PHARMACOLOGICAL RESEARCH
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2022
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IF 10.334
Yuhang Li,Yitian Li,Sennan Xu,Yue Chen,Pan Zhou,Ting Hu,Hua Li,Ying Liu,Yaping Xu,Jie Ren,Yan Qiu,Canzhong Lu
Psoriasis is an incurable autoimmune disease that affects 2–3% of the world’s population. Limited understanding of its pathogenesis hinders the development of therapies for the disease. Herein, we reported that N-acylethanolamine acid amidase (NAAA), a cysteine enzyme that catalyzes the hydrolysis of fatty acid ethanolamides (FAEs), was upregulated in psoriasis patients and imiquimod (IMQ)-induced mouse model of psoriasis. The upregulated NAAA contributes to the progression of psoriasis via enhancing dendritic cell (DCs) maturation. Transgenic expression of NAAA in mice accelerated the development of psoriasis, whereas genetic ablation of NAAA or local administration of NAAA inhibitor F96 ameliorated psoriasis. NAAA expressed in dendritic cells (DCs), but not in macrophages, T cells, or keratinocytes plays a critical role in psoriasis development. In addition, the results showed that NAAA degrades palmitoylethanolamide (PEA) and reduces PEA-PPARα-mediated dissociation of NF-κB p65 from Sirtuin 1 (SIRT1), subsequently, repressing the acetylation of p65 and down-regulating IL10 production. The decreased IL10 then leads to the maturation of DCs, thus promoting the development of psoriasis. These results provide new insights into the pathophysiological mechanism of psoriasis and identify NAAA as a novel target for the treatment of psoriasis.
研究领域:
免疫学
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皮肤病学
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药理学
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DOI
PubMed
高影响因子
Scientific Reports
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2019
·Vol. 9
·期 1
·1-11
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IF 4.011
Hu Chunhui,Zhao Shuxue,Li Kuiran,Yu Hao
A novel Alcaligenes sp. strain P156, which can utilize nicotinamide as its sole source of carbon, nitrogen and energy, was enriched and isolated from soil in a solid waste treatment plant. Aerobic growth and degradation with nicotinamide were characterized. Seven nicotinamide degradation-related genes were obtained by sequence alignment from the genome sequence of strain P156. Four genes, designated naaA , naaD , naaE and naaF , were cloned and heterologously expressed. Nicotinamide degradation is initiated by deamination to form nicotinic acid catalyzed by the nicotinamidase NaaA, which shares highest amino acid sequence identity (27.2%) with nicotinamidase from Arabidopsis thaliana . Nicotinic acid is converted to 6-hydroxynicotinic acid, which is further oxidized to 2,5-dihydroxypyridine (2,5-DHP). 2,5-DHP is then transformed to a ring-cleavage product, N -formylmaleamic acid, by an Fe 2+ dependent dioxygenase NaaD. N -formylmaleamic acid is transformed to fumaric acid through maleamic acid and maleic acid by NaaE and NaaF, respectively. To our knowledge, this is the first report of the complete microbial degradation of nicotinamide in bacteria. Nicotinamide is considered as a model compound for the study of microbial degradation of pyridinic compounds, and the nicotinamide degrading related genes in strain P156 were distributed differently from the reported similar gene clusters. Therefore, this study contribute to the knowledge on the degradation of pyridinic compounds.
研究领域:
微生物学
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环境科学
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基因组学
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DOI
PubMed
高影响因子
MINERALS ENGINEERING
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2019
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IF 3.315
Wenjie Zou,Lu Gong,Jun Huang,Mingfei Pan,Zhenzhen Lu,Chunbao Sun,Hongbo Zeng
Selective flocculation is an efficient separation method for processing fine coal. In this work, one type of hydrophobically modified polyacrylamide, poly(AM-NaAA-C 16 DMAAC) (HMPAM), was synthesized and used as flocculants of coal. The adsorption and interaction of HMPAM on model coal surface under the influence of KCl concentration were compared with a commercial polyacrylamide (PAM) using quartz crystal microbalance with dissipation monitoring (QCM-D), multi-angle laser light scattering (MALLS) and atomic force microscope (AFM). The QCM-D results showed that the adsorption amounts of both PAM and HMPAM on model coal surface increased with increasing KCl concentration, and the amount of HMPAM was much higher than that of PAM in 100 mM KCl solution. This result could be due to the fact that the high salinity (e.g., 100 mM KCl) led to the compressed conformation of the polymers and significantly compressed electric double layer repulsion. The conformational changes were determined using MALLS. The AFM force measurement results showed that the adhesion between the polymers and model coal surface increased with increasing the KCl concentrations due to the compressed electric double layer, and the average adhesion of PAM was about one order of magnitude smaller than that of HMPAM. Such difference was mainly ascribed to the hydrophobic attraction between the hydrophobic chain of HMPAM and model coal surface. Meanwhile, the attractive hydrophobic interaction between the hydrophobic chains induced the formation of multiple layers of HMPAM, which was in consistence with the QCM-D results. The fundamental insights into the interaction mechanisms of HMPAM/PAM on model coal surface will benefit the rational development of effective polymer additives for fine coal preparation.
