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Alexander Kros, Georgina Such, and Vincent Rotello introduce the RSC Pharmaceutics and RSC Chemical Biology themed collection on Endocytosis and cellular delivery.
PRMT1 and PRMT4 (CARM1) are the epigenetic regulators concerned with the methylation of arginine residues, acting on both the histone and non-histone proteins, regulating chromatin dynamics, gene expression and signaling pathways. Impaired control and imbalanced regulation of this induces various types of cancers. This review provides a comprehensive assessment of the structure-activity relationship (SAR) of various small-molecule inhibitors targeting PRMT1 and PRMT4. A range of chemical frameworks like tetrazole, furan, thiazole, tetrahydroisoquinoline derivatives and many others were identified. These derivatives act through various mechanisms to inhibit the overexpressed PRMT1 and PRMT4. Significant SAR insights underscore the essential role within individual structural motifs, including the contribution of electron-withdrawing and electron-donating groups, which depict the activity, selectivity and potency for inhibition, electrostatic interactions and π-π stacking of structural units. Docking studies emphasize the key interaction of ligand molecules with the active site of the target. This review forms a solid foundation for the rational development of the next generation PRMT1 and PRMT4 inhibitors with better therapeutic potential by systematically correlating the chemical structure with biological activity across a number of classes through SAR and computational studies.
Rosanoid diterpenoids, including ent-rosane and rosane diterpenoids, are structurally unique and bioactive subclass diterpenes characterized by a tricyclic carbon skeleton. This work aims to provide a comprehensive review of the literature on these diterpenoids from 1975. to September 2025., including their occurrence, structural diversity, and biological activities. An extensive literature search was conducted through scientific databases (ScienceDirect, PubMed, Scopus, Web of Science, and Google Scholar) and publishers' webpages (Elsevier, Wiley, ACS, RSC, Taylor & Francis, Springer, Bentham, Thieme, and MDPI), covering reports from 1975 to September 2025. Rosanoid diterpenoids have been isolated from various natural sources, including fungi, liverworts, and higher plant families such as Euphorbiaceae, Lamiaceae, Alismataceae, Asteraceae, Velloziaceae, and Celastraceae. They are predominantly found in Euphorbia species, revealing their chemotaxonomic relevance to the Euphorbiaceae family. These compounds exhibit extensive structural diversity, encompassing a broad spectrum of biological activities, including anti-inflammatory, antimicrobial, antiviral, cytotoxic, enzyme-inhibitory, neuroactive, and anti-adipogenic effects. The reported findings highlight the chemical variability and pharmacological potential of rosanoid diterpenoids, making them promising building blocks for future drug discovery and natural product development. However, further studies are warranted to explore their pharmacokinetics, mechanisms of action, safety profiles, and biosynthetic pathways.
Osteosarcoma remains one of the most challenging malignancies due to its aggressive nature, metastatic potential, and resistance to conventional therapies. Recent advances have underscored the pivotal role of microRNAs (miRNAs) in the regulation of key oncogenic and tumor suppressor pathways involved in osteosarcoma progression, including PI3K/AKT, Wnt/β-catenin, and TGF-β signaling. The modulation of miRNAs offers a promising therapeutic avenue, but effective delivery systems are essential to realize their full potential. Natural compounds derived from plants, such as flavonoids, resveratrol, quercetin, and epigallocatechin-3-gallate, have demonstrated notable capacity to modulate miRNA expression, inducing apoptosis, inhibiting proliferation, and reducing metastasis with fewer adverse effects compared to traditional chemotherapy. These bioactive molecules possess intrinsic anti-inflammatory, antioxidant, and osteogenic properties, which, when combined with miRNA regulation, can synergistically impede osteosarcoma progression. Nanotechnology-based delivery systems, including multilayered nanoparticles, magnetic nanostructures, and biodegradable nanocarriers, have emerged as effective platforms to overcome these obstacles. These nanocarriers can be engineered for targeted, controlled, and sustained release of therapeutic agents, enhancing accumulation at tumor sites while minimizing systemic toxicity. Additionally, functionalization with targeting ligands such as folic acid or antibodies further improves specificity towards osteosarcoma cells. This review emphasizes the potential of combining natural compounds with nanotechnology to develop innovative, targeted, and effective therapies for osteosarcoma. It highlights the opportunities for future research to optimize delivery systems, elucidate mechanisms of action, and establish clinical applicability. By harnessing the biological benefits of natural agents and the precision of nanomedicine, these approaches hold significant promise for improving therapeutic outcomes and reducing adverse effects in osteosarcoma treatment.
