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排序方式: 共有109条查询结果,搜索用时 15 毫秒
41.
Ibrahim H. Eissa Radwan El-Haggar Mohammed A. Dahab Marwa F. Ahmed Hazem A. Mahdy Reem I. Alsantali Alaa Elwan Nicolas Masurier Samar S. Fatahala 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1587
A novel series of 2-thioacetamide linked benzoxazole-benzamide conjugates 1–15 was designed as potential inhibitors of the vascular endothelial growth factor receptor-2 (VEGFR-2). The prepared compounds were evaluated for their potential antitumor activity and their corresponding selective cytotoxicity was estimated using normal human fibroblast (WI-38) cells. Compounds 1, 9–12 and 15 showed good selectivity and displayed excellent cytotoxic activity against both HCT-116 and MCF-7 cancer cell lines compared to sorafenib, used as a reference compound. Furthermore, compounds 1 and 11 showed potent VEGFR-2 inhibitory activity. The cell cycle progression assay showed that 1 and 11 induced cell cycle arrest at G2/M phase, with a concomitant increase in the pre-G1 cell population. Further pharmacological studies showed that 1 and 11 induced apoptosis and inhibited the expression of the anti-apoptotic Bcl-2 and Bcl-xL proteins in both cell lines. Therefore, compounds 1 and 11 might serve as promising candidates for future anticancer therapy development. 相似文献
42.
Maha M. Eissa Riham M. El-Moslemany Alyaa A. Ramadan Eglal I. Amer Mervat Z. El-Azzouni Labiba K. El-Khordagui 《PloS one》2015,10(11)
Miltefosine (MFS) is an alkylphosphocholine used for the local treatment of cutaneous metastases of breast cancer and oral therapy of visceral leishmaniasis. Recently, the drug was reported in in vitro and preclinical studies to exert significant activity against different developmental stages of schistosomiasis mansoni, a widespread chronic neglected tropical disease (NTD). This justified MFS repurposing as a potential antischistosomal drug. However, five consecutive daily 20 mg/kg doses were needed for the treatment of schistosomiasis mansoni in mice. The present study aims at enhancing MFS efficacy to allow for a single 20mg/kg oral dose therapy using a nanotechnological approach based on lipid nanocapsules (LNCs) as oral nanovectors. MFS was incorporated in LNCs both as membrane-active structural alkylphospholipid component and active antischistosomal agent. MFS-LNC formulations showed high entrapment efficiency (EE%), good colloidal properties, sustained release pattern and physical stability. Further, LNCs generally decreased MFS-induced erythrocyte hemolytic activity used as surrogate indicator of membrane activity. While MFS-free LNCs exerted no antischistosomal effect, statistically significant enhancement was observed with all MFS-LNC formulations. A maximum effect was achieved with MFS-LNCs incorporating CTAB as positive charge imparting agent or oleic acid as membrane permeabilizer. Reduction of worm load, ameliorated liver pathology and extensive damage of the worm tegument provided evidence for formulation-related efficacy enhancement. Non-compartmental analysis of pharmacokinetic data obtained in rats indicated independence of antischistosomal activity on systemic drug exposure, suggesting possible gut uptake of the stable LNCs and targeting of the fluke tegument which was verified by SEM. The study findings put forward MFS-LNCs as unique oral nanovectors combining the bioactivity of MFS and biopharmaceutical advantages of LNCs, allowing targeting via the oral route. From a clinical point of view, data suggest MFS-LNCs as a potential single dose oral nanomedicine for enhanced therapy of schistosomiasis mansoni and possibly other diseases. 相似文献
43.
Overproduction of NO by inducible NO synthase (iNOS) has been implicated in the pathogenesis of many diseases. iNOS is active only as a homodimer in which the subunits align in a head-to-head manner, with the N-terminal oxygenase domains forming the dimer interface and a zinc metal center stabilizing the dimer. Thus, dimerization represents a critical locus for therapeutic interventions for regulation of NO synthesis. We have recently shown that intracellular iNOS forms dimers that are "undisruptable (UD)" by heat, SDS, strong denaturants, and/or reducing agents. Our data further suggest that the zinc metal center plays a role in forming and/or stabilizing iNOS undisruptable dimers (UD-dimers). In this study, we show that a mAb directed against a unique epitope at the oxygenase domain of human iNOS preferentially recognizes UD-dimers. This observation has implications for the mechanism of formation and regulation of dimer formation of iNOS. Our data suggest that UD-dimers of iNOS, in spite of SDS-PAGE denaturation, still maintain features of the quaternary structure of iNOS particularly at its N-terminal end and including head-to-head contact of the oxygenase domains. 相似文献
44.
David T. Burns Sandra Donkervoort Juliane S. Müller Ellen Knierim Diana Bharucha-Goebel Eissa Ali Faqeih Stephanie K. Bell Abdullah Y. AlFaifi Dorota Monies Francisca Millan Kyle Retterer Sarah Dyack Sara MacKay Susanne Morales-Gonzalez Michele Giunta Benjamin Munro Gavin Hudson Mena Scavina Carsten G. Bönnemann 《American journal of human genetics》2018,102(5):858-873
45.
