Article
Medicine, Research & Experimental
Selina T. Somani, Maxwell Zeigler, Emily E. Fay, Maggie Leahy, Bethanee Bermudez, Rheem A. Totah, Mary F. Hebert
Summary: The study found that changes in arachidonic acid metabolites during pregnancy may be associated with the cytochrome P450 pathway, which plays an important role in healthy pregnancy.
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)
Review
Biochemistry & Molecular Biology
Zeqi Shi, Zuowen He, Dao Wen Wang
Summary: Inflammation plays a crucial role in various systemic illnesses, and EETs have been found to have anti-inflammatory effects, reducing inflammation and remodeling of blood vessels. EETs also play important roles in other pathological conditions. Manipulating the AA-CYP450-EETs-sEH pathway has shown potential in alleviating inflammatory diseases, highlighting the importance of this research field.
Review
Pharmacology & Pharmacy
Mohammed A. W. ElKhatib, Fadumo Ahmed Isse, Ayman O. S. El-Kadi
Summary: The incidence of heart failure (HF) is preceded by cardiac hypertrophy (CH). Arachidonic acid (AA) metabolism is modulated during cardiac hypertrophy. Studies have shown that AA metabolites mediated by cytochrome P450 (CYP) play a role in the pathogenesis of cardiac hypertrophy. Inflammation has been found to affect the expression of CYPs and their metabolites in the heart. Pro-inflammatory metabolites such as HETEs are implicated in cardiac hypertrophy, while anti-inflammatory EETs have cardioprotective properties. This review highlights the impact of inflammation on CYP-derived AA metabolites and cardiac hypertrophy, and discusses potential anti-inflammatory strategies for the treatment of cardiac hypertrophy and heart failure.
DRUG METABOLISM REVIEWS
(2023)
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)
Article
Plant Sciences
Shu-Ming Li, Zheng-Xi Zhang, Zhang-Hai Li
Summary: The highly oxygenated indole alkaloid speradine F (4) with a 6/5/6/5/5/5 hexacyclic skeleton was isolated from a culture of Penicillium palitans, together with its precursors beta-cyclopiazonic acid (beta-CPA, 5) and cyclopiazonic acid (CPA, 1). Gene deletion and heterologous expression led to the identification of the responsible five-gene spe cluster for the speradine skeleton formation. Precursor supply experiments proved that 1 was enzymatically converted, via 2-oxoCPA (2), to speradine A (3), which subsequently undergoes multistep nonenzymatic hydroxylations to 4.
JOURNAL OF NATURAL PRODUCTS
(2023)
Article
Multidisciplinary Sciences
Laurentijn Tilleman, Kaat Rubben, Wim Van Criekinge, Dieter Deforce, Filip Van Nieuwerburgh
Summary: This study tested the effectiveness of Targeted Locus Amplification (TLA) combined with Illumina or Nanopore sequencing in accurate genotyping and phasing of pharmacogenes. The results showed limited nucleotide mapping on target and incomplete coverage of genes with both sequencing methods. However, the optimized primer pair for the CYP2D6 gene in the Nanopore dataset resulted in correct haplotypes, indicating the potential reliability of this method with patient-specific primer design and optimization.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Freeborn Rwere, Sangchoul Im, Lucy Waskell
Summary: By altering the 140s FMN binding loop of CYPOR, the activity with cyt P450s can be affected, with the mutant activity primarily determined by its ability to reduce ferric cyt P450. The different behaviors of the mutants are mainly due to the altered structure and mobility of the loop.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Multidisciplinary Sciences
Lulu Ni, Ping Miao, Jian Jiang, Fang Wan, Jiangan Li, Min Ai, Lingzhong Kong, Su Tu
Summary: This study found that Glycyrrhiza promotes the metabolism of toxic components of Aconitum by upregulating the expression of CYP3A, reducing the content of heart failure-related markers, and improving the myocardial energy metabolism disorder, thus alleviating the development of congestive heart failure.
Article
Biochemistry & Molecular Biology
Yoo-Bin Lee, Vitchan Kim, Sung-Gyu Lee, Gyu-Hyeong Lee, Changmin Kim, Eunseo Jeong, Donghak Kim
Summary: This study demonstrates that allelic variations of human cytochrome P450 2C8 can significantly affect drug metabolism and the production of fatty acid-derived signal molecules. Functional analysis of four newly identified allelic variants showed that V181I, I244V, and L361F variants resulted in a significant reduction in enzyme activity. The L361F variant also exhibited a significant decrease in the efficiency of arachidonic acid epoxidation reactions. These findings suggest that individuals carrying these newly identified P450 2C8 allelic variations may have altered metabolism of clinical medicines and fatty acid-derived signal molecules.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Guillaume Feugray, Tony Pereira, Michele Iacob, Lucile Moreau-Grange, Gaetan Prevost, Valery Brunel, Robinson Joannides, Jeremy Bellien, Thomas Duflot
Summary: This study found that there were no significant differences in ARA metabolite levels between T2D patients and healthy volunteers, but HTN patients showed alterations in ARA metabolite correlation patterns with increased 20-, 19-, 15-, and 8-HETE. Additionally, a decrease in 20-HETE was observed during both hyperglycemic and hyperinsulinemic clamps, suggesting a potential link to glucose tolerance and insulin signaling regulation.
