Search Results (17,201)

Ethanol is a pervasive chemical stressor in fermentative environments and represents a major ecological challenge for Drosophila melanogaster, a species that naturally inhabits decaying fruits. Although ethanol tolerance has traditionally been attributed to detoxification and antioxidant pathways, accumulating evidence indicates that immune-related genes, particularly those encoding immune deficiency (IMD) pathway-associated antimicrobial peptides (IMD-AMPs), contribute importantly to chemical stress adaptation. Previous studies have demonstrated that IMD-AMP induction is required for ethanol tolerance; however, whether elevated IMD-AMP expression alone is sufficient to enhance tolerance has remained unresolved. In this study, we investigated the functional significance of IMD-AMP upregulation in ethanol tolerance using dietary propolis as an experimental immune-modulating agent. D. melanogaster were reared throughout their life cycle on propolis-supplemented diets and subsequently exposed to ethanol. Propolis-fed flies exhibited significantly enhanced survival under ethanol stress compared with control flies. Notably, this increased tolerance was not accompanied by upregulation of classical ethanol metabolism genes or broad induction of antioxidant-related genes. Instead, propolis feeding increased baseline and early-stage expression of IMD-AMP genes, including Diptericin A (DptA), Diptericin B (DptB), Attacin (AttC), and Metchnikowin (Mtk) before and during ethanol exposure. These findings suggest IMD-AMP upregulation is positively associated with enhanced ethanol tolerance in D. melanogaster. Our results establish a proactive role for immune-related pathways in chemical stress resistance and extend the functional scope of AMPs beyond pathogen defense. This study identifies IMD-AMPs as key effectors linking immune activation to physiological adaptation under ethanol-induced chemical stress. Full article

To maintain homeostatic conditions and optimal function during stressors, mitochondria initiate retrograde signaling. The mitochondrial integrated stress response (ISR) and unfolded protein response (UPR^mt) are critical quality control mechanisms activated during instances of mitochondrial perturbations. Restoration of mitochondrial homeostasis is orchestrated by three transcription factors, ATF4, CHOP, and ATF5, which upregulate protective genes to counteract stress. As the health and function of skeletal muscle are heavily dependent on a highly adaptive mitochondrial network, defining how mitochondrial health is maintained across various conditions is essential. Although several studies demonstrate the importance of these responses following instances of stress, the signaling mechanisms required to initiate such pathways remain poorly characterized in skeletal muscle. This review examines how the mitochondrial ISR/UPR^mt and related transcription factors respond to organellar stress by emphasizing the molecular events that occur during exercise, aging and muscle disuse. By consolidating the literature, this work aims to highlight the current understanding of mitochondrial stress response signaling within skeletal muscle and thus emphasize areas for future research and potential therapeutic strategies during divergent metabolic conditions. Full article

Obesity is a major global health challenge characterized by chronic low-grade inflammation, oxidative stress, and an increased risk of cardiometabolic disorders. Although sex-related differences in inflammatory and redox biomarkers have been reported in obese populations, the molecular mechanisms underlying this heterogeneity remain incompletely understood. In this study, we applied a proteomics-based approach to investigate urinary extracellular vesicles from 45 obese individuals (BMI 30–40 kg/m²; age 50–70 years) in order to identify molecular signatures associated with metabolic dysregulation. Shotgun proteomics analysis performed by nanoLC–MS/MS enabled the identification of 3822 proteins. Hierarchical clustering of proteomic profiles revealed two distinct molecular groups, predominantly enriched in males (Group I) and females (Group II). Label-free quantitative analysis identified 466 differentially abundant proteins between the two clusters. Functional enrichment analysis highlighted pathways associated with immune response, metabolic regulation, and redox homeostasis, including glycolysis/gluconeogenesis, lysosome activity, leukocyte transendothelial migration, and glutathione, cysteine and methionine metabolism. Notably, proteins related to ferroptosis were enriched, suggesting the involvement of iron-dependent oxidative cell death mechanisms in the metabolic imbalance observed in a subset of subjects. Furthermore, the non-enzymatic glycosylation of urinary proteins was significantly higher in Group I compared with Group II (p = 0.0002), indicating increased formation of advanced glycation products in individuals with a more pronounced pro-oxidant state. Preliminary follow-up data suggested a higher incidence of pathological events, including cardiovascular complications, among individuals belonging to Group I. Overall, these findings demonstrate that urinary proteomic profiling can identify distinct molecular phenotypes among obese individuals and highlight oxidative stress, ferroptosis, and protein glycation as potential determinants of metabolic vulnerability, supporting the use of non-invasive proteomic approaches for improved risk stratification in obesity. Full article

