Search Results (1,724)

Patulin (PAT) is a fatal mycotoxin that exerts serious threats to human and animal health. Biodegradation of PAT is considered to be one of the promising ways for controlling its contamination. In this study, Lactiplantibacillus plantarum 6076 (LP 6076) with reliable removal efficiency on PAT was screened out from three lactic acid bacteria (LAB) strains. It was found that the PAT was eliminated through degradation by LP 6076, and the intracellular proteins played a crucial role in PAT degradation with the induction of PAT. The proteomic analysis showed that the response of LP 6076 to PAT was by a concerted effort to repair DNA damage, in parallel to adaptive changes in cell wall biosynthesis and central metabolism. Eleven differentially expressed proteins with high fold changes were picked out and identified as PAT degradation candidate enzymes. The 3D structures of the candidate enzymes were predicted, and molecular docking between the enzymes and PAT was performed. Five enzymes, including Acetoin utilization AcuB protein (AU), GHKL domain-containing protein (GHLK), Dihydroneopterin aldolase (DA), YdeI/OmpD-associated family protein (YDEL), and Transcription regulator protein (TR), could dock with PAT with lower affinity and shorter distance. Through molecular docking analysis, DA was ultimately identified as a potential key degrading enzyme. The choice of DA was substantiated by its superior combination of strong binding affinity and a productive binding pose with PAT. VAL84 and GLN51 residues of DA were likely the active sites, forming four hydrogen bonds with PAT. Our study could accelerate the commercial application of biodegradation toward PAT decontamination. Full article

Background/Objectives: Osteoporosis is a multifactorial skeletal disorder in which chronic inflammation, dysregulated cytokine signaling, and metabolic imbalance contribute to excessive bone resorption and impaired bone formation. Asiatic acid has demonstrated bone-protective effects, but its molecular mechanisms in osteoporosis remain incompletely understood. This study aimed to investigate the anti-osteoporotic mechanisms of asiatic acid using an integrative in silico strategy. Methods: Network pharmacology analysis was performed to identify osteoporosis-related molecular targets of asiatic acid. Molecular docking was used to predict the binding modes and affinities between asiatic acid and its target proteins. Molecular dynamics simulation was used to assess the structural stability and interaction persistence of the asiatic acid–protein complex. Results: Network pharmacology identified 135 overlapping targets between asiatic acid and osteoporosis, with IL-6, STAT3, PPARG, and NFKB1 emerging as key hubs. KEGG analysis indicated the PPAR signaling pathway as a potential mechanism underlying the anti-osteoporotic effect. Molecular docking showed strong binding energies of asiatic acid with all predicted target proteins, with the highest affinity observed for IL-6, involving key residues ASN61, LEU62, GLU172, LYS66, and ARG168. Consistently, molecular dynamics simulation confirmed stable binding of asiatic acid to IL-6, with persistent interactions with ASN61, LYS66, LEU62, LEU64, and GLN154 mediated by hydrogen bonds, water bridges, and hydrophobic interactions. Conclusions: This integrative in silico study provides mechanistic insight into the potential anti-osteoporotic actions of asiatic acid, implicating IL-6 as a plausible upstream molecular target. These results establish a robust mechanistic framework for future translational studies exploring asiatic acid as a natural therapeutic candidate for osteoporosis. Full article

