Search Results (5,256)

Introduction: Osteoarthritis (OA), a leading cause of disability among the elderly, is characterized by progressive joint tissue destruction. Fucoidan, a sulfated polysaccharide with known anti-inflammatory and antioxidant properties, has been investigated for its potential to protect against interleukin-1 beta (IL-1β)-induced articular tissue damage. Methods: Human primary chondrocytes and synovial fibroblasts were pre-treated with 100 μg/mL fucoidan before stimulation with 1 ng/mL of IL-1β. The protective effects of fucoidan were assessed by measuring oxidative stress markers and catabolic enzyme levels. These in vitro findings were corroborated using a rat anterior cruciate ligament transection-induced OA model. To explore the underlying mechanisms, particularly the interaction between microRNAs (miRs) and heme oxygenase-1 (HO-1), five candidate miRs were identified in silico and experimentally validated. Luciferase reporter assays were used to confirm direct interactions. Results: Fucoidan exhibited protective effects against IL-1β-induced oxidative stress and catabolic processes in both chondrocytes and synovial fibroblasts, consistent with in vivo observations. Fucoidan treatment restored HO-1 expression while reducing inducible nitric oxide synthase and matrix metalloproteinase levels in IL-1β-stimulated cells. Notably, this study revealed that fucoidan modulates the miR-22/HO-1 pathway, a previously uncharacterized mechanism in OA. Specifically, miR-22 was upregulated by IL-1β and subsequently attenuated by fucoidan. Luciferase reporter assays confirmed a direct interaction between miR-22 and HO-1. Conclusion: The results demonstrate that fucoidan mitigates OA-related oxidative stress in chondrocytes and synovial fibroblasts through the novel modulation of the miR-22/HO-1 axis. The miR-22/HO-1 pathway represents a crucial therapeutic target for OA, and fucoidan may offer a promising therapeutic intervention. Full article

Caffeine is a widely consumed psychoactive compound known to influence drug metabolism and efficacy through interactions with key enzymes such as cytochrome P450 3A4 (CYP3A4). This study investigates the molecular impact of caffeine on the binding behavior of imatinib, a first-line BCR-ABL tyrosine kinase inhibitor, using molecular docking simulations. Structural optimization and lipophilicity analyses were conducted using HyperChem, while docking was performed with HEX software (Version 8.0.0) against the CYP3A4 receptor (PDB ID: 1W0E). Two administration scenarios were evaluated: concurrent caffeine–imatinib complex formation and sequential administration with caffeine pre-bound to CYP3A4. The caffeine–imatinib complex exhibited a predicted increase in lipophilicity (logP = 3.09) compared to imatinib alone (logP = −1.29), which may indicate the potential for enhanced membrane permeability and tissue distribution. Docking simulations revealed stronger binding affinity of the complex to CYP3A4 (−350.53 kcal/mol) compared to individual compounds, and improved imatinib binding when CYP3A4 was pre-complexed with caffeine (−294.14 kcal/mol vs. −288.19 kcal/mol). Frontier molecular orbital analysis indicated increased reactivity of the complex (ΔE = 7.74 eV), supporting the hypothesis of altered pharmacodynamic behavior. These findings suggest that caffeine may modulate imatinib’s metabolic profile and therapeutic efficacy by enhancing receptor binding and altering drug distribution. The study underscores the importance of evaluating dietary components during drug development and therapeutic planning, particularly for agents metabolized by CYP3A4. Full article

