• The Korean Journal of Physiology and Pharmacology
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• v.26 no.3
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• pp.207-218
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• 2022

Aging in mammals, including humans, is accompanied by loss of bone and muscular function and mass, characterized by osteoporosis and sarcopenia. Although resistance exercise training (RET) is considered an effective intervention, its effect is blunted in some elderly individuals. Fibroblast growth factor (FGF) and its receptor, FGFR, can modulate bone and muscle quality during aging and physical performance. To elucidate this possibility, the FGFR inhibitor NVP-BGJ398 was administrated to C57BL/6n mice for 8 weeks with or without RET. Treatment with NVPBGJ398 decreased grip strength, muscular endurance, running capacity and bone quality in the mice. FGFR inhibition elevated bone resorption and relevant gene expression, indicating altered bone formation and resorption. RET attenuated tibial bone resorption, accompanied by changes in the expression of relevant genes. However, RET did not overcome the detrimental effect of NVP-BGJ398 on muscular function. Taken together, these findings provide evidence that FGFR signaling may have a potential role in the maintenance of physical performance and quality of bone and muscles.

• Food Science of Animal Resources
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• v.42 no.6
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• pp.1046-1060
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• 2022

This study aimed to investigate the effects of the metabolites of Latilactobacillus curvatus BYB3 and indole-activated aryl hydrocarbon receptor (AhR) to increase the tight junction (TJ) proteins in an in vitro model of intestinal inflammation. In a Western blot assay, the metabolites of L. curvatus BYB3 reduced the TJ demage in lipoploysaccharide (LPS) stimulated-Caco-2 cells. This reduction was a result of upregulating the expression of TJ-associated proteins and suppressing the nuclear factor-κB signaling. Immunofluorescence images consistently revealed that LPS disrupted and reduced the expression of TJ proteins, while the metabolites of L. curvatus BYB3 and indole reversed these alterations. The protective effects of L. curvatus BYB3 were observed on the intestinal barrier function when measuring transepithelial electrical resistance. Using high-performance liquid chromatography analysis the metabolites, the indole-3-latic acid and indole-3-acetamide concentrations were found to be 1.73±0.27 mg/L and 0.51±0.39 mg/L, respectively. These findings indicate that the metabolites of L. curvatus BYB3 have increasing mRNA expressions of cytochrome P450 1A1 (CYP1A1) and AhR, and may thus be applicable for therapy of various inflammatory gut diseases as postbiotics.

• The Korean Journal of Nuclear Medicine
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• v.31 no.4
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• pp.421-426
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• 1997

We evaluated the in vivo kinetics, distribution, and pharmacology of N-(4-[$^{18}F$]fluoromethylbenzyl)spiperone ([$^{18}F$]FMBS), a newly developed derivative of spiperone, as a potentially more selective radiotracer for the dopamine (DA) $D_2$ receptors. Mice received 1.9-3.7 MBq (1.8-3.6 nmol/kg) of [$^{18}F$]FMBS by tail vein injection. The time course and regional distribution of the tracer in brain were assessed. Blocking studies were carried out by intravenously preinjecting DA $D_2$ receptor blockers (spiperone, butaclamol) as well as drugs with high affinity for DA $D_1$ (SCH 23390), DA transporter (GBR 12909), and serotonin $S_2$ ($5-HT_2$) (ketanserin) sites. After injection of the tracer, the radioactivity in striatum increased steadily over time, resulting in a striatal-to-cerebellar ratio of 4.8 at 120 min postinjection. By contrast, the radioactivity in cerebellum, frontal cortex, and remaining cortex washed out rapidly. Preinjection of unlabeled FMBS (1 mg/kg) and spiperone (1 mg/kg) reduced [$^{18}F$]FMBS striatal-to-cerebellar ratio by 41% and 80%, respectively. (+)-Butaclamol (1 mg/kg) blocked 80% of the striatal [$^{18}F$]FMBS binding, while (-)-butaclamol (1 mg/kg) did not. Preinjection of SCH 23390 (1 mg/kg) and GBR 12909 (5 mg/kg) had no significant effect on [$^{18}F$]FMBS binding. Ketanserin (1 mg/kg), a ligand for the $5-HT_2$ receptors, did not cause significant inhibition either in striatum, in frontal cortex, or the remaining cortex. The results demonstrate that [$^{18}F$]FMBS labels DA $D_2$ receptors selectively in vivo in the mouse brain. It may hold promise as a selective radiotracer for studying DA $D_2$ receptors in vivo by PET.