Type 2 diabetes mellitus (T2DM) involves chronic hyperglycemia, insulin resistance, low-grade inflammation, and oxidative stress that drive cardiometabolic and renal damage despite current therapies. Sodium–glucose cotransporter (SGLT) inhibitors have reshaped the treatment landscape, but residual risk and safety concerns highlight the need for new agents that combine glucose-lowering efficacy with redox–inflammatory modulation. LASSBio-1986 is a synthetic N-acylhydrazone (NAH) derivative designed as a gliflozin-like scaffold with the potential to interact with SGLT1/2 while also influencing oxidative and inflammatory pathways. Here, we integrated in silico and in vivo approaches to characterize LASSBio-1986 as a multifunctional antidiabetic lead in murine models of glucose dysregulation. PASS and target class prediction suggested a broad activity spectrum and highlighted transporter- and stress-related pathways. Molecular docking indicated high-affinity binding to both SGLT1 and SGLT2, with a modest energetic preference for SGLT2, and ADME/Tox predictions supported favorable oral drug-likeness. In vivo, intraperitoneal LASSBio-1986 improved oral glucose tolerance and reduced glycemic excursions in an acute glucose challenge model in C57BL/6 mice, while enhancing hepatic and skeletal muscle glycogen stores. In a dexamethasone-induced insulin-resistance model, LASSBio-1986 improved insulin sensitivity, favorably modulated serum lipids, attenuated thiobarbituric acid-reactive substances (TBARS), restored reduced glutathione (GSH) levels, and rebalanced pro- and anti-inflammatory cytokines in metabolic tissues, with efficacy broadly comparable to dapagliflozin. These convergent findings support LASSBio-1986 as a preclinical, multimodal lead that targets SGLT-dependent glucose handling while mitigating oxidative and inflammatory stress in models relevant to T2DM. Chronic disease models, formal toxicology, and pharmacokinetic studies, particularly with oral dosing, will be essential to define its translational potential. Full article

Background: Triple-negative breast cancer (TNBC), defined by the absence of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) expression, is associated with increased BRCA1/2 mutation rates. Extracellular vesicles (EVs) play a pivotal role in TNBC progression. This study aimed to analyze BRCA1/2 mutations and identify EV-related biomarkers for TNBC by employing TNBC-related datasets and EV-related genes (EVRGs). Methods: Initially, BRCA1/2 mutations in TNBC patients were examined. Differentially expressed EVRGs (DE-EVRGs) were identified by integrating the results of both differential expression analysis and weighted gene co-expression network analysis (WGCNA). Biomarkers were identified using Receiver Operating Characteristic (ROC) and Kaplan–Meier (K–M) analyses. Finally, functional enrichment, drug prediction, molecular docking, and reverse transcription quantitative polymerase chain reaction (RT-qPCR) analyses were performed. Results: Waterfall plots indicated that TP53 exhibited the highest mutation frequency in both the mutation (MUT) and wild-type (WT) group. Four distinct types of immune cells (for example, eosinophils and neutrophils) showed significantly elevated expression levels in the WT group. Notably, PLA2G5 was identified as a biomarker of TNBC and its expression was significantly lower in TNBC (p = 0.0025). Functional analysis demonstrated that PLA2G5 is enriched in the “drug metabolism cytochrome P450” pathway. Finally, 20 drugs targeting PLA2G5 were identified, among which leukotriene C4 demonstrated a binding affinity of −7.2 kcal/mol. This finding suggests that leukotriene C4 has potential therapeutic applications for the treatment of TNBC. Conclusions: Our study found significant differences between the MUT and WT groups, identifying PLA2G5 as a biomarker for TNBC and offering a theoretical basis for TNBC treatment. Full article

Background: Haemonchus contortus is a gastrointestinal nematode that affects small ruminants and exhibits widespread resistance to commercial anthelmintics. This has driven interest in natural compounds such as fatty acids and sterols; however, their biological relevance against resistant parasite strains remains insufficiently understood. Methods: The nematicidal potential of four fatty acids (palmitic, linoleic, pentadecanoic, and stearic acids) and two sterols (β-sitosterol and ergosterol), all of them commercially available in Mexico, was evaluated against infective L3 larvae of a benzimidazole-resistant H. contortus strain. In vitro larval mortality and migration inhibition assays were performed, and molecular docking analyses were conducted to explore interactions with the glutamate-gated chloride channel (GluCl) using AutoDock4. Statistical analyses were performed using ANOVA followed by Tukey’s post hoc test (p < 0.05). Results: Molecular docking indicated strong binding affinities of ergosterol and β-sitosterol to GluCl, comparable to that of ivermectin. In vitro assays showed that fatty acids, particularly linoleic acid, produced more pronounced effects on larval motility, suggesting predominantly nematostatic activity. No clear dose–response relationship was observed in migration assays, and in vitro mortality remained limited across treatments. Conclusions: The results highlight a disconnect between in silico binding affinity and in vitro biological activity, particularly in a drug-resistant H. contortus strain. Integrating in vitro bioassays with computational approaches provides valuable mechanistic insight but also underscores the limitations of affinity-based predictions for assessing anthelmintic efficacy. Full article

