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1.
Weilan Ye 《The EMBO journal》2014,33(8):786-787
Since metastatic lesions of solid tumors are the major cause of mortality in cancer patients, understanding the molecular mechanisms of metastasis is of paramount importance. Although extensive knowledge has been accumulated regarding the early steps in metastasis—starting with the departure of cancer cells from their primary sites, to their transit through the hematogenous and/or lymphatic systems, and ending with their entrance into the parenchyma of distant organs—it is difficult if not impossible to translate such knowledge into medicine due to the challenge of identifying patients with only primary tumors but otherwise pristine organs. In other words, autopsy studies indicate that a large proportion of patients already harbor dormant, undetectable micrometastases at the time of cancer diagnosis (Hensel et al, 2013 ). Accordingly, stopping tumor cell dissemination is too late for these patients. Therefore, understanding the survival and outgrowth of micrometastases may hold greater promise to combat metastatic disease. 相似文献
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Bayesian nonparametric inference for panel count data with an informative observation process 下载免费PDF全文
In this paper, the panel count data analysis for recurrent events is considered. Such analysis is useful for studying tumor or infection recurrences in both clinical trial and observational studies. A bivariate Gaussian Cox process model is proposed to jointly model the observation process and the recurrent event process. Bayesian nonparametric inference is proposed for simultaneously estimating regression parameters, bivariate frailty effects, and baseline intensity functions. Inference is done through Markov chain Monte Carlo, with fully developed computational techniques. Predictive inference is also discussed under the Bayesian setting. The proposed method is shown to be efficient via simulation studies. A clinical trial dataset on skin cancer patients is analyzed to illustrate the proposed approach. 相似文献
4.
P2X7 receptor inhibition attenuated sympathetic nerve sprouting after myocardial infarction via the NLRP3/IL‐1β pathway 下载免费PDF全文
Hesheng Hu Xiaolu Li Mei Xue Wenjuan Cheng Ye Wang Xinran Li Na Yang Yugen Shi Suhua Yan 《Journal of cellular and molecular medicine》2017,21(11):2695-2710
Mounting evidence supports the hypothesis that inflammation modulates sympathetic sprouting after myocardial infarction (MI). The myeloid P2X7 signal has been shown to activate the nucleotide‐binding and oligomerization domain‐like receptor family pyrin domain‐containing 3 (NLRP3) inflammasome, a master regulator of inflammation. We investigated whether P2X7 signal participated in the pathogenesis of sympathetic reinnervation after MI, and whether NLRP3/interleukin‐1β (IL‐1β) axis is involved in the process. We explored the relationship between P2X7 receptor (P2X7R) and IL‐1β in the heart tissue of lipopolysaccharide (LPS)‐primed naive rats. 3′‐O‐(4‐benzoyl) benzoyl adenosine 5′‐triphosphate (BzATP), a P2X7R agonist, induced caspase‐1 activation and mature IL‐1β release, which was further neutralized by a NLRP3 inhibitor (16673‐34‐0). MI was induced by coronary artery ligation. Following infarction, a marked increase in P2X7R was localized within infiltrated macrophages and observed in parallel with an up‐regulation of NLRP3 inflammasome levels and the release of IL‐1β in the left ventricle. The administration of A‐740003 (a P2X7R antagonist) significantly prevented the NLRP3/IL‐1β increase. A‐740003 and/or Anakinra (an IL‐1 receptor antagonist) significantly reduced macrophage infiltration as well as macrophage‐based IL‐1β and NGF (nerve growth factor) production and eventually blunted sympathetic hyperinnervation, as assessed by the immunofluorescence of tyrosine hydroxylase (TH) and growth‐associated protein 43 (GAP 43). Moreover, the use of Anakinra partly attenuated sympathetic sprouting. This indicated that the effect of P2X7 on neural remodelling was mediated at least partially by IL‐1β. The arrhythmia score of programmed electric stimulation was in accordance with the degree of sympathetic hyperinnervation. In vitro studies showed that BzATP up‐regulated secretion of nerve growth factor (NGF) in M1 macrophages via IL‐1β. Together, these data indicate that P2X7R contributes to neural and cardiac remodelling, at least partly mediated by NLRP3/IL‐1β axis. Therapeutic interventions targeting P2X7 signal may be a novel approach to ameliorate arrhythmia following MI. 相似文献
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MiR‐122 modification enhances the therapeutic efficacy of adipose tissue‐derived mesenchymal stem cells against liver fibrosis 下载免费PDF全文
