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Brassinolide (BL) alleviates salt injury in cotton seedlings; however, little is known about the molecular mechanisms of this response. In this study, digital gene expression analysis was performed to better understand the regulatory pathways of BL in NaCl-stressed cotton (Gossypium hirsutum L.). Compared with control plants (CK), a total of 1 162 and 7 659 differentially expressed genes (DEGs) were detected in the leaves and roots of NaCl-treated plants, respectively. Most of the DEGs in NaCl-treated plants, compared to CK, were regulated by BL. Moreover, expression patterns of DEGs in BL+NaCl treated plants were similar to those in CK plants; however, the responses of DEGs in the leaves and roots of NaCl-treated plants to BL differed. In the roots, BL-regulated DEGs were involved in protein biosynthesis, whereas in the leaves, BL promoted photosynthesis in NaCl-stressed cotton. BL treatment also significantly increased the overall biomass, chlorophyll a + b content in leaves, and the protein content in roots in NaCl-stressed cotton. The downregulation of stress-responsive genes in BL+NaCl-stressed leaves was also found. These results suggest that BL can alleviate NaCl injury in cotton plants. 相似文献
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Lin Xiao Can Chen Zhendong Li Sumin Zhu Johan Ck Tay Xi Zhang Shijun Zha Jieming Zeng Wee Kiat Tan Xin Liu Wee Joo Chng Shu Wang 《Cytotherapy》2018,20(3):420-435
Vγ9Vδ2 T cells are a minor subset of lymphocytes in the peripheral blood that has been extensively investigated for their tolerability, safety and anticancer efficacy. A hindrance to the broad application of these cells for adoptive cellular immunotherapy has been attaining clinically appropriate numbers of Vγ9Vδ2 T cells. Furthermore, Vγ9Vδ2 T cells exist at low frequencies among cancer patients. We, therefore, sought to conceive an economical method that allows for a quick and robust large-scale expansion of Vγ9Vδ2 T cells. A two-step protocol was developed, in which peripheral blood mononuclear cells (PBMCs) from healthy donors or cancer patients were activated with Zometa and interleukin (IL)-2, followed by co-culturing with gamma-irradiated, CD64-, CD86- and CD137L-expressing K562 artificial antigen-presenting cells (aAPCs) in the presence of the anti-CD3 antibody OKT3. We optimized the co-culture ratio of K562 aAPCs to immune cells, and migrated this method to a G-Rex cell growth platform to derive clinically relevant cell numbers in a Good Manufacturing Practice (GMP)-compliant manner. We further include a depletion step to selectively remove αβ T lymphocytes. The method exhibited high expansion folds and a specific enrichment of Vγ9Vδ2 T cells. Expanded Vγ9Vδ2 T cells displayed an effector memory phenotype with a concomitant down-regulated expression of inhibitory immune checkpoint receptors. Finally, we ascertained the cytotoxic activity of these expanded cells by using nonmodified and chimeric antigen receptor (CAR)–engrafted Vγ9Vδ2 T cells against a panel of solid tumor cells. Overall, we report an efficient approach to generate highly functional Vγ9Vδ2 T cells in massive numbers suitable for clinical application in an allogeneic setting. 相似文献
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Shu Jia Baoman Li Jingyang Huang Alexei Verkhratsky Liang Peng 《Neurochemical research》2018,43(8):1692-1701
Here we present the data indicating that chronic treatment with three antibipolar drugs, lithium, carbamazepine and valproic acid regulates Cav-1/PTEN/PI3K/AKT/GSK-3β signalling pathway and glycogen content in primary cultured astrocytes. All three drugs down-regulate gene expression of Caveoline 1 (Cav-1), decrease membrane content of phosphatase and tensin homolog (PTEN), increase activity of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and serine-threonine kinase (AKT), and elevate glycogen synthase kinase 3β (GSK-3β) phosphorylation thus suppressing its activity. As expected, treatment with any of these three drugs increases glycogen content in astrocytes. Our findings indicate that regulation of glycogen content via Cav-1/PTEN/AKT/GSK-3β pathway by the three anti-bipoar drugs may be responsible for therapeutic effects of these drugs, and Cav-1 is an important signal element that may contribute to pathogenesis of various CNS diseases and regulation of its gene expression may be one of the underlying mechanisms of drug action for antibipolar drugs and antidepressants currently in clinical use. 相似文献
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Tai‐Wen Lin Chi‐Chih Chen Shu‐Mei Wu Yu‐Ching Chang Yi‐Chuan Li Yu‐Wang Su Chwan‐Deng Hsiao Hsin‐Yang Chang 《The Plant journal : for cell and molecular biology》2019,99(1):128-143
In mammals and yeast, tail‐anchored (TA) membrane proteins destined for the post‐translational pathway are safely delivered to the endoplasmic reticulum (ER) membrane by a well‐known targeting factor, TRC40/Get3. In contrast, the underlying mechanism for translocation of TA proteins in plants remains obscure. How this unique eukaryotic membrane‐trafficking system correctly distinguishes different subsets of TA proteins destined for various organelles, including mitochondria, chloroplasts and the ER, is a key question of long standing. Here, we present crystal structures of algal ArsA1 (the Get3 homolog) in a distinct nucleotide‐free open state and bound to adenylyl‐imidodiphosphate. This approximately 80‐kDa protein possesses a monomeric architecture, with two ATPase domains in a single polypeptide chain. It is capable of binding chloroplast (TOC34 and TOC159) and mitochondrial (TOM7) TA proteins based on features of its transmembrane domain as well as the regions immediately before and after the transmembrane domain. Several helices located above the TA‐binding groove comprise the interlocking hook‐like motif implicated by mutational analyses in TA substrate recognition. Our data provide insights into the molecular basis of the highly specific selectivity of interactions of algal ArsA1 with the correct sets of TA substrates before membrane targeting in plant cells. 相似文献
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Multiple evidence shows that metformin serves as a potential agent for Colorectal Cancer (CRC) treatment, while its molecular mechanisms still require detailed investigation. Here, we revealed that metformin specifically suppressed the proliferation of CRC cells by causing G1/S arrest, and INHBA is a potential target for metformin to play an anti-proliferation effect in CRC. We verified the oncogene role of INHBA by knocking down and overexpressing INHBA in CRC cells. Silencing INHBA abrogated the cell growth, while overexpression INHBA promotes the proliferation of CRC cells. As an oncogene, INHBA was aberrant overexpression in CRC tissues and closely related to the poor prognosis of CRC patients. In mechanism, INHBA is an important ligand of TGF-β signaling and metformin blocked the activation of TGF-β signaling by targeting INHBA, and then down-regulated the activity of PI3K/Akt pathway, leading to the reduction of cyclinD1 and cell cycle arrest. Together, these findings indicate that metformin down-regulates the expression of INHBA, then attenuating TGF-β/PI3K/Akt signaling transduction, thus inhibiting the proliferation of CRC. Our study elucidated a novel molecular mechanism for the anti-proliferation effect of metformin, providing a theoretical basis for the application of metformin in CRC therapy.Subject terms: Colorectal cancer, Cell growth, Target identification 相似文献