components of the primary antioxidant glutathione system; key detoxification enzymes—glutathione S-transferase and glutaredoxin 2—were depleted 18- to 19-fold, while the stress protein HchA was reduced by over 63-fold. Concurrently, the patterns point toward a crippling of central energy metabolism; iron–sulfur enzymes in the TCA cycle, including aconitate hydratase (8.1-fold decrease) and succinate dehydrogenase (13.9-fold decrease), were severely suppressed, and oxidative phosphorylation was impaired (e.g., 4.7-fold decrease in NADH dehydrogenase subunit B). We propose that this coordinated disruption creates a lethal feedback loop leading to metabolic paralysis. Consequently, this work provides a detailed and testable mechanistic hypothesis for SeNPs action, positioning them as a candidate for a potent, multi-targeted antimicrobial strategy against drug-resistant pathogens. Full article

Phosphate is emerging as an active mediator of oxidative stress and vascular injury in chronic kidney disease (CKD). This emerging pathophysiological framework, referred to as “Phosphatopathy”, describes the systemic syndrome driven by chronic phosphate overload and characterized by oxidative stress, inflammation, endothelial dysfunction, vascular calcification, cellular senescence, and metabolic imbalance. Beyond being a biochemical marker, phosphate overload triggers NOX-derived reactive oxygen species (ROS), activates Wnt/β-catenin and TGF-β signaling, and disrupts the FGF23–Klotho axis, promoting endothelial dysfunction, vascular calcification, and left ventricular hypertrophy (LVH). These pathways converge with systemic inflammation and energy imbalance, contributing to the malnutrition–inflammation–atherosclerosis (MIA) syndrome. Experimental and clinical data reveal that the phosphate/urinary urea nitrogen (P/UUN) ratio is a sensitive biomarker of inorganic phosphate load, while emerging regulators such as microRNA-125b and calciprotein particles integrate phosphate-driven oxidative and inflammatory responses. Therapeutic strategies targeting phosphate burden—rather than serum phosphate alone—include dietary restriction of inorganic phosphate, non-calcium binders, magnesium and zinc supplementation, and activation of important pathways related to the activation of antioxidant defense such as AMP-activated protein kinase (AMPK) and SIRT1. This integrative framework redefines phosphate as a modifiable upstream trigger of oxidative and metabolic stress in CKD. Controlling phosphate load and redox imbalance emerges as a convergent strategy to prevent vascular calcification, improve arterial stiffness, and reduce cardiovascular risk through personalized, mechanism-based interventions. Full article

Background/Objectives: Colistin (polymyxin E) has re-emerged as a last-hope treatment against MDR Gram-negative pathogens due to the development of extensively drug-resistant Gram-negative bacteria. Unfortunately, rapid global resistance towards colistin has emerged, which represents a major public health concern. In this context (CBD), a lipophilic molecule derived from Cannabis sativa, exhibits antimicrobial activity mainly against Gram-positive bacteria but is generally ineffective against Gram-negative species. However, synergistic antibacterial activity between CBD and polymyxin B has been reported. The objective of this work is to analyze the colistin–CBD synergy against clinically relevant Gram-negative isolates displaying diverse mechanisms of colistin resistance and to explore the basis of the possible mechanism of action involved in the first steps of this synergy. Methods: Microbiological assays, minimal inhibitory concentration, cell culture, synergy tests by checker board and time kill, biofilm inhibition evaluation by crystal violet and MTT, SEM (scanning electron microscopy), molecules interaction analysis by nuclear magnetic resonance (NMR). Results: The colistin–CBD combination displayed synergy in colistin resistant Gram-negative bacteria and also disrupted preformed biofilms and killed bacteria within them. Time-kill assays revealed rapid bactericidal activity and SEM showed mild surface alterations on bacterial outer membranes after sublethal colistin monotherapy. Furthermore, a series of sequential treatment assays on colistin-resistant Escherichia coli showed that simultaneous exposure to both compounds was required for activity, as introducing a washing step between treatments abolished the antibacterial effect. In order to obtain deeper insight into this mechanism, NMR analyses were performed, revealing specific molecular interactions between CBD and colistin molecules. Conclusions: These results provide evidence for the first time that both molecules engage through a specific and structurally meaningful interaction and only display synergy when acting together on colistin-resistant bacteria. Full article

