Article
Biochemistry & Molecular Biology
Christophe Morisseau, Sean D. Kodani, Shizuo G. Kamita, Jun Yang, Kin Sing Stephen Lee, Bruce D. Hammock
Summary: Epoxy-fatty acids (EpFAs) are endogenous lipid mediators with diverse biological activities; soluble epoxide hydrolase (sEH) is the primary enzyme for degrading EpFAs in vivo; recent studies suggest that microsomal epoxide hydrolase and epoxide hydrolase-3 also play significant roles in the metabolism of EpFAs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Pharmacology & Pharmacy
Saraswati Patel, Jyoti Shukla, Smita Jain, Vartika Paliwal, Neetika Tripathi, Sarvesh Paliwal, Swapnil Sharma
Summary: This study evaluates the analgesic and anti-inflammatory activity of Tubocurarine (d-TC) and suggests its repositioning in the treatment of pain and inflammation-related issues. The results showed significant inhibitory effects of d-TC on pain and inflammation in both in vitro and in vivo models, as well as good oral absorption capability.
BIOCHEMICAL PHARMACOLOGY
(2022)
Article
Neurosciences
Jing Ren, Cheng-Lin Lu, Jie Huang, Jun Fan, Fang Guo, Jia-Wen Mo, Wei-Yuan Huang, Peng-Li Kong, Xiao-Wen Li, Li-Rong Sun, Xiang-Dong Sun, Xiong Cao
Summary: Anxiety disorders, affecting approximately 16% of the global population, have been found to involve soluble epoxide hydrolase (sEH) in the central nucleus of the amygdala (CeA). This study demonstrates that sEH is enriched in CeA neurons and regulates anxiety-related behaviors in adult male mice. sEH(CeA) neurons modulate anxiety by maintaining excitability and directly projecting to the bed nucleus of the stria terminalis (BNST), producing both anxiolytic and anxiogenic effects.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Chemistry, Physical
Eva D. Schuiten, Christoffel P. S. Badenhorst, Gottfried J. Palm, Leona Berndt, Michael Lammers, Jan Mican, David Bednar, Jiri Damborsky, Uwe T. Bornscheuer
Summary: The study identified an epoxide hydrolase called CorEH that exhibits dehalogenase activity, suggesting a rare example of a protein with dual enzymatic functions. Despite the much lower dehalogenase activity compared to epoxide hydrolase activity, the presence of multiple activities in one naturally occurring protein demonstrates significant diversity.
Article
Biochemistry & Molecular Biology
Vladimir Burmistrov, Christophe Morisseau, Denis A. Babkov, Tatiana Golubeva, Dmitry Pitushkin, Elena Sokolova, Vladimir Vasipov, Yaroslav Kuznetsov, Sergey Bazhenov, Uliana S. Novoyatlova, Nikolay A. Bondarev, Ilya Manukhov, Victoria Osipova, Nadezhda Berberova, Alexander A. Spasov, Gennady M. Butov, Bruce D. Hammock
Summary: The newly synthesized inhibitor compounds showed effective inhibitory activity against inflammation and exhibited low cytotoxicity in cell assays.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Jang Hoon Kim, Yun-Chan Huh, Mok Hur, Woo Tae Park, Youn-Ho Moon, Tae Il Kim, Yong Il Kim, Seon Mi Kim, Jeonghoon Lee, Ik Soo Lee
Summary: A Glycyrrhiza uralensis extract showed potential inhibition of sEH, a target enzyme for treating inflammation and cardiovascular disease. Compounds 1-11 were isolated and tested, with compound 10 exhibiting the strongest inhibitory activity. Further evaluation in cells and animals is needed for compound 10.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Die Hu, Bo-Chun Hu, Zheng Wen, Dong Zhang, You-Yi Liu, Jia Zang, Min-Chen Wu
Summary: The study identified AuEH2 from Aspergillus usamii as a promising enzyme for the kinetic resolution of o-nitrostyrene oxide, showing high activity and enantiomeric selectivity. The enzyme exhibited regioselectivity towards racemic 4a and was able to achieve nearly perfect kinetic resolution under certain conditions, producing highly pure products.
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
(2021)
Article
Biochemistry & Molecular Biology
Vengai Mavangira, Matthew J. Kuhn, Angel Abuelo, Christophe Morisseau, Bruce D. Hammock, Lorraine M. Sordillo
Summary: Comparative analysis of sEH activity and oxidant status between healthy dairy cows and those with coliform mastitis revealed increased sEH activity in mammary tissue and elevated oxidant levels in milk of the mastitis group, suggesting potential therapeutic targets for coliform mastitis.
