Enzyme-mediated drug-drug interactions: a review of and methodologies, regulatory guidance, and translation to the clinic.

Enzyme-mediated pharmacokinetic drug-drug interactions can be caused by altered activity of drug metabolizing enzymes in the presence of a perpetrator drug, mostly inhibition or induction. We identified a gap in the literature for a state-of-the art detailed overview assessing this type of DDI risk in the context of drug development. This manuscript discusses and methodologies employed during the drug discovery and development process to predict clinical enzyme-mediated DDIs, including the determination of clearance pathways, metabolic enzyme contribution, and the mechanisms and kinetics of enzyme inhibition and induction.

Transporter-mediated drug-drug interactions: regulatory guidelines, and methodologies and translation, special populations, and the blood-brain barrier.

This review, part of a special issue on drug-drug interactions (DDIs) spearheaded by the International Society for the Study of Xenobiotics (ISSX) New Investigators, explores the critical role of drug transporters in absorption, disposition, and clearance in the context of DDIs. Over the past two decades, significant advances have been made in understanding the clinical relevance of these transporters. Current knowledge on key uptake and efflux transporters that affect drug disposition and development is summarized.

Dynamic Expression of Follicle-Stimulating Hormone and Estrogen mRNA Receptors Associated with microRNAs and in Canine Follicles during the Estrous Cycle.

The genes encoding for estrogen receptor () and follicle-stimulating hormone receptor () play crucial roles in ovarian follicular development. This study aimed to determine the expression levels of miRNAs predicted against and mRNAs in follicular cells related to their target genes during the estrous cycle in canines. Antral follicles were dissected from 72 ovaries following ovariohysterectomies.

Rhenium-Based Electrocatalysts for Water Splitting.

Due to the contamination and global warming problems, it is necessary to search for alternative environmentally friendly energy sources. In this area, hydrogen is a promising alternative. Hydrogen is even more promising, when it is obtained through water electrolysis operated with renewable energy sources.

Epigenetics in drug disposition & drug therapy: symposium report of the 24 North American meeting of the International Society for the Study of Xenobiotics (ISSX).

The 24th North American International Society for the Study of Xenobiotics (ISSX) meeting, held virtually from September 13 to 17, 2021, embraced the theme of "Broadening Our Horizons." This reinforces a key mission of ISSX: striving to share innovative science related to drug discovery and development. Session speakers and the ISSX New Investigators Group, which supports the scientific and professional development of student and early career ISSX members, elected to highlight the scientific content presented during the captivating session titled, "Epigenetics in Drug Disposition & Drug Therapy.

Altered Metabolism of Polycyclic Aromatic Hydrocarbons by UDP-Glycosyltransferase 3A2 Missense Variants.

The UDP-glycosyltransferase (UGT) family of enzymes are important in the metabolism of a variety of exogenous substances including polycyclic aromatic hydrocarbons (PAHs), a potent class of environmental carcinogens. As compared to the majority of UGT enzymes, which utilize UDP-glucuronic acid as a cosubstrate, UGT3A2 utilizes alternative cosubstrates (UDP-glucose and UDP-xylose). UGT3A2 is expressed in aerodigestive tract tissues and was highly active against multiple PAHs with both cosubstrates.

UDP-Glycosyltransferase 3A Metabolism of Polycyclic Aromatic Hydrocarbons: Potential Importance in Aerodigestive Tract Tissues.

Polycyclic aromatic hydrocarbons (PAHs) are potent carcinogens and are a primary risk factor for the development of lung and other aerodigestive tract cancers in smokers. The detoxification of PAHs by glucuronidation is well-characterized for the UDP-glycosyltransferase (UGT) 1A, 2A, and 2B subfamilies; however, the role of the UGT3A subfamily in PAH metabolism remains poorly understood. UGT3A enzymes are functionally distinct from other UGT subfamilies (which use UDP-glucuronic acid as a cosubstrate) due to their utilization of alternative cosubstrates (UDP--acetylglucosamine for UGT3A1, and UDP-glucose and UDP-xylose for UGT3A2).

Testosterone and cortisol modulate the effects of empathy on aggression in children.

This study aimed to analyze the potential moderating role of circulating testosterone, cortisol and estradiol levels on the attenuating effect of empathy on aggression in children. Participants were 139 children (80 boys and 59 girls) from the 3rd year of primary school (age 8). Their aggressive behavior was measured by the Direct and Indirect Aggression Scale, an instrument which uses peer rating; empathy was measured using the Empathy Quotient-Child Version.

Developmental trajectories of aggressive behavior in children from ages 8 to 10: The role of sex and hormones.

Objectives: This study explored the developmental trajectory of aggressive behavior from age 8 to age 10 in school-aged children, taking into account possible sex differences, as well as the involvement of certain hormones.

Methods: Participants were 90 children (49 boys and 41 girls) from four schools. At the beginning of the study, the children were 8-year old and were in 3rd grade of primary school.

Milk Thistle Constituents Inhibit Raloxifene Intestinal Glucuronidation: A Potential Clinically Relevant Natural Product-Drug Interaction.

Women at high risk of developing breast cancer are prescribed selective estrogen response modulators, including raloxifene, as chemoprevention. Patients often seek complementary and alternative treatment modalities, including herbal products, to supplement prescribed medications. Milk thistle preparations, including silibinin and silymarin, are top-selling herbal products that may be consumed by women taking raloxifene, which undergoes extensive first-pass glucuronidation in the intestine.

Parenting styles and hormone levels as predictors of physical and indirect aggression in boys and girls.

This study examines the relationship between parenting style, androgen levels, and measures of physical and indirect aggression. Peer ratings of aggression were obtained from 159 eight-year-old children (89 boys and 70 girls). Parenting styles (authoritative, authoritarian or permissive) were assessed using the Parenting Styles and Dimensions Questionnaire (PSDQ).