Search Results (18,391)

Chemical examination of Penicillium steckii HJT-A-10, an endophytic fungus derived from Rhodiola tibetica, led to the isolation of ten metabolites. Structural elucidation by spectroscopic methods revealed that two of these were previously unreported compounds (1 and 2), though the absolute stereochemistry of 2 remained provisional; the other eight isolates (3–10) were identified as known compounds. All ten metabolites were tested for their capacity to inhibit nitric oxide (NO) production in RAW 264.7 macrophages stimulated with lipopolysaccharide (LPS). Compounds 1–4 and 7–10 exhibited marked inhibitory effects. Among the two new compounds, 2 displayed stronger activity, with an IC₅₀ value of 19.01 µM. To explore the potential mechanisms of action, network pharmacology and molecular docking analyses were subsequently conducted to predict the relevant targets and signaling pathways. Full article

Ultraviolet (UV) exposure accelerates skin aging through wavelength-dependent effects. Ultraviolet A (UVA) penetrates relatively deeply into the dermis and promotes oxidative stress and extracellular-matrix remodeling, whereas ultraviolet B (UVB) is absorbed predominantly in the epidermis and produces direct DNA damage and inflammation; nevertheless, UVB can also alter dermal fibroblast matrix metabolism in experimental models. The present study specifically used UVB irradiation (peak wavelength, 306 nm) to examine inflammatory collagen loss. UVB-induced cellular injury activates the NOD-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome, leading to caspase-1-dependent maturation of interleukin-1β (IL-1β), activation of nuclear factor-κB (NF-κB), and matrix metalloproteinase (MMP)-associated collagen degradation. Pulsed electromagnetic field (PEMF) stimulation is a non-optical biophysical modality that may modulate inflammatory and matrix responses. Here, we characterized the effects of PEMF exposure using Corefacial on UVB-induced dermal collagen loss in association with the A2A adenosine receptor (A2AAR)/cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway. In UVB-exposed fibroblasts, PEMF restored A2AAR and PKA protein levels, cAMP levels, and the pNLRP3/NLRP3 ratio, similar to the effects of the A2AAR agonist CGS-21680. PEMF also reduced apoptosis-associated speck-like protein containing a caspase-recruitment domain (ASC), caspase-1 activation markers, IL-1β secretion, NF-κB nuclear translocation, and MMP2/MMP3/MMP9 expression and increased the levels of collagen I and collagen III. In the in vivo UVB model, PEMF similarly increased A2AAR and PKA protein levels, cAMP levels, and the pNLRP3/NLRP3 ratio, while attenuating IL-1β/NF-κB/MMP-associated responses and preserving dermal collagen. These findings are consistent with, but do not prove, involvement of A2AAR/cAMP/PKA-related signaling and inhibitory NLRP3 phosphorylation in the PEMF response. These results should be interpreted as evidence from a UVB-specific experimental model rather than a comprehensive model of solar photoaging. Full article

Background/Objectives: Bacillus spp. are often isolated from airborne microbiota. Five Bacillus strains (AD12–16) isolated from dust during a sandstorm in Kuwait were characterized for their potential to produce antimicrobial compounds, biosurfactants and siderophores by genotypic and phenotypic approaches. Methods: Whole-genome sequencing was performed, and biosynthetic gene clusters (BGCs) were predicted using antiSMASH. Antimicrobial activities were determined by agar-well diffusion assays. Siderophore and biosurfactant production were determined by Arnow’s and drop-collapse assays, respectively. The active metabolites were separated, fractionated, and analyzed by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and LC–MS/MS. Results: Genome mining identified many BGCs associated with known secondary metabolites such as bacillibactin and bacilysin, as well as a number of unassigned clusters. The isolates exhibited distinct antimicrobial profiles, with Bacillus subtilis AD16 displaying the highest antimicrobial activity against multidrug-resistant pathogens. Biosurfactant- and siderophore-associated activities varied among the isolates. Active fractions demonstrated bactericidal activity, while LC–MS/MS analysis revealed molecular features tentatively assigned to siderophore- and lipopeptide-associated metabolite classes based on accurate mass and MS/MS fragmentation patterns. Conclusions: The combination of unassigned BGCs, antimicrobial activity, and incompletely characterized molecular features highlights unexplored biosynthetic potential in sandstorm-derived Bacillus. Further purification and structural characterization are required to establish the identities and biological functions of the active metabolites. Full article

