• Bulletin of the Korean Chemical Society
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• v.32 no.spc8
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• pp.2973-2977
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• 2011

It has been known that the inertial dynamics has a little effect on the reaction rate in solutions. In this work, however, we find that for diffusion-controlled reactions between a ligand and a receptor on the cell surface there is a noticeable inertial dynamic effect on the reaction rate. We estimate the magnitude of the inertial dynamic effect by comparing the approximate analytic results obtained with and without the inertial dynamic effect included. The magnitude of the inertial dynamic effect depends on the friction coefficient of the ligand as well as on the relative scale of the receptor size to the distance traveled by the ligand during its velocity relaxation time.

• The Korean Journal of Pain
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• v.31 no.2
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• pp.73-79
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• 2018

All drugs have both favorable therapeutic and untoward adverse effects. Conventional opioid analgesics possess both analgesia and adverse reactions, such as nausea, vomiting, and respiratory depression. The opioid ligand binds to ${\mu}$ opioid receptor and non-selectively activates two intracellular signaling pathways: the G protein pathway induce analgesia, while the ${\beta}$-arrestin pathway is responsible for the opioid-related adverse reactions. An ideal opioid should activate the G protein pathway while deactivating the ${\beta}$-arrestin pathway. Oliceridine (TRV130) has a novel characteristic mechanism on the action of the ${\mu}$ receptor G protein pathway selective (${\mu}$-GPS) modulation. Even though adverse reactions (ADRs) are significantly attenuated, while the analgesic effect is augmented, the some residual ADRs persist. Consequently, a G protein biased ${\mu}$ opioid ligand, oliceridine, improves the therapeutic index owing to increased analgesia with decreased adverse events. This review article provides a brief history, mechanism of action, pharmacokinetics, pharmacodynamics, and ADRs of oliceridine.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.292.2-293
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• 2003

In the gene therapy. viral gene delivery systems are limited in use because of several drawbacks like host immune reactions. Hence, non-viral gene delivery systems such as cationic polymers or synthetic gene carriers are being widely investigated to overcome the problems in the use of viral vectors. We synthesized a new conjugate of polyethyleniminet carrying galactose moieties as a targeting ligand for asialoglycoprotein (ASGP) receptors of hepatocytes. (omitted)

• Proceedings of the Korean Society of Applied Pharmacology
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• 2000.04a
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• pp.17-19
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• 2000

Heterotrimeric G Proteins transduce ligand binding to a wide variety of seven transmembrane cell surface receptors into intracellular signals. The currently accepted model for the activation of G protein suggests that ligand-activated receptor accelerates GDP-GTP exchange reactions on the ${\alpha}$ subunit of the heterotrimeric G protein. At least seventeen distinct isoforms of the G${\alpha}$ subunit protein have been identified in mammalian organisms. Among them, the G${\alpha}$q family consists of five members whose ${\alpha}$ subunits show different expression patterns. G${\alpha}$q and G${\alpha}$11 seem to be almost ubiquitously expressed, whereas G${\alpha}$14 is predominantly expressed in spleen, lung, kidney and testis. G${\alpha}$16 and its murine counterpart G${\alpha}$15 are expressed in hematopoietic cells and has been shown to couple a wide variety of receptors to phosphoinositide-specific phospholipase C activity. Beta-isoforms of phospholipase C were shown to be activated by all members of G${\alpha}$q family, i.e., G${\alpha}$q, G${\alpha}$11, G${\alpha}$l4 and G${\alpha}$16 subunits either in reconstitution system. or in experiments using cDNA transfection with intact Cos-7 cells.

• The Korean Journal of Pain
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• v.30 no.2
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• pp.86-92
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• 2017

Osteoblasts, originating from mesenchymal cells, make the receptor activator of the nuclear factor kappa B ligand (RANKL) and osteoprotegerin (OPG) in order to control differentiation of activated osteoclasts, originating from hematopoietic stem cells. When the RANKL binds to the RANK of the pre-osteoclasts or mature osteoclasts, bone resorption increases. On the contrary, when OPG binds to the RANK, bone resorption decreases. Denosumab (AMG 162), like OPG (a decoy receptor), binds to the RANKL, and reduces binding between the RANK and the RANKL resulting in inhibition of osteoclastogenesis and reduction of bone resorption. Bisphosphonates (BPs), which bind to the bone mineral and occupy the site of resorption performed by activated osteoclasts, are still the drugs of choice to prevent and treat osteoporosis. The merits of denosumab are reversibility targeting the RANKL, lack of adverse gastrointestinal events, improved adherence due to convenient biannual subcutaneous administration, and potential use with impaired renal function. The known adverse reactions are musculoskeletal pain, increased infections with adverse dermatologic reactions, osteonecrosis of the jaw, hypersensitivity reaction, and hypocalcemia. Treatment with 60 mg of denosumab reduces the bone resorption marker, serum type 1 C-telopeptide, by 3 days, with maximum reduction occurring by 1 month. The mean time to maximum denosumab concentration is 10 days with a mean half-life of 25.4 days. In conclusion, the convenient biannual subcutaneous administration of 60 mg of denosumab can be considered as a first-line treatment for osteoporosis in cases of low compliance with BPs due to gastrointestinal trouble and impaired renal function.