Microplastics and nanoplastics (<5 mm and <1 μm, respectively) are emerging contaminants now ubiquitous across environmental matrices and increasingly recognized for their impacts on human health. These particles commonly adsorb or contain endocrine-disrupting chemicals—such as bisphenol-A and phthalate additives—that together trigger complex biological responses. This review examines the central role of oxidative stress in mediating the toxicity of microplastics and associated endocrine disruptors across multiple organ systems. We discuss mechanisms including cellular uptake, reactive oxygen species generation, mitochondrial dysfunction, impairment of antioxidant defenses, and activation of key signaling pathways. Organ-specific effects on reproductive health, cardiovascular function, hepatic metabolism, gut barrier integrity, and neurological systems are highlighted. Current evidence strongly supports oxidative stress as a pivotal mechanism linking microplastic exposure to systemic toxicity, underscoring important implications for public health policy and clinical intervention strategies. Full article

Cancer remains a leading cause of mortality worldwide, and new chemical leads are essential for developing potent anticancer therapies. Evidence suggests that Pseudomonas aeruginosa (Pa) may suppress tumorigenesis, although the underlying mechanisms remain largely unclear. This study characterized a novel small molecule quinolone, JH62 (E-2-(tridec-4-en-1-yl)-quinolin-4(1H)-one, C₂₂H₃₁NO), from Pa. JH62 exhibited broad-spectrum anticancer activity, inhibiting the proliferation of A549 lung cancer cells in a time- and dose-dependent manner with an IC₅₀ of 15 μM, while showed low cytotoxicity toward normal cells. In xenograft mice model, treatment with JH62 (10 mg/kg) reduced tumor weight and volume by 73% and 79%, respectively. Mechanistically, treatment with JH62 induced structural and functional disruption of mitochondria in cancer cells, triggered autophagic cell death, and did not cause DNA damage. Genetic analysis confirmed that JH62 biosynthesis depends on the pqsABCDE gene cluster and that JH62 positively regulates its own production. ADMET profiling further indicated promising drug-like properties for future development. These findings establish JH62 as a promising anticancer lead compound derived from microbial metabolism. Full article

Background: The (COVID-19) pandemic profoundly disrupted daily routines and physical activity (PA), especially among university students, due to restrictions and limited access to sports facilities. As this group is particularly vulnerable to sedentary lifestyles and mental health issues, understanding their PA patterns is crucial. This study explores overall and domain-specific PA levels and the influence of sociodemographic factors, offering insights for promoting sustainable PA strategies in higher education during and beyond health crises. Methods: A cross-sectional online survey was conducted among University of Foggia students during the pandemic. The participants completed the validated Italian IPAQ-Long to assess PA across various domains. Associations with demographics and perceived barriers were analyzed via t tests, ANOVA, and nonparametric tests. Results: A total of 301 students completed the survey. Despite barriers such as limited living space, low income, and sports facility closures, 66% of the participants reported high PA levels, mainly through work-related and leisure activities. This remains insufficient. PA varied significantly by gender, income, residence, and employment status: males reported higher leisure PA, whereas females engaged more in active transport and domestic activities. Rural residents and those with moderate incomes demonstrated higher overall PA, whereas employed students presented lower activity levels. These findings underscore the complex socioeconomic and environmental factors shaping PA behavior during an unprecedented global health crisis. Conclusions: The findings reveal that students’ resilience in maintaining PA is a coping mechanism despite socioeconomic and environmental barriers. Tailored, accessible PA initiatives integrated into university curricula can enhance student well-being, academic performance, and long-term health during and after public health emergencies. Universities should adopt accessible, equity-oriented PA initiatives to promote physical and mental health and enhance public-health preparedness during future emergencies. Full article

