Search Results (768)

Loquat (Eriobotrya japonica Lindl.) is a subtropical evergreen fruit tree that accumulates abundant bioactive triterpene compounds with diverse pharmaceutical activities. Its leaves have been used in traditional Chinese medicine for over 1000 years. Methyl jasmonate (MeJA) is a conserved elicitor that stimulates plant secondary metabolism. However, the regulatory mechanisms of terpenoid biosynthesis after MeJA treatment in loquat callus remain largely unknown. In this study, we employed an integrated targeted metabolomic and transcriptomic approach to investigate the effect of exogenous MeJA on terpenoid biosynthesis in loquat callus. In total, 131 terpenoid compounds were detected, including 112 triterpenes, six triterpene saponins, seven diterpenoids, three sesquiterpenoids and three monoterpenoids. After MeJA treatment, a total of 55 and 33 differential metabolites (DEMs) were identified at 24 h and 48 h, respectively. Most DEMs were triterpene compounds, displaying increased accumulation. Among them, ursolic acid showed the highest accumulation at 24 h, and betulinic acid was most abundant at 48 h. Meanwhile, transcriptome analysis showed significant upregulation of terpenoid biosynthesis genes, including EjFPSs, EjSQEs, EjOSC2 and EjCYP716A2, as well as genes related to jasmonic acid (JA)-mediated signaling and JA-responsive genes in loquat callus treated with MeJA. Overall, these results provide a deeper understanding of the mechanism of terpenoid accumulation in loquat callus induced by MeJA and establish a theoretical basis for utilizing plant cell culture techniques to achieve production of the valuable terpenoid metabolites that are applied in the functional food and pharmacological industries. Full article

Adult neurogenesis, the process of generating new, functional neurons in the mature central nervous system, represents a key mechanism of brain plasticity and a potential source of regeneration. This process occurs primarily within specialised neurogenic niches: the subgranular zone of the hippocampal dentate gyrus (SGZ) and the subependymal zone (SEZ). It is regulated by a complex network of endogenous factors (e.g., hormones, neurotrophins, growth factors) and exogenous factors (environment, stress, diet, physical activity). Impairments in neurogenesis are linked to the pathogenesis of neurodegenerative diseases, such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). In their course, chronic inflammation, mitochondrial dysfunction, oxidative stress, and the accumulation of pathological proteins (β-amyloid, Tau protein, α-synuclein) create a microenvironment that inhibits the proliferation, differentiation, and survival of new neurons. This results in the exacerbation of cognitive and memory deficits. A review of the literature indicates that modulating neurogenesis through non-pharmacological interventions (e.g., a diet rich in anti-inflammatory compounds, physical exercise) and targeted therapeutic strategies represents a promising, albeit complex, research avenue. The primary challenge remains not only stimulating neuron generation but also ensuring their proper maturation, survival, and functional integration into existing neuronal circuits. A deeper understanding of the molecular and environmental mechanisms regulating adult neurogenesis may open new therapeutic possibilities for slowing the progression of neurodegenerative diseases. Full article

Plant defence elicitors have emerged as pivotal components of sustainable fruit crop protection, aligning with One Health principles by reducing chemical residues while enhancing ecosystem and human health. These exogenous agents—ranging from phytohormones, peptides, and cell-wall fragments to botanical extracts—activate or prime innate immune responses in fruit crops through pattern-triggered immunity (PTI), systemic acquired resistance (SAR), and induced systemic resistance (ISR) pathways. Over the last decade, advances in receptor biochemistry, genomics, metabolomics, and epigenetics have transformed this field. Recent mechanistic advances reveal that oligosaccharide elicitors derived from chitosan and laminarin are perceived by membrane-localised pattern recognition receptors (PRRs) that confer broad-spectrum resistance against fungal, bacterial, and viral pathogens in fruits. By contrast, no specific protein receptor has been identified for harpin proteins, the emerging evidence indicating that harpin perception may occur through direct interaction with plasma-membrane lipids or lipid-associated proteins. The One Health approach is supported by elicitors, biodegradability, minimal environmental persistence, and the ability to reduce synthetic fungicide usage by 30–70%. However, challenges remain regarding batch-to-batch variability, sensory acceptance due to bitter compounds, regulatory hurdles for novel food approvals, and the need for optimised application protocols that consider the fruit genotype and developmental stage. The future integration of nanotechnology for targeted delivery, the artificial-intelligence-driven screening of active molecules, and synergistic combinations with biocontrol agents promises to overcome these limitations, positioning plant defence elicitors as cornerstone tools for resilient, health-promoting fruit production systems. Full article

