American journal of physiology. Gastrointestinal and liver physiology最新文献

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Simultaneous optical imaging of gastric slow waves and contractions in the in vivo porcine stomach. 体内猪胃慢波和收缩的同步光学成像
IF 4.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-08-27 DOI: 10.1152/ajpgi.00033.2024
Haley N Patton, Hanyu Zhang, Garrett A Wood, Bijay Guragain, Nipuni D Nagahawatte, Linley A Nisbet, Leo K Cheng, Gregory P Walcott, Jack M Rogers
{"title":"Simultaneous optical imaging of gastric slow waves and contractions in the in vivo porcine stomach.","authors":"Haley N Patton, Hanyu Zhang, Garrett A Wood, Bijay Guragain, Nipuni D Nagahawatte, Linley A Nisbet, Leo K Cheng, Gregory P Walcott, Jack M Rogers","doi":"10.1152/ajpgi.00033.2024","DOIUrl":"10.1152/ajpgi.00033.2024","url":null,"abstract":"<p><p>Gastric peristalsis is governed by electrical \"slow waves\" generally assumed to travel from proximal to distal stomach (antegrade propagation) in symmetric rings. Although alternative slow-wave patterns have been correlated with gastric disorders, their mechanisms and how they alter contractions remain understudied. Optical electromechanical mapping, a developing field in cardiac electrophysiology, images electrical and mechanical physiology simultaneously. Here, we translate this technology to the in vivo porcine stomach. Stomachs were surgically exposed and a fluorescent dye (di-4-ANEQ(F)PTEA) that transduces the membrane potential (<i>V</i><sub>m</sub>) was injected through the right gastroepiploic artery. Fluorescence was excited by LEDs and imaged with one or two 256 × 256 pixel cameras. Motion artifact was corrected using a marker-based motion-tracking method and excitation ratiometry, which cancels common-mode artifact. Tracking marker displacement also enabled gastric deformation to be measured. We validated detection of electrical activation and <i>V</i><sub>m</sub> morphology against alternative nonoptical technologies. Nonantegrade slow waves and propagation direction differences between the anterior and posterior stomach were commonly present in our data. However, sham experiments suggest they were a feature of the animal preparation and not an artifact of optical mapping. In experiments to demonstrate the method's capabilities, we found that repolarization did not always follow at a fixed time behind activation \"wavefronts,\" which could be a factor in dysrhythmia. Contraction strength and the latency between electrical activation and contraction differed between antegrade and nonantegrade propagation. In conclusion, optical electromechanical mapping, which simultaneously images electrical and mechanical activity, enables novel questions regarding normal and abnormal gastric physiology to be explored.<b>NEW & NOTEWORTHY</b> This article introduces a novel method for imaging gastric electrophysiology and mechanical function simultaneously in anesthetized, open-abdomen pigs. We demonstrate it by observing propagating slow-wave depolarization and repolarization along with the strength, spatial distribution, and direction of contractions. In addition, we observe that in this animal preparation, slow waves often do not propagate from the proximal to distal stomach and are frequently asymmetric between the anterior and posterior sides of the stomach.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G765-G782"},"PeriodicalIF":4.3,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Machine learning application to histology for the study of cholangiopathies (BiliQML): A chance to put liver biopsy back to its former glory? 将机器学习应用于胆道病组织学研究(BiliQML):让肝脏活检重现昔日辉煌的机会?
