Article
Neurosciences
Youyang Qu, Jinlu Cao, Di Wang, Shu Wang, Yujie Li, Yulan Zhu
Summary: This study elucidates the protective effects of 14,15-EET on cerebral microvascular endothelial cells (MECs) and its potential mechanisms in oxygen glucose deprivation and reperfusion (OGD/R) injury. The findings show that 14,15-EET can protect MECs from OGD/R injury by regulating the SIRT1/FOXO3a signaling pathway and TSPO protein.
FRONTIERS IN CELLULAR NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Jacqueline Wen Hui Leow, Ravi Kumar Verma, Amos Boon Hao Lim, Hao Fan, Eric Chun Yong Chan
Summary: The study characterized the atypical substrate inhibition kinetics of CYP2J2 metabolism of AA to 14,15-EET, revealing complete substrate inhibition phenomenon. Molecular dynamics simulations confirmed the conformational stability of CYP2J2 with dual AA substrate binding. Eadie-Hofstee plots demonstrated that complete substrate inhibition of CYP2J2 by AA was not attenuated even at high concentrations of xenobiotic inhibitors.
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
(2021)
Article
Physiology
Agnieszka Walkowska, Ludek Cervenka, John D. Imig, John R. Falck, Janusz Sadowski, Elzbieta Kompanowska-Jezierska
Summary: The study demonstrated that in spontaneously hypertensive rats, both EET-A and AAA induced renal vasodilation but did not show additive effects. Both agents have a definite therapeutic potential for hypertension and deserve further experimental and clinical testing for novel antihypertensive therapy.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Mouad Hamzaoui, Clothilde Roche, David Coquerel, Thomas Duflot, Valery Brunel, Paul Mulder, Vincent Richard, Jeremy Bellien, Dominique Guerrot
Summary: Inhibition of soluble epoxide hydrolase reduces cardiac remodeling and dysfunction associated with chronic kidney disease. These beneficial effects may be mediated by preventing endothelial dysfunction, independent of kidney preservation and antihypertensive effects, indicating a therapeutic potential in preventing type 4 cardiorenal syndrome.
FRONTIERS IN MOLECULAR BIOSCIENCES
(2021)
Article
Multidisciplinary Sciences
Fred E. Fregoso, Trevor van Eeuwen, Gleb Simanov, Grzegorz Rebowski, Malgorzata Boczkowska, Austin Zimmet, Alexis M. Gautreau, Roberto Dominguez
Summary: The Arp2/3 complex inhibitor Arpin controls cell migration by interrupting a feedback loop involving Rac-WAVE-Arp2/3 complex. This study reveals the mechanism of Arpin's inhibition through structural, biochemical, and cellular studies. The findings show that Arpin binds to Arp3, a component of the complex, similarly to nucleation-promoting factors (NPFs) that activate the complex. However, Arpin only binds to one site on Arp3, unlike NPFs that bind to two sites. Mutagenesis studies further elucidate the molecular basis for Arpin's inhibition compared to NPFs.
NATURE COMMUNICATIONS
(2022)
Article
Biochemistry & Molecular Biology
Huaming Tang, Yuanli Kuang, Wan Wu, Bing Peng, Qianmei Fu
Summary: Recent studies have shown that quercetin, the main active component of saffron, inhibits breast carcinoma (BC) progression by down-regulating CYP3A4 to decrease the metabolization of AA to EETs, thereby blocking the nuclear translocation of p-Stat3 and impeding BC development.
MOLECULAR MEDICINE
(2023)
Review
Physiology
Jinsheng Lai, Chen Chen
Summary: Epoxyeicosatrienoic acids (EETs) are metabolites of arachidonic acid produced by cytochrome P450 (CYP) epoxygenases, with beneficial effects against inflammation, fibrosis, and apoptosis in cardiovascular diseases. Studies have shown that increasing EET levels can protect against cardiovascular diseases such as hypertension, myocardial infarction, and heart failure. Therefore, upregulation of EETs may be a potential therapeutic strategy for cardiovascular diseases.
