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31.
Alexandra Elliott Laura Schoenlaub Danielle Freches William Mitchell Guoquan Zhang 《Infection and immunity》2015,83(8):3104-3113
Coxiella burnetii is an obligate intracellular Gram-negative bacterium that causes the zoonotic disease Q fever. Although Q fever is mainly transmitted by aerosol infection, study of the immune responses in the lung following pulmonary C. burnetii infection is lacking. Neutrophils are considered the first immune cell to migrate into the lung and play an important role in host defense against aerosol infection with microbial pathogens. However, the role of neutrophils in the host defense against C. burnetii infection remains unclear. To determine the role of neutrophils in protective immunity against C. burnetii infection, the RB6-8C5 antibody was used to deplete neutrophils in mice before intranasal infection with C. burnetii. The results indicated that neutrophil-depleted mice developed more severe disease than their wild-type counterparts, suggesting that neutrophils play an important role in host defense against C. burnetii pulmonary infection. We also found that neither CXC chemokine receptor 2 (CXCR2) nor interleukin-17 (IL-17) receptor (IL-17R) deficiency changed the severity of disease following intranasal C. burnetii challenge, suggesting that keratinocyte-derived chemokine and IL-17 may not play essential roles in the response to C. burnetii infection. However, significantly higher C. burnetii genome copy numbers were detected in the lungs of IL-1R−/− mice at 14 days postinfection. This indicates that IL-1 may be important for the clearance of C. burnetii from the lungs following intranasal infection. Our results also suggest that neutrophils are involved in protecting vaccinated mice from C. burnetii challenge-induced disease. This is the first study to demonstrate an important role for neutrophils in protective immunity against C. burnetii infection. 相似文献
32.
Y.R. Song B. Wu Y.T. Yang J. Chen L.J. Zhang Z.W. Zhang H.Y. Shi C.L. Huang J.X. Pan P. Xie 《Brazilian journal of medical and biological research》2015,48(11):973-982
Bipolar disorder (BD) is a common psychiatric mood disorder affecting more than 1-2%
of the general population of different European countries. Unfortunately, there is no
objective laboratory-based test to aid BD diagnosis or monitor its progression, and
little is known about the molecular basis of BD. Here, we performed a comparative
proteomic study to identify differentially expressed plasma proteins in various BD
mood states (depressed BD, manic BD, and euthymic BD) relative to healthy controls. A
total of 10 euthymic BD, 20 depressed BD, 15 manic BD, and 20 demographically matched
healthy control subjects were recruited. Seven high-abundance proteins were
immunodepleted in plasma samples from the 4 experimental groups, which were then
subjected to proteome-wide expression profiling by two-dimensional electrophoresis
and matrix-assisted laser desorption/ionization-time-of-flight/time-of-flight tandem
mass spectrometry. Proteomic results were validated by immunoblotting and
bioinformatically analyzed using MetaCore. From a total of 32 proteins identified
with 1.5-fold changes in expression compared with healthy controls, 16 proteins were
perturbed in BD independent of mood state, while 16 proteins were specifically
associated with particular BD mood states. Two mood-independent differential
proteins, apolipoprotein (Apo) A1 and Apo L1, suggest that BD pathophysiology may be
associated with early perturbations in lipid metabolism. Moreover, down-regulation of
one mood-dependent protein, carbonic anhydrase 1 (CA-1), suggests it may be involved
in the pathophysiology of depressive episodes in BD. Thus, BD pathophysiology may be
associated with early perturbations in lipid metabolism that are independent of mood
state, while CA-1 may be involved in the pathophysiology of depressive episodes. 相似文献
33.
