Pharmacologic characterization of TBP1901, a prodrug form of aglycone curcumin, and CRISPR-Cas9 screen for therapeutic targets of aglycone curcumin

プロドラッグ型クルクミン注射製剤の抗腫瘍効果及び治療標的の包括的な解析 --安全性の高い抗がん薬としての開発に期待--. 京都大学プレスリリース. 2022-10-21.Curcumin (aglycone curcumin) has antitumor properties in a variety of malignancies via the alteration of multiple cancer-related biological pathways; however, its clinical application has been hampered due to its poor bioavailability. To overcome this limitation, we have developed a synthesized curcumin β-D-glucuronide sodium salt (TBP1901), a prodrug form of aglycone curcumin. In this study, we aimed to clarify the pharmacologic characteristics of TBP1901. In β-glucuronidase (GUSB)-proficient mice, both curcumin β-D-glucuronide and its active metabolite, aglycone curcumin, were detected in the blood after TBP1901 injection, whereas only curcumin β-D-glucuronide was detected in GUSB-impaired mice, suggesting that GUSB plays a pivotal role in the conversion of TBP1901 into aglycone curcumin in vivo. TBP1901 itself had minimal antitumor effects in vitro, whereas it demonstrated significant antitumor effects in vivo. Genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 screen disclosed the genes associated with NF-κB signaling pathway and mitochondria were among the highest hit. In vitro, aglycone curcumin inhibited NF-kappa B signaling pathways whereas it caused production of reactive oxygen species (ROS). ROS scavenger, N-acetyl-L-cysteine, partially reversed antitumor effects of aglycone curcumin. In summary, TBP1901 can exert antitumor effects as a prodrug of aglycone curcumin through GUSB-dependent activation

Recent global movement on mental health

The Mental Health Gap Action Programme (mhGAP) proposed by the World Health Organization (WHO) is a planned action that aims at providing uniform medical care, especially mental health care and services, to all people worldwide, regardless of economic status. Because not only the levels of medical care, but also the political and economic situations vary among countries, it is extremely difficult for a plan to be successfully implemented in every country with standardized methodology, even if the directionality is ethically correct and ideal. Against this background, authorized personnel provide mental health care activities across the globe, and they report on activities and promote mutual understanding at the WHO mhGAP Forum, an informal meeting convened yearly in Geneva. The 5th mhGAP meeting was attended by 48 member states and 58 partner organizations. From Japan, 5 professionals attended the meeting and presented different viewpoints. Among various policies proposed at the Forum, one in particular about training and recruiting health professionals for low-income countries has gained a special consensus. In addition, the importance of training medical professionals who are not specialized in psychiatry and the importance of developing educational programs for educators were emphasized. It is important for Japan to proactively participate in mhGAP to contribute to global mental health initiative

Interfacial Waves in a Horizomtal Channel (Behavior of a Solitary Wave on Flowing Liquid)

Experiments and numerical calculations were carried out on the dynamic behavior of the solitary wave of a flowing liquid. Data on the wave propagation velocity, the wave profile, and the liquid velocity profile were presented. Results of the numerical calculations agreed with the experimental results in respect of the above-mentioned qualities which characterize the solitary wave. Thus, the applicability of this numerical calculation method was verified. Based on the experimental results and the numerical calculations, simple correlation equations, which express the relationships between the solitary waves of the stationary liquid and of the stratified liquid flow were deduced. The applicability of Benjamin’s theory on the solitary wave of a flowing liquid was also verified

Two-Phase Pressure Drop in a Tube with Large Deformation by Transmural Pressure

The purpose of this report is to discuss pressure drop characteristics in a flexible and/ or collapsible tube where the flow area and the shape change depending on a transmural pressure across the tube wall. Single-and two-phase pressure drop and void fraction were measured in a vertical tube under various external pressure conditions. The results of numerical simulation agreed with the experimental results

Chemistry of layered d-metal pnictide oxides and their potential as candidates for new superconductors

Layered d-metal pnictide oxides are a unique class of compounds which consists of characteristic d-metal pnictide layers and metal oxide layers. More than 100 of these layered compounds, including the recently discovered Fe-based superconducting pnictide oxides, can be classified into 9 structure types. These structure types and the chemical and physical properties of the characteristic d-metal pnictide layers and metal oxide layers of the layered d-metal pnictide oxides are reviewed and discussed. Furthermore, possible approaches to design new superconductors based on these layered d-metal pnictide oxides are proposed.Comment: 29 pages including 6 tables and 2 figure

Impact Force by Transient Liquid Slug Flowing Out of Horizontal Pipes （1st Report, Experimental Study）

An impact force of a transient liquid slug was measured in air-water horizontal two-phase Flow system. The time response of the impact force was characterized by the initial impact force, maximum force, acting period of force and mean effective force which were discussed with reference to the volumetric liquid and gas fluxes and also to the Flow characteristics of the transient slug Flow in horizontal pipes