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21.
Naveed Anjum Chikan 《Journal of biomolecular structure & dynamics》2013,31(8):1794-1804
In today’s world, the pursuit of a novel anti-cancer agent remains top priority because of the fact that the global burden of this malady is continuously increasing. Our work is no different from others in searching for new therapeutic solutions. To achieve this, we are looking into Epigenetics, the phenomenon governed by hypermethylation and hypomethylation of tumor suppressor genes and oncogenes, respectively. Our target for this study is an important intermediary methyl-CpG binding protein named kaiso. In our study, we have used the X-ray crystallographic structure of Kaiso for virtual screening and molecular dynamics simulations to study the binding modes of possible inhibitors. The C2H2 domain comprising LYS539 was used for screening the inter bio screen Database having 48,531 natural compounds. Our approach of using computer-aided drug designing methods helped us to remove the execrable compounds and narrowed our focus on a selected few for molecular simulation studies. The top ranked compound (chem. ID 28127) exhibited the highest binding affinity and was also found to be stable throughout the 20 ns timeframe. This compound is therefore a good starting point for developing strong inhibitors. 相似文献
22.
Karin E. van Straaten Jong Bum Ko Rajendra Jagdhane Shazia Anjum David R. J. Palmer David A. R. Sanders 《The Journal of biological chemistry》2013,288(47):34121-34130
NtdA from Bacillus subtilis is a sugar aminotransferase that catalyzes the pyridoxal phosphate-dependent equatorial transamination of 3-oxo-α-d-glucose 6-phosphate to form α-d-kanosamine 6-phosphate. The crystal structure of NtdA shows that NtdA shares the common aspartate aminotransferase fold (Type 1) with residues from both monomers forming the active site. The crystal structures of NtdA alone, co-crystallized with the product α-d-kanosamine 6-phosphate, and incubated with the amine donor glutamate reveal three key structures in the mechanistic pathway of NtdA. The structure of NtdA alone reveals the internal aldimine form of NtdA with the cofactor pyridoxal phosphate covalently attached to Lys-247. The addition of glutamate results in formation of pyridoxamine phosphate. Co-crystallization with kanosamine 6-phosphate results in the formation of the external aldimine. Only α-d-kanosamine 6-phosphate is observed in the active site of NtdA, not the β-anomer. A comparison of the structure and sequence of NtdA with other sugar aminotransferases enables us to propose that the VIβ family of aminotransferases should be divided into subfamilies based on the catalytic lysine motif. 相似文献
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Md. Ejaz Ahmed Mohd. Moshahid Khan Hayate Javed Kumar Vaibhav Andleeb Khan Rizwana Tabassum Mohammad Ashafaq Farah Islam Mohammed M. Safhi Fakhrul Islam 《Neurochemistry international》2013
Alzheimer’s disease (AD) is a progressive neurodegenerative disorder resulting in cognitive decline and enhancement of oxidative loads in the brain. Flavonoids have been considered to exert human health benefits by anti-oxidant and anti-inflammatory properties. The present study is aimed to elucidate the neuroprotective effect of catechin hydrate (CH), a natural flavanoid with potential antioxidant and anti-inflammatory properties, on intracerebroventricular streptozotocin (ICV-STZ) induced neuronal loss and memory impairment. To test this hypothesis, male Wistar rats were pretreated with CH (10 and 20 mg/kg bwt) orally once daily for 21 days and then bilaterally injected with ICV-STZ (3 mg/kg bwt), while sham group rats receive the same volume of vehicle. After 2 weeks of ICV-STZ infusion, rats were tested for cognitive performance using Morris water maze (MWM) test and then sacrifice for biochemical and histopathological assays. CH was found to be successful in upregulating the antioxidant status and prevented the memory loss. The expression of choline acetyl transferase (ChAT) was decreased in ICV-STZ group and CH pretreatment increases the expression of ChAT. Moreover, inflammatory mediators like TNF-α, IL-1β levels and expression of iNOS were significantly attenuated by CH pretreatment. The study suggests that CH is effective in preventing memory loss, ameliorating the oxidative stress and might be beneficial for the treatment of sporadic dementia of Alzheimer’s type (SDAT). 相似文献
24.
Thermophilic (55°C) and moderately hyperthermophilic (65°C) fermentation of poultry manure triggers release of high heavy metal concentrations leading to enhanced genotoxicity
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Proper disposal of waste from poultry industries may be done by thermophilic anaerobic digestion. Particularly, thermophilic fermentation exhibits pivotal advantages. However, not only the accrued waste material (digestate) serves as organic fertilizer but also poses environmental problems when the pollutant release is poorly synchronized with the environmental demand. To minimize environmental risks, additional hyperthermophilic (moderately hyperthermophilic) treatment of animal by‐products is necessary, but concurrent release of pollutants is notably increased. To estimate the quantity and quality of pollutants released, we analyzed various organic compounds as well as 21 metals and tested their genotoxic/mutagenic potential by using the Allium cepa assay and the Ames test. As, Cd, Ni, and W were not detected or had low concentration (0.01–0.47 mg/kg) and were considered of little relevance. Co, Cr, Ni, Pb, and Mo were detected at concentrations up to 5.76 mg/kg. Fe, Mn, Zn, and Cu had the highest concentrations and were accumulated to inhibitory levels. Phenolic compounds were detected in negligible concentrations. We found that approximately 30% of onion root chromosomes were permanently damaged by high heavy metal concentrations released from the digestates. Higher temperatures and longer fermentation times fostered an increased release of pollutants above permissible limits. 相似文献
25.
