Search Results (5,296)

Obstructive sleep apnea (OSA), characterized by intermittent hypoxia (IH), is strongly associated with metabolic syndrome and metabolic dysfunction-associated steatotic liver disease (MASLD). IH exacerbates MASLD progression through oxidative stress, inflammation, and lipid accumulation. This study aims to investigate the impact of oxygen normalization on metabolic dysfunction in OSA patients using continuous positive airway pressure (CPAP) therapy, and in mice exposed to IH followed by a reoxygenation period. In the clinical study, 76 participants (44 OSA patients and 32 controls) were analyzed. OSA patients had higher insulin resistance, triglycerides, very low density lipoprotein (VLDL) content, and liver enzyme levels, along with a higher prevalence of liver steatosis. After 18 months of CPAP therapy, OSA patients showed significant improvements in insulin resistance, lipid profiles (total cholesterol and VLDL), liver function markers (AST and albumin), and steatosis risk scores (Fatty Liver Index and OWLiver test). In the experimental study, IH induced hepatic lipid accumulation, oxidative stress, and inflammation, and reoxygenation reversed these deleterious effects in mice. At the molecular level, IH downregulated fatty acid oxidation (FAO)-related genes, thus impairing the FAO process. Reoxygenation maintained elevated levels of lipogenic genes but restored FAO gene expression and activity, suggesting enhanced lipid clearance despite ongoing lipogenesis. Indeed, serum β hydroxybutyrate, a key marker of hepatic FAO in patients, was impaired in OSA patients but normalized after CPAP therapy, supporting improved FAO function. CPAP therapy improves lipid profiles, liver function, and MASLD progression in OSA patients. Experimental findings highlight the therapeutic potential of oxygen normalization in reversing IH-induced liver damage by FAO pathway restoration, indicating a metabolic reprogramming in the liver. Full article

To investigate the responses and mechanisms of slash pine under low orthophosphate (Pi) stress and to identify Pi-efficient lines, we analyzed 12 indices related to biomass, root traits, and tissue Pi concentration across 13 slash pine lines subjected to varying Pi treatments. The composite assessment value of low-phosphorus tolerance (D) was calculated by evaluating these 12 response indicators through principal component analysis, in conjunction with the fuzzy membership function method. Nine low-phosphorus tolerance factors (LPTFs)—including above-ground fresh weight (0.69), below-ground fresh weight (0.52), total root length (0.56), root surface area (0.63), root volume (0.67), above-ground Pi concentration (0.78), below-ground Pi concentration (0.52), bioconcentration factor (0.77), and P utilization efficiency (−0.76)—showed significant correlations with D (p < 0.05). Utilizing these nine LPTFs, cluster analysis classified the 13 lines into the following three groups according to their low-phosphorus (P) tolerance: high-P-efficient, medium-P-efficient, and low-P-efficient lines. Under low Pi and Pi-deficiency treatments, line 27 was identified as a high-P-efficient line, while lines 1, 6, and 9 were classified as low-P-efficient lines. Notably, eight genes (SPX1, SPX3, SPX4, PHT1;1, PAP23, SQD1, SQD2, NPC4) and five genes (SPX1, SPX3, SPX4, PAP23, SQD1) were significantly up-regulated in the roots and leaves of both line 27 and line 9 under low-phosphorus stress, respectively. However, the high-P-efficient line 27 exhibited a stronger regulatory capacity with a higher expression of two genes (SPX4, SQD2) in the roots and nine genes (SPX1, SPX3, SPX4, PHT1;1, PAP10, PAP23, SQD1, SQD2, NPC4) in the leaves under low Pi stress. These findings reveal differential responses to low Pi stress among slash pine lines, with line 27 displaying superior low-P tolerance, enabling better adaptation to low Pi environments and the maintenance of normal growth, development, and physiological activities. Full article