Exposure to air pollution is linked to adverse health outcomes. To better reflect real-world conditions, we employed a mobile exposure system enabling direct field exposure of the human airway epithelial model MucilAir™ to ambient air in a traffic-burdened locality. This study represents a follow-up to our previous work, in which a 5-day exposure period under extreme traffic-related pollution conditions resulted in premature cell loss. Under different meteorological conditions characterized by increased precipitation and lower particle number concentrations, MucilAir™ cultures were exposed to traffic-polluted air for 2 days. The exposure resulted in a mild but significant increase in cytotoxicity markers, including lactate dehydrogenase release and elevated levels of 15-F_2t-isoprostane, indicating induction of the cellular stress response rather than severe cytotoxicity. A transcriptomic analysis revealed extensive gene expression changes; the enrichment of the pathways related to polycyclic aromatic hydrocarbon detoxification and amino acid biosynthesis suggests adaptive metabolic responses to oxidative and genotoxic stress. In parallel, the pathways associated with epithelial proliferation and repair, extracellular matrix organization, focal adhesion, and immune signaling were suppressed, indicating potential disruption of the epithelial homeostasis. Overall, these findings demonstrate that 2 days of exposure to real-world traffic-polluted air elicits adaptive stress responses in airway epithelial cells while simultaneously impairing the processes essential for epithelial integrity, potentially leading to airway dysfunction. Full article

Precision nano-fertilization offers transformative potential for sustainable improvement of grape quality, yet the underlying molecular mechanisms remain poorly understood. Here, we investigated the effects of foliar-applied nano zero-valent iron (nZVI) and potassium dihydrogen phosphate (KH₂PO₄), in combination, on berry quality and secondary metabolic reprogramming in Vitis vinifera cv. Marselan. The combined nZVI/KH₂PO₄ treatment improved photosynthetic capacity, Fe/P co-accumulation, and berry quality traits including soluble solid content, sugar–acid ratio, and phenolic and aroma metabolite profiles. Crucially, integrated transcriptomic and metabolomic profiling identified 631 differentially expressed genes and 838 differentially accumulated metabolites, converging on flavonoid biosynthesis and glutathione metabolism as the dominant regulatory axes. Correlation network analysis pinpointed five hub regulatory genes—VvHCT, VvFLS1, VvLAR1/2, VvUGT88F5, and VvODC—as central orchestrators of nanomaterial-driven metabolic reprogramming: VvHCT and VvFLS1 coordinately redirected carbon flux toward hydroxycinnamic acid conjugates and flavonol accumulation, while VvLAR1/2 governed proanthocyanidin polymerization, and VvUGT88F5 modulated glycosylation-dependent metabolite stabilization. Notably, VvODC linked polyamine metabolism to glutathione-mediated stress buffering, revealing a previously uncharacterized crosstalk between nano-iron signaling and antioxidant reprogramming. These findings establish a mechanistic framework in which nZVI and KH₂PO₄ synergistically remodel the secondary metabolome through discrete yet interconnected transcriptional nodes, providing molecular targets for nano-enabled precision viticulture and broader applications of engineered nanomaterials in high-value crop improvement. Full article

Heat stress is a major constraint to productivity and physiological homeostasis in laying hens. This study investigated integrated responses to acute heat stress using a multi-omics approach, including performance traits, serum biochemical parameters, histology, hepatic transcriptomics, cecal metagenomics, and metabolomics. Acute heat stress impaired productive performance, as reflected by changes in egg production and reduced eggshell strength, and induced systemic physiological disturbances, including increased stress- and injury-related blood indicators and disrupted metabolic and electrolyte balance. Histological analysis confirmed liver and intestinal tissue damage. Hepatic transcriptomics revealed inflammatory activation and suppression of metabolic pathways, particularly those involved in lipid metabolism, energy production, and redox homeostasis. Cecal metagenomic and metabolomic analyses showed altered microbial composition and functional potential, along with disruptions in amino acid, lipid, and energy metabolism. Collectively, these findings suggest that acute heat stress is associated with coordinated inflammatory responses and metabolic reprogramming, together with liver and intestinal injury and gut microbiota–metabolite alterations. The study provides a framework for understanding early heat stress responses and highlights potential targets for nutritional and microbiota-based interventions in poultry production. Importantly, serum biochemical indicators such as D-lactic acid and aspartate aminotransferase may serve as potential early biomarkers for monitoring heat-stress-induced physiological disturbances. Full article

