Article
Multidisciplinary Sciences
Cristian Thom, Janosch Ehrenmann, Santiago Vacca, Yann Waltenspuehl, Jendrik Schoeppe, Ohad Medalia, Andreas Plueckthun
Summary: The study reveals the structures of the neurokinin 1 receptor bound to its downstream signal mediators G(q) and G(s), as well as the conformational changes of the receptor under different ligand and antagonist actions.
Article
Biochemistry & Molecular Biology
Charlene Gadais, Justyna Piekielna-Ciesielska, Jolien De Neve, Charlotte Martin, Anna Janecka, Steven Ballet
Summary: Opioid agonists are commonly used for pain relief, but their side effects can be problematic. Designed multiple ligands (DMLs) offer a promising approach by targeting both opioid and non-opioid pathways involved in pain perception. Newly designed opioid agonist-NK2 or -NK3 antagonists show potential for future opioid hybrid development.
Article
Biochemistry & Molecular Biology
Julian A. Harris, Bryan Faust, Arisbel B. Gondin, Marc Andre Damgen, Carl-Mikael Suomivuori, Nicholas A. Veldhuis, Yifan Cheng, Ron O. Dror, David M. Thal, Aashish Manglik
Summary: The neuropeptide substance P activates the neurokinin-1 receptor through interactions deep within the receptor, while interactions between the neuropeptide and the receptor extracellular loops regulate G protein signaling selectivity. This study sheds light on how different stimuli can lead to distinct G protein signaling at the same receptor.
NATURE CHEMICAL BIOLOGY
(2022)
Article
Gastroenterology & Hepatology
Karim Atmani, Fabien Wuestenberghs, Maximilien Baron, Illona Boulete, Charlene Guerin, Wafa Bahlouli, David Vaudry, Jean Claude do Rego, Jean-Nicolas Cornu, Anne-Marie Leroi, Moise Coeffier, Mathieu Meleine, Guillaume Gourcerol
Summary: A new model of cross-organ visceral sensitization between the bladder and the colon was developed in mice. Intravesical injections of acetic acid induced long-lasting colorectal hypersensitivity to distension, which was mediated by neuroglial interactions, MAPK-p38 phosphorylation, and the NK1 receptor.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Physiology
Hiroyuki Nakamori, Hikaru Hashitani
Summary: In the isolated segments of rat proximal colon, the dopamine reuptake inhibitor GBR 12909 causes dilation, while the D-1-like receptor antagonist SCH 23390 induces tonic constriction, suggesting that neurally released dopamine stimulates enteric inhibitory efferent neurons.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Chemistry, Organic
Ruyuan Ma, Yan-En Wang, Dan Xiong, Jianyou Mao
Summary: A tandem Madelung indole synthesis using methyl benzoate and N-methyl-o-toluidine as reactants has been discovered. The combination of LiN-(SiMe3)2 and CsF is crucial for the high efficiency of this tandem reaction, which produces a diverse array of N-methyl-2-phenylindoles. The scalability and poststructural modifications of this indole synthesis have also been demonstrated.
Article
Gastroenterology & Hepatology
Timothy J. Hibberd, Marcello Costa, David J. Smolilo, Lauren J. Keightley, Simon J. Brookes, Phil G. Dinning, Nick J. Spencer
Summary: Colonic motor complexes (CMCs) are the main neurogenic activity that initiates propulsion in the guinea pig distal colon. In this study, it was found that CMCs, evoked by an intraluminal pellet, could be restored during nicotinic receptor blockade by pharmacological agents that directly or indirectly enhance the excitability of intrinsic primary afferent neurons (IPANs). IPANs are the only enteric neurons in the colon that contain calcitonin gene-related peptide (CGRP). Blocking CGRP receptors decreased the frequency of CMCs, implicating their role in CMC initiation. These results support the involvement of IPANs in the initiation of CMCs.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Article
Engineering, Biomedical
Guocheng Fang, Hongxu Lu, Russul Al-Nakashli, Robert Chapman, Yingqi Zhang, Lining Arnold Ju, Gungun Lin, Martina H. Stenzel, Dayong Jin
Summary: This study presents a method to model peristalsis in human colon tumor organoids on a microfluidic chip. The chip allows the control of peristalsis amplitude and rhythm, and enables high throughput culture of organoids. Results show the importance of mimicking mechanical stimuli in the physiological environment when evaluating nanoparticles in vitro.
