Article
Pharmacology & Pharmacy
Ivan Tochitsky, Sooyeon Jo, Nick Andrews, Masakazu Kotoda, Benjamin Doyle, Jaehoon Shim, Sebastien Talbot, David Roberson, Jinbo Lee, Louise Haste, Stephen M. Jordan, Bruce D. Levy, Bruce P. Bean, Clifford J. Woolf
Summary: BW-031 is a novel cationic sodium channel inhibitor that can be applied locally to inhibit inflammatory pain as well as effectively suppress cough in a guinea pig model of citric acid-induced cough.
BRITISH JOURNAL OF PHARMACOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Pyung Sun Cho, Han Kyu Lee, Young In Choi, Seung In Choi, Ji Yeon Lim, Minseok Kim, Hyun Kim, Sung Jun Jung, Sun Wook Hwang
Summary: This study identified GPR171 as a promising molecular target for peripheral pain modulation by demonstrating its ability to attenuate pain signals through modulation of nociceptive ion channels in a specific subpopulation of somatosensory neurons.
Article
Cell Biology
Norihiko Yokoi, Yuko Fukata, Kei Okatsu, Atsushi Yamagata, Yan Liu, Makoto Sanbo, Yuri Miyazaki, Teppei Goto, Manabu Abe, Hidetoshi Kassai, Kenji Sakimura, Dies Meijer, Masumi Hirabayashi, Shuya Fukai, Masaki Fukata
Summary: The percentage of protein function required to prevent disease symptoms is a crucial question in genetic disorders. This study found that dual phosphorylation of ADAM22 by PKA regulates high-affinity binding of ADAM22 to dimerized 14-3-3, protecting LGI1-ADAM22 from degradation. Results suggest that targeting PKA or 14-3-3 could increase LGI1-ADAM22 complexes beyond necessary levels for epilepsy treatment.
Article
Pharmacology & Pharmacy
Eva Villalba-Riquelme, Roberto De La Torre-Martinez, Asia Fernandez-Carvajal, Antonio Ferrer-Montiel
Summary: Paclitaxel significantly enhances excitability in sensory neurons and displays a potential sex dimorphism in chemotherapy-induced peripheral neuropathy. Female DRG neurons are more sensitive to paclitaxel sensitization than male neurons.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Pharmacology & Pharmacy
Steve Peigneur, Cristina da Costa Oliveira, Flavia Cristina de Sousa Fonseca, Kirsten L. McMahon, Alexander Mueller, Olivier Cheneval, Ana Cristina Nogueira Freitas, Hana Starobova, Igor Dimitri Gama Duarte, David J. Craik, Irina Vetter, Maria Elena de Lima, Christina I. Schroeder, Jan Tytgat
Summary: This study aims to downsize larger venom-derived Na-V inhibitors into smaller, more drug-like molecules to bridge the gap between drug leads and candidates. By designing a series of small, stable and novel Na-V probes through molecular engineering, the researchers were able to demonstrate potent analgesic activity and subtype selectivity in vitro and in vivo.
BIOCHEMICAL PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Rohit Pal, Bhupinder Kumar, Md. Jawaid Akhtar, Pooja A. Chawla
Summary: Voltage-gated sodium channel blockers are important targets for managing central nervous system diseases such as epilepsy, chronic pain, psychiatric disorders, and spasticity. These drugs work by reducing excitotoxicity and improving symptoms, with several new drugs in development to target abnormal neuronal excitability. Despite extensive research, there has been no groundbreaking discovery yet in controlling seizures through sodium channel blockers, and ongoing efforts are focused on developing more potent anticonvulsant drugs with minimized toxicity.
BIOORGANIC CHEMISTRY
(2021)
Article
Multidisciplinary Sciences
Xi Liu, Zhi Qiao, Yuming Chai, Zhi Zhu, Kaijie Wu, Wenliang Ji, Daguang Li, Yujie Xiao, Lanqun Mao, Chao Chang, Quan Wen, Bo Song, Yousheng Shu
Summary: Midinfrared stimulation (MIRS) is a potential neuromodulation approach that exerts nonthermal, long-distance, and reversible modulatory effects on ion channel activity, neuronal signaling, and sensorimotor behavior. This method provides gain control over spiking activities and modulates startle responses, making it suitable for clinical application.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Genetics & Heredity
Chuanman Zhou, Qian Zhou, Xiaohui He, Yunxia He, Xiaoqin Wang, Xiaowei Zhu, Yujia Zhang, Long Ma
Summary: This study investigates the effects of K2P and NALCN on behavior using the nematode Caenorhabditis elegans as a model. It finds that the K2P gene twk-40 can regulate motor behavior in C. elegans, and identifies five other K2P genes that may have similar effects. Additionally, it suggests that some K2P and NALCN may oppositely affect behavior in C. elegans.
