Search Results (30,309)

Background and Objectives: Fireweed (Chamerion angustifolium L.) possesses antibacterial, antioxidant, anti-inflammatory, and anti-cancer properties. This study evaluated the effects of aqueous fireweed leaf extracts and their major compound, oenothein B, on the viability and mitochondrial function of Caco-2 colon cancer cells, emphasizing the impact of leaf fermentation. Materials and Methods: Cells were treated for 48 h with oenothein B and aqueous extracts from unfermented (NF) and fermented leaves (F 24 h, F 48 h). Cell viability and mitochondrial function were assessed by MTT assay and high–resolution respirometry. Results: IC₅₀ values were 0.843 mg/mL (NF), 1.548 mg/mL (F 24 h), 1.931 mg/mL (F 48 h), and 0.09 mg/mL (57 µM) (oenothein B). Mitochondrial respiration decreased in up to 67% (glutamate/malate) and 61% (succinate) in both fermented and unfermented groups, while oenothein B increased in leak respiration by 34–73% but reduced oxidative respiration by 24%. Conclusions: Aqueous extracts of fireweed from both unfermented and fermented leaves significantly reduced Caco-2 cell viability and mitochondrial function. Oenothein B on its own had a stronger effect on cell viability, but a weaker effect on mitochondrial function, compared to fireweed extracts. Full article

A major bottleneck in evaluating the environmental health implications of micro-nanoplastics (MNPs) is the inadequacy of analytical techniques for their precise quantification within complex environmental and biological matrices. Additionally, there is a conspicuous paucity of studies addressing environmentally relevant, photo-aged MNPs. In this study, the effects of UV aging on toxicity and bioavailability were investigated utilizing inductively coupled plasma mass spectrometry (ICP-MS)-traceable 25 nm gold-core polystyrene shell nanoplastics (AuPS25 NPs) and a triculture small intestinal epithelium (SIE) model coupled with simulated digestions to mimic physiological bio-transformations post-ingestion. Employing dynamic light scattering (DLS), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and X-ray photoelectron spectroscopy (XPS), the physicochemical and morphological alterations of AuPS25 NPs as a function of UV exposure time were investigated, revealing significant photo-oxidation within 14 days. Toxicological evaluations demonstrated that, contrasting with un-aged AuPS25 NPs, the digesta from UV-aged AuPS25 NPs at oral concentrations of 4 and 40 µg/mL weakened barrier integrity by ~15% and ~18% and heightened cytotoxicity by ~4.3% and ~5.4%, respectively. Although the NP translocation rates were similar for both aged and un-aged PS NPs, the uptake by SIE of aged AuPS25 NPs was significantly higher, reaching 72.2% at 4 µg/mL and 59.2% at 40 µg/mL. In contrast, less than 0.5% of the un-aged PS NPs at both 4 µg/mL and 40 µg/mL were taken up by SIE. These findings highlight the imperative to integrate environmentally aged MNPs into toxicological assessments, as they facilitate “real-world” MNPs. Finally, the use of ICP-MS-traceable core–shell MNPs enables the identification and quantification of PS MNPs in cell lysates and biological media via ICP-MS, showcasing the use of such a tracer MNP approach in cellular uptake and in vivo biokinetic studies. Full article

