Article
Anesthesiology
Michael Morgan, Jenny Thai, Vida Nazemian, Richard Song, Jason J. Ivanusic
Summary: This study explored the role of innervation of knee joint articular tissues and surrounding bone in osteoarthritis (OA) pain. The findings suggest that early OA pain is driven by nerves that innervate the joint capsule, while late OA pain involves the recruitment of nerves that innervate the subchondral bone. These results highlight the importance of targeting bone innervation for the development of mechanism-based therapies for late OA pain.
Review
Cell Biology
Katharina Held, Balazs Istvan Toth
Summary: Ion channels play a crucial role in regulating neural processes in the brain, and disruptions in their functions can lead to various neurological disorders. TRP ion channels are key players in the development and physiological functions of the central nervous system, influencing processes like neurite growth and synaptic plasticity. TRPM3, a non-selective cation channel, is emerging as a new player in the brain with potential roles in neuropathological processes.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2021)
Article
Immunology
Anne Musters, Giulia Balzaretti, Barbera D. C. van Schaik, Aldo Jongejan, Linda van der Weele, Sander W. Tas, Antoine H. C. van Kampen, Niek de Vries
Summary: This study found that in patients with rheumatoid arthritis (RA), different joints may share the same dominant B-cell clones, although the degree of overlap is lower than that of T-cell clones. These findings suggest that B-cell clonal responses in RA may be more localized, pointing to antigen-selective influx, proliferation, and/or maturation of B-cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Cell Biology
Mark A. Landy, Megan Goyal, Katherine M. Casey, Chen Liu, Helen C. Lai
Summary: The transcription factor Prdm12 plays a crucial role in nociceptor neurogenesis, with mutations causing congenital insensitivity to pain. While constitutive loss of Prdm12 affects proliferation during sensory neurogenesis, adult knockout in dorsal root ganglia (DRGs) shows dispensability for most pain-sensation and injury-induced hypersensitivity. Transcriptomic analysis suggests that PRDM12 acts as a transcriptional activator in adulthood, highlighting its changing function over developmental time.
Article
Medicine, Research & Experimental
Hehua Dai, Andressa Pena, Lynne Bauer, Amanda Williams, Simon C. Watkins, Geoffrey Camirand
Summary: This study demonstrates that regulatory T cells (Tregs) suppress immune responses within inflamed grafts through CD73 activity. Tregs selectively target antigen-presenting cells (APCs) that are simultaneously contacted by effector cells, reducing MHC-II expression on APCs and hindering effector cell function.
Article
Veterinary Sciences
Dohee Lee, Sanggu Kim, Yoonhoi Koo, Yeon Chae, Juwon Wang, Soochong Kim, Taesik Yun, Mhan-Pyo Yang, Byeong-Teck Kang, Hakhyun Kim
Summary: This study evaluated the expression of vitamin D receptor and two enzymes involved in vitamin D metabolism in the canine pancreas. The results showed a decrease in vitamin D receptor expression in inflamed pancreases, indicating a potential role of the pancreas in regulating vitamin D metabolism and suggesting its involvement in the pathophysiology of pancreatitis.
FRONTIERS IN VETERINARY SCIENCE
(2023)
Review
Immunology
Chenyu Li, Donglu Qin, Jiarui Hu, Yang Yang, Die Hu, Bilian Yu
Summary: The incidence of heart failure with preserved ejection fraction is increasing in patients with obesity, diabetes, hypertension, and in the aging population. However, there is a lack of adequate clinical treatment. This review article establishes the existence of obese heart failure with preserved ejection fraction and elaborates on the inflammation mechanisms and potential therapeutic approaches.
FRONTIERS IN IMMUNOLOGY
(2022)
Review
Clinical Neurology
Vladimir N. Nikolenko, Ekaterina M. Shelomentseva, Maria M. Tsvetkova, Elina Abdeeva, Dmitriy B. Giller, Juliya Babayeva, Evgeny E. Achkasov, Liliya Gavryushova, Mikhail Y. Sinelnikov
Summary: Nociceptors in the human body play a crucial role in responding to potentially harmful stimuli by forming pain signals, with variations in function and structure across different tissues, and serving as key protective units in maintaining defensive homeostasis.
JOURNAL OF PAIN RESEARCH
(2022)
Review
Immunology
Emine Kahraman, Ricardo Ribeiro, Meriem Lamghari, Estrela Neto
Summary: Osteoarthritis is a painful and disabling musculoskeletal disorder with no effective treatments currently available. Establishing reliable models to understand the molecular mechanisms and discover new therapeutic targets is urgently needed. Different models, including cell culture, scaffolds, and bioprinting tools, have been developed to replicate joint tissue in vitro. Dynamic conditions have been achieved using bioreactors and fluid systems. Organ-on-a-chip platforms have the potential to simulate the biological, chemical, and mechanical features of arthritic joint.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Medicine, Research & Experimental
Catriona T. Prendergast, Robert A. Benson, Hannah E. Scales, Caio Santos Bonilha, John J. Cole, Iain McInnes, James M. Brewer, Paul Garside
Summary: This study used mouse models and RNA-Seq analysis to identify key molecular pathways and genes regulating immune cell migration, and discovered specific genes associated with rheumatoid arthritis. The findings are important for identifying therapeutic targets for arthritis and other inflammatory disorders.
