Long-Range Halogen Dance Reaction in 4,5-Dihalogeno-2-(Sulfur-Containing Heterocyclyl)thiazole.

We have investigated the base-induced long-range halogen dance reactions of 4,5-dibromo- or 4-bromo-5-iodothiazoles bearing sulfur-containing aromatic heterocycles at the C2-position. We have found that the reaction occurs in bithiazole regioisomers or (thiophenyl)thiazole derivatives, in which the C-5 halo group on the thiazole halogen donor regioselectively migrates to a halogen acceptor ring after treatment with lithium bis(trimethylsilyl)amide. The substrate with a thiophen-2-yl substituent required highly basic P4-t-Bu to induce the halogen dance reaction.

USP2 Mitigates Reactive Oxygen Species-Induced Mitochondrial Damage via UCP2 Expression in Myoblasts.

Ubiquitin-specific protease 2 (USP2) maintains mitochondrial integrity in culture myoblasts. In this study, we investigated the molecular mechanisms underlying the protective role of USP2 in mitochondria. The knockout (KO) of the gene or the chemical inhibition of USP2 induced a robust accumulation of mitochondrial reactive oxygen species (ROS), accompanied by defects in mitochondrial membrane potential, in C2C12 myoblasts.

Sublingual immune cell clusters and dendritic cell distribution in the oral cavity.

The oral mucosa is the first line of defense against pathogenic bacteria and plays a vital role in maintaining tolerance to food antigens and commensal bacteria. We used CD11c reporter mice to visualize dendritic cells (DCs), a key immune cell population, in the oral cavity. We identified differences in DC density in each oral tissue region.

Developing Method for Minor Acidic -Glycan Analysis in Mucin and Cancer Cell Samples.

Minor acidic glycans, such as sulfated and phosphorylated glycans, constitute only a small fraction of biological glycome, making their analysis a considerable challenge. In this study, we developed a technique to analyze minor acidic -glycans in biological samples. First, efficient reaction conditions for the release of -glycans from the proteins were determined.

Questionnaire on the Current Status and Awareness of Palliative Medicine by Community Cooperation Pharmacies.

Community cooperation pharmacies are equipped to prepare narcotics and sterile injectable drugs for palliative medicine at home for cancer pain and end-of-life care; however, to the best of our knowledge, the actual status of the system to provide palliative medicine at home has not yet been examined. Therefore, in this study, given that home palliative medicine is one of the accreditation criteria for community cooperation pharmacies, a questionnaire survey was conducted among managing pharmacists engaged in community cooperation pharmacies to investigate the actual status of the system to provide appropriate services, mainly pain management, to patients who need home palliative medicine. An analysis of responses to the questionnaire showed that pharmacists working in community cooperation pharmacies had a high level of understanding of the proper use of rescue doses of medical narcotics and patient guidance.

IL-4 acts on skin-derived dendritic cells to promote the T2 response to cutaneous sensitization and the development of allergic skin inflammation.

Background: Atopic dermatitis is characterized by scratching and a T2-dominated local and systemic response to cutaneously encountered antigens. Dendritic cells (DCs) capture antigens in the skin and rapidly migrate to draining lymph nodes (dLNs) where they drive the differentiation of antigen-specific naive T cells.

Objective: We sought to determine whether non-T-cell-derived IL-4 acts on skin-derived DCs to promote the T2 response to cutaneously encountered antigen and allergic skin inflammation.

Structure-activity relationship studies of pyrogallol as a calcineurin/NFAT signaling suppressor.

Previously, we have shown that pyrogallol alleviated nasal symptoms and suppressed IL-9 gene up-regulation in allergy model rats by inhibiting calcineurin/NFAT signaling. As pyrogallol has antioxidative activity, it may be responsible for inhibiting calcineurin/NFAT signaling-mediated IL-9 gene expression. However, the relationship between antioxidative activity and suppression of IL-9 gene expression has not been elucidated yet.

16S rRNA amplicon sequencing of intestinal microbiota in Eurasian Wigeon around Osaka, Japan.

