Distinct associations of different sedentary behaviors with health-related attributes among older adults

Objective: Leisure-time sedentary behaviors (LTSBs) have been associated adversely with health outcomes. However, limited research has focused on different categories of LTSB. We aimed at identifying categories of LTSBs and examining their separate associations with indices of health among Japanese older adults. Methods: A postal survey collected data on self-reported health, psychological distress, body mass index, moderate-to-vigorous physical activity (MVPA), LTSBs (five behaviors) and socio-demographic characteristics from 1,580 Japanese older adults (67% response rate; 65-74 years) in 2010. Exploratory factor analysis was used to classify LTSBs. Odds ratios (ORs) were calculated for associations of LTSB categories with self-reported health, psychological distress, overweight, and lower MVPA. Data were analyzed in 2013. Results: Two categories of LTSB: passive sedentary time (consisting of TV time, listening or talking while sitting, and sitting around) and mentally-active sedentary time (consisting of computer-use and reading books or newspapers) were identified. Higher passive sedentary time was associated with a higher odds of being overweight (OR: 1.39, [95% CI: 1.08-1.80]), and lower MVPA (1.26, [1.02-1.54]). Higher mentally-active sedentary time was associated with lower odds of lower MVPA (0.70, [0.57-0.86]). Conclusions: Two types of sedentary time-passive and mentally-active-may play different roles in older adults' well-being

Single-cell dynamics of pannexin-1-facilitated programmed ATP loss during apoptosis

死にゆく細胞のATP濃度変化を詳細に可視化することに成功 --積極的にATP濃度を下げる因子を明らかに--. 京都大学プレスリリース. 2020-10-22.ATP is essential for all living cells. However, how dead cells lose ATP has not been well investigated. In this study, we developed new FRET biosensors for dual imaging of intracellular ATP level and caspase-3 activity in single apoptotic cultured human cells. We show that the cytosolic ATP level starts to decrease immediately after the activation of caspase-3, and this process is completed typically within 2 hr. The ATP decrease was facilitated by caspase-dependent cleavage of the plasma membrane channel pannexin-1, indicating that the intracellular decrease of the apoptotic cell is a ‘programmed’ process. Apoptotic cells deficient of pannexin-1 sustained the ability to produce ATP through glycolysis and to consume ATP, and did not stop wasting glucose much longer period than normal apoptotic cells. Thus, the pannexin-1 plays a role in arresting the metabolic activity of dead apoptotic cells, most likely through facilitating the loss of intracellular ATP

Experimental model for the irradiation-mediated abscopal effect and factors influencing this effect

Radiotherapy (RT) is the primary treatment for cancer. Ionizing radiation from RT induces tumor damage at the irradiated site, and, although clinically infrequent, may cause regression of tumors distant from the irradiated site-a phenomenon known as the abscopal effect. Recently, the abscopal effect has been related to prolongation of overall survival time in cancer patients, though the factors that influence the abscopal effect are not well understood. The aim of this study is to clarify the factors influencing on abscopal effect. Here, we established a mouse model in which we induced the abscopal effect. We injected MC38 (mouse colon adenocarcinoma) cells subcutaneously into C57BL/6 mice at two sites. Only one tumor was irradiated and the sizes of both tumors were measured over time. The non-irradiated-site tumor showed regression, demonstrating the abscopal effect. This effect was enhanced by an increase in the irradiated-tumor volume and by administration of anti-PD1 antibody. When the abscopal effect was induced by a combination of RT and anti-PD1 antibody, it was also influenced by radiation dose and irradiated-tumor volume. These phenomena were also verified in other cell line, B16F10 cells (mouse melanoma cells). These findings provide further evidence of the mechanism for, and factors that influence, the abscopal effect in RT

Combination treatment with highly bioavailable curcumin and NQO1 inhibitor exhibits potent antitumor effects on esophageal squamous cell carcinoma

Background: Esophageal squamous cell carcinoma (ESCC) is one of the most intractable cancers, so the development of novel therapeutics has been required to improve patient outcomes. Curcumin, a polyphenol from Curcuma longa, exhibits various health benefits including antitumor effects, but its clinical utility is limited because of low bioavailability. Theracurmin® (THC) is a highly bioavailable curcumin dispersed with colloidal submicron particles. Methods: We examined antitumor effects of THC on ESCC cells by cell viability assay, colony and spheroid formation assay, and xenograft models. To reveal its mechanisms, we investigated the levels of reactive oxygen species (ROS) and performed microarray gene expression analysis. According to those analyses, we focused on NQO1, which involved in the removal of ROS, and examined the effects of NQO1-knockdown or overexpression on THC treatment. Moreover, the therapeutic effect of THC and NQO1 inhibitor on ESCC patient-derived xenografts (PDX) was investigated. Results: THC caused cytotoxicity in ESCC cells, and suppressed the growth of xenografted tumors more efficiently than curcumin. THC increased ROS levels and activated the NRF2–NMRAL2P–NQO1 expressions. Inhibition of NQO1 in ESCC cells by shRNA or NQO1 inhibitor resulted in an increased sensitivity of cells to THC, whereas overexpression of NQO1 antagonized it. Notably, NQO1 inhibitor significantly enhanced the antitumor effects of THC in ESCC PDX tumors. Conclusions: These findings suggest the potential usefulness of THC and its combination with NQO1 inhibitor as a therapeutic option for ESCC

