Article
Pharmacology & Pharmacy
Lina Huang, Dilip Sharma, Xiaozhou Feng, Zhiqiang Pan, Shaogen Wu, Daisy Munoz, Alex Bekker, Huijuan Hu, Yuan-Xiang Tao
Summary: The study found that RALY, an RNA-binding protein, plays a role in nerve trauma-induced nociceptive hypersensitivity by regulating the expression of translation initiation factor Eif4g2 in dorsal root ganglion neurons. Interventions targeting RALY expression levels could alleviate the development and maintenance of pain hypersensitivity.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Review
Cell Biology
Risa Domoto, Fumiko Sekiguchi, Maho Tsubota, Atsufumi Kawabata
Summary: Neuroimmune crosstalk plays a crucial role in both somatic and visceral pathological pain, with macrophages interacting with neurons to regulate pain signals in peripheral tissues; recent studies have uncovered different characteristics and mediators of macrophages from various sources, highlighting their multitasking abilities in homeostatic conditions.
Article
Immunology
Jing Xu, Shinan Wu, Junfei Wang, Jianmei Wang, Yi Yan, Mengye Zhu, Daying Zhang, Changyu Jiang, Tao Liu
Summary: The study revealed that NOX2-induced oxidative stress promotes the sensitization of DRGs and persistent pain by increasing the plasma membrane translocation of PKC epsilon.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Biochemistry & Molecular Biology
Paula G. Socuellamos, Luis A. Olivos-Ore, Maria Victoria Barahona, Pilar Cercos, Marta Perez Pascual, Marina Arribas-Blazquez, Jose Ramon Naranjo, Carmen Valenzuela, Marta Gutierrez-Rodriguez, Antonio R. Artalejo
Summary: Neuropathic pain is a chronic form of pain resulting from damage to neural cells. This study evaluated the analgesic effects of IQM-PC332, a new ligand that modulates ion channels, in rats with neuropathic pain. The results showed that IQM-PC332 reduced mechanical sensitivity and modulated ion currents in nerve cells, indicating its potential as a lead compound for novel analgesics.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Anesthesiology
Michael Tal, Anne Minert, Marshall Devor
Summary: Resection of neuromas after 14 days of nerve transection can reduce ectopic discharge and does not exacerbate pain. The concern of resurgence in ectopia and increased pain after proximal nerve resection is not validated by our experiments, suggesting that resecting neuromas can be a therapeutic strategy.
Article
Anesthesiology
Dongman Chao, Christina M. Mecca, Guoliang Yu, Ian Segel, Michael S. Gold, Quinn H. Hogan, Bin Pan
Summary: Dorsal root ganglion field stimulation can relieve neuropathic pain by blocking spontaneous activity in injured neurons, leading to reduced pain behavior and ongoing pain. The effects are more significant in injured neurons, affecting both pain behavior and ongoing pain.
Article
Neurosciences
Kexing Wan, Min Jia, Hong Zhang, Yuye Lan, Suixi Wang, Kailing Zhang, Zixiao Wang, He Zhu, Xunan Zheng, Yi Luo, Lei Pei, Caihua Wu, Yongmin Liu, Man Li
Summary: Neuropathic pain affects 7-10% of the general population worldwide. Electroacupuncture effectively relieves neuropathic pain symptoms without side effects, but the underlying molecular mechanisms are unclear. In this study, a rat model of neuropathic pain was induced and RNA sequencing was used to identify dysregulated genes. It was found that electroacupuncture inhibited ferroptosis and alleviated pain through the SAT1/ALOX15 pathway. These findings provide insights into the mechanisms of electroacupuncture and offer a new therapeutic target for neuropathic pain.
MOLECULAR NEUROBIOLOGY
(2023)
Article
Neurosciences
Long He, Jing Cao, Bao-Chun Jiang, Jian-Jun Yang, Yuan-Xiang Tao, Yanqiu Ai
Summary: In this study, it was found that spinal nerve ligation upregulated CCAAT/enhancer-binding protein-beta (C/EBP beta) expression in injured dorsal root ganglion, leading to the upregulation of toll-like receptor 7 (TLR7). The activation of TLR7 was associated with cold/thermal hyperalgesia and mechanical allodynia. Mechanistically, an increased binding of C/EBP beta to T1r7 promoter was observed. These findings highlight the importance of C/EBP beta in nerve trauma-induced TLR7 upregulation.
