Search Results (1,545)

Background/Objectives: Melanoma is a highly aggressive cancer with a strong metastatic potential, and therapeutic resistance remains a major clinical challenge despite advances in targeted therapies and immunotherapies. Secreted frizzled-related protein 1 (sFRP1) exhibits context-dependent roles in cancer; however, its function in metastatic melanoma remains poorly defined. This study investigated the role of sFRP1 in melanoma progression and evaluated the anti-tumor effects of the pharmacological compound WAY-316606. Methods: sFRP1 expression was quantified in metastatic melanoma cell lines, xenograft models, and TCGA datasets. The anti-tumor effects of WAY-316606 on cell viability, cell cycle progression, cell migration and invasion, and expression of extracellular matrix (ECM)-related genes were assessed using WST assays, flow cytometry, wound healing and transwell invasion assays, and quantitative real-time PCR, respectively. Results: sFRP1 expression was consistently elevated in metastatic melanoma cell lines, xenograft models, and TCGA datasets, and high sFRP1 expression was associated with poor overall survival. WAY-316606 selectively suppressed melanoma cell viability with minimal cytotoxic effects on non-tumorigenic cells, and induced G1 phase cell cycle arrest. Furthermore, WAY-316606 markedly impaired the migratory and invasive capacities of metastatic melanoma cells, accompanied by downregulation of key ECM remodeling and fibrosis-related genes, including VIM, CCN2, FN1, and TGFBI. sFRP1 knockdown partially phenocopied the anti-migratory and gene expression effects of WAY-316606. Conclusions: Collectively, our findings identify sFRP1-asscoaited signaling contribute to aggressive melanoma phenotypes and highlight the therapeutic potential of its pharmacological inhibition using WAY-316606. Full article

Some microorganisms present in the cultivation environment serve as biocontrol agents and contribute to enhanced mushroom production. However, the native bacteria naturally associated with commercial cultivation bags of Pleurotus ostreatus, as well as their growth-promoting roles and underlying mechanisms, remain poorly understood. This study aimed to identify native bacteria that promote Pleurotus ostreatus development and to investigate the underlying mechanisms. Four native bacteria, including Brevibacterium epidermidis (P6), Acinetobacter soli (A7), Pseudomonas parafulva (A8), and Pseudomonas hunanensis (A12), were isolated based on their ability to promote mycelial growth of P. ostreatus. B. epidermidis P6 shortened complete mycelial colonization time from ~30 d to 14 d in dual cultivation bags. All four strains increased fresh mushroom yield, with B. epidermidis P6, A. soli A7, and P. parafulva A8 increasing the number of basidiomata, while P. hunanensis A12 enhanced their size. These strains produced exopolysaccharides that enhanced mycelial growth. Additionally, B. epidermidis P6, A. soli A7, and P. parafulva A8 also secreted extracellular crude proteins that also promoted mycelial growth. Bi-plates and further gas chromatography–mass spectrometry analysis demonstrated that volatile organic compounds from P. hunanensis A12, including acetone, 2-butanone, benzaldehyde, and 1-undecene, enhanced fungal mycelial growth. The mycelial growth rates of Ganoderma lucidum and Pleurotus pulmonarius were also enhanced by these four strains. These results reveal that four native bacterial strains promote mushroom development through complex mechanisms. Full article

This study evaluated olive leaf extract (OLE) as a multifunctional dermocosmetic candidate for sebum-related and inflammatory responses relevant to oily and acne-prone skin using an axis-aligned in vitro panel: (i) sebocyte lipogenesis, (ii) inflammatory mediator production in keratinocytes, and (iii) fibroblast-mediated collagen gel contraction. In addition, supportive mechanistic evidence for the sebum-related effects of OLE was obtained by examining signaling proteins associated with sebocyte lipogenesis, including PPAR-γ and SREBP-1. As a result, OLE significantly inhibited linoleic acid-induced lipid accumulation in SEB-1 sebocytes without cytotoxicity. In HaCaT keratinocytes, OLE significantly reduced the production of pro-inflammatory cytokines, including IL-8, TNF-α, and PGE₂, induced by Cutibacterium acnes or UVB. In dermal fibroblast-containing collagen gels, OLE enhanced fibroblast-mediated gel contraction. Additionally, analysis of the main mechanisms of lipid inhibition using SEB-1 sebocytes revealed that OLE exerts a dual regulatory role in lipid synthesis and inflammation by downregulating AKT and ERK phosphorylation and inhibiting PPAR-γ and SREBP-1 expression. Furthermore, among the tested extracts, the 70% ethanol extract (OLE70) exhibited the strongest antioxidant activity, the greatest gel contraction response, and the highest content of oleuropein, a major bioactive phenolic compound derived from olive. Like OLE, oleuropein also showed sebum-regulatory activity by reducing lipid accumulation in SEB-1 sebocytes, an inhibitory effect on IL-8 expression in HaCaT keratinocytes, and an inhibitory effect on the expression of PPAR-γ and SREBP-1, which are involved in sebum secretion. Taken together, these findings suggest that OLE and its major phenolic constituent, oleuropein, may modulate sebum-related, inflammatory, oxidative, and dermal remodeling-associated responses in skin cell models. These results should be interpreted as exploratory and provide a basis for further mechanistic and translational investigation. Full article

