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Mohamed H. Hekal Abeer M. El-Naggar Fatma S. M. Abu El-Azm Wael M. El-Sayed 《RSC advances》2020,10(7):3675
Background and aim: The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives. Methods: The synthetic reactions were carried out under both conventional and ultrasonic irradiation conditions. The anti-proliferative activity of the newly synthesized compounds against two human epithelial cell lines; liver (HepG2) and breast (MCF-7) in addition to normal fibroblasts (WI-38) was investigated. In addition to molecular docking studies, the possible mechanism(s) of action were also explored. Results: In general, an improvement in synthetic rates and yields was observed when reactions were carried out under sonication compared with classical conditions. The structures of the products were established based on analytical and spectral data. Derivatives 2e and 7d, in addition to compound 1, had significant and selective anti-proliferative activity against liver and breast cancer cell lines without harming normal fibroblasts. These derivatives arrested the cell cycle progression and/or induced apoptosis. This has been manifested by the elevation in the expression of p53 and caspase 3, down-regulation of cdk1, and a reduction in the concentrations of MAPK and Topo II at submicromolar concentrations. The latter results confirmed the molecular docking study. Conclusions: Compound 1 had the best profile on the gene and protein levels (arresting cell cycle and inducing apoptosis). The ability of compounds 1 and 2e to inhibit both MAPK and Topo II nominates these derivatives as potential candidates for further anticancer and antitumor studies.The current study reports the synthesis and biological evaluation of two novel series of 4-(5-mercapto-1,3,4-oxadiazol-2-yl)phthalazin-1(2H)-one derivatives. 相似文献
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Mostafa M. El-Naggar Ahmed A. Elayat M. Salleh M. Ardawi Mohammad Tahir 《Anatomical record (Hoboken, N.J. : 2007)》1993,237(4):489-497
Although there is a recent increase in the use of the isolated pancreatic islets of the rat in the transplantation and functional studies, there has been no detailed quantitative assessment on the size and cellular constituents of islets after the isolation procedure. The present work was undertaken to study the size classes of the isolated islets and the morphometry of their cellular populations. Islets of the rat pancreas were isolated by using the intraductal collagenase digestion technique, the most commonly used procedure for the isolation of pancreatic islets. Different endocrine cells of the isolated islets were stained by immunoperoxidase staining techniques. The distribution of the cellular constituents of the isolated islets was similar to that of the intact islets of the normal pancreas; A, D, and PP cells were peripherally arranged around the centrally located B cells. However, morphometric quantitative study showed that the percent volume and percent number of A, D, and PP cells of the isolated islets were lower than those of the corresponding intact ones. Further, the mean true diameter of the isolated islets was lower than that of the intact ones. These data indicate loss of islet cells during the process of isolation. Most of the lost cells were from the periphery of islets. This may provide an explanation for the incomplete metabolic control and recurrence of hyperglycemia encountered after isolated islet transplantation in the treatment of diabetes mellitus. It seems that further refinements of the isolation techniques are necessary to obtain islet tissue with total cellular integrity, before a complete success in transplantation could be achieved. © 1993 Wiley-Liss, Inc. 相似文献
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CHENGGANG YI MD YONG PAN MD YAN ZHEN MM LINXI ZHANG MD XUDONG ZHANG MD MAOGUO SHU MD YAN HAN MD SHUZHONG GUO MD 《Dermatologic surgery》2006,32(12):1437-1443
BACKGROUND: A recent discovery showed that endothelial progenitor cells (EPCs) could augment collateral vessel growth to ischemic tissues. OBJECTIVE: The objective was to demonstrate the effects of EPCs on the vasculogenesis and survival of free transplanted fat tissues in nude mice. METHODS: EPCs from human donors were cultured in vitro for 7 days. Human fat tissues were injected subcutaneously into the scalps of 20 6-week-old nude male mice. EPCs stained with CM-DiI were mixed with the transplanted fat tissues and injected into the mice. EBM-2 medium was used as control group. The animals were euthanized 15 weeks after the procedure. Graft volume were measured, and histologic evaluation was performed. The central part of fat tissues was histologically evaluated 15 weeks after the fat injection. RESULTS: The survival volume of the experimental group was significantly greater than that of the control group (p< .05). Less cyst formation and fibrosis was obtained in the experimental group. Histologic evaluation of the central part of fat tissues 15 weeks after the fat injection showed that capillary densities increased markedly in the experimental group mice. CONCLUSION: The results indicate that EPCs have the ability to enhance the survival and the quality of the transplanted fat tissues. 相似文献
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Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. 总被引:4,自引:0,他引:4
Peng Hou Dingxie Liu Yuan Shan Shuiying Hu Kimberley Studeman Stephen Condouris Yangang Wang Ariel Trink Adel K El-Naggar Giovanni Tallini Vasily Vasko Mingzhao Xing 《Clinical cancer research》2007,13(4):1161-1170
PURPOSE: To investigate the overall occurrence and relationship of genetic alterations in the phosphatidylinositol 3-kinase (PI3K)/Akt pathway in thyroid tumors and explore the scope of this pathway as a therapeutic target for thyroid cancer. EXPERIMENTAL DESIGN: We examined collectively the major genetic alterations and their relationship in this pathway, including PIK3CA copy number gain and mutation, Ras mutation, and PTEN mutation, in a large series of primary thyroid tumors. RESULTS: Occurrence of any of these genetic alterations was found in 25 of 81 (31%) benign thyroid adenoma (BTA), 47 of 86 (55%) follicular thyroid cancer (FTC), 21 of 86 (24%) papillary thyroid cancer (PTC), and 29 of 50 (58%) anaplastic thyroid cancer (ATC), with FTC and ATC most frequently harboring these genetic alterations. PIK3CA copy gain was associated with increased PIK3CA protein expression. A mutual exclusivity among these genetic alterations was seen in BTA, FTC, and PTC, suggesting an independent role of each of them through the PI3K/Akt pathway in the tumorigenesis of the differentiated thyroid tumors. However, coexistence of these genetic alterations was increasingly seen with progression from differentiated tumor to undifferentiated ATC. Their coexistence with BRAF mutation was also frequent in PTC and ATC. CONCLUSIONS: The data provide strong genetic implication that aberrant activation of PI3K/Akt pathway plays an extensive role in thyroid tumorigenesis, particularly in FTC and ATC, and promotes progression of BTA to FTC and to ATC as the genetic alterations of this pathway accumulate. Progression of PTC to ATC may be facilitated by coexistence of PI3K/Akt pathway-related genetic alterations and BRAF mutation. The PI3K/Akt pathway may thus be a major therapeutic target in thyroid cancers. 相似文献
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Breast feeding and dietary habits were studied prospectively in a cohort of children under the age of five years in a rural Somali community. The median duration of breast feeding was 19.5 months. However, all the children also received cow's milk by cup from the first day of life and onwards. Energy supplements (mainly sugar and oil) as well as additional water were given daily from early infancy. Staples, protein-rich foods (beans and meat), vegetables and fruits were usually introduced when the children reached the age of 12-18 months. There was a seasonal variation with the lowest intake of protein-rich and vitamin-rich foods during the rains in May to June. Thus, there was a complete absence of exclusive breast feeding. Energy-reinforced cow's milk and human milk dominated the diet up to the age of one year. Staples were mixed with oil and supplemented with milk, thereby leading to a much higher energy density in the complementary food than is usually the case in African communities. 相似文献