The impact of building up the limb muscle mass by the resistance exercise with the intake of milk in middle-aged and elderly women

Background: In the rapidly aging Japanese society, the most serious disorder to prevent is sarcopenia for extending healthy life expectancy. Objective: This study was carried out to clarify whether five kinds of specific and simple resistance exercise performing at home for the short term (42 days) with theintake of whole milk could help to increase the limb muscle mass in middle-aged and elderly women. Participants and measurements: Subjects were 39 healthy women aged 50 to 80 years who gave the consent to participate in the present study. Body composition, physical fitness, food and nutrient intake were measured. Oral glucose-tolerance test (OGTT) was also performed. Groups and results: Subjects were categorized in two groups; Group I with the increase of the limb muscle mass after exercise and Group II with no increase. Body weight before exercise (Group I, 51.6±5.5 kg vs Group II, 58.5±10.3 kg), the body mass index (BMI) (21.7±2.5 kg/m2 vs 24.3±3.9 kg/m2), the limb muscle mass (14.4±1.3 kg vs 15.6±2.0 kg), the skeletal muscle mass index (SMI) (6.0±0.5 kg/m2 vs 6.5±0.7 kg/m2), were all significantly high in Group II. The intake of milk before exercise in Group I (162.1±103.7 g/day) was significantly higher than in Group II (92.5±63.3 g/day). The blood glucose level at 30 min after glucose loading in Group I before exercise was significantly higher than that in Group Ⅱ (199.3 ± 31.1 mg/dl vs 177.0±34.1 mg/dl). Conclusion: The subjects in Group I could successfully increase the limb muscle mass, but the subjects in Group II, whose weight, BMI, the limb muscle mass were significantly high before exercise, could not increase the muscle mass by resistance exercise with the intake of milk. It was considered that the resistance exercise carried out in this study was not strong enough for Group II. We assumed that the BMI value could be the indicator of the strength of exercise for building up the muscle mass in middle-aged and elderly individuals

Isolation of a point-mutated p47 lacking binding affinity to p97ATPase

Abstractp47, a p97-binding protein, functions in Golgi membrane fusion together with p97 and VCIP135, another p97-binding protein. We have succeeded in creating p47 with a point mutation, F253S, which lacks p97-binding affinity. p47 mapping experiments revealed that p47 had two p97-binding regions and the F253S mutation occurred in the first p97-binding site. p47(F253S) could not form a complex with p97 and did not caused any cisternal regrowth in an in vitro Golgi reassembly assay. In addition, mutation corresponding to the p47 F253S mutation in p37 and ufd1 also abolished their binding ability to p97.Structured summaryMINT-7987189, MINT-7987207, MINT-7987303: p47 (uniprotkb:O35987) binds (MI:0407) to p97 (uniprotkb:Q01853) by pull down (MI:0096)MINT-7987226: p97 (uniprotkb:P46462) binds (MI:0407) to p47 (uniprotkb:O35987) by pull down (MI:0096)MINT-7987348: p97 (uniprotkb:P46462) physically interacts (MI:0915) with Ufd1 (uniprotkb:P70362) by pull down (MI:0096)MINT-7987264: p97 (uniprotkb:P46462) and p47 (uniprotkb:O35987) bind (MI:0407) by competition binding (MI:0405)MINT-7987326: p97 (uniprotkb:P46462) binds (MI:0407) to p37 (uniprotkb:Q0KL01) by pull down (MI:0096

Reduction of lung metastasis, cell invasion, and adhesion in mouse melanoma by statin-induced blockade of the Rho/Rho-associated coiled-coil-containing protein kinase pathway