Animal-processing by-products contain collagen, myofibrillar proteins, blood proteins, whey proteins, and egg proteins that can be converted into peptide-rich food ingredients. Within a single application-oriented framework, this review integrates source heterogeneity, process control, peptide-profile characterization, tiered functional evidence, food-matrix performance, and regulatory substantiation. Evidence is evaluated for antioxidant, ACE-inhibitory, antimicrobial, DPP-IV-inhibitory, anti-inflammatory, mineral-binding, and taste-modulating functions, while distinguishing chemical assays, cell models, animal studies, human interventions, and tests in real-food matrices. Potential applications include functional foods, dietary supplements, natural preservation, flavor systems, texture modification, active packaging, and oral delivery. Translation remains limited by raw-material heterogeneity, batch variability, sensory defects, processing and gastrointestinal instability, uncertain bioavailability, incomplete safety assessment, and poorly defined regulatory claims. Future work should prioritize source traceability, peptide fingerprints, food-matrix validation, human exposure data, and scalable food-grade production. Compositionally defined peptide mixtures with reproducible functionality may be more practical than single highly purified sequences. Full article

Curcuma lampangensis, a critically endangered species endemic to Thailand, has been successfully propagated in vitro; however, its phytochemical profile and biological activities remain uncharacterized. This study compared eight ethanol and ethyl acetate extracts from the aerial and belowground tissues of wild and in vitro-derived plants. Total phenolic and flavonoid contents, DPPH and ABTS radical-scavenging activities, and tyrosinase-inhibitory activity were evaluated alongside chemical profiling by HPLC-DAD, targeted LC–MS/MS, and GC–MS. The ethyl acetate extract of wild belowground tissues showed the highest TPC (5.21 mg GAE/g DW), while the ethyl acetate extract of in vitro-derived aerial tissues exhibited the highest TFC (1.59 mg QE/g DW) and ABTS activity (63.11%). The ethanol extract of wild belowground tissues showed the strongest DPPH activity (70.48%), and the ethyl acetate extract of in vitro-derived belowground tissues demonstrated the greatest tyrosinase inhibition (52.12%). HPLC and LC–MS/MS revealed a diverse phenolic and flavonoid profile, with p-coumaric acid, 4-hydroxybenzoic acid, chlorogenic acid, and quercetin consistently detected across all extracts, while ferulic and caffeic acids were widely distributed. GC–MS tentatively identified ethyl palmitate, linoleic acid ethyl ester, and ethyl oleate as predominant constituents. These findings demonstrate that in vitro-derived biomass retains appreciable phytochemical and biological properties, supporting its use as a renewable, conservation-compatible material for further characterization and bioactivity-guided research. Full article

The search for new compounds capable of inhibiting the activity of enzymes involved in the development of neurodegenerative diseases, including Alzheimer’s disease, has attracted continuing interest for many years. Natural isothiocyanates and their synthetic analogs, as well as compounds containing a 1,3,5-triazine core, constitute a group of molecules with complex mechanisms of action involving multiple molecular targets. Although literature data confirm the activity of both isothiocyanates and s-triazines, these two active fragments have not yet been combined, and it remains unclear whether a synergistic effect can be achieved. In this study, 11 novel isothiocyanate–triazine conjugates, consisting of a 1,3,5-triazine core substituted with aliphatic or cyclic secondary amines and a phosphorus analogue of isothiocyanate [6-(isothiocyanatohexyl)phosphonate)ethyl], were synthesized with yields of 46–80%. The pharmacokinetic profiles and parameters related to Lipinski’s rule of five were determined for all compounds. All compounds were evaluated as inhibitors of acetylcholinesterase (AChE) and β-secretase (BACE1). Compound 1i showed the highest inhibitory activity against AChE (IC₅₀ = 0.182 ± 0.02 µM), while compound 1b exhibited the strongest inhibition of BACE1 (IC₅₀ = 8.48 ± 2.18 µM). To explore the potential of these multifunctional derivatives, plausible enzyme-ligand binding models were proposed based on molecular docking simulations. Full article

