Inflammatory bowel disease (IBD) is one of the most common diseases in the gastrointestinal tract related to aberrant inflammation. Pyroptosis, which is characterized by inflammasome formation, the activation of caspase-1, and the separation of the N- and C-terminals of GSDMD, might be related to IBD pathogenesis. NEK7 is an important component of the NLRP3 inflammasome in macrophages. We attempted to investigate the mechanism of NEK7 interacting with NLRP3 to modulate the pyroptosis in IBD. NEK7 mRNA and protein expression and pyroptosis-associated factors, including Caspase-1 (p45, p20), NLRP3, and GSDMD, were upregulated in IBD tissues. NEK7 knockdown abolish ATP + LPS-induced pyroptosis in vitro and improved DSS-induced chronic colitis in vivo. NEK7 interacted with NLRP3, as revealed by Co-IP and GST pull-down assays, to exert its effects. Moreover, short-term LPS treatment alone induced no significant changes in NEK7 protein level. TLR4/NF-κB signaling in MODE-K cells could be activated by LPS treatment. LPS-induced NEK7 upregulation could be significantly reversed by JSH-23, an inhibitor of p65. Furthermore, LUC and ChIP assays revealed that RELA might activate the transcription of NEK7 via targeting its promoter region. LPS-induced TLR4/NF-κB activation causes an increase in NEK7 expression by RELA binding NEK7 promoter region. In conclusion, NEK7 interacts with NLRP3 to modulate NLRP3 inflammasome activation, therefore modulating the pyroptosis in MODE-K cells and DSS-induced chronic colitis in mice. We provide a novel mechanism of NEK7-NLRP3 interaction affecting IBD via pyroptosis.
Abstract. A novel evodiamine (EVO)-phospholipid complex (EPLC) was designed to improve the bioavailability of EVO. A central composite design approach was employed for process optimization. EPLC were characterized by differential scanning calorimetry, ultraviolet spectroscopy, Fourier transformed infrared spectroscopy, 1 H-NMR spectroscopy, matrix-assisted laser desorption/ionization time-offlight spectroscopy, apparent solubility, and dissolution rate. After oral administration of EPLC, the concentrations of EVO at different time points were determined by high-performance liquid chromatography. The optimal formulation for EPLC was obtained where the values of X 1 , X 2 , and X 3 were 2, 0.5, and 2.5 mg/mL, respectively. The average particle size and zeta potential of EPLC with the optimized formulation were 246.1 nm and −26.94 mV, respectively. The EVO and phospholipids in the EPLC were associated with non-covalent interactions. The solubility of EPLC in water and the dissolution rate of EPLC in phosphate-buffered solution (pH 6.8) were substantially enhanced. The plasma EVO concentration-time curves of EPLC and free EVO were both in accordance with the two-compartment model. The peak concentration and AUC 0−∞ of EPLC were increased, and the relative bioavailability was significantly increased to 218.82 % compared with that of EVO.
We have developed a novel approach for the rapid visual detection of Cu(2+) based on an anionic polythiophene derivative (sodium poly(2-(4-methyl-3-thienyloxy)propanesulfonate, PMTPS) using click chemistry. The method relies on the disassembly of PMTPS aggregates in the presence of cationic surfactant through electrostatic and hydrophobic interactions. In the assay of Cu(2+) detection, a cationic surfactant was formed via a click reaction catalyzed by copper(I), which was derived in situ from copper(II) and promoted the disassembly of PMTPS aggregates leading to the distinct solution color change from purple to yellow. This polymer probe has excellent sensitivity and selectivity for Cu(2+) with a detectable range in the micromolar regime by naked eyes and can be used for monitoring Cu(2+) concentrations below the safety limit in real-world samples.
Closely following the rapid development of artificial intelligence, studies of the human brain and neurobiology are focusing on the biological mechanisms of neurons and synapses. Herein, a memory system employing a nanoporous double-layer structure for simulation of synaptic functions is described. The sponge-like double-layer porous (SLDLP) oxide stack of Pt/porous LiCoO2/porous SiO2/Si is designed as presynaptic and postsynaptic membranes. This bionic structure exhibits high ON–OFF ratios up to 108 during the stability test, and data can be maintained for 105 s despite a small read voltage of 0.5 V. Typical synaptic functions, such as nonlinear transmission characteristics, spike-timing-dependent plasticity, and learning-experience behaviors, are achieved simultaneously with this device. Based on the hydrodynamic transport mechanism of water molecules in porous sponges and the principle of water storage, the synaptic behavior of the device is discussed. The SLDLP oxide memristor is very promising due to its excellent synaptic performance and potential in neuromorphic computing.
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