Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan最新文献

As the role of pharmacists expands from product-focused to patient-focused care, the development of pharmacist scientists with a balanced clinical and research mindset is expected in Pharmaceutical education. The 2022 revision of the Model Core Curriculum for Pharmacy Education emphasizes scientific inquiry as a fundamental competency for pharmacists. Although graduation research is crucial in promoting this exploration, the current approach to the 6-year pharmacy education program that began in 2006 needs to be re-evaluated. We surveyed undergraduate pharmacy students and practicing pharmacists to investigate their perspectives on graduation research. Those who value the cognitive and methodological skills gained through research have a positive view, whereas those who judge it based on its direct applicability to practice are more critical. The 2022 revision of the Model Core Curriculum for Pharmacy Education aims to develop the ability to identify and solve unknown problems through scientific thinking and appropriate research activities from a pharmaceutical perspective. Graduation research is the only opportunity in undergraduate education for students to experience the full research process-formulating clinical questions into research questions, planning studies, collecting and analyzing data, examining results, and presenting findings-thereby cultivating logical thinking skills and an understanding of research ethics. Universities are responsible for training pharmacists in the research capabilities needed to contribute to future healthcare. Hence, this issue requires collective consideration with clinical pharmacists. It is expected that all stakeholders will share a common understanding that the goal of graduation research is to cultivate a research mindset that pharmacists should naturally possess.

Bio-related nanoparticles are key players in intercellular communication and represent the ultimate goal of nanotechnology as material-transport systems. Biological membranes support the functionality of bio-related nanoparticles; therefore, understanding the correlation between membrane molecular characteristics and the functions of bioparticles is essential. In this study, we developed foundational technologies for measuring the biological membranes of bioparticles by integrating fields such as separation science, materials chemistry, and omics. Furthermore, we developed a new methodology for incorporating the functions of natural bioparticles into artificial nanomaterials.

LM1010, a high-performance liquid chromatography system for therapeutic drug monitoring (TDM) of various agents in clinical practice, is currently approved in Japan. Unlike conventional systems, LM1010 can rapidly measure clinical samples, and data analysis is based on the absolute calibration curve method and fully automated. However, the analytical performance of the LM1010 for the measurement of serum concentrations of linezolid (LZD) has not yet been evaluated. In this study, we aimed to evaluate the analytical performance of LM1010 and confirm the long-term stability of LZD at -30°C. One hundred forty-eight serum samples were collected from 25 patients (17 men and 8 women) who received LZD. Serum concentrations of LZD were measured using LM1010 and liquid chromatography-tandem mass spectrometry (LC-MS/MS). Three LM1010 instruments were used to confirm the differences in the measured values. A Passing-Bablok regression analysis demonstrated a strong correlation between LM1010 and LC-MS/MS (r=0.991), and comparable results were observed among the three LM1010 instruments (r=0.982-0.998). Bland-Altman analyses revealed that the average difference between LM1010 and LC-MS/MS methods was 1.7%, and similar results were observed among the three LM1010 instruments. The long-term stability of serum LZD in samples stored at -30°C for 48 weeks was also confirmed. These results suggest that LM1010 can be used for TDM of LZD in clinical practice.

Synaptic plasticity is a key mechanism underlying long-term memory and learning, with proposed associations with altered actin cytoskeleton and gene expression in neurons. Myocardin-related transcription factor (MRTF) family members, abundantly expressed in the brain, have actin-binding motifs at the N-terminus and act as cofactors of serum response factor (SRF). Rho signaling may promote MRTF's release from G-actin and subsequent translocation into the nucleus, and increases SRF-dependent gene expression. MRTF is therefore thought to act as a link between morphological change and gene expression in neurons. In this review, we focus on the neurotrophin, brain-derived neurotrophic factor (BDNF). BDNF plays crucial roles in neuronal survival, gene expression, and dendritic growth, which are essential for neuronal plasticity. As previous studies suggest that BDNF triggers the activation of MRTF/SRF-mediated signal transduction, we have studied how this supposed regulatory ligand is involved in the functional MRTF changes in neurons. We review the BDNF-mediated roles of MRTF in neuronal morphology and gene expression and briefly discuss the possible involvement of MRTF in neurodevelopmental disorders, such as autism spectrum disorder and intellectual disability.