Nanostructured bimetallic Ni-Pt catalysts supported on KIT-5 mesoporous silica were developed and assessed for their efficiency in the continuous dry reforming of methane (DRM) to generate synthesis gas. Both monometallic variants (Ni/KIT-5 and Pt/KIT-5) and a range of bimetallic Ni-Pt/KIT-5 catalysts were synthesized using co-impregnation and sequential impregnation methods. Comprehensive characterization of the catalysts was conducted through techniques such as high-resolution scanning electron microscopy (HR-SEM), X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET) surface area analysis, thermogravimetric analysis (TGA), and Fourier-transform infrared spectroscopy (FT-IR). In the monometallic Ni-based catalysts, nickel primarily existed in the form of NiO. In contrast, the bimetallic catalysts exhibited surface species such as Ni2O3 and NiPt2O4. In the bimetallic Ni-Pt catalysts, thermally stable PtO2 and NiPt2O4 phases were identified. Reduction in hydrogen led to the development of Ni-Pt alloy phases on the surface, which enhanced the overall catalytic performance. The bimetallic Ni-Pt catalysts outperformed their monometallic counterparts in DRM activity. The nanofibrous structure of KIT-5, characterized by its interconnected pore network, provided improved accessibility to active sites and facilitated efficient diffusion of reactants and products. Among the catalysts evaluated, the 9.5%Ni-0.5%Pt/KIT-5 composition achieved the highest conversions of both methane and carbon dioxide, while maintaining a relatively low H2/CO product ratio. Durability assessments at 700 °C over a period of six hours demonstrated high thermal stability and negligible deactivation due to carbon deposition. Post-reaction analyses of the spent catalysts using XRD and HR-SEM revealed minimal structural deterioration. TGA measurements indicated that carbon deposition resulted in approximately 10% weight loss, suggesting the presence of mainly amorphous carbon and confirming the catalyst's excellent resistance to coking. The fibrous architecture of KIT-5 effectively suppressed nickel particle sintering and carbon build-up. These findings underscore the potential of Ni-Pt/KIT-5 systems, particularly with optimized metal loadings, as robust and coke-resistant catalysts for syngas production via dry reforming of methane.
The present study focused on developing and evaluating lincomycin HCl (LCH)-loaded chitosan nanoparticles (CSNPs) incorporated into a nanogel system to improve wound healing. CSNPs were prepared via ionic gelation using sodium tripolyphosphate (STPP) as a cross-linker. The optimized formulation showed a mean particle size of 174.3 nm, a polydispersity index (PDI) of 0.267, a zeta potential of +29.4 mV, and a drug entrapment efficiency of 83.7%. FTIR, DSC, and XRD analyses confirmed successful drug encapsulation and stability with no chemical interactions. The formulation demonstrated sustained release (>75% in 24 hours) following non-Fickian kinetics. Antibacterial testing revealed improved efficacy against Staphylococcus aureus and Escherichia coli with inhibition zones of 45 mm ± 2.76 and 38 mm ± 2.15, respectively. In vivo wound healing studies in rats demonstrated almost complete wound closure within 14 days in the treated group, compared to significantly slower healing in the control group. These results show that the LCH-CSNP nanogel provides controlled drug release, effective antimicrobial action, and accelerated wound healing, highlighting its potential as a topical therapeutic platform.
The corrosion inhibition performance of three sulfonamide-based compounds, namely 4-methyl-N-(pyridin-2-yl)benzenesulfonamide (SAP4), N,N'-benzene-1,4-diylbis(4-methylbenzenesulfonamide) (SAP5), and N,N'-(cyclohexane-1,2-diyl)bis(4-methylbenzenesulfonamide) (SAP6), was investigated for mild steel in 1 M HCl using combined theoretical and experimental approaches. Density functional theory (DFT) calculations provided insight into the electronic properties and reactive sites of the molecules, while Monte Carlo simulations suggested favorable adsorption on the Fe (110) surface. Experimental results from potentiodynamic polarization (PDP) and electrochemical impedance spectroscopy (EIS) demonstrated high inhibition efficiencies, reaching approximately 94%, 95%, and 89% for SAP4, SAP5, and SAP6, respectively, at 1 × 10-3 M. The polarization results indicate that the inhibitors affect both anodic and cathodic reactions, suggesting a predominantly mixed-type inhibition behavior. Adsorption studies revealed that the inhibitors follow the Langmuir isotherm model, with high correlation coefficients and negative values of (-36.66 to -35.32 kJ mol-1), indicating spontaneous adsorption involving both physical and chemical interactions. The effect of temperature was evaluated over the range of 298-328 K, where the inhibitors maintained relatively high inhibition efficiencies, although a slight decrease was observed with increasing temperature. Surface analysis further confirmed the formation of a protective adsorbed film on the mild steel surface. Overall, the combined findings highlight the potential of sulfonamide-based compounds, particularly SAP5, as effective corrosion inhibitors for mild steel in acidic environments.
This research focuses on the protective impacts of gallic acid (GAL) on OMP-instigated anxiety. In this experiment, 48 male Sprague-Dawley rats were grouped into 6 (n = 8): (I) VEH + VEH (1 mL kg-1), (II) VEH + GAL [low dose; (50 mg kg-1)] (III) VEH + GAL [high dose; (100 mg kg-1)] (IV) VEH + OMP (20 mg kg-1), (V) GAL (low dose) + OMP V) GAL (high dose) + OMP. The animals were administered their corresponding drugs intraperitoneally (IP) for four weeks, once daily. Subsequently, during the treatment period, behavioral tests were performed, including open field activity (OFA) and home cage activity (HCA) to assess locomotion and elevated plus maze (EPM), and light-dark activity (LDA) for anxious-like symptoms, respectively. Following behavioral assessments, the rats were decapitated, and their hippocampus was removed. The hippocampus was utilized for biochemical, neurochemical, and histopathological examinations. The results revealed that OMP produced hypolocomotion, anxiety-like behavior, elevated oxidative-stress biomarkers and inflammatory-cytokines, and reduced the activity of antioxidant enzymes and serotonin metabolism. Administration of GAL (both doses) increased (p < 0.05) locomotor activity, reduced (p < 0.05) anxiety, decreased (p < 0.05) oxido-neuroinflammation, and normalized (p < 0.05) 5-HT metabolism and histopathological alteration, followed by OMP. 5-HT1A receptor analysis exhibited OMP-administration sensitized relative expression of 5-HT1A receptors, while GAL at both doses (p < 0.05) decreased 5-HT1A receptor expression in VEH and OMP-administered rats. It is proposed that GAL, as an antioxidant and neuromodulator, can be used for reducing OMP-induced hypolocomotion, anxiety, and associated neurological problems.