Article
Chemistry, Medicinal
Juan Martin-Lopez, Sandra Codony, Clara Bartra, Christophe Morisseau, Maria Isabel Loza, Coral Sanfeliu, Bruce D. Hammock, Jose Brea, Santiago Vazquez
Summary: Pharmacological inhibition of soluble epoxide hydrolase (sEH) has potential therapeutic effects for pain and inflammatory diseases. New potent inhibitors have been developed, but low stability of some compounds requires further research.
Article
Biotechnology & Applied Microbiology
Harshada M. Salvi, Ganapati D. Yadav
Summary: Epoxide hydrolases are enzymes widely found in nature that catalyze the hydrolysis of epoxides to diols without the need for a cofactor. A method for immobilization of epoxide hydrolase based on biomimetic mineralization has been reported, resulting in organic-inorganic hybrid nanoflowers with higher catalytic activity and stability. The nanoflowers, consisting of enzyme epoxide hydrolase and Ca2+ ions, exhibit a unique hierarchical flower-like structure and have been applied for styrene oxide hydrolysis. Factors affecting morphology, catalytic activity, and stability were studied to understand the activity recovery of the synthesized hybrid nanoflowers.
JOURNAL OF BIOTECHNOLOGY
(2021)
Article
Pharmacology & Pharmacy
Jingyi Xu, Xing Qiu, Gary Yu, Maria Ly, Jun Yang, Rona M. Silva, Xun Zhang, Mang Yu, Yinong Wang, Bruce Hammock, Kent E. Pinkerton, Dewei Zhao
Summary: Exposure to tobacco smoke has been linked to osteonecrosis of the femoral head, with soluble epoxide hydrolase inhibitors potentially offering protective effects, particularly in hypertensive rats.
Article
Psychiatry
Sevilla D. Detera-Wadleigh, Layla Kassem, Emily Besancon, Fabiana Lopes, Nirmala Akula, Heejong Sung, Meghan Blattner, Laura Sheridan, Ley Nadine Lacbawan, Joshua Garcia, Francis Gordovez, Katherine Hosey, Cassandra Donner, Claudio Salvini, Thomas Schulze, David T. W. Chen, Bryce England, Joanna Cross, Xueying Jiang, Winston Corona, Jill Russ, Barbara Mallon, Amalia Dutra, Evgenia Pak, Joe Steiner, Nasir Malik, Theresa de Guzman, Natia Horato, Mariana B. Mallmann, Victoria Mendes, Amanda L. Duck, Antonio E. Nardi, Francis J. McMahon
Summary: Genome-wide and copy number variant association studies have identified risk alleles associated with BD, MDD, and SCZ, but the biological characterization of these alleles is limited by the inaccessibility of live human brain cells and inadequate animal models. Human-derived iPSCs provide a renewable cellular reagent that can be differentiated into disease-relevant cells and 3D brain organoids with the full complement of genetic variants. A new iPSC resource comprising clinical, genomic, and cellular data from families with BD and related conditions allows for functional genomic studies of these disorders.
TRANSLATIONAL PSYCHIATRY
(2023)
Article
Chemistry, Physical
Claudia Sanfilippo, Angela Patti
Summary: Some vegetable flours, particularly soybean, mung bean, and red mung bean, were found to contain epoxide hydrolase activity. A freeze-dried enzymatic preparation was successfully obtained from the flours, which maintained most of the activity of the fresh suspension and offered advantages in handling, reproducibility, and stability. By optimizing the use of the enzymatic preparations, high yield and stereochemical purity of trans-(4R)-limonene oxide and cis(4S)-limonene oxide were achieved.
MOLECULAR CATALYSIS
(2022)
Article
Plant Sciences
Jang Hoon Kim, Ji Hyeon Park, Sung Cheol Koo, Yun-Chan Huh, Mok Hur, Woo Tae Park, Youn-Ho Moon, Tae Il Kim, Byoung Ok Cho
Summary: This study evaluated the efficacy of cis-khellactone, a compound isolated from Peucedanum japonicum, as an anti-inflammatory agent. The compound was found to be a competitive inhibitor of sEH and could inhibit pro-inflammatory cytokines. Molecular docking and dynamics simulations revealed the binding pose of cis-khellactone within the active site of sEH, suggesting its dependency on the Trp336-Gln384 loop. These findings highlight the potential of cis-khellactone as a natural therapeutic candidate for inflammation treatment.