Zhenzhen Zhang Mark Garzotto Tomasz M. Beer Philippe Thuillier Stephen Lieberman Motomi Mori 《Nutrition and cancer》2016,68(8):1309-1319
Animal and human studies suggest fish oil and green tea may have protective effect on prostate cancer. Fatty acid synthase (FAS) has been hypothesized to be linked to chemoprotective effects of both compounds. This study evaluated the independent and joint effects of fish oil (FO) and green tea supplement (epigallocatechin-3-gallate, EGCG) on FAS and Ki-67 levels in prostate tissue. Through a double-blinded, randomized controlled trial with 2 × 2 factorial design, 89 men scheduled for repeat prostate biopsy following an initial negative prostate biopsy were randomized into either FO alone (1.9 g DHA + EPA/day), EGCG alone (600 mg/day), a combination of FO and EGCG, or placebo. We used linear mixed-effects models to test the differences of prostate tissue FAS and Ki-67 by immunohistochemistry between pre- and post-intervention within each group, as well as between treatment groups. Results did not show significant difference among treatment groups in pre-to-post-intervention changes of FAS (P = 0.69) or Ki-67 (P = 0.26). Comparing placebo group with any of the treatment groups, we did not find significant difference in FAS or Ki-67 changes (all P > 0.05). Results indicate FO or EGCG supplementation for a short duration may not be sufficient to produce biologically meaningful changes in FAS or Ki-67 levels in prostate tissue. 相似文献
34.
目的以基因表达数据集资料为研究对象,分析BCAN基因在肾透明细胞癌中的表达情况以及对患者预后的影响。方法在Oncomine数据库中挖掘BCAN在肾透明细胞癌(ccRCC)中的表达情况。从TCGA数据库中获取ccRCC患者临床资料和目的基因的表达信息并进行统计分析。利用GEO数据库中GSE73731数据集的ccRCC样本进行基因富集分析。利用String数据库分析与BCAN相关的蛋白。结果BCAN低表达组的ccRCC患者在病理分期及T分期方面低于高表达组(P<0.001;P=0.001);N分期及M分期差异无统计学意义(P>0.05)。BCAN低表达组患者的总生存期优于高表达组(P=0.033)。BCAN基因高表达组的样本主要富集在KRAS信号通路。结论BCAN可以通过多种途径来促进肿瘤细胞的侵袭能力,有望成为ccRCC不良预后的重要生物标志物之一。 相似文献
35.
Yinlei
Wen Huaguang Zhang Hanguang Su He Ren 《Optimal control applications & methods.》2020,41(4):1233-1250
In this article, a model-free off-policy reinforcement learning algorithm is applied to address the optimal tracking problem based on multiplayer non-zero-sum games for discrete-time linear systems. In contrast to the traditional method and the policy iteration method for solving the optimal tracking problems, the proposed algorithm operates with the system data rather than the knowledge of the system dynamics. For performing the proposed algorithm, an auxiliary augmented system is constructed via assembling the original system and the reference trajectory while a discount factor is introduced into the performance indexes. It is analyzed that the solutions of the proposed algorithm converge to the Nash equilibrium and the result is not influenced by the probing noise. Two simulations are presented to verify the feasibility and effectiveness of the proposed algorithm. 相似文献
36.
37.
目的 利用频域光学相干断层扫描深度增强(enhanced depth imaging spectral domain optical coherence tomography,EDI SD-OCT)观察糖尿病黄斑水肿(diabetic macular edema,DME)患者脉络膜厚度(choroidal thickness,CT)的变化及结构特点,探讨DME病变程度与CT的关系。方法 纳入2型糖尿病患者共123例204眼,其中69眼诊断为DME(DME组),135眼无黄斑水肿为对照组。DME眼依据OCT形态学特点进一步分为视网膜弥漫性增厚(diffuse retinal thickness,DRT)型(34眼)、黄斑囊样水肿(cystoid macular edema,CME)型(19眼)和浆液性视网膜脱离(serous retinal detachment,SRD)型(16眼),利用EDI-OCT分别测量黄斑中心凹下CT和以黄斑为中心上、下、鼻、颞500 μm、1000 μm、1500 μm、2000 μm处CT。结果 DME组黄斑中心凹下CT为(326.72±90.15)μm,对照组为(320.17±106.46)μm,两组之间无统计学差异,但黄斑中心凹下CT与视网膜厚度间具有明显正相关关系(r=0.270,P=0.025)。DME亚型CT分别为:DRT型(303.94±81.47)μm、CME型(304.42±73.98)μm和SRD型(401.63±88.80)μm,SRD型CT明显高于其他亚型(P<0.05),此外,SRD型的周边CT同样呈现均匀一致的增厚;鼻侧CT从500 μm至2000 μm呈距离敏感性降低(P<0.05),但SRD型鼻侧CT降低幅度明显变缓(P=0.195)。结论 SRD型黄斑水肿患者CT在中心凹下及周边部均显著增厚,CT与DME病变程度之间有一定相关性。 相似文献
38.