Plastic pollution in marine environments poses a new global threat. Microplastics (MPs) can bioaccumulate in marine organisms, leading to oxidative stress (OS). This study investigates MP accumulation and associated OS responses in six invertebrate species (Bivalvia, Gastropoda, and Malacostraca) and three key fish species of the Bulgarian Black Sea ecosystems. The target hydrobionts were collected from nine representative coastal habitats of the northern and southern aquatory. MPs were quantified microscopically, and OS biomarkers (lipid peroxidation, glutathione, and antioxidant enzymes) were analyzed spectrometrically in fish liver and gills and invertebrate soft tissues (STs). The specific OS (SOS) index was calculated as a composite indicator of the ecological impact, incl. MP effects. The results revealed species-specific MP bioaccumulation, with the highest concentrations in Palaemon adspersus, Rathke (1837) (0.99 ± 1.09 particles/g ST) and the least abundance in Bittium reticulatum (da Costa, 1778) (0.0033 ± 0.0025 particles/g ST). In Sprattus sprattus (Linnaeus, 1758), the highest accumulation of MPs was present (2.01 ± 2.56 particles/g muscle). The correlation analyses demonstrated a significant association between MP counts and catalase activity in all examined species. The SOS index varied among species, reflecting different stress responses, and this indicated that OS levels were linked to ecological conditions of the habitat and the species-specific antioxidant defense potential to overcome multiple stressors. These findings confirmed the importance of environmental conditions, including MP pollution and the evolutionarily developed capacity of marine organisms to tolerate and adapt to environmental stress. This study emphasizes the need for novel approaches in monitoring MPs and OS to better assess potential ecological risks. Full article

Selenium (Se) is an essential trace element critical for animal growth and immune function. This study investigated the dietary selenium requirement of juvenile large yellow croaker (Larimichthys crocea) through an 8-week feeding trial. Five experimental diets were formulated by supplementing a basal diet with selenium polysaccharides (Se-PS) at 0, 20, 30, 40, and 50 mg/kg, resulting in analyzed Se concentrations of 0.35, 0.54, 0.71, 0.93, and 1.11 mg/kg, respectively. The results demonstrated that growth performance and feed efficiency improved with increasing dietary selenium, peaking at 0.93 mg/kg before declining at higher levels. Antioxidant enzyme activities—superoxide dismutase (SOD) and catalase (CAT)—in serum and liver tissues exhibited a dose-dependent increase, reaching maximal levels at 1.11 mg/kg. Conversely, malondialdehyde (MDA), a marker of oxidative stress, progressively decreased in both serum and liver, attaining its lowest concentration at 1.11 mg/kg, though this did not differ significantly from the 0.93 mg/kg group (p = 0.056). Tissue selenium accumulation was highest at these optimal dietary levels. Based on the growth performance, oxidative stress response, and tissue selenium retention, the recommended dietary selenium requirement for juvenile large yellow croaker is 0.93 mg/kg. These findings highlight the importance of optimal Se supplementation in aquafeeds to enhance growth and physiological health in farmed fish. Full article

The extensive use of pesticides has significant implications for public health and the environment. Breeding crop plants is the most effective and environmentally friendly approach to improve the plants’ resistance. However, it is time-consuming and costly, and it is sometimes difficult to achieve satisfactory results. Plants induce defense responses to natural elicitors by interpreting multiple genes that encode proteins, including enzymes, secondary metabolites, and pathogenesis-related (PR) proteins. These responses characterize systemic acquired resistance. Humic substances trigger positive local and systemic physiological responses through a complex network of hormone-like signaling pathways and can be used to induce biotic and abiotic stress resistance. This study aimed to assess the effect of humic substances on the activity of phenylalanine ammonia-lyase (PAL), peroxidase (POX), and β-1,3-glucanase (GLU) used as a resistance marker in various plant species, including orange, coffee, sugarcane, soybeans, maize, and tomato. Seedlings were treated with a dilute aqueous suspension of humic substances (4 mM C L⁻¹) as a foliar spray or left untreated (control). Leaf tissues were collected for enzyme assessment two days later. Humic substances significantly promoted the systemic acquired resistance marker activities compared to the control in all independent assays. Overall, all enzymes studied in this work, PAL, GLUC, and POX, showed an increase in activity by 133%, 181%, and 149%, respectively. Among the crops studied, citrus and coffee achieved the highest activity increase in all enzymes, except for POX in coffee, which showed a decrease of 29% compared to the control. GLUC exhibited the highest response to HS treatment, the enzyme most prominently involved in increasing enzymatic activity in all crops. Plants can improve their resistance to pathogens through the exogenous application of HSs as this promotes the activity of enzymes related to plant resistance. Finally, we consider the potential use of humic substances as a natural chemical priming agent to boost plant resistance in agriculture Full article

