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51.
Schmidt-Bleek K Schell H Schulz N Hoff P Perka C Buttgereit F Volk HD Lienau J Duda GN 《Cell and tissue research》2012,347(3):567-573
Bone healing commences with an inflammatory reaction which initiates the regenerative healing process leading in the end to
reconstitution of bone. An unbalanced immune reaction during this early bone healing phase is hypothesized to disturb the
healing cascade in a way that delays bone healing and jeopardizes the successful healing outcome. The immune cell composition
and expression pattern of angiogenic factors were investigated in a sheep bone osteotomy model and compared to a mechanically-induced
impaired/delayed bone healing group. In the impaired/delayed healing group, significantly higher T cell percentages were present
in the bone hematoma and the bone marrow adjacent to the osteotomy gap when compared to the normal healing group. This was
mirrored in the higher cytotoxic T cell percentage detected under delayed bone healing conditions indicating longer pro-inflammatory
processes. The highly activated periosteum adjourning the osteotomy gap showed lower expression of hematopoietic stem cell
markers and angiogenic factors such as heme oxygenase and vascular endothelial growth factor. This indicates a deferred revascularization
of the injured area due to ongoing pro-inflammatory processes in the delayed healing group. Results from this study suggest
that there are unfavorable immune cells and factors participating in the initial healing phase. In conclusion, identifying
beneficial aspects may lead to promising therapeutical approaches that might benefit further by eliminating the unfavorable
factors. 相似文献
52.
Hååg P Bektic J Bartsch G Klocker H Eder IE 《The Journal of steroid biochemistry and molecular biology》2005,96(3-4):251-258
We investigated the effects of androgen receptor (AR) down regulation with a small interference RNA molecule (siRNA_AR(start)) on androgen sensitive LNCaP and androgen independent LNCaPabl prostate cancer cells, the latter representing an in vitro model for the development of therapy resistance in prostate cancer. Although LNCaPabl cells express increased levels of AR in comparison with androgen sensitive LNCaP cells, the protein was significantly down regulated in response to siRNA_AR(start) treatment. This AR down regulation resulted in a marked cell growth inhibition in both cell lines. By contrast, DU-145 prostate cancer cells, which lack AR expression, were not inhibited by the siRNA_AR(start). In consequence to AR down regulation, both cell lines, LNCaP and LNCaPabl, shared a highly similar gene expression profile in terms of major changes in cell cycle regulatory genes. The cell cycle inhibitor p21(Waf1/Cip1) as well as cyclin D1 were significantly up regulated by siRNA_AR(start) treatment, considering a switch in cyclin expression towards cell cycle retardation. Control molecules had moderate effects on cell proliferation and gene expression, respectively. In summary, we found that AR inhibition with siRNA induces cell growth retardation in androgen sensitive as well as in androgen independent prostate cancer cells and thus may represent an interesting approach to combat hormone-refractory prostate cancer. 相似文献
53.
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55.
Trost E Blom J Soares Sde C Huang IH Al-Dilaimi A Schröder J Jaenicke S Dorella FA Rocha FS Miyoshi A Azevedo V Schneider MP Silva A Camello TC Sabbadini PS Santos CS Santos LS Hirata R Mattos-Guaraldi AL Efstratiou A Schmitt MP Ton-That H Tauch A 《Journal of bacteriology》2012,194(12):3199-3215
Corynebacterium diphtheriae is one of the most prominent human pathogens and the causative agent of the communicable disease diphtheria. The genomes of 12 strains isolated from patients with classical diphtheria, endocarditis, and pneumonia were completely sequenced and annotated. Including the genome of C. diphtheriae NCTC 13129, we herewith present a comprehensive comparative analysis of 13 strains and the first characterization of the pangenome of the species C. diphtheriae. Comparative genomics showed extensive synteny and revealed a core genome consisting of 1,632 conserved genes. The pangenome currently comprises 4,786 protein-coding regions and increases at an average of 65 unique genes per newly sequenced strain. Analysis of prophages carrying the diphtheria toxin gene tox revealed that the toxoid vaccine producer C. diphtheriae Park-Williams no. 8 has been lysogenized by two copies of the ω(tox)(+) phage, whereas C. diphtheriae 31A harbors a hitherto-unknown tox(+) corynephage. DNA binding sites of the tox-controlling regulator DtxR were detected by genome-wide motif searches. Comparative content analysis showed that the DtxR regulons exhibit marked differences due to gene gain, gene loss, partial gene deletion, and DtxR binding site depletion. Most predicted pathogenicity islands of C. diphtheriae revealed characteristics of horizontal gene transfer. The majority of these islands encode subunits of adhesive pili, which can play important roles in adhesion of C. diphtheriae to different host tissues. All sequenced isolates contain at least two pilus gene clusters. It appears that variation in the distributed genome is a common strategy of C. diphtheriae to establish differences in host-pathogen interactions. 相似文献
56.
