Graphical AbstractOur study confirmed significant anti-oxidative stress and neuroprotective effects of exogenous irisin in KA-induced SE. Moreover, the BDNF/UCP2 pathway may contribute to the mechanism underlying the neuroprotective effects of irisin.

Background: With the development of radiological technologies, radiotherapy has been gradually widely used in the clinic to intracranial tumours and become standardised. However, the related central nervous system disorders are still the most obvious complications after radiotherapy. This study aims to quantify the effectiveness of anlotinib, a small molecule inhibitor of multiple receptor tyrosine kinases, in mitigating acute phase of radiation-induced brain injury (RBI) in a mouse model. Methods:The onset and progression of RBI were investigated in vivo. All mice, (except for the sham group) were irradiated at a single-fraction of 20 Gy and treated with different doses of anlotinib (0, 0.2 and 0.8 mg/kg, respectively). The expression levels of glial fibrillary acidic protein (GFAP), hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and phosphorylated vascular endothelial growth factor receptor-2 (p-VEGFR2) were assessed by western blot. Histological changes were identified by luxol fast blue (LFB) staining. Results:The expression levels of GFAP, HIF-1α, and VEGF were downregulated following treatment with anlotinib. However, anlotinib failed to inhibit the development of demyelination. Cerebral edema [as measured by brain water content (BWC)] was also mitigated following treatment with anlotinib.Conclusions: In summary, treatment with anlotinib significantly mitigated the adverse effects of acute RBI in a dose-dependent manner by downregulating the activation of astrocytes, improving brain hypoxia, and alleviating cerebral edema.

Background: Apelin is an emerging endogenous ligand, which is involved in proliferation and angiogenesis in certain cancers. However, few studies have reported its functions and underlying mechanisms in human gastric cancer (GC). Therefore, the present study aimed to investigate the effect of Apelin expression in human GC and the underlying mechanisms of Apelin in the promotion of proliferation both in vitro and in vivo.Methods: A total of 178 patients diagnosed with GC under postoperative care were enrolled for the study to investigate clinicopathological and immunohistochemical factors of Apelin expression. Survival of patients was analyzed using the Kaplan-Meier method and Cox regression model. We adopted quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), western blot and ELISA to analyze human GC specimens and cell lines. The role and mechanisms of Apelin were evaluated by performing in vitro and in vivo experiments to analyze exogenous Apelin and its overexpression in human GC cells. Results: The expression of Apelin was higher in human gastric cancer cells than in adjacent normal tissues. Apelin, which was overexpressed in vessel invasion (P <0.01), lymph node metastasis (P <0.01), late-staged tumor (T) status (P <0.05), pathological type (P <0.05) and nerve invasion (P <0.05), also exhibited a positive correlation with vascular endothelial growth factor (VEGF). Apelin overexpression or exogenous Apelin activated downstream of ERK/Cyclin D1/MMP-9 signaling pathway to promote MGC-803 cell proliferation and invasion in vitro. Apelin overexpression promoted angiogenesis aiming at accelerating growth of subcutaneous xenograft in vivo.Conclusions: This study has elucidated the relationship between Apelin and its clinicopathological features in human GC, and the role of Apelin in tumor cell proliferation in human GC cell lines. This is the first study to elucidate underlying mechanisms of Apelin in the proliferation of GC. Apelin can be a potential therapeutic target for human GC.