ABSTRACT
BACKGROUND/AIMS: Epigallocatechin-3-gallate (EGCG) has neuroprotective effects and the ability to resist amyloidosis. This study observed the protective effect of EGCG against neuronal injury in rat models of middle cerebral artery occlusion (MCAO) and investigated the mechanism of action of PI3K/AKT/eNOS signaling pathway. METHODS: Rat models of permanent MCAO were established using the suture method. Rat behavior was measured using neurological deficit score. Pathology and apoptosis were measured using HE staining and TUNEL. Oxidative stress and brain injury markers were examined using ELISA. Apoptosis-related proteins and PI3K/AKT/eNOS signaling pathway were determined using western blot assay and immunohistochemistry. RESULTS: EGCG decreased neurological function score, protected nerve cells, inhibited neuronal apoptosis, and inhibited oxidative stress injury and brain injury markers level after MCAO. EGCG reduced the apoptotic rate of neurons, increased the expression of Bcl-2, and decreased the expression of Caspase-3 and Bax. After LY294002 suppressed the PI3K pathway, the protective effect of EGCG decreased after administration of PI3K inhibitors. CONCLUSION: EGCG has a protective effect on rat brain injury induced by MCAO, possibly by modulating the PI3K/AKT/eNOS signaling pathway.
Subject(s)
Apoptosis/drug effects , Catechin/analogs & derivatives , Infarction, Middle Cerebral Artery/drug therapy , Nitric Oxide Synthase Type III/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction/drug effects , Animals , Brain Ischemia/drug therapy , Brain Ischemia/metabolism , Catechin/pharmacology , Chromones/pharmacology , Infarction, Middle Cerebral Artery/metabolism , Male , Morpholines/pharmacology , Neuroprotective Agents/pharmacology , Rats , Rats, Sprague-Dawley , Reperfusion Injury/drug therapy , Reperfusion Injury/metabolismABSTRACT
Epidemiological studies in recent years have found that the incidence of gastric signet ring cell carcinoma (SRCC) has increased significantly. In this paper, we first reviewed cell origin and biomarkers of SRCC, and the relationship between SRCC and various pathological types of gastric cancer. The early diagnosis rate of gastric SRCC is low, which may be due to the unclear mechanism of pathology and precancerous lesions. In clinical practice, SRCC has the characteristics of low differentiation and high degree of malignancy. Most of patients with gastric cancer Borrmann IV(diffuse infiltrative type) are gastric SRCC, and their prognosis is poor. The average age of gastric SRCC was 55 to 61 years old. Besides, in female, the incidence of SRCC was significantly higher than that of non-SRCC gastric cancer. It is found that the expressions of estrogen and progesterone receptors in SRCC tissues are high. The relationship between gastric SRCC and sex hormones may be the cause of gender differences in the pathogenesis of gastric SRCC. Due to the low risk of lymph node metastasis in early SRCC, endoscopic mucosal resection and endoscopic submucosal dissection can be performed for <3 cm, submucosal invasive, medium differentiated tumors, or <3 cm, highly differentiated, ulcerative and submucosal lesions. For non-metastatic advanced gastric SRCC, surgical resection and adequate lymph node dissection should be performed owing to the high risk of lymph node metastasis. Adjuvant chemotherapy is also considered to improve the long-term prognosis of patients. Taxane therapy may be more effective in gastric SRCC. Recent data show that gastric SRCC and diffuse gastric cancer are more sensitive to mitomycin C, doxorubicin and docetaxel than intestinal type gastric cancer, but are not sensitive to fluorouracil and cisplatin. These treatment perspectives still need to be confirmed in future studies.