Callistemon citrinus has shown antioxidant and anti-inflammatory properties in certain tissues. However, its impact on the brain remains unproven. This study investigates the effect of C. citrinus extract and phytosomes on the oxidative status of the brains of rats fed a high-fat–fructose diet (HFD). Fifty-four male Wistar rats were randomly divided into nine groups (n = 6). Groups 1, 2, and 3 received a standard chow diet; Group 2 also received the vehicle, and Group 3 was supplemented with C. citrinus extract (200 mg/kg). Groups 4, 5, 6, 7, 8, and 9 received a high-fat diet (HFD). Additionally, groups 5, 6, 7, 8, and 9 were supplemented with orlistat at 5 mg/kg, C. citrinus extract at 200 mg/kg, and phytosomes loaded with C. citrinus at doses of 50, 100, and 200 mg/kg, respectively. Administration was oral for 16 weeks. Antioxidant enzymes, biomarkers of oxidative stress, and fatty acid content in the brain were determined. A parallel artificial membrane permeability assay (PAMPA) was employed to identify compounds that can cross the intestinal and blood–brain barriers. The HFD group (group 4) increased body weight and adipose tissue, unlike the other groups. The brain fatty acid profile showed slight variations in all of the groups. On the other hand, group 4 showed a decrease in the activities of antioxidant enzymes SOD, CAT, and PON. It reduced GSH level, while increasing GPx activity as well as MDA, 4-HNE, and AOPP levels. C. citrinus extract and phytosomes restore the antioxidant enzyme activities and mitigate oxidative stress in the brain. C. citrinus modulates oxidative stress in brain tissue through 1.8-cineole and α-terpineol, which possess antioxidant and anti-inflammatory properties. Full article

Microbes perform diverse and vital functions in animals, plants, and humans, and among them, plant-associated microbiomes, especially endophytes, have attracted growing scientific interest in recent years. Numerous plant species thriving in diverse environments have been shown to host endophytic microbes. While endophytic bacteria commonly colonize plant tissues such as stems, roots, and leaves, seed-associated endophytes generally exhibit lower diversity compared to those in other plant compartments. Nevertheless, seed-borne microbes are of particular importance, as they represent the initial microbial inoculum that influences a plant’s critical early developmental stages. The seed endophytic microbiome is of particular interest due to its potential for vertical transmission and its capacity to produce a broad array of phytohormones, enzymes, antimicrobial compounds, and other secondary metabolites. Collectively, these functions contribute to enhanced plant biomass and yield, especially under abiotic and biotic stress conditions. Despite their multifaceted roles, seed microbiomes remain underexplored in plant ecology, and their potential benefits are not yet fully understood. This review highlights recent advances in our understanding of the diversity, community composition, mechanisms of action, and agricultural significance of seed endophytic microbes. Furthermore, it synthesizes current insights into how seed endophytes promote plant health and productivity and proposes future research directions to fully harness their potential in sustainable agriculture. Full article

In this study, an artificially simulated enhanced UV-B radiation treatment of 96 kJ/m²·d⁻¹ was applied with natural sunlight as the control. By observing changes in biological tissue damage, peroxidase (POD) enzyme activity, and hormone content, combined with transcriptome analysis and quantitative fluorescence PCR validation, this study preliminarily elucidated the physiological mechanisms of plant-specific peroxidase (POD) in responding to enhanced UV-B radiation stress. Enhanced UV-B treatment significantly inhibited biological tissue growth, particularly during the rapid growth stage. At this stage, the treatment exhibited higher malondialdehyde (MDA) content, indicating increased oxidative stress due to the accumulation of reactive oxygen species (ROS). Despite the inhibition in growth, the treatment showed improvements in the accumulation of organic nutrients as well as the contents of abscisic acid (ABA), salicylic acid (SA), and methyl jasmonate (MeJA). Additionally, an increase in POD activity and lignin content was observed in the treatment, especially during the middle period of the rapid growth period. Transcriptome analysis revealed that two POD multigene family members, LOC123198833 and LOC123225298, were significantly upregulated under enhanced UV-B radiation, which was further validated through qPCR. In general, enhanced UV-B radiation triggered a defence response in biological tissue by upregulating POD genes, which can effectively help to scavenge excess ROS. Full article

