Role of bacterial toxins, bile acids, and free fatty acids in colonic water malabsorption in tropical sprue

1987 ◽  
Vol 32 (5) ◽  
pp. 500-505 ◽  
Author(s):  
B. S. Ramakrishna ◽  
V. I. Mathan
Diabetes ◽  
1993 ◽  
Vol 42 (11) ◽  
pp. 1626-1634 ◽  
Author(s):  
A. Avogaro ◽  
P. Beltramello ◽  
L. Gnudi ◽  
A. Maran ◽  
A. Valerio ◽  
...  

2019 ◽  
Author(s):  
Mohammad Aziz ◽  
Saeed Al Mahri ◽  
Amal Alghamdi ◽  
Maaged AlAkiel ◽  
Monira Al Aujan ◽  
...  

Abstract Background Colorectal cancer is a worldwide problem which has been associated with changes in diet and lifestyle pattern. As a result of colonic fermentation of dietary fibres, short chain free fatty acids are generated which activate Free Fatty Acid Receptors 2 and 3 (FFAR2 and FFAR3). FFAR2 and FFAR3 genes are abundantly expressed in colonic epithelium and play an important role in the metabolic homeostasis of colonic epithelial cells. Earlier studies point to the involvement of FFAR2 in colorectal carcinogenesis. Methods Transcriptome analysis console was used to analyse microarray data from patients and cell lines. We employed shRNA mediated down regulation of FFAR2 and FFAR3 genes which was assessed using qRT-PCR. Assays for glucose uptake and cAMP generation was done along with immunofluorescence studies. For measuring cell proliferation, we employed real time electrical impedance based assay available from xCelligence. Results Microarray data analysis of colorectal cancer patient samples showed a significant down regulation of FFAR2 gene expression. This prompted us to study the FFAR2 in colorectal cancer. Since, FFAR3 shares significant structural and functional homology with FFAR2, we knocked down both these receptors in colorectal cancer cell line HCT 116. These modified cell lines exhibited higher proliferation rate and were found to have increased glucose uptake as well as increased level of GLUT1. Since, FFAR2 and FFAR3 signal through G protein subunit (Gαi), knockdown of these receptors was associated with increased cAMP. Inhibition of PKA did not alter the growth and proliferation of these cells indicating a mechanism independent of cAMP/PKA pathway. Conclusion: Our results suggest role of FFAR2/FFAR3 genes in increased proliferation of colon cancer cells via enhanced glucose uptake and exclude the role of protein kinase A mediated cAMP signalling. Alternate pathways could be involved that would ultimately result in increased cell proliferation as a result of down regulated FFAR2/FFAR3 genes. This study paves the way to understand the mechanism of action of short chain free fatty acid receptors in colorectal cancer.


2016 ◽  
Vol 68 (6) ◽  
pp. 1339-1344 ◽  
Author(s):  
Elżbieta Płonka-Półtorak ◽  
Paweł Zagrodzki ◽  
Jadwiga Kryczyk-Kozioł ◽  
Tuomas Westermarck ◽  
Pekka Kaipainen ◽  
...  

2011 ◽  
Vol 49 (5) ◽  
pp. 1129-1140 ◽  
Author(s):  
Mohamed A. El-Moselhy ◽  
Ashraf Taye ◽  
Sara Shaaban Sharkawi ◽  
Suzan F.I. El-Sisi ◽  
Ahmed Fahmy Ahmed

Diagnostics ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 167
Author(s):  
Erin B. Evangelista ◽  
Sandi A. Kwee ◽  
Miles M. Sato ◽  
Lu Wang ◽  
Christoph Rettenmeier ◽  
...  

Background: Hepatocellular carcinoma (HCC) pathogenesis involves the alteration of multiple liver-specific metabolic pathways. We systematically profiled cancer- and liver-related classes of metabolites in HCC and adjacent liver tissues and applied supervised machine learning to compare their potential yield for HCC biomarkers. Methods: Tumor and corresponding liver tissue samples were profiled as follows: Bile acids by ultra-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS), phospholipids by LC-MS/MS, and other small molecules including free fatty acids by gas chromatography—time of flight MS. The overall classification performance of metabolomic signatures derived by support vector machine (SVM) and random forests machine learning algorithms was then compared across classes of metabolite. Results: For each metabolite class, there was a plateau in classification performance with signatures of 10 metabolites. Phospholipid signatures consistently showed the highest discrimination for HCC followed by signatures derived from small molecules, free fatty acids, and bile acids with area under the receiver operating characteristic curve (AUC) values of 0.963, 0.934, 0.895, 0.695, respectively, for SVM-generated signatures comprised of 10 metabolites. Similar classification performance patterns were observed with signatures derived by random forests. Conclusion: Membrane phospholipids are a promising source of tissue biomarkers for discriminating between HCC tumor and liver tissue.


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