FRONTIERS IN PHYSIOLOGY
(2021)
Article
Biochemistry & Molecular Biology
Theresa Aliwarga, Jean C. Dinh, Scott Heyward, Bhagwat Prasad, Sina A. Gharib, Rozenn N. Lemaitre, Nona Sotoodehnia, Rheem A. Totah
Summary: This study investigates how cardiovascular disease (CVD) can influence total EET levels by altering protein expression and activity of enzymes involved in their biosynthesis and degradation. The findings suggest that CVD can lead to decreased EET levels in heart tissues by affecting the protein levels and activity of enzymes such as CYP2J2, NADPH-Cytochrome P450 oxidoreductase (POR), and soluble epoxide hydrolase (sEH).
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Oncology
Ying Fu, Xiuzhi Zhang, Xujun Liang, Yongheng Chen, Zhuchu Chen, Zhefeng Xiao
Summary: This study found that CapG is up-regulated in nasopharyngeal carcinoma tissues and cells. CapG promotes migration and invasion of nasopharyngeal carcinoma cells, possibly through the phosphorylation of MLC2. In contrast, Rac1 activation has no significant impact on cell motility in nasopharyngeal carcinoma.
WORLD JOURNAL OF SURGICAL ONCOLOGY
(2022)
Article
Engineering, Biomedical
Stephen Coyle, Bryant Doss, Yucheng Huo, Hemang Raj Singh, David Quinn, K. Jimmy Hsia, Philip R. LeDuc
Summary: Cell alignment is crucial for various biological functions and tissue engineering applications. This study explores the roles of surface topographies and cell-cell interactions in inducing cell alignment. The results indicate that cell alignment depends on both surface topologies and cell confluency, suggesting the interplay between cell-cell and cell-matrix interactions. Understanding these mechanisms is important for scaffold design, tissue repair, and the development of biohybrid robotic systems.
ACTA BIOMATERIALIA
(2022)
Article
Nutrition & Dietetics
Nouralhuda Alateyah, Mohammed Alsafran, Kamal Usman, Allal Ouhtit
Summary: Breast cancer is a common malignancy with conventional medicine failing to establish efficient treatment modalities. However, complementary and alternative medicine modalities are drawing attention. A study found that a super-combination of extracts from Qatari medicinal plants inhibited the growth and migration of breast cancer cells and induced apoptosis through specific pathways. Future experiments aim to validate these findings in vivo.
Article
Oncology
Zilong Yan, Qingen Da, Zhangfu Li, Qirui Lin, Jing Yi, Yanze Su, Guanyin Yu, Qingqi Ren, Xu Liu, Zewei Lin, Jianhua Qu, Weihua Yin, Jikui Liu
Summary: This study reveals the significant correlation between NEK7 and the expression of pyroptosis marker GSDMD in HCC, and downregulation of NEK7 inhibits HCC cell viability and tumor growth. It is also found that knockdown of NEK7 upregulates the expression of pyroptosis markers NLRP3, Caspase-1, and GSDMD, and affects the interaction between HCC cells and hepatic stellate cells.
FRONTIERS IN ONCOLOGY
(2022)
Article
Physics, Fluids & Plasmas
Hamid Khataee, Andras Czirok, Zoltan Neufeld
Summary: The study modeled the migration pattern of neural crest cells and found that increasing the rate of cell influx into the domain can transition from random movement to organized collective migration, leading to maximized migration alignment and minimized migration time. These results indicate that cell density is a key factor in the coordination of collective migration, and efficient long-distance migration can be achieved without external chemotactic information.
Article
Biochemistry & Molecular Biology
Shinichiro Koike, Ming-Fo Hsu, Ahmed Bettaieb, Bryan Chu, Naoki Matsumoto, Christophe Morisseau, Peter J. Havel, Mark O. Huising, Bruce D. Hammock, Fawaz G. Haj
Summary: The study identified that upregulation of soluble epoxide hydrolase (sEH) expression in beta-cells under diet-induced metabolic stress could lead to beta-cell dysfunction. Genetic deficiency of sEH enhanced glucose-stimulated insulin secretion in mice, improving systemic glucose control and reducing oxidative stress and beta-cell death. Inhibition of sEH showed potential in mitigating high fat diet-induced beta-cell loss and dedifferentiation.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Letter
Medicine, General & Internal
Petr Kala, Tomas Hnat, Karolina Padrova, Karel Kotaska, Josef Veselka
Summary: This study investigated the levels of plasma eicosanoids (14,15-EET and 14,15-DHET) in patients with heart failure (HF) compared to age- and sex-matched controls. The results showed that both eicosanoids were significantly higher in the HF group. These findings suggest elevated peripheral plasma eicosanoid levels in patients with HF.
