Search Results (5,246)

This study investigated the biosynthesis of magnetite nanoparticles mediated by chia mucilage (CM-Fe₃O₄ NPs) and their application in the co-encapsulation of Lactobacillus rhamnosus GG (LGG) using spray drying. CM-Fe₃O₄ NPs were synthesized by combining CM extract with iron salts, in which hydroxyl and carbonyl groups of CM acted as natural ligands for Fe²⁺/Fe³⁺ ions. A response surface design was applied to optimize synthesis parameters, focusing on size distribution and zeta potential, and confirming the influence of pH on colloidal stability. Characterization by FE-SEM, DLS, XRD, UV-Vis, and FTIR revealed spherical particles with an inorganic core (50–300 nm) and a hydrated organic coating (600–900 nm), consistent with a spinel structure functionalized by CM. Spray-drying encapsulation tests showed that incorporating CM-Fe₃O₄ NPs did not compromise bacterial viability, maintaining optimal moisture content and survival. Growth curves and confocal microscopy corroborated the physiological compatibility of the nanoparticles, with no alterations in LGG morphology or growth dynamics. Under simulated gastrointestinal conditions, co-encapsulated microcapsules exhibited slightly improved survival in the gastric phase and significantly greater viability in the initial intestinal phase. These results suggest that CM-Fe₃O₄ NPs modulate matrix degradation and promote controlled release, ensuring therapeutic concentrations of LGG in the intestine. Overall, the CM-Fe₃O₄ nanocomposite system integrates the protective properties of biopolymers with the functional advantages of iron nanoparticles, offering dual functionality: probiotic stabilization and potential iron supplementation. This innovative, food-grade approach supports the development of next-generation functional foods with combined therapeutic and nutritional benefits. Full article

Iron oxide nanoparticles have emerged as multifunctional compounds with prominent potential in cancer theranostics, particularly in photothermal therapy (PTT) and photodynamic therapy (PDT). Their unique electronic and crystal structures, such as the dispersion of Fe²⁺ and Fe³⁺ ions and d-orbital splitting, contribute to their magnetic and catalytic properties. In PTT, Fe₃O₄ nanoparticles exhibit moderate near-infrared (NIR) absorption and photothermal conversion efficiency, which can be enhanced through adjustments in particle size, surface modification, and combinations with other components. In PDT, Fe₃O₄ nanoparticles demonstrate intrinsic peroxidase-like catalytic activity, facilitating Fenton and photo-Fenton reactions that generate reactive oxygen species (ROS), including hydroxyl radicals (^•OH), thereby amplifying oxidative stress in cancer cells. These nanoparticles can also function as carriers for photosensitisers (PS), promoting targeted delivery and enhanced ROS generation. Multifunctional nanomaterials that integrate Fe₃O₄ with other therapeutic agents and targeting ligands have demonstrated synergistic antitumour effects through amplified photothermal, photodynamic, chemodynamic, and chemotherapeutic mechanisms. Despite certain drawbacks, such as relatively low NIR absorption and challenges in optimising delivery and light activation, ongoing improvements in Fe₃O₄-based nanoplatforms present significant potential for enhancing treatment outcomes and the precision of cancer therapy. This article systematically explores the synergistic role of Fe₃O₄ nanoparticles in PTT and PDT, encompassing their magnetic and catalytic characteristics. Additionally, it focuses on multifunctional hybrid nanoplatforms that combine Fe₃O₄ with targeting or imaging agents, highlighting their potential to enhance therapeutic precision. Full article

