Transcriptomic Landscape of Treatment-Naive Ulcerative Colitis
JOURNAL OF CROHNS & COLITIS
Authors: Taman, Hagar; Fenton, Christopher G.; Hensel, Inga V.; Anderssen, Endre; Florholmen, Jon; Paulssen, Ruth H.
Abstract
Background and Aims: Ulcerative colitis [UC] is a chronic inflammatory disease that effects the gastrointestinal tract and is considered one of the most prominent and common forms of inflammatory bowel disease [IBD]. This study aimed to define and describe the entire transcriptomic landscape in a well-stratified, treatment-naive UC patient population compared with control patients by using next-generation technology, RNA-Seq. Methods: Mucosal biopsies from treatment-naive UC patients [n = 14], and healthy controls [n = 16] underwent RNA-Seq. Principal component analysis [PCA], cell deconvolution methods, and diverse statistical methods were applied to obtain and characterise a dataset of significantly differentially expressed genes [DEGs]. Results: Analyses revealed 1480 significantly DEGs in treatment-naive UC when compared with controls. Cell populations of monocytes, T cells, neutrophils, B cells/lymphoid cells, and myeloid cells were increased during inflammation, whereas the fraction of epithelial cells were reduced in UC, which is reflected by the DEGs; 79 DEGs were identified as IBD susceptibility genes, and 58 DEGs were expressed in a gender-specific manner. MUC5B, REG3A, DEFA5, and IL33 might be considered as colorectal cancer [CRC] risk factors following UC in males. AQP9 together with CLDN2 may have a role regulating tissue-specific physiological properties in tight junctions in UC. An additional functional role for AQP9 in the synthesis and/or the function of mucus can be implied. Conclusions: This study reveals new potential players in UC pathogenesis in general, and provides evidence for a gender-dependent pathogenesis for UC. These results can be useful for the development of personalised treatment strategies for UC in the future.
Antitumor Activity of Diterpenoids from Jatropha gossypiifolia: Cell Cycle Arrest and Apoptosis-Inducing Activity in RKO Colon Cancer Cells
JOURNAL OF NATURAL PRODUCTS
Authors: Zhang, Chun-Yan; Zhang, Li Jun; Lu, Zhi-Cheng; Ma, Chen-Yun; Ye, Ying; Rahman, Khalid; Zhang, Hong; Zhu, Jian-Yong
Abstract
Nine new minor diterpenoids, jatrogossones A-I (1-9), and six known analogues (10-15) were separated from an extract of the branches and leaves of Jatropha gosspiifolia. Compounds 4-6 and 10, possessing a 5/11 fused-ring skeleton, and 8, 9, and 13, with a 5/9/5 fused-ring skeleton, represent rare diterpenoid skeletons that have been found only in compounds isolated from plants of the Jatropha genus. The absolute configurations of 1-10 were defined by using a combination of electronic circular dichroism data analysis and single-crystal X-ray diffraction data. The cytotoxicity of the diterpenoids was evaluated using RKO and LOVO colon cancer cells in which regenerating islet-derived protein 3-alpha (Reg3A) is highly expressed. Compound 12 exhibited cytotoxicity against RKO colon cancer cells with an IC50 value of 2.6 mu M. Morphological features of apoptosis and antimigration activities were evaluated in 12-treated RKO cells. Compound 12 effectively induced apoptosis of RKO, which was associated with G(2)/M-phase cell cycle arrest. Flow cytometric analysis showed that the treatment by 12 significantly induced RKO cell apoptosis in a dose-dependent manner.