Effect of mRNA formulated with lipid nanoparticles on the transcriptomic and epigenetic profiles of F4/80 liver-associated macrophages.

Delivery of an mRNA formulated with lipid nanoparticles (LNPs) induces robust humoral and cell-mediated branches of the immune response. Depending on the LNP formula, mRNA encoding proteins can be detected in the liver upon intramuscular administration of mRNA/LNP in mice. This study investigated the impact of mRNA/LNP administration on liver-associated macrophages at the transcriptomic and epigenetic levels in a mouse model.

A polycomb group protein EED epigenetically regulates responses in lipopolysaccharide tolerized macrophages.

Background: To avoid exaggerated inflammation, innate immune cells adapt to become hypo-responsive or "tolerance" in response to successive exposure to stimuli, which is a part of innate immune memory. Polycomb repressive complex 2 (PRC2) mediates the transcriptional repression by catalyzing histone H3 lysine 27 trimethylation (H3K27me3) but little is known about its role in lipopolysaccharide (LPS)-induced tolerance in macrophages.

Result: We examined the unexplored roles of EED, a component of the PRC2, in LPS tolerant macrophages.

Loss of O-methylguanine DNA methyltransferase (MGMT) in macrophages alters responses to TLR3 stimulation and enhances DNA double-strand breaks and mitophagy.

O-methylguanine-DNA methyltransferase (MGMT) is a DNA damage repair enzyme. The roles of this enzyme in immune cells remain unclear. In this study, we explored the roles of MGMT in bone marrow-derived murine macrophages (BMMs) via the use of MGMT knockout (KO) mice.

Stability and release mechanism of double emulsification (W1/O/W2) for biodegradable pH-responsive polyhydroxybutyrate/cellulose acetate phthalate microbeads loaded with the water-soluble bioactive compound niacinamide.

Microbeads of biodegradable polyhydroxybutyrate (PHB) offer environmental benefits and economic competitiveness. The aim of this study was to encapsulate a water-soluble bioactive compound, niacinamide (NIA), in a pH-responsive natural matrix composed of PHB and cellulose acetate phthalate (CAP) by double emulsification (W1/O/W2) to improve the encapsulation efficiency (%EE) and loading capacity (%LC). PHB was produced in-house by Escherichia coli JM109 pUC19-23119phaCAB without the inducing agent isopropyl β-D-1-thiogalactopyranoside (IPTG).

O-methylguanine DNA methyltransferase regulates β-glucan-induced trained immunity of macrophages via farnesoid X receptor and AMPK.

Trained immunity is the heightened state of innate immune memory that enhances immune response resulting in nonspecific protection. Epigenetic changes and metabolic reprogramming are critical steps that regulate trained immunity. In this study, we reported the involvement of O-methylguanine DNA methyltransferase (MGMT), a DNA repair enzyme of lesion induced by alkylating agents, in regulation the trained immunity induced by β-glucan (BG).

A novel "turn-on" fluorescent probe based on thiocarbamoyl-DHP for Hg detection in water samples and living cells.

In this study, two fluorescent sensing probes, dihydropyridine (DHP) derivatives (DHP-CT1 and DHP-CT2) bearing phenoxy thiocarbonyl group, have been developed for Hg detection. The tandem trimerization-cyclization of methylpropiolate with ammonium acetate gave 1.4-DHP and 1,2-DHP derivatives, which were reacted with O-phenylcarbonochloridothioate to produce DHP-CT1 and DHP-CT2, respectively.

Pyrene-Labeled and Quaternized Chitosan: Synthesis, Characterization, and Its Potential Application for Fluorescently Trackable Nucleic Acid Delivery into Cells.