Background/Objectives: We focused on the expression of a novel immune marker, cytoplasmic stimulator of interferon genes (STING), in the cohort of primary renal cell cancer (RCC) with venous tumor thrombus (VTT), in conjunction with the assessment of tumor-infiltrating leucocytes (TILs). Methods: The study group comprised 82 patients with clear cell RCC and VTT, operated on in the years 2012–2019 in two university urological centers. Tissue microarrays were constructed, and respective antibodies were used for staining purposes. The biomarkers were analyzed in primary RCC and VTT. Results: The frequency of STING expression in both analyzed compartments was similar (p = 0.18). Its presence correlated with no clinicopathological features but for necrosis in VTT only (p = 0.0023). PD-L1 expression in the primary tumor was associated with STING in tumor cells in the same compartment (p = 0.02). On the contrary, VISTA expression was correlated with the presence of STING in VTT. TIL presence was associated with positive PD-L1 (p = 0.008) and STING (p < 0.05) expression in the primary tumor. Strong STING expression in VTT was associated with inferior overall survival (OS) (p = 0.0061). TIL presence emerged as a robust prognostic factor for OS in both primary tumor (p = 0.021) and VTT (p = 0.034). Conclusions: We presented for the first time the prognostic values of STING in a contemporary cohort of RCC patients with VTT. STING expression in VTT showed prognostic potential, while TIL assessment proved to be a particularly valuable prognostic tool that can be readily implemented in routine pathological evaluation. Full article

Galectin-3 (Gal-3) is a histologic marker of pancreatic cancer and a potential therapeutic target. This study aimed to characterize a novel sulfated agarose-derived oligosaccharide (DP9) from marine algae, Gracilaria lemaneiformis, evaluate its Gal-3 inhibitory activity, and investigate its anti-pancreatic cancer mechanisms. Through controlled acid hydrolysis, a series of odd-numbered oligosaccharides (DP3-11) were obtained, in which DP9 showed the strongest Gal-3 inhibition in hemagglutination assays. Structural analysis confirmed DP9’s unique composition including an alternating β (1→4)-D-galactose and α (1→3)-3,6-anhydro-L-galactose backbone, featuring partial 6-O-methylation on β-D-galactose and 6-O-sulfation on 3,6-anhydro-α-L-galactose residues. Molecular docking revealed DP9’s binding to Gal-3’s carbohydrate recognition domain through key hydrogen bonds (His158, Arg162, Lys176, Asn179 and Arg186) and hydrophobic interactions (Pro117, Asn119, Trp181 and Gly235), with the sulfate group enhancing binding affinity. In vitro studies demonstrated DP9’s selective anti-pancreatic cancer activity against BxPC-3 cells, including inhibition of cell proliferation; S-phase cell cycle arrest; induction of apoptosis; and suppression of migration and invasion. Mechanistically, DP9 attenuated the Gal-3/EGFR/AKT/FOXO3 signaling pathway while showing minimal cytotoxicity to normal cells. This study first demonstrated that agarose-derived odd-numbered oligosaccharides (DP9) can serve as effective Gal-3 inhibitors, which proved its potential as a marine oligosaccharide-based therapeutic agent for pancreatic cancer. Full article

Noni (Morinda citrifolia L.) juice is increasingly recognized for its potential health-promoting properties. In this research, the bioactive compounds and physiological effects of commercial noni juice products in Korea were assessed. Noni juice was found to contain high levels of total phenolics (6.39 ± 1.45 mg gallic acid equivalents (GAE)/g) and proanthocyanidins (8.64 ± 6.20 mg catechin equivalents (CE)/g). Furthermore, it exhibited potent antioxidant activities, with 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radical scavenging activities of 44.03 ± 14.88% and 55.91 ± 2.62%, respectively, which exceeded those reported for common fruit juices such as apple, orange, and blueberry. Additionally, noni juice reduced lipid accumulation by 5.92% and reactive oxygen species (ROS) levels by 7.23% in 3T3-L1 adipocytes; improved fusion index to 81.44% and restored myotube diameter by 37.24% in dexamethasone-induced C2C12 cells; and suppressed LPS-induced nitric oxide (NO) production. These results suggested that noni juice has anti-inflammatory, anti-obesity, anti-muscle atrophy, and antioxidant properties, supporting its potential as a functional health beverage. Full article

