Search Results (38,461)

Cyclophosphamide (CTX)-induced premature ovarian failure (POF) is characterized by disruption of the follicular microenvironment, granulosa-cell loss, endocrine imbalance, and oxidative-inflammatory injury. Here, we evaluated two multi-bioactive formulations developed to enhance ovarian stress resilience: a base formulation containing coenzyme Q10, calcium L-5-methyltetrahydrofolate, and Vitex agnus-castus extract (Base), and a urolithin A-enriched formulation (Base + U). Using a CTX-induced female C57BL/6 mouse model, we integrated phenotypic, histological, endocrine, oxidative-inflammatory, and transcriptional readouts to assess efficacy and mechanistic consistency. CTX markedly reduced ovarian index, disrupted estrous cyclicity, shifted follicle development toward atresia, increased granulosa-cell apoptosis, and caused endocrine dysregulation, including decreased anti-Müllerian hormone and estradiol and increased GnRH, FSH, and LH. CoQ10, Base, and Base + U each partially alleviated these abnormalities, improving ovarian index and coat condition, showing a trend toward improved follicular distribution, and normalizing hormone profiles. CTX also induced an ovarian oxidative-inflammatory shift, as reflected by decreased GSH-Px, increased MDA, and elevated IL-1β, IL-6, and TNF-α, all of which were attenuated by the interventions. Notably, Base + U more effectively reduced lipid peroxidation and TNF-α than Base alone. Consistently, ovarian transcripts related to follicle responsiveness and steroid regulation, including Fshr, Esr1, and Hsd17b2, were restored, whereas hypothalamic qRT-PCR analysis did not reveal robust transcriptional alterations within the intervention window. These findings suggest that the urolithin A-enhanced formulation partially alleviates CTX-induced ovarian dysfunction by suppressing oxidative-inflammatory stress and preserving granulosa-cell and follicle fate. Full article

Parkinson’s disease (PD) involves oxidative stress, proteotoxic aggregation, and neurotransmitter dysfunction, yet current therapies remain largely symptomatic. This study investigated whether Jujube polysaccharides (ZJP), a food-derived polysaccharide, confer neuroprotective and anti-aging benefits in Caenorhabditis elegans. ZJP was characterized for physicochemical features, antioxidant capacity, and in vivo safety. Effects were evaluated in wild-type N2 and PD models by measuring lifespan, locomotion, pharyngeal pumping, chemotaxis, α-syn::YFP fluorescence intensity, dopaminergic neuron integrity, adenosine triphosphate (ATP), reactive oxygen species (ROS), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and lipofuscin. Stress resilience was assessed under heat (37 °C) and H₂O₂ exposure. RT-qPCR profiled genes related to stress responses and neurotransmission. ZJP showed no detectable toxicity at tested doses. ZJP extended mean lifespan in N2 (10.3–14.1%) and NL5901 (9.1%), improved locomotion, pharyngeal pumping, and chemotaxis, reduced lipofuscin (26.8–50.6%), and increased survival under heat (23.6%) and oxidative stress (38.1%). In PD models, ZJP reduced α-syn::YFP fluorescence by up to 54.9%, protected dopaminergic neurons, and increased ATP. It also lowered ROS and MDA levels while raising SOD and CAT activities. Gene expression changes were associated with enhanced oxidative stress resistance and with altered expression of genes involved in SKN-1/DAF-16-related stress-response signaling. These findings provide preliminary evidence that ZJP may promote longevity, stress resilience, and neuroprotection in C. elegans models of PD, supporting its potential as a candidate for further investigation in neuroprotection. Full article

Microplastic pollution has attracted significant attention in recent years due to evidence that these particles can accumulate in organisms’ tissues and organs and induce adverse health effects, with oxidative stress being a key underlying mechanism of toxicity. The present study investigated the effects of polystyrene microplastics (0.1 μm in diameter) administered at a dose of 0.1 mg/day/animal for 4 weeks, followed by a 2-week recovery period without exposure, on oxidative stress markers in the liver, kidney, and spleen and on hematological and blood biochemical parameters in mice. The results showed a statistically significant increase in white blood cell counts, including lymphocytes, granulocytes, and monocytes, at week 5, indicating the development of an inflammatory response. During the last week of the recovery period (week 6), values returned to levels that approached baseline. Changes in lipid peroxidation demonstrated an induction of oxidative stress, accompanied by alterations in glutathione levels and antioxidant enzyme activities, with a tendency toward recovery after cessation of polystyrene microplastic exposure. In conclusion, these findings demonstrated that even short-term exposure to low doses of polystyrene microplastics could trigger oxidative stress and inflammatory responses, highlighting their potential health risks and the need for further investigation into their long-term biological effects. Full article