Article
Multidisciplinary Sciences
Matthieu Leuillier, Thomas Duflot, Severine Menoret, Hind Messaoudi, Zoubir Djerada, Deborah Groussard, Raphael G. P. Denis, Laurence Chevalier, Ahmed Karoui, Baptiste Panthu, Pierre-Alain Thiebaut, Isabelle Schmitz-Afonso, Severine Nobis, Cynthia Campart, Tiphaine Henry, Camille Sautreuil, Serge H. Luquet, Olivia Beseme, Catherine Feliu, Helene Peyret, Lionel Nicol, Jean-Paul Henry, Sylvanie Renet, Paul Mulder, Debin Wan, Laurent Tesson, Jean-Marie Heslan, Angeline Duche, Sebastien Jacques, Frederic Ziegler, Valery Brunel, Gilles J. P. Rautureau, Christelle Monteil, Jean-Luc do Rego, Jean-Claude do Rego, Carlos Afonso, Bruce Hammock, Anne-Marie Madec, Florence Pinet, Vincent Richard, Ignacio Anegon, Christophe Guignabert, Christophe Morisseau, Jeremy Bellien
Summary: The physiological role of the N-terminal phosphatase activity (sEH-P) of soluble epoxide hydrolase (sEH-H) was investigated using CRISPR/Cas9 to generate a knock-in (KI) rat line lacking sEH-P activity. The study found that sEH-P KI rats exhibited decreased metabolism of lysophosphatidic acids, decreased weight and fat mass gain, and increased insulin sensitivity. Moreover, sEH-P KI rats showed increased lipolysis and enhanced energy expenditure, which potentiated brown adipose thermogenesis. Additionally, sEH-P KI rats fed a high-fat diet did not experience weight gain, fat mass accumulation, insulin resistance, or hepatic steatosis, and they also exhibited enhanced cardiac mitochondrial activity and protection against ischemia-reperfusion injury. Overall, the findings highlight the importance of sEH-P in energy and fat metabolism and its potential therapeutic significance in the management of obesity and cardiac complications.
JOURNAL OF ADVANCED RESEARCH
(2023)
Article
Allergy
Kudret C. Ozdemir, Ramune Jacobsen, Morten Dahl, Eskild Landt
Summary: The study aimed to identify and rank factors associated with medication adherence among adults with asthma. The results showed that recent asthma attacks, higher age, and use of allergy medication were the three most important factors associated with asthma medication adherence. The study emphasized the importance of communicating the significance of medication adherence to the general population.
Review
Endocrinology & Metabolism
Takahito Doi, Borge G. Nordestgaard, Anne Langsted
Summary: Recent studies have shown that including remnant cholesterol in risk assessment can significantly improve the accuracy of reclassifying individuals at risk of developing myocardial infarction and ischemic heart disease, both in primary and secondary prevention settings.
CURRENT OPINION IN ENDOCRINOLOGY DIABETES AND OBESITY
(2023)
Article
Ophthalmology
Katrine L. L. Rasmussen, Anne Tybjaerg-Hansen, Borge G. Nordestgaard, Ruth Frikke-Schmidt
Summary: This study aims to determine the association between genetic variations in the apolipoprotein E (APOE) gene and the risk of age-related macular degeneration (AMD). The results suggest that structural variations in the APOE gene may be important for the risk of AMD in individuals of European ancestry.
JAMA OPHTHALMOLOGY
(2023)
Letter
Cardiac & Cardiovascular Systems
Liv Tybjaerg Nordestgaard, Borge Gronne Nordestgaard, Anne Tybjaerg-Hansen
Article
Cardiac & Cardiovascular Systems
Berit Storgaard Hedegaard, Christian Sorensen Bork, Helle Lynge Kanstrup, Kristian Korsgaard Thomsen, Merete Heitmann, Lia Evi Bang, Finn Lund Henriksen, Lars Juel Andersen, Thomas Gohr, Mette Rauhe Mouridsen, Anne Merete Boas Soja, Frank-Peter Elpert, Tomas Joen Jakobsen, Anette Sjol, Albert Marni Joensen, Borge Gronne Nordestgaard, Ib Christian Klausen, Erik Berg Schmidt
Summary: This study investigated the percentage of familial hypercholesterolaemia (FH) among patients referred to Danish lipid clinics and evaluated the impact of genetic testing on FH diagnosis. The results showed that genetic testing increased the diagnosis rate of FH from 22% to 37%. Therefore, a more widespread use of genetic testing is recommended for evaluating a possible FH diagnosis and potential cascade screening.