Nutrient-sensing nuclear receptors (NSNRs), including PPARs, FXR, LXRs, RAR/RXR, VDR, and related orphan receptors, integrate a molecular interface that allows diet to communicate directly with the genome. By binding fatty acids, bile acids, sterols, vitamins, polyphenols, and other food-derived metabolites, NSNRs translate qualitative and quantitative features of the diet into coordinated transcriptional programmes across metabolically active organs. This ligand-dependent signalling network integrates dietary information to orchestrate inter-organ lipid and glucose metabolism, mitochondrial function, thermogenesis, and immune response, thereby enabling the organism to adapt dynamically to fasting–feeding cycles. In this review, we synthesise current evidence on the integrated roles of major NSNRs in the liver, skeletal muscle, white and brown adipose tissue, and kidney, emphasising how receptor networks within and between metabolic organs collectively govern energy expenditure, substrate partitioning, and systemic metabolic flexibility. We propose a conceptual framework in which diet functions as an “external endocrine organ”, acting as the primary source of chemically diverse NSNR ligands, while metabolic tissues serve as secondary signal amplifiers and integrators. Through circulating lipid species, bile acids, oxysterols, and other metabolites, these organs engage in continuous bidirectional communication that reprograms NSNR activity across tissues. We then examine how the global shift from minimally processed, nutrient-rich foods to nutrient-poor, energy-dense ultra-processed diets leads to a reduction in NSNR ligand diversity, promoting hepatic steatosis, muscle metabolic inflexibility, adipose tissue dysfunction, renal lipotoxicity, and chronic low-grade inflammation, ultimately causing obesity, type 2 diabetes, and cardiometabolic disease. Finally, we explore strategies to restore NSNR function, including Mediterranean and plant-based dietary patterns, as well as diets enriched with ω-3 polyunsaturated fatty acids, monounsaturated fats, and polyphenols. By integrating molecular, physiological, and clinical evidence, this review aims to clarify how NSNR networks translate dietary cues into coordinated inter-organ metabolism and how nutrient-poor diets lead to metabolic diseases trough a loss of metabolic information, rather than merely by energy excess. This framework supports a paradigm shift from calorie-centred nutrition to diet quality as the main therapeutic target for preventing metabolic diseases and promoting health. Full article

Lung cancer remains the leading cause of cancer-related mortality worldwide, with non-small cell lung cancer accounting for the majority of cases and exhibiting persistent challenges related to therapy resistance and metastatic progression. Increasing evidence indicates that dysregulated G protein-coupled receptor signaling and ion channel activity function cooperatively as master regulators of tumor cell proliferation, migration, survival, and therapeutic response. Cannabinoids, including phytocannabinoids such as delta-9-tetrahydrocannabinol and cannabidiol, as well as endogenous endocannabinoids, are uniquely positioned to modulate both G protein-coupled receptors and ion channels, thereby influencing key oncogenic signaling networks. This review synthesizes current knowledge on the role of major ion channel families, including transient receptor potential channels, potassium channels, and sodium channels, and principal G protein-coupled receptor pathways involved in lung cancer progression. We further discuss how cannabinoids reprogram these interconnected signaling systems through canonical cannabinoid receptors, non-classical targets such as G protein-coupled receptor 55 and adenosine receptors, and direct modulation of ion channel activity. Special attention is given to G protein-coupled receptor–ion channel coupling within membrane microdomains and to the capacity of cannabinoids to act as biased ligands, redirecting downstream pathways, such as the phosphoinositide 3-kinase–protein kinase B–mechanistic target of rapamycin and epidermal growth factor receptor signaling, toward apoptosis and reduced metastatic potential. Emerging strategies, including cannabinoid-based combination therapies, selective receptor biasing, and targeted delivery systems, are also highlighted. Altogether, cannabinoid-driven rewiring of G protein-coupled receptor and ion channel signaling represents a promising mechanistic framework for developing innovative therapeutic approaches against lung cancer. Full article

Protein glycation is a nonenzymatic modification that links sugar chemistry to molecular aging and chronic disease. Sequential reactions involving Schiff bases, Amadori products, and reactive α dicarbonyl intermediates generate advanced glycation end products (AGEs) that irreversibly alter protein structure and function. AGEs also act as ligands for the receptor for advanced glycation end products (RAGE), initiating oxidative stress, inflammation, and tissue remodeling. This review synthesizes the molecular pathways of AGE formation, their structural diversity, and the biological factors influencing glycation kinetics. Advances in analytical detection methods—including fluorescence spectroscopy, LC–MS/MS, and immunochemical approaches—are highlighted for their role in monitoring AGE accumulation. Particular attention is given to the contribution of glycation to diabetes, cardiovascular disease, neurodegeneration, and cancer, alongside emerging therapeutic strategies to limit AGE formation or block AGE–RAGE signaling. Glycation thus represents a central mechanism in human disease pathogenesis and an emerging therapeutic frontier. Full article

