Regulation of the MDM2-P53 pathway and tumor growth by PICT1 via nucleolar RPL11

PICT1 (also known as GLTSCR2) is considered a tumor suppressor because it stabilizes phosphatase and tensin homolog (PTEN), but individuals with oligodendrogliomas lacking chromosome 19q13, where PICT1 is located, have better prognoses than other oligodendroglioma patients. To clarify the function of PICT1, we generated Pict1-deficient mice and embryonic stem (ES) cells. Pict1 is a nucleolar protein essential for embryogenesis and ES cell survival. Even without DNA damage, Pict1 loss led to p53-dependent arrest of cell cycle phase G1 and apoptosis. Pict1-deficient cells accumulated p53, owing to impaired Mdm2 function. Pict1 binds Rpl11, and Rpl11 is released from nucleoli in the absence of Pict1. In Pict1-deficient cells, increased binding of Rpl11 to Mdm2 blocks Mdm2-mediated ubiquitination of p53. In human cancer, individuals whose tumors express less PICT1 have better prognoses. When PICT1 is depleted in tumor cells with intact P53 signaling, the cells grow more slowly and accumulate P53. Thus, PICT1 is a potent regulator of the MDM2-P53 pathway and promotes tumor progression by retaining RPL11 in the nucleolu

特別養護老人ホームにおける給食の給与栄養量と食品群別提供量

目的：特別養護老人ホームの入所者への給食の食品群別提供量を明らかにすることを目的とした。併せて，給食のエネルギー量・各種栄養素量（以下，給与栄養量と略記）についての検討もおこなった。方法：神戸市内の特別養護老人ホーム計3施設の管理栄養士から，1年間分の給食（朝食，昼食，間食，夕食）献立のうち，普通食の献立表を入手した。これらより1人1日当たりの給与栄養量及び食品群別提供量を算定した。そして，①給与栄養量と日本人の食事摂取基準2015年版に示された高齢者（70歳以上）の食事摂取基準の値とを比較した。②給与栄養量と平成27年国民健康・栄養調査報告による70歳以上の者の摂取栄養量とを比較した。③食品群別提供量と国民健康・栄養調査報告による70歳以上の者の食品群別摂取量とを比較した。結果：給与栄養量のうち，食物繊維，ビタミンA，ビタミンB1，ビタミンB2，食塩相当量，カルシウム，及びマグネシウムの各栄養素量は，食事摂取基準と差があった。給与栄養量と摂取栄養量とを比較したところ，意味のある差を認めたのは，エネルギーとナトリウムに加え，脂質，炭水化物，食物繊維，ビタミンD，食塩相当量，及び銅であった。食品群別提供量と食品群別摂取量とを比較したところ，果実類，砂糖・甘味料類，豆類，及び油脂類において意味のある差を認めた。結論：特別養護老人ホームで提供している給食の給与栄養量は日本人の食事摂取基準や国民健康・栄養調査報告での摂取栄養量と比較してどのような栄養素について差があったのか，また特別養護老人ホームでの食品群別提供量は国民健康・栄養調査報告での食品群別摂取量と比較してどのような食品群について差があったのかについて明らかにした。今回の給食の給与栄養量及び食品群別提供量の成績は，特別養護老人ホームの1年間に亘る給食提供の実態を明らかにする資料として重要である

An Adenylyl Cyclase, CyaA, of Myxococcus xanthus Functions in Signal Transduction during Osmotic Stress

An adenylyl cyclase gene (cyaA) present upstream of an osmosensor protein gene (mokA) was isolated from Myxococcus xanthus. cyaA encoded a polypeptide of 843 amino acids with a predicted molecular mass of 91,187 Da. The predicted cyaA gene product had structural similarity to the receptor-type adenylyl cyclases that are composed of an amino-terminal sensor domain and a carboxy-terminal catalytic domain of adenylyl cyclase. In reverse transcriptase PCR experiments, the transcript of the cyaA gene was detected mainly during development and spore germination. A cyaA mutant, generated by gene disruption, showed normal growth, development, and germination. However, a cyaA mutant placed under conditions of ionic (NaCl) or nonionic (sucrose) osmostress exhibited a marked reduction in spore formation and spore germination. When wild-type and cyaA mutant cells at developmental stages were stimulated with 0.2 M NaCl or sucrose, the mutant cells increased cyclic AMP accumulation at levels similar to those of the wild-type cells. In contrast, the mutant cells during spore germination had mainly lost the ability to respond to high-ionic osmolarity. In vegetative cells, the cyaA mutant responded normally to osmotic stress. These results suggested that M. xanthus CyaA functions mainly as an ionic osmosensor during spore germination and that CyaA is also required for osmotic tolerance in fruiting formation and sporulation

A patient with pachydermoperiostosis harboring SLCO2A1 variants with a history of differentiating from acromegaly

Pachydermoperiostosis (PDP) is a rare hereditary disease characterized by digital clubbing, pachydermia, and periostosis. We describe a Japanese male patient with PDP who was differentially diagnosed with acromegaly by identification of compound heterozygous variants in SLCO2A1. Recent studies have reported various clinical manifestations, as well as skeletal and dermal features, in patients with PDP. Genetic testing provided not only PDP diagnosis and differentiation from acromegaly, but also information about possible complications and comorbidities throughout life