Lutein is a dietary xanthophyll carotenoid with recognized antioxidant and immunomodulatory potential, yet the molecular basis underlying its nutritional effects in laying hens remains insufficiently understood. Here, liver transcriptomic profiling and 16S rRNA sequencing were combined to investigate the response of laying hens to dietary lutein supplementation. A total of 951 differentially expressed genes were identified in the liver, indicating marked transcriptional remodeling after lutein supplementation. Functional enrichment, gene set enrichment, and weighted gene co-expression network analyses consistently showed that these changes were mainly associated with metabolic regulation, redox/stress adaptation, and immune-related communication. In parallel, lutein supplementation changed cecal microbial community structure and shifted specific microbial biomarkers. Integrated correlation analyses further identified candidate host–microbiota association patterns, including a KLF2/FOXO3/Faecalibacterium axis and a KLF2/IL8L2/Prevotellaceae_Ga6A1_group axis. Overall, dietary lutein was associated with coordinated changes in the hepatic transcriptional profile and cecal microbial community structure, which converged on these two functional directions. These findings provide new insight into the nutritional effects of lutein in laying hens and identify candidate pathways and microbial nodes for future functional validation in poultry feeding systems. Full article

Salinity is a critical agricultural threat that reduces the productivity of several crops. Tomato (Solanum lycopersicum) is the world’s second most significant horticultural commodity, which struggles due to salt concentrations in irrigation water, even in hydroponic systems. This research evaluated seed priming treatments (hydro-, halo-, bacterio-, and halo-bacteriopriming) at different phenological stages under two salinity conditions (0 and 16 mM NaCl) to improve crop production. After evaluating physiological variables and multivariate statistical analyses, this study’s main breakthroughs are: Priming treatments modified the physiological, nutritional, and productive metabolism of tomato plants. Bacterio- and halo-bacteriopriming using an endophytic and halophytic bacterial consortium reduced germination time, enhancing uniformity and synchronizing seedling emergence. Bacteriopriming enhanced N, P, Ca and Zn absorption in seedlings. In the vegetative and reproductive stages, bacteriopriming consistently increased concentrations of K, Mg, and Zn in leaves and fruits but depleted Na uptake. Improving the nutritional balance resulted in not only a higher concentration of chlorophyll but also an increase in the yield and beta-carotene concentration in tomato fruits. The results demonstrated that halo-bacteriopriming may be a biotechnological strategy for mitigating saline stress, optimizing tomato growth and nutraceutical quality, because it outperformed the plant response in all stages of development compared to the control and hydro- and haloprimed treatments. Full article

Renal tubular epithelial cells (RTECs) are increasingly recognized as key players in kidney diseases. They integrate metabolic, inflammatory, and fibrotic signals. This article reviews new data suggesting that RTECs could function as central integrators within diagnostic networks, linking cellular stress responses to detectable blood and urine biomarkers. We discuss the latest advances in multi-omics, extracellular vesicles, and single-cell technologies that enable precise identification of RTEC states. Finally, we discuss the potential of RTEC-centric diagnostics and highlight current limitations in early disease recognition, stratification, and the development of personalized therapeutic interventions. Full article