Article
Biochemistry & Molecular Biology
Sarah M. Glass, Yasuhiro Tateishi, F. Peter Guengerich, Hong-Jaan Wang
Summary: Cytochrome P450 (P450, CYP) 27C1 is expressed in human skin and catalyzes the 3,4-desaturation of retinoids. The function of the desaturated retinoids in human skin is currently unknown. The study suggests that the desaturation process may serve as a protective mechanism to maintain active retinoid levels in the body.
ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS
(2023)
Review
Medicine, Research & Experimental
Yanfang Zhang, Liangcai Gao, Bingyi Yao, Shengbo Huang, Yuanjin Zhang, Jie Liu, Zongjun Liu, Xin Wang
Summary: Epoxyeicosatrienoic acids (EETs) play a crucial role in heart function and their metabolic pathway serves as an important target for drug development and prevention of cardiotoxicity, showing promising prospects for cardiovascular disease treatment.
Article
Chemistry, Multidisciplinary
Alecia R. Gee, Isobella S. J. Stone, Tegan P. Stockdale, Tara L. Pukala, James J. De Voss, Stephen G. Bell
Summary: We have achieved efficient oxidation reactions on unactivated carbon-hydrogen bonds by modifying the enzyme structure.
CHEMICAL COMMUNICATIONS
(2023)
Article
Biochemistry & Molecular Biology
Emmanuelle Pineau, Vincent Sauveplane, Etienne Grienenberger, Jean-Etienne Bassard, Frederic Beisson, Franck Pinot
Summary: Data mining led to the identification and characterization of a new fatty acid epoxygenase in Arabidopsis thaliana, named CYP77B1, capable of converting plant fatty acids into specific diols. The enzyme showed highest expression in flower bud and was mainly present in pistil during open flower stage. The study also suggested a specific function of CYP77B1 in flowering plants based on phylogenetic analysis.
Review
Dermatology
Karan Agrawal, Raja K. Sivamani, John W. Newman
SKIN RESEARCH AND TECHNOLOGY
(2019)
Article
Multidisciplinary Sciences
Anita Rajamani, Kamil Borkowski, Samir Akre, Andrea Fernandez, John W. Newman, Scott Simon, Anthony G. Passerini
SCIENTIFIC REPORTS
(2019)
Article
Chemistry, Analytical
Theresa L. Pedersen, Ira J. Gray, John W. Newman
Summary: The goal of this research was to develop a high-throughput, cost-effective method for metabolic profiling of lipid mediators and hormones involved in the regulation of inflammation and energy metabolism. The method showed low intra- and inter-batch variability for most metabolites, but higher variability for serum oxylipins and some bile acids. Application to two cohorts of elderly individuals revealed routine detection of 86 metabolites and provided valuable insights for large cohort studies.
ANALYTICA CHIMICA ACTA
(2021)
Article
Nutrition & Dietetics
Riley L. Hughes, William H. Horn, Peter Finnegan, John W. Newman, Maria L. Marco, Nancy L. Keim, Mary E. Kable
Summary: The study found that consumption of RS2-enriched wheat leads to reduced postprandial glycemia, altered gut microbiota composition, and increased fermentation activity.
Article
Biochemistry & Molecular Biology
Tagreed A. Mazi, Kamil Borkowski, John W. Newman, Oliver Fiehn, Christopher L. Bowlus, Souvik Sarkar, Karen Matsukuma, Mohamed R. Ali, Dorothy A. Kieffer, Yu-Jui Y. Wan, Kimber L. Stanhope, Peter J. Havel, Valentina Medici
Summary: In this study, Hispanics were found to have a higher rate and severity of nonalcoholic fatty liver disease compared to other ethnicities. Metabolomic profiling showed signs of metabolic dysregulation in Hispanics, independent of obesity, with higher plasma triglycerides and free fatty acids. Ethnicity-related differences in liver and plasma metabolomic profiles may modulate the risk for progression of NAFLD to NASH.
FREE RADICAL BIOLOGY AND MEDICINE
(2021)
Article
Cardiac & Cardiovascular Systems
Sridevi Krishnan, Erik R. Gertz, Sean H. Adams, John W. Newman, Theresa L. Pedersen, Nancy L. Keim, Brian J. Bennett
Summary: The study showed that following a diet based on the 2010 Dietary Guidelines for Americans for 8 weeks did not improve endothelial function or reduce plasma TMAO concentrations.
NUTRITION METABOLISM AND CARDIOVASCULAR DISEASES
(2022)
Article
Biochemistry & Molecular Biology
Deena B. Snoke, Austin Angelotti, Kamil Borkowski, Rachel M. Cole, John W. Newman, Martha A. Belury
Summary: Dietary lipid sources have a significant impact on lipid mediator profiles in adipose tissues and plasma, which in turn affects energy metabolism. Changes in lipid mediators vary between tissues, and these mediators play important roles in regulating adipose tissue expansion and function. There is a relationship between brown adipose tissue and plasma lipid mediators in mice consuming a linoleate-rich safflower oil diet.
