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排序方式: 共有126条查询结果,搜索用时 31 毫秒
41.
42.
Lakshmi Ganapathi Simon Van Haren David J. Dowling Ilana Bergelson Nikunj M. Shukla Subbalakshmi S. Malladi Rajalakshmi Balakrishna Hiromi Tanji Umeharu Ohto Toshiyuki Shimizu Sunil A. David Ofer Levy 《PloS one》2015,10(8)
Background
Newborns and young infants are at higher risk for infections than adults, and manifest suboptimal vaccine responses, motivating a search for novel immunomodulators and/or vaccine adjuvants effective in early life. In contrast to most TLR agonists (TLRA), TLR8 agonists such as imidazoquinolines (IMQs) induce adult-level Th1-polarizing cytokine production from human neonatal cord blood monocytes and are candidate early life adjuvants. We assessed whether TLR8-activating IMQ congeners may differ in potency and efficacy in inducing neonatal cytokine production in vitro, comparing the novel TLR7/8-activating IMQ analogues Hybrid-2, Meta-amine, and Para-amine to the benchmark IMQ resiquimod (R848).Methods
TLRA-induced NF-κB activation was measured in TLR-transfected HEK cells. Cytokine production in human newborn cord and adult peripheral blood and in monocyte-derived dendritic cell cultures were measured by ELISA and multiplex assays. X-ray crystallography characterized the interaction of human TLR8 with Hybrid-2.Results
Hybrid-2 selectively activated both TLR7 and 8 and was more potent than R848 in inducing adult-like levels of TNF-α, and IL-1β. Consistent with its relatively high in vitro activity, crystallographic studies suggest that absence in Hybrid-2 of an ether oxygen of the C2-ethoxymethyl substituent, which can engage in unfavorable electrostatic and/or dipolar interactions with the carbonyl oxygen of Gly572 in human TLR8, may confer greater efficacy and potency compared to R848.Conclusions
Hybrid-2 is a selective and potent TLR7/8 agonist that is a candidate adjuvant for early life immunization. 相似文献43.
Rajalakshmi Chockalingam 《Molecular simulation》2015,41(13):1110-1121
The self-association behaviour of atactic poly(methacrylic acid) (a-PMA) in water was investigated by atomistic molecular dynamics (MD) simulations. Simulations show that interchain association of a-PMA occurs only in its un-neutralised form, by hydrogen bonding between –COOH groups, which is in agreement with the experimental observation. Chain conformations, dihedral angle distributions, hydration behaviour, scattering structure factor and enthalpy-of-hydration (i.e. aqueous solvation) were analysed as a function of concentration for un-neutralised PMA, across dilute to concentrated regimes. The average 〈Rg〉 of the chain remains unaffected in solution and also for amorphous undissolved a-PMA phase, confirming the occurrence of the approximate theta-solution condition for the first time, as revealed by simulations, in a polar hydrogen-bonding polymer aqueous solution. Chain hydration behaviour and scattering structure factor show significant changes in concentrated regime. Scattering intensity collapse occurs in concentrated PMA solution, due to the existence of the swollen regime captured for the first time by explicit-MD-simulations. The hydration of PMA is driven by H-bonding, specifically between H atoms of the COOH groups and O atoms of water molecules in the closest coordination shell. The enthalpy of hydration of PMA is dominated by PMA–water interactions (charges and H-bonding). The thermodynamic contributions of PMA–PMA and PMA–water interactions towards the electrostatics as well as the dispersion components of the total solvation-enthalpy become more favourable than water–water interactions. 相似文献
44.
Daisy P Singh SK Vijayalakshmi P Selvaraj C Rajalakshmi M Suveena S 《Bioinformation》2011,6(4):167-168
Pharmacophore feature is defined by a set of chemical structure patterns having the active site of drug like molecule. Pharmacophore can be used to assist in building hypothesis about desirable chemical properties in drug molecule and hence it can be used to refine and modify drug candidates. We predicted the pharmacophoric features of 150 medicinal compounds from plants for anti-cancer, anti-carcinogenic, anti-diabetic, anti-microbial, and anti-oxidant. Estimation of pharmacophoric feature is necessary to ensure the optimal supramolecular interaction with a biological target and to trigger or block its biological response. We subsequently make this data available to open access using a database at the URL: http://www.hccbif.info/index.htm AVAILABILITY: The database is available for free at http://www.hccbif.info/index.htm. 相似文献
45.
