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https://www.readbyqxmd.com/read/29758331/liver-regeneration-requires-yap1-tgf%C3%AE-dependent-epithelial-mesenchymal-transition-in-hepatocytes
#1
Seh-Hoon Oh, Marzena Swiderska-Syn, Mark L Jewell, Richard T Premont, Anna Mae Diehl
BACKGROUND: Chronic failure of mechanisms that promote effective regeneration of dead hepatocytes causes replacement of functional hepatic parenchyma with fibrous scar and ultimately results in cirrhosis. Therefore, defining and optimizing mechanisms that orchestrate effective regeneration might prevent cirrhosis. We hypothesized that effective regeneration of injured livers requires hepatocytes to evade the growth inhibitory actions of TGF-β since TGF-β signaling inhibits mature hepatocyte growth but drives cirrhosis pathogenesis...
May 11, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29751149/an-inhibitor-of-soluble-epoxide-hydrolase-ameliorates-diabetes-induced-learning-and-memory-impairment-in-rats
#2
Nathani Minaz, Rema Razdan, Bruce D Hammock, Sumanta Kumar Goswami
BACKGROUND: Pharmacological inhibition of soluble epoxide hydrolase (sEH) enhances the synaptic function in the CNS and has a protective role in cognitive decline. We hypothesized that the sEH inhibitor TPPU might prevent the diabetes-induced decline in learning and memory which is associated with alteration in the level of neurotransmitters and oxidative stress. METHODS: Type 1 diabetes was induced in rats and the animals were treated with TPPU for 8 weeks. The learning and memory functions were assessed by the Barnes maze and a step-down test...
May 8, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29735655/soluble-epoxide-hydrolase-plays-a-key-role-in-the-pathogenesis-of-parkinson-s-disease
#3
Qian Ren, Min Ma, Jun Yang, Risa Nonaka, Akihiro Yamaguchi, Kei-Ichi Ishikawa, Kenta Kobayashi, Shigeo Murayama, Sung Hee Hwang, Shinji Saiki, Wado Akamatsu, Nobutaka Hattori, Bruce D Hammock, Kenji Hashimoto
Parkinson's disease (PD) is characterized as a chronic and progressive neurodegenerative disorder, and the deposition of specific protein aggregates of α-synuclein, termed Lewy bodies, is evident in multiple brain regions of PD patients. Although there are several available medications to treat PD symptoms, these medications do not prevent the progression of the disease. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with the pathogenesis of PD. Here we found that MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced neurotoxicity in the mouse striatum was attenuated by subsequent repeated administration of TPPU, a potent sEH inhibitor...
May 7, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29732612/synthesis-of-substituted-fluorobenzimidazoles-as-inhibitors-of-5-lipoxygenase-and-soluble-epoxide-hydrolase-for-anti-inflammatory-activity
#4
B Nandha, Sureshbabu A Ramareddy, Hazra Kuntal
A new series of 4-((5-fluoro-6-(substituted)-1H-benzo[d]imidazol-2-ylthio)methyl)-benzoic acids 4a-o and 2-(5-fluoro-6-(substituted)-1H-benzo[d]imidazol-2-ylthio)-2-methylpropanoic acids 8a-e were synthesized, and their inhibitory potencies against soluble epoxide hydrolase (sEH) and 5-lipoxygenase (5-LOX) were investigated. These molecules were designed based on the combination of 5-LOX and sEH pharmacophores, resulting in hybrid analogs with potent sEH and 5-LOX inhibitory activity. Compound 4g showed remarkable activity with IC50 values of less than 1 μM (0...
May 7, 2018: Archiv der Pharmazie
https://www.readbyqxmd.com/read/29717935/expression-of-soluble-epoxide-hydrolase-in-renal-tubular-epithelial-cells-regulates-macrophage-infiltration-and-polarization-in-iga-nephropathy
#5
Qian Wang, Yan Liang, Yingjin Qiao, Xiangya Zhao, Yi Yang, Shengnan Yang, Bing Li, Qianru Zhao, Ling Dong, Songxia Quan, Rui Tian, Zhangsuo Liu
Tubulointerstitial inflammatory cell infiltration and activation contribute to kidney inflammation and fibrosis. Epoxyeicosatrienoic acids (EETs), which are rapidly metabolized to dihydroxyeicosatrienoic acids by the soluble epoxide hydrolase (sEH), have multiple biological functions, including vasodilation, anti-inflammatory action, and others. Inhibition of sEH has been demonstrated to attenuate inflammation in many renal disease models. However, the relationship between sEH expression and macrophage polarization in kidney remains unknown...
