排序方式: 共有149条查询结果,搜索用时 31 毫秒
141.
Tarek S. Ibrahim Mohamed M. Hawwas Azizah M. Malebari Ehab S. Taher Abdelsattar M. Omar Thikryat Neamatallah Zakaria K. Abdel-Samii Martin K. Safo Yaseen A. M. M. Elshaier 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):802
A new series of quinoline derivatives of combretastatin A-4 have been designed, synthesised and demonstrated as tubulin polymerisation inhibitors. These novel compounds showed significant antiproliferative activities, among them, 12c exhibited the most potent inhibitory activity against different cancer cell lines (MCF-7, HL-60, HCT-116 and HeLa) with IC50 ranging from 0.010 to 0.042 µM, and with selectivity profile against MCF-10A non-cancer cells. Further mechanistic studies suggest that 12c can inhibit tubulin polymerisation and cell migration, leading to G2/M phase arrest. Besides, 12c induces apoptosis via a mitochondrial-dependant apoptosis pathway and caused reactive oxygen stress generation in MCF-7 cells. These results provide guidance for further rational development of potent tubulin polymerisation inhibitors for the treatment of cancer.
Highlights
- A novel series of quinoline derivatives of combretastatin A-4 have been designed and synthesised.
- Compound 12c showed significant antiproliferative activities against different cancer cell lines.
- Compound 12c effectively inhibited tubulin polymerisation and competed with [3H] colchicine in binding to tubulin.
- Compound 12c arrested the cell cycle at G2/M phase, effectively inducing apoptosis and inhibition of cell migration.
142.
Although genes have specific phenotypic consequences in a given species, this functional relationship can clearly change during the course of evolution. Many cases of evolutionary dissociations between homologous genes and homologous morphological features are now known. These dissociations have interesting and important implications for understanding the genetic basis for evolutionary change in morphology. 相似文献
143.
Regulation of mRNA translation has been held responsible for effects of diet, age, alcohol, hormones, hibernation, disease and hypoxia on protein synthesis in animal tissues. Dietary effects are due to concentrations of amino acids and insulin in circulation that affect activities of two key translational regulators, eukaryotic initiation factor 2 (F2) and eukaryotic initiation factor 4E binding protein 1 (Bp). To construct a platform for prediction of global protein synthesis to nutritional stimuli, a dynamic, mechanistic model of translational control in whole tissues was developed. The model was composed of a set of differential equations which describe the dynamics of 11 state variables: tRNA and acyl-tRNA for leucine (Leu), limiting (Laa) and other amino acids (Oaa), inactivated F2 with GDP (F2d), activated F2 with GTP (F2t), F4e, Bp and its complex with F4e (4eBp), available mRNA start codons (AUG), and active ribosomes (Arib). Material was assumed to flow from one variable to another according to mass-action kinetics or Michaelis-Menten form. Uncharged tRNA inhibit GTP exchange on eIF2, and free amino acids and insulin inhibit reversible sequestration of F4e by Bp. Initial conditions and parameters were set for a skeletal muscle fractional synthesis rate of 10%/d and ribosome transit time of 80 s. Between amino acid concentrations of 500 and 4000×103 nM, protein synthesis increased from 0.9 to 11.7%/d at 0 μU/mL insulin, and from 5.0 to 12.8%/d at 30 μU/mL insulin. Predicted responses to graded levels of a deficient amino acid were asymptotic. A single parameter accomodated differences between tissues in insulin sensitivity. Seven parameters must be changed to simulate initiation and elongation rates in more active tissues such as liver, or in tissues of older mature animals. An increase in uncharged tRNA during insulin stimulation highlighted the physiological importance of coordinated regulation of amino acid supply by insulin. In conclusion, the regulation of F4e release from Bp by Ins and Leu, and of F2d recycling by uncharged tRNA can be tied together to describe a wide range of FSR values across tissues and physiological states. 相似文献
144.
