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81.
Multiple different approaches are being used to activate the immune system against breast cancer. Vaccine therapy in general
follows the principle that injections of various substances ultimately result in the presentation of tumor peptides to the
patient’s immune system. We proposed a potential in silico DNA vaccine against breast cancer by integrating high affinity
T cell (MHC-I and MHC-II) and B cell (continuous and discontinuous) epitopes. The matching of the HLA haplotype and antigen
was performed to provide the appropriate peptide epitope suitable for majority of the patients. The immunogenic nature of
the antigenic construct was also enhanced by the administration of consensus epitopes. The potency of DNA vaccines depends
on the efficient expression and presentation of the encoded antigen of interest and the chances of efficient expression of
our antigenic construct in host organism was also verified by in silico approaches. An attempt was made to overcome the limited
potency of the DNA vaccine by targeting DNA to professional antigen-presenting cells (APCs). A higher immune response theoretically
corresponds to a higher survival rate of patients. Therefore, optimization studies were also employed to enhance the immunogenicity
of proposed in silico DNA vaccine. 相似文献
82.
83.
Background
Nanoparticles (NPs) can potentially cause adverse effects on organ, tissue, cellular, subcellular and protein levels due to their unusual physicochemical properties. Advances in nanotechnology have identified promising candidates for many biological and biomedical applications. Since the properties of NPs differ from that of their bulk materials, they are being increasingly exploited for medical uses and other industrial applications. The aim of the present study was to investigate the particle-size effect of gold nanoparticles (GNPs) on the hepatic tissue in an attempt to cover and understand the toxicity and the potential threat of their therapeutic and diagnostic use. 相似文献84.
Use of small interfering RNA (siRNA) is a promising approach for AML treatment as the siRNA molecule can be designed to specifically target proteins that contribute to aberrant cell proliferation in this disease. However, a clinical-relevant means of delivering siRNA molecules must be developed, as the cellular delivery of siRNA is problematic. Here, we report amphiphilic carriers combining a cationic polymer (2 kDa polyethyleneimine, PEI2) with lipophilic moieties to facilitate intracellular delivery of siRNA to AML cell lines. Complete binding of siRNA by the designed carriers was achieved at a polymer:siRNA ratio of ~0.5 and led to siRNA/polymer complexes of ~100 nm size. While the native PEI2 did not display cytotoxicity on AML cell lines THP-1, KG-1 and HL-60, lipid-modification on PEI2 slightly increased the cytotoxicity, which was consistent with increased interaction of polymers with cell membranes. Cellular delivery of siRNA was dependent on the nature of lipid substituent and the extent of lipid substitution, and varied among the three AML cell lines used. Linoleic acid-substituted polymers performed best among the prepared polymers and gave a siRNA delivery equivalent to better performing commercial reagents. Using THP-1 cells and a reporter (GFP) and an endogenous (CXCR4) target, effective silencing of the chosen targets was achieved with 25 to 50 nM of siRNA concentrations, and without adversely affecting subsequent cell growth. We conclude that lipid-substituted PEI2 can serve as an effective delivery of siRNA to leukemic cells and could be employed in molecular therapy of leukemia. 相似文献
85.
U Bashir Aamir N Badar MR Mehmood N Nisar RM Suleman S Shaukat S Sharif J Kamran SS Zaidi BM Kazi L Gubareva X Xu R Garten A Klimov 《PloS one》2012,7(8):e41866
Background
In early 2009, a novel influenza A(H1N1) virus that emerged in Mexico and United States rapidly disseminated worldwide. The spread of this virus caused considerable morbidity with over 18000 recorded deaths. The new virus was found to be a reassortant containing gene segments from human, avian and swine influenza viruses.Methods/Results
The first case of human infection with A(H1N1)pdm09 in Pakistan was detected on 18th June 2009. Since then, 262 laboratory-confirmed cases have been detected during various outbreaks with 29 deaths (as of 31st August 2010). The peak of the epidemic was observed in December with over 51% of total respiratory cases positive for influenza. Representative isolates from Pakistan viruses were sequenced and analyzed antigenically. Sequence analysis of genes coding for surface glycoproteins HA and NA showed high degree of high levels of sequence identity with corresponding genes of regional viruses circulating South East Asia. All tested viruses were sensitive to Oseltamivir in the Neuraminidase Inhibition assays.Conclusions
Influenza A(H1N1)pdm09 viruses from Pakistan form a homogenous group of viruses. Their HA genes belong to clade 7 and show antigenic profile similar to the vaccine strain A/California/07/2009. These isolates do not show any amino acid changes indicative of high pathogenicity and virulence. It is imperative to continue monitoring of these viruses for identification of potential variants of high virulence or drug resistance. 相似文献86.
Ryuichi Takahashi Khurram Bashir Yasuhiro Ishimaru Naoko K. Nishizawa Hiromi Nakanishi 《Plant signaling & behavior》2012,7(12):1605-1607
The P1B-type heavy metal ATPases (HMAs) are diverse in terms of tissue distribution, subcellular localization, and metal specificity. Functional studies of HMAs have shown that these transporters can be divided into two subgroups based on their metal-substrate specificity: a copper (Cu)/silver (Ag) group and a zinc (Zn)/cobalt (Co)/cadmium (Cd)/lead (Pb) group. Studies on Arabidopsis thaliana and metal hyperaccumulator plants indicate that HMAs play an important role in the translocation or detoxification of Zn and Cd in plants. Rice possesses nine HMA genes, of which OsHMA1–OsHMA3 belong to the Zn/Co/Cd/Pb subgroup. OsHMA2 plays an important role in root-to-shoot translocation of Zn and Cd, and participates in Zn and Cd transport to developing seeds in rice. OsHMA3 transports Cd and plays a role in the sequestration of Cd into vacuoles in root cells. Modification of the expression of these genes might be an effective approach for reducing the Cd concentration in rice grains. 相似文献
87.
