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91.
miR‐495 sensitizes MDR cancer cells to the combination of doxorubicin and taxol by inhibiting MDR1 expression 下载免费PDF全文
Zhenyou Zou Ruyi Zou Dan Zong Yonghong Shi Jinyao Chen Jie Huang Jiahui Zhu Liguan Chen Xiaoyan Bao Yuan Liu Weihao Liu Wenhui Huang Jingsang Hu Zhi Chen Xiaojie Lao Chaoqun Chen Xiaoli Huang Yao Lu Xueyin Ni Daoquan Fang Dengqiang Wu Shuangshuang Lu Mingzhu Jiang Chenyang Qiu Yuya Wu Qisha Qiu Yanyuan Dong Yangyang Su Chenmin Zhao Zhihe Zhong Jing Cai Yong Liang 《Journal of cellular and molecular medicine》2017,21(9):1929-1943
MDR1 is highly expressed in MDR A2780DX5 ovarian cancer cells, MDR SGC7901R gastric cancer cells and recurrent tumours. It pumps cytoplasmic agents out of cells, leading to decreased drug accumulation in cells and making cancer cells susceptible to multidrug resistance. Here, we identified that miR‐495 was predicted to target ABCB1, which encodes protein MDR1. To reduce the drug efflux and reverse MDR in cancer cells, we overexpressed a miR‐495 mimic in SGC7901R and A2780DX cells and in transplanted MDR ovarian tumours in vivo. The results indicated that the expression of MDR1 in the above cells or tumours was suppressed and that subsequently the drug accumulation in the MDR cells was decreased, cell death was increased, and tumour growth was inhibited after treatment with taxol‐doxorubicin, demonstrating increased drug sensitivity. This study suggests that pre‐treatment with miR‐495 before chemotherapy could improve the curative effect on MDR1‐based MDR cancer. 相似文献
92.
In this study, the early stage of interfacial crystallisation behaviour of low molecular weight polyethylene (PE) and isotactic polypropylene (iPP) oligomer on the surface of carbon nanotubes (CNTs) with different diameters, chiralities and topography structures was studied using MD simulations. We started to simulate the effect of CNTs chirality and diameter on PE molecular chain orientation, and then the effect of CNTs topography structure on PE and iPP molecular chain orientation was investigated. Finally, some experiments were carried out to prove the simulated results. Our study shows that for CNTs with a diameter comparable with the radius of gyration (Rg) of a polymer chain, an easy orientation of PE chains along CNTs axis is observed for all the systems of the CNTs with different chiralities due to a geometric confinement effect. For CNTs with a much larger diameter, multiple orientation of PE chains is induced on its surface due to the lattice matching between graphite lattice and PE molecular chains. In this case, the chirality of CNTs dominates the orientation of graphite lattice, which determines the orientation of PE chains arrangement on CNTs surface. More importantly, it was found that the groove structure formed by CNT bundles is very useful for the stabilisation of polymer chain, and thus facilitates the orientation of molecular chain along the long axis of CNTs. As a result, a novel nanohybrid shish–kebab (NHSK) structure with CNTs acting as central shish while polymer lamellae as kebab can be successfully obtained for both PE with zigzag conformation and iPP with helical conformation. This simulation result was well supported by the experimental observation. Our study could provide not only a deep understanding of the origin of the polymer chain orientation on CNTs surface but also the guidance for the preparation of polymer/CNTs nanocomposites with novel NHSK structure. 相似文献
93.
江苏省海滩植被演替的研究 总被引:1,自引:0,他引:1
宗世贤 《植物资源与环境学报》1992,1(1):13-17
江苏省海滩植被可分为滨海盐土植被、盐沼植被及海滩沙生植被三个基本类型。本文论述了这些植被类型的演替规律。滨海盐土植被与盐沼植被的演替,外因于土壤盐分含量递减与有机质含量的递增;海滩沙生植被的演替,外因于土壤沙颗粒大小及其相应的土壤含水量的变化,所以海滩植被演替为外因动态演替。 相似文献
94.