<p>Abstract</p> <p>Background</p> <p>Melanomas are highly malignant and have high metastatic potential; hence, there is a need for new therapeutic strategies to prevent cell metastasis. In the present study, we investigated whether statins inhibit tumor cell migration, invasion, adhesion, and metastasis in the B16BL6 mouse melanoma cell line.</p> <p>Methods</p> <p>The cytotoxicity of statins toward the B16BL6 cells were evaluated using a cell viability assay. As an experimental model, B16BL6 cells were intravenously injected into C57BL/6 mice. Cell migration and invasion were assessed using Boyden chamber assays. Cell adhesion analysis was performed using type I collagen-, type IV collagen-, fibronectin-, and laminin-coated plates. The mRNA levels, enzyme activities and protein levels of matrix metalloproteinases (MMPs) were determined using RT-PCR, activity assay kits, and Western blot analysis, respectively; the mRNA and protein levels of vary late antigens (VLAs) were also determined. The effects of statins on signal transduction molecules were determined by western blot analyses.</p> <p>Results</p> <p>We found that statins significantly inhibited lung metastasis, cell migration, invasion, and adhesion at concentrations that did not have cytotoxic effects on B16BL6 cells. Statins also inhibited the mRNA expressions and enzymatic activities of matrix metalloproteinases (MMPs). Moreover, they suppressed the mRNA and protein expressions of integrin α₂, integrin α₄, and integrin α₅and decreased the membrane localization of Rho, and phosphorylated LIM kinase (LIMK) and myosin light chain (MLC).</p> <p>Conclusions</p> <p>The results indicated that statins suppressed the Rho/Rho-associated coiled-coil-containing protein kinase (ROCK) pathways, thereby inhibiting B16BL6 cell migration, invasion, adhesion, and metastasis. Furthermore, they markedly inhibited clinically evident metastasis. Thus, these findings suggest that statins have potential clinical applications for the treatment of tumor cell metastasis.</p

理科指導法における模擬授業の実践と評価

本研究の目的は，理科指導法における模擬授業の実践を通して，学生が授業観察の視点を深めることができたかどうかを 明らかにすることである。その目的を達成するために模擬授業後の学生によるコメントの分析と，全ての模擬授業が終了し た後の学生の振り返りの記述の分析を行なった。その結果，次の二つのことが分かった。 (1) 模擬授業を行うことで教師の振る舞いについて指摘する数は減り，教授について指摘する割合が顕著に増加した。小 学校教育全般に対する指摘は減少し，理科授業全般や単元固有のことについて指摘する数が増加した。 (2) 模擬授業を通して，理科の授業ができるポイントを見つけることができたと評価する学生は99 パーセントに達した。 理科の指導がうまくなったと評価する学生は半数を超えた

Usefulness of Palliative Prognostic Index, Objective Prognostic Score, and Neutrophil–Lymphocyte Ratio/Albumin Ratio As Prognostic Indicators for Patients Without Cancer Receiving Home-Visit Palliative Care : A Pilot Study at a Community General Hospital

Background: Although the palliative prognostic index (PPI), objective prognostic score (OPS), and neutrophil–lymphocyte ratio/albumin ratio (NLR/Alb) are well-known prognostic indicators for cancer patients, they do not provide clarity when it comes to predicting prognosis in patients without cancer who receive home-visit palliative care. Objective: The aim of this study was to determine whether PPI, OPS, and NLR/Alb can predict prognosis for patients without cancer who received home-visit palliative care. Design: This is a retrospective study. Setting/Subjects: We recruited 58 patients without cancer who received home-visit palliative care from Tokushima Prefectural Kaifu Hospital, Japan, and died at home or at the hospital within seven days of admission between January 2009 and March 2023. Measurements: The PPI, OPS, and NLR/Alb of the study patients were evaluated at regular intervals, and statistical analysis was performed on the relationship between these indices and the time to death. Results: Simple regression analysis showed that PPI, OPS, and NLR/Alb were negatively correlated with the period until death (p < 0.001). The survival curves of the groups classified according to PPI, OPS, and NLR/Alb were significantly stratified. The predictive capacities of PPI, OPS, and NLR/Alb for death within 21 days were as follows: PPI (area under the curve [AUC]: 0.71; sensitivity: 59%; specificity: 68%), OPS (AUC: 0.73; sensitivity: 88%; specificity: 47%), and NLR/Alb (AUC: 0.72; sensitivity: 72%; specificity: 73%). Conclusions: PPI, OPS, and NLR/Alb were useful in predicting the survival period and short-term prognosis within 21 days for patients without cancer who received home-visit palliative care

卵巣摘出ラットに対する低分子化ライチポリフェノール「OligonolⓇ」の肥満予防効果

　成人女性は女性ホルモンであるエストロゲンの分泌の低下および停止により、概ね50歳前後で閉経を迎え、それに伴う身体変化として体重増加、体脂肪の増加がみられる。今回、生体内への吸収性を高めた低分子化ライチポリフェノール（a standardized oligomerized-polyphenol from Litchi chinensis fruit extract）である「Oligonol®」を閉経モデルである卵巣摘出ラットに対して2か月間の経口投与を行い、その肥満予防効果を検討した。　結果、Oligonol®100mg/kg経口投与により、食餌摂取量の増加抑制に伴い体重変化率、血清レプチン濃度の増加抑制がみられた。ラットにおける卵巣摘出は摂食量の増加を通じて肥満を誘発するが、Oligonol®100mg/kg経口投与は、摂食量を摘出前のレベルに近づけることで、体重増加と血清レプチン濃度も摘出前のレベルに近づけることが示唆された

Targeting critical kinases and anti-apoptotic molecules overcomes steroid resistance in MLL-rearranged leukaemia.

