Search Results (1,142)

Background/Objectives: Mesenchymal stem cells (MSCs) are deemed to be a highly safe model for autologous and allogeneic cellular therapy, owing to their inherent lack of HLA-DR expression, immunomodulatory properties, homing ability, and plasticity allowing differentiation into different cell types. The interest in activating autophagic signaling in MSCs has recently grown due to its significant potential in maintaining stemness, enhancing paracrine signaling, and providing therapeutic benefits for cancer and neurodegenerative diseases. This study aimed to explore the impact of autophagy induction on enhancing the therapeutic potential of MSCs by maintaining their plasticity and to assess different induction agents. Methods: In this study, MSCs were first extracted from the fat tissue of Sprague–Dawley (SD) rats and characterized phenotypically and molecularly by their positive expression of stemness markers CD29, CD106, and CD44, and their negative expression of hematopoietic surface markers CD14, CD34, and CD45, using a flow cytometry approach. Isolated MSCs were then treated separately with two FDA-approved autophagy inducers: Lithium Chloride and Trehalose, following assessment of autophagy activity. Results: Treated MSCs showed significant increases in autophagic activity at both the transcriptional and translational levels. The successful induction of autophagy in MSCs was confirmed through the elevated expression of autophagy-related genes such as ATG3, ATG13, ATG14, P62, and ULK1. These data were confirmed by the significant upregulation in LC3 protein expression and the formation of autophagosomes, which was detected using a transmission electron microscope. Furthermore, the expression of Oct4, Sox2, and Nanog genes was significantly enhanced after treatment with Trehalose and Lithium Chloride compared with untreated control MSCs which may indicate an upregulation of pluripotency. Meanwhile, Lithium Chloride and Trehalose did not significantly induce cellular apoptosis, indicated by the Bax/Bcl-2 expression ratio, and significantly decreased the expression of the antioxidant markers SOD and GPx. Conclusions: Treatment of MSCs with Trehalose and, in particular, Lithium Chloride significantly activated autophagic signaling, which showed a profound effect in enhancing cells’ pluripotency, reinforcing the usage of treated MSCs for autologous and/or allogenic cellular therapy. However, further in vivo studies for activating autophagy in cellular grafts should be conducted before their use in clinical trials. Full article

Background: Cigarette smoking disrupts cellular energy metabolism and remains a major global health problem. The Mediterranean diet, characterized by antioxidant and anti-inflammatory properties, has been implicated in the regulation of metabolic pathways. Objective: This study aimed to examine the association between adherence to the Mediterranean diet and the expression of energy metabolism-related genes in smokers aged 18–55 years. Methods: Smokers were classified according to their Mediterranean Diet Adherence Screener (MEDAS) scores into an adhering group (n = 24) and a non-adhering group (n = 24). Participant characteristics were recorded, blood samples were collected, and total RNA was isolated. Gene expression analysis was performed using a custom RT-qPCR array targeting energy metabolism-related genes. Pathway enrichment analysis was conducted using EnrichR Reactome 2024, and gene–metabolite relationships were explored using MetaboAnalyst 6.0 to support pathway-level interpretation. Results: Smoking was associated with coordinated upregulation of genes involved in glycolysis, glucose transport, lipid metabolism, amino acid metabolism, the pentose phosphate pathway, and redox regulation, consistent with a metabolically stressed state. In contrast, adherence to the Mediterranean diet was associated with lower expression of genes related to glycolytic flux, lipid β-oxidation, and amino acid turnover, alongside relatively higher engagement of tricarboxylic acid cycle-related pathways and reduced activation of redox-associated processes. Conclusions: Adherence to the Mediterranean diet was associated with differences in the expression of genes involved in cellular energy metabolism among smokers, suggesting a potential modulatory role of dietary patterns in smoking-related metabolic alterations. Full article

