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https://www.readbyqxmd.com/read/28332266/11-12-epoxyeicosatrienoic-acid-induces-vasodilator-response-in-the-rat-perfused-mesenteric-vasculature
#1
S M Bihzad, M H M Yousif
Epoxyeicosatrienoic acids (EETs) are endogenous ligands that undergo hydrolysis by soluble epoxide hydrolase (sEH). The responses of 11, 12-EET in comparison with other vasodilator agonists including carbachol and sodium nitroprusside (SNP) were investigated. The effect of 1-cyclohexyl-3-dodecyl urea (CDU), a sEH, was tested on the vasodilator effect induced by 11, 12-EET in the perfused mesenteric beds isolated from normo-glycaemic and type-1 STZ-diabetic rats. In the perfused mesenteric beds of control and diabetic animals, 11, 12-EET produced vasodilation in a dose-dependent manner...
January 2017: Autonomic & Autacoid Pharmacology
https://www.readbyqxmd.com/read/28296232/inhibitors-of-soluble-epoxide-hydrolase-minimize-ischemia-reperfusion-induced-cardiac-damage-in-normal-hypertensive-and-diabetic-rats
#2
Oliul Islam, Prashanth Patil, Sumanta K Goswami, Rema Razdan, Mohammed N Inamdar, Mohammed Rizwan, Jubin Mathew, Bora Inceoglu, Kin S Stephen Lee, Sung H Hwang, Bruce D Hammock
AIM: We designed a study to evaluate the cardioprotective effect of two soluble epoxide hydrolase (sEH) inhibitors, 1-(1-propanoylpiperidin-4-yl)-3-(4-trifluoromethoxy)phenyl)urea (TPPU) and trans-4-{4-[3-(4-trifluoromethoxyphenyl)-ureido]cyclohexyloxy}benzoic acid (t-TUCB), in ischemia-reperfusion (IR) model. METHODS: Cardioprotective effects of the sEH inhibitors were evaluated against IR-induced myocardial damage in hearts from normal, hypertensive and diabetic rats using Langendorff's apparatus...
March 15, 2017: Cardiovascular Therapeutics
https://www.readbyqxmd.com/read/28293507/soluble-epoxide-hydrolase-inhibition-and-epoxyeicosatrienoic-acid-treatment-improve-vascularization-of-engineered-skin-substitutes
#3
Dorothy M Supp, Jennifer M Hahn, Kevin L McFarland, Kelly A Combs, Kin Sing Stephen Lee, Bora Inceoglu, Debin Wan, Steven T Boyce, Bruce D Hammock
BACKGROUND: Autologous engineered skin substitutes comprised of keratinocytes, fibroblasts, and biopolymers can serve as an adjunctive treatment for excised burns. However, engineered skin lacks a vascular plexus at the time of grafting, leading to slower vascularization and reduced rates of engraftment compared with autograft. Hypothetically, vascularization of engineered skin grafts can be improved by treatment with proangiogenic agents at the time of grafting. Epoxyeicosatrienoic acids (EETs) are cytochrome P450 metabolites of arachidonic acid that are inactivated by soluble epoxide hydrolase (sEH)...
December 2016: Plastic and Reconstructive Surgery. Global Open
https://www.readbyqxmd.com/read/28281333/discovering-drugs-with-dna-encoded-library-technology-from-concept-to-clinic-with-an-inhibitor-of-soluble-epoxide-hydrolase
#4
Svetlana Belyanskaya, Yun Ding, James Callahan, Aili Lazaar, David Israel
DNA encoded chemical library technology was developed with the vision of becoming a transformational platform for drug discovery. The hope was that a new screening paradigm for low molecular weight drugs would be enabled by combining the vast molecular diversity achievable with combinatorial chemistry, the information encoding attributes of DNA, the power of molecular biology and a streamlined selection-based discovery process. We describe the discovery and early clinical development of GSK2256294, an inhibitor of the enzyme soluble epoxide hydrolase (sEH, EPHX2) using Encoded Library Technology (ELT)...
March 9, 2017: Chembiochem: a European Journal of Chemical Biology
https://www.readbyqxmd.com/read/28279529/soluble-epoxide-hydrolase-inhibitors-of-indolinone-alkaloids-and-phenolic-derivatives-from-cimicifuga-dahurica-turcz-maxim
#5
Nguyen Phuong Thao, Bui Thi Thuy Luyen, Ji Sun Lee, Jang Hoon Kim, Young Ho Kim
The aim of this study was to search for potential therapeutic agents by identifying novel inhibitors of soluble epoxide hydrolase (sEH) from natural plants using an in silico approach. We found that an ethanolic extract from the roots of Cimicifuga dahurica (Turcz.) Maxim. significantly inhibited sEH in vitro. In a phytochemical investigation using assay-guided fractionation of the dichloromethane extract of C. dahurica, we isolated two new indolinone alkaloids (5 and 6) and five related constituents (1-4, and 7) and established their structures based on an extensive analysis using 1D and 2D NMR, and MS methods...
