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141.
Hamada H. H. Mohammed Amer Ali Abd El-Hafeez Kareem Ebeid Aml I. Mekkawy Mohammed A. S. Abourehab Emad I. Wafa Suhaila O. Alhaj-Suliman Aliasger K. Salem Pradipta Ghosh Gamal El-Din A. Abuo-Rahma Alaa M. Hayallah Samar H. Abbas 《Journal of enzyme inhibition and medicinal chemistry》2022,37(1):1346
A series of novel 1,2,3-triazole-linked ciprofloxacin-chalcones 4a-j were synthesised as potential anticancer agents. Hybrids 4a-j exhibited remarkable anti-proliferative activity against colon cancer cells. Compounds 4a-j displayed IC50s ranged from 2.53-8.67 µM, 8.67–62.47 µM, and 4.19–24.37 µM for HCT116, HT29, and Caco-2 cells; respectively, whereas the doxorubicin, showed IC50 values of 1.22, 0.88, and 4.15 µM. Compounds 4a, 4b, 4e, 4i, and 4j were the most potent against HCT116 with IC50 values of 3.57, 4.81, 4.32, 4.87, and 2.53 µM, respectively, compared to doxorubicin (IC50 = 1.22 µM). Also, hybrids 4a, 4b, 4e, 4i, and 4j exhibited remarkable inhibitory activities against topoisomerase I, II, and tubulin polymerisation. They increased the protein expression level of γH2AX, indicating DNA damage, and arrested HCT116 in G2/M phase, possibly through the ATR/CHK1/Cdc25C pathway. Thus, the novel ciprofloxacin hybrids could be exploited as potential leads for further investigation as novel anticancer medicines to fight colorectal carcinoma. 相似文献
142.
Shankargouda Patil Hytham N. Fageeh Hammam Ibrahim Fageeh Wael Ibraheem Abdulrahman Saleh Alshehri Ashraf Al-Brakati Salem Almoammar Mohammad Almagbol Harisha Dewan Samar Saeed Khan Hosam Ali Baeshen Vikrant R Patil A. Thirumal Raj Shilpa Bhandi 《Saudi Journal of Biological Sciences》2022,29(5):3568-3576
Gingival mesenchymal stem cells (GMSCs) have significant regenerative potential. Their potential applications range from the treatment of inflammatory diseases, wound healing, and oral disorders. Preconditioning these stem cells can optimize their biological properties. Hypoxia preconditioning of MSCs improves stem cell properties like proliferation, survival, and differentiation potential. This research explored the possible impact of hypoxia on the pluripotent stem cell properties that GMSCs possess. We evaluated the morphology, stemness, neurotrophic factors, and stemness-related genes. We compared the protein levels of secreted neurotrophic factors between normoxic and hypoxic GMSC-conditioned media (GMSC-CM). Results revealed that hypoxic cultured GMSC’s had augmented expression of neurotrophic factors BDNF, GDNF, VEGF, and IGF1 and stemness-related gene NANOG. Hypoxic GMSCs showed decreased expression of the OCT4 gene. In hypoxic GMSC-CM, the neurotrophic factors secretions were significantly higher than normoxic GMSC-CM. Our data demonstrate that culturing of GMSCs in hypoxia enhances the secretion of neurotrophic factors that can lead to neuronal lineage differentiation. 相似文献
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145.
Charles Coudray Patrice Faure Samar Rachidi Andre Jeunet Marie Jeanne Richard Anne Marie Roussel Alain Favier 《Biological trace element research》1992,32(1-3):161-170
Chromium VI compounds have been shown to be carcinogenic in occupationally exposed humans, and to be genotoxic, mutagenic,
and carcinogenic in a variety of experimental systems. In contrast, most chromium III compounds are relatively nontoxic, noncarcinogenic,
and nonmutagenic. Reduction of Cr6+ leads to reactive intermediates, such as Cr5+, Cr4+, or other radical species. The molecular mechanism for the intracellular Cr6+ reduction has been the focus of recent studies, but the details are still not understood.
Our study was initiated to compare the effect of Cr6+-hydroxyl radical formation and Cr6+-induced lipid peroxidation vs those of Cr3+. Electron spin responance measurements provide evidence for the formation of long-lived Cr5+ intermediates in the reduction of Cr6+ by glutathione reductase in the presence of NADPH and for the hydroxyl radical formation during the glutathione reductase
catalyzed reduction of Cr6+. Hydrogen peroxide suppresses Cr5+ and enhances the formation of hydroxyl radical. Thus, Cr5+ intermediates catalyze generation of hydroxyl radicals from hydrogen peroxide through a Fenton-like reaction.
Comparative effects of Cr6+ and Cr3+ on the development of lipid peroxidation were studied by using rat heart homogenate. Heart homogenate was incubated with
different concentrations of Cr6+ compounds at 22°C for 60 min. Lipid peroxidation was determined as thiobarbituric acid reacting materiels (TBA-RM). The results
confirm that Cr6+ induces lipid peroxidation in the rat heart homogenate. These observations might suggest a possible causative role of lipid
peroxidation in Cr6+ toxicity. This enhancement of lipid peroxidation is modified by the addition of some metal chelators and antioxidants. Thus,
strategies for combating Cr6+ toxicity should take into account the role of the hydroxy radicals, and hence, steps for blocking its chain propagation and
preventing the formation of lipid peroxides. 相似文献
146.