Background: The clinical efficacy of the BCL-2 inhibitor venetoclax in acute myeloid leukemia (AML) is significantly undermined by the frequent emergence of drug resistance, which precipitates disease progression and poor patient outcomes. However, the molecular landscape of this resistance remains insufficiently understood. Methods: To address this, we developed venetoclax-resistant AML cell models and utilized transcriptomic profiling integrated with comprehensive in vitro and in vivo functional assays. Results: Resistant cells demonstrated sustained proliferation even under the suppression of BCL-2, MCL-1, and key intrinsic apoptotic markers, including cleaved PARP and caspase-9, indicating a bypass mechanism independent of classical BCL-2 signaling. Compared to their sensitive counterparts, resistant Kasumi-1 (VENK) and MV4-11 (VENM) cells exhibit aggressive growth phenotypes in vitro and in vivo, characterized by larger, more numerous spheroids and colonies, alongside heightened tumorigenicity in murine models. Transcriptomic profiling and KEGG analysis identified the neuroactive ligand–receptor interaction (NLRI) pathway as a significant signaling node shared between these resistant lines. While multiple NLRI-associated genes were altered, CHRNB4 was consistently and significantly downregulated in both VENK and VENM cells and tumors. Re-expression of CHRNB4 in resistant cells, a primary gain-of-function approach, significantly impaired colony formation, and tumor growth in vivo. Clinically, CHRNB4 downregulation correlates with shortened overall survival and diminished response to venetoclax. Conclusions: Our findings implicate the NLRI pathway in venetoclax resistance and identify CHRNB4 as a robust prognostic indicator and a promising therapeutic target for developing next-generation AML strategies. Full article

Bidentate ligands, derived from the 1,3-dicarbonyl framework, play a central role in coordination chemistry, catalysis, and materials science due to their tuneable donor properties and structural versatility. This review examines and compares three closely related ligand classes, β-diketones (O,O′ donors), imino-β-diketones or enaminones (N,O donors), and di-imino-β-diketones or β-diketiminates (N,N′ donors), to elucidate how systematic substitution of oxygen by nitrogen affects structure and properties. The discussion integrates spectroscopic data (NMR and IR), crystallographic findings, electrochemical measurements, and density functional theory (DFT) calculations reported in the literature. Across these systems, tautomerism plays a decisive role, with conjugation-stabilized enol or enamine forms generally preferred in solution and the solid state. Frontier molecular orbital analyses show extensive delocalization over the chelate backbone and, when present, aromatic substituents. Electrochemical studies reveal consistent correlations between experimental reduction potentials and calculated LUMO energies for O,O′-, N,O-, and N,N′-bidentate ligands. Overall, the comparison demonstrates that donor atom substitution within a conserved conjugated scaffold provides a systematic approach to tuning acidity, coordination behaviour, and redox properties, offering a coherent framework for understanding structure–property relationships in 1,3-dicarbonyl-derived chelating ligands. Full article

In this work, density functional theory (DFT) was used to comparatively investigate the thermodynamic and electronic factors governing the association of Cd(II), Hg(II), and Pd(II) with native chitosan (CTS) and functionalized derivatives (CTS–COOH, CTS–COO−, CTS–NH³⁺, and CTS–SH). Representative acid–base states were considered to approximate changes in site availability, and a uniform explicit microhydration scheme was adopted to enable controlled relative comparisons across metals and materials. Within this framework, the calculated free energies suggest metal-dependent affinity regimes: the carboxylic microenvironment favors Cd(II), the thiolated microenvironment provides the most favorable association for Hg(II), and native CTS affords the strongest calculated stabilization for Pd(II). Geometry optimizations show that most complexes retain the first hydration sphere of the metal, indicating that stabilization is dominated by outer-sphere association rather than by systematic first-sphere ligand substitution. ESP/MEP maps reveal that the heterogeneity and directionality of the electrostatic landscape govern selectivity. In contrast, NCI analysis supports a cooperative contribution of weak interactions and second-sphere organization. These results provide a comparative electronic framework to guide future experimental validation of selective metal capture by functionalized chitosan materials. Full article

Molecular docking is a foundational technique in computational drug discovery, widely used to generate binding hypotheses, prioritize compounds, and support target-selectivity studies. The continued growth of open-source docking resources, together with improvements in scoring functions, sampling strategies, and hardware acceleration, has substantially lowered barriers to teaching, early-stage hit identification, and reproducible research. Beyond standalone docking engines, the open-source ecosystem now encompasses browser-accessible tools, preparation and analysis utilities, integrative modeling platforms, and AI-augmented methods for pose prediction, rescoring, and virtual screening. These developments have made docking workflows more accessible, customizable, and transparent across diverse research settings. This review examines open-source docking from a workflow-centered perspective, spanning study design, structural-data acquisition, binding-site definition, receptor and ligand preparation, docking execution, and post-docking validation. It further evaluates how open AI methods are being incorporated into these stages to expand structural coverage, improve screening efficiency, and support contemporary structure-based drug design. Collectively, this review outlines a practical and evidence-based framework for the effective use of open-source docking and virtual-screening pipelines in modern drug discovery. Full article