Puerarin is a naturally occurring isoflavone with reported anticancer activity, yet its topical translation is constrained by limited stability and suboptimal dermal delivery. A Puerarin-loaded proniosomal gel was developed as a potential dermal delivery platform, and we performed an initial assessment of its antimelanoma activity and safety. The gel was produced by coacervation–phase separation using Span 60, Tween 80, phosphatidylcholine, and cholesterol. Physicochemical characterization included pH, entrapment efficiency, rheology, FTIR, DSC, and vesicle properties (DLS, PDI, ζ-potential). In silico geometry optimization and docking were carried out for melanoma-associated targets (MITF and DNMT3B). Biological effects were investigated in vitro on A375 melanoma cells using MTT, morphological analysis, and nuclear/mitochondrial staining, while irritation potential was evaluated in ovo by HET-CAM. The optimized formulation exhibited a skin-compatible pH and an entrapment efficiency of 62 ± 0.26%. DLS indicated a multimodal population, with a major number-weighted vesicle population in the 100–200 nm range, and a ζ-potential of −34.9 ± 0.14 mV. FTIR and DSC supported component incorporation without evidence of chemical incompatibility. The gel showed non-Newtonian, pseudoplastic, thixotropic flow, which is advantageous for topical use. Docking predicted meaningful affinities of Puerarin toward MITF and DNMT3B. The formulation reduced A375 viability in a dose-dependent manner (to 44.66% at 200 µg/mL) and, at higher concentrations, produced nuclear condensation and disruption of the mitochondrial network. HET-CAM classified the gel as non-irritant. The Puerarin-loaded proniosomal gel represents a promising topical platform with preliminary in vitro antimelanoma cytotoxic potential, warranting additional studies to validate skin delivery, efficacy, and safety. Full article

Background/Objectives: Recent reports have demonstrated the antiparasitic activity of 1,4-dihydropyridine (1,4-DHPs). This study aimed to assess the in vitro antischistosomal activity of 24 1,4-DHPs against Schistosoma mansoni adult worms. Methods: Sixteen hexahydroquinolines (1–16) and eight Hantzsch esters (17–24) previously obtained through a multicomponent Hantzsch reaction were tested in vitro against Schistosoma mansoni adult worms. In silico studies with the most active compounds were also carried out. Results: Among the tested compounds, the Hantzsch esters 20 (diethyl 4-(4-bromophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) and 21 (diethyl 4-(3-fluorophenyl)-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylate) provided the lowest IC₅₀ (15.2 and 13.1 µM, respectively) and the highest selectivity for this parasite (SI = 2.31 and >4.59, respectively). Conclusions: Docking studies revealed that compound 21 has a high affinity for the S. mansoni target (PDB ID: 6UY4). Furthermore, ADMET predictions indicated that compound 21 meets the drug-likeness criteria without violating any Lipinski, Veber, or Egan’s rules. Full article

Understanding how supercritical CO₂ and water interact with mineral surfaces is essential for predicting the stability and sealing performance of geological storage formations. Yet, the combined effects of mineral surface chemistry and confined pore geometry on interfacial structure and fluid dynamics remain insufficiently resolved at the molecular scale. In this study, molecular dynamics simulations were employed to quantify how methylated SiO₂, hydroxylated SiO₂, and kaolinite regulate CO₂–H₂O interfacial behavior through variations in wettability and electrostatic interactions. The results show a clear hierarchy in water affinity across the three minerals. On methylated SiO₂, the water cluster remains spherical and poorly anchored, with a contact angle of ~140°, consistent with the weakest water–surface Coulomb attractions (only −400 to −1400 kJ/mol). Hydroxylated SiO₂ significantly enhances hydration, forming a cylindrical water layer with a reduced contact angle of ~61.3° and strong surface–water electrostatic binding (~−18,000 to −20,000 kJ/mol). Kaolinite exhibits the highest hydrophilicity, where water forms a continuous bridge between the two walls and the contact angle further decreases to ~24.5°, supported by the strongest mineral–water electrostatic interactions (−23,000 to −25,000 kJ/mol). Meanwhile, CO₂–water attractions remain moderate (typically −2800 to −3500 kJ/mol) but are sufficient to influence CO₂ distribution within the confined domain. These findings collectively reveal that surface functionalization and mineral type govern interfacial morphology, fluid confinement, and electrostatic stabilization in the sequence methylated SiO₂ < hydroxylated SiO₂ < kaolinite. This molecular-level understanding provides mechanistic insight into how mineral wettability controls CO₂ trapping, fluid segregation, and pore-scale sealing behavior in subsurface carbon-storage environments. Full article