Review
Neurosciences
Hyun Jin Jung, Ronny Priefer
Summary: Tachykinin NK2 receptors are widely distributed in the body and have potential therapeutic effects for various diseases, such as asthma and irritable bowel syndrome. NK2 receptor antagonists show promise as possible treatments for these conditions.
AUTONOMIC NEUROSCIENCE-BASIC & CLINICAL
(2021)
Article
Multidisciplinary Sciences
Thanh Tan Vo, Geun Ho Im, Kayoung Han, Minah Suh, Patrick J. Drew, Seong-Gi Kim
Summary: In this study, the hemodynamic responses elicited by optogenetic stimulation of PV interneurons were investigated using electrophysiology, fMRI, OIS, and pharmacological applications. The findings showed that activation of PV neurons induced an early vasoconstrictive response and a later ultraslow vasodilation response. The ultraslow response was mediated by neuropeptide substance P released from PV neurons and was dependent on the brain state.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Review
Oncology
Matti Aapro, Rudolph M. Navari, Eric Roeland, Li Zhang, Lee Schwartzberg
Summary: This study compared the efficacy of intravenous NEPA with oral NEPA and other NK(1)RA regimens, showing that intravenous NEPA has significant advantages in the treatment of nausea and vomiting, potentially offering a safer and more effective option.
CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY
(2021)
Article
Gastroenterology & Hepatology
Marcello Costa, Lauren J. Keightley, Timothy J. Hibberd, Lukasz Wiklendt, Phil G. Dinning, Simon J. Brookes, Nick J. Spencer
Summary: The study identified three major neurally mediated motor patterns in the mouse large intestine, each involving extended ensembles of enteric neurons firing at close to 2 Hz. These motor patterns demonstrate distinct functional differences between proximal and distal colon, suggesting a potential organizational principle in other mammalian species, including humans.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Article
Chemistry, Organic
Kaoru Funaki, Hidetsugu Tabata, Yusuke Nakazato, Yuka Takahashi, Tomohiko Tasaka, Hideyo Takahashi, Hideaki Natsugari, Tetsuta Oshitari
Summary: By performing the 5N-acylation reaction on 1N-methyl-1,5-benzodiazepin-2ones using (S)-2-phenylpropanoyl and (S)-2-phenylbutanoyl chlorides, the (a1S,a2S,S)-atropisomer (I) was obtained with high diastereoselectivity over the (a1R,a2R,S)-isomer (II). The preferential formation of I can be attributed to the thermodynamically preferable pi-pi stacking interaction between two benzene rings in the benzodiazepine ring and the acyl chloride during the reaction.
JOURNAL OF ORGANIC CHEMISTRY
(2022)
Article
Gastroenterology & Hepatology
Marcello Costa, Lauren J. Keightley, Timothy J. Hibberd, Lukasz Wiklendt, David J. Smolilo, Phil G. Dinning, Simon J. Brookes, Nick J. Spencer
Summary: Two distinct types of colonic motor complexes (CMCs) were identified in isolated mouse colon, complete and incomplete CMCs, with differences in the duration of smooth muscle action potentials, propagation speed, and frequency. Recognizing these different patterns of motility will be important for future interpretation of murine colonic motility recordings. Alternating patterns of motor activity in the proximal colon, but not in the distal colon, may reflect specific neural mechanisms for fecal pellet formation.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Article
Gastroenterology & Hepatology
Hiroyuki Nakamori, Kenta Noda, Retsu Mitsui, Hikaru Hashitani
Summary: The roles of enteric dopaminergic neurons in the generation of colonic peristalsis were investigated by studying the effects of various neurotransmitter blockers on peristaltic waves in rat colonic segments. Dopaminergic neurons appeared to facilitate nitrergic neurons via D-1-like receptors to stabilize asynchronous contractile activity resulting in the generation of colonic peristalsis.
NEUROGASTROENTEROLOGY AND MOTILITY
(2021)
Article
Transplantation
Veerle P. W. M. Wijtvliet, Kevin K. Arien, Steven Abrams, Marie M. Couttenye, Fabienne Mestrez, Joachim Marien, Benedicte Y. De Winter, Pierre Van Damme, Lissa Pipeleers, Karl Martin Wissing, Daniel Abramowicz, Kristien J. Ledeganck
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Article
Medicine, General & Internal
Sanae Makhout, Eline Vermeiren, Karolien van de Maele, Luc Bruyndonckx, Benedicte Y. De Winter, Kim Van Hoorenbeeck, Stijn L. Verhulst, Annelies Van Eyck
Summary: The study found that BDNF levels were comparable in children with obesity, both with and without OSA, and showed an interaction effect of OSA and endothelial function on BDNF levels. However, after one year of weight loss therapy, there was no change in BDNF levels.