Printed electronics have emerged as a versatile manufacturing platform for next-generation biosensors, enabling on-demand and low-cost fabrication of functional devices on flexible, stretchable, and unconventional substrates. One major challenge in this field lies in the sintering of printed features, as conventional high-temperature processing is incompatible with polymeric substrates and thermally sensitive biological components. Low-temperature sintering inks, typically processed below 200 °C or even at room temperature, have become a critical enabling technology for bio-integrated electronics. This review provides an overview of the current state-of-the-art and key challenges associated with low-temperature sintering inks for printed bioelectronics. We discuss inks based on metal nanoparticles, metal–organic decomposition precursors, metal oxides, chalcogenides, and hybrid material systems. The emphasis is on how ink chemistry, ligand selection, and precursor structure govern rheology, stability, and sintering behavior. In addition, key low-temperature sintering and curing strategies, including thermal, photonic, laser, plasma, microwave, and chemical sintering, are compared in terms of energy delivery, densification mechanisms, and substrate compatibility. Finally, we outline emerging directions towards low temperature and room-temperature sintering inks, and sustainable biobased ink formulations, and discuss their applications for wearable, implantable, and soft biosensing platforms. Full article

Thyroid hormones (THs) and estrogen (E2) play essential roles in neuronal differentiation and plasticity during brain development. S-equol, a plant-derived isoflavone metabolite, is a selective E2 receptor (ER) ligand that exhibits neurotrophic effects; however, its interaction with TH receptor (TR) signaling remains unclear. In this study, we investigated the effects of S-equol on TRβ-associated transcriptional activity and neuronal morphogenesis in mouse neuroblastoma-derived Neuro-2a cells or rat C6 glioma cells. Luciferase reporter assays demonstrated that S-equol significantly enhanced T3-induced TRβ transcriptional activity in a concentration- and time-dependent manner. Additionally, exposure to S-equol or T3 alone promoted neurite outgrowth and wound closure, whereas co-exposure to both compounds resulted in a more significant enhancement of these processes. Furthermore, mRNA expression levels of synapse-related genes (Dlg4, Syn1, Syp, Camk2b, and Bdnf) were significantly increased by S-equol co-exposure in the presence of T3. In silico docking analysis revealed that S-equol exhibited moderate to high binding affinity for TRβ (−8.7 kcal/mol), ERα, and ERβ, suggesting a structural basis for TR–ER crosstalk. Collectively, these findings indicate that S-equol functions as a dual-acting modulator that may modulate T3 signaling involving TR–ER interaction. Although S-equol may exert beneficial effects on neurodevelopment, it may also act as an endogenous endocrine modulator that alters the fine regulation of TH action during development, warranting careful evaluation from physiological and toxicological perspectives. Full article

6(5H)-phenanthridinone derivatives, as an important class of alkaloids, have broad application value in drug development and functional material synthesis. In this study, a nickel-catalyzed synthetic strategy was developed, using 2-bromobenzamide compounds as starting materials. Through an intermolecular cyclization reaction, a series of 6(5H)-phenanthridinone derivatives bearing amide substituents was efficiently constructed. The optimal reaction system was identified: Ni(acac)₂/Zn as the catalyst, PCy₃ as the ligand, toluene as the solvent, Cs₂CO₃ as the base, under an argon atmosphere at 150 °C for 12 h. The target products were obtained in yields up to 88%. Further substrate scope exploration demonstrated the excellent generality of this method, successfully synthesizing 21 derivatives with various substitution patterns, achieving yields ranging from 51% to 92%, and showing good compatibility with multiple functional groups such as alkyl, aryl, and heterocyclic moieties. Importantly, the reaction remained stable during gram-scale experiments, successfully yielding the desired compound at 85%. This work not only provides an approach for the precise construction of the 6(5H)-phenanthridinone framework but also opens an efficient pathway for the controlled synthesis of amide-substituted derivatives. Full article

