Image_1_m6A-related lncRNAs are potential biomarkers for the prognosis of COAD patients.jpeg

BackgroundColon adenocarcinoma (COAD) is the most common subtype of colon cancer. However, the 5-year survival rate of COAD patients remains unsatisfactory. N6-methyladenosine (m6A) and long noncoding RNAs (lncRNAs) play essential roles in the occurrence and development of COAD. Herein, we are committed to establish and validate a prognostic m6A-related lncRNA signature.MethodsWe obtained m6A-related lncRNAs by coexpression. The m6A-related lncRNA risk signature (m6ALncSig) was developed via univariate, LASSO, and multivariate Cox regression analyses. Kaplan-Meier (KM) survival curves, gene set enrichment analysis (GSEA), and nomogram generation were conducted to assess m6ALncSig. In addition, the potential immunotherapeutic signatures were also discussed. Real-time PCR and CCK8 analysis were performed to evaluate the expression and functions of lncRNA UBA6-AS1, which was selected.ResultsThe risk signature comprising 14 m6A-related lncRNAs (m6ALncSig) was established, which possessed a superior predictive ability of prognosis. Meanwhile, m6ALncSig was linked to immune cell infiltration. The level of UBA6-AS1 expression was validated in 17 pairs of COAD samples. In cell function experiments, UBA6-AS1 knockdown attenuated cell proliferation capacity.ConclusionsCollectively, m6ALncSig could serve as an independent predictive factor for COAD and accurately estimate the outcome for COAD patients. Importantly, UBA6-AS1 was first identified as an oncogene in COAD.</p

Identification, classification, and transcription profiles of the B-type response regulator family in pear

<div><p>Type-B response regulators (B-RRs) are transcription factors that function in the final step of two-component signaling systems. In model plants, B-RRs have been shown to play important roles in cytokinin signal transduction. However, the functions of B-RRs in pear have not been well studied. In this report, we conducted a genome-wide analysis and identified 11 putative genes encoding B-PpRR proteins based on the published genome sequence of <i>Pyrus bretschneideri</i>. A phylogenetic tree of the <i>B-PpRR</i> family was constructed, and the motif distribution, chromosome localization, and gene structure of <i>B-PpRR</i> family genes were determined. Gene transcript profiles, which were determined from transcriptome data, indicated that <i>B-PpRR</i> genes potentially function during pear fruit development, bud dormancy, and light/hormone-induced anthocyanin accumulation. Treatment of the fruitlets of ‘Cuiguan’ pear (<i>Pyrus pyrifolia</i>), which never accumulates anthocyanin, with the cytokinin N-(2-chloro-4-pyridyl)- N′-phenylurea (CPPU) clearly induced anthocyanin accumulation. Anthocyanins accumulated in the skin of fruitlets by 16 days after CPPU treatment, along with the significant activation of most anthocyanin biosynthetic genes. Analyses of <i>B-PpRR</i> transcript levels suggested that <i>B-PpRR</i> genes mediated this accumulation of anthocyanins. These findings enrich our understanding of the function of <i>B-PpRR</i> genes in the physiological processes of pear.</p></div

³¹P NMR 2D Mapping of Creatine Kinase Forward Flux Rate in Hearts with Postinfarction Left Ventricular Remodeling in Response to Cell Therapy

<div><p>Utilizing a fast ³¹P magnetic resonance spectroscopy (MRS) 2-dimensional chemical shift imaging (2D-CSI) method, this study examined the heterogeneity of creatine kinase (CK) forward flux rate of hearts with postinfarction left ventricular (LV) remodeling. Immunosuppressed Yorkshire pigs were assigned to 4 groups: 1) A sham-operated normal group (SHAM, n = 6); 2) A 60 minutes distal left anterior descending coronary artery ligation and reperfusion (MI, n = 6); 3) Open patch group; ligation injury plus open fibrin patch over the site of injury (Patch, n = 6); and 4) Cell group, hiPSCs-cardiomyocytes, -endothelial cells, and -smooth muscle cells (2 million, each) were injected into the injured myocardium pass through a fibrin patch (Cell+Patch, n = 5). At 4 weeks, the creatine phosphate (PCr)/ATP ratio, CK forward flux rate (Flux _PCr→ATP), and k constant of CK forward flux rate (<i>k</i>_PCr→ATP) were severely decreased at border zone myocardium (BZ) adjacent to MI. Cell treatment results in significantly increase of PCr/ATP ratio and improve the value of <i>k</i>_PCr→ATP and Flux _PCr→ATP in BZ myocardium. Moreover, the BZ myocardial CK total activity and protein expression of CK mitochondria isozyme and CK myocardial isozyme were significantly reduced, but recovered in response to cell treatment. Thus, cell therapy results in improvement of BZ bioenergetic abnormality in hearts with postinfarction LV remodeling, which is accompanied by significantly improvements in BZ CK activity and CK isozyme expression. The fast 2D ³¹P MR CSI mapping can reliably measure the heterogeneity of bioenergetics in hearts with post infarction LV remodeling.</p></div

Injected hiPSC-derived cardiac cells increased CK-MT and CK-M levels and total CK activity.

