Article
Anesthesiology
Elaine F. Toniolo, Achla Gupta, Adriano C. Franciosi, Ivone Gomes, Lakshmi A. Devi, Camila S. Dale
Summary: The interaction between CB1R and opioid receptors may be targeted for the treatment of diabetic neuropathy. CB1R-MOR and CB1R-DOR complexes are involved in diabetic neuropathy, and the peptide endocannabinoid hemopressin shows potential as a therapeutic for this condition.
Article
Multidisciplinary Sciences
Jianming Han, Jingying Zhang, Antonina L. Nazarova, Sarah M. Bernhard, Brian E. Krumm, Lei Zhao, Jordy Homing Lam, Vipin A. Rangari, Susruta Majumdar, David E. Nichols, Vsevolod Katritch, Peng Yuan, Jonathan F. Fay, Tao Che
Summary: This article investigates the interaction between KOR receptor and G-protein heterotrimers, revealing that different subtypes of G-protein have different binding affinity and allosteric activity for drugs, laying the foundation for further research on pathway-selective agonists for therapeutic potential.
Article
Pharmacology & Pharmacy
Kelly F. Paton, Dan Luo, Anne C. La Flamme, Thomas E. Prisinzano, Bronwyn M. Kivell
Summary: This study investigated the effects of Salvinorin A analogues in a preclinical model of chemotherapy-induced neuropathic pain. The results showed that these analogues were effective in reducing pain and could be potential drugs for treating this condition.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Genis Ona, Frederic Sampedro, Sergio Romero, Marta Valle, Valle Camacho, Carolina Migliorelli, Miguel Angel Mananas, Rosa Maria Antonijoan, Montserrat Puntes, Jimena Coimbra, Maria Rosa Ballester, Maite Garrido, Jordi Riba
Summary: This study characterized the neuropharmacological effects of the highly selective KOR agonist salvinorin-A, revealing that it induces dramatic psychotomimetic effects with a generalized decrease in cerebral blood flow and electric activity within the cerebral cortex.
INTERNATIONAL JOURNAL OF NEUROPSYCHOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Ross van de Wetering, Amy Ewald, Susan Welsh, Lindsay Kornberger, Samuel E. Williamson, Bryan D. McElroy, Eduardo R. Butelman, Thomas E. Prisinzano, Bronwyn M. Kivell
Summary: This preclinical study evaluated the G-protein-biased analogue of SalA, 16-BrSalA, for its anticocaine effects and side effects, and found that it has improved pharmacokinetic profiles and fewer side effects.
Article
Biochemistry & Molecular Biology
Anita J. L. Leembruggen, Yuqing Lu, Haozhe Wang, Volkan Uzungil, Thibault Renoir, Anthony J. J. Hannan, Lincon A. A. Stamp, Marlene M. M. Hao, Joel C. C. Bornstein
Summary: Glutamate is a major neurotransmitter in the central nervous system that plays a role in excitatory neurotransmission and synaptic plasticity. While it has a smaller role in neurotransmission in the enteric nervous system, this study found that Group-I metabotropic glutamate receptors (mGlu1 and mGlu5) have complex roles in gastrointestinal function. mGlu5 was found to affect excitatory enteric neurotransmission, while mGlu1 affected colonic motor complexes.
Article
Pharmacology & Pharmacy
Priscila Vazquez-Leon, Abraham Miranda-Paez, Hugo Sanchez-Castillo, Bruno A. Marichal-Cancino
Summary: KOR stimulation/blockade in D-PAG during alcohol withdrawal may induce anxiety-like behaviors and alter alcohol intake/preference, exerting greater effects on withdrawal animals compared to naive ones.
PHARMACOLOGICAL REPORTS
(2023)
Article
Cell Biology
Elena Layunta, Raquel Forcen, Laura Grasa
Summary: The study found that TLR2 and TLR4 play a role in modulating the motor responses to ACh in the mouse ileum. TLR2 primarily acts on muscarinic M2 and M3, and nicotinic alpha 3 beta 4 ACh receptors, while TLR4 primarily acts on muscarinic M3, and nicotinic alpha 3 beta 4 and alpha 7 ACh receptors.
Article
Biochemistry & Molecular Biology
Kristina Puls, Gerhard Wolber
Summary: The natural product Salvinorin A (SalA) is a nitrogen-lacking agonist for the kappa opioid receptor (KOR) and shows potential as a new analgesic to address the opioid crisis. However, SalA has poor pharmacokinetic properties and a short duration of action, making the rational design of improved analogs necessary. In this study, the binding mode of SalA to the active state KOR was determined and the important interactions for its activity were identified. This knowledge will contribute to the understanding of KOR activation and the development of novel analgesics.
