Search Results (11,641)

This study systematically explored the interaction mechanisms between two KRAS G12C inhibitors (Sotorasib and Adagrasib) and human serum albumin (HSA) via UV-vis spectroscopy, fluorescence spectroscopy, three-dimensional fluorescence spectroscopy, and molecular docking methods. The experimental findings demonstrated that both drugs caused static quenching of HSA fluorescence, with binding constants of 13.64 × 10³ M⁻¹ (Sotorasib) and 63.67 × 10³ M⁻¹ (Adagrasib), demonstrating significant selectivity differences in their binding affinities. UV spectral analysis demonstrated distinct microenvironmental perturbations: Sotorasib and Adagrasib induced a shift (∆λ = 7 nm and ∆λ = 8 nm, respectively) at 211 nm, consistent with altered polarity in HSA’s binding pockets. Fluorescence spectroscopy confirmed a 1:1 binding stoichiometry, with Stern-Volmer analysis validating static quenching as the dominant mechanism. Three-dimensional fluorescence spectra further highlighted Adagrasib’s stronger conformational impact, reducing tyrosine and tryptophan residue fluorescence intensities by 16% (Peak 1) and 10% (Peak 2), respectively, compared to Sotorasib. Molecular docking revealed divergent binding modes: Sotorasib occupied Sudlow Site I via three hydrogen bonds and hydrophobic interactions (∆G = −24.60 kJ·mol⁻¹), whereas Adagrasib bound through one hydrogen bond and hydrophobic forces (∆G = −30.92 kJ·mol⁻¹), with stability differences attributed to structural characteristics. This study uses multispectral technology and molecular docking to reveal the binding mechanism of Sotorasib and Adagrasib with HSA, providing a theoretical basis for designing highly targeted albumin nanocarriers. The strong binding properties of Adagrasib and HSA may reduce the toxicity of free drugs, providing direction for the development of long-acting formulations. Full article

Peptides derived from protein sources in food exhibit a diverse array of biological activities. The screening, preparation, and functional investigation of bioactive peptides have become a focal area of research. This review summarizes the status of peptide activity mining, including the latest research progress in protein sources, peptide functions, and processing conditions. It critically evaluates the limitations of current bioactive peptide screening methods, including the drawbacks of traditional methods and molecular simulations. The potential of using molecular simulation for the virtual screening of potentially bioactive peptides is summarized. This includes virtual enzymatic digestion, molecular docking, simulation of non-thermal processing technologies, and the construction of organelle/cell models. The driving role of artificial intelligence in molecular simulation is also discussed. In addition, the structural information, mechanism, and structural analysis technique of action of the popular target proteins of foodborne bioactive peptides are summarized to provide a better reference for virtual-reality combinations. Full article

Type 2 diabetes is a multifactorial disease characterized by chronic hyperglycemia, insulin resistance, oxidative stress, inflammation, and dyslipidemia, factors that contribute to the development of long-term complications. In this context, the 2-aminobenzothiazole scaffold has emerged as a promising candidate due to its broad spectrum of biological properties. In this study, we performed a multidisciplinary evaluation of benzothiazole derivatives (5a–d, 8a–d, 11a–d, and 12c–d), starting with the in silico prediction of their properties, along with molecular docking against aldose reductase (ALR2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). All compounds complied with the main rules of pharmacological similarity and optimal affinity, highlighting 8d (ΔG = −8.39 kcal/mol for ALR2 and −7.77 kcal/mol for PPAR-γ). Selected compounds from families C and D were synthesized in moderate yields (~60%) and showed low acute oral toxicity (LD₅₀ > 1250 mg/Kg). Compounds 8c and 8d inhibited ALR2 at concentrations below 10 µM. In vivo studies using a streptozotocin-induced diabetic rat model with a high-fat diet revealed that compound 8d produced sustained antihyperglycemic effects and reduced insulin resistance, dyslipidemia, and polydipsia, without inducing hepatotoxicity or displaying intrinsic antioxidant or anti-inflammatory activity. These findings suggest that 8d is a promising candidate for further development in diabetes-related therapeutic strategies. Full article

