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81.
Gospodarska E Kupniewska-Kozak A Goch G Dadlez M 《Biochimica et biophysica acta》2011,1814(5):592-609
Alzheimer's disease (AD) symptoms correlate with the concentration of soluble, although not necessarily monomeric forms of Aβ peptide in the brain parenchyma. The RAGE receptor has been implicated as the protein responsible for active transport of Aβ from blood circulation to the brain. In murine models of AD, inhibition of the Aβ:RAGE interaction decreases the levels of Aβ in the brain. Inhibition of the Aβ:RAGE interaction would be a promising alternative for the therapy of AD. Rational design of an Aβ:RAGE interaction blocker requires detailed knowledge of the structure of the complex. However, the binding domain of RAGE is natively unfolded in physiological conditions, which severely hampers the application of classic methods of protein structure analysis to the design of an antagonist. Here, alternative methods are used to characterize the structural properties of the RAGE-ligand binding domain and to monitor the binding of a series of truncated variants of Aβ. Using intrinsic RAGE tryptophan fluorescence and mass spectrometry of non-covalent protein-ligand complexes we have identified shorter versions of Aβ that bind to the RAGE V-domain. We have also shown in cell culture experiments that a selected shortened version of Aβ effectively inhibits full-length Aβ, RAGE-mediated, cell uptake. Thus, a truncated version of Aβ capable of blocking its receptor-mediated internalization was established, revealing the binding code and providing the lead compound in the process of drug design. 相似文献
82.
Carmen A Ambarus Troy Noordenbos Maria JH de Hair Paul P Tak Dominique LP Baeten 《Arthritis research & therapy》2012,14(2):R74-14
Introduction
Synovial tissue macrophages play a key role in chronic inflammatory arthritis, but the contribution of different macrophage subsets in this process remains largely unknown. The main in vitro polarized macrophage subsets are classically (M1) and alternatively (M2) activated macrophages, the latter comprising interleukin (IL)-4 and IL-10 polarized cells. Here, we aimed to evaluate the polarization status of synovial macrophages in spondyloarthritis (SpA) and rheumatoid arthritis (RA).Methods
Expression of polarization markers on synovial macrophages, peripheral blood monocytes, and in vitro polarized monocyte-derived macrophages from SpA versus RA patients was assessed by immunohistochemistry and flow cytometry, respectively. The polarization status of the intimal lining layer and the synovial sublining macrophages was assessed by double immunofluorescence staining.Results
The expression of the IL-10 polarization marker cluster of differentiation 163 (CD163) was increased in SpA compared with RA intimal lining layer, but no differences were found in other M1 and M2 markers between the diseases. Furthermore, no significant phenotypic differences in monocytes and in vitro polarized monocyte-derived macrophages were seen between SpA, RA, and healthy controls, indicating that the differential CD163 expression does not reflect a preferential M2 polarization in SpA. More detailed analysis of intimal lining layer macrophages revealed a strong co-expression of the IL-10 polarization markers CD163 and cluster of differentiation 32 (CD32) but not any of the other markers in both SpA and RA. In contrast, synovial sublining macrophages had a more heterogeneous phenotype, with a majority of cells co-expressing M1 and M2 markers.Conclusions
The intimal lining layer but not synovial sublining macrophages display an IL-10 polarized-like phenotype, with increased CD163 expression in SpA versus RA synovitis. These differences in the distribution of the polarized macrophage subset may contribute to the outcome of chronic synovitis. 相似文献83.
Autologous disc cell implantation, growth factors and gene therapy appear to be promising therapies for disc regeneration. Unfortunately, the replicative lifespan and growth kinetics of human nucleus pulposus (NP) cells related to host age are unclear. We investigated the potential relations among age, replicative lifespan and growth rate of NP cells, and determined the age range that is suitable for cell-based biological therapies for degenerative disc diseases. We used NP tissues classified by decade into five age groups: 30s, 40s, 50s, 60s and 70s. The mean cumulative population doubling level (PDL) and population doubling rate (PDR) of NP cells were assessed by decade. We also investigated correlations between cumulative PDL and age, and between PDR and age. The mean cumulative PDL and PDR decreased significantly in patients in their 60s. The mean cumulative PDL and PDR in the younger groups (30s, 40s and 50s) were significantly higher than those in the older groups (60s and 70s). There also were significant negative correlations between cumulative PDL and age, and between PDR and age. We found that the replicative lifespan and growth rate of human NP cells decreased with age. The replicative potential of NP cells decreased significantly in patients 60 years old and older. Young individuals less than 60 years old may be suitable candidates for NP cell-based biological therapies for treating degenerative disc diseases. 相似文献
84.