BACKGROUND: Acute lymphoblastic leukaemia with mixed lineage leukaemia gene rearrangement (MLL-ALL) frequently affects infants and is associated with a poor prognosis. Primary refractory and relapsed disease due to resistance to glucocorticoids (GCs) remains a substantial hurdle to improving clinical outcomes. In this study, we aimed to overcome GC resistance of MLL-ALL. METHODS: Using leukaemia patient specimens, we performed bioinformatic analyses to identify target genes/pathways. To test inhibition of target pathways in vivo, we created pre-clinical therapeutic mouse patient-derived xenograft (PDX)-models by transplanting human MLL-ALL leukaemia initiating cells (LIC) into immune-deficient NSG mice. Finally, we conducted B-cell lymphoma-2 (BCL-2) homology domain 3 (BH3) profiling to identify BH3 peptides responsible for treatment resistance in MLL-leukaemia. FINDINGS: Src family kinases (SFKs) and Fms-like tyrosine kinase 3 (FLT3) signaling pathway were over-represented in MLL-ALL cells. PDX-models of infant MLL- ALL recapitulated GC-resistance in vivo but RK-20449, an inhibitor of SFKs and FLT3 eliminated human MLL-ALL cells in vivo, overcoming GC-resistance. Further, we identified BCL-2 dependence as a mechanism of treatment resistance in MLL-ALL through BH3 profiling. Furthermore, MLL-ALL cells resistant to RK-20449 treatment were dependent on the anti-apoptotic BCL-2 protein for their survival. Combined inhibition of SFKs/FLT3 by RK-20449 and of BCL-2 by ABT-199 led to substantial elimination of MLL-ALL cells in vitro and in vivo. Triple treatment combining GCs, RK-20449 and ABT-199 resulted in complete elimination of MLL-ALL cells in vivo. INTERPRETATION: SFKs/FLT3 signaling pathways are promising targets for treatment of treatment-resistant MLL-ALL. Combined inhibition of these kinase pathways and anti-apoptotic BCL-2 successfully eliminated highly resistant MLL-ALL and demonstrated a new treatment strategy for treatment-resistant poor-outcome MLL-ALL. FUNDING: This study was supported by RIKEN (RIKEN President\u27s Discretionary Grant) for FI, Japan Agency for Medical Research and Development (the Basic Science and Platform Technology Program for Innovative Biological Medicine for FI and by NIH CA034196 for LDS. The funders had no role in the study design, data collection, data analysis, interpretation nor writing of the report

Transdiagnostic association between subjective insomnia and depressive symptoms in major psychiatric disorders

In psychiatric disorders, comorbid depressive symptoms are associated with clinically important issues such as reduced quality of life, a poor prognosis, and increased suicide risk. Previous studies have found a close relationship between insomnia and depressive symptoms in major depressive disorder (MDD), and that actively improving insomnia heightens the improvement of depressive symptoms. This study aimed to investigate whether the association between insomnia and depressive symptoms is also found in other psychiatric disorders besides MDD. The subjects were 144 patients with MDD (n = 71), schizophrenia (n = 25), bipolar disorder (n = 22), or anxiety disorders (n = 26). Sleep status was assessed subjectively and objectively using the Athens Insomnia Scale (AIS) and sleep electroencephalography (EEG), respectively. Sleep EEG was performed using a portable EEG device. Depressive symptoms were assessed using the Beck Depression Inventory. Subjective insomnia, as defined by the AIS, was associated with depressive symptoms in all disorders. Moreover, in schizophrenia, a relation between depressive symptoms and insomnia was also found by objective sleep assessment methods using sleep EEG. Our findings suggest that the association between subjective insomnia and depressive symptoms is a transdiagnostic feature in major psychiatric disorders. Further studies are needed to clarify whether therapeutic interventions for comorbid insomnia can improve depressive symptoms in major psychiatric disorders, similar to MDD