The uptake and accumulation of nanoplastics by plants have emerged as a major research focus. Exogenous selenium nanoparticles (SeNPs) are widely used to mitigate the toxicity of abiotic stresses, such as nanoplastics (NPs) and polyethylene (PE—NPs) nanoplastics, and represent a feasible strategy to enhance plant performance. However, the molecular mechanisms by which SeNPs alleviate the phytotoxicity of microplastics and nanoplastics remain poorly defined. To address this gap, we used Pistia stratiotes L. (P. stratiotes) as a model and silicon dioxide nanoparticles (SiO₂NPs) as a comparator, integrating physiological assays, ultrastructural observations, and proteomic analyses. We found that NP stress caused ultrastructural damage in root tips, exacerbated oxidative stress, and intensified membrane lipid peroxidation. SeNPs treatment significantly mitigated NP-induced oxidative injury and metabolic suppression. Compared to the NPs group, SeNPs increased T-AOC by 38.2% while reducing MDA and ·OH by 33.3% and 89.6%, respectively. Antioxidant enzymes were also elevated, with CAT and POD rising by 47.1% and 39.2%. SeNPs further enhanced the photosynthetic capacity and osmotic adjustment, reflected by increases in chlorophyll a, chlorophyll b, and soluble sugar by 49.7%, 43.8%, and 27.0%, respectively. In contrast, proline decreased by 17.4%, indicating stress alleviation rather than an osmotic compensation response. Overall, SeNPs outperformed SiO₂NPs. These results indicate that SeNPs broadly strengthen anti-oxidative defenses and metabolic regulation in P. stratiotes, effectively alleviating NP-induced oxidative damage. Proteomics further showed that SeNPs specifically activated the MAPK signaling cascade, phenylpropanoid biosynthesis, and energy metabolic pathways, enhancing cell-wall lignification to improve the mechanical barrier and limiting NPs translocation via a phytochelatin-mediated vacuolar sequestration mechanism. SiO₂NPs produced similar but weaker alleviative effects. Collectively, these findings elucidate the molecular basis by which SeNPs mitigate NPs’ phytotoxicity and provide a theoretical foundation and practical outlook for using nanomaterials to enhance phytoremediation in aquatic systems. Full article

Since forkhead box P3 (FOXP3) is a hallmark of regulatory T (Treg) cells, the expansion of FOXP3⁺ adult T-cell leukemia/lymphoma (ATL) cells is believed to contribute to immune suppression and the pathogenesis of ATL. However, the mechanisms underlying the expansion of FOXP3⁺ ATL cells remain unclear. OX40, a co-stimulatory molecule, is expressed in ATL cells, and OX40 signaling has been shown to promote the differentiation and proliferation of Treg cells in mouse models. To investigate the mechanisms driving the expansion of FOXP3⁺ ATL cells, we examined the expression of OX40 and its ligand, OX40L. Our findings revealed that OX40 expression was elevated in patients with ATL and with a high frequency of FOXP3⁺ ATL cells. Flow cytometric analysis of peripheral blood mononuclear cells (PBMCs) from patients with acute ATL cultured for 18 h demonstrated that FOXP3⁻ and FOXP3⁺ cells predominantly expressed OX40L and OX40, respectively. Furthermore, small interfering RNA-mediated FOXP3 knockdown in HTLV-1-infected cell lines increased OX40L expression. These results suggest that interactions between FOXP3⁻ OX40L⁺ cells and FOXP3⁺ OX40⁺ cells may promote the proliferation of FOXP3⁺ ATL cells. Full article

This research explored the chemical composition of the soft coral Sarcophyton sp., leading to the discovery of six previously unreported cembranoids, sarcophynoids D–I (1–6), and three known analog compounds (7–9). Structural elucidation of the new metabolites was achieved by spectroscopic methods, including one- and two-dimensional (1D and 2D) NMR (COSY, HSQC and HMBC), high-resolution electrospray ionization mass spectrometry (HRESIMS), quantum mechanical NMR (QM-NMR) methods, electronic circular dichroism (ECD) calculations, and comparison with literature data. All isolated substances were screened for antibacterial activities, and most exhibited moderate inhibitory effects against six pathogenic bacterial strains, with MIC values between 8 and 64 μg/mL. In addition, the effects of these compounds on LPS and IFN-γ stimulated RAW264.7 cells, focused on the release of NO and TNF-α, were also evaluated, but were inactive at 20 μM. Full article