MOLECULAR NEUROBIOLOGY
(2022)
Article
Neurosciences
Jianxiong Wei, Shuyang Chang, Siyi Liu, Lixia Tian, Xuan Zhu, Shuo Wang, Xiaoqiong Zhou, Yuying Wang, Linping Xu, Fu-Quan Huo, Lingli Liang
Summary: In this study, researchers investigated the role of LSD1, a histone demethylase and transcriptional co-repressor, in radicular pain. They found that LSD1 was upregulated in compressed and injured nerve ganglia, suggesting it may contribute to pain hypersensitivities. These findings suggest that LSD1 could serve as a potential target for the treatment of radicular pain and neuropathic pain.
BRAIN RESEARCH BULLETIN
(2022)
Article
Immunology
Wen Chen, Xiaotong Wang, Qingyu Sun, Yurui Zhang, Jing Liu, Tingting Hu, Weihua Wu, Chao Wei, Meng Liu, Yumeng Ding, Dianxin Liu, Yingzi Chong, Peipei Wang, Hongwei Zhu, Weihua Cui, Jiannan Zhang, Qian Li, Fei Yang
Summary: The NLRP3 pathway is activated in the DRG of the DNP model, and TET2 is involved in DNP hypersensitivity by upregulating the TXNIP/NLRP3 pathway.
JOURNAL OF NEUROINFLAMMATION
(2022)
Article
Biochemistry & Molecular Biology
Nea Korvenlaita, Lauri Louhivuori
Summary: Increasing evidence suggests that macrophages play an important role in peripheral nerve injury (PNI) and associated pain. Differences in in vivo models and methodologies may explain the variations between peripheral nerve macrophages and dorsal root ganglia (DRG) macrophages. Using single-nucleus transcriptomic analysis, this study compared the effects of sciatic nerve transection, spinal nerve transection, and nerve crush on DRG macrophage phenotypes. The findings demonstrate unique and time-dependent gene expression profiles of DRG macrophages in the different PNI models, suggesting a carefully orchestrated response of various DRG macrophage subtypes in PNI.
Article
Immunology
Juping Xing, Hongji Wang, Lisha Chen, Hanxi Wang, Huan Huang, Jiabao Huang, Changshui Xu
Summary: This study investigated the role of Cx43 in neuropathic pain mediated by the P2X4 receptor in rats with chronic constriction injury (CCI). The results showed that blocking Cx43 can alleviate neuropathic pain in CCI rats through the P2X4, p38, ERK, and NF-kB signaling pathways. These findings suggest that Cx43 may be a promising therapeutic target for the development of novel pharmacological agents in the management of neuropathic pain.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Anesthesiology
Luyao Zhang, Xiang Li, Xiaozhou Feng, Tolga Berkman, Ruining Ma, Shibin Du, Shaogen Wu, Congcong Huang, Akwasi Amponsah, Alex Bekker, Yuan-Xiang Tao
Summary: Nerve trauma-induced alternations of gene expression in the neurons of DRG participate in nerve trauma-caused nociceptive hypersensitivity. ELF1 plays a role in nerve trauma-caused nociceptive hypersensitivity by upregulating MMP9 in injured DRG. ELF1 may be a potential target for managing neuropathic pain.
Article
Biochemistry & Molecular Biology
Valentina Dzreyan, Moez Eid, Stanislav Rodkin, Maria Pitinova, Svetlana Demyanenko
Summary: This study investigated the expression and localization of E2F1 after axonal injury and found that axotomy increased the expression of E2F1 in neurons. The study also suggested that E2F1 and downstream targets could be potential molecular targets for the development of neuroprotective agents.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biology
Qi Chen, Xi-Yin Zhang, Yu-Pu Wang, Yun-Jie Fu, Feng Cao, Yi-Nuo Xu, Jin-Ge Kong, Na-Xi Tian, Yu Xu, Yun Wang
Summary: This study created a novel rat model called spared nerve crush (SNC) that successfully recapitulated neuropathic pain and axonal regeneration after peripheral nerve injury (PNI). The study revealed the intrinsic link between neuropathic pain and axonal regeneration and identified Adcyap1 as a potential gene contributing to both processes.
Review
Biochemistry & Molecular Biology
Timothy Warwick, Ralf P. P. Brandes, Matthias S. S. Leisegang
Summary: This article summarizes recent progress in the prediction of DNA:DNA:RNA triplex formation and highlights important DNA:DNA:RNA triplexes. The study shows that DNA:DNA:RNA triplexes play an important role in gene expression regulation.
