Fig 2: Schematic illustration of the role of uterine epithelial and stromal STAT3 in uterine receptivity and embryo attachment. Epithelial STAT3 regulates the formation of slit-like structure in uterine lumen, and stromal STAT3 suppresses proliferative activity and estrogenic response in the epithelium, thus controlling uterine receptivity and embryo attachment. PGR, progesterone receptor; LIF, leukemia inhibitory factor; LIFR, LIF receptor.

Fig 3: Graphical summary of the miR-93/STAT3 pathway in AOH injury.In AOH eyes, downregulated miR-93 releases the repression of downstream target genes of STAT3. Retinal microglial cells markedly activate and overproduce inflammatory cytokines, ultimately leading to retinal ganglion cell (RGC) death. Supplementation with miR-93 can represses STAT3 by binding to the 3′UTR of STAT3, regulating microglia-mediated neuro-inflammation and protecting RGCs against AOH. Thus, miR-93 may serve as a novel target for neuroprotective therapy in glaucoma.

Fig 4: MiR-93 targeted the STAT3 gene.A Bioinformatics analysis predicted interactions between miR-93 and STAT3. The 3′-UTR of STAT3 contains a conserved binding site for miR-93. B The miR-93-dependent change in luciferase activity was abolished after the introduction of mutations in the STAT3 binding site, indicating that STAT3 gene is a target of miR-93. C As measured by qRT-PCR, miR-93 mimic transfection significantly decreased the STAT3 mRNA level in primary retinal microglial cells. Compared with the NC: *P < 0.05. Compared with the control: ***P < 0.001. Compared with the miR-93 transfection group: #P < 0.05. n = 3 independent cultures. NC negative control, wt wild type, mut mutant type.

Fig 5: (20S)G-Rh2 interacted with Anxa2-Y23D mutant and inhibited related STAT3 activation. Myc-tagged wild-type, Y23A mutant, and Y23D mutant of Anxa2 was over-expressed in HepG2 cells. (A) Cellular thermal shift assay was performed with (20S)G-Rh2 at indicated temperature gradient in Anxa2-over-expressed HepG2 cells, and determined by immuno-blotting. (B) Thermal shift assay was performed with purified Anxa2 mutant and (20S)G-Rh2 gradient at 55 °C, and determined by immuno-blotting. (C–E) HepG2 cells with Anxa2 over-expression were treated with (20S)G-Rh2. Immuno-precipitation with anti-Anxa2 antibody (C) and protein level (D) were determined by immuno-blotting. STAT3 activation was determined via reporter gene assay (E). (F,G) Expression of four VEGFs in (20S)G-Rh2-treated HepG2 cell was determined by qRT-PCR (F) and immuno-blotting (G). Significance analysis was shown as * (p < 0.05), ** (p < 0.01) and *** (p < 0.001).