The intensification of aquaculture often leads to dissolved oxygen depletion, posing a significant hypoxic stress to aquatic organisms such as the mudskipper (Boleophthalmus pectinirostris). Identifying compounds that can mitigate hypoxic damage is therefore of great importance. This study investigated the protective effects of puerarin and dexamethasone against acute hypoxic stress in mudskippers. Four experiment groups were formulated: fish in the control group (HC) and the hypoxia group (HH) were injected with NaCl, fish in the puerarin group (HP) were injected with puerarin, and fish in the dexamethasone group (HD) were injected with dexamethasone, then the HH, HP, and HD groups were treated with a hypoxia condition sustained for 48 h. Compared with the HC and HP groups, the HH group showed significantly reduced activities of protein kinase B (Akt), glycogen synthase kinase (GSK-3β), lactate dehydrogenase (LDH), and pyruvate kinase (PK) in the liver at 24 and 48 h. The gene transcription levels of GSK-3β and Akt in the liver and gill of mudskipper were the smallest, but p53, VEGF, HIF-1, and BNIP3 in the liver of fish in the HH group were significantly highest. The gene transcription levels of GSK-3β and Akt in the liver of mudskippers in the HP group were observably lower than those of mudskippers in the HD group at 24 h, but HIF-1 was significantly higher. On the contrary, at 48 h, the mRNA expression levels of GSK-3β and Akt in the liver of fish in the HP group were significantly higher than those of fish in the HD group, but HIF-1 was significantly lower. The results indicated that mudskippers suffering from hypoxia led to oxygen homeostasis disturbances and apoptosis, but exogenous puerarin or dexamethasone could mitigate the adverse effects. The mRNA of HIF-1 regulation has an important role in enhancing hypoxia tolerance. Full article

Brassinosteroids are recognized regulators of anthocyanin and proanthocyanidin biosynthesis in grapevine; however, their spatiotemporal effects remain insufficiently characterized. This study examined the stage-specific impacts of exogenous 24-epibrassinolide and brassinazole on these phenolic compounds in Cabernet Sauvignon. Treatments were applied at fruit set and veraison, with skin and seed tissues collected across six developmental stages. Berry ripening and quality parameters were evaluated, and phenolic profiles were quantified via HPLC. The results revealed that both 24-epibrassinolide and brassinazole significantly influenced grape maturation and phenolic biosynthesis in a timing-dependent manner. Specifically, 24-epibrassinolide application at fruit set increased the content of proanthocyanidins and trihydroxylated subunits, as well as the galloylation percentage, in both skins and seeds, while also altering their composition and subunit architecture. In contrast, veraison-stage treatment reduced these parameters in seeds but promoted them in skins, highlighting a tissue-specific response within the same developmental window. Moreover, compared with fruit-set treatment, 24-epibrassinolide application at veraison more significantly enhanced total anthocyanin content in skins, predominantly through the accumulation of specific monomeric forms. Together, based on two consecutive growing seasons (2022–2023) in Vitis vinifera L. cv. Cabernet Sauvignon, these findings demonstrate that brassinosteroid regulation of anthocyanin and proanthocyanidin biosynthesis in grape berries depends not only on the tissue but also on the phenological stage of application. In conclusion, this study reveals distinct spatiotemporal patterns in the regulation of phenolic biosynthesis by 24-epibrassinolide in grapevine, providing new insights into the hormone-mediated modulation of secondary metabolism and suggesting a potential agronomic strategy for precisely shaping the phenolic profile of wine grapes through stage-targeted brassinosteroid application. Full article

Cellular senescence (CSEN) is caused by a variety of factors that trigger complex molecular pathways. These include telomere shortening, oncogene activation and replicative stress, as well as DNA damage caused by genotoxic anticancer drugs and endogenous and exogenous genotoxins. Here, we review the induction of CSEN by exogenous genotoxic insults resulting from food and environmental exposures. The available data show that genotoxins/carcinogens in tobacco smoke and smokeless tobacco, in the environment, in food, beverages and life-style products induce CNS. The exposures include N-nitroso compounds, polycyclic aromatic hydrocarbons, heterocyclic aromatic amines, acrylamide, heavy metals, fine dust, mycotoxins, phytotoxins, and phycotoxins. Also, heme in red meat contributes to CSEN as it catalyzes the formation of genotoxic species in the colon. Induction of CSEN by external genotoxins/carcinogens is bound on the DNA damage response pathway (DDR), which relies on activation of the ATM/ATR-CHK2/CHK1-p53-p21 axis and the p53-independent p16/p14 axis, eliciting cyclin-dependent kinase inhibition and permanent cell cycle arrest. Other factors that can be involved are DREAM, MAPK, cGAS/Sting, and NF-κB. The accumulation of non-repaired DNA damage triggering CSEN following external genotoxic exposures may contribute significantly to the amelioration of senescent cells and organ failure with age in humans. Senescent cells drive, via the senescence-associated secretory phenotype (SASP), inflammation that is involved in many diseases, including cancer. Although most of the studies were performed with in vitro cell systems, the consequences of CSEN induction by genotoxic nutritional components and environmental exposures seem to be underestimated. Since CSEN correlates with aging, it is reasonable to conclude that exogenous genotoxic pollutants contribute significantly to the aging process through CSEN induction. In light of these findings, it is deduced that reducing genotoxin exposures and using “rejuvenation” supplements (senotherapeutics) are reasonable strategies to counteract cellular senescence and the aging process. Full article