Background/Objectives: Bleomycin is an antineoplastic antibiotic used in the management of various malignancies. Nevertheless, its benefits are constrained by the development of pulmonary fibrosis. Amentoflavone, a biflavonoid, exhibits diverse pharmacological activities, including anti-inflammatory, antiviral, antioxidant, and antitumor effects, whereas alogliptin possesses antioxidant and anti-inflammatory properties. This study aimed to assess the potential protective effects of alogliptin and/or amentoflavone in a murine model of bleomycin-induced pulmonary fibrosis and to clarify the underlying mechanisms. Methods: Fifty male C57BL/6 mice were randomly divided into 5 equal groups: control, bleomycin, bleomycin + alogliptin, bleomycin + amentoflavone, and bleomycin + alogliptin + amentoflavone. The assessed endpoints included lung weight/body weight index, lung tissue fibrotic mediators, oxidative stress parameters, proinflammatory cytokines, and pyroptotic and autophagy mediators. Also, the bronchoalveolar lavage fluid (BALF) was evaluated for total and differential leukocytic counts and lactate dehydrogenase (LDH) activity. Moreover, vascular responses to potassium chloride, phenylephrine, and carbachol, together with tracheal responses to carbachol were determined. Lung tissues were further examined histopathologically and immunohistochemically. Results: Treatment with alogliptin and/or amentoflavone significantly decreased the lung weight/body weight index and BALF LDH activity, concomitant with mitigation of lung tissue oxidative stress parameters, fibrotic mediators, apoptosis, and pyroptosis with a significant augmentation of autophagy signals, alongside marked improvement in the lung architecture and vascular and airway reactivity compared with the bleomycin group. These effects were most pronounced with animals treated with the alogliptin/amentoflavone combination. Conclusions: These findings suggest that combined alogliptin and amentoflavone may constitute a promising strategy to prevent bleomycin-induced lung fibrosis. Full article

Background/Objectives: Although creatine monohydrate is widely recognized as an effective ergogenic aid in strength and power sports, its role in endurance and mixed-sport disciplines remains less clearly established. This scoping review aimed to map the current evidence regarding the effects of creatine supplementation on performance, recovery-related outcomes, and body composition in endurance and mixed-sport contexts. Methods: A scoping review of randomized controlled trials published between 1996 and 2025 was conducted. Eligible studies evaluated creatine supplementation in endurance and mixed-sport contexts, including both sport-specific and broader exercise populations when the exercise protocol, testing model, or outcomes were relevant to endurance or mixed-sport performance, recovery, or body composition. A total of 38 studies met the inclusion criteria. Outcomes were categorized into exercise performance, biochemical markers related to recovery and exercise stress, and body composition parameters. Results: Creatine supplementation was most often associated with reported favorable changes in repeated-sprint performance and high-intensity power output, particularly during intermittent, sprint-based, or power-endurance tasks. Several studies reported favorable changes in sprint performance, peak power, or total work output relative to placebo or baseline values in cycling, swimming, rowing, and canoeing/kayaking protocols, although findings were not uniform across studies and not all favorable within-group changes were placebo-superior. Some studies also reported favorable changes in end-phase sprint capacity during prolonged exercise. Findings related to recovery were less consistent. Selected studies reported reductions in inflammatory markers, including C-reactive protein (CRP) and tumor necrosis factor α (TNF-α), whereas markers of muscle damage showed mixed responses. Most supplementation protocols involved a 5–7-day loading phase of 20 g/day, occasionally followed by a maintenance dose of 2–5 g/day. Small increases in total body mass were commonly observed, while evidence regarding fat-free mass and aerobic outcomes remained limited or inconsistent. Conclusions: Current evidence suggests that creatine supplementation may be most relevant in selected endurance and mixed-sport contexts involving repeated high-intensity efforts, sprint finishes, or power-endurance demands, rather than for endurance performance broadly. In contrast, evidence for recovery-related biochemical responses, body composition changes, and aerobic adaptations remains equivocal. Further well-controlled, sport- or context-specific, and field-based studies are needed to better clarify the role of creatine in endurance and mixed-sport exercise. Full article

Hypersaline environments are unique ecosystems harboring specialized microbial communities with significant biotechnological potential. This study provides a comprehensive characterization of the taxonomic diversity and functional potential of two Tunisian salterns, Abbassia (Kerkennah) and Thyna (Sfax), using an integrated approach that combines 16S/18S rRNA gene amplicons (Illumina and full-length Nanopore) with shotgun metagenomics. Taxonomic profiling revealed a high species richness (S ≈ 1250 taxa); however, the Abbassia site was characterized by extreme taxonomic polarization, with over 95% of the community dominated by specialized halophilic Bacillota (Salinicoccus and Jeotgalicoccus). In contrast, Thyna exhibited a more even distribution dominated by Pseudomonadota and methanogenic Archaea. Beyond taxonomy, functional annotation via the HUMAnN 3.0 pipeline identified site-specific metabolic specializations. Abbassia was enriched in biosynthetic pathways and robust stress-response mechanisms, including ectoine biosynthesis and ppGpp-mediated stringent response, reflecting adaptation to stable hypersaline conditions. Conversely, Thyna’s microbiome prioritized energy extraction and nutrient recycling, with a high abundance of fermentation and glyoxylate cycle pathways. These findings demonstrate that environmental filtering shapes not only the microbial structure but also the metabolic landscape, highlighting the ecological plasticity of microbial life in extreme Tunisian salterns. Full article