IF 3.9 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-10-08 DOI: 10.1152/ajpgi.00173.2024
Camilla Venturin, Luca Fabris
{"title":"Machine learning application to histology for the study of cholangiopathies (BiliQML): A chance to put liver biopsy back to its former glory?","authors":"Camilla Venturin, Luca Fabris","doi":"10.1152/ajpgi.00173.2024","DOIUrl":"10.1152/ajpgi.00173.2024","url":null,"abstract":"","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G733-G736"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
AHCC inhibited hepatic stellate cells activation by regulation of cytoglobin induction via TLR2-SAPK/JNK pathway and collagen production via TLR4-NF-κβ pathway. AHCCⓇ通过TLR2-SAPK/JNK途径调节细胞色素诱导和TLR4-NFκB途径调节胶原蛋白生成,从而抑制肝星状细胞的活化。
IF 3.9 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-09-24 DOI: 10.1152/ajpgi.00134.2024
Hayato Urushima, Tsutomu Matsubara, Gu Qiongya, Atsuko Daikoku, Misako Takayama, Chiho Kadono, Hikaru Nakai, Yukinobu Ikeya, Hideto Yuasa, Kazuo Ikeda
{"title":"AHCC inhibited hepatic stellate cells activation by regulation of cytoglobin induction via TLR2-SAPK/JNK pathway and collagen production via TLR4-NF-κβ pathway.","authors":"Hayato Urushima, Tsutomu Matsubara, Gu Qiongya, Atsuko Daikoku, Misako Takayama, Chiho Kadono, Hikaru Nakai, Yukinobu Ikeya, Hideto Yuasa, Kazuo Ikeda","doi":"10.1152/ajpgi.00134.2024","DOIUrl":"10.1152/ajpgi.00134.2024","url":null,"abstract":"<p><p>Cirrhosis, which represents the end stage of liver fibrosis, remains a life-threatening condition without effective treatment. Therefore, prevention of the progression of liver fibrosis through lifestyle habits such as diet and exercise is crucial. The functional food AHCC, a standardized extract of cultured Lentinula edodes mycelia produced by Amino Up Co., Ltd. (Sapporo, Japan)] has been reported to be effective in improving the pathophysiology of various liver diseases. In this study, the aim was to analyze the influence of AHCC on hepatic stellate cells, which are responsible for liver fibrosis. Eight-week-old male C57BL6/j mice were induced with liver fibrosis by intraperitoneal injection of carbon tetrachloride. Simultaneously, they were orally administered 3% AHCC to investigate its impact on the progression of liver fibrosis. Using the human hepatic stellate cell (HHSteC) line, we analyzed the influence of AHCC on the expression of molecules related to hepatic stellate cell activation. The administration of AHCC resulted in reduced expression of collagen1a, α smooth muscle actin (αSMA), and heat shock protein 47 in the liver. Furthermore, the expression of cytoglobin, a marker for quiescent hepatic stellate cells, was enhanced. In vitro study, it was confirmed that AHCC inhibited αSMA by inducing cytoglobin via upregulating the stress-activated protein kinase/Jun NH<sub>2</sub>-terminal kinase (SAPK/JNK) pathway through Toll-like receptor (TLR) 2. In addition, AHCC suppressed collagen1a production by hepatic stellate cells through TLR4-NF-κβ pathway. AHCC was suggested to suppress hepatic fibrosis by inhibition of hepatic stellate cells activation. Daily intake of AHCC from mild fibrotic stages may have the potential to prevent the progression of liver fibrosis.<b>NEW & NOTEWORTHY</b> AHCC, a standardized extract of cultured <i>Lentinula edodes</i> mycelia, suppresses liver fibrosis progression by induction of cytoglobin via the Toll-like receptor 2 (TLR2)-stress-activated protein kinase/Jun NH<sub>2</sub>-terminal kinase (SAPK/JNK) pathway and the inhibition of collagen production via the TLR4-NFκβ pathway in hepatic stellate cells. Daily oral administration of AHCC from the stage of MASLD may have the potential to prevent disease progression to MASH with fibrosis.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G741-G753"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Hepatic bile acid accretion correlates with cholestatic liver injury and therapeutic response in Cyp2c70 knockout mice with a humanized bile acid composition. 使用人源化胆汁酸成分的 Cyp2c70 基因敲除小鼠的肝脏胆汁酸蓄积与胆汁淤积性肝损伤和治疗反应相关。
IF 3.9 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-10-01 DOI: 10.1152/ajpgi.00129.2024
Caroline Klindt, Jennifer K Truong, Ashley L Bennett, Kimberly J Pachura, Diran Herebian, Ertan Mayatepek, Tom Luedde, Matthias Ebert, Saul J Karpen, Paul A Dawson
