• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.11.1-11.12
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• 2018

USP15 has been shown to stabilize transcription factors, to be amplified in many cancers and to mediate cancer cell survival. However, the underlying mechanism by which USP15 regulates multiple myeloma (MM) cell proliferation and apoptosis has not been established. Here, our results showed that USP15 mRNA expression was upregulated in MM patients. USP15 silencing induced MM cell proliferation inhibition, apoptosis, and the expression of nuclear and cytoplasmic NF-${\kappa}Bp65$, while USP15 overexpression exhibited an inverse effect. Moreover, in vivo experiments indicated that USP15 silencing inhibited MM tumor growth and NF-${\kappa}Bp65$ expression. PDTC treatment significantly inhibited USP15 overexpression-induced cell proliferation, apoptosis inhibition, and NF-${\kappa}Bp65$ expression. USP15 overexpