Opposite angiogenic outcome of curcumin against ischemia and Lewis lung cancer models: in silico, in vitro and in vivo studies

AbstractThe aim of this study was to investigate the angiogenic effects of curcumin on an ischemia and lung cancer model. To induce ischemia combined with lung cancer models, unilateral femoral arteries of C57BL/6 mice were disconnected on one side of the mouse and Lewis lung carcinoma (LLC) cells were xenografted on the opposite side. Angiogenic effects and underlying mechanisms associated with curcumin were investigated. Molecular target(s), signaling cascades and binding affinities were detected by Western blot, two-dimensional gel electrophoresis (2-DE), computer simulations and surface plasmon resonance (SPR) techniques. Curcumin promoted post-ischemic blood recirculation and suppressed lung cancer progression in inbred C57BL/6 mice via regulation of the HIF1α/mTOR/VEGF/VEGFR cascade oppositely. Inflammatory stimulation induced by neutrophil elastase (NE) promoted angiogenesis in lung cancer tissues, but these changes were reversed by curcumin through directly reducing NE secretion and stimulating α1-antitrypsin (α1-AT) and insulin receptor substrate-1 (IRS-1) production. Meanwhile, curcumin dose-dependently influenced endothelial cells (EC) tube formation and chicken embryo chorioallantoic membrane (CAM) neovascularization. Curcumin had opposite effects on blood vessel regeneration under physiological and pathological angiogenesis, which was effected through negative or positive regulation of the HIF1α/mTOR/VEGF/VEGFR cascade. Curcumin had the promise as a new treatment modality for both ischemic conditions and lung cancer simultaneously in the clinic

Notch Signaling Mediates TNF-α-Induced IL-6 Production in Cultured Fibroblast-Like Synoviocytes from Rheumatoid Arthritis

It has been reported that Notch family proteins are expressed in synovium tissue and involved in the proliferation of synoviocyte from rheumatoid arthritis (RA). The aim of this paper was to investigate whether Notch signaling mediated TNF-α-induced cytokine production of cultured fibroblast-like synoviocytes (FLSs) from RA. Exposure of RA FLSs to TNF-α (10 ng/ml) led to increase of Hes-1, a target gene of Notch signaling, and a marked upregulation of Notch 2, Delta-like 1, and Delta-like 3 mRNA levels. Blockage of Notch signaling by a γ-secretase inhibitor (DAPT) inhibited IL-6 secretion of RA FLSs in response to TNF-α while treatment with recombinant fusion protein of Notch ligand Delta-like 1 promoted such response. TNF-α stimulation also induced IL-6 secretion in OA FLSs; however, the Hes-1 level remained unaffected. Our data confirm the functional involvement of Notch pathway in the pathophysiology of RA FLSs which may provide a new target for RA therapy

Monitoring Enzyme Reaction and Screening of Inhibitors of Acetylcholinesterase by Quantitative Matrix-Assisted Laser Desorption/Ionization Fourier Transform Mass Spectrometry

A matrix-assisted laser desorption/ionization Fourier transform mass spectrometry (MALDI-FTMS)–based assay was developed for kinetic measurements and inhibitor screening of acetylcholinesterase. Here, FTMS coupled to MALDI was applied to quantitative analysis of choline using the ratio of choline/acetylcholine without the use of additional internal standard, which simplified the experiment. The Michaelis constant (Km) of acetylcholinesterase (AChE) was determined to be 73.9 μmol L−1 by this approach. For Huperzine A, the linear mixed inhibition of AChE reflected the presence of competitive and noncompetitive components. The half maximal inhibitory concentration (IC50) value of galantamine obtained for AChE was 2.39 μmol L−1. Inhibitory potentials of Rhizoma Coptidis extracts were identified with the present method. In light of the results the referred extracts as a whole showed inhibitory action against AChE. The use of high-resolution FTMS largely eliminated the interference with the determination of ACh and Ch, produced by the low-mass compounds of chemical libraries for inhibitor screening. The excellent correlation with the reported kinetic parameters confirms that the MS-based assay is both accurate and precise for determining kinetic constants and for identifying enzyme inhibitors. The obvious advantages were demonstrated for quantitative analysis and also high-throughput characterization. This study offers a perspective into the utility of MALDI-FTMS as an alternate quantitative tool for inhibitor screening of AChE

Socially Beneficial Metaverse: Framework, Technologies, Applications, and Challenges

In recent years, the maturation of emerging technologies such as Virtual Reality, Digital twins, and Blockchain has accelerated the realization of the metaverse. As a virtual world independent of the real world, the metaverse will provide users with a variety of virtual activities that bring great convenience to society. In addition, the metaverse can facilitate digital twins, which offers transformative possibilities for the industry. Thus, the metaverse has attracted the attention of the industry, and a huge amount of capital is about to be invested. However, the development of the metaverse is still in its infancy and little research has been undertaken so far. We describe the development of the metaverse. Next, we introduce the architecture of the socially beneficial metaverse (SB-Metaverse) and we focus on the technologies that support the operation of SB-Metaverse. In addition, we also present the applications of SB-Metaverse. Finally, we discuss several challenges faced by SB-Metaverse which must be addressed in the future.Comment: 28 pages, 6 figures, 3 table

N2O emission reduction in the biological nitrogen removal process for wastewater with low C/N ratios: mechanisms and strategies

Urban wastewater, as the main influent type of Waste Water Treatment Plants (WWTPs), has the characteristic of low carbon to nitrogen ratio (C/N). In the biological nitrogen removal (BNR) process, insufficient carbon source often affects the nitrogen removal efficiency and leads to more N2O emissions. We review recent researches on N2O emissions in the BNR process of wastewater with low C/N. The availability of carbon sources affects heterotrophic denitrification (HD) and autotrophic nitrification/denitrification processes, which are the main reasons for N2O emissions in BNR. For the sustainable development of BNR in WWTPs, we introduce strategies suitable for reducing N2O emissions in the BNR process of low C/N wastewater from two aspects: traditional process innovation and new process development. These strategies mainly include carbon source addition, adjustment of aeration strategy, optimization of oxidation ditch and biofilm facilities, and application of Anammox related processes. In the future, it is still necessary to further deepen this research direction through the normalization of N2O emission quantification standards, exploration of N2O metabolism mechanisms, assessment of environmental effects of emission reduction strategies, and practical application of new processes