Bile, important for cholesterol homeostasis, is a potential target of hypercholesterolemia management. Bile sequestration by orally administered resins, while mostly effective in reducing blood cholesterol, presents several side effects and disadvantages. Thus, widely available natural edible minerals such as clinoptilolite with adsorptive properties offer an alternative for bile sequestration. In an experimental setting mimicking the physiological conditions of digestion/absorption (pH, temperature, and retention times) with a series of assessment methods, scanning electron microscopy-energy dispersion X-ray analysis (SEM-EDX), X-ray diffraction (XRD), Fourier transform infrared analysis (FT-IR), thermogravimetric differential thermal analysis (TG-DTA), and molecular docking modeling, the ability of natural unmodified clinoptilolite to retain bile, while mixed with a simulated high-fat meal, was investigated. Our results demonstrate that clinoptilolite sequesters bile via adsorption of macromicelles at 75.4% efficiency, when the former is administered at a reasonable dose of 4% (w/w) of a meal's weight. This work provides the possibility of clinoptilolite utilization as a bile-sequestering/cholesterol-reducing agent.
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Am J Physiol Gastrointest Liver Physiol
September 2024
Department of Biomedical Engineering, Medical College of Wisconsin, Milwaukee, Wisconsin, United States.
Ischemia-reperfusion injury (IRI) is an intrinsic risk associated with liver transplantation. Ex vivo hepatic machine perfusion (MP) is an emerging organ preservation technique that can mitigate IRI, especially in livers subjected to prolonged warm ischemia time (WIT). However, a method to quantify the biological response to WIT during MP has not been established.
View Article and Find Full Text PDFLangmuir
March 2024
Department of Chemistry, Indian Institute of Science Education and Research Bhopal, Bhopal Bypass Road, Bhopal 462 066, Madhya Pradesh, India.
Conformational changes play a seminal role in modulating the activity of proteins. This concept becomes all the more relevant in the context of metalloproteins, owing to the formation of specific conformation(s) induced by internal perturbations (like a change in pH, ligand binding, or receptor binding), which may carry out the binding and release of the metal ion/ions from the metal binding center of the protein. Herein, we investigated the conformational changes of an iron-binding protein, monoferric human serum transferrin (Fe-hTF), using several spectroscopic approaches.
View Article and Find Full Text PDFSci Transl Med
January 2024
Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Environmental enteric dysfunction (EED) is a diffuse small bowel disorder associated with poor growth, inadequate responses to oral vaccines, and nutrient malabsorption in millions of children worldwide. We identify loss of the small intestinal Paneth and goblet cells that are critical for innate immunity, reduced villous height, increased bile acids, and dysregulated nicotinamide adenine dinucleotide (NAD) synthesis signaling as potential mechanisms underlying EED and which also correlated with diminished length-for-age score. Isocaloric low-protein diet (LPD) consumption in mice recapitulated EED histopathology and transcriptomic changes in a microbiota-independent manner, as well as increases in serum and fecal bile acids.
View Article and Find Full Text PDFJ Agric Food Chem
January 2024
Laboratory of Food Proteins and Colloids, School of Food Science and Engineering, Guangdong Province Key Laboratory for Green Processing of Natural Products and Product Safety, South China University of Technology, Guangzhou 510640, China.
Soy protein is widely known to have serum triglyceride (TG) and cholesterol-lowering effects associated with a reduced risk of cardiovascular disease. Recent studies highlighted that the extension region (ER) domain of soy 7S globulin (β-conglycinin) is a key component responsible for the serum TG-lowering effect via modulation of bile acid (BA) homeostasis. Here, we studied the sequestration of BAs by ER peptides during intestinal digestion and assessed the anti-inflammatory effects of ER peptides using Caco-2/HT29-MTX/RAW264.
View Article and Find Full Text PDFAm J Physiol Gastrointest Liver Physiol
January 2024
Department of Pediatrics and Steele Children's Research Center, University of Arizona, Tucson, Arizona, United States.
Necrotizing enterocolitis (NEC) is the most common gastrointestinal emergency in premature infants. Evidence indicates that bile acid homeostasis is disrupted during NEC: ileal bile acid levels are elevated in animals with experimental NEC, as is expression of the apical sodium-dependent bile acid transporter (Asbt). In addition, bile acids, which are synthesized in the liver, are extensively modified by the gut microbiome, including via the conversion of primary bile acids to more cytotoxic secondary forms.
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