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Purpose. This study aimed to evaluate the expression of microRNAs (miRNAs) and inflammasomes in diabetes‐induced retinal cells and to determine their role in the pathogenesis of diabetic retinopathy (DR). Methods. To establish diabetes‐induced cell models, ARPE‐19 cells were treated with high glucose. The expression levels of five miRNAs (miR‐185, miR‐17, miR‐20a, miR‐15a, and miR‐15b) were measured in high glucose‐treated ARPE‐19 cells using real‐time quantitative polymerase chain reaction. Western blotting was performed to measure inflammasome expression in cellular models. miR‐17 was selected as the target miRNA, and inflammasome expression was measured following the transfection of an miR‐17 mimic into high glucose‐treated ARPE‐19 cells. Results. In high glucose‐treated ARPE‐19 cells, miRNA expression was substantially downregulated, whereas that of inflammasome components was significantly increased. Following the transfection of the miR‐17 mimic into high glucose‐treated ARPE‐19 cells, the levels of inflammasome components were significantly decreased. Conclusions. This study investigated the relationship between miRNAs and inflammasomes in diabetes‐induced cells using high glucose‐treated ARPE‐19 cells. These findings suggested that miR‐17 suppresses inflammasomes, thereby reducing the subsequent inflammatory response and indicating that miRNAs and inflammasomes could serve as new therapeutic targets for DR. [ABSTRACT FROM AUTHOR]

Natural killer (NK) cells are crucial in the innate immune response and show promise in cancer immunotherapy, but face challenges in activation and targeted gene delivery. In this study, bifunctional lipid nanoparticles (DLNPs) containing 1,2‐dioleoyl‐3‐trimethylammonium‐propane (DOTAP), designed to bolster the antitumor efficacy of chimeric antigen receptor‐modified NK (CAR‐NK) cells by facilitating activation and efficient CAR mRNA delivery are introduced. The DLNPs, created by functionalizing FDA‐approved LNP compositions, exhibit excellent mRNA encapsulation and colloidal stability. NK cells primed with DLNPs show increased cytotoxicity against cancer cells via extracellular signal‐regulated kinase/Mitogen‐Activated Protein Kinase pathway modulation and mitochondrial dynamics changes. The DLNPs enter NK cells predominantly through clathrin‐mediated endocytosis, boosting mRNA delivery and overcoming NK cells' resistance to genetic manipulation. CAR‐NK cells targeting glypican‐3, prevalent in hepatocellular carcinoma, show significant therapeutic effects in an orthotopic mouse model. These findings underscore the potential of DLNPs in enhancing CAR‐NK cell therapy for solid tumors, marking a significant stride in NK cell‐based cancer immunotherapy and broadening prospects for NK cell‐related disease interventions. [ABSTRACT FROM AUTHOR]

Since the coronavirus pandemic, mRNA vaccines have revolutionized the field of vaccinology. Lipid nanoparticles (LNPs) are proposed to enhance mRNA delivery efficiency; however, their design is suboptimal. Here, a rational method for designing LNPs is explored, focusing on the ionizable lipid composition and structural optimization using machine learning (ML) techniques. A total of 213 LNPs are analyzed using random forest regression models trained with 314 features to predict the mRNA expression efficiency. The models, which predict mRNA expression levels post-administration of intradermal injection in mice, identify phenol as the dominant substructure affecting mRNA encapsulation and expression. The specific phospholipids used as components of the LNPs, as well as the N/P ratio and mass ratio, are found to affect the efficacy of mRNA delivery. Structural analysis highlights the impact of the carbon chain length on the encapsulation efficiency and LNP stability. This integrated approach offers a framework for designing advanced LNPs and has the potential to unlock the full potential of mRNA therapeutics., (© 2024 The Author(s). Small published by Wiley‐VCH GmbH.)

Catheter-associated urinary tract infection (CAUTI) is the most common healthcare-associated infection; however, current therapeutic strategies remain insufficient for standard clinical application. A novel urinary catheter featuring a dual-layer nanoengineering approach using zinc (Zn) and silver nanoparticles (AgNPs) is successfully fabricated. This design targets microbial resistance, minimizes cytotoxicity, and maintains long-term efficacy. The inner AgNPs layer provides immediate antibacterial effects against the UTI pathogens, while the outer porous Zn layer controls zero-order Ag release and generates reactive oxygen species, thus enhancing long-term bactericidal performance. Enhanced antibacterial properties of Zn/AgNPs-coated catheters are observed, resulting in 99.9% of E. coli and 99.7% of S. aureus reduction, respectively. The Zn/AgNPs-coated catheter significantly suppresses biofilm with sludge formation compared to AgNP-coated and uncoated catheters (all, p < 0.05). The Zn/AgNP-coated catheter in a rabbit model demonstrated a durable, effective barrier against bacterial colonization, maintaining antimicrobial properties during the catheter indwelling period with significantly reduced inflammation and epithelial disruption compared with AgNP and uncoated groups. This innovation has the potential to revolutionize the design of antimicrobial medical devices, particularly for applications requiring long-term implantation. Although further preclinical studies are required to verify its efficacy and safety, this strategy seems to be a promising approach to preventing CAUTI-related complications., (© 2024 The Author(s). Advanced Healthcare Materials published by Wiley‐VCH GmbH.)