Article
Biochemistry & Molecular Biology
Celine Dalle, Jeremy Tournayre, Malwina Mainka, Alicja Basiak-Rasala, Melanie Petera, Sophie Lefevre-Arbogast, Jessica Dalloux-Chioccioli, Melanie Deschasaux-Tanguy, Lucie Lecuyer, Emmanuelle Kesse-Guyot, Leopold K. Fezeu, Serge Hercberg, Pilar Galan, Cecilia Samieri, Katarzyna Zatonska, Philip C. Calder, Mads Fiil Hjorth, Arne Astrup, Andre Mazur, Justine Bertrand-Michel, Nils Helge Schebb, Andrzej Szuba, Mathilde Touvier, John W. Newman, Cecile Gladine
Summary: The oxylipin signature of patients with metabolic syndrome enhances MetS phenotyping and may ultimately help to better stratify the risk of cardiometabolic diseases.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Bruce A. Watkins, Allon N. Friedman, Jeffrey Kim, Kamil Borkowski, Shaun Kaiser, Oliver Fiehn, John W. Newman
Summary: Hemodialysis patients have higher blood pressure, inflammation levels, and cardiovascular disease risk compared to healthy subjects. They also have unusually low levels of n-3 polyunsaturated fatty acids. This study found that these differences in specific fatty acid levels resulted in changes in endocannabinoids and oxylipins, which help explain the severe inflammation and cardiovascular disease observed in these patients.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Biochemistry & Molecular Biology
Austin Angelotti, Deena B. Snoke, Kate Ormiston, Rachel M. Cole, Kamil Borkowski, John W. Newman, Tonya S. Orchard, Martha A. Belury
Summary: Long-chain omega-3 polyunsaturated fatty acids (LC n-3 PUFA) may alleviate chemotherapy-induced cardiotoxicity by modulating heart gene expression and lipid species.
Article
Biochemistry & Molecular Biology
Kristen L. James, Erik R. Gertz, Catherine P. Kirschke, Hooman Allayee, Liping Huang, Mary E. Kable, John W. Newman, Charles B. Stephensen, Brian J. Bennett
Summary: In this study, a mixed macronutrient tolerance test was conducted to investigate the changes in plasma TMAO levels in response to different factors. It was found that TMAO levels increased with age in females but not in males. The relationship between TMAO levels and fecal microbiome and FMO3 genotype was limited, while a strong correlation between TMAO levels and TNF-alpha was observed.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Medicine, General & Internal
Iryna Rybak, Kelly N. Haas, Simran K. Dhaliwal, Waqas A. Burney, Aunna Pourang, Simran S. Sandhu, Jessica Maloh, John W. Newman, Robert Crawford, Raja K. Sivamani
Summary: This study aimed to investigate the effects of oral spore-based probiotic ingestion on the gut microbiome, plasma short-chain fatty acids (SCFAs), and skin biophysical properties. The results showed that probiotic supplementation led to a decrease in facial sebum excretion rate and an overall increase in transepidermal water loss (TEWL). Participants with acne showed improvements in lesion counts and markers of gut permeability. The gut microbiome of the nonacne population had an increase in Akkermansia, while those with acne had an increase in Lachnospiraceae and Ruminococcus gnavus. Preliminary evidence suggests the potential use of spore-based probiotic supplementation for modulating the gut microbiome and increasing SCFAs in both acne and nonacne populations.
JOURNAL OF CLINICAL MEDICINE
(2023)
Article
Nutrition & Dietetics
Bruce A. Watkins, John W. Newman, George A. Kuchel, Oliver Fiehn, Jeffrey Kim
Summary: This study investigated the effects of dietary polyunsaturated fatty acids (PUFA) on the endocannabinoid system (ECS) and found that DHA-enriched diet can alter energy metabolism and fatty acid metabolism, reducing the risk of obesity and type 2 diabetes.
Article
Biochemistry & Molecular Biology
Anita Wen, Ying Zhu, Sook Wah Yee, Brian I. Park, Kathleen M. Giacomini, Andrew S. Greenberg, John W. Newman
Summary: The Thiamine Transporter 2 (THTR2) encoded by SLC19A3 plays an undefined role in maintaining tissue thiamine levels. In this study, the impact of THTR2 on thiamine status and metabolism was evaluated in mice. The loss of THTR2 resulted in lower plasma and brain thiamine levels and altered brain metabolome. This suggests that THTR2 mutation or inhibition may affect thiamine storage and metabolism in the brain.
Article
Nutrition & Dietetics
Virginia M. Artegoitia, Sridevi Krishnan, Ellen L. Bonnel, Charles B. Stephensen, Nancy L. Keim, John W. Newman
Summary: The study revealed that differences in dietary patterns by sex and age can help individuals distinguish whether they have risk factors for cardiometabolic disease, and sex-specific dietary patterns can more accurately predict the presence of CMDrf.