Search Results (5,921)

This study systematically analyzed the multidimensional effects of Lactobacillus fermentation on Pueraria lobata (PL) and investigated the potential mechanisms underlying its hypolipidemic activity. Results indicated that fermentation significantly increased the total acid content from 1.02 to 3.48 g·L⁻¹, representing a 2.41-fold increase. Although slight reductions were observed in total flavonoids (8.67%) and total phenolics (6.72%), the majority of bioactive components were well preserved. Other antioxidant capacities were retained at >74.71% of baseline, except hydroxyl radical scavenging. Flavor profiling showed increased sourness and astringency, accompanied by reduced bitterness, with volatile compounds such as β-pinene and trans-2-hexenyl butyrate contributing to a distinct aromatic profile. Untargeted metabolomics analysis revealed that fermentation specifically enhanced the abundance of low-concentration isoflavone aglycones, including daidzein and genistein, suggesting a compositional shift that may improve hypolipidemic efficacy. Integrated network pharmacology and computational modeling predicted that eight key components, including genistein, could stably bind to ten core targets (e.g., AKT1 and MMP9) primarily through hydrogen bonding and hydrophobic interactions, potentially regulating lipid metabolism via the PI3K-AKT, PPAR, and estrogen signaling pathways. This study reveals the role of Lactobacillus fermentation in promoting the conversion of isoflavone glycosides to aglycones in PL and constructs a multi-dimensional “components-targets-pathways-disease” network, providing both experimental evidence and a theoretical foundation for further research on the lipid-lowering mechanisms of fermented PL and the development of related functional products. Full article

Chronic inflammatory bowel disease, ulcerative colitis (UC), currently lacks specific drugs for clinical treatment, and screening effective therapeutic agents from natural plants represents a critical research strategy. This study aimed to investigate the therapeutic potential of the flavonoid extract of Polygonum viviparum L. (TFPV) against UC. Liquid chromatography-mass spectrometry (LC-MS) was used to identify the chemical components of TFPV, while cell and animal models were employed to evaluate its anti-inflammatory effects on lipopolysaccharide (LPS)-induced inflammation. The mechanism of anti-inflammatory action was further investigated using a mouse model of UC induced by dextran sulfate sodium (DSS). The results revealed the identification of 32 bioactive components in TFPV, with major compounds such as kaempferol, luteolin, galangin, and quercetin. TFPV effectively mitigated inflammatory damage induced by LPS in IPEC-J2 cells and C57BL/6 mice. In the UC modeled by DSS, TFPV attenuated intestinal inflammation by reducing pro-inflammatory cytokines IL-1β, IL-6, and TNF-α; increasing the anti-inflammatory cytokine IL-10; up-regulating tight junction protein expression such as Claudin-1, Occludin, and ZO-1; and inhibiting the expression of PI3K, AKT, NF-κB, and IL-17 proteins. Analysis of mice fecal samples through 16S rRNA gene sequencing demonstrated that TFPV adjusted the equilibrium of gut microbiota by boosting the abundance of Dubosiella and diminishing that of Enterococcus, Romboutsia, and Enterobacter. Untargeted metabolomics analysis further revealed that TFPV reduced inosine and ADP levels while increasing dGMP levels by the regulation of purine metabolism, ultimately resulting in decreased uric acid levels and thereby alleviating intestinal inflammation. Additionally, TFPV safeguarded the intestinal mucosal barrier by enhancing the expression of tight junctions. In conclusion, TFPV alleviates UC by blocking the PI3K/AKT/NF-κB and IL-17 signaling pathways, lessening intestinal inflammation and injury, safeguarding intestinal barrier integrity, balancing gut microbiota, and lowering uric acid levels, suggesting its promise as a therapeutic agent for UC. Full article

