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排序方式: 共有305条查询结果,搜索用时 31 毫秒
91.
Swapan S. Jain Mallikarjunachari V.N. Uppuladinne Emily C. McLaughlin Weiqing Wang Sheneil Black 《Journal of biomolecular structure & dynamics》2013,31(2):234-243
Ligand recognition in purine riboswitches is a complex process requiring different levels of conformational changes. Recent efforts in the area of purine riboswitch research have focused on ligand analogue binding studies. In the case of the guanine xanthine phosphoribosyl transferase (xpt) riboswitch, synthetic analogues that resemble guanine have the potential to tightly bind and subsequently influence the genetic expression of xpt mRNA in prokaryotes. We have carried out 25 ns Molecular Dynamics (MD) simulation studies of the aptamer domain of the xpt G-riboswitch in four different states: guanine riboswitch in free form, riboswitch bound with its cognate ligand guanine, and with two guanine analogues SJ1 and SJ2. Our work reveals novel interactions of SJ1 and SJ2 ligands with the binding core residues of the riboswitch. The ligands proposed in this work bind to the riboswitch with greater overall stability and lower root mean square deviations and fluctuations compared to guanine ligand. Reporter gene assay data demonstrate that the ligand analogues, upon binding to the RNA, lower the genetic expression of the guanine riboswitch. Our work has important implications for future ligand design and binding studies in the exciting field of riboswitches. 相似文献
92.
Background
Esophageal squamous cell carcinoma (ESCC) develops as a result of complex epigenetic, genetic and environmental interactions. Epigenetic changes like, promoter hypermethylation of multiple tumour suppressor genes are frequent events in cancer, and certain habit-related carcinogens are thought to be capable of inducing aberrant methylation. However, the effects of environmental carcinogens depend upon the level of metabolism by carcinogen metabolizing enzymes. As such key interactions between habits related factors and carcinogen metabolizing gene polymorphisms towards modulating promoter methylation of genes are likely. However, this remains largely unexplored in ESCC. Here, we studied the interaction of various habits related factors and polymorphism of GSTM1/GSTT1 genes towards inducing promoter hypermethylation of multiple tumour suppressor genes.Methodology/Principal Findings
The study included 112 ESCC cases and 130 age and gender matched controls. Conditional logistic regression was used to calculate odds ratios (OR) and multifactor dimensionality reduction (MDR) was used to explore high order interactions. Tobacco chewing and smoking were the major individual risk factors of ESCC after adjusting for all potential confounding factors. With regards to methylation status, significantly higher methylation frequencies were observed in tobacco chewers than non chewers for all the four genes under study (p<0.01). In logistic regression analysis, betel quid chewing, alcohol consumption and null GSTT1 genotypes imparted maximum risk for ESCC without promoter hypermethylation. Whereas, tobacco chewing, smoking and GSTT1 null variants were the most important risk factors for ESCC with promoter hypermethylation. MDR analysis revealed two predictor models for ESCC with promoter hypermethylation (Tobacco chewing/Smoking/Betel quid chewing/GSTT1 null) and ESCC without promoter hypermethylation (Betel quid chewing/Alcohol/GSTT1) with TBA of 0.69 and 0.75 respectively and CVC of 10/10 in both models.Conclusion
Our study identified a possible interaction between tobacco consumption and carcinogen metabolizing gene polymorphisms towards modulating promoter methylation of tumour suppressor genes in ESCC. 相似文献93.
Neurochemical Research - Fenugreek (Trigonella foenum-graecum) seeds and roots of wild yam (Dioscorea villosa) possess nutritional and medicinal properties and have been used for centuries in... 相似文献
94.
