Pharmacological premature termination codon readthrough of ABCB11 in bile salt export pump deficiency: an in vitro study

Hepatology ◽  
2020 ◽  
Author(s):  
Rachida Amzal ◽  
Alice Thébaut ◽  
Martine Lapalus ◽  
Marion Almes ◽  
Brigitte Grosse ◽  
...  
Keyword(s):  
Bile Salt ◽  
Premature Termination ◽  
In Vitro Study ◽  
Premature Termination Codon ◽  
Vitro Study ◽  
Termination Codon ◽  
Bile Salt Export Pump

scholarly journals Novel deep intronic mutation in the coagulation factor XIII a chain gene leading to unexpected RNA splicing in a patient with factor XIII deficiency

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Deng ◽  
Dan Li ◽  
Heng Mei ◽  
Liang Tang ◽  
Hua-fang Wang ◽  
...  
Keyword(s):  
Factor Xiii ◽  
Premature Termination ◽  
Coagulation Factor ◽  
Premature Termination Codon ◽  
Termination Codon ◽  
Chinese Family ◽  
Acceptor Site ◽  
Coagulation Factor Xiii ◽  
Fxiii Deficiency

Abstract Background Coagulation factor XIII (FXIII) plays an essential role in maintaining hemostasis by crosslinking fibrin. Deficiency in FXIII affects clot stability and increases the risk of severe bleeding. Congenital FXIII deficiency is a rare disease. Recently, we identified a Chinese family with FXIII deficiency and investigated the pathogenesis of congenital FXIII deficiency, contributing non-coding pathogenic variants. Methods We performed common tests, coding sequencing by targeted next-generation sequencing (NGS), whole-genome sequencing and splice-sites prediction algorithms. The pathogenesis was investigated via minigene and nonsense-mediated mRNA decay (NMD) by experiments in vitro. Results The proband is homozygote for a novel deep intronic c.799-12G > A mutation in the F13A1 gene. Through direct sequencing of the minigenes mRNA, we found 10 bases of intron 6 insert in the mRNA of mutant minigenes mRNA. The relative expression of EGFP-F13A1 was higher by suppression of NMD in vitro. Furthermore, we found the proband with enhanced thrombin generation (TG). Conclusion We reported a novel deep intronic c.799-12G > A mutation of F13A1 which produced a new acceptor site and frame shifting during translation introducing a premature termination codon. Our results support the premature termination codon triggered NMD. We need to pay attention to the position of potential alterable splicing sites while counselling and genetic test. The finding of enhanced TG indicated that we should be aware of the risk of thrombosis in patients with FXIII deficiency during replacement therapy.

scholarly journals An In Vitro Study of the Probiotic Potential of a Bile-Salt-Hydrolyzing Lactobacillus fermentum Strain, and Determination of Its Cholesterol-Lowering Properties

2003 ◽  
Vol 69 (8) ◽  
pp. 4743-4752 ◽  
Author(s):  
Dora I. A. Pereira ◽  
Anne L. McCartney ◽  
Glenn R. Gibson
Keyword(s):  
Bile Salt ◽  
Cholesterol Metabolism ◽  
In Vitro Study ◽  
Vitro Study ◽  
Lactobacillus Fermentum ◽  
Cholesterol Lowering ◽  
Major Mechanism ◽  
Probiotic Potential ◽  
Human Intestinal Microbiota

ABSTRACT This study evaluated the use of a bile-salt-hydrolyzing Lactobacillus fermentum strain as a probiotic with potential hypocholesterolemic properties. The effect of L. fermentum on representative microbial populations and overall metabolic activity of the human intestinal microbiota was investigated using a three-stage continuous culture system. Also, the use of galactooligosaccharides as a prebiotic to enhance growth and/or activity of the Lactobacillus strain was evaluated. Administration of L. fermentum resulted in a decrease in the overall bifidobacterial population (ca. 1 log unit). In the in vitro system, no significant changes were observed in the total bacterial, Lactobacillus, Bacteroides, and clostridial populations through L. fermentum supplementation. Acetate production decreased by 9 to 27%, while the propionate and butyrate concentrations increased considerably (50 to 90% and 52 to 157%, respectively). A general, although lesser, increase in the production of lactate was observed with the administration of the L. fermentum strain. Supplementation of the prebiotic to the culture medium did not cause statistically significant changes in either the numbers or the activity of the microbiota, although an increase in the butyrate production was seen (29 to 39%). Results from this in vitro study suggest that L. fermentum KC5b is a candidate probiotic which may affect cholesterol metabolism. The short-chain fatty acid concentrations, specifically the molar proportion of propionate and/or bile salt deconjugation, are probably the major mechanism involved in the purported cholesterol-lowering properties of this strain.

Bile salt-induced cytotoxicity and ursodeoxycholate cytoprotection: in-vitro study in perifused rat hepatocytes

1997 ◽  
Vol 9 (7) ◽  
pp. 703-709 ◽  
Author(s):  
Paolo Pazzi ◽  
Anna C. Puviani ◽  
Mauro Dalla Libera ◽  
Giovanni Guerra ◽  
Daniele Ricci ◽  
...  
Keyword(s):  
Bile Salt ◽  
In Vitro Study ◽  
Rat Hepatocytes ◽  
Vitro Study
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