Search Results (262)

Background/Objectives: Fraxetin (7,8-dihydroxy-6-methoxycoumarin), a coumarin constituent of Cortex Fraxini (Qinpi) used in traditional Chinese medicine, is metabolised mainly by UGT1A9, but its potential to inhibit UGT enzymes and cause herb–drug interactions (HDIs) is largely unstudied. Methods: Fraxetin and four related coumarins were screened against 11 recombinant human UGTs; isoforms inhibited ≥80% underwent full kinetic analysis with 4-methylumbelliferone as probe. Binding was examined by molecular docking on AlphaFold structures with PLIP, triplicate 100 ns molecular dynamics, and MM/GBSA and MM/PBSA free-energy calculations, and interaction risk by FDA 2020 in vitro–in vivo extrapolation (IVIVE). Results: Fraxetin alone inhibited both UGT1A1 and UGT1A9 by >80% and was characterised in detail, acting as a mainly competitive mixed-type inhibitor (UGT1A1 IC₅₀ 15.99 μM, K_i 8.32 μM; UGT1A9 IC₅₀ 8.44 μM, K_i 5.90 μM). A structure–activity comparison identified a dual-element pharmacophore comprising the C-6 methoxy group and the 7,8-dihydroxycoumarin aglycone. MM/GBSA favoured UGT1A9 over UGT1A1 (ΔΔG = −4.06 kcal/mol, p = 0.005), concordant with the kinetic ranking. IVIVE predicted a borderline systemic signal (R₁ > 1.02) but an intestinal R_1,gut approximately five- to seven-fold above the high-risk threshold of 11 after capping the luminal concentration at fraxetin aqueous solubility. Conclusions: This is the first characterisation of fraxetin as a moderate-potency inhibitor of UGT1A1 and UGT1A9 and points to a previously under-recognised herb–drug interaction risk concentrated in the intestinal lumen rather than systemically; the finding constitutes an interaction signal requiring clinical confirmation rather than an established risk. Full article

The purpose of this study was to investigate the adverse effects of 1.5 μg·L⁻¹ environmentally relevant chlorantraniliprole (CAP) on oxidase biomarkers (juvenile, 2.5 g) for 2, 4, and 8 h and transcriptomic response (adult, 254.8 g) for 96 and 192 h in American shad Alosa sapidissima (Wilson, 1981). American shad is sensitive to pollutants and has become an important economic fish in China, especially for recirculating the aquaculture system and photovoltaic farming. For juvenile shad under short-time CAP exposure, acid phosphatase (ACP) and aryl hydrocarbon receptase (AHR) at the protein level significantly increased at 2 h, and for longer-time exposure, alkaline phosphatase (AKP), polyphenol oxidase enzyme (PPO), and tumor necrosis factor alpha (TNFα) at the protein level significantly decreased; ryanodine receptase (RYR) at the protein level was significantly increased at 8 h. Interestingly, malondialdehyde (MDA) contents, biomarkers of oxidative stress, were significantly decreased for depletion at 2 h and 4 h, while they increased for eliminating free radicals at 8 h via longer-time CAP exposure duration. With the same CAP exposure for adult shad, the number of congested and dilated sinuses of the liver changed, with fine granular brown pigmentation and vacuolization of hepatocytes at 96 h, while the sinuses and central veins were dilated and edematous degeneration occurred at 192 h for longer-time exposure. The detected enzymatic activities, except for adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), significantly decreased, and MDA contents significantly increased in adult shad at 96 and 192 h. Ribosome, proteasome, spliceosome, protein processing in endoplasmic reticulum, oxidative phosphorylation, glycerophospholipid metabolism, biosynthesis of amino acids, ferroptosis, peroxisome, apoptosis, necroptosis, and mTOR signaling pathways were the most significantly enriched pathways. For qPCR verification, the genes ppa2, pla1a, psmb13a, pkz and stat1b were significantly upregulated, while hspa8b, capn2, tram2, asns, bcl2l1, diablo, and prkcb were downregulated in adult shad. The results reveal elevated oxidative stress causing time-dependent hepatic damage via 1.5 μg·L⁻¹ CAP exposure both in juvenile and adult shad. Full article