Nitriles are important organic compounds that are frequently found in pharmaceuticals, natural products, agrichemicals, and functional materials. In addition, nitriles serve as versatile building blocks in synthetic chemistry, as the nitrile moiety can be readily transformed into a variety of valuable functional groups, such as carbonyl derivatives, amines, and heterocycles. However, conventional methods for nitrile synthesis often rely on highly toxic metal cyanides, such as copper(I) cyanide (CuCN) and potassium cyanide (KCN). In this review, I introduce our recent works on a cyanide- and transition metal-free approach for the synthesis of (hetero)aromatic and aliphatic nitriles from N-acyl (2-nitrophenyl)sulfonamides via a base-promoted desulfonylative Smiles rearrangement. The reactions proceeded under operationally simple conditions using potassium acetate as a base and 1,3-dimethyl-2-imidazolidinone as a solvent. This method enables the efficient preparation of a wide range of nitriles, including those bearing primary, secondary, and tertiary carbon centers, with broad functional group compatibility and in good to excellent yields.

Although the primary effects of most drugs have been well verified, their secondary effects remain less understood. Therefore, concomitant medications used to prevent side effects may attenuate the efficacy of the primary therapeutic agent. In this study, we investigated whether concomitant medications that maximize therapeutic efficacy can be used to reduce the effectiveness of the main therapeutic agent. In particular, we focused on anti-vascular endothelial growth factor (anti-VEGF) drugs, which are essential for cancer treatment. We demonstrated that the therapeutic outcome of anti-VEGF drugs can be changed by the concomitant use of gastric acid secretion inhibitors and identified a potential involvement of estrogen receptors in the mechanism underlying this interaction. Therefore, we are examining the mechanism in detail and conducting further studies, including the exploration of drugs that may exert stimulatory or inhibitory effects on estrogen receptors as a secondary action, through omics data analysis. This approach can be applied to a wide variety of drugs and is expected to improve therapeutic outcomes of various drug treatments.

Bioactive molecules are mostly chiral, and their enantiomers often exhibit different biological properties, including pharmacological effects and toxicity. Recent biochemical studies have revealed that certain trace-level chiral metabolites are associated with specific pathological conditions, including chronic kidney disease and metabolic disorders. This finding highlights the importance of enantioselective imaging techniques that can help visualize the spatial distribution and dynamic behavior of individual enantiomers. Although enantioselective biochemical analyses, such as those based on chromatography or electrophoresis, have proven effective in separating enantiomers, progress in enantioselective imaging methods has been limited. Ion mobility spectrometry/mass spectrometry imaging (IMS/MSI) has emerged as a powerful tool with the potential to enable the enantioselective imaging of minor chiral metabolites. However, suitable chemical structures that can achieve both sufficient resolving power for the target enantiomer in IMS and high ionization efficiency in MSI remain unclear. This review highlights the development of enantioselective imaging methods based on on-tissue chiral derivatization and IMS/MSI. After exploring suitable chiral derivatization reagents, we designed a new charged chiral tag that enabled complete separation of a pair of enantiomers by IMS, sensitive detection of D,L-2-hydroxyglutaric acid by mass spectrometry, and the visualization of their distribution in the mouse testis by IMS/MSI. This approach can be further expanded to analyze other chiral molecules and has great potential for unveiling the enantioselective distribution and dynamics of minor chiral metabolites in biological tissues.

Food-derived components with physiological effects have been attracting attention in recent years, and studies have comprehensively analyzed these components. In this study, we sought to identify food components with functional properties for the prevention and improvement of metabolic syndrome. We performed a luciferase reporter assay using fatty acid synthase (FAS) and low-density lipoprotein receptor (LDL) receptor gene promoters. Naturally occurring isothiocyanate sulforaphane impaired FAS promoter activity and reduced sterol regulatory element-binding protein (SREBP) target gene expression in human hepatoma Huh-7 cells. Sulforaphane reduced SREBP proteins by promoting the degradation of the SREBP precursor. Furthermore, we screened LDL receptor promoter effectors and observed that extract from sweet cherry peduncles induces LDL receptor gene promoter activity. Several analytical and chemical methods revealed that chrysin 7O-β-D-glucopyranoside in cherry peduncle extract stimulated LDL receptor gene promoter activity. Thus, this comprehensive search for components that alter the expression of genes associated with lipid metabolism led to the discovery of new functions of food components.