Background: Nanotechnology provides innovative strategies to enhance drug delivery and therapeutic efficacy through advanced nanocarrier systems. Objectives: This study aimed to develop and optimize a nanostructured lipid carrier (NLC) co-encapsulating curcumin (CUR) and resveratrol (RESV) using a fractional factorial design to develop a topical formulation with antioxidant and anti-inflammatory properties. Methods: NLCs were produced via hot emulsification followed by high-pressure homogenization, and their physicochemical characteristics, drug content, stability, release profile, antioxidant activity, skin delivery, and cellular compatibility were evaluated. Results: The optimized formulation exhibited an average particle size of approximately 300 nm, a polydispersity index below 0.3, and high drug loading for both compounds. Stability studies over 90 days revealed no significant changes in physicochemical parameters, confirming the formulation’s robustness. In vitro release assays demonstrated sustained release of both actives, with 58.6 ± 2.9% of CUR and 97 ± 3% of RESV released after 72 h. Antioxidant activity, assessed by the DPPH and ABTS assays, showed concentration-dependent radical-scavenging effects, indicating antioxidant potential. Skin permeation/retention experiments using porcine skin showed enhanced retention of CUR and RESV within the tissue, with no detectable permeation, indicating suitability for topical delivery. In addition, in vitro cell assays using human keratinocytes showed concentration-dependent responses and acceptable cellular compatibility. Conclusions: Overall, this study demonstrates the successful application of nanotechnology and experimental design to develop stable and efficient lipid-based nanocarriers containing natural polyphenol for topical therapy targeting oxidative and inflammatory skin disorders. Full article

Postbiotics, defined as non-viable microorganisms or their structural and metabolic components, have attracted attention for their documented health effects, including modulation of gut homeostasis and inflammatory responses. Tributyrin is among the most promising postbiotics studied, and its safety profile enables it to exert its beneficial effects. However, tributyrin activity must be maintained after its uptake, underscoring the importance of selecting appropriate delivery strategies, such as its incorporation into electrospun composites. Combining postbiotics and natural antioxidants, such as Spirulina and its components, to improve their properties can be a great strategy. Therefore, the present work aimed to produce tributyrin–Spirulina composites via electrospinning. The composites obtained were characterized, and their antioxidant activity and cytotoxicity were determined. All formulations were successfully produced by electrospinning, as the composites retained the bonds of their respective components. In terms of antioxidant activity, the combination of tributyrin and C-phycocyanin was the most promising among the bioactive compounds studied. Overall, the viability and cytotoxicity results indicate that interactions among bioactive composition, redox regulation, and adhesion-dependent survival govern cellular responses to electrospun zein fibers. Tributyrin promotes metabolic adaptation over time, whereas Spirulina-derived fractions are more sensitive to formulation and culture conditions. Full article

Sinensetin, a polymethoxylated flavone abundant in citrus fruits, has been recognized for its broad biological activities and wide use in traditional medicine around the world. Emerging clinical evidence from flavonoid-enriched orange juice interventions indicates antioxidant and anti-inflammatory effects, aligning with extensive preclinical data. In this review, we explored in vitro and in vivo findings on the anti-inflammatory and anticancer actions of sinensetin and delineated the underlying cellular pathways, especially in terms of proposed targets for sinensetin. In inflammatory settings, sinensetin attenuates NF-κB activation, lowers pro-inflammatory cytokines (e.g., TNF-α, IL-6), and enhances antioxidant defenses, supporting its reported antioxidant, anti-bacterial, anti-viral, and anti-obesity properties. Across multiple tumor models, sinensetin suppresses oncogenic signaling—including β-catenin, PI3K/AKT, VEGF, NRF2, P53, and MKK6—concomitant with reduced proliferation, migration, and survival signaling. We further discuss emerging immunological effects, including modulation of innate immune cell activation and cytokine production, which may contribute to tumor microenvironment reprogramming and inflammation resolution. Together, these mechanistic insights position sinensetin as a promising lead for chemopreventive and adjunct therapeutic strategies. Our efforts aim to provide insights into the future translational development and clinical evaluation of sinensetin and its derivatives. Full article