<p>Myocardial tissue was harvested from the border zone of infarction in Sham, MI, Patch, and Cell+Patch animals. (A) The harvested tissues were analyzed via Western-blot to determine the amount of protein present for each of three creatine kinase isoforms (CK-MT: mitochondria, CK-M: myocardium, CK-B: brain) and for glyceraldehyde-3-phosphate dehydrogenase (GAPDH). (B) CK-MT, (C) CK-M, and (D) CK-B protein levels were quantified via densitometry, normalized to GAPDH protein levels, and presented as a percentage of the amount present in Sham animals. (E) Total CK activity in the harvested tissues was measured spectrophotometrically. *<i>P</i><0.05, **<i>P</i><0.01.</p

Chromosomal distribution and structures of <i>B-PpRR</i> genes in pear.

<p>a. Distribution of nine <i>B-PpRR</i> genes on six pear chromosomes; remaining two <i>B-PpRR</i> genes were located on scaffolds that have not been mapped to chromosomes. b. Gene structure of <i>B-PpRR</i> genes. Gray rectangles represent exons, lines represent introns.</p

Transcript profile of <i>B-PpRR</i> genes in different development stages of different pears.

<p>Transcription profiles in different fruits were determined from transcriptome data. Transcript levels were normalized with min-max method. Samples were collected at 0, 7, 35, and 85 days after full bloom and maturity. XQ, <i>Pyrifolia</i> cv. Xueqing.</p

TSH increased SREBP-2 protein levels and the expression of its target genes, HMGCR and HMGCS, in HepG2 cells.

<p>(A) HepG2 cells were pretreated with TSH (4 μM) for 24 or 48 h. Whole cell lysates were subjected to Western blotting (WB) using an SREBP-2 antibody that recognizes both the SREBP-2 precursor and nuclear active forms. (P) and (N) denote the precursor and nuclear active forms of SREBP-2, respectively. (B-C) Densitometric quantifications of SREBP-2 (P) and SREBP-2 (N) are shown. Densitometry was performed using ImageJ (version 1.45) and normalized to β-actin. The data are presented as the mean ± SEM. *<i>p</i>< 0.05 versus zero concentration of TSH, ^#<i>p</i> < 0.05 versus TSH (24h). (D) HepG2 cells were treated with TSH (4 μM) for 24 or 48 h and then were harvested to monitor the mRNA expression of HMGCR and HMGCS. β-actin was used for normalization, and the control was set to 1 in the Real-Time PCR data. All the experiments were performed in duplicate. *<i>p</i> < 0.05 versus zero concentration of TSH.</p

Anthocyanin induction in <i>P</i>. <i>pyrifolia cv</i>. Cuiguan by N-(2-chloro-4-pyridyl)- N′-phenylurea (CPPU) treatment.

<p>a. Anthocyanin accumulation and phenotypes of ‘Cuiguan’ at 0, 3, 7, 11, 16, 21, and 31 days after 30 mg/L CPPU or water treatment. b. Transcript levels of anthocyanin biosynthetic genes and regulatory genes. c. Transcript levels of cytokinin receptor genes. d. Transcript levels of group II <i>B-PpRR</i> genes after CPPU treatment. Values shown are mean ± standard error of three replicates.</p

Transcript profiles of <i>B-PpRR</i> genes during bud dormancy.

<p>Transcription profiles during bud dormancy were determined from transcriptome data. Transcript levels were normalized with min-max method. Samples of <i>P</i>. <i>pyrifolia</i> white pear group cv. Suli were collected from Nov. 15 2011 to Feb. 15 2012. Transcription profiles of <i>P</i>. <i>pyrifolia</i> ‘Kosui’ corresponded to endo (endodormancy) and eco (transitional state of endodormancy and ecodormancy) stages.</p

Quantitative RT-PCR primers.

<p>Quantitative RT-PCR primers.</p