Coconut meat (solid endosperm) is a valuable oilseed product with significant nutritional and functional properties, yet the quality changes during maturation remain unclear. This study investigated the effects of maturity on nutrients, antioxidant and α-amylase inhibitory activities, and volatile organic compounds in coconut meat of the Wenye No. 3 variety at 8, 10, and 12 months after pollination (named CM-8, CM-10 and CM-12, respectively). Results showed that moisture content decreased from 81.15% to 61.73%, while fat (8.61% to 17.53%), protein (0.60% to 1.29%), and total soluble sugars (2.13% to 4.84%) increased from CM-8 to CM-12. Total phenolic content declined with maturity, whereas ABTS scavenging activity was significantly higher at CM-12 than at CM-10, and hydroxyl radical scavenging activity was similarly elevated at CM-10 and CM-12. α-Amylase inhibitory activity peaked at CM-10 (20.4%). Phosphorus, magnesium, zinc, and copper peaked at CM-12. Lauric acid predominated at all stages, with unsaturated fatty acids transiently increasing at CM-10. GC-IMS identified 31 volatile compounds, with esters and alcohols dominating in CM-8 and CM-10, while aldehydes accumulated in CM-12. These findings provide theoretical guidance for staged harvesting and graded utilization of coconut in the processing industry. Full article

Protein kinases are the most intensively targeted protein family for small-molecule drugs, and the large volume of inhibitory-assay data reported for them makes the family particularly well suited to data-driven and machine-learning approaches to drug discovery. This data, however, is scattered across heterogeneous assays, reports and publications, and its reuse for modeling requires substantial curation. Here, we present Kinoteca, a curated database of kinase inhibitory-activity data derived from ChEMBL and accessible through a web interface for browsing, filtering, visualization and download. Kinoteca reconciles the multiple raw independent measurements reported for each combination of compound, kinase and activity type into a single fused activity value, together with a dispersion score based on the mean unsigned error (MUE) that quantifies how consistent the underlying measurements were. The database currently organizes curated data for 585 kinases and arranges them along biologically meaningful groupings such as kinome family, pathway and source organism. Curated activities can be filtered by the physicochemical properties of the assayed molecules or by measurement quality, explored through summary statistics, activity distributions and structural clustering, and exported either as curated or semi-raw data tables or as molecular structure files. These data formats are suitable for the direct training of machine learning models, such as activity prediction models. By delivering reconciled, analysis-ready data with its provenance preserved, Kinoteca aims to lower the barrier to reproducible, data-driven kinase drug discovery. Full article

Skin hyperpigmentation caused by excessive melanin production has led to increasing interest in the development of effective anti-melanogenic agents. In this study, the anti-melanogenic effects and underlying mechanisms of nicotinamide mononucleotide (NMN) were investigated using α-MSH-induced B16F10 melanoma cells. NMN maintained over 80% cell viability at concentrations below 0.5% and significantly reduced α-MSH-induced melanin accumulation and melanin content. In addition, in situ tyrosinase assay demonstrated that NMN effectively suppressed intracellular melanogenesis. However, NMN did not exhibit direct inhibitory activity against mushroom tyrosinase. Molecular docking analysis further revealed that NMN did not directly interact with the catalytic copper-binding site of tyrosinase. Furthermore, tyrosinase zymography and Western blot analyses demonstrated that NMN suppressed melanogenesis primarily through downregulation of tyrosinase protein expression rather than direct inhibition of tyrosinase catalytic activity. Collectively, these findings suggest that NMN suppresses melanogenesis through regulation of melanogenic signaling pathways, indicating its potential utility for hyperpigmentation-related applications. Full article