Corilagin is a hydrolyzable ellagitannin and naturally occurring polyphenolic compound widely distributed in medicinal plants. It is also present in longan (Dimocarpus longan), known as lumyai in Thailand, a subtropical fruit extensively cultivated across China and Southeast Asia. Corilagin has been reported to exhibit strong antioxidant, anti-inflammatory, hepatoprotective, and anticancer activities through modulation of multiple cellular signaling pathways. However, despite these well-established pharmacological properties, its potential role in regulating bone marrow mesenchymal stem cell (BM-MSC) differentiation has not been fully explored in biomedical applications. In this study, we investigated the effects of corilagin on BM-MSC viability, protein-binding interactions, and lineage-specific differentiation toward osteogenic and chondrogenic pathways. Cytotoxicity assessment using human synovial SW-982 cells demonstrated that corilagin maintained cell viability at concentrations ranging from 1.56 to 50 µg/mL within 48 h, whereas prolonged exposure resulted in a time-dependent reduction in viability. In BM-MSCs, corilagin significantly enhanced osteogenic and chondrogenic differentiation in a dose-dependent manner, as evidenced by increased mineral deposition and cartilage matrix formation, as revealed by Alizarin Red S, Toluidine Blue, and Alcian Blue staining. Quantitative analyses further showed the upregulation of key lineage-specific genes, including Runx2 and osteopontin (OPN) for osteogenesis and Sox9 and aggrecan for chondrogenesis. Protein-binding assays confirmed the molecular interaction capacity of corilagin, supporting its biological activity. Overall, these findings demonstrate that corilagin promotes MSC-mediated osteogenic and chondrogenic differentiation while maintaining acceptable cytocompatibility, highlighting its potential as a natural small-molecule candidate for bone and cartilage tissue engineering and other biomedical fields with regenerative medicine applications. Full article

Cellular senescence is a stress-induced process that contributes to adipose tissue dysfunction by promoting inflammation, impaired adipogenesis, and insulin resistance, alterations that are closely associated with age-related cellular dysfunction and metabolic disorders. In this study, we evaluated the protective role of chlorogenic acid (CGA), a polyphenol with known antioxidant and anti-inflammatory properties, against oxidative stress-induced senescence in murine 3T3-L1 adipocytes. The results obtained showed that CGA treatment significantly alleviated the senescent phenotype by restoring Lamin B1 levels and the Bcl-2/Bax ratio. Additionally, CGA downregulated key senescence-related cell cycle progression markers, modulating p53, p21, and MAPK signaling. CGA also restored insulin signaling through the PI3K-AKT-GLUT4 axis and improved glucose uptake, while attenuating oxidative stress, inflammatory cytokine expression, and extracellular matrix remodeling factors associated with SASP. Collectively, these findings support the role of CGA as a promising senotherapeutic nutraceutical able to reduce adipocyte senescence and its metabolic consequences, offering novel insights for the development of dietary supplements targeting age-related cellular dysfunction. Full article

Sacha inchi (P. volubilis L.), an ancient oilseed crop native to the Amazon, is gaining attention for its high nutritional value particularly due to its ω-3-, -6-, -9-rich oil. However, most research has focused mainly on oil characterization, neglecting the potential of its by-products, such as the Sacha inchi oil-press cake (i.e., the solid residue after oil extraction). This study explores the chemical composition of Sacha inchi oil press-cake powder, focusing on fatty acid and amino acid profiles, antinutrient factors, total phenolic content, antioxidant activity, and the bioactivity of its extracts on cellular models. Fatty acid analysis revealed a high proportion of polyunsaturated fatty acids, especially α-linolenic acid (42.52%), making it a valuable resource for health-promoting applications. The protein content was also significant (41.86%), with a balanced amino acid composition, including essential amino acids such as leucine, valine, and isoleucine, which are vital for muscle protein synthesis and energy metabolism, in food and/or feed applications. Antinutritional factors were detected, including saponins (1050.1 ± 1.1 mg/100 g), alkaloids (2.1 ± 0.5 mg/100 g), and tannins (6.2 ± 0.9 mg/100 g). While these phytotoxins could limit their use in food applications, their potential antimicrobial activity highlights promising pharmacological opportunities. Total phenolic content (TPC) and antioxidant activity (AO) were evaluated using two extract mixtures differing in composition and polarity, with the acetone/water/acetic acid solvent (80/19/1 v/v/v) showing the highest antioxidant properties. The extract obtained showed cytotoxic effects against Panc-1 cancer cells, highlighting its potential in nutraceutical and pharmaceutical applications. This study underscores the unexploited potential of Sacha inchi by-products, such as the oil press-cake, as a sustainable resource of bioactive compounds for functional products, supporting circular bio-economy strategies by plant-based waste and local biodiversity valorization. Full article