Leucine-rich-repeat kinase 2 (LRRK2) is a multidomain protein highly expressed in immune cells and implicated in the regulation of immune functions including immune signaling, cytokine release and autophagy. LRRK2 is one of the therapeutic targets in Parkinson’s Disease (PD). Aberrant activation of LRRK2 can also contribute to intestinal inflammation, mainly in inflammatory bowel disease (IBD). Hence the modulation of LRRK2 may influence gut inflammation providing an improvement in disease outcomes. Over the years, microRNAs (miRNAs) have acquired much attention thanks to their potential as therapeutic targets in several pathological conditions, including inflammatory disorders. In this study, we aimed to examine the ability of miR-369-3p in the modulation of autophagy targeting LRRK2 expression. Bioinformatics analysis revealed that Lrrk2 is a target gene of miR-369-3p, and LRRK2 expression was increased in ulcerative colitis patients compared with that in a healthy control. In in vitro analysis, we validated that mimic transfection with miR-369-3p in Raw264.7 significantly reduced the expression of LRRK2 both in basal and inflammatory conditions. Moreover, the inhibition of LRRK2 limited the nuclear translocation of Nuclear factor kappa B (NF-κB) induced by lipopolysaccharide (LPS) stimulation. In turn, we found that, in inflammatory conditions, the intracellular increase in miR-369-3p precluded the inhibition of autophagy by LRRK2 by restoring autophagy marker light chain 3 (LC3)II/I ratio, BECLIN-1 and decreasing p62 expression. Furthermore, we detected that the upregulation of miR-369-3p decreased the release of pro-inflammatory mediators Tumor necrosis factor (TNF), C-C motif ligand 2/Monocyte chemoattractant protein-1 (CCL2/MCP-1), C-C motif ligand 3/Macrophage inflammatory protein-1 alpha (CCL3/MIP-1α) and C-C motif ligand 5/Regulated on activation, normal T-cell expressed and secreted (CCL5/RANTES) and increased the anti-inflammatory cytokine interleukin 10 (IL-10) in response to LPS. This study supports the anti-inflammatory potential of miR-369-3p in immune cells and suggests the potential of miR-369-3p as a therapeutic agent in the treatment of acute intestinal inflammatory conditions such as ulcerative colitis. Full article

Polygonatum odoratum, a medicinal and edible plant widely used in traditional Chinese medicine and daily diets, has potential in managing various disorders, but its anti-pruritic mechanisms remain unclear. This study aimed to explore its multi-target anti-pruritic effects by integrating network pharmacology, molecular docking, molecular dynamics (MD) simulations, GeneMANIA functional association analysis (GMFA), and GEO dataset validation. Bioactive components and pruritus-related targets were identified from public databases, and interaction networks between Polygonatum odoratum and pruritus targets, as well as the antihistamine levocetirizine, were constructed. Core targets were screened, and functional enrichment analyses were performed using DAVID and KEGG. Molecular docking (AutoDock Vina) and MD simulations (AMBER20) assessed the binding energy and stability of core components with key targets. The analysis identified 5 active components, 208 related targets, and 113 pruritus-associated targets, including 10 core targets. Enrichment analysis highlighted the PI3K/Akt and IL-17 signaling pathways, while MCODE clustering suggested involvement in arachidonic acid metabolism and serotonergic synapse. GMFA supported these findings. Molecular docking showed strong binding energy (<−5 kcal/mol), and MD simulations confirmed stable ligand–target complexes. GEO dataset validation reinforced key results. This study suggests that Polygonatum odoratum may exert anti-pruritic effects through the combined actions of inflammation suppression, skin barrier repair, and neural modulation, revealing a novel multi-target mechanism for pruritus therapy and potential synergy with levocetirizine. Full article

Peroxisome proliferator-activated receptor γ (PPARγ), encoded by the PPARG gene on chromosome 3p25.2 in humans, is a ligand-dependent transcription factor that belongs to the nuclear receptor family. In various tissues, PPARγ controls cell differentiation, proliferation, or fusion. Its essential role in the development and functions of the placenta is now well established. To date, the specific functions of its RNA isoforms, encoded by ten exons, in trophoblast biology, including cell fusion and invasion, remain unknown. As translation is mainly regulated by the 5′UTR sequences of mature mRNA, this region was analyzed, and four previously unreported exonic sequences were revealed. Their expressions were confirmed and quantified in villous cytotrophoblasts from term placenta and in chorionic villi from both first-trimester and term placenta. Distinct expression patterns were observed: one exon showed weak expression in placental and chorionic cells, another exhibited stable expression throughout pregnancy, while two exons specific to villous cytotrophoblasts displayed increased expression during the first trimester, suggesting a role in oxygen-responsive mechanisms. Among these, one may be involved in villous trophoblast differentiation. These findings demonstrate that the PPARG gene is composed of 14 exons and is highly regulated depending on cell type and the stage of cell differentiation. Full article