FRONTIERS IN MEDICINE
(2022)
Article
Endocrinology & Metabolism
Francesca De Ridder, Kristien J. Ledeganck, Benedicte De Winter, Rie Braspenning, Danae Delbeke, Eric Renard, Paolo Pozzilli, Silvia Pieralice, Dirk Vissers, Christophe De Block
Summary: This study assessed trends in glucose, lactate, and ketones during anaerobic and aerobic exercise in individuals with type 1 diabetes (T1D) and compared the differences between the two types of exercise. It was found that omitting pre-meal insulin and basal insulin could prevent hypoglycemia but resulted in hyperglycemia due to excessive carbohydrate intake. No ketosis was observed during or after the exercises.
DIABETES-METABOLISM RESEARCH AND REVIEWS
(2022)
Article
Pharmacology & Pharmacy
Hannah Ceuleers, Nikita Hanning, Michelle De Bruyn, Joris G. De Man, Heiko U. De Schepper, Qian Li, Liansheng Liu, Steven Abrams, Annemieke Smet, Jurgen Joossens, Koen Augustyns, Ingrid De Meester, Pankaj J. Pasricha, Benedicte Y. De Winter
Summary: This study aimed to investigate the efficacy of serine protease inhibition on visceral pain in different animal models and explore the protease profiling. The results showed that serine protease inhibitors significantly reduced visceral hypersensitivity in the animal models and altered proteolytic activity in acute colitis. This study provided evidence for serine protease inhibitors as a promising therapeutic strategy for abdominal pain in gastrointestinal diseases.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Microbiology
Adam L. Edwinson, Lu Yang, Stephanie Peters, Nikita Hanning, Patricio Jeraldo, Pratik Jagtap, Joshua B. Simpson, Tzu-Yi Yang, Praveen Kumar, Subina Mehta, Asha Nair, Margaret Breen-Lyles, Lakshmikanth Chikkamenahalli, Rondell P. Graham, Benedicte De Winter, Robin Patel, Surendra Dasari, Purna Kashyap, Timothy Griffin, Jun Chen, Gianrico Farrugia, Matthew R. Redinbo, Madhusudan Grover
Summary: Intestinal protease activity is suppressed by gut microbiota through the production of unconjugated bilirubin. In irritable bowel syndrome patients, an altered gut microbiota composition results in increased protease activity.
NATURE MICROBIOLOGY
(2022)
Article
Education & Educational Research
Marijke Avonts, Nele R. Michels, Katrien Bombeke, Niel Hens, Samuel Coenen, Olivier M. Vanderveken, Benedicte Y. De Winter
Summary: This study investigates the impact of Peer-Assisted Learning (PAL) on peer teachers' academic scores and competencies. The results suggest that higher achieving students are more likely to volunteer for peer tutoring and PAL has a positive impact on medical expert, collaborator, scholar, and professional roles.
BMC MEDICAL EDUCATION
(2022)
Article
Gastroenterology & Hepatology
Tom Breugelmans, Wout Arras, Lauren-Emma Boen, Eliah Borms, Lisa Kamperdijk, Joris De Man, Els Van de Vijver, Ann Van Gils, Benedicte Y. De Winter, Nicolette Moes, Annemieke Smet
Summary: This study found that colonic mucin expression is disturbed in pediatric IBD patients and is associated with disease activity and presentation. These findings suggest that mucin expression can serve as a molecular marker to aid in the diagnosis and management of the disease.
INFLAMMATORY BOWEL DISEASES
(2023)
Article
Pathology
Cedric Peleman, Winnok H. De Vos, Isabel Pintelon, Ann Driessen, Annelies Van Eyck, Christophe Van Steenkiste, Luisa Vonghia, Joris De Man, Benedicte Y. De Winter, Tom Vanden Berghe, Sven M. Francque, Wilhelmus J. Kwanten
Summary: A new image analysis method was used to quantify the differences between liver lobule zones in NAFLD. The results showed that this method accurately measured the distribution of hypoxia markers in the steatotic liver and overcame the impact of steatosis on pathologists' interpretation.
