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41.
42.
Changsung Kim 《BMB reports》2015,48(5):256-265
Cardiovascular and neurodegenerative diseases are major health threats in many
developed countries. Recently, target tissues derived from human embryonic stem
(hES) cells and induced pluripotent stem cells (iPSCs), such as cardiomyocytes
(CMs) or neurons, have been actively mobilized for drug screening. Knowledge of
drug toxicity and efficacy obtained using stem cell-derived tissues could
parallel that obtained from human trials. Furthermore, iPSC disease models could
be advantageous in the development of personalized medicine in various parts of
disease sectors. To obtain the maximum benefit from iPSCs in disease modeling,
researchers are now focusing on aging, maturation, and metabolism to
recapitulate the pathological features seen in patients. Compared to pediatric
disease modeling, adult-onset disease modeling with iPSCs requires proper
maturation for full manifestation of pathological features. Herein, the success
of iPSC technology, focusing on patient-specific drug treatment,
maturation-based disease modeling, and alternative approaches to compensate for
the current limitations of patient iPSC modeling, will be further discussed.
[BMB Reports 2015; 48(5): 256-265] 相似文献
43.
44.
Yunhe Meng Xixi Shao Yan Wang Yumei Li Xiaojian Zheng Gongyuan Wei Seon-Won Kim Chonglong Wang 《Biotechnology and bioengineering》2020,117(11):3499-3507
Squalene is a lipophilic and non-volatile triterpene with many industrial applications for food, pharmaceuticals, and cosmetics. Metabolic engineering focused on optimization of the production pathway suffer from little success in improving titers because of a limited space of the cell membrane accommodating the lipophilic product. Extension of cell membrane would be a promising approach to overcome the storage limitation for successful production of squalene. In this study, Escherichia coli was engineered for squalene production by overexpression of some membrane proteins. The highest production of 612 mg/L was observed in the engineered E. coli with overexpression of Tsr, a serine chemoreceptor protein, which induced invagination of inner membrane to form multilayered structure. It was also observed an increase in unsaturated fatty acid in membrane lipids composition, suggesting cellular response to maintain membrane fluidity against squalene accumulation in the engineered strain. This study potentiates the capability of E. coli for squalene production and provides an effective strategy for the enhanced production of such compounds. 相似文献
45.
88 rice and 75 soybean samples were collected from 8 provinces of Korea from March through September in 1988. The Fusarium mycotoxins, zearalenone was analyzed by direct competitive enzyme linked immunosorbent assay. 10.2% of rice and 9.3 % of soybean samples contained detectable zearalenone. The average levels of zearalenone of rice and soybean samples were 11.78μg/kg and 7.70μ/kg, respectively. 相似文献
46.
We have previously reported that in vitro HCV infection of cells of hepatocyte origin attenuates complement system at multiple steps, and attenuation also occurs in chronically HCV infected liver, irrespective of the disease stage. However, none of these regulations alone completely impaired complement pathways. Modulation of the upstream proteins involved in proteolytic processing of the complement cascade prior to convertase formation is critical in promoting the function of the complement system in response to infection. Here, we examined the regulation of C2 complement expression in hepatoma cells infected in vitro with cell culture grown virus, and validated our observations using randomly selected chronically HCV infected patient liver biopsy specimens. C2 mRNA expression was significantly inhibited, and classical C3 convertase (C4b2a) decreased. In separate experiments for C3 convertase function, C3b deposition onto bacterial membrane was reduced using HCV infected patient sera as compared to uninfected control, suggesting impaired C3 convertase. Further, iC3b level, a proteolytically inactive form of C3b, was lower in HCV infected patient sera, reflecting impairment of both C3 convertase and Factor I activity. The expression level of Factor I was significantly reduced in HCV infected liver biopsy specimens, while Factor H level remained unchanged or enhanced. Together, these results suggested that inhibition of C3 convertase activity is an additional cumulative effect for attenuation of complement system adopted by HCV for weakening innate immune response. 相似文献
47.
J-H Kim K W Park E-W Lee W-S Jang J Seo S Shin K-A Hwang J Song 《Cell death and differentiation》2014,21(4):594-603
The central regulator of adipogenesis, PPARγ, is a nuclear receptor that is linked to obesity and metabolic diseases. Here we report that MKRN1 is an E3 ligase of PPARγ that induces its ubiquitination, followed by proteasome-dependent degradation. Furthermore, we identified two lysine sites at 184 and 185 that appear to be targeted for ubiquitination by MKRN1. Stable overexpression of MKRN1 reduced PPARγ protein levels and suppressed adipocyte differentiation in 3T3-L1 and C3H10T1/2 cells. In contrast, MKRN1 depletion stimulated adipocyte differentiation in these cells. Finally, MKRN1 knockout MEFs showed an increased capacity for adipocyte differentiation compared with wild-type MEFs, with a concomitant increase of PPARγ and adipogenic markers. Together, these data indicate that MKRN1 is an elusive PPARγ E3 ligase that targets PPARγ for proteasomal degradation by ubiquitin-dependent pathways, and further depict MKRN1 as a novel target for diseases involving PPARγ. 相似文献
48.
Yarrowia lipolytica KCCM50506, which transforms isobutyric acid to L-#-hydroxy isobutyric acid (L-#-HIBA), was screened. Chemostat cultures were carried out in jar fermentors at dilution rates of 0.02 hу to 0.12 hу. L-#-HIBA fermentation-regulating factors were determined to be specific growth rate, and concentrations of glucose and isobutyric acid in fermentor from analysis of steady-state data. The specific productivity of L-#-HIBA increased as the specific growth rate increased, apparently as a growth-associated type of product formation. A fed-batch culture was carried out under optimum conditions where the concentrations of glucose and isobutyric acid in the fermentor were maintained at 23 g lу and 9 g lу, respectively. The concentrations of cells and L-#-HIBA obtained at the end of fermentation were 20 g lу and 49 g lу, respectively, corresponding to 2.0 and 2.7 times more than concentrations in batch culture. 相似文献
49.
Plasmonics - We investigate aluminum nanopatch/nanohole arrays surrounded by a dielectric material on plastic substrates for large area color printing. In this specific arrangement, metallic... 相似文献
50.
Tristan J. Iseli Nigel Turner Xiao-Yi Zeng Gregory J. Cooney Edward W. Kraegen Sheng Yao Yang Ye David E. James Ji-Ming Ye 《PloS one》2013,8(4)
We recently showed that bitter melon-derived triterpenoids (BMTs) activate AMPK and increase GLUT4 translocation to the plasma membrane in vitro, and improve glucose disposal in insulin resistant models in vivo. Here we interrogated the mechanism by which these novel compounds activate AMPK, a leading anti-diabetic drug target. BMTs did not activate AMPK directly in an allosteric manner as AMP or the Abbott compound (A-769662) does, nor did they activate AMPK by inhibiting cellular respiration like many commonly used anti-diabetic medications. BMTs increased AMPK activity in both L6 myotubes and LKB1-deficient HeLa cells by 20–35%. Incubation with the CaMKKβ inhibitor, STO-609, completely attenuated this effect suggesting a key role for CaMKKβ in this activation. Incubation of L6 myotubes with the calcium chelator EGTA-AM did not alter this activation suggesting that the BMT-dependent activation was Ca2+-independent. We therefore propose that CaMKKβ is a key upstream kinase for BMT-induced activation of AMPK. 相似文献