Against the backdrop of rising multidrug-resistant Acinetobacter baumannii (MDR AB) threats, this study explores the in vitro antibacterial activity and mechanism of Senecio scandens (a Miao ethnic medicinal herb) crude extract. Using 10 clinical MDR AB strains, we reassessed antibiotic sensitivity and then applied microbroth dilution to determine MIC/MBC, time-kill curves for bactericidal kinetics, and SEM/TEM for structural changes. Proteomics identified downregulated proteins, cross-referenced with VFDB/CARD to target membrane-related proteins (msbA, lptD), while molecular docking validated the strong binding of linarin/hyperoside to these targets. qPCR confirmed lptD/msbA mRNA downregulation (p < 0.05) by linarin/hyperoside (MIC = 312.5 μmol/L). The extract showed concentration-dependent bactericidal effects (MIC = 640 μg/mL), disrupting cell wall/membrane integrity. This study first reveals that linarin and hyperoside inhibit MDR AB by downregulating lptD/msbA, compromising outer membrane integrity, offering novel therapeutic candidates. Full article

Background/Objectives: Edgeworthia chrysantha is rich in coumarin and flavonoid dimers, which may exhibit diverse pharmacological activities. However, to date, no metabolomics studies have been conducted and its bioactive constituents related to glucose metabolism remain uncharacterized. This study aimed to conduct a comprehensive chemical analysis combined with bioactivity assays to evaluate its efficacy in promoting glucose uptake. Methods: Chemical profiling of three parts (leaf, stem, and root) of E. chrysantha was performed using UPLC-Q-TOF-MS/MS spectrometry, followed by metabolomics analysis. Based on the chemical profiles and glucose uptake activity, compounds were isolated from the root. Their structures were elucidated using spectroscopic techniques, including UV, NMR, and mass spectrometry. The glucose uptake activity of the isolated compounds was assessed using a 2-NBDG assay. Results: Metabolic analysis revealed distinct chemical compositions among the plant parts. Dimeric coumarins and biflavonoids were abundant in the root, whereas flavonoid monomers were predominant in the leaf. Bioactivity-guided isolation yielded nine compounds (1–9), among which compound 1, a newly identified coumarin glycoside, exhibited significant glucose uptake-enhancing activity. Molecular docking analysis further suggested that compound 1 activates AMPK through an allosteric site, thereby promoting glucose uptake. Conclusions: These findings provide a comprehensive chemical and metabolomic characterization of E. chrysantha and highlight its potential as a functional food ingredient for glucose-lowering effects. Full article

Molecularly imprinted polymers (MIPs) have emerged as promising materials for selectively targeting biomolecules, including quorum sensing autoinducers that regulate bacterial communication and biofilm formation. In this study, both single-template and dual-template strategies were employed to design and synthesize MIPs capable of capturing autoinducer-2 analogs using (3R,4S)-tetrahydro-3,4-furandiol (T1) or (R/S) 2,2-dimethyl-1,3-dioxolane-4-methanol (T2) as the templates. This approach offers translational potential of a complementary or non-antibiotic strategy to conventional antimicrobial therapies in mitigating biofilm-associated infections. Computational modeling guided the rational selection of functional monomers, predicting favorable interaction energies (ΔE_C up to −135 kcal·mol⁻¹) and optimal hydrogen-bonding patterns to enhance template–polymer affinity. The synthesized MIPs were characterized using spectroscopic and microscopic techniques to confirm imprinting efficiency and structural integrity. The adsorption capacity measurements demonstrated higher adsorption capacity and selectivity of MIPs compared to non-imprinted polymers, with the highest selectivity equal to 3.36 for T1 and 3.14 for T2 on MIPs fabricated from methacrylic acid. Preliminary microbiological evaluations using Chromobacterium violaceum ATCC 12472 reveal that the MIPs prepared from 2-hydroxyethyl methacrylate effectively inhibited violacein production by up to 78.2% at 5.0 mg·mL⁻¹, consistent with quorum sensing interference. These findings highlight the feasibility of employing molecular imprinting to target autoinducer-2 analogs, introducing a novel synthetic strategy for disrupting bacterial communication. This further suggests that molecular imprinting can be leveraged to develop potent quorum-sensing inhibitors, an approach that offers translational potential as an alternative to conventional antimicrobial strategies to mitigate biofilm-associated infections. Full article

