Simvastatin inhibits 20-Hydroxyeicosatetraenoic acid formation: docking and in vitro assay.

Introduction: 20-Hydroxyeicosatetraenoic acid (20-HETE), a metabolite of arachidonic acid catalyzed mainly by cytochrome P450 (CYP) enzymes CYP4A11 and CYP4F2, plays a role in cardiovascular homeostasis. Elevated levels of 20-HETE are associated with hypertension. Accordingly, 20-HETE is a potential target for therapeutic interventions.

Identification of UDP-Glucuronosyltransferase mRNA in human platelets: differential levels in smokers and non-smokers.

Background: UDP-glucuronosyl transferases (UGTs) are major enzymes of phase II drug metabolism, yet their expression in human platelets remains underexplored. Objectives: This study aimed to characterize the mRNA expression profile of UGT isoforms in human platelets and to assess differences between cigarette smokers and nonsmokers.

Methods: Total RNA was extracted from platelet-rich plasma (PRP), buffy coat (BC), and liver samples.

Lauric acid modulates cytochrome 4V2 expression in the human THP1 macrophages.

Objectives: Macrophages play a major role in the inflammation. Recently, the expression of some cytochrome P450 (CYP450) 4 family enzymes was identified in the macrophages including CYP4V2, which metabolizes saturated fatty acids. Lauric acid is unsaturated fatty acid, which can induce inflammation.

Genetic Polymorphisms in Cytochrome P450 Enzymes Involved in Vitamin D Metabolism and the Vitamin D Receptor: Their Clinical Relevance.

Individual variations in the active form of vitamin D (Vit.D) arise from a combination of dietary intake, sun exposure, and genetic factors, making it complex and challenging to maintain optimal levels. Among Vit.

Exploring the Influence of Genetic Variants , , and on COVID-19 Severity and Long-COVID-19 Symptoms.

There is increasing evidence regarding the importance of vitamin D in the prognosis of coronavirus disease 2019 (COVID-19). Genetic variants in the vitamin D receptor () gene affect the response to vitamin D and have been linked to various diseases. This study investigated the associations of the major genetic variants , , and with the severity and long post-infection symptoms of COVID-19.

Clinical Significance of NAT2 Genetic Variations in Type II Diabetes Mellitus and Lipid Regulation.

Background: N-acetyltransferase 2 (NAT2) enzyme is a Phase II drug-metabolizing enzyme that metabolizes different compounds. Genetic variations in can influence the enzyme's activity and potentially lead to the development of certain diseases.

Aim: This study aimed to investigate the association of variants with the risk of Type II diabetes mellitus (T2DM) and the lipid profile among Jordanian patients.

CYP2C19 Contributes to THP-1-Cell-Derived M2 Macrophage Polarization by Producing 11,12- and 14,15-Epoxyeicosatrienoic Acid, Agonists of the PPARγ Receptor.

Although the functional roles of M1 and M2 macrophages in the immune response and drug resistance are important, the expression and role of cytochrome P450s (CYPs) in these cells remain largely unknown. Differential expression of the 12 most common CYPs (CYP1A1, 1A2, 1B1, 2B6, 2C8, 2C9, 2C19, 2D6, 2E1, 2J2, 3A4, and 3A5) were screened in THP-1-cell-derived M1 and M2 macrophages using reverse transcription PCR. CYP2C19 was highly expressed in THP-1-cell-derived M2 macrophages, but it was negligibly expressed in THP-1-cell-derived M1 macrophages at the mRNA and protein levels as analyzed by reverse transcription quantitative PCR and Western blot, respectively.

Effects of Vitamin D Receptor Genotype on Lipid Profiles and Retinopathy Risk in Type 2 Diabetes Patients: A Pilot Study.

Genetic polymorphisms affect lipid profiles and are associated with disease complications. Genetic variants in the vitamin D receptor (VDR) gene are associated with type 2 diabetes mellitus (T2DM). In this study, we investigated the effects of VDR genotypes on the lipid profile and disease complications of T2DM patients in a Jordanian population.