Review
Biochemistry & Molecular Biology
Tomasz Guzel, Dagmara Mirowska-Guzel
Summary: Serotonin is a neurotransmitter that acts in both the central nervous system and peripheral structures, also functioning as a hormone in platelets. It modulates CNS neurons, pain transmission, and platelet aggregation. Serotonin also influences muscle motility in the gut, bronchi, uterus, and vessels. Its synthesis starts with hydroxylation and decarboxylation of tryptophan. 5-HT receptors in the brain and gut are targets for drugs that modify serotonin neurotransmission.
Article
Biochemistry & Molecular Biology
Nicholas S. Akins, Mohammed F. Salahuddin, Pankaj Pandey, Seong Jong Kim, Fakhri Mahdi, Md Imdadul H. Khan, Emaya M. Moss, Charlie J. Worth, Madeline M. Keane, Amar G. Chittiboyina, Robert J. Doerksen, Jason J. Paris, Hoang V. Le
Summary: The KOR is involved in the regulation of reward and mood, and drug abuse increases its activation. Long-acting KOR antagonists have been shown to alleviate withdrawal symptoms, but their use in humans comes with safety concerns. This study found that a short-acting KOR antagonist showed efficacy in reducing withdrawal behavior in mice, and computational studies provided insights for the design of future antagonists.
ACS CHEMICAL NEUROSCIENCE
(2023)
Review
Immunology
Marta Brzozowska, Jaroslaw Calka
Summary: Galanin (GAL) is a broad-spectrum peptide commonly found in the gastrointestinal tract, where it regulates motility and secretion. Studies have shown that fluctuations in GAL levels are observed during the development of digestive disorders, suggesting a potential correlation with disease progression.
FRONTIERS IN IMMUNOLOGY
(2021)
Review
Immunology
Md Reyaz Alam, Shamsher Singh
Summary: Parkinson's disease is a neurodegenerative disorder characterized by the loss of dopaminergic neurons, resulting in motor and non-motor symptoms. Recent research suggests that targeting opioid and cannabinoid receptors as well as the NLRP3 pathway may provide novel therapeutic approaches for Parkinson's disease management.
INFLAMMOPHARMACOLOGY
(2023)
Article
Medicine, General & Internal
Anne-Marie Wegeberg, Davide Bertoli, Niels Ejskjaer, Birgitte Brock, Asbjorn Mohr Drewes, Christina Brock
Summary: Gastrointestinal function is altered in asymptomatic individuals with diabetes, with prolongation of colonic and whole-gut transit times in type 1 diabetes patients, decreased transpyloric pH rise in both type 1 and type 2 diabetes, and decreased ileocaecal pH fall in type 2 diabetes. Further investigations are needed to identify risk factors or predictors for diabetic enteropathy, especially when glycaemic control is impaired.
JOURNAL OF INTERNAL MEDICINE
(2022)
Article
Oncology
Lubomir Vecera, Petr Prasil, Josef Srovnal, Emil Berta, Monika Vidlarova, Tomas Gabrhelik, Pavla Kourilova, Martin Lovecek, Pavel Skalicky, Jozef Skarda, Zdenek Kala, Pavel Michalek, Marian Hajduch
Summary: Patients with pancreatic cancer who received morphine for postoperative analgesia had longer cancer-specific survival compared to those who received piritramide. Additionally, high expressions of cannabinoid receptor 2 (CB2) and opioid growth factor receptor (OGFR) genes were associated with improved overall survival, while high expression of delta opioid receptor gene shortened survival.
Editorial Material
Gastroenterology & Hepatology
Christopher N. Andrews, Keith A. Sharkey
ALIMENTARY PHARMACOLOGY & THERAPEUTICS
(2023)
Article
Gastroenterology & Hepatology
Crystal Woods, Amanda R. Flockton, Laurie E. Wallace, Catherine M. Keenan, Wendy B. Macklin, Keith A. Sharkey, Jaime Belkind-Gerson
Summary: Proteolipid protein 1 (Plp1) is highly expressed in enteric glia and plays a regulatory role in gut motility and barrier function, possibly through the Erk1/2 pathway. The absence of myelin in the enteric nervous system suggests another role for Plp1 in the gut.
