Search Results (2,488)

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

Background/Objective: Sepsis-associated acute kidney injury (SA-AKI) is a substantial contributor to mortality in critically ill patients. This study aimed to investigate the impact of gum acacia (GA) and dexamethasone (DEX) combination on lipopolysaccharide (LPS)-induced SA-AKI in rats. Methods: Thirty-six male Sprague Dawley rats were separated into six groups, including the control, GA group, LPS-induced AKI group, DEX + LPS group, GA + LPS group, and GA + DEX + LPS group. AKI was induced in rats using LPS (10 mg/kg, i.p.). GA was administered orally (7.5 g/kg) for 14 days before LPS injection, and DEX was injected (1 mg/kg, i.p.) 2 h after LPS injection. Results: LPS injection significantly (p < 0.05, vs. control group) impaired renal function, as evidenced through increased levels of kidney function biomarkers, decreased creatinine clearance, and histopathological alterations in the kidneys. LPS also significantly (p < 0.05, vs. control group) elevated levels of oxidative stress markers, while it reduced levels of antioxidant enzymes. Furthermore, LPS triggered an inflammatory response, manifested by significant (p < 0.05, vs. control group) upregulation of Toll-like receptor 4, myeloid differentiation primary response 88, interleukin-1β, tumor necrosis factor-α, and nuclear factor-κB, along with increased expression of high-mobility group box 1. Administration of GA significantly ameliorated LPS-induced renal impairment by enhancing antioxidant defenses and suppressing inflammatory pathways (p < 0.05, vs. LPS group). Furthermore, GA-DEX-treated rats showed improved kidney function, reduced oxidative stress, and attenuated inflammatory markers (p < 0.05, vs. LPS group). Conclusions: The GA-DEX combination exhibited potent renoprotective effects against LPS-induced SA-AKI, possibly due to their antioxidant and anti-inflammatory properties. These results suggest that the GA-DEX combination could be a promising and effective therapeutic agent for managing SA-AKI. 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

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

Ischemic stroke is a serious disease that frequently occurs in the elderly and is characterized by a complex pathophysiology and a limited number of effective therapeutic agents. Salvianolic acid A (SAL-A) is a natural product derived from the rhizome of Salvia miltiorrhiza, which possesses diverse pharmacological activities. This study aims to investigate the effect and mechanisms of SAL-A in inhibiting ferroptosis to improve ischemic stroke. Brain injury, oxidative stress and ferroptosis-related analysis were performed to evaluate the effect of SAL-A on ischemic stroke in photochemical induction of stroke (PTS) in mice. Lipid peroxidation levels, antioxidant protein levels, tissue iron content, nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial morphology changes were detected to explore its mechanism. SAL-A significantly attenuated brain injury, reduced malondialdehyde (MDA) and long-chain acyl-CoA synthase 4 (ACSL4) levels. In addition, SAL-A also amplified the antioxidative properties of glutathione (GSH) when under glutathione peroxidase 4 (GPX4), and the reduction in ferrous ion levels. In vitro, brain microvascular endothelial cells (b.End.3) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R) were used to investigate whether the anti-stroke mechanism of SAL-A is related to Nrf2. Following OGD/R, ML385 (Nrf2 inhibitor) prevents SAL-A from inhibiting oxidative stress, ferroptosis, and mitochondrial dysfunction in b.End.3 cells. In conclusion, SAL-A inhibits ferroptosis to ameliorate ischemic brain injury, and this effect is mediated through Nrf2. Full article

