Review
Pharmacology & Pharmacy
Phuong T. Nguyen, Vladimir Yarov-Yarovoy
Summary: This review focuses on recent progress, current challenges, and future opportunities in developing sodium channel targeting small molecules and peptides as non-addictive therapeutics for treating pain.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Biochemistry & Molecular Biology
Xin Wu, Liang Hong
Summary: Calmodulin (CaM) is a small protein that serves as a ubiquitous signal transducer, regulating neuronal plasticity, muscle contraction, and immune response. It interacts with ion channels and plays regulatory roles in cellular electrophysiology. Mutations in CaM-binding IQ domain can lead to various diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Jennifer R. Deuis, Lotten Ragnarsson, Samuel D. Robinson, Zoltan Dekan, Lerena Chan, Ai-Hua Jin, Poanna Tran, Kirsten L. McMahon, Shengnan Li, John N. Wood, James J. Cox, Glenn F. King, Volker Herzig, Irina Vetter
Summary: A peptide named β-theraphotoxin-Eo1a was discovered from the venom of the Tanzanian black and olive baboon tarantula, which modulates the function of Na(V)1.8 channels. Eo1a increases the peak current of Na(V)1.8 and causes significant shifts in the voltage-dependence of activation and steady-state fast inactivation.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Altin Sula, David Hollingworth, Leo C. T. Ng, Megan Larmore, Paul G. DeCaen, B. A. Wallace
Summary: This study identified a previously unidentified receptor site within the NavMs voltage-gated sodium channel, where tamoxifen and its metabolic products bind, inhibiting sodium conductance and potentially leading to the development of new drugs for sodium channelopathies.
Review
Pharmacology & Pharmacy
Daohua Jiang, Jiangtao Zhang, Zhanyi Xia
Summary: Voltage-gated sodium channels are crucial for the rapid rising-phase of action potentials, and their mutations can lead to various human diseases. Recent studies using cryo-EM structures have provided valuable insights into the mechanism of eukaryotic Na-V channels, offering templates for drug development.
FRONTIERS IN PHARMACOLOGY
(2022)
Review
Chemistry, Medicinal
James R. Groome
Summary: This article reviews the study of marine toxins, particularly on their actions on sodium ion channels regulated by transmembrane voltage and neurotransmitters. The focus is on the diverse conotoxin peptides and their potential applications in evolutionary relationships, biological actions, disease therapy, and understanding the structure of ion channels at the atomic level.
Article
Chemistry, Medicinal
Nace Zidar, Tihomir Tomasic, Danijel Kikelj, Martina Durcik, Jan Tytgat, Steve Peigneur, Marc Rogers, Alexander Haworth, Robert W. Kirby
Summary: Voltage-gated sodium channels (Navs) play a crucial role in neurotransmission and their dysfunction is associated with various neurological disorders. In this study, a new series of aryl and acylsulfonamides were discovered as state-dependent inhibitors of Nav1.3 channels. These compounds displayed strong selective activity against the inactivated state of the Nav1.3 channel, with weaker activity against Nav1.5 and Nav1.7 channels. These findings provide a valuable tool for further evaluation of Nav1.3 channel as a potential drug target.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2023)
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
Pharmacology & Pharmacy
Paz Duran, Santiago Loya-Lopez, Dongzhi Ran, Cheng Tang, Aida Calderon-Rivera, Kimberly Gomez, Harrison J. Stratton, Sun Huang, Ya-ming Xu, E. M. Kithsiri Wijeratne, Samantha Perez-Miller, Zhiming Shan, Song Cai, Anna T. Gabrielsen, Angie Dorame, Kyleigh A. Masterson, Omar Alsbiei, Cynthia L. Madura, Guoqin Luo, Aubin Moutal, John Streicher, Gerald W. Zamponi, A. A. Leslie Gunatilaka, Rajesh Khanna
Summary: This study identified argentatin C, a compound derived from the Native American medicinal plant Parthenium incanum, which can block the activity of voltage-gated sodium and calcium channels and has potential as a novel treatment for painful conditions. Experimental results demonstrated that argentatin C decreased ion currents and excitability in sensory neurons and relieved postsurgical pain in a mouse model. Therefore, argentatin C may serve as an alternative therapy for chronic pain management.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Scott P. Fraser, Rustem Onkal, Margaux Theys, Frank Bosmans, Mustafa B. A. Djamgoz
Summary: The neonatal splice variant of Na(V)1.5 (nNa(V)1.5) in breast and colon cancer cells can be pharmacologically distinguished from the adult counterpart (aNa(V)1.5) by specific antibodies and toxins. This finding may contribute to the development of low molecular weight compounds as non-toxic therapeutic drugs for cancers expressing nNa(V)1.5.
