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81.
Sadaf Mutahir Muhammad Asim Khan Abdulrahman Abdulaziz Almehizia Amr Salah Abouzied Nasrin Eldirdiri Khalifa Ahmed Mohamed Naglah Haishan Deng Moamen Salaheldeen Refat Weam Mohamed Ali Khojali Bader Huwaimel 《化学与生物多样性》2023,20(8):e202300241
Mannich bases consisting of 1,3,4-oxadiazole-2-thione ( 3 a – 3 l ) bearing various substituents were synthesized and found potent jack bean urease inhibitors. The prepared compounds showed significantly good inhibitory activities with IC50 values from 9.45±0.05 to 267.42±0.23 μM. The compound 3 k containing 4-chlorophenyl (−R) and 4-hydroxyphenyl (−R′) was most active with IC50 9.45±0.05 μM followed by 3 e (IC50 22.52±0.15 μM) in which −R was phenyl and −R′ was isopropyl group. However, when both −R and −R′ were either 4-chlorophenyl groups ( 3 l ) or only −R′ was 4-nitrophenyl ( 3 i ), both compounds were found inactive. The detailed binding affinities of the produced compounds with protein were explored through molecular docking and data-supported in-vitro enzyme inhibition profiles. Drug likeness was confirmed by in silico ADME investigations and molecular orbital analysis (HOMO-LUMO) and electrostatic potential maps were got from DFT calculations. ESP maps exposed that there are two potential binding sites with the most positive and most negative parts. 相似文献
82.
83.
Ambreen Asim Ashok Kumar Srinivasan Muthuswamy Shalu Jain Sarita Agarwal 《Journal of biomedical science》2015,22(1)
Down syndrome (DS) is one of the commonest disorders with huge medical and social cost. DS is associated with number of phenotypes including congenital heart defects, leukemia, Alzeihmer’s disease, Hirschsprung disease etc. DS individuals are affected by these phenotypes to a variable extent thus understanding the cause of this variation is a key challenge. In the present review article, we emphasize an overview of DS, DS-associated phenotypes diagnosis and management of the disease. The genes or miRNA involved in Down syndrome associated Alzheimer’s disease, congenital heart defects (AVSD), leukemia including AMKL and ALL, hypertension and Hirschprung disease are discussed in this article. Moreover, we have also reviewed various prenatal diagnostic method from karyotyping to rapid molecular methods - MLPA, FISH, QF-PCR, PSQ, NGS and noninvasive prenatal diagnosis in detail. 相似文献
84.
Amani Elsayed Mayyas Al-Remawi Nidal Qinna Asim Farouk Khaldoun A. Al-Sou’od Adnan A. Badwan 《AAPS PharmSciTech》2011,12(3)
The present work explores the possibility of formulating an oral insulin delivery system using nanoparticulate complexes made from the interaction between biodegradable, natural polymer called chitosan and anionic surfactant called sodium lauryl sulfate (SLS). The interaction between chitosan and SLS was confirmed by Fourier transform infrared spectroscopy. The nanoparticles were prepared by simple gelation method under aqueous-based conditions. The nanoparticles were stable in simulated gastric fluids and could protect the encapsulated insulin from the GIT enzymes. Additionally, the in vivo results clearly indicated that the insulin-loaded nanoparticles could effectively reduce the blood glucose level in a diabetic rat model. However, additional formulation modifications are required to improve insulin oral bioavailability.KEY WORDS: chitosan, insulin, nanoparticles, oral delivery system, sodium lauryl sulfate 相似文献
85.
The increasing incidence of hospital-acquired infections caused by drug-resistant pathogens, host toxicity, the poor efficacy of drugs and high treatment costs has drawn attention to the potential of natural products as antifungals in mucocutaneous infections and combinational therapies. Moreover, cellular and subcellular targets for these compounds may provide better options for the development of novel antifungal therapies. Eugenol, methyl eugenol and estragole are phenylpropanoids found in essential oil. They are known to possess pharmacological properties including antimicrobial activity. Induction of oxidative stress characterized by elevated levels of free radicals and an impaired antioxidant defence system is implicated as a possible mechanism of cell death. An insight into the mechanism of action was gained by propidium iodide cell sorting and oxidative stress response to test compounds in Candida albicans. The extent of lipid peroxidation (LPO) of cytoplasmic membranes was estimated to confirm a state of oxidative stress. Activity levels of primary defence enzymes and glutathione were thus further determined. Whereas these compounds cause fungal cell death by disrupting membrane integrity at minimum inhibitory concentrations (MIC), sub-MIC doses of these compounds significantly impair the defence system in C. albicans. The study has implications for understanding microbial cell death caused by essential oil components eliciting oxidative stress in Candida. The formation of membrane lesions by these phenylpropanoids thus appears to be the result of free radical cascade-mediated LPO. 相似文献
86.
87.