Petroleum ether extract of cotton leaves was the most attractive to the hatched larvae of Spodoptera littoralis, and it remained so even after removal of the chlorophyll and other pigments. Steam distillation of this filtrate gave a volatile oil which also proved highly attractive to the larvae. In this fraction, 12 components were identified by thin-layer chromatography. Of these components, α-terpineol, citronellol and α-pinene were the most attractive, whereas humulene and linalool were less attractive. The remaining non-volatile lipid fraction was also attractive to the larva. In this fraction the unsaponifiable matter contained the attractive ingredients. This fraction proved to be a hydrocarbon. The infrared spectrum and nuclear magnetic resonance showed only typical hydrocarbon bonds. 相似文献
147.
Rimner A Al Makdessi S Sweidan H Wischhusen J Rabenstein B Shatat K Mayer P Spyridopoulos I 《Free radical biology & medicine》2005,38(4):535-544
Cholesterol oxidation products (oxysterols) are markers for in vitro LDL oxidation. They are potent inducers of programmed cell death and are also found in high concentrations inside atherosclerotic lesions. Among physiologically occurring oxysterols, 7beta-OH-cholesterol suggests an increase of lipid peroxidation in vivo. In the underlying study, we quantified free plasma oxysterols by means of gas chromatography in patients with stable coronary artery disease (CAD). Total free plasma oxysterols were elevated more than 2-fold in patients with stable CAD (233 +/- 49 vs 108 +/- 19 ng/ml, n = 22, P < 0.05) compared to a control group (n = 20) with similar atherogenic risk profile and angiographically normal coronary arteries. We found that 7-ketocholesterol, as well as the beta-isomers of epoxide (25.7 +/- 10.0 vs 7.3 +/- 1.4 ng/ml, P = 0.07) and 7beta-OH-cholesterol (65.1 +/- 15.7 vs 19.4 +/- 8.9 ng/ml, P < 0.01), was mainly responsible for this increase. To elucidate a potential relevance of oxysterol stereospecificity in regard to endothelial damage, we further conducted in vitro experiments using human arterial endothelial cells (HAECs). Surprisingly, beta-isomers exerted an up to 10-fold higher amount of cell death in equivalent doses when compared to alpha-isomers. The greater cytotoxic potential of beta-isomers was due to increased apoptosis, preceded by mitochondrial release of cytochrome c with subsequent caspase-3 activation. Stereospecific release of cytochrome c depended on the presence of an intact cytoplasmic membrane, hinting at the existence of a putative oxysterol receptor or a direct stereospecific effect on membrane biology. Finally, both isoforms of oxysterols directly released cytochrome c only in conjunction with protein containing cytosol and endoplasmatic reticulum. Free plasma oxysterol levels, particularly 7-ketocholesterol, beta-epoxide and 7beta-OH-cholesterol, are elevated in patients with stable CAD, independent of their LDL cholesterol levels. Due to the highly increased cytotoxicity of oxysterol beta-isomers in vitro, they may represent important atherogenic risk factors. 相似文献
148.
A.M. Rizk F.M. Hammouda M.M. El-Missiry H.M. Radwan F.J. Evans 《Phytochemistry》1984,23(10):2377-2379
An ether soluble resin was prepared by extraction and partition of the latex of Euphorbia royleana. This resin demonstrated pronounced pro-inflammatory activity on mammalian skin and was separated into biologically active and inactive fractions by dry column chromatography. The inactive fraction was further separated by adsorption and partition thin-layer methods. The least polar zone consisted of an inseparable mixture of four tetra-esters of the macrocyclic diterpene ingol, whilst the more polar fraction consisted of a mixture of four tri-esters of the same diterpene. 相似文献
149.
One of the functions associated with the oral streptococcal surface protein I/II is to bind to human extracellular matrix molecules or blood components, which could act as opportunistic ligands in pathological circumstances. In order to understand the relative specificity of the binding repertoire of this bacterial adhesin, we examined by infrared measurements the mode of binding of the protein I/II from Streptococcus mutans OMZ175 (I/IIf) to fibronectin and fibrinogen. This approach revealed the beta-structure forming capacity of I/IIf upon interaction with both proteins. The forming of intermolecular beta-structures may provide a non-selective way of interaction between I/IIf and its possible targets. 相似文献
150.
Antonyuk S Elam JS Hough MA Strange RW Doucette PA Rodriguez JA Hayward LJ Valentine JS Hart PJ Hasnain SS 《Protein science : a publication of the Protein Society》2005,14(5):1201-1213
The His46Arg (H46R) mutant of human copper-zinc superoxide dismutase (SOD1) is associated with an unusual, slowly progressing form of familial amyotrophic lateral sclerosis (FALS). Here we describe in detail the crystal structures of pathogenic H46R SOD1 in the Zn-loaded (Zn-H46R) and metal-free (apo-H46R) forms. The Zn-H46R structure demonstrates a novel zinc coordination that involves only three of the usual four liganding residues, His 63, His 80, and Asp 83 together with a water molecule. In addition, the Asp 124 "secondary bridge" between the copper- and zinc-binding sites is disrupted, and the "electrostatic loop" and "zinc loop" elements are largely disordered. The apo-H46R structure exhibits partial disorder in the electrostatic and zinc loop elements in three of the four dimers in the asymmetric unit, while the fourth has ordered loops due to crystal packing interactions. In both structures, nonnative SOD1-SOD1 interactions lead to the formation of higher-order filamentous arrays. The disordered loop elements may increase the likelihood of protein aggregation in vivo, either with other H46R molecules or with other critical cellular components. Importantly, the binding of zinc is not sufficient to prevent the formation of nonnative interactions between pathogenic H46R molecules. The increased tendency to aggregate, even in the presence of Zn, arising from the loss of the secondary bridge is consistent with the observation of an increased abundance of hyaline inclusions in spinal motor neurons and supporting cells in H46R SOD1 transgenic rats. 相似文献