Article
Chemistry, Medicinal
Fabian H. Knaup, Christian Meyners, Wisely Oki Sugiarto, Saskia Wedel, Margherita Springer, Carlo Walz, Thomas M. Geiger, Mathias Schmidt, Marco Sisignano, Felix Hausch
Summary: In recent years, selective inhibition of FKBP51 has been considered as a potential treatment for chronic pain, obesity-induced diabetes, or depression. Through structure-based drug design exploration, thiophenes were unexpectedly discovered as highly efficient cyclohexyl replacements, enabling similar selectivity for FKBP51 as SAFit-type inhibitors. The inclusion of thiophene-containing motifs stabilizes a flipped-out conformation of Phe(67) of FKBP51, enabling selectivity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Medicine, Research & Experimental
Florestan J. Koll, Severine Banek, Luis Kluth, Jens Koellermann, Katrin Bankov, Felix K. -H. Chun, Peter J. Wild, Andreas Weigert, Henning Reis
Summary: We analyzed the immune cells in the tumor microenvironment of 101 patients with muscle-invasive urothelial bladder cancer using multiplex immunohistochemistry. We found that high concentrations of macrophages were associated with increased risk of death, while high concentrations of Tregs were associated with decreased risk of death. We also identified two clusters, one with a high concentration of macrophages and the other with a high concentration of Tregs, which were associated with the worst and best survival rates, respectively.
JOURNAL OF TRANSLATIONAL MEDICINE
(2023)
Review
Pharmacology & Pharmacy
Andreas Friebe, Jan R. R. Kraehling, Michael Russwurm, Peter Sandner, Achim Schmidtko
Summary: Increasing cGMP levels is a unique therapeutic approach that has been approved for the treatment of various diseases. The understanding of cGMP signaling pathways at different levels and in different models is crucial for maximizing treatment opportunities and minimizing potential risks. The biannual international cGMP conference serves as an important forum for researchers to share their findings and advancements in cGMP research. This review provides an overview of the contributions to the 10th cGMP Conference and recent key achievements in the field.
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
(2023)
Article
Oncology
Veronika Lutz, Veronique M. Hellmund, Felix S. R. Picard, Hartmann Raifer, Teresa Ruckenbrod, Matthias Klein, Tobias Bopp, Rajkumar Savai, Peter Duewell, Corinna U. Keber, Andreas Weigert, Ho-Ryun Chung, Malte Buchholz, Andre Menke, Thomas M. Gress, Magdalena Huber, Christian Bauer
Summary: Signaling through IL18R induces exhaustion of CD8(+) T cells, characterized by expression of coinhibitory receptors and loss of effector function. This exhaustion is mediated by an NLRP3-expressing tumor microenvironment that releases IL18. These findings suggest that NLRP3-mediated IL18R signaling could be a potential target for immunotherapy in pancreatic carcinoma.
CANCER IMMUNOLOGY RESEARCH
(2023)
Article
Physiology
Timothy Warwick, Giulia Karolin Buchmann, Beatrice Pflueger-Mueller, Manuela Spaeth, Christoph Schuermann, Wesley Abplanalp, Lukas Tombor, David John, Andreas Weigert, Martin Leo-Hansmann, Stefanie Dimmeler, Ralf P. Brandes
Summary: Treatment of vascular stenosis with angioplasty can cause acute vascular damage, leading to restenosis. Single-cell RNA sequencing analysis of mouse carotid tissue after wire injury revealed the presence of smooth muscle cells that are also associated with atherosclerosis and myocardial infarction. These cells, called SEM cells, show specific gene expression patterns that could be targeted therapeutically to combat restenosis development.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Immunology
Maximilian Haist, Justus Kaufmann, Ivan-Maximiliano Kur, Stefanie Zimmer, Stephan Grabbe, Heinz Schmidberger, Andreas Weigert, Arnulf Mayer
Summary: In this study, the infiltration of CD8 T cells and the expression of PD-L1 were found to be significantly associated with the efficacy and survival of chemoradiotherapy in patients with oropharyngeal cancer. However, tumor cell proliferation and the expression of stem cell markers showed no independent prognostic effect.
FRONTIERS IN IMMUNOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Verena Wilmes, Ivan M. Kur, Andreas Weigert, Marcel A. Verhoff, Elise Gradhand, Silke Kauferstein
Summary: This study examines the expression of iNOS and NT production in postmortem human myocardial infarction hearts. The results demonstrate that resident macrophages are the main source of iNOS expression in these hearts, and there is a correlation between iNOS and NT production, indicating the involvement of iNOS in oxidative stress.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2023)
Review
Cardiac & Cardiovascular Systems
Sabine Steffens, Katrin Schroeder, Martina Krueger, Christoph Maack, Katrin Streckfuss-Boemeke, Johannes Backs, Rolf Backofen, Bettina Baessler, Yvan Devaux, Ralf Gilsbach, Jordi Heijman, Jochen Knaus, Rafael Kramann, Dominik Linz, Allyson L. Lister, Henrike Maatz, Lars Maegdefessel, Manuel Mayr, Benjamin Meder, Sara Y. Nussbeck, Eva A. Rog-Zielinska, Marcel H. Schulz, Albert Sickmann, Goekhan Yigit, Peter Kohl
Summary: Sharing and documentation of cardiovascular research data are essential but challenges like lack of time, incentives, funding, standardization, and legal understanding exist. More tools, education, and training are needed for effective data sharing and an open science culture. Long-term effort is required for FAIR RDM.