BRITISH JOURNAL OF PHARMACOLOGY
(2022)
Article
Physiology
Jamie S. S. Lindner, Salil R. R. Rajayer, Briana J. J. Martiszus, Stephen M. M. Smith
Summary: The calcium-sensing receptor agonist, cinacalcet, regulates neuronal excitability by modulating the voltage-dependence of voltage-gated sodium channel (VGSC) currents. This regulation is achieved by shifting the voltage-dependence of VGSC currents and involves an unidentified inhibitory molecule that is G-protein dependent.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Environmental Sciences
Mohammad Akhoundi, Dahlia Chebbah, Denis Sereno, Anthony Marteau, Julie Jan, Christiane Bruel, Nohal Elissa, Arezki Izri
Summary: In bed bug populations in France, mutations in the kdr gene related to resistance to pyrethroids, including V419L and L925I, were found. These mutations may affect the resistance of bed bugs to insecticides.
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
(2021)
Article
Pharmacology & Pharmacy
Eva Fuchs, David Alexander Christian Messerer, Georg Karpel-Massler, Michael Fauler, Thomas Zimmer, Bettina Jungwirth, Karl Josef Foehr
Summary: In addition to its classical anti-cancer activity, the tumor therapeutic drug TIC10 may enhance its anti-tumor properties by blocking voltage-gated sodium channels.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Agronomy
Linlin Yuan, Kun Zhang, Zhenglei Wang, Limin Xian, Kaiyang Liu, Shaoying Wu
Summary: The sodium channel of Drosophila suzukii was cloned and found to have diverse gating properties and RNA editing.
PEST MANAGEMENT SCIENCE
(2023)
Article
Entomology
Haung Naw, Tuan Cuong Vo, Huong Giang Le, Jung-Mi Kang, Yi Yi Mya, Moe Kyaw Myint, Tong-Soo Kim, Ho-Joon Shin, Byoung-Kuk Na
Summary: This study identified high levels of kdr mutations in the Ae. aegypti population in the Mandalay area of Myanmar, suggesting widespread resistance to pyrethroid insecticides. The results underscore the need for an effective vector control program in Myanmar to address the increasing resistance in mosquitoes.
Article
Rheumatology
Aleksandra M. Kostic, Valia P. Leifer, Faith Selzer, David J. Hunter, A. David Paltiel, Antonia F. Chen, Malcolm K. Robinson, Tuhina Neogi, Jamie E. Collins, Stephen P. Messier, Robert R. Edwards, Jeffrey N. Katz, Elena Losina
Summary: This study aimed to evaluate the cost-effectiveness of Roux-en-Y gastric bypass (RYGB), laparoscopic sleeve gastrectomy (LSG), and lifestyle nonsurgical weight loss (LNSWL) interventions in knee osteoarthritis patients with class III obesity considering total knee replacement (TKR). The results showed that LSG and RYGB were cost-effective interventions, while immediate TKR without weight loss was not economically efficient.
ARTHRITIS CARE & RESEARCH
(2023)
Article
Rheumatology
Patrick Corrigan, David T. Felson, Cara L. Lewis, Tuhina Neogi, Michael P. LaValley, K. Doug Gross, Michael C. Nevitt, Cora E. Lewis, James C. Torner, Joshua J. Stefanik
Summary: The study aimed to investigate the relationship between unilateral knee pain severity and temporal asymmetry during walking, as well as the associations of temporal asymmetry with changes in ipsilateral and contralateral knee pain over 2 years in individuals with mild-to-moderate unilateral knee pain. The study included participants with unilateral knee pain from the Multicenter Osteoarthritis Study, and gait and pain assessments were conducted at baseline and 2 years. The results showed that unilateral knee pain severity was not associated with temporal asymmetry during walking. However, certain measures of temporal asymmetry during self-selected and fast walking were related to longitudinal knee pain outcomes.
ARTHRITIS CARE & RESEARCH
(2023)
Review
Andrology
Jolijn Van Cauwenberghe, Christophe De Block, Dirk Vanderschueren, Leen Antonio
Summary: Current available evidence suggests that traditional antidiabetic drugs have limited effects on testosterone levels, while GLP-1 receptor analogues show promising results for improving both testosterone levels and obesity in men with low testosterone levels. However, further studies are needed due to limited data and heterogeneous study groups.