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
(2023)
Review
Physiology
Keith A. Sharkey, Gary M. Mawe
Summary: The gastrointestinal tract is the most complex organ system in the body, controlling digestion and defense functions through the enteric nervous system. This system interacts with the immune system, gut microbiota, and epithelium to maintain mucosal defense and barrier function. Recent developments have improved our understanding of the molecular architecture, function, and regulation of the enteric nervous system, highlighting its importance in maintaining intestinal homeostasis.
PHYSIOLOGICAL REVIEWS
(2023)
Article
Medicine, Research & Experimental
Tomasz Mackiewicz, Jakub Wlodarczyk, Marta Zielinska, Marcin Wlodarczyk, Adam Durczynski, Piotr Hogendorf, Lukasz Dziki, Jakub Fichna
Summary: This study measured the expression of GPR35 in colorectal cancer (CRC) and pancreatic adenocarcinoma (PDAC) patients using real-time polymerase chain reaction (RT-PCR). The results showed significantly higher GPR35 expression in tumor samples compared to paired healthy samples, and correlations with tumor characteristics were observed. These findings suggest the potential prognostic value of GPR35 testing in CRC and PDAC patients.
ADVANCES IN CLINICAL AND EXPERIMENTAL MEDICINE
(2023)
Review
Medicine, General & Internal
Jakub Wlodarczyk, Jacek Burzynski, Bartlomiej Czerwinski, Mateusz Prusisz, Katarzyna Socala, Ewa Poleszak, Jakub Fichna, Kasper Marynczak, Marcin Wlodarczyk, Lukasz Dziki
Summary: Crohn's disease is a subtype of chronic inflammatory bowel diseases characterized by skip lesions and transmural inflammation. It can affect the entire gastrointestinal tract and persistent pain is one of the main symptoms. This study aims to provide an abbreviated summary of the current knowledge on the origins and treatment of pelvic pain in Crohn's disease.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Pharmacology & Pharmacy
Marek Pajak, Magdalena Wozniczka, Miroslawa Swiatek, Bartlomiej Czerwinski, Jakub Wlodarczyk, Jakub Fichna
Summary: The complexation properties of two synthetic nucleosides, beta-D-ribofuranoside-4-pyrimidinone (ribo) and beta-D-deoxyribofuranoside-4-pyrimidinone (deoxy), with Ag(I) ions in aqueous solution were investigated. The stability constants of the coordination entities formed were calculated and the percentage of each entity in solution was estimated. The results suggest that these coordination entities have potential antiviral, antibacterial, and antitumor properties, as well as potential applications in nanobiotechnology.
ACTA POLONIAE PHARMACEUTICA
(2023)
Review
Pharmacology & Pharmacy
Karolina Merecz, Mikolaj Hirsa, Olga Biniszewska, Jakub Fichna, Aleksandra Tarasiuk
Summary: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects approximately 10% of the global population. Recent studies have shown that antagonism of the serotonin 5-HT3 receptor is an effective treatment for IBS-D. The modulation of serotonin function plays a crucial role in maintaining intestinal homeostasis.
EXPERT OPINION ON PHARMACOTHERAPY
(2023)
Article
Neurosciences
Jean-Baptiste Cavin, Preedajit Wongkrasant, Joel B. Glover, Onesmo B. Balemba, Wallace K. MacNaughton, Keith A. Sharkey
Summary: The enteric nervous system regulates the functions of the gastrointestinal tract, and its response to changes in the gut lumen is not well understood. This study used live-cell confocal recordings to investigate neuronal response to luminal mechanical and chemical stimuli. The results show that intestinal distension regulates the excitability of enteric neural circuits via mechanosensitive channels, and the content of the intestinal lumen dynamically regulates the excitability of enteric neural circuits.
JOURNAL OF PHYSIOLOGY-LONDON
(2023)
Article
Toxicology
Szymon Lipiec, Agata Gurba, Izabela M. Agnieszczak, Andrzej Antoni Szczepankiewicz, Przemyslaw Szymanski, Przemyslaw Taciak, Remigiusz Szczepaniak, Lukasz Szeleszczuk, Hanna Nieznanska, Jakub Wlodarczyk, Jakub Fichna, Lukasz P. Bialy, Izabela Mlynarczuk-Bialy
Summary: Metal-based agents in cancer therapy, like cisplatin and its derivates, have established clinical applications but also can induce serious side effects. Thus, metallotherapeutic alternatives for platinum derivatives are developed and intensively studied. Platinum is replaced by several transition metals including gold. Especially gold (III) complexes can have the same square-planar structure and are isoelectric with platinum (II).