Mathivanan J Rohini K Gope ML Anandh B Gope R 《Molecular and cellular biochemistry》2007,302(1-2):67-77
A total of 40 human brain tumor samples were analyzed for tumor-specific alterations at the RB1 gene locus. Gliomas were more
prevalent in younger males and meningiomas in older females. Southern blot analysis revealed loss of heterozygosity (LOH)
at the intron 1 locus of RB1 gene in 19.4% of informative cases and this is the first report showing LOH at this locus in
human brain tumors. Levels of RB1 mRNA and protein, pRb, and the percentage of hyperphosphorylated form of pRb were also analyzed
in these tumors. Normal human fibroblast cell line WI38 was used as control in northern and western analysis. Normal sized
RB1 mRNA and protein were present in all the tumor samples. Majority of the gliomas had 2.0-fold or higher levels of RB1 mRNA
and most meningiomas had less than 2.0-fold of RB1 mRNA compared to control WI38 cells. The total pRb levels were 2.0-fold
or higher in all the tumor samples compared to control. More than 50% of pRb existed in hyperphosphorylated form in all gliomas
except two. However, six out of 13 meningiomas had less than 50% of total pRb in the hyperphosphorylated form. These results
indicate that the increased percentage of hyperphosphorylated form of pRb in gliomas could provide growth advantage to these
tumors. Presence of LOH at the RB1 gene locus and the increased levels of RB1 RNA and protein and increased percentage of
hyperphosphorylated form of pRb are indicative of an overall deregulation of pRb pathway in human brain tumors. 相似文献
46.
The effect of salt concentration and valency on intermolecular structure and solvation thermodynamic properties of aqueous solution containing polyacrylicacid (PAA) chains and multi-valent salts calcium chloride (CaCl2) and aluminium chloride (AlCl3) as a function of charge density was investigated using atomistic molecular dynamic simulations with explicit solvent. Salt-free solution favours the self-association of uncharged (acidic form) PAA chains facilitated by inter-chain hydrogen bonds. The ionised (charged) PAA chains are not associated in salt-free aqueous solutions and undergo self-association in the salt solutions due to bridging effect induced by condensed salt ions in agreement with scattering investigations available in literature. The collapse behaviour of PAA in presence of CaCl2 and re-expansion behaviour of PAA chains in case of AlCl3 salt solutions are observed. The rigidity of PAA chains decrease with increase in salt concentration, in agreement with experimental results available in literature. The trivalent salt favours relatively the greater extent of shrinking of PAA chains as well as inter-chain interactions as compared to divalent salts as evident from radius-of-gyration, H-bond and pair-wise solvation enthalpy data. The conformation and hydration behaviour of the acid form of PAA chains are not significantly altered by added salt ions. The hydration behaviour of ionised PAA chains is significantly reduced by added salts due to screening effect of the condensed salt ions. The pair correlation functions of solutions species such as Ca2+, Al3+, Na+ and Cl? with respect to PAA oxygen show the greater affinity of PAA units with the higher valency Al3+ ions over Ca2+ and Na+ in solution. With increase in concentration of AlCl3 and CaCl2 salts, a decrease in effective charge density of ionised PAA chains is observed from the existence of unfavourable PAA–water, PAA–Ca2+ and PAA–Al3+ interactions. 相似文献
47.
Approximately 48.2% of couples of 15 to 49 years of age practice family planning methods in India. Female sterilization accounts
for 34.2%, with male sterilization declining from 3·4% in 1992–93 to 1·9% in 1998–99. Use of the condom increased to 3·1%
from 2·4%. There is an urgent need for research to develop new contraceptive modalities especially for men and also for women
and to make existing methods more safe, affordable and acceptable. Current efforts in India to develop a male contraceptive
are mainly directed towards (i) development of antispermatogenic agents to suppress sperm production, (ii) prevention of sperm
maturation, (iii) prevention of sperm transport through vas deferens or rendering these sperm infertile and (iv) prevention
of sperm deposition. Research work in the field of prevention of sperm transport through vas deferens has made significant
advances. Styrene maleic anhydride (SMA) disturbed the electrical charge of spermatozoa leading to acrosome rupture and consequent
loss in fertilizing ability of sperm. A multicentre phase-III clinical trial using SMA is continuing and it is hoped that
the SMA approach would be available in the near future as an indigenously developed injectable intra-vasal male contraceptive.
