Coixendide efficacy in combination with temozolomide in glioblastoma and transcriptome analysis of the mechanism

Abstract The purpose of this study was to explore the role of coixendide (Coix) combine with temozolomide (TMZ) in the treatment of Glioblastoma (GBM) and explore its possible mechanism. CCK-8 was used to determine the inhibitory rate of Coix group, TMZ group and drug combination group on GBM cells, and the combination index (CI) was calculated to determine whether they had synergistic effect. Then RNA was extracted from each group, transcriptome sequencing was performed, and differentially expressed genes (DEGs) were identified. The possible mechanism was analyzed by GO enrichment analysis and KEGG enrichment analysis. The CI of Coix and TMZ indicating a synergistic effect when TMZ concentration is 0.1 mg/ml and Coix concentration is 2 mg/ml. Transcriptome sequencing analysis showed that interferon (IFN) related genes were down-regulated by Coix and up-regulated by TMZ and combined drugs, however, the up-regulation induced by combined drugs was less than that of TMZ. Besides IFN related genes, cholesterol metabolism pathway were also been regulated. Coix and TMZ have synergistic effects in the treatment of GBM at certain doses. RNA-Seq results suggested that the abnormal on genetic materials caused by DNA damage induced by TMZ treatment can be sensed by IFN related genes and activates antiviral IFN signaling, causing the activation of repairing mechanism and drug resistance. Coix inhibits IFN related genes, thereby inhibits drug resistance of TMZ. In addition, the activation of ferroptosis and the regulation of DEGs in cholesterol metabolism pathway were also contributed to the synergistic effects of Coix and TMZ

Effects of Platycodins Folium on Depression in Mice Based on a UPLC-Q/TOF-MS Serum Assay and Hippocampus Metabolomics

Major depressive disorder (MDD), also known as depression, is a state characterized by low mood and aversion to activity. Platycodins Folium (PF) is the dried leaf of Platycodon grandiflorum, with anti-inflammatory and antioxidative activities. Our previous research suggested that PF was rich in flavonoids, phenols, organic acids, triterpenoid saponins, coumarins and terpenoids. This study aimed to investigate the antidepressant effect of PF using lipopolysaccharide (LPS)-induced depressive mice. Several behavior tests (sucrose preference test (SPT), forced swimming test (FST) and tail suspension test (TST)) and biochemical parameters (IL-6, TNF-α and SOD levels) were used to evaluate the antidepressive effect of PF on LPS-induced depression model. Furthermore, a UPLC-Q/TOF-MS-based metabolomics approach was applied to explore the latent mechanism of PF in attenuating depression. As a result, a total of 21 and 11 metabolites that potentially contribute to MDD progress and PF treatment were identified in serum and hippocampus, respectively. The analysis of metabolic pathways revealed that lipid metabolism, amino acid metabolism, energy metabolism, arachidonic acid metabolism, glutathione metabolism and inositol phosphate metabolism were disturbed in a model of mice undergoing MDD and PF treatment. These results help us to understand the pathogenesis of depression in depth, and to discover targets for clinical diagnosis and treatment. They also provide the possibility of developing PF into an anti-depressantive agent

Cloning and Characterization of a <i>Phragmites australis</i> Phytochelatin Synthase (<i>PaPCS</i>) and Achieving Cd Tolerance in Tall Fescue

<div><p>The production of phytochelatins (PCs) provides an important means for plants to achieve tolerance to cadmium (Cd) toxicity. A reed gene encoding PC synthase (<i>PaPCS</i>) was isolated and its function tested through its heterologous expression in a strain of yeast sensitive to Cd. Subsequently, the Cd sensitive and high biomass accumulating species tall fescue was transformed either with <i>PaPCS</i> or <i>PaGCS</i> (a glutamyl cysteine synthetase gene of reed) on their own (single transformants), or with both genes together in the same transgene cassette (double transformant). The single and double transformants showed greater Cd tolerance and accumulated more Cd and PC than wild type plants, and their Cd leaf/root ratio content was higher. The ranking in terms of Cd and PC content for the various transgenic lines was double transformants><i>PaGCS</i> single transformants><i>PaPCS</i> single transformants>wild type. Thus <i>PaGCS</i> appears to exert a greater influence than <i>PaPCS</i> over PC synthesis and Cd tolerance/accumulation. The double transformant has interesting potential for phytoremediation.</p></div

Ratio of Cd root/leaf content.

<p>Values are mean ± standard error (n = 4). For each variable, values followed by different letters differ significantly between the strains (Student's t-test, P<0.05).</p

BnDGAT1s Function Similarly in Oil Deposition and Are Expressed with Uniform Patterns in Tissues of Brassica napus

As an allotetraploid oilcrop, Brassica napus contains four duplicated Acyl-CoA:diacylglycerol acyltransferase 1 (DGAT1) genes, which catalyze one of the rate-limiting steps in triacylglycerol (TAG) biosynthesis in plants. While all four BnDGAT1s have been expressed functionally in yeast, their expression patterns in different germplasms and tissues and also consequent contribution to seed oil accumulation in planta remain to be elucidated. In this study, the coding regions of the four BnDGAT1s were expressed in an Arabidopsis dgat1 mutant. All four BnDGAT1s showed similar effects on oil content and fatty acid composition, a result which is different from that observed in previous studies of their expression in yeast. Expression patterns of BnDGAT1s were analyzed in developing seeds of 34 B. napus inbred lines and in different tissues of 14 lines. Different expression patterns were observed for the four BnDGAT1s, which suggests that they express independently or randomly in different germplasm sources. Higher expression of BnDGAT1s was correlated with higher seed oil content lines. Tissue-specific analyses showed that the BnDGAT1s were expressed in a uniform pattern in different tissues. Our results suggest that it is important to maintain expression of the four BnDGAT1s for maximum return on oil content

Short term response of plants to Cd exposure/After 0–120 h, the leaves were sampled for (A) MDA content, (B) SOD activity, (C) POD activity.

<p>TP-1, TP-2: carriers of <i>PaPCS</i>; TG-1, TG-2: carriers of <i>PaGCS</i>; T(GP)-1, T(GP)-2: carriers of <i>PaGCS-PaPCS</i>; WT: wild type <i>F. arundinacea</i>. Vertical bars indicate the standard error of the mean (<i>n</i> = 4).</p

Functional testing of <i>PaPCS</i> in the Cd sensitive yeast strain YK44.

<p>Yeast cells harboring either an empty pYES2 vector or pYES2-PaPCS were cultured and inoculated into 40 µL YPGAL medium in 10⁻¹, 10⁻², and 10⁻³ concentrations in the presence of 100 µM CdCl₂. After 48 h, the growth of transgenic cells heterologously expressing <i>PaPCS</i> was compared to control cells carrying an empty pYES2 vector. All experiments were done in quadruplicate.</p

Cd²⁺ accumulation of transgenic lines and wild type after exposure to 150 µM CdCl₂ for five days.

<p>The Cd content of the roots, leaves and total plant was measured in four plants per line. TP-1, TP-2: carriers of <i>PaPCS</i>; TG-1, TG-2: carriers of <i>PaGCS</i>; T(GP)-1, T(GP)-2: carriers of <i>PaGCS-PaPCS</i>; WT: wild type <i>F. arundinacea</i>. Vertical bars indicate the standard error of the mean(<i>n</i> = 4). Different letters indicate significant differences according to a Tukey test (P<0.01).</p