Rich and slim, but relatively short Explaining the halt in the secular trend in Japan

An almost complete halt in the secular trend in stature at a relatively low level is observed in Japan since the late 1980s with average height of around 171 cm for males and 158 cm for females at age 18. Unidentified characteristics in the Japanese genetic pool or in the nutritional intake do not provide a convincing explanation. Japan is unique among OECD countries in combining contrasted health outcomes: a stagnation of height suggests a decline in biological well-being, but this picture is not consistent with high life expectancy and extremely low prevalence of infant mortality, overweight/obesity, and other pathologies. Individual data that could allow investigating the influence of socio-economic and other environmental conditions are unavailable. As a second best, we take advantage of the regional variance in average height and other indicators across the 47 Japanese prefectures and use data covering the period 1950-2005. A positive and significant influence of income and housing conditions on height is identified but the effect is fading. Caloric restraint of pregnant women, and the decrease in sleeping time observed since the 1980s appear as possible explanatory variables of the halt in the secular trend and a symptom of a decline in well-being. Public health policy implications are considered.height, income, housing, sleep, sexual dimorphism, Japan

複数異種移植マウスモデルにおけるPentagamavunone-1の膵臓癌に対する単剤および併用療法としての前臨床評価

We previously reported that pentagamavunone-1 (PGV-1) effectively inhibited cell proliferation in many types of human tumors, including pancreatic cancer, by inducing M phase (prometaphase) arrest, senescence, and apoptosis with few side effects. However, a detailed evaluation of the effects of PGV-1 on pancreatic cancer cells in an in vivo setting has not yet been conducted. The present study investigated the potential efficacy of PGV-1 as both monotherapy and combination therapy for pancreatic cancer using multiple xenograft mouse assays. A cell-line derived xenograft model (CDX-M) with pancreatic cancer cell line and a patient-derived xenograft mouse model (PDX-M) using resected pancreatic cancer samples without neoadjuvant chemotherapy were established in both heterotopic and orthotopic manners. PGV-1 effectively suppressed tumor formation at the heterotopic and orthotopic sites in CDX-M than in untreated mice. Combination therapy with PGV-1 and gemcitabine more effectively suppressed tumor formation than monotherapy with PGV-1 or gemcitabine when administered after tumor formation. Monotherapy with PGV-1 or gemcitabine less effectively suppressed tumor formation in PDX-M than in CDX-M, whereas combination therapy with PGV-1 and gemcitabine more effectively suppressed tumor formation. PGV-1 as monotherapy and combination therapy with gemcitabine effectively inhibited tumor formation and has potential as an anticancer candidate for pancreatic cancer.権利情報：© The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/

Small mitochondrial ARF (smARF) is located in both the nucleus and cytoplasm, induces cell death, and activates p53 in mouse fibroblasts

AbstractThe ARF transcript produces two proteins, the full-length ARF, p19ARF, and a short mitochondrial version, smARF. To explore the functional difference between the two, we generated GFP-fused expression vectors for each protein and introduced them into NIH3T3 murine fibroblasts, which sustains a global deletion in the INK4a locus but contains a functional p53 gene. GFP-p19ARF was located within the nucleolus as previously reported, whereas GFP-smARF was detected mainly in the nucleoplasm. GFP-smARF induced cell death although to a slightly lesser extent than p19ARF. GFP-smARF stabilized p53 thereby inducing expression of the target genes, MDM2 and p21. We suggest that smARF has functions other than mitochondria-mediated autophagy, and induces p53 expression and cell death via a novel mechanism