Background: Acute lung injury (ALI) and its severe form, acute respiratory distress syndrome (ARDS), remain major causes of morbidity and mortality, yet no targeted pharmacological therapy is available. Excessive neutrophil and macrophage infiltration drives reactive oxygen species (ROS) production and cytokine release, leading to alveolar–capillary barrier disruption and fatal respiratory failure. Methods: We applied an integrative multi-omics strategy combining single-cell transcriptomics, peripheral blood proteomics, and lung tissue proteomics in a lipopolysaccharide (LPS, 10 mg/kg)-induced mouse ALI model to identify key signaling pathways. Harpagide, an iridoid glycoside identified from our natural compound screen, was evaluated in vivo (40 and 80 mg/kg) and in vitro (0.1–1 mg/mL). Histopathology, oxidative stress markers (SOD, GSH, and MDA), cytokine levels (IL-6 and IL-1β), and signaling proteins (HIF-1α, p-PI3K, p-AKT, Nrf2, and HO-1) were quantitatively assessed. Direct target engagement was probed using surface plasmon resonance (SPR), the cellular thermal shift assay (CETSA), and 100 ns molecular dynamics (MD) simulations. Results: Multi-omics profiling revealed robust activation of HIF-1, PI3K/AKT, and glutathione-metabolism pathways following the LPS challenge, with HIF-1α, VEGFA, and AKT as core regulators. Harpagide treatment significantly reduced lung injury scores by ~45% (p < 0.01), collagen deposition by ~50%, and ROS accumulation by >60% relative to LPS (n = 6). The pro-inflammatory cytokines IL-6 and IL-1β were reduced by 55–70% at the protein level (p < 0.01). Harpagide dose-dependently suppressed HIF-1α and p-AKT expression while enhancing Nrf2 and HO-1 levels (p < 0.05). SPR confirmed direct binding of Harpagide to HIF-1α (KD = 8.73 µM), and the CETSA demonstrated enhanced thermal stability of HIF-1α. MD simulations revealed a stable binding conformation within the inhibitory/C-TAD region after 50 ns. Conclusions: This study reveals convergent immune–microenvironmental regulatory mechanisms across cellular and tissue levels in ALI and demonstrates the protective effects of Harpagide through multi-pathway modulation. These findings offer new insights into the pathogenesis of ALI and support the development of “one-drug, multilayer co-regulation” strategies for systemic inflammatory diseases. Full article

Drug repurposing refers to the systematic identification of new therapeutic uses for existing drugs. Unlike traditional de novo drug discovery, which is expensive and time-consuming, repurposing leverages compounds with already established safety, pharmacokinetic, and pharmacodynamic profiles. In this study, we propose a drug repositioning model based on low-dimensional transcriptomic representations to investigate the relationship between known anticancer drugs and non-anticancer compounds. We analyzed LINCS L1000 data (1170 drugs; 824 anticancer, 346 non-anticancer). Data were projected with UMAP, PCA, and t-SNE. For each anticancer drug and for each method, we retrieved the k = 5 nearest non-anticancer neighbors and ranked candidates by recurrence frequency across all anticancer queries. We identified Ergometrine, Mupirocin, and (S)-blebbistatin among the most frequent non-anticancer drugs with a close association with drugs known to be anticancer. In addition, we performed a local neighborhood enrichment around the three candidates. Regarding Ergometrine (DB01253), in UMAP, 44/50 neighbors were anticancer (88.0% vs. global baseline 70.5%; hypergeometric BH-adjusted p = 0.0039). Considering (S)-blebbistatin (DB01944) in UMAP, 41/50 neighbors were anticancer (82.0% vs. 70.5%; BH-adjusted p = 0.0435). Mupirocin (DB00410) in UMAP had 44/50 neighbors as anticancer (88.0% vs. 70.5%; BH-adjusted p = 0.0039). Future research should explore the three drugs with in vivo models, investigating their possible synergies. Full article

In this study, Cu(II) complexes containing the bidentate ligand N,N-dimethylethylendiamine (dmen), i.e., [Cu^II(dmen)₂(CH₃COO)₂], [Cu^II(dmen)₂(NO₃)₂], and [Cu^II(dmen)₂Cl₂], were developed to explore molecular catalysis for the oxygen reduction reaction (ORR). Cyclic voltammetry and UV–vis spectroelectrochemical and electrochemical impedance spectroscopy experiments were performed in the absence and presence of oxygen. The UV–vis spectroscopy results suggested that the aforementioned Cu(II) complexes present an octahedral geometry in the solid state; meanwhile, they show a square pyramidal geometry in an aqueous solution. It is proposed that the chemical species [Cu^I(dmen)₂H₂O]⁺ reacts with O₂, exhibiting an outer-sphere electron transfer mechanism. The same UV–vis spectroelectrochemical response obtained with and without O₂ indicated a direct electron transfer from Cu(II) to Cu(I), with the regeneration of catalyst and the absence of other intermediate species. Among the reported compounds, [Cu(dmen)₂(NO₃)₂] exhibited the highest catalytic rate (TOF = 1.3 × 10⁴ s⁻¹). The impedance spectroscopy results showed that the resistance charge transfer (R_ct) of the redox pair Cu^II|Cu^I decreased in the presence of O₂ from 36.391 kΩ to 5.54 kΩ. For a better understanding of the effect of aliphatic amines on the ORR, a comparison with the complex [Cu(1,10-phen)₂NO₃]NO₃ is also presented. Full article