The SARS-CoV-2 non-structural proteome remains the most clinically validated and strategically important landscape for direct-acting small-molecule antiviral drug discovery. The success of inhibitors targeting the main protease (M^pro, Nsp5) and RNA-dependent RNA polymerase (RdRp, Nsp12) has firmly established viral replication enzymes as tractable, druggable, and therapeutically relevant targets, while setting clear benchmarks for translational antiviral development. Building on this foundation, a second wave of non-structural protein (Nsp) targets has emerged with increasing translational promise, including the papain-like protease (PL^pro), the bifunctional Nsp14 proofreading and capping machinery, Nsp16 2′-O-methyltransferase, Nsp13 helicase, and Nsp15 endoribonuclease. In parallel, additional components such as Nsp1 and the Mac1 domain of Nsp3 continue to expand the antiviral design space, although they remain at earlier stages of chemical validation. In this review, we comprehensively assess SARS-CoV-2 non-structural proteins through a medicinal chemistry and translational lens, with an emphasis on structural tractability, mechanism of action, quality of chemical matter, cellular and in vivo antiviral evidence, evolutionary conservation, resistance liabilities, and developability. Particular attention is given to the features that distinguish tool compounds from genuinely actionable leads and to the opportunities for rational combination regimens that extend beyond first-generation protease- and polymerase-centred therapy. Collectively, the non-structural proteome offers the strongest foundation for next-generation and potentially broader-spectrum coronavirus antivirals with improved resilience to viral evolution. Full article

Phosphoglycerate kinase (PGK) is a vital glycolytic enzyme that provides energy and carbon skeletons to support fatty acid synthesis. However, the PGK gene family has not been characterized in soybean (Glycine max), and its role in soybean oil accumulation remains unclear. Here, we identified six GmPGK genes in soybean, all of which encode proteins containing conserved PGK domains. Phylogenetic analysis clustered soybean PGK proteins into three groups. Analysis of GmPGK promoters revealed relatively abundant cis-elements related to plant growth, development, and phytohormone response. Expression profiling showed that GmPGK5 transcript abundance increases progressively with oil accumulation during seed development, and is significantly higher in the high-oil variety NN1138-2. Overexpression of GmPGK5 significantly increased total fatty acid content in soybean hairy roots. A single nucleotide polymorphism (SNP) located at Chr15:49447855 within the GmPGK5 promoter was significantly associated with both seed oil content and seed weight in natural soybean accessions. Based on this SNP, a derived cleaved amplified polymorphic sequence (dCAPS) marker was developed to facilitate soybean molecular breeding. Our findings suggest that GmPGK5 may positively regulate fatty acid accumulation in soybean. The identified natural variation and dCAPS marker provide potential valuable tools for marker-assisted selection to improve soybean oil content and seed weight. Full article

The fruiting bodies of shiitake mushrooms (Lentinula edodes) are highly susceptible to postharvest quality deterioration due to their loose tissue, high moisture, and active metabolism. Low-dose ultraviolet-C (UV-C) irradiation, a green, safe, low-cost, and efficient physical treatment especially suitable for high-moisture and metabolically active produce, offers a promising solution to this problem for the postharvest preservation of shiitake mushrooms. In this study, the effects of different doses of UV-C irradiation (2.5, 5.0, and 7.5 kJ·m⁻²) on the postharvest quality of shiitake mushrooms were systematically compared by measuring weight loss, respiration intensity, cap opening percentage, firmness, color (L*, a*, b*), electrolyte leakage, MDA content, antioxidant enzyme activities (SOD, CAT, POD, PAL), chitin content, chitinase activity, and the expression of LeCHI and LeCDA genes. The results showed that UV-C irradiation at 5 kJ m⁻² significantly delayed the increase in weight loss (by approximately 32% at day 15 compared to control) and reduced respiration rate (by 25–35% during days 3–9) and cap opening rate (27.3% vs. 48.0% in control at day 15) while maintaining higher firmness and better color retention over the control group. Furthermore, this treatment effectively inhibited electrolyte leakage and malondialdehyde accumulation, enhanced the activities of SOD, POD, CAT, and PAL, maintained chitin content, and downregulated the expression of chitinase and cell wall degradation-related genes. Thus, 5 kJ m⁻² UV-C irradiation is effective in maintaining postharvest quality and extending the storage time of shiitake mushrooms. Full article