Cardiovascular disease (CVD) and dementia may share common pathogenic factors such as atherosclerosis and hyperlipoproteinemia. Dyslipidemia-induced oxidative stress contributes to dementia comorbidity in CVD. Abelmoschus esculentus (AE, okra) potentiates in alleviating hyperlipidemia and diabetes-related cognitive impairment. This study evaluated the effects of AE in hyperlipidemic ApoE^−/− mice treated with streptozotocin (50 mg/kg) and fed a high-fat diet (17% lard oil, 1.2% cholesterol). AE fractions F1 or F2 (0.65 mg/kg) were administered for 8 weeks. AE significantly reduced serum LDL-C, HDL-C, triglycerides, and glucose, improved cognitive and memory function, and protected hippocampal neurons. AE also lowered oxidative stress markers (8-hydroxy-2′-deoxyguanosine, 8-OHdG) and modulated neuronal nuclei (NeuN) and doublecortin (DCX) expression. In vitro, AE promoted neurite outgrowth and neuronal differentiation in retinoic acid (RA)-differentiated human SH-SY5Y cells under metabolic stress (glucose and palmitate), alongside the upregulation of heme oxygenase-1 (HO-1), Nuclear factor-erythroid 2-related factor 2 (Nrf2), and brain-derived neurotrophic factor (BDNF). These findings suggest AE may counter cognitive decline via oxidative stress regulation and the enhancement of neuronal differentiation. Full article

Oxidative stress is a defining and pervasive driver of neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and amyotrophic lateral sclerosis (ALS). As a molecular accelerant, reactive oxygen species (ROS) and reactive nitrogen species (RNS) compromise mitochondrial function, amplify lipid peroxidation, induce protein misfolding, and promote chronic neuroinflammation, creating a positive feedback loop of neuronal damage and cognitive decline. Despite its centrality in promoting disease progression, attempts to neutralize oxidative stress with monotherapeutic antioxidants have largely failed owing to the multifactorial redox imbalance affecting each patient and their corresponding variation. We are now at the threshold of precision redox medicine, driven by advances in syndromic multi-omics integration, Artificial Intelligence biomarker identification, and the precision of patient-specific therapeutic interventions. This paper will aim to reveal a mechanistically deep assessment of oxidative stress and its contribution to diseases of neurodegeneration, with an emphasis on oxidatively modified proteins (e.g., carbonylated tau, nitrated α-synuclein), lipid peroxidation biomarkers (F2-isoprostanes, 4-HNE), and DNA damage (8-OHdG) as significant biomarkers of disease progression. We will critically examine the majority of clinical trial studies investigating mitochondria-targeted antioxidants (e.g., MitoQ, SS-31), Nrf2 activators (e.g., dimethyl fumarate, sulforaphane), and epigenetic reprogramming schemes aiming to re-establish antioxidant defenses and repair redox damage at the molecular level of biology. Emerging solutions that involve nanoparticles (e.g., antioxidant delivery systems) and CRISPR (e.g., correction of mutations in SOD1 and GPx1) have the potential to transform therapeutic approaches to treatment for these diseases by cutting the time required to realize meaningful impacts and meaningful treatment. This paper will argue that with the connection between molecular biology and progress in clinical hyperbole, dynamic multi-targeted interventions will define the treatment of neurodegenerative diseases in the transition from disease amelioration to disease modification or perhaps reversal. With these innovations at our doorstep, the future offers remarkable possibilities in translating network-based biomarker discovery, AI-powered patient stratification, and adaptive combination therapies into individualized/long-lasting neuroprotection. The question is no longer if we will neutralize oxidative stress; it is how likely we will achieve success in the new frontier of neurodegenerative disease therapies. Full article

