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511.
Ul Haq Zaheer Uddin Reaz Wai Lam Kok Wadood Abdul Lajis Nordin Haji 《Journal of molecular modeling》2011,17(5):1149-1161
Structure-based 3D-QSAR approaches (CoMFA and CoMSIA) were applied to understand the structural requirements of the Cyclin-dependent
kinase 5/p25 inhibitors. Cyclin-dependent kinase 5 (CDK5) is believed to play an important role in the development of the
central nervous system during the process of mammalian embryogenesis. Genetic algorithm based docking program (GOLD) was successfully
utilized to orient the compounds inside the binding pocket of the CDK5/p25 structure. The adapted alignment method with the
suitable parameters resulted in a reliable model. Furthermore, the final model was robust enough to forecast the activities
of test compounds, satisfactorily. The contour maps were produced around the functional groups to understand the SAR requirements.
Moreover, we also investigate the structural attributes of the inhibitors which make them selective toward CDK5/p25 over its
close counterpart, i.e., CDK2. The study could be helpful to rationalize the new compounds with better inhibition and selectivity
profiles against CDK5/p25. 相似文献
512.
Ali Usman Ashfaq Shaheen N Khan Zafar Nawaz Sheikh Riazuddin 《Genetic vaccines and therapy》2011,9(1):1-5
Hepatitis C virus (HCV) is a major cause of chronic liver diseases including steatosis, cirrhosis and hepatocellular carcinoma. Currently, there is no vaccine available for prevention of HCV infection due to high degree of strain variation. The current treatment of care, Pegylated interferon α in combination with ribavirin is costly, has significant side effects and fails to cure about half of all infections. The development of in-vitro models such as HCV infection system, HCV sub-genomic replicon, HCV producing pseudoparticles (HCVpp) and infectious HCV virion provide an important tool to develop new antiviral drugs of different targets against HCV. These models also play an important role to study virus lifecycle such as virus entry, endocytosis, replication, release and HCV induced pathogenesis. This review summarizes the most important in-vitro models currently used to study future HCV research as well as drug design. 相似文献
513.
O. Zethner Bashir M. Khan M. Ismail Chaudhry B. Bolet Sharfuddin Khan Habibullah Khan Hanif Gul L. Øgaard M. Zaman Gul Nawaz 《BioControl》1987,32(5):449-455
Agrotis segetum Schiff granulosis virus (AsGV) propagated in Denmark was supplied against naturally occurring cutworm populations (A. ipsilon and to a less extentA. segetum) in experimental field plots of tobacco, okra, potato and sugar beet in northern Pakistan. AsGV doses varied between 4 ×
107 and 4 × 1011 capsules per m2 plot, and no. of applications between 1 and 3.
One treatment with AsGV did not reduce cutworm damage significantly to tobacco seedlings and potato plants.
Two treatments with AsGV reduced cutworm damage significantly. In tobacco, reduction was 64–82%, in okra and potato 85% and
77% respectively. Damage in sugar beet was reduced 78%.
Three treatments with AsGV dis not reduce damage significantly better than two treatments.
AsGV and the chemical insecticides Tamaran and Dieldrin, andBacillus thuringiensis (Thuricide) were about equally effective, reducing damage by 85%, 79%, 87% and 69%, respectively. No difference was found
between the efficiency of highly purified AsGV to which activated charcoal was added and partially purified AsGV without charcoal.
相似文献
514.
Marijana Samardzija Andrea Corna Raquel Gomez-Sintes Mohamed Ali Jarboui Angela Armento Jerome E. Roger Eleni Petridou Wadood Haq Francois Paquet-Durand Eberhart Zrenner Pedro de la Villa Günther Zeck Christian Grimm Patricia Boya Marius Ueffing Dragana Trifunovi 《Cell death and differentiation》2021,28(4):1317
Cone photoreceptor cell death in inherited retinal diseases, such as Retinitis Pigmentosa (RP), leads to the loss of high acuity and color vision and, ultimately to blindness. In RP, a vast number of mutations perturb the structure and function of rod photoreceptors, while cones remain initially unaffected. Extensive rod loss in advanced stages of the disease triggers cone death by a mechanism that is still largely unknown. Here, we show that secondary cone cell death in animal models for RP is associated with increased activity of histone deacetylates (HDACs). A single intravitreal injection of an HDAC inhibitor at late stages of the disease, when the majority of rods have already degenerated, was sufficient to delay cone death and support long-term cone survival in two mouse models for RP, affected by mutations in the phosphodiesterase 6b gene. Moreover, the surviving cones remained light-sensitive, leading to an improvement in visual function. RNA-seq analysis of protected cones demonstrated that HDAC inhibition initiated multi-level protection via regulation of different pro-survival pathways, including MAPK, PI3K-Akt, and autophagy. This study suggests a unique opportunity for targeted pharmacological protection of secondary dying cones by HDAC inhibition and creates hope to maintain vision in RP patients even in advanced disease stages.Subject terms: Neuroscience, Neurological disorders 相似文献
515.