May 2, 2018: American Journal of Physiology. Renal Physiology
https://www.readbyqxmd.com/read/29717038/lipidomic-profiling-reveals-soluble-epoxide-hydrolase-as-a-therapeutic-target-of-obesity-induced-colonic-inflammation
#6
Weicang Wang, Jun Yang, Jianan Zhang, Yuxin Wang, Sung Hee Hwang, Weipeng Qi, Debin Wan, Daeyoung Kim, Jia Sun, Katherine Z Sanidad, Haixia Yang, Yeonhwa Park, Jun-Yan Liu, Xinfeng Zhao, Xiaohui Zheng, Zhenhua Liu, Bruce D Hammock, Guodong Zhang
Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. Considering the obesity epidemic in Western countries, it is important to identify novel therapeutic targets for obesity-induced colonic inflammation, to develop targeted strategies for prevention. Eicosanoids are endogenous lipid signaling molecules involved in regulating inflammation and immune responses. Using an LC-MS/MS-based lipidomics approach, we find that obesity-induced colonic inflammation is associated with increased expression of soluble epoxide hydrolase (sEH) and its eicosanoid metabolites, termed fatty acid diols, in colon tissue...
May 1, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29703148/deletion-of-soluble-epoxide-hydrolase-attenuates-mice-hyperoxic-acute-lung-injury
#7
Li-Ping Liu, Bin Li, Tian-Kui Shuai, Lei Zhu, Yu-Min Li
BACKGROUND: Recent studies reported that soluble epoxide hydrolase (sEH) plays an important role in lung diseases. However, the role of sEH in hyperoxia-induced ALI is unclear. METHODS: ALI was induced by exposure to 100% oxygen in an airtight cage for 72 h in wild-type (WT) and sEH gene deletion (EPHX2-/- ) mice. ALI was assessed by the lung dry/wet ratio, alveolar capillary protein leak, and the infiltration of inflammatory cells in the lung. RESULTS: Hyperoxia elevated sEH activity in WT mice...
April 27, 2018: BMC Anesthesiology
https://www.readbyqxmd.com/read/29683949/a-rare-case-of-hemophagocytic-lymphohistiocytosis-associated-with-myelodysplastic-syndrome-and-trisomy-8-in-a-pediatric-patient
#8
Seh Hyun Kim, Dae Yong Yi, Na Mi Lee, Sin Weon Yun, Soo Ahn Chae, In Seok Lim
Hemophagocytic lymphohistiocytosis (HLH) is a rare disease resulting in clinical and biochemical manifestations of extreme inflammation. Myelodysplastic syndrome (MDS) represents a heterogenous group of clonal hematopoietic disorders. The development of MDS is common in children with trisomy of chromosome 8. Here, we report a fatal case of 8-year-old girl who was admitted to the emergency department with status epilepticus, and later diagnosed with HLH associated with MDS and trisomy of chromosome 8. We believe this is the first reported case of HLH associated with MDS and trisomy 8 in a pediatric patient...
April 20, 2018: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/29678220/analysis-of-the-vidas-%C3%A2-staph-enterotoxin-iii-set3-for-detection-of-staphylococcal-enterotoxins-g-h-and-i-in-foods
#9
Jennifer M Hait, Angela T Nguyen, Sandra M Tallent
Background : Staphylococcal food poisoning (SFP) frequently causes illnesses worldwide. SFP occurs from the ingestion of staphylococcal enterotoxins (SEs) preformed in foods by enterotoxigenic strains of Staphylococcus species, primarily S. aureus . SEG, SEH, and SEI induce emesis and have been implicated in outbreaks. Immunological-based methods are deemed the most practical methods for the routine analysis of SEs in foods given their ease of use, sensitivity, specificity, and commercial availability. These kits are routinely used to test for SEA-SEE...
April 20, 2018: Journal of AOAC International
https://www.readbyqxmd.com/read/29665449/role-of-seh-r287q-in-ldlr-expression-ldl-binding-to-ldlr-and-ldl-internalization-in-bel-7402-cells
#10
Ling Tang, Guoliang Wang, Long Jiang, Panpan Chen, Wei Wang, Juan Chen, Luya Wang
OBJECTIVES: Familial hypercholesterolemia (FH) is an autosomal dominant disorder of cholesterol metabolism. Three recognized genes (LDLR, APOB and PCSK9) present in only 20-30% of patients with possible FH cases. Additional FH-causing genes need to be explored. The present study found an isolated gene change, sEH R287Q, in a core family of FH. In this study, we aimed to investigate the roles of R287Q on sEH expression and on LDLR expression, LDL binding to LDLR and LDL internalization...