Article
Gastroenterology & Hepatology
Nikita Hanning, Rosanne Verboven, Joris G. De Man, Hannah Ceuleers, Heiko U. De Schepper, Annemieke Smet, Benedicte Y. De Winter
Summary: This study showed that single-day or multi-day orogastric gavages do not have a significant effect on gut physiology in mice. However, multi-day gavages result in a slight increase in stress levels and altered gastrointestinal motor function. Despite this, the intestinal barrier function remains unaffected.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Kristien J. Ledeganck, Annelies Van Eyck, Kristien Wouters, Eline Vermeiren, Benedicte Y. De Winter, Stijn Verhulst, Kim Van Hoorenbeeck, Annick France, Hilde Dotremont, Marieke den Brinker, Dominique Trouet
Summary: This study investigated the relationship between urinary EGF, serum renin, and blood pressure in children with obesity or T1DM. The results showed that the urinary EGF/urinary creatinine ratio is correlated with SBP and MAP in boys with obesity as well as boys with T1DM. Multiple regression analysis revealed that sex and pulse pressure were independently associated with renin in obese males. Sex, the presence of diabetes, age, the glomerular filtration rate, and both pulse pressure and mean arterial pressure were independently associated with urinary EGF/urinary creatinine in male subjects. In conclusion, pulse pressure and mean arterial pressure are negatively associated with the functional integrity of the nephron, as reflected by a decreased expression of urinary EGF, in boys with either obesity or diabetes.
Article
Cell Biology
Tom Breugelmans, Wout Arras, Baptiste Oosterlinck, Aranzazu Jauregui-Amezaga, Michael Somers, Bart Cuypers, Kris Laukens, Joris G. De Man, Heiko U. De Schepper, Benedicte Y. De Winter, Annemieke Smet
Summary: This study investigates the role of MUC13 in disrupting epithelial barrier integrity and the involvement of MUC1 in inflammatory bowel diseases (IBD). The results demonstrate that MUC13 overexpression affects the expression of junctional proteins and barrier mediators, leading to intestinal barrier dysfunction. Furthermore, MUC13 modulates several signaling pathways, including JAK1/STAT3, SNAI1/ZEB1, and ROCK2/MAPK, in cooperation with MUC1. The findings suggest that aberrant MUC13 signaling plays an active role in inducing intestinal barrier dysfunction during inflammation.
Article
Gastroenterology & Hepatology
K. Van Malderen, J. G. De Man, B. Y. De Winter, H. U. De Schepper
Summary: This study aimed to evaluate the characteristics of a population visiting a patient-centered informative website about IBS. The study found that red flag symptoms and psychological comorbidities were common, and despite seeking medical help and receiving therapy, most patients still experienced moderate to severe symptoms with a significant impact on their quality of life. Furthermore, there was an urgent need for high-quality information and education for both healthcare professionals and patients.
ACTA GASTRO-ENTEROLOGICA BELGICA
(2023)
Review
Gastroenterology & Hepatology
Tom Breugelmans, Baptiste Oosterlinck, Wout Arras, Hannah Ceuleers, Joris De Man, Georgina L. Hold, Benedicte Y. De Winter, Annemieke Smet
Summary: Mucins play a crucial role in the gastrointestinal mucosal barrier and are involved in bidirectional interactions with the gut microbiota. They are also associated with various cell signaling pathways and have potential applications in the diagnosis, follow-up, and treatment of gastrointestinal diseases.
LANCET GASTROENTEROLOGY & HEPATOLOGY
(2022)
Meeting Abstract
Transplantation
Arno Verleye, Veerle Wijtvliet, Daniel Abramowicz, Kristien Ledeganck
NEPHROLOGY DIALYSIS TRANSPLANTATION
(2022)
Article
Gastroenterology & Hepatology
Denise van der Graaff, Shivani Chotkoe, Benedicte De Winter, Joris De Man, Christophe Casteleyn, Jean-Pierre Timmermans, Isabel Pintelon, Luisa Vonghia, Wilhelmus J. Kwanten, Sven Francque
Summary: In non-alcoholic fatty liver disease (NAFLD), hepatic blood flow is impaired and the blood pressure in the liver blood vessels is increased as a result of an increased response of the liver vasculature to vasoconstrictors. Using drugs to block the constriction of the intrahepatic vasculature, the resistance of the liver blood vessels decreases and the increased portal pressure is reduced. Moreover, blocking the vasoconstrictive endothelin-1 pathway restored parenchymal architecture and reduced disease severity.
