PI3K/Akt and ERK1/2 pathways are responsible for sodium butyrateinduced inhibition of neuronal apoptosis in rats with cerebral infarction.

The aim of this study was to elucidate the neuronal protection effect of sodium butyrate (NaB) on neuronal apoptosis in rats with cerebral infarction (CI), and the involvement of the phosphatidilinositol 3-kinase/protein kinase B (PI3K/Akt) and extracellular-signal-regulated kinase 1/2 (ERK1/2) pathways. MI model in rats was performed by middle cerebral artery occlusion (MCAO). Three hours after reperfusion, gastric administration of 5 or 10 mg/kg NaB was performed. Neurological deficit score, infarct size and brain edema were evaluated in rats after 24 h of reperfusion. Enzyme-linked immunosorbent assay (ELISA) was conducted to determine contents of oxidative stress factors. Lactate dehydrogenase (LDH) activity, cell viability and apoptosis in extracted neurons were determined. Moreover, expression levels of Bcl-2, Bax, Akt and ERK1/2 were examined. NaB treatment markedly reduced infarct size and brain edema content in CI rats, and NaB treatment improved viability, decreased LDH activity and reversed contents of malondialdehyde (MDA) and superoxide dismutase (SOD) in a dose-dependent manner. In addition, NaB treatment dose-dependently reduced apoptotic rate and Bax level, as well as enhanced Bcl-2 level. Protein levels of Akt and ERK1/2 were markedly upregulated in NaB-treated neurons. NaB treatment alleviates neuronal apoptosis via the PI3K/Akt and ERK1/2 pathways in CI rats, thus protecting the deterioration of CI.

Effects of homeodomain-interacting protein kinase 2 on renal tubular epithelial cells.

OBJECTIVE: To research the role of homeodomain-interacting protein kinase 2 (HIPK2) on the oxidative stress (OS) and apoptosis induced by hypoxia/reoxygenation (H/R) of normal rat kidney-52E (NRK-52E) cells, through the JAK2/STAT3 signaling pathway MATERIALS AND METHODS: First, we transfected the NRK-52E cells with small interfering RNA (siRNA) of HIPK2 by LipofectamineTM 2000, Real Time-Polymerase Chain Reaction (RT-PCR) and Western blot (WB) were used to test the efficiency of transfection after 48 h. After cells were treated with H/R, we tested cell apoptosis by Cell Counting Kit-8 (CCK-8) assay, flow cytometry, TUNEL staining, PCR, and Western blot. RESULTS: After NRK-52E cells were transfected with siRNA-HIPK2, the protein expression of HIPK2 was remarkably decreased. Cell apoptosis and OS in the H/R group were significantly increased. However, in the HIPK2-siRNA + H/R group, apoptosis and OS were markedly decreased compared with the H/R group. CONCLUSIONS: Inhibition of HIPK2 expression can promote H/R-induced proliferation of NRK-52E cells through the JAK2/STAT3 signaling pathway, relieve the OS response, and reduce apoptosis.

FERMT1 mediates epithelial-mesenchymal transition to promote colon cancer metastasis via modulation of ß-catenin transcriptional activity.

We previously demonstrated that fermitin family member 1 (FERMT1) was significantly overexpressed in colon cancer (CC) and associated with poor metastasis-free survival. This study aimed to investigate the precise role of FERMT1 in CC metastasis and the mechanism by which FERMT1 is involved in the epithelial-mesenchymal transition (EMT). Correlations between FERMT1 and EMT markers (E-cadherin, Slug, N-cadherin and ß-catenin) were examined via immunohistochemistry in a cohort of CC tissues and adjacent normal colon mucosae. A series of in vitro and in vivo assays were performed to elucidate the function of FERMT1 in CC metastasis and underlying mechanisms. The upregulated expression of FERMT1 in CC tissues correlated positively with that of Slug, N-cadherin and ß-catenin, but correlated inversely with E-cadherin expression. Altered FERMT1 expression led to marked changes in the proliferation, migration, invasion and EMT markers of CC cells both in vitro and in vivo. Investigations of underlying mechanisms found that FERMT1 interacted directly with ß-catenin and activated the Wnt/ß-catenin signaling pathway by decreasing the phosphorylation level of ß-catenin, enhancing ß-catenin nuclear translocation and increasing the transcriptional activity of ß-catenin/TCF/LEF. Activation of the Wnt/ß-catenin pathway by CHIR99021 reversed the effect of FERMT1 knockdown, whereas inhibition of the Wnt/ß-catenin pathway by XAV939 impaired the effect of FERMT1 overexpression on EMT and cell motility. In conclusion, findings of this study suggest that FERMT1 activates the ß-catenin transcriptional activity to promote EMT in CC metastasis.