Malignant neuroblastomas are solid tumors in children. Available therapeutic agents are not highly effective for treatment
of malignant neuroblastomas. Therefore, new treatment strategies are urgently needed. We tested the efficacy of combination
of SU5416 (SU), an inhibitor of the vascular endothelial growth factor receptor-2 (VEGFR-2), and (−)-epigallocatechin-3-gallate
(EGCG), a polyphenolic compound from green tea, for controlling growth of human malignant neuroblastoma SH-SY5Y and SK-N-BE2
cells. Combination of 20 μM SU and 50 μM EGCG synergistically inhibited cell survival, suppressed expression of VEGFR-2, inhibited
cell migration, caused cell cycle arrest, and induced apoptosis. Combination of SU and EGCG effectively blocked angiogenic
and survival pathways and modulated expression of cell cycle regulators. Apoptosis was induced by down regulation of Bcl-2,
activation of caspase-3, and cleavage of the DNA repair enzyme poly(ADP-ribose) polymerase (PARP). Taken together, this combination
of drugs can be a promising therapeutic strategy for controlling the growth of human malignant neuroblastoma cells. 相似文献
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97.
Guruprasad K Kadur G Bhattacharjee S Swapan B Kataria S Sunita K Yadav S Sanjeev Y Tiwari A Arjun T Baroniya S Sanjay B Rajiv A Abhinav R Mohanty P 《Photosynthesis research》2007,94(2-3):299-306
Exclusion of UV (280–380 nm) radiation from the solar spectrum can be an important tool to assess the impact of ambient UV
radiation on plant growth and performance of crop plants. The effect of exclusion of UV-B and UV-A from solar radiation on
the growth and photosynthetic components in soybean (Glycine max) leaves were investigated. Exclusion of solar UV-B and UV-B/A radiation, enhanced the fresh weight, dry weight, leaf area
as well as induced a dramatic increase in plant height, which reflected a net increase in biomass. Dry weight increase per
unit leaf area was quite significant upon both UV-B and UV-B/A exclusion from the solar spectrum. However, no changes in chlorophyll
a and b contents were observed by exclusion of solar UV radiation but the content of carotenoids was significantly (34–46%) lowered.
Analysis of chlorophyll (Chl) fluorescence transient parameters of leaf segments suggested no change in the F
v/F
m value due to UV-B or UV-B/A exclusion. Only a small reduction in photo-oxidized signal I (P700+)/unit Chl was noted. Interestingly the total soluble protein content per unit leaf area increased by 18% in UV-B/A and 40%
in UV-B excluded samples, suggesting a unique upregulation of biosynthesis and accumulation of biomass. Solar UV radiation
thus seems to primarily affect the photomorphogenic regulatory system that leads to an enhanced growth of leaves and an enhanced
rate of net photosynthesis in soybean, a crop plant of economic importance. The presence of ultra-violet components in sunlight
seems to arrest carbon sequestration in plants.
An erratum to this article can be found at 相似文献
98.
Glioblastoma patients receive anti-inflammatory agent for alleviation of vasogenic edema and pain prior to surgery, radiotherapy,
and chemotherapy. Oxidative stress is an important mechanism of action of some chemotherapeutic agents in the treatment of
glioblastoma. So, we examined the modulatory effects of methylprednisolone (MP, a steroidal anti-inflammatory agent) and indomethacin
(IM, a non-steroidal anti-inflammatory agent) on apoptosis in rat C6 glioblastoma cells following oxidative stress with hydrogen
peroxide (H2O2). Exposure of C6 cells to 1 mM H2O2 for 24 h caused significant amounts of morphological and biochemical features of apoptosis. Expressions of Bax and Bcl-2
at mRNA and protein levels were altered resulting in an increase in Bax : Bcl-2 ratio in apoptotic cells, which also exhibited
overexpression of 80 kDa calpain and an increase in calpain-cleaved 145 kDa α-spectrin breakdown product. Immunofluorescent
and propidium iodide labeling detected caspase-3-p20 fragment in apoptotic cells, indicating activation of caspase-3 as well.