Vonoprazan-Based Third-Line Therapy Has a Higher Eradication Rate against Sitafloxacin-Resistant Helicobacter pylori

Eradication of Helicobacter pylori (H. pylori) is an effective strategy for preventing various gastrointestinal diseases such as gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. However, the eradication success rate is decreasing because of a recent increase in drug-resistant strains of H. pylori. Here, we evaluated the success rate of eradication therapy with vonoprazan (VPZ), a new potassium-competitive acid blocker, against drug-resistant H. pylori. In total, 793 patients who received H. pylori eradication therapy were investigated retrospectively. All underwent esomeprazole (EPZ)-based triple therapy (n = 386) or VPZ-based triple therapy (n = 407) for first-, second- and third-line H. pylori eradication for 7 days. The overall success rates of first- and third-line H. pylori eradication were significantly higher for VPZ-based triple therapy (88.4% and 93.0%, respectively, per protocol (PP)) than for EPZ-based triple therapy (69.5% and 56.5%, respectively, PP). Moreover, the success rates of first- and third-line eradication of clarithromycin (CLR)- and sitafloxacin (STFX)-resistant H. pylori were significantly higher for VPZ-based triple therapy (72.0% and 91.7%, PP) than for EPZ-based triple therapy (38.5% and 20.0%, PP). In addition, patient age did not affect the eradication rate of VPZ-based first-line therapy, whereas the success rate of EPZ-based therapy was lower in patients under 65 years of age. Our results clearly demonstrated that VPZ-based therapy achieved a higher eradication rate even against CLR- and STFX-resistant H. pylori, and that patient age did not affect the eradication rate of VPZ-based therapy. These findings suggest that dual therapy using VPZ and amoxicillin may be sufficient for standard H. pylori eradication, and may thus also be beneficial for avoiding antibiotic misuse

A novel validated method for predicting the risk of re-hospitalization for worsening heart failure and the effectiveness of the diuretic upgrading therapy with tolvaptan.

Increased re-hospitalization due to acute decompensated heart failure (ADHF) is a modern issue in cardiology. The aim of this study was to investigate risk factors for re-hospitalization due to worsening heart failure, and the effect of tolvaptan (TLV) on decreasing the number of re-hospitalizations. This was a multicenter, retrospective study. The re-hospitalization factors for 1191 patients with ADHF were investigated; patients receiving continuous administration of TLV when they were discharged from the hospital (n = 194) were analyzed separately. Patients were classified into 5 risk groups based on their calculated Preventing Re-hospitalization with TOLvaptan (Pretol) score. The total number of patients re-hospitalized due to worsening heart failure up to one year after discharge from the hospital was 285 (23.9%). Age ≥80 years, duration since discharge from the hospital after previous heart failure 7.2 mg/dl, left ventricular ejection fraction (LVEF) 44.7 ml/m2, loop diuretic dose ≥20 mg/day, hematocrit <31.6%, and estimated glomerular filtration rate (eGFR) <50 ml/min/1.73m2 were independent risk factors for re-hospitalization for worsening heart failure. There was a significant reduction in the re-hospitalization rate among TLV treated patients in the Risk 3 group and above. In conclusions, age, duration since previous heart failure, diabetes mellitus, hemoglobin, uric acid, LVEF, LAVI, loop diuretic dose, hematocrit, and eGFR were all independent risk factors for re-hospitalization for worsening heart failure. Long-term administration of TLV significantly decreases the rate of re-hospitalization for worsening heart failure in patients with a Pretol score of 7

The Possible Effects of Zinc Supplementation on Postpartum Depression and Anemia

Background and Objectives: The effects of postpartum zinc supplementation are still unclear. Our purpose in this study is to investigate the association between Zn supplementation and postpartum depression, defined by an Edinburgh Postnatal Depression Scale (EPDS) score &ge; 9, and the effect on the hematological status of postpartum women. Materials and Methods: We first investigated whether zinc supplementation affected the perioperative levels of zinc, hemoglobin, and hematocrit in 197 cases who underwent cesarean section and had postpartum anemia. Next, logistic regression analyses were performed on 148 eligible cases to determine the association between zinc supplementation and postpartum depression. Results: Postpartum zinc supplementation significantly improved the status of maternal blood zinc levels and reduced the risk of developing postpartum depression (adjusted odds ratio: 0.249; 95% confidence interval: 0.062&ndash;0.988; p = 0.048). Iron supplementation is a standard and effective strategy for treating anemia; however, the combination of oral iron plus zinc supplementation resulted in slightly significant negative effects on postpartum hemoglobin and hematocrit compared to oral iron supplementation only. Conclusions: Postpartum zinc supplementation causes a significant positive effect on postpartum depression (EPDS score &ge; 9). Zinc supplementation had a negative but transient influence on the hematological status in women with postpartum anemia treated with oral iron supplementation; however, the differences were not clinically significant. Thus, we did not regard it as an adverse effect to be considered, and postpartum zinc supplementation may be viewed as beneficial in postpartum women