Blue mold of pome fruit, caused by Penicillium expansum, is controlled through postharvest applications of thiabendazole (TBZ), pyrimethanil (PYR), and fludioxonil (FDL). However, multi-fungicide-resistant isolates have emerged in the U.S. Pacific Northwest and their impact on decay control in long-term storage is unknown. This study evaluated the fitness of P. expansum isolates sensitive to all three postharvest fungicides (wild-types) and those resistant to TBZ (single-resistant), TBZ and PYR, or PYR and FDL (dual-resistant), and triple-resistant to the three fungicides. On nutrient-poor media, resistant isolates showed reduced conidial germination, whereas no significant differences were observed in germination, mycelial growth, or sporulation between phenotypes on nutrient-rich media at 1.5 and 20 °C. Regardless of their sensitivity phenotype, FDL-resistant isolates showed increased sensitivity to osmotic and oxidative stresses. Pathogenicity and virulence were not affected by the sensitivity phenotype on apples after six months of storage at 1.5 °C. Analysis of cumulative fitness changes indicated fitness loss under low-temperature in vitro and increased fitness under fungicide selection pressure on fruit in most resistant phenotypes. Gene expression analysis showed differential regulation of fitness-related genes, with most being up-regulated by TBZ. Overall, the results suggest that resistance in P. expansum may carry context-dependent fitness penalties, especially under high-stress conditions. Full article

To minimize the deleterious effects of oxidative stress and improve oocyte competence, we assessed the impact of melatonin during in vitro pre-maturation (pre-IVM) in bovine cumulus–oocyte complexes (COCs). We compared three groups: control (conventional IVM), pre-IVM control (without melatonin), and pre-IVM + MTn (with melatonin). The analyses included levels of reactive oxygen species (ROS), mitochondrial activity, oocyte lipid content, and the expression of genes related to oxidative stress and lipid metabolism in oocytes and cumulus cells. We also examined embryo quality by evaluating kinetics of development and gene expression. The pre-IVM + MTn group exhibited an increase (p ≤ 0.05) in ROS levels and a decrease (p ≤ 0.05) in lipid content, while maintaining mitochondrial activity similar (p > 0.05) to that of the control group. Regarding gene expression, the effect of pre-IVM, independent of melatonin, was characterized by a decrease in FABP3 transcripts in cumulus cells and reductions in GSS and NFE2L2 transcripts in oocytes (p ≤ 0.05). The pre-IVM + MTn group also displayed a decrease (p ≤ 0.05) in CAT and SOD2 transcript levels. In terms of embryonic development, the pre-IVM + MTn group achieved a higher blastocyst rate on D7 (p ≤ 0.05) compared to the control group (30.8% versus 25.8%), but with similar rates (p > 0.05) to the pre-IVM control group (30.8% versus 35.9%). However, there was a decrease in the levels of the PLAC8 transcript. This study indicates that, under the conditions tested, melatonin did not significantly benefit oocyte competence. Full article

Anthropogenic noise pollution is a significant global environmental issue that adversely affects the behavior, physiology, and auditory functions of aquatic species. However, studies on the effects of underwater noise on early developmental stages of fish remain scarce, particularly regarding the differential impacts of daytime versus nighttime noise exposure. In this study, zebrafish (Danio rerio) embryos were exposed to control group (no additional noise), daytime noise (100–1000 Hz, 130 dB, from 08:00 to 20:00) or nighttime noise (100–1000 Hz, 130 dB, from 20:00 to 08:00) for 5 days, and their embryonic development and oxidative stress levels were analyzed. Compared to the control group, the results indicated that exposure to both daytime and nighttime noise led to delays in embryo hatching time and a significant decrease in larval heart rate. Notably, exposure to nighttime noise significantly increased the larval deformity rate. Noise exposure, particularly at night, elevated the activities of catalase (CAT) and glutathione peroxidase (GPX), as well as the concentration of malondialdehyde (MDA), accompanied by upregulation of antioxidant-related gene expression levels. Nighttime noise exposure significantly increased the abnormality rate of otolith development in larvae and markedly downregulated the expression levels of otop1 related to otolith development regulation, while daytime noise exposure only induced a slight increase in the otolith abnormality rate. After noise exposure, the number of lateral neuromasts in larvae decreased slightly, yet genes (slc17a8 and capgb) related to hair cell development were significantly upregulated. Overall, this study demonstrates that both daytime and nighttime noise can induce oxidative stress and impair embryonic development of zebrafish, with nighttime noise causing more severe damage. Full article