The co-occurrence of mucilage and phenolic compounds within the same secretory cell is rarely documented in plants. Recently, such cells were reported in vegetative and floral organs of sensitive legumes (Mimosa), but without detailed subcellular analysis. To address this gap, we used transmission electron microscopy to examine the organelles involved in biosynthesis, the intracellular sites of metabolite storage, and the secretion processes across floral and foliar organs in five Mimosa species. Secretory epidermal cells of sepals, petals, and leaf blades produce both mucilage and phenolics, with no significant differences between organ types. Dictyosomes, rough endoplasmic reticulum, and plastids predominated in the cytoplasm of the secretory cell during biosynthesis. Dictyosomes may mediate mucilage production, the rough endoplasmic reticulum may be involved in phenolic synthesis, and plastids may contribute to the biosynthesis of both compounds. These metabolites are stored in distinct cellular domains: phenolics accumulate in a large vacuole near the outer periclinal wall, while mucilage is deposited between the microfibrils of the inner periclinal wall. This spatial separation is evident by the distention of the inner periclinal wall due to mucilage accumulation. The absence of karyokinesis and phragmoplast formation during metabolite segregation confirms that these secretory cells have two different functional domains, forming a uniseriate rather than biseriate epidermis. Notably, the inclusion of several species in the ultrastructural analyses enhances the significance of these findings. Full article

Clonostachys rosea is a promising biological control agent (BCA) against several plant pathogens, but its sensitivity to solar radiation limits its field efficacy. The biochemical changes occurring in C. rosea under light are still unknown, and no studies have assessed its antagonistic potential against Phytophthora cinnamomi and Phytophthora × cambivora, the main causal agents of ink disease in sweet chestnut. In this study, C. rosea was isolated from asymptomatic sweet chestnut plants in a forestry area affected by ink disease. We evaluated its in vitro antagonistic capacity against both oomycetes under dark and light conditions and investigated the metabolomic and volatilomic changes through HPLC-QToF-MS and GC-MS analyses. Under dark conditions, C. rosea exhibited remarkable inhibitory activity against both oomycetes in a dual-culture assay and through secreted secondary metabolites, including sorbicillinol and vertinolide, derivatives known for their biological activities. Light exposure significantly reduced antagonistic efficacy and secondary metabolite diversity. Volatilomic analyses revealed moderated differences between conditions, with volatile compounds whose biological roles remain uncharacterized and warrant further investigation. These findings indicate that light conditions critically affect the antagonistic potential of C. rosea, highlighting the importance of environmental factors in optimizing its use for the biological control of ink disease in chestnut. Full article

Background/Objectives. Inflammation, comprising many complex and finely coordinated immunological processes, represents a vital protective mechanism of the human body. By regulating inflammatory processes, cytokines play a key role in the modulation of the immune system. Secondary plant compounds such as polyphenols influence cellular immunological processes which might contribute to ensuring a physiologically healthy immune status. Methods/Results. This study investigated eleven polyphenol-rich extracts from red fruit beverages in terms of potential inhibitory effects on pro-inflammatory cytokine secretion of leukemic monocyte THP-1 cells. Extracts originating from fruit juice (apple), fruit juice concentrate (red grape, black currant, pomegranate, elderberry, aronia), fruit juice puree (cranberry, blueberry) or fruit juice pulp (strawberry, sour cherry) were obtained by adsorption onto Amberlite^® XAD-7 resin. The Folin–Ciocalteu assay showed a high content of phenolic compounds in the eleven extracts and HPLC-DAD-ESI-MSⁿ analysis revealed that the extracts contained various anthocyanins in addition to copigments and polymers. Further screening using Lumit^® Immunoassay showed that all tested extracts caused a reduction in pro-inflammatory cytokine secretion (interleukins (IL): IL-1β, IL-6, IL-8 and tumor necrosis factor TNF-α). The extracts from red grape and black currant were the most active ones. Conclusions. Overall, our results showed that polyphenol-rich fruit extracts can inhibit inflammatory processes in vitro. In vivo studies on the anti-inflammatory effect of fruit juice will be a promising approach to determine the fruit juice-dependent, health-promoting effects in humans. Full article

