Tauroursodeoxycholic acid (TUDCA) improves intestinal barrier function associated with TGR5-MLCK pathway and the alteration of serum metabolites and gut bacteria in weaned piglets

Journal of Animal Science and Biotechnology/Journal of animal science and biotechnology, Journal Year: 2022, Volume and Issue: 13(1)

Published: June 8, 2022

Tauroursodeoxycholic acid (TUDCA), a hydrophilic bile acid, is the main medicinal component of bear and commonly used to treat variety hepatobiliary diseases. Meanwhile, TUDCA has been shown modulate intestinal barrier function alleviate DSS-induced colitis in mice. However, effect on weaned piglets remains largely unclear.The porcine IPEC-J2 epithelial cells were investigate effects explore possible underlying mechanisms. In vivo, 72 healthy randomly allocated into 2 groups according their gender body weight, fed basal diet with 0 (control, CON) 200 mg/kg for 30 d, respectively. Three female three male reflecting average bodyweight slaughtered each group samples collected. vitro, subjected 100 μmol/L mechanisms.Our results demonstrated that dietary supplementation significantly reduced diarrhea incidence piglets, possibly attributing TUDCA-enhanced immunity. addition, altered serum metabolites relative abundance certain gut bacteria, which might contribute improved function. Furthermore, in-vitro showed E. coli-induced impairment increased Takeda G-coupled protein receptor 5 (TGR5) expression. knockdown TGR5 inhibition myosin light chain kinase (MLCK) pathway abolished TUDCA-improved coli-treated cells, indicating involvement TGR5-MLCK this process.These findings associated alteration bacteria suggesting potential application improving health piglet production.

Language: Английский

---

Integrative systems analysis identifies genetic and dietary modulators of bile acid homeostasis

Cell Metabolism, Journal Year: 2022, Volume and Issue: 34(10), P. 1594 - 1610.e4

Published: Sept. 12, 2022

Bile acids (BAs) are complex and incompletely understood enterohepatic-derived hormones that control whole-body metabolism. Here, we profiled postprandial BAs in the liver, feces, plasma of 360 chow- or high-fat-diet-fed BXD male mice demonstrated both genetics diet strongly influence BA abundance, composition, correlation with metabolic traits. Through an integrated systems approach, mapped hundreds quantitative trait loci modulate identified known unknown regulators homeostasis. In particular, discovered carboxylesterase 1c (Ces1c) as a genetic determinant tauroursodeoxycholic acid (TUDCA), species established disease-preventing actions. The association between Ces1c TUDCA was validated using data from independent mouse cohorts knockout model. Collectively, our unique resource to dissect physiological importance determinants traits, underscored by identification CES1C master regulator levels.

Language: Английский

---

A Review on Recent Advancement on Age-Related Hearing Loss: The Applications of Nanotechnology, Drug Pharmacology, and Biotechnology

Pharmaceutics, Journal Year: 2021, Volume and Issue: 13(7), P. 1041 - 1041

Published: July 8, 2021

Aging is considered a contributing factor to many diseases such as cardiovascular disease, Alzheimer’s and hearing loss. Age-related loss, also termed presbycusis, one of the most common sensory impairments worldwide, affecting in five people over 50 years age, this prevalence growing annually. Associations have emerged between presbycusis detrimental health outcomes, including social isolation mental health. It remains largely untreatable apart from aids, with no globally established prevention strategies clinical setting. Hence, review aims explore pathophysiology potential therapies, based on recent advancement bile acid-based bio-nanotechnologies. A comprehensive online search was carried out using following keywords: drugs, acids, nanotechnology, more than 150 publications were directly relevant. Evidence multifaceted oxidative stress chronic inflammation involvement cellular damage apoptosis that associated loss hair cells, damaged inflamed stria vascularis, neuronal signalling continues emerge. New robust effective therapies require drug delivery deeper into various layers cochlea. Bile nanotechnology has gained wide interest its permeation-enhancing ability for numerous applications treating presbycusis.

Language: Английский

---

Effects of PB‐TURSO on the transcriptional and metabolic landscape of sporadic ALS fibroblasts

Annals of Clinical and Translational Neurology, Journal Year: 2022, Volume and Issue: 9(10), P. 1551 - 1564

Published: Sept. 9, 2022

Abstract Objective ALS is a rapidly progressive, fatal disorder caused by motor neuron degeneration, for which there great unmet therapeutic need. AMX0035, combination of sodium phenylbutyrate (PB) and taurursodiol (TUDCA, TURSO), has shown promising results in early clinical trials, but its mechanisms action remain to be elucidated. Therefore, our goal was obtain an unbiased landscape the molecular effects AMX0035 patient‐derived cells. Methods We investigated transcriptomic metabolomic profiles primary skin fibroblasts from sporadic patients healthy controls ( n = 12/group) treated with PB, TUDCA, or PB–TUDCA (Combo). Data were evaluated multiple approaches including differential gene expression metabolite abundance, Gene Ontology metabolic pathway analysis, weighted co‐expression correlation analysis (WGCNA), combined multiomics integrated analysis. Results Combo changed many more genes metabolites than either PB TUDCA individually. Most changes unique affected involved nucleocytoplasmic transport, unfolded protein response, mitochondrial function, RNA metabolism, innate immunity. WGCNA showed significant correlations between modules parameters that abolished treatment. Interpretation This study first explore It shows greater distinct impact compared individual compounds provides clues drug targets action, may underlie benefits this investigational combination.

Language: Английский

---

Activation of the bile acid receptors TGR5 and FXR in the spinal dorsal horn alleviates neuropathic pain

CNS Neuroscience & Therapeutics, Journal Year: 2023, Volume and Issue: 29(7), P. 1981 - 1998

Published: March 7, 2023

Abstract Aims Beyond digestion, bile acids have been recognized as signaling molecules with broad paracrine and endocrine functions by activating plasma membrane receptor (Takeda G protein‐coupled 5, TGR5) the nuclear farnesoid X (FXR). The present study investigated role of in alleviating neuropathic pain TGR5 FXR. Method Neuropathic was induced spared nerve injury (SNI) sciatic nerve. or FXR agonist injected intrathecally. Pain hypersensitivity measured Von Frey test. amount detected using a acid assay kit. Western blotting immunohistochemistry were used to assess molecular changes. Results We found that downregulated, whereas expression cytochrome P450 cholesterol 7ahydroxylase (CYP7A1), rate‐limiting enzyme for synthesis, upregulated exclusively microglia spinal dorsal horn after SNI. Furthermore, receptors increased glial cells GABAergic neurons on day 7 Intrathecal injection either SNI alleviated established mechanical allodynia mice, effects blocked antagonist. Bile agonists inhibited activation ERK pathway horn. All above allodynia, cells, abolished intrathecal GABA A antagonist bicuculline. Conclusion These results suggest counteracts allodynia. effect mediated potentiating function receptors, which then neuronal sensitization

Language: Английский

---