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Bile acid synthesis plays a key role in regulating whole body cholesterol homeostasis. Transcriptional factor EB (TFEB) is a nutrient and stress-sensing transcriptional factor that promotes lysosomal biogenesis. Here we report a role of TFEB in regulating hepatic bile acid synthesis. We show that TFEB induces cholesterol 7α-hydroxylase (CYP7A1) in human hepatocytes and mouse livers and prevents hepatic cholesterol accumulation and hypercholesterolemia in Western diet-fed mice. Furthermore, we find that cholesterol-induced lysosomal stress feed-forward activates TFEB via promoting TFEB nuclear translocation, while bile acid-induced fibroblast growth factor 19 (FGF19), acting via mTOR/ERK signaling and TFEB phosphorylation, feedback inhibits TFEB nuclear translocation in hepatocytes. Consistently, blocking intestinal bile acid uptake by an apical sodium-bile acid transporter (ASBT) inhibitor decreases ileal FGF15, enhances hepatic TFEB nuclear localization and improves cholesterol homeostasis in Western diet-fed mice. This study has identified a TFEB-mediated gut-liver signaling axis that regulates hepatic cholesterol and bile acid homeostasis., TFEB is a transcriptional regulator of lysosomal biogenesis, activated upon starvation or lysosomal stress. Here the authors report that TFEB regulates hepatic bile acid synthesis downstream of FGF19 signaling.

The present study aimed to determine the effects of cigarette smoke on the regulation of hepatic cytochrome P450 (CYP) and glutathione S-transferase (GST) enzymes in male BALB/c mice exposed to nose-only cigarette smoke for 4 days. There were no significant increases in serum liver injury markers (alanine aminotransferase and aspartate aminotransferase) or oxidative stress (total antioxidant capacity, malondialdehyde, and glutathione disulfide/reduced glutathione) following cigarette smoke exposure, but malondialdehyde was elevated in the bronchoalveolar lavage fluid of smoke-exposed mice. Additionally, the hepatic microsomal protein levels of Cyp1a and Cyp2b, and the activities of ethoxyresorufin O-deethylase, pentoxyresorufin O-depenylase, and chlorzoxazone 6-hydrxylase, were elevated in smoke-exposed mice. Interestingly, the hepatic activities of GST toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene, and ethacrynic acid, but not cumene hydroperoxide were enhanced by cigarette smoke exposure, which was consistent with the increased expression levels of mu- and pi-class GSTs, but not alpha-class GSTs, observed in immunoblot analyses. These findings indicate that the short-term inhalation of cigarette smoke induces drug-metabolizing enzymes such as CYP1A, CYP2B, and mu/pi-class GSTs in the absence of hepatic injury and oxidative stress. Furthermore, smoking may alter hepatic drug metabolism, as well as the disposition and toxicity of xenobiotics, including some therapeutic drugs and cigarette smoke constituents.

This is the first report of an analytical plasma in a polymer (polydimethylsiloxane, PDMS) microchip. The plasma channel has dimensions 2 mm diameter × 50 mm long, is operated at atmospheric pressure in Ar, 27.12 MHz and 70 W, and is viewed axially through a purged fiber optic cable. CF4 gas at 0.1% in argon yields mainly C2 emission bands. This PDMS microchip is manufactured easily, inexpensive, and more tolerant to fluorocarbons than microchip plasmas in silica. Based on these initial results, this PDMS microchip plasma could become useful as a sensor for the fluorocarbon gases emitted in semiconductor process or as a gas chromatography (GC) detector for potential application.

A typical electrothermal vaporization (ETV) using a tantalum was built for low-pressure ICP-AES. The analytical performance of the ETV was tested and compared with that of a PFA pneumatic nebulizer with a double membrane desolvator (DMD). The limits of detection of the ETV were obtained in the range of 3.4 ng to 758 ng for Zn, Cu, Co, Fe, and Mg, while those of the PFA nebulizer were in the range of 53 ppb to 286 ppb. A relative standard deviation (RSD) of 4.3 - 8.5% for ETV was obtained, while 2.15 - 6.84% RSD was found for DMD.