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91.
Varisli L Gonen-Korkmaz C Debelec-Butuner B Erbaykent-Tepedelen B Muhammed HS Bogurcu N Saatcioglu F Korkmaz KS 《DNA and cell biology》2011,30(6):419-429
As the molecular mechanism of β-catenin deregulation is not well understood, and stabilized β-catenin is known to translocate into the nucleus and activate genes for proliferation, a novel regulatory factor, hematological and neurological expressed 1 (HN1), for Akt-GSK3β-β-catenin axis is reported here. In our studies, HN1 gene structure was characterized. HN1 expression was found to be epidermal growth factor-responsive in PC-3 cells, and protein expression was also upregulated in PC-3 and LNCaP but not in DU145 cells. Additionally, HN1 was found to be downregulated by the specific AKT inhibitor wortmannin but not with PI3K or MAPK inhibitors, LY294002 and PD98059, respectively, in PC-3 and MCF-7 cells. Further, siRNA-mediated knockdown of HN1 resulted in considerable increase in Akt((S473)) and GSK3β((S9),(Y216)) phosphorylations; moreover, subsequent accumulation of β-catenin, increase in c-myc expression, and nuclear accumulation of cyclin D1 were observed in PC-3 cells. Knockdown of HN1 also resulted in prolongation of G(1) phase in cell cycle, increasing tetraploidy, presumably because of cells escaping from abnormal mitosis in PC-3 cells. Consistently, overexpression of HN1 reversed the cell-cycle-specific observations, resulted in accumulation of cells in G(2)/M, and reduced the proliferation rate, which were investigated using flow cytometry and methylthiazol tetrazolium assays. As activating mutations of β-catenin have been demonstrated in late-stage tumors, and β-catenin stabilization was correlated with poor prognosis in previous reports, epidermal growth factor-upregulated HN1 expression might have a role in deregulating the AKT-GSK3β((S9))-mediated signaling as a novel compensating mechanism. 相似文献
92.
Sayyed A Hamidi Richard Z Lin Anthony M Szema Sergey Lyubsky Ya Ping Jiang Sami I Said 《Respiratory research》2011,12(1):141
Background
Pulmonary Arterial Hypertension (PAH) remains a therapeutic challenge, and the search continues for more effective drugs and drug combinations. We recently reported that deletion of the vasoactive intestinal peptide (VIP) gene caused the spontaneous expression of a PH phenotype that was fully corrected by VIP. The objectives of this investigation were to answer the questions: 1) Can VIP protect against PH in other experimental models? and 2) Does combining VIP with an endothelin (ET) receptor antagonist bosentan enhance its efficacy?Methods
Within 3 weeks of a single injection of monocrotaline (MCT, s.c.) in Sprague Dawley rats, PAH developed, manifested by pulmonary vascular remodeling, lung inflammation, RV hypertrophy, and death within the next 2 weeks. MCT-injected animals were either untreated, treated with bosentan (p.o.) alone, with VIP (i.p.) alone, or with both together. We selected this particular combination upon finding that VIP down-regulates endothelin receptor expression which is further suppressed by bosentan. Therapeutic outcomes were compared as to hemodynamics, pulmonary vascular pathology, and survival.Results
Treatment with VIP, every other day for 3 weeks, begun on the same day as MCT, almost totally prevented PAH pathology, and eliminated mortality for 45 days. Begun 3 weeks after MCT, however, VIP only partially reversed PAH pathology, though more effectively than bosentan. Combined therapy with both drugs fully reversed the pathology, while preventing mortality for at least 45 days.Conclusions
1) VIP completely prevented and significantly reversed MCT-induced PAH; 2) VIP was more effective than bosentan, probably because it targets a wider range of pro-remodeling pathways; and 3) combination therapy with VIP plus bosentan was more effective than either drug alone, probably because both drugs synergistically suppressed ET-ET receptor pathway. 相似文献93.
Thabèt Yangui Sami Sayadi Hanen Chakroun Abdelhafidh Dhouib 《Engineering in Life Science》2011,11(5):511-516
Hydroxytyrosol‐rich extract (HRE) and hydroxytyrosol‐rich olive mill wastewater (HROMW) were used as exogenous growth enhancers to stimulate tomato seedling vigor. The tomato seeds soaking in 10% w/v HROMW or HRE solutions were optimum in maximally enhancing seedling performance according to biochemical seed vigor parameters. Biochemical parameters as the average glucose‐6‐phosphate dehydrogenase (G6PDH) activity in HRE‐treated seeds (915.11 nmoles min?1 mg?1 protein) was higher than control (629.58 nmoles min?1 mg?1 protein) and correlated with the increased phenolic content (3530 μg g?1 fw) and 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH)‐based antioxidant activity (70.60%), respectively. Some key enzymes, guaiacol peroxidase (GPX) (6100.65 nmoles min?1 mg?1 protein) and catalase (2.04 μmoles min?1 mg?1 protein), were also higher in response to treatments and correlated with enhanced phenolic content and antioxidant activity. This study supports the hypothesis that the exogenous phenolic application stimulates the pentose phosphate pathway through an over‐expression of endogenous phenolic synthesis and an increase in free‐radical scavenging antioxidant activity. Therefore, the current study indicates the enhancement of seed vigor by HRE especially and HROMW as reflected by the stimulation of biochemical responses. 相似文献
94.