Ahmad AS Zia S Sayeed I Ansari MA Ahmad M Salim S Yousuf S Islam F 《Biological trace element research》2005,103(1):59-68
The effect of 0.05, 0.1, and 0.2 mg sodium selenite/kg body weight ip on the activities of neurobehavioral, acetyl cholinesterase,
monoamine oxidase, and the content of dopamine and its metabolites in circadian rhythm centers of male Wistar rats was studied
after 7 d of treatment. The results show an appreciable increase in locomotion, stereo-events, distance traveled, and average
speed at the dose of 0.1 and 0.2 mg sodium selenite/kg. The data have shown hyperactivity of animals with various doses of
sodium selenite, and it was significant and dose-dependent after 3 d of treatment. The activity of acetylcholinesterase (AChE)
was inhibited dose dependently, and it was significant in preoptic area with 0.1 or 0.2 mg sodium selenite/kg. Conversely,
in the posterior hypothalamus its activity was significantly elevated with the dose of 0.2 mg sodium selenite/kg, but its
alteration in brain stem was not significant. Monoamine oxidase (MAO) activity was increased in preoptic area with the dose
of 0.1 mg sodium selenite/kg, but its alteration in posterior hypothalamus and brain stem was not significant. The content
of dopamine (DA), 3,4-dihydroxyphenyl acetic acid (DOPAC), and homovanilic acid (HVA) was elevated dose dependently and it
was significant with the doss of 0.1 and 0.2 mg sodium selenite/kg, but the content of DOPAC and HVA in posterior hypothalamus
was not significant with the dose of 0.1 mg sodium selenite/kg. 相似文献
88.
BackgroundWithaferin A, which is a naturally derived steroidal lactone, has been found to prevent angiogenesis and metastasis in diverse tumor models. It has also been recognized by different groups for prominent anti-carcinogenic roles. However, in spite of these studies on withanolides, their detailed anti-metastatic mechanism of action remained unknown. The current study has poised to address the machinery involved in invasion regulation by stable derivative of Withaferin A, 3-azido Withaferin A (3-azidoWA) in human cervical HeLa and prostate PC-3 cells.Conclusion/SignificanceFor this report, we found that 3-azidoWA suppressed motility and invasion of HeLa and PC-3 cells in MMP-2 dependent manner. Our in vitro result strongly suggests that sub-toxic doses of 3-azidoWA enhanced the secretion of extracellular Par-4 that abolished secretory MMP-2 expression and activity. Depletion of secretory Par-4 restored MMP-2 expression and invasion capability of HeLa and PC-3 cells. Further, our findings implied that 3-azidoWA attenuated internal phospho-ERK and phospho-Akt expression in a dose dependent manner might play a key role in inhibition of mouse angiogenesis by 3-azidoWA. 相似文献
89.
Background
The identification of health care professionals who are incompetent, impaired, exploitative or have criminal intent is important for public safety. It is unclear whether psychiatrists are more likely to commit medical misconduct offences than non-psychiatrists, and if the nature of these offences is different.Aim
The aim of this study was to compare the characteristics of psychiatrists disciplined in Canada and the nature of their offences and disciplinary sentences for the ten years from 2000 through 2009 to other physicians disciplined during that timeframe.Methods
Utilizing a retrospective cohort design, we constructed a database of all physicians disciplined by provincial licensing authorities in Canada for the ten years from 2000 through 2009. Demographic variables and information on type of misconduct violation and penalty imposed were also collected for each physician disciplined. We compared psychiatrists to non-psychiatrists for the various outcomes.Results
There were 82 (14%) psychiatrists of 606 physicians disciplined in Canada in the ten years from 2000 through 2009, double the national proportion of psychiatrists. Of those disciplined psychiatrists, 8 (9.6%) were women compared to 29% in the national cohort. A total of 5 (6%) psychiatrists committed at least two separate offenses, accounting for approximately 11% of the total violations. A higher proportion of psychiatrists were disciplined for sexual misconduct (OR 3.62 [95% Confidence Interval [CI] 2.45–5.34]), fraudulent behavior (OR 2.32 [95% CI 1.20–4.40]) and unprofessional conduct (OR 3.1 [95% CI 1.95–4.95]). As a result, psychiatrists had between 1.85–4.35 greater risk of having disciplinary penalties in almost all categories in comparison to other physicians.Conclusion
Psychiatrists differ from non-psychiatrist physicians in the prevalence and nature of medical misconduct. Efforts to decrease medical misconduct by psychiatrists need to be conducted and systematically evaluated. 相似文献90.
Xiong X Cui P Hossain S Xu R Warner B Guo X An X Debnath AK Cowburn D Kotula L 《Biochimica et biophysica acta》2008,1783(5):737-747
Here we report c-Abl kinase inhibition mediated by a phosphotyrosine located in trans in the c-Abl substrate, Abi1. The mechanism, which is pertinent to the nonmyristoylated c-Abl kinase, involves high affinity concurrent binding of the phosphotyrosine pY213 to the Abl SH2 domain and binding of a proximal PXXP motif to the Abl SH3 domain. Abi1 regulation of c-Abl in vivo appears to play a critical role, as demonstrated by inhibition of pY412 phosphorylation of the nonmyristoylated Abl by coexpression of Abi1. Pervanadate-induced c-Abl kinase activity was also reduced upon expression of the wild type Abi1 but not by expression of the Y213 to F213 mutant Abi1 in LNCaP cells, which are naturally deficient in the regulatory pY213. Our findings suggest a novel mechanism by which Abl kinase is regulated in cells. 相似文献