Hydrogel Transformed from Nanoparticles for Prevention of Tissue Injury and Treatment of Inflammatory Diseases.

Functional hydrogels responsive to physiological and pathological signals have extensive biomedical applications owing to their multiple advanced attributes. Herein, engineering of functional hydrogels is reported via transformable nanoparticles in response to the physiologically and pathologically acidic microenvironment. These nanoparticles are assembled by a multivalent hydrophobic, pH-responsive cyclodextrin host material and a multivalent hydrophilic guest macromolecule. Driven by protons, the pH-responsive host-guest nanoparticles can be transformed into hydrogel, resulting from proton-triggered hydrolysis of the host material, generation of a hydrophilic multivalent host compound, and simultaneously enhanced inclusion interactions between host and guest molecules. By in situ forming a hydrogel barrier, the orally delivered transformable nanoparticles protect mice from ethanol- or drug-induced gastric injury. In addition, this type of nanoparticles can serve as responsive and transformable nanovehicles for therapeutic agents to achieve triggerable and sustained drug delivery, thereby effectively treating typical inflammatory diseases, including periodontitis and arthritis in rats. With combined advantages of nanoparticles and hydrogels, together with their good in vivo safety, the engineered transformable nanoparticles hold great promise in tissue injury protection and site-specific/local delivery of molecular and cellular therapeutic agents.

LncRNA UCC promotes epithelial-mesenchymal transition via the miR-143-3p/SOX5 axis in non-small-cell lung cancer.

Long non-coding RNAs (lncRNAs) have been found to play regulatory roles in cancers; for example, UCC was reported to promote colorectal cancer progression. However, the function of UCC in non-small-cell lung cancer (NSCLC) remains unclear. Therefore, mRNA and protein levels were assessed using qPCR and western blots. Cell viability was assessed by colony-formation assays. The interaction between lncRNAs and miRNAs was detected by dual-luciferase reporter and RIP assays. The tumorigenesis of NSCLC cells in vivo was determined by xenograft assays. LncRNA UCC was highly expressed in both NSCLC tissues and cells. Knockdown of UCC expression suppressed the proliferation of NSCLC cells. In addition, a dual-luciferase reporter system and RIP assays showed that UCC specifically bound to miR-143-3p and acted as a sponge of miR-143-3p in NSCLC cells. The miR-143-3p inhibitor rescued the inhibitory effect of sh-UCC on the proliferation of NSCLC cells. Moreover, miR-143-3p and UCC showed opposite effects on the expression of SOX5, which promoted EMT in NSCLC cells. In addition, in a mouse model, knockdown of UCC expression alleviated EMT and NSCLC progression in vivo, which was consistent with the in vitro results. In the current study, we found that UCC induced the proliferation and migration of NSCLC cells both in vitro and in vivo by inducing the expression of SOX5 via miR-143-3p and subsequently promoted EMT in NSCLC.