Possible Progression of Mass-flow Processes around Young Intermediate-mass Stars Based on High-resolution Near-infrared Spectroscopy. I. Taurus

We used the WINERED spectrograph to perform near-infrared high-resolution spectroscopy (resolving power R = 28,000) of 13 young intermediate-mass stars in the Taurus star-forming region. Based on the presence of near- and mid-infrared continuum emission, young intermediate-mass stars can be classified into three different evolutionary stages: Phases I, II, and III in the order of evolution. Our obtained spectra (λ = 0.91–1.35 μm) depict He i λ10830 and Pβ lines that are sensitive to magnetospheric accretion and winds. We also investigate five sources each for Pβ and He i lines that were obtained from previous studies along with our targets. We observe that the Pβ profile morphologies in Phases I and II corresponded to an extensive variety of emission features; however, these features are not detected in Phase III. We also observe that the He i profile morphologies are mostly broad subcontinuum absorption lines in Phase I, narrow subcontinuum absorption lines in Phase II, and centered subcontinuum absorption features in Phase III. Our results indicate that the profile morphologies exhibit a progression of the dominant mass-flow processes: stellar wind and probably magnetospheric accretion in the very early stage, magnetospheric accretion and disk wind in the subsequent stage, and no activities in the final stage. These interpretations further suggest that opacity in protoplanetary disks plays an important role in mass-flow processes. Results also indicate that He i absorption features in Phase III sources, associated with chromospheric activities even in such young phases, are characteristics of intermediate-mass stars

Menahydroquinone-4 Prodrug: A Promising Candidate Anti-Hepatocellular Carcinoma Agent

Recently, new therapeutics have been developed for hepatocellular carcinoma (HCC). However, the overall survival rate of HCC patients is still unsatisfactory; one of the reasons for this is the high frequency of recurrence after radical treatment. Consequently, to improve prognosis, it will be important to develop a novel anti-tumor agent that is especially effective against HCC recurrence. For clinical application, long-term safety, together with high anti-tumor efficacy, is desirable. Recent studies have proposed menahydroquinone-4 1,4-bis-N,N-dimethylglycinate hydrochloride (MKH-DMG), a prodrug of menahydroquinone-4 (MKH), as a promising candidate for HCC treatment including the inhibition of recurrence; MKH-DMG has been shown to achieve good selective accumulation of MKH in tumor cells, resulting in satisfactory inhibition of cell proliferation in des-γ-carboxyl prothrombin (DCP)-positive and DCP-negative HCC cell lines. In a spleen-liver metastasis mouse model, MKH-DMG has been demonstrated to have anti-proliferation and anti-metastatic effects in vivo. The characteristics of MKH-DMG as a novel anti-HCC agent are presented in this review article

Prodrugs for Skin Delivery of Menahydroquinone-4, an Active Form of Vitamin K₂₍₂₀₎, Could Overcome the Photoinstability and Phototoxicity of Vitamin K₂₍₂₀₎

The effective delivery of menahydroquinone-4 (MKH), an active form of menaquinone-4 (MK-4, vitamin K2(20)), to the skin is beneficial in the treatment of various skin pathologies. However, its delivery through the application of MK-4 to the skin is hampered due to the photoinstability and phototoxicity of MK-4. This study aimed to evaluate the potential of ester prodrugs of MKH for its delivery into the skin to avoid the abovementioned issues. The ester prodrugs, MKH 1,4-bis-N,N-dimethylglycinate hydrochloride (MKH-DMG) and MKH 1,4-bis-hemisuccinate (MKH-SUC), were prepared using our previously reported methods. Photostability was determined under artificial sunlight and multi-wavelength light irradiation, phototoxicity was determined by intracellular ROS formation and cell viability of UVA-irradiated human epidermal keratinocyte cells (HaCaT), and delivery of MKH into HaCaT cells was assessed by measuring menaquinone-4 epoxide (MKO) levels. MKH prodrugs showed higher photostability than MK-4. Although MK-4 induced cellular ROS and reduced cell viability after UVA irradiation, MKH prodrugs did not affect either ROS generation or cell viability. MKH prodrugs enhanced intracellular MKO, indicating effective delivery of MKH and subsequent carboxylation activity. In conclusion, these MKH prodrugs show potential for the delivery of MKH into the skin without photoinstability and phototoxicity

Novel Cationic Prodrug of Ubiquinol-10 Enhances Intestinal Absorption via Efficient Formation of Nanosized Mixed-Micelles with Bile Acid Anions