Article
Rheumatology
Walter Reinisch, Wayne Hellstrom, Radboud J. E. M. Dolhain, Suresh Sikka, Rene Westhovens, Rajiv Mehta, Timothy Ritter, Ursula Seidler, Oleksandr Golovchenko, Vladimir Simanenkov, Olena Garmish, Slawomir Jeka, Radka Moravcova, Vijay Rajendran, Franck-Olivier Le Brun, Sarah Arterburn, Timothy R. Watkins, Robin Besuyen, Dirk Vanderschueren
Summary: The phase 2 MANTA and MANTA-RAy studies aimed to determine the impact of the oral Janus kinase 1 inhibitor filgotinib on semen parameters and sex hormones in men with inflammatory diseases. Results showed that once daily filgotinib 200 mg for 13 weeks had no measurable impact on semen parameters or sex hormones.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Letter
Rheumatology
Paul Studenic, Daniel Aletaha, Tanja A. Stamm, Maarten de Wit, Diane Lacaille, Josef S. Smolen, David Felson
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Matthew C. Baker, Khushboo Sheth, Rong Lu, Di Lu, Ericka P. von Kaeppler, Archana Bhat, David T. Felson, William H. Robinson
Summary: This retrospective cohort study found that patients with atopic disease have a higher incidence of osteoarthritis (OA) compared to non-exposed patients. The study showed that patients with asthma or atopic dermatitis had a higher risk of developing OA, particularly those with both conditions. These findings suggest a potential link between allergic pathways and the prevention or treatment of OA.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Endocrinology & Metabolism
Vanessa Dubois, Silvia Ciancia, Stefanie Doms, Sarah El Kharraz, Vera Sommers, Na Ri Kim, Karel David, Jolien Van Dijck, Roger Valle-Tenney, Christa Maes, Leen Antonio, Brigitte Decallonne, Geert Carmeliet, Frank Claessens, Martine Cools, Dirk Vanderschueren
Summary: Transgender youth are increasingly seeking pediatric gender services. Some receive long-term puberty suppression with GnRHa before starting GAH. The effects of GnRHa on bone composition and mass accrual during early puberty are unknown, as well as the impact of subsequent GAH and the timing of its introduction.
JOURNAL OF BONE AND MINERAL RESEARCH
(2023)
Article
Public, Environmental & Occupational Health
K. Walker-Bone, G. J. Macfarlane, K. Burton, A. M. McConnachie, R. Zhang, G. T. Jones
Summary: Arm pain is a common problem in the workplace. Advicing workers to keep using their arms as much as possible leads to less disability at 6 months, especially for those who lift heavy weights or believe work caused their symptoms. Early physiotherapy, however, made no difference to disability outcomes. Similar results were seen amongst workers diagnosed with lateral epicondylitis.
OCCUPATIONAL MEDICINE-OXFORD
(2023)
Review
Anesthesiology
Christopher Eccleston, Emma Begley, Hollie Birkinshaw, Ernest Choy, Geert Crombez, Emma Fisher, Anna Gibby, Rachael Gooberman-Hill, Sharon Grieve, Amber Guest, Abbie Jordan, Amanda Lilywhite, Gary J. Macfarlane, Candida McCabe, John McBeth, Anthony E. Pickering, Tamar Pincus, Hannah M. Sallis, Samantha Stone, Danielle Van der Windt, Diego Vitali, Elaine Wainwright, Colin Wilkinson, Amanda C. de C. Williams, Anica Zeyen, Edmund Keogh
Article
Rheumatology
Louise Linde, Lykke M. Ornbjerg, Stylianos Georgiadis, Simon H. Rasmussen, Ulf Lindstrom, Johan Askling, Brigitte Michelsen, Daniela Di Giuseppe, Johan K. Wallman, Bjorn Gudbjornsson, Thorvardur Jon Love, Dan C. Nordstrom, Timo Yli-Kerttula, Lucie Nekvindova, Jiri Vencovsky, Florenzo Iannone, Alberto Cauli, Anne Gitte Loft, Bente Glintborg, Karin Laas, Ziga Rotar, Matija Tomsic, Gary J. Macfarlane, Burkhard Moller, Marleen van de Sande, Catalin Codreanu, Michael J. Nissen, Merih Birlik, Sukran Erten, Maria J. Santos, Elsa Vieira-Sousa, Merete L. Hetland, Mikkel Ostergaard
Summary: In bio-naive patients with PsA initiating a TNF inhibitor (TNFi), baseline predictors of Disease Activity index for PsA in 28 joints (DAPSA28) remission and moderate response at 6 months, as well as drug retention at 12 months were identified, indicating potential generalizability from country to disease level.