85.
Jayaraman Selvaraj Umapathy Vidhya Rekha Shazia Fathima JH Venkatacalam Sivabalan Rajagopal Ponnulakshmi Veeraraghavan Vishnupriya Malathi Kullappan Radhika nalinakumari Sreekandan Surapaneni Krishna Mohan 《Bioinformation》2021,17(1):167
It is of interest to document the moelcular docking analysis of SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) with compounds from Plectranthus amboinicus. Hence, we report the binding features of rutin, Luteolin, Salvianolic acid A, Rosmarinic acid and p-Coumaric acid with the target protein SARS-CoV-2 linked RNA dependent RNA polymerase (RdRp) for further consideration. 相似文献
86.
Jayaraman Selvaraj Shazia Fathima JH Venkatacalam Sivabalan Umapathy Vidhya Rekha Rajagopal Ponnulakshmi Veeraraghavan Vishnupriya Malathi Kullappan Radhika Nalinakumari Sreekandan Surapaneni Krishna Mohan Periyasamy Vijayalakshmi 《Bioinformation》2021,17(1):200
Cornulin (CRNN) is linked with tumour progression. Therefore, it is of interest to document data on the molecular modeling of cornulin (CRNN) for docking with phytocompounds (Pyrazinamide, Anisotine, Vasicinone, Vasicoline) from Justicia adhatoda L. Thus, we document the optimal binding features of these compounds with the cornulin model for further consideration. 相似文献
87.
Proliferation of three murine marrow-derived stromal cell lines, LC1, LC2, and LC3, depended on initial cell density. For LC2 and LC3, the cell density-dependence was negated by conditioned-media, indicating growth dependence on a soluble growth factor. For LC1, conditioned-media failed to stimulate proliferation, suggesting growth dependence on direct cell-cell contact. 相似文献
88.
Camarodont sea urchins possess a rapidly evolving actin gene family whose
members are expressed in distinct cell lineages in a developmentally
regulated fashion. Evolutionary changes in the actin gene family of
echinoids include alterations in number of family members, site of
expression, and gene linkage, and a dichotomy between rapidly and slowly
evolving isoform-specific 3' untranslated regions. We present sequence
comparisons and an analysis of the actin gene family in two congeneric sea
urchins that develop in radically different modes, Heliocidaris
erythrogramma and H. tuberculata. The sequences of several actin genes from
the related species Lytechinus variegatus are also presented. We compare
the features of the Heliocidaris and Lytechinus actin genes to those of the
the actin gene families of other closely related sea urchins and discuss
the nature of the evolutionary changes among sea urchin actins and their
relationship to developmental mode.
相似文献
89.
90.
Stable expression of mammalian beta 1,4-galactosyltransferase extends the N-glycosylation pathway in insect cells 总被引:5,自引:2,他引:3
An established lepidopteran insect cell line (Sf9) was cotransfected with
expression plasmids encoding neomycin phosphotransferase and bovine beta
1,4-galactosyltransferase. Neomycin-resistant transformants were selected,
assayed for beta 1,4-galactosyltransferase activity, and the transformant
with the highest level of enzymatic activity was characterized. Southern
blots indicated that this transformed Sf9 cell derivative contained
multiple copies of the galactosyltransferase- encoding expression plasmid
integrated at a single site in its genome. One-step growth curves showed
that these cells supported normal levels of baculovirus replication.
Baculovirus infection of the transformed cells stimulated beta
1,4-galactosyltransferase activity almost 5-fold by 12 h postinfection.
This was followed by a gradual decline in activity, but the infected cells
still had about as much activity as uninfected controls as late as 48 h
after infection and they were able to produce a beta 1,4-galactosylated
virion glycoprotein during infection. Infection of the transformed cells
with a conventional recombinant baculovirus expression vector encoding
human tissue plasminogen activator also resulted in the production of a
galactosylated end-product. These results demonstrate that stable
transformation can be used to add a functional mammalian
glycosyltransferase to lepidopteran insect cells and extend their N-
glycosylation pathway. Furthermore, stably-transformed insect cells can be
used as modified hosts for conventional baculovirus expression vectors to
produce foreign glycoproteins with "mammalianized" glycans which more
closely resemble those produced by higher eucaryotes.
相似文献