Search

High fat diet (HFD) is a risk factor for various diseases in humans and animals. Metabolic disease‑induced brain injury is becoming an increasingly popular research topic. Carnosic acid (CA) is a phenolic diterpene synthesized by plants belonging to the Lamiaceae family, which exhibits multiple biological activities. In the present study, a mouse model of HFD‑induced metabolic syndrome was generated. The body weight, liver weight, daily food intake, daily caloric intake, serum TG, serum TC, serum insulin and serum glucose of animals treated with CA were recorded. Additionally, the gene and protein expression levels of inflammatory cytokines, NF‑κB signaling componnts, and caspase‑3 were evaluated in the various CA treatment groups via immunohistochemical analysis, western blotting, reverse transcription‑quantitative PCR. CA treatment significantly decreased HFD‑induced metabolic syndrome by decreasing the serum levels of triglycerides, total cholesterol, insulin and glucose. Furthermore, CA served a protective role against brain injury by inhibiting the inflammatory response. CA significantly decreased the protein expression levels of various pro‑inflammatory cytokines in serum and brain tissues, including interleukin (IL)‑1β, IL‑6 and tumor necrosis factor‑α, regulated by the NF‑κB signaling pathway. In addition, CA was revealed to promote the expression levels of anti‑apoptotic Bcl‑2, and to decrease the expression levels of pro‑apoptotic Bax and matrix metallopeptidase 9. The present results suggested that CA was able to alleviate brain injury by modulating the inflammatory response and the apoptotic pathway. Administration of CA may represent a novel therapeutic strategy to treat metabolic disease‑induced brain injury in the future.

Objective. Oral squamous cell carcinoma (OSCC) represents the most common maxillofacial malignancy. This study elucidated the clinicopathological value and molecular mechanisms of PSMA3 antisense RNA 1 (PSMA3-AS1) in OSCC. Methods. Totally, 135 OSCC patients were recruited. PSMA3-AS1 expression and its prognostic value were assessed in this cohort. si-PSMA3-AS1 was transfected into HN4 and CAL-27 OSCC cells. Then, cell proliferation was evaluated by CCK-8, colony formation, and EdU staining. Migration and invasion were investigated through wound healing, transwell, and western blot. The PSMA3-AS1/miR-136-5p and miR-136-5p/FN1 interactions were validated by dual luciferase report, real-time quantitative polymerase chain reaction (RT-qPCR), and western blot. Results. PSMA3-AS1 upregulation was determined in OSCC tissues. The upregulation indicated pessimistic patients’ outcomes. Multivariate Cox regression analyses confirmed PSMA3-AS1 as an independent prognostic indicator. Its upregulation was also found in OSCC cells. Under transfection with si-PSMA3-AS1, proliferation, migration, and invasion were all restrained in HN4 and CAL-27 OSCC cells. Furthermore, its knockdown induced the increase in E-cadherin expression and the reduction in N-cadherin and Vimentin expression. PSMA3-AS1 was a sponge of miR-136-5p. Mutual inhibition was found between two and the interactions were confirmed by dual luciferase report. It was confirmed that FN1 was a target of miR-136-5p. FN1 expression was increased by miR-136-5p inhibitors, which was lessened by si-PSMA3-AS1 cotransfection. Conclusion. Collectively, PSMA3-AS1 as a risk factor facilitated malignant behaviors of OSCC cells, related to the miR-136-5p/FN1 axis. Hence, PSMA3-AS1 as a potential therapeutic target for OSCC deserved further exploration.