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Young Seung Lee Jae‐Young Chung Sang Bong Jeon Ae‐Kyoung Lee Hyung‐Do Choi 《Bioelectromagnetics》2019,40(7):445-457
This paper proposes a novel in vitro exposure system operating at millimeter‐wave (mmWave) 28 GHz, one of the frequency bands under consideration for fifth generation (5G) communication. We employed the field uniformity concept along cross‐sectional observation planes at shorter distances from the radiation antenna for better efficiency and a small‐size system. A choke‐ring antenna was designed for this purpose in consideration of a wider beamwidth (BW) and a symmetric far‐field pattern across three principal planes. The permittivity of Dulbecco's modified Eagle's medium solution was measured to examine the specific absorption rate (SAR) of the skin cell layer inside a Petri dish model for a three‐dimensional (3D) cell culture in vitro experiment. The best deployment of Petri dishes, taking into account a geometrical field symmetry, was proposed. Local SAR values within the cell layer among the Petri dishes were determined with different polarization angles. It was determined that this polarization effect should be considered when the actual exposure and deployment were conducted. We finally proposed an in vitro exposure system based on the field uniformity including downward exposure from an antenna for 3D cell culture experiments. A small‐size chamber system was obtained, and the size was estimated using the planar near‐field chamber design rule. Bioelectromagnetics. 2019;40:445–457. © 2019 Bioelectromagnetics Society 相似文献
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Hae Yon Jeon Jinwook Choi Lianne Kraaier Young Hoon Kim David Eisenbarth Kijong Yi JuGyeong Kang Jin Woo Kim Hyo Sup Shim JooHyeon Lee DaeSik Lim 《The EMBO journal》2022,41(8)
Tissue homeostasis requires lineage fidelity of stem cells. Dysregulation of cell fate specification and differentiation leads to various diseases, yet the cellular and molecular mechanisms governing these processes remain elusive. We demonstrate that YAP/TAZ activation reprograms airway secretory cells, which subsequently lose their cellular identity and acquire squamous alveolar type 1 (AT1) fate in the lung. This cell fate conversion is mediated via distinctive transitional cell states of damage‐associated transient progenitors (DATPs), recently shown to emerge during injury repair in mouse and human lungs. We further describe a YAP/TAZ signaling cascade to be integral for the fate conversion of secretory cells into AT1 fate, by modulating mTORC1/ATF4‐mediated amino acid metabolism in vivo. Importantly, we observed aberrant activation of the YAP/TAZ‐mTORC1‐ATF4 axis in the altered airway epithelium of bronchiolitis obliterans syndrome, including substantial emergence of DATPs and AT1 cells with severe pulmonary fibrosis. Genetic and pharmacologic inhibition of mTORC1 activity suppresses lineage alteration and subepithelial fibrosis driven by YAP/TAZ activation, proposing a potential therapeutic target for human fibrotic lung diseases. 相似文献
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Zarka Sarwar Nusrat Nabi Sameer Ahmed Bhat Syed Qaaifah Gillani Irfana Reshi Misbah Un Nisa Guillaume Adelmant Jarrod A. Marto Shaida Andrabi 《The Journal of biological chemistry》2022,298(2)
Deleted in Breast Cancer 1 (DBC1) is an important metabolic sensor. Previous studies have implicated DBC1 in various cellular functions, notably cell proliferation, apoptosis, histone modification, and adipogenesis. However, current reports about the role of DBC1 in tumorigenesis are controversial and designate DBC1 alternatively as a tumor suppressor or a tumor promoter. In the present study, we report that polyoma small T antigen (PyST) associates with DBC1 in mammalian cells, and this interaction leads to the posttranslational downregulation of DBC1 protein levels. When coexpressed, DBC1 overcomes PyST-induced mitotic arrest and promotes the exit of cells from mitosis. Using both transient and stable modes of PyST expression, we also show that cellular DBC1 is subjected to degradation by LKB1, a tumor suppressor and cellular energy sensor kinase, in an AMP kinase-independent manner. Moreover, LKB1 negatively regulates the phosphorylation as well as activity of the prosurvival kinase AKT1 through DBC1 and its downstream pseudokinase substrate, Tribbles 3 (TRB3). Using both transient transfection and stable cell line approaches as well as soft agar assay, we demonstrate that DBC1 has oncogenic potential. In conclusion, our study provides insight into a novel signaling axis that connects LKB1, DBC1, TRB3, and AKT1. We propose that the LKB1–DBC1–AKT1 signaling paradigm may have an important role in the regulation of cell cycle and apoptosis and consequently tumorigenesis. 相似文献
86.
