Calcium Supplementation Modifies the Relative Amounts of Bile Acids in Bile and Affects Key Aspects of Human Colon Physiology

Abstract Background When regional citrate anticoagulation used in continuous renal replacement therapy, one of the key aspects to achieve safe and effective extracorporeal circulation is the management of calcium ions. For calcium-free RCA-CVVH, the anticoagulant effects of different calcium supplementation pathways have not yet been explored. In this trial, we would test our hypothesis that compared with the SCV, when calcium was infused through the VL-FV, the arterial iCa2+ was lower. Methods This is a prospective randomized cross-over trial involving 24 patients undergoing RCA-CVVH. The patients were randomly divided into two groups: VL-FV—SCV group and SCV—VL-FV group. The difference of iCa2+ between arterial iCa2+ and post-filtration iCa2+ was compared. Secondary indicators included the incidence rates of catheter dysfunction and hypocalcemia. Discussion This is the first trial on the anticoagulant effects of calcium-free RCA-CVVH through different calcium supplement routes. We will confirm that the arterial iCa2 + level is slightly lower when calcium is infused in the VL-FV than in the SCV, and the incidence rates of catheter dysfunction and hypocalcemia will help us to determine which site is safer. Trial Registration CHiCTR registry: ChiCTR1800020046. Registered on 12 December 2018. (http://www.chictr.org.cn/listbycreater.aspx). Keywords: Continuous venous-venous hemofiltration, regional citrate anticoagulation, calcium, effect, safety, cross-over trial

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Development of a human primary gut-on-a-chip to model inflammatory processes

Scientific Reports ◽

10.1038/s41598-020-78359-2 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Claudia Beaurivage ◽

Auste Kanapeckaite ◽

Cindy Loomans ◽

Kai S. Erdmann ◽

Jan Stallen ◽

...

Keyword(s):

Human Colon ◽

In Vitro Models ◽

Intestinal Epithelial ◽

Activated Macrophages ◽

Polarized Secretion ◽

Inflammatory Processes ◽

Inflammatory Bowel ◽

Key Aspects

AbstractInflammatory bowel disease (IBD) is a complex multi-factorial disease for which physiologically relevant in vitro models are lacking. Existing models are often a compromise between biological relevance and scalability. Here, we integrated intestinal epithelial cells (IEC) derived from human intestinal organoids with monocyte-derived macrophages, in a gut-on-a-chip platform to model the human intestine and key aspects of IBD. The microfluidic culture of IEC lead to an increased polarization and differentiation state that closely resembled the expression profile of human colon in vivo. Activation of the model resulted in the polarized secretion of CXCL10, IL-8 and CCL-20 by IEC and could efficiently be prevented by TPCA-1 exposure. Importantly, upregulated gene expression by the inflammatory trigger correlated with dysregulated pathways in IBD patients. Finally, integration of activated macrophages offers a first-step towards a multi-factorial amenable IBD platform that could be scaled up to assess compound efficacy at early stages of drug development or in personalized medicine.

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Bile acids induce MUC2 overexpression in human colon carcinoma cells

Cancer ◽

10.1002/cncr.21015 ◽

2005 ◽

Vol 103 (8) ◽

pp. 1606-1614 ◽

Cited By ~ 22

Author(s):

Shumei Song ◽

James C. Byrd ◽

Ja Seok Koo ◽

Robert S. Bresalier

Keyword(s):

Bile Acids ◽

Colon Carcinoma ◽

Human Colon ◽

Carcinoma Cells ◽

Colon Carcinoma Cells ◽

Human Colon Carcinoma

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Effects of specific bile acids on c-fos messenger RNA levels in human colon carcinoma Caco-2 cells

European Journal of Pharmaceutical Sciences ◽

10.1016/s0928-0987(00)00111-1 ◽

2000 ◽

Vol 11 (4) ◽

pp. 291-298 ◽

Cited By ~ 14

Author(s):

Rosanna Di Toro ◽

Gabriele Campana ◽

Giovanna Murari ◽

Santi Spampinato

Keyword(s):

Bile Acids ◽

Colon Carcinoma ◽

Messenger Rna ◽

Human Colon ◽

Human Colon Carcinoma ◽

Rna Levels

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Effect of Bile Acids on Butyrate-Sensitive and -Resistant Human Colon Adenocarcinoma Cells

Nutrition and Cancer ◽

10.1207/s15327914nc5302_10 ◽

2005 ◽

Vol 53 (2) ◽

pp. 208-219 ◽

Cited By ~ 8

Author(s):

Pablo Perez-Ramos ◽

Nieves Olmo ◽

Javier Turnay ◽

Emilio Lecona ◽

Gonzalo Gonzalez de Buitrago ◽

...