Mpindi JP Sara H Haapa-Paananen S Kilpinen S Pisto T Bucher E Ojala K Iljin K Vainio P Björkman M Gupta S Kohonen P Nees M Kallioniemi O 《PloS one》2011,6(2):e17259
Background
Meta-analysis of gene expression microarray datasets presents significant challenges for statistical analysis. We developed and validated a new bioinformatic method for the identification of genes upregulated in subsets of samples of a given tumour type (‘outlier genes’), a hallmark of potential oncogenes.Methodology
A new statistical method (the gene tissue index, GTI) was developed by modifying and adapting algorithms originally developed for statistical problems in economics. We compared the potential of the GTI to detect outlier genes in meta-datasets with four previously defined statistical methods, COPA, the OS statistic, the t-test and ORT, using simulated data. We demonstrated that the GTI performed equally well to existing methods in a single study simulation. Next, we evaluated the performance of the GTI in the analysis of combined Affymetrix gene expression data from several published studies covering 392 normal samples of tissue from the central nervous system, 74 astrocytomas, and 353 glioblastomas. According to the results, the GTI was better able than most of the previous methods to identify known oncogenic outlier genes. In addition, the GTI identified 29 novel outlier genes in glioblastomas, including TYMS and CDKN2A. The over-expression of these genes was validated in vivo by immunohistochemical staining data from clinical glioblastoma samples. Immunohistochemical data were available for 65% (19 of 29) of these genes, and 17 of these 19 genes (90%) showed a typical outlier staining pattern. Furthermore, raltitrexed, a specific inhibitor of TYMS used in the therapy of tumour types other than glioblastoma, also effectively blocked cell proliferation in glioblastoma cell lines, thus highlighting this outlier gene candidate as a potential therapeutic target.Conclusions/Significance
Taken together, these results support the GTI as a novel approach to identify potential oncogene outliers and drug targets. The algorithm is implemented in an R package (Text S1). 相似文献95.
Cancer therapy is facing the big challenge of destroying selectively tumour cells without harming the normal tissues. Chemotherapy was trying from the beginning to kill malignant cells because of their proliferative activity since normal cells are in general quiescent. Meanwhile side effects were produced due to the destruction of some normal cells that need regular proliferation. The discovery of biomarkers led to the identification of molecular targets within tumour cells in order to kill them selectively. Chemistry followed the progress of biomarkers biotechnology by the production of target specific antagonists which were the subject of many patents. Meanwhile novel problems of tumour resistance appeared and made the battle against cancer a non stop development of new strategies and new weapons. As a consequence, paralleled activities of patenting biomarkers and chemical antagonists are continuously generated. The offer of chemistry does not actually limit the efficiency of Targeted therapy but the identification of biomarkers is still missing the exclusive specificity to tumour cells. 相似文献
96.
Congenital anomalies of the kidney and urinary tract (CAKUT) are the most common cause of chronic kidney disease in children. This disease group includes a spectrum of urinary tract defects including vesicoureteral reflux, duplex kidneys and other developmental defects that can be found alone or in combination. To identify new regulators of CAKUT, we tested the genetic cooperativity between several key regulators of urogenital system development in mice. We found a high incidence of urinary tract anomalies in Pax2;Emx2 compound heterozygous mice that are not found in single heterozygous mice. Pax2+/−;Emx2+/− mice harbor duplex systems associated with urinary tract obstruction, bifid ureter and a high penetrance of vesicoureteral reflux. Remarkably, most compound heterozygous mice refluxed at low intravesical pressure. Early analysis of Pax2+/−;Emx2+/− embryos point to ureter budding defects as the primary cause of urinary tract anomalies. We additionally establish Pax2 as a direct regulator of Emx2 expression in the Wolffian duct. Together, these results identify a haploinsufficient genetic combination resulting in CAKUT-like phenotype, including a high sensitivity to vesicoureteral reflux. As both genes are located on human chromosome 10q, which is lost in a proportion of VUR patients, these findings may help understand VUR and CAKUT in humans. 相似文献
97.
98.
Reetta Hämäläinen Mira H. Kajanus Jukka T. Forsman Sami M. Kivelä Janne-Tuomas Seppänen Olli J. Loukola 《Ecology letters》2023,26(4):490-503
Recent work has shown that animals frequently use social information from individuals of their own species as well as from other species; however, the ecological and evolutionary consequences of this social information use remain poorly understood. Additionally, information users may be selective in their social information use, deciding from whom and how to use information, but this has been overlooked in an interspecific context. In particular, the intentional decision to reject a behaviour observed via social information has received less attention, although recent work has indicated its presence in various taxa. Based on existing literature, we explore in which circumstances selective interspecific information use may lead to different ecological and coevolutionary outcomes between two species, such as explaining observed co-occurrences of putative competitors. The initial ecological differences and the balance between the costs of competition and the benefits of social information use potentially determine whether selection may lead to trait divergence, convergence or coevolutionary arms race between two species. We propose that selective social information use, including adoption and rejection of behaviours, may have far-reaching fitness consequences, potentially leading to community-level eco-evolutionary outcomes. We argue that these consequences of selective interspecific information use may be much more widespread than has thus far been considered. 相似文献
99.
Aspergillus niger broth culture on wheat bran was assessed for olive wastewater (OW) hydrolysis in order to release hydroxytyrosol (HT). The enzyme profiles of this culture broth gave essentially (IU/L): 3000 β-glucosidase and 100 esterase. Hydrolysis activity of A. niger enzyme preparation was evaluated by using three substrates: raw OW, phenolic fraction extracted from OW by ethyl acetate and its corresponding exhausted fraction. Large amounts of free simple phenolics were released from exhausted fraction and raw OW after enzymatic treatment. HPLC analyses show that HT was the main phenolic compound. One step of ethyl acetate extraction of hydrolysed OW allowed the recovery of 0.8 g of HT per litre of OW. The antioxidant activity of extracts from OW and exhausted fraction, measured by DPPH method, was drastically enhanced after hydrolysis treatment. This study demonstrates that hydrolysed OW is a potential source of bioactive phenolic compounds with promising applications in food and pharmaceutical industries. 相似文献
100.