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Multi-drug resistance leads to the failure of chemotherapy for cancers. Our previous study showed that overexpression of CA916798 led to multi-drug resistance. However, the underlying mechanisms remain unknown. In the current study, we observed that the levels of phosphorylated AKT, phosphorylated mTOR and CA916798 all increased in the drug resistant human adenocarcinoma samples and paralleled with the change of drug resistance. The results of immunofluorescence and Co-IP indicated that the positive correlation of CA916798 expression with AKT1 activation might be associated with drug resistance of lung adenocarcinoma. Furthermore, AKT1 stimulated CA916798 expression through mTOR pathway in both A549 and A549/CDDP cell lines, which was also observed in the xenografted tumor in nude mice. The results showed that CA916798 located in the downstream of PI3K/AKT/mTOR pathway. Inhibition of PI3K by LY294002 could efficiently reduce CA916798 expression and tumor size in vivo as well. Additionally, LY294002 combined with rapamycin inhibited CA916798 expression and tumor size stronger than LY294002 alone. Our findings may also provide a new explanation for synergistic anti-tumor effects of PI3K and mTORC1 inhibitors. [ABSTRACT FROM AUTHOR]

The plant architecture of higher plants is regulated through environmental and genetic factors, as well as phytohormones. Phytohormones play a critical role in regulating shoot branching. We determined the branching phenotype of D16 and N99-6, the content of strigolactones, the genetic expression level, and the interaction between auxin and strigolactones. We found that the branching development of the two soybean varieties under shading was significantly slower than that under normal light. The average branch length of N99-6 decreased by 40.9% after shading; however, the branch length of D16 was not significantly affected. Meanwhile, the branch formation rate in D16 was significantly higher than in N99-6. In addition, after shading treatment, the content of strigolactones in D16 and N99-6 axillary buds increased significantly, and the expression of phytochrome genes, PhyA and PhyB, showed opposite changes. However, strigolactone synthesis gene GmMAX4 and signal transduction gene GmMAX2 expression levels of D16 were lower than those of N99-6 after 24 h of shading. In addition, the application of strigolactone inhibitor TIS108 and auxin inhibitor NPA to soybean had no significant effect on the branch phenotype. The expression of the GmMAX2 gene was significantly up-regulated after the external application of the auxin analog, and the expression of auxin transporter gene GmPINI was significantly down-regulated after external application of the strigolactone analog under shade. In this study, we investigated the adverse effect of shade on soybean branching development, which may be due to the interaction of strigolactones with auxins. [ABSTRACT FROM AUTHOR]

Background: In our previous study, we indicated that scutellarin (SCU) induced an anticancer effect in A549 cells. However, whether SCU regulates the radiosensitivity of non‐small cell lung cancer (NSCLC) and its related mechanism is still unclear. Methods: In this study, we explored the anticancer effect induced by iodine‐125 (125I) and SCU at a sensitizing concentration in A549 and H1975 cells. Cellular apoptosis and proliferation were detected by flow cytometry, Bcl‐2/Bax expression level, cell cycle, CCK‐8, and EdU staining. A tumor model using nude mice was also carried out to investigate the combined effect of 125I and SCU in vivo. In addition, the expression level of AKT/mTOR pathway was detected to investigate whether it is linked to the anticancer effect of 125I and SCU. Results: SCU at a sensitizing concentration promoted the 125I‐induced apoptosis and antiproliferative effect in A549 and H1975 cells. Moreover, the same results were obtained in vivo. Based on our findings, the AKT/mTOR pathway was significantly downregulated after combined treatment with 125I and SCU. Conclusions: The results of our study suggested that SCU promotes the anticancer effects induced by 125I in NSCLC cells by downregulating the AKT/mTOR pathway and lays a foundation for future application of this combined treatment. [ABSTRACT FROM AUTHOR]

