Article
Anesthesiology
Caroline M. Kopruszinski, Moe Watanabe, Ashley L. Martinez, Luiz Henrique Moreira de Souza, David W. Dodick, Aubin Moutal, Volker Neugebauer, Frank Porreca, Edita Navratilova
Summary: Repeated stress can cause hyperalgesic priming, and the underlying mechanisms are not fully understood. This study investigated the effects of repeated administration of kappa opioid receptor (KOR) agonists and the potential involvement of prolactin (PRL) and prolactin receptor (PRLR) isoforms in sensory neurons. The results showed that KOR agonists increased circulating PRL and induced allodynia, which resolved within 14 days. Hyperalgesic priming was observed in both sexes after KOR agonist administration, but downregulation of PRLR isoforms was observed only in female mice. The study suggests a PRL/PRLR dependence in female nociceptors, which may contribute to pain in stress-related pain disorders in females.
Article
Pharmacology & Pharmacy
Rink-Jan Lohman, Karnaker Reddy Tupally, Ajit Kandale, Peter J. Cabot, Harendra S. Parekh
Summary: Kappa opioid receptors have great potential as analgesic targets. Modified dynorphin peptides have been developed as safer KOP receptor agonists. These peptides showed selective and potent KOP receptor activity, improved metabolic stability, and promising analgesic efficacy in animal models.
FRONTIERS IN PHARMACOLOGY
(2023)
Article
Multidisciplinary Sciences
Edward L. Stahl, Cullen L. Schmid, Agnes Acevedo-Canabal, Cai Read, Travis W. Grim, Nicole M. Kennedy, Thomas D. Bannister, Laura M. Bohn
Summary: G protein-biased mu opioid receptor agonists demonstrate stability in a wash-resistant signaling state and reversibility by antagonists. These biased agonists stimulate G protein signaling in mouse brains without competing with full agonist activation.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Chemistry, Multidisciplinary
Yifeng Tang, Jeremiah Y. Kim, Carman K. M. Ip, Azadeh Bahmani, Qing Chen, Matthew G. Rosenberger, Aaron P. Esser-Kahn, Andrew L. Ferguson
Summary: A machine learning-enabled active learning pipeline was developed to guide the screening and discovery of small molecule immunomodulators that can improve immune responses. By using high throughput screening and data-driven predictive models, novel small molecules with enhanced or suppressed innate immune signaling capacity were discovered, and chemical design rules were extracted.
Article
Chemistry, Medicinal
Thanigaimalai Pillaiyar, Francesca Rosato, Monika Wozniak, Jeremy Blavier, Maelle Charles, Celine Laschet, Thales Kronenberger, Christa E. Mueller, Julien Hanson
Summary: This study identified a selective GPR27 agonist and a series of new derivatives and analogs, including potent agonists with higher efficacies than the lead compound. Docking studies predicted the putative binding site and interactions of an agonist with GPR27, providing important new tools for further characterizing the (patho)physiological roles of GPR27.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Chemistry, Multidisciplinary
Haoqing Wang, Florian Hetzer, Weijiao Huang, Qianhui Qu, Justin Meyerowitz, Jonas Kaindl, Harald Huebner, Georgios Skiniotis, Brian K. Kobilka, Peter Gmeiner
Summary: This study reported the structure of the mu-opioid receptor agonist PZM21 bound to mu OR in complex with G(i) protein, and its derivative FH210 with extremely low efficacy for arrestin recruitment. The study revealed a potential mechanism to reduce beta-arrestin recruitment by mu OR, holding promise for developing next-generation analgesics with fewer adverse effects.
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
(2022)
Article
Biochemical Research Methods
Jooseong Oh, Hyi-Thaek Ceong, Dokyun Na, Chungoo Park
Summary: In this study, a machine learning model was developed to identify GPCR agonists and antagonists. The model showed high accuracy in classifying ligands and can be applied in virtual screening for potential GPCR-binding agonists and antagonists.
BMC BIOINFORMATICS
(2022)
Article
Multidisciplinary Sciences
Gregory A. Wyant, Wenyu Yu, IIias P. Doulamis, Rio S. Nomoto, Mossab Y. Saeed, Thomas Duignan, James D. McCully, William G. Kaelin Jr
Summary: Kynurenic acid (KynA) has tissue-protective effects in ischemia models, and this study demonstrates that activation of GPR35 and interaction with ATPIF1 may be the underlying mechanism. These findings provide a rationale for developing specific GPR35 agonists for the treatment of ischemic diseases.