Heat stress transcription factor (Hsf) families play important roles in abiotic stress responses. However, previous studies reported that HsfBs genes may play diverse roles in response to heat stress. Here, we conducted functional analysis on a woodland strawberry Class B Hsf gene, FvHsfB1a, to improve thermotolerance. The structure of FvHsfB1a contains a typical Hsf domain for DNA binding at the N-terminus, and FvHsfB1a belongs to the B1 family of Hsfs. The FvHsfB1a protein was localized in the nucleus. The FvHsfB1a gene was expressed in various strawberry tissues and highly induced by heat treatment. Under heat stress conditions, ectopic expression of FvHsfB1a in Arabidopsis improves thermotolerance, with higher germination and survival rates, a longer primary root length, higher proline and chlorophyll contents, lower malonaldehyde (MDA) and O²⁻ contents, better enzyme activities, and greater expression of heat-responsive and stress-related genes compared to WT. FvWRKY75 activates the promoter of the FvHsfB1a gene through recognizing the W-box element. Similarly, FvWRKY75-OE lines also displayed a heat-tolerant phenotype, exhibiting more proline and chlorophyll contents, lower MDA and O²⁻ contents, and higher enzyme activities under heat stress. Taken together, our study indicates that FvHsfB1a is a positive regulator of heat stress. Full article

Obesity remains a major global health challenge with limited therapeutic options. Bromelain, a proteolytic enzyme complex derived from pineapple, has been recognized for its natural anti-inflammatory, anti-edematous, and appetite-suppressing properties. This study aimed to investigate the effects of bromelain on hypothalamic neuropeptides and metabolic markers in a high-fat diet (HFD)-induced obesity model in rats. Thirty-six male Wistar albino rats were randomly divided into four groups: standard diet (SD), standard diet with bromelain (SDBro), high-fat diet (HFD), and high-fat diet with bromelain (HFDBro). Obesity was induced by a 3-month HFD regimen, followed by bromelain supplementation (200 mg/kg/day, orally) for one month. Hypothalamic tissues were analyzed via ELISA for neuropeptide Y (NPY), pro-opiomelanocortin (POMC), glucose transporter 2 (GLUT2), fibroblast growth factor 2 (FGF2), and insulin-like growth factor 1 receptor (IGF1R). While NPY levels showed no significant changes, POMC increased in the HFD and was normalized with bromelain. GLUT2 was downregulated in the HFD and significantly restored by bromelain. FGF2 levels remained unchanged. IGF1R was upregulated in the HFD but reduced by bromelain, with an unexpected increase in SDBro. Overall, bromelain partially reversed HFD-induced disruptions in hypothalamic energy-regulating pathways, particularly affecting GLUT2 and POMC. These findings highlight bromelain’s potential role in central metabolic regulation under dietary stress. Full article

