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931.
932.
Kyo Chul Koo Doo Hee Shim Chang Mo Yang Saet-Byul Lee Shi Mun Kim Tae Young Shin Kwang Hyun Kim Ho Geun Yoon Koon Ho Rha Jae Myun Lee Sung Joon Hong 《PloS one》2013,8(11)
Background
Natural cytotoxicity, mediated by natural killer (NK) cells plays an important role in the inhibition and elimination of malignant tumor cells. To investigate the immunoregulatory role of NK cells and their potential as diagnostic markers, NK cell activity (NKA) was analyzed in prostate cancer (PCa) patients with particular focus on NK cell subset distribution.Methods
Prospective data of NKA and NK cell subset distribution patterns were measured from 51 patients initially diagnosed with PCa and 54 healthy controls. NKA was represented by IFN-γ levels after stimulation of the peripheral blood with Promoca®. To determine the distribution of NK cell subsets, PBMCs were stained with fluorochrome-conjugated monoclonal antibodies. Then, CD16+CD56dim and CD16−CD56bright cells gated on CD56+CD3− cells were analyzed using a flow-cytometer.Results
NKA and the proportion of CD56bright cells were significantly lower in PCa patients compared to controls (430.9 pg/ml vs. 975.2 pg/ml and 2.3% vs. 3.8%, respectively; p<0.001). Both tended to gradually decrease according to cancer stage progression (p for trend = 0.001). A significantly higher CD56dim-to-CD56bright cell ratio was observed in PCa patients (41.8 vs. 30.3; p<0.001) along with a gradual increase according to cancer stage progression (p for trend = 0.001), implying a significant reduction of CD56bright cells in relation to the alteration of CD56dim cells. The sensitivity and the specificity of NKA regarding PCa detection were 72% and 74%, respectively (best cut-off value at 530.9 pg/ml, AUC = 0.786).Conclusions
Reduction of CD56bright cells may precede NK cell dysfunction, leading to impaired cytotoxicity against PCa cells. These observations may explain one of the mechanisms behind NK cell dysfunction observed in PCa microenvironment and lend support to the development of future cancer immunotherapeutic strategies. 相似文献933.
Under previously developed culture conditions, mouse and human intestinal epithelia can be cultured and expanded over long periods. These so-called organoids recapitulate the three-dimensional architecture of the gut epithelium, and consist of all major intestinal cell types. One key advantage of these ex vivo cultures is their accessibility to live imaging. So far the establishment of transgenic fluorescent reporter organoids has required the generation of transgenic mice, a laborious and time-consuming process, which cannot be extended to human cultures. Here we present a transfection protocol that enables the generation of recombinant mouse and human reporter organoids using BAC (bacterial artificial chromosome) technology. 相似文献
934.
935.
Jarom Heijmans Jooske F. van Lidth de Jeude Bon-Kyoung Koo Sanne L. Rosekrans Mattheus C.B. Wielenga Marc van de Wetering Marc Ferrante Amy S. Lee Jos J.M. Onderwater James C. Paton Adrienne W. Paton A. Mieke Mommaas Liudmila L. Kodach James C. Hardwick Daniël W. Hommes Hans Clevers Vanesa Muncan Gijs R. van den Brink 《Cell reports》2013,3(4):1128-1139
Highlights? ER stress is induced at the stem cell to TA cell transition in the intestinal epithelium ? ER stress causes loss of stemness in intestinal epithelial stem cells ? Loss of stemness depends on eIF2alpha signaling ? PERK-eIF2alpha signaling is required for normal stem cell differentiation 相似文献
936.
