Recent Advances on Small-Molecule Antagonists Targeting TLR7.

Toll-like receptor 7 (TLR7) is a class of pattern recognition receptors (PRRs) recognizing the pathogen-associated elements and damage and as such is a major player in the innate immune system. TLR7 triggers the release of pro-inflammatory cytokines or type-I interferons (IFN), which is essential for immunoregulation. Increasing reports also highlight that the abnormal activation of endosomal TLR7 is implicated in various immune-related diseases, carcinogenesis as well as the proliferation of human immunodeficiency virus (HIV). Hence, the design and development of potent and selective TLR7 antagonists based on small molecules or oligonucleotides may offer new tools for the prevention and management of such diseases. In this review, we offer an updated overview of the main structural features and therapeutic potential of small-molecule antagonists of TLR7. Various heterocyclic scaffolds targeting TLR7 binding sites are presented: pyrazoloquinoxaline, quinazoline, purine, imidazopyridine, pyridone, benzanilide, pyrazolopyrimidine/pyridine, benzoxazole, indazole, indole, and quinoline. Additionally, their structure-activity relationships (SAR) studies associated with biological activities and protein binding modes are introduced.

[MiR-218 inhibits HTR-8 cells migration and invasion by targeting SOX4].

OBJECTIVE: To verify whether miR-218 could inhibit human trophoblastic cell (HTR-8 cells) migration and invasion by target-ing sex determining region Y-box 4(SOX4). METHODS: The serum samples were collected from 46 hypertensive disorder complicating pregnan-cy (HDCP) and 50 normal pregnant women. RT-PCR was used to test the expression of miR-218 in the serum. In vitro, MiR-218 was trans-fe cted into HTR-8 cells. The HTR-8 cells were divided into three groups:normal control group, mimic control and miR-218 mimic group. The migratory and invasion ability of HTR-8 cells was tested, and the expressions of matrix metalloproteinase-2(MMP-2), MMP-9 and Sox4 were also investigated in the cells of each group. Luciferase assay was used to confirme whether Sox4-3'-UTR was the target gene of miR-218. RESULTS: The expression of miR-218 was decreased in the serum of HDCP patients compared with the normal pregnant woman(P < 0.01). In vit-ro, compared with the control group, the invasion and migration ability of HTR-8 cells and the expression of MMP-2 MMP-9 and SOX4 were decreased in the miR-218 group (P < 0.01); The Luciferase activity of the SOX4-3'-UTR plasmid was significantly suppressed by miR-218 (P < 0.01); Over expression of SOX4 could reverse the effect of miR-218 on HTR-8 cells(P < 0.01). CONCLUSIONS: The expression of miR-218 decreases in the serum of HDPC patients and miR-218 inhibits HTR-8 cells invasion by targeting SOX4-3'-UTR.