Xyloglucan endotransglucosylase/hydrolases (XTHs) are a class of cell wall-associated enzymes involved in the construction and remodeling of cellulose/xyloglucan crosslinks. However, knowledge of this gene family in the model monocot Brachypodium distachyon is limited. A total of 29 BdXTH genes were identified from the whole genome, and these were further divided into three subgroups (Group I/II, Group III, and the Ancestral Group) through evolutionary analysis. Gene structure and protein motif analyses indicate that closely clustered BdXTH genes are relatively conserved within each group. A highly conserved amino acid domain (DEIDFEFLG) responsible for catalytic activity was identified in all BdXTH proteins. We detected three pairs of segmentally duplicated BdXTH genes and five groups of tandemly duplicated BdXTH genes, which played vital roles in the expansion of the BdXTH gene family. Cis-elements related to hormones, growth, and abiotic stress responses were identified in the promoters of each BdXTH gene, and when roots were treated with two abiotic stresses (salinity and drought) and four plant hormones (IAA, auxin; GA3, gibberellin; ABA, abscisic acid; and BR, brassinolide), the expression levels of many BdXTH genes changed significantly. Transcriptional analyses of the BdXTH genes in 38 tissue samples from the publicly available RNA-seq data indicated that most BdXTH genes have distinct expression patterns in different tissues and at different growth stages. Overexpressing the BdXTH27 gene in Brachypodium led to reduced root length in transgenic plants, which exhibited higher cellulose levels but lower hemicellulose levels compared to wild-type plants. Our results provide valuable information for further elucidation of the biological functions of BdXTH genes in the model grass B. distachyon. Full article

Cinnamaldehyde (CA) is a potential substitute for antibiotic growth promoters in animal breeding. In this study, we investigated its effects as a dietary supplement on growth performance, serum antioxidant capacity, intestinal digestive enzyme activities, intestinal morphology, and caecal microbiota in meat rabbits. Weaned meat rabbits (n = 450) were randomly assigned to five groups, Groups A, B, C, D, and E, and fed 0, 50, 100, 150, and 200 mg/kg CA diets, respectively, for 47 days. Biological samples including serum (antioxidants), duodenal/caecal content (enzymes), intestinal tissue (morphology), and caecal digesta (microbiota) were collected at day 47 postweaning for analysis. Groups C and D showed significantly higher final body weights than Group A, with Group D (150 mg/kg CA) demonstrating superior growth performance including 11.73% longer duodenal villi (p < 0.05), 28.6% higher microbial diversity (p < 0.01), and 62% lower diarrhoea rate versus controls. Digestive enzyme activity as well as serum antioxidant capacity increased with increasing CA dose, Microbiota analysis revealed CA increased fibre-fermenting Oscillospiraceae (+38%, p < 0.01) while reducing Ruminococcaceae (−27%, p < 0.05). Thus, dietary CA supplementation at 150 mg/kg was identified as the optimal CA dose for improving meat rabbit production. These findings highlight CA as a functional feed additive for promoting sustainable rabbit production. Full article

Barium chloride (BaCl₂), a known environmental pollutant, induces organ-specific oxidative stress through disruption of redox homeostasis. This study evaluated the protective effects and safety profile of sodium copper chlorophyllin (SCC) and ascorbic acid (ASC) against BaCl₂-induced oxidative damage in the liver and brain of mice using a two-phase experimental protocol. Animals received either SCC (40 mg/kg), ASC (160 mg/kg), or their combination for 14 days prior to BaCl₂ exposure (150 mg/L in drinking water for 7 days), allowing evaluation of both preventive and therapeutic effects. Toxicological and behavioral assessments confirmed the absence of systemic toxicity or neurobehavioral alterations following supplementation. Body weight, liver and kidney indices, and biochemical markers (Aspartate Aminotransferase (ASAT), Alanine Aminotransferase (ALAT), creatinine) remained within physiological ranges, and no anxiogenic or locomotor effects were observed. In the brain, BaCl₂ exposure significantly increased SOD (+49%), CAT (+66%), GPx (+24%), and GSH (+26%) compared to controls, reflecting a robust compensatory antioxidant response. Although lipid peroxidation (MDA) showed a non-significant increase, SCC, ASC, and their combination reduced MDA levels by 42%, 37%, and 55%, respectively. These treatments normalized antioxidant enzyme activities and GSH, indicating an effective neuroprotective effect. In contrast, the liver exhibited a different oxidative profile. BaCl₂ exposure increased MDA levels by 80% and GSH by 34%, with no activation of SOD, CAT, or GPx. Histological analysis revealed extensive hepatocellular necrosis, vacuolization, and inflammatory infiltration. SCC significantly reduced hepatic MDA by 39% and preserved tissue architecture, while ASC alone or combined with SCC exacerbated inflammation and depleted hepatic GSH by 71% and 78%, respectively, relative to BaCl₂-exposed controls. Collectively, these results highlight a differential, organ-specific response to BaCl₂-induced oxidative stress and the therapeutic potential of SCC and ASC. SCC emerged as a safer and more effective agent, particularly in hepatic protection, while both antioxidants demonstrated neuroprotective effects when used individually or in combination. Full article

