Development of a human FaFg prediction system for polyphenols using human induced pluripotent stem cell-derived small intestinal epithelial cells.

Precise prediction of the fraction of compounds reaching the portal vein (FaFg) in humans, which could indicate the rate-limiting step of polyphenol metabolism, is particularly important for accurately evaluating the efficacy and safety of polyphenols. In this study, we aimed to develop a novel in vitro method to predict human FaFg of polyphenols using commercially available human induced pluripotent stem cell-derived small intestinal epithelial cells (hiPSC-SIECs). First, the chemicals were used at fixed test concentrations, considering their physicochemical properties and cytotoxicity.

The high-light-sensitivity mechanism and optogenetic properties of the bacteriorhodopsin-like channelrhodopsin GtCCR4.

Channelrhodopsins are microbial light-gated ion channels that can control the firing of neurons in response to light. Among several cation channelrhodopsins identified in Guillardia theta (GtCCRs), GtCCR4 has higher light sensitivity than typical channelrhodopsins. Furthermore, GtCCR4 shows superior properties as an optogenetic tool, such as minimal desensitization.

Determination of human FF of polyphenols using allometric scaling.

Certain polyphenols exhibit low permeability; precise prediction of their intestinal absorption is important for understanding internal exposure in humans. Intestinal availability, which represents the fraction of administered compounds that reach the portal blood (FF), is calculated by dividing bioavailability (F) by hepatic availability (F), and F is obtained from pharmacokinetic data from both intravenous (i.v.

Proton-transporting heliorhodopsins from marine giant viruses.

Rhodopsins convert light into signals and energy in animals and microbes. Heliorhodopsins (HeRs), a recently discovered new rhodopsin family, are widely present in archaea, bacteria, unicellular eukaryotes, and giant viruses, but their function remains unknown. Here, we report that a viral HeR from Emiliania huxleyi virus 202 (V2HeR3) is a light-activated proton transporter.

TAT Rhodopsin Is an Ultraviolet-Dependent Environmental pH Sensor.

In many rhodopsins, the retinal Schiff base p remains very high, ensuring Schiff base protonation captures visible light. Nevertheless, recently we found that TAT rhodopsin contains protonated and unprotonated forms at physiological pH. The protonated form displays a unique photochemical behavior in which the primary K intermediate returns to the original state within 10 s, and the lack of photocycle completion poses questions about the functional role of TAT rhodopsin.

Novel optogenetics tool: Gt_CCR4, a light-gated cation channel with high reactivity to weak light.

Optogenetics is a growing technique which allows manipulation of biological events simply by illumination. The technique is appreciated especially in the neuroscience field because of its availability in controlling neuronal functions. A light-gated cation channel, Cr_ChR2 from Chlamydomonas reinhardtii, is the first and mostly applied to optogenetics for activating neuronal excitability.