Light-dependent protochlorophyllide oxidoreductase (LPOR, E.C.1.3.1.33) plays a crucial role in the biosynthesis of chlorophyll in plants. Therefore, inactivating LPOR can hinder the production of chlorophyll to achieve the effect of weed control. In this research, utilizing an active substructure splicing method, 20 new 1,2,4-oxadiazole compounds targeting LPOR were synthesized. Among them, compounds 5j, 5k and 5q exhibited superior inhibitory efficacy in greenhouse herbicidal trials. In vitro enzyme activity assays indicated that 5q significantly inhibited Arabidopsis thaliana LPOR (AtLPOR), with an IC₅₀ value of 17.63 μM. Furthermore, compound 5q exhibited superior crop safety and holds potential application prospects for weed management in cotton. Molecular docking and dynamic simulations were employed to elucidate the binding mode and molecular mechanism of 5q with AtLPOR. These experimental and theoretical results indicate that 5q is a promising candidate for the development of novel herbicides targeting LPOR. Full article

Effective treatment of central nervous system (CNS) infections remains a major challenge, as most therapeutic agents do not efficiently cross the blood–brain barrier (BBB) and the blood–cerebrospinal fluid barrier (BCSFB). Coumarin derivatives are of particular interest due to their broad pharmacological activity, favorable safety profile, and potential to penetrate biological barriers. Eight novel coumarin-based peptidomimetics functionalized with trifluoromethyl or methyl scaffolds were synthesized and evaluated as antimicrobial agents with the ability to cross the blood–brain barrier. Antimicrobial activity of the investigated compounds was tested against Staphylococcus aureus and multiple Escherichia coli strains (K12, R2, R3, R4) using minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) assays. Cytotoxicity was assessed in vitro in BALB/c-3T3 mouse fibroblasts and αT3-1 pituitary gonadotrope cells using the MTT assay. In vivo studies were performed in sheep to assess transfer of the compounds from blood to cerebrospinal fluid (CSF). All synthesized derivatives demonstrated antimicrobial activity and acceptable cytotoxicity, comparable to those of clinically used antibiotics. CF₃-modified coumarin peptidomimetics show promise as antimicrobial agents with the potential to penetrate the BBB/BCSFB. These findings support further investigation of coumarin-based scaffolds as a platform for the development of novel therapeutics for CNS infections. Full article

The growing potassium (K) demand and supply–demand imbalance in intensive agriculture require the development of multi-nutrient K fertilizers. Polyhalite (POLY), a multi-nutrient natural mineral rich in K, calcium, magnesium, and sulfur, can enhance soil nutrient diversity and fertility. However, research on its synergistic application with nitrogen (N) fertilizer remains limited. Therefore, this study was designed to apply three different fertilizer composites at four N concentration gradients through field plot experiments to evaluate crop productivity and nutrient use efficiency. Results revealed that the application of both compound fertilizers with N fertilizer increased maize yield, ranging from 1.03% to 11.53%, compared with the PK control. Moreover, 25-7-8 (MOP)(POLY26%) achieved a maximum yield of 9499.88 kg/ha at the N1 (170 kg/ha) level. This represents a significant increase of 11.53% compared with the PK control. Moreover, the application of compound fertilizer containing POLY could significantly increase the N fertilizer utilization rate; improve the quality of maize; and exert a significant effect on soil pH, EC, and nutrient content. This study paves the way for broader application of POLY by establishing its novel role as a sustainable nutrient source. It provides critical strategic guidance for advancing global resource-efficient agriculture. Full article

In this study, the use of spent coffee waste as a green precursor of polyphenolic compounds, which are subsequently employed as reducing agents for the synthesis of zero-valent iron nanoparticles (nZVI) aimed at the efficient removal of dyes from aqueous systems, has been investigated. The nanoparticles, generated in situ in the presence of controlled amounts of hydrogen peroxide, were applied in the removal of organic dyes—including methylene blue, methyl orange, and orange G—through a heterogeneous Fenton-like catalytic process. The synthesized nZVI were thoroughly characterized by nitrogen adsorption at 77 K, scanning electron microscopy (SEM), transmission electron microscopy (TEM), Fourier-transform infrared spectroscopy (FT-IR), and powder X-ray diffraction (XRD). A statistical design of experiments and response surface methodology were employed to evaluate the effect of polyphenol, Fe(III), and H₂O₂ concentrations on dye removal efficiency. Results showed that under optimized conditions, a 100% removal efficiency could be achieved. This work highlights the potential of nZVI synthesized from agro-industrial waste through sustainable routes as an effective solution for water remediation, contributing to circular economy strategies and environmental protection. Full article