• Journal of Microbiology and Biotechnology
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• v.25 no.2
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• pp.274-279
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• 2015

Receptor activator of nuclear factor-kappa B ligand (RANKL) is a critical factor in osteoclastogenesis. It makes osteoclasts differentiate and multinucleate in bone remodeling. In the present study, RANKL was expressed as a soluble maltose binding protein (MBP)-fusion protein using the Escherichia coli maltose binding domain tag system (pMAL) expression vector system. The host cell E. coli DH5α was cultured and induced by isopropyl β-_D-1-thiogalactopyranoside for rRANKL expression. Cells were disrupted by sonication to collect soluble MBP-fused rRANKL. The MBP-fusion rRANKL was purified with MBP Trap affinity chromatography and treated with Tobacco Etch Virus nuclear inclusion endopeptidase (TEV protease) to remove the MBP fusion protein. Dialysis was then carried out to remove binding maltose from the cleaved rRANKL solution. The cleaved rRANKL was purified with a second MBP Trap affinity chromatography to separate unsevered MBP-fusion rRANKL and cleaved MBP fusion protein. The purified rRANKL was shown to have biological activity by performing in vitro cell tests. In conclusion, biologically active rRANKL was successfully purified by a simple two-step chromatography purification process with one column.

• Journal of Ginseng Research
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• v.32 no.4
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• pp.315-323
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• 2008

In the previous studies, we isolated the compound K rich fractions (CKRF) and showed that CKRF inhibited Toll-like receptor (TLR) 4- or TLR9-induced inflammatory signaling. To extend our previous studies,1) we investigated the molecular mechanisms of CKRF in the TLR4-associated signaling via nuclear factor (NF)-${\kappa}B$, and in vivo role of CKRF for induction of tolerance in lipopolysaccharide (LPS)-induced septic shock. In murine bone marrow-dervied macrophages, CKRF significantly inhibited the induction of mRNA expression of proinflammatory mediators such as tumor necrosis factor-${\alpha}$, interleukin-6, cyclooxygenase-2, and inducible nitric oxide synthase. In addition, CKRF significantly attenuated the transcriptional activities of TLR4/LPS-induced NF-${\kappa}B$. Nuclear translocation of NF-${\kappa}B$ in response to LPS stimulation was significantly abrogated by pre-treatment with CKRF. Furthermore, CKRF inhibited the recruitment of p65 to the interferon-sensitive response element flanking region in response to LPS. Finally, oral administration of CKRF significantly protected mice from Gram-negative bacterial LPS-induced lethal shock and inhibited systemic inflammatory cytokine levels. Together, these results demonstrate that CKRF modulates the TLR4-dependent NF-${\kappa}B$ activation, and suggest a therapeutic role for Gram-negative septic shock.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.3
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• pp.1007-1010
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• 2015

Background: The clinical significance of bilateral breast cancer is unclear and its influence on prognosis is controversial. Materials and Methods: Between 2005 and 2009 we identified 110 cases of bilateral breast cancer (BBC) ; 49 patients had synchronous (duration between the occurrence of carcinoma in both breasts was less than 12 months) and 61 had metachronous (duration was more than one year with no ipsilateral local recurrence). We compared the patient characteristics including age, menopausal status, clinical stage, tumor size, histological classification, lymph node status, and hormone receptor and Her-2 status. We also compared the treatment given and overall and disease free survival (DFS) of both groups. Results: Synchronous cases tend to present more aggressively than metachronous cases and age at first presentation adversely affects survival. The 5 year overall survival was 78.7% for metachronous and 60% for synchronous. Patients with positive hormonal status had better five year disease free survival in metachronous compared to synchronous cases, at 76% and 63%, respectively. Age at first presentation >45years had better DFS (65%) compared to those with age ${\leq}45$ years (52%) at 5 years follow up. Conclusions: Patients with synchronous breast cancer may have worse prognosis. Young age and hormone receptor negative were risk factors in our study. Close follow up and early detection of contralateral breast cancer is mandatory.

