Aldehydes alter TGF-β signaling and induce obesity and cancer.

Obesity and fatty liver diseases-metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic dysfunction-associated steatohepatitis (MASH)-affect over one-third of the global population and are exacerbated in individuals with reduced functional aldehyde dehydrogenase 2 (ALDH2), observed in approximately 560 million people. Current treatment to prevent disease progression to cancer remains inadequate, requiring innovative approaches. We observe that Aldh2 and Aldh2Sptbn1 mice develop phenotypes of human metabolic syndrome (MetS) and MASH with accumulation of endogenous aldehydes such as 4-hydroxynonenal (4-HNE).

Impaired reciprocal regulation between SIRT6 and TGF-β signaling in fatty liver.

Dysregulated transforming growth factor-beta (TGF-β) signaling contributes to fibrotic liver disease and hepatocellular cancer (HCC), both of which are associated with fatty liver disease. SIRT6 limits fibrosis by inhibiting TGF-β signaling through deacetylating SMAD2 and SMAD3 and limits lipogenesis by inhibiting SREBP1 and SREBP2 activity. Here, we showed that, compared to wild-type mice, high-fat diet-induced fatty liver is worse in TGF-β signaling-deficient mice (SPTBN1 ) and the mutant mice had reduced SIRT6 abundance in the liver.

Digital cholangioscopy can detect residual biliary stones missed by occlusion cholangiogram in ERCP: a prospective tandem study.

After stone removal in endoscopic retrograde cholangiopancreatography (ERCP), an occlusion cholangiogram (OC) is performed to confirm bile duct clearance. OC can miss residual stones that can lead to recurrent biliary symptoms. The aim of this study was to assess if digital peroral cholangioscopy (POC) increased the diagnostic yield of residual biliary stones that are missed with OC.

Incremental yield of dysplasia detection in Barrett's esophagus using volumetric laser endomicroscopy with and without laser marking compared with a standardized random biopsy protocol.

Background And Aims: Volumetric laser endomicroscopy (VLE) is a new wide-field advanced imaging technology for Barrett's esophagus (BE). No data exist on incremental yield of dysplasia detection. Our aim is to report the incremental yield of dysplasia detection in BE using VLE.

Defective mucosal movement at the gastroesophageal junction in patients with gastroesophageal reflux disease.

Background: Little is known about the role of muscularis mucosa at the gastroesophageal junction (GEJ).

Aim: To evaluate the movement of the mucosa/muscularis-mucosa/submucosa (MMS) at the GEJ in normal subjects and in patients with gastroesophageal reflux disease (GERD).

Methods: Gastroesophageal junctions of 20 non-GERD subjects and 10 patients with GERD were evaluated during 5 mL swallows using two methods: in high-resolution endoluminal ultrasound and manometry, the change in the GEJ luminal pressures and cross-sectional area of esophageal wall layers were measured; in abdominal ultrasound, the MMS movement at the GEJ was analyzed.

Ileocecal valve dysfunction in small intestinal bacterial overgrowth: a pilot study.

Aim: To explore whether patients with a defective ileocecal valve (ICV)/cecal distension reflex have small intestinal bacterial overgrowth.

Methods: Using a colonoscope, under conscious sedation, the ICV was intubated and the colonoscope was placed within the terminal ileum (TI). A manometry catheter with 4 pressure channels, spaced 1 cm apart, was passed through the biopsy channel of the colonoscope into the TI.

Circular smooth muscle contributes to esophageal shortening during peristalsis.

Aim: To study the angle between the circular smooth muscle (CSM) and longitudinal smooth muscle (LSM) fibers in the distal esophagus.

Methods: In order to identify possible mechanisms for greater shortening in the distal compared to proximal esophagus during peristalsis, the angles between the LSM and CSM layers were measured in 9 cadavers. The outer longitudinal layer of the muscularis propria was exposed after stripping the outer serosa.

The esophagogastric junction.

The following discussion of the esophagogastric junctions includes commentaries on the three component structures of the sphincteric segment between the stomach and the esophagus; the pressure contributions from the three sphincteric components in normal subjects and in gastroesophageal reflux (GERD) patients; the mechanism of action of endoscopic plication to determine the underlying pathophysiology of GERD; and in vitro muscle strip studies of defects within the gastroesophageal sphincteric segment potentially leading to GERD.

Pharmacologic specificity of nicotinic receptor-mediated relaxation of muscarinic receptor precontracted human gastric clasp and sling muscle fibers within the gastroesophageal junction.

Relaxation of gastric clasp and sling muscle fibers is involved the transient lower esophageal sphincter relaxations underlying the pathophysiology of gastroesophageal reflux disease (GERD). These fibers do not contribute tone to the high-pressure zone in GERD patients, indicating their role in pathophysiology. This study identifies some mediators of the nicotine-induced relaxation of muscarinic receptor precontracted gastric clasp and sling fibers.

Comparison of human and porcine gastric clasp and sling fiber contraction by M2 and M3 muscarinic receptors.

To compare the gastroesophageal junction of the human with the pig, M(2) and M(3) receptor densities and the potencies of M(2) and M(3) muscarinic receptor subtype selective antagonists were determined in gastric clasp and sling smooth muscle fibers. Total muscarinic and M(2) receptors are higher in pig than human clasp and sling fibers. M(3) receptors are higher in human compared with pig sling fibers but lower in human compared with pig clasp fibers.

Minimally invasive measurement of esophageal variceal pressure and wall tension (with video).

Background: There is no simple method to measure intravariceal pressure in patients with esophageal varices.

Objective: Our purpose was to develop a new noninvasive technique to measure resting intravariceal pressure and wall tension.

Design: A model was developed.

Quantitation of the contractile response mediated by two receptors: M2 and M3 muscarinic receptor-mediated contractions of human gastroesophageal smooth muscle.

Although muscarinic receptors are known to mediate tonic contraction of human gastrointestinal tract smooth muscle, the receptor subtypes that mediate the tonic contractions are not entirely clear. Whole human stomachs with attached esophagus were procured from organ transplant donors. Cholinergic contractile responses of clasp, sling, lower esophageal circular (LEC), midesophageal circular (MEC), and midesophageal longitudinal (MEL) muscle strips were determined.