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Death Receptor-Mediated Apoptosis and Lymphocyte Homeostasis
Published in Richard K. Burt, Alberto M. Marmont, Stem Cell Therapy for Autoimmune Disease, 2019
Lixin Zheng, Richard M. Siegel, Jagan R. Muppidi, Felicita Hornung, Michael J. Lenardo
There are other molecules that have been suggested to have roles in thymic selection. Nur77 and Nor-1, are homologous orphan nuclear steroid receptors that have been shown to promote negative selection in a redundant fashion.50,51 The retinoic acid-related orphan receptor (RORy) seems to provide survival signals during thymic selection.52 Additional molecules like thymocyte glucocorticoid receptors (GR),53 cyclin-dependent kinase 2 (Cdk2),54 and helix-loop-helix proteins like enhancer binding (E) proteins and inhibitor of DNA binding (Id) proteins55,56 are also believed to play roles in thymic selection and thymocyte differentiation. How all these molecules act in concert has yet to be determined.
Thioredoxin-Based Peptide Aptamers: Development and Applications
Published in Rakesh N. Veedu, Aptamers, 2017
David S. Burz, Sergey Reverdatto, Alexander Shekhtman
The earliest study employed Y2H selection to isolate PAs against human cyclin-dependent kinase 2 (Cdk2) from a combinatorial library of 2.9 × 109 molecules containing 20-amino-acid-residue peptide inserts constrained within the TrxA active site loop [3]. The 20-repeat sequence, NNG/T, contained a G or a T at the third position of the codon to reduce the frequency of stop codons, while maintaining the maximum diversity of amino acids. Fourteen PAs were isolated, and six were characterized in vitro and found to have nanomolar binding affinity for Cdk2 and to inhibit phosphorylation of histone H1 by Cdk2/cyclin E kinase, most likely by competing with its H1 substrate.
Effects of Endovascular Intervention on Vascular Smooth Muscle Cell Function
Published in Jiro Nagatomi, Eno Essien Ebong, Mechanobiology Handbook, 2018
Brad Winn, Bethany Acampora, Jiro Nagatomi, Martine LaBerge
The experimental setup developed by Acampora et al. also allowed investigation of cell response to various pharmacologic treatments encountered during vascular intervention. For example, the authors investigated the effect of combined shear and strain in the presence of heparin, an anticoagulant commonly administered during angioplasty procedures [82]. In addition to its properties as an anticoagulant, heparin has also been shown to decrease SMC migration and proliferation [82–84]. A common clinical protocol is to administer a 3–5 min 10,000 unit bolus IV injection of heparin immediately prior to balloon angioplasty [85]. When simulated in vitro, this 10,000 unit bolus injection of heparin was held in contact with the cells for 5 min followed by a 100 μg/mL heparin dosage for 24 h and resulted in decreased rat aortic SMC proliferation [82]. Thus, the aim of the study by Acampora et al. was to test the efficacy of the drug treatment in minimizing intimal hyperplasia following balloon injury. Furthermore, Fasciano et al. demonstrated a decrease in rat SMC proliferation using 100 μg/mL heparin under static conditions as compared to a negative control [86]. This was thought to be due to a block in the G1 to S phase, caused by an inhibition of cyclin-dependent kinase 2 activity. This is in agreement with other studies reported in the literature in which SMC proliferation decreased following heparin administration [82–84,86–88]. A unique finding in the Acampora study was the differential expression of calponin, a calcium-binding protein that inhibits the ATPase activity of myosin, in response to changes in mechanical environment [82]. It was shown that the cells subjected to concurrent strain and fluid shear in the presence of heparin exhibited decreased calponin expression compared to a static control. However, heparin administration to static SMCs increased calponin expression compared to a static control [82]. The results of this study demonstrate a dependency of calponin expression by SMCs in response to heparin administration under varying culture conditions. This differential response of SMCs under static versus dynamic culture conditions clearly illustrates the importance of studying SMCs subjected to physiological levels of mechanical stimuli. A dynamic in vitro simulator is a useful tool with which to investigate SMC response to new pharmaceutical treatments when cultured under physiological mechanical conditions. The in vitro application of mechanical stimuli including cyclic strain and fluid shear is necessary in order to gather experimental data more likely to mirror the in vivo response, and thus be of significant value in the clinical realm. Future improvements to this model may include the addition of a model stent strut to represent an artery after the deployment of a stent. This would allow for rapid evaluation of various stent treatments and coatings for improved cell–biomaterial interaction as well as drug elution. Additionally, coculturing SMCs and ECs together may more closely mimic the native artery.
Nanostructured assemblies of liquid-crystalline supermolecules: from display to medicine
Published in Liquid Crystals, 2019
We investigated how the mesogenic molecules affect the cell cycle [88]. Figure 32 shows the profiles of Western blotting for cell cycle-related enzymes in A549 lung cancer cells. Compound I-7 was found to suppress CDK2 expression. CDK2 is a cell cycle-regulating protein in the G1 phase. CDK 2 is bound with cycline E via one or more hydrogen bonds to become an enzyme which permits G1 to S transition. A key interaction between CDK2 and Cycline E is a hydrogen bond. The cyanobiphenyl derivative is thought to be interacted with CDK2 via hydrogen bonding; therefore, cycline E cannot be interacted with CDK 2 (Figure 33). Thus, G1 arrest occurs. The cyanobiphenyl derivative inhibits the synthesis of enzymes needed for DNA replication.