Mechanisms Driving Fasting-Induced Protection from Genotoxic Injury in the Small Intestine
Am J Physiol Gastrointest Liver Physiol. 2024 Feb 13. doi: 10.1152/ajpgi.00126.2023. Online ahead of print.ABSTRACTGenotoxic agents like doxorubicin (DXR) can cause damage to the intestines that can be ameliorated by fasting. How fasting is protective and the optimal timing of fasting and refeeding remain unclear. Here, our analysis of fasting/refeeding-induced global intestinal transcriptional changes revealed metabolic shifts and implicated the cellular energetic hub mTORC1 in protecting from DXR-induced DNA damage. Our analysis of specific transcripts and proteins in intestinal tissue and tissue extracts showed that fas...
Source: Am J Physiol Gastroi... - February 13, 2024 Category: Gastroenterology Authors: Kali Deans-Fielder Timothy Wu Thanh Nguyen Sarah To Yang-Zhe Huang Steven J Bark Jason C Mills Noah F Shroyer Source Type: research
A Mathematical Model of ENaC and Slc26a6 Regulation by CFTR in Salivary Gland Ducts
Am J Physiol Gastrointest Liver Physiol. 2024 Feb 13. doi: 10.1152/ajpgi.00168.2023. Online ahead of print.ABSTRACTCystic Fibrosis (CF) is a genetic disease caused by the mutations of CFTR, the cystic fibrosis transmembrane conductance regulator gene. Cftr is a critical ion channel expressed in the apical membrane of mouse salivary gland striated duct cells. Although Cftr is primarily a Cl- channel, its knockout leads to higher salivary Cl- and Na+concentrations and lower pH. Mouse experiments show that the activation of Cftr up-regulates ENaC (Epithelial Na+Channel) protein expression level and Slc26a6 (a 1Cl- : 2HCO3- ex...
Source: Am J Physiol Gastroi... - February 13, 2024 Category: Gastroenterology Authors: Shan Su Amanda Wahl John Rugis Vinod Suresh David Yule James Sneyd Source Type: research
Blueberry anthocyanins improve liver fibrosis by regulating NCOA4 ubiquitination through TRIM7 to affect ferroptosis of hepatic stellate cells
CONCLUSION: Our study discovered that anthocyanins could improve liver fibrosis by regulating NCOA4 ubiquitination through TRIM7, thereby affecting HSC ferroptosis levels.PMID:38290991 | DOI:10.1152/ajpgi.00227.2023 (Source: Am J Physiol Gastroi...)
Source: Am J Physiol Gastroi... - January 30, 2024 Category: Gastroenterology Authors: Likun Liu Jinhui Du Haiqing Fan Yue Yu Yilin Luo Fang Gu Hui Yu Xin Liao Source Type: research
Role of mechanoregulation in mast cell-mediated immune inflammation of the smooth muscle in pathophysiology of esophageal motility disorders
Am J Physiol Gastrointest Liver Physiol. 2024 Jan 30. doi: 10.1152/ajpgi.00258.2023. Online ahead of print.ABSTRACTMajor esophageal disorders involve obstructive transport of bolus to the stomach, causing symptoms of dysphagia and impaired clearing of the refluxed gastric contents. These may occur due to mechanical constriction of the esophageal lumen or loss of relaxation associated with deglutitive inhibition, as in achalasia-like disorders. Recently, immune inflammation has been identified as an important cause of esophageal strictures and the loss of inhibitory neurotransmission. These disorders are also associated wit...
Source: Am J Physiol Gastroi... - January 30, 2024 Category: Gastroenterology Authors: Raj K Goyal Satish Rattan Source Type: research
NADPH oxidase 1 promotes hepatic steatosis in obese mice and is abrogated by augmented skeletal muscle mass
Conclusion: Taken together, these data suggest hypermuscularity attenuates Srebp1 expression in db/db mice through a NOX1-dependent mechanism.PMID:38258487 | DOI:10.1152/ajpgi.00153.2023 (Source: Am J Physiol Gastroi...)
Source: Am J Physiol Gastroi... - January 23, 2024 Category: Gastroenterology Authors: Sebastian Larion Caleb A Padgett James D Mintz Jennifer A Thompson Joshua T Butcher Eric J Belin de Chantem èle Stephen Haigh Sandeep Khurana David J Fulton David W Stepp Source Type: research
Gastrointestinal dysmotility in rodent models of Parkinson's disease
Am J Physiol Gastrointest Liver Physiol. 2024 Jan 23. doi: 10.1152/ajpgi.00225.2023. Online ahead of print.ABSTRACTMultiple studies describe prodromal, non-motor dysfunctions that affect the quality of life of patients who subsequently develop Parkinson's disease (PD). These prodromal dysfunctions comprise a wide array of autonomic issues, including severe gastrointestinal (GI) motility disorders such as dysphagia, delayed gastric emptying and chronic constipation. Indeed, strong evidence from studies in humans and in animal models suggests that the GI tract and its neural, mainly vagal, connection to the central nervous s...