Wahab HS 《Journal of molecular modeling》2012,18(6):2709-2716
The semi-empirical MSINDO method has been used to investigate the mode of adsorption of benzoic acid on the nano anatase TiO(2) (100) surface. The (100) surface is modeled with a Ti(36)O(90)H(36) cluster. Molecular dynamics simulations for the adsorption behavior of benzoic acid indicate it is linked to the TiO(2) surface through interactions from the oxygen atoms of the carboxylic acid moiety with surface titanium atoms. The benzoic acid may be positioned with its aromatic ring either parallel or perpendicular relative to the surface, however the perpendicular adsorption mode is more stable. The calculated substrate-surface interaction energy is influenced by the number of linkages between the substrate and the surface as well as the degree of hydrogen bonding between the acid hydrogen and lattice oxygen atom. The greater stability of the perpendicular adsorption orientation is ascribed to the higher number of linkages between the substrate and the surface. It is concluded that the simplified model is sufficiently detailed to elucidate surface interactions. 相似文献
88.
Santosh Kumar Ramachandra Jadhav Krunal Arvind Patel Bhushan Bhalchandra Dholakia Bashir Mohammad Khan 《Bioinformation》2012,8(19):943-949
Medicinal plants are extensively utilized in traditional and herbal medicines, both in India and around the world due to the
presence of diverse low molecular weight natural products such as flavonoids, alkaloids, terpenoids and sterols. Flavonoids which
have health benefits for humans are the large class of phenylpropanoid-derived secondary metabolites and are mostly glycosylated
by UDP-glycosyltransferases (UGTs). Although large numbers of different UGTs are known from higher plants, very few protein
structures have been reported till now. In the present study, the three-dimensional model of flavonoid specific glycosyltransferases
(WsFGT) from Withania somnifera was constructed based on the crystal structure of plant UGTs. The resulted model was assessed
by various tools and the final refined model revealed GT-B type fold. Further, to understand the sugar donors and acceptors
interactions with the active site of WsFGT, docking studies were performed. The amino acids from conserved PSPG box were
interacted with sugar donor while His18, Asp110, Trp352 and Asn353 were important for catalytic function. This structural and
docking information will be useful to understand the glycosylation mechanism of flavonoid glucosides.
Abbreviations
DOPE - Discrete Optimized Potential Energy, PDB - Protein Data Bank, PSPG - Plant Secondary Product Glycosyltransferase, RMSD - Root Mean Squared Deviation, UDP - Uridine diphosphate, UGT - UDP-glycosyltransferases. 相似文献89.
Wani SA Ahmad F Zargar SA Dar ZA Dar PA Tak H Fomda BA 《The Journal of parasitology》2008,94(3):591-593
Soil-transmitted helminths (STHs) remain a major threat to the health of children throughout the world, mostly in developing nations. The aim of the present study was to determine any relationship between STHs and hemoglobin status in school children of Kashmir Valley (India). Stool and blood samples were collected from 382 male and female school children in the age group of 5-15 yr from all 6 school districts of the Kashmir Valley. Finger-prick blood samples were used to collect the hemoglobin, which was then measured on-site by Sahli's acid hematin method; stool samples were processed using both simple smear and zinc sulphate concentration methods. Of the 382 children surveyed, 299 (78.27%) were infected with Ascaris lumbricoides, Trichuris trichiura, or both. Children infected by STHs were found to have lower mean values of hemoglobin than uninfected children. The present study reveals that STHs are abundant among school children of Kashmir Valley, creating a negative effect on the hemoglobin values and indicating the necessity of implementing control measures. 相似文献
90.
Herrera FE Chesi A Paleologou KE Schmid A Munoz A Vendruscolo M Gustincich S Lashuel HA Carloni P 《PloS one》2008,3(10):e3394
The interplay between dopamine and alpha-synuclein (AS) plays a central role in Parkinson's disease (PD). PD results primarily from a severe and selective devastation of dopaminergic neurons in substantia nigra pars compacta. The neuropathological hallmark of the disease is the presence of intraneuronal proteinaceous inclusions known as Lewy bodies within the surviving neurons, enriched in filamentous AS. In vitro, dopamine inhibits AS fibril formation, but the molecular determinants of this inhibition remain obscure. Here we use molecular dynamic (MD) simulations to investigate the binding of dopamine and several of its derivatives onto conformers representative of an NMR ensemble of AS structures in aqueous solution. Within the limitations inherent to MD simulations of unstructured proteins, our calculations suggest that the ligands bind to the (125)YEMPS(129) region, consistent with experimental findings. The ligands are further stabilized by long-range electrostatic interactions with glutamate 83 (E83) in the NAC region. These results suggest that by forming these interactions with AS, dopamine may affect AS aggregation and fibrillization properties. To test this hypothesis, we investigated in vitro the effects of dopamine on the aggregation of mutants designed to alter or abolish these interactions. We found that point mutations in the (125)YEMPS(129) region do not affect AS aggregation, which is consistent with the fact that dopamine interacts non-specifically with this region. In contrast, and consistent with our modeling studies, the replacement of glutamate by alanine at position 83 (E83A) abolishes the ability of dopamine to inhibit AS fibrillization. 相似文献