With the rising concerns about climate change and continuous increase in the salinity of soil, it is essential to understand the C-cycling functioning of saline soil to better predict the ecological functions and health of soil. Microbes play critical roles in C-cycling. However, limited research has been conducted to understand the impact of soil salinity on the microbial functional genes involved in C-cycling. In this study, effects of varying soil salinity levels in wetlands on the C-cycling functions and diversity of soil microbes were investigated by metagenomic sequencing. The results showed a higher relative abundance of genes related to decomposition of easily degradable organic C at low salinity. On the other hand, higher abundance of genes participating in the decomposition of recalcitrant organic C were observed at high salinity. These findings indicate distinct metabolic bias of soil microbes based on the salinity levels. Proteobacteria and Actinobacteria were dominant in soils with low to medium salinity levels, while Bacteroidetes phyla was prominent in highly saline soils. Furthermore, partial least squares path modeling (PLS-PM) identified electrical conductivity, total nitrogen, and total phosphorus as key regulators of C-cycling gene expression. Overall, the present study highlights the intricate connections between salinity, microbial attributes, and carbon metabolism in soil, suggesting that the soil microbes adapt to saline stress through divergent eco-adaptations. The findings of this study highlight the significance of exploring these microbial interactions for effective management and conservation of saline wetlands. Full article

Tetrabromobisphenol A (TBBPA), a widely utilised brominated flame retardant, demonstrates toxicological effects in aquatic organisms. Tea polyphenols (TPs), natural compounds found in tea leaves, exhibit both antioxidant and anti-inflammatory activities. The kidney is one of the major metabolic organs in common carp and serves as a target organ for toxic substances. This study evaluated the therapeutic potential of TPs in mitigating TBBPA-induced nephrotoxicity in common carp. Common carp were exposed to 0.5 mg/L TBBPA in water and/or fed a diet supplemented with 1 g/kg TPs for 14 days. In vitro, primary renal cells were treated with 60 μM TBBPA and/or 2.5 μg/L TPs for 24 h. Methods included histopathology, TUNEL assay for apoptosis, ROS detection, and molecular analyses. Antioxidant enzymes (SOD, CAT) and inflammatory cytokines (IL-1β, IL-6, TNF-α) were quantified using ELISA kits. Results showed that TBBPA induced oxidative stress, and activated the ROS-PI3K/AKT-NF-κB pathway, thereby resulting in inflammatory responses. TBBPA upregulated apoptosis-related genes (Caspase-3, Bax, and Bcl-2) and induced apoptosis. TBBPA upregulated the expression of RIPK3/MLKL, thereby exacerbating necroptosis. TPs intervention significantly mitigated these effects by reducing ROS, suppressing NF-κB activation, and restoring antioxidant enzyme activities (SOD, CAT). Moreover, TPs attenuated apoptosis and necrosis in the carp kidney, thereby enhancing the survival ability and immunity of common carp. Full article

The amygdala is composed of several nuclei, including the lateral nucleus which is the main receiving area for the input from cortical and subcortical brain regions. It mediates fear, anxiety, stress, and pain across species. Evidence suggests that the endocannabinoid system may be a promising target for modulating these processes. Cannabinoid and cannabinoid-related receptors have been identified in the amygdala of rodents, carnivores, and humans, but not in horses. This study aimed to investigate the gene expression of cannabinoid receptors 1 (CB1R) and 2 (CB2R), transient receptor potential vanilloid 1 (TRPV1), and peroxisome proliferator-activated receptor gamma (PPARγ) within the lateral nucleus of six equine amygdalae collected post mortem from an abattoir using quantitative real-time PCR, cellular distribution, and immunofluorescence. mRNA expression of CB1R and CB2R, but not TRPV1 or PPARγ, was detected. The percentage of immunoreactivity (IR) was calculated using ImageJ software. Cannabinoid receptor 1 immunoreactivity was absent in the somata but was strongly detected in the surrounding neuropil and varicosities and CB2R-IR was observed in the varicosities; TRPV1-IR showed moderate expression in the cytoplasm of somata and processes, while PPARγ-IR was weak-to-moderate in the neuronal nuclei. These findings demonstrate endocannabinoid system components in the equine amygdala and may support future studies on Cannabis spp. molecules acting on these receptors. Full article