Guohua Lou Ying Yang Feifei Liu Bingjue Ye Zhi Chen Min Zheng Yanning Liu 《Journal of cellular and molecular medicine》2017,21(11):2963-2973
Mesenchymal stem cell (MSC) transplantation alone may be insufficient for treatment of liver fibrosis because of complicated histopathological changes in the liver. Given that miR‐122 plays an essential role in liver fibrosis by negatively regulating the proliferation and transactivation of hepatic stellate cells (HSCs), this study investigated whether miR‐122 modification can improve the therapeutic efficacy of adipose tissue‐derived MSCs in treating liver fibrosis. MiR‐122‐modified AMSCs (AMSC‐122) were constructed through lentivirus‐mediated transfer of pre‐miR‐122. MiR‐122‐modified AMSCs expressed high level of miR‐122, while they retained their phenotype and differentiation potential as naïve AMSCs. AMSC‐122 more effectively suppressed the proliferation of and collagen maturation in HSCs than scramble miRNA‐modified AMSCs. In addition, AMSC‐derived exosomes mediated the miR‐122 communication between AMSCs and HSCs, further affecting the expression levels of miR‐122 target genes, such as insulin‐like growth factor receptor 1 (IGF1R), Cyclin G(1) (CCNG1) and prolyl‐4‐hydroxylase α1 (P4HA1), which are involved in proliferation of and collagen maturation in HSCs. Moreover, miR‐122 modification enhanced the therapeutic efficacy of AMSCs in the treatment of carbon tetrachloride (CCl4)‐induced liver fibrosis by suppressing the activation of HSCs and alleviating collagen deposition. Results demonstrate that miR‐122 modification improves the therapeutic efficacy of AMSCs through exosome‐mediated miR‐122 communication; thus, miR‐122 modification is a new potential strategy for treatment of liver fibrosis. 相似文献
6.
Jinglan Hong Xiaofei Han Yilu Chen Meng Wang Liping Ye Congcong Qi Xiangzhi Li 《The International Journal of Life Cycle Assessment》2017,22(7):1054-1064
Purpose
The improper handling of industrial hazardous waste (IHW), which comprises large amounts of toxic chemicals, heavy metals, or irradiation substances, is a considerable threat to human health and the environment. This study aims to quantify the life cycle environmental impacts of IHW landfilling and incineration in China, to identify its key factors, to improve its potential effects, and to establish a hazardous waste disposal inventory.Methods
Life cycle assessment was conducted using the ReCiPe model to estimate the environmental impact of IHW landfilling and incineration. The characterization factors for the human toxicity and freshwater ecotoxicity categories shown in the ReCiPe were updated based on the geographies, population, food intake, and environmental conditions in China.Results and discussion
The overall environmental burden was mainly attributed to the carcinogen category. The national carcinogen burden in 2014 at 37.8 CTUh was dominated by diesel consumption, cement and sodium hydroxide production, direct emission, transportation, and electricity generation stages caused by direct mercury and arsenic emissions, as well as indirect chromium emission. Although the atmospheric mercury emission directly caused by IHW incineration was comparative with the emission levels of developed countries, the annual direct mercury emission accounted for approximately 0.1% of the national mercury emission.Conclusions
The key factors contributing to the reduction of the national environmental burden include the increasing diesel and electricity consumption efficiency, the reduction of cement and sodium hydroxide use, the development of air pollutant controlling systems, the reduction of transport distance between IHW disposers to suppliers, and the improvement of IHW recycling and reuse technologies.7.
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A new species of the genus Amolops Cope,1865 is described from Xinduqiao,Kangding,Sichuan.It was previously identified as Amolops kangtingensis,which is synonymized to Amolops mantzorum in this study.The new species,Amolops xinduqiao sp.nov.,is distinguished from all other congeners by the following combination of characters:(1) medium body size,adult males SVL 41.2-47.5 mm (n=15,average 43.9 mm),adult females SVL 48.5-56.6 mm (n=15,average 52.5 mm);(2) head length equal to width or slightly wider than long;(3) tympanum small,but distinct;(4) vomerine teeth in two tiny rows,separated by a space about one vomerine teeth row;(5) bony projections on lower jaw absent;(6) dorsolateral folds usually absent;(7) tarsal folds or glands on tarsus absent;(8) circummarginal groove on disc of finger Ⅰ absent;(9) tibiotarsal articulation reaching nostril or beyond;(10) webs of toe Ⅳ reaching to distal articulation,other toes fully webbed to disc;and (11) vocal sac absent in males. 相似文献
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