Chloroplasts are the primary sites of photosynthesis, but growing evidence highlights their broader role as central hubs that coordinate plant responses to environmental challenges. They retain a semi-autonomous genetic system and communicate extensively with the nucleus through anterograde and retrograde signalling pathways, enabling coordinated cellular regulation. Beyond energy conversion, chloroplasts host key biosynthetic pathways and dynamically adjust their metabolic and redox states in response to developmental and environmental cues. This review summarizes the current knowledge of chloroplast functions in response to abiotic and biotic stresses, emphasizing their contribution to plant resilience, productivity and sustainability. Under abiotic stress, chloroplasts undergo structural, metabolic and redox reprogramming to maintain photosynthetic efficiency and metabolic homeostasis. During biotic stress, they act as a powerful signalling platform that integrates immune responses with metabolic and redox regulation. These functions rely on overlapping signalling pathways that are differentially tuned to support acclimation or defence. By coordinating stress responses with photosynthetic activity and metabolic efficiency, chloroplasts play a central role in sustaining plant productivity and represent promising targets for enhancing crop resilience and agricultural sustainability under climate change and increasing pathogen pressure. Full article

This study aimed to investigate the regulatory effect and cryoprotective mechanism of melatonin (MT) on the physiological functions of Lactobacillus plantarum FQR during freezing and freeze-drying. Results indicated that the addition of 5 mg/mL MT as a cryoprotectant maximized the freeze-drying survival rate to 32.04 ± 2.14%. MT effectively alleviated low-temperature and freeze-drying stress by reducing extracellular alkaline phosphatase activity, enhancing intracellular lactate dehydrogenase activity, and decreasing extracellular β-galactosidase activity without significant differences. Higher survival rates in defining medium further suggested that MT reduced damage to cell wall and membrane structures during lyophilisation, decreased membrane permeability, and preserved cellular physiological functions. In addition, MT supported cellular energy metabolism and protein synthesis, enhanced transmembrane potential to facilitate ATP transport, and helped maintain intracellular and extracellular pH balance. The prepared freeze-drying protectant containing 69.80 mg/mL exopolysaccharides (EPS) and 4.25 mg/mL MT showed better protective effects than the control group. MT also increased bound water content, lowered the freezing point of the solution, and inhibited ice crystal formation. Transcriptomic analysis revealed that amino acid biosynthesis, amino acid metabolism, and ABC transport systems were the primary pathways affected by MT treatment. These findings demonstrate that MT improves freeze-drying tolerance by maintaining membrane integrity, regulating cellular metabolism, and enhancing oxidative stress resistance. Given its natural biosynthetic origin, generally recognized as safe (GRAS) status, and absence of residual solvents or allergenic proteins, MT can be safely considered for incorporation into food and nutraceutical products. This study underscores the practical relevance of MT as a functional component in compound cryoprotectants, providing a feasible strategy to enhance the viability, stability, and industrial applicability of Lactobacillus plantarum during freeze-drying and storage. Full article