影响祁连山区域地貌-水文系统各地理要素的主成分分析 总被引:1,自引:0,他引:1
祁连山区域地貌复杂,从而引起水文系统以及生态系统的复杂性。水文系统是引起生态系统复杂的重要原因之一。对影响祁连山区域地貌——水文系统的9个重要地理要素:即流域盆地的总高度、流域的海拔高度、流域周长、河道总长度、河道总数、平均分叉率、河谷最大坡度(度)、河源数以及流域面积进行了综合分析,将其归为3类,即流域盆地的规模,流域侵蚀状况和流域河系形态。在此基础上,认为若要在以后对影响祁连山区域地貌——水文系统地理要素进行分析时,可以直接选取流域面积,流域盆地出口的海拔高度和河道分叉率作为3类地理要素的代表,进行区域地貌——水文系统分析,从而能够降低分析问题的疑难程度与复杂性。 相似文献
95.
Bao-Qin Liu Zhen-Xian Du Zhi-Hong Zong Chao Li Ning Li Qiang Zhang De-Hui Kong Hua-Qin Wang 《Autophagy》2013,9(6):905-916
Emerging lines of evidence have shown that blockade of ubiquitin-proteasome system (UPS) activates autophagy. The molecular players that regulate the relationship between them remain to be elucidated. Bcl-2 associated athanogene 3 (BAG3) is a member of the BAG co-chaperone family that regulates the ATPase activity of heat shock protein 70 (HSP70) chaperone family. Studies on BAG3 have demonstrated that it plays multiple roles in physiological and pathological processes, including antiapoptotic activity, signal transduction, regulatory role in virus infection, cell adhesion and migration. Recent studies have attracted much attention on its role in initiation of autophagy. The current study, for the first time, demonstrates that proteasome inhibitors elicit noncanonical autophagy, which was not suppressed by inhibitors of class III phosphatidylinositol 3-kinase (PtdIns3K) or shRNA against Beclin 1 (BECN1). In addition, we demonstrate that BAG3 is ascribed to activation of autophagy elicited by proteasome inhibitors and MAPK8/9/10 (also known as JNK1/2/3 respectively) activation is also implicated via upregulation of BAG3. Moreover, we found that noncanonical autophagy mediated by BAG3 suppresses responsiveness of HepG2 cells to proteasome inhibitors. 相似文献
96.
Lewis‐Adduct Mediated Grain‐Boundary Functionalization for Efficient Ideal‐Bandgap Perovskite Solar Cells with Superior Stability 下载免费PDF全文
Yingxia Zong Zhongmin Zhou Min Chen Nitin P. Padture Yuanyuan Zhou 《Liver Transplantation》2018,8(27)
State‐of‐the‐art perovskite solar cells (PSCs) have bandgaps that are invariably larger than 1.45 eV, which limits their theoretically attainable power conversion efficiency. The emergent mixed‐(Pb, Sn) perovskites with bandgaps of 1.2–1.3 eV are ideal for single‐junction solar cells according to the Shockley–Queisser limit, and they have the potential to deliver higher efficiency. Nevertheless, the high chemical activity of Sn(II) in these perovskites makes it extremely challenging to control their physical properties and chemical stability, thereby leading to PSCs with relatively low PCE and stability. In this work, the authors employ the Lewis‐adduct SnF2·3FACl additive in the solution‐processing of ideal‐bandgap halide perovskites (IBHPs), and prepare uniform large‐grain perovskite thin films containing continuously functionalized grain boundaries with the stable SnF2 phase. Such Sn(II)‐rich grain‐boundary networks significantly enhance the physical properties and chemical stability of the IBHP thin films. Based on this approach, PSCs with an ideal bandgap of 1.3 eV are fabricated with a promising efficiency of 15.8%, as well as enhanced stability. The concept of Lewis‐adduct‐mediated grain‐boundary functionalization in IBHPs presented here points to a new chemical route for approaching the Shockley–Queisser limit in future stable PSCs. 相似文献
97.