February 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28267313/facile-route-to-rare-heterobimetallic-aluminum-copper-and-aluminum-zinc-selenide-clusters
#6
Bin Li, Jiancheng Li, Rui Liu, Hongping Zhu, Herbert W Roesky
Heterobimetallic aluminum-copper and aluminum-zinc clusters were prepared from the reaction of LAl(SeH)2 [1; L = HC(CMeNAr)2 and Ar = 2,6-iPr2C6H3] with (MesCu)4 and ZnEt2, respectively. The resulting clusters with the core structures of Al2Se4Cu4 and Al2Se4Zn3 exhibit unique metal-organic frameworks. This is a novel pathway for the synthesis of aluminum-copper and aluminum-zinc selenides. The products have been characterized by spectroscopic methods and single-crystal X-ray structural characterization.
March 7, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28259677/soluble-epoxide-hydrolase-inhibition-alleviates-neuropathy-in-akita-ins2-akita-mice
#7
Karen Wagner, Jennifer Gilda, Jun Yang, Debin Wan, Christophe Morisseau, Aldrin V Gomes, Bruce D Hammock
The soluble epoxide hydrolase (sEH) is a regulatory enzyme responsible for the metabolism of bioactive lipid epoxides of both omega-6 and omega-3 long chain polyunsaturated fatty acids. These natural epoxides mediate cell signaling in several physiological functions including blocking inflammation, high blood pressure and both inflammatory and neuropathic pain. Inhibition of the sEH maintains the level of endogenous bioactive epoxy-fatty acids (EpFA) and allows them to exert their generally beneficial effects...
March 1, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28259037/altered-soluble-epoxide-hydrolase-derived-oxylipins-in-patients-with-seasonal-major-depression-an-exploratory-study
#8
Marie Hennebelle, Yurika Otoki, Jun Yang, Bruce D Hammock, Anthony J Levitt, Ameer Y Taha, Walter Swardfager
Many cytochrome p450-derived lipids promote resolution of inflammation, in contrast to their soluble epoxide hydrolase(sEH)-derived oxylipin breakdown products. Here we compare plasma oxylipins and precursor fatty acids between seasons in participants with major depressive disorder with seasonal pattern (MDD-s). Euthymic participants with a history of MDD-s recruited in summer-fall were followed-up in winter. At both visits, a structured clinical interview (DSM-5 criteria) and the Beck Depression Inventory II (BDI-II) were administered...
February 27, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28255523/inhibition-of-soluble-epoxide-hydrolase-as-a-novel-approach-to-high-dose-diazepam-induced-hypotension
#9
Arzu Ulu, Bora Inceoglu, Jun Yang, Vikrant Singh, Stephen Vito, Heike Wulff, Bruce D Hammock
CONTEXT: Hypotension is one of the dose limiting side effects of benzodiazepines (BZDs), in particular of diazepam (DZP) which is still widely used in the clinic. Currently, only one FDA approved antidote exists for BZD overdose and novel approaches are needed to improve management of DZP overdose, dependency and withdrawal. OBJECTIVE: Here, we hypothesized that increasing bioactive lipid mediators termed epoxy fatty acids (EpFAs) will prevent hypotension, as was shown previously in a murine model of LPS-induced hypotension...
June 2016: Journal of Clinical Toxicology
https://www.readbyqxmd.com/read/28255506/spinal-epidural-hematoma-related-to-vertebral-fracture-in-an-atypical-rigid-diffuse-idiopathic-skeletal-hyperostosis-a-case-report
#10
José Ramírez Villaescusa, Marcela Restrepo Pérez, David Ruiz Picazo
INTRODUCTION: Spinal epidural hematoma (SEH) is a rare disease that causes cord compression and neurologic deficit. Spontaneous SEH is related to minor trauma, bleeding disorders, and anticoagulant medications. Posttraumatic SEH has been associated with low-energy spine hyperextension injuries in patients with ankylosing spinal disorders such as ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis (DISH). A variant named atypical DISH-like with SEH is reported. OBJECTIVE: To describe the management, diagnosis, and treatment of an unusual SEH case in a patient causing delayed neurologic deficit with rigid atypical DISH-like spine...
