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A metabolic illness known as non-alcoholic fatty liver disease (NAFLD), affects more than one-quarter of the world's population. Bile acids (BAs), as detergents involved in lipid digestion, show an abnormal metabolism in patients with NAFLD. However, BAs can affect other organs as well, such as the brain, where it has a neuroprotective effect. According to a series of studies, brain disorders may be extrahepatic manifestations of NAFLD, such as depression, changes to the cerebrovascular system, and worsening cognitive ability. Consequently, we propose that NAFLD affects the development of brain disease, through the bile acid signaling pathway. Through direct or indirect channels, BAs can send messages to the brain. Some BAs may operate directly on the central Farnesoid X receptor (FXR) and the G protein bile acid-activated receptor 1 (GPBAR1) by overcoming the blood–brain barrier (BBB). Furthermore, glucagon-like peptide-1 (GLP-1) and the fibroblast growth factor (FGF) 19 are released from the intestine FXR and GPBAR1 receptors, upon activation, both of which send signals to the brain. Inflammatory, systemic metabolic disorders in the liver and brain are regulated by the bile acid-activated receptors FXR and GPBAR1, which are potential therapeutic targets. From a bile acid viewpoint, we examine the bile acid signaling changes in NAFLD and brain disease. We also recommend the development of dual GPBAR1/FXR ligands to reduce side effects and manage NAFLD and brain disease efficiently. [ABSTRACT FROM AUTHOR]

(1) Background: Open, laparoscopic, and endoscopic choledocholithotomy (OC, LC, and EC, respectively) are accepted choledocholithiasis treatment modalities. However, an assessment of the nationwide trends in their outcomes is lacking. This nationwide population-based analysis evaluated treatment outcomes of choledocholithiasis in Taiwan; (2) Methods: A total of 13,139,306 individuals were randomly enrolled from the Longitudinal Health Insurance Database (LHID) between 2000 to 2013 for cohort analysis. All patients with newly diagnosed choledocholithiasis aged 18 years or older who were treated during the study period were enrolled and allocated to the OC, LC, EC, or combined endoscopy and open choledocholithotomy (CEOC) groups. Age, readmission, retained stone, comorbidities, hospital stay, medical cost, complications, mortality were analyzed; (3) Results: A total of 58,064 individuals met the inclusion criteria, including 46.54%, 1.10%, 47.52%, and 4.85% who underwent OC, LC, EC, and CEOC, respectively. The endpoint characteristics showed that the LC group had higher readmission, longer hospital stay, and higher medical cost. Cox regression analysis showed that the adjusted hazard ratio (HR) of complications for EC was 1.259 times higher than that for OC. The adjusted HRs of readmission within 90 days for LC, EC, and CEOC were higher than that of OC. The adjusted HR of retreatment with surgery was higher in LC. The adjusted HR of retreatment with endoscopy was higher in CEOC. The adjusted HR of mortality in EC was 1.603 times that of OC; (4) Conclusions: Different choledocholithiasis treatments lead to different outcomes. However, further studies on other large or national data sets are required to support these findings. [ABSTRACT FROM AUTHOR]

Transforming growth factor (TGF)-β1, a cytokine that can be expressed in the brain, is a key regulator of the brain's responses to injury and inflammation. Alzheimer's disease (AD), the most common neurodegenerative disorder, involves inflammatory processes in the brain in addition to the hallmarks, amyloid-β (Aβ) plaques and neurofibrillary tangles. Recently, we have shown that T-helper (Th) 17 cells, a subpopulation of CD4+ T-cells with high proinflammation, also participate in the brain inflammatory process of AD. However, it is poorly known whether TGF-β1 ameliorates the lymphocyte-mediated neuroinflammation and, thereby, alleviates neurodegeneration in AD. Herein, we administered TGF-β1 via the intracerebroventricle (ICV) in AD model rats, by Aβ1-42 injection in both sides of the hippocampus, to show the neuroprotection of TGF-β1. The TGF-β1 administration after the Aβ1-42 injection ameliorated cognitive deficit and neuronal loss and apoptosis, reduced amyloid precursor protein (APP) expression, elevated protein phosphatase (PP)2A expression, attenuated glial activation and alleviated the imbalance of the pro-inflammatory/anti-inflammatory responses of T-lymphocytes, compared to the Aβ1-42 injection alone. These findings demonstrate that TGF-β1 provides protection against AD neurodegeneration and suggest that the TGF-β1 neuroprotection is implemented by the alleviation of glial and T-cell-mediated neuroinflammation.