Organic cation transporter 2 (OCT2) and
multidrug and toxin extrusion 1 and 2-K (MATE1/2-K) are critically involved in
renal secretion, pharmacokinetics (PK), and toxicity of cationic drugs.
Drug-drug interactions (DDIs) at OCT2 and/or MATE1/2-K have been shown to
result in clinical impacts on PK, therapeutic efficacy
and are probably involved in the renal accumulation of drugs. In this work, an
overview of OCT2 and MATE1/2-K is presented. The primary structure, membrane
location, functional properties, and clinical impact of OCT2 and MATE1/2-K are
described. In addition, clinical aspects of
DDIs in OCT2 and MATE1/2-K and their involvement in drug nephrotoxicity are
compiled.
The
severe acute respiratory syndrome
coronavirus 2 (SARS-CoV-2) Omicron variant has multiple receptor-binding
domain (RBD) mutations. Some of these mutations can increase infectivity and
reduce antibody affinity. In this study, the authors successfully developed a
rapid screening assay to simultaneously identify RBD mutations in the Omicron
and Delta variants using high-resolution melting (HRM) analysis. As this
HRM-based genotyping assay does not require sequence-specific probes, unlike the
TaqMan probe assay, it is easy to perform and cost-effective. This simple
method may contribute to the rapid identification and prevention of the potential
widespread infection of SARS-CoV-2 variants.
It has long been known that the chronic skin lesions
of atopic dermatitis (AD) patients show increased amounts of Th1 cells in
addition to Th2 cells. However, it has remained unclear whether these Th1 cells
actually participate in the exacerbation of skin inflammation. In this paper,
the authors showed that Langerhans cells (LCs) augmented CCL5 production by
responding to Th1 cytokine, IFN-g while presenting antigen to Th cells, and that this
augmentation of CCL5 production would contribute to infiltration of eosinophils
and other Th1 cells into skin lesions, followed by expansion of chronic
inflammation in the skin.
Breed and organ-dependent sex differences in the mRNA amounts of several drug
transporters in the liver and kidney were found in pigs. In Meishan pigs, the
sex differences in the amounts of hepatic MDR1, OATP1B3, and OCT1 mRNAs and in those
of renal MRP2, OAT1, OAT2, OAT3, and OCT2 mRNAs were found. However, no such
sex differences were observed in Landrace pigs. Furthermore,
additional experiments using castrated and/or testosterone propionate-treated
pigs suggested that breed-dependent sex differences in the gene expression of
drug transporters, especially hepatic OCT1 and renal OAT1, were primarily due
to the difference in serum testosterone concentration.
Brown
adipose tissue (BAT) specifically regulates energy expenditure via heat
production. Hence, BAT may have the potential to combat obesity in humans. The activity of BAT is directly regulated by β-adrenergic
stimulation. In this study, the authors report the effects of Nobiletin (NOB),
a natural polymethoxylated flavone present in citrus fruits, on BAT activation
using β-adrenergic agonists. NOB can enhance the thermogenic functions of brown
adipocytes and promote brown adipokine secretion due to enhanced β-adrenergic
stimulation. NOB could be a promising candidate for activating BAT under
β-adrenergic stimulation and preventing the onset of obesity.