The rising incidence of viral infections demands the creation of innovative, biocompatible antiviral drugs with broad-spectrum effectiveness. This study combines the green synthesis, optimization, and characterization of silver nanoparticles (AgNPs) utilizing Dacryodes edulis (D. edulis) extract, assessing their antiviral, and antimicrobial characteristics. AgNPs were synthesized through the bio-reduction of silver nitrate with D. edulis water extract as a reducing, capping and stabilizing agent. The synthesis was refined through a Design of Experiments methodology. The characterization techniques, UV-Vis, Fourier-transform infrared, transmission electron microscopy, and dynamic light scattering, validated the successful synthesis of AgNPs with an average size of 101.56 ± 28.22 nm (TEM) and 156 ± 0.81 nm (DLS), a polydispersity index of 0.34, and a zeta potential of −22 mV. High-resolution liquid chromatography–tandem mass spectrometry analysis identified some bioactive compounds which enhance the antimicrobial and antiviral properties of the samples. Enzyme kinetics experiments revealed substantial inhibitory efficacy against the SARS-CoV-2 papain-like protease (PL-pro), with AgNPs exhibiting a lower IC₅₀ (0.271 ± 0.051 mg/mL) than the D. edulis extract (0.337 ± 0.043 mg/mL). The AgNPs exhibited MIC of 0.063 mg/mL for E. coli, 0.125 mg/mL for S. aureus and 0.08 mg/mL for S. pyrogens. The corresponding MBC values were 0.125 mg/mL, 0.25 mg/mL and 0.31 mg/mL, respectively. The fungal strains C. glabrata and C. albicans displayed MIC of 0.63 mg/mL and 0.31 mg/mL, respectively, and MBC values of 0.63 mg/mL and 0.31 mg/mL, respectively. This study underscores the potential of D. edulis-derived AgNPs as a cost-efficient, environmentally sustainable, and highly bioactive antibacterial and antiviral nanomaterial, facilitating the advancement of nanotechnology-based therapies for viral infections. Full article

The caliciviruses include important human and animal pathogens such as norovirus, sapovirus and feline calicivirus. Viral reverse genetics is performed to understand the fundamental biology of these viruses, as well as a potential route to generate live-attenuated vaccines. Calicivirus reverse genetics systems have typically relied on either the production of in vitro-transcribed RNA or plasmid-based rescue, either from a mammalian promoter or through supplementing with helper enzymes through means of a helper virus. Here, we present a novel system integrating vaccinia capping enzymes D1R and D12L encoded on plasmids as part of a system for murine norovirus (MNV) reverse genetics. The addition of D1R, D12L and T7 RNA polymerase-expressing plasmids increases the viral titres of rescued MNV in both BSR-T7 cells and transgenic BSR-T7 cells expressing murine CD300LF (BSR-T7^CD300LF), and viral protein abundance. When the murine norovirus receptor is expressed in BSR-T7^CD300LF, viral titres increased 100–1000-fold compared to standard BSR-T7 cells. This system offers a robust, increased throughput means of assessing viral mutants over parallel in vitro transcription and capping reactions for multiple mutants, without requiring a helper virus. Full article

Liver fibrosis is driven by persistent oxidative stress and inflammatory signaling, with transforming growth factor-β (TGF-β) acting as a key profibrotic mediator. Rutin (Ru) is a plant-derived flavonoid with antioxidant and anti-inflammatory effects, but its low bioavailability limits therapeutic efficacy. This study investigated whether rutin-phytoreduced gold nanoparticles (RuAuNPs) enhanced rutin delivery leading to antifibrotic and anti-inflammatory effects in a rat model of liver fibrosis. Liver fibrosis was induced by oral administration of thioacetamide (TAA, 150 mg/kg body weight, p.o.) for six weeks. Following fibrosis induction, the animals were treated with free rutin (30 mg/kg body weight), RuAuNPs (0.3 mg/kg body weight), or AuNPs (0.3 mg/kg body weight), both expressed as nanoparticle mass, all administered orally for four weeks. RuAuNPs were synthesized by green rutin-mediated reduction and further characterized by TEM, DLS, and FTIR spectroscopy; they were spherical, showing an average hydrodynamic size of 104.1 nm (PDI 0.345). FTIR confirmed rutin capping. Biological effects were evaluated by liver morphology (H&E histology, TEM), biochemical assessment of liver aminotransferases and glico-lipidic status, ELISA and spectrophotometry measurement of redox biomarkers (lipid peroxidation, glutathione status, antioxidant enzymes), cytokines (TNF-α, IL-1β, IL-6), and TGF-β. TAA-induced hepatic injury and remodeling with increased profibrotic signaling, oxidative stress, and inflammation. Free rutin slightly ameliorated the liver damage, whereas RuAuNP improved histological features, reduced TGF-β and pro-inflammatory cytokines, decreased lipid peroxidation, and supported antioxidant defenses. Overall, RuAuNP may enhance rutin efficacy in TAA-induced liver fibrosis, with novelty stemming from the integrated in vivo evaluation of tissue changes and key profibrotic/oxidative/inflammatory pathway. Full article