HER2 G776S mutation promotes oncogenic potential in colorectal cancer cells when accompanied by loss of APC function

Clinical cancer genome sequencing detects oncogenic variants that are potential targets for cancer treatment, but it also detects variants of unknown significance. These variants may interact with each other to influence tumor pathophysiology, however, such interactions have not been fully elucidated. Additionally, the effect of target therapy for those variants also unclarified. In this study, we investigated the biological functions of a HER2 mutation (G776S mutation) of unknown pathological significance, which was detected together with APC mutation by cancer genome sequencing of samples from a colorectal cancer (CRC) patient. Transfection of the HER2 G776S mutation alone slightly increased the kinase activity and phosphorylation of HER2 protein, but did not activate HER2 downstream signaling or alter the cell phenotype. On the other hand, the HER2 G776S mutation was shown to have strong oncogenic potential when loss of APC function was accompanied. We revealed that loss of APC function increased Wnt pathway activity but also increased RAS-GTP, which increased ERK phosphorylation triggered by HER2 G776S transfection. In addition, afatinib, a pan-HER tyrosine kinase inhibitor, suppressed tumor growth in xenografts derived from HER2 G776S-transfected CRC cells. These findings suggest that this HER2 mutation in CRC may be a potential therapeutic target

XRF ニヨル ショウワキチ タイキチュウ フユウリュウシジョウ ブッシツ ノ トクセイカ

本研究では,南極昭和基地に蛍光X線分析顕微鏡を持ち込んで大気中浮遊粒子状物質の分析を行い,各成分の季節変化を調査した.粒子状物質は海洋起源であるNa,Mg,S,Cl,K,Caを多く含むことが明らかとなった.また,ブリザードなどの強風時には土壌起源と考えられるSi,Feも検出されたことから,強風によって土壌成分が巻き上げられていることが示唆される.Sは夏季に増加し,冬季に減少する傾向を示した.S以外の海洋起源粒子は夏季に減少し,ブリザード時に増加する傾向を示した.The particle size distribution has been continuously measured by optical particle counter at Syowa Station. Physical and chemical properties of particulate matter have been analyzed in the laboratory after arriving in Japan. However, the properties of particles may be changed in this case. In the present work, the atmospheric particulate matter at Syowa Station, Antarctica was characterized by X-ray fluorescence spectroscopy (XRF) at Syowa Station. The advantages of this method have non destructive, rapid and simple analysis. The particle samples were collected on a Teflon filter; the obtained particles were measured by XRF (HORIBA, X-ray Analytical Microscope XGT-5000) on site soon for elemental analysis. The obtained results show that collected particles mainly contain sea salt (Na, Mg, Cl, K, Ca) and soil (Si, Fe) origin components. The particles from sea salt and soil origin increased under blizzard and strong wind condition. Sulfur increased in summer, and decreased in winter while particles from sea salt decreased in summer

ヘリウム マイクロハ ユウドウ プラズマ ハッコウ ブンセキホウ (He-MIP-AES) ニヨル ショウワキチ タイキチュウ エアロゾル ノ トクセイカ

本研究では南極昭和基地大気中のエアロゾルに関し,個々の粒子に関する粒径分布,成分組成,化学状態の情報が同時に得られるヘリウムマイクロ波誘導プラズマ発光分析装置(He-MIP-AES)を現地に持ち込み分析を行った.その結果,Na,Mg,Caの元素を含む粒子数が多く,海塩起源の粒子を多く含んでいることが明らかとなった.また,Si,Feなどが検出されていることから土壌起源粒子が含まれていることが明らかとなった.風速が強く,降雪があるときは,土壌成分の巻き上げや,雪氷からの海塩成分の飛散等により粒子数が増加する傾向にあった.Atmospheric aerosols at Syowa Station, Antarctica were characterized by helium microwave induced plasma atomic emission spectrometry (He-MIP-AES). The He-MIP-AES can be considered as a suitable method for the characterization of the atmospheric particulate matter since measurements of grain size distribution, elemental analysis for each particle, and chemical state analysis can be available simultaneously. Previous characterization methods such as XRF, PIXE and ICP-MS cannot provide in situ analysis and they need a long time to measure of the distribution of the particle diameter and elemental analysis of each particle. The particle samples in the atmosphere were collected on the membrane lter at Syowa Station in Antarctica. The obtained particles were analyzed by the He-MIP-AES (HORIBA, particle analyzer DP-1000). Elemental analysis, chemical state analysis, and grain diameter distribution analysis were performed. The collected particles mainly contain sea salt (Na, Mg and Ca) and soil origin constituents (Si and Fe). The counts of each element increase under blizzard and strong wind condition