Carrduggan0404

The aims of this study were to investigate the expression of prolyl 4-hydroxylase subunit alpha-1 (P4HA1) and its relationship with clinicopathological features in lung cancer (LC), breast cancer (BC), and head and neck cancer (HNSC) and to discuss the possibility of P4HA1 being a potential diagnostic and prognostic biomarker. Data on the RNA expression profile, protein expression profile, and relevant clinical information were downloaded from The Cancer Genome Atlas (TCGA) and The Human Protein Atlas databases. The relationship between P4HA1 mRNA expression and clinicopathological features was evaluated. Survival analysis was performed to assess overall survival (OS) and relapse-free survival (RFS). The multivariate Cox regression model was employed to analyze the independent prognostic factors. Finally, protein-protein interaction networks were constructed and enrichment analysis was performed to identify the latent P4HA1-related terms and pathways. This study showed that P4HA1 was upregulated in three types of tumor tissues (p  less then  0.05) and high P4HA1 was significantly relevant to the clinical features of patients with LC, BC, or HNSC. Survival analysis indicated that patients with high P4HA1 had unfavorable clinical outcomes. Multivariate analysis showed that the high P4HA1 expression was an independent prognostic factor for poor OS and RFS in LC and HNSC patients. Bioinformatic analysis was performed to predict P4HA1-interacted proteins and further evaluate possible signal pathways. In the current study, the rising P4HA1 was identified in LC, BC, and HNSC and significantly correlated with the clinicopathological features of patients. High P4HA1, suggesting poor clinical outcomes, could be used as an early diagnostic and prognostic biomarker for patients with aforementioned tumors.Global DNA hydroxymethylation mediated by the ten-eleven translocation (TET) enzyme was induced in allergen-induced airway hyper-responsiveness (AHR) in mouse lung tissues and specifically in isolated airway smooth muscle (ASM) cells. TET is an α-ketoglutarate (α-KG)-dependent enzyme, and the production of α-KG is catalyzed by isocitrate dehydrogenase (IDH). However, the role of IDHs in the regulation of DNA hydroxymethylation in ASM cells is unknown. In comparison with non-asthmatic cells, asthmatic ASM cells exhibited a higher TET activity and IDH2 (not IDH-1 and -3) gene expression level. We modified the expression of IDH2 in ASM cells from human asthmatics by small interference RNA (siRNA), and the α-KG level, TET activity, global DNA hydroxymethylation, cell proliferation, and expression of ASM phenotypic genes were examined. Inhibition of IDH2 in asthmatic ASM cells decreased the α-KG level, TET activity, and global DNA hydroxymethylation and reversed the aberrant ASM phenotypes (including decreased cell proliferation and ASM phenotypic gene expression). Specifically, asthmatic cells transfected with siRNA against IDH2 (siIDH2) showed decreased 5hmC level at the transforming growth factor beta 2 (TGFB2) promoter determined by oxidative bisulfite sequencing (oxBS-seq). Taken together, our findings revealed that IDH2 plays an important role in the epigenetic regulation of ASM phenotypic changes in asthmatic ASM cells, suggesting that IDH2 is a potential therapeutic target for reversing the abnormal phenotypes seen in asthma.Over the past 66 years our knowledge of the role of endothelium in the regulation of cardiovascular function and dysfunction has advanced from the assumption that it is a single layer of cells that serves as a barrier between the blood stream and vascular smooth muscle, to an understanding of its role as an essential endocrine-like organ. In terms of historical contributions, we pay particular credit to 1. The Canadian scientist, Dr. Rudolf Altschul who, based on pathological changes in the appearance of the endothelium advanced the argument in 1954 that "one is only as old as one's endothelium"; and 2. The American scientist, Dr. Robert Furchgott, a 1998 Nobel Prize winner in Physiology or Medicine, who identified the importance of the endothelium in the regulation of blood flow. This review provides a brief history of how our knowledge of endothelial function has advanced and now recognize that the endothelium produces a plethora of signalling molecules possessing paracrine, autocrine and, arguably, systemic hormone functions. In addition, the endothelium is a therapeutic target for the anti-diabetic drugs, metformin, glucagon-like peptide I (GLP-1) receptor agonists and inhibitors of the sodium-glucose co-transporter 2 (SGLT2) that offset the vascular disease associated with diabetes.In mouse development, differentiation of the inner cell mass (ICM) and trophectoderm (TE) during the transition from the morula to blastocyst stage is regulated by the Hippo pathway; however, the functions of the Hippo pathway in porcine embryogenesis have not been investigated. In the present study, we examined the gene expression patterns of the Hippo pathway members yes-associated protein 1 (YAP1) and large tumor suppressor 2 (LATS2) and the functions of these genes during porcine preimplantation development using RNA interference. Both YAP1 and LATS2 mRNA levels were shown high in the in vitro matured oocytes and 1-cell stage embryos and fell progressively with development. YAP1 nuclear localization was detected at the morula and blastocyst stages. Downregulation of either YAP1 or LATS2 inhibited porcine preimplantation development and affected the expression levels of POU class 5 homeobox 1 (OCT-4) and SRY-related HMG-box gene 2 (SOX2), transcription factors necessary for the ICM/TE differentiation. Proteasome inhibitor Taken together, YAP1 and LATS2 are essential for porcine preimplantation development, and it is possible that the Hippo pathway has important roles in porcine ICM/TE segregation.Introduction Breastfeeding is a protective factor for women and children. Women who smoke cigarettes during pregnancy are less likely to initiate or persist in breastfeeding. However, less is known about why this is the case. Materials and Methods The present study (n = 247) prospectively examined maternal/child factors that influence breastfeeding in a low-income, racially diverse at-risk sample of smoking and nonsmoking women. Pregnant women were recruited at their first prenatal appointment in an urban hospital and followed through 24-month postnatally. Women reported on the average number of cigarettes smoked/day during pregnancy, psychopathology, breastfeeding behavior, and infant reactivity. Results Although a greater number of cigarettes smoked/day during pregnancy was associated with a lower likelihood of initiating or persisting in breastfeeding, maternal age, education, and infant reactivity offered predictive utility above and beyond maternal smoking. Conclusion Smokers were less likely to initiate breastfeeding and breastfed for shorter duration than demographically similar nonsmokers; however, one of the mechanisms for reduced breastfeeding may be the psychosocial factors of younger age and lower education.