Background/Objectives: OS is characterized by marked tumor heterogeneity, stemness-associated phenotypes, metastatic potential, and poor prognosis. FZD4 is an important Wnt signaling receptor involved in stem cell regulation and tumor progression, but its role and microRNA-mediated regulation in OS remain unclear. The aim of this study was to investigate the relationship between FZD4 expression, OS stemness, malignant progression, and upstream microRNA regulation. Methods:Human OS single-cell RNA sequencing data were analyzed using Seurat, CytoTRACE, and Monocle2. Tumor cell subpopulations, developmental potential, and pseudotime trajectories were evaluated. Functional enrichment analyses were performed to identify pathways associated with high FZD4 expression. MicroRNA–mRNA interaction analysis was used to predict upstream regulatory microRNAs, and immunohistochemistry, Western blotting, and in vitro and in vivo experiments were performed for validation. Results: FZD4 was mainly enriched in OS tumor cell subpopulations and was significantly associated with poor prognosis. Tumor cells with high FZD4 expression showed increased developmental potential, stemness features, and enrichment in early developmental states. Functional enrichment analysis indicated activation of epithelial–mesenchymal transition, angiogenesis, inflammatory response, KRAS signaling, hypoxia, glycolysis, and Wnt-related pathways. Clinical validation confirmed elevated expression of FZD4, OCT4, and SOX2 in OS tissues. FZD4 knockdown inhibited OS cell stem-like phenotypes and malignant behaviors, proliferation, and migration, while miR-424-5p suppressed these malignant phenotypes by targeting FZD4. Importantly, rescue experiments demonstrated that restoration of FZD4 substantially reversed the inhibitory effects of miR-424-5p mimics on sphere formation, migration/invasion, proliferation, and stemness-associated cell populations. Conclusions: Our findings identify miR-424-5p as an upstream suppressor of FZD4 and demonstrate that the miR-424-5p/FZD4 axis regulates stem-like and malignant phenotypes of OS cells, at least partly through Wnt/β-catenin signaling. This axis may represent a potential therapeutic target for OS. Full article

Background: Opioid use during pregnancy is linked to preterm birth, fetal growth restriction, and Neonatal Opioid Withdrawal Syndrome. While the placenta is the primary regulator of the uterine environment, the precise molecular mechanisms by which opioids dismantle placental function remain poorly defined. Methods: The transcriptomic landscape of opioid-exposed human placentas from a unique Hawai’i-based cohort was characterized. Results: Transcriptional signatures were defined by genes involved in translational inhibition and metabolic attenuation. Integrative network modeling predicted a prominent stress-signaling hub centered on p38 Mitogen-Activated Protein Kinase and Extracellular Signal-Related Kinase 1/2, paralleling a broad suppression of ribosomal protein transcripts (Ribosomal Protein 27S, -29, and -39). This response was further characterized by the inhibition of the Myelecytomatosis Proto-Oncogene regulatory hub, predicting a loss of mitochondrial phosphate transport through associated genes (via Solute Carrier Family 25A3) and cell-cycle progression (via S-Phase Kinase-Associated Protein 1). Additionally, the genes in this model suggested upregulation of antisense regulatory brakes, such as RAP2C Antisense RNA 1, which might further reinforce this inhibitory state. Conclusion: The findings suggest that prenatal opioid exposure is associated with the disruption of placental homeostasis. This may be coordinated by protein synthesis and bioenergetic flux, as inferred from the modeled eukaryotic Translation Initiation Factor-mediated Integrated Stress Response. These findings establish a localized, clinical baseline of human placental stress, highlighting candidate molecular regulatory nodes to guide future mechanistic studies and biomarker discovery in exposed pregnancies. Full article