March 2017: Geriatric Orthopaedic Surgery & Rehabilitation
https://www.readbyqxmd.com/read/28229153/calculations-of-current-densities-for-neutral-and-doubly-charged-persubstituted-benzenes-using-effective-core-potentials
#11
Markus Rauhalahti, Stefan Taubert, Dage Sundholm, Vincent Liégeois
Magnetically induced current density susceptibilities and ring-current strengths have been calculated for neutral and doubly charged persubstituted benzenes C6X6 and C6X6(2+) with X = F, Cl, Br, I, At, SeH, SeMe, TeH, TeMe, and SbH2. The current densities have been calculated using the gauge-including magnetically induced current (GIMIC) method, which has been interfaced to the Gaussian electronic structure code rendering current density calculations using effective core potentials (ECP) feasible. Relativistic effects on the ring-current strengths have been assessed by employing ECP calculations of the current densities...
February 23, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28218739/suppression-of-islet-homeostasis-protein-thwarts-diabetes-mellitus-progression
#12
Seh-Hoon Oh, Marda L Jorgensen, Clive H Wasserfall, Altin Gjymishka, Bryon E Petersen
During progression to type 1 diabetes, insulin-producing β-cells are lost through an autoimmune attack resulting in unrestrained glucagon expression and secretion, activation of glycogenolysis, and escalating hyperglycemia. We recently identified a protein, designated islet homeostasis protein (IHoP), which specifically co-localizes within glucagon-positive α-cells and is overexpressed in the islets of both post-onset non-obese diabetic (NOD) mice and type 1 diabetes patients. Here we report that in the αTC1...
February 20, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28218273/discovery-of-the-first-dual-inhibitor-of-the-5-lipoxygenase-activating-protein-and-soluble-epoxide-hydrolase-using-pharmacophore-based-virtual-screening
#13
Veronika Temml, Ulrike Garscha, Erik Romp, Gregor Schubert, Jana Gerstmeier, Zsofia Kutil, Barbara Matuszczak, Birgit Waltenberger, Hermann Stuppner, Oliver Werz, Daniela Schuster
Leukotrienes (LTs) are pro-inflammatory lipid mediators derived from arachidonic acid (AA) with roles in inflammatory and allergic diseases. The biosynthesis of LTs is initiated by transfer of AA via the 5-lipoxygenase-activating protein (FLAP) to 5-lipoxygenase (5-LO). FLAP inhibition abolishes LT formation exerting anti-inflammatory effects. The soluble epoxide hydrolase (sEH) converts AA-derived anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatetraenoic acids (di-HETEs). Its inhibition consequently also counteracts inflammation...
February 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28207867/thermal-stability-and-structural-changes-in-bacterial-toxins-responsible-for-food-poisoning
#14
Paulina Regenthal, Jesper S Hansen, Ingemar André, Karin Lindkvist-Petersson
The staphylococcal enterotoxins (SEs) are secreted by the bacteria Staphylococcus aureus and are the most common causative agent in staphylococcal food poisoning. The staphylococcal enterotoxin A (SEA) has been associated with large staphylococcal food poisoning outbreaks, but newer identified SEs, like staphylococcal enterotoxin H (SEH) has recently been shown to be present at similar levels as SEA in food poisoning outbreaks. Thus, we set out to investigate the thermo-stability of the three-dimensional structures of SEA, SEH and staphylococcal enterotoxin E (SEE), since heat inactivation is a common method to inactivate toxins during food processing...
2017: PloS One
https://www.readbyqxmd.com/read/28188798/in-silico-investigation-of-cycloartane-triterpene-derivatives-from-cimicifuga-dahurica-turcz-maxim-roots-for-the-development-of-potent-soluble-epoxide-hydrolase-inhibitors
#15
Nguyen Phuong Thao, Jang Hoon Kim, Bui Thi Thuy Luyen, Nguyen Tien Dat, Young Ho Kim
In our search for natural soluble epoxide hydrolase (sEH) inhibitors from plants, we found that an ethanolic extract of the roots of Cimicifuga dahurica (Turcz.) Maxim. significantly inhibits sEH in vitro. A phytochemical study on the dichloromethane fraction of C. dahurica resulted in the isolation of two new cycloartane triterpenoids (1 and 6), together with 13 known cycloartane analogues (2-5 and 7-15). The structures of compounds were determined by spectroscopic methods. All of the triterpenoid derivatives inhibited sEH enzymatic activity in a concentration-dependent manner, and 13 of the tested compounds showed significant activity...