Article
Pharmacology & Pharmacy
Alexander R. French, Richard M. van Rijn
Summary: Kappa opioid receptor (icOR) agonists are considered safer alternatives to clinically used mu opioid receptor (mu OR) analgesics with no abuse liability and respiratory depression effects. However, they have their own limiting adverse effects that hinder clinical translation. Recent studies suggest that these effects may be due to distinct intracellular signaling pathways, leading to the hypothesis that biased icOR agonists away from ll-arrestin signaling could have improved therapeutic windows. Overall, G-protein-biased icOR agonists generally have better therapeutic windows compared to unbiased agonists, although study design limits strong conclusions in this regard. The development of biased icOR agonists and new tools in the field puts icOR research in a position to advance our understanding and translation of biased icOR agonists to clinical use.
PHARMACOLOGICAL RESEARCH
(2022)
Review
Biochemistry & Molecular Biology
Samo Lesnik, Eva Bertalan, Urban Bren, Ana-Nicoleta Bondar
Summary: This paper discusses the relationship between the structure, function, and dynamics of opioid receptors, with a focus on the usefulness of computational studies to evaluate protonation-coupled opioid-receptor interactions.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Review
Biochemistry & Molecular Biology
Thian-Sze Wong, Guangzhi Li, Shiliang Li, Wei Gao, Geng Chen, Shiyi Gan, Manzhan Zhang, Honglin Li, Song Wu, Yang Du
Summary: Neuropsychiatric disorders are complex and have various causes. Finding effective treatment targets is difficult due to the heterogeneous nature of these diseases. However, the growing knowledge of G protein-coupled receptors (GPCRs) provides a potential avenue for drug discovery. Understanding the molecular mechanisms and structures of GPCRs can aid in the development of effective drugs. This review provides an overview of the role of GPCRs in neurodegenerative and psychiatric diseases, highlights new opportunities for GPCR targets, and discusses recent progress in GPCR drug development.
SIGNAL TRANSDUCTION AND TARGETED THERAPY
(2023)
Article
Optics
Hui Chen, Zi-Fan Zhao, Wei-Jie Li, Ze-Di Cheng, Jiao-Diao Suo, Bo -Lin Li, Meng-Lin Guo, Bo-Yu Fan, Qiang Zhou, You Wang, Hai-Zhi Song, Xiao-Bin Niu, Xiao-Yu Li, Konstantin Yu. Arutyunov, Guang-Can Guo, Guang-Wei Deng
Summary: This study proposes a gate-tunable bolometer based on two strongly coupled graphene nanomechanical resonators. The properties of one bolometer can be measured directly by tracking the resonance frequency shifts, while the other bolometer can be indirectly measured through mechanical coupling. The sensitivity and response bandwidth of both bolometers can be independently adjusted by tuning the corresponding gate voltages. The method has the potential to optimize the design of large-scale bolometer arrays and open new horizons in infrared/terahertz astronomy and other fields.
Article
Physics, Multidisciplinary
Zhengang Shi, Xiongwen Chen, Shaohua Xiang
Summary: We investigate the routing scheme of single photons in a photonic quantum network. The proposed router consists of two one-dimensional waveguides and a whispering-gallery-mode resonator interacting with two-level atoms. The study demonstrates that quantum interference caused by atoms can be utilized to control the transport of single photons in the waveguides. By adjusting the amplitude of the intermode backscattering strength and the position of the atom, perfect transmission and reflection of single photons can be achieved when only one atom is considered. For the case of two atoms, deterministic transfer of nonresonant photon input from one port of the first waveguide to one of the selected output ports of the second waveguide can be achieved by properly designing the distance between the two atoms. The routing properties are also analyzed regarding the losses of the atoms and resonator.
EUROPEAN PHYSICAL JOURNAL PLUS
(2023)
Article
Engineering, Environmental
Ju Huang, Binsong Wang, Zhengjia Hao, Zerun Zhou, Yang Qu
Summary: The study focuses on enhancing charge separation and broadening the light response in order to achieve effective photocatalysts for the degradation of antibiotics. The coupling of defected WO3 quantum dots to graphitic carbon nitride nanosheets showed high activity in photo-degradation of antibiotic pollutants, attributed to Z-scheme heterojunction and localized surface plasmon resonance effect. Factors affecting degradation efficiency, such as pH and solution concentration, were also evaluated, highlighting the potential for high-efficiency broadband photocatalysis.
