Review
Biochemistry & Molecular Biology
Amir Asgari, Paul Jurasz
Summary: Megakaryocytes are important members of the hematopoietic system, responsible for regulating vascular homeostasis through platelets. The process of megakaryopoiesis generates mature megakaryocytes which release proplatelets into blood vessels. Nitric oxide (NO) plays a modulatory role in hematopoiesis and hemostasis. This review summarizes the effect of NO and its signaling on megakaryopoiesis and thrombopoiesis under physiological and pathophysiological conditions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Gastroenterology & Hepatology
Yan-Rong Li, Yan Li, Yuan Jin, Mang Xu, Hong-Wei Fan, Qian Zhang, Guo-He Tan, Jing Chen, Yun-Qing Li
Summary: This study investigates the effects of nitric oxide (NO) on colonic motility in a rat model of ulcerative colitis (UC), and the role of the enteric nervous system (ENS) in UC-related colonic motility. The results suggest that changes in the expression of nitric oxide synthase (NOS) in nitrergic neurons can influence colonic motility, and intervention in NOS activity may prevent colonic motor dysfunction in UC.
WORLD JOURNAL OF GASTROENTEROLOGY
(2022)
Article
Pharmacology & Pharmacy
Felix Javier Jimenez-Jimenez, Blanca G. Agundez, Javier Gomez-Tabales, Hortensia Alonso-Navarro, Laura Turpin-Fenoll, Jorge Millan-Pascual, Monica Diez-Fairen, Ignacio Alvarez, Pau Pastor, Marisol Calleja, Rafael Garcia-Ruiz, Santiago Navarro-Munoz, Marta Recio-Bermejo, Jose Francisco Plaza-Nieto, Esteban Garcia-Albea, Elena Garcia-Martin, Jose A. G. Agundez
Summary: The study investigated the association between variants in the endothelial nitric oxide synthase gene and the risk for idiopathic restless legs syndrome in a Caucasian Spanish population, finding that common NOS3 SNPs were not associated with the risk for RLS. There were weak statistical associations between certain NOS3 SNPs and response to dopamine agonists and clonazepam, but these findings require further confirmation.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Cell & Tissue Engineering
Ryo Hotta, Ahmed Rahman, Sukhada Bhave, Rhian Stavely, Weikang Pan, Shriya Srinivasan, Geoffrey de Couto, Luis Rodriguez-Borlado, Richard Myers, Alan J. Burns, Allan M. Goldstein
Summary: This study demonstrates that transplanted enteric neuronal stem cells (ENSCs) can form effective neuromuscular connections and improve colonic motor function in a model of colonic dysmotility. Multiple injections of ENSCs led to an improved response, paving the way for optimized clinical trial design.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Medicine, Research & Experimental
George J. Dugbartey
Summary: Kidney transplantation is the preferred treatment for patients with kidney failure. However, ischemia-reperfusion injury (IRI) poses a significant challenge to the long-term success of this intervention. Nitric oxide (NO) has emerged as a potential candidate for mitigating IRI and preventing graft rejection in kidney transplantation. This review provides an overview of the sources and protective effects of endogenous and exogenous NO in kidney transplantation.
BIOMEDICINE & PHARMACOTHERAPY
(2023)
Article
Biochemistry & Molecular Biology
Fabio Arias, Francisco Franco-Montalban, Miguel Romero, Juan Duarte, M. Dora Carrion, M. Encarnacion Camacho
Summary: This paper describes the design, synthesis, and biological evaluation of selective inhibitors of inducible nitric oxide synthase (iNOS). The most potent and selective compound showed inhibitory activity against iNOS without undesirable cardiovascular effects. In silico analysis predicted good drug-likeness properties for promising compounds, which also exhibited adequate cell viability. Docking studies revealed a unique binding mode for one compound and explained its selectivity towards iNOS.
BIOORGANIC CHEMISTRY
(2022)
Editorial Material
Plant Sciences
Francisco J. Corpas, Salvador Gonzalez-Gordo, Jose M. Palma
Summary: Nitric oxide is a crucial signaling molecule in plant physiological processes, but the enzymatic generation of nitric oxide in higher plants is still controversial.