Article
Multidisciplinary Sciences
A. Catalina Velez-Ortega, Ruben Stepanyan, Stephanie E. Edelmann, Sara Torres-Gallego, Channy Park, Desislava A. Marinkova, Joshua S. Nowacki, Ghanshyam P. Sinha, Gregory I. Frolenkov
Summary: TRPA1 channels are expressed in nociceptive neurons and in the cochlea, and their function in the cochlea is unknown. This study shows that TRPA1 activation in the supporting cells of the cochlea causes prolonged calcium responses, leading to contractions of pillar and Deiters' cells. TRPA1 channels are activated by oxidative stress and extracellular ATP, which are present after acoustic trauma. TRPA1 deficiency results in larger but less prolonged temporary shift in hearing thresholds, indicating its contribution to cochlear sensitivity regulation after noise exposure.
NATURE COMMUNICATIONS
(2023)
Article
Pharmacology & Pharmacy
Martin Kruse, Rayne J. Whitten
Summary: Phosphoinositides, despite being a minor component of cell lipids, play essential roles in regulating neuronal activities. Activation of neurotransmitter receptors can rapidly deplete phosphoinositide levels, significantly impacting neuronal behavior. A comprehensive model has been developed to study the connection between muscarinic acetylcholine signaling, phosphoinositide metabolism, and action potential firing in sympathetic neurons.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Li Yu, Kojun Tsuji, Izumi Ujihara, Qi Liu, Nikoleta Pavelkova, Takanori Tsujimura, Makoto Inoue, Sonya Meeker, Eric Nisenbaum, Jeff S. McDermott, Jeff Krajewski, Bradley J. Undem, Marian Kollarik, Brendan J. Canning
Summary: The study suggests that the NaV 1.7 channel plays a role in regulating cough and is a potential therapeutic target, but systemic administration of NaV 1.7 inhibitors may lead to side effects such as hypotension and respiratory depression. Topical application of NaV 1.7 inhibitors showed promising antitussive effects, indicating a possible alternative therapeutic strategy to minimize systemic side effects.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Pharmacology & Pharmacy
Jannis Koerner, Simone Albani, Vishal Sudha Bhagavath Eswaran, Anna B. Roehl, Giulia Rossetti, Angelika Lampert
Summary: This article reviews the interaction between local anesthetics and voltage-gated sodium channels, discussing their mechanisms, effects, and specificity, and provides new perspectives for research.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Multidisciplinary Sciences
Goragot Wisedchaisri, Tamer M. Gamal El-Din, Ning Zheng, William A. Catterall
Summary: Gain-of-function mutations in the voltage-gated sodium channel NaV1.7, specifically in the S4-S5 intracellular linker, lead to severe inherited pain syndromes. Through structural analysis, it has been discovered that these mutations create new hydrogen bonds, stabilizing the activated state of the channel and causing a negative shift in voltage dependence of activation. This study provides important insights into the mechanisms behind hyperexcitability of NaV1.7 and severe pain in inherited erythromelalgia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Cell Biology
Feng Xiong, Rui Mao, Lijuan Zhang, Ruohan Zhao, Kunyue Tan, Chunxia Liu, JunBo Xu, Guanghong Du, Tongtong Zhang
Summary: sEVs-derived circNPHP4 may serve as a potential therapeutic target or diagnostic marker for CAD patients. circNPHP4 affects the adhesion between monocytes and coronary artery endothelial cells by modulating the expression of EGFR through miR-1231, and its overexpression is closely correlated with disease risk in CAD patients.
CELL DEATH & DISEASE
(2021)
Article
Biochemistry & Molecular Biology
Rama A. Hussein, Marwa Ahmed, Stefan H. Heinemann
Summary: Selenomethionine (SeMet) readily replaces methionine (Met) residues in proteins during translation, but little is known about its effect on electrical excitability and ion channels. SeMet mis-incorporation sensitizes voltage-gated sodium (NaV) channels to oxidative stress, resulting in loss of inactivation and diminished current.