Manganese (Mn) excess and low pH often coexist in some citrus orchard soils. Little information is known about the underlying mechanism by which raising pH reduces Mn toxicity in citrus plants. ‘Sour pummelo’ (Citrus grandis (L.) Osbeck) seedlings were treated with 2 (Mn2) or 500 (Mn500) μM Mn at a pH of 3 (P3) or 5 (P5) for 25 weeks. Raising pH mitigated Mn500-induced increases in Mn, iron, copper, and zinc concentrations in roots, stems, and leaves, as well as nitrogen, phosphorus, potassium, calcium, magnesium, sulfur, copper, iron, and zinc distributions in roots, but it mitigated Mn500-induced decreases in nitrogen, phosphorus, potassium, calcium, magnesium, sulfur, and boron concentrations in roots, stems, and leaves, as well as nutrient imbalance. Raising pH mitigated Mn500-induced necrotic spots on old leaves, yellowing of young leaves, decreases in seedling growth, leaf chlorophyll concentration, and CO₂ assimilation (A_CO2), increase in root dry weight (DW)/shoot DW, and alterations of leaf chlorophyll a fluorescence (OJIP) transients and related indexes. Further analysis indicated that raising pH ameliorated Mn500-induced impairment of nutrient homeostasis, leaf thylakoid structure by iron deficiency and competition of Mn with magnesium, and photosynthetic electron transport chain (PETC), thereby reducing Mn500-induced declines in A_CO2 and subsequent seedling growth. These results validated the hypothesis that raising pH reduced Mn toxicity in ‘Sour pummelo’ seedlings by (a) reducing Mn uptake, (b) efficient maintenance of nutrient homeostasis under Mn stress, (c) reducing Mn excess-induced impairment of thylakoid structure and PEPC and inhibition of chlorophyll biosynthesis, and (d) increasing A_CO2 and subsequent seedling growth under Mn excess. Full article

Salinization of olive orchards constitutes a front-line agronomic challenge for farmers, consumers, and the scientific community as food security, olive logistics, and land use become more unsustainable and problematic. Plantlets of two olive varieties (var. Kalamon and var. Koroneiki) were tested for their performance under soil saline conditions, in which L-methionine, choline-Cl, and L-proline betaine were applied foliarly to alleviate adverse effects. The ‘Kalamon’ variety ameliorated its photosynthetic rates when L-proline betaine and L-methionine were administered at low saline exposure. The stressed varieties achieved higher leaf transpiration rates in the following treatment order: choline-Cl > L-methionine > L-proline betaine. Choline chloride supported stomatal conductance in stressed var. Kalamon olives without this pattern, which was also followed by var. Koroneiki. Supplementation regimes created a mosaic of responses on varietal water use efficiency under stress. The total phenolic content in leaves increased in both varieties after exogenous application only at the highest levels of saline stress. None of the substances applied to olive trees could stand alone as a tool to mitigate salinity stress in order to be recommended as a solid agronomic practice. The residual exploitation of amino acids by the olive orchard microbiome must also be considered as part of an environmentally friendly, integrated strategy to mitigate salinity stress. Full article

Background: Acetaminophen (APAP) is a popular and safe pain reliever. Due to its widespread availability, it is commonly implicated in intentional or unintentional overdoses, which result in severe liver impairment. Pristimerin (Prist) is a natural triterpenoid that has potent antioxidant and anti-inflammatory properties. Our goal was to explore the protective effects of Prist against APAP-induced acute liver damage. Method: Mice were divided into six groups: control, Prist control, N-acetylcysteine (NAC) + APAP, APAP, and two Prist + APAP groups. Prist (0.4 and 0.8 mg/kg) was given for five days and APAP on day 5. Liver and blood samples were taken 24 h after APAP administration and submitted for different biochemical and molecular assessments. Results: Prist counteracted APAP-induced acute liver damage, as it decreased general liver dysfunction biomarkers, and attenuated APAP-induced histopathological lesions. Prist decreased oxidative stress and enforced hepatic antioxidants. Notably, Prist significantly reduced the genetic and protein expressions of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-II), p-phosphatidylinositol-3-kinase (p-PI3K), p-protein kinase B (p-AKT), and the inflammatory cytokines: nuclear factor kappa B (NF-κB), tumor necrosis factor-α (TNF-α), and interleukins-(IL-6 and IL-1β) in hepatic tissues. Additionally, the m-RNA and protein levels of the apoptotic Bcl2-associated X protein (BAX) and caspase-3 were lowered and the anti-apoptotic B-cell leukemia/lymphoma 2 (BCL-2) was increased upon Prist administration. Conclusion: Prist ameliorated APAP-induced liver injury in mice via its potent anti-inflammatory/antioxidative and anti-apoptotic activities. These effects were mediated through modulation of NF-κB/iNOS/COX-II/cytokines, PI3K/AKT, and BAX/BCL-2/caspase-3 signaling pathways. Full article

Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate the effect of a stress management protocol with diaphragmatic breathing (DB) and physiotherapy exercise on stress, body composition, cardiorespiratory and metabolic markers of children and adolescents with morbid obesity. Methods: The study included 31 children and adolescents (5–18 years old) with morbid obesity (22 in the intervention arm and 9 controls). All participants completed anxiety questionnaires and a self-perception scale. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), blood pressure (BP) and SpO₂ were measured. Fasting glucose, uric acid, triglycerides, HbA1c, (AST/SGOT), (ALT/SGPT), HDL, LDL, insulin, ACTH, cortisol, HOMA-IR, 17-OH, S-DHEA, SHBG were assessed, and anthropometric measurements were also performed. Results: In the intervention group, 4 months after the treatment, an improvement was noted in the BMI, BMI z-score, waist-to-height ratio, FEV1, SpO₂, pulse and systolic BP. HDL increased, ALT/SGPT and insulin resistance improved. Positive changes were observed in temporary and permanent stress and self-esteem of children in the intervention group, including anxiety, self-perception, physical appearance, etc. Conclusions: A combined exercise and DB protocol has a positive effect on stress, by improving body composition, reducing insulin resistance, and ameliorating physical and mental health and quality of life of pediatric patients with morbid obesity. Full article

Background: Aicardi-Goutières Syndrome (AGS) is a rare neuroinflammatory condition characterized by early-onset symptoms that extend outside the nervous system. Due to the rarity of the disease, the pathogenesis is not well understood, and its diagnosis and treatment remain elusive. We recently demonstrated mitochondrial abnormalities and increased reactive oxygen species (ROS) levels in lymphoblastoid cell lines (LCLs) derived from RNASEH2B- and RNASEH2A-mutated AGS patients. On this background, we turned our attention to metformin, the first-choice drug for type 2 diabetes, as a possible treatment acting on oxidative stress in RNASEH2-mutant AGS cells. Methods and Results: By means of flow cytometry, we found that metformin treatment significantly decreases ROS production in RNASEH2B- and RNASEH2A-mutated AGS LCLs. Of note, metformin treatment reduces the green JC-1 monomeric signal and, concurrently, increases the red JC-1 signal in both mutated LCLs, accounting for restoration of the mitochondrial membrane potential. Immunofluorescence staining shows a decrease in 8-oxoG levels only in RNASEH2B- mutated AGS LCLs. Finally, the significant upregulation of Forkhead Box O3 (FOXO3), cytochrome C somatic (CYCS), and superoxide dismutase 2 (SOD2) mRNA levels in RNASEH2B-mutated AGS LCLs after metformin treatment points to FOXO3 signaling as a possible mechanism to reduce oxidative stress. Conclusions: In conclusion, even if these pilot results need to be confirmed on a larger cohort, we shed light on metformin treatment as a valid approach to ameliorate oxidative stress-related inflammation in AGS patients. Full article

The present study focuses on investigating the contribution of puppetry as a pedagogical and psychosocial tool in special education, addressing the literature gap in the systematic documentation of the experiences of special education teachers, concerning its use in daily teaching practice. The main objective is to capture the way in which puppetry enhances the learning, social and therapeutic support of students with complex educational and psychosocial needs. The study employs a qualitative phenomenological approach, conducting semi-structured interviews with eleven special education teachers who integrate puppetry into their teaching. Qualitative data were analyzed using thematic analysis. The findings highlight that puppetry significantly enhances cognitive function, concentration, memory and language development, while promoting the active participation, cooperation, social inclusion and self-expression of students. In addition, the use of the puppet acts as a means of psycho-emotional empowerment, supporting positive behavior and helping students cope with stress and behavioral difficulties. Participants identified peer support, material adequacy and training as key factors for effective implementation, while conversely, a lack of resources and time is cited as a key obstacle. The integration of puppetry in everyday school life seems to ameliorate a more personalized, supportive and experiential learning environment, responding to the diverse and complex profiles of students attending special schools. Continuous training for teachers, along with strengthening the collaboration between the arts and special education, is essential for the effective use of puppetry in the classroom. Full article