ARCHIVES OF MEDICAL SCIENCE
(2023)
Article
Biochemistry & Molecular Biology
John D. Imig, Md Abdul Hye Khan, Anna Burkhan, Guan Chen, Adeniyi Michael Adebesin, John R. Falck
Summary: The study demonstrated the effective targeted delivery of EET analogs to the kidney, reducing the required drug dosage and potential side effects. EET-F01 showed comparable effectiveness to EET-A in decreasing cisplatin nephrotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biochemistry & Molecular Biology
Ankit Gilani, Kevin Agostinucci, Sakib Hossain, Jonathan Pascale, Victor Garcia, Adeniyi Michael Adebesin, John R. Falck, Michal Laniado Schwartzman
Summary: The study found that 20-HETE interferes with insulin signaling and contributes to diet-driven insulin resistance, with potential involvement of its receptor GPR75. Administration of a 20-HETE antagonist attenuated weight gain and prevented the development of hyperglycemia and impaired glucose metabolism in mice.
PROSTAGLANDINS & OTHER LIPID MEDIATORS
(2021)
Article
Endocrinology & Metabolism
Kakali Ghoshal, Xiyue Li, Dungeng Peng, John R. Falck, Raghunath Reddy Anugu, Manuel Chiusa, John M. Stafford, David H. Wasserman, Roy Zent, James M. Luther, Ambra Pozzi
Summary: In this study, researchers found that the administration of a water-soluble EET analog can improve insulin signaling in a genetic model of hepatic insulin resistance. The EET analog enhances hepatic insulin signaling, decreases expression of gluconeogenic genes, and increases expression of glycogenic genes. Mechanistically, the EET analog stabilizes membrane-associated IR beta and potentiates insulin signaling.
Article
Peripheral Vascular Disease
Tamas Kriska, Anja Herrnreiter, Sandra L. Pfister, Adeniyi Adebesin, John R. Falck, William B. Campbell
Summary: The macrophage 12/15-LO pathway enhances the action of Ang II in hypertension development, mainly by promoting endothelial synthesis of a superoxide-derived TP agonist.
Article
Peripheral Vascular Disease
Kevin Agostinucci, Rebecca Hutcheson, Sakib Hossain, Jonathan Pascale, Elizabeth Villegas, Frank Zhang, Adeniyi Michael Adebesin, John R. Falck, Sachin Gupte, Victor Garcia, Michal Laniado Schwartzman
Summary: The study suggests that overexpression of Cyp4a12 in VSMC is sufficient to induce hypertension, potentially involving the activation of Rho-kinase, increased myosin light chain phosphorylation, and activation of the contractile apparatus. The 20-HETE receptor GPR75 may represent a novel target for the treatment of hypertension and associated vascular conditions.
JOURNAL OF HYPERTENSION
(2022)
Article
Pharmacology & Pharmacy
Iwona Baranowska, Olga Gawrys, Agnieszka Walkowska, Krzysztof H. Olszynski, Ludek Cervenka, John R. Falck, Adeniyi M. Adebesin, John D. Imig, Elzbieta Kompanowska-Jezierska
Summary: Numerous studies have shown that metabolites of arachidonic acid, specifically epoxyeicosatrienoic acids (EETs) and 20-Hydroxyeicosatetraenoic acid (20-HETE), play important roles in blood pressure regulation, vascular tone, and renal function control. In this study, the researchers tested the effectiveness of EET-A and AAA in treating spontaneously hypertensive rats (SHR) and found that the combination treatment not only reduced blood pressure but also increased nitric oxide levels.
