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61.
Mahmoud Abd El-Monem El-Hasab Eman Esmat El-Bastawissy Tarek Faathy El-Moselhy 《Journal of biomolecular structure & dynamics》2018,36(7):1713-1727
HCV NS3 protease domain has been one of the most attractive targets for developing new drugs for HCV infection and many drugs were successfully developed, but all of them were designed for targeting HCV genotype 1 infection. HCV genotype 4a dominant in Egypt has paid less attention. Here, we describe our protocol of virtual screening in identification of novel potential potent inhibitors for HCV NS3 of genotype 4a using homology modeling, PLIF (protein–ligand interaction fingerprint), docking, pharmacophore, and dynamic simulation. A high-quality 3D model of HCV NS3 protease of genotype 4a was constructed using crystal structure of HCV NS3 protease of genotype 1b (PDB ID: 4u01) as a template. PLIF was generated using five crystal structures of HCV NS3 (PDB ID: 4u01, 3kee, 4ktc, 4i33, and 5epn) which revealed the most important residues and their interactions with the co-crystalized ligands. A 3D pharmacophore model consisting of six features was developed from the generated PLIF data and then used as a screening filter for 11,244 compounds. Only 423 compounds passed the pharmacophore filter and entered the docking-based virtual screening stage. The highest ranked five hits from docking result (compound (C1–C5)) were selected for further analysis. They exhibited stronger interaction and higher binding affinity than HCV NS3 protease ligands. Dynamic simulation of the protein–best lead complex was performed to validate and augment the virtual screening results and it showed that these compounds have a strong binding affinity and could be very effective in treating HCV genotype 4a infections. 相似文献
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Aim of our study was to compare anterior cervical fusion with fusion augmented with dynamic implants and with the first generation-plate. Methods. Patients with radiculopathy and/or myelopathy were included in a prospective cohort study. Clinical outcome was assessed according to the Nurick, Odom, and SF 36 scales. Rotation and translation of screws, and quality of fusion (Tribus) were assessed at the 6-week and 4-year follow-up examinations. Neurodecompression was performed in 81 patients (one-level N = 45, two-level N = 26 and multi-level N = 10) in the period from January 2001 to September 2003. 50 male and 31 female patients were divided into three groups, depending upon type of fusion: 1. Augmented with dynamic implants (N = 33), 2. Augmented with H-plate (N = 33), and 3. Non-augmented (N = 15), one-level. There were no significant differences in clinical outcomes between the groups. Dynamization was detected in both augmented groups: axial in the dynamic implant group (mean translation +/- SD = 2.67 +/- 0.79 mm), and angular in the H-plate group (angle of rotation 7.2 degrees +/- 3.04 degrees). Six-week fusion was significantly better in the dynamic implants and non-augmented groups, as compared with the H-plate group. Two patients in the H-plate group developed pseudoarthrosis, 7 patients in the dynamic implant group had supradjacent segment heterotopic ossification and two of these additional ankylosis. Three patients in the non-augmented group had dislodgement of the bone graft with transient dysphagia in one of them. Our results suggest that selection of implants is not crucial for clinical outcome. Subsidence is allowed with both fixation systems. Fusion is faster and more effective in the axially dynamized group. 相似文献
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Glycinebetaine in saline conditions: an assessment of the current state of knowledge 总被引:1,自引:0,他引:1
Salt stress is one of the environmental threats that have devastating impacts on plant distribution, growth and production. Different plants are believed to have salt tolerance mechanisms that occur at the cellular level. One facet of the cellular mechanisms of adaptation to salinity stress is to accumulate either inorganic and/or organic solutes. Glycinebetaine (GB), as well as other organic solutes, has been referred to as compatible solutes, for the reason that they are innocent with essential biochemical reactions even at high concentrations. GB has been assumed to be involved in osmotic adjustment and/or osmoprotection of cellular functional macromolecules and, hence, can improve tolerance to saline conditions. However, the exact mechanism and direct evidences for such correlative data are still lacking despite many attempts to improve growth under saline conditions by exogenous application as well as genetic engineering of metabolic pathways involved in metabolism of GB. Despite the enormous amount of information accumulated in this regard, the exact function of GB in the adaptation to saline environments is not fully clear to this point, and even GB functions have been argued. Because of that, inconsistencies exist in the published data regarding GB accumulation and functions under salt stress. In this review, we provide an update on evidence supporting each of these arguments to reassess how GB affects plant growth and physiological traits under salt imposition, and whether its effects correlate with salt tolerance. 相似文献