Silver nanoparticles were biosynthesized using the culture supernatant of Staphylococcus sp. YRA, a strain isolated from Colombian mining sediments. Synthesis was optimized at 1 mM AgNO₃, pH 7, 40 °C and 7 μg/mL extract, producing spherical, protein-capped AgNPs with primary sizes in the tens-of-nanometers range (~35–90 nm by SEM), while DLS indicated larger hydrodynamic diameters (~250–320 nm) consistent with aggregation in suspension (ζ-potential −16.6 mV). These nanoparticles remained stable over 6 months. Characterization by UV–Vis, SEM, AFM, EDS and FTIR confirmed extracellular protein-mediated reduction and capping. The AgNPs showed antibacterial activity against multidrug-resistant clinical isolates (Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Salmonella bongori, Enterococcus spp.), with inhibition zones of 8–16 mm at 400–1000 μg/mL. Biofilm formation was reduced by >50% at 700 μg/mL in both Gram-positive and Gram-negative strains. In Phaseolus vulgaris (P. vulgaris), low concentrations (5–100 μg/mL) increased growth and chlorophyll content, while 500 μg/mL caused moderate inhibition. FTIR analysis identified amide and thiol groups from bacterial enzymes as capping agents. These results suggest Staphylococcus sp. YRA as a bacterial platform for AgNPs production with antibiofilm activity against MDR pathogens and acceptable phytotoxicity profile for potential applications. Full article

Biogenic copper-based nanoparticles have attracted attention as potent antimicrobial agents synthesised via environmentally sustainable routes using plants, microorganisms, and biological waste. Green synthesis leverages phytochemicals, enzymes, and proteins as natural reducing and stabilising agents, enabling nanoparticle formation under mild, non-toxic conditions without hazardous reagents. The resulting nanoparticles are typically spherical, <100 nm in size, and enriched with bioactive surface functionalities that contribute to broad-spectrum antimicrobial activity against bacteria, fungi, and biofilms. Their antimicrobial effects arise from interconnected mechanisms, including the generation of reactive oxygen species, the release of Cu² ions, membrane disruption, and interference with vital metabolic and genetic processes. Hybrid systems such as Ag–Cu, Zn–CuO, and CuS nanoparticles further enhance efficacy through synergistic redox and photothermal effects. These properties support applications in medical coatings, wound dressings, food packaging, aquaculture disease management, and sustainable crop protection. However, toxicity is highly context-dependent, influenced by factors such as nanoparticle size, shape, surface chemistry, capping agent, concentration, exposure medium, and the biological system. Small or weakly capped NPs can induce cytotoxicity, hemolysis, developmental defects, or growth inhibition, whereas functionalization or capping can improve selectivity and biocompatibility. Standardised physicochemical characterisation, harmonised toxicity testing, and mechanistic understanding are critical for the safe translation of biogenic CuNPs into regulatory-approved applications. This review summarises recent advances (2015–2025) in the biogenic synthesis of copper-based nanoparticles, highlighting how biological systems govern nanoparticle morphology, stability, and antimicrobial efficiency. It integrates mechanistic insights, compares monometallic and hybrid systems, and evaluates emerging applications in medicine, agriculture, aquaculture, and food safety. The review also identifies current limitations and future directions for standardisation, toxicity evaluation, and regulatory approval. Full article

