Reactive oxygen species-mediated cytotoxic and DNA-damaging mechanism of -hydroxycytidine, a metabolite of the COVID-19 therapeutic drug molnupiravir.

Molnupiravir is a prodrug of the antiviral ribonucleoside analogue -hydroxycytidine (NHC), for use in the treatment of coronavirus disease 2019 (COVID-19). However, it is generally considered that NHC-triphosphate is incorporated into the host genome to induce mutations. In our previous preliminary report, we proposed oxidative DNA damage by NHC cytidine deaminase (CDA)-mediated ROS formation.

Immunohistochemical analyses reveal FoxP3 expressions in spleen and colorectal cancer in mice treated with AOM/DSS, and their suppression by glycyrrhizin.

We previously demonstrated that glycyrrhizin (GL) suppressed inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer (CC). In this study, we found an accumulation of regulatory T cells (Tregs) in the spleen and suppression by GL in model mice. ICR mice were divided into four groups: Control, GL, CC, and GL-treated CC (CC+GL), and were sacrificed 20 weeks after AOM/DSS treatment.

Oxidative DNA damage: Induction by fructose, in vitro, and its enhancement by hydrogen peroxide.

Sucrose and high-fructose corn syrup comprise nearly equal amounts of glucose and fructose. With the use of high-fructose corn syrup in the food industry, consumption of fructose, which may be a tumor promoter, has increased dramatically. We examined fructose-induced oxidative DNA damage in the presence of Cu(II), with or without the addition of HO.

Myricetin causes site-specific DNA damage via reactive oxygen species generation by redox interactions with copper ions.

Myricetin (MYR), found in tea and berries, may have preventive effects on diseases, including Alzheimer's disease and cancer. However, MYR is also a mutagen, inducing DNA damage in the presence of metal ions. We have studied the molecular mechanisms of DNA damage by MYR in the presence of Cu(II) (MYR+Cu).

Insights into the clinical development of regenerative medical products through a comparison of three cell-based products recently approved for limbal stem cell deficiency.

Three regenerative medical products for limbal stem cell deficiency (LSCD), a rare and intractable ocular surface disease, have recently been approved in Japan. To our knowledge, this is the first time multiple stem-cell-based medical products have been approved for the same ocular disease. Development plans and study designs for each product differ, resulting in differences in indications.

A blue-shifted anion channelrhodopsin from the Colpodellida alga Vitrella brassicaformis.

Microbial rhodopsins, a family of photoreceptive membrane proteins containing the chromophore retinal, show a variety of light-dependent molecular functions. Channelrhodopsins work as light-gated ion channels and are widely utilized for optogenetics, which is a method for controlling neural activities by light. Since two cation channelrhodopsins were identified from the chlorophyte alga Chlamydomonas reinhardtii, recent advances in genomic research have revealed a wide variety of channelrhodopsins including anion channelrhodopsins (ACRs), describing their highly diversified molecular properties (e.

Detection of Membrane Potential-Dependent Rhodopsin Fluorescence Using Low-Intensity Light Emitting Diode for Long-Term Imaging.

Microbial rhodopsin is a family of photoreceptive membrane proteins that commonly consist of a seven-transmembrane domain and a derivative of vitamin-A, retinal, as a chromophore. In 2011, archaeorhodopsin-3 (AR3) was shown to exhibit voltage-dependent fluorescence changes in mammalian cells. Since then, AR3 and its variants have been used as genetically encoded voltage indicators, in which mostly intense laser stimulation (1-1000 W/cm) is used for the detection of dim fluorescence of rhodopsin, leading to high spatiotemporal resolution.

Oxidative DNA Damage by N4-hydroxycytidine, a Metabolite of the SARS-CoV-2 Antiviral Molnupiravir.

Molnupiravir is an antiviral agent recently used for treating coronavirus disease 2019 (COVID-19). Here, we demonstrate that N4-hydroxycytidine (NHC), a molnupiravir metabolite, treated with cytidine deaminase (CDA) induced Cu(II)-mediated oxidative DNA damage in isolated DNA. A colorimetric assay revealed hydroxylamine generation from CDA-treated NHC.

Targeting fructose metabolism by glucose transporter 5 regulation in human cholangiocarcinoma.

Alterations in cellular metabolism may contribute to tumor proliferation and survival. Upregulation of the facilitative glucose transporter (GLUT) plays a key role in promoting cancer. GLUT5 mediates modulation of fructose utilization, and its overexpression has been associated with poor prognosis in several cancers.

Enantiodivergent Chemoenzymatic Dynamic Kinetic Resolution: Conversion of Racemic Propargyl Alcohols into Both Enantiomers.

Natural lipases typically recognize enantiomers of alcohols based on the size differences of substituents near the carbinol moiety and selectively react with the R enantiomers of secondary alcohols. Therefore, lipase-catalyzed dynamic kinetic resolution (DKR) of racemic secondary alcohols produces only R enantiomers. We report herein a method for obtaining S enantiomers by DKR of secondary 3-(trialkylsilyl)propargyl alcohols by using a well-known R-selective Pseudomonas fluorescens lipase in combination with a racemization catalyst VMPS4, in which the silyl group reverses the size relationship of substituents near the carbinol moiety.

Contribution of Dislocations in SiC Seed Crystals on the Melt-Back Process in SiC Solution Growth.

