Nanog as an important transcription factor plays a pivotal role in maintaining pluripotency and in reprogramming the epigenome of somatic cells. Its ability to function on committed somatic cells and embryos has been well defined in mouse and human, but rarely in pig. To better understand Nanog's function on reprogramming in porcine fetal fibroblast (PFF) and nuclear transfer (NT) embryo, we cloned porcine Nanog CDS and constructed pcDNA3.1 (þ)/Nanog and pEGFP-C1/Nanog overexpression vectors and transfected them into PFFs. We studied the cell biological changes and the expression of Nanog, Oct4, Sox2, Klf4, C-myc, and Sall4 in transfected PFFs. We also detected the development potential of the cloned embryos harboring Nanog stably overexpressed fibroblasts and the expression of Oct4, Sox2, and both endogenous and exogenous Nanog in these embryos. The results showed that transient overexpression Nanog in PFF could activate the expression of Oct4 (5-fold), C-myc (2-fold), and Sall4 (5-fold) in somatic cells, but they could not be maintained during G418 selection. In NT embryos, although Nanog overexpression did not have a significant effect on blastocyst development rate and blastocyst cell number, it could significantly activate the expression of endogenous Nanog, Oct4, Sox2 to 160-fold, 93-fold, and 182-fold, respectively (P < 0.05). Our results demonstrate that Nanog could interact with and activate other pluripotent genes both in PFFs and embryos. Anat Rec, 294:1809Rec, 294: -1817Rec, 294: , 2011. V V C 2011 Wiley-Liss, Inc.
Acetaminophen (APAP) is an antipyretic and analgesic, which is commonly associated with drug‐induced hepatic injury. C2‐ceramide plays a key role in mediating cell life activities, and oltipraz was extensively studied as a cancer chemopreventive agent. Glutathione S‐transferase A1 (GSTA1) acts as a vital liver detoxification enzyme. Hepatocyte nuclear factor 1 (HNF‐1) regulates various cellular signaling pathways. In this study, we investigated the effects of C2‐ceramide and oltipraz on APAP‐induced hepatocyte injury and the changes of HNF‐1 and GSTA1. Results showed that C2‐ceramide (6 μmol/L) exacerbated APAP‐induced hepatocyte injury and caused a significant decrease (P < .01) in HNF‐1 and GSTA1 expressions. Meanwhile, GSTA1 content in supernatant was significantly increased (P < .01). In contrast, oltipraz (8 μmol/L) reduced the injury and significantly elevated (P < .01) HNF‐1 and GSTA1 expressions while GSTA1 content in supernatant was significantly decreased (P < .01). In conclusion, these findings revealed that C2‐ceramide inhibited HNF‐1 and GSTA1 expression and exacerbated hepatocyte injury, while oltipraz treatment results in the reduction of hepatocyte injury, and promoted HNF‐1 and GSTA1 expression. Additionally, the changes in HNF‐1 and GSTA1 were related to APAP‐induced hepatocyte injury. These results were useful to investigate the mechanism of an antipyretic and analgesic drug combination.
Hematologic and biochemical reference intervals (RIs) are important indicators in physiology, pathology, and toxicology research. Accurate biological RIs are essential for early detection and timely diagnosis and treatment of diseases. It is necessary to establish specific RIs for each animal species and strain. Pigs are becoming a more accepted animal model in diverse clinical disease research, such as classical swine fever, erysipelas suis, swine plague, and porcine hepatitis E virus. Pigs are very similar in physiology and anatomy to people; therefore, pigs can be used as xenograft donors. 1,2 Piglets can also be used as an accurate model to study human congenital and hereditary diseases during the newborn period. 3 The specific-pathogen-free (SPF) animals are used as experimental animals due to their internationally recognized standard and can be used in a variety of scientific experiments, including vaccine manufacturing, biological identification, human tumor xenotransplantation, preclinical pharmacology studies, and carcinogenicity trials. 4,5 SPF pigs are suitable for establishing disease models for pig diseases as well as human diseases.
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