The oxidative stability of meat products is a crucial factor determining quality, shelf life, and consumer acceptance, as lipid and protein oxidation promote undesirable changes in sensory attributes and nutritional content. Antioxidant capacity (AOC) assays such as total phenolic content (TPC), ferric reducing antioxidant power (FRAP), 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS^•+), and 2,2-diphenyl-1-picrylhydrazyl (DPPH^•) are commonly applied in meat systems to assess the AOC associated with both intrinsic muscle components (endogenous) and the protective effects of natural ingredients (exogenous added compounds), i.e., antioxidants. Although differences in analytical methodologies limit direct comparisons among studies, it has been demonstrated that meat products inherently contain compounds that modulate oxidative reactions, with their effectiveness influenced by meat type, processing, and storage conditions. Within this framework, natural ingredients, including plant- and fungal-derived ingredients and their by-products, have gained attention as sources of natural antioxidants, whose capacity depends on the extraction method, the solvent used, and their behavior during gastrointestinal digestion, as evaluated using simulated gastrointestinal digestion (sGD) models. Numerous studies have shown that incorporating natural extracts or powders into meat products enhances AOC during refrigerated storage, with the effect generally depending on the concentration used. Moreover, several natural antioxidant treatments maintain or even enhance their AOC when assessed under sGD conditions. Full article

The gut microbiota’s (GM) regulation of inflammation and oxidative stress is supported by existing evidence, and its dysregulation relates to brain disease. Indeed, probiotics and prebiotics have been shown to improve cognitive function. This is associated with a stronger gut and blood–brain barrier and less gut inflammation. Oligofructose-enriched inulin alters the GM, reduces body fat, and lowers interleukin-6 (IL-6) in obese patients. Moreover, by increasing glutathione (GSH), the ketogenic diet (KD) prevents seizures and also benefits the intestinal short-chain fatty acid (SCFA) profile. Given the evidence on managing epileptic conditions, the aim of this review is to assess how changing the gut microbiota (GM) can be a therapeutic method for preventing neurodegenerative dysfunctions associated with epileptic seizure onset and progression, with a focus on innovative supplement strategies, including endogenous and exogenous antioxidants, nutrition, and new phyto-therapies. Indeed, though drugs are the main treatment for epilepsy, the KD and other supplements are increasingly being considered. These compounds affect neuronal excitability, neurotransmitter release, and neuroinflammation, thus providing an anticonvulsant effect. Specifically, the KD prevents seizures by increasing GSH levels, which represents a crucial endogenous antioxidant that plays a key role in counteracting neuroinflammation and gut microbiota dysfunction. Furthermore, due to their antioxidant and anti-inflammatory properties, plant extract derivatives may be new agents that could reduce neuroinflammation in seizures, affecting the gut–brain axis (GBA) through the intestinal microbiota. In conclusion, data suggest that further clinical studies are needed to explore how the GM impacts epilepsy, and how specific nutraceuticals might offer probiotic benefits. Thus, a combined effect of nutraceuticals and functional food might be appealing, potentially resulting in a more beneficial therapeutic outcome. Full article