A chemical complementation approach reveals genes and interactions of flavonoids with other pathways
Abraham J. K. Koo Andres Bohorquez‐Restrepo Gregg A. Howe Erich Grotewold 《The Plant journal : for cell and molecular biology》2013,74(3):383-397
In addition to the classical functions of flavonoids in the response to biotic/abiotic stress conditions, these phenolic compounds have been implicated in the modulation of various developmental processes. These findings suggest that flavonoids are more integral components of the plant signaling machinery than traditionally recognized. To understand how flux through the flavonoid pathway affects plant cellular processes, we used wild‐type and chalcone isomerase mutant (transparent testa 5, tt5) seedlings grown under anthocyanin inductive conditions, in the presence or absence of the flavonoid intermediate naringenin, the product of the chalcone isomerase enzyme. Because flavonoid biosynthetic genes are expressed under anthocyanin inductive conditions regardless of whether anthocyanins are formed or not, this system provides an excellent opportunity to specifically investigate the molecular changes associated with increased flux through the flavonoid pathway. By assessing genome‐wide mRNA accumulation changes in naringenin‐treated and untreated tt5 and wild‐type seedlings, we identified a flavonoid‐responsive gene set associated with cellular trafficking, stress responses and cellular signaling. Jasmonate biosynthetic genes were highly represented among the signaling pathways induced by increased flux through the flavonoid pathway. In contrast to studies showing a role for flavonoids in the control of auxin transport, no effect on auxin‐responsive genes was observed. Taken together, our data suggest that Arabidopsis can sense flavonoids as a signal for multiple fundamental cellular processes. 相似文献
937.
Lipase-catalyzed caffeic acid phenethyl ester (CAPE) synthesis in ionic liquid, 1-ethyl-3-methylimidazolium bis[(trifluoromethyl)sulfonyl]imide ([Emim][Tf2N]), was investigated in this study. The effects of several reaction conditions, including reaction time, reaction temperature, substrate molar ratio of phenethyl alcohol to caffeic acid (CA), and weight ratio of enzyme to CA, on CAPE yield were examined. In a single parameter study, the highest CAPE yield in [Emim][Tf2N] was obtained at 70 °C with a substrate molar ratio of 30:1 and weight ratio of enzyme to CA of 15:1. Based on these results, response surface methodology (RSM) with a 3-level-4-factor central composite rotatable design (CCRD) was adopted to evaluate enzymatic synthesis of CAPE in [Emim][Tf2N]. The four major factors were reaction time (36–60 h), reaction temperature (65–75 °C), substrate molar ratio of phenethyl alcohol to CA (20:1–40:1), and weight ratio of enzyme to CA (10:1–20:1). A quadratic equation model was used to analyze the experimental data at a 95 % confidence level (p < 0.05). A maximum conversion yield of 99.8 % was obtained under the optimized reaction conditions [60 h, 73.7 °C, substrate molar ratio of phenethyl alcohol to CA (27.1:1), and weight ratio of enzyme to CA (17.8:1)] established by our statistical method, whereas the experimental conversion yield was 96.6 ± 2 %. 相似文献
938.
Bae GS Kim MS Jeong J Lee HY Park KC Koo BS Kim BJ Kim TH Lee SH Hwang SY Shin YK Song HJ Park SJ 《Biochemical and biophysical research communications》2011,(3):382-388
Piperine is a phenolic component of black pepper (Piper nigrum) and long pepper (Piper longum), fruits used in traditional Asian medicine. Our previous study showed that piperine inhibits lipopolysaccharide-induced inflammatory responses. In this study, we investigated whether piperine reduces the severity of cerulein-induced acute pancreatitis (AP). Administration of piperine reduced histologic damage and myeloperoxidase (MPO) activity in the pancreas and ameliorated many of the examined laboratory parameters, including the pancreatic weight (PW) to body weight (BW) ratio, as well as serum levels of amylase and lipase and trypsin activity. Furthermore, piperine pretreatment reduced the production of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, and IL-6 during cerulein-induced AP. In accordance with in vivo results, piperine reduced cell death, amylase and lipase activity, and cytokine production in isolated cerulein-treated pancreatic acinar cells. In addition, piperine inhibited the activation of mitogen-activated protein kinases (MAPKs). These findings suggest that the anti-inflammatory effect of piperine in cerulein-induced AP is mediated by inhibiting the activation of MAPKs. Thus, piperine may have a protective effect against AP. 相似文献
939.
940.