Fasting period after Rybelsus administration influences clinical benefit

Glucagon-like peptide 1 receptor agonists (GLP-1 RAs) have been attracted attention for various beneficial effects. Among them, oral semaglutide (Rybelsus) was developed using the absorption enhancer sodium N-(8-[2-hydroxybenzoyl] amino) caprylate (SNAC). The relationship between the bioavailability and post-dose fasting time period was analyzed. The results showed that i) its bioavailability with drinking 50mL and 120mL of water together was almost similar, ii) bioavailability for 240mL intake was about 2/3 of 50-120mL, iii) general availability would be about 1.4% for 50-120ml water, and 0.8% for 240mL of water. Tolerability and safety of Rybelsus showed similar results for healthy subjects, patients with renal and/or hepatic impairment. From mentioned above, Rybelsus has been one of the topic agents with characteristic mechanism of SNAC and clinical benefit of GLP-1RA. It will be expected to be applied widely in actual diabetic practice

Effective and convenient treatment of Xultophy with lower doses for elderly diabetic patient

The case is an 82-year-old female patient with Type 2 Diabetes Mellitus (T2DM) for 22 years. She developed right empyema in early January, 2021 and was treated by antibiotics and CT-guided drainage. After improving the status, she was transferred to Hayashi hospital, Tokushima, Japan. Treatment for T2DM was initially multiple daily insulin injection (MDI), but it could not continue because of injection several times a day by the family. Then, Xultophy was started once a day, which brought satisfactory glucose variability with lower doses. Consequently, Xultophy would be effective and useful agent from bio-psycho-social points of view

High variability of expression profiles of homeologous genes for Wnt, Hh, Notch, and Hippo signaling pathways in Xenopus laevis

Cell signaling pathways, such as Wnt, Hedgehog (Hh), Notch, and Hippo, are essential for embryogenesis, organogenesis, and tissue homeostasis. In this study, we analyzed 415 genes involved in these pathways in the allotetraploid frog, Xenopus laevis. Most genes are retained in two subgenomes called L and S (193 homeologous gene pairs and 29 singletons). This conservation rate of homeologs is much higher than that of all genes in the X. laevis genome (86.9% vs 60.2%). Among singletons, 24 genes are retained in the L subgenome, a rate similar to the average for all genes (82.8% vs 74.6%). In addition, as general components of signal transduction, we also analyzed 32 heparan sulfate proteoglycan (HSPG)-related genes and eight TLE/Groucho transcriptional corepressors-related genes. In these gene sets, all homeologous pairs have been retained. Transcriptome analysis using RNA-seq data from developmental stages and adult tissues demonstrated that most homeologous pairs of signaling components have variable expression patterns, in contrast to the conservative expression profiles of homeologs for transcription factors. Our results indicate that homeologous gene pairs for cell signaling regulation have tended to become subfunctionalized after allotetraploidization. Diversification of signaling pathways by subfunctionalization of homeologs may enhance environmental adaptability. These results provide insights into the evolution of signaling pathways after polyploidization

ジンソクナ バイスタンダー シンパイ ソセイホウ ニヨリ トツゼンシ オ マヌガレ シャカイ フッキ デキタ コウコウセイ ノ 2 ショウレイ

Bystander CPR means that people who find cardiopulmonary arrest perform cardiopulmonary resuscitation on the spot. Quick CPR contributes to increase in the rate of returning to the society as well as one-month survival rate and neurological prognosis. We report our experience with two high school students who underwent quick Bystander CPR, avoided sudden death, and returned to the society. ［Case 1］ Eighteen-year-old man : He collapsed suddenly in his home. Bystander CPR was performed by his family until emergency crews arrived there. Automated external defibrillator （AED） worked twice and his heartbeat started again. In electrocardiogram, coved type ST elevation in lead V1 was observed, and he was diagnosed as Brugada syndrome. We implanted an implantable cardioverter-defibrillator. Since his condition was stable, he was discharged on the 19th day. ［Case 2］ Seventeen-year-old woman : She collapsed suddenly walking with her family. Her father confirmed that she had no response, and started Bystander CPR. Her father got AED quickly and AED worked once, and she started to breathe again. She was admitted to our hospital for a work-up. Torsades de pointes （TdP） was observed in monitor electrocardiogram, and her QTc time was 513 msec in 12‐lead electrocardiogram. She was diagnosed as congenital long QT syndrome because genetic test showed that she had LQT2. Her QTc time was improved （approximately 350 msec） by medication, and she was discharged on the 25th day. Utstein-style statistics in Japan shows that the rate of returning to the society can be doubled by performing Bystander CPR on patients with cardiopulmonary arrest. However, performing rate of Bystander CPR is less than 50％ in Japan. In order to increase survival rate of patients with cardiopulmonary arrest for the future, it is important to inform people about CPR and to promote CPR, and in fact, we have been promoting CPR

The glycosylphosphatidylinositol-linked aspartyl protease Yps1 is transcriptionally regulated by the calcineurin-Crz1 and Slt2 MAPK pathways in Candida glabrata.

In the pathogenic fungus Candida glabrata, the YPS1 gene, which encodes a glycosylphosphatidylinositol-linked aspartyl protease, is required for cell wall integrity and virulence. Although the expression of YPS1 has been studied in Saccharomyces cerevisiae, the transcriptional regulation of this gene in C. glabrata is not well understood. Here, we report that C. glabrata Yps1 is required for cell growth at elevated temperatures, and that the heat-induced expression of YPS1 is regulated predominantly by the calcineurin-Crz1 pathway and partially by the Slt2 MAPK pathway. Although a total of 11 YPS genes are present in the C. glabrata genome, the loss of transcriptional induction in a calcineurin mutant was observed only for YPS1. The results of a YPS1 promoter-lacZ reporter assay using a series of constructs with mutated promoter elements indicated that the transcription factor Crz1 binds to multiple sites in the promoter region of YPS1. To date, as none of the putative Crz1 targets in C. glabrata have been characterized using a Δcrz1 mutant, monitoring the expression of YPS1 represents an effective method for measuring the activity of the calcineurin-Crz1 signaling pathway in this fungus

Genome evolution in the allotetraploid frog Xenopus laevis

To explore the origins and consequences of tetraploidy in the African clawed frog, we sequenced the Xenopus laevis genome and compared it to the related diploid X. tropicalis genome. We characterize the allotetraploid origin of X. laevis by partitioning its genome into two homoeologous subgenomes, marked by distinct families of ???fossil??? transposable elements. On the basis of the activity of these elements and the age of hundreds of unitary pseudogenes, we estimate that the two diploid progenitor species diverged around 34 million years ago (Ma) and combined to form an allotetraploid around 17-18 Ma. More than 56% of all genes were retained in two homoeologous copies. Protein function, gene expression, and the amount of conserved flanking sequence all correlate with retention rates. The subgenomes have evolved asymmetrically, with one chromosome set more often preserving the ancestral state and the other experiencing more gene loss, deletion, rearrangement, and reduced gene expression.ope