Seo-Jung Han Jae Eun Jung Do Hee Oh Minsup Kim Jae-Min Kim Kyung-Sook Chung Hee-Soo Han Jeong-Hun Lee Kyung-Tae Lee Hee Jin Jeong In Ho Park Eunkyeong Jeon Jeon-Soo Shin Dongkeun Hwang Art E. Cho Duck-Hyung Lee Taebo Sim 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1257
Identification of highly selective type II kinase inhibitors is described. Two different chiral peptidomimetic scaffolds were introduced on the tail region of non-selective type II kinase inhibitor GNF-7 to enhance the selectivity. Kinome-wide selectivity profiling analysis showed that type II kinase inhibitor 7a potently inhibited Lck kinase with great selectivity (IC50 of 23.0 nM). It was found that 7a and its derivatives possessed high selectivity for Lck over even structurally conserved all Src family kinases. We also observed that 7a inhibited Lck activation in Jurkat T cells. Moreover, 7a was found to alleviate clinical symptoms in DSS-induced colitis mice. This study provides a novel insight into the design of selective type II kinase inhibitors by adopting chiral peptidomimetic moieties on the tail region. 相似文献
87.
Previously, we showed that estradiol replacement in ovariectomized rats produced prominent increases in serum and liver alpha-tocopherol (alphaTP). The present study was conducted to examine whether the estrogen-induced increase in the liver concentrations of alphaTP affects its biliary secretion and the fatty acid compositions of hepatic and biliary lipids. Ten ovariectomized rats were assigned to two groups: five rats were implanted subcutaneously with time-release estradiol pellets (OXE; 25 microg/day/rat) and five with placebo (OXP). Twice daily rats were pair-fed a modified AIN-93G diet containing soybean oil. At 5 weeks, bile was collected via a bile cannula hourly for 8 hours during duodenal infusion of a lipid emulsion (565 micromol triolein and 396 micromol Na-taurocholate/24 mL phosphate buffered saline, pH 6.45) at 3.0 mL/hr. During the 8-hour period, no difference was noted in the hourly rate of bile flow (0.95 mL/hr in OXE rats vs. 0.99 mL/hr in OXP rats). The biliary output of alphaTP for 8 hours was higher in OXE rats (51.6 +/- 3.6 nmol) than OXP rats (31.7 +/- 2.9 nmol). Likewise, the liver concentration of alphaTP was higher in OXE rats (81.9 +/- 3.5 nmol/g liver) than in OXP rats (53.3 +/- 7.4 nmol/g liver). The biliary secretion of phospholipids (PL) for 8 hours was significantly (P < 0.05) higher in OXE rats (55.1 +/- 4.9 micromol) than in OXP rats (42.3 +/- 4.7 micromol). Among the PL fatty acids, the outputs of 20:4 and 22:6n-3 were increased most markedly by estradiol replacement. The total outputs of 22:6n-3 for 8 hours in OXE and OXP rats were 2.95 +/- 0.20 micromol and 1.37 +/- 0.23 micromol, respectively. In the liver, the concentrations of PL 22:5n-3 and 22:6n-3 were elevated significantly in OXE rats. The present results suggest that estradiol may protect hepatic PL and membranes against oxidative damage by improving the liver status of alphaTP. 相似文献
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Characteristics of the killing mechanism of human natural killer cells against hepatocellular carcinoma cell lines HepG2 and Hep3B 总被引:3,自引:0,他引:3
Kim HR Park HJ Park JH Kim SJ Kim K Kim J 《Cancer immunology, immunotherapy : CII》2004,53(5):461-470
Purpose Unlike normal hepatocytes, most hepatocellular carcinomas (HCCs) are quite resistant to death receptor-mediated apoptosis when the cell surface death receptor is cross linked with either agonistic antibodies or soluble death ligand proteins in vitro. The resistance might play an essential role in the escape from the host immune surveillance; however, it has not been directly demonstrated that HCCs are actually resistant to natural killer (NK) cell-mediated death. Therefore, this study investigated the molecular mechanism of NK cell-mediated cytotoxicity against the HCCs, HepG2, and Hep3B, using two distinct cytotoxic assays: a 4-h 51Cr-release assay and a 2-h [3H] thymidine release assay which selectively measures the extent of necrotic and apoptotic target cell death, respectively.Methods Most of the target cells exhibited marked morphologic changes when they were co-incubated with the NK cells, and the NK cytotoxicity against these HCCs was comparable to that against K562, a NK-sensitive leukemia cell line, when the cytotoxicity was assessed by a 4-h 51Cr release assay.Results The NK cells also induced significant apoptotic cell death in the Hep3B targets, but not in the HepG2 targets, when the cytotoxicity was assessed by a 2-h [3H]-thymidine release assay. In agreement with these results, procaspase-3 was activated in the Hep3B targets, but not in the HepG2 targets. Interestingly, mildly fixed NK cells had no detectable activity in the 4-h 51Cr release assay against both HepG2 and Hep3B targets, while they were similarly effective as the untreated NK cells in the 2-h [3H]-thymidine release assay, suggesting that the level of apoptotic cell death of the Hep3B targets is granule independent and might be primarily mediated by the death ligands of the NK cells.Conclusion This study found that a tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL)/TRAIL receptor interaction is involved in the NK cell-mediated apoptotic death of the Hep3B targets, but a Fas/Fas ligand (FasL) interaction is not. 相似文献