Objective. Coronary heart disease (CHD) has been regarded as a serious and common disease in the modern society. This study aims to investigate the effect of Granule of BU-XIN RUAN-MAI (BXRM) on angina pectoris of coronary heart disease and to explore the molecular mechanisms underlying Granule of BU-XIN RUAN-MAI-mediated protective activity against this disease. Methods. The effects of Granule of BU-XIN RUAN-MAI on clinical symptoms of patients' angina were indicated by hemorheology indicators including high shear of blood viscosity, low shear of blood viscosity, plasma viscosity, erythrocyte rigidity index, D-D dimer, fibrinogen content, and lipid content. The effects of Granule of BU-XIN RUAN-MAI on isoprenaline-induced myocardial cell injury were determined by conducting H&E staining and by performing ELISA to examine the serum content of MDA, SOD, Na+/K+-ATPase, cAMP, and the content of inflammatory factors in isoprenaline-induced rats. Meanwhile, western blot and real time PCR were used to determine the expression of genes involved in oxidation and energy metabolism, and real time PCR was also used for determination of miR-542-3p expression. Luciferase reporter assay was conducted to test the binding sites of miR-542-3p on GABARAP 3′UTR. The chemical compositions of Granule of BU-XIN RUAN-MAI were determined by liquid LC-QTOF-MS. Results. Granule of BU-XIN RUAN-MAI significantly attenuated the clinical symptoms of patients' angina by improving the patients' heart rate and by decreasing the level of hemorheology indicators and also by reducing the serum content of TC, TG, LDL, and elevated HDL content. H&E staining demonstrated that Granule of BU-XIN RUAN-MAI ameliorated the myocardial ischemia in a dose-dependent manner. Besides, Granule of BU-XIN RUAN-MAI downregulated serum MDA content and upregulated the content of SOD, Na+/K+-ATPase, and cAMP in isoprenaline-induced rats. Granule of BU-XIN RUAN-MAI significantly improved oxidation stress by increasing PPARα expression, and it inhibited inflammation by downregulating expression and contents of IL-6, IL-1β, and TNF-α. Then, Granule of BU-XIN RUAN-MAI-containing serum increased the SOD content, and reduced the MDA content in angiotensin II-stimulated HUVEC cells. The granule of BU-XIN RUAN-MAI-containing serum obviously downregulated protein expressions of P40phox, P47phox, and P67phox in plasma membrane, and it significantly increased protein levels of P40phox, P47phox, and P67phox in the cytoplasm of HUVEC cells. Furthermore, GABARAP was reduced in heart tissues of ISO-induced rats and in angiotensin II-stimulated cell lines, and GABARAP was required for the inhibitory activity of Granule of BU-XIN RUAN-MAI on oxidation and inflammation in vivo and in vivo. GABARAP could be upregulated by Granule of BU-XIN RUAN-MAI by inhibiting the expression of miR-542-3p, which may significantly enhance oxidation and inflammation by targeting GABARAP in cardiomyocytes. Moreover, the silencing of GABARAP could obviously reverse the granule of BU-XIN RUAN-MAI-mediated protective activity against coronary heart disease, and interfering GABARAP expression also could partly block the anti-miR-542-3p-controlled oxidation and inflammation in cardiomyocytes. Besides, salidroside, loganin, and polydatin were the main compounds of granules of BU-XIN RUAN-MAI. Conclusion. Granule of BU-XIN RUAN-MAI is an excellent prescription for treatment of coronary heart disease by suppressing inflammation and NAPDH-mediated oxidative stress. The miR-542-3p/GABARAP axis is required for Granule of BU-XIN RUAN-MAI, exhibiting its protective activity against the pectoris of coronary heart disease. [ABSTRACT FROM AUTHOR]

Abstract: Porcine circovirus type 2 (PCV2) infection has been suggested as an acquired immunodeficiency disorder. However, the immunopathogenesis of PCV2 infection is still not fully clarified. In the present study, 35 inguinal lymph nodes (LNs) with different levels of PCV2 load obtained from postwaening multisystemic wasting syndrome (PMWS)-affected pigs and 7 from healthy subclinically PCV2-infected pigs were selected. The LNs were subsequently ranked by their PCV2 loads to mimic the progression of PCV2 infection-associated lesion development. The expressions of 96 selected immune genes in these LNs were assessed by the integration of several reverse transcription quantitative real-time polymerase chain reaction experiments. Hierarchical cluster analysis of the gene expression profiles resulted in 5 major clusters (A, B, C, D, and E). Different clusters of immune gene expression profiles were compatible with the divergent functions of various immune cell subpopulations. 61 out of 96 selected genes belonged to cluster C and were mainly involved in the activation of dendritic cells and B and T lymphocytes. The expression levels of these genes were generally up-regulated in the LNs obtained from PMWS-affected pigs with relatively lower PCV2 loads. However, the up-regulated level tended to reduce or turned into down-regulation as the PCV2 load increased. Genes belonging to cluster B, involved in T cell receptor signaling, became silenced as the PCV2 load increased. The expression profiles of macrophage-associated genes were either independent from or positively correlated with the PCV2 load, such as those in clusters A and E and in cluster D, respectively. In addition, the principle component analysis of the expression of the 96 selected genes in the 42 inguinal LNs revealed that 53.10% and 72.29% of the total data variants could be explained by the top-3 and top-7 principle components, respectively, suggesting that the disease development of PCV2 infection may be associated with a few major and some minor factors. In conclusion, assessment of immune gene expression profiles in LNs supports a close interaction between immune activation and suppression during the progression of PMWS development. [Copyright &y& Elsevier]