The safety and efficacy of available oral contraceptives were evaluated. An indigenously developed oral contraceptive ‘Centchorman’,
which is a nonsteroidal, weakly estrogenic but potently antiestrogenic, was found to be safe and effective and is now being
marketed in India since 1991 as a ‘once a week’ pill. Cyclofem and Mesigyna have been recommended as injectable contraceptives
with proper counselling and service delivery by Indian studies. It has been recommended that these injectable contraceptives
be added to the existing range of contraceptive methods available in the National Family Planning Programme. Based on the
Indian studies CuT 200 was also recommended. Studies have indicated the advantage of intrauterine devices (IUD); they are
long acting, relatively easily removed and fertility returns rapidly after their removal. Recent studies have recommended
CuT 200 for use up to 5 years. The combination of some plant products i.e.Embelia ribes, Borax andPiper longum has been found to be safe and effective as a female contraceptive and the results of phase-I clinical trials are encouraging.
Research work is going on in the country in various areas with special reference to hormonal contraceptive — a three monthly
injectable contraceptive, immuno-contraceptives, antiprogestins, etc. 相似文献
48.
We have compared the expression of the retinoblastoma (Rb) and p53 genes in normal human fibroblasts, colon carcinoma cell
lines, matched pairs of colorectal tumor tissues and adjacent normal mucosa and in synchronized human diploid fibroblast cell
line W138. The increased expression of Rb and p53 RNA was observed in a majority of colorectal cancers in comparison to adjacent
normal mucosa and is accompanied by proportional increase in the expression of histone H3 gene. The Rb and p53 RNA levels
varied significantly between the various colon carcinoma cell lines. However, we found that the expression of Rb and p53 RNA
is regulated differently in cell cycle synchronized normal human fibroblasts. The Rb mRNA level did not change with the position
in the cell cycle and did not differ significantly whether the cells were serum deprived or in 10% serum. But p53 mRNA expression
follows the same pattern as histone H3 mRNA. 相似文献
49.
Effects of Nutritional Rehabilitation on the Content and Lipid Composition of Brain Gray and White Matter of Neonatally Undernourished Rats 总被引:2,自引:2,他引:0
Abstract: Neonatal undernutrition affects the content and lipid concentrations of gray and white matter. Nutritional rehabilitation reverses the deficit observed in gray matter. In the case of white matter the lipid concentration but not the content comes back to normal. 相似文献
50.
In an effort to understand the possible role of Rb in cellular growth control, we have investigated the abundance and the
state of phosphorylation of Rb protein (pRb) in normal and colon tumor cell lines as well as in matched colon tumors, adenomas
and adjoining normal colonic mucosa. Resting normal human fibroblast cell lines were found to have only unphosphorylated pRb
and phosphorylation of pRb occurred when the cells entered G1-S phase. In general, the colon tumor tissues had atleast 1.5–2.0
fold increase in the abundance of pRb and 1.5–2.5 fold increase in the percentage of its phosphorylation as compared to the
corresponding normal colonic mucosa. Whereas, the adenomas had similar pRb level and its phosphorylation status as observed
in the normal colonic mucosa. The actively growing tumor cell lines had approximately two fold higher total pRb than normal
cell lines. Although, the percentage of phosphorylated form in growing tumor cell lines as well as normal cell lines were
almost equal, it was still considerably higher than normal colonic mucosa. Moreover, DNA binding assay revealed reduced binding
affinity of pRb from colon tumor cell line SW480 as compared to the normal cell line W138. These results suggest that the
abundance of pRb and its phosphorylation level may have a role in the cellular growth control in human colonic epithelium. 相似文献