Article
Multidisciplinary Sciences
Honghua Liu, Chang She, Zhiliang Huang, Lei Wei, Qian Li, Han Peng, Mailan Liu
Summary: Uncertainty analysis and optimization were performed to improve the reliability and effectiveness of laser thermal pain treatment. Significant operational parameters were identified through univariate analysis and a regression model was used to determine their relationship with the constraint and target functions. Confidence distributions were obtained through interval uncertainty analysis, leading to the establishment of a nonlinear interval optimization model. The model was transformed into a deterministic optimization approach and solved using a genetic algorithm to achieve an optimal solution. The results demonstrate improved treatment efficacy and temperature control stability, highlighting the importance of accounting for parameter uncertainties in laser thermal pain treatment.
SCIENTIFIC REPORTS
(2023)
Article
Gastroenterology & Hepatology
Carla Montironi, Florian Castet, Philipp K. Haber, Roser Pinyol, Miguel Torres-Martin, Laura Torrens Fontanals, Agavni Mesropian, Huan Wang, Marc Puigvehi, Miho Maeda, Wei Qiang Leow, Elizabeth Harrod, Patricia Taik, Jigjidsuren Chinburen, Erdenebileg Taivanbaatar, Enkhbold Chinbold, Manel Sole Arques, Michael Donovan, Swan Thung, Jaclyn Neely, Vincenzo Mazzaferro, Jeffrey Anderson, Sasan Roayaie, Myron Schwartz, Augusto Villanueva, Scott L. Friedman, Andrew Uzilov, Daniela Sia, Josep M. Llovet
Summary: This study characterizes the immunogenomic contexture of hepatocellular carcinoma (HCC) and defines inflamed and non-inflamed tumors. Two distinct patterns of CTNNB1 are associated with differential immune evasion and may help predict immune response in HCC.
Article
Endocrinology & Metabolism
Wanlin Dai, Ziqi Liu, Shaojie Yang, Jing Kong
Summary: Cardiovascular disease is the leading cause of death worldwide and is associated with obesity, visceral adiposity, and unhealthy perivascular adipose tissue. Inflammatory polarization of immune cells and abnormal levels of adipose-related cytokines play a crucial role in the pathogenesis of metabolic disorders. Understanding the relationship between obesity and vascular injury can help improve obesity-induced inflammatory responses.
Article
Biochemistry & Molecular Biology
Eleonora Persoons, Sara Kerselaers, Thomas Voets, Joris Vriens, Katharina Held
Summary: Sex hormone steroidal drugs, including pregnenolone sulphate (PS), were found to modulate the ion channel TRPM3. These drugs have both activating and inhibiting effects on TRPM3, with a common steroidal interaction site. They exhibit increased activity on TRPM3 at physiological temperatures and in channels with disease-associated mutations, providing valuable insights into TRPM3 gating and sensitivity to ligands.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Vibhu Kumar, Vijay Kumar, Kirti Devi, Ajay Kumar, Rehan Khan, Ravindra Pal Singh, Sivasubramanian Rajarammohan, Kanthi Kiran Kondepudi, Kanwaljit Chopra, Mahendra Bishnoi
Summary: The study investigated the effects of TRPA1/TRPV1 modulation on colonic mucus production and gut health. It found that modulation of TRPA1/TRPV1 resulted in damaged mucosal lining, increased gut permeability, and altered transcriptional profile of related genes. These results suggest caution should be exercised when considering TRPA1/TRPV1 modulation as a therapeutic option for pain caused by IBD.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Editorial Material
Gastroenterology & Hepatology
Pieter Vanden Berghe
Article
Clinical Neurology
Wenting Guo, Haibo Wang, Arun Kumar Tharkeshwar, Julien Couthouis, Elke Braems, Pegah Masrori, Evelien Van Schoor, Yannan Fan, Karan Ahuja, Matthieu Moisse, Maarten Jacquemyn, Rodrigo Furtado Madeiro da Costa, Madhavsai Gajjar, Sriram Balusu, Tine Tricot, Laura Fumagalli, Nicole Hersmus, Rekin's Janky, Francis Impens, Pieter Vanden Berghe, Ritchie Ho, Dietmar Rudolf Thal, Rik Vandenberghe, Muralidhar L. Hegde, Siddharthan Chandran, Bart De Strooper, Dirk Daelemans, Philip Van Damme, Ludo Van den Bosch, Catherine Verfaillie
Summary: In this study, we identified NEK6 as a novel therapeutic target for C9orf72 FTD/ALS by performing a kinome-wide CRISPR/Cas9 knock-out screen in human induced pluripotent stem cell-derived cortical neurons. NEK6 was found to regulate poly(PR)-mediated p53-related DNA damage.