{"title":"Hepatic bile acid accretion correlates with cholestatic liver injury and therapeutic response in <i>Cyp2c70</i> knockout mice with a humanized bile acid composition.","authors":"Caroline Klindt, Jennifer K Truong, Ashley L Bennett, Kimberly J Pachura, Diran Herebian, Ertan Mayatepek, Tom Luedde, Matthias Ebert, Saul J Karpen, Paul A Dawson","doi":"10.1152/ajpgi.00129.2024","DOIUrl":"10.1152/ajpgi.00129.2024","url":null,"abstract":"<p><p><i>Cyp2c70</i> knockout (KO) mice lack the liver enzyme responsible for synthesis of 6-hydroxylated muricholate bile acid species and possess a more hydrophobic human-like bile acid composition. <i>Cyp2c70</i> KO mice develop cholestatic liver injury that can be prevented by the administration of an ileal bile acid transporter (IBAT) inhibitor. In this study, we investigated the potential of an ileal bile acid transporter (IBAT) inhibitor (SC-435) and steroidal farnesoid X receptor (FXR) agonist (cilofexor) to modulate established hepatobiliary injury and the consequent relationship of intrahepatic bile acid content and hydrophobicity to the cholestatic liver injury phenotype. Oral administration of SC-435, cilofexor, or combined treatment for 2 wk markedly reduced serum markers of liver injury and improved histological and gene expression markers of fibrosis, liver inflammation, and ductular reaction in male and female <i>Cyp2c70</i> KO mice, with the greatest benefit in the combination treatment group. The IBAT inhibitor and FXR agonist significantly reduced intrahepatic bile acid content but not hepatic bile acid pool hydrophobicity, and markers of liver injury were strongly correlated with intrahepatic total bile acid and taurochenodeoxycholic acid accretion. Biomarkers of liver injury increased linearly with similar hepatic thresholds for pathological accretion of hydrophobic bile acids in male and female <i>Cyp2c70</i> KO mice. These findings further support targeting intrahepatic bile acid retention as a component of treatments for cholestatic liver disease.<b>NEW & NOTEWORTHY</b> Bile acids are implicated as a common contributor to the pathogenesis and progression of cholestatic liver disease. Using a mouse model with a humanized bile acid composition, we demonstrated that mono and combination therapy using an IBAT inhibitor and FXR nonsteroidal agonist were effective at reducing hepatic bile acid accretion and reversing liver injury, without reducing hepatic bile acid hydrophobicity. The findings support the concept of a therapeutically tractable threshold for bile acid-induced liver injury.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G789-G809"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339460","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Parenteral nutrition results in peripheral ileal to hepatic circadian discordance in mice. 肠外营养导致小鼠外周回肠与肝脏昼夜节律不一致。
IF 3.9 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-09-20 DOI: 10.1152/ajpgi.00042.2024
Colin T Shearn, Aimee L Anderson, Michael W Devereaux, Ronald J Sokol
{"title":"Parenteral nutrition results in peripheral ileal to hepatic circadian discordance in mice.","authors":"Colin T Shearn, Aimee L Anderson, Michael W Devereaux, Ronald J Sokol","doi":"10.1152/ajpgi.00042.2024","DOIUrl":"10.1152/ajpgi.00042.2024","url":null,"abstract":"<p><p>We have developed a mouse model of parenteral nutrition-associated liver disease (PNALD) in which parenteral nutrition (PN) infusion results in cholestatic liver injury. In the liver, the master circadian genes <i>Arntl</i>/Bmal drive rhythmic gene expression and regulate circadian expression of hepatic functions including bile acid synthesis. The aim of this study was to examine the effect of continuous PN on ileal and hepatic expression of circadian regulatory (CR) genes, farnesoid X receptor (FXR) signaling, and bile acid synthesis in mice. Wild-type mice were exposed to ad libitum Chow or continuous soy oil lipid emulsion-based PN infusion through a central venous catheter for 4 days (PN). Water was provided ad libitum, but no nutrients were provided enterally. On <i>day 4</i>, separate groups of Chow and PN-fed mice were euthanized every 6 h (7 AM, 1 PM, 7 PM, and 1 AM), and ileal, hepatic tissue and serum harvested. From tissue samples, the relative expression of circadian transcription factors and FXR signaling was assessed. Administration of 4-day PN increased hepatic injury, inflammatory cytokine expression, and gut permeability. In the ileum, PN activated FXR and induced expression of <i>Fgf15</i> and <i>Nr0b2</i>. In the liver, expression of FXR-downstream targets was dysregulated. PN administrations impacted hepatic and ileal circadian transcription factor mRNA expression, which was discordant between the two organs. Dysregulation of circadian regulatory machinery is in part due to discordance of the gut-liver axis during PN. Pharmacological targeting of CR as a therapeutic strategy for PNALD thus deserves further investigation.<b>NEW & NOTEWORTHY</b> This study used a novel short-term model of parenteral nutrition (PN) that is translationally relevant. We find that short-term PN is sufficient to induce hepatic and ileal changes in circadian transcription factor expression and to prevent normal concordant coordination of circadian transcription factors between the ileum and liver. These data suggest that targeting circadian transcription may have some clinical benefit in patients receiving parenteral nutrition.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G754-G764"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142279174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The gut microbiota as a link between Alzheimer's disease and obesity. 小评论:肠道微生物群是阿尔茨海默病与肥胖之间的联系。
