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To obtain insight into potential mechanisms underlying the influence of rootstock on scion growth, we performed a comparative analysis of 'Shatangju' mandarin grafted onto 5 rootstocks: Fragrant orange (Citrus junons Sieb. ex. Tanaka), Red tangerine (Citrus reticulata Blanco), 'Shatangju' mandarin (Citrus reticulata Blanco), Rough lemon (Citrus jambhiri Lush) and Canton lemon (Citrus limonia Osbeck). The tree size of 'Shatangju' mandarin grafted onto Canton lemon and Rough lemon were the largest, followed by self-rooted rootstock trees, and the lowest tree sizes correspond to ones grafted on Red tangerine and Fragrant orange rootstocks. The levels of indoleacetic acid (IAA) and gibberellin (GA) were significantly and positively related to growth vigor. The differences of gene expression in leaves of trees grafted onto Red tangerine, Canton lemon and 'Shatangju' mandarin were analyzed by RNA-Seq. Results showed that more differentially expressed genes involved in oxidoreductase function, hormonal signal transduction and the glycolytic pathway were enriched in 'Red tangerine vs Canton lemon'. qRT-PCR analysis showed that expression levels of ARF1, ARF8, GH3 and IAA4 were negatively correlated with the growth vigor and IAA content. The metabolism of GA was influenced by the differential expression of KO1 and GA2OX1 in grafted trees. In addition, most of antioxidant enzyme genes were up-regulated in leaves of trees grafted onto Red tangerine, resulting in a higher peroxidase activity. We concluded that different rootstocks significantly affected the expression of genes involved in auxin signal transduction pathway and GA biosynthesis pathway in the grafted plants, and then regulated the hormone levels and their signal pathways.

Mitochondrial functions are crucial for pancreatic β-cell survival and glucose-induced insulin secretion. Hexarelin (Hex) is a synthetic small peptide ghrelin analogue, which has been shown to protect cardiomyocytes from the ischemia-reperfusion process. In this study, we used in vitro and in vivo models of streptozotocin (STZ)-induced β-cell damage to study the protective effect of Hex and the associated mechanisms. We found that STZ produced a cytotoxic effect in a dose- and time-dependent manner in MIN6 cells (a mouse β-cell line). Hex (1.0 μM) decreased the STZ-induced damage in β-cells. Rhodamine 123 assay and superoxide DHE production assay revealed that Hex ameliorated STZ-induced mitochondrial damage and excessive superoxide activity in β-cells. In addition, Hex significantly reduced STZ-induced expression of cleaved Caspases-3, Caspases-9 and the ratio of pro-apoptotic protein Bax to anti-apoptotic protein Bcl-2 in MIN6 cells. We further examined the in vivo effect of Hex in a rat model of type 1 diabetes induced by STZ injection. Hex ameliorated STZ-induced decrease in plasma insulin and protected the structure of islets from STZ-induced disruption. Hex also ameliorated STZ-induced expression of cleaved Caspase-9 and the Bax in β-cells. In conclusion, our data indicate that Hex is able to protects β-cell mass from STZ-caused cytotoxic effects involving mitochondrial pathways in vitro and in vivo. Hex may serve as a potential protective agent for the management of diabetes.

Aripiprazole is a wide-used antipsychotic drug with therapeutic effects on both positive and negative symptoms of schizophrenia, and reduced side-effects. Although aripiprazole was developed as a dopamine D2 receptor (D2R) partial agonist, all other D2R partial agonists that aimed to mimic aripiprazole failed to exert therapeutic effects in clinic. The present in vivo study aimed to investigate the effects of aripiprazole on the D2R downstream cAMP-PKA and Akt-GSK3β signalling pathways in comparison with a D2R antagonist – haloperidol and a D2R partial agonist – bifeprunox. Rats were injected once with aripiprazole (0.75mg/kg, i.p.), bifeprunox (0.8mg/kg, i.p.), haloperidol (0.1mg/kg, i.p.) or vehicle. Five brain regions – the prefrontal cortex (PFC), nucleus accumbens (NAc), caudate putamen (CPu), ventral tegmental area (VTA) and substantia nigra (SN) were collected. The protein levels of PKA, Akt and GSK3β were measured by Western Blotting; the cAMP levels were examined by ELISA tests. The results showed that aripiprazole presented similar acute effects on PKA expression to haloperidol, but not bifeprunox, in the CPU and VTA. Additionally, aripiprazole was able to increase the phosphorylation of GSK3β in the PFC, NAc, CPu and SN, respectively, which cannot be achieved by bifeprunox and haloperidol. These results suggested that acute treatment of aripiprazole had differential effects on the cAMP-PKA and Akt-GSK3β signalling pathways from haloperidol and bifeprunox in these brain areas. This study further indicated that, by comparison with bifeprunox, the unique pharmacological profile of aripiprazole may be attributed to the relatively lower intrinsic activity at D2R.