New pyrazole/pyrimidine derivatives endowed with azobenzenes were synthesized using microwave and traditional methods. Our compounds were assessed for cytotoxicity against HepG2, MCF-7, HCT-116 and A549 cell lines as dual inhibitors of EGFRT790M and VEGFR-2. A docking study was carried out to show the binding affinities and orientations of our derivatives in the active sites of VEGFR-2 and EGFRT790M. The data of the docking study were highly correlated with the biological data. The HCT116 and A549 cell lines were extremely affected by our derivatives. Derivative 12 showed the greatest activity against A549, HepG2, MCF-7 and HCT116 cells, with IC50 = 5.12, 6.77, 5.85 and 5.25 µM, respectively. It showed higher cytotoxicity than erlotinib (IC50 = 5.49, 7.73, 8.20 and 13.91 µM, respectively) and lower cytotoxicity than sorafenib (IC50 = 4.04, 4.00, 5.58 and 5.05 µM, respectively) against the tested cell lines. The cytotoxicity of the highly active derivatives 5, 6, 8, 9, 10 and 12 against the MCF-10 healthy cell lines was evaluated. The assessed derivatives showed low cytotoxicity against MCF-10 cells, with IC50 = 50.90-55.50 µM. Additionally, all derivatives were assessed as dual VEGFR-2 and EGFRT790M inhibitors. Compounds 12, 8 and 10 displayed very good inhibitions toward VEGFR-2, with IC50 = 0.90, 0.95 and 1.00 µM, respectively. Similarly, structures 12, 8, 10, 5 and 9 showed strong EGFRT790M inhibitions, with IC50 = 0.25, 0.30, 0.33, 0.35 and 0.40 µM, respectively. In addition, in silico ADMET predictions were calculated for the highly active derivatives 8, 10 and 12 and correlated to Lipinski's rule of five using erlotinib and sorafenib as standard ligands. The results presented our derivatives as promising candidates for advanced manipulations to get more potent anticancer agents with advanced VEGFR-2 and EGFRT790M inhibitions.
In this work, a novel portable paper-based sensor is developed using a porphyrin-embedded molecularly imprinted polymer for caffeine quantification. This study entraps tetraphenylporphyrin (TPP) within the template-induced cavities of cellulose molecular aggregation-polished porous particles, thereby modulating TPP's optical response. All techniques (FTIR, XRD, and TEM) demonstrated successful polymer formation with selective binding cavities and reversible caffeine interactions via non-covalent forces. The sensor covered a linear range of 1-100 µM with a 1.62 µM limit of detection and a Stern-Volmer correlation (R 2 = 0.99). Stability was demonstrated with high selectivity, an imprinted factor of ∼3, over 85% response after five cycles, and less than <10% signal loss over 30 days. Average recoveries of 93-99% (real-samples analysis - tea, coffee) provide a cost-effective and readily interpretable approach for the field-based monitoring of caffeine.
[This retracts the article DOI: 10.1039/D4RA06398H.].
Poly(β-amino ester) (PBAE)-based nanoparticles have emerged as promising carriers for RNA delivery, yet clear design rules linking formulation parameters to performance are still lacking. In this study, a Quality by Design (QbD)-guided and Design of Experiments (DoE)-driven approach was combined with high-throughput microfluidics to rapidly identify formulations with favorable physicochemical properties and consistent critical quality attributes (CQAs). Response Surface Modeling revealed that high total flow rates (TFR ≥ 10), nitrogen to phosphorus (N/P) ratios ≥10, and a Flow Rate Ratio (FRR) of 1 : 3 (buffer : ethanol) led to the formation of smaller, more stable particles. Among the polymers tested, a polymer candidate with a balanced composition of hydrophobic and hydrophilic side chains demonstrated optimal intraparticle stability and gene silencing performance. Notably, transfection efficiency depended strongly on formulation parameters beyond polymer type and N/P ratio, with flow rate ratio emerging as a key driver of gene knockdown kinetics. The lead formulation achieved ∼95% gene knockdown even after two weeks of storage at 4 °C. Scale-up production of the lead candidate confirmed the transferability of optimized Critical Process Parameters (CPPs) and preserved CQA profiles, validating the robustness of the design space. This study establishes a robust and scalable QbD-guided workflow for the development of microfluidically manufactured siRNA nanoparticles, enabling rapid optimization, reliable scale-up, and clinically relevant performance.