A 10-week growth experiment was conducted to evaluate the physiological effects of dietary phosphorus supplementation on red swamp crayfish (Procambarus clarkii) feeding diets with high Clostridium autoethanogenum protein (CAP) levels. Six isonitrogenous and isolipid diets were formulated: The FM diet contained 10% fishmeal, which is equivalent to a dietary phosphorus level of 1.41%, and the CAP, CAPSP1, CAPSP2, and CAPSP3 diets substituted all fishmeal with CAP and supplemented with 0, 2.5%, 3%, and 3.5% Ca(H₂PO₄)₂, respectively (corresponding to dietary phosphorus levels of 0.66%, 1.27%, 1.40%, and 1.52%). A total of 600 crayfish with an initial mean weight of (5.01 ± 0.02) g were selected and randomly assigned to 15 cages for feeding and sampled at the end of the experiment. Results indicate that high-dose CAP replacing fishmeal caused abnormal hepatopancreatic tissue structure in crayfish, exacerbating lipid deposition and oxidative stress. Compared with the CAP group, the specific growth rate (SGR) of crayfish in the CAPSP2 and CAPSP3 groups significantly increased (p < 0.05). The activities of antioxidant enzymes and lipid-degrading enzymes in the hepatopancreas, along with the relative expression of related genes, were significantly enhanced (p < 0.05). Metabolomic analysis demonstrated significant differences in major differential metabolites and metabolic pathways between the CAP group crayfish and the CAPSP2 group (p < 0.05). CAPSP2 group crayfish exhibited a higher content of phosphatidylcholine (PC) and lysophosphatidylcholine (LPC), with significant enrichment in glycerophospholipid metabolism and fatty acid metabolism pathways (p < 0.05). Overall, supplementing dietary phosphorus levels to 1.40–1.52% effectively mitigated growth retardation, oxidative damage, and lipid metabolism disorders induced by high-proportion CAP replacement of fishmeal. Full article

Yeast-derived biomolecules are redefining the boundaries of green nanotechnology. Biosurfactants, exopolysaccharides, enzymes, pigments, proteins, and organic acids—when sourced from carbohydrate-rich lignocellulosic hydrolysates—offer a molecular toolbox capable of directing, stabilizing, and functionalizing nanoparticles (NPs) with unprecedented precision. Beyond their structural diversity and intrinsic biocompatibility, these biomolecules anchor a paradigm shift: the convergence of biorefineries with nanotechnology to deliver multifunctional materials for the circular bioeconomy. This review explores: (i) the expanding portfolio of metallic and metal oxide NPs synthesized through yeast biomolecules; (ii) molecular-level mechanisms of reduction, capping, and surface tailoring that dictate NP morphology, stability, and reactivity; (iii) synergistic roles in intensifying lignocellulosic processes—from enhanced hydrolysis to catalytic upgrading; and (iv) frontier applications spanning antimicrobial coatings, regenerative packaging, precision agriculture, and environmental remediation. We highlight structure–function relationships, where amphiphilicity, charge distribution, and redox activity govern resilience under saline, acidic, and thermally harsh industrial matrices. Yet, critical bottlenecks remain: inconsistent yields, limited comparative studies, downstream recovery hurdles, and the absence of comprehensive life-cycle and toxicological evaluations. To bridge this gap, we propose a translational roadmap coupling standardized characterization with real hydrolysate testing, molecular libraries linking biomolecule chemistry to NP performance, and integrated techno-economic and environmental assessments. By aligning yeast biotechnology with nanoscience, we argue that yeast-biomolecule-driven nanoplatforms are not merely sustainable alternatives but transformative solutions for next-generation lignocellulosic biorefineries. Full article

Histone deacetylases (HDACs) are pivotal epigenetic regulators that control gene expression, cell proliferation, and differentiation, and their dysregulation is closely associated with the onset and progression of multiple cancers. The therapeutic importance of these enzymes is reflected by FDA approval of HDAC inhibitors for oncology indications. Despite this clinical success, most FDA-approved agents employ conventional zinc-binding groups (ZBGs) such as hydroxamic acid and 2-aminoanilide, which are frequently linked to metabolic instability, genotoxicity, and poor pharmacokinetic behavior. These limitations have spurred the development of structurally diverse and safer HDAC inhibitors incorporating alternative ZBGs. This review provides a comprehensive analysis of recently developed HDAC inhibitors reported in the last few years, emphasizing their structure–activity relationships (SARs), chemical scaffolds, and binding features—including cap, linker, and ZBG motifs. Both hydroxamate-based and non-hydroxamate inhibitors, such as benzamides, hydrazides, and thiol-containing analogs, are critically evaluated. Moreover, the potency and selectivity profiles of these inhibitors are summarized across different cancer and normal cell lines, as well as specific HDAC isoforms, providing a clearer understanding of their therapeutic potential. Emerging dual-target HDAC inhibitors, such as HDAC–tubulin, HDAC–PI3K and HDAC–CDK hybrids, are also discussed for their synergistic anticancer effects. Full article