• Molecules and Cells
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• v.43 no.1
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• pp.34-47
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• 2020

The circadian clock regulates various physiological processes, including bone metabolism. The nuclear receptors Reverbs, comprising Rev-erbα and Rev-erbβ, play a key role as transcriptional regulators of the circadian clock. In this study, we demonstrate that Rev-erbs negatively regulate differentiation of osteoclasts and osteoblasts. The knockdown of Rev-erbα in osteoclast precursor cells enhanced receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast formation, as well as expression of nuclear factor of activated T cells 1 (NFATc1), osteoclast-associated receptor (OSCAR), and tartrate-resistant acid phosphatase (TRAP). The overexpression of Rev-erbα leads to attenuation of the NFATc1 expression via inhibition of recruitment of c-Fos to the NFATc1 promoter. The overexpression of Rev-erbα in osteoblast precursors attenuated the expression of osteoblast marker genes including Runx2, alkaline phosphatase (ALP), bone sialoprotein (BSP), and osteocalcin (OC). Rev-erbα interfered with the recruitment of Runx2 to the promoter region of the target genes. Conversely, knockdown of Rev-erbα in the osteoblast precursors enhanced the osteoblast differentiation and function. In addition, Rev-erbα negatively regulated osteoclast and osteoblast differentiation by suppressing the p38 MAPK pathway. Furthermore, intraperitoneal administration of GSK4112, a Rev-erb agonist, protects RANKL-induced bone loss via inhibition of osteoclast differentiation in vivo. Taken together, our results demonstrate a molecular mechanism of Rev-erbs in the bone remodeling, and provide a molecular basis for a potential therapeutic target for treatment of bone disease characterized by excessive bone resorption.

• Journal of Korean Medicine Rehabilitation
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• v.29 no.2
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• pp.135-147
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• 2019

Objectives This study was performed to evaluate the effect of Pyrola japonica extract (NJ) and its principal constituent, homoarbutin (HA) on osteoclast differentiation and gene expression and bone resorption. The osteoclastogenesis and gene expression were determined in receptor activator of nuclear factor kappa B ligand (RANKL)-stimulated RAW264.7 cell. Methods In order to evaluate the effect of HA extracted from NJ on bone resorption, osteoclasts were used to be differentiated and formed by stimulating RAW264.7 cells with RANKL. Tartarate-resistant acid phosphatase (TRAP) (+) polynuclear osteoclast formation ability was evaluated, and differentiation control genes including cathepsin K, matrix metalloproteinases-9 (MMP-9), and TRAP in osteoclast differentiation were analyzed by real-time polymerase chain reaction (PCR). Immunoblotting was performed to measure the effect of mitogen-activated protein kinase (MAPK) factors on bone resorption, and the effect of osteoclasts on osteoclast differentiation was measured. Results Both NJ and high concentration of HA blocked RANKL-stimulated differentiation from RAW264.7 cell to TRAP-positive multinucleated cells. NJ reduced RANKL-induced expression of TRAP, cathepsin K. Both NJ and high concentration of HA inhibited RANKL-mediated expression of MMP-9, nuclear factor of activated T-cells, cytoplasmic 1, and cellular Jun-fos. NJ suppressed RANKL-stimulated expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase, tumor necrosis factor-alpha, and levels of interleukins. Both NJ and HA decreased bone resorption in osteoclast-induced bone pit formation model. Conclusions These results suggest that NJ and HA blocked bone resorption by decreasing RANKL-mediated osteoclastogenesis through down-regulation of genes for osteoclast differentiation.

• Proceedings of the PSK Conference
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• 2003.04a
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• pp.207.3-208
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• 2003

Peroxisome proliferator-activated receptor (PPAR), a member of the nuclear hormone receptor superfamily, is a transcription factor activated by specific natural or synthetic ligands. It is involved in various cellular processes including adipogenesis, inflammation, cell cycle progression and carcinogenesis. Here, we report the production and characterization of a PPARgamma subtype-specific monoclonal antibody P${\gamma}$ 48.34A, which was raised against full-length human PPARgamma protein. (omitted)

• Proceedings of the Korean Society of Veterinary Pathology Conference
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• 2003.10a
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• pp.11-11
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• 2003

Peroxisome proliferator-activated receptor (PPAR) is nuclear hormone receptors that can be activated by a variety of compounds. Two PPAR gamma isoforms are expressed at the protein level in mouse, gamma 1 and gamma 2. And PPAR gamma is intimately associated with cell differentiation and proliferation[1]. So aim of this study, investigated where express PPAR gamma in mouse gastric cancer tissues, including human gastric cancer cell lines and expression pattern of PPAR gamma. (omitted)