The current study focuses on the development of pH-sensitive hydrogels for the controlled release of mesalamine at a specific pH. A free radical polymerization technique was used, and the formulated hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis, scanning electron microscopy, swelling and drug release studies. FTIR confirmed the successful formation of a polymeric network with efficient incorporation of the drug. TGA revealed that the hydrogel demonstrated significantly improved thermal stability compared to the unmodified polymer, with SEM images showing a rough surface with a notable porous structure. Swelling and drug release behaviors were assessed at 37 °C in buffer solutions simulating gastric (pH 1.2) and intestinal (pH 7.4) conditions. The results demonstrated significantly higher swelling ratios and drug release rates at pH 7.4, indicating pH-responsive characteristics of the formulation, favoring enhanced drug release in the intestinal conditions. Increasing the concentrations of hyaluronic acid and acrylic acid led to enhanced porosity, improved swelling behavior, increased drug loading capacity, faster release rates, and a higher gel fraction, while simultaneously reducing the sol fraction. These observations suggested that the developed pH-sensitive hydrogel holds considerable potential as an effective carrier for pH-responsive, site-specific drug delivery systems. This study highlights the significant advancements in the design of hydrogels with tailored properties for controlled drug release, offering new opportunities for precision medicine.
Osteoporosis is a chronic metabolic bone disease that leads to decreased mineral density and causes damage to bone microarchitecture. Elderly persons are more susceptible to bone fractures and have reduced bone strength due to osteoporosis. Conventional pharmacological treatments are the key therapies, but increasing evidence highlights the potential of nutritional interventions to support bone health. Macronutrients, especially proteins from soy, legumes, nuts, seeds, and whole grains, supply essential amino acids vital for type I collagen synthesis, osteoblast differentiation, and bone-forming signalling pathways, promoting bone regeneration and structural integrity. Micronutrients from green leafy vegetables, including magnesium, potassium, vitamin K, vitamin C, zinc, and boron, contribute to mineral homeostasis, enhance calcium absorption, manage oxidative stress, and impact key pathways in bone remodeling, such as RANKL/OPG, Wnt/β-catenin, estrogen modulation, and antioxidant mechanisms. This review examines the current research on the usefulness of macronutrients and micronutrients from numerous plant sources in promoting bone tissue regeneration and reducing dependence on synthetic anti-osteoporotic treatment. It highlights their roles as sustainable, low-risk supplements to traditional osteoporosis treatments by integrating molecular insights with dietary knowledge.
Liposomal or polymeric nanoparticles have been instrumental in improving the delivery of poorly soluble chemotherapeutics and those with dose limiting toxicity such as doxorubicin (DOX). More recently, nanoformulations have been shown to enable simultaneous delivery of emerging biomolecules such as siRNA. However, for larger nucleic acids such as mRNA, this remains challenging. In this study, we developed a poly(β-amino ester) (PBAE) based platform, capable of co-formulating mRNA and doxorubicin into nanoparticles. To demonstrate proof of concept using therapeutically relevant cargo, immunomodulatory interleukin-12 (IL-12) was selected as a model mRNA. IL-12 is a pro-inflammatory cytokine that promotes anti-tumour immunity partly through amplifying effector cytokines such as interferon-γ (IFNγ). We found that PBAE complexed DOX and mRNA into positively charged nanoparticles of 120 nm and size-exclusion chromatography indicated a DOX loading efficiency of over 97%. Co-association of both DOX and mRNA was characterised at a single nanoparticle level by nano-flow cytometry. Following delivery to B16F10 murine melanoma cells, more than 95% of cells were double-positive for DOX and Cy5-labelled mRNA, and confocal microscopy confirmed co-localised regions of DOX with mRNA. Interestingly, nanoformulated