Treatment of cells with 1 μM MP or 10 μM IM alone did not induce apoptosis. Pretreatment (1 h) with either 1 μM MP or 10 μM
IM significantly inhibited H2O2 mediated apoptosis in C6 cells. Thus, pretreatment of glioblastoma with an anti-inflammatory agent, either steroidal or non-steroidal,
may compromise the action of a chemotherapeutic agent that mediates therapeutic action via oxidative stress. 相似文献
99.
Glioblastoma is the most malignant human brain tumor that shows poor response to existing therapeutic agents. Search continues
for an effective therapy for controlling this deadliest brain tumor. Curcumin (CCM), a polyphenolic compound from Curcuma longa, possesses anti-cancer properties in both in vitro and in vivo. In the present investigation, we evaluated the therapeutic
efficacy of CCM against human malignant glioblastoma U87MG cells. Trypan blue dye exclusion test showed decreased viability
of U87MG cells with increasing dose of CCM. Wright staining and ApopTag assay, respectively, showed the morphological and
biochemical features of apoptosis in U87MG cells treated with 25 μM and 50 μM of CCM for 24 h. Western blotting showed activation
of caspase-8, cleavage of Bid to tBid, increase in Bax:Bcl-2 ratio, and release of cytochrome c from mitochondria followed by activation of caspase-9 and caspase-3 for apoptosis. Also, CCM treatments increased cytosolic
level of Smac/Diablo to suppress the inhibitor-of-apoptosis proteins and down regulated anti-apoptotic nuclear factor kappa
B (NFκB), favoring the apoptosis. Increased activities of calpain and caspase-3 cleaved 270 kDa α-spectrin at specific sites
generating 145 kDa spectrin break down product (SBDP) and 120 kDa SBDP, respectively, leading to apoptosis in U87MG cells.
Results show that CCM is an effective therapeutic agent for suppression of anti-apoptotic factors and activation of calpain
and caspase proteolytic cascades for apoptosis in human malignant glioblastoma cells.
Special issue in honor of Naren Banik. 相似文献
100.
Transgenics for the expression of β-carotene biosynthetic pathway in the endosperm were developed in indica rice background
by introducing phytoene synthase (psy) and phytoene desaturase (crtI) genes through Agrobacterium-mediated transformation, employing non-antibiotic positive selectable marker phosphomannose isomerase (pmi). Twenty-seven transgenic lines were characterized for the structural organization of T-DNA inserts and the expression of
transgenes in terms of total carotenoid and β-carotene accumulation in the endosperm. Ten lines were also studied for the
inheritance of transgenic loci to the T1 progenies. Copy number and sites of integration of the transgenes ranged from one to four. Almost 50% of the transgenic lines
showed rearrangement of T-DNA inserts. However, most of the rearrangements occurred in the crtI expression cassette which is adjacent to the right T-DNA border. Differences in copy numbers of psy and crtI were also observed indicating partial T-DNA integration. Beyond T-DNA border transfer was also detected in 25% of the lines.
Fifty percent of the lines studied showed single Mendelian locus inheritance, while two lines showed bi-locus inheritance
in the T1 progenies. Some of the lines segregating in 3:1 ratio showed two sites of integration on restriction digestion analysis indicating
that the T-DNA insertion sites were tightly linked. Three transgenic lines showed nonparental types in the segregating progenies,
indicating unstable transgenic locus. Evidences from the HPLC analysis showed that multiple copies of transgenes had a cumulative
effect on the accumulation of carotenoid in the endosperm. T1 progenies, in general, accumulated more carotenoids than their respective parents, the highest being 6.77 μg/g of polished
seeds. High variation in the carotenoid accumulation was observed within the T1 progenies which could be attributed to the variation in the structural organization and expression of transgenes, minor variations
in the genetic background within the progeny plants, or differences in the plant microenvironments. The study identified lines
worthy of further multiplication and breeding based on transgene structural integrity in the segregating progeny and high
expression levels in terms of the β-carotene accumulation. 相似文献