CLINICAL RESEARCH IN CARDIOLOGY
(2023)
Article
Cell Biology
Tobias F. Primke, Rebecca Ingelfinger, Mohammed A. F. Elewa, Igor Macinkovic, Andreas Weigert, Matthias P. Fabritius, Christoph A. Reichel, Angelika Ullrich, Uli Kazmaier, Luisa D. Burgers, Robert Fuerst
Summary: Research has found that depolymerizing microtubule-targeting agents can reduce inflammation by inhibiting the expression of pro-inflammatory molecules and decreasing leukocyte adhesion to endothelial cells. These agents not only affect leukocytes but also significantly decrease the inflammatory response of vascular endothelial cells. The study sets a baseline for further exploration of the anti-inflammatory effects of depolymerizing microtubule-targeting agents.
Article
Cell Biology
Santiago Bianconi, Karla M. C. Oliveira, Kari-Leticia Klein, Jakob Wolf, Alexander Schaible, Katrin Schroeder, John Barker, Ingo Marzi, Liudmila Leppik, Dirk Henrich
Summary: Electrical stimulation (EStim) has been shown to promote bone healing, but its long-term effects were not significant in this study. Pretreating MSCs with EStim did not significantly improve bone tissue engineering treatments for large bone defects. The bone healing environment may counteract the pro-osteogenic effects of EStim seen in vitro.
Article
Respiratory System
Annemarie Aue, Nils Englert, Leon Harrer, Fabian Schwiering, Annika Gaab, Peter Koenig, Ralf Adams, Achim Schmidtko, Andreas Friebe, Dieter Groneberg
Summary: By utilizing PDGFRβ-tdTomato mice, researchers found that lung pericytes can differentiate into two types of α-SMA expressing myofibroblasts, and the expression of NO-GC decreases during lung fibrosis. This finding reveals the origin and characteristics of myofibroblasts in pulmonary fibrosis.
RESPIRATORY RESEARCH
(2023)
Meeting Abstract
Medicine, Research & Experimental
Florestan Koll, Jens Koellermann, Luis Kluth, Severine Banek, Felix Chun, Andreas Weigert, Peter Wild, Henning Reis
LABORATORY INVESTIGATION
(2023)
Article
Cardiac & Cardiovascular Systems
Frederike Boos, James A. Oo, Timothy Warwick, Stefan Guenther, Judit Izquierdo Ponce, Melina Lopez, Diba Rafii, Giulia Buchmann, Minh Duc Pham, Zahraa S. Msheik, Tianfu Li, Sandra Seredinski, Shaza Haydar, Sepide Kashefiolasl, Karl H. Plate, Ruediger Behr, Matthias Mietsch, Jaya Krishnan, Soni S. Pullamsetti, Sofia-Iris Bibli, Rabea Hinkel, Andrew H. Baker, Reinier A. Boon, Marcel H. Schulz, Ilka Wittig, Francis J. Miller, Ralf P. Brandes, Matthias S. Leisegang
Summary: Long non-coding RNA LINC00607 is highly enriched in human endothelial cells and plays a regulatory role in angiogenesis by interacting with chromatin remodeler BRG1 to maintain ERG target gene transcription. Knockdown or knockout of LINC00607 attenuates VEGF-A-induced angiogenic sprouting and integration into vascular networks. Overexpression of LINC00607 restores normal endothelial function. These findings provide new insights into the role of lncRNAs in endothelial cells and their potential implications in cardiovascular disease.
BASIC RESEARCH IN CARDIOLOGY
(2023)
Article
Biology
Pauline Hog, Silvia Kuntschar, Peter Rappl, Arnaud Huard, Andreas Weigert, Bernhard Bruene, Tobias Schmid
Summary: Macrophages are a versatile immune cell group involved in inflammatory reactions. This study reveals that prostaglandin E-2 (PGE(2)) may contribute to the regulation of Lyve1 expression and impact inflammatory responses. PGE(2) synergizes with dexamethasone to enhance Lyve1 expression, while CD44 expression remains unchanged. Lyve1-expressing macrophages integrate inflammatory stimuli with extracellular matrix-derived signals.