Purple waxy corn cobs (PWCCs) represent an underutilized agricultural waste rich in anthocyanins with promising cosmeceutical potential. This study investigated niosome-based encapsulation to enhance the stability and bioactivity of PWCC anthocyanin extracts. PWCC extract was macerated in 50% ethanol. The extract exhibited a high total anthocyanin content (3.02 ± 0.81 mg C3GE/L), while cyanidin-3-glucoside identified as the major anthocyanin (1.17 ± 0.02 mg/g dry weight). Furthermore, the extracts showed strong antioxidant activities as evidence by DPPH, ABTS, and FRAP assays. The optimized niosome preparations synthesized by the probe sonication method exhibited better entrapment efficiency (80–85%), nanoscale particle size (185–296 nm), and stable zeta potential (−29 to −32 mV). TEM verification of the spherical morphology and FT-IR spectra confirmed the successful loading of anthocyanins. The thermal stability test exhibited negligible changes in the particle size and zeta potential. Furthermore, in vitro release profile followed the Higuchi model, indicating enhanced release kinetics. Biological assays demonstrated moderate UVB protection effects and potent anti-melanogenesis activity in B16F10 cells. Notably, formulation N5 exhibited the highest tyrosinase inhibition and melanin synthesis suppression. These findings indicate that niosome-based encapsulation represents a promising strategy for enhancing the stability, bioavailability, and biological efficacy of anthocyanin extracts, especially in the cosmetic and pharmaceutical industries. Full article

Chronic obstructive pulmonary disease (COPD) is characterized by persistent airflow limitation associated with enhanced chronic airway inflammation. Growth factors implicated in COPD’s inflammatory processes may serve as biomarkers for disease progression and exacerbation risk. This study evaluated the relationship between serum growth factors and COPD exacerbations over one year. Serum levels of eleven growth factors, including brain-derived neurotrophic factor (BDNF), leukemia inhibitory factor (LIF), fibroblast growth factor-2 (FGF-2), vascular endothelial growth factor (VEGF), nerve growth factor (NGF), epidermal growth factor (EGF), and stem cell factor (SCF), were measured in COPD patients at baseline. Participants were followed prospectively for one year, and associations between these biomarkers and acute exacerbations (AE) and frequent acute exacerbations (Frequent AE) were assessed using statistical analyses and receiver operating characteristic (ROC) curves. Among the study population, 42 patients experienced at least one AE within the follow-up period. Lower serum FGF-2 levels were significantly associated with increased AE risk (adjusted odds ratio significant after covariate adjustment). ROC analysis identified FGF-2 ≤ 9.12 pg/mL as a predictor of AE (AUC = 0.614, sensitivity = 64.3%, specificity = 57.1%, p = 0.032). For Frequent AE, eight patients experienced multiple exacerbations and exhibited significantly lower levels of NGF, EGF, FGF-2, and LIF. After adjustment, NGF remained significantly predictive; NGF ≤ 25.23 pg/mL demonstrated strong discriminatory power for Frequent AE (AUC = 0.797, p < 0.001). However, interpretations are limited by the small Frequent AE subgroup. Serum growth factors, particularly FGF-2 and NGF, are associated with COPD exacerbation risk. Lower serum FGF-2 may indicate a higher likelihood of acute exacerbations, while lower NGF strongly predicts frequent exacerbations. Larger studies and longer follow-ups are needed to confirm these biomarkers’ predictive utility. Full article