Effects of glutamine-supplemented enteral or parenteral nutrition on apoptosis of intestinal mucosal cells in rats with severe acute pancreatitis.

BACKGROUND: Hhigh mortality of the severe acute pancreatitis (SAP) is caused by the damage of intestinal mucosal barrier. Glutamine (Gln) has been used to protect the intestinal mucosal barrier in the treatments of many severe diseases. AIM: To explore the impact of glutamine on the apoptosis of intestinal mucosa and Bax expression in rats with SAP. MATERIALS AND METHODS: Eighty male SD rats were randomly divided into five groups: sham-operated group, SAP + parenteral nutrition (PN) group, SAP + enteral nutrition (EN) group, SAP + EN + Gln group, and SAP + PN + Gln group. Rats were sacrificed 4 days and 7 days after nutritional support. The intestinal epithelial apoptosis and the expression of Bax were examined by TUNEL assay and immunohistochemical staining, respectively. RESULTS: The apoptotic index (AI) of SAP groups was higher than that of sham-operated group. After 7 days treatment, the AI of SAP + EN + Gln group was significantly lower than that of the SAP + EN or SAP + PN group. In addition, the AI of the SAP groups after 7 days treatment was significantly lower than that of the same groups at 4 days after treatment. Furthermore, the Bax expression of SAP + EN + Gln group was significantly lower than that in the SAP + EN or SAP + PN group. However, no significant differences were observed between SAP + EN + Gln group and SAP + PN + Gln group in AI and Bax expression. CONCLUSIONS: Combination of Gln and parenteral nutrition or enteral nutrition inhibits the apoptosis of intestinal epithelial cells and maintains the integrity of the intestinal mucosal barrier.

[Correlation of changes in serum zinc with serum proteins and alkaline phosphatase in rabbits with burns].

We report herein the correlation of changes in serum zinc with serum proteins, serum alkaline phosphatase (AKP) activity and body weight in 15% TBSA I. burned rabbits. Serum zinc concentration reduced immediately from 181.4 to 112.4 micrograms/dl, then gradually increased and finally approached normal on 15 postburn day. Similar changes were found in serum AKP activity. AKP activity in the burned group was much lower than that in the control group. Total serum protein and albumin contents were significantly reduced and was not recovered to normal levels on 15 postburn day. Serum albumin/globulin decreased but without a turnover. Body weight dropped to a minimum on 9 postburn day and was recovered on 15 postburn day. These results reveal a correlation of serum zinc concentration with serum protein, suggesting that zinc is closely related to protein synthesis. We conclude that serum AKP activity could be used as a diagnostic criterion of postburn hypozincemia as well as an index to assess the effectiveness of supplemental zinc in burns.

Endoscopic diagnosis of gastric cancer: an analysis of 872 cases in China.

Endoscopic examination was performed on 15,888 selected cases between 1974 and 1981 in Hunan Province of China. Eight hundred and seventy-two cases (5.5%) of gastric cancer were suspected endoscopically. Twenty-seven of these 872 cases (3.1% of total gastric cancers) were early gastric cancers. Six hundred and seventy-one of the 872 cases were further investigated, and 661 were proved, giving a 98.5% positive rate. The authors collected a total of 92,190 endoscopic examination cases in China; 7,379 cases (8.0%) were gastric cancer, and 219 of these 7,379 were early cases (3% of all gastric cancer). The results compared with the reports from the United States, Europe, and Japan show that the incidence of gastric cancer and detection of early gastric cancer by endoscopy were much lower in China, the United States, and Europe than in Japan.