ABSTRACT
The aim of this study was to elucidate the concise effects of a traditional herb pair, Curcumae rhizoma-Sparganii rhizoma (CRSR), on uterine leiomyoma (UL) by analyzing transcriptional profiling. The UL rat model was made by intramuscular injection of progesterone and gavage administration of diethylstilbestrol. From 11 weeks of the establishment of the model, rats of the UL+CRSR group were gavaged daily with CRSR (6.67 g/kg). The serum concentrations of progesterone (P) and estradiol (E2) were determined by radioimmunoassay, the uterine index was measured by caliper measurement, and the pathological status was observed by hematoxylin and eosin stain. Gene expression profiling was checked by NimbleGen Rat Gene Expression Microarrays. The results indicated that the uterine mass of UL+CRSR rats was significantly shrunk and serum P and E2 levels significantly reduced compared to UL animals and nearly to the level of normal rats. Results of microarrays displayed the extensive inhibition of CRSR upon the expression of proliferation and deposition of extracellular matrix (ECM)-related genes, and significantly regulated a wide range of metabolism disorders. Furthermore, CRSR extensively regulated key pathways of the UL process, such as MAPK, PPAR, Notch, and TGF-β/Smad. Regulation of the crucial pathways for the UL process and ECM metabolism may be the underlying mechanisms of CRSR treatment. Further studies will provide clear clues for effectively treating UL with CRSR.
Subject(s)
Animals , Female , Rats , Uterine Neoplasms/drug therapy , Plant Extracts/pharmacology , Gene Expression Regulation, Neoplastic/drug effects , Curcuma/chemistry , Rhizome/chemistry , Leiomyoma/drug therapy , Transcription Factors , Uterine Neoplasms/genetics , Uterine Neoplasms/metabolism , Radioimmunoassay , Rats, Sprague-Dawley , Oligonucleotide Array Sequence Analysis , Disease Models, Animal , Leiomyoma/genetics , Leiomyoma/metabolismABSTRACT
Oligodendrocytes (OLs) are myelinating glial cells that form myelin sheaths around axons to ensure rapid and focal conduction of action potentials. Here, we found that an axonal outgrowth regulatory molecule, AATYK (apoptosis-associated tyrosine kinase), was up-regulated with OL differentiation and remyelination. We therefore studied its role in OL differentiation. The results showed that AATYK knockdown inhibited OL differentiation and the expression of myelin genes in vitro. Moreover, AATYK-deficiency maintained the proliferation status of OLs but did not affect their survival. Thus, AATYK is essential for the differentiation of OLs.
Subject(s)
Animals , Mice , Rats , Animals, Newborn , Apoptosis Regulatory Proteins , Genetics , Metabolism , Cell Differentiation , Physiology , Cell Proliferation , Genetics , Cells, Cultured , Cuprizone , Toxicity , Demyelinating Diseases , Metabolism , Pathology , Embryo, Mammalian , Gene Expression Regulation, Developmental , Genetics , Ki-67 Antigen , Metabolism , Mice, Inbred C57BL , Myelin Basic Protein , Metabolism , Myelin Proteolipid Protein , Metabolism , Myelin Sheath , Metabolism , Oligodendroglia , Metabolism , Protein-Tyrosine Kinases , Genetics , Metabolism , RNA, Small Interfering , Genetics , Metabolism , Rats, Sprague-DawleyABSTRACT
<p><b>OBJECTIVE</b>To investigate the value of 11C-PD153035 as an EGFR imaging agent in C6 tumor-bearing rat.</p><p><b>METHODS</b>The tumor-bearing rats were generated by subcutaneous injection of glioma C6 cells. Positron emission tomography/computer tomography (PET/CT) scans started as soon as intravenous injection of 11C-PD153035 (15-20 MBq/0.3 ml) was completed, images were collected continuously. The region of interest (ROI) was used to study the percentage of radioactivity in major organs and implanted tumors in the rats. The accumulation and blocking study in vitro was completed.</p><p><b>RESULTS</b>There were significant differences in 11C-PD153035 uptake among major organs. The maximum uptake in the organs ranked in the following order: liver > gastrointestinal tract > kidney > lung > brain > muscle. Radioactivity could be also observed in the tumors. The radioactivity ratio (T/NT, target/non-target) peaked (4.15) at 40 - 50 min post injection. The in vitro blocking study showed that 11C-PD153035 uptaken by C6 cells could be blocked by PD153035.</p><p><b>CONCLUSION</b>The results of this study show that 11C-PD153035 can be uptaken by EGFR-expressing tumors. 11C-PD153035 has a potential as a bioprobe to yield useful information for both diagnosis and therapy of tumors. However, the high concentration of 11C-PD153035 in the gastrointestinal tract is unfavorably affecting the tumor detection in these organs.</p>