Article
Medical Laboratory Technology
Jesper Qvist Thomassen, Borge G. Nordestgaard, Anne Tybjaerg-Hansen, Ruth Frikke-Schmidt
Summary: This study found that high plasma concentrations of calcium ions were associated with increased risk of Alzheimer's disease (AD), but no genetic associations were found. This suggests that the observational findings may be due to reverse causation or residual confounding.
CLINICAL CHEMISTRY
(2023)
Review
Biochemistry & Molecular Biology
Benjamin N. Wadstrom, Kasper M. Pedersen, Anders B. Wulff, Borge G. Nordestgaard
Summary: The purpose of this review is to compare the evidence for inflammation and low-density lipoprotein (LDL) cholesterol in atherosclerotic cardiovascular disease (ASCVD). Recent findings suggest that IL-6 mediated inflammation may cause ASCVD along with LDL cholesterol. Future research should focus on improving anti-inflammatory therapy and implementing more effective LDL cholesterol lowering therapy.
CURRENT OPINION IN LIPIDOLOGY
(2023)
Article
Public, Environmental & Occupational Health
Liv Tybjaerg Nordestgaard, Mette Christoffersen, Shoaib Afzal, Borge Gronne Nordestgaard, Anne Tybjaerg-Hansen, Ruth Frikke-Schmidt
Summary: Genetic variants in ABCA1 associated with high HDL cholesterol concentrations are also associated with higher risk of AMD, suggesting a role for ABCA1 in AMD pathogenesis.
EUROPEAN JOURNAL OF EPIDEMIOLOGY
(2023)
Article
Cardiac & Cardiovascular Systems
Sofie Taageby Nielsen, Rikke Mohr Lytsen, Nina Strandkjaer, Ida Juul Rasmussen, Anne-Sophie Sillesen, R. Ottilia B. Vogg, Anna Axelsson Raja, Borge G. Nordestgaard, Pia R. Kamstrup, Kasper Iversen, Henning Bundgaard, Anne Tybjaerg-Hansen, Ruth Frikke-Schmidt
Summary: This study investigated lipid parameters in infants during the first 14-16 months of life and found that factors such as sex, gestational age, birth weight, breastfeeding, and parental lipid concentrations influenced lipid parameters. It was also found that high concentrations of lipid traits at birth were associated with high concentrations at 2 and 14-16 months.
EUROPEAN HEART JOURNAL
(2023)
Editorial Material
Cardiac & Cardiovascular Systems
Anne Tybjaerg-Hansen, Borge G. Nordestgaard, Mette Christoffersen
EUROPEAN HEART JOURNAL
(2023)
Review
Peripheral Vascular Disease
Takahito Doi, Anne Langsted, Borge G. Nordestgaard
Summary: East Asia has a significant population and ischemic heart disease is a major cause of death in this region. However, the evidence on lipoproteins and lipoprotein cholesterol with risk of ASCVD mainly comes from White people in Europe and North America, lacking representation of East Asian populations. Understanding the association between lipoproteins and lipoprotein cholesterol with risk of ASCVD in East Asia is important for both East Asian and non-East Asian populations worldwide.
JOURNAL OF ATHEROSCLEROSIS AND THROMBOSIS
(2023)
Article
Endocrinology & Metabolism
Berit Storgaard Hedegaard, Borge Gronne Nordestgaard, Helle Lynge Kanstrup, Kristian Korsgaard Thomsen, Jan Bech, Lia Evi Bang, Finn Lund Henriksen, Lars Juel Andersen, Thomas Gohr, Linnea Hornbech Larsen, Anne Merete Boas Soja, Frank-Peter Elpert, Tomas Joen Jakobsen, Anette Sjol, Albert Marni Joensen, Ib Christian Klausen, Erik Berg Schmidt, Christian Sorensen Bork
Summary: This study investigated the presence of lipoprotein(a) in individuals referred to Danish lipid clinics and found that elevated lipoprotein(a) played a role in a quarter of individuals who met the diagnosis criteria for clinical familial hypercholesterolemia (FH).