Source: Am J Physiol Gastroi... - January 23, 2024 Category: Gastroenterology Authors: Carolina Pellegrini R Alberto Travagli Source Type: research
Inhibition of visceral adipose tissue-derived pathogenic signals by activation of adenosine A < sub > 2A < /sub > R improves hepatic and cardiac dysfunction of NASH mice
This study explores the effects of four-weeks A2AR agonist PSB0777 treatment on the VAT-driven pathogenic signals in hepatic and cardiac dysfunction of non-alcoholic steatohepatitis (NASH) obese mice. Among NASH mice with cardiac dysfunction, simultaneous decrease in the A2AR、AC、cAMP and PKA levels were observed in VAT, liver, and heart. PSB0777 treatment significantly restores AC、cAMP, PKA, HSL levels, decreased SREBP-1/FASN, MCP-1 and CD68 levels, reduces infiltrated CD11b+F4/80+ cells and adipogenesis in VAT of NASH+PSB0777 mice. The changes in VAT were accompanied by the suppression of hepatic and cardiac lipogen...
Source: Am J Physiol Gastroi... - January 22, 2024 Category: Gastroenterology Authors: Chia-Chang Huang Hsiao-Yun Yeh Roger Lin Tsai-Ling Liao Hsiao-Chin Shen Ying-Ying Yang Han-Chieh Lin Source Type: research
NHE3 inhibitor tenapanor maintains intestinal barrier function, decreases visceral hypersensitivity, and attenuates TRPV1 signaling in colonic sensory neurons
Am J Physiol Gastrointest Liver Physiol. 2024 Jan 22. doi: 10.1152/ajpgi.00233.2023. Online ahead of print.ABSTRACTThe pathogenesis of irritable bowel syndrome (IBS) is multifactorial, characterized in part by increased intestinal permeability and visceral hypersensitivity. Increased permeability is associated with IBS severity and abdominal pain. Tenapanor is FDA-approved for the treatment of IBS with constipation (IBS-C) and has demonstrated improvements in bowel motility and a reduction in IBS-related pain; however, the mechanism by which tenapanor mediates these functions remains unclear. Here, the effects of tenapanor...
Source: Am J Physiol Gastroi... - January 22, 2024 Category: Gastroenterology Authors: Andrew J King Lin Chang Qian Li Liansheng Liu Yaohui Zhu Pankaj J Pasricha Ji Wang Matthew Siegel Jeremy S Caldwell Susan Edelstein David P Rosenbaum Kenji Kozuka Source Type: research
Implicating the Cholecystokinin B Receptor in Liver Stem Cell Oncogenesis
Am J Physiol Gastrointest Liver Physiol. 2024 Jan 22. doi: 10.1152/ajpgi.00208.2023. Online ahead of print.ABSTRACTHepatocellular carcinoma (HCC) is the fastest growing cause of cancer-related deaths worldwide. Chronic inflammation and fibrosis are the greatest risk factors for the development of HCC. Although the cell of origin for HCC is uncertain, many theories believe this cancer may arise from liver progenitor cells or stem cells. Here, we describe the activation of hepatic stem cells that over-express the cholecystokinin-B receptor (CCK-BR) after liver injury with either a DDC diet (0.1% 3, 5-diethoxy-carbonyl 1,4-di...
Source: Am J Physiol Gastroi... - January 22, 2024 Category: Gastroenterology Authors: Martha D Gay Jack C Drda Wenqiang Chen Yimeng Huang Amal A Yassin Tetyana Duka Hongbin Fang Narayan Shivapurkar Jill P Smith Source Type: research
A functional interplay between the two BMP-SMAD pathway inhibitors TMPRSS6 and FKBP12 regulates < em > hepcidin < /em > expression < em > in vivo < /em >
Am J Physiol Gastrointest Liver Physiol. 2024 Jan 22. doi: 10.1152/ajpgi.00305.2023. Online ahead of print.ABSTRACTThe Activin A Receptor type I ALK2 is a critical component of the BMP-SMAD signaling that, in the presence of ligands, phosphorylates cytosolic SMAD1/5/8 and modulates important biological processes, including bone formation and iron metabolism. In hepatocytes, the BMP-SMAD pathway controls the expression of hepcidin, the liver peptide hormone that regulates body iron homeostasis via the BMP receptors ALK2 and ALK3, and the hemochromatosis proteins. The main negative regulator of the pathway in the liver is th...