Calotropis procera, a drought-tolerant shrub widely used in folk medicine, was evaluated for its antimicrobial potential and safety using an integrative in vitro/in silico workflow. Ethanolic leaf extract (EE-CP) displayed a dose-dependent inhibition of Staphylococcus aureus ATCC 2913 and Escherichia coli ATCC 35218, reaching 93% and 52% of the amoxicillin control, respectively (MIC 207 µg mL⁻¹ and 149 µg mL⁻¹). GC-MS and LC-HRMS profiling revealed cardenolides (strophanthidin, gitoxigenin) and indole derivatives as major constituents. Pharmacophore mapping highlighted the essential glycosyltransferase MurG as a likely bacterial target; molecular docking showed that strophanthidin and NCGC00384918 bind MurG more strongly than the native substrate UDP-GlcNAc (ΔG ≤ −9.4 kcal mol⁻¹), a result corroborated by 100 ns molecular dynamics simulations and MM-PBSA binding energies (−96.4 and −49.3 kcal mol⁻¹). EE-CP caused <10% hemolysis up to 1.5 mg mL⁻¹ and exhibited LC₅₀ values of 302 µg mL⁻¹ (human lymphocytes) and 247 µg mL⁻¹ (BHK-21 cells), indicating a narrow but exploitable therapeutic window. Collectively, these findings constitute the first report on Colombian C. procera demonstrating potent anti-Staphylococcus activity, MurG-targeted cardenolides, and acceptable erythrocyte compatibility. This study supports EE-CP as a promising source of lead molecules and antibiotic adjuvants, warranting guided fractionation and in vivo validation to optimize efficacy and mitigate cytotoxicity. Full article

In vitro cytotoxicity of three (E)-3-(4′-X-benzylidene)-1-indanones (2a-c) displayed lower cytotoxicity towards murine P388 and L1210 leukemic cells as well as human Molt 4/C8 and CEM T-lymphocytes than the respective six- (3a-c) and seven-membered (4a-c) analogs. To study whether thiol reactivity—as a possible basis of their mechanism of action—correlates with the observed cytotoxicities, kinetics of the non-enzyme catalyzed reactions with reduced glutathione (GSH) and N-acetylcysteine (NAC) of 2a-c were investigated. Furthermore, it was also the aim of the work to compare the thiol reactivity of the open-chain chalcones (1) and their carbocyclic analogs (2-4) with different ring sizes (n = 5–7). The reactivity of the compounds and the stereochemical outcome of the reactions were evaluated using high-pressure liquid chromatography–mass spectrometry (HPLC-MS). Molecular modeling calculations were performed to rationalize the high initial rate and low conversion of the 2a indanone in comparison with those of the carbocyclic analog tetralone (3a) and benzosuberone (4a). Thiol reactivity and cancer cell cytotoxicity showed a dependence on both the ring size and the nature of aromatic substituents. Full article

Skin pathogenic microbes continue to seriously endanger humans, particularly resistant strains. Nanomaterials/composites are promising answers for this. Black mulberry (MB) polysaccharides were employed for biosynthesizing/capping selenium nanoparticles (SeNPs); their conjugations alongside chitosan (Cht) nanoforms were constructed and assessed for skin pathogens’ (Staphylococcus aureus bacteria and Candida albicans yeast) suppression and destruction. The biosynthesis of SeNPs with MB was verified using FTIR analysis and UV-vis spectroscopy. The nanocomposites were constructed from Cht–MB-SeNPs at concentrations of 2:1 (F1), 1:1 (F2), and 1:2 (F3). The SeNPs had a mean diameter of 46.19 nm, whereas the F-2 nanocomposites had the lowest particle diameter (212.42 nm) compared to F-1 (239.88 nm) and F-3 (266.16 nm) nanocomposites. The F-2 nanocomposites significantly exhibited the strongest antimicrobial efficacy against skin pathogens, with 26.3 and 27.1 mm inhibition zones and 22.5 and 20.0 μg/mL inhibitory concentrations against bacteria and C. albicans yeast, respectively. The scanning imaging of microbes exposed to nanocomposite emphasized the severe destruction/lyses of microbial cells within 10 h. Loading of cotton fabrics with nanomaterials, particularly with Cht/MB-SeNP nanocomposites, generated potent durable antimicrobial textiles that could prohibit microbial growth, with inhibition zones of 6.2 mm against C. albicans and 3.7 mm against S. aureus; the textiles could preserve their antimicrobial actions after two washing cycles. The biogenic construction of Cht/MB-SeNP nanocomposites can provide innovative solutions to manage and control skin pathogens. Full article