Cancer remains a leading cause of mortality worldwide, arising from a complex interplay of genetic, epigenetic, and environmental factors. Although the role of micronutrients in cancer development has received limited attention, growing evidence suggests that vitamins, particularly vitamin D, may influence oncogenic pathways. This hypothesis manuscript explores the potential interaction between vitamin D and the oncogenic long non-coding RNA HOTAIR, providing a novel mechanistic explanation for the inverse correlation between vitamin D status and cancer risk. We support our hypothesis with in silico docking evidence, suggesting that vitamin D binds to bioactive domains within the structured regions of HOTAIR, potentially disrupting its interaction with chromatin regulators such as PRC2. This concept may offer a novel approach to cancer prevention and therapy. Full article

This study proposed a pH-driven co-precipitation strategy to overcome the limitations of traditional physical blending in functional improvement of a dual-protein system. The results demonstrated that, in comparison with the soy-pea blended protein (SPBP), the soy-pea co-precipitated protein (SPCP) showed a decrease in α-helix and β-sheet content, accompanied by in an increase in random coil structure. SPCP exhibited decreased fluorescence intensity, smaller particle size (from 392.2 to 176.1 nm) with increased absolute zeta-potential values (from −13.7 to −19.7 mV), reduced surface hydrophobicity (from 21,987.3 to 9744.8), and increased content of disulfide bonds. Structural optimization of SPCP significantly bolstered intermolecular interactions between SPI and PPI. Molecular docking simulations also validated the presence of abundant hydrophobic interactions and hydrogen bonds within in the blend system. These modifications significantly enhanced the solubility of SPCP (especially SPCP8.0). The rheological analysis further revealed that the storage modulus (G′) and loss modulus (G″) of SPCP8.0 were both higher than those of SPBP, while its tan δ was lower than that of SPBP, indicating synergistic interactions between proteins. These interactions contributed to the formation of a more stable three-dimensional network structure, thereby conferring it with superior gel properties. These findings provide theoretical foundations for improving the functional properties of plant-based dual-protein and their applications in plant-based meat production. Full article

As benthic filter feeders, bivalve mollusks serve as ideal biological indicators. Bisphenol A (BPA) and its substitutes (BPS, BPF, and BPAF) are endocrine disruptors with reproductive toxicity, targeting estrogen receptors (ERs). However, their binding sites and affinity for shellfish ERs remain unclear. This study aims to identify ER binding sites of BPA and its substitutes, compare toxicity via molecular docking, and validate results through exposure experiments. The full-length cDNA of Corbicula fluminea ER was cloned using the RACE technique for the first time, the sequence length is 2138bp. Homologous models of LBD sequences from Danio rerio, C. fluminea, Azumapecten farreri, and Ruditapes philippinarum ERs were constructed via homology modeling and screened for optimal fit. Hydrogen bonds were observed during the docking process, with interaction sites including Glu-66, Arg-177, and other amino acid residues. Exposure experiments (1, 10, and 100 μg/L) showed an enhancement in ER mRNA expression. Based on the docking energies and results of the exposure experiments, it was concluded that the toxicity of BPA and BPS is similar and greater than that of BPF and BPAF. This study provides data for a reproductive risk assessment and aquatic toxicological monitoring of bisphenols. Full article

Background/Objectives: Disruption of AMPAR trafficking at excitatory synapses contributes to impaired synaptic plasticity and memory formation in several neurological and psychiatric disorders. Arc, an immediate early gene product, has been shown to interact with the AMPAR auxiliary subunit TARPγ2, affecting receptor mobility and synaptic stabilization. Methods: To investigate the in vivo functional effects and protein interactions of the Arc-TARPγ2 interfering peptide RIPSYR, we performed in vivo electrophysiology and spatial memory assessments in male rats. as well as proteomic analyses of peptide-protein interactions in synaptosome lysates. We then used in silico docking to evaluate candidate binding partners. Results: In the present study, in vivo electrophysiological measurements revealed that RIPSYR administration altered early-phase long-term potentiation at CA3 synapses of male rats. Subsequent behavioral testing that assessed spatial memory performance revealed depleted memory retrieval after 24 h, indicating that the peptide has a systemic effect on experience-dependent plasticity. Then, we examined the molecular interactome of RIPSYR using magnetic bead-based immunoprecipitation and subsequent LC-MS identification on synaptosome lysates, and identified additional candidate binding partners, suggesting that the peptide may have broader modulatory effects. RIPSYR binding to the other putative binding partners are investigated by in silico methods. Conclusion: Our results raise the question of how the molecular interactions of RIPSYR contribute to its sum effects on electrophysiology and behavior. Full article