Ultraviolet B radiation is a major cause of skin aging, cellular senescence, and inflammaging, mediated by the excessive production of reactive oxygen species (ROS) and induction of apoptosis. This study evaluated the photo-protective effects of astaxanthin, one of the strongest natural antioxidants, in UVB-treated keratinocytes. The antioxidant capacity of astaxanthin was evaluated using ABTS, DPPH, and NBT/riboflavin/SOD assays. HaCaT cells were exposed to 30 mJ/cm² of UVB radiation. Photoprotective effects and accumulated ROS were evaluated in UVB-irradiated HaCaT cells by MTT and DCFH-DA assays. Nitric oxide levels were quantified using the Griess reagent. Apoptosis was assessed by dual staining using acridine orange/ethidium bromide, lysosomal integrity by acridine orange uptake, and cell migration by scratch assay. Cell adhesion was assessed on ECM-coated Nunc plates. Finally, we formulated a 0.5% astaxanthin-enriched cream. Astaxanthin mitigated UVB-induced damage by reducing intracellular ROS levels by 3.7-fold, decreasing nitric oxide production to 29.8 ± 7.7% at the highest concentration, and maintaining lysosomal integrity. The carotenoid significantly enhanced cell viability, increasing it from 60.64 ± 8.3% in UV-treated cells to 102.1 ± 3.22% at 40 µM. Moreover, treated cells showed a significant reduction (p < 0.001) in the apoptotic rate (37.7 ± 3.1 vs. 87.7 ± 3.8 in UVB-irradiated cells, as evidenced by reduced chromatin condensation and nuclear fragmentation. Astaxanthin also enhanced tissue repair, as evidenced by increased cell migration and adhesion to several extracellular matrix (ECM) proteins (poly-L-lysine, laminin, fibrinogen, vitronectin and collagen I). In silico molecular docking predicted strong binding affinities between astaxanthin and key cellular targets, including JAK2 (−9.9 kcal/mol, highest affinity), STAT3, FAK, COX-2, NF-k-B, MMP2, and MMP9. The formulated cream demonstrated an in vitro SPF of 7.2 ± 2.5. Astaxanthin acts as a multifunctional photoprotective compound, providing a strong rationale for its incorporation into cosmetic and dermatological formulations, as further supported by the successful formulation and in vitro SPF estimation of an astaxanthin-enriched cream. Full article

Oxidative stress is a key driver of chronic inflammatory diseases. Anodendron affine is a native Formosan plant species in Taiwan that remains largely underexplored phytochemically and bioactivity. To reveal the bioactive constituents and assess its potential as a source of anti-inflammatory antioxidants, we performed bioactivity-guided fractionation and evaluated the inhibition of superoxide anion (O₂^•−) generation in formyl-L-methionyl-L-leucyl-L-phenylalanine-stimulated human neutrophils. Molecular docking simulations were employed to model interactions with Formyl peptide receptor 1 (FPR1) and the Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex, including neutrophil cytosol factor 1 (p47phox) and NADPH oxidase 2 (NOX2), to propose a theoretical mechanism of action. Phytochemical investigation led to the isolation of two new compounds, methyl 4,5-O-diferuloyl-3-methoxyquinate (1) and 16-pregnen-3,12,20-trione (2), together with four known compounds. Notably, 4-hydroxy-3-prenylbenzoic acid (5) exhibited potent inhibitory activity (IC₅₀ = 17.65 ± 0.97 μM), surpassing the activity of the positive control, ibuprofen (IC₅₀ = 27.85 ± 3.56 μM). Docking studies suggested that anodendrosin H (4) and 4-hydroxy-3-prenylbenzoic acid (5) exhibit high predicted binding affinity to p47phox and NOX2. Based on these results, compounds 1, 4, and 5 from A. affine were identified as potential lead candidates for the development of novel anti-inflammatory therapeutics. Full article

