SLCO1C1 (Solute Carrier Organic Anion Transporter Family Member 1C1)

Reductions in Mct8 mRNA expression were confirmed by immunohistochemical analysis. Our findings suggest that alteration of TH, WNT, and NOTCH signalling may be associated with impaired oligodendrocyte maturation and myelination in IUGR, providing insight into the mechanisms underlying white matter injury in IUGR infants.

Daily oral intake of plasticizer DEHP may induce cerebellar demyelination, contributing to neurodegeneration in the elderly. These results highlight that inappropriate exposure to environmental pollutants, such as DEHP, could increase the risk of cerebellar dysfunction and neurodegeneration in elderly individuals.

All compounds reveal potential cytotoxicity for several types of cancer cells. These findings may guide further experimental studies to identify medical and pharmacological applications of tarragon extracts or specific compounds that can be isolated from these extracts.

However, the poor expression of several important THTMTs, together with the low amount of TH transport, indicate that the HIBCPP cells lack key features that drive TH transport in the BCSFB. The HIBCPP cells could serve as a model to further study the mechanisms of TTR driven TH transport, but for the identification of THTMTs more in vivo accurate BCSFB models are necessary.

However, the poor expression of several important THTMTs, together with the low amount of TH transport, indicate that the HIBCPP cells lack key features that drive TH transport in the BCSFB. The HIBCPP cells could serve as a model to further study the mechanisms of TTR driven TH transport, but for the identification of THTMTs more in vivo accurate BCSFB models are necessary.

Zotizalkib (TPX-0131), a fourth-generation macrocyclic anaplastic lymphoma kinase (ALK) inhibitor, is designed to overcome resistance due to secondary ALK mutations in non-small cell lung cancer (NSCLC)...ABCB1-mediated efflux of zotizalkib was completely inhibited by elacridar, a dual ABCB1/ABCG2 inhibitor, increasing brain exposure without any signs of acute CNS-related toxicities...Notably, the hepatic expression of human CES1 did not affect zotizalkib plasma exposure or tissue distribution. The obtained pharmacokinetic insights may be useful for the further development and optimization of therapeutic efficacy and safety of zotizalkib and related compact macrocyclic ALK inhibitors.

Conclusively, our research showed that arachidonic acid mitigates cholestatic liver disease by upregulating Oatp1, promoting bile acid uptake by hepatocytes and participating in intestinal-hepatic circulation. Overall, these results suggest that supplementing foods with arachidonic acid in the daily diet may be an effective treatment strategy for cholestatic liver disease.

T1 mapping based on gadoxetic acid-enhanced MRI may be useful for diagnosis of hepatic SOS, and MRI parameters were associated with OATP1 levels.

Opnurasib (JDQ443) is a newly developed oral KRASG12C inhibitor, with a binding mechanism distinct from the registered KRASG12C inhibitors sotorasib and adagrasib...The Abcb1a/b transporter activity could be almost completely reversed by co-administration of elacridar, a dual ABCB1/ABCG2 inhibitor, increasing the brain penetration without any behavioral or postural signs of acute CNS-related toxicity...Plasma Ces1c therefore likely binds opnurasib, increasing its retention in plasma. The obtained pharmacokinetic insights may be useful for further optimization of the clinical efficacy and safety of opnurasib, and might reveal potential drug-drug interaction risks.

Various indices, including signal intensity-based methods and MR relaxometry, have been proposed for the estimation of liver function and prediction of PHLF using gadoxetic acid-enhanced MRI. Recent developments in MR techniques, including high-resolution hepatobiliary phase images using deep learning image reconstruction and whole-liver T1 map acquisition, have enabled a more detailed and accurate estimation of liver function in gadoxetic acid-enhanced MRI.

The predicted binding energies correlated with the transport profiles, with T derivatives exhibiting higher binding energies when compared to prodrugs with a DIT promoiety. Interestingly, the prodrugs also showed utilization of oatp1a4/1a5/1a6 in mouse primary astrocytes, which was further supported by docking studies and a great potential for improved brain drug delivery.

Altogether, our studies underscore an oligodendrocyte differentiation impairment and altered oligodendrocyte structural parameters in the global absence of Mct8 and Oatp1c1. Both mechanisms most likely do not only cause the abnormal myelination state but also contribute to compromised neuronal functionality in Mct8/Oatp1c1 deficient animals.