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM
(2023)
Article
Oncology
Pooja K. Middha, Xiaoliang Wang, Sabine Behrens, Manjeet K. Bolla, Qin Wang, Joe Dennis, Kyriaki Michailidou, Thomas U. Ahearn, Irene L. Andrulis, Hoda Anton-Culver, Volker Arndt, Kristan J. Aronson, Paul L. Auer, Annelie Augustinsson, Thais Baert, Laura E. Beane Freeman, Heiko Becher, Matthias W. Beckmann, Javier Benitez, Stig E. Bojesen, Hiltrud Brauch, Hermann Brenner, Angela Brooks-Wilson, Daniele Campa, Federico Canzian, Angel Carracedo, Jose E. Castelao, Stephen J. Chanock, Georgia Chenevix-Trench, Emilie Cordina-Duverger, Fergus J. Couch, Angela Cox, Simon S. Cross, Kamila Czene, Laure Dossus, Pierre-Antoine Dugue, A. Heather Eliassen, Mikael Eriksson, D. Gareth Evans, Peter A. Fasching, Jonine Figueroa, Olivia Fletcher, Henrik Flyger, Marike Gabrielson, Manuela Gago-Dominguez, Graham G. Giles, Anna Gonzalez-Neira, Felix Grassmann, Anne Grundy, Pascal Guenel, Christopher A. Haiman, Niclas Hakansson, Per Hall, Ute Hamann, Susan E. Hankinson, Elaine F. Harkness, Bernd Holleczek, Reiner Hoppe, John L. Hopper, Richard S. Houlston, Anthony Howell, David J. Hunter, Christian Ingvar, Karolin Isaksson, Helena Jernstroem, Esther M. John, Michael E. Jones, Rudolf Kaaks, Renske Keeman, Cari M. Kitahara, Yon-Dschun Ko, Stella Koutros, Allison W. Kurian, James V. Lacey, Diether Lambrechts, Nicole L. Larson, Susanna Larsson, Loic Le Marchand, Flavio Lejbkowicz, Shuai Li, Martha Linet, Jolanta Lissowska, Maria Elena Martinez, Tabea Maurer, Anna Marie Mulligan, Claire Mulot, Rachel A. Murphy, William G. Newman, Sune F. Nielsen, Borge G. Nordestgaard, Aaron Norman, Katie M. O'Brien, Janet E. Olson, Alpa V. Patel, Ross Prentice, Erika Rees-Punia, Gad Rennert, Valerie Rhenius, Kathryn J. Ruddy, Dale P. Sandler, Christopher G. Scott, Mitul T. Shah, Xiao-Ou Shu, Ann Smeets, Melissa C. Southey, Jennifer Stone, Rulla M. Tamimi, Jack A. Taylor, Lauren R. Teras, Katarzyna Tomczyk, Melissa A. Troester, Therese Truong, Celine M. Vachon, Sophia S. Wang, Clarice R. Weinberg, Hans Wildiers, Walter Willett, Stacey J. Winham, Alicja Wolk, Xiaohong Yang, M. Pilar Zamora, Wei Zheng, Argyrios Ziogas, Alison M. Dunning, Paul D. P. Pharoah, Montserrat Garcia-Closas, Marjanka K. Schmidt, Peter Kraft, Roger L. Milne, Sara Lindstroem, Douglas F. Easton, Jenny Chang-Claude
Summary: A genome-wide study identified two independent SNP-risk factor pairs associated with breast cancer risk and estrogen receptor positive (ER +) breast cancer risk. Overall, gene-environment interactions have a very small contribution to the heritability of breast cancer. At the population level, these interactions do not significantly contribute to risk prediction for breast cancer.
BREAST CANCER RESEARCH
(2023)
Article
Public, Environmental & Occupational Health
Nina Odgaard Nielsen, Eirikur Benedikz, Morten Dahl, Jeanette Praestegaard, Marianne Lindahl
Summary: The aim of this study was to evaluate the self-reported health status and wellbeing of refugee families from Syria 2-4 years after resettlement in Denmark, and compare it with a Danish reference population, to determine the need for specialized health care. The study involved 90 individuals from Syria aged 13-56 years, and found that the refugee families had poorer health and wellbeing compared to the Danish population. The findings highlight the importance of providing systematic and specialized health care services to resettled refugees.
JOURNAL OF MIGRATION AND HEALTH
(2023)
Article
Cardiac & Cardiovascular Systems
Jiao Luo, Jesper Qvist Thomassen, Borge G. Nordestgaard, Anne Tybjaerg-Hansen, Ruth Frikke-Schmidt
Summary: This study investigated the associations between neutrophil counts and nine cardiovascular endpoints using observational and genetic approaches. The results showed that high neutrophil counts were associated with an increased risk of all cardiovascular outcomes. Genetic studies also supported this finding. No robust associations were found for other types of leukocytes in the two-sample MR analysis.
EUROPEAN HEART JOURNAL
(2023)
