We investigated the neuroprotective effects of baicalin and the role of gut microbiota in a mouse model of cerebral ischemia-reperfusion injury. Repeated cerebral ischemia-reperfusion significantly increased plasma levels of trimethylamine (TMA), trimethylamine-N-oxide (TMAO), and clusterin (a neuroinflammation biomarker). These changes correlated with cognitive decline; short-term memory deficits; abnormal long term potentiation (LTP); decreased functional connectivity (FC) between various brain regions; reduced plasticity and dendritic spine density in the hippocampus; increased levels of the pro-inflammatory cytokines IL-1β, IL-6, and TNFα; and altered the gut microbial composition. Treatment with 50-100 mg/Kg baicalin for 7 days after cerebral ischemia-reperfusion significantly restored normal plasma levels of TMA, TMAO, and clusterin. Baicalin treatment also suppressed neuroinflammation, remodeled the gut microbial composition back to normal, and improved cognition, memory, LTP, cerebral FC, and hippocampal neuronal plasticity. The neuroprotective effects of baicalin were diminished when mice undergoing repeated cerebral ischemia-reperfusion were pretreated with broad-spectrum antibiotics to deplete gut microbial populations. This suggests the neuroprotective effects of baicalin in cerebral ischemiareperfusion injury are mediated by the gut microbiota. It thus appears that baicalin ameliorates neuropathology in a repeated cerebral ischemia-reperfusion model mice by remodeling the gut microbiota.

Glioblastoma multiforme (GBM) is a lethal brain tumor in adults. Despite advances in treatments, such as surgery, radiotherapy and chemotherapy, high‑grade glioma remains fatal. The molecular and cellular mechanisms for GBM are not entirely clear and further studies are required to elucidate these. MicroRNAs (miRNAs) are small, non‑coding, endogenous RNAs that are involved in cell differentiation and proliferation, and have been suggested to play a role in a variety of types of cancer. In this study, we investigated the role of miR-124 in the inhibition of proliferation of GBM cells. The downregulation of miR-124 in human GBM tumor cell lines was detected using quantitative RT-PCR. To assess the function of miR-124, we constructed stable cell lines, U87-124 and U373-124, which overexpressed miR-124 using lentiviral vectors. Overexpression of miR-124 inhibited the proliferation of GBM cancer cells in vitro. Using integrated bioinformatics analysis, SOS1 was found to be a direct target for miR-124, which is frequently upregulated in gliomas. Dual‑luciferase reporter assays confirmed that the SOS1 mRNA 3'‑untranslated regions (UTR) was directly targeted by miR-124 and that the mutated 3'UTR was not affected. This was revealed to be mechanistically associated with the induction of SOS/Ras/Raf/ERK and the suppression of ERK activity, which was achieved by silencing SOS1. This study therefore indicates an important role for miR-124 in the regulation of growth in the molecular etiology of GBM, and offers a potential strategy for the use of miR-124 in cancer treatment.

The lncRNA ALMS1-IT1 may promote malignant progression of lung adenocarcinoma via AVL9-mediated activation of the cyclin-dependent kinase pathway

Background: S100A9, which is expressed in prostate cancer, has been reported in association with prostate cancer progression. However, the role of S100A9 in prostate cancer metastasis is largely unknown. The aim of this study was to investigate the effect of S100A9 on prostate cancer cell invasion and the involved mechanisms. Materials and methods: Integrin β1 expression in PC-3 and DU-145 cells was determined by quantitative real-time polymerase chain reaction (PCR) (qRT-PCR) and Western blot. Cellular invasion was measured by transwell invasion assay. Western blot was used to determine protein expression. Concentrations of S100A9 and fibronectin were analyzed by enzyme-linked immunosorbent assay. The protein interaction was detected by immunoprecipitation. The NF-κB activity was measured by luciferase reporter assay. The DU-145 cells metastasis in vivo was determined in mice xenograft models after S100A9 overexpression. Results: S100A9 promoted prostate cancer cells invasion, integrin β1 expression and fibronectin secretion. Further investigation evidenced that S100A9 interacted with Toll-like receptor 4 (TLR4) and activated NF-κB, which was responsible for tumor cell invasion, integrin β1 up-regulation and focal adhesion kinase (FAK) phosphorylation. Furthermore, integrin β1 inhibition led to decreased FAK phosphorylation and reduced tumor cell invasion. Overexpression of S100A9 increased xenograft tumor micro-metastases, integrin β1 expression and induced NF-κB and FAK activation in vivo. Conclusion: Our study demonstrated that S100A9 promotes prostate cancer cell invasion, and one of the underlying molecular mechanisms is that S100A9 activates integrin β1/FAK through TLR4/NF-κB signaling leading to metastasis of prostate cancer cell.

The aim of this study was to research the mechanism of circMAN2B2 in the development of glioma. In our study, we found that circMAN2B2 has a higher expression in glioma tissues and cells, which was negatively related to the overall survival of glioma patients. The cell counting kit-8 assay, 5-ethynyl-2′-deoxyuridine labeling assay, transwell assay, and the nude mice assay indicated that knockdown of circMAN2B2 inhibited the cell proliferation, invasion, migration and decreased tumor size. In terms of mechanism, knockdown of circMAN2B2 increased the expression of miR-1205. Moreover, circMAN2B2 regulated S100A8 expression by inhibiting miR-1205. We also showed that knockdown of S100A8 inhibited cell proliferation, invasion, and migration. Increasing S100A8 expression rescued the effect of si-circMAN2B2. In conclusion, circMAN2B2 could improve cell proliferation, invasion, and migration of the glioma by inhibiting miR-1205 and promoting the expression of S100A8. K E Y W O R D ScircMAN2B2, glioma, miR-1205, S100A8