Pregabalin, as the active ingredient of various medications, is used in humans to treat generalized anxiety disorder (GAD), epilepsy, fibromyalgia, and neuropathic pain. In animals, pregabalin is used as an anesthetic. The aim of the present study was to test the effect of pregabalin on the developmental parameters of Sarcophaga argyrostoma (Robineau-Desvoidy, 1830) (Diptera: Sarcophagidae), a fly used in forensic entomology. A culture of S. argyrostoma larvae was conducted on mouse carcasses. Two doses of the active substance were used in the experiment: 100 mg/kg (dose 1) and 300 mg/kg (dose 2). A control sample (without the drug) was used for comparison. The duration of the life cycle, the body weight of individual developmental stages (larvae, pupae, and adults), and their mortality were studied. The study showed that (1) pregabalin prolonged the life cycle of S. argyrostoma—dose 1 by two days and dose 2 by three days; (2) pregabalin caused an increase in body weight at each stage of development (larvae, pupae, and adults); (3) pregabalin caused high mortality among pupae. The highest mortality was observed in the treatment with 300 mg/kg. The preliminary results indicate that estimation of the time of death based on analysis of the developmental stages of S. argyrostoma on a carcass with a high content of pregabalin may be distorted relative to a case without the impact of this exogenous substance. Research on the effect of pregabalin on flies used in forensic entomology should be expanded to investigate how this compound affects the life cycles of these insects. Full article

Multiple sclerosis (MS) is characterized by progressive mitochondrial dysfunction affecting complexes I, III, and IV of the electron transport chain, contributing to axonal energy failure and neurodegeneration. This review examines the potential of combining β-hydroxybutyrate (βHB), epigallocatechin-3-gallate (EGCG), and ellagic acid (EA) as a multi-target therapeutic strategy to restore mitochondrial function in patients with MS. Experimental and clinical studies demonstrate that each compound exerts complementary mechanisms. Ketone bodies provide an alternative energy substrate and restore complex I activity via sirtuin-dependent pathways. EGCG acts predominantly at the peripheral level by reducing systemic inflammation and oxidative stress. EA-derived urolithins effectively cross the blood–brain barrier to directly enhance mitochondrial biogenesis and respiratory chain function in the central nervous system. Clinical trials have reported improvements in fatigue, cognition, mood, and muscle function following supplementation with these compounds. The convergence of their actions on energy restoration, reactive oxygen species reduction, and epigenetic modulation of protective pathways suggests their synergistic potential. Optimized delivery strategies, including exogenous ketone salts, liposomal EGCG, and microencapsulated EA, may overcome bioavailability limitations and interindividual variability in the gut microbiota metabolism. Full article

Neutrophils are the most numerous population of peripheral blood leukocytes and play a key role in innate immunity, participating in antibacterial, antifungal, antiviral, and antitumor responses. Their activity can be modulated by endogenous and exogenous factors, including pesticides, among which fungicides such as the commonly used imazalil (IMZ) constitute a significant group. The objective of this study was to assess the effect of IMZ (at an environmental dose of 0.07 ng/mL, as well as 10- and 100-fold higher doses) on selected functions of neutrophils. This study demonstrated that neutrophils incubated with IMZ at a dose detectable in the serum, exhibited lower phagocytotic capacity. In addition, at a 10-fold higher dose, this compound reduced the chemotactic capacity of neutrophils and led to increased activity of NADPH oxidase in these cells. Furthermore, it was observed that at the highest concentration used in this study IMZ intensified the production of nitric oxide. The exposure of neutrophils—the first line of defense—to IMZ affected their locomotion and pathogen-eliminating function. Moreover, the response of neutrophils was not proportionate to the concentration of IMZ used in the study. Full article

Toxic Cd (cadmium) pollution in agricultural soil has been drawing global attention. Using exogenous regulators to detoxify Cd in crops is a promising approach to alleviate Cd stress and prevent Cd accumulation in human bodies through the food chain. Natural compounds show great potential due to their environmentally friendly properties. We have found that thymol (a plant-derived natural compound) protects plants from Cd stress. To extend the application of thymol in agriculture, further studies are needed to understand the detailed mechanism by which thymol induces Cd tolerance and limits Cd accumulation in crops. In this study, hydroponic experiments using the roots of Brassica rapa L. exposed to a nutrient solution containing Cd (3 µM) and thymol (15 µM) were conducted to investigate the mechanism of thymol-induced Cd tolerance. Pot experiments with different vegetables (B. rapa, water spinach, and pepper) growing in Cd-polluted soil (0.5 µM Cd) were carried out to investigate the role of foliar spraying of thymol (15 µM) in decreasing the Cd content in vegetables. In the hydroponic study, thymol enhanced the shoot fresh weight and root fresh weight of B. rapa by 313% and 125%, respectively, upon Cd exposure. Thymol detoxifies Cd-induced ROS accumulation by increasing the activity of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) in B. rapa by 8.9–33.6%, 12.9–31.6%, and 57.8–135%, respectively. The thymol-activated AsA-GSH (ascorbic acid-glutathione) cycle also contributed to the decrease in ROS level. Thymol also reduced the Cd content in the shoots and roots of B. rapa by 55.7% and 46.6%, respectively, which was associated with the modulation of the expression of a set of genes accounting for Cd accumulation and transport. In the pot study, foliar spraying of thymol significantly decreased the Cd content in various vegetables, including leafy vegetables (B. rapa and two water spinach varieties, with leaf Cd decreasing by 40.5–45.9%) and solanaceous fruits and vegetables (three pepper varieties, with fruit Cd decreasing by 26.9–35.8%), which was accompanied by a growth-promoting effect. The results from this study elucidate the multifaceted function of thymol in helping vegetables detoxify Cd and decrease Cd bioaccumulation, shedding new light on developing thymol as a potential plant regulator to safeguard agroproduct security in Cd-polluted environments. Full article