Hamed?Ebrahimzadeh Mehran?E.?ShariatpanahiEmail author Behzad?Ahmadi Hassan?Soltanloo Mahmoud?Lotfi Eissa?Zarifi 《Journal of Plant Growth Regulation》2018,37(4):1127-1134
In this study, the effect of spraying mother plants with various levels of putrescine, spermidine, and cycocel (each at 0, 50, 500, and 5000 mg/l) were assessed on the frequency of haploid embryos produced from unfertilized ovaries and subsequent regeneration of derived embryos. Significantly higher haploid embryos were obtained when mother plants were sprayed with putrescine at 500 mg/l (5.2 embryos/fruit), spermidine at 50 mg/l (4.8 embryos/fruit), and cycocel at 50 mg/l (5.2 embryos/fruit) as compared to the control (without spraying, 3.2 embryos/fruit). However, embryogenesis induction was decreased drastically as the concentration of all the three compounds tested was increased and the lowest haploid embryos were observed when 5000 mg/l of spermidine (0.4 embryos/fruit) or cycocel (2.0 embryos/fruit) were applied. Only spermidine at 50 mg/l led to 100% regeneration into fully developed plantlets. The seed setting and size of fruits were also affected by polyamines and cycocel applications. Ploidy analysis using a flow cytometer indicated that all regenerated plantlets contain the gametic chromosome number (n?=?x?=?7) of parental plants and the results of chromosome counting also confirmed the haploid nature of regenerated plantlets. It can be concluded that the induction of haploid embryogenesis from unfertilized ovaries after pollination with irradiated pollen and subsequent conversion of derived embryos into the plantlets could be improved in Cucumis sativus L. by applying appropriate levels of putrescine, spermidine, and cycocel. 相似文献
46.
N.?A.?El-FaramawyEmail author I.?El-Somany A.?Mansour A.?M.?Maghraby H.?Eissa A.?Wieser 《Radiation and environmental biophysics》2018,57(1):63-68
Tooth enamel samples from molar teeth of camel were prepared using a combined procedure of mechanical and chemical tooth treatment. Based on electron paramagnetic resonance (EPR) spectroscopy, the dose response of tooth enamel samples was examined and compared to that of human enamel. The EPR dose response of the tooth enamel samples was obtained through irradiation to gamma doses from 1 Gy up to 100 kGy. It was found that the radiation-induced EPR signal increased linearly with gamma dose for all studied tooth enamel samples, up to about 15 kGy. At higher doses, the dose response curve leveled off. The results revealed that the location of the native signal of camel tooth enamel was similar to that of enamel from human molars at 2.00644, but different from that of enamel from cows and goats. In addition, the peak-to-peak width (ΔH pp) for human and camel molar teeth was similar. It was also found that the response of camel enamel to gamma radiation was 36% lower than that of human enamel. In conclusion, the results indicate the suitability of camel teeth for retrospective gamma dosimetry. 相似文献
47.
M. J. Kearsey M. D. Hayward F. D. Devey S. Arcioni M. P. Eggleston M. M. Eissa 《TAG. Theoretical and applied genetics. Theoretische und angewandte Genetik》1987,75(1):66-75
Summary The genetical control of heading date and dry matter production in an F2 population of Lolium perenne are presented from analyses of triple-test-crosses and basic generations. The data is derived from spaced plant trials at sites in the United Kingdom (UK) and Italy in different years. Despite the wide initial cross between UK bred material and an Italian accession, there was no significant evidence for epistasis, while additive and dominance variation were generally present with partial to complete dominance for all traits. Linear regression onto the environmental means accounted for all the GxE variation for dry matter production in the establishment and aftermath cuts, but not for heading date or the hay cut. The b values measuring responsiveness to the environment were clearly heritable and showed partial dominance. Predictions of the likely performance of recombinant inbred lines and second cycle hybrids were sufficiently promising to support further investigation of these approaches to breeding in this crop. 相似文献
48.
Hanan?E. Shamseldin Eissa Faqeih Ali Alasmari Maha?S. Zaki Joseph?G. Gleeson Fowzan?S. Alkuraya 《American journal of human genetics》2016,98(1):210-215
Brain channelopathies represent a growing class of brain disorders that usually result in paroxysmal disorders, although their role in other neurological phenotypes, including the recently described NALCN-related infantile encephalopathy, is increasingly recognized. In three Saudi Arabian families and one Egyptian family all affected by a remarkably similar phenotype (infantile encephalopathy and largely normal brain MRI) to that of NALCN-related infantile encephalopathy, we identified a locus on 2q34 in which whole-exome sequencing revealed three, including two apparently loss-of-function, recessive mutations in UNC80. UNC80 encodes a large protein that is necessary for the stability and function of NALCN and for bridging NALCN to UNC79 to form a functional complex. Our results expand the clinical relevance of the UNC79-UNC80-NALCN channel complex. 相似文献
49.
M.F.M. Eissa M.M. Abd-Elgawad W.A. El-Nagdi 《Archives Of Phytopathology And Plant Protection》2013,46(4):436-444
The seasonal fluctuations of nematodes associated with the rhizosphere of both banana cvs. Williams and Hindi throughout one year indicated a fairly negative correlation between the prevailing soil temperatures and the population densities of Criconemoides spp., Helicotylenchus exallus, Hoplolaimus spp. and Meloidogyne incognita. 相似文献
50.
Jin Na Shin Elmoataz Abdel Fattah Abhisek Bhattacharya Soyoung Ko N. Tony Eissa 《The Journal of biological chemistry》2013,288(50):35886-35895
The association between altered proteostasis and inflammatory disorders has been increasingly recognized, but the underlying mechanisms are not well understood. In this study, we show that deficiency of either autophagy or sequestosome 1 (p62 or SQSTM) led to inflammasome hyperactivation in response to LPS and ATP in primary macrophages and in mice in vivo. Importantly, induction of protein misfolding by puromycin, thapsigargin, or geldanamycin resulted in inflammasome activation that was more pronounced in autophagy- or p62-deficient macrophages. Accumulation of misfolded proteins caused inflammasome activation by inducing generation of nonmitochondrial reactive oxygen species and lysosomal damage, leading to release of cathepsin B. Our results suggest that altered proteostasis results in inflammasome activation and thus provide mechanisms for the association of altered proteostasis with inflammatory disorders. 相似文献