FRONTIERS IN PHARMACOLOGY
(2022)
Meeting Abstract
Biochemistry & Molecular Biology
Jonathan V. Pascale, Alexandra Wolf, Melissa-Maria Kulaprathazhe, Samir Ali, Namhee Kim, Ghezal Froogh, Adeniyi M. Adebesin, John R. Falck, Michal L. Schwartzman, Victor Garcia
Article
Pharmacology & Pharmacy
Juan A. Azcona, Samantha Tang, Elizabeth Berry, Frank F. Zhang, Radha Garvey, John R. Falck, Michal Laniado Schwartzman, Tao Yi, Thomas M. Jeitner, Austin M. Guo
Summary: This study reveals that neutrophil-derived MPO and HOCl contribute to postischemic compensatory angiogenesis by activating the HIF-1α and CYP4A11 signaling pathway, leading to increased production of 20-HETE. These findings potentially identify novel therapeutic targets for the treatment of ischemia and diseases associated with abnormal angiogenesis.
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2022)
Article
Cardiac & Cardiovascular Systems
Bahar Tunctan, Sefika Pinar Senol, Meryem Temiz-Resitoglu, Dilsah Ezgi Yilmaz, Demet Sinem Guden, Omer Bahceli, Mehmet Furkan Horat, Seyhan Sahan-Firat, Ayse Nihal Sari, John R. Falck, Raghunath Reddy Anugu, Kafait U. Malik
Summary: By activating the GPR75 signaling pathway, 5,14-HEDGE exerts its protective effects against LPS-induced hypotension and tachycardia in arterial tissues.
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY
(2022)
Article
Chemistry, Multidisciplinary
Sailu Munnuri, John R. Falck
Summary: In this study, Iminodirhodium reactive intermediates were generated from O-tosyloximes and utilized for three challenging transformations, including remote C-H functionalization, desaturative annulation, and directed desaturation. These reactions, which have been underexplored in previous studies, were successfully achieved under mild conditions.
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
(2022)
Meeting Abstract
Cardiac & Cardiovascular Systems
Ahmed Darwesh, Deanna Sosnowski, Robert Valencia, Anne Konkel, John Falck, Wolf-Hagen Schunck, John Seubert
JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
(2022)
Article
Cell Biology
Sofia Cardenas, Cecilia Colombero, Mariana Cruz, Eduardo Mormandi, Adeniyi Michael Adebesin, John R. Falck, Susana Nowicki
Summary: The membrane receptor GPR75 plays a role in regulating the expression and transcriptional activity of androgen receptor (AR) in prostate cancer (PCa) cells mediated by 20-hydroxyeicosatetraenoic acid (20-HETE). This suggests that targeting 20-HETE/GPR75 could be a potential strategy to limit the expression of AR-driven phenotype in PCa cells.
MOLECULAR AND CELLULAR ENDOCRINOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Kathleen Lukaszewicz, John R. R. Falck, Julian Lombard
Summary: In Dahl salt-sensitive rats, impaired vascular relaxation can be restored by restoring physiological levels of angiotensin II, inhibiting 20-HETE production, or introducing a normally functioning renin allele. However, chronically low angiotensin II levels in SS rats were found to upregulate cytochrome P450-4A and increase the production of the vasoconstrictor 20-HETE. The renin-angiotensin system and the CYP4A/20-HETE pathway both contribute to vascular dysfunction in the Dahl SS rat, but they are independent of each other.
Meeting Abstract
Oncology
Jianxun Lei, Zhijun Guo, Julissa Molina-Vega, Paloma Cervantes, Swaathi Jayaraman, John R. Hawse, Carlos Perez, Juan Abrahante, Xiaojia Tang, Krishna Kalari, Jinhua Wang, John R. Falck, Carol Lange, Matthew P. Goetz, David Potter
Article
Chemistry, Multidisciplinary
Raghunath Reddy Anugu, John R. Falck
Summary: In this study, benzylic/allylic alcohols are converted to anilines and/or nitriles as well as N-heterocycles via a site-selective C(sp(2))-C(sp(3)) cleavage reaction using commercial hydroxylamine-O-sulfonic acid (HOSA) and Et3N in a simple, one-pot process. It is noteworthy that cyclic benzylic/allylic alcohols undergo bis-functionalization, leading to increased complexity and step-economy.