DOX had increased nuclear accumulation by 1.7-fold relative to free DOX, which correlated with a significantly reduced cell viability of 12.9% with PBAE-DOX/mRNA, compared to 26.6% for free DOX at the same dose. Moreover, despite this strong cytotoxic effect, reporter mRNA translation remained robust, with luciferase expression approximately two orders of magnitude above non-transfected controls at the highest DOX doses. Co-formulation of IL-12 mRNA and DOX with PBAE demonstrated effective IL-12 protein secretion in transfected B16F10 cells with a simultaneous DOX dose dependent reduction in viability. Secreted IL-12 was bioactive, inducing dose-dependent STAT4 phosphorylation and IFNγ secretion in primary mouse splenocytes. Furthermore, in a syngeneic melanoma mouse model, intratumoural administration of PBAE-DOX/IL-12 mRNA achieved significantly elevated levels of IL-12 and IFNγ in the tumour compared to the saline control, confirming delivery of DOX, as well as IL-12 protein secretion, and immunostimulatory activity in vivo. These findings demonstrate that PBAE is a promising platform for co-delivery of cytokine encoded mRNA with DOX in a single formulation, establishing feasibility for advanced chemoimmunotherapy approaches.
A novel, sensitive, and environmentally sustainable spectrofluorimetric method was developed for ivabradine determination based on the fluorescence quenching of erythrosin B. The method exploits the formation of a stable 1 : 1 ground-state complex between anionic erythrosin B and cationic ivabradine through electrostatic interactions. To elucidate the interaction mechanism, comprehensive mechanistic studies using Stern-Volmer analysis, thermodynamic parameters determination, and Job's method confirmed static quenching with spontaneous complex formation. Furthermore, quantum mechanical calculations using PM3 methodology revealed multiple interaction sites with binding distances of 1.7-3.6 Å, involving electrostatic interactions and hydrogen bonding. Subsequently, Box-Behnken experimental design optimization identified optimal conditions: pH 5.6, buffer volume 1.1 mL, erythrosin B concentration 25 µg mL-1, and reaction time 4.0 minutes. Under these optimized conditions, the method demonstrated excellent analytical performance with linear response over 0.02-2.0 µg mL-1 (r 2 = 0.9995), superior sensitivity (LOD = 6.46 ng mL-1), high accuracy, and precision. The practical applicability was demonstrated through successful application to commercial tablets and spiked human plasma samples, confirming utility for both pharmaceutical quality control and bioanalytical applications. Therefore, the developed method represents a significant advancement in green analytical chemistry, offering a cost-effective, rapid, and environmentally friendly alternative for ivabradine monitoring in pharmaceutical and clinical settings.
Antimicrobial resistance (AMR) and cancer are major health concerns that require efficient treatment strategies. An environmentally friendly extracellular biosynthesis of cadmium telluride quantum dots (CdTe QDs) was achieved using Paenibacillus dendritiformis, an endophytic bacterial strain. The biosynthesized CdTe QDs exhibited optical, physicochemical, and structural characteristics that were evaluated using UV-vis and photoluminescence spectroscopies, revealing a strong green fluorescence. Its monoclinic structure was revealed by XRD, and biomolecular capping was detected using FTIR spectroscopy. The zeta (ζ)-potential was evaluated to check their colloidal stability and negative surface charge of the particles, while FE-SEM revealed their surface morphology. Reactive oxygen species (ROS) production can be triggered by CdTe QDs, affecting essential biomolecules and bacterial membranes. The CdTe QDs also show the largest zone of inhibition of 20 mm against amoxicillin-resistant bacterial strains, Klebsiella pneumoniae (AMX 87) and Enterobacter hormaechei (AMX 03). They additionally exhibit anticancer activity against the human cervical cancer (HeLa) cell line with an IC50 of 60 µg mL-1 and the human lung cancer (A549) cell line with an IC50 of 65 µg mL-1. These results demonstrate the potential of biosynthesized CdTe QDs as an effective nanomaterial for treating AMR and cancer.