Keyword(s):

Bile Acids ◽

Colon Adenocarcinoma ◽

Human Colon ◽

Adenocarcinoma Cells ◽

Human Colon Adenocarcinoma ◽

Colon Adenocarcinoma Cells

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Sulphation of lithocholic acid in the colon-carcinoma cell line CaCo-2

Biochemical Journal ◽

10.1042/bj3430533 ◽

1999 ◽

Vol 343 (3) ◽

pp. 533-539 ◽

Cited By ~ 6

Author(s):

Bente HALVORSEN ◽

Bengt Frode KASE ◽

Kristian PRYDZ ◽

Sedegheh GARAGOZLIAN ◽

Marianne S. ANDRESEN ◽

...

Keyword(s):

Bile Acids ◽

Cell Line ◽

Colon Carcinoma ◽

Carcinoma Cell ◽

Lithocholic Acid ◽

Human Colon ◽

Carcinoma Cell Line ◽

Gel Chromatography ◽

Colon Carcinoma Cell Line ◽

Increased Risk

High levels of bile acids in the colon may correlate with an increased risk of colon cancer, but the underlying mechanisms are not known. Proteoglycan structures have been shown to change when human colon cells differentiate in vitro. The expression of [35S]sulphated molecules was used as a phenotypic marker to study the effects of bile acids on the human-colon-carcinoma cell line CaCo-2. [35S]sulphated compounds were isolated from the medium of cell fractions of cells metabolically labelled with [35S]sulphate in the absence and presence of cholic acid, deoxycholic acid, chenodeoxycholic acid and lithocholic acid (LA). Labelled molecules were analysed by gel chromatography, HPLC and SDS/PAGE in combination with chemical and enzymic methods. The expression of 35S-labelled proteoglycans was not affected by any of the bile acids tested. However, the level of sulphated metabolites increased 7-18-fold in different experiments during a 22 h labelling period in the presence of an LA concentration of 10 μg/ml (26.6 nmol/ml) compared with controls. Further analyses showed that this was due, at least in part, to the sulphation of LA itself. This sulphation of LA was a rapid process followed by secretion back to the medium. Brefeldin A did not reduce the sulphation of LA, indicating that this conversion takes place in the cytosol, rather than in the Golgi apparatus of the CaCo-2 cells. LA in colon may be sulphated efficiently by the colonocytes to reduce the toxic effects of this particular bile acid. Sulphation may possibly be an important protective mechanism in the colon.

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Structural Variations and Functional Ramifications of Bile Acids (BA) on Tight Junctions (TJ) in Human Colon T84 Cells

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.575.15 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Ugne Dinsmonaite ◽

M. Haq ◽

F. Donner ◽

P. Whitman ◽

T. Couri ◽

...

Keyword(s):

Bile Acids ◽

Tight Junctions ◽

Human Colon ◽

Structural Variations ◽

T84 Cells

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Bile acids inhibit NAD+-dependent 15-hydroxyprostaglandin dehydrogenase transcription in colonocytes

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00133.2009 ◽

2009 ◽

Vol 297 (3) ◽

pp. G559-G566 ◽

Cited By ~ 11

Author(s):

Akira Miyaki ◽

Peiying Yang ◽

Hsin-Hsiung Tai ◽

Kotha Subbaramaiah ◽

Andrew J. Dannenberg

Keyword(s):