Cold stress impairs crop productivity through cascading inhibition of root growth, nitrogen (N) metabolism, and photosynthesis, yet the systematic linkages among these physiological disruptions remain poorly understood. It is crucial to elucidate the mechanisms by which cold-tolerant varieties maintain root growth and N-metabolizing enzyme homeostasis. This two-year field study investigated how cold duration at the tillering stage impacted root traits, N metabolism, photosynthesis, and their relationships with the yield of two japonica rice varieties differing in cold tolerance. A cold-tolerant (Dongnong 428) and a cold-sensitive variety (Songjing 10) were grown in a paddy field for two consecutive growing seasons in 2021 and 2022. Cold water (15 °C) was irrigated for 0 (denoted as D0), 5 (D5), 10 (D10), and 15 days (D15) during the tillering stage. Compared to D0, cold-water treatments significantly reduced root traits and total dry weight of both varieties. Cold stress significantly impaired N metabolism and photosynthesis, leading to significant reductions in N efficiency. The magnitude of these changes turned to greater with cold-water treatment duration. Dongnong 428 showed stronger cold tolerance, attributed to its maintenance of superior root traits and photosynthetic performance, as well as higher activities of enzymes in the roots, which sustained N assimilation and utilization. These factors primarily contributed to Dongnong 428 achieving 11.6–20.9% higher yields compared to Songjing 10. Cold stress during the tillering stage disrupts root growth and photosynthesis, impairs plant N acquisition ability, resulting in substantial yield loss. Cold-tolerant varieties maintain superior root morphology/functionality and photosynthetic performance. Full article

With new emerging diseases such as COVID-19 and an increasing incidence of cancer, there remains a significant need for investigating new therapeutic options to treat a wide range of ailments and disorders. Peppermint (Mentha × piperita) and white snakeroot (Ageratina altissima) have been used medicinally by native people in the Midwestern United States for centuries. However, the antiproliferative and antimicrobial properties of the aqueous extracts of these plants remain unclear. In this study, we evaluate the therapeutic potential of peppermint and white snakeroot aqueous leaf extracts by examining their activity against mammalian cancer cells, bacteria, and viruses. Both peppermint and snakeroot extracts showed no reductions in viability at concentrations lower than 25 mg/mL and 10 mg/mL, respectively, in two different cancer lines, HEp-2 and DBT-9 cells, in vitro. While treatment with the snakeroot extract resulted in significant disruption to cytoskeletal organization in HEp-2 cells at a concentration of 10 mg/mL, peppermint and snakeroot extracts did not have a major impact on the viability or proliferation of the cancer cell lines tested. Peppermint and snakeroot were then evaluated for antibacterial activity against four different bacterial pathogens. Significant inhibition of bacterial replication was observed for E. coli (at concentrations greater than 0.1 mg/mL) and S. aureus (at concentrations greater than 1 mg/mL) treated with either peppermint or snakeroot extracts. No significant activity was observed against the bacterial strains P. aeruginosa and S. pyogenes. Peppermint (EC₅₀ = 2.36 mg/mL) and snakeroot (EC₅₀ = 2.64 mg/mL) significantly reduce infectivity and replication (at concentrations above 0.2 mg/mL) of the major human pathogen, human respiratory syncytial virus (hRSV). However, testing for antiviral activity against a mouse coronavirus (murine hepatitis virus, MHV) showed no impact on replication at concentrations up to 2.5 mg/mL. Lastly, chemical analysis of the extracts identified several prominent compounds, which were subsequently evaluated for their biological contributions to the observed plant extract phenotypes. Two of the identified compounds, 1,8-cineole (Eucalyptol) and menthol, show significant antimicrobial activity. We report that aqueous extracts of peppermint and white snakeroot exhibit specific antibacterial and antiviral activities that support further investigation for therapeutic potential. Full article