Background/Objectives: In the search for potent non-sugar α-glucosidase inhibitors with improved safety profiles, a novel flavonoid glycoside was isolated for the first time from the stem bark of Albizia saponaria (Fabaceae). The objective of this study was to elucidate its chemical structure and evaluate its therapeutic potential as an anti-hyperglycemic agent compared to known related flavonoids and a standard clinical drug. Methods: Comprehensive structural elucidation was performed using high-resolution mass spectrometry and multidimensional 1D/2D NMR (¹H, ¹³C, HSQC-DEPT, COSY, and CIGAR). To assess its inhibitory efficacy and pharmacokinetic profiles, an in silico comparative study was conducted against a database of related flavonoids (Quercitrin, Hyperoside, and Isoquercitrin) and the clinical drug Acarbose. This involved molecular docking simulations against human intestinal maltase-glucoamylase (PDB ID: 3TOP) alongside integrated ADMET modeling and toxicological screening. Results: The compound was successfully identified as 4′,7-dihydroxyflavan-3′-O-β-D-glucoside (1). Molecular docking revealed that Compound 1 exhibited a superior predicted binding affinity of −9.5 kcal/mol, outperforming Quercitrin (−9.3 kcal/mol), Hyperoside (−8.3 kcal/mol), Isoquercitrin (−7.9 kcal/mol), and Acarbose (−7.2 kcal/mol). This strong thermodynamic stability is driven by a robust conventional hydrogen-bonding network with key active site residues (Arg1377, Gln1372, and Gly1365), successfully overriding a localized electrostatic strain at Asp1279. Furthermore, ADMET modeling demonstrated a highly desirable local pharmacokinetic framework; its low Caco-2 permeability (−6.432) and low human intestinal absorption (HIA = 0.120) favor targeted luminal retention in the gastrointestinal tract, mirroring Acarbose while minimizing systemic exposure. Crucially, toxicological screening unveiled a significant safety advantage for Compound 1, marked by negligible CYP3A4 interaction (0.004) and a remarkably low risk of Drug-Induced Liver Injury (DILI = 0.213) compared to the high-risk hepatotoxic profile of Acarbose (DILI = 0.882) and the reference flavonoids (DILI > 0.69). Conclusions: These predictive findings establish Compound 1 as a highly promising, low-toxicity natural scaffold for anti-hyperglycemic drug development. Its superior binding affinity and minimized hepatotoxicity risk warrant subsequent in vitro and in vivo functional validation. Full article

The composition of honey is complex and can vary depending on its botanical and geographical origin. This study evaluated the phenolic acid profile (PAP), antioxidant activity, and antimicrobial properties of honey samples from different geographical origins, such as Romania (nine types: multiflower, thyme, manna, hawthorn, black locust, linden, rapeseed, mint, and pasture), Malaysia (Tualang), New Zealand (Manuka), and Spain (chestnut). Twelve different varieties of honey were analyzed, one sample for each type, and all analyses were performed in triplicate. Phenolic acids were extracted by solid-phase extraction (SPE) using C18 cartridges, followed by high-performance liquid chromatography with diode-array detection (HPLC-DAD) analysis at 310 nm. Antioxidant activity was assessed using the 2,2′-diphenyl-1-picrylhydrazyl (DPPH) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assays. Antimicrobial activity was evaluated by agar diffusion and broth microdilution to determine the minimum inhibitory concentration (MIC), while microbial anti-adherence activity was assessed using the crystal violet staining assay to determine the minimum anti-adherence inhibitory concentration (MAIC). The tested microorganisms included the reference strains Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, and Candida albicans ATCC 10231, as well as two C. albicans isolates (24114 and 5329). Several phenolic acids, including chlorogenic, caffeic, ferulic, trans-cinnamic, 3-O-methylgallic, p-coumaric, and syringic acids, were identified at varying concentrations across the analyzed honey samples. Rapeseed honey exhibited the highest overall concentration of phenolic acids. Among the honey samples analyzed, chestnut honey had the highest concentration of cinnamic acid, mint honey the highest concentration of ferulic acid, and multiflower honey the highest concentration of syringic acid. Tualang honey exhibited the highest antioxidant activity by both methods, reaching 2.103 mg TE/g honey for DPPH and 1.701 mg TE/g honey for ABTS. Tualang honey also exhibited the strongest antimicrobial activity against C. albicans and P. aeruginosa, whereas multifloral honey was the most active against E. faecalis. The analyzed honey extracts differed in their phenolic acid composition and biological activities, including antioxidant, antimicrobial, and anti-adherence effects of microorganisms on substrates. While associations were observed between selected phenolic acids and some of the evaluated biological activities, the overall biological properties of honey are more likely to arise from the combined contribution of multiple bioactive constituents than from individual compounds alone. The novelty of this study lies in the comparative assessment of the PAP obtained following SPE, and the biological activities of different types of honey from various botanical and geographical sources. Full article