Despite the widespread use of vaccines against SARS-CoV-2, COVID-19 continues to pose global health challenges, requiring efficient drug screening and repurposing strategies. This study presents a novel hybrid framework that integrates deep learning (DL) with molecular docking to accelerate the identification of potential therapeutics. The framework comprises three crucial steps: (1) a previously developed DL model is employed to rapidly screen candidate compounds, selecting those with predicted interaction scores above a cut-off value of 0.8; (2) AutoDock Vina version 1.5.6 and LeDock version 1.0 are used to evaluate binding affinities, with a threshold of <−7.0 kcal·mol⁻¹; and (3) predicted drug–protein binding sites are evaluated to determine their overlap with known active residues of the target protein. We first validated the framework using four experimentally confirmed COVID-19 drug–target pairs and then applied it to identify potential inhibitors of the SARS-CoV-2 main protease (M^Pro). Among 29 drug candidates selected based on antiviral, anti-inflammatory, or anti-cancer properties, only Enasidenib met all three selection criteria, showing promise as an M^Pro inhibitor. However, further experimental and clinical studies are required to confirm its efficacy against SARS-CoV-2. This work provides an interpretable strategy for virtual screening and drug repurposing, which can be readily adapted to other DL models and docking tools. Full article

Background/Objectives: Coronavirus disease 2019 (COVID-19) has been a global pandemic since 2019, but effective therapeutic treatments for it remain limited. Shuqing Granule (SG) is a traditional Chinese medicine containing ingredients such as indirubin, shinpterocarpin, naringenin, and quercetin. It exhibits anti-inflammatory and antiviral activities as well as broad-spectrum antiviral effects, yet its potential role in the treatment of COVID-19 remains unclear. This study thus aimed to explore the therapeutic effects of SG on COVID-19, with a focus on its potential anti-SARS-CoV-2 activity linked to these bioactive ingredients. Methods: The potential therapeutic ability of SG was investigated by combining network pharmacology, molecular docking, and experimental verification. First, key ingredients in SG and their corresponding targets, as well as COVID-19-related targets, were identified. Then, enrichment analyses were performed to highlight potential key pathways. Additionally, molecular docking was conducted to assess the binding capacity of the key ingredients to ACE2. Finally, experiments such as Western blot and ELISA were conducted to verify the effect of SG. Results: The results showed that 15 key ingredients such as quercetin in SG could affect overlapping targets such as RELA. Molecular docking results showed that key ingredients in SG, such as isoliquiritigenin, formononetin, shinpterocarpin, indirubin, naringenin, kaempferol, and 7-Methoxy-2-methylisoflavone, might bind to angiotensin-converting enzyme II (ACE2)—a critical receptor in the process of COVID-19 infection—thereby exerting antiviral effects. Experiments such as Western blot and ELISA further demonstrated that SG could reduce inflammation induced by the SARS-CoV-2 S1 protein by 50%. This effect might be achieved by downregulating ACE2 expression by 1.5 times and inhibiting the NF-κB signaling pathway. Conclusions: This study confirmed that SG has potential as a candidate for COVID-19 treatment. It also provided a new approach for the application of traditional Chinese medicine in combating the virus. Full article

The present study reports the sono-chemical synthesis of novel nanosized Cr(III), Mn(II), and Pd(II) complexes incorporating the chloro-2-(quinolin-8-yliminomethyl)-phenol imine ligand. The synthesized complexes were characterized using various spectroscopic and analytical techniques, including Fourier-transform infrared (FT-IR) spectroscopy, ultraviolet–visible (UV–Vis) spectroscopy, scanning electron microscopy (SEM), and thermal gravimetric analysis (TGA). The results confirmed the successful coordination of the ligand-to-metal centers, forming stable nanosized metal complexes with distinct physicochemical properties. Biological evaluations, including antimicrobial and antioxidant assays, revealed that the synthesized complexes exhibited enhanced biological activity compared to the free ligand, demonstrating potent antibacterial and antifungal properties against various pathogenic strains. The potential of the complexes to serve as efficient free-radical inhibitors was determined by employing DPPH radical scavenging assays, which underscored their significant antioxidant properties. Furthermore, molecular docking studies were conducted to elucidate the binding interactions of the metal complexes with biological targets, providing insights into their mechanism of action. The findings suggest that the synthesized nanosized Cr(III), Mn(II), and Pd(II) complexes possess promising biological properties, making them potential candidates for pharmaceutical and biomedical applications. The study also demonstrates the effectiveness of sono-chemical synthesis in producing nanosized metal complexes with enhanced physicochemical and biological characteristics. Full article