TRENDS IN PLANT SCIENCE
(2022)
Article
Medicine, Research & Experimental
Joao Victor Silva-Silva, Carla J. Moragas-Tellis, Maria S. S. Chagas, Paulo Victor R. Souza, Davyson L. Moreira, Celeste S. F. de Souza, Kerolain F. Teixeira, Arthur R. Cenci, Aldo S. de Oliveira, Fernando Almeida-Souza, Maria D. Behrens, Katia S. Calabrese
Summary: This study evaluated the leishmanicidal activity of a crude extract and anthocyanidin-rich fractions from Arrabidaea chica, as well as three isolated anthocyanidins. The results showed promising anti-leishmanial effects of these compounds, indicating their potential as therapeutic agents for leishmaniasis.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Pharmacology & Pharmacy
Tatsiana Suvorava, Sara Metry, Stephanie Pick, Georg Kojda
Summary: Vascular tone regulation by nitric oxide is a crucial physiological function, with endothelial dysfunction potentially being an underlying cause of hypertension. Increasing eNOS activity reduces blood pressure, while decreasing activity has the opposite effect. These findings have important implications for pre-hypertensive treatment.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Miriam M. Cortese-Krott, Tatsiana Suvorava, Francesca Leo, Sophia K. Heuser, Anthea LoBue, Junjie Li, Stefanie Becher, Rebekka Schneckmann, Tanu Srivrastava, Ralf Erkens, Georg Wolff, Joachim P. Schmitt, Maria Grandoch, Jon O. Lundberg, John Pernow, Brant E. Isakson, Eddie Weitzberg, Malte Kelm
Summary: This study reveals that red blood cell endothelial nitric oxide synthase (RBC eNOS) plays a role in limiting infarct size in acute myocardial infarction (AMI) and regulates coronary blood flow and cardiac function. These findings suggest that RBC eNOS signaling may represent a novel target for interventions in ischemia/reperfusion after myocardial infarction.
Article
Biochemistry & Molecular Biology
Divya Seth, Colin T. Stomberski, Precious J. McLaughlin, Richard T. Premont, Kathleen Lundberg, Jonathan S. Stamler
Summary: The aim of this study was to investigate the interactions between nitric oxide synthase (NOS) isoforms and proteins, as well as the mechanisms by which they mediate S-nitrosylation. The results showed that each NOS isoform interacts with and S-nitrosylates many proteins, but a large proportion of S-nitrosylated proteins are not associated with NOS. Additionally, the interactomes and S-nitrosylomes of individual NOS isoforms are largely unique, indicating specific roles for each isoform in S-nitrosylation.
ANTIOXIDANTS & REDOX SIGNALING
(2023)
Letter
Cell & Tissue Engineering
Despoina Mademtzoglou, Perla Geara, Philippos Mourikis, Frederic Relaix
Summary: The Cre-lox system is commonly used for genetic studies, but in muscle stem cell research, it can cause inherent regeneration defects. Therefore, appropriate experimental design and controls are needed to prevent misinterpretation of experimental data in muscle stem cell genetic studies.
STEM CELL RESEARCH & THERAPY
(2023)
Article
Horticulture
Sitthisak Intarasit, Bualuang Faiyue, Jamnong Uthaibutra, Kobkiat Saengnil
Summary: The research aimed to investigate the impact of chlorine dioxide (ClO2) on the browning of longan pericarp. The findings indicated that ClO2 fumigation reduced the activities of RNS producing enzymes, resulting in lower nitrosative stress levels and reduced pericarp browning.
SCIENTIA HORTICULTURAE
(2022)
Article
Biochemistry & Molecular Biology
Shinya Yokomizo, Malte Roessing, Atsuyo Morita, Timo Kopp, Emiyu Ogawa, Wataru Katagiri, Susanne Feil, Paul L. Huang, Dmitriy N. Atochin, Satoshi Kashiwagi
Summary: This study provides evidence that NIR-II laser enhances bioavailable NO in endothelial cells, suggesting its potential use in restoring endothelial NO and treating or preventing cardiovascular diseases.
Article
Biochemistry & Molecular Biology
Tijana Suboticki, Olivera Mitrovic Ajtic, Dragoslava Djikic, Marijana Kovacic, Juan F. Santibanez, Milica Tosic, Vladan P. Cokic
Summary: In various systems, hydroxyurea has been shown to stimulate the release of nitric oxide or activate nitric oxide synthase. Through inhibiting nitric oxide metabolites, hydroxyurea is able to inhibit the growth of mature erythroid colonies and impact the presence of iNOS immunoreactive CFU-E.
