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To investigate the effects of the combination of all-trans retinoic acidand tofacitinib on human fibroblast-like synoviocytes from rheumatoid arthritis and explorethe mechanisms of autophagy and apoptosis in the NF-κB signalingpathway.
Cells were adaptively cultured and stimulated with TNF-α and IL-1β.Subsequently, HFLS-RA cells were intervened with ATRA, tofacitinib, and their combination.Cell proliferation rate, migration ability, inflammatory cytokine concentrations, and apoptosis levels were detected. Different concentrations of ATRA, autophagy inhibitor (3-MA), andtheir combination were also used to intervene, and relevant protein expressions were detected by Western Blotting.
The combined use of ATRA and tofacitinib inhibited the proliferation and migration of HFLS-RA cells, upregulated IL-6 and IL-10 levels, downregulated IL-17 and VEGF levels, and promoted early apoptosis. Different concentrations ofATRA downregulated Bcl-2, upregulated IκBα, and affected the expression of XIAP, P65, and IKKα/β. The combination of autophagy inhibitor 3-MA and ATRA further upregulated IκBα, downregulated Bcl-2, IKKα/β, and P65.
ATRA may inhibit the activationof the NF-κB pathway by suppressing cell proliferation and migration, downregulating IL-6levels, and inducing apoptosis.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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