Introduction: The availability of toxicokinetic data is critical for detecting and monitoring the intake of psychoactive substances. Timely characterization of novel psychoactive substances (NPS) is particularly important to assess their abuse potential and inform public health responses. Methods: Toxicometabolomics offers a powerful approach to characterize xenobiotic metabolism through high-resolution profiling of biochemical transformations. It thus allows the finding of exogenous biomarkers, such as new drug metabolites, and endogenous biomarkers, which could be indications of acute drug ingestions or sample manipulation, as well as offering information on the mode of action of drugs. In this study, we applied a liquid chromatography–high-resolution mass spectrometry workflow to investigate the toxicometabolomics of two N1-sulfonated N,N-dimethyltryptamine derivatives with potential for both therapeutic use and recreational abuse. Results: Zebrafish (Danio rerio), an increasingly valuable model for preclinical pharmacology and toxicology studies, along with pooled human liver S9 fractions were used to elucidate metabolic pathways and identify key phase I and phase II biotransformations. Furthermore, untargeted metabolomics revealed significant downregulation of L-threonine associated with compound exposure. Conclusions: These findings advance the current understanding of tryptamine metabolism and underscore the utility of toxicometabolomics in the analytical evaluation of NPS. Full article

Drought is a slow-onset hazard whose economic impacts can propagate across sectors with multi-year delays. This study develops a non-linear autoregressive model with exogenous drought inputs (ARX) to assess whether U.S. drought severity, measured by the Drought Severity and Coverage Index (DSCI), contains incremental predictive information for monthly stock returns. Using weekly DSCI and stock price data from 2013 to 2023, we constructed monthly compound returns and multi-year drought lags spanning 1–5 years for four sector-representative firms: a water utility (American Water Works, AWK), two food service firms (Chipotle Mexican Grill, CMG; Starbucks, SBUX), and an industrial manufacturer (Tesla, TSLA). We compared regularized linear ARX baselines (Elastic Net, Ridge) with a non-linear Histogram Gradient Boosting Regressor (HGB) ARX model and used permutation importance to diagnose drought-relevant lag horizons. Results showed a clear, delayed drought signal for the water utility, with a dominant ~48-month drought lag, consistent with multi-year transmission through operations, regulation, and investment cycles. In contrast, drought lags added limited or unstable information for the food service firms and negligible information for TSLA, whose dynamics were dominated by non-drought drivers. Overall, the findings indicate that drought–return relationships are sector-specific and can emerge at multi-year lags, and that non-linear ARX models provide a flexible tool for detecting these delayed climate-risk signals. Full article

Blumea balsamifera (L.) DC. is the primary source plant of natural borneol, an important ethnic medicine in China. But its quality and yield are severely threatened by the polyphagous pest Spodoptera litura Fabricius during cultivation. In order to elucidate the mechanism of the chemical defense response induced by methyl jasmonate (MeJA) in B. balsamifera plants against S. litura. This study investigated the MeJA-mediated chemical defense in B. balsamifera against S. litura by integrating insect bioassays, enzymatic analysis, and metabolomics. Results demonstrated that exogenous MeJA application significantly inhibited larval feeding preference and consumption, suppressed relative growth rates, and reduced pupal weights. Physiologically, MeJA treatment rapidly upregulated the activities of jasmonic acid (JA) biosynthetic and antioxidant enzymes. Crucially, metabolomic profiling revealed that MeJA triggered a metabolic reconfiguration, specifically promoting the accumulation of defensive secondary metabolites. Notably, key bioactive compounds, including secoisolariciresinol diglucoside and isochlorogenic acid C, were significantly enriched alongside elevated endogenous JA levels. These findings suggest that MeJA enhances the resistance of B. balsamifera not merely by activating enzymatic defense but by reprogramming the phenylpropanoid and phenolic metabolic pathways. The above results indicate that exogenous MeJA can induce the activation of the chemical defense system in B. balsamifera plants and enhance their resistance to S. litura. Full article