The melt-back process has a significant effect on the quality of solution-grown SiC crystals. However, the phenomena surrounding the SiC dissolution into the molten alloy during the melt-back process have not been clarified. In this study, the behavior of 4H-SiC dissolution into molten alloy was investigated by using high-temperature in situ observation and subsequent KOH etching, and the effects of different doping conditions and crystal polarity were studied.

Dissipative Kerr soliton microcombs for FEC-free optical communications over 100 channels.

The demand for high-speed and highly efficient optical communication techniques has been rapidly growing due to the ever-increasing volume of data traffic. As well as the digital coherent communication used for core and metro networks, intensity modulation and direct detection (IM-DD) are still promising schemes in intra/inter data centers thanks to their low latency, high reliability, and good cost performance. In this work, we study a microresonator-based frequency comb as a potential light source for future IM-DD optical systems where applications may include replacing individual stabilized lasers with a continuous laser driven microresonator.

Mechanism of reactive oxygen species generation and oxidative DNA damage induced by acrylohydroxamic acid, a putative metabolite of acrylamide.

Acrylamide is formed during the heating of food and is also found in cigarette smoke. It is classified by the International Agency for Research on Cancer as a probable human carcinogen (Group 2A). Glycidamide, an epoxide metabolite of acrylamide, is implicated in the mechanism of acrylamide carcinogenicity.

Glycyrrhizin and its derivatives promote hepatic differentiation via sweet receptor, Wnt, and Notch signaling.

The acute liver disease is involved in aberrant release of high-mobility group box 1 (HMGB1). Glycyrrhizin (GL), a traditional Chinese medicine for liver disease, binds to HMGB1, thereby inhibits tissue injury. However the mode of action of GL for chronic liver disease remains unclear.

Proton transfer pathway in anion channelrhodopsin-1.

Anion channelrhodopsin from (ACR1) has Asp234 (3.2 Å) and Glu68 (5.3 Å) near the protonated Schiff base.

Direct evaluation of hole effective mass of SnS-SnSe solid solutions with ARPES measurement.

Valence band dispersions of single-crystalline SnSSe solid solutions were observed by angle-resolved photoemission spectroscopy (ARPES). The hole effective masses, crucial factors in determining thermoelectric properties, were directly evaluated. They decrease slightly with increasing Se content in the low Se composition range but sharply in the high Se composition range.

Chemoprevention by aspirin against inflammation-related colorectal cancer in mice.

Inflammation is a primary risk factor for cancer. Epidemiological studies previously demonstrated that aspirin decreased the incidence of cancer and specifically reduced the risk of colorectal cancer. However, the number of animal studies that have confirmed the efficacy of aspirin remains limited.

Glycyrrhizin ameliorates melanoma cell extravasation into mouse lungs by regulating signal transduction through HMGB1 and its receptors.

Metastasis, which accounts for the majority of all cancer-related deaths, occurs through several steps, namely, local invasion, intravasation, transport, extravasation, and colonization. Glycyrrhizin has been reported to inhibit pulmonary metastasis in mice inoculated with B16 melanoma. This study aimed to identify the mechanism through which glycyrrhizin ameliorates the extravasation of melanoma cells into mouse lungs.

Functional expression of the eukaryotic proton pump rhodopsin OmR2 in Escherichia coli and its photochemical characterization.

Microbial rhodopsins are photoswitchable seven-transmembrane proteins that are widely distributed in three domains of life, archaea, bacteria and eukarya. Rhodopsins allow the transport of protons outwardly across the membrane and are indispensable for light-energy conversion in microorganisms. Archaeal and bacterial proton pump rhodopsins have been characterized using an Escherichia coli expression system because that enables the rapid production of large amounts of recombinant proteins, whereas no success has been reported for eukaryotic rhodopsins.

Glycyrrhizin Attenuates Carcinogenesis by Inhibiting the Inflammatory Response in a Murine Model of Colorectal Cancer.

Glycyrrhizin (GL), an important active ingredient of licorice root, which weakens the proinflammatory effects of high-mobility group box 1 (HMGB1) by blocking HMGB1 signaling. In this study, we investigated whether GL could suppress inflammation and carcinogenesis in an azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced murine model of colorectal cancer. ICR mice were divided into four groups ( = 5, each)-control group, GL group, colon cancer (CC) group, and GL-treated CC (CC + GL) group, and sacrificed after 20 weeks.

Nitrative DNA damage in lung epithelial cells exposed to indium nanoparticles and indium ions.

Indium compounds have been widely used in manufacturing displays of mobile phones, computers and televisions. However, inhalation exposure to indium compounds causes interstitial pneumonia in exposed workers and lung cancer in experimental animals. 8-Nitroguanine (8-nitroG) is a mutagenic DNA lesion formed under inflammatory conditions and may participate in indium-induced carcinogenesis.

CD44v9 Induces Stem Cell-Like Phenotypes in Human Cholangiocarcinoma.

Our previous study demonstrated an overexpression of CD44 variant 9 (CD44v9) in human cholangiocarcinoma (CCA) tissues that was associated with inflammation-related tumor development. However, the participation of CD44v9 in cholangiocarcinogenesis remains poorly understood. Therefore, in this study, we examined the potential roles of CD44v9 in CCA cells to understand the carcinogenic mechanism.