Type II diabetes mellitus (T2DM), a chronic metabolic disorder characterized by insulin resistance, is often accompanied by dysregulated bile acid metabolism. Although gastrodin, a bioactive compound derived from Gastrodia elata, has demonstrated potential in diabetes management, its therapeutic mechanisms remain incompletely understood. The aim of this study is to investigate the therapeutic effects and potential mechanisms of gastrodin on T2DM mice from the perspective of bile acid metabolism. In this study, we found that gastrodin could not only reduce lipid accumulation, reduce inflammation, improve antioxidant capacity, alleviate oxidative stress, change the composition of intestinal flora, and improve the disorder of flora caused by the disease in T2DM mice, but also target Yin yang 1 (YY1) to reduce the expression level of YY1 in the liver under a high-fat diet condition. At the same time, YY1 negatively regulates the expression level of Farnesoid X Receptor (FXR), which increases the expression level of FXR, inhibits the enzyme activity of Cholesterol-7α-hydroxylase (CYP7A1) through Small Heterodimer Partner (SHP), reduces the production of chenodeoxycholic acid (CDCA) in the liver, and further affects the production of secondary bile acids through liver–intestinal circulation, promoting the secretion of Glucagon-Like Peptide-1 (GLP-1) and insulin, thereby reducing blood glucose. At the same time, combined with the results of HE staining, gastrodin can reduce the pathological damage of the liver and pancreas in type II diabetic mice, repairing their normal morphology and function. It provides a direct pathological basis for the improvement of diabetes and liver complications, provides theoretical support for the subsequent research and development of precision targeted drugs, provides experimental basis for the development of new natural hypoglycemic drugs, and promotes the transformation and application of the modernization of traditional Chinese medicine in the field of metabolic diseases. Full article

The restriction of antimicrobial growth promoters in livestock production has intensified the search for nutritional strategies that support intestinal health while modulating inflammatory processes. Chronic or dysregulated inflammation can impair gut function and animal performance, highlighting the need for functional feed additives. Brown macroalgae are rich in bioactive compounds with immunomodulatory properties, though their mechanisms remain incompletely understood. In this study, the anti-inflammatory and barrier-protective effects of aqueous extracts from Ascophyllum nodosum (AN) and Fucus vesiculosus (FV) were investigated using complementary in vitro and in vivo models. Extracts were prepared by aqueous solid–liquid extraction and tested in lipopolysaccharide (LPS)-stimulated RAW264.7 and THP-1 macrophages, HEK-Blue TLR4 reporter cells, and Drosophila melanogaster models of intestinal inflammation and infection. Both extracts significantly reduced LPS-induced nitric oxide production in RAW264.7 macrophages in a concentration-dependent manner. In THP-1 macrophages, AN and FV attenuated secretion of inflammatory mediators, including TNF-α, IL-6, IL-33, CXCL9, CXCL10, CXCL11, and CCL7. Reporter assays demonstrated selective inhibition of TLR4-dependent NF-κB activation. In Drosophila melanogaster, supplementation reduced intestinal barrier disruption, mortality, and infection-induced immune activation. Overall, AN and FV attenuate inflammatory signaling and protect intestinal integrity via TLR4-dependent NF-κB inhibition, supporting their potential as functional feed additives to enhance gut health and resilience in livestock. Full article

Diabetes mellitus is a chronic and increasingly prevalent metabolic disorder characterized by persistent hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. Despite the availability of pharmacological agents that effectively manage blood glucose levels, many are associated with adverse effects, limited efficacy over time, and high costs. Consequently, there is growing interest in alternative therapies, especially those derived from traditional medicinal plants, that have long been employed in various cultures for managing diabetes. Recent advances in phytochemistry have identified bioactive plant secondary metabolites with promising antidiabetic properties. This review aims to provide a comprehensive overview of plant-derived compounds that exhibit inhibitory activity against key diabetes-related enzymes, including α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl peptidase-4 (DPP-4). These enzymes play critical roles in glucose metabolism and insulin signaling pathways. The review highlights the structural diversity of these natural inhibitors, their mechanisms of action, and their effectiveness in preclinical models. Understanding the molecular interactions and pharmacological profiles of these metabolites may facilitate the development of safer and more effective antidiabetic agents. Full article