Per- and polyfluoroalkyl substances (PFASs), as a class of “permanent chemicals” with high environmental persistence and bioaccumulation, have attracted much attention. In this study, we focused on the molecular mechanism of the interaction between perfluoroalkyl acids (PFAAs) and peroxisome proliferator-activated receptor δ (PPARδ). Using molecular docking, binding free energy calculation, and structural analysis, we systematically investigated the binding modes, key amino acid residues, and binding energies of 20 structurally diverse PFAAs with PPARδ. The results showed that the binding energies of PFAAs with PPARδ were significantly affected by the molecular weight, the number of hydrogen bond donors, and the melting point of PFAAs. PFAAs with smaller molecular weights and fewer hydrogen bond donors showed stronger binding affinity. The binding sites were concentrated in high-frequency amino acid residues such as TRP-256, ASN-269, and GLY-270, and the interaction forces were dominated by hydrogen and halogen bonds. PFAAs with branched structure of larger molecular weight (e.g., 3m-PFOA, binding energy of −2.92 kcal·mol⁻¹; 3,3m₂-PFOA, binding energy of −2.45 kcal·mol⁻¹) had weaker binding energies than their straight-chain counterparts due to spatial site-blocking effect. In addition, validation group experiments further confirmed the regulation law of binding strength by physicochemical properties. In order to verify the binding stability of the key complexes predicted by molecular docking, and to investigate the dynamic behavior under the conditions of solvation and protein flexibility, molecular dynamics simulations were conducted on PFBA, PFOA, 3,3m₂-PFOA, and PFHxA. The results confirmed the dynamic stability of the binding of the high-affinity ligands selected through docking to PPARδ. Moreover, the influence of molecular weight and branched structure on the binding strength was quantitatively verified from the perspectives of energy and RMSD trajectories. The present study revealed the molecular mechanism of PFAAs interfering with metabolic homeostasis through the PPARδ pathway, providing a theoretical basis for assessing its ecological and health risks. Full article

Nanoparticles interact dynamically with proteins, often leading to adsorption-induced conformational changes that alter protein function and contribute to corona formation. Here we investigated the adsorption and unfolding of a model protein GB1 on latex nanoparticle surfaces using a combination of mutational analysis, equilibrium binding assays, stopped-flow kinetics and Φ-value interpretation. Seven site-directed variants of GB1 were studied to dissect residue-specific contributions to adsorption energetics. Fluorescence binding isotherms revealed that D46A and T53A mutations weakened surface affinity, while kinetic analysis demonstrated that D46A reduced adsorption rate by ~6-fold and produced a dramatic unfolding/refolding shift, identifying Asp46 as a key docking site. Φ-value analysis further highlighted Asp46 and Thr53 as central residues in the adsorption transition state, whereas mutations in the hydrophobic core or distal loops had negligible effects. These results support a dock–loosen–unfold mechanism in which electrostatic recognition initiates binding, followed by hydrophobic exposure and hairpin stabilization. This residue-level sampling of key sites advances mechanistic understanding of protein–nanoparticle interactions and suggests strategies for tuning surface charge to control corona formation. Our approach provides a generalizable method to map adsorption transition states, with implications for designing safer nanomaterials, predicting protein corona composition, and harnessing protein unfolding in biosensing applications. Full article