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
Gastroenterology & Hepatology
Kelsi N. Dodds, Lee Travis, Melinda A. Kyloh, Lauren A. Jones, Damien J. Keating, Nick J. Spencer
Summary: The interaction between the gastrointestinal tract and brain is important for human health and disease. This study finds that there is no close physical contact between spinal afferent nerves and 5-HT-containing EC cells in the mouse colonic mucosa. This suggests that substances released from colonic EC cells are unlikely to act via synaptic transmission to neighboring spinal afferents.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2022)
Review
Surgery
David A. Wattchow, David Smolilo, Tim Hibberd, Nick J. Spencer, Simon J. H. Brookes, Roberto De Giorgio, Paul T. Heitmann, Marcello Costa, Phil G. Dinning
Summary: This article discusses the advantages and opportunities for surgeons and basic scientists to conduct research on the nervous system of the intestines. It highlights the translation of findings from animal studies to human subjects, which has greatly expanded our knowledge of the human enteric nervous system. These findings have led to therapeutic trials for gastrointestinal disorders.
ANZ JOURNAL OF SURGERY
(2022)
Article
Gastroenterology & Hepatology
Alyce M. Martin, Lauren A. Jones, Lai Wei, Nick J. Spencer, Kenton M. Sanders, Seungil Ro, Damien J. Keating
Summary: This study demonstrates the important role of mucosal 5-HT release in distension-evoked colonic motility. When EC cells are absent, SERT inhibition no longer alters gut motility, indicating that ENS 5-HT does not regulate gut motility.
NEUROGASTROENTEROLOGY AND MOTILITY
(2022)
Article
Neurosciences
Jing Feng, Tim J. Hibberd, Jialie Luo, Pu Yang, Zili Xie, Lee Travis, Nick J. Spencer, Hongzhen Hu
Summary: Through chemogenetic strategy, reduction of CAL neurons in the colon led to decreased colonic length and pellet sizes without overt inflammation. Interestingly, there was an increase in frequency and decrease in size of colonic motor complexes (CMCs) with lack of preferential anterograde migration. This suggests that calretinin neurons may play a role in pacing, force, and polarity of CMCs in the large bowel.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Review
Pharmacology & Pharmacy
Nick J. Spencer, Damien J. Keating
Summary: This article discusses the recent findings regarding the functional role of endogenous 5-HT in enterochromaffin cells and enteric neurons in gut motility and other major homeostatic pathways. The advancements in recording techniques and access to genetically modified animals have led to significant changes in our understanding of the role of gut-derived 5-HT. Experimental data suggests that the major patterns of GI motility and transit still occur even without endogenous 5-HT, and 5-HT3 receptor antagonists are more potent in inhibiting GI motility in segments lacking endogenous 5-HT.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Neurosciences
Timothy J. Hibberd, Wai Ping Yew, Kelsi N. Dodds, Zili Xie, Lee Travis, Simon J. Brookes, Marcello Costa, Hongzhen Hu, Nick J. Spencer
Summary: This study comprehensively quantified CGRP+ myenteric neurons in mouse colon, which aligns with the expected range of an intrinsic primary afferent neuron (IPAN) marker.
JOURNAL OF COMPARATIVE NEUROLOGY
(2022)
Article
Gastroenterology & Hepatology
Paul T. Heitmann, Lauren Keightley, Lukasz Wiklendt, David A. Wattchow, Simon S. J. Brookes, Nicholas J. Spencer, Marcello Costa, Phil G. Dinning
Summary: This study aimed to describe the effects of loperamide on neuromuscular function in the human colon. The findings suggest that loperamide primarily alters colonic function by acting on inhibitory motor neurons or alternative non-opioid receptor pathways.
NEUROGASTROENTEROLOGY AND MOTILITY
(2022)
Article
Neurosciences
Zili Xie, Jing Feng, Timothy J. Hibberd, Bao Nan Chen, Yonghui Zhao, Kaikai Zang, Xueming Hu, Xingliang Yang, Lvyi Chen, Simon J. Brookes, Nick J. Spencer, Hongzhen Hu
Summary: By ablating the sensory channels TRPV1 and Piezo2 from colon-innervating neurons, the visceromotor responses (VMR) induced by colorectal distention (CRD) are significantly reduced in mice. Selective ablation of Piezo2 channels in TRPV1 lineage neurons reduces mechanically evoked visceral afferent action potential firing and CRD-induced VMR under physiological conditions, as well as in mouse models of zymosan-induced IBS and partial colon obstruction (PCO). These findings demonstrate the important role of the mechanosensitive Piezo2 channels in TRPV1-lineage neurons in visceral mechanosensitivity and nociception under physiological conditions, as well as in visceral hypersensitivity under pathological conditions.