The present study aimed to standardize germinated oat extracts (GOEs) by profiling avenanthramides (AVNs) and phenolic acids and evaluate their neuroprotective effects against Aβ_1-42-induced cytotoxicity in human neuroblastoma (SH-SY5Y) cells. GOEs were standardized to contain 1652.56 ± 3.37 µg/g dry weight (dw) of total AVNs, including 468.52 ± 17.69 µg/g AVN A, 390.33 ± 10.26 µg/g AVN B, and 641.22 ± 13.89 µg/g AVN C, along with 490.03 ± 7.83 µg/g dw of ferulic acid, using a validated analytical method. Treatment with AVN C and GOEs significantly inhibited Aβ_1-42-induced cytotoxicity (p < 0.05). Furthermore, both AVNs and GOEs markedly reduced Aβ_1-42-induced reactive oxygen species (ROS) generation in SH-SY5Y cells, showing significant scavenging activity at concentrations of 25 μg/mL (AVNs) and 50 μg/mL (GOEs) (p < 0.05). RT-PCR analysis revealed that AVNs and GOEs effectively downregulated the expression of inflammation- and apoptosis-related genes triggered by Aβ_1-42 exposure. These findings suggest that GOEs rich in AVNs may serve as a potential functional ingredient for enhancing memory function through the inhibition of neuroinflammation and oxidative stress. Full article

Ferroptosis is a distinct form of regulated cell death driven by iron-dependent lipid peroxidation participating in various diseases. The nuclear factor erythroid 2-related factor 2 (Nrf2) is a central regulator of cellular redox homeostasis and a key determinant of ferroptosis resistance. Nrf2 activates the expression of downstream antioxidant genes to protect cells from oxidative stress and ferroptosis. Consequently, precise regulation of Nrf2 expression is crucial. Recent studies have revealed that complex epigenetic mechanisms involving DNA methylation, histone modifications, and non-coding RNA networks regulate Nrf2 expression. DNA methylation usually suppresses while histone acetylation promotes Nrf2 expression. The influences of histone methylation on NFE2L2 are site- and methylation degree-dependent. m6A modification stabilizes NFE2L2 mRNA to promote Nrf2 expression and thereby inhibit ferroptosis. This article summarizes current understanding of the epigenetic mechanisms controlling Nrf2 expression and Nrf2-mediated ferroptosis pathways and their implications in disease models. The challenges associated with the epigenetic regulation of Nrf2 and future research directions are also discussed. A comprehensive understanding of this regulatory interplay could open new avenues for intervention in ferroptosis-related diseases by fine-tuning cellular redox balance through the epigenetic modulation of Nrf2. Full article