Bacillus-derived lipopeptides are known to possess diverse biological activities, including antimicrobial and anticancer properties, though the mechanisms of such effects at the molecular level remain incompletely understood. We investigated whether non-ribosomal peptide metabolites from Bacillus can directly interact with transmembrane receptors implicated in oxidative stress regulation and cancer progression (NOX4, EGFR, PDGFR, and OCTN2) using molecular docking and 200 ns molecular dynamics simulations of 11 lipopeptide metabolites. Molecular docking revealed several strong ligand–protein interactions, with plipastatin and fengycin emerging as lead compounds demonstrating the highest binding affinities to multiple receptors. For NOX4, iturin D showed the strongest docking score of −7.85 kcal/mol. Fengycin demonstrated a high docking score of −7.38 kcal/mol for PDGFR and −8.1 kcal/mol for EGFR. Plipastatin showed the strongest docking scores of −11.12 kcal/mol for EGFR and −8.7 kcal/mol for OCTN2. Molecular dynamics simulations confirmed complex stability for these lead compounds, with protein RMSD remaining stable at ~1.5 Å and ligand RMSD between 1.9 and 6 Å over 200 ns. Our findings suggest that plipastatin and fengycin may act as modulators of key receptors involved in oxidative stress and cancer-related signaling. However, those in silico predictions require experimental validation. This work provides the first computational evidence of potential lipopeptide–receptor interactions and establishes a foundation for future experimental investigation of probiotic-derived therapeutics. Full article

Background/Objectives: Diabetes mellitus is a serious global disease characterized by chronic hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. It represents a major health concern affecting millions of people worldwide. This condition can lead to severe complications significantly affecting patients’ quality of life. Due to the limitations and side effects of current therapies, the search for safer and more effective antidiabetic agents, particularly from natural sources, has gained considerable attention. This study investigates the antidiabetic potential of seaweed-derived compounds through structure-based virtual screening targeting α-glucosidase. Methods: A library of compounds derived from the Seaweed Metabolite Database was subjected to a hierarchical molecular docking protocol against α-glucosidase. Extra Precision (XP) docking was employed to identify the top-ranked ligands based on their binding affinities. Drug-likeness was assessed according to Lipinski’s Rule of Five, followed by pharmacokinetic and toxicity predictions to evaluate ADMET properties. Density Functional Theory (DFT) calculations were performed to analyze the electronic properties and chemical reactivity of the selected compounds. Furthermore, molecular dynamics simulations were carried out to examine the stability and dynamic behavior of the ligand–enzyme complexes. Results: Following XP docking and ADMET prediction, four promising compounds were selected: Colensolide A, Rhodomelol, Callophycin A, and 7-(2,3-dibromo-4,5-dihydroxybenzyl)-3,7-dihydro-1H-purine-2,6-dione. Molecular dynamics simulations further confirmed the structural stability and strong binding interactions of these compounds within the α-glucosidase active site. Conclusions: This investigation demonstrated the important role of seaweed-derived compounds in inhibiting α-glucosidase activity. Further experimental validation is warranted to confirm their biological activity and therapeutic potential. Full article

Perinatal depression (PND) is a severe mood disorder affecting mothers during pregnancy and postpartum, with implications for both maternal and neonatal health. Emerging evidence suggests that gut microbiota-derived metabolites play a critical role in neuroinflammation and neurotransmission. In this study, we employed an in silico approach to evaluate the pharmacokinetic and therapeutic potential of metabolites produced by Lactobacillus helveticus and Bifidobacterium longum in targeting key proteins implicated in PND, including BDNF, CCL2, TNF, IL17A, IL1B, CXCL8, IL6, IL10. The ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) profiles of selected microbial metabolites, including acetate, lactate, formate, folic acid, riboflavin, kynurenic acid, γ-aminobutyric acid, and vitamin B12 were assessed using computational tools to predict their bioavailability and safety. Enrichment analysis was performed to identify biological pathways and molecular mechanisms modulated by these metabolites, with a focus on neuroinflammation, stress response, and neurogenesis. Additionally, molecular docking studies were conducted to evaluate the binding affinities of these metabolites toward the selected PND-associated targets, providing insights into their potential as neuroactive agents. Our findings suggest that specific microbial metabolites exhibit favorable ADMET properties and strong binding interactions with key proteins implicated in PND pathophysiology. These results highlight the therapeutic potential of gut microbiota-derived metabolites in modulating neuroinflammatory and neuroendocrine pathways, paving the way for novel microbiome-based interventions for perinatal depression. Further experimental validation is warranted to confirm these computational predictions and explore the clinical relevance of these findings. Full article