• The Korean Journal of Nuclear Medicine
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• v.33 no.6
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• pp.461-465
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• 1999

Scintillation proximity assay (SPA) is a unique type of radioimmunoassay and makes it possible to use radioisotopes for monitoring binding reactions continuously without separation procedure. Microbeads containing a fluorophor are covalently linked to antibody or receptor. When a radiolabeled antigen or ligand is added it binds to the beads and the emitted short range electrons, excite the fluorophor in the beads. The light emitted can be measured in a scintillation counter. $^3H$ or $^{125}I$ has been used for SPA. The sensitivities achieved with SPA are comparable to the sensitivities of other procedures. SPA is applicable to immunology, receptor binding, monitoring interactions of biomolecules and study for the kinetics of interaction between receptors and ligands.

• The korean journal of orthodontics
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• v.35 no.4 s.111
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• pp.262-274
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• 2005

Tooth movement is a result of mutual physiologic responses between the periodontal ligament and alveolar bone stimulated by mechanical strain. The PDL cell and osteoblast are known to have an influence on bone formation by controlling collagen synthesis and alkaline phosphatase activation. Moreover. recent studies have shown that the PDL cell and osteoblast release osteoprotegerin (OPG) and the receptor activator of nuclear factor ぉ ligand (RANKL) to control the level of osteoclast differentiation and activation which in turn influences bone resorption. In this study. progressively increased, continuous tensional force was applied to PDL cells. The objective was to find out which kind of biochemical reactions occur after tensional force application and to illuminate the alveolar bone resorption and apposition mechanism. Continuous and progressively increased tensile force was applied to PDL cells cultured on a petriperm dish with a flexible membrane The amount of $PGE_2$ and ALP synthesis were measured after 1, 3, 0 and 12 hours of force application. Secondly RT-PCR analysis was carried out for OPG and RANKL which control osteoclast differentiation and MMP-1 -8, -9, -13 aud TIMP-1 which regulate the resolution of collagen and resorption of the osteoid layer According to the results. we concluded that progressively increased, concluded force application to human PDL cells reduces $PGE_2$ synthesis, and increases OPG mRNA expression.

• Journal of Gastric Cancer
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• v.16 no.1
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• pp.1-7
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• 2016

Epstein-Barr virus-associated gastric carcinoma (EBVaGC) is one of the four subtypes of gastric carcinoma (GC), as defined by the novel classification recently proposed by The Cancer Genome Atlas. EBVaGC has several clinicopathological features such as longer survival and higher frequency of lymphoepithelioma-like carcinoma (LELC) and carcinoma with Crohn's disease-like lymphoid reaction that distinguish it from EBV-negative GC. The intensity and pattern of host cellular immune response in GC have been found to significantly correlate with the prognosis of patients with GC, suggesting that immune reaction and tumor microenvironment have critical roles in the progression of GC, and in particular, EBVaGC. Here, we reviewed the cellular and molecular mechanisms underlying prominent immune reactions in patients with EBVaGC. In EBVaGC, deregulation of the expression of immune response-related genes promotes marked intra-or peritumoral immune cell infiltration. The expression of programmed death receptor-ligand 1 is known to be increased in EBVaGC, and therefore, it has been proposed as a favorable prognostic factor for patients with EBVaGC, albeit some data supporting this claim are controversial. Overall, the underlying mechanisms and clinical significance of the host cellular immune response in patients with EBVaGC have not been thoroughly elucidated. Therefore, further research is necessary to better understand the role of tumor microenvironment in EBVaGC.

• IMMUNE NETWORK
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• v.23 no.5
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• pp.37.1-37.11
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• 2023

Forkhead box P3-positive (Foxp3⁺)-inducible Tregs (iTregs) are readily generated by TGF-β1 at low TCR signaling intensity. TGF-β1-mediated Foxp3 expression is further enhanced by retinoic acid (RA) and lactoferrin (LF). However, the intensity of TCR signaling required for induction of Foxp3 expression by TGF-β1 in combination with RA and LF is unknown. Here, we found that either RA or LF alone decreased TGF-β1-mediated Foxp3 expression at low TCR signaling intensity. In contrast, at high TCR signaling intensity, the addition of either RA or LF strongly increased TGF-β1-mediated Foxp3 expression. Moreover, decreased CD28 stimulation was more favorable for TGF-β1/LF-mediated Foxp3 expression. Lastly, we found that at high signaling intensities of both TCR and CD28, combined treatment with TGF-β1, RA, and LF induced robust expression of Foxp3, in parallel with powerful suppressive activity against responder T cell proliferation. Our findings that TGFβ/RA/LF strongly generate high affinity Ag-specific iTreg population would be useful for the control of unwanted hypersensitive immune reactions such as various autoimmune diseases.