Olsen CE Liguori AE Zong Y Lantz RC Burgess JL Boitano S 《American journal of physiology. Lung cellular and molecular physiology》2008,295(2):L293-L302
As part of the innate immune defense, the polarized conducting lung epithelium acts as a barrier to keep particulates carried in respiration from underlying tissue. Arsenic is a metalloid toxicant that can affect the lung via inhalation or ingestion. We have recently shown that chronic exposure of mice or humans to arsenic (10-50 ppb) in drinking water alters bronchiolar lavage or sputum proteins consistent with reduced epithelial cell migration and wound repair in the airway. In this report, we used an in vitro model to examine effects of acute exposure of arsenic (15-290 ppb) on conducting airway lung epithelium. We found that arsenic at concentrations as low as 30 ppb inhibits reformation of the epithelial monolayer following scrape wounds of monolayer cultures. In an effort to understand functional contributions to epithelial wound repair altered by arsenic, we showed that acute arsenic exposure increases activity and expression of matrix metalloproteinase (MMP)-9, an important protease in lung function. Furthermore, inhibition of MMP-9 in arsenic-treated cells improved wound repair. We propose that arsenic in the airway can alter the airway epithelial barrier by restricting proper wound repair in part through the upregulation of MMP-9 by lung epithelial cells. 相似文献
98.
Chao Ding Shaopeng Chen Cunlong Zhang Guangnan Hu Wei Zhang Lulu Li Yu Zong Chen Chunyan Tan Yuyang Jiang 《Bioorganic & medicinal chemistry》2017,25(1):27-37
By merging the critical pharmacophore of EGFR/HER2 and HDAC inhibitors into one compound, a novel series of EGFR, HER-2, and HDAC multitarget inhibitors were synthesized. Compounds 9a–l contained 4-anilinoquinazolines with C-6 triazole-linked long alkyl chains of hydroxamic acid and displayed excellent inhibition against these enzymes (compound 9d exhibited the best inhibitory potency on wild-type EGFR, HDAC1, and HDAC6 with IC50 values 0.12 nM, 0.72 nM and 3.2 nM individually). Furthermore, compounds 9b and 9d potently inhibited proliferation of five human cancer cell lines (with IC50 values between 0.49 and 8.76 μM). Further mechanistic study revealed that compound 9d also regulated the phosphorylation of EGFR and HER2 and histone H3 hyperacetylation on the cellular level and induced remarkable apoptosis in BT-474 cells. Therefore, our study suggested that a system network-based multi-target drug design strategy might provided an alternate drug design method, by taking into account the synergy effect of EGFR, HER-2 and HDAC. 相似文献
99.
Probing the Conformation of the Fibronectin III1�C2
Domain by Fluorescence Resonance Energy
Transfer
Nancy W. Karuri Zong Lin Hays S. Rye Jean E. Schwarzbauer 《The Journal of biological chemistry》2009,284(6):3445-3452
Fibronectin (FN) matrix is crucial for cell and tissue functions during
embryonic development, wound healing, and oncogenesis. Assembly of FN matrix
fibrils requires FN domains that mediate interactions with integrin receptors
and with other FN molecules. In addition, regulation of FN matrix assembly
depends on the first two FN type III modules, III1 and
III2, which harbor FN-binding sites. We propose that interactions
between these two modules sequester FN-binding sites in soluble FN and that
these sites become exposed by FN conformational changes during assembly. To
test the idea that III1–2 has a compact conformation, we
constructed CIIIY, a conformational sensor of III1–2 based on
fluorescent resonance energy transfer between cyan and yellow fluorescent
proteins conjugated at its N and C termini. We demonstrate energy transfer in
CIIIY and show that fluorescent resonance energy transfer was eliminated by
proteolysis and by treatment with mild denaturants that disrupted
intramolecular interactions between the two modules. We also show that
mutations of key charged residues resulted in conformational changes that
exposed binding sites for the N-terminal 70-kDa FN fragment. Collectively,
these results support a conformation-dependent mechanism for the regulation of
FN matrix assembly by III1–2.Fibronectin (FN)3
is a 500-kDa modular dimeric protein and a major component of the
extracellular matrix. It exists in the blood and other body fluids as a
soluble compact molecule and undergoes cell-mediated assembly to form an
insoluble three-dimensional fibrillar matrix (reviewed in Ref.
1). The process of FN matrix
assembly has been implicated in embryonic development, wound healing, and
cancer
(2–4).