Source: Am J Physiol Gastroi... - January 22, 2024 Category: Gastroenterology Authors: Mariateresa Pettinato Mariam Aghajan Shuling Guo Letizia Bavuso Volpe Rossana Carleo Antonella Nai Alessia Pagani Sandro Altamura Laura Silvestri Source Type: research
Short-term and long-term effects of unilateral external carotid artery ligation on orofacial functions in rats
This study was performed to investigate the effects of ECA ligation (ECAL) on immediate and long-term changes in masticatory and swallowing functions as well as the jaw-opening reflex evoked in the digastric muscle. The experiments were carried out using male Sprague-Dawley rats. In the acute experiment, the digastric reflex evoked by low-threshold electrical stimulation of the inferior alveolar nerve and the swallow reflex, identified by digastric and thyrohyoid electromyographic (EMG) bursts, were compared between before and 1 hour after ECAL. The chronic experiment was conducted on freely moving rats. EMGs of the masset...
Source: Am J Physiol Gastroi... - January 16, 2024 Category: Gastroenterology Authors: Titi Chotirungsan Yuhei Tsutsui Nobuaki Saka Satomi Kawada Nozomi Dewa Jin Magara Takanori Tsujimura Makoto Inoue Source Type: research
A ganglionic intestino-intestinal reflex activated by acute noxious challenge
Am J Physiol Gastrointest Liver Physiol. 2024 Jan 16. doi: 10.1152/ajpgi.00145.2023. Online ahead of print.ABSTRACTTo investigate noxious stimulation- responsive neural circuits that could influence the gut, we recorded from intestinally directed (efferent) nerve filaments dissected from mesenteric nerves close to the small intestine in anaesthetized rats. These exhibited baseline multiunit activity that was almost unaffected by vagotomy and reduced only slightly by cutting the splanchnic nerves. The activity was halved by hexamethonium treatment. When an adjacent gut segment received an intraluminal stimulus, 2,4,6-trinit...
Source: Am J Physiol Gastroi... - January 16, 2024 Category: Gastroenterology Authors: Martin J Stebbing Anthony D Shafton Catherine E Davey Madeleine R DiNatale John B Furness Robin M McAllen Source Type: research
Characterisation of Mitochondria-associated ER membranes in the enteric nervous system under physiological and pathological conditions
Am J Physiol Gastrointest Liver Physiol. 2024 Jan 16. doi: 10.1152/ajpgi.00224.2023. Online ahead of print.ABSTRACTAlterations in endoplasmic reticulum-mitochondria associations and in mitochondria-associated ER membrane (MAM) behaviour have been reported in the brain in several neurodegenerative diseases. Despite the emerging role of the gut-brain axis in neurodegenerative disorders, the biology of MAM in the enteric nervous system (ENS) has not previously been studied. Therefore, we set out to characterise the MAM in the distal colon of wild type C57BL/6J mice and in senescence accelerated mouse prone 8 (SAMP8), a mouse ...
Source: Am J Physiol Gastroi... - January 16, 2024 Category: Gastroenterology Authors: Giada Delfino Jean Baptiste Briand Thibauld Oullier L éa Nienkemper Jenny Greig Jo ëlle Véziers Michel Neunlist Pascal Derkinderen Sebastien Paillusson Source Type: research
Morphological, molecular, and functional characterization of mouse glutamatergic myenteric neurons
In conclusion, VGLUT2-ENs are a functionally unique group of enteric neurons with single aborally projecting long axons that traverse multiple myenteric ganglia and are activated indirectly by colorectal mechanical stretch. This knowledge will provide a solid foundation for subsequent studies on the potential interactions of VGLUT2-EN with extrinsic colorectal afferents via glutamatergic neurotransmission.PMID:38193160 | DOI:10.1152/ajpgi.00200.2023 (Source: Am J Physiol Gastroi...)
Source: Am J Physiol Gastroi... - January 9, 2024 Category: Gastroenterology Authors: Jia Liu Shaopeng Zhang Sharareh Emadi Tiantian Guo Longtu Chen Bin Feng Source Type: research
Comparison of etiologic and physiologic characteristics of fecal incontinence in men and women
CONCLUSIONS: Significantly different etiologic factors and physiologic characteristics for FI were found in men. Acknowledging these differences is significant and may yield better treatment options.PMID:38193161 | DOI:10.1152/ajpgi.00113.2023 (Source: Am J Physiol Gastroi...)
Source: Am J Physiol Gastroi... - January 9, 2024 Category: Gastroenterology Authors: Reuma Margalit-Yehuda Carla Maradey-Romero Yana Davidov Edward Ram Dan Carter Source Type: research
