Loss of MLKL ameliorates liver fibrosis by inhibiting hepatocyte necroptosis and hepatic stellate cell activation.

Background: Liver fibrosis affects millions of people worldwide without an effective treatment. Although multiple cell types in the liver contribute to the fibrogenic process, hepatocyte death is considered to be the trigger. Multiple forms of cell death, including necrosis, apoptosis, and necroptosis, have been reported to co-exist in liver diseases. Mixed lineage kinase domain-like protein (MLKL) is the terminal effector in necroptosis pathway. Although necroptosis has been reported to play an important role in a number of liver diseases, the function of MLKL in liver fibrosis has yet to be unraveled. Methods and Results: Here we report that MLKL level is positively correlated with a number of fibrotic markers in liver samples from both patients with liver fibrosis and animal models. Mlkl deletion in mice significantly reduces clinical symptoms of CCl4- and bile duct ligation (BDL) -induced liver injury and fibrosis. Further studies indicate that Mlkl-/- blocks liver fibrosis by reducing hepatocyte necroptosis and hepatic stellate cell (HSC) activation. AAV8-mediated specific knockdown of Mlkl in hepatocytes remarkably alleviates CCl4-induced liver fibrosis in both preventative and therapeutic ways. Conclusion: Our results show that MLKL-mediated signaling plays an important role in liver damage and fibrosis, and targeting MLKL might be an effective way to treat liver fibrosis.

Spermine alleviates experimental autoimmune encephalomyelitis via regulating T cell activation and differentiation.

Multiple sclerosis (MS) is a chronic neuroinflammatory disease which causes demyelination, axonal damage and even disability. Th1 and Th17 cells, more precisely, the IFNγ/IL17a double producing CD4+ T cells, have been known to play critical roles in the pathogenesis of MS and EAE, a mouse model of MS. Polyamines not only regulate the immune system, but also are essential for the normal function of the central nervous system (CNS). In this study, we demonstrate that the supplementation of spermine (SPM), a biogenic polyamine, significantly suppresses EAE progression in both preventative and therapeutic ways. Further study suggests that spermine significantly reduces IFNγ+/IL17a-, IFNγ-/IL17a+ and IFNγ+/IL17a+ cells in periphery, and thus reducing the infiltration of these pathogenic cells into the CNS. In vitro, spermine has been shown to suppress the activation and proliferation of CD4+ T cells and also significantly impede the polarization of T effector cells in a dose-dependent manner, accompanied by the inhibition of ERK phosphorylation. Consistently, a number of MEK/ERK inhibitors (including PD0325901, FR180204 and selumetinib) have been found to mimic the effects of spermine in inhibiting CD4+ T cell activation and T effector cell differentiation. Collectively, spermine alleviates EAE progression by inhibiting CD4+ T cells activation and T effector cell differentiation in a MAPK/ERK-dependent manner, suggesting this pathway might be a target to develop effective therapies for MS.

Gelation and foaming properties of fatty acid mixtures in sunflower oil.

BACKGROUND: The development of lipid-lowering products has become the focus of the food industry due to increasing consumer awareness of the relationship between diet and health. Recently, edible oleofoams have drawn attention due to their enormous potential in reformulating food products with reduced fat content and unique mouth feel. RESULTS: We have developed an edible oleofoam system by whipping oleogel composed of fatty acid mixtures in sunflower oil. The crystal morphology, gelation properties, and foaming properties of these oleogels could be tailored by changing the ratio of stearic acid (SA) and myristic acid (MA). Specifically, SA/MA = 2:8 (2S8M) was demonstrated to have superior foaming capability and foam stability, likely due to the densely packed and uniformly distributed crystals formed at this fatty acid ratio. Small lipid crystals in 2S8M absorbed to the air-oil interface more efficiently, and together with the strengthened network established in the bulk phase, helped stabilize the foam structure. As a result, the 2S8M oleofoam showed excellent foaming properties: strong plasticity, significantly increased overrun (up to 63.56 ± 2.58%), and significantly improved foam stability. The X-ray diffraction (XRD) results indicated that the diffraction pattern observed for 2S8M samples at d-spacing of 4.20 and 3.79 Å was related to the characteristic peak of ß' type crystals, which were responsible for the enhanced foaming capability of 2S8M oleogels. Oleophobic property of 2S8M increased, as indicated by wettability in oil phase, which could possibly drive crystals to the air-oil interface. CONCLUSIONS: These results highlighted the importance of lipid crystal morphology in determining the whippability of oleogels. © 2021 Society of Chemical Industry.

Microfibrillated cellulose enhancement to mechanical and conductive properties of biocompatible hydrogels.

A combination of conductive polymer with natural biomass is an ideal alternative to the classical conductive materials. In this study, PPy/SA/TOMFC composite hydrogels were fabricated by incorporation of TEMPO-oxidized microfibrillated cellulose (TOMFC) into the alginate-based matrix along with the in situ polymerization of pyrrole monomer. It was found that the mechanical and conductive properties of the composite hydrogels were associated with the concentration of TOMFC, which facilitated the formation of more compact 3D network structures and the growing of PPy conductive network. The mechanical properties of the synthesized hydrogels were significantly enhanced by incorporation of higher amount of TOMFC. In addition, with the introduction of 5.0 wt% TOMFC, the electrical conductivity of composite hydrogels could be ten times higher than that of PPy/SA hydrogels. Moreover, the obtained PPy/SA/TOMFC hydrogels exhibited tunable swelling properties and good biocompatibility, making them promising candidates for the use as biomaterial.