Bile Salt
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2021 ◽  
Vol 8 ◽  
Zeyu Sun ◽  
Chenjie Huang ◽  
Yixian Shi ◽  
Rusha Wang ◽  
Jun Fan ◽  

Hepatitis B virus (HBV) can hijack the host bile acids (BAs) metabolic pathway during infection in cell and animal models. Additionally, microbiome was known to play critical role in the enterohepatic cycle of BAs. However, the impact of HBV infection and associated gut microbiota on the BA metabolism in chronic hepatitis B (CHB) patients is unknown. This study aimed to unveil the distinct BA profiles in chronic HBV infection (CHB) patients with no or mild hepatic injury, and to explore the relationship between HBV, microbiome and BA metabolism with clinical implications.Methods: Serum BA profiles were compared between CHB patients with normal ALT (CHB-NALT, n = 92), with abnormal ALT (CHB-AALT, n = 34) and healthy controls (HCs, n = 28) using UPLC-MS measurement. Hepatic gene expression in CHB patients were explored using previously published transcriptomic data. Fecal microbiome was compared between 30 CHB-NALT and 30 HCs using 16S rRNA sequencing, and key microbial function was predicted by PICRUSt analysis.Results: Significant higher percentage of conjugated BAs and primary BAs was found in CHB patients even without apparent liver injury. Combinatory BA features can discriminate CHB patients and HCs with high accuracy (AUC = 0.838). Up-regulation of BA importer Na+ taurocholate co-transporting peptide (NTCP) and down-regulation of bile salt export pump (BSEP) was found in CHB-NALT patients. The microbial diversity and abundance of Lactobacillus, Clostridium, Bifidobacterium were lower in CHB-NALT patients compared to healthy controls. Suppressed microbial bile salt hydrolases (BSH), 7-alpha-hydroxysteroid dehydrogenase (hdhA) and 3-dehydro-bile acid Delta 4, 6-reductase (BaiN) activity were found in CHB-NALT patients.Conclusion: This study provides new insight into the BA metabolism influenced both by HBV infection and associated gut microbiome modulations, and may lead to novel strategy for clinical management for chronic HBV infection.

2021 ◽  
Vol 14 (10) ◽  
pp. 1021
Islam Zaki ◽  
Reham A. I. Abou-Elkhair ◽  
Ali H. Abu Almaaty ◽  
Ola A. Abu Ali ◽  
Eman Fayad ◽  

Cancer is a multifaceted disease. With the development of multi drug resistance, the need for the arousal of novel targets in order to avoid these drawbacks increased. A new series of acrylamide derivatives was synthesized from starting material 4–(furan–2–ylmethylene)–2–(3,4,5–trimethoxyphenyl)oxazol–5(4H)–one (1), and they are evaluated for their inhibitory activity against b-tubulin polymerization. The target molecules 2–5 d were screened for their cytotoxic activity against breast cancer MCF-7 cell line. The results of cytotoxicity screening revealed that compounds 4e and 5d showed good cytotoxic profile against MCF-7 cells. Compounds 4e produced significant reduction in cellular tubulin with excellent b-tubulin polymerization inhibition activity. In addition, compound 4e exhibited cytotoxic activity against MCF-7 cells by cell cycle arrest at pre-G1 and G2/M phases, as shown by DNA flow cytometry assay. Aiming to enhance the limited aqueous solubility and, hence, poor oral bioavailability of the prepared lead acrylamide molecule, 4e-charged PEGylated bilosomes were successfully fabricated via thin film hydration techniques as an attempt to improve these pitfalls. Twenty-three full factorial designs were manipulated to examine the influence of formulation variables: types of bile salt including either sodium deoxy cholate (SDC) or sodium tauro cholate (STC), amount of bile salt (15 mg or 30 mg) and amount of DSPE–mPEG-2000 amount (25 mg or 50 mg) on the characteristics of the nanosystem. The F7 formula of entrapment efficiency (E.E% = 100 ± 5.6%), particle size (PS = 280.3 ± 15.4 nm) and zeta potential (ZP = −22.5 ± 3.4 mv) was picked as an optimum formula with a desirability value of 0.868. Moreover, prominent enhancement was observed at the compound’s cytotoxic activity (IC50 = 0.75 ± 0.03 µM) instead of (IC50 = 2.11 ± 0.19 µM) for the unformulated 4e after being included in the nano-PEGylated bilosomal system.

2021 ◽  
Vol 9 (10) ◽  
pp. 2038
Qiqi Pan ◽  
Xudan Shen ◽  
Leilei Yu ◽  
Fengwei Tian ◽  
Jianxin Zhao ◽  

Lactobacillus salivarius has drawn attention because of its promising probiotic functions. Tolerance to the gastrointestinal tract condition is crucial for orally administrated probiotics to exert their functions. However, previous studies of L. salivarius have only focused on the bile salt resistance of particular strains, without uncovering the common molecular mechanisms of this species. Therefore, in this study, we expanded our research to 90 L. salivarius strains to explore their common functional genes for bile salt resistance. First, the survival rates of the 90 L. salivarius strains in 0.3% bile salt solutions were determined. Comparative genomics analysis was then performed to screen for the potential functional genes related to bile salt tolerance. Next, real-time polymerase chain reaction and gene knockout experiments were conducted to further verify the tolerance-related functional genes. The results indicated that the strain-dependent bile salt tolerance of L. salivarius was mainly associated with four peptidoglycan synthesis-related genes, seven phosphotransferase system-related genes, and one chaperone-encoding gene involved in the stress response. Among them, the GATase1-encoding gene showed the most significant association with bile salt tolerance. In addition, four genes related to DNA damage repair and substance transport were redundant in the strains with high bile salt tolerance. Besides, cluster analysis showed that bile salt hydrolases did not contribute to the bile salt tolerance of L. salivarius. In this study, we determined the global regulatory genes, including LSL_1568, LSL_1716 and LSL_1709, for bile salt tolerance in L. salivarius and provided a potential method for the rapid screening of bile salt-tolerant L. salivarius strains, based on PCR amplification of functional genes.

Tchamba Mbiada Mervie Noël ◽  
Bouba Adji Mohammadou ◽  
Nodem Shanang Francky Steve ◽  
Léopold Ngoune Tatsadjieu ◽  
Mbarga Manga Joseph Arsene ◽  

Background and Aim: Lactic acid bacteria (LAB) became a field of interest by scientists in recent years due to their technological and probiotic properties. The aim of this work was to study the technological and probiotic properties of LAB isolated from the bottle gourds (calabashes)of milk fermentation, in Mbéré, Cameroun. Methods: Five different bottle gourds from milk fermentation were collected and used for LAB isolation. These LABs were characterized using conventional cultural method, the technological (such as proteolytic, lipolytic activities) and probiotic properties (including acid and bile salt tolerance, cholesterol assimilation and antioxidant activities) were assessed. Results: From these samples, 30 LABs were isolated and among them, 21 exhibited great lipolytic and proteolytic activities with the maximum values of 18 and 29 mm respectively. In addition, 10 LAB isolates showed interesting antimicrobial activity against pathogens germs tested and good tolerance ability under acid and bile salt stress after 24h of incubation. Cholesterol assimilation and antioxidant tests revealed that isolated BC4 and BC3 have the greatest activity (35 and 39 mm respectively) while, BC4 and BL4 have the greatest antioxidant activity (IC50 = 0,15 and 0,13 respectively). Conclusion: LAB isolated from the bottle gourds (calabashes) of milk fermentation, in Mbéré, Cameroon can be used to develop dairy industry and manage the cardiovascular diseases.

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