ABSTRACT
An unprecedented fluoroarylation of 1,1-difluoroallenes with a cost-effective nucleophilic fluoride reagent and aryldiazonium salts is reported. This visible light promoted gold-catalyzed reaction allows a stereo- and regioselective incorporation of both the fluorine atom and aryl group, enabling a straightforward construction of multi-substituted trifluoromethyl alkenes. Under the mild reaction conditions, a nice tolerance of diverse functional groups is achieved. The high regioselectivity for fluorine-incorporation is rationalized by considering the thermodynamic driving force of trifluoromethyl group formation, whereas the counterintuitive stereoselectivity that aryl is installed on the side of the bulkier γ-substituent is interpreted by alleviating the increasing 1,3-allylic interaction in the gold-coordinated allene intermediate en route to the product.
ABSTRACT
In this study, we constructed a tumor necrosis factor α (TNF-α)-induced synovial cell inflammatory model using human synoviocytes (HS) cell line to explore the function of miR-98 in rheumatoid arthritis (RA). miR-98 mimics or miR-98 inhibitor were transfected into HS cells to up-regulate or down-regulate the expression of miR-98. The proliferation and apoptosis of HS cells were determined using CCK8 assay and flow cytometry, respectively. TargetScan website was utilized to predict the targets of miR-98. Luciferase assay was carried out to verify that IL-10 is a target of miR-98. Western blot was performed to analyze the expression of IL-10, apoptosis-related and NF-κB signaling pathway-related proteins. Our results demonstrated that the expression of miR-98 was up-regulated in HS cells stimulated by TNF-α. Down-regulation of miR-98 by inhibitor in TNF-α-stimulated HS cells dramatically inhibited cell proliferation and promoted cell apoptosis compared with the miR-98 inhibitor NC group. The protein expression of Bcl-2 was declined while the levels of Bax and Bim were increased by miR-98 inhibitor in TNF-α-stimulated HS cells. IL-10 was predicted and verified as a target of miR-98. qRT-PCR and western blot results revealed that the level of IL-10 was negatively regulated by miR-98. Finally, we identified that down-regulation of miR-98 reduced the expression level of p-p65 and p-IκBα in TNF-α-stimulated HS cells. In summary, our present study demonstrated that down-regulation of miR-98 inhibited the proliferation and promoted the apoptosis of TNF-α-stimulated HS partly by targeting IL-10 and regulating NF-κB signaling pathway, insinuating miR-98 as a candidate biomarker in RA.