TOXICOLOGY IN VITRO
(2023)
Article
Immunology
Adam Makaro, Mikolaj Swierczynski, Kacper Pokora, Barbara Sarniak, Radzislaw Kordek, Jakub Fichna, Maciej Salaga
Summary: Inflammatory bowel diseases (IBD) is a chronic and relapsing inflammation in the gastrointestinal tract. The incidence and prevalence of IBD are high and increasing, and current therapeutic strategies are suboptimal. This study focused on gliflozins, a group of anti-diabetic drugs, and found that they have anti-inflammatory properties. In vitro experiments showed that two gliflozins, EMPA and DAPA, suppressed nitric oxide production in macrophages, and in vivo experiments demonstrated that EMPA alleviated colitis in mice. Our findings suggest that SGLT-2 inhibitors have anti-inflammatory effects independent of their hypoglycemic effects.
INFLAMMOPHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Marcin Sochal, Marta Ditmer, Agata Binienda, Agata Gabryelska, Piotr Bialasiewicz, Renata Talar-Wojnarowska, Jakub Fichna, Ewa Malecka-Wojciesko
Summary: Inflammatory bowel disease (IBD) patients often experience sleep and mood disorders which may be related to the disruption of the brain-gut axis. This study found that IBD patients had lower expression of BDNF mRNA but higher concentrations of proBDNF and BDNF protein compared to healthy controls. BDNF protein levels were positively correlated with sleep efficiency in the IBD group and depression severity was associated with BDNF mRNA and protein levels in the remission group.
Article
Gastroenterology & Hepatology
Abdel Aziz Shaheen, Gilaad G. Kaplan, Keith A. Sharkey, B. Cord Lethebe, Mark G. Swain
Summary: This study evaluated the impact of major depressive disorder (MDD) and antidepressant use on survival among patients with chronic viral hepatitis. The results showed that MDD was more prevalent in HCV patients and they were more likely to use antidepressants compared to HBV patients. However, MDD did not affect disease progression or survival in both HBV and HCV cohorts. The use of certain antidepressants was associated with poor decompensated cirrhosis-free survival. Further study should be conducted on the use of antidepressants in viral hepatitis patients.
HEPATOLOGY COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Marcin Sochal, Alicja Witkowska, Agata Binienda, Agata Gabryelska, Piotr Bialasiewicz, Jakub Fichna, Renata Talar-Wojnarowska, Ewa Malecka-Wojciesko
Summary: The study investigates the impact of the serotonergic pathway on the pathogenesis and course of inflammatory bowel diseases (IBDs), and its relationship with sleep and mood disorders. The results show that patients with active IBD have higher levels of 5-HT and SERT protein expression, which are positively correlated with insomnia severity. After treatment, only 5-HT levels are decreased.
JOURNAL OF CLINICAL MEDICINE
(2023)
Review
Biology
Marcin Wlodarczyk, Adam Makaro, Mateusz Prusisz, Jakub Wlodarczyk, Marta Nowocien, Kasper Marynczak, Jakub Fichna, Lukasz Dziki
Summary: Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease characterized by transmural inflammation in the gastrointestinal tract. Chronic fatigue is a common and often underestimated symptom in CD patients, with a higher prevalence compared to the general population. Its underlying causes and mechanisms are complex and not fully understood. Routine screening and a comprehensive, multidisciplinary approach, including psychological support, may play a crucial role in managing CD patients with chronic fatigue. Further research is needed to predict, prevent, identify, and treat fatigue associated with CD. This review aims to summarize the current knowledge on the etiology, diagnosis, and treatment of chronic fatigue in CD patients.
Article
Pharmacology & Pharmacy
Christopher D. Drummond-Main, Younghee Ahn, Mitchell Kesler, Cezar Gavrilovici, Do Young Kim, Ivana Kiroski, Samantha L. Baglot, Amy Chen, Keith A. Sharkey, Matthew N. Hill, G. Campbell Teskey, Jong M. Rho
Summary: This study found that CBD affects mitochondrial function and neuronal integrity, reducing mitochondrial respiration and calcium uptake, and leading to learning and memory deficits. These effects are independent of CB1 receptor and mitochondrial G-protein-coupled receptor 55.
CANNABIS AND CANNABINOID RESEARCH
(2023)