IF 3.9 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-10-08 DOI: 10.1152/ajpgi.00174.2024
Karla Lucia F Alvarez, Gonzalo Davila-Del-Carpio
{"title":"The gut microbiota as a link between Alzheimer's disease and obesity.","authors":"Karla Lucia F Alvarez, Gonzalo Davila-Del-Carpio","doi":"10.1152/ajpgi.00174.2024","DOIUrl":"10.1152/ajpgi.00174.2024","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a degenerative disease that causes a progressive decline in memory and thinking skills. Over the past few years, diverse studies have shown that there is no single cause of AD; instead, it has been reported that factors such as genetics, lifestyle, and environment contribute to the pathogenesis of the disease. In this sense, it has been shown that obesity during middle age is one of the most prominent modifiable risk factors for AD. Of the multiple potential mechanisms linking obesity and AD, the gut microbiota (GM) has gained increasing attention in recent years. However, the underlying mechanisms that connect the GM with the process of neurodegeneration remain unclear. Through this narrative review, we present a comprehensive understanding of how alterations in the GM of people with obesity may result in systemic inflammation and affect pathways related to the pathogenesis of AD. We conclude with an analysis of the relationship between GM and insulin resistance, a risk factor for AD that is highly prevalent in people with obesity. Understanding the crosstalk between obesity, GM, and the pathogenesis of AD will help to design new strategies aimed at preventing neurodegeneration.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G727-G732"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142387334","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Formal degree programs in physiology promote careers of clinical scientists and benefit basic science departments. 生理学正规学位课程促进临床科学家的职业发展,并使基础科学部门受益。
IF 3.9 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-10-01 DOI: 10.1152/ajpgi.00196.2024
Irving Joshua, Hiram C Polk, Anne Macleod, R Maurice Eichenberger, Sarah A Gardner, Dale Schuschke, Susan Galandiuk
{"title":"Formal degree programs in physiology promote careers of clinical scientists and benefit basic science departments.","authors":"Irving Joshua, Hiram C Polk, Anne Macleod, R Maurice Eichenberger, Sarah A Gardner, Dale Schuschke, Susan Galandiuk","doi":"10.1152/ajpgi.00196.2024","DOIUrl":"10.1152/ajpgi.00196.2024","url":null,"abstract":"<p><p>Physiologists may play critical roles in the development of clinician-scientists who aspire to an academic career. The complexity of contemporary biomedical science and economic matters regarding postgraduate education pose real conundrums. We report a more than 22-year follow-up of surgical trainees pursuing bench laboratory science experience through a collaboration between a physiology postgraduate program and a surgical researcher program within a single public medical school. The sources and resources include selection, funding, physiology classroom work, and laboratory studies with personal involvement by faculty that have seldom been recorded, especially with longer term career outcomes. These selected PhD candidates have subsequently pursued several lines of activity, many with distinguished careers and major influences upon future generations of academic surgeons.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G737-G740"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142339459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Large animal models enhance the study of crypt-mediated epithelial recovery from prolonged intestinal ischemia reperfusion injury. 大型动物模型有助于研究隐窝介导的上皮细胞从长期肠道缺血再灌注损伤中恢复。
IF 3.9 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-10-15 DOI: 10.1152/ajpgi.00236.2024
Caroline A McKinney-Aguirre, Cecilia R Schaaf, Elizabeth Goya-Jorge, John M Freund, Liara M Gonzalez
{"title":"Large animal models enhance the study of crypt-mediated epithelial recovery from prolonged intestinal ischemia reperfusion injury.","authors":"Caroline A McKinney-Aguirre, Cecilia R Schaaf, Elizabeth Goya-Jorge, John M Freund, Liara M Gonzalez","doi":"10.1152/ajpgi.00236.2024","DOIUrl":"10.1152/ajpgi.00236.2024","url":null,"abstract":"<p><p>Intestinal ischemia and reperfusion injury (IRI) is a deadly and common condition. Death is associated with sepsis due to insufficient epithelial repair, requiring stem cell-driven regeneration, typically beginning 48 h after injury. Animal models are critical to advancing this field. To effectively study epithelial healing, models must survive clinically relevant intestinal ischemic injury extending to the crypt. Although mouse models are indispensable to intestinal research, their application for studying epithelial repair following severe IRI may be limited. Ischemic injury was induced in mouse and porcine jejunum for