Sevoflurane induces ho-1-mrna expression by regulating P13K/Akt/P70S6K signaling pathway and affects neuronal apoptosis

Purpose: To determine the effect of sevoflurane (SE) on neuronal apoptosis, and the mechanism involved.Methods: Sixty healthy male Sprague-Dawley rats were assigned to control, model and SE groups. Sham surgery was performed in control group, while middle cerebral artery infarction (MCAO) was established in model group. The expression of HO-1 mRNA was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Apoptosis, autophagy and protein content of P13K/Akt/P70S6K signaling pathway were assessed by Western blot assay.Results: Apoptosis was significantly lower in SE rats, relative to model rats. There were markedly higher protein levels of LC3 II / I, beclin-1, bad, Bcl-2 and caspase-3 in model and SE groups than in control rats (p < 0.05). The HO-1 mRNA was significantly up-regulated in model and SE groups, relative to controls, but it was significantly up-regulated in SE group, relative to model rats (p < 0.05). The expression levels of phosphorylated proteins of the P13K/Akt /P70S6K signal-related proteins in model and SE groups were significantly up-regulated, relative to control, but elevated in SE mice, when compared to model mice (p < 0.05).Conclusion: SE improves the behavior of MCAO rats, reduces cerebral infarction, and inhibits apoptosis and autophagy of nerve cells by regulating autophagy and apoptosis-related proteins through a mechanism that may be related to the induction of HO-1-mRNA expression by regulating P13K/Akt /P70S6K signal pathway. This provides new insights for the development of anti-neuronal apoptosis drugs

Prenatal infection promotes olanzapine-induced obesity in rats: implications for antipsychotic-induced obesity in schizophrenia

Abstract of a poster presentation

Differential responses to genotoxic agents between induced pluripotent stem cells and tumor cell lines

Given potential values of induced pluripotent stem (iPS) cells in basic biomedical research and regenerative medicine, it is important to understand how these cells regulate their genome stability in response to environmental toxins and carcinogens. The present study characterized the effect of Cr(VI), a well-known genotoxic agent and environmental carcinogen, on major molecular components of DNA damage response pathways in human iPS cells. We compared the effect of Cr(VI) on human iPS cells with two established cell lines, Tera-1 (teratoma origin) and BEAS-2B (lung epithelial origin). We also studied the effect of hydrogen peroxide and doxorubicin on modulating DNA damage responses in these cell types. We demonstrated that ATM and p53 phosphorylation is differentially regulated in human iPS cells compared with Tera-1 and BEAS-2B cells after exposure to various genotoxic agents. Moreover, we observed that inhibition of CK2, but not p38, promotes phosphorylation of p53(S392) in iPS cells. Combined, our data reveal some unique features of DNA damage responses in human iPS cells

Survey and alignment of the synchrotron SIS18

Mesenteric fat belongs to visceral fat. An increased deposition of mesenteric fat contributes to obesity associated complications such as type 2 diabetes and cardiovascular diseases. We have investigated the therapeutic effects of bardoxolone methyl (BARD) on mesenteric adipose tissue of mice fed a high-fat diet (HFD). Male C57BL/6J mice were administered oral BARD during HFD feeding (HFD/BARD), only fed a high-fat diet (HFD), or fed low-fat diet (LFD) for 21 weeks. Histology and immunohistochemistry were used to analyse mesenteric morphology and macrophages, while Western blot was used to assess the expression of inflammatory, oxidative stress, and energy expenditure proteins. Supplementation of drinking water with BARD prevented mesenteric fat deposition, as determined by a reduction in large adipocytes. BARD prevented inflammation as there were fewer inflammatory macrophages and reduced proinflammatory cytokines (interleukin-1 beta and tumour necrosis factor alpha). BARD reduced the activation of extracellular signal-regulated kinase (ERK) and Akt, suggesting an antioxidative stress effect. BARD upregulates energy expenditure proteins, judged by the increased activity of tyrosine hydroxylase (TH) and AMP-activated protein kinase (AMPK) and increased peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and uncoupling protein 2 (UCP2) proteins. Overall, BARD induces preventive effect in HFD mice through regulation of mesenteric adipose tissue

Regulatory Mechanisms of Strigolactones on the Development of Lateral Branches in Cucumber

Cucumber (Cucumis sativus L.) belongs to the cucumber genus of the Cucurbitaceae family, and the selection of cultivars with minimal or no lateral branches can enhance the cultivation management efficiency. The growth of lateral branches is inhibited by strigolactone. To investigate the regulatory mechanism of strigolactone on the lateral branch development in cucumber, the cultivar LZ1 exhibiting multiple lateral branches was selected as the experimental material. The axillae of the plants were infiltrated with 1, 5, and 10 μmol·L−1 germination releaser 24 (GR24) at the four- to five-leaf stage. It was identified that 1 μmol·L−1 GR24 exhibited the most potent inhibitory effect on cucumber lateral branches. Additionally, exogenous strigolactone decreased the auxin content in the apical bud and axillae and increased the auxin content in the stem. This inhibited polar auxin transport in the axillary bud and promoted polar auxin transport in the apical bud. The content of strigolactone in the axilla region of cucumbers was elevated, whereas the synthesis and expression of cytokinin in the same area were reduced. A low concentration of GR24 induced the expression of cucumber branched 1 (csbrc1), whereas a high concentration of GR24 downregulated the expression of cucumber lateral suppressor (cscls) and blind (csblind), which inhibited the growth of cucumber lateral branches

Bardoxolone methyl prevents the development and progression of cardiac and renal pathophysiologies in mice fed a high-fat diet

Obesity caused by the consumption of a high-fat (HF) diet is a major risk factor for the development of associated complications, such as heart and kidney failure. A semi-synthetic triterpenoid, bardoxolone methyl (BM) was administrated to mice fed a HF diet for 21 weeks to determine if it would prevent the development of obesity-associated cardiac and renal pathophysiologies. Twelve week old male C57BL/6J mice were fed a lab chow (LC), HF (40% fat), or a HF diet supplemented with 10 mg/kg/day BM in drinking water. After 21 weeks, the left ventricles of hearts and cortex of kidneys of mice were collected for analysis. Histological analysis revealed that BM prevented HF diet-induced development of structural changes in the heart and kidneys. BM prevented HF diet-induced decreases in myocyte number in cardiac tissue, although this treatment also elevated cardiac endothelin signalling molecules. In the kidneys, BM administration prevented HF diet-induced renal corpuscle hypertrophy and attenuated endothelin signalling. Furthermore, in both the hearts and kidneys of mice fed a HF diet, BM administration prevented HF diet-induced increases in fat accumulation, macrophage infiltration and tumour necrosis factor alpha (TNFα) gene expression. These findings suggest that BM prevents HF diet-induced developments of cardiac and renal pathophysiologies in mice fed a chronic HF diet by preventing inflammation. Moreover, these results suggest that BM has the potential as a therapeutic for preventing obesity-induced cardiac and renal pathophysiologies

Bardoxolone methyl: a potential therapeutic for the prevention of anti-psychotic drug-induced obesity?

Abstract of a presentation