CSN5/Jab1 controls multiple events in the mammalian cell cycle

AbstractThe COP9 signalosome (CSN) complex is critical for mammalian cell proliferation and survival, but it is not known how the CSN affects the cell cycle. In this study, MEFs lacking CSN5/Jab1 were generated using a CRE-flox system. MEFs ceased to proliferate upon elimination of CSN5/Jab1. Rescue experiments indicated that the JAMM domain of CSN5/Jab1 was essential. CSN5/Jab1-elimination enhanced the neddylation of cullins 1 and 4 and altered the expression of many factors including cyclin E and p53. CSN5/Jab1-elimination inhibited progression of the cell cycle at multiple points, seemed to initiate p53-independent senescence and increased the ploidy of cells. Thus, CSN5/Jab1 controls different events of the cell cycle, preventing senescence and endocycle as well as the proper progression of the somatic cell cycle.Structured summaryMINT-8046253: Csn1 (uniprotkb:Q99LD4) physically interacts (MI:0914) with Csn5 (uniprotkb:O35864), Csn8 (uniprotkb:Q8VBV7), Csn3 (uniprotkb:O88543), Csn7b (uniprotkb:Q8BV13) and Csn6 (uniprotkb:O88545) by anti bait coimmunoprecipitation (MI:0006

A proposal on the first Japanese practical guidance for the return of individual genomic results in research settings

Aizawa, Y., Nagami, F., Ohashi, N. et al. A proposal on the first Japanese practical guidance for the return of individual genomic results in research settings. J Hum Genet (2019). doi:10.1038/s10038-019-0697-y

Distribution of Lenticular Astigmatism in a Pre-Cataract Surgery Population

Recently custom ablation of LASIK (laserin situ keratomileusis) has rapidly evolved. It could achieve supervision temporarily, but we suspect that the vision could deteriorate due to against-the rule astigmatism decades after the operation. To clarify this concern, we evaluated distribution of the total and corneal astigmatism of 101 eyes of 65 pre-cataract surgery patients (meanage:73 years). Then we calculated the lenticular astigrlatism by vector analysis. The mean amounts of total and corneal astigmatism were 1.22±1.50D and 0.97±0.84D each. The percentages of no astigmatism: oblique: with-the-rule: against-the-rule were 32: 4: 15: 50 and 7: 28: 26: 40, respectively. The mean amount of lenticular astigrlatism measured by vector analysis was 1.6± 1.4D. The percentage of no astigmatism: oblique: with-the-rule: against-the-rule was 2: 0: 39: 59. This biased distribution of astigmatism might have contributed to the biased distribution (no and against-the-rule) of total astigmatism. These data indicate that in a pre-cataract surgery population against-the-rule astigmatism is predominant in both corneal and lenticular astigmatism. We suspect that custom correction of adolescent eyes, in which with-the-rule astigmatism is predominant, might elicit more against-the-rule astigmatism when they reach pre-cataract surgery age population, leading to a decline in quality of vision

Potassium-competitive acid blocker-associated gastric mucosal lesions

Since the introduction of vonoprazan, a potassium-competitive acid blocker (P-CAB), it has been demonstrated to reversibly inhibit gastric acid secretion by engaging in potassium-competitive ionic binding to H+/K+-ATPase. In contrast, proton pump inhibitors (PPIs) achieve H+/K+-ATPase inhibition through covalent binding to cysteine residues of the proton pump. Reported cases have indicated an emerging trend of P-CAB-related gastropathies, similar to those associated with PPIs, as well as unique gastropathies specific to P-CAB use, such as the identification of web-like mucus. Pathologically, parietal cell profusions, which show a positively correlated with hypergastrinemia, have a higher incidence in P-CAB users compared to PPI users. Thus, this review aims to summarize the endoscopic and pathological findings reported to date concerning P-CAB-related gastric mucosal lesions. Additionally, it seeks to discuss the differences between the PPIs and P-CABs in terms of the formation and frequency of associated gastropathies. This review highlights the evident differences in the mechanism of action and potency of acid inhibition between P-CABs and PPIs, notably contributing to differences in the formation and frequency of associated gastropathies. It emphasizes the necessity to distinguish between P-CAB-related and PPI-related gastropathies in the clinical setting