Background: Type 2 diabetes (T2D) has become a serious global public health concern. Liubao tea (LBT) has demonstrated beneficial effects on gut microbiota and glucose-lipid metabolism, holding promising therapeutic potential for T2D; however, its underlying mechanisms remain unclear. This study aims to elucidate the potential mechanisms of Liubao tea extract (LBTE) against T2D. Methods: LC-MS technology was used to identify the chemical components of LBTE and combined with network pharmacology and molecular docking to screen its potential active ingredients and targets for improving T2D. Therapeutic efficacy was assessed in high-fat diet/streptozotocin (HFD/STZ)-induced diabetic mice via serum biochemical analyses and histopathological examinations. Serum metabolomics, 16S rRNA sequencing, quantification of short-chain fatty acids (SCFAs), quantitative real-time PCR (qPCR), and antibiotic-treated pseudo-germ-free models were employed to elucidate the underlying mechanisms. Results: LBTE effectively reduced blood glucose levels and improved lipid metabolism, primarily by promoting hepatic glycogen synthesis and suppressing glycerophospholipid synthesis. LBTE also alleviated hepatic inflammation by modulating inflammatory cytokine expression. Additionally, LBTE reshaped the gut microbiota profiles by decreasing harmful bacteria and increasing SCFA-producing bacteria, resulting in elevated fecal SCFAs. SCFAs contributed to improving hepatic metabolism and inflammation, enhancing intestinal barrier function. Notably, these effects were abolished by antibiotic-induced microbiota depletion, confirming the microbiota-dependent mechanism of LBTE. Quercetin, luteolin, genistein, and kaempferol were considered as potential active ingredients contributing to the antidiabetic effects of LBTE. Conclusions: These findings provide novel perspectives on the viability of LBTE as a complementary strategy for T2D prevention and management. Full article

As a highly disabling chronic inflammatory disease, rheumatoid arthritis (RA) necessitates novel interventions. Liupao tea is a traditional Chinese dark tea known for its favorable anti-inflammatory properties. This study aims to elucidate the active ingredients and action mechanisms underlying the therapeutic effects of Liupao tea extract (LPTE) in RA. LPTE was preliminarily characterized by LC-MS technology. Network pharmacology and molecular docking predicted anti-RA compounds, targets, and pathways, with key compounds identified using chemical standards. The effect of LPTE on the collagen-induced arthritis mouse model was evaluated through serum biochemical analysis, micro-CT imaging, and histopathological analyses. Integrated serum metabolomics, 16S rRNA sequencing, MetOrigin analysis, SCFA metabolomics, and quantitative real-time PCR elucidated gut–joint axis mechanisms. LPTE effectively attenuated RA symptoms by reducing bone destruction and joint inflammation. Notably, LPTE reshaped gut microbiota by enriching key families such as Monoglobaceae, Eggerthellaceae, and Desulfovibrionaceae, thereby promoting SCFA production. Increased SCFA levels enhanced intestinal barrier integrity and exerted joint-protective and anti-inflammatory effects by upregulating tight junction proteins and activating SCFA receptors. LPTE also modulated arachidonic acid metabolism by affecting key genes such as Alox5, Ptgs2, and Cbr1. These effects collectively reduced the levels of pro-inflammatory cytokines and increased the expression of anti-inflammatory cytokines in joints. Additionally, quercetin, luteolin, ellagic acid, and kaempferol were identified as major anti-RA bioactive compounds in LPTE. Taken together, this study provides preliminary evidence that LPTE mitigates RA by regulating the gut–joint axis mediated via fatty acid metabolism. Full article