ABSTRACT
The type-1 cannabinoid receptor (CB1R) is a potential therapeutic target in several pathological conditions, including neuropsychological disorders and neurodegenerative diseases. Owing to their structural diversity, it is not easy to derive general structure-activity relationships (SARs) for CB1R ligands. In this study, CB1R ligands were classified into six structural families, and the corresponding SAR was determined for their affinities for CB1R. In addition, we determined their functional activities for the activation of extracellular signal-regulated kinases (ERKs). Among derivatives of indol-3-yl-methanone, the highest ligand affinity was observed when a pentyl and a naphthalenyl group were attached to the N1 position of the indole ring and the carbon site of the methanone moiety, respectively. In the case of adamantane indazole-3-carboxamide derivatives, the presence of fluorine in the pentyl group, the substituent at the N1 position of the indazole ring, strongly increased the affinity for CB1R. For (naphthalen-1-yl) methanone derivatives, the presence of 4-alkoxynaphthalene in the methanone moiety was more beneficial for the affinity to CB1R than that of a heterocyclic ring. The functional activities of the tested compounds, evaluated through ERK assay, were correlated with their affinity for CB1R, suggesting their agonistic nature. In conclusion, this study provides valuable insight for designing novel ligands for CB1R, which can be used to control psychiatric disorders and drug abuse.
ABSTRACT
Adsorption is one of the most common methods of pollution treatment. The selectivity for pollutants and recyclability of adsorbents are crucial to reduce the treatment cost. Layered double hydroxide (LDH) materials are one type of adsorbent with poor recyclability. Prussian blue (PB) is a sturdy and inexpensive metal-organic framework material that can be used as the precursor for synthesizing paramagnetic ferroferric oxide (Fe3O4). It is intriguing to build some reusable adsorbents with magnetic separation by integrating LDH and PB. In this work, paramagnetic Fe3O4-calcined LDH (Fe3O4@cLDH) core-shell adsorbent was designed and prepared by the calcination of PB-ZnAl layered double hydroxide (PB@LDH) core-shell precursor, which exhibits high anionic dyes selectivity in wastewater solutions. The paramagnetism and adsorption capability of Fe3O4@cLDH come from the Fe3O4 core and calcined ZnAl-LDH shell, respectively. Fe3O4@cLDH shows an adsorption capacity of 230 mg g-1 for acid orange and a high selectivity for anionic dyes in cation-anion mixed dye solutions. The regeneration process indicates that the high selectivity for anions is related to the specific hydration recovery process of ZnAl-LDH. The synergistic effect of the paramagnetic Fe3O4 core and calcined ZnAl-LDH shell makes Fe3O4@cLDH an excellent magnetic separation adsorbent with high selectivity to anions.
ABSTRACT
BACKGROUND: LncRNAs play an important role in tumor initiation and development. However, the underlying involvement of lncRNA expression in colorectal carcinoma remains to be clarified. METHODS: All analyses were performed in R software v4.0, SPSS v13.0, and GraphPad Prism 8. The "limma" package was used to identify differentially expressed lncRNAs between two groups with the threshold of |logFC| >1 and P <0.05. The "Survival" package was used to conduct survival analysis. HCT8 and SE480 cell lines were used to conduct further phenotype experiments, including transwell, wound-healing, CCK8 and colony formation assay. Gene set enrichment analysis was used to explore the biological pathway difference in high and low IGFL2-AS1 patients. RESULTS: The lncRNA IGFL2-AS1 was highly expressed in colon adenocarcinoma (COAD) tissue and cell lines (HCT116, HCT8, HCT129, and SW480). The COAD patients with high IGFL2-AS1 were associated with a worse prognosis. Meanwhile, the knockdown of IGFL2-AS1 could significantly suppress the proliferation and invasion of COAD cells. Gene set enrichment analysis showed that the top five biological pathways involving IGFL2-AS1 were angiogenesis, epithelial-mesenchymal transition, KRAS signaling, myogenesis, and coagulation. Western blot results showed that the inhibition of IGFL2-AS1 could significantly reduce the N-cadherin, HIF1A and KRAS protein expression, yet increase the E-cadherin protein level. IGFL2-AS1 was also positively correlated with M0 macrophages, M2 macrophages, and neutrophils but negatively correlated with CD4+ memory T cells and CD8+ T cells. CONCLUSION: IGFL1-AS1 could seriously worsen patient outcomes and facilitate COAD progression, thus serving as an independent tumor marker.