Background: The candidate therapeutic peptide TnP demonstrates broad, system-level regulatory capacity, revealed through integrated network analysis from transcriptomic data in zebrafish. Our study primarily identifies TnP as a multifaceted modulator of drug metabolism, wound healing, proteolytic activity, and pigmentation pathways. Results: Transcriptomic profiling of TnP-treated larvae following tail fin amputation revealed 558 differentially expressed genes (DEGs), categorized into four functional networks: (1) drug-metabolizing enzymes (cyp3a65, cyp1a) and transporters (SLC/ABC families), where TnP alters xenobiotic processing through Phase I/II modulation; (2) cellular trafficking and immune regulation, with upregulated myosin genes (myhb/mylz3) enhancing wound repair and tlr5-cdc42 signaling fine-tuning inflammation; (3) proteolytic cascades (c6ast4, prss1) coupled to autophagy (ulk1a, atg2a) and metabolic rewiring (g6pca.1-tg axis); and (4) melanogenesis-circadian networks (pmela/dct-fbxl3l) linked to ubiquitin-mediated protein turnover. Key findings highlight TnP’s unique coordination of rapid (protease activation) and sustained (metabolic adaptation) responses, enabled by short network path lengths (1.6–2.1 edges). Hub genes, such as nr1i2 (pxr), ppara, and bcl6aa/b, mediate crosstalk between these systems, while potential risks—including muscle hypercontractility (myhb overexpression) or cardiovascular effects (ace2-ppp3ccb)—underscore the need for targeted delivery. The zebrafish model validated TnP-conserved mechanisms with human relevance, particularly in drug metabolism and tissue repair. TnP’s ability to synchronize extracellular matrix remodeling, immune resolution, and metabolic homeostasis supports its development for the treatment of fibrosis, metabolic disorders, and inflammatory conditions. Conclusions: Future work should focus on optimizing tissue-specific delivery and assessing genetic variability to advance clinical translation. This system-level analysis positions TnP as a model example for next-generation multi-pathway therapeutics. Full article

As the size of the elderly population increases, the need for an improved understanding of what leads to the age-related decline in physiological function continues to grow. SAMP8 mice were selected for their accelerated aging phenotype. The low levels of glyoxalase 1 (Glo1), the main enzyme that removes the reactive dicarbonyl methylglyoxal (MGO), in the cerebral cortex of SAMP8 mice prompted us to produce the first transgenic mice overexpressing Glo1 against the SAMP8 background, aimed at rescuing the accelerated aging phenotype. Selected health and biochemical endpoints were assessed in ten-month-old SAMP8 mice overexpressing Glo1. Glo1 overexpression increased median survival in males (21%) and females (4.6%), which was associated with better memory performance. Glo1 overexpression also increased synaptic markers (synaptophysin and SNAP25) as well as markers of mitochondrial function (NDUFB8, SDHB) and negative modulators of oxytosis/ferroptosis (NQO1, FTH1, and GPx4) in the cerebral cortex. For all parameters analyzed, the effect of Glo1 overexpression was more pronounced in males. Overall, the data support the beneficial effects of overexpressing Glo1 in multiple tissues, especially in SAMP8 males, suggesting a possible gender effect of MGO in aging. Both modulation of oxytosis/ferroptosis and mitochondrial metabolism warrant further investigation as potential mechanisms underlying the improved health span of Glo1 mice. Full article