Folate deficiency promotes cervical squamous carcinoma SiHa cells progression by targeting miR-375/FZD4/ß-catenin signaling.

Epidemiological studies suggest an association between folate deficiency (FD) and cervical squamous cell carcinoma (SCC) progression. However, the underlying mechanism is unclear. Our study showed that FD-driven downregulation of miR-375 promoted proliferation of SCC SiHa cells and progression of xenograft tumors developed from SiHa; however, the exact mechanism of this process remained unclear. The current study aimed to elucidate the underlying mechanisms by which FD promotes the progression of SiHa cells by downregulating miR-375 expression. The results showed that miR-375 acted as a suppressor of SCC and inhibited the proliferation, migration, and invasion of SiHa cells. The FZD4 gene was identified as a target gene of miR-375, which can reverse the anti-onco effect of miR-375 and promote the proliferation and migration of SiHa cells. Furthermore, the regulatory effects of miR-375 and FZD4 on SiHa cells may be achieved by activating the ß-catenin signaling pathway. Moreover, FD may regulate the expression of miR-375 by regulating its DNA methylation level in the promoter region. In conclusion, our study reveals that FD regulates the miR-375/FZD4 axis by increasing the methylation of the miR-375 promoter, thereby activating ß-catenin signaling to promote SiHa cells progression. This study may provide new insights into the role of folic acid in the prevention and treatment of SCC.

Oral treatment with glycyrrhizin inhibits NLRP3 inflammasome activation and promotes microglial M2 polarization after traumatic spinal cord injury.

The inflammatory response induced by traumatic spinal cord injury (SCI) involves the activation of NLRP3 inflammasomes, which are closely related to the activation of microglia. Microglial polarization between M1/M2 phenotypes is a pivotal regulatory factor in neuroinflammatory responses to traumatic SCI-induced secondary injuries, and altering this polarization could be beneficial. Glycyrrhizin is a neuroprotective agent with a potent anti-inflammatory property in different neurological disorders and could potentially be useful in SCI. In this study, we investigated the potency of oral treatment with glycyrrhizin to reduce inflammation and improve functional recovery after traumatic SCI by inhibiting NLRP3 inflammasome activation and promoting microglial M2 polarization. After inducing traumatic SCI by dropping a 10 g impactor on the T9 and T10 spinal segments of male Sprague-Dawley rats, the animals were given glycyrrhizin orally immediately after injury and every 12 h for the next 3 d. Behavioral scores improved in glycyrrhizin-treated animals compared to the SCI group. The functional improvement in glycyrrhizin-treated rats paralleled the decreased expression of NLRP3 inflammasome components, such as ASC, NLRP3, and cleaved caspase-1, as well as IL-1ß and IL-18. At the histopathological level, oral treatment with glycyrrhizin diminished the SCI-enhanced production of Iba-1+CD86+ cells (M1 microglia) but improved the release of Iba-1+CD206+ cells (M2 microglia). Likewise, oral therapy with glycyrrhizin significantly enriched the protein expression levels of M2 microglia-related markers (CD206 and Arg-1) but reduced those of M1 microglia-related markers (CD86 and iNOS) in the injured spinal cord. These findings support and extend the knowledge on post-traumatic SCI glycyrrhizin-mediated neuroprotection. Glycyrrhizin's regulation of NLRP3 inflammasome activation and microglial polarization might be a new approach to understanding the anti-inflammatory potency of glycyrrhizin.