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61.
Wenwen Li Kaku Goto Yasuo Matsubara Sayaka Ito Ryosuke Muroyama Qiang Li Naoya Kato 《PloS one》2015,10(5)
Objectives
Mutations in hepatitis B virus (HBV) X region (HBx) play important roles in hepatocarcinogenesis while the results remain controversial. We sought to clarify potential hepatocellular carcinoma (HCC)-characteristic mutations in HBx from HBV genotype C-infected patients and the distribution of those mutations in different disease phases and genotypes.Methods
HBx sequences downloaded from an online global HBV database were screened and then classified into Non-HCC or HCC group by diagnosis information. Patients'' data of patient age, gender, country or area, and viral genotype were also extracted. Logistic regression was performed to evaluate the effects of mutations on HCC risk.Results
1) Full length HBx sequences (HCC: 161; Non-HCC: 954) originated from 1115 human sera across 29 countries/areas were extracted from the downloaded 5956 HBx sequences. Genotype C occupied 40.6% of Non-HCC (387/954) and 89.4% of HCC (144/161). 2) Sixteen nucleotide positions showed significantly different distributions between genotype C HCC and Non-HCC groups. 3) Logistic regression showed that mutations A1383C (OR: 2.32, 95% CI: 1.34-4.01), R1479C/T (OR: 1.96, 95% CI: 1.05-3.64; OR: 5.15, 95% CI: 2.53-10.48), C1485T (OR: 2.40, 95% CI: 1.41-4.08), C1631T (OR: 4.09, 95% CI: 1.41-11.85), C1653T (OR: 2.58, 95% CI: 1.59-4.19), G1719T (OR: 2.11, 95% CI: 1.19-3.73), and T1800C (OR: 23.59, 95% CI: 2.25-247.65) were independent risk factors for genotype C HBV-related HCC, presenting different trends among individual disease phases. 4) Several genotype C HCC risk mutations pre-existed, even as major types, in early disease phases with other genotypes.Conclusions
Mutations associated with HCC risk were mainly located in HBx transactivation domain, viral promoter, protein/miRNA binding sites, and the area for immune epitopes. Furthermore, the signatures of these mutations were unique to disease phases leading to HCC, suggesting molecular counteractions between the virus and host during hepatocarcinogenesis. 相似文献62.
Hyeon-Ki Kim Masayuki Konishi Masaki Takahashi Hiroki Tabata Naoya Endo Shigeharu Numao Sun-Kyoung Lee Young-Hak Kim Katsuhiko Suzuki Shizuo Sakamoto 《PloS one》2015,10(9)
Purpose
To compare the effects of endurance exercise performed in the morning and evening on inflammatory cytokine responses in young men.Methods
Fourteen healthy male participants aged 24.3 ± 0.8 years (mean ± standard error) performed endurance exercise in the morning (0900–1000 h) on one day and then in the evening (1700–1800 h) on another day with an interval of at least 1 week between each trial. In both the morning and evening trials, the participants walked for 60 minutes at approximately 60% of the maximal oxygen uptake () on a treadmill. Blood samples were collected to determine hormones and inflammatory cytokines at pre-exercise, immediately post exercise, and 2 h post exercise.Results
Plasma interleukin (IL)-6 and adrenaline concentrations were significantly higher immediately after exercise in the evening trial than in the morning trial (P < 0.01, both). Serum free fatty acids concentrations were significantly higher in the evening trial than in the morning trial at 2 h after exercise (P < 0.05). Furthermore, a significant correlation was observed between the levels of IL-6 immediately post-exercise and free fatty acids 2 h post-exercise in the evening (r = 0.68, P < 0.01).Conclusions
These findings suggest that the effect of acute endurance exercise in the evening enhances the plasma IL-6 and adrenaline concentrations compared to that in the morning. In addition, IL-6 was involved in increasing free fatty acids, suggesting that the evening is more effective for exercise-induced lipolysis compared with the morning. 相似文献63.
64.
Mai Tsuchiya Yuka Nakajima Naoya Hirata Tamaki Morishita Hiroyuki Kishimoto Yasunari Kanda Keiji Kimura 《Biochemical and biophysical research communications》2014
Cancer stem cells (CSCs) have several distinctive characteristics, including high metastatic potential, tumor-initiating potential, and properties that resemble normal stem cells such as self-renewal, differentiation, and drug efflux. Because of these characteristics, CSC is regarded to be responsible for cancer progression and patient prognosis. In our previous study, we showed that a ubiquitin E3 ligase carboxyl terminus of Hsc70-interacting protein (CHIP) suppressed breast cancer malignancy. Moreover, a recent clinical study reported that CHIP expression levels were associated with favorable prognostic parameters of patients with breast cancer. Here we show that CHIP suppresses CSC properties in a population of breast cancer cells. CHIP depletion resulted in an increased proportion of CSCs among breast cancers when using several assays to assess CSC properties. From our results, we propose that inhibition of CSC properties may be one of the functions of CHIP as a suppressor of cancer progression. 相似文献
65.
Kota Asano Mitsumi Arito Manae S. Kurokawa Kazuki Omoteyama Kazuki Okamoto Naoya Suematsu Kazuo Yudoh Hiroshi Nakamura Moroe Beppu Tomohiro Kato 《Biochemical and biophysical research communications》2014
Layilin (LAYN) is thought to be involved in reorganization of cytoskeleton structures, interacting with merlin, radixin, and talin. Also, LAYN is known to be one of the receptors for hyaluronic acid (HA). 相似文献
66.
