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991.
Hongbiao Huang Ningning Liu Changshan Yang Siyan Liao Haiping Guo Kai Zhao Xiaofen Li Shouting Liu Lixia Guan Chunjiao Liu Li Xu Change Zhang Wenbin Song Bing Li Ping Tang Q. Ping Dou Jinbao Liu 《PloS one》2012,7(12)
Combinations of proteasome inhibitors and histone deacetylases (HDAC) inhibitors appear to be the most potent to produce synergistic cytotoxicity in preclinical trials. We have recently confirmed that L-carnitine (LC) is an endogenous HDAC inhibitor. In the current study, the anti-tumor effect of LC plus proteasome inhibitor bortezomib (velcade, Vel) was investigated both in cultured hepatoma cancer cells and in Balb/c mice bearing HepG2 tumor. Cell death and cell viability were assayed by flow cytometry and MTS, respectively. Gene, mRNA expression and protein levels were detected by gene microarray, quantitative real-time PCR and Western blot, respectively. The effect of Vel on the acetylation of histone H3 associated with the p21cip1 gene promoter was examined by using ChIP assay and proteasome peptidase activity was detected by cell-based chymotrypsin-like (CT-like) activity assay. Here we report that (i) the combination of LC and Vel synergistically induces cytotoxicity in vitro; (ii) the combination also synergistically inhibits tumor growth in vivo; (iii) two major pathways are involved in the synergistical effects of the combinational treatment: increased p21cip1 expression and histone acetylation in vitro and in vivo and enhanced Vel-induced proteasome inhibition by LC. The synergistic effect of LC and Vel in cancer therapy should have great potential in the future clinical trials. 相似文献
992.
Booklice (order Psocoptera) in the genus Liposcelis are major pests to stored grains worldwide and are closely related to parasitic lice (order Phthiraptera). We sequenced the mitochondrial (mt) genome of Liposcelis bostrychophila and found that the typical single mt chromosome of bilateral animals has fragmented into and been replaced by two medium-sized chromosomes in this booklouse; each of these chromosomes has about half of the genes of the typical mt chromosome of bilateral animals. These mt chromosomes are 8,530 bp (mt chromosome I) and 7,933 bp (mt chromosome II) in size. Intriguingly, mt chromosome I is twice as abundant as chromosome II. It appears that the selection pressure for compact mt genomes in bilateral animals favors small mt chromosomes when small mt chromosomes co-exist with the typical large mt chromosomes. Thus, small mt chromosomes may have selective advantages over large mt chromosomes in bilateral animals. Phylogenetic analyses of mt genome sequences of Psocodea (i.e. Psocoptera plus Phthiraptera) indicate that: 1) the order Psocoptera (booklice and barklice) is paraphyletic; and 2) the order Phthiraptera (the parasitic lice) is monophyletic. Within parasitic lice, however, the suborder Ischnocera is paraphyletic; this differs from the traditional view that each suborder of parasitic lice is monophyletic. 相似文献
993.
Background
Cataract and geographic atrophy (GA, also called advanced “dry” age-related macular degeneration) are the two major causes of visual impairment in the developed world. The association between cataract surgery and the development of GA was controversial in previous studies.Methods/Principal Findings
We performed a meta-analysis by pooling the current evidence in literature and found that cataract is associated with an increased risk of geographic atrophy with a summary odds ratio (OR) of 3.75 (95% CI: 95% CI: 1.84–7.62). However, cataract surgery is not associated with the risk of geographic atrophy (polled OR = 3.23, 95% CI: 0.63–16.47). Further experiments were performed to analyze how the αA-crystallin, the major component of the lens, influences the development of GA in a mouse model. We found that theαA-crystallin mRNA and protein expression increased after oxidative stress induced by NaIO3 in immunohistochemistry of retinal section and western blot of posterior eyecups. Both functional and histopathological evidence confirmed that GA is more severe in αA-crystallin knockout mice compared to wild-type mice.Conclusions
Therefore, αA-crystallin may protect against geographic atrophy. This study provides a better understanding of the relationship between cataract, cataract surgery, and GA. 相似文献994.
Background
Because few definitive markers are available for hepatic cancer stem cells (HCSCs), based on physical rather than immunochemical properties, we applied a novel method to enrich HCSCs.Methodology
After hepatic tumor cells (HTCs) were first isolated from diethylinitrosamine-induced F344 rat HCC model using percoll discontinuous gradient centrifugation (PDGC) and purified via differential trypsinization and differential attachment (DTDA), they were separated into four fractions using percoll continuous gradient centrifugation (PCGC) and sequentially designated as fractions I–IV (FI–IV). Morphological characteristics, mRNA and protein levels of stem cell markers, proliferative abilities, induced differentiation, in vitro migratory capacities, in vitro chemo-resistant capacities, and in vivo malignant capacities were determined for the cells of each fraction.Findings
As the density of cells increased, 22.18%, 11.62%, 4.73% and 61.47% of primary cultured HTCs were segregated in FI–FIV, respectively. The cells from FIII (density between 1.041 and 1.062 g/ml) displayed a higher nuclear-cytoplasmic ratio and fewer organelles and expressed higher levels of stem cell markers (AFP, EpCAM and CD133) than cells from other fractions (P<0.01). Additionally, in vitro, the cells from FIII showed a greater capacity to self-renew, differentiate into mature HTCs, transit across membranes, close scratches, and carry resistance to chemotherapy than did cells from any other fraction; in vivo, injection of only 1×104 cells from FIII could generate tumors not only in subcutaneous tissue but also in the livers of nude mice.Conclusions
Through our novel method, HCSC-like cells were successfully enriched in FIII. This study will greatly contribute to two important areas of biological interest: CSC isolation and HCC therapy. 相似文献995.