April 14, 2018: Gene
https://www.readbyqxmd.com/read/29662467/multilocus-sequence-typing-and-virulence-associated-gene-profile-analysis-of-staphylococcus-aureus-isolates-from-retail-ready-to-eat-food-in-china
#11
Xiaojuan Yang, Shubo Yu, Qingping Wu, Jumei Zhang, Shi Wu, Dongli Rong
The aim of this study was to characterize the subtypes and virulence profiles of 69 Staphylococcus aureus isolates obtained from retail ready-to-eat food in China. The isolates were analyzed using multilocus sequence typing (MLST) and polymerase chain reaction (PCR) analysis of important virulence factor genes, including the staphylococcal enterotoxin (SE) genes ( sea , seb , sec , sed , see , seg , seh , sei , sej ), the exfoliative toxin genes ( eta and etb ), the toxic shock syndrome toxin-1 gene ( tst ), and the Panton-Valentine leucocidin-encoding gene ( pvl )...
2018: Frontiers in Microbiology
https://www.readbyqxmd.com/read/29656630/etiopathogenesis-of-traumatic-spinal-epidural-hematoma
#12
Francesco Ciro Tamburrelli, Maria Concetta Meluzio, Giulia Masci, Andrea Perna, Aaron Burrofato, Luca Proietti
Spinal epidural hematoma (SEH) is a rare cause of nerve root or cord compression; its pathogenesis is not always clearly recognizable. The aim of this paper was to investigate possible etiopathological factors in a consecutive series of patients affected by traumatic SEH treated at our institution. Seven patients with neurologic impairment due to traumatic SEH were retrospectively analyzed after diagnosis and surgical treatment. Thoracic localization was found in 5 cases, and lumbar and cervical localization were found in 1 patient each...
March 2018: Neurospine
https://www.readbyqxmd.com/read/29625231/the-oxidized-linoleic-acid-metabolite-12-13-dihome-mediates-thermal-hyperalgesia-during-inflammatory-pain
#13
Béla Zimmer, Carlo Angioni, Tabea Osthues, Andy Toewe, Dominique Thomas, Sandra C Pierre, Gerd Geisslinger, Klaus Scholich, Marco Sisignano
Eicosanoids play a crucial role in inflammatory pain. However, there is very little knowledge about the contribution of oxidized linoleic acid metabolites in inflammatory pain and peripheral sensitization. Here, we identify 12,13-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME), a cytochrome P450-derived linoleic acid metabolite, as crucial mediator of thermal hyperalgesia during inflammatory pain. We found 12,13-DiHOME in increased concentrations in peripheral nervous tissue during acute zymosan- and complete Freund's Adjuvant-induced inflammatory pain...
April 3, 2018: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29615440/inhibition-of-soluble-epoxide-hydrolase-2-ameliorates-diabetic-keratopathy-and-impaired-wound-healing-in-mouse-corneas
#14
Haijing Sun, Patrick Lee, Chenxi Yan, Nan Gao, Jiemei Wang, Xianqun Fan, Fu-Shin Yu
EPHX2 (soluble Epoxide Hydrolase 2, sEH) converts biologically active epoxyeicosatrienoic acids (EETs), anti-inflammatory and pro-fibrinolytic effectors into the less biologically active metabolites, dihydroxyeicostrienoic acids. We sought to characterize the expression and the function of EPHX2 in diabetic corneas and during wound healing. The expression of EPHX2 at both mRNA and protein levels, as well as sEH enzymatic activity, were markedly upregulated in the tissues/cells, including corneal epithelial cells as well as the retina of human type-2, mouse type-1 (STZ-induced) and/or type-2 diabetes...
April 3, 2018: Diabetes
https://www.readbyqxmd.com/read/29614224/orally-available-soluble-epoxide-hydrolase-phosphodiesterase-4-dual-inhibitor-treats-inflammatory-pain
#15
Rene Blöcher, Karen M Wagner, Raghavender R Gopireddy, Todd R Harris, Hao Wu, Bogdan Barnych, Sung Hee Hwang, Yang K Xiang, Ewgenij Proschak, Christophe Morisseau, Bruce D Hammock
Inspired by previously discovered enhanced analgesic efficacy between soluble epoxide hydrolase (sEH) and phosphodiesterase 4 (PDE4) inhibitors, we designed, synthesized and characterized 21 novel sEH/PDE4 dual inhibitors. The best of these displayed good efficacy in in vitro assays. Further pharmacokinetic studies of a subset of 4 selected compounds led to the identification of a bioavailable dual inhibitor N-(4-methoxy-2-(trifluoromethyl)benzyl)-1-propionylpiperidine-4-carboxamide (MPPA). In a lipopolysaccharide induced inflammatory pain rat model, MPPA rapidly increased in the blood (Tmax = 30 min; Cmax = 460 nM) after oral administration of 3 mg/kg and reduced inflammatory pain with rapid onset of action correlating with blood levels over a time course of 4 hours...