The mycotoxin zearalenone (ZEN), commonly found in contaminated food and feed, poses a significant threat to human and animal health, particularly to reproductive function. Mitigating its toxicity represents a critical research priority in food safety. Apigenin (AP) is a naturally occurring dietary flavonoid with phytoestrogenic properties and exhibits diverse pharmacological activities. In this study, we investigated the protective effects of AP against ZEN-induced apoptosis and oxidative stress in Swine Testis (ST) cells and elucidated its underlying mechanisms. The identity of ST cells was verified via RT-PCR and agarose gel electrophoresis. ST cells were treated with 40 μM ZEN and 1 μM and 0.1 μM AP for 24 h. Cell viability was detected via CCK8 and EdU assays, cytotoxicity was evaluated via LDH assay, cell cycle and apoptosis levels were analyzed via flow cytometry, and the mechanism by which AP alleviated the damage caused by ZEN to ST cells was preliminarily revealed using RNA-Seq technology. Further, the expression levels of related genes and proteins were detected by qRT-PCR and Western blot. Our results show that 1 μM or 0.1 μM AP effectively attenuated the cytotoxicity induced by 40 μM ZEN in ST cells, as evidenced by restored cell viability, reduced the LDH level, normalized cell cycle progression, reduced apoptotic rates, and enhanced antioxidant capacity. RNA-Seq analysis was coupled with molecular validation and used to elucidate the mechanisms underlying AP-mediated protection against ZEN-induced cellular injury. It is shown that ZEN suppressed the expression of LRP5, a pivotal gene in the Wnt signaling pathway, along with its downstream effector c-Myc. Conversely, treatment with 1 μM or 0.1 μM AP upregulated the expression of LRP5, iASPP, and TRAF2 at both transcriptional and translational levels. Importantly, the protective effects of AP were abrogated with IWR-1-endo, a specific Wnt pathway inhibitor, confirming pathway dependency. Collectively, our findings show that AP alleviates ZEN-induced oxidative stress and apoptosis in ST cells through the upregulation of LRP5 and subsequent activation of the Wnt signaling pathway. This study provides molecular evidence supporting the potential clinical application of AP as a preventive agent against ZEN-induced reproductive toxicity. Full article

Skin aging is driven largely by oxidative stress, chronic inflammation, and mitochondrial dysfunction, processes closely linked to cellular senescence and declining NRF2 activity. Numerous dietary phytochemicals—such as curcumin (from turmeric), resveratrol (from grapes), sulforaphane (from cruciferous vegetables), zerumbone, and salvianolic acid B—abundant in fruits, vegetables, herbs, and traditional food sources, exhibit potent antioxidant and anti-inflammatory properties. This review systematically elucidates the molecular mechanisms by which these compounds mitigate skin aging, primarily through modulating the NRF2 signaling pathway. We further integrate insights from clinical trials of NRF2-targeting agents to inform the translational potential of these dietary bioactives. Molecular docking analyses confirm that these food-derived compounds interact directly with the KEAP1-NRF2 complex, promoting NRF2 activation. Transcriptomic analyses of skin-related datasets (GSE35160, GSE71910, GSE185129) further validate the downregulation of key NRF2-regulated cytoprotective genes (e.g., FTH1, FTL, HMOX1, SLC7A11) involved in antioxidant defense and the suppression of pro-inflammatory mediators. Based on this mechanistic foundation, we discuss the translational potential of these food-derived bioactives and the rationale for their future incorporation into skin-health-promoting nutraceuticals. We highlight how these food-derived phenolics and other bioactives may be incorporated into functional foods or nutraceuticals to support skin health from within, offering a dietary strategy to delay aging. We acknowledge that key translational challenges, such as oral bioavailability and optimal formulation, require further investigation. Further research is warranted to bridge these mechanistic insights into effective human applications. Full article

