Artesunate inhibits macrophage-like phenotype switching of vascular smooth muscle cells and attenuates vascular inflammatory injury in atherosclerosis via NLRP3.

Inflammation is one of the main pathogenic factors of atherosclerosis (AS), and the phenotypic transformation of macrophages in human vascular smooth muscle cells (HVSMCs) contributes to the inflammatory injury of blood vessels and the formation of atherosclerotic plaques. Artesunate reportedly exerts anti-inflammatory activity against AS. Herein, we aimed to explore the artesunate-mediated anti-inflammatory and HVSMC phenotypic switch effects against AS and elucidate potential underlying mechanisms. In vitro, artesunate decreased expression of NLRP3, caspase-1, and interleukin (IL)- 1ß. Artesunate significantly inhibited low-density lipoprotein (LDL) expression in HVSMCs and macrophages. In vivo, artesunate reduced atherosclerotic plaque formation in high-fat diet (HFD)-fed ApoE-/- mice, as well as decreased NLRP3 and CD68 expression in atherosclerotic plaques. Artesunate decreased serum levels of triglycerides and increased high-density lipoprotein levels in HFD-med mice; however, serum levels of total cholesterol and LDL were unaltered. Treatment with artesunate substantially increased α-smooth muscle actin expression in aortic tissues while inhibiting expression levels of NLRP3, IL-1ß, heparinase, matrix metalloproteinase 9, and Krüppel-like factor 4 (KLF4). Collectively, our findings suggest that artesunate-mediated effects may involve inhibition of the ERK1/2/NF-κB/IL-1ß pathway in HVSMCs via the downregulation of NLRP3 expression. Thus, artesunate could serve as a novel strategy to treat AS by inhibiting AS plaque formation and suppressing macrophage-like phenotype switching of HVSMCs.

WLJP-025p, a homogeneous Lonicera japonica polysaccharide, attenuates atopic dermatitis by regulating the MAPK/NFκB/AP-1 axis via Act1.

Atopic dermatitis (AD) is usually treated with steroids, but long-term use is not an effective cure because side effects and disease aggravation. Therefore, more effective and safer treatments are needed. Using dexamethasone as the positive control, the mechanism of action of water-extracted homogeneous honeysuckle Lonicera japonica polysaccharide (WLJP-025p) to alleviate AD was studied. Mice were administered 2,4-dinitrochlorobenzene in their bare back and right ear to mimic an AD model. The efficacy of WLJP-025p in AD was assessed by measuring right ear thickness and skin lesion scores, pathological observation (haematoxylin-eosin and toluidine blue staining), and serum IgE and IL-1ß concentrations. The expression of relevant genes and proteins in the serum and back skin was detected using RT-qPCR, ELISA, western blotting, and immunofluorescence. Molecular docking and dynamic simulation of WLJP-025p and Act1 were performed. WLJP-025p considerably alleviated skin hyperplasia and pathological abnormalities in AD mice and inhibited the expression of Act1, Nucleus-P65, Nucleus-AP-1, and MAPK-related proteins in skin tissues. WLJP-025p formed a stable conformation with Act1, inhibited splenic Th17 differentiation, IL-17 release, and upregulated the expression of related skin barrier proteins. In conclusion, WLJP-025p affects the inflammation regulation via the MAPK/NFκB/AP-1 axis by binding to Act1, promotes the recovery of epithelial barrier function, and alleviates AD in mice.

Microstructure and Oxidation Behavior of Fe-25Mn-9Al-8Ni-1C-xTi Alloy Prepared by Vacuum Arc Melting.

In this study, Fe-25Mn-9Al-8Ni-1C-xTi alloy (x = 0, 0.1, 0.2, 0.3, 0.4 wt.%) was prepared by vacuum arc melting, and the corresponding microstructure and oxidation behavior at 600 °C were studied. The results show that Fe-25Mn-9Al-8Ni-1C-xTi alloy mainly contains austenite phase, ferrite phase and TiC phase. With Ti content increasing, the austenite phase content decreases, while the contents of ferrite phase and TiC phase increase. The oxidation performance test results show that the addition of Ti element greatly reduces the oxidation weight gain of the alloys at the initial oxidation stage. With the extension of the oxidation time and the further increase of the Ti content, the alloys oxidation weight gain shows a trend of first increasing and then decreasing. When the Ti content is 0.2 wt.%, the oxidation weight gain of this series of alloy reaches the lowest value during the stable oxidation period. Compared with Fe-25Mn-9Al-8Ni-1C alloy, its weight gain per unit area is reduced by 21.1%. Fe-25Mn-9Al-8Ni-1C-xTi alloy oxide layer exhibits a double-layer structure. The outer oxygen layer is mainly loose iron-oxides, while in the inner oxygen layer, the oxides are mainly composed of manganese-oxides and aluminum-oxides, which are relatively dense.