Toxicant-associated steatohepatitis (TASH) is caused by environmental toxicants rather than metabolic factors; however, its pathogenic mechanisms remain poorly understood. Polychlorinated biphenyl 138 (PCB138), a persistent lipophilic contaminant that bioaccumulates in adipose tissue, may promote TASH through unclear mechanisms. In this study, we investigated whether PCB138 induces liver injury via hepatic iron dysregulation and adipose-liver inflammatory signaling. Male C57BL/6 mice received intraperitoneal PCB138 (1, 5, 10, or 50 mg/kg, four injections over six weeks). HepG2 hepatocytes were treated with PCB138 with or without ferric ammonium citrate (FAC), and PCB138-exposed 3T3-L1 adipocytes were co-cultured with HepG2 cells using a Transwell system. PCB138 dose-dependently increased serum transaminase and hepatic non-heme iron levels, with Hamp upregulation, macrophage infiltration, and fibrosis. In HepG2 cells, PCB138 synergized with FAC to elevate intracellular Fe²⁺, induced Hamp, suppressed Slc40a1, and upregulated inflammatory/profibrotic genes. In Transwell co-cultures, TNF-α, IL-6, and IL-1β from PCB138-exposed adipocytes amplified hepatic iron dysregulation and fibrotic responses. These findings demonstrated that PCB138 induced TASH through hepatic iron dysregulation and adipose-derived inflammatory signaling, independent of steatosis. These results highlighted the iron–adipose axis as a novel mechanistic link between PCB138 exposure and liver injury, offering potential therapeutic targets. Full article

The colonic epithelium renews rapidly and must balance proliferation with apoptosis to preserve barrier integrity. We investigated whether grape antioxidant dietary fiber (GADF), a grape pomace-derived dietary fiber matrix naturally rich in high molecular weight non-extractable polyphenols, modulates barrier integrity, through proliferation/cell cycle and apoptosis. To gain mechanistic insight, we examined the role of heat-shock proteins (Hsps), and AMP-activated protein kinase (AMPK)–mTOR–lipid-metabolism signaling in healthy proximal colon. Male Wistar rats received either a cellulose-based control diet or an isoenergetic diet where cellulose was replaced with 5% GADF for four weeks. Morphometric analysis, immunohistochemistry, Western blotting, TUNEL, and caspase activity assays quantified cell cycle, apoptotic, Hsps, and metabolic pathways. GADF strengthened the epithelial barrier, increasing goblet cells, occludin, and ZO-1, while reducing crypt depth. Proliferation was suppressed, as indicated by reduced PCNA, cyclins E and D1, and higher p-p53^Ser392, p21^Cip1/Waf1, and p27^Kip1 levels, consistent with G1 arrest. Apoptosis was attenuated, with increased mitochondrial Bcl-2/Bax and Bcl-xL/Bax ratios, lower cytosolic cytochrome c and apoptosis-inducing factor (AIF), and reduced caspase-9 and caspase-3 activities. Hsp27, but not Hsp70, was selectively induced. GADF activated AMPK and p-Raptor, enhanced ACC1 phosphorylation and CPT1, and supported a shift toward fatty acid β-oxidation. Correlation analysis revealed a strong association between Hsp27 and p-p53^Ser392, suggesting potential links between barrier proteins and metabolic pathways. In conclusion, GADF preserves barrier integrity and redirects metabolism via AMPK–Hsp27 signaling, thereby promoting colonic homeostasis. These findings highlight grape pomace as a sustainable source of functional ingredients for nutritional strategies to reinforce epithelial defenses and reduce disease risk. Full article