April 3, 2018: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29588470/soluble-epoxide-hydrolase-inhibition-decreases-reperfusion-injury-after-focal-cerebral-ischemia
#16
Ranran Tu, Jillian Armstrong, Kin Sing Stephen Lee, Bruce D Hammock, Adam Sapirstein, Raymond C Koehler
Epoxyeicosatrienoic acids (EETs) are produced by cytochrome P450 epoxygenases from arachidonic acid, and their rapid metabolism is mainly through soluble epoxide hydrolase (sEH). EETs exert vasodilatory, anti-inflammatory, anti-apoptotic, and pro-angiogenic effects. Administration of sEH inhibitors before or at the onset of stroke is protective, but the effects of post-treatment at reperfusion, when inflammation is augmented, has not been as well studied. We tested the hypothesis that 1-Trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl)urea (TPPU), a potent and highly selective sEH inhibitor, suppresses inflammation and protects the brain when administered at reperfusion...
March 27, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29580941/increased-epoxyeicosatrienoic-acids-may-be-part-of-a-protective-mechanism-in-human-ulcerative-colitis-with-increased-cyp2j2-and-reduced-soluble-epoxide-hydrolase-expression
#17
Yi-Er Qiu, Jun Qin, Yang Luo, Shao-Lan Qin, Yi-Fei Mu, Ran Cun, Hou-Li Jiang, Jian-Jun Chen, Min-Hao Yu, Ming Zhong
BACKGROUND: Previous preclinical evidence has suggested that the elevation of epoxyeicosatrienoic acids (EETs) derived from the cytochrome P450 (CYP) epoxygenases-dependent metabolism of arachidonic acid has important anti-inflammatory effects. However, the levels of EETs and their synthetic and metabolic enzymes in human ulcerative colitis has not been evaluated. METHOD: To evaluate EETs and the expression of relevant CYP isoforms and the metabolizing enzyme, soluble epoxide hydrolase (sEH), tissue biopsies were collected from 16 pairs of ulcerative colitis patients' tissues and matched with adjacent non-inflamed tissues...
March 23, 2018: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/29574653/effect-of-soluble-epoxide-hydrolase-in-hyperoxic-acute-lung-injury-in-mice
#18
Ping-Song Li, Wei Tao, Liu-Qing Yang, Yu-Sheng Shu
Hyperoxic acute lung injury is a serious complication of oxygen therapy that causes high mortality. Inhibition of soluble epoxide hydrolase (sEH) has been reported to have protective effect on lipopolysaccharide-induced acute lung injury (ALI). This study investigates whether sEH plays any role in the pathogenesis of hyperoxic ALI. Wild-type and sEH gene knockout (sEH-/- ) mice were exposed to 100% O2 for 72 h to induce hyperoxic ALI. Hyperoxia caused infiltration of inflammatory cells, elevation of interleukin-1β and interleukin-6 levels, and deterioration of alveolar capillary protein leak as well as wet/dry weight ratio in the lung...
March 24, 2018: Inflammation
https://www.readbyqxmd.com/read/29572983/halogen-chalcogen-and-pnicogen-bonding-involving-hypervalent-atoms
#19
Steve Scheiner, Jia Lu
The additional substituents arising from hypervalency present a number of complicating issues for the formation of noncovalent bonds. The XF5 molecule (X=Cl, Br, I) was allowed to form a halogen bond with NH3 as base. Hypervalent chalcogen bonding iss examined by way of YF4 and YF6 (Y=S, Se, Te), and ZF5 (Z=P, As, Sb) is used to model pnicogen bonding. Pnicogen bonds are particularly strong, with interaction energies approaching 50 kcal/mol, and also involve wholesale rearrangement from trigonal bipyramidal in the monomer to square pyramidal in the complex, subject to a large deformation energy...
March 23, 2018: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29567338/novel-piperidine-derived-amide-seh-inhibitors-as-mediators-of-lipid-metabolism-with-improved-stability
#20
Stevan Pecic, Amir A Zeki, Xiaoming Xu, Gina Y Jin, Shuwei Zhang, Sean Kodani, Marlin Halim, Christophe Morisseau, Bruce D Hammock, Shi-Xian Deng
We have previously identified and reported several potent piperidine-derived amide inhibitors of the human soluble epoxide hydrolase (sEH) enzyme. The inhibition of this enzyme leads to elevated levels of epoxyeicosatrienoic acids (EETs), which are known to possess anti-inflammatory, vasodilatory, and anti-fibrotic effects. Herein, we report the synthesis of 9 analogs of the lead sEH inhibitor and the follow-up structure-activity relationship and liver microsome stability studies. Our findings show that isosteric modifications that lead to significant alterations in the steric and electronic properties at a specific position in the molecule can reduce the efficacy by up to 75-fold...
March 19, 2018: Prostaglandins & Other Lipid Mediators
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