Pseudomonas fluorescens is a major psychrotrophic bacterium responsible for spoilage in refrigerated foods, particularly dairy products, where deterioration is driven by biofilm formation, quorum sensing (QS) regulation, and the secretion of thermostable lipases. Conventional control strategies reduce bacterial loads but often fail to prevent enzymatic spoilage. Plant-derived phenolic compounds have been widely reported as QS inhibitors and lipase modulators in various biological systems; however, evidence specifically addressing their effects on P. fluorescens regulatory networks and bacterial lipases remains limited. This review critically examines current knowledge on QS-mediated biofilm formation and lipase production in P. fluorescens and analyzes the reported inhibitory activity of phenolic compounds, with emphasis on oak (Quercus spp.)-derived metabolites. While flavonoids and phenolic acids such as quercetin, gallic acid, and p-coumaric acid have demonstrated QS inhibition and antilipolytic activity in other Pseudomonas species and pancreatic models, direct mechanistic validation in P. fluorescens lipases is scarce. Moreover, most studies rely on crude plant extracts without comprehensive metabolomic characterization, and the potential contribution of additional oak metabolites, including terpenoids, remains largely unexplored. Identifying these gaps is essential for advancing toward integrative approaches that combine enzymology, molecular modeling, and validation in food-relevant systems. Full article

Polycystic ovarian syndrome (PCOS) affects over 116 million women globally and is typically linked with excess androgens such as testosterone. Many patients, however, display classic PCOS symptoms despite normal serum androgen. One proposed mechanism for these cases involves a shortened CAG (i.e., encodes glutamine) repeat length in the androgen receptor (AR) gene, which increases AR activity without elevating testosterone. Fewer glutamine repeats alter the AR’s N-terminal domain and may contribute to strengthened interactions with co-activators and enhanced transcription of androgen-regulated genes. Heightened AR activity in hypothalamus neurons stimulates increased pulsatile release of gonadotropin-releasing hormone (GnRH), which disrupts pituitary secretion dynamics and favors luteinizing hormone (LH) over follicle-stimulating hormone (FSH). This altered LH/FSH ratio leads to impaired folliculogenesis, anovulation and other hallmark PCOS symptoms. Targeting AR activity directly, for example by using compounds that covalently modify the AR N-terminal domain to suppress activity, may therefore offer a more precise treatment strategy for PCOS. Full article

Natural bioactive compounds present promising avenues for the prevention and therapeutic intervention of cancer. Octacosanol has garnered significant attention for its distinctive biological properties, yet its specific antitumor effects and underlying mechanisms remain unclear. This study systematically evaluated its antitumor effects and elucidated the associated molecular mechanisms. We confirmed that it dose-dependently inhibited A549 cell proliferation in vitro. It also remarkably suppressed cell invasion and migration by downregulating MMP2 and MMP9 expression, an effect that was associated with reduced phosphorylation of JAK3/STAT3 and PI3K/AKT, suggesting a potential regulatory role of these signalling cascades. Meanwhile, it significantly inhibited tumor cell VEGF secretion and VEGF-mediated neoangiogenesis by modulating the PI3K/AKT signaling axis. Mouse experiments demonstrated that octacosanol significantly reduced tumor p-AKT, MMP2, and MMP9 levels, indicating its in vivo anti-metastatic effect. It also remarkably decreased tumor microvessel density, alongside reduced VEGF and vascular endothelial marker CD31 expression, further verifying its potent anti-angiogenic activity. This work provides evidence of octacosanol’s dual anti-metastatic and anti-angiogenic effects in lung cancer and offers novel mechanistic insights into its activity against this highly prevalent malignancy. These findings establish a solid foundation for further exploration and development of octacosanol as a promising adjuvant for clinical antitumor therapy. Full article

