Lee, Seonhwa

Abstract Accurate, noninvasive biomarkers for diagnosis and longitudinal monitoring of metabolic dysfunction–associated steatohepatitis (MASH) remain an urgent unmet clinical need. Here, we describe an electrochemical immunoassay that involves capturing hepatic extracellular vesicles (EVs) on antibody-modified electrodes followed by detecting EV-borne biomarkers using redox active gold nanoparticles (AuNPs). The intensity of electrochemical redox signal represents a quantitative measure of biomarker abundance. Three MASH-associated biomarkers—S100A11, TNF-α, and TGF-β1—were analyzed on hepatic EVs to assess steatotic, inflammatory, and fibrotic states of the diseased liver. The electrochemical signals for individual biomarkers were added into a composite EV MASH score. Plasma samples from 28 patients with MASH, 22 healthy controls, and 27 patients with non-MASH liver disease were scored in this manner, revealing 100% accuracy in the training cohort and >90% accuracy in an independent validation cohort. Our electrochemical immunosensor represents a minimally invasive liquid liver biopsy, offering a promising alternative to solid liver biopsies for screening and monitoring of MASH. One Sentence Summary Circulating hepatic extracellular vesicles carry biomarkers of liver injury enabling accurate, minimally invasive MASH diagnosis in blood.

Abstract Vaccine‐induced immune thrombotic thrombocytopenia (VITT) is a new disorder that emerged in the wake of coronavirus disease 2019 (COVID‐19) vaccination. It is a rare but life‐threatening condition that requires an aggressive course of treatment to improve patient outcomes. Currently, the diagnosis of VITT relies on a comprehensive panel of criteria, including a history of recent vaccination, platelet count, positive enzyme linked immunosorbent assays (ELISA) result for a closely related thrombotic disorder, heparin‐induced thrombocytopenia (HIT), and platelet factor 4 (PF4)‐dependent functional assays. The study describes a technically simple antigenic assay designed to detect autoimmune antibodies associated with VITT. It is first shown that cross‐linked platelet factor 4 (c‐PF4) represents an antigenic target specific for VITT/VITT‐like Abs. This antigenic target is then incorporated into a microfluidic electrochemical biosensor and specific and sensitive detection of VITT/VITT‐like antibodies is demonstrated in a fully automated manner while using microliter volumes of patient sera. Fifty‐five serum samples are tested using the microfluidic electrochemical biosensor and demonstrated high accuracy for the detection of VITT sera and VITT‐like monoclonal gammopathy of thrombotic ignificance (MGTS) antibodies compared to healthy controls and HIT patients. It is envisioned that the microfluidic electrochemical biosensor will be used in combination with other clinical criteria to enable timely, sensitive, and specific diagnosis of VITT.

Abstract Background: The antibiotic resistance of pathogenic microbes due to the overuse of antibiotics is a growing threat to the public health and can eventually reduce the therapeutic effects of antibiotics. Hydrogel-based systems for local delivery of antibiotics can be a solution to this problem. Metal-organic frameworks (MOFs) have received considerable interest for use as antimicrobial materials due to their high porosity, large surface area to volume, diverse structures, and tunable topologies. Methods: In this study, we developed MOF-encapsulated and dual (photo & chemical)-crosslinkable alginate hydrogel as an antimicrobial scaffold. We synthesized antimicrobial Cu(AZPY)-MOF using solvothermal reaction and encapsulated them in an alginate-based hydrogel via visible light photo-crosslinking and calcium ion-induced chemical-crosslinking processes. Results: Powder X-ray diffraction, Fourier-transform infrared spectroscopy, thermogravimetric analysis, and scanning electron microscopy confirmed the successful fabrication of Cu(AZPY)-MOF encapsulated alginate hydrogel. The mechanical strength of the dual-crosslinked hydrogels was better than that of the photo-crosslinked hydrogel. Encapsulation of Cu(AZPY)-MOF in an alginate hydrogel resulted in a further increase in the mechanical strength of the hydrogel owing to the additional interaction of alginate with Cu-MOF. Moreover, the Cu(AZPY)-MOF encapsulated alginate hydrogel exhibited excellent antibacterial and antifungal properties against two bacterial strains (i.e., MRSA and S. mutans) and one fungal strain (C. albicans) as well as negligible cytotoxicity toward MEFs. Conclusions: The antimicrobial agents encapsulated dual-crosslinkable alginate hydrogel developed in this study is a promising candidate for use in tissue engineering and biomedical field.

Compared to most of nano-sized particles, core–shell-structured nanoflowers have received great attention as bioactive materials because of their high surface area with the flower-like structures. In this study, core–shell-structured Si-based NiO nanoflowers, Si@NiO, were prepared by a modified chemical bath deposition method followed by thermal reduction. The crystal morphology and basic structure of the composites were characterized by powder X-ray diffraction (PXRD), Fourier-transform infrared spectroscopy (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), specific surface area (BET) and porosity analysis (BJT), and inductively coupled plasma optical emission spectrometry (ICP-OES). The electrochemical properties of the Si@NiO nanoflowers were examined through the redox reaction of ascorbic acid with the metal ions present on the surface of the core–shell nanoflowers. This reaction favored the formation of reactive oxygen species. The Si@NiO nanoflowers showed excellent anticancer activity and low cytotoxicity toward the human breast cancer cell line (MCF-7) and mouse embryonic fibroblasts (MEFs), respectively, demonstrating that the anticancer activities of the Si@NiO nanoflowers were primarily derived from the oxidative capacity of the metal ions on the surface, rather than from the released metal ions. Thus, this proves that Si-based NiO nanoflowers can act as a promising candidate for therapeutic applications.