Breast cancer remains a leading cause of morbidity and mortality among women globally, with increasing incidence projected in the coming years. Despite advances in standard oncologic therapies, there is a growing interest in supportive interventions that enhance treatment efficacy and reduce adverse effects. This review critically evaluates preclinical and clinical data on the medicinal mushroom Coriolus versicolor and its bioactive compounds—primarily polysaccharide-K, polysaccharopeptide, and laccase—as potential adjuvants in breast cancer therapy. A systematic PubMed search identified 11 original studies from 2010 to 2025 examining the impact of C. versicolor on breast cancer cell lines, animal models, and human subjects. Findings consistently demonstrate antiproliferative, pro-apoptotic, necroptotic, anti-invasive, and immunomodulatory effects across various breast cancer subtypes, including triple-negative breast cancer. One phase I clinical trial also reported good tolerability and immunological benefits in patients post-chemotherapy. The review highlights molecular mechanisms involving apoptosis, necroptosis, and modulation of the tumor microenvironment. While promising, these results underscore the need for standardized preparations, pharmacokinetic data, and larger placebo-controlled trials. Overall, C. versicolor shows potential as a safe, natural adjunct to conventional therapy, offering prospects for integrative strategies in breast cancer management. Full article

The reaction of 4,4′-bipyridine (C₁₀H₈N₂) with the alkali metal pentacyanocyclopentadienides [Na{C₅(CN)₅}(MeOH)] and [KC₅(CN)₅] gives the coordination polymers [Na{C₅(CN)₅}(EtOH)(H₂O)(C₁₀H₈N₂)] (1) and [K{C₅(CN)₅}(H₂O)₂] • 2 (C₁₀H₈N₂) (2) after recrystallization from EtOH. Both compounds show octahedral coordination around the metal ion with a NaN₄O₂ and KN₂O₄ environment. The [C₅(CN)₅] acts as a 1,1-bridging ligand in 1 and a 1,2-bridging ligand in 2. The 4,4′-bipyridine acts as a N,N′-bridging ligand between dimeric [Na₂(EtOH)₂(H₂O)₂(µ-{C₅(CN)₅}₂] units, while it acts only as a guest molecule in the voids between polymeric [K(µ-H₂O)_4/2{µ-C₅(CN)₅}_2/2]_∞ chains. Both compounds employ multiple hydrogen bonds and π stacking to stabilize the crystalline structures. Full article

Olive pomace (OP) contains phytotoxic compounds that can impair plant growth and soil quality. Composting provides an effective method for detoxifying olive pomace (OP) and improving its suitability for agricultural use. Therefore, this study investigated the phytotoxic effects of raw olive pomace filtrate (OPF) on seed germination in radish (Raphanus sativus L.) and barley (Hordeum vulgare L.), as well as the impact of composted olive pomace (COP) on their growth. Seeds were exposed to OPF at concentrations of 0% (control), 1%, 3%, 5%, 10%, 20%, and 100%. Additionally, three composting treatments were evaluated: R1 (control: OP + barley straw), R2 (OP + barley straw + urea), and R3 (OP + barley straw + sheep litter). Results showed that OPF at concentrations of 10%, 20%, and 100% significantly reduced seed germination, with complete inhibition at concentrations > 10%. The COP treatments showed different physicochemical properties, such as R2 exhibiting better nutrient availability (C/N = 19, oil content = 0.04%). R3 had the highest concentrations of K (40,430.2 mg/kg) and P (6022.68 mg/kg). Results also indicated that R1 significantly reduced radish dry biomass production compared to barley, although R2 performed slightly better than R1 and R3. The findings highlight the need for proper compost stabilization to minimize the phytotoxicity and improve the agricultural potential of COP for improving soil health. Full article