JOURNAL OF NEUROCHEMISTRY
(2023)
Article
Chemistry, Medicinal
Jose Luis Diaz, Felix Cuevas, Ana Oliva, Daniel Font, M. Angeles Sarmentero, Paula Alvarez-Bercedo, Jose M. Lopez-Valbuena, Miquel A. Pericas, Raquel Enrech, Ana Montero, Sandra Yeste, Alba Vidal-Torres, Ines Alvarez, Pilar Perez, Cruz Miguel Cendan, Enrique J. Cobos, Jose Miguel Vela, Carmen Almansa
Summary: A new series of sigma-1 receptor ligands were synthesized and optimized for improved aqueous solubility, resulting in potent antagonists with good in vitro characteristics. Two compounds with differential brain-to-plasma ratio distribution exhibited effective analgesic profiles, making them promising preclinical candidates for pain treatment.
JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Veterinary Sciences
Cristina Perea, Ana Vazquez-Agredos, Leandro Ruiz-Leyva, Ignacio Moron, Jesus Martin Zuniga, Cruz Miguel Cendan
Summary: Research on caloric restriction in rodents has shown that long-term CR can be optimized technically and related to the well-being of animals by grouping them, particularly related mice. In a study involving grouped female and male littermates and unrelated mice, CR was only possible in related mice, resulting in less aggressive behavior compared to unrelated male mice. Stress levels, as measured by ACTH concentrations, showed no difference between ad libitum and CR conditions.
FRONTIERS IN VETERINARY SCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Leandro Ruiz-Leyva, Ana Vazquez-Agredos, Ana M. Jimenez-Garcia, Olga Lopez-Guarnido, Antonio Pla, Ricardo Marcos Pautassi, Ignacio Moron Henche, Cruz Miguel Cendan
Summary: The present study validates a novel model of voluntary ethanol consumption in male Wistar rats, in which ethanol access follows binge eating, and demonstrates a significant increase in ethanol consumption after binge eating compared to control eating. This model shows remarkable potential for research on different stages of alcohol addiction and assessing interactions between alcohol consumption and other addictive-like behaviors.
Article
Biochemical Research Methods
Elena Rojano, Fernando M. Jabato, James R. Perkins, Jose Cordoba-Caballero, Federico Garcia-Criado, Ian Sillitoe, Christine Orengo, Juan A. G. Ranea, Pedro Seoane-Zonjic
Summary: This study introduces DomFun, a Ruby gem based on tripartite network analysis, for protein domain-function association and function prediction. The results show that using Simpson index and Stouffer's method combined with FunFam domain-function associations provides the best performance in multiple tests. Additionally, using FunFams and predicting GO molecular function yields better results compared to GO biological process terms.
BMC BIOINFORMATICS
(2022)
Review
Genetics & Heredity
Juan Luque, Ingrid Mendes, Beatriz Gomez, Beatriz Morte, Miguel Lopez de Heredia, Enrique Herreras, Virginia Corrochano, Juan Bueren, Pia Gallano, Rafael Artuch, Cristina Fillat, Luis A. Perez-Jurado, Lluis Montoliu, Angel Carracedo, Jose M. Millan, Susan M. Webb, Francesc Palau, Pablo Lapunzina
Summary: CIBERER, a thematic area of CIBER, focuses on rare disease research. It aims to facilitate collaboration between biomedical and clinical research groups and provide new tools for the diagnosis and therapy of low-prevalence diseases.
Article
Critical Care Medicine
Alexander T. Fields, Man-Cheung Lee, Fahima Mayer, Yale A. Santos, Cedric M. Bainton, Zachary A. Matthay, Rachael A. Callcut, Nasima Mayer, Joseph Cuschieri, Kord M. Kober, Roland J. Bainton, Lucy Zumwinkle Kornblith
Summary: The study found evidence of fine-tuning of the platelet transcriptome through differential alternative splicing of platelet RNA in trauma patients, which may have relevance to downstream platelet signaling. Additional investigations of the trauma platelet transcriptome should be pursued to improve our understanding of the platelet functional responses to trauma on a molecular level.