Article
Medicine, General & Internal
Asri Maharani, Altug Didikoglu, Terence W. O'Neill, Neil Pendleton, Maria Merce Canal, Antony Payton
Summary: This study aimed to determine the associations between early life risk factors and the development of frailty in middle-aged and older adults, as well as the potential pathways via education. The results showed that breastfeeding and normal birth weight were associated with a lower frailty index, while maternal smoking, perinatal diseases, and birth month with longer day length were associated with a higher frailty index. The educational level mediated the relationship between these early life factors and frailty index.
Article
Geriatrics & Gerontology
Nadjia Amini, Jolan Dupont, Laurence Lapauw, Laura Vercauteren, Leen Antonio, Terence W. W. O'Neill, Dirk Vanderschueren, Neil Pendleton, Giulia Rastrelli, Mario Maggi, Felipe F. F. Casanueva, Jolanta Slowikowska-Hilczer, Margus Punab, Ilpo T. T. Huhtaniemi, Frederick C. W. Wu, Sabine Verschueren, Jos Tournoy, Evelien Gielen
Summary: This study aimed to investigate the cross-sectional and longitudinal associations between sarcopenia and cognitive performance in middle-aged and older men. The study found that several components of sarcopenia were associated with domain-specific cognitive performance. Longitudinally, baseline and change in subdomains of cognition predicted change in muscle function in specific subgroups.
JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE
(2023)
Editorial Material
Rheumatology
David Felson, Martin K. Lotz, Yuxuan Jin, Morgan Jones, Jason S. Kim, Kurt Spindler
Summary: Animal models have shown promising treatments for post traumatic osteoarthritis, but human trials have mostly failed to find effective treatments. This viewpoint suggests that the frequent failure in drug and treatment development for osteoarthritis may be due to the advanced disease stage of the patients in trials and proposes that mirroring the animal model approach could be more successful. It suggests selecting trial participants who are likely to quickly develop post traumatic osteoarthritis as a way forward.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Rheumatology
Abhishek Abhishek, Sara K. Tedeschi, Tristan Pascart, Augustin Latourte, Nicola Dalbeth, Tuhina Neogi, Amy Fuller, Ann Rosenthal, Fabio Becce, Thomas Bardin, Hang-Korng Ea, Georgios Filippou, John Fitzgerald, AnnaMaria Iagnocco, Frederic Liote, Geraldine M. McCarthy, Roberta Ramonda, Pascal Richette, Francisca Sivera, Mariano Andres, Edoardo Cipolletta, Michael Doherty, Eliseo Pascual, Fernando Perez-Ruiz, Alexander So, Tim L. Jansen, Minna J. Kohler, Lisa K. Stamp, Janeth Yinh, Antonella Adinolfi, Uri Arad, Thanda Aung, Eva Benillouche, Alessandra Bortoluzzi, Jonathan Dau, Ernest Maningding, Meika A. Fang, Fabiana A. Figus, Emilio Filippucci, Janine Haslett, Matthijs Janssen, Marian Kaldas, Maryann Kimoto, Kelly Leamy, Geraldine M. Navarro, Piercarlo Sarzi-Puttini, Carlo Scire, Ettore Silvagni, Silvia Sirotti, John R. Stack, Linh Truong, Chen Xie, Chio Yokose, Alison M. Hendry, Robert Terkeltaub, William J. Taylor, Hyon K. Choi
Summary: The ACR and EULAR have developed the first-ever validated classification criteria for symptomatic CPPD disease, which include the presence of calcium pyrophosphate crystals in synovial fluid and certain symptoms and laboratory findings. These criteria are of great importance for advancing research in CPPD disease.
ANNALS OF THE RHEUMATIC DISEASES
(2023)
Article
Endocrinology & Metabolism
Adrian Heald, Michael J. Cook, Leen Antonio, Jos Tournoy, Parisa Ghaffari, Fahmida Mannan, Helene Fachim, Dirk Vanderschueren, Ian Laing, Geoff Hackett, Felipe F. Casanueva, Ilpo T. Huhtaniemi, Mario Maggi, Giulia Rastrelli, Jolanta Slowikowska-Hilczer, Fred Wu, Terence W. O'Neill
Summary: This study found no association between androgen receptor CAG repeat number and mortality in European men. However, a post-hoc analysis showed a potential association in men with lower baseline testosterone concentrations, which requires further investigation.
CLINICAL ENDOCRINOLOGY
(2023)