The aim of this study was to develop a prodrug of ubiquinol-10 (UqH-10), the active form of ubiquinone-10 (Uq-10), for oral delivery. Bioavailability of UqH-10 is hampered by its high susceptibility to oxidation and water-insolubility. We prepared three novel N,N-dimethylglycine ester derivatives of UqH-10, including a 1-monoester (UqH-1-DMG), 4-monoester (UqH-4-DMG), and 1,4-bis-ester (UqH-DMG), and assessed their physicochemical properties in vitro and in vivo. UqH-DMG spontaneously formed an aqueous micelle solution comprising 20 nm particles at 36.5 °C. Cationic UqH-DMG formed nano-sized (5 nm) mixed-micelles with taurocholic acid. Reconversion of the derivatives to UqH-10 was accelerated in human liver microsomes. The oral bioavailability of UqH-10 after administration of UqH-derivatives or Uq-10 was determined in fasted and postprandial rats secreting normal and high levels of bile, respectively. In fasted rats, plasma UqH-10 after UqH-derivatives administration reached Cmax at 2–3 h and after Uq-10 administration, it remained low. The AUC0-24h of UqH-10 after UqH-derivatives administration was 2–3-fold higher than that after Uq-10 administration. In postprandial rats, the Tmax of UqH-10 after UqH-derivatives administration was an hour earlier than after Uq-10 administration. In conclusion, cationic UqH-derivatives are convenient prodrugs that enhance UqH-10 bioavailability by forming nanosized mixed-micelles with intestinal bile acids

Antitumor Effects and Delivery Profiles of Menahydroquinone-4 Prodrugs with Ionic or Nonionic Promoiety to Hepatocellular Carcinoma Cells

Hepatocellular carcinoma (HCC) shows poor prognosis owing to its very frequent recurrence even after curative treatment. Thus, an effective and safe long-term chemopreventive agent is strongly in demand. Menahydroquinone-4 (MKH) is an active form of menaquinone-4 (MK-4, vitamin K2) that is involved in the synthesis of vitamin K-dependent proteins in the liver. We hypothesized that efficient delivery of MKH might be critical to regulate HCC proliferation. The discovery of a suitable prodrug targeting HCC in terms of delivery and activation could reduce the clinical dose of MK-4 and maximize efficacy and safety. We previously showed that MKH dimethylglycinate (MKH-DMG) enables effective delivery of MKH into HCC cells and exhibits strong antitumor effects compared with MK-4. In this study, we prepared anionic MKH hemi-succinate (MKH-SUC) and non-ionic MKH acetate (MKH-ACT), in addition to cationic MKH-DMG, and evaluated MKH delivery profiles and antitumor effects in vitro. MKH-SUC showed the highest uptake and the most efficient release of MKH among the examined compounds and exhibited rapid and strong antitumor effects. These results indicate that MKH-SUC might have a good potential as an MKH delivery system for HCC that overcomes the limitations of MK-4 as a clinical chemopreventive agent

Fe i Lines in 0.91–1.33 μm Spectra of Red Giants for Measuring the Microturbulence and Metallicities

For a detailed analysis of stellar chemical abundances, high-resolution spectra in the optical have mainly been used, while the development of near-infrared (NIR) spectrograph has opened new wavelength windows. Red giants have a large number of resolved absorption lines in both the optical and NIR wavelengths, but the characteristics of the lines in different wave passbands are not necessarily the same. We present a selection of Fe I lines in the z′, Y, and J bands (0.91–1.33 μm). On the basis of two different lists of lines in this range, the Vienna Atomic Line Database (VALD) and the catalog published by Meléndez & Barbuy in 1999 (MB99), we selected sufficiently strong lines that are not severely blended and compiled lists with 107 Fe I lines in total (97 and 75 lines from VALD and MB99, respectively). Combining our lists with high-resolution (λ/Δλ=28,000) and high signal-tonoise (>500) spectra taken with an NIR spectrograph, WINERED, we present measurements of the iron abundances of two prototype red giants: Arcturus and μLeo. A bootstrap method for determining the microturbulence and abundance together with their errors is demonstrated. The standard deviations of log Fe values from individual Fe I lines are significantly smaller when we use the lines from MB99 instead of those from VALD. With the MB99 list, we obtained x = 1.20 0.11 km s-1 and log Fe = 7.01 0.05 dex for Arcturus, and x = 1.54 0.17 km s-1 and log Fe = 7.73 0.07 dex for μLeo. These final values show better agreements with previous values in the literature than the corresponding values we obtained with VALD