المؤلفون: Koh, Cai Hong, Wu, Jianjun, Chung, Ying Ying, Liu, Zhenfeng, Zhang, Rong-Rong, Chong, Ketpin, Korzh, Vladimir, Ting, Sherwin, Oh, Steve, Shim, Winston, Tian, Hai-Yan, Wei, Heming

المصدر: Scientific Reports ; volume 7, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: A correction to this article has been published and is linked from the HTML version of this paper. The error has been fixed in the paper.

الإتاحة: https://doi.org/10.1038/s41598-017-09613-3Test
https://www.nature.com/articles/s41598-017-09613-3.pdfTest
https://www.nature.com/articles/s41598-017-09613-3Test

المؤلفون: Koh, Cai Hong, Wu, Jianjun, Chung, Ying Ying, Liu, Zhenfeng, Zhang, Rong-Rong, Chong, Ketpin, Korzh, Vladimir, Ting, Sherwin, Oh, Steve, Shim, Winston, Tian, Hai-Yan, Wei, Heming

المصدر: Scientific Reports ; volume 7, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: The current study explored the Na + /K + -ATPase (NKA) inhibition-independent proarrhythmic mechanisms of cardiac glycosides (CGs) which are well-known NKA inhibitors. With the cytosolic Ca 2+ chelated by EGTA and BAPTA or extracellular Ca 2+ replaced by Ba 2+ , effects of bufadienolides (bufalin (BF) and cinobufagin (CBG)) and cardenolides (ouabain (Oua) and pecilocerin A (PEA)) on the L-type calcium current ( I Ca,L ) were recorded in heterologous expression Cav1.2-CHO cells and human embryonic stem cell-derived cardiomyocytes (hESC-CMs). BF and CBG demonstrated a concentration-dependent (0.1 to 100 µM) I Ca,L inhibition (maximal ≥50%) without and with the NKA activity blocked by 10 µM Oua. BF significantly shortened the action potential duration at 1.0 µM and shortened the extracellular field potential duration at 0.01~1.0 µM. On the other hand, BF and CBG at 100 µM demonstrated a strong inhibition (≥40%) of the rapidly activating component of the delayed rectifier K + current ( I Kr ) in heterologous expression HEK293 cells and prolonged the APD of the heart of day-3 Zebrafish larva with disrupted rhythmic contractions. Moreover, hESC-CMs treated with BF (10 nM) for 24 hours showed moderate yet significant prolongation in APD90. In conclusion, our data indicate that CGs particularly bufadienolides possess cytosolic [Ca 2+ ] i - and NKA inhibition- independent proarrhythmic potential through I Ca,L and I Kr inhibitions.

الإتاحة: https://doi.org/10.1038/s41598-017-02496-4Test
https://www.nature.com/articles/s41598-017-02496-4Test
https://www.nature.com/articles/s41598-017-02496-4.pdfTest

المؤلفون: Tang, Hong-Jin, Ruan, Li-Jun, Tian, Hai-Yan, Liang, Guang-Ping, Ye, Wen-Cai, Hughes, Eleri, Esmann, Mikael, Fedosova, Natalya U., Chung, Tse-Yu, Tzen, Jason T. C., Jiang, Ren-Wang, Middleton, David A.

المصدر: Scientific Reports ; volume 6, issue 1 ; ISSN 2045-2322

مصطلحات موضوعية: Multidisciplinary

الوصف: Cardiotonic steroids (CTS) are clinically important drugs for the treatment of heart failure owing to their potent inhibition of cardiac Na + , K + -ATPase (NKA). Bufadienolides constitute one of the two major classes of CTS, but little is known about how they interact with NKA. We report a remarkable stereoselectivity of NKA inhibition by native 3β-hydroxy bufalin over the 3α-isomer, yet replacing the 3β-hydroxy group with larger polar groups in the same configuration enhances inhibitory potency. Binding of the two 13 C-labelled glycosyl diastereomers to NKA were studied by solid-state NMR (SSNMR), which revealed interactions of the glucose group of the 3β- derivative with the inhibitory site, but much weaker interactions of the 3α- derivative with the enzyme. Molecular docking simulations suggest that the polar 3β-groups are closer to the hydrophilic amino acid residues in the entrance of the ligand-binding pocket than those with α-configuration. These first insights into the stereoselective inhibition of NKA by bufadienolides highlight the important role of the hydrophilic moieties at C3 for binding, and may explain why only 3β-hydroxylated bufadienolides are present as a toxic chemical defence in toad venom.

الإتاحة: https://doi.org/10.1038/srep29155Test
https://www.nature.com/articles/srep29155.pdfTest
https://www.nature.com/articles/srep29155Test

المؤلفون: Jingyi Cai, Gang Tian, Bai Xue, Ding Xing Jin, Zhi Sheng Wang, Si Qiang Liu, Tian Hai Yan, Quan Hui Peng, De Wu, Hua Wei Zou, Li Zhi Wang

المصدر: Scientific Reports
Scientific Reports, Vol 8, Iss 1, Pp 1-15 (2018)

مصطلحات موضوعية: 0301 basic medicine, Firmicutes, lcsh:Medicine, Butyrate, Real-Time Polymerase Chain Reaction, Article, Microbiology, Caecum, 03 medical and health sciences, RNA, Ribosomal, 16S, medicine, Animals, Enteropathy, lcsh:Science, Alistipes, Phylogeny, Bifidobacterium, Multidisciplinary, Bacteria, biology, lcsh:R, High-Throughput Nucleotide Sequencing, Sequence Analysis, DNA, biology.organism_classification, medicine.disease, Small intestine, Gastrointestinal Microbiome, Intestinal Diseases, 030104 developmental biology, medicine.anatomical_structure, lcsh:Q, Rabbits, hormones, hormone substitutes, and hormone antagonists, Akkermansia muciniphila

الوصف: Epizootic rabbit enteropathy (ERE) is reproduced successfully in the present study by feeding rabbits a low-fibre diet, and high-throughput sequencing and quantitative real-time PCR (qPCR) analysis were applied to examine the microbial variations in the stomach, small intestine and caecum. The evenness was disturbed and the richness was decreased in the ERE groups. When the rabbits were suffering from ERE, the abundance of the Firmicutes was decreased in three parts of the digestive tract, whereas the Proteobacteria was increased in the stomach and caecum, the Bacteroidetes and Verrucomicrobia were increased in the small intestine. Correlation analysis showed that the reduced concentrations of TVFA and butyrate in the caeca of the ERE group were attributed to the decreased abundances of genera such as Lactobacillus, Alistipes and other fibrolytic bacteria and butyrate- producing bacteria such as Eubacterium and Faecalibacterium. It is concluded that, in terms of microorganisms, the overgrowth of Bacteroides fragilis, Clostridium perfringen, Enterobacter sakazakii and Akkermansia muciniphila and inhibition of Bifidobacterium spp. and Butyrivibrio fibrisolvens in the stomach, small intestine and caecum resulted in a decrease in butyrate yield, leading to the incidence of ERE, and the probability of developing ERE could be manipulated by adjusting the dietary fibre level.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::af06205ac9cce07dd10dec4cec14d051Test
https://doi.org/10.1038/s41598-018-30178-2Test