A chitosan derivative (Pyr-CS-HTAP) having pyrene (Pyr) and -[(2-hydroxyl-3-trimethylammonium)] propyl (HTAP) units conjugated at C6 and C2 positions, respectively, was synthesized and characterized. Dynamic light scattering and scanning electron microscopy revealed that Pyr-CS-HTAP self-assembled into spherical nanoparticles with a hydrodynamic diameter of 211 ± 5 nm and a ζ-potential of +49 mV. The successful binding of Pyr-CS-HTAP with nucleic acid was ascertained by fluorescence resonance energy-transfer analysis and gel electrophoresis.

Screening of compounds to identify novel epigenetic regulatory factors that affect innate immune memory in macrophages.

Trained immunity and tolerance are part of the innate immune memory that allow innate immune cells to differentially respond to a second encounter with stimuli by enhancing or suppressing responses. In trained immunity, treatment of macrophages with β-glucan (BG) facilitates the production of proinflammatory cytokines upon lipopolysaccharide (LPS) stimulation. For the tolerance response, LPS stimulation leads to suppressed inflammatory responses during subsequent LPS exposure.

The chemotherapeutic drug carboplatin affects macrophage responses to LPS and LPS tolerance via epigenetic modifications.

Following re-exposure to lipopolysaccharide (LPS), macrophages exhibit an immunosuppressive state known as LPS tolerance, which is characterized by repressed proinflammatory cytokine production. LPS-induced tolerance in macrophages is mediated in part by epigenetic changes. Carboplatin, an anticancer chemotherapeutic drug, exerts its effect by inhibiting DNA replication and transcription, as well as through epigenetic modifications.

Polymerized Luteolin Nanoparticles: Synthesis, Structure Elucidation, and Anti-Inflammatory Activity.

Luteolin is an anti-inflammatory flavonoid commonly found in many edible plants. The compound is popularly consumed as a supplement regardless of its poor water solubility (27.8 μg/mL at 25 °C) and low bioavailability.

Solid Composite Material for Delivering Viable Cells into Skin Tissues Detachable Dissolvable Microneedles.

Delivering cells to desired locations in the body is needed for disease treatments, tissue repairs, and various scientific investigations such as animal models for drug development. Here, we report the solid composite material that when embedded with viable cells, can temporarily keep cells alive. Using the material, we also show the fabrication of detachable dissolvable microneedles (DMNs) that can instantly deliver viable cells into skin tissue.

Notch signaling regulates the responses of lipopolysaccharide-stimulated macrophages in the presence of immune complexes.

Macrophages exhibit diverse effector phenotypes depending on the stimuli and their microenvironment. Classically activated macrophages are primed with interferon (IFN)γ and stimulated with pathogen-associated molecular patterns. They produce inflammatory mediators and inflammatory cytokines, such as IL-12.

Notch signaling regulates expression of Mcl-1 and apoptosis in PPD-treated macrophages.

Macrophages are cellular targets for infection by bacteria and viruses. The fate of infected macrophages plays a key role in determining the outcome of the host immune response. Apoptotic cell death of macrophages is considered to be a protective host defense that eliminates pathogens and infected cells.

Signal amplification of microarray-based immunoassay by optimization of nanoliposome formulations.

The use of microarray-based immunoassay is often limited by its sensitivity. To increase the sensitivities of such an immunoassay, liposome encapsulation was explored. Two different liposome formations and several preparation methods were examined to optimize encapsulation and signal-enhancing efficacy for enzyme-linked immunosorbent assay (ELISA) and antibody array.

Gold nanoparticles/horseradish peroxidase encapsulated polyelectrolyte nanocapsule for signal amplification in Listeria monocytogenes detection.

Bioconjugate nanocapsules were fabricated by using polystyrene sulfonate (PSS) to encapsulate gold nanoparticles (AuNPs) bearing adsorbed horseradish peroxidase (HRP). The average size of nanocapsule was in a range 150-400 nm. The efficiency of the capsules to enhance signals in an immunoassay was demonstrated by using an enzyme linked immunosorbent assay (ELISA) to detect the food-borne pathogen -Listeria monocytogenes.