ALZHEIMERS & DEMENTIA
(2023)
Article
Obstetrics & Gynecology
Brecht Geysenbergh, Anne-Sophie Boes, Celine Bafort, Anne-Sophie van Rompuy, Sara Neyens, Sharon Lie Fong, Sophie Debrock, Joris Vriens, Peter De Loecker, Eline Dancet, Thomas D'Hooghe, Karen Peeraer
Summary: This study aimed to investigate the prevalence of chronic endometritis (CE) in infertile women, its impact on reproductive outcomes, and the accuracy of hysteroscopy as a screening tool for CE. The study included 514 asymptomatic patients with infertility who underwent hysteroscopy and endometrial biopsy (EMB). CE was identified in 2.8% of patients starting assisted reproductive technologies (ART). The clinical pregnancy rate (CPR) did not differ significantly between patients with CE and the entire cohort of patients without CE, but was significantly lower in the 2 years after EMB in patients with CE compared to matched controls. Hysteroscopy had low sensitivity and high specificity in diagnosing CE.
GYNECOLOGIC AND OBSTETRIC INVESTIGATION
(2023)
Article
Biology
Lydie Burglen, Evelien Van Hoeymissen, Leila Qebibo, Magalie Barth, Newell Belnap, Felix Boschann, Christel Depienne, Katrien De Clercq, Andrew G. L. Douglas, Mark P. Fitzgerald, Nicola Foulds, Catherine Garel, Ingo Helbig, Katharina Held, Denise Horn, Annelies Janssen, Angela M. Kaindl, Vinodh Narayanan, Christina Prager, Mailys Rupin-Mas, Alexandra Afenjar, Siyuan Zhao, Vincent Th Ramaekers, Sarah M. Ruggiero, Simon Thomas, Stephanie Valence, Lionel Van Maldergem, Tibor Rohacs, Diana Rodriguez, David Dyment, Thomas Voets, Joris Vriens
Summary: TRPM3 is a plasma membrane cation channel that is sensitive to temperature and neurosteroids and is expressed in various types of cells. Rare variants in TRPM3 have been found in individuals with developmental and epileptic encephalopathy, but the connection between TRPM3 activity and neurological disorders is not well understood. In this study, we identified additional heterozygous missense variants in TRPM3 in 10 patients with a range of neurodevelopmental symptoms. These variants cause a gain-of-function phenotype, leading to increased channel activity and altered calcium levels in cells. Treatment with the TRPM3 antagonist primidone reduced the increased channel activity, suggesting that TRPM3 antagonists could be a potential therapy for these disorders.
Article
Pharmacology & Pharmacy
Jan Daniluk, Thomas Voets
Summary: TRPV1 antagonists have pH-dependent effects on channel inhibition, but their modality selectivity is not strict. The antagonistic efficacy of TRPV1 antagonists is limited at acidic pH, which may restrict their analgesic efficacy in injured tissues.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Clinical Neurology
Lena-Luise Becker, Denise Horn, Felix Boschann, Evelien Van Hoeymissen, Thomas Voets, Joris Vriens, Christine Prager, Angela M. Kaindl
Summary: DEE-SWAS is an age-dependent disease that causes cognitive decline. This study reports on two children with DEE-SWAS and developmental delay/regression, who had missense variants in the TRPM3 gene. Treatment with primidone improved their developmental regression, psychomotor development, and eliminated CSWS.
Article
Pharmacology & Pharmacy
Noemie Luyts, Jan Daniluk, Ana Cristina Nogueira Freitas, Bahar Bazeli, Annelies Janssens, Marie Mulier, Wouter Everaerts, Thomas Voets
Summary: In this study, the effect of Phenazopyridine (PAP) on pain-related Transient Receptor Potential (TRP) channels was investigated. The results showed that PAP can rapidly and reversibly inhibit the cold and menthol sensitivity of TRPM8 channels. This suggests that the inhibition of TRPM8 may be the mechanism underlying the analgesic activity of PAP.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2023)
Article
Gastroenterology & Hepatology
Dieudonne Buh Kum, Hannah Vanrusselt, Abel Acosta Sanchez, Valerio Taverniti, Eloi R. Verrier, Thomas F. Baumert, Cheng Liu, Jerome Deval, Nikky Corthout, Sebastian Munck, Leonid Beigelman, Lawrence M. Blatt, Julian A. Symons, Pierre Raboisson, Andreas Jekle, Sandrine Vendeville, Yannick Debing
Summary: This study uncovers a novel mechanism of action for CAM-As in the treatment of chronic hepatitis B, where HBc aggregation induces cell death, leading to hepatocyte proliferation and loss of covalently closed circular DNA or its equivalent, possibly assisted by an induced innate immune response.