CHEMICAL ENGINEERING JOURNAL
(2021)
Article
Materials Science, Multidisciplinary
Jia-Yu Li, Xin-Yu Wang, Jian Tian, Xiao-Li Zhang, Feng Shi
Summary: This study introduces Co/Fe bimetallic oxide quantum dots-coupled g-C3N4 nanosheets (CoFeO QDs/g-C3N4 NSs) composites that efficiently degrade organic pollutants under neutral conditions. The degradation efficiency of rhodamine B (RhB) reached 98.32% within 90 min for CoFeO QDs/g-C3N4 NSs composites under the photo-Fenton condition. The formed heterojunction between CoFeO QDs and g-C3N4 NSs enhances charge transfer and efficient charge separation, making it an effective and stable photo-Fenton catalyst for degrading organic contaminants.
Article
Biochemical Research Methods
Hi Chul Kim, David Shum, Hyang Sook Seol, Se Jin Jang, Ssang-Goo Cho, Yong-Jun Kwon
Article
Biochemical Research Methods
Hi Chul Kim, Jin Yeong Heo, Tae-Kyu Lee, Ssang-Goo Cho, Yong-Jun Kwon
Article
Genetics & Heredity
Jin-Ku Lee, Zhaoqi Liu, Jason K. Sa, Sang Shin, Jiguang Wang, Mykola Bordyuh, Heejin Cho, Oliver Elliott, Timothy Chu, Seung Won Choi, Daniel I. S. Rosenbloom, In-Hee Lee, Yong Jae Shin, Hyun Ju Kang, Donggeon Kim, Sun Young Kim, Moon-Hee Sim, Jusun Kim, Taehyang Lee, Yun Jee Seo, Hyemi Shin, Mijeong Lee, Sung Heon Kim, Yong-Jun Kwon, Jeong-Woo Oh, Minsuk Song, Misuk Kim, Doo-Sik Kong, Jung Won Choi, Ho Jun Seol, Jung-Il Lee, Seung Tae Kim, Joon Oh Park, Kyoung-Mee Kim, Sang-Yong Song, Jeong-Won Lee, Hee-Cheol Kim, Jeong Eon Lee, Min Gew Choi, Sung Wook Seo, Young Mog Shim, Jae Ill Zo, Byong Chang Jeong, Yeup Yoon, Gyu Ha Ryu, Nayoung K. D. Kim, Joon Seol Bae, Woong-Yang Park, Jeongwu Lee, Roel G. W. Verhaak, Antonio Iavarone, Jeeyun Lee, Raul Rabadan, Do-Hyun Nam
Article
Biochemical Research Methods
Il Doh, Yong-Jun Kwon, Bosung Ku, Dong Woo Lee
Article
Clinical Neurology
Anna Golebiewska, Ann-Christin Hau, Anais Oudin, Daniel Stieber, Yahaya A. Yabo, Virginie Baus, Vanessa Barthelemy, Eliane Klein, Sebastien Bougnaud, Olivier Keunen, May Wantz, Alessandro Michelucci, Virginie Neirinckx, Arnaud Muller, Tony Kaoma, Petr Nazarov, Francisco Azuaje, Alfonso De Falco, Ben Flies, Lorraine Richart, Suresh Poovathingal, Thais Arns, Kamil Grzyb, Andreas Mock, Christel Herold-Mende, Anne Steino, Dennis Brown, Patrick May, Hrvoje Miletic, Tathiane M. Malta, Houtan Noushmehr, Yong-Jun Kwon, Winnie Jahn, Barbara Klink, Georgette Tanner, Lucy F. Stead, Michel Mittelbronn, Alexander Skupin, Frank Hertel, Rolf Bjerkvig, Simone P. Niclou
ACTA NEUROPATHOLOGICA
(2020)
Article
Multidisciplinary Sciences
Ibrahim Boussaad, Gerald Cruciani, Silvia Bolognin, Paul Antony, Claire M. Dording, Yong-Jun Kwon, Peter Heutink, Eugenio Fava, Jens C. Schwamborn, Rejko Krueger
Summary: A comprehensive and complex automated platform for high throughput screenings (HTS) in a translational research setting is described, which is designed for maintenance and expansion of different cell types. The platform allows automation of all cultivation steps and is flexible for development of methods for variable cell types.
SCIENTIFIC REPORTS
(2021)
Article
Oncology
Andy Chevigne, Bassam Janji, Max Meyrath, Nathan Reynders, Giulia D'Uonnolo, Tomasz Uchanski, Malina Xiao, Guy Berchem, Markus Ollert, Yong-Jun Kwon, Muhammad Zaeem Noman, Martyna Szpakowska
Summary: In this study, the atypical chemokine receptor ACKR2 was found to reduce the availability of the CXC chemokine CXCL10 for CXCR3, shedding new light on the complexity of the chemokine network and the potential role of CXCL10 regulation by ACKR2 in tumor immunology. This discovery highlights the importance of systematically reassessing chemokine-receptor interactions, as important interactions may remain unexplored.