Sarcopenia is an age-related syndrome characterized by the progressive loss of skeletal muscle mass, strength, and function, significantly impairing older adults’ independence and quality of life. Given their anti-inflammatory, antioxidant, and metabolic regulatory properties, n-3 polyunsaturated fatty acids (n-3 PUFAs) have emerged as a promising nutritional strategy to mitigate this muscle degeneration. This review systematically synthesizes existing evidence regarding the association between n-3 PUFAs and sarcopenia. To capture the relevant literature, we searched PubMed, Web of Science, CNKI, and Wanfang Data using a combination of subject headings and free-text terms. We supplemented primary search terms—such as “n-3 polyunsaturated fatty acids,” “omega-3 fatty acids,” “sarcopenia,” and “muscle mass”—with mechanism-related keywords like “inflammation,” “muscle satellite cells,” and “oxidative stress.” We also manually screened the reference lists of the included literature. Our inclusion criteria encompassed interventional studies, observational studies, and high-quality reviews, while excluding conference abstracts, duplicate publications, and studies with incomplete data. This review first outlines the established biological mechanisms linking n-3 PUFAs to the pathological progression of sarcopenia, specifically detailing how these fatty acids improve muscle satellite cell function, suppress inflammation and oxidative stress, and ameliorate metabolic disorders. Next, we critically evaluate recent clinical studies and reviews, analyzing sources of study heterogeneity such as variations in sample size, intervention dose and duration, outcome measures, and baseline participant characteristics. We also highlight current research hotspots—including specialized pro-resolving mediators (SPMs), the gut–organ axis, combined interventions, and precision nutrition strategies—while emphasizing the functional differences between EPA and DHA to guide future intervention designs. Current evidence indicates that while n-3 PUFA supplementation can improve muscle strength and physical performance in older adults, its effects on muscle mass remain inconsistent. Addressing key research gaps, particularly the lack of standardized core outcome measures and unclear dose–response relationships, is critical. Ultimately, future research must prioritize developing high-bioavailability formulations, conducting personalized trials based on baseline n-3 PUFA status, and deepening investigations into inter-organ networks to translate these nutritional insights into effective sarcopenia prevention and management strategies. Full article

Geroprotective molecules are currently being actively investigated for the prevention of skin aging. An overview of geroprotectors in dermatology encompasses agents such as antioxidants, ultraviolet (UV) photoprotective agents, chemical peels, and carbon dioxide (CO₂) lasers, each with inherent limitations, including poor tolerability in individuals with sensitive skin. Regarding biostimulators, high-molecular-weight peptides (exceeding 500 kDa) exhibit limited cutaneous bioavailability, underscoring the need for low-molecular-weight geroprotective compounds. One such candidate is dehydroepiandrosterone DHEA, a neurosteroid with anti-aging and anti-stress properties, which also serves as a precursor to sex steroids. Although topical hormone replacement therapy with estrogens and androgens is being utilized, it remains confined to formal hormone replacement regimens and is associated with a significant adverse effect profile. The aim of this review was to analyze the key molecular mechanisms underlying the effects of DHEA on the skin, with particular emphasis on its metabolism and sex- and age-dependent mechanisms of action. Additionally, this review seeks to elucidate the factors contributing to the absence of approved topical DHEA formulations and to outline the potential of DHEA as an anti-aging agent in dermatological applications. DHEA has demonstrated significant skin-improving effects in several studies; its investigation has been predominantly confined to postmenopausal women. Furthermore, the outcome measures employed in these studies lacked specificity. DHEA is not permitted for use in cosmetic products within the European Union due to its hormonal activity. Its use is only allowed as an extemporaneous formulation under the established regulatory frameworks of individual countries. The indications for its use and the appropriate dosage for men and women must be clearly defined based on the results of future clinical studies. Promising research directions include the pharmacogenetic characterization of steroidogenic enzymes and sex hormone receptors, as well as the evaluation of DHEA in both sexes, specifically in premenopausal women and in men presenting with late-onset hypogonadism. Additionally, the biological effects of the primary metabolites of DHEA, androstenedione, and 5-androstenediol, on the cutaneous function remain unexplored, including their potential anti-aging activity mediated through retinoid receptor activation. Full article