We report 16S rRNA gene amplicon data on the succession of intestinal microbiomes in migratory bird, Eurasian Wigeon (Mareca Penelope) wintering around Osaka, Japan. This study could serve as baseline data for comparison with microbiomes in migratory birds.

Viscosity-Induced Emission of 5-(Diarylmethylene)imidazolone with Extended Conjugation via Attachment of N-Methylpyrrole at the 2-Position.

We have developed a series of 2-monoaryl-5-diarylmethylene analogs of the green fluorescent protein chromophore to study their viscosity-induced emission (VIE) properties. The analogs were synthesized by a condensation with methyl imidate and N-(diarylmethylene)glycinate. Among the analogs, the N-methylpyrrol-2-yl-substituted analog 1h induced the most remarkable VIE behavior in triglyceride and lipid bilayers probably due to the high π-electron-rich property of the pyrrole ring.

Fluorescence tracking demonstrates T cell recirculation is transiently impaired by radiation therapy to the tumor.

T cells recirculate through tissues and lymphatic organs to scan for their cognate antigen. Radiation therapy provides site-specific cytotoxicity to kill cancer cells but also has the potential to eliminate the tumor-specific T cells in field. To dynamically study the effect of radiation on CD8 T cell recirculation, we used the Kaede mouse model to photoconvert tumor-infiltrating cells and monitor their movement out of the field of radiation.

CD4 T cell heterogeneity in gestational age and preeclampsia using single-cell RNA sequencing.

A balance between pro-inflammatory decidual CD4 T cells and regulatory T cells ( Tregs) is important for maintaining fetomaternal tolerance. Using single-cell RNA-sequencing and T cell receptor repertoire analysis, we determined that diversity and clonality of decidual CD4 T cell subsets depend on gestational age. Th1/Th2 intermediate and Th1 subsets of CD4 T cells were clonally expanded in both early and late gestation, whereas Tregs were clonally expanded in late gestation.

Development of an Improved Adenovirus Vector and Its Application to the Treatment of Lifestyle-Related Diseases.

The number of patients with lifestyle-related diseases such as type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), has continued to increase worldwide. Therefore, development of innovative therapeutic methods targeting lifestyle-related diseases is required. Gene therapy has attracted considerable attention as an advanced medical treatment.

Anxiety and its risk factors among non-Japanese residents living in Japan undergoing COVID-19 situation: A cross-sectional survey.

Introduction: In the context of collective efforts taken in Japan to control the spread of COVID-19, the state of emergency and social distancing have caused a negative impact on the mental health of all residents, including foreign communities in Japan. This study aimed to evaluate the level of anxiety and its associated factors among non-Japanese residents residing in Japan during the COVID-19 pandemic.

Methods: A web-based survey in 13 languages was conducted among non-Japanese residents living in Japan during the COVID-19 situation.

Neuroinflammation following anti-parkinsonian drugs in early Parkinson's disease: a longitudinal PET study.

The progression of neuroinflammation after anti-parkinsonian therapy on the Parkinson's disease (PD) brain and in vivo evidence of the therapy purporting neuroprotection remain unclear. To elucidate this, we examined changes in microglial activation, nigrostriatal degeneration, and clinical symptoms longitudinally after dopamine replacement therapy in early, optimally-controlled PD patients with and without zonisamide treatment using positron emission tomography (PET). We enrolled sixteen PD patients (Hoehn and Yahr stage 1-2), and age-matched normal subjects.

Substrate-Dependent Alteration in the C- and O-Prenylation Specificities of Cannabis Prenyltransferase.

CsPT4 is an aromatic prenyltransferase that synthesizes cannabigerolic acid (CBGA), the key intermediate of cannabinoid biosynthesis in Cannabis sativa, from olivetolic acid (OA) and geranyl diphosphate (GPP). CsPT4 has a catalytic potential to produce a variety of CBGA analogs via regioselective C-prenylation of aromatic substrates having resorcylic acid skeletons including bibenzyl 2,4-dihydroxy-6-phenylethylbenzoic acid (DPA). In this study, we further investigated the substrate specificity of CsPT4 using phlorocaprophenone (PCP) and 2',4',6'-trihydroxydihydrochalcone (THDC), the isomers of OA and DPA, respectively, and demonstrated that CsPT4 catalyzed both C-prenylation and O-prenylation reactions on PCP and THDC that share acylphloroglucinol substructures.