Background: Frostbite injury creates an ischemic, hypoxic, and acidic microenvironment that often triggers severe oxidative stress and inflammation. Current therapeutic approaches are limited by low drug delivery efficiency and an inability to adequately regulate multiple pathological pathways. Although oxyresveratrol (OR) exhibits excellent antioxidant and anti-inflammatory activities, its application is hampered by poor aqueous solubility and low stability. Methods: We constructed Oxyresveratrol@Zeolitic Imidazolate Framework-8 nanoparticles (OR@ZIF-8) and further embedded them in a sodium hyaluronate (HA) matrix to form an OR@ZIF-8@HA composite hydrogel. The physicochemical properties and pH-responsive drug release behavior of the system were characterized. Its antioxidant activity, ability to promote cell migration, and capacity to modulate macrophage polarization were evaluated in cellular assays. The therapeutic efficacy was further investigated using a mouse frostbite model, with wound repair analyzed via histological staining. Results: The OR@ZIF-8 nanoparticles achieved a cumulative release rate of 75.46 ± 3.68% under acidic conditions within 36 h. In vitro experiments demonstrated that the formulation significantly scavenged TNF-α and IL-6, by 161.85 ± 19.43% and 125.37 ± 12.65%, respectively, and increased the level of IL-10 by 44.97 ± 4.57%. In a scratch assay, it promoted wound healing, achieving a closure rate of 97.55 ± 2.77% after 36 h. In vivo studies revealed that the OR@ZIF-8@HA treatment group achieved a wound healing rate of 96.14 ± 4.12% on day 14. Conclusions: The OR@ZIF-8@HA composite hydrogel effectively overcomes the limitations of OR application via intelligent pH-responsive delivery. Through synergistic multi-mechanistic actions, it significantly accelerates frostbite wound healing, offering a novel and efficient therapeutic strategy for frostbite management. Full article

Due to their complexity, both genotypic and phenotypic, neurodegenerative diseases are one of the main causes of death globally nowadays. Among phytochemicals of high scientific interest, based on experimental studies, pentacyclic triterpenoids (TTs), including mainly betulin, betulinic, and ursolic acid, became targets of scientific research in recent years, especially in terms of their biological activity and pharmacological potential. Due to their anti-inflammatory and antioxidant properties, as well as their involvement in cellular signal transductions, they have been observed to act as anticancer, chemopreventive, and neuroprotective agents. The aim of this review is to update the reader on the diversity, bioavailability, pharmacological properties, and neuroprotective effects of TTs, as biomolecules that can interfere with metabolic mechanisms related to neurodegeneration and restoring of neuronal integrity. Recent data were analyzed, with a particular focus on mechanistic insights related to their neuroprotective effects. Starting with their biosynthetic pathways, bioavailability, and involvement in specific metabolic pathways, their impact on neurological pathology and benefits as natural neuroprotection agents through specific signaling pathways are presented. Furthermore, emphasis will also be put on current challenges and future strategies that could develop TTs into effective compounds for neuroprotection and personalized medicine. Full article