Bile Acid ◽

Bile Acids ◽

Signal Transduction Pathway ◽

Human Colon ◽

Colorectal Carcinogenesis ◽

Human Colon Cancer ◽

Early Growth Response ◽

Extracellular Signal ◽

Colon Cancer Cell Lines ◽

Key Enzyme

Multiple lines of evidence have suggested a role for both bile acids and prostaglandins (PG) in gastrointestinal carcinogenesis. Levels of PGE2 are determined by both synthesis and catabolism. Previously, bile acid-mediated induction of cyclooxygenase-2 (COX-2) was found to stimulate PGE2 synthesis. NAD+-dependent 15-hydroxyprostaglandin dehydrogenase (15-PGDH), the key enzyme responsible for the catabolism of PGE2, has been linked to colorectal carcinogenesis. In this study, we determined whether bile acids altered the expression of 15-PGDH in human colon cancer cell lines. Treatment with unconjugated bile acids (chenodeoxycholate and deoxycholate) suppressed the transcription of 15-PGDH, resulting in reduced amounts of 15-PGDH mRNA, protein, and enzyme activity. Conjugated bile acids were less potent suppressors of 15-PGDH expression than unconjugated bile acids. Treatment with chenodeoxycholate activated protein kinase C (PKC), leading in turn to increased extracellular signal-regulated kinase (ERK) 1/2 activity. Small molecules that inhibited bile acid-mediated activation of PKC and ERK1/2 also blocked the downregulation of 15-PGDH. Bile acids induced early growth response factor-1 (Egr-1) and Snail, a repressive transcription factor that bound to the 15-PGDH promoter. Silencing Egr-1 or Snail blocked chenodeoxycholate-mediated downregulation of 15-PGDH. Together, these data indicate that bile acids activate the signal transduction pathway PKC → ERK1/2 → Egr-1 → Snail and thereby suppress 15-PGDH transcription. Bile acids appear to increase the release of PGs from cells by downregulating catabolism in addition to stimulating synthesis. These results provide new mechanistic insights into the link between bile acids and gastrointestinal carcinogenesis.

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Deoxycholic and chenodeoxycholic bile acids induce apoptosis via oxidative stress in human colon adenocarcinoma cells

APOPTOSIS ◽

10.1007/s10495-011-0633-x ◽

2011 ◽

Vol 16 (10) ◽

pp. 1054-1067 ◽

Cited By ~ 44

Author(s):

Juan Ignacio Barrasa ◽

Nieves Olmo ◽

Pablo Pérez-Ramos ◽

Angélica Santiago-Gómez ◽

Emilio Lecona ◽

...

Keyword(s):

Oxidative Stress ◽

Bile Acids ◽

Colon Adenocarcinoma ◽

Human Colon ◽

Adenocarcinoma Cells ◽

Human Colon Adenocarcinoma ◽

Colon Adenocarcinoma Cells

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Relationships between Ion and Water Movement in the Human Jejunum, Ileum and Colon during Perfusion with Bile Acids

Clinical Science ◽

10.1042/cs0450593 ◽

1973 ◽

Vol 45 (5) ◽

pp. 593-606 ◽

Cited By ~ 8

Author(s):

D. L. Wingate ◽

E. Krag ◽

H. S. Mekhjian ◽

S. F. Phillips

Keyword(s):

Ion Exchange ◽

Bile Acids ◽

Water Movement ◽

Human Colon ◽

Bulk Flow ◽

Mucosal Cell ◽

Slight Variation ◽

Low Concentrations ◽

Net Flux ◽

Lower Magnitude

1. Perfusion of the human jejunum with low concentrations of glycine-conjugated bile acids in physiological solutions induced net fluid flow that varied between absorption and secretion, with only slight variation of the luminal osmotic and ionic milieu. 2. Transmucosal net flux rates for water and the principal ions were calculated. Regression analysis of the flux data was consistent with the concept of a ‘net transported fluid’ which was iso-osmotic with respect to the lumen, with a superimposed fixed net anion exchange unaffected by the rate or direction of bulk flow. 3. Recalculation of earlier data from comparable studies of the human colon showed similar relationships consistent with varying iso-osmotic bulk flow and fixed ion exchange, the latter differing from that found in the proximal bowel. 4. Studies were performed also in the human ileum. Variable iso-osmotic bulk flow was again encountered, but ion exchange was of a lower magnitude than in the jejunum or colon. Qualitatively, ion exchange in the ileum was intermediate between the jejunum and colon. 5. These analyses suggest that transmucosal bulk flow and ion exchange may be quantitatively and spatially independent processes. They provide support for the hypothesis that bulk flow may be intercellular (and hence extracellular), while ion exchange may take place across the luminal face of the mucosal cell. 6. Secretory agents, such as the dihydroxy bile acids, provide a useful means of analysing solute-solvent flow relationships in greatly differing bulk flow conditions with relatively stable physicochemical parameters.

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