Susan E. Hickman Alexia M. Torke Greg A. Sachs Rebecca L. Sudore Anne L. Myers Qing Tang Giorgos Bakoyannis Bernard J. Hammes 《Journal of pain and symptom management》2019,57(6):1143-1150.e5
ContextIt is especially important that patients are well informed when making high-stakes, preference-sensitive decisions like those on the Physician Orders for Life-Sustaining Treatment (POLST) form. However, there is currently no way to easily evaluate whether patients understand key concepts when making these important decisions.ObjectivesTo develop a POLST knowledge survey.MethodsExpert (n = 62) ratings of key POLST facts were used to select items for a POLST knowledge survey. The survey was administered to nursing facility residents (n = 97) and surrogate decision-makers (n = 112). A subset (n = 135) were re-administered the survey after a standardized advance care planning discussion to assess the scale's responsiveness to change.ResultsThe 19-item survey demonstrated adequate reliability (α = 0.72.). Residents' scores (x = 11.4, standard deviation 3.3) were significantly lower than surrogate scores (x = 14.7, standard deviation 2.5) (P < 0.001). Scores for both groups increased significantly after administration of a standardized advance care planning discussion (P < 0.001). Although being a surrogate, age, race, education, cognitive functioning, and health literacy were significantly associated with higher POLST Knowledge Survey scores in univariate analyses, only being a surrogate (P < 0.001) and being white (P = 0.028) remained significantly associated with higher scores in multivariate analyses.ConclusionThe 19-item POLST Knowledge Survey demonstrated adequate reliability and responsiveness to change. Findings suggest the survey could be used to identify knowledge deficits and provide targeted education to ensure adequate understanding of key clinical decisions when completing POLST. 相似文献
39.
40.
Jinju Wang Shuzhen Chen Wenfeng Zhang Yanfang Chen Ji C. Bihl 《CNS Neuroscience & Therapeutics》2020,26(12):1255
AimsWe previously showed that the protective effects of endothelial progenitor cells (EPCs)‐released exosomes (EPC‐EXs) on endothelium in diabetes. However, whether EPC‐EXs are protective in diabetic ischemic stroke is unknown. Here, we investigated the effects of EPC‐EXs on diabetic stroke mice and tested whether miR‐126 enriched EPC‐EXs (EPC‐EXsmiR126) have enhanced efficacy.MethodsThe db/db mice subjected to ischemic stroke were intravenously administrated with EPC‐EXs 2 hours after ischemic stroke. The infarct volume, cerebral microvascular density (MVD), cerebral blood flow (CBF), neurological function, angiogenesis and neurogenesis, and levels of cleaved caspase‐3, miR‐126, and VEGFR2 were measured on day 2 and 14.ResultsWe found that (a) injected EPC‐EXs merged with brain endothelial cells, neurons, astrocytes, and microglia in the peri‐infarct area; (b) EPC‐EXsmiR126 were more effective than EPC‐EXs in decreasing infarct size and increasing CBF and MVD, and in promoting angiogenesis and neurogenesis as well as neurological functional recovery; (c) These effects were accompanied with downregulated cleaved caspase‐3 on day 2 and vascular endothelial growth factor receptor 2 (VEGFR2) upregulation till day 14.ConclusionOur results indicate that enrichment of miR126 enhanced the therapeutic efficacy of EPC‐EXs on diabetic ischemic stroke by attenuating acute injury and promoting neurological function recovery. 相似文献