996.
Juan Jiao Lin Dou Miao Li Yonggang Lu Han-Bang Guo Yong Man Shu Wang Jian Li 《Molecular and cellular biochemistry》2012,370(1-2):103-113
In type 2 diabetes, pancreatic β-cells cannot secret enough insulin compensate for insulin resistance, which are often accompanied by abnormality in lipid metabolism such as hypertriglyceridemia. It is reported that oxidative stress is involved in pancreatic β-cell dysfunction. However, molecular mechanisms linking between excessive generations of reactive oxygen species (ROS) and β-cell dysfunction and apoptosis induced by high levels of very low-density lipoprotein (VLDL) are poorly understood. In this study, we test the hypothesis that NADPH oxidase 2 (NOX2)-derived ROS may play a key role in dysfunction and apoptosis of pancreatic β-cell induced by VLDL. Our results show that the ApoCIII transgenic mice displayed increased serum TG levels, enhanced generation of ROS and impaired insulin content in pancreatic β-cells. In vitro, the treatment of pancreatic NIT-1 cells with 1?mg/ml VLDL for 12?h stimulated NOX2-derived ROS generation, decreased expression and secretion of insulin. Furthermore, we found that VLDL induced dysfunction and apoptosis of pancreatic β-cells through JNK and p53 pathways, which were rescued by siRNA-mediated NOX2 reduction. In conclusion, our data demonstrate a critical role of NOX2-derived ROS in dysfunction and apoptosis through JNK and p53 pathways in pancreatic β-cells induced by VLDL. 相似文献
997.
998.
Agnathia-otocephaly is a rare, often lethal malformation characterized by absence or hypoplasia of the mandible, microstomia, hypoglossia/aglossia, and variable anterior midline fusion of the ears (melotia, synotia). Etiologies have been linked to both genetic and teratogenic factors and to date, a definitive, commonly identifiable cause has not been recognized. Mouse and human genetic studies have implicated OTX2 and PRRX1 as potential candidate genes for agnathia-otocephaly. In this study we report a sporadic case of agnathia-otocephaly complex with associated features of maldevelopment and examine the roles of OTX2 and PRRX1. The proband, a male born at 31 weeks, displayed severe micrognathia, microstomia, posteriorly-rotated and low set ears, and downward slanting palpebral fissures. Mutation analysis was performed after sequencing the entire coding regions of OTX2 and PRRX1 genes isolated from the proband and his parents. After thorough analysis, no DNA variations were detected. This suggests that mutations in different genes or environmental causes are responsible. 相似文献
999.
Shuo-Zeng Dou Kazuki Yokouchi Xin Yu Liang Cao Mari Kuroki Tsuguo Otake Katsumi Tsukamoto 《Environmental Biology of Fishes》2012,95(4):481-490
The migratory history of tapertail anchovy Coilia nasus in the Yangtze River Estuary, China was investigated using otolith Sr:Ca ratios and two-dimensional images of the Sr level from an X-ray electron probe microanalyzer (EPMA). The results showed that 17 of the 22 young-of-the-year (YOY) specimens had low Sr:Ca ratios (1.2–2.4?×?10?3;1.5?±?0.3?×?10?3) at the central otolith area, indicating their riverine origin and initial freshwater residence. In addition, 11 of the 14 adult specimens had low Sr:Ca ratios (1.3–2.2?×?10?3; 1.7?±?0.4?×?10?3) at the central otolith area but showed alternating changes between high (>4.0?×?10?3) and low (<2.5?×?10?3) values outside of this region, reflecting their riverine origin and the migration between freshwater and estuarine habitats. These 28 specimens represented the anadromous population in this region. The other 5 YOY specimens had high Sr:Ca ratios (3.6–5.9?×?10?3; 4.8?±?0.8?×?10?3) throughout the life history. Similarly, the other 3 adult specimens had high Sr:Ca ratios (4.0–5.7?×?10?3; 4.8?±?0.7?×?10?3) at the central otolith area but showed alternating changes between low and high values outside this region, suggesting that estuarine-origin non-anadromous individuals occurred in this region. The average of the otolith Sr:Ca ratios and Sr level mapping along the life-history transects could be used as a scalar for charting the migratory history of the tapertail anchovy in the Yangtze River Estuary: <2.0?×?10?3 for freshwater residence and 3.5–6.0?×?10?3 for estuarine residence. 相似文献
1000.
Shuo-Zeng Dou Yosuke Amano Xin Yu Liang Cao Kotaro Shirai Tsuguo Otake Katsumi Tsukamoto 《Environmental Biology of Fishes》2012,95(4):431-443
The elemental signature in otolith nuclei was determined using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS) for stock discrimination of adult anadromous tapertail anchovy, Coilia nasus, in five Chinese estuaries. Five elements (Na, Mg, K, Sr, and Ba) were well detected in the otolith nuclei of the adult fish. Results showed that the elemental composition in the otolith nuclei varied substantially among the estuaries. Age and fish length data showed no significant influences on the elemental concentration ratios across the sample sites. The Sr:Ca and Ba:Ca ratios were inter-site distinct and could be used as natal tags for discriminating among stocks. Discriminant function analyses (DFA) showed that these ratios can be used in discriminating the Liaohe River estuary (LD, 92.3?%), the Yangtze River estuary (CJ, 86.7?%), and the Yellow River estuary (HH, 76.9?%) samples with high classification accuracy, followed by the Haihe River estuary (BH, 58.3?%) and the Daguhe River estuary (JZ, 46.2?%) samples. An overall classification accuracy rate of 72.7?% from the discriminant functions indicated that elemental fingerprinting appeared to have the potential to discriminate between tapertail anchovy stocks in these estuaries. 相似文献