Farah El Najjar Nicolás Cifuentes-Mu?oz Jing Chen Haining Zhu Ursula J. Buchholz Carole L. Moncman Rebecca Ellis Dutch 《PLoS pathogens》2016,12(9)
Paramyxovirus spread generally involves assembly of individual viral particles which then infect target cells. We show that infection of human bronchial airway cells with human metapneumovirus (HMPV), a recently identified paramyxovirus which causes significant respiratory disease, results in formation of intercellular extensions and extensive networks of branched cell-associated filaments. Formation of these structures is dependent on actin, but not microtubule, polymerization. Interestingly, using a co-culture assay we show that conditions which block regular infection by HMPV particles, including addition of neutralizing antibodies or removal of cell surface heparan sulfate, did not prevent viral spread from infected to new target cells. In contrast, inhibition of actin polymerization or alterations to Rho GTPase signaling pathways significantly decreased cell-to-cell spread. Furthermore, viral proteins and viral RNA were detected in intercellular extensions, suggesting direct transfer of viral genetic material to new target cells. While roles for paramyxovirus matrix and fusion proteins in membrane deformation have been previously demonstrated, we show that the HMPV phosphoprotein extensively co-localized with actin and induced formation of cellular extensions when transiently expressed, supporting a new model in which a paramyxovirus phosphoprotein is a key player in assembly and spread. Our results reveal a novel mechanism for HMPV direct cell-to-cell spread and provide insights into dissemination of respiratory viruses. 相似文献
26.
Balancing economic costs and ecological outcomes of passive and active restoration in agricultural landscapes: the case of Brazil
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Pedro H. S. Brancalion Daniella Schweizer Ulysse Gaudare Julia R. Mangueira Fernando Lamonato Fabiano T. Farah André G. Nave Ricardo R. Rodrigues 《Biotropica》2016,48(6):856-867
Forest restoration requires strategies such as passive restoration to balance financial investments and ecological outcomes. However, the ecological outcomes of passive restoration are traditionally regarded as uncertain. We evaluated technical and legal strategies for balancing economic costs and ecological outcomes of passive versus active restoration in agricultural landscapes. We focused in the case of Brazil, where we assessed the factors driving the proportion of land allocated to passive and active restoration in 42 programs covering 698,398 hectares of farms in the Atlantic Forest, Atlantic Forest/cerrado ecotone and Amazon; the ecological outcomes of passive and active restoration in 2955 monitoring plots placed in six restoration programs; and the legal framework developed by some Brazilian states to balance the different restoration approaches and comply with legal commitments. Active restoration had the highest proportion of land allocated to it (78.4%), followed by passive (14.2%) and mixed restoration (7.4%). Passive restoration was higher in the Amazon, in silviculture, and when remaining forest cover was over 50 percent. Overall, both restoration approaches showed high levels of variation in the ecological outcomes; nevertheless, passively restored areas had a smaller percentage canopy cover, lower species density, and less shrubs and trees (dbh > 5 cm). The studied legal frameworks considered land abandonment for up to 4 years before deciding on a restoration approach, to favor the use of passive restoration. A better understanding of the biophysical and socioeconomic features of areas targeted for restoration is needed to take a better advantage of their natural regeneration potential. 相似文献
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Javid Sadri Nahand Farah Bokharaei-Salim Arash Salmaninejad Abolfazl Nesaei Fatemeh Mohajeri Azadeh Moshtzan Alireza Tabibzadeh Mohammad Karimzadeh Mohsen Moghoofei Arezo Marjani Shoeleh Yaghoubi Hossein Keyvani 《Journal of cellular physiology》2019,234(8):12188-12225
Hepatocellular carcinoma (HCC) is known as one of the major health problems worldwide. Pathological analysis indicated that a variety of risk factors including genetical (i.e., alteration of tumor suppressors and oncogenes) and environmental factors (i.e., viruses) are involved in beginning and development of HCC. The understanding of these risk factors could guide scientists and clinicians to design effective therapeutic options in HCC treatment. Various viruses such as hepatitis B virus (HBV) and hepatitis C virus (HCV) via targeting several cellular and molecular pathways involved in HCC pathogenesis. Among various cellular and molecular targets, microRNAs (miRNAs) have appeared as key players in HCC progression. miRNAs are short noncoding RNAs which could play important roles as oncogenes or tumor suppressors in several malignancies such as HCC. Deregulation of many miRNAs (i.e., miR-222, miR-25, miR-92a, miR-1, let-7f, and miR-21) could be associated with different stages of HCC. Besides miRNAs, exosomes are other particles which are involved in HCC pathogenesis via targeting different cargos, such as DNAs, RNAs, miRNAs, and proteins. In this review, we summarize the current knowledge of the role of miRNAs and exosomes as important players in HCC pathogenesis. Moreover, we highlighted HCV- and HBV-related miRNAs which led to HCC progression. 相似文献