February 7, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28185955/endothelial-nox4-based-nadph-oxidase-regulates-atherosclerosis-via-soluble-epoxide-hydrolase
#16
Pingping Hu, Xiaojuan Wu, Alok R Khandelwal, Weimin Yu, Zaicheng Xu, Lili Chen, Jian Yang, Robert M Weisbrod, Kin Sing Stephen Lee, Francesca Seta, Bruce D Hammock, Richard A Cohen, Chunyu Zeng, Xiaoyong Tong
Nox4-based NADPH oxidase is a major reactive oxygen species-generating enzyme in the vasculature, but its role in atherosclerosis remains controversial. OBJECTIVE: Our goal was to investigate the mechanisms of endothelial Nox4 in regulating atherosclerosis. APPROACH AND RESULTS: Atherosclerosis-prone conditions (disturbed blood flow, type I diabetes, and Western diet) downregulated endothelial Nox4 mRNA in arteries. To address whether the downregulated endothelial Nox4 was directly involved in the development of atherosclerosis, we generated mice carrying a human Nox4 P437H dominant negative mutation (Nox4DN), driven by the endothelial specific promoter Tie-2, on atherosclerosis-prone genetic background (ApoE deficient mice) to mimic the effect of decreased endothelial Nox4...
February 6, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28182526/hippocampal-processing-of-ambiguity-enhances-fear-memory
#17
Ugwechi Amadi, Seh Hong Lim, Elizabeth Liu, Michael V Baratta, Ki A Goosens
Despite the ubiquitous use of Pavlovian fear conditioning as a model for fear learning, the highly predictable conditions used in the laboratory do not resemble real-world conditions, in which dangerous situations can lead to unpleasant outcomes in unpredictable ways. In the current experiments, we varied the timing of aversive events after predictive cues in rodents and discovered that temporal ambiguity of aversive events greatly enhances fear. During fear conditioning with unpredictably timed aversive events, pharmacological inactivation of the dorsal hippocampus or optogenetic silencing of cornu ammonis 1 cells during aversive negative prediction errors prevented this enhancement of fear without affecting fear learning for predictable events...
February 2017: Psychological Science
https://www.readbyqxmd.com/read/28104457/genetic-deletion-of-soluble-epoxide-hydrolase-provides-cardioprotective-responses-following-myocardial-infarction-in-aged-mice
#18
REVIEW
K Lockhart Jamieson, Victor Samokhvalov, Maria Akhnokh, Kyra Lee, Woo Jung Cho, Abhijit Takawale, Xiuhua Wang, Zamaneh Kassiri, John M Seubert
BACKGROUND: Pathophysiological responses, including cardiovascular complications, often alter with age. Cardioprotective effects of epoxyeicosatrienoic acids (EETs) toward acute myocardial ischemia-reperfusion injury have been well documented. However, biological relevance of EET-evoked cardioprotection in the ageing myocardium remains unknown. EETs are metabolized to less active metabolites by the enzyme soluble epoxide hydrolase (sEH). This study uses permanent occlusion of the left anterior descending artery (LAD) in young and aged sEH null and WT mice to compare cardiac and mitochondrial function following ischemic injury...
January 16, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28097044/study-on-the-single-dose-toxicity-of-shineumhur-pharmacopuncture-injected-into-the-muscles-of-rats
#19
Hohyun Jeong, Eunhye Cha, Jongcheol Lee, Seongjin Lee, Manyong Park, Dongwoung Kim, Bongkeun Song, Jongdeok Lee, Sungchul Kim
OBJECTIVES: This study was carried out to analyze the single dose toxicity of ShinEumHur (SEH) pharmacopuncture injected into the muscles of Sprague-Dawley rats. METHODS: The SEH pharmacopuncture was made in a clean room at the Korean Pharmacopuncture Institute (K-GMP). After the mixing process with sterile distilled water had been completed, the pH was controlled to between 7.0 and 7.5. All experiments were conducted at Biotoxtech, an institution authorized to perform non-clinical studies under the Good Laboratory Practice (GLP) regulations...
December 2016: Journal of Pharmacopuncture
https://www.readbyqxmd.com/read/28096362/catalytic-oxidation-of-li2s-on-the-surface-of-metal-sulfides-for-li-s-batteries
#20
Guangmin Zhou, Hongzhen Tian, Yang Jin, Xinyong Tao, Bofei Liu, Rufan Zhang, Zhi Wei Seh, Denys Zhuo, Yayuan Liu, Jie Sun, Jie Zhao, Chenxi Zu, David Sichen Wu, Qianfan Zhang, Yi Cui
Polysulfide binding and trapping to prevent dissolution into the electrolyte by a variety of materials has been well studied in Li-S batteries. Here we discover that some of those materials can play an important role as an activation catalyst to facilitate oxidation of the discharge product, Li2S, back to the charge product, sulfur. Combining theoretical calculations and experimental design, we select a series of metal sulfides as a model system to identify the key parameters in determining the energy barrier for Li2S oxidation and polysulfide adsorption...
January 31, 2017: Proceedings of the National Academy of Sciences of the United States of America
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