Birte Arlt Guido Mastrobuoni Jasmin Wuenschel Kathy Astrahantseff Angelika Eggert Stefan Kempa Hedwig E. Deubzer 《Journal of enzyme inhibition and medicinal chemistry》2021,36(1):1282
The small-molecule inhibitor of phosphoglycerate dehydrogenase, NCT-503, reduces incorporation of glucose-derived carbons into serine in vitro. Here we describe an off-target effect of NCT-503 in neuroblastoma cell lines expressing divergent phosphoglycerate dehydrogenase (PHGDH) levels and single-cell clones with CRISPR-Cas9-directed PHGDH knockout or their respective wildtype controls. NCT-503 treatment strongly reduced synthesis of glucose-derived citrate in all cell models investigated compared to the inactive drug control and independent of PHGDH expression level. Incorporation of glucose-derived carbons entering the TCA cycle via pyruvate carboxylase was enhanced by NCT-503 treatment. The activity of citrate synthase was not altered by NCT-503 treatment. We also detected no change in the thermal stabilisation of citrate synthase in cellular thermal shift assays from NCT-503-treated cells. Thus, the direct cause of the observed off-target effect remains enigmatic. Our findings highlight off-target potential within a metabolic assessment of carbon usage in cells treated with the small-molecule inhibitor, NCT-503. 相似文献
57.
Ferdinand Bohlmann Rajinder K. Gupta Jasmin Jakupovic Harold Robinson Robert M. King 《Phytochemistry》1981,20(7):1609-1612
The re-investigation of Eremanthus glomerulatus afforded three new germacranolides and a guaianolide, while from E. mollis two known furanoheliangolides and a new phenylpropanol derivative were isolated. The germacranolides most probably are precursors of the widespread glaucolides. The structures were elucidated by spectroscopic methods. The chemotaxonomic situation is discussed briefly. 相似文献
58.
Ferdinand Bohlmann Jasmin Jakupovic Robert M. King Harold Robinson 《Phytochemistry》1981,20(7):1613-1622
The aerial parts of L. santosii afforded three new diterpenes, a phenylpropanol, three eudesmane derivatives, three germacranolides, seventeen guaianolides and four rearranged guaianolides of a, so far, unknown type. Furthermore, several known compounds were isolated. The structures of the new compounds, the separations of which caused difficulties, were elucidated by spectroscopic methods and by some chemical transformations. The chemotaxonomic situation is discussed briefly. 相似文献
59.
The investigation of Pegolettia senegalensis afforded several new sesquiterpene lactones, eight cis-6,12-germacra-trans,trans-1(10),4,11-trienolides, five cis-6,12-eudesmanolides, two elemanolides, 8,14-cyclogermacra-1(10),4,7(11)-trien-6,12-olide with a new carbon skeleton, three germacra-1(10),4,11(13)-trien-12-oic acids with ester residues at C-8, 18-hydroxygeranyl nerol, 1,3-dihydroxyoctadecane and a mixture of esters of 3,4-dihydroxy-dihydrocinnamyl alcohol. The structures were elucidated by high field 1HNMR spectroscopy and some chemical transformations. The C-10 configuration of 6,12-cis-eudesmanolides from Calostephane divaricata and Inula crithmoides most likely has to be corrected. The chemotaxonomic situation of the genus Pegolettia and biogenetic considerations are discussed briefly. 相似文献