Pistacia lentiscus L. var. Chia is an endemic tree cultivated in the Southern part of Chios Greek Island. Chios mastiha, the aromatic resin secreted from this tree, has been used as traditional remedy since ancient times to cure many peptic system diseases and as a nutritional agent. Nowadays, Chios mastiha has been widely investigated for its biological activities and its chemical composition. A major part of Chios mastiha’s bioactive compounds are triterpenoids, which are proposed to interfere with glucocorticoid receptor (GR) signaling, acting as selective GR agonists. In this study a specific “neutral fraction” of Chios mastiha resin, a portion devoid of acidic triterpenoids, was investigated regarding its biological potential and chemical composition. The study aimed to determine if the neutral triterpenoids, the non-carboxylic ones, within this fraction drive Chios mastiha’s interference with GR signaling and whether it exhibits anti-inflammatory, apoptotic, and potential antilipidemic activities. The phytochemical characterization of this specific resin portion, applying ¹H NMR and HPLC-QTOF-MS/MS analysis, identified novel unidentified Chios mastiha’s phenolic components (apigenin, astragalin, diosmetin, flavidin, genistein), a complex mixture of fatty acids (palmitic, stearic, oleic), non-carboxylic triterpenoids (lupeol, β-amyrin, keto-oleanolic aldehyde), and a trace of terpenoids. Biological assessment of DEX-induced GR transcriptional activation revealed that neutral triterpenoid fractions only minimally contribute to GR transcriptional activation while positively regulating GR and its target, phosphoenolpyruvate carboxykinase (PEPCK), protein levels. Additionally, negative regulation of the peroxisome proliferator-activated receptor alpha (PPARα) protein levels as well as inhibition of the TNFα-induced NF-κΒ activity and reduction in the p65 subunit of NF-κΒ protein levels, were observed, indicating potential antilipidemic and anti-inflammatory Chios mastiha’s neutral fraction activities, which were attributed to its composition in triterpenoids, fatty acids, and novel phenolic compounds. Moreover, mitochondrial-dependent induction of apoptosis accompanied by reduction in cell viability was observed in lupeol, β-amyrin, and fatty acids-enriched fractions. The plethora of bioactive compounds associated with a variety of Chios mastiha’s neutral fraction render Chios mastiha a valuable food additive and nutritional agent. Full article

Gamma irradiation serves as a robust platform for the structural diversification of natural compounds, utilizing high-energy reactions with free radicals to generate novel scaffolds with improved biological properties. In present study, p-coumaric acid was exposed to ionizing radiation at various doses to induce molecular transformations. Significant degradation of the precursor was confirmed at a dose of 60 kGy, which provided the optimal range for the generation of radiolysis products. The chromatographic fraction of the resulting mixture afforded two novel derivatives, 1 and 2, along with a known analog 3. Comprehensive spectroscopic characterization assigned their structures as (3R,4R)-3-hydroxymethyl-4-(4-hydroxyphenyl)-dihydrofuran-2(3H)one (1), (3R*,4S*)-3-hydroxymethyl-4-(4-hydroxyphenyl)-dihydrofuran-2(3H)-one (2), and (4S)-4-(4-hydroxyphenyl)-dihydrofuran-2(3H)-one (3). The anti-inflammatory effects of the isolates were evaluated using lipopolysaccharide-stimulated RAW264.7 macrophages. While neither the parent compound p-coumaric acid nor its derivatives exhibited significant cytotoxicity at concentrations up to 40 μM, their anti-inflammatory potencies varied significantly. Notably, compound 1 exhibited potent inhibitory effects on pro-inflammatory signaling, significantly inhibiting the production of TNF-α, IL-6, and IL-12p70, surpassing the bioactivity of the parent compound. Compound 2 displayed a similar, attenuated inhibitory trend, suppressing the secretion of TNF-α and IL-12p70. Compound 3 modulated the immune response by promoting anti-inflammatory cytokine IL-10 production, despite an inconsistent suppressive effect on pro-inflammatory cytokines. These results suggest that gamma-induced radiolysis is a useful strategy for enhancing the therapeutic potential of dietary phenolic compounds. Full article

The increasing global demand for animal-derived food products, combined with growing environmental and public health concerns, has intensified the search for sustainable strategies in livestock production. Among emerging nutritional approaches, phytogenic feed additives (PFAs) have gained attention as natural alternatives to conventional synthetic growth promoters. PFAs, derived from herbs, spices, essential oils, and plant extracts, contain diverse bioactive compounds such as phenolics, flavonoids, alkaloids, terpenoids, and saponins. These compounds exhibit antimicrobial, antioxidant, anti-inflammatory, and immunomodulatory activities that can support animal health, productivity, and product quality. Current research indicates that PFAs positively influence digestive physiology by modulating gut microbiota, improving intestinal integrity, and stimulating digestive enzyme secretion. These mechanisms enhance nutrient utilization, feed efficiency, and growth performance. In addition, the antioxidant and immunomodulatory properties of plant-derived compounds strengthen the ability of animals to cope with physiological stress and disease, potentially reducing reliance on synthetic antimicrobials and supporting antibiotic-free production systems. PFAs may also improve reproductive performance and physiological stability, particularly in small livestock species and indigenous breeds. Beyond productivity benefits, phytogenic additives contribute to environmental sustainability by improving feed conversion efficiency and reducing nutrient excretion. The present literature review confirms that although variability in plant composition and the need for standardization remain challenges, PFAs represent a valuable component of integrated nutritional strategies aimed at achieving resilient, environmentally responsible, and economically sustainable livestock production systems. Full article