571 research outputs found
Midkine inhibitors: application of a simple assay procedure to screening of inhibitory compounds
<p>Abstract</p> <p>Background</p> <p>Midkine is a heparin-binding cytokine and is involved in etiology of various diseases. Thus, midkine inhibitors are expected to be helpful in treatment of many diseases.</p> <p>Methods</p> <p>We developed a simple assay for midkine activity based on midkine-dependent migration of osteblastic cells. Midkine inhibitors were searched as materials that inhibit this midkine activity. To develop peptides that inhibit midkine activity, we constructed models in which C-terminal half of midkine interacted with α<sub>4</sub>β<sub>1</sub>-integrin. Low molecular weight compounds which are expected to bind to midkine with high affinity were searched by <it>in silico </it>screening with the aid of Presto-X2 program.</p> <p>Results</p> <p>Among peptides in putative binding sites of midkine and the integrin, a peptide derived from β<sub>1</sub>-integrin and that derived from the first β sheet of the C-terminal half of midkine significantly inhibited midkine activity. Two low molecular weight compounds found by <it>in silico </it>screening exhibited no toxicity to target cells, but inhibited midkine activity. They are trifluoro compounds: one (PubChem 4603792) is 2-(2,6-dimethylpiperidin-1-yl)-4-thiophen-2-yl-6-(trifluoromethy)pyrimidine, and the other has a related structure.</p> <p>Conclusions</p> <p>The assay procedure is helpful in screening midkine inhibitors. All reagents described here might become mother material to develop clinically effective midkine inhibitors.</p
Midkine in Inflammation
The 13 kDa heparin-binding growth factor midkine (MK) was originally identified as a molecule involved in the orchestration of embryonic development. Recent studies provided evidence for a new role of MK in acute and chronic inflammatory processes. Accordingly, several inflammatory diseases including nephritis, arthritis, atherosclerosis, colitis, and autoimmune encephalitis have been shown to be alleviated in the absence of MK in animal models. Reduced leukocyte recruitment to the sites of inflammation was found to be one important mechanism attenuating chronic inflammation when MK was absent. Furthermore, MK was found to modulate expression of proinflammatory cytokines and the expansion of regulatory T-cells. Here, we review the current understanding of the role of MK in different inflammatory disorders and summarize the knowledge of MK biology
Combined use of baking soda and electric toothbrushing for removal of artificial extrinsic stain on enamel surface : an in vitro study
This study aimed to investigate the combined effect of baking soda and electric toothbrushing on the removal of artificial extrinsic stain in vitro. Material and Methods: Flat enamel surfaces of 15 bovine incisors were artificially stained
Closing Duality Gaps of SDPs through Perturbation
Let be a primal-dual pair of SDPs with a nonzero finite
duality gap. Under such circumstances, and are weakly
feasible and if we perturb the problem data to recover strong feasibility, the
(common) optimal value function as a function of the perturbation is not
well-defined at zero (unperturbed data) since there are ``two different optimal
values'' and , where and are
the optimal values of and respectively. Thus, continuity of
is lost at zero though is continuous elsewhere. Nevertheless, we show
that a limiting version of is a well-defined monotone decreasing
continuous bijective function connecting and with
domain under the assumption that both and have
singularity degree one. The domain corresponds to directions of
perturbation defined in a certain manner. Thus, ``completely fills''
the nonzero duality gap under a mild regularity condition. Our result is tight
in that there exists an instance with singularity degree two for which
is not continuous.Comment: 26 pages. Comments welcom
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