Reinforced concrete (RC) buildings are the most common structural system in urbanising regions. In many cases, architectural constraints and uneven distribution of structural elements often create eccentricity between the centre of mass (CM) and the centre of rigidity (CR). This eccentricity may induce torsional effects during earthquakes that can significantly influence structural response and increase seismic vulnerability. This study investigates the impact of in-plan irregularity on the seismic performance of RC buildings using nonlinear numerical analyses. Three-dimensional models of four- and six-storey RC buildings with moment resisting frames were developed in OpenSees, where different levels of irregularity were introduced by artificially shifting the lumped mass to generate controlled eccentricities without modifying the structural configuration. Seismic performance was evaluated using nonlinear incremental dynamic analysis (IDA) based on forty ground motion records under bidirectional excitation. The results indicate that increasing CM–CR eccentricity amplifies inter-storey drift demands and elevates the probability of damage due to intensified torsional stresses. The adverse effect is most pronounced when eccentricity aligns with the direction of lower stiffness, whereas eccentricity in the stiffer direction has a limited impact on severe damage states, particularly for taller buildings. These findings provide valuable insights for risk-informed assessment, retrofitting, and prioritisation of existing plan-irregular RC buildings. Full article

Forest tree provenances have evolved diverse and complex mechanisms to acclimate to changes in environmental conditions. Pedunculate oak (Quercus robur L.), along with other European tree species, is increasingly exposed to the adverse effects of climate change, particularly prolonged drought periods and severe drought stress. Understanding the species’ capacity to acclimate to expected environmental changes requires knowledge of key functional traits linked to drought tolerance, such as leaf structure and gas exchange. To explore the acclimation mechanisms of pedunculate oak provenances to repeated drought events, a study was conducted under controlled conditions with plants from nine provenances spanning a north–south gradient across eastern Europe, from Estonia to Italy. The study consisted of two parts: first, leaf structural traits were analyzed after three years of experimentally induced drought by comparing drought and control treatments; second, both treatments were subjected to subsequent drought to analyze differences in gas exchange trait responses. Results demonstrated ecotypic differentiation among provenances in morphological, but not in gas exchange traits, suggesting that provenance adaptedness to drier habitats is more closely associated with structural than physiological traits. Provenances originating from drier habitats showed lower specific leaf area but also different acclimation to repeated drought events, including a stronger reduction in stomatal density and a smaller increase in leaf dry matter content, compared to provenances from more humid habitats. Gas exchange acclimation occurred through a shift in the strategy of photosynthesis down-regulation. These findings emphasize the importance of investigating multiple functional traits rather than focusing solely on individual key traits. Full article

Glutamine is the most abundant amino acid in human plasma and tissues and plays essential roles in cellular metabolism, biosynthesis, and redox homeostasis. Beyond these canonical functions, glutamine availability and utilization have emerged as key regulators of multiple cellular stress responses, including the integrated stress response, endoplasmic reticulum stress, metabolic checkpoint signaling, and autophagy. During viral infection, host glutamine metabolism is frequently reprogrammed to meet the energetic and biosynthetic demands of viral replication, thereby inducing or reshaping glutamine-linked stress pathways. Increasing evidence indicates that these stress responses are not merely secondary consequences of infection but actively influence key stages of the viral life cycle, including viral entry, genome replication, protein synthesis, and host antiviral responses. In this review, we summarize current advances in understanding how glutamine metabolism regulates cellular stress responses in the context of both viral and non-viral infections, and how these pathways, in turn, modulate viral pathogenesis and host defense. We discuss the context-dependent roles of glutamine-linked stress signaling in either promoting viral replication or restricting infection, depending on viral species, host cell type, and metabolic conditions. Finally, we highlight emerging concepts and unresolved questions, including the potential of targeting glutamine metabolism and associated stress pathways as host-directed antiviral strategies. A deeper understanding of the interplay between glutamine metabolism, cellular stress responses, and viral infection may provide new insights into disease mechanisms and inform the development of novel therapeutic approaches. Full article