Dysregulation of cyclin-dependent kinases (CDKs) drives uncontrolled cell cycle progression in several malignancies, making CDK4 and CDK6 appealing therapeutic targets. This paper details the rational design, synthesis, and thorough assessment of fifteen new pyrazolo[1,5-a]pyrimidine derivatives (19a-o) as cyclin-dependent kinase inhibitors. Structure-activity relationship research identified compound 19i as the primary candidate, exhibiting enhanced antiproliferative efficacy against HCT-116 colorectal cancer cells with an IC50 of 1.02 μM, slightly higher than that of doxorubicin (IC50, 1.08 μM). Mechanistic investigations demonstrated that 19i generates significant G0/G1 phase cell cycle arrest and substantial apoptotic cell death, with total apoptosis reaching 47.76% of the treated cells. ELISA analysis verified the activation of p53-dependent intrinsic apoptosis, evidenced by a 6.90-fold increase in p53, a 3.03-fold increase in Bax, a 0.39-fold decrease in Bcl-2, and a 9.56-fold increase in caspase-3 activity. Biochemical kinase tests revealed significant suppression of CDK4 (IC50 0.087 μM) and CDK6 (IC50 0.114 μM). Molecular docking revealed essential binding interactions, including hydrogen bonds with Lys35 and Val101, aromatic π-π stacking, and a new halogen bond with Glu94. Molecular dynamics simulations validated prolonged protein conformational stability and efficient target engagement. These findings collectively designate the pyrazolo[1,5-a]pyrimidine scaffold as a viable framework for CDK-targeted anticancer therapies.
Neuroinflammation, oxidative stress, and glutamate-mediated excitotoxicity are central pathological mechanisms underlying epileptogenesis and seizure propagation. In the present study, a series of rationally designed sulfonamide pyrazole derivatives was evaluated for their anticonvulsant potential using pentylenetetrazol (PTZ)- and pilocarpine-induced seizure models in mice. Among the tested compounds, compound 6d emerged as the most promising candidate, exhibiting superior anticonvulsant efficacy. In the PTZ model, compound 6d afforded 90% seizure protection with complete survival, outperforming the reference drug sodium valproate. In the pilocarpine-induced status epilepticus model, compound 6d significantly prolonged seizure onset latency, markedly suppressed seizure severity (reducing Racine scores by >80%), and ensured 100% survival. Mechanistic investigations revealed that compound 6d exerted pronounced neuroprotective effects in hippocampal tissue by significantly attenuating oxidative stress (malondialdehyde and nitrite levels), neuroinflammation (TNF-α and IL-6), and excitotoxicity (glutamate levels), with greater efficacy than valproate. Importantly, sub-chronic oral administration of compound 6d did not induce detectable hepatic, renal, or cardiac toxicity, indicating a favorable preliminary safety profile. Collectively, these findings identify compound 6d as a promising lead anticonvulsant agent with multimodal neuroprotective actions and support its further preclinical development as a potential disease-modifying therapy for epilepsy.
Engineered living materials (ELMs), which integrate live microorganisms into biocompatible matrices, are emerging as powerful platforms for therapeutic applications. Among these, hydrogels encapsulating engineered live biotherapeutic products (eLBPs) offer enhanced microbial stability, targeted delivery, and functional versatility for treating human disease. By protecting microbes from environmental stress and immune clearance while supporting nutrient diffusion and activity, hydrogel systems address key challenges in microbial therapeutic delivery. This review highlights recent advances in hydrogel-based delivery of eLBPs, focusing on material design, microbial engineering, and performance metrics critical for clinical translation. We provide a framework for designing next-generation living materials for human health, emphasizing opportunities and challenges in bringing these systems from bench to bedside.