NLRC3 is a member of the pattern recognition receptors nucleotide-binding oligomerization domain (NOD)-like receptors (NLRs) family, and plays a pivotal regulatory role in modulating the activation of immune cells. In macrophages, NLRC3 inhibits the activation of the NF-κB signaling pathway, the STING/TBK1 signaling pathway, and the formation of the inflammasome. In the context of T cells immune response, NLRC3 prevents the activation of T cells by regulating the function of dendritic cells and directly influencing the function of T cells. Different from other pattern recognition receptors, NLRC3 is more closely associated with regulatory activity than pathogens recognition, it influences the fates of cells, for example, prevents proliferation, promotes apoptosis and inhibits pyroptosis. These cellular functions regulated by NLRC3 are involved in the development processes of a variety of diseases, such as infectious disease, sterile inflammatory diseases, and cancer. However, its characteristics, function and regulatory mechanism in immune response and immune-related diseases have not been addressed fully. In this review, we elaborate the potential roles of NLRC3 from several different levels, include molecular mechanism, cellular functions in the immune-related diseases.
Woody peony (Paeonia × suffruticosa Andr.) has many cultivars with genetic variances. The flower essential oil is valued in cosmetics and fragrances. This study was to investigate the chemical diversity of essential oils of eleven representative cultivars and their potential target network. Hydro-distillation afforded yields of 0.11–0.25%. Essential oils were analyzed by GC-MS and GC-FID which identified 105 compounds. Three clusters emerged from multivariate analysis, representative of phloroglucinol trimethyl ether (‘Caihui’), citronellol (‘Jingyu’, ‘Zhaofen’ and ‘Baiyuan Zhenghui’) and mixed (the rest of the cultivars) chemotypes. ‘Zhaofen’ and ‘Jingyu’ also exhibited low levels of other rose-related compounds. The main components were subjected to a target network approach. Drug-likeness screening gave 20 compounds with predictive blood–brain barrier permeation. Compound target network identified six key compounds, namely nerol, citronellol, geraniol, geranic acid, cis-3-hexen-1-ol and 1-hexanol. Top enriched terms in GO, KEGG and DisGeNET were mostly related to the central nervous system (CNS). Protein—protein interactions revealed a core network of 14 targets, 11 of which were CNS-related (targets for antidepressants, analgesics, antipsychotics, anti-Alzheimer’s and anti-Parkinson’s agents). This work provides useful information on the production of woody peony essential oils with specific chemotypes and reveals their potential importance in aromatherapy for alternative treatment of CNS disorders.
This study aimed to explore clinical significance of interleukin-1 receptor-associated kinase 1 (IRAK1) in the diagnosis, prognosis, and targeted therapy of hepatocellular carcinoma. A systematic analysis based on the cancer genome atlas (TCGA) indicated that IRAK1 was highly expressed in 18 cancer types (p < 0.01) and may be a pan-cancer biomarker. In hepatocellular carcinoma, the alteration rate of IRAK1 was rather high (62.4%), in which mRNA high relative to normal predominated (58.9%). Higher expression was associated with shorter overall survival (p < 0.01). IRAK1 expression correlated positively with pathology stage and tumor grade (for the latter there was only a slight trend). Interestingly, it correlated positively with TP53 mutation (p < 0.001), suggesting a possible strategy for targeting TP53 via IRAK1. Immunohistochemistry experiments confirmed a higher positive rate of IRAK1 in carcinoma than in para-carcinoma tissues (χ2 = 18.006, p < 0.001). Higher tumor grade correlated with more strongly positive staining. Molecular docking revealed cryptotanshinone, matrine, and harmine as the best hit compounds with inhibition potential for IRAK1. Our findings suggest that IRAK1 may play biologically predictive roles in hepatocellular carcinoma. The suppression of IRAK1/NF-κB signaling via inhibition of IRAK1 by the hit compounds can be a potential strategy for the targeted therapy.
Hydrosol volatiles from flowers of ten Paeonia × suffruticosa Andr. cultivars were analyzed by gas chromatography-mass spectrometry (GC-MS) and GC-flame ionization detector (GC-FID) for the first time. Fifty components were identified representing 97.6 -99.8% of total composition, in which oxygenated compounds (87.4 -99.8%) predominated. Hydrosol volatiles of five and two cultivars presented chemotypes of 2-phenylethanol (48.0 -79.5%) and 1,3,5-trimethoxybenzene (72.8%, 50.2%), respectively. Hydrosol volatiles of 'XYTH' rich in β-citronellol (57.2%) probably represented a newly defined chemotype with β-citronellol percentage over 50%. 'GFCC' hydrosol volatiles presented a balanced profile with 1,3,5-trimethoxybenzene (31.9%), β-citronellol (31.5%) and 2-phenylethanol (23.0%). 'LHZL' hydrosol volatiles were distinct from others due to occurrence of 6,9-heptadecadiene (2.0%), 2-heptanol (1.8%), pentadecane (1.5%), (Z)-3-nonen-1-ol (1.1%) and geraniol (15.7%). Chemotype characterization of P. × suffruticosa Andr. hydrosols was of significance considering numerous cultivars of the species and potential applications of the hydrosols.
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