Premature ovarian insufficiency (POI) is an important factor in female infertility and is often associated with oxidative stress. Alginate oligosaccharides (AOSs), derived from the degradation of alginate, have been demonstrated to have protective effects against various oxidative stress-related diseases. However, the impact of AOSs on POI has not been previously explored. The current study explored the effects of AOSs on ovarian dysfunction in a mouse model of POI induced by D-galactose (D-gal). Female C57BL/6 mice were randomly divided into five groups: the control (CON), POI model (D-gal), and low-, medium-, and high-dose AOS groups (AOS-L, 100 mg/kg/day; AOS-M, 150 mg/kg/day; AOS-H, 200 mg/kg/day). For 42 consecutive days, mice in the D-gal, AOS-L, AOS-M, and AOS-H groups received daily intraperitoneal injections of D-gal (200 mg/kg/day), whereas those in the CON group received equivalent volumes of sterile saline. Following D-gal injection, AOSs were administered via gavage at the specified doses; mice in the CON and D-gal groups received sterile saline instead. AOS treatment markedly improved estrous cycle irregularities, normalized serum hormone levels, reduced granulosa cell apoptosis, and increased follicle counts in POI mice. Moreover, AOSs significantly reduced ovarian oxidative stress and senescence in POI mice, as indicated by lower levels of malondialdehyde (MDA), higher activities of catalase (CAT) and superoxide dismutase (SOD), and decreased protein expression of 4-hydroxynonenal (4-HNE), nitrotyrosine (NTY), 8-hydroxydeoxyguanosine (8-OHdG), and p16 in ovarian tissue. Analysis of the gut microbiota through 16S rRNA gene sequencing and short-chain fatty acid (SCFA) analysis revealed significant differences in gut microbiota composition and SCFA levels (acetic acid and total SCFAs) between control and D-gal-induced POI mice. These differences were largely alleviated by AOS treatment. AOSs changed the gut microbiota by increasing the abundance of Ligilactobacillus and decreasing the abundance of Clostridiales, Clostridiaceae, Marinifilaceae, and Clostridium_T. Additionally, AOSs mitigated the decline in acetic acid and total SCFA levels observed in POI mice. Notably, the total SCFA level was significantly correlated with the abundance of Ligilactobacillus, Marinifilaceae, and Clostridium_T. In conclusion, AOS intervention effectively mitigates ovarian oxidative stress, restores gut microbiota homeostasis, and regulates the microbiota–SCFA axis, collectively improving D-gal-induced POI. Therefore, AOSs represent a promising therapeutic strategy for POI management. Full article

The deterioration of uterine calcium transport capacity induced by aging is a common problem for late-laying period hens, causing decline in eggshell quality. This study aimed to investigate the effects and possible regulatory mechanisms of dietary puerarin (PU) on calcium transport and eggshell quality in aged hens. Two hundred eighty-eight Hubbard Efficiency Plus broiler breeder hens (50-week-old) were randomly allocated to three dietary treatments containing 0, 40, or 200 mg/kg puerarin (PU), with 8 replicates of 12 birds each, for an 8-week trial. The results demonstrated that dietary PU ameliorated the eggshell thickness and strength, which in turn reduced the broken egg rate (p < 0.05). Histological analysis showed that PU improved uterus morphology and increased epithelium height in the uterus (p < 0.05). Antioxidative capacity was significantly improved via upregulation of Nrf2, HO-1, and GPX1 mRNA expression in the uterus (p < 0.05), along with enhanced total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-PX) activity, and decreased levels of the oxidative stress marker malondialdehyde (MDA) (p < 0.05). Meanwhile, PU treatment reduced the apoptotic index of the uterus, followed by a significant decrease in expression of pro-apoptotic genes Caspase3 and BAX and the rate of BAX/BCL-2. Additionally, calcium content in serum and uterus, as well as the activity of Ca²⁺-ATPase in the duodenum and uterus, were increased by dietary PU (p < 0.05). The genes involved in calcium transport including ERα, KCNA1, CABP-28K, and OPN in the uterus were upregulated by PU supplementation (p < 0.05). The 16S rRNA gene sequencing revealed that dietary PU supplementation could reverse the age-related decline in the relative abundance of Bacteroidota within the uterus (p < 0.05). Overall, dietary PU can improve eggshell quality and calcium transport through enhanced antioxidative defenses and mitigation of age-related uterine degeneration. Full article

Fungicides are compounds with potentially toxic effects on the human body, but the molecular mechanisms of their action have not yet been explained. The effect of cyprodinil on cell viability, apoptosis level, cell membrane function, cell morphology and expression of antioxidant enzyme genes in the A-375 and DLD-1 cell lines was examined. The cell lines were selected because they can be an excellent in vitro model of neoplastic changes occurring in the skin and large intestine after exposure to a fungicide. The fungicide selected for the study is commonly used in Poland to protect crops against fungi. Our results showed that the tested compound increased cell viability and proliferation, probably activated by mechanisms related to oxidative stress. Cyprodinil caused an increase in glutathione level (in A-375 by about 37% and in DLD-1 by about 28%) and oxidative stress enzymes activity, but not in apoptosis level. Its membrane interactions and its penetration into cells was concentration dependent. It is worth emphasizing that the novelty of our work lies in the use of non-traditional toxicological methods based on molecular analyses using human cell lines. This allowed us to demonstrate not only the toxicity of a single substance but also its behavior within cellular structures. Our findings suggest that cyprodinil may have tumor-promoting properties in skin and colorectal cancer cells. Full article