Diabetic chronic wounds face multiple intractable healing obstacles including sustained inflammation, severe infection, insufficient angiogenesis and defective collagen deposition. Current dressings fail to simultaneously relieve all these pathological defects. Herein, we constructed a carrier-free binary self-assembled Glycyrrhizic acid monoammonium salt–Berberine (GB) hydrogel composed of berberine and glycyrrhizic acid monoammonium salt, which forms interconnected nanofiber networks via one-pot thermally assisted small-molecule co-assembly without chemical crosslinking or exogenous polymer carriers. Relying on intermolecular non-covalent interactions, this single supramolecular material integrates anti-inflammatory, broad-spectrum antibacterial, pro-angiogenic, and collagen-regenerative multifunctions, which simultaneously ameliorates multiple core pathological obstacles of diabetic wounds within one formulation. We systematically characterized its physicochemical features, biocompatibility, and antibacterial and anti-inflammatory activities, as well as in vivo wound repair performance. This hydrogel formed uniform nanofibrous architectures with favorable viscoelastic properties and pH-dependent sustained release. In vitro assays verified its outstanding biosafety, broad-spectrum bacteriostasis against Escherichia coli and Staphylococcus aureus, and potent inhibitory effects on pro-inflammatory cytokines TNF-α and IL-6, with bacterial inhibition rates reaching ~88% against E. coli and ~70% against S. aureus. In diabetic mouse full-thickness infected wound models, the GB hydrogel simultaneously alleviated local inflammation, accelerated wound closure and facilitated ordered collagen deposition and mature microvessel formation, achieving a 73.10% wound closure rate at day 7 and 58.01% collagen deposition fraction at day 14, thus exhibiting equivalent or superior repair capacity compared with commercial hydrogel dressings. This carrier-free supramolecular system based on natural herbal small molecules provides a safe, convenient, and integrated therapeutic strategy for diabetic infected chronic wounds, with promising clinical translation potential. Full article

Species of the genus Aristolochia are recognized as a rich source of structurally diverse specialized metabolites; however, the volatile chemical composition and biological properties of several Neotropical species remain poorly characterized. In particular, no information is currently available on the essential oil of Aristolochia lingulata Ule ex Pilg., which motivated this chemical, enantioselective, and preliminary biological investigation. The leaf essential oil was analyzed by GC-MS and GC-FID using nonpolar and polar stationary phases, while enantioselective GC-MS was employed to determine the distribution of selected chiral metabolites. Biological activity was evaluated through acetylcholinesterase, butyrylcholinesterase, pancreatic lipase, DPPH, and ABTS assays. A total of 57 constituents were identified and quantified, accounting for 93.5% and 91.3% of the oil on the two stationary phases. Sesquiterpene hydrocarbons and oxygenated sesquiterpenoids predominated, with dauca-5,8-diene, trans-(E)-nerolidol, β-chamigrene, β-cyclocitral, limonene, δ-amorphene, τ-muurolol, and manool among the main constituents. The oil showed moderate acetylcholinesterase inhibition (IC₅₀ = 79.8 ± 0.3 µg/mL), whereas weaker inhibition was observed against butyrylcholinesterase (IC₅₀ = 176.1 ± 3.3 µg/mL) and pancreatic lipase (IC₅₀ = 190.8 ± 9.4 µg/mL). Radical scavenging activity was also weak in the DPPH and ABTS assays (SC₅₀ = 849.7 ± 7.4 and 338.0 ± 3.9 µg/mL, respectively). Overall, this study provides the first characterization of the essential oil of A. lingulata, revealing a distinctive sesquiterpene-rich volatile profile and moderate enzyme-inhibitory activity. These findings expand the phytochemical knowledge of Neotropical Aristolochia species and provide a basis for further investigation of their bioactive constituents, mechanisms of action, and toxicological safety. Full article