Protein kinase C (PKC) plays a role in cardioprotection through reduction of intracellular Ca(2+) concentration Ca(2+)(i) during ischemic preconditioning (IPC). Cardioprotection against ischemic ...post-conditioning (PC) could be associated with reduced Ca(2+)(i) through PKC. The calcium-sensing receptor (CaR), G protein-coupled receptor, causes accumulation of inositol phosphate (IP) to increase the release of intracellular Ca(2+). However, this phenomenon can be negatively regulated by PKC through phosphorylation of Thr-888 of the CaR. This study tested the hypothesis that the prevention of cardiomyocyte damage by PC is associated with Ca(2+)(i) reduction through an interaction of PKC with the CaR. Isolated rat hearts were subjected to 40min of ischemia followed by 90min of reperfusion. The hearts were post-conditioned after the 40min of ischemia by three cycles of 30s of reperfusion and 30s of re-ischemia applied before the 90min of reperfusion. Immunolocalization of PKCepsilon in the cell membrane was observed with IPC and PC, and in hearts exposed to GdCl(3) during PC. CaR was expressed in cardiac cell membrane and interacted with PKC in IPC, PC, and exposure to GdCl(3) during PC groups. On laser confocal microscopy, intracellular Ca(2+) was significantly decreased with IPC, PC, and exposure to GdCl(3) during PC compared with the I/R and PKC inhibitor groups, and cell structure was better preserved and promoted the recovery of cardiac function after reperfusion in the same groups. These results suggested that PKC is involved in cardioprotection against PC through negative feedback of a CaR-mediated reduction in Ca(2+)(i).
To evaluate the effect of the levels of IGF-I in the epididymis and the expression of IGF-I in the testis of adult male rat after the administration of cyclophosphamide.
Ninety-six male adult rats (8 ...weeks age) were divided into 6 groups. The doses given to the rats of the groups 1 to 5 were 10, 20, 40, 80 and 100 mg/(kg x d), respectively. The remaining group was served as control. All those rats were sacrificed and IGF-I were quantitatively determined by ELISA techniques 2 and 4 weeks after the administration of the drug (by gastric fudge). Immunohistochemical SP technique was used to examine expression of IGF-I in rat testis.
The levels of cell factors (IGF-I) in the epididymis of the rats were gradually reduced with the increasing time and dose after administration of the drug. In the mean time the expression of IGF-I in the tissues of the testis of those rats were also gradually reduced.
In the time of oligozoospermia/azoospermia induced by the administration of cyclophosphamide, the expression levels of
EGFR and KRAS mutations are the two most common driver mutations in non-small cell lung cancer (NSCLC). Molecular target-based therapy using small molecules such as gefitinib has been used for ...inhibiting EGFR with good initial responses; however, drug resistance is common when using a mono-targeting strategy. At present, KRAS remains an undruggable target. As such, the development of new drugs targeting the downstream of KRAS and EGFR and their crosstalk pathways is critically needed to effectively treat NSCLC. The present study aimed to elucidate the anticancer effects of PI3K (BKM120) and MEK (PD1056309) inhibitors on NSCLC cell lines with KRAS or EGFR mutations. Inhibition of the EGFR and KRAS downstream P13K pathway using BKM120 significantly inhibited the growth of NSCLC cell lines with either EGFR or KRAS mutations. In addition, significant cell cycle arrest and induction of apoptosis were observed following BKM120 treatment. Notably, although the A549 and H358 NSCLC cell lines harbor the same KRAS mutation, A549 cells were less sensitive than H358 cells in the response to BKM120 treatment. Similarly, PC-9 and H1650 cells harbor the same EGFR mutation, however, H1650 was less sensitive to BKM120. Different sensitivity between NSCLC cell lines with the same oncogenic mutation suggests that multiple crosstalk pathways exit. Combined usage of BKM120 and PD1056309 synergistically enhanced apoptosis in the A549 cells and mildly enhanced apoptosis in the H1650 and H358 cells, suggesting the crosstalk of the MEK pathway with the P13K/Akt pathways in these cell lines. Overall, our findings suggest that inhibition of EGFR and KRAS downstream with a P13K/Akt inhibitor could be useful for treating NSCLC. However, for NSCLC exhibiting crosstalk with other survival pathways, such as the MEK pathway, combination treatment is required.
With consecutive occurrences of drought disasters in China in recent years, it is important to estimate their potential impacts on regional crop production. In this study, we detect the impacts of ...drought on wheat and maize yield and their changes at a 0.5＆#176;＆#215;0.5＆#176; grid scale in the wheat-maize rotation planting area in the North China Plain under the A1B climate change scenario using the Decision Support System for Agrotechnology Transfer （DSSAT） model and the outputs of the regional climate modeling system-Providing Regional Climates for Impacts Studies （PRECIS）. Self-calibrating palmer drought severity index was used as drought recognition indicator. Two time slices used for the study were the baseline （1961-1990） and 40 years of 2011-2050. The results indicate that the potential planting region for double crop system of wheat-maize would expend northward. The statistic conclusions of crop simulations varied considerably between wheat and maize. In disaster-affected seasons, wheat yield would increase in the future compared with baseline yields, whereas in opposite for maize yield. Potential crop yield reductions caused by drought would be lower for wheat and higher for maize, with a similar trend found for the ratio of potential crop yield reductions for both crops. It appears that the negative impact of drought on maize was larger than that on wheat under climate change A1B scenario.
Aenasius bambawalei is one of the most important parasitoids attacking Phenacoccus solenopsis. Studies were conducted to measure and compare its developmental rate, and parasitism using A. bambawalei ...feeding on 4 species of Malvaceae. Maximum parasitism and shortest developmental rate were measured on Hibiscus rosa-sinensis. Implications of our results for rearing this parasitoid are discussed.
Objective Newly identified human rhinovirus C （HRV-C） and human bocavirus （HBoV） cannot propagate in vitro in traditional cell culture models; thus obtaining knowledge about these viruses and ...developing related vaccines are difficult. Therefore, it is necessary to develop a novel platform for the propagation of these types of viruses.Methods A platform for culturing human airway epithelia in a three-dimensional （3D） pattern using Matrigel as scaffold was developed. The features of 3D culture were identified by immunochemical staining and transmission electron microscopy. Nucleic acid levels of HRV-C and HBoV in 3D cells at designated time points were quantitated by real-time polymerase chain reaction {PCR）. Levels of cytokines, whose secretion was induced by the viruses, were measured by ELISA.Results Properties of bronchial-like tissues, such as the expression of biomarkers CK5, ZO-2, and PCK, and the development of cilium-like protuberances indicative of the human respiration tract, were observed in 3D-cultured human airway epithelial （HAE） cultures, but not in monolayer-cultured cells. Nucleic acid levels of HRV-C and HBoV and levels of virus-induced cytokines were also measured using the 3D culture system.Conclusion Our data provide a preliminary indication that the 3D culture model of primary epithelia using a Matrigel scaffold in vitro can be used to propagate HRV-C and HBoV.
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