Demand for Pharmacogenomics and Personalized Medicine in the United Arab Emirates.

The application of personalized medicine (PM) is rapidly evolving [...

Advances in Personalized Medicines along with Functional Genomics and Pharmacogenomics.

State-of-the-art research on the human genome has produced remarkable research achievements in pharmacogenomics and functional genomics, and these research results are making an invaluable contribution to the advancement of personalized medicine [...

The Functionality of UDP-Glucuronosyltransferase Genetic Variants and their Association with Drug Responses and Human Diseases.

UDP-glucuronosyltransferases (UGTs) are phase II drug-metabolizing enzymes that metabolize endogenous fatty acids such as arachidonic acid metabolites, as well as many prescription drugs, such as opioids, antiepileptics, and antiviral drugs. The and genes are highly polymorphic, and their genetic variants may affect the pharmacokinetics and hence the responses of many drugs and fatty acids. This study collected data and updated the current view of the molecular functionality of genetic variants on genes that impact drug responses and the susceptibility to human diseases.

Molecular toxicological alterations in the mouse hearts induced by sub-chronic thiazolidinedione drugs administration.

Thiazolidinediones are well-known anti-diabetic drugs. However, they are not widely used due to their cardiotoxic effects. Therefore, in this study, we aimed to determine the molecular toxicological alterations induced in the mouse hearts after thiazolidinedione administration.

The Association of IgE Levels with Genetic Polymorphisms among Asthmatic Patients.

Total serum immunoglobulin E (IgE) is elevated in multiple allergic diseases and is considered a good predictor of atopy. Several studies have been performed on the association of IgE levels with the polymorphism of the gene in asthmatic patients. The aim of this study was to determine whether there is an association between IgE levels and the genetic polymorphisms of the gene (T1, T2, T + 1, V4, S1, S2, and Q-1) in both healthy and asthmatic patients among Jordanians.

Estrogen Sulfotransferase (SULT1E1): Its Molecular Regulation, Polymorphisms, and Clinical Perspectives.

Estrogen sulfotransferase (SULT1E1) is a phase II enzyme that sulfates estrogens to inactivate them and regulate their homeostasis. This enzyme is also involved in the sulfation of thyroid hormones and several marketed medicines. Though the profound action of SULT1E1 in molecular/pathological biology has been extensively studied, its genetic variants and functional studies have been comparatively rarely studied.

Glucocorticoid receptor dimerization in the cytoplasm might be essential for nuclear localization.

The glucocorticoid receptor (GR) plays an important role in steroid-dependent regulation of metabolism, development, and the immune response in humans. Although GR is known to be activated by the binding of glucocorticoid, the mechanism of action is poorly understood. We investigated dimerization of GR in the cytoplasm and nuclear trans-localization in response to treatment with the ligand dexamethasone.

No impact of soluble epoxide hydrolase rs4149243, rs2234914 and rs751142 genetic variants on the development of type II diabetes and its hypertensive complication among Jordanian patients.

Background: Human soluble epoxide hydrolase plays a major role in cardiovascular homoeostasis. Genetic variants in the EPHX2 gene among different ethnic groups are associated with cardiovascular complications, such as hypertension. However, no reports regarding the association of EPHX2 genotype with hypertension among type II diabetic (T2D) patients of Middle Eastern Jordanian origin exist.

Mechanistic Implications of Biomass-Derived Particulate Matter for Immunity and Immune Disorders.

Particulate matter (PM) is a major and the most harmful component of urban air pollution, which may adversely affect human health. PM exposure has been associated with several human diseases, notably respiratory and cardiovascular diseases. In particular, recent evidence suggests that exposure to biomass-derived PM associates with airway inflammation and can aggravate asthma and other allergic diseases.

Repression of PPARγ reduces the ABCG2-mediated efflux activity of M2 macrophages.