Article
Physiology
David J. J. Smolilo, Timothy J. J. Hibberd, Marcello Costa, Phil G. G. Dinning, Lauren J. J. Keightley, Dayan De Fontgalland, David A. Wattchow, Nick J. J. Spencer
Summary: The speed of pellet propulsion in the isolated guinea pig distal colon in vitro is higher than in vivo measurements, suggesting inhibitory mechanisms from outside the gut. The study aimed to investigate the effects of sympathetic nerve stimulation on different motor behaviors of the distal colon. Results showed that electrical stimulation of colonic nerves inhibited transient neural events (TNEs) and pellet propulsion, while significant inhibition of colonic motor complexes (CMCs) required higher frequencies of stimulation. The findings suggest differential sensitivities to sympathetic input among distinct neurogenic motor behaviors of the colon and raise the possibility of paradoxical effects of CMCs on pellet movement suppression in vivo.
PHYSIOLOGICAL REPORTS
(2023)
Article
Pharmacology & Pharmacy
Stewart Ramsay, Nick J. Spencer, Vladimir Zagorodnyuk
Summary: The aim of this study is to determine the role of endocannabinoids, anandamide (AEA) and 2-arachidonolylglycerol (2-AG), in regulating mechanosensitivity of probable nociceptive neurons innervating the bladder - capsaicin-sensitive mucosal afferents. The results showed that AEA potentiated the mechanical response of mucosal afferents, while 2-AG inhibited their response. These findings have important implications for understanding the role of endocannabinoids in regulating bladder sensation and function.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Immunology
Nabil Parkar, Julie E. Dalziel, Nick J. Spencer, Patrick Janssen, Warren C. McNabb, Wayne Young
Summary: Gastrointestinal (GI) motility relies on the enteric nervous system (ENS) and is crucial for digestion. Dysfunction in the ENS can lead to constipation. Animal models have been developed to mimic constipation symptoms through pharmacological manipulations, and studies have shown an association between altered GI motility and gut microbial population. However, little is known about the changes in gut microbiota resulting from slowed GI motility induced by medication, and the current understanding is based on studies using faecal samples which do not accurately represent the intestinal microbiome. This study aimed to investigate how delayed GI transit, caused by opioid receptor agonism in the ENS, affects caecal microbiota composition, and the results showed significant differences in microbial composition between treatment groups, with Bacteroides being relatively abundant in the group with slowed GI transit.
FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY
(2023)
Article
Gastroenterology & Hepatology
Bao Nan Chen, Adam Humenick, Wai Ping Yew, Lukasz Wiklendt, Phil G. Dinning, Nick J. Spencer, David A. Wattchow, Marcello Costa, Simon J. H. Brookes
Summary: This study used multiplexed immunohistochemistry to classify myenteric neurons of human colon into 20 classes. Cell morphology, soma size, and associations with axon terminals were quantified, providing a comprehensive understanding of the human myenteric plexus.
CELLULAR AND MOLECULAR GASTROENTEROLOGY AND HEPATOLOGY
(2023)
Review
Physiology
Timothy J. Hibberd, Stewart Ramsay, Phaedra Spencer-Merris, Phil G. Dinning, Vladimir P. Zagorodnyuk, Nick J. Spencer
Summary: This review discusses the role of peripheral clocks in regulating major colonic functions, including colonic motility, absorption, hormone secretion, permeability, and pain signalling. It also describes the interactions between pathophysiological states such as irritable bowel syndrome and ulcerative colitis and circadian rhythmicity.
FRONTIERS IN PHYSIOLOGY
(2023)
Review
Surgery
David A. Wattchow, Simon J. Brookes, Nick J. Spencer, Paul T. Heitmann, Roberto De Giorgio, Marcello Costa, Phil. G. Dinning
Summary: Motor function of the colon is crucial for health, and our understanding of its mechanisms is based on various experimental techniques. This article synthesizes key findings from these approaches to help surgeons better manage colonic conditions.
ANZ JOURNAL OF SURGERY
(2023)