Excessive glucocorticoids induced by stress trigger hepatic lipid metabolism disorder and oxidative stress in poultry, impairing growth performance and welfare. At the same time, resveratrol (RSV) has antioxidant and lipid-regulating properties, but the protective mechanisms in corticosterone (CORT)-challenged broilers remain unclear. This study investigated RSV’s effects on CORT-induced hepatic damage in AA broilers, with 240 one-day-old broilers randomized into three groups: control (basal diet), CORT (basal diet + 4 mg/kg BW CORT intraperitoneal injection), and RSV (400 mg/kg RSV-supplemented diet + CORT injection). Growth performance, hepatic redox status, serum biochemistry, liver histopathology, and gene/protein expression related to antioxidant/lipid metabolism were determined. The growth performance of AA broilers injected with CORT was significantly affected, showing reduced body weight gain (p < 0.05), increased abdominal fat content (p < 0.05), and hepatomegaly (p < 0.05). The addition of RSV in the diet significantly reduced abdominal fat accumulation and hepatomegaly (p < 0.05), improving the growth performance of broilers; Effects of RSV on liver function and lipid metabolism of CORT-treated AA broilers: After CORT injection, serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) activity and total bile acid (TBA) content significantly increased (p < 0.05). Hepatic total cholesterol (TC) and triglycerides (TG) increased after CORT injection (p < 0.05), causing severe liver damage. RSV supplementation could reverse the increases in serum ALP, ALT, and AST activity (p < 0.05) and reduce TBA content in stressed broilers (p < 0.05). TC and TG levels in the liver decreased under the alleviation of RSV (p < 0.05), and serum TG levels declined (p < 0.05). Microscopic and ultrastructural observations showed that after CORT injection, hepatic tissue cells were swollen, scattered fat vacuoles were present, pores were enlarged, and intracellular lipid droplets appeared. The RSV group significantly alleviated hepatocyte damage, reduced vacuolation, showed uniform chromatin, and decreased lipid droplets. RSV significantly mitigated the CORT-induced increase in SREBP-1 mRNA and protein expression and the decrease in PPARα protein expression; CORT caused a decline in the antioxidant function of AA broiler livers, with significant decreases in SOD and GSH-PX (p < 0.05), and the expression of Nrf2 and its downstream genes also showed a decreasing trend. Compared to the CORT group, the RSV group exhibited significant increases in liver CAT, SOD, and GSH-PX (p < 0.05), and Nrf2 protein expression was elevated (p < 0.05). In summary, resveratrol can alleviate the decline in growth performance, liver steatosis, and hepatic oxidative stress in AA broilers induced by CORT, downregulate lipogenic genes such as SREBP-1c, regulate liver lipid metabolism, and mitigate CORT-induced hepatic oxidative stress in broilers by upregulating the Nrf2 pathway. Full article

Context/Objective: Fungi of the genus Tolypocladium are known for their diverse metabolic capabilities and medicinal potential. Indole diterpenoids (IDTs) represent a structurally unique class of fungal metabolites. Beyond their established roles as mycotoxins, these compounds have recently shown promise for neuroprotective effects. The objective of this study was to isolate and characterize novel IDTs from Tolypocladium album DWS131 and evaluate their neuroprotective activities and underlying mechanisms. Methods: IDTs were isolated through comprehensive chromatographic techniques. Their structures were elucidated using HRESIMS data, 1D/2D NMR spectra, and quantum chemical calculations. Neuroprotective effects were evaluated using glutamate (Glu)-induced R28 cells in vitro and N-methyl-D-aspartic acid-induced mouse models in vivo. A total of 48 mice were utilized for in vivo evaluations, divided into two separate experimental cohorts. In each cohort, mice were randomly assigned to four groups (n = 6 per group). Post-intravitreal injection, retinal survival and visual function were assessed via Brn3a-stained flat-mounts, H&E staining, f-VEP, f-ERG, and OptoDrum. Mechanisms involving the SLC7A11/GPX4/ACSL4 axis were investigated by Western blotting and immunofluorescence. Results: Seven previously undescribed paxilline-type IDTs, tolypindoles A–G (1–7), and two known analogues (8–9) were identified. Compounds 8 and 9 exhibited significant neuroprotection closely associated with the attenuation of oxidative stress and the modulation of ferroptosis-related pathways in Glu-induced R28 cells. In vivo, they preserved retinal ganglion cells, maintained retinal structure, and protected visual function, with compound 8 demonstrating superior efficacy. Mechanistic investigations revealed that both compounds modulate the SLC7A11/GPX4/ACSL4 signaling axis. Conclusions: This study expands the chemical diversity of T. album DWS131. Compounds 8 and 9, characterized by isopentenyl moieties, highlight a promising therapeutic potential for retinal neurodegenerative diseases such as glaucoma. Full article