Semen cryopreservation is associated with sperm vulnerability to oxidative stress and ice crystal-induced damage, adversely affecting in vitro fertilization (IVF) success. This study aimed to investigate the effects of freezing diluent supplemented with antioxidant limonin (Lim), myo-inositol (MYO), and the ice crystal formation inhibitor L-proline (LP) through sperm motility, morphological integrity, and antioxidant capacity. The Lim (150 mM), MYO (90 mM), and LP (100 mM) significantly ameliorated the quality of post-thaw sperm in Debao boar, and combined treatment of these agents significantly enhanced sperm motility, structural integrity, and antioxidant capacity compared with individual agents (p < 0.05). Notably, the combined use of these agents reduced glycerol concentration in the freezing diluent from 3% to 2%. Meanwhile, the integrity of the sperm plasma membrane, acrosome membrane, and mitochondrial membrane potential was significantly improved (p < 0.05), and the result of IVF revealed the total cell count of the blastocysts was also greater in the 2% glycerol group (p < 0.05). In conclusion, the newly developed freezing diluent for semen, by adding Lim (150 mM), MYO (90 mM), and LP (100 mM), can enhance the quality of frozen–thawed Debao boar sperm and reduce the concentration of glycerol from 3% to 2% as high concentrations of glycerol can impair the quality of thawed sperm and affect in vitro fertilization outcomes. In conclusion, the improved dilution solution formulated demonstrated efficacy in enhancing the quality of porcine spermatozoa following cryopreservation and subsequent thawing. Full article

Objectives: Saffron, a traditional Chinese medicine, is renowned for its pharmacological effects in promoting blood circulation, resolving blood stasis, regulating menstruation, detoxification, and alleviating mental disturbances. Trans-crocetin, its principal bioactive component, exhibits significant anti-hypoxic activity. The clinical development and therapeutic efficacy of trans-crocetin are limited by its instability, poor solubility, and low bioavailability. Conversion of trans-crocetin into trans-sodium crocetinate (TSC) enhances its solubility, stability, and bioavailability, thereby amplifying its anti-hypoxic potential. Methods: This study integrates network pharmacology with in vivo and in vitro validation to elucidate the molecular targets and mechanisms underlying TSC’s therapeutic effects against high-altitude acute lung injury (HALI), aiming to identify novel treatment strategies. Results: TSC effectively reversed hypoxia-induced biochemical abnormalities, ameliorated lung histopathological damage, and suppressed systemic inflammation and oxidative stress in HALI rats. In vitro, TSC mitigated CoCl₂-induced hypoxia injury in human pulmonary microvascular endothelial cells (HPMECs) by reducing inflammatory cytokines, oxidative stress, and ROS accumulation while restoring mitochondrial membrane potential. Network pharmacology and pathway analysis revealed that TSC primarily targets the EGFR/PI3K/AKT/NF-κB signaling axis. Molecular docking and dynamics simulations demonstrated stable binding interactions between TSC and key components of this pathway. ELISA and RT-qPCR confirmed that TSC significantly downregulated the expression of EGFR, PI3K, AKT, NF-κB, and their associated mRNAs. Conclusions: TSC alleviates high-altitude hypoxia-induced lung injury by inhibiting the EGFR/PI3K/AKT/NF-κB signaling pathway, thereby attenuating inflammatory responses, oxidative stress, and restoring mitochondrial function. These findings highlight TSC as a promising therapeutic agent for HALI. Full article