Background/Objectives:Pereskia aculeata and Pereskia grandifolia belong to the Cactaceae family, despite their foliar and woody stem characteristics. Both species are commonly known as Ora-pro-nóbis (derived from Latin, meaning “pray for us”), a name rooted in their historical use in colonial Brazil due to their nutritional value, particularly P. aculeata, which is frequently described as a high-protein food source. The goal of the present study was to compare these species based on phytochemical composition and antioxidant capacity. Methods: Both species were investigated for their chemical antioxidant properties (DPPH and phosphomolybdenum complex) and cellular anti-ROS activity using the CACO-2 cell line. A comprehensive phytochemical analysis was performed using LC-MS and GC-MS. Results: P. aculeata exhibited a more abundant content of phenolics and flavonoids, with greater structural variability in phenolic compounds and glycosylated flavonoids than P. grandifolia. Still, P. aculeata showed a more potent chemical antioxidant effect. By contrast, in P. grandifolia, a series of novel saponins was now discovered and characterized. In addition, the compounds from this species exhibited a greater cellular antioxidant activity than those of P. aculeata. Tryptophan-derived alkaloids, such as abrine (N-methyltryptophan), were present in both species, but hypaphorine only in P. aculeata. Conclusions: Both species of Pereskia exhibit potential health benefits, including distinct antioxidant activity, among other unexplored effects, given their significant variability in phytochemicals. These differences could be investigated in greater depth using combined LC-MS and GC-MS, thereby enabling more confident structural investigations of these natural compounds. Full article

Several antioxidants play an important role in improving athletic performance. Increased inflammation and oxidative stress during physical performance result in the production of free radicals, including reactive oxygen species (ROS), which leads to fatigue, muscle damage, and impaired performance. However, moderate and transient increases in ROS are physiologically essential, acting as signaling mediators that trigger adaptive cellular responses. Despite their harmful effects on athletic performance, ROS may also enhance physical protection by acting as signaling molecules against increased physical stress. Healthy dietary patterns such as the Mediterranean diet (MD) may contribute to decrease oxidative stress thanks to its content in fruits, vegetables, olive oil, legumes, and herbs/spices. Indeed, the beneficial effects of the MD can be attributed not only to its antioxidant properties but also to its well-documented anti-inflammatory effects, lipid-modulating actions, immune-supportive functions, and modulation of gut microbiota composition, which collectively influence metabolic and physiological resilience. The MD also plays a key role in competitive sport and training. In addition, several researchers have reported that the MD is essential for reducing risk of injury and illness, recovering and adapting between bouts of activity, and enhancing performance. In this context, following the key principles of an MD could also represent a useful framework for good dietary in competitive athletes. In this narrative review, we discuss the potential effects of antioxidants in sport and the impact of individual foods or compounds of the MD on oxidative stress and exercise performance in competitive athletes and physically active individuals. The potential modifications which could be made to the MD will be highlighted to maximize health and performance effects, in accordance with contemporary sports nutrition practices. Full article

Onion (Allium cepa L.) peels represent a major agro-industrial by-product and are a rich source of polyphenols, with recognized antioxidant properties. This study compared the polyphenolic profile of two onion cultivars peels: red “Rossa di Tropea” and yellow “Recas”. Their digestive stability, intestinal bioavailability, and antioxidant activity were evaluated. Hydroalcoholic extracts were characterized by HPLC-DAD, subjected to a static gastrointestinal digestion model, and assessed for transport across differentiated Caco-2 monolayers. Antioxidant properties were determined using DPPH, FRAP, Cellular Antioxidant Activity (CAA), and intracellular glutathione (GSH) assays. Red peels contained a higher total polyphenol content (28.44 mg/g DW) than yellow peels (15.61 mg/g DW), including anthocyanins uniquely present in the red cultivar. Digestive stability varied markedly between cultivars, with yellow peels showing greater intestinal recovery (72.7%) than red peels (49.1%). Glycosylated flavonols were more stable and exhibited moderate intestinal transport (Papp = 1.1–9.9 × 10⁻⁶ cm·s⁻¹), whereas quercetin aglycone showed low permeability. Red peel extracts demonstrated stronger chemical antioxidant activity, while yellow peels were more effective in cell-based assays, displaying higher CAA values and inducing a pronounced increase in intracellular GSH. Overall, onion peel extracts exhibit promising antioxidant and biological properties. However, their limited bioavailability highlights the need for formulation strategies to enhance gastrointestinal stability and intestinal uptake, supporting their potential use as sustainable functional ingredients. Full article