Oxidative stress arises from an imbalance between reactive oxygen species (ROS) and antioxidant defense mechanisms and disrupts the structural integrity of macromolecules such as lipids, proteins, and DNA. This biochemical imbalance triggers the pathogenesis of cardiovascular and neurodegenerative diseases and leads to lipid oxidation and quality degradation in food systems. Plant-derived bioactive compounds (BACs) such as polyphenols and terpenes develop versatile molecular strategies to mitigate this oxidative damage. In addition to their direct radical scavenging effects, polyphenols stimulate the synthesis of endogenous antioxidant enzymes such as superoxide dismutase (SOD) and catalase (CAT) by activating the Nrf2–Keap1 signaling pathway. Terpenes, on the other hand, create a specialized protective shield in lipid-based matrices through “chain-breaking” reactions and a “slingshot” mechanism that externally halts the oxidation of γ-terpinene. In food engineering applications, these compounds meet the demand for “clean-label” products by providing alternatives to synthetic antioxidants such as BHA and BHT. Specific terpenes, such as carnosic acid, demonstrate higher performance in inhibiting lipid oxidation compared to their synthetic counterparts. Although BAC use extends the shelf life of products while maintaining color and flavor stability, potential interactions with protein digestibility necessitate dosage management. From a clinical perspective, these compounds suppress inflammatory responses by inhibiting the NF-κB pathway and contribute to the prevention of chronic diseases by modulating the gut microbiota. This review evaluates the capacity of BACs to manage oxidative stress in food preservation technologies and human health through a mechanistic and application-based approach. Full article

Background: Effective prevention of jellyfish stings is crucial for human safety during marine activities. Traditional protective methods are often limited in terms of coverage area and duration of protection; Methods: This study designed and tested a novel jellyfish-repellent textile by coating waterproof polyester fabric with copper ion-loaded multicompartmental nanoparticles, which repel jellyfish by disrupting their cellular membranes and physiological functions. The nanoparticles were synthesized to enable spatial separation of components, enhance stability, and allow controlled copper ion release. They were applied to the fabric in one step via high-voltage electrostatic spray technology, followed by characterization using SEM and FT-IR. The copper sulfate release profile and nanoparticle adhesion were analyzed. Jellyfish-repellent efficacy was evaluated, along with biocompatibility tests including skin sensitization (Magnusson and Kligman method), skin irritation (Draize test), and cytotoxicity (MTT assay on L929 cells and human dermal fibroblasts). Results: SEM confirmed the formation of uniform multicompartmental nanoparticles with sizes ranging from 2.28 to 3.15 μm. FT-IR verified successful anchoring of Cu²⁺ ions to fabric fibers through coordination with hydroxyl groups. Drug release tests demonstrated water-triggered controlled release of copper ions lasting over 168 h, with nanoparticle retention rates exceeding 70% on all fabrics. The textile showed significant effectiveness in repelling jellyfish. Moreover, no apparent sensitization, irritation, or cytotoxicity was observed. Conclusions: A novel jellyfish-repellent textile was successfully developed using copper ion-loaded multicompartmental nanoparticles. This textile provides a promising solution for preventing jellyfish stings and contributes to the advancement of protective gear for marine activities. Full article

Scheuermann’s kyphosis (SK) is a rigid dorsal kyphosis of unclear pathophysiological origin. The aim of this review is to summarise current theories and both clinical and experimental findings regarding the underlying mechanisms of SK. Emerging evidence highlights the significant role of excessive mechanical loading as a major contributor to defective growth of the cartilaginous vertebral endplate. This is associated with the formation of Schmorl’s nodes, disruption of the ring apophysis, and compromised intervertebral disc integrity—ultimately resulting in vertebral body wedging and thickening of the anterior longitudinal ligament. In addition, numerous studies have investigated the genetic contribution and underlying molecular mechanisms involved in the pathogenesis of SK. Recent in vivo findings suggest an association between asymmetric mechanosensory activation of cerebrospinal fluid (CSF), contacting neurons, and defective Reissner fibre signalling, which may contribute to abnormal spinal morphogenesis in the sagittal thoracic plane. These findings indicate a potential link between altered CSF dynamics and the development of SK. Taken together, the evidence supports a multifactorial aetiology, with both genetic and biomechanical factors playing central roles in the development of Scheuermann’s kyphosis. The interpretation of the underlying pathophysiological mechanism could result in the early detection of the subjects that may have genetical predisposition for SK appearance and the development of target molecular treatments in order to counter the progression of the deformity. Full article