FN is composed of type I–III modules, and sets of these modules comprise
binding domains for cells and for other extracellular matrix components (see
Fig. 1A). Three of
these binding domains are essential for matrix assembly
(1). Integrin receptor
interactions with the cell-binding domain tether disulfide-bonded FN dimers to
the cell surface, where FN-FN interactions involving the N-terminal assembly
domain form dimers into fibrils. In addition to these essential domains, other
FN-binding sites have been implicated in assembly. In particular, the
III1–2 FN-binding domain plays a regulatory role in matrix
assembly. Within this domain reside a cryptic FN-binding site in
III1 and a site available for FN binding in the native form of
III2
(5–8).
Recombinant FN lacking III1 is assembled into a matrix at wild-type
levels, but that lacking the III1–2 domain results in short
immature FN fibrils (8).
Peptides derived from the III1–2 domain or antibodies against
III1–2 block matrix assembly by cultured cells
(9–11).
Furthermore, FN binding to this region is enhanced when FN is mechanically
stretched (12). Taken
together, these results suggest that conformational changes in the
III1–2 domain may control its interactions during FN
assembly.Open in a separate windowFIGURE 1.The FN III1–2 FRET conformational sensor.
A, representation of the domain structure of FN and major interaction
sites. FN is composed of repeating modules that form binding domains for other
FN molecules, cell receptors, and other extracellular matrix components as
indicated. The first two type III modules III1 and III2
(black), have FN-binding sites and regulate FN matrix assembly. The
N-terminal 70-kDa region contains a matrix assembly domain with FN-binding
activity. The cell-binding domain (cell), the heparin-binding domain
(heparin), the dimerization site (SS), and the alternatively
spliced type IIIA (A), IIIB (B), and variable regions
(V) are indicated. 70kD, N-terminal 70-kDa FN fragment.
B, schematic of proposed model of III1–2 domain
conformation. Panel i, in solution, the FN-binding sites in
III1 and III2 (hatched areas) are sequestered
through domain orientations that are facilitated by the linker between modules
(thin line). Panel ii, binding sites are exposed through
conformational changes resulting from cell-mediated extension of FN
(arrows). The length of the linker and the height and width of the
modules are drawn to scale for a linear peptide and published data on FN type
III modules, respectively. C, ribbon diagram representation of CIIIY,
a FRET sensor of the model in B (panel i), oriented with N
and C termini 50 Å apart. CIIIY consists of the III1–2
domain with CFP at the N terminus and YFP at the C terminus.To more fully understand the roles of native and cryptic FN-binding sites
in matrix assembly, the conformational dynamics of III1–2
must be characterized. One approach to this problem is to tag
III1–2 with fluorescent probes, which, in conjunction with
fluorescent resonance energy transfer (FRET), create a molecular
conformational sensor. FRET involves the radiationless transfer of energy from
an excited donor fluorophore to an acceptor fluorophore, a process that is
very sensitive to the distance between the two fluorophores
(13–15).
Two fluorescent protein variants, cyan fluorescent protein (CFP) and yellow
fluorescent protein (YFP), are highly related to green fluorescent protein
(GFP). Because the emission spectrum of CFP is well matched to the excitation
spectrum of YFP, these two fluorophores have been widely used as a
donor-acceptor pair in FRET studies
(13–15).In this study, we describe a FRET conformational sensor designed to test
the idea that intramolecular interactions between III1 and
III2 sequester key FN-binding and assembly sites. We show that
III1–2 with CFP and YFP fused to the N and C termini,
respectively, displays a clear FRET signal, indicating that the attached
fluorescent proteins and thus the ends of III1–2 are in close
proximity. FRET data from III1–2 mutants support the presence
of a stabilizing intermodule salt bridge that regulates FN-binding
activity. 相似文献
100.
A new species of Orchidaceae, Calanthe yaoshanensis Z. X. Ren & H. Wang from northeastern Yunnan, China, is described and illustrated. It is morphologically similar to C. brevicornu Lindley, from which it differs by having a glabrous column and an elliptical middle lobe with three triangular lamellae. The morphological differences between C. yaoshanensis and related species are discussed. The habitat was investigated and its conservation status was assessed as a ‘Critically Endangered’ (CR). 相似文献