Liquid Chromatography and Capillary Electrophoresis Analysis of 2AA-Labeled O-Glycans.

To reveal O-glycan structures in mucins, it is necessary to release covalently bound O-glycans from the polypeptide backbone and derivatize to a form suitable for structural analysis. Various derivatization methods can now be applied in the analysis of O-glycans following the development of O-glycan release methods. Among the many derivatization methods available, we prefer to use fluorescent labeling with 2-aminobenzoic acid (anthranilic acid, 2AA).

9-Fluorenylmethyl Chloroformate Labeling for O-Glycan Analysis.

Structural analysis of O-glycans from mucins and characterization of the interaction of these glycans with other biomolecules are essential for a full understanding of mucins. Various techniques have been developed for the structural and functional analysis of glycans. While 9-fluorenylmethyl chloroformate (Fmoc-Cl) is generally used to protect amino groups in peptide synthesis, it can also be used as a glycan-labeling reagent for structural analysis.

Identification of differentially methylated regions associated with both liver fibrosis and hepatocellular carcinoma.

Background: Liver fibrosis is a major risk factor for hepatocellular carcinoma (HCC). We have previously reported that differentially methylated regions (DMRs) are correlated with the fibrosis stages of metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, the methylation levels of those DMRs in liver fibrosis and subsequent HCC were examined.

Overexpression of lysophospholipid acyltransferase, LPLAT10/LPCAT4/LPEAT2, in the mouse liver increases glucose-stimulated insulin secretion.

Postprandial hyperglycemia is an early indicator of impaired glucose tolerance that leads to type 2 diabetes mellitus (T2DM). Alterations in the fatty acid composition of phospholipids have been implicated in diseases such as T2DM and nonalcoholic fatty liver disease. Lysophospholipid acyltransferase 10 (LPLAT10, also called LPCAT4 and LPEAT2) plays a role in remodeling fatty acyl chains of phospholipids; however, its relationship with metabolic diseases has not been fully elucidated.

Synthesis and Biological Evaluation of a Novel Sugar-Conjugated Platinum(II) Complex Having a Tumor-Targeting Effect.

We designed and synthesized a novel platinum complex conjugated with 2-fluorinated 2-deoxyglucoside, named FGC-Pt, to capitalize on the Warburg effect and metabolic trapping properties of [F]2-deoxy-2-fluoro-d-glucose (FFDG). Then, we conducted comprehensive in vitro and in vivo studies to evaluate the effects of FGC-Pt. In vitro cytotoxicity assays using HeLa cells revealed that FGC-Pt exhibited concentration-dependent cytotoxicity, even though its cytotoxic effect was less pronounced than that of cisplatin.

Moesin affects the plasma membrane expression and the immune checkpoint function of CD47 in human ovarian clear cell carcinoma.

Among major histological subtypes of epithelial ovarian cancer, a higher incidence of ovarian clear cell carcinoma (OCCC) is observed in East Asian populations, particularly in Japan. Despite recent progress in the immune checkpoint inhibitors for a wide variety of cancer cell types, patients with OCCC exhibit considerably low response rates to these drugs. Hence, urgent efforts are needed to develop a novel immunotherapeutic approach for OCCC.

Catalytic Potential of Prenyltransferase to Expand Cannabinoid Scaffold Diversity.

Biologically active cannabinoids are derived from cannabigerolic acid (CBGA), which is biosynthesized by aromatic prenyltransferase CsPT4. We exploit the catalytic versatility of CsPT4 to synthesize various CBGA analogues, including a geranylated bibenzyl acid, the precursor to bibenzyl cannabinoids of liverwort origin. The synthesized natural and new-to-nature cannabinoids exhibit potent cytotoxicity in human pancreatic cancer cells.