Article
Oncology
Hichul Kim, Victoria El-Khoury, Nadine Schulte, Tianzuo Zhan, Johannes Betge, Loic Cousin, Emanuele Felli, Patrick Pessaux, Arnaud Ogier, Oliver Opitz, Bosung Ku, Matthias P. Ebert, Yong-Jun Kwon
Summary: This study presents a case of a patient with metastatic lung atypical carcinoid who achieved disease stability for 2 years using personalized functional profiling-guided treatment.
CANCER BIOLOGY & THERAPY
(2022)
Article
Multidisciplinary Sciences
Peter A. Barbuti, Jochen Ohnmacht, Bruno F. R. Santos, Paul M. Antony, Francois Massart, Gerald Cruciani, Claire M. Dording, Lukas Pavelka, Nicolas Casadei, Yong-Jun Kwon, Rejko Kruger
Summary: The study assessed the functional impact of the p.A30P SNCA mutation on dopaminergic neurons derived from a Parkinson's disease patient. Various impairments in neuronal function were identified, providing insights for potential disease-modifying compound screenings and drug discovery strategies in the future.
SCIENTIFIC REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Miriam Ratliff, Hichul Kim, Hao Qi, Minsung Kim, Bosung Ku, Daniel Dominguez Azorin, David Hausmann, Rajiv K. Khajuria, Areeba Patel, Elena Maier, Loic Cousin, Arnaud Ogier, Felix Sahm, Nima Etminan, Lukas Bunse, Frank Winkler, Victoria El-Khoury, Michael Platten, Yong-Jun Kwon
Summary: The genetic and cellular heterogeneity of glioblastoma poses challenges for effective uniform treatment, especially at recurrence. To address this, personalized strategies and stratification of potential targeted therapies within a clinically relevant timeframe are necessary. Functional profiling of drug candidates against patient-derived glioblastoma organoids (PD-GBO) holds promise in preclinically discovering effective personalized treatments. A PD-GBO-based profiling platform was established and successfully identified potential treatment options for three out of four patients in a turnaround time of 13-15 days. This approach proves to be a complement and potentially an alternative to current molecular profiling efforts, providing a clinically relevant time period for personalized treatment discovery. The use of PD-GBO platforms is also warranted for preclinical identification of new drugs against morphological glioblastoma features.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Cell & Tissue Engineering
Aurore Vuidel, Loic Cousin, Beatrice Weykopf, Simone Haupt, Zahra Hanifehlou, Nicolas Wiest-Daessle, Michaela Segschneider, Joohyun Lee, Yong-Jun Kwon, Michael Peitz, Arnaud Ogier, Laurent Brino, Oliver Bruestle, Peter Sommer, Johannes H. Wilbertz
Summary: Combining multiple cellular phenotypes can improve the accuracy of midbrain dopaminergic neuron models for Parkinson's disease. Machine learning classification can detect chemical compound treatments related to LRRK2.
Article
Genetics & Heredity
Yoonhee Nam, Harim Koo, Yingxi Yang, Sang Shin, Zhihan Zhu, Donggeon Kim, Hee Jin Cho, Quanhua Mu, Seung Won Choi, Jason K. Sa, Yun Jee Seo, Yejin Kim, Kyoungmin Lee, Jeong-Woo Oh, Yong-Jun Kwon, Woong-Yang Park, Doo-Sik Kong, Ho Jun Seol, Jung-Il Lee, Chul-Kee Park, Hye Won Lee, Yeup Yoon, Jiguang Wang
Summary: In this study, we investigated the molecular characteristics associated with temozolomide (TMZ) sensitivity in isocitrate dehydrogenase wild-type (IDH-wt) glioblastoma patients. We developed a machine learning model to predict TMZ response and demonstrated the potential clinical value of this model. Additionally, a webserver was created for public access to the prediction model.
Article
Multidisciplinary Sciences
Jin Yeop Kim, Dong Min Lee, Hyun Goo Woo, Ki Deok Kim, Hong Jae Lee, Yong-Jun Kwon, Kyeong Sook Choi
SCIENTIFIC REPORTS
(2019)
Article
Oncology
Doo-Yi Oh, Kyungsoo Jung, Ji-Young Song, Seokhwi Kim, Sang Shin, Yong-Jun Kwon, Ensel Oh, Woong-Yang Park, Sang Yong Song, Yoon-La Choi
Article
Multidisciplinary Sciences
Hi Chul Kim, Gi-Hwan Kim, David Shum, Ssang-Goo Cho, Eun Ju Lee, Yong-Jun Kwon