Article
Multidisciplinary Sciences
Maria Francesca Viola, Marta Chavero-Pieres, Elodie Modave, Marcello Delfini, Nathalie Stakenborg, Maria Cuende Estevez, Naomi Fabre, Iris Appeltans, Tobie Martens, Katy Vandereyken, Hannah Theobald, Jens Van Herck, Philippe Petry, Simon Verheijden, Sebastiaan De Schepper, Alejandro Sifrim, Zhaoyuan Liu, Florent Ginhoux, Mohamad Azhar, Andreas Schlitzer, Gianluca Matteoli, Katrin Kierdorf, Marco Prinz, Pieter Vanden Berghe, Thierry Voet, Guy Boeckxstaens
Summary: Development and maturation of the enteric nervous system (ENS) relies on the actions of resident macrophages, which prune synapses and phagocytose enteric neurons in early life. After weaning, these macrophages continue to interact closely with the ENS and acquire a neurosupportive phenotype. This interaction is mediated by transforming growth factor-beta produced by the ENS, and disruption of this communication leads to loss of enteric neurons and altered intestinal transit.
Article
Anesthesiology
Vincenzo Davide Aloi, Silvia Joao Poseiro Coutinho Pinto, Rita Van Bree, Katrien Luyten, Thomas Voets, Joris Vriens
Summary: Chemotherapy-induced peripheral neuropathic pain (CIPNP) is a common adverse effect in cancer patients receiving cytostatic drugs. Current treatment options for CIPNP are limited and unsatisfactory. This study suggests that TRPM3 could be a potential target for the treatment of neuropathic pain in chemotherapy patients.
Correction
Multidisciplinary Sciences
Franziska Bierbuesse, Anais C. Bourges, Vincent Gielen, Viola Monkemoller, Wim Vandenberg, Yi Shen, Johan Hofkens, Pieter Vanden Berghe, Robert E. Campbell, Benjamien Moeyaert, Peter Dedecker
NATURE COMMUNICATIONS
(2023)
Article
Virology
Hannah Vanrusselt, Dieudonne Buh Kum, Valerio Taverniti, Cheng Liu, Abel Acosta Sanchez, Nikky Corthout, Sebastian Munck, Thomas F. Baumert, Leonid Beigelman, Lawrence M. Blatt, Julian A. Symons, Jerome Deval, Pierre Raboisson, Eloi R. Verrier, Andreas Jekle, Sandrine Vendeville, Yannick Debing
Summary: This study reports on the first non-HAP CAM-As (capsid assembly modulators) ALG-005398 and ALG-005863, providing a detailed in vitro intracellular characterization. These non-HAP CAM-As showed potent inhibition of HBV DNA production and blocked the establishment of cccDNA.
JOURNAL OF VIROLOGY
(2023)
Article
Multidisciplinary Sciences
Thomas Plum, Rebecca Binzberger, Robin Thiele, Fuwei Shang, Daniel Postrach, Candice Fung, Marina Fortea, Nathalie Stakenborg, Zheng Wang, Anke Tappe-Theodor, Tanja Poth, Duncan A. A. MacLaren, Guy Boeckxstaens, Rohini Kuner, Claudia Pitzer, Hannah Monyer, Cuiyan Xin, Joseph V. Bonventre, Satoshi Tanaka, David Voehringer, Pieter Vanden Berghe, Jessica Strid, Thorsten B. Feyerabend, Hans-Reimer Rodewald
Summary: The physiological functions of mast cells are not well understood. Mast cells are involved in type 2 immunity and promote allergic diseases through the interaction with immunoglobulin E (IgE). However, allergic symptoms may also facilitate the elimination of allergens, toxins, and parasites and trigger future antigen avoidance. In this study, mast cells were found to be crucial for antigen-specific avoidance behavior in inbred mice. This behavior prevented immune activation and inflammation in the stomach and small intestine. Antigen avoidance was dependent on IgE and regulated by Th2 cytokines in the immunization phase and by IgE in the execution phase. Mucosal mast cells quickly detected the ingestion of antigens. Multiple signaling pathways between mast cells and the brain were identified. Inhibition of leukotriene synthesis impaired avoidance, but no single pathway interruption completely abolished it, suggesting complex regulation. Overall, antigen avoidance mediated by mast cells may play an important role in preventing immunopathology and repeated ingestion of toxins.