Helbok R Shaker E Beer R Chemelli A Sojer M Sohm F Broessner G Lackner P Beck M Zangerle A Pfausler B Thome C Schmutzhard E 《BMC neurology》2012,12(1):32
ABSTRACT: BACKGROUND: Vasospasm-related delayed cerebral ischemia (DCI) significantly impacts on outcome after aneurysmal subarachnoid hemorrhage (SAH). Erythropoietin (EPO) may reduce the severity of cerebral vasospasm and improve outcome, however, underlying mechanisms are incompletely understood. In this study, the authors aimed to investigate the effect of EPO on cerebral metabolism and brain tissue oxygen tension (PbtO2). METHODS: Seven consecutive poor grade SAH patients with multimodal neuromonitoring (MM) received systemic EPO therapy (30.000 IU per day for 3 consecutive days) for severe cerebral vasospasm. Cerebral perfusion pressure (CPP), mean arterial blood pressure (MAP), intracranial pressure (ICP), PbtO2 and brain metabolic changes were analyzed during the next 24 hours after each dose given. Statistical analysis was performed with a mixed effects model. RESULTS: A total of 22 interventions were analyzed. Median age was 47 years (32-68) and 86% were female. Three patients (38%) developed DCI. MAP slightly decreased 2 hours after intervention (P<0.04) without significantly affecting CPP and ICP. PbtO2 significantly increased over time (P<0.05) to a maximum of 7+/-4mmHg increase 16 hours after infusion. Brain metabolic parameters did not change over time. CONCLUSIONS: EPO increases PbtO2 in poor grade SAH patients with severe cerebral vasospasm. The effect on outcome needs further investigation. 相似文献
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Alexander Z. Wei Lanyi N. Chen Marlana Orloff Charlotte E. Ariyan Maryam Asgari Christopher A. Barker Elizabeth Buchbinder Sunandana Chandra Kasey Couts Michael M. Frumovitz Andrew Futreal Jeffrey E. Gershenwald Ehab Y. Hanna Benjamin Izar Amy K. LeBlanc Mario M. Leitao Jr. Evan J. Lipson David Liu Martin McCarter Jennifer L. McQuade Yana Najjar Suthee Rapisuwon Sara Selig Alexander N. Shoushtari Iwei Yeh Gary K. Schwartz Jun Guo Sapna P. Patel Richard D. Carvajal 《Pigment cell & melanoma research》2023,36(6):542-556
Mucosal melanoma remains a rare cancer with high mortality and a paucity of therapeutic options. This is due in significant part to its low incidence leading to limited patient access to expert care and downstream clinical/basic science data for research interrogation. Clinical challenges such as delayed and at times inaccurate diagnoses, and lack of consensus tumor staging have added to the suboptimal outcomes for these patients. Clinical trials, while promising, have been difficult to activate and accrue. While individual institutions and investigators have attempted to seek solutions to such problems, international, national, and local partnership may provide the keys to more efficient and innovative paths forward. Furthermore, a mucosal melanoma coalition would provide a potential network for patients and caregivers to seek expert opinion and advice. The Melanoma Research Foundation Mucosal Melanoma Meeting (December 16, 2022, New York, USA) highlighted the current clinical challenges faced by patients, providers, and scientists, identified current and future clinical trial investigations in this rare disease space, and aimed to increase national and international collaboration among the mucosal melanoma community in an effort to improve patient outcomes. The included proceedings highlight the clinical challenges of mucosal melanoma, global clinical trial experience, basic science advances in mucosal melanoma, and future directions, including the creation of shared rare tumor registries and enhanced collaborations. 相似文献
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148.
Ehab HASSANEEN Alaa El‐Din SALLAM Ahmad ABO‐GHALIA Yoshiyuki MORIYAMA Kenji TOMIOKA 《Entomological Science》2011,14(3):278-282
Pigment‐dispersing factor (PDF) is an important neurotransmitter in insect circadian systems. In the cricket Gryllus bimaculatus, it affects nocturnal activity, the free‐running period and photic entrainment. In this study, to investigate whether these effects of PDF occur through a circadian molecular machinery, we measured mRNA levels of clock genes period (per) and timeless (tim) in crickets with pdf expression knocked‐down by pdf RNAi. The pdf RNAi decreased per and tim mRNA levels during the night to reduce the amplitude of their oscillation. The phase of the rhythm advanced by about 4 h in terms of trough and/or peak phases. On the other hand, pdf mRNA levels were little affected by per and tim RNAi treatment. These results suggest that PDF affects the circadian rhythm at least in part through the circadian molecular oscillation while the circadian clock has little effect on the pdf expression. 相似文献
149.
Di-isononyl phthalate (DIP) is considered a high molecular weight subtype of phthalates that are commonly used (to make plastics more durable) and could easily affect the gastrointestinal tract (GIT). Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are the main active components of fish oil (FO), and their antiinflammatory potential was previously documented. The current study was designed to investigate the protective potential of fish oil against the impact of DIP exposure on the colon of albino Wistar rats. Sixty albino Wistar rats were divided into control group received corn oil for ten days. DIP treated group received DIP. Diisononyl phthalate + fish oil treated group received both DIP and FO three groups: the control group received corn oil for ten days, the DIP treated group received DIP, and the DIP + FO treated group received both DIP and FO.. FO was found to preserve the histological architecture, tight junction, and cell cycle of the colon. In conclusion, the current study provided an evidence that FO has a protective potential against DIP, and further examination are suggested to fully understand the molecular basis of this potential as a step for further clinical applications.Key words: Di-isononyl phthalate, gastrointestinal tract, fish oil, tight junction, apoptosis 相似文献