The performance of native landraces of Capsicum annuum L. under contrasting production systems remains poorly understood, limiting their evaluation under locally relevant production scenarios. This study evaluated the phenological and productive responses of five genotypes (four native landraces and one commercial cultivar) under two systems representing locally relevant production conditions: open-field (OF) and a substrate-based hydroponic system under low-technology, passively ventilated tunnel-type greenhouse conditions (GH), to describe genotype-specific responses under contrasting production conditions during the 2023 growing season in Puebla, Mexico. Agroclimatic and agronomic variables were analyzed using independent ANOVA by system and canonical correlation analysis (CCA). The GH system exhibited restrictive microclimatic conditions, with maximum temperatures exceeding 48 °C and photosynthetically active radiation reduced by approximately 53% compared to OF conditions. Environmental conditions were not standardized between systems; therefore, the results reflect the contrasting microclimates of locally relevant production systems and provide a context-specific assessment of genotype performance. Under the specific conditions evaluated, yield was lower in GH compared to OF across all genotypes. The commercial cultivar Serrano Tampico achieved the highest yield (1.118 kg per plant under OF), while Mixteco Largo and Cola de Ratón produced the highest number of fruits. The CCA identified genotype-specific associations between environmental and agronomic variables, suggesting distinct performance patterns under contrasting production conditions, with native landraces exhibiting better agronomic performance under OF conditions. Overall, the results provide a context-specific characterization of genotype performance under contrasting production conditions. Full article

Aesthetic medicine is shifting from symptomatic correction to biological structural restoration. Regenerative aesthetics represents a frontier in dermatology, focusing on the restoration of the skin microenvironment to enhance cellular vitality and tissue resilience. Central to this approach is the concept of “skin bed preparation”, a strategic priming phase designed to optimize the physiological terrain before the delivery of advanced aesthetic interventions. This review explores the molecular and cellular mechanisms by which skin bed preparation modulates the extracellular matrix (ECM) and the dermal niche to maximize the efficacy of subsequent treatments and promote long-term skin longevity. Evidence suggests that biostimulatory priming utilizing senolytics, senomorphics, mitochondrial, and/or epigenetic rejuvenators rehabilitates the fibroblast–collagen interactome. By reducing oxidative stress and chronic low-grade inflammation, these preparatory steps transition the skin from a catabolic to an anabolic state. This metabolic reset ensures that subsequent procedures, such as laser therapy, injectable fillers, encounter a responsive cellular environment, resulting in superior collagen induction and prolonged clinical outcomes. Optimizing the skin microenvironment via regenerative aesthetics is not merely an adjunctive step but a fundamental requirement for therapeutic success. Integrating skin bed preparation into clinical protocols provides a synergistic framework that enhances immediate procedural results while addressing the underlying hallmarks of skin aging, ultimately redefining the trajectory of skin health and longevity. Full article

Cadmium (Cd), a highly mobile and phytotoxic heavy metal, threatens plant growth and food safety and has increased interest in woody plant-based phytoremediation. However, the genome-wide characteristics of the NAC transcription factor family and its role in Cd tolerance remain largely unknown in pomegranate (Punica granatum L.), a stress-tolerant woody plant. In this study, 121 PgNAC genes were identified from the chromosome-level genome of the pomegranate cultivar ‘Tunisia’. Phylogenetic analysis classified these genes into two major groups and 16 subgroups. PgNAC genes were unevenly distributed across the eight chromosomes and showed evident clustered distribution patterns. Synteny and Ka/Ks analyses further revealed that segmental and tandem duplication jointly shaped the expansion of the PgNAC family, while the duplicated pairs have largely evolved under strong purifying selection. Conserved motif and gene structure analyses showed that PgNAC proteins possessed a highly conserved N-terminal NAM domain, whereas their C-terminal regions were relatively divergent. Promoter analysis further identified abundant hormone- and stress-responsive cis-elements, suggesting diverse regulatory roles of the PgNAC family. Transcriptome profiling identified PgNAC87, a member of the NAP subfamily, as a Cd-responsive candidate gene that was consistently upregulated in both roots and leaves under Cd stress. Heterologous overexpression of PgNAC87 in tobacco significantly enhanced Cd tolerance, as reflected by alleviated growth inhibition, increased antioxidant enzyme activities and osmotic adjustment substances, and reduced oxidative damage. Collectively, our results clarify the evolutionary features of the PgNAC family and its involvement in Cd-induced transcriptional regulation, while highlighting PgNAC87 as a potential genetic target for enhancing Cd tolerance in pomegranate and related woody species. Full article