Global warming and associated environmental changes are reducing arable land and intensifying salinization risks, posing growing threats to food security. Soil salinity is an increasing threat to agricultural productivity worldwide, particularly in arid and semi-arid areas. Wheat (Triticum aestivum L.) is one of the most important and widely cultivated cereal crops for human consumption and livestock feed. However, with increasing water scarcity and the incidence of salt-affected lands, wheat productivity is increasingly affected by salinity. Previous studies have investigated salinity tolerance mechanisms mainly at the seedling and reproductive stages of wheat; however, comparatively fewer studies integrate rapid biochemical and physiological responses during the first hours of germination stress exposure together with transcriptional analyses during early seedling establishment, even though this stage is critical for stand establishment. Here, we evaluated early physiological and transcriptional responses of salt-tolerant, moderate, and sensitive wheat cultivars exposed to 0 or 150 mM NaCl during germination and the early seedling stage. Tolerant and sensitive cultivars showed contrasting germination performance under salinity. Physiological analysis showed that salt-tolerant cultivars exhibited higher proline accumulation and higher antioxidant enzyme activities (CAT, SOD, and GR), while maintaining lower MDA levels under salinity compared with sensitive cultivars. Notably, tolerant cultivars showed marked upregulation of TaHKT1;4, TaP5CS, TaMYB, and TaDHN genes associated with ion homeostasis, osmoprotectant metabolism, and stress-responsive regulation. These responses represent integrated early-stage biochemical, physiological, and transcriptional indicators of salinity responsiveness rather than direct predictors of final yield performance. Full article

Background: Traumatic brain injury (TBI) remains a major cause of neurological morbidity and mortality. Mitochondria, being embedded as one of the key organelles disrupted after injury, play a central role in regulating neuronal metabolism, oxidative balance, and cell survival, hence the growing interest in their role after TBI. Methods: We present a narrative review of the literature on mitochondrial dysfunction after TBI to highlight the potential role in diagnosis, monitoring, prognostication and treatment strategies. Following SANRA guidelines we conducted a synthesis of 159 selected references published between 1997 and 2026, including 70 references published from 2020 onward. Results: Mitochondrial dysfunction underpins bioenergetic failure through the impairment of critical regulatory pathways, including oxidative phosphorylation, dysregulated reactive oxygen species production, and dysregulated calcium handling. These changes trigger downstream processes of oxidative damage, epigenetic and proteomic remodeling, and activation of regulated cell death pathways such as apoptosis, necroptosis, and ferroptosis in the context of an inflammatory milieu. As such, mitochondrial-derived molecules (such as mitochondrial DNA and microRNA) are emerging candidate biomarkers of TBI severity and prognosis. Additionally, therapeutic approaches under investigation include inhibition of the mitochondrial permeability transition pore, mitigation of mitochondrial oxidative stress using targeted antioxidants, restoration of NAD⁺-dependent metabolic pathways, and metabolic support through ketogenic interventions. Conclusions: Mitochondrial biology is advancing our understanding of TBI and offers a promising framework for improving its management. Full article

Agaricus subrufescens (AS) is a medicinal mushroom with notable bioactivity and the capacity to accumulate trace elements. In this study, selenium-enriched A. subrufescens (SAS) was cultivated, and its protective effects against alcoholic liver disease (ALD) were investigated, with an emphasis on clarifying the underlying mechanisms. The results showed that the yield and antioxidant capacity of mushrooms in a 10 mg·kg⁻¹ Se treatment group were increased. Nutritional analysis revealed that SAS contained considerable levels of crude protein (350.00 g·kg⁻¹), crude fiber (7.8%), free amino acids (250.20 g·kg⁻¹), and other bioactive constituents. Furthermore, the hepatoprotective effects of AS/SAS were studied in male Kunming mice with alcohol-induced liver injury. The body growth, liver index, serum and liver biochemical parameters, histopathological features of liver, hepatic mRNA levels and liver metabolomics were investigated. The results demonstrated that SAS significantly reduced hepatic lipid accumulation, enhanced antioxidant capacity, regulated the mRNA expression of key genes involved in lipid metabolism, oxidative stress, and inflammatory responses, and modulated liver metabolic characteristics. These findings provide theoretical evidence for the potential of SAS as a functional food against alcohol-induced liver injury. Full article