up to 3 h, with up to 72 h of reperfusion. Histologic damage was scored by Chiu-Park grade, and animal survival was assessed. Findings were compared between species. A mouse IRI literature review was performed to evaluate the purported degree of injury, duration of recovery, and reported survival rates. In mice and pigs, 3 h of ischemia induced severe, reliable injury extending into the crypt. However, at 48 h, mouse survival was only 23.5% compared with 100% survival in pigs. In literature, ischemia was induced for >1 h in only 4 of 102 mouse studies and none to 3 h. Recovery was attempted for 48 h in only six reports. Forty-seven studies reported intestinal crypt injury. Of those that featured histologic intestinal crypt damage, survival rates at 48 h ranged from 10 to 50% (median 30%). Mouse models are not ideal for studying intestinal stem cell-mediated recovery from severe IRI. Alternative large animal models, like pigs, are recommended.<b>NEW & NOTEWORTHY</b> Additional research is needed to improve recovery from severe intestinal ischemia. The selection of the ideal animal model is critical to facilitating this work. Based on our experimentation and literature review, porcine models, with increased translatability and an improved ability to survive both prolonged ischemia and the recovery period, appear to be the most appropriate choice for future studies.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G783-G788"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456093","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of Fabry disease-associated lyso-Gb3 on mouse colonic ion transport and motility. 法布里病相关溶菌酶-Gb3对小鼠结肠离子转运和运动的影响特征。
IF 3.9 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-10-15 DOI: 10.1152/ajpgi.00220.2024
Cecilia Delprete, Friederike Uhlig, Marco Caprini, Niall P Hyland
{"title":"Characterization of Fabry disease-associated lyso-Gb<sub>3</sub> on mouse colonic ion transport and motility.","authors":"Cecilia Delprete, Friederike Uhlig, Marco Caprini, Niall P Hyland","doi":"10.1152/ajpgi.00220.2024","DOIUrl":"10.1152/ajpgi.00220.2024","url":null,"abstract":"<p><p>Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by a deficiency in α-galactosidase A leading to the accumulation of globotriaosylceramide (Gb<sub>3</sub>) and subsequent increase in globotriaosylsphingosine (lyso-Gb<sub>3</sub>) in different cells and organs, including the gastrointestinal (GI) tract. GI symptoms represent some of the earliest manifestations of FD and significantly impact quality of life. The origin of these symptoms is complex, and the exact mechanisms remain poorly understood. Here, we sought to determine whether lyso-Gb<sub>3</sub> contributes to the pathophysiology of GI symptoms associated with FD by examining its effects on mouse colonic ion transport and motility ex vivo using Ussing chambers and organ baths, respectively. Lyso-Gb<sub>3</sub> significantly increased colonic baseline short-circuit current (<i>I</i><sub>sc</sub>). This increase in <i>I</i><sub>sc</sub> was insensitive to inhibition of the cystic fibrosis transmembrane conductance regulator and Na-K-Cl cotransporter 1, suggesting that the increase in <i>I</i><sub>sc</sub> is Cl<sup>-</sup> ion independent. This response was also insensitive to inhibition by the neurotoxin, tetrodotoxin. In addition, pretreatment with lyso-Gb<sub>3</sub> did not significantly influence subsequent responses to either veratridine or capsaicin implying that the response to lyso-Gb<sub>3</sub> does not involve the enteric nervous system. In terms of colonic motility, lyso-Gb<sub>3</sub> did not significantly influence colonic tone, spontaneous contractility, or cholinergic-induced contractions. These data suggest that lyso-Gb<sub>3</sub> significantly influences ion transport in mouse colon, but that accumulation of Gb<sub>3</sub> may be a prerequisite for the more pronounced disturbances in GI physiology characteristic of FD.<b>NEW & NOTEWORTHY</b> Fabry disease-associated lyso-Gb<sub>3</sub> significantly influences mouse colonic ion transport in a Cl<sup>-</sup> ion-independent manner.</p>","PeriodicalId":7725,"journal":{"name":"American journal of physiology. Gastrointestinal and liver physiology","volume":" ","pages":"G810-G817"},"PeriodicalIF":3.9,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142456090","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Rise in plasma bile acids following hypoabsorptive bariatric surgeries predicts beneficial metabolic and homeostatic outcomes in male rats. 低吸收减肥手术后血浆胆汁酸的升高预示着雄性大鼠的代谢和体内平衡将得到改善。
IF 4.3 3区 医学
American journal of physiology. Gastrointestinal and liver physiology Pub Date : 2024-12-01 Epub Date: 2024-10-15 DOI: 10.1152/ajpgi.00289.2023
Paulette Mukorako, Audrey-Anne Lavoie, Jocelyn Trottier, Natacha Lemoine, Laurent Biertho, Stéfane Lebel, Julie Plamondon, André Tchernof, David H St-Pierre, André Marette, Olivier Barbier, Denis Richard
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