Optimizing methyl‐eugenol aromatherapy to maximize posttreatment effects to enhance mating competitiveness of male Bactrocera carambolae (Diptera: Tephritidae)
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Ihsan ul Haq Marc J.B. Vreysen Carlos Cacéres Todd E. Shelly Jorge Hendrichs 《Insect Science》2015,22(5):661-669
Methyl‐eugenol (ME) (1,2‐dimethoxy‐4‐(2‐propenyl)benzene), a natural phytochemical, did enhance male Bactrocera carambolae Drew & Hancock (Diptera: Tephritidae) mating competitiveness 3 d after ingestion. Enhanced male mating competitiveness can significantly increase the effectiveness of the sterile insect technique (SIT). ME application to mass reared sterile flies by feeding is infeasible. ME application by aromatherapy however, would be a very practical way of ME application in fly emergence and release facilities. This approach was shown to enhance mating competitiveness of B. carambolae 3 d posttreatment (DPT). Despite this added benefit, every additional day of delaying release will reduce sterile fly quality and will add cost to SIT application. The present study was planned to assess the effects of ME‐aromatherapy on male B. carambolae mating competitiveness 1DPT and 2DPT. ME aromatherapy 1DPT or 2DPT did enhance mating competitiveness of B. carambolae males whereas ME feeding 1DPT and 2DPT did not. Male mating competitiveness was enhanced by the ME aromatherapy irrespective if they received 1DPT, 2DPT or 3DPT. ME aromatherapy, being a viable approach for its application, did enhance mating competitiveness of male B. carambolae 1 d posttreatment as ME feeding did 3 d after ingestion. 相似文献
516.
Tahira Younis Faiza Jabeen Ali Hussain Bilal Rasool Ali Raza Ishaq Atif Nawaz Heba A. S. El-Nashar Mohamed El-Shazly 《化学与生物多样性》2023,20(3):e202200755
Fraxinus xanthoxyloides is a perennial shrub belonging to family Oleaceae, traditionally used for malaria, jaundice, pneumonia, inflammation, and rheumatism. Our study is aimed to assess the total phenolics (TPC), flavonoids (TFC), terpenoids contents (TTC) and antioxidant profiling of F. xanthoxyloides methanol bark extract (FXBM) and its fractions, hexane, chloroform, ethyl acetate and aqueous, along with high-performance liquid chromatography with diode-array detection (HPLC-DAD). Further, the antioxidant and pulmonary protective potential was explored against carbon tetrachloride (CCl4)-induced CCl4-induced pulmonary tissue damage in rats. The highest TPC, TFC and TTC were found in FXBM (133.29±4.19 mg/g), ethyl acetate fraction (279.55±10.35 mg/g), and chloroform fraction (0.79±0.06 mg/g), respectively. The most potent antioxidant capacity was depicted by FXBM (29.21±2.40 μg/mg) and ethyl acetate fraction (91.16±5.51 μg/mg). The HPLC-DAD analysis revealed the predominance of gallic, chlorogenic, vanillic and ferulic acid in FXBM. The administration of CCl4 induced oxidative stress, suppressed antioxidant enzymes′ activities including catalase, peroxidase, superoxide dismutase, glutathione peroxidase, glutathione-S-transferase, and glutathione reductase. Further, it increased thiobarbituric acid reactive substances (TBARS) and H2O2 levels, induced DNA injuries and reduced the total protein and glutathione content in lung tissues. The treatment of rats with FXBM restored these biochemical parameters to the normal level. Moreover, the histopathological studies of lung tissues demonstrated that FXBM protected rats′ lung tissues from oxidative damage restoring normal lung functions. Thus, F. xanthoxyloides bark extract is recommended as adjuvant therapy as protective agent for patients with lung disorders. 相似文献
517.
Genetic Ablation of the Steroid Receptor Coactivator-Ubiquitin Ligase, E6-AP, Results in Tissue-Selective Steroid Hormone Resistance and Defects in Reproduction
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Carolyn L. Smith Darryll G. DeVera Dolores J. Lamb Zafar Nawaz Yong-Hui Jiang Arthur L. Beaudet Bert W. OMalley 《Molecular and cellular biology》2002,22(2):525-535
The E6-associated protein (E6-AP), although originally identified as a ubiquitin ligase, has recently been shown to function as a coactivator of steroid receptor-dependent gene expression in in vitro assays. In order to determine whether E6-AP acts as a coactivator in vivo, physiological parameters associated with male and female sex steroid action were assessed in the E6-AP null mouse. Gonadal size was reduced in E6-AP null male and female mice in comparison to wild-type controls in conjunction with reduced fertility in both genders. Consistent with this observation, defects in sperm production and function, as well as ovulation were observed. In comparison to wild-type controls, induction of prostate gland growth induced by testosterone and uterine growth by estradiol were significantly reduced. In contrast, estrogen and progesterone-stimulated growth of virgin mammary gland was not compromised by E6-AP ablation despite E6-AP expression in this tissue. This latter finding contrasts with the impaired estrogen and progesterone-induced mammary gland development observed previously for steroid receptor coactivator type 1 (SRC-1) and SRC-3 female knockout mice. Taken together, these results are consistent with a role for E6-AP in mediating a subset of steroid hormone actions in vivo. Nevertheless, differences observed between SRC and E6-AP knockout phenotypes indicate that these two families of steroid receptor coactivators are not functionally equivalent and supports the hypothesis that coactivators contribute to tissue-specific steroid hormone action. 相似文献