γ-Glutamylcysteine ameliorates blood-brain barrier permeability and neutrophil extracellular traps formation after ischemic stroke by modulating Wnt/ß-catenin signalling in mice.

During the inflammatory response after stroke, the blood-brain barrier (BBB) is significantly disrupted, compromising its integrity. This disruption allows many peripheral neutrophils to infiltrate the injury site in the brain and release neutrophil extracellular traps (NETs), which further increase BBB permeability. In this study, we aimed to investigate the protective effects of γ-Glutamylcysteine (γ-GC), an immediate precursor of GSH, against BBB breakdown and NET formation after ischemic stroke. Our data indicated that γ-GC treatment effectively attenuated BBB damage, decreased neutrophil infiltration, and suppressed the release of NETs, ultimately leading to the amelioration of ischemic injury. Transcriptomic data and subsequent validation studies revealed that mechanistically, γ-GC exerts its effect by activating the Wnt/ß-catenin pathway after ischemic stroke. This research suggests that γ-GC may hold promise as a therapeutic agent for alleviating brain injury following an ischemic stroke.

GM-CSF Promotes the Development of Dysfunctional Vascular Networks in Moyamoya Disease.

Moyamoya disease (MMD) is a chronic occlusive cerebrovascular disease with the development of a network of abnormal vessels. Immune inflammation is associated with the occurrence and development of MMD. However, the mechanisms underlying the formation of the abnormal vascular network remain unclear. Twenty-eight patients with MMD, 26 ischemic stroke patients, and 26 unrelated healthy volunteers were enrolled in this study The data showed that the levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were higher in MMD patients than in healthy controls (P <0.01), and GM-CSF was mainly from Th1 and Th17 cells in MMD. We found that increased GM-CSF drove monocytes to secrete a series of cytokines associated with angiogenesis, inflammation, and chemotaxis. In summary, our findings demonstrate for the first time the important involvement of GM-CSF in MMD and that GM-CSF is an important factor in the formation of abnormal vascular networks in MMD.

Infiltrating myeloid cell-derived properdin markedly promotes microglia-mediated neuroinflammation after ischemic stroke.

BACKGROUND: Emerging evidence has shown that myeloid cells that infiltrate into the peri-infarct region may influence the progression of ischemic stroke by interacting with microglia. Properdin, which is typically secreted by immune cells such as neutrophils, monocytes, and T cells, has been found to possess damage-associated molecular patterns (DAMPs) properties and can perform functions unrelated to the complement pathway. However, the role of properdin in modulating microglia-mediated post-stroke neuroinflammation remains unclear. METHODS: Global and conditional (myeloid-specific) properdin-knockout mice were subjected to transient middle cerebral artery occlusion (tMCAO). Histopathological and behavioral tests were performed to assess ischemic brain injury in mice. Single-cell RNA sequencing and immunofluorescence staining were applied to explore the source and the expression level of properdin. The transcriptomic profile of properdin-activated primary microglia was depicted by transcriptome sequencing. Lentivirus was used for macrophage-inducible C-type lectin (Mincle) silencing in microglia. Conditioned medium from primary microglia was administered to primary cortex neurons to determine the neurotoxicity of microglia. A series of cellular and molecular biological techniques were used to evaluate the proinflammatory response, neuronal death, protein-protein interactions, and related signaling pathways, etc. RESULTS: The level of properdin was significantly increased, and brain-infiltrating neutrophils and macrophages were the main sources of properdin in the ischemic brain. Global and conditional myeloid knockout of properdin attenuated microglial overactivation and inflammatory responses at the acute stage of tMCAO in mice. Accordingly, treatment with recombinant properdin enhanced the production of proinflammatory cytokines and augmented microglia-potentiated neuronal death in primary culture. Mechanistically, recombinant properdin served as a novel ligand that activated Mincle receptors on microglia and downstream pathways to drive primary microglia-induced inflammatory responses. Intriguingly, properdin can directly bind to the microglial Mincle receptor to exert the above effects, while Mincle knockdown limits properdin-mediated microglial inflammation. CONCLUSION: Properdin is a new medium by which infiltrating peripheral myeloid cells communicate with microglia, further activate microglia, and exacerbate brain injury in the ischemic brain, suggesting that targeted disruption of the interaction between properdin and Mincle on microglia or inhibition of their downstream signaling may improve the prognosis of ischemic stroke.