Even though subclasses of macrophage have distinct roles during progression of infectious diseases, it remains poorly understood whether there is a subset-specific difference in drug responses. Here, we report that ABCG2 was expressed specifically in M2-like macrophages and that it controlled their efflux activities. Abcg2 expression is markedly induced during polarization of PMA-primed macrophages toward an M2 type.

Identification and functional study of genetic polymorphisms in cyclic nucleotide phosphodiesterase 3A (PDE3A).

Phosphodiesterase 3A (PDE3A) is an enzyme that plays an important role in the regulation of cyclic adenosine monophosphate (cAMP)-mediated intracellular signaling in cardiac myocytes and platelets. PDE3A hydrolyzes cAMP, which results in a decrease in intracellular cAMP levels and leads to platelet activation. Whole-exome sequencing of 50 DNA samples from a healthy Korean population revealed a total of 13 single nucleotide polymorphisms including five missense variants, D12N, Y497C, H504Q, C707R, and A980V.

The Protective Effect of Metformin against Oxandrolone-Induced Infertility in Male Rats.

Background: Oxandrolone is a synthetic testosterone analog that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus.

Thymoquinone Suppresses Migration of Human Renal Carcinoma Caki-1 Cells through Inhibition of the PGE-Mediated Activation of the EP2 Receptor Pathway.

Renal cell carcinoma (RCC) is likely to metastasize to other organs, and is often resistant to conventional chemotherapies. Thymoquinone (TQ), a phytochemical derived from the seeds of , has been shown to inhibit migration and metastasis in various cancers. In this study, we assessed the effect of TQ on the migratory activity of human RCC Caki-1 cells.

Identification and functional characterization of CYP4V2 genetic variants exhibiting decreased activity of lauric acid metabolism.

The objectives of the present study were to identify CYP4V2 genetic variants and characterize their functional consequences. A total of 26CYP4V2 genetic variants were identified, including seven novel variants in 60 randomly selected healthy subjects. Six protein-coding variants were studied, including three novel variants (L22V, R287T, and G410C) and three previously reported variants (R36S, Q259K, and H331P).

Inhibition of 20-hydroxyeicosatetraenoic acid (20-HETE) glucuronidation by non-steroidal anti-inflammatory drugs in human liver microsomes and recombinant UDP-glucuronosyltransferase enzymes.

20-hydroxyeicosatetraenoic acid (20-HETE) is an arachidonic acid metabolite which is known to increase platelet aggregation and cardiovascular risk. In this study, nine non-steroidal anti-inflammatory drugs (NSAIDs) selected by chemical structures were screened to determine their effects on the glucuronidation of 20-HETE using human liver microsomes (HLMs). Then, the combined effects of the selected NSAID and genetic polymorphisms in UDP-glucuronosyltransferase (UGT) were investigated.

Simultaneous determination of eight arginine-related metabolites in cellular extracts using liquid chromatography-tandem mass spectrometry.

A simple, sensitive, and rapid liquid chromatography (LC)-tandem mass spectrometry (MS/MS) method was developed for the simultaneous determination of arginine and its pathway-related metabolites (ornithine, proline, citrulline, glutamate, agmatine, spermidine, and spermine) in cellular extracts. Cells were lysed and cellular proteins precipitated by the addition of acetonitrile followed by ultra-sonication. Supernatants were analyzed using a Chromolith High Resolution RP-18 endcapped column (100 × 4.

Molecular Functionality of Cytochrome P450 4 (CYP4) Genetic Polymorphisms and Their Clinical Implications.

Enzymes in the cytochrome P450 4 (CYP4) family are involved in the metabolism of fatty acids, xenobiotics, therapeutic drugs, and signaling molecules, including eicosanoids, leukotrienes, and prostanoids. As CYP4 enzymes play a role in the maintenance of fatty acids and fatty-acid-derived bioactive molecules within a normal range, they have been implicated in various biological functions, including inflammation, skin barrier, eye function, cardiovascular health, and cancer. Numerous studies have indicated that genetic variants of genes cause inter-individual variations in metabolism and disease susceptibility.