2,197 research outputs found

    Origin of Difference in the Reactivity of Aliphatic and Aromatic Guanidine-containing Pharmaceuticals Toward [18F]Fluorination: Coulombic Forces and Hydrogen Bonding

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    Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151351/1/bkcs11842.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151351/2/bkcs11842_am.pd

    Leukotactin-1/CCL15-induced chemotaxis signaling through CCR1 in HOS cells

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    AbstractLeukotactin-1 (Lkn-1)/CCL15 is a recently cloned CC-chemokine that binds to the CCR1 and CCR3. Although Lkn-1 has been known to function as a chemoattractant for neutrophils, monocytes and lymphocytes, its cellular mechanism remains unclear. To understand the mechanism of Lkn-1-induced chemotaxis signaling, we examined the chemotactic activities of human osteogenic sarcoma cells expressing CCR1 in response to Lkn-1 using inhibitors of signaling molecules. Inhibitors of Gi/Go protein, phospholipase C (PLC) and protein kinase Cδ (PKCδ) inhibited the chemotactic activity of Lkn-1 indicating that Lkn-1-induced chemotaxis signal is transduced through Gi/Go protein, PLC and PKCδ. The activities of PLC and PKCδ were also enhanced by Lkn-1 stimulation. Chemotactic activity of Lkn-1 was inhibited by the treatment of cycloheximide and actinomycin D suggesting that newly synthesized proteins are needed for chemotaxis. Nuclear factor-κB (NF-κB) inhibitor reduced chemotactic activity of Lkn-1. DNA binding activity of NF-κB was also enhanced by Lkn-1 stimulation. These results suggest that Lkn-1 transduces the signal through Gi/Go protein, PLC, PKCδ, NF-κB and newly synthesized proteins for chemotaxis

    R-parity Violation and Semileptonic Decays of B-meson

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    We investigate the effects of R-parity violation on the semileptonic decays of B-meson in the minimal supersymmetric standard model with explicit R-parity violation and discuss its physical implications. We find that the semileptonic decays of B-meson can be largely affected by the R-parity violation.Comment: 10 pages, LaTex file, no figure. References and a table are added. Tables are improve

    KIOM-79, an Inhibitor of AGEs–Protein Cross-linking, Prevents Progression of Nephropathy in Zucker Diabetic Fatty Rats

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    Advanced glycation end products (AGEs) have been implicated in the development of diabetic complications, including diabetic nephropathy. KIOM-79, an 80% ethanolic extract obtained from parched Puerariae Radix, gingered Magnolia Cortex, Glycyrrhiza Radix and Euphorbia Radix, was investigated for its effects on the development of renal disease in Zucker diabetic fatty rats, an animal model of type 2 diabetes. In vitro inhibitory effect of KIOM-79 on AGEs cross-linking was examined by enzyme-linked immunosorbent assay (ELISA). KIOM-79 (50 mg/kg/day) was given to Zucker diabetic fatty rats for 13 weeks. Body and kidney weight, blood glucose, glycated hemoglobin, urinary albumin and creatinine excretions were monitored. Kidney histopathology, collagen accumulation, fibrinogen and transforming growth factor-beta 1 (TGF-β1) expression were also examined. KIOM-79 reduced blood glucose, kidney weight, histologic renal damage and albuminuria in Zucker diabetic fatty rats. KIOM-79 prevented glomerulosclerosis, tubular degeneration, collagen deposition and podocyte apoptosis. In the renal cortex, TGF-β1, fibronectin mRNA and protein were significantly reduced by KIOM-79 treatment. KIOM-79 reduces AGEs accumulation in vivo, AGE–protein cross-linking and protein oxidation. KIOM-79 could be beneficial in preventing the progression of diabetic glomerularsclerosis in type 2 diabetic rats by attenuating AGEs deposition in the glomeruli

    Red ginseng extract blocks histamine-dependent itch by inhibition of H1R/TRPV1 pathway in sensory neurons

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    Background: Korean Red Ginseng—a steamed root of Panax ginseng Meyer—has long been used as a traditional medicine in Asian countries. Its antipruritic effect was recently found, but no molecular mechanisms were revealed. Thus, the current study focused on determining the underlying molecular mechanism of Korean Red Ginseng extract (RGE) against histamine-induced itch at the peripheral sensory neuronal level. Methods: To examine the antipruritic effect of RGE, we performed in vivo scratching behavior test in mice, as well as in vitro calcium imaging and whole-cell patch clamp experiments to elucidate underlying molecular mechanisms. Results: The results of our in vivo study confirmed that RGE indeed has an antipruritic effect on histamine-induced scratching in mice. In addition, RGE showed a significant inhibitory effect on histamine-induced responses in primary cultures of mouse dorsal root ganglia, suggesting that RGE has a direct inhibitory effect on sensory neuronal level. Results of further experiments showed that RGE inhibits histamine-induced responses on cells expressing both histamine receptor subtype 1 and TRPV1 ion channel, indicating that RGE blocks the histamine receptor type 1/TRPV1 pathway in sensory neurons, which is responsible for histamine-dependent itch sensation. Conclusion: The current study found for the first time that RGE effectively blocks histamine-induced itch in peripheral sensory neurons. We believe that the current results will provide an insight on itch transmission and will be helpful in understanding how RGE exerts its antipruritic effects
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