Differences of wax-based emulsion gel in 3D printing performance: Crystal distribution and droplet stability.

Six kinds of natural waxes were used for emulsion gels preparation. The differences in printing performance were explored based on the crystal distribution and droplet stability. Firstly, the effect of crystal distribution was investigated through microstructures and rheological properties. It was found that the dense crystal network/interfacial crystallization could stabilize the droplet and provide modulus to ensure the self-supporting behavior after printing, whereas excessive crystal could lead to droplet rupture and coalescence. Furthermore, all emulsion gels could recrystallize by heating, which could enhance the performance of 3D printing. Then, the droplet stability was investigated after storing/freeze-thawing. It was found that emulsion gels with dense crystal networks/interfacial crystallization had more stable droplets, which ensure the continuous extrusion during printing. Finally, printing performance was investigated comprehensively. Three emulsion gels with denser crystal networks/interfacial crystallization had higher recovery rates (16.17-21.15%) and more stable droplets, which perform better in 3D printing correspondingly.

Thermal-reversible lacquer wax-based oleofoams in dual stabilization with high ambient stability.

In this study, the effect of the content of the lacquer wax and whipping time on the overrun was explored. It was found that an appropriate amount of wax content and whipping time could promote crystal dual stabilization through the Pickering mechanism and the close packing in the bulk phase. Otherwise, it would result in low overrun caused by high viscous and crystal bridging. The addition of polyglycerol polyricinoleate (PGPR) could effectively enhance the overrun by apace absorbing. At the same time, adding PGPR also improved the contact angle, which was beneficial to the adsorption at the A-O interface. The 8 wt% oleogel was partially substituted by high-melting fat palm stearin (POs) and oleofoams were prepared based on blended fat. POs increased the melting point, structural strength, and ß'-form crystal of oleofoams, thus improving the storage and temperature stability. The oleofoam has a maximum overrun of 189% and could maintain the shape of the decorating over 15 d at the ambient temperature, showing great potential in low-fat food applications and other delivery systems.

Comparative study of natural wax-based W/O emulsion gels: Microstructure and macroscopic properties.

In this paper, six kinds of natural wax, including sunflower wax (SFX), rice bran wax (RBX), carnauba Brazilian wax (CBX), beeswax (BWX), candelilla wax (CDX), and sugarcane wax (SGX) were used to prepare water-in-oil (W/O) emulsion gels. Microstructures and rheological properties of all emulsion gels were investigated by microscopy, confocal laser scanning microscope (CLSM), scanning electron microscopy (SEM), and rheometer, respectively. By comparing polarized light images of wax-based emulsion gels and corresponding wax-based oleogels, it could be found that dispersed water droplets greatly affected the crystal distribution and hindered crystal growth. Polarized light microscopy and CLSM images proved that natural wax could perform a dual-stabilization mechanism by interfacial crystallization and crystal networks. SEM images illustrated all waxes except SGX were platelets and formed networks by stacking on top of each other, while flocs-like SGX was easier to adsorb on the interface and formed a "crystalline shell". The surface area and pore formed by different wax varied wildly, which accounted for their differences in the gelation ability, oil binding capacity, and strength of the crystal network. The rheological study showed that all wax had solid-like properties and wax-based oleogels with denser crystal networks correspond to emulsion gels with higher modules. The dense crystal network and interfacial crystallization could improve the stability of W/O emulsion gels proved by recovery rates and critical strain. All the above proved that natural wax-based emulsion gels can be used as stable, low-fat, and thermal-sensitive fat mimics.