Background: Metabolic dysfunction-associated steatotic liver disease (MASLD) is a frequent manifestation of obesity and other metabolic diseases. Autotaxin (ATX), an enzyme involved in the generation of lysophosphatidic acid (LPA), has recently emerged as a potential biomarker of metabolic inflammation and liver disease progression. Vegetable-based dietary interventions have been shown to reduce liver steatosis, but evidence of the impact of this dietary approach on ATX levels remains limited. Objectives: To evaluate the short-term effects of a bioactive vegetable-enriched diet from the Brassicaceae and Asteraceae families on serum ATX levels and liver-related parameters in individuals with obesity and MASLD, with a specific focus on sex differences. Methods: In this two-month pilot study, 44 obese adults (BMI > 30 kg/m²) underwent clinical and instrumental assessments at baseline (T0) and after the dietary intervention (T1). Results: After the intervention, serum ATX levels significantly decreased (from 206.3 ± 52.8 to 191.7 ± 45.7 ng/mL, p < 0.001), and there were improvements in metabolic parameters (BMI, waist circumference, blood pressure, fat mass, insulin, HOMA-IR, triglycerides, total and LDL cholesterol) and liver indices (CAP, ALT, AST, γGT). The multivariate GEE model confirmed a significant reduction in ATX, independent of age, sex, FFM, LPA, LSM, Hemoglobin A1c, and PAI-1 (β = −9.87, p < 0.001). When stratified by sex, women exhibited a more pronounced reduction in ATX levels (β = −12.24; p = 0.005) compared to men (β = −9.43; p = 0.014). Conclusions: A short-term, vegetable-enriched dietary intervention can significantly reduce serum ATX levels and improve metabolic and liver-related parameters in individuals with MASLD. Sex-specific analysis reveals a greater ATX-lowering effect in women, suggesting potential sex-based differences in ATX metabolism or dietary responsiveness. These findings suggest that ATX may serve as a modifiable biomarker responsive to nutritional intervention and a potential therapeutic target in metabolic liver disease. Full article

Intestinal barrier dysfunction and microRNA dysregulation are proposed contributors to progression of metabolic dysfunction-associated steatotic liver disease (MASLD). We aimed to assess selected protein and miRNA biomarkers of intestinal permeability in relation to MASLD severity. We included 104 patients with MASLD and 57 healthy controls. Serum lipopolysaccharide-binding protein (LBP), diamine oxidase (DAO), tumor necrosis factor alpha (TNF-α), interleukin 6 (IL-6), and miRNAs (miR-21, miR-29a, miR-122) were measured. Multivariable logistic regression identified independent predictors of steatosis and fibrosis severity. Patients with MASLD showed higher LBP levels (p = 0.002) and increased serum miR-122 expression (p < 0.0001) compared with controls. LBP correlated with CAP values (Rho = 0.23, p = 0.02) and was elevated in advanced steatosis (p = 0.04). DAO levels correlated with CAP (Rho = 0.22, p = 0.02) and were higher in advanced steatosis (p = 0.04) but decreased in advanced fibrosis (p = 0.04). MiR-122 correlated with fibrosis indices (TE: Rho = 0.22, p = 0.03; APRI: Rho = 0.41, p = 0.0001) and liver enzymes (ALT: Rho = 0.40, AST: Rho = 0.50, both p < 0.0001). Logistic regression identified elevated miR-122 and reduced miR-21 as independent predictors of MASLD, while DAO and transaminases predicted advanced steatosis. Elevated serum miR-122, alongside reduced miR-21, independently predict MASLD. DAO is associated with steatosis severity, while miR-122 reflects fibrotic progression. Full article