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.
The optimal post-operative adjuvant treatment for completely resected gastric cancer with D2 lymphadenectomy remains controversial. The present study was a phase II trial on post-operative chemoradiotherapy in 30 patients with gastric cancer. Patients with stage II to IV (M0) gastric cancer received two cycles of chemotherapy prior to and following chemoradiotherapy. The chemotherapy consisted of a 2-h infusion of oxaliplatin (100 mg/m2) and folinic acid (100 mg/m2), which was followed by a 46-h continuous infusion of 5-fluorouracil (5-FU; 2,400 mg/m2) through a portable pump, repeated every 3 weeks. The chemoradiotherapy consisted of 45 Gy of radiotherapy for 5 weeks and 5-FU continuous infusion (350 mg/m2/day). In total, 30 patients were enrolled in this study. All patients underwent the chemoradiotherapy treatment as planned. A total of 10 (33.3%) patients relapsed; two (6.7%) locoregional relapses and mediastinum metastases, four (13.3%) peritoneal relapses, and four (13.3%) distant metastases. The three-year overall survival and disease-free survival rates were 72.7 and 65%, respectively. The toxicities of chemotherapy and radiotherapy, consisting of neutropenia, nausea and hand-foot syndrome, were observed. In conclusion, post-operative chemoradiotherapy following complete resection of gastric cancer with D2 lymphadenectomy is feasible in a significant subset of patients.
The previous studies have demonstrated the excellent neuroprotective effects of xenon. In this study, we verified the anti-seizure and neuroprotective roles of xenon in epileptogenesis and evaluated the involvement of oxidative stress and iron accumulation in the protective roles of xenon. Epileptogenesis was induced by pentylenetetrazole (PTZ) treatment in Sprague-Dawley rats. During epileptogenesis, we found increased levels of iron and oxidative stress accompanied by elevated levels of divalent metal transporter protein 1 and iron regulatory protein 1, which are closely associated with iron accumulation. Meanwhile, the levels of autophagy and mitophagy increased, alongside significant neuronal damage and cognitive deficits. Xenon treatment reversed these effects: oxidative stress and iron stress were reduced, neuronal injury and seizure severity were attenuated, and learning and memory deficits were improved. Thus, our results confirmed the neuroprotective and anti-seizure effects of xenon treatment in PTZ-induced epileptogenesis. The reduction in oxidative and iron stress may be the main mechanisms underlying xenon treatment. Thus, this study provides a potential intervention strategy for epileptogenesis.
Background: Apelin is a recently identified endogenous ligand associated with proliferation and angiogenesis of several cancers. However, only few studies have reported on the functions and the role of apelin in gastric cancer (GC). Therefore, in the present study, we investigated the association and the mechanisms underlying Apelin expression and proliferation of GC cells both in vitro and in vivo.Methods: We enrolled 178 postoperative care GC patients to investigate clinicopathological and immunohistochemical factors associated with Apelin expression. The relationship between Survival of patients and apelin expression was evaluated using Kaplan-Meier method and Cox regression analyses. The expression of apelin mRNA and its proteins in GC tissues and cell lines were analyzed using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), western blot and ELISA. The role and mechanisms underlying regulation of Apelin expression in human GC cells were evaluated through several in vitro and in vivo experiments. Results: Apelin was over expressed in human GC cells, relative to adjacent normal tissues. The over expression of apelin was associated with vessel invasion (P <0.01), lymph node metastasis (P <0.01), late-staged tumor (T) (P <0.05), worse pathological type (P <0.05), nerve invasion (P <0.05). In addition, expression of apelin strongly and positively correlated with that of vascular endothelial growth factor (VEGF). Over-expression of apelin promoted proliferation and invasion of MGC-803 cell via the ERK/Cyclin D1/MMP-9 signaling pathway. Apelin over-expression also promoted angiogenesis of GC cells, accelerating growth of subcutaneous xenograft of the cancer cells in vivo.Conclusions: Over-expression of apelin promotes proliferation and metastasis of GC cells via the ERK/Cyclin D1/MMP-9 signaling pathway and is associated with adverse events of the cancer. Consequently, apelin is a potential therapeutic target for human GC.
Background: Apelin is a recently identified endogenous ligand associated with proliferation and angiogenesis of several cancers. However, only few studies have reported on the functions and the role of apelin in gastric cancer (GC). Therefore, in the present study, we investigated the association and the mechanisms underlying Apelin expression and proliferation of GC cells both in vitro and in vivo.Methods: We enrolled 178 postoperative care GC patients to investigate clinicopathological and immunohistochemical factors associated with Apelin expression. The relationship between Survival of patients and apelin expression was evaluated using Kaplan-Meier method and Cox regression analyses. The expression of apelin mRNA and its proteins in GC tissues and cell lines were analyzed using quantitative real-time reverse transcription-polymerase chain reaction (RT-PCR), western blot and ELISA. The role and mechanisms underlying regulation of Apelin expression in human GC cells were evaluated through several in vitro and in vivo experiments. Results: Apelin was over expressed in human GC cells, relative to adjacent normal tissues. The over expression of apelin was associated with vessel invasion (P <0.01), lymph node metastasis (P <0.01), late-staged tumor (T) (P <0.05), worse pathological type (P <0.05), nerve invasion (P <0.05). In addition, expression of apelin strongly and positively correlated with that of vascular endothelial growth factor (VEGF). Over-expression of apelin promoted proliferation and invasion of MGC-803 cell via the ERK/Cyclin D1/MMP-9 signaling pathway. Apelin over-expression also promoted angiogenesis of GC cells, accelerating growth of subcutaneous xenograft of the cancer cells in vivo.Conclusions: Over-expression of apelin promotes proliferation and metastasis of GC cells via the ERK/Cyclin D1/MMP-9 signaling pathway and is associated with adverse events of the cancer. Consequently, apelin is a potential therapeutic target for human GC.
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