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Hypoxia-inducible factor (HIF) activators aid the treatment of renal anemia and ischemia. Recently, PyrzA (5-(1-acetyl-5-phenylpyrazolidin-3-ylidene)-1,3-dimethylbarbituric acid), a HIF activator by PHD inhibition without a 2-oxoglutarate moiety was reported. However, PyrzA has low lipophilicity, and it was necessary to improve its solubility by synthesizing derivatives. In this study, we synthesized and evaluated a higher lipophilic derivative of PyrzA and found that it exhibited higher HIF activity and stabilizing ability at low concentrations compared to Roxadustat, a commercially available HIF activator., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: S.U. is a chief operation officer, and S-i.K. and T.T. are advisory members for Tetra Create Co., Ltd. All other authors declare no conflicts of interest. Compounds 1a and 9c are available from Tetra Create Co., Ltd., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Hypoxia-inducible factor-α (HIF-α) activation has shown promising results in the treatment of ischemia, such as stroke, myocardial infarction, and chronic kidney disease. A number of HIF-α activators have been developed to improve the symptoms of these diseases. Many feature 2-oxoglutarate (2-OG) scaffolds that interact with the active centers of prolyl hydroxylase domain-containing proteins (PHDs), displacing the coenzyme 2-OG. This stabilizes HIF-α. Therefore, the specificity of the 2-OG analogs is not high. Here, we identified 5-(1-acetyl-5-phenylpyrazolidin-3-ylidene)-1,3-dimethylbarbituric acid (PyrzA) among over 10 000 compounds as a novel HIF activator that does not contain a 2-OG scaffold. In cultured cells, PyrzA enhanced HIF-α stability and upregulated the expression of HIF target genes. Interestingly, PyrzA decreased HIF-1α prolyl hydroxylation, suggesting that PyrzA may activate HIF to prevent the degradation of HIF-α. These results indicate that PyrzA stabilizes HIF via a novel mechanism and could be a potential HIF activator candidate., Competing Interests: The authors declare the following competing financial interest(s): S-i.K. and T.T. are advisory members for Tetra Create Co., Ltd. All other authors declare no conflicts of interest., (© 2022 American Chemical Society.)

In Japan, humanoid robots has been introduced in the medical and elderly care environment. The application program of Care Prevention Gymnastics Exercises for Pepper (Pepper-CPGE) made by Xing Company, Japan is a body-brain gymnastics recreation program for 40 minutes tailored to the elderly's functional level. It consists of moving, watching/healing, and playing. "Move the body" exercise and other active range of motion activities are done according to the music. Pepper-CPGE was introduced as a clinical trial at the Mifune hospital, beginning in May 2018. At the units where clinical trials are done, 80% of the patients are with mental illness diagnosis with decreased physical functions often moving by wheelchair only. When Pepper-CPGE was introduced, the following changes were observed : (1) communication between patients and nurses during rehabilitation care using Pepper-CPGE was increased ; (2) patients wereinteractive, engaged, and actively participated in the Care Prevention Gymnastic Exercises using Pepper-CPGE ; (3) patients had fun and enjoyed talking to Pepper-CPGE. Interventions using Pepper-CPGE appear to be an effective rehabilitation strategy to increase engagement and participation of elderly patients who require long-term care and rehabilitation. J. Med. Invest. 66 : 50-53, February, 2019.

Bacterial strains were isolated from samples of Japanese rice vinegar (komesu) and unpolished rice vinegar (kurosu) fermented by the traditional static method. Fermentations have never been inoculated with a pure culture since they were started in 1907. A total of 178 isolates were divided into groups A and B on the basis of enterobacterial repetitive intergenic consensus-PCR and random amplified polymorphic DNA fingerprinting analyses. The 16S ribosomal DNA sequences of strains belonging to each group showed similarities of more than 99% with Acetobacter pasteurianus. Group A strains overwhelmingly dominated all stages of fermentation of both types of vinegar. Our results indicate that appropriate strains of acetic acid bacteria have spontaneously established almost pure cultures during nearly a century of komesu and kurosu fermentation.

An open reading frame with a sequence homologous to Escherichia coli Na+/H+ antiporter A (ENhaA) was found in the total genomic sequence of Helicobacter pylori, a pathogenic bacterium of gastric inflammation, and was named HNhaA. The primary sequences and the hydropathy profiles of ENhaA and HNhaA were very homologous except for one additional region found in HNhaA. This sequence has about 40 hydrophilic amino acid residues inserted at the position next to residue 235 of ENhaA which corresponds to residue 245 of HNhaA. HNhaA was expressed in E. coli mutants deficient in Na+/H+ antiporters and complemented the salt-sensitive phenotype of the mutants. Membrane vesicles prepared from these transformants of HNhaA using mutants deficient in the antiporters had the antiporter activities. Surprisingly, the antiporter activity in the transformant membranes was high at acidic and neutral pH, while ENhaA did not function at these pHs. A hydrophilic region around residue 235 in ENhaA and the additional hydrophilic region of about 40 residues in the same region found in HNhaA might be responsible for this difference in activity by acting as putative pH sensors.