miR-29c-3p Increases Cell Viability and Suppresses Apoptosis by Regulating the TNFAIP1/NF-κB Signaling Pathway via TNFAIP1 in Aß-Treated Neuroblastoma Cells.

Alzheimer's disease (AD) is the most common cause of dementia among older people in worldwide. miR-29c-3p was reported to play a role in AD development. However, the detail function of miR-29c-3p in AD remains unclear. The aim of this research is to analyze the functional mechanism of miR-29c-3p in AD. The RNA levels of miR-29c-3p and Tumor necrosis factor-α-inducible protein-1 (TNFAIP1) were detected by Quantitative real time polymerase chain (qRT-PCR) reaction. Western blot assay was carried out to examine the protein levels of TNFAIP1, Bax, B-cell lymphoma-2 (Bcl-2), Cleaved caspase 3, and Nuclear factor-k-gene binding (NF-κB). The interaction between miR-29c-3p and TNFAIP1 was predicted by online tool TargrtScan and verified using the dual luciferase reporter assay and RNA immunoprecipitation RIP (RIP) assay. Besides, cell proliferation and apoptosis rate were determined by 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2-H-tetrazolium bromide (MTT) assay and flow cytometry analysis, respectively. Aß treatment decreased miR-29c-3p expression and increased TNFAIP1 expression. Overexpression of miR-29c-3p mitigated the effects of Aß on proliferation and apoptosis. Similarly, knockdown of TNFAIP1 also reversed the effects of Aß on cell progression. Interestingly, miR-29c-3p suppressed the expression of TNFAIP1 via binding to 3'UTR of TNFAIP1 mRNA. As expected, overexpression of TNFAIP1 reversed the effects of miR-29c-3p on Aß-mediated cell progression. Besides, we also confirmed that miR-29c-3p affected Aß-mediated cell progression by regulating TNFAIP1/NF-κB signaling pathway. In conclusion, our findings confirmed that miR-29c-3p attenuated Aß-induced neurotoxicity through regulation of NF-κB signaling pathway by directly targeting TNFAIP1, providing the potential value for the treatment of AD patients.

[Effects of total paeony glucosides on mRNA expressions of Toll receptors and interleukin-33 in the brain tissue of D-galactose induced aging rats: an experimental research].

OBJECTIVE: To investigate effects of total paeony glucosides (TPGs) on the expressions of Toll receptors (TLR4) and interleukin-33 (IL-33) in the brain tissue of D-galactose-induced aging rats. METHODS; Fifty SD rats were randomly divided into 5 groups, i.e., the blank control group, the model group, the high dose TPG group, the middle dose TPG group, and the low dose TPG group, 10 in each group. Equal volume of normal saline was subcutaneously injected to rats in the blank control group, while 10% D-galactose was subcutaneously injected to rats in the rest groups at 0.125 mL/g, once a day for 8 successive weeks to induce the aging rat model. TPG was administered at 300 mg/kg, 150 mg/kg, and 75 mg/kg to rats in the high, middle, and low dose TPG groups while injecting D-galactose from the 5th week of model preparation, once daily for 4 successive weeks. Equal volume of normal saline was administered to rats in the blank control group and the model group, once daily. The capability for learning and memory was detected using Morris water. The mRNA expressions of TLR4 and IL-33 in the brain tissue were detected using ELISA. RESULTS: Compared with the blank control group, the capability for learning and memory decreased in the model group with statistical difference (P < 0.05). Compared with the model group, the capability for learning and memory was obviously improved in all the medicated groups in a dose-dependent manner, showing statistical difference (P < 0.05). Compared with the blank control group, mRNA expressions of TLR4 and IL-33 in the brain tissue obviously increased after medication in the model group, showing statistical difference (P < 0.05). Compared with the model group, mRNA expressions of TLR4 and IL-33 in the brain tissue obviously decreased after medication in all the medicated groups in a dose-dependent manner, showing statistical difference (P < 0.05). CONCLUSION: TPGs improved D-galactose induced aging rats' capability for learning and memory through regulating changes of TLR4 and IL-33 expressions.