Polyamines, particularly spermidine, have emerged as key dietary factors with roles in cellular health, autophagy, and longevity. However, strategies for scalable production of polyamine-rich food ingredients remain limited. Here, we report the development of a high-spermidine-producing Saccharomyces cerevisiae strain, 3L63, obtained via ultraviolet mutagenesis of the K7 strain. This strain exhibited a 5.9-fold increase in the total polyamine content, with spermidine being the most abundant. A scalable fermentation system of up to 10⁴ L was established, yielding a dried yeast product that met food safety criteria. Whole-genome sequencing identified mutations in central metabolic pathways, including ARG3, and functional enrichment analysis suggested broad metabolic rewiring, supporting an enhanced biosynthetic capacity, including polyamines. Free amino acid profiling revealed higher arginine levels in 3L63 than in K7, which is consistent with its role as a polyamine precursor. The 3L63 yeast-derived product was enriched in essential amino acids and polyamines. Functionally, this strain promoted the proliferation of normal and senescent human dermal fibroblasts, and its autophagy-inducing activity exceeded that of equivalent concentrations of pure spermidine, suggesting synergistic effects of yeast-derived bioactive compounds. This study demonstrates a non-genetically modified, high-spermidine yeast strain as a promising functional food ingredient with potential applications in healthy aging. Full article

Background/Objectives: Cancer progression is characterized by the suppression of apoptosis, activation of metastatic processes, and dysregulation of cell proliferation. The proper functioning of these mechanisms relies on critical signaling pathways, including Phosphoinositide 3-kinase/Protein kinase B/mammalian Target of Rapamycin (PI3K/Akt/mTOR), Mitogen-Activated Protein Kinase (MAPK), and Signal Transducer and Activator of Transcription 3 (STAT3). Although curcumin and resveratrol exhibit anticancer properties and affect these pathways, their pharmacokinetic limitations, including poor bioavailability and low solubility, restrict their clinical application. The aim of our study was to evaluate the synergistic anticancer potential of curcumin and resveratrol through hybrid molecules rationally designed from these compounds to mitigate their pharmacokinetic limitations. Furthermore, we analyzed the multi-target anticancer effects of these hybrids on the AKT serine/threonine kinase 1 (AKT1), MAPK, and STAT3 pathways using in silico molecular modeling approaches. Methods: Three hybrid molecules, including a long-chain (ELRC-LC) and a short-chain (ELRC-SC) hybrid, an ester-linked hybrid, and an ether-linked hybrid (EtLRC), were designed using the Avogadro software (v1.2.0), and their geometry optimization was carried out using Density Functional Theory (DFT). The electronic properties of the structures were characterized through Frontier Molecular Orbital (FMO), Molecular Electrostatic Potential (MEP), and Fourier Transform Infrared (FTIR) analyses. The binding energies of the hybrid molecules, curcumin, resveratrol, their analogs, and the reference inhibitor were calculated against the AKT1, MAPK, and STAT3 receptors using molecular docking. The stabilities of the best-fitting complexes were evaluated through 100 ns molecular dynamics (MD) simulations, and their binding free energies were estimated using the Molecular Mechanics/Poisson–Boltzmann Surface Area (MM/PBSA) method. Results: DFT analyses demonstrated stable electronic characteristics for the hybrids. Molecular docking analyses revealed that the hybrids exhibited stronger binding compared to curcumin and resveratrol. The binding energy of −11.4 kcal/mol obtained for the ELRC-LC hybrid against AKT1 was particularly remarkable. Analysis of 100 ns MD simulations confirmed the conformational stability of the hybrids. Conclusions: Hybrid molecules have been shown to exert multi-target mechanisms of action on the AKT1, MAPK, and STAT3 pathways, and to represent potential anticancer candidates capable of overcoming pharmacokinetic limitations. Our in silico-based study provides data that will guide future in vitro and in vivo studies. These rationally designed hybrid molecules, owing to their receptor affinity, may serve as de novo hybrid inhibitors. Full article

The environmental fate of nickel (Ni) is dictated by its interaction with organic matter (OM), yet the specific roles of OM source and molecular size remain unclear. This study investigated the binding characteristics of Ni with size-fractionated dissolved OM (DOM) from the water column and alkaline-extractable OM (AEOM) from sediments in a tropical wetland. Using ultrafiltration and spectroscopy, we found that sedimentary AEOM was predominantly high-molecular-weight (HMW) and terrestrial compounds, whereas aquatic DOM was dominated by low-molecular-weight (LMW), microbial-derived compounds. Counterintuitively, the highest Ni binding affinity (NiBA) for both DOM and AEOM occurred in the smallest-molecular-weight fraction (<0.3 kDa). Predictive models confirmed this divergence: the model for the more chemically homogeneous AEOM was highly predictive (r = 0.89), while the model for the complex DOM was less robust (r = 0.70). Our findings demonstrate that LMW fractions are hotspots for Ni binding, challenging the common assumption that larger molecules are more reactive. We conclude that biogeochemical processing in sediments creates an OM pool that is chemically distinct and more predictable than that in the overlying water. This distinction is critical for accurately assessing Ni mobility and ecological risk in aquatic systems. Full article