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Relative effects of parasitism by Microplitis rufiventris on the development of the third instar Spodoptera littoralis (preferable, optimal host) with the development of penultimate (5th) and last (6th) instars (suboptimal hosts) were investigated. Newly molted 6th instar hosts were more acceptable for parasitization by the wasp female than older hosts. In singly parasitized 3rd instar hosts, 82.0 +/- 3.9% of the parasitoid eggs developed to full-grown instar wasp larvae. However, parasitoid eggs deposited singly in 73.9 +/- 3.3% of 5th and 100% of 6th instar hosts failed to develop. Superparasitization in the 3rd instar hosts reduced the production of pseudoparasitized larvae and, conversely, all parasitized hosts yielded viable parasitoid offspring. In suboptimal hosts, the development interaction between the parasitoid and its host larvae was highly influenced by the age of hosts at parasitism, load of deposited eggs, and other parasitoid factors. The latter factors, e.g., mainly calyx fluid particles, might be involved in establishing parasitoid eggs in the suboptimal hosts. In the last two host instars, superparasitization significantly increased the number of parasitoid larvae successfully reaching their final instar. Variation in host quality, e.g., physiological status, might be attributed, in part, to the partial breakdown of the solitary habit observed in the earlier instars. More parasitoid eggs developed to mature parasitoid larvae in hosts superparasitized as 6th instar than parasitoid eggs laid in 5th instar hosts. Superparasitization significantly lengthened the developmental period of 5th and 6th host instars and inhibited their development to the pupal stage. Studying parasitoid development in suboptimal instars of its habitual host provided physiological insight, as shown here. The results may have implication for biological control and in vitro mass rearing programs with solitary parasitoids. 相似文献
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We compared the production of pseudoparasitization by Microplitis rufiventris females in most (third) and less (fourth) preferred instars of Spodoptera littoralis larvae at 20+/-1 and 27+/-1 degrees C. The parasitized hosts were classified into hosts producing parasitoids (type A hosts) and hosts producing no parasitoids, i.e., pseudoparasitized hosts (type B hosts). The latter were further classified into: (a) pseudoparasitized hosts with "well" arrested development (type B1 hosts); (b) pseudoparasitized hosts with partially arrested development (type B2 hosts); and (c) pseudoparasitized hosts that successfully pupated to apparently normal host pupae (type B3 hosts). The present series of experiments showed that parasitization by M. rufiventris was clearly affected by host instar, age within an instar and rearing temperature. Production of type B hosts was less when third instar S. littoralis larvae were exposed to the wasp females than when the host larvae were in fourth instar. The production of type A hosts was much greater when early or mid ages of an instar was stung by the wasp females comparing with stung late age of the same instar. Production of type B hosts may be due to one or overall of the following: (a) dosage dilution of M. rufiventris female's factors in the different age classes of the instar; (b) endocrine system (physiological state) at parasitization time, i.e., early vs late age of the instar; (c) growth rate of host larvae. The lowest production of type B hosts was at highest growth rate; and (d) temperature, larger proportions of type B hosts were produced at 27+/-1 than at 20+/-1degrees C. The three types host development (B1, B2 and B3) are possibly representing three levels of host resistance (host control) resulting in partial or complete failure of parasitoid control. Type A hosts represent complete success of parasitoid control. The results suggest that the impact of parasitoid factor(s) on developmental arrest is affected by host age at the time of parasitism and/or by temperature. 相似文献
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Youssef-Elabd EM McGee KC Tripathi G Aldaghri N Abdalla MS Sharada HM Ashour E Amin AI Ceriello A O'Hare JP Kumar S McTernan PG Harte AL 《The Journal of nutritional biochemistry》2012,23(1):39-50
A post-prandial increase in saturated fatty acids (SFAs) and glucose (Glc) activates an inflammatory response, which may be prolonged following restoration of physiological SFAs and Glc levels — a finding referred to as ‘metabolic memory'.This study examined chronic and oscillating SFAs and Glc on the inflammatory signalling pathway in human adipose tissue (AT) and adipocytes (Ads) and determined whether Ads are subject to “metabolic memory.”Abdominal (Abd) subcutaneous (Sc) explants and Ads were treated with chronic low glucose (L-Glc): 5.6 mM and high glucose (H-Glc): 17.5 mM, with low (0.2 mM) and high (2 mM) SFA for 48 h. Abd Sc explants and Ads were also exposed to the aforementioned treatment regimen for 12-h periods, with alternating rest periods of 12 h in L-Glc.Chronic treatment with L-Glc and high SFAs, H-Glc and high SFAs up-regulated key factors of the nuclear factor-κB (NFκB) pathway in Abd Sc AT and Ads (TLR4, NFκB; P<.05), whilst down-regulating MyD88. Oscillating Glc and SFA concentrations increased TLR4, NFκB, IKKβ (P<.05) in explants and Ads and up-regulated MyD88 expression (P<.05). Both tumor necrosis factor α and interleukin 6 (P<.05) secretion were markedly increased in chronically treated Abd Sc explants and Ads whilst, with oscillating treatments, a sustained inflammatory effect was noted in absence of treatment.Therefore, SFAs may act as key instigators of the inflammatory response in human AT via NFκB activation, which suggests that short-term exposure of cells to uncontrolled levels of SFAs and Glc leads to a longer-term inflammatory insult within the Ad, which may have important implications for patients with obesity and Type 2 diabetes. 相似文献
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Lövei GL Lewinsohn TM Dirzo R Elhassan EF Ezcurra E Freire CA Gui FR Halley JM Tibazarwa JM Jiang MX Katebaka R Kinyamario J Kymanywa S Liu FQ Liu SS Liu WX Liu YQ Lu BR Minot EO Qiang S Qiu BL Shen H Soberon J Sujii ER Tang JW Uludag A Vitule JR Wan FH Wang FH Yang GQ Zhang XY You MS;Biological Invasions in Megadiverse Regions Network 《Trends in ecology & evolution》2012,27(1):2-3
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Navashenaq Jamshid Gholizadeh Shabgah Arezoo Gowhari Hashemi Esmat Alsadat Seyedzadeh Mir Hadi Shokri Fazel Razavi Seyed Alireza Kardar Gholam Ali 《International journal of peptide research and therapeutics》2019,25(2):413-418
International Journal of Peptide Research and Therapeutics - Tumor cells in breast cancer are immunogenic and express proteins that can induce immune responses. One important antigen is human... 相似文献