JOURNAL OF TRAUMA AND ACUTE CARE SURGERY
(2022)
Article
Multidisciplinary Sciences
Rafael Nunez, Maria Jose Rodriguez, Francisca Palomares, Francisca Gomez, Fernando M. Jabato, Jose Cordoba-Caballero, Pedro Seoane, Jorge Losada, Javier Rojo, Maria Jose Torres, James Richard Perkins, Cristobalina Mayorga
Summary: Investigating food allergy-tolerance mechanisms induced through allergen-specific immunotherapy revealed distinct gene expression patterns and pathways in the desensitized and tolerant groups, with the desensitized group enriched for genes related to chronic inflammatory response and the tolerant group showing genes associated with cytokine receptor activity and glucocorticoid receptor binding.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Agustin Salguero, Leonardo Marengo, Enrique Portillo-Salido, Leandro Ruiz-Leyva, Cruz Miguel Cendan, Ignacio Moron Henche, Ricardo Marcos Pautassi
Summary: The study explored the effects of sigma-1 receptors (S1-R) activation on ethanol-induced conditioned taste aversion (CTA) in early adolescence and terminal adolescence/emerging adulthood in female Wistar rats. The results showed that S1-R activation attenuated the learning of ethanol-induced CTA at terminal adolescence but not at early adolescence. Additionally, S1-R activation did not significantly affect binge-like ethanol intake in terminal adolescents.
NEUROSCIENCE LETTERS
(2022)
Review
Genetics & Heredity
Juan A. G. Ranea, James Perkins, Monica Chagoyen, Elena Diaz-Santiago, Florencio Pazos
Summary: Network and systemic approaches are valuable in studying human pathologies to understand molecular mechanisms and potential treatment options. The conventional partitioning of diseases into discrete categories may not adequately capture the heterogeneity of diseases. Clinical phenotypes, which are directly observable and closer to the molecular basis of pathology, play an important role in personalized medicine and are being incorporated into pathology research.
Article
Neurosciences
Manuela Schmidt, Julia Regina Sondermann, David Gomez-Varela, Cankut Cubuk, Queensta Millet, Myles J. Lewis, John N. Wood, Jing Zhao
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Biographical-Item
Immunology
Amanda G. G. Fisher, Matthias Merkenschlager
Article
Anesthesiology
Man-Cheung Lee, Andrew Bartuska, Jeffrey Chen, Richard K. Kim, Safwan Jaradeh, Fred Mihm
Summary: Paroxysmal sympathetic hyperactivity (PSH) is an autonomic disorder in patients with severe acquired brain injury. Stellate ganglion blockade (SGB) may interrupt the pathophysiology of PSH and provide a promising therapeutic option. A case report showed near-complete resolution of sympathetic events in a patient with PSH after SGB for 140 days. SGB overcomes the limitations of systemic medications and may recalibrate aberrant autonomic states.
REGIONAL ANESTHESIA AND PAIN MEDICINE
(2023)
Article
Biology
Hannah J. J. Gleneadie, Beatriz Fernandez-Ruiz, Alessandro Sardini, Mathew Van de Pette, Andrew Dimond, Rab K. K. Prinjha, James McGinty, Paul M. W. French, Hakan Bagci, Matthias Merkenschlager, Amanda G. G. Fisher
Summary: Duchenne muscular dystrophy (DMD) is a genetic disorder caused by mutations in the dystrophin gene (Dmd), leading to progressive muscle weakening. A study using mouse models and myoblasts found that chromatin-modifying drugs can increase the expression of utrophin (Utrn), a protein that can compensate for Dmd deficiency. Inhibitors of PRC2 and ERK1/2 were identified to enhance Utrn expression, offering potential therapeutic strategies for DMD.
COMMUNICATIONS BIOLOGY
(2023)
Article
Multidisciplinary Sciences
Manuel Corpas, Carmen de Mendoza, Victor Moreno-Torres, Ilduara Pintos, Pedro Seoane, James R. Perkins, Juan A. G. Ranea, Segun Fatumo, Tamas Korcsmaros, Jose Manuel Martin-Villa, Pablo Barreiro, Octavio Corral, Vicente Soriano
Summary: Characterization of host genetic factors contributing to COVID-19 severity reveals a possible role of T cell response dysfunction, as indicated by the identification of variants in the T cell receptor beta locus associated with severe COVID-19.
Article
Health Care Sciences & Services
Andrea Olmos, Sasha Steen, Christy K. Boscardin, Joyce M. Chang, Genevieve Manahan, Anthony R. Little, Man-Cheung Lee, Linda L. Liu
Summary: A quality improvement initiative was implemented to increase the use of multimodal analgesia in adult patients undergoing general anesthesia at an academic tertiary care center. The study aimed to increase adoption of a perioperative multimodal analgesia protocol across a broad population of surgical patients. Results showed reduced opioid use in the post-anesthesia care unit and 48 hours postoperatively after the implementation of a perioperative pragmatic multimodal analgesic intervention.