研究领域:
矿物加工工程
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界面化学
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高分子化学
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DOI
高影响因子
MINERALS ENGINEERING
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2019
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IF 3.315
Wenjie Zou,Lu Gong,Jun Huang,Zhijun Zhang,Chunbao Sun,Hongbo Zeng
Selective flocculation separation has been widely used in fine coal flocculation. In order to promote the adsorption selectivity of flocculants onto coal surface, hydrophobically modified polyacrylamide P(AM-NaAA-C 16 DMAAC) was synthesized. The adsorption of P(AM-NaAA-C 16 DMAAC) on model clay and coal surfaces (i.e., silica, alumina and asphaltene surfaces) was investigated using quartz crystal microbalance with dissipation (QCM-D) monitoring technique. Floc size distribution, Fourier transform infrared spectrum, zeta potential measurement and selective flocculation flotation test were also conducted to study the performance of P(AM-NaAA-C 16 DMAAC) in the separation of fine coal. QCM-D measurements showed that a thin and rigid adsorption layer was formed on silica and alumina surfaces after injecting 1 mM sodium hexapolyphosphate (Calgon). This pre-formed layer inhibited the further adsorption of P(AM-NaAA-C 16 DMAAC) on silica and alumina. Meanwhile, the asphaltene surface could not be passivated by calgon due to the weak and reversible adsorption. Thus, a significant amount of P(AM-NaAA-C 16 DMAAC) (20 mg/L) absorbed on the calgon-treated asphaltene surface in 100 mM KCl solution was detected. With 20 mg/L P(AM-NaAA-C 16 DMAAC) in 100 mM KCl and 1 mM calgon solution, the maximum diameters of 10%, 50% and 90% of the cumulative volume distributions of the floc, i.e., d 10 (20.29 μm), d 50 (45.55 μm) and d 90 (89.99 μm) of the coal floc were 7.42, 3.20 and 2.19 times of those of kaolinite floc, respectively. Clean coal with a combustible recovery of 80.87% and ash content of 9.78% was obtained at a dosage of 5 g/t of P(AM-NaAA-C 16 DMAAC) and 900 g/t kerosene. Experimental results demonstrated that selective flocculation flotation with P(AM-NaAA-C 16 DMAAC) could enhance the recovery of fine coal particles with a lower dosage of collector. Our work sheds lights on the fundamental and practical understanding of the hydrophobic interactions in the selective flocculation of coal in the industries, and rational development of flocculants with better selectivity and flocculation efficiency.
研究领域:
化学工程
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材料科学
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矿物加工工程
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DOI
高影响因子
JOURNAL OF ETHNOPHARMACOLOGY
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2023
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IF 5.4
Wei Jia,Xiwen He,Wenhui Jin,Jinping Gu,Siyu Yu,Jianlin He,Zhiwei Yi,Bing Cai,Huiyuan Gao,Longhe Yang
Ethnopharmacological relevance Ramulus Cinnamomi , the dried twig of Cinnamomum cassia (L.) J.Presl., is a traditional Chinese medicine (TCM) with anti-inflammatory effects. The medicinal functions of Ramulus Cinnamomi essential oil (RCEO) have been confirmed, although the potential mechanisms by which RCEO exerts its anti-inflammatory effects have not been fully elucidated. Aim of the study To investigate whether N -acylethanolamine acid amidase (NAAA) mediates the anti-inflammatory effects of RCEO. Materials and methods RCEO was extracted by steam distillation of Ramulus Cinnamomi , and NAAA activity was detected using HEK293 cells overexpressing NAAA. N -Palmitoylethanolamide (PEA) and N -oleoylethanolamide (OEA), both of which are NAAA endogenous substrates, were detected by liquid chromatography with tandem mass spectrometry (HPLC-MS/MS). The anti-inflammatory effects of RCEO were analyzed in lipopolysaccharide (LPS)-stimulated RAW264.7 cells, and the cell viability was measured with a Cell Counting Kit-8 (CCK-8) kit. The nitric oxide (NO) in the cell supernatant was measured using the Griess method. The level of tumor necrosis factor-α (TNF-α) in the RAW264.7 cell supernatant was determined using an enzyme-linked immunosorbent assay (ELISA) kit. The chemical composition of RCEO was assessed by gas chromatography-mass spectroscopy (GC-MS). The molecular docking study for (E)- cinnamaldehyde and NAAA was performed by using Discovery Studio 2019 software (DS2019). Results We established a cell model for evaluating NAAA activity, and we found that RCEO inhibited the NAAA activity with an IC 50 of 5.64 ± 0.62 μg/mL. RCEO significantly elevated PEA and OEA levels in NAAA-overexpressing HEK293 cells, suggesting that RCEO might prevent the degradation of cellular PEA and OEA by inhibiting the NAAA activity in NAAA-overexpressing HEK293 cells. In addition, RCEO also decreased NO and TNF-α cytokines in lipopolysaccharide (LPS)-stimulated macrophages. Interestingly, the GC-MS assay revealed that more than 93 components were identified in RCEO, of which (E)- cinnamaldehyde accounted for 64.88%. Further experiments showed that (E)- cinnamaldehyde and O -methoxycinnamaldehyde inhibited NAAA activity with an IC 50 of 3.21 ± 0.03 and 9.62 ± 0.30 μg/mL, respectively, which may represent key components of RCEO that inhibit NAAA activity. Meanwhile, docking assays revealed that (E)- cinnamaldehyde occupies the catalytic cavity of NAAA and engages in a hydrogen bond interaction with the TRP181 and hydrophobic-related interactions with LEU152 of human NAAA. Conclusions RCEO showed anti-inflammatory effects by inhibiting NAAA activity and elevating cellular PEA and OEA levels in NAAA-overexpressing HEK293 cells. (E) -cinnamaldehyde and O- methoxycinnamaldehyde, two components in RCEO, were identified as the main contributors of the anti-inflammatory effects of RCEO by modulating cellular PEA levels through NAAA inhibition.
研究领域:
药理学
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免疫学
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细胞生物学
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生物化学
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中医
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DOI
PubMed
高影响因子
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