We have previously shown that murine resident peritoneal macrophages (PEMs) are activated in response to uptake of oligomannose-coated
liposomes (OMLs), leading to production of interleukin (IL)-12. To understand the mechanism of activation of PEMs by OMLs,
in the present study we investigated the role of a mannose-binding C-type lectin receptor, SIGNR1, in production of proinflammatory
cytokines by PEMs, in which SIGNR1 acts as a physiological receptor for OMLs. Engagement of SIGNR1 on PEMs with an anti-SIGNR1-specific
rat IgM antibody, ERTR9, induced production of IL-12 and tumor necrosis factor (TNF)-α from PEMs, while secretion of IL-6
and IL-1β was not detected with the same treatment. The level of phosphorylated IκB kinase in PEMs also increased in response to ERTR9 treatment of the cells. Treatment of PEMs with a specific nuclear factor
kappa-B (NFκB) inhibitor, BAY11-7082, reduced ERTR9-dependent IL-12 production. Intraperitoneal treatment with BAY11-7082
also led to reduction of subsequent OML-induced IL-12 production from PEMs. These results indicate that SIGNR1-mediated intercellular
signaling may induce production of cytokines such as IL-12 through NFκB activation. 相似文献
67.
Hayashida S Kuramoto Y Koyanagi S Oishi K Fujiki J Matsunaga N Ikeda E Ohdo S Shimeno H Soeda S 《Chronobiology international》2010,27(9-10):1735-1753
Acute thrombotic events frequently occur in the early morning among hyperlipidemic patients. The activity of plasminogen activator inhibitor-1 (PAI-1), a potent inhibitor of the fibrinolytic system, oscillates daily, and this is considered one mechanism that underlies the morning onset of acute thrombotic events in hyperlipidemia. Although several studies have reported the expression of the PAI-1 gene is under the control of the circadian clock system, the molecular mechanism of the circadian transactivation of PAI-1 gene under hyperlipidemic conditions remains to be elucidated. Here, the authors investigated whether hyperlipidemia induced by a high-fat diet (HFD) enhances the daily oscillation of plasma PAI-1 activity in mice. The mRNA levels of the PAI-1 gene were increased and rhythmically fluctuated with high-oscillation amplitude in the livers of wild-type mice fed with the HFD. Circadian expression of proxisome proliferator-activated receptor-α (PPARα) mRNA was also augmented as well as that of PAI-1. Chromatin immunoprecipitation showed the HFD-induced hyperlipidemia significantly increased the binding of PPARα to the PAI-1 promoter. Luciferase reporter analysis using primary hepatocytes revealed CLOCK/BMAL1-mediated PAI-1 promoter activity was synergistically enhanced by cotransfection with PPARα/retinoid X receptor-α (RXRα), and this synergistic transactivation was repressed by negative limbs of the circadian clock, PERIOD2 and CRYPTOCHROME1. As expected, HFD-induced PAI-1 mRNA expression was significantly attenuated in PPARα-null mice. These results suggest a molecular link between the circadian clock and lipid metabolism system in the regulation of PAI-1 gene expression, and provide an aid for understanding why hyperlipidemia increases the risk of acute thrombotic events in the morning. 相似文献
68.
69.
Functional and morphological responses of endothelial cells (ECs) to fluid shear stress are thought to be mediated by several mechanosensitive molecules. However, how the force due to fluid shear stress applied to the apical surface of ECs is transmitted to the mechanosensors is poorly understood. In the present paper, we performed an analysis of an intracellular mechanical field by observation of the deformation behaviors of living ECs exposed to shear stress with a novel experimental method. Lateral images of human umbilical vein ECs before and after the onset of flow were obtained by confocal microscopy, and image correlation and finite element analysis were performed for quantitative analyses of subcellular strain due to shear stress. The shear strain of the cells changed from 1.06 ± 1.09% (mean ± SD) to 4.67 ± 1.79% as the magnitude of the shear stress increased from 2 to 10 Pa. The nuclei of ECs also exhibited shear deformation, which was similar to that observed in cytoplasm, suggesting that nuclei transmit forces from apical to intracellular components, as well as cytoskeletons. The obtained strain-stress relation resulted in a mean shear modulus of 213 Pa for adherent ECs. These results provide a mechanical perspective on the investigation of flow-sensing mechanisms of ECs. 相似文献
70.
Native predators are postulated to have an important role in biotic resistance of communities to invasion and community resilience. Effects of predators can be complex, and mechanisms by which predators affect invasion success and impact are understood for only a few well-studied communities. We tested experimentally whether a native predator limits an invasive species’ success and impact on a native competitor for a community of aquatic insect larvae in water-filled containers. The native mosquito Aedes triseriatus alone had no significant effect on abundance of the invasive mosquito Aedes albopictus. The native predatory midge Corethrella appendiculata, at low or high density, significantly reduced A. albopictus abundance. This effect was not caused by trait-mediated oviposition avoidance of containers with predators, but instead was a density-mediated effect caused by predator-induced mortality. The presence of this predator significantly reduced survivorship of the native species, but high predator density also significantly increased development rate of the native species when the invader was present, consistent with predator-mediated release from interspecific competition with the invader. Thus, a native predator can indirectly benefit its native prey when a superior competitor invades. This shows the importance of native predators as a component of biodiversity for both biotic resistance to invasion and resilience of a community perturbed by successful invasion. 相似文献