Melanoma is a highly aggressive skin cancer with limited therapeutic response. Targeting intracellular signaling pathways and promoting tumor cell differentiation are promising therapeutic strategies. Pentoxifylline (PTX) and norcantharidin (NCTD) have demonstrated antitumor properties, but their combined mechanisms of action in melanoma remain poorly understood. The effects of PTX (30 and 60 mg/kg) and NCTD (0.75 and 3 mg/kg), administered alone or in combination, in a DBA/2J murine B16-F1 melanoma model via intraperitoneal and intratumoral (IT) routes were evaluated. Tumor growth was monitored, and molecular analyses included RNA sequencing and immunofluorescence quantification of PI3K, AKT1, mTOR, ERBB2, BRAF, and MITF protein levels, and molecular docking simulations were performed. In the final stage of the experiment, combination therapy significantly reduced tumor volume compared to monotherapies, with the relative tumor volume decreasing from 18.1 ± 1.2 (SD) in the IT Control group to 0.6 ± 0.1 (SD) in the IT combination-treated group (n = 6 per group; p < 0.001). RNA-seq revealed over 3000 differentially expressed genes in intratumoral treatments, with enrichment in pathways related to oxidative stress, immune response, and translation regulation (KEGG and Reactome analyses). Minimal transcript-level changes were observed for BRAF and PI3K/AKT/mTOR genes; however, immunofluorescence showed reduced total and phosphorylated levels of PI3K, AKT1, mTOR, BRAF, and ERBB2. MITF protein levels and pigmentation increased, especially in PTX-treated groups, indicating enhanced melanocytic differentiation. Docking analyses predicted direct binding of both drugs to PI3K, AKT1, mTOR, and BRAF, with affinities ranging from −5.7 to −7.4 kcal/mol. The combination of PTX and NCTD suppresses melanoma progression through dual mechanisms: inhibition of PI3K/AKT/mTOR signaling and promotion of tumor cell differentiation. Full article

Selenium stress can adversely affect plants by inhibiting growth, impairing oxidative stress resistance, and inducing toxicity. In this experiment, we investigated the effect of exogenous 24-epibrassinolide (24-EBL; 2.0 mg/L), a brassinosteroid (BR), on alleviating selenium stress in peach trees by analyzing its impact on biomass, selenium accumulation, and the expression of selenium metabolism-related genes in peach seedlings. The results demonstrated that 24-EBL could effectively mitigate biomass loss in peach seedlings exposed to selenium stress. Compared to the Se treatment alone, the 24-EBL+Se treatment resulted in a significant 16.55% increase in root selenium content and a more pronounced 30.39% increase in selenium content in the aboveground parts. Regarding the subcellular distribution, the cell wall was the primary site of Se deposition, accounting for 42.3% and 49.8% in the root and aboveground parts, respectively, in the Se treatment. 24-EBL further enhanced Se distribution at this site, reaching 42.9% and 63.2% in root and aboveground parts, respectively, in the 24-EBL+Se treatment. The 24-EBL+Se treatment significantly increased the contents of different chemical forms of Se, including ethanol-soluble, water-soluble, and salt-soluble Se. The quantitative real-time PCR (qRT-PCR) results indicated that the Se treatment promoted the expression of organic Se assimilation genes (SATs, OAS-TL B, and OAS-TL C), and 24-EBL application further increased their expression. Meanwhile, the Se-only treatment up-regulated the organic Se metabolism gene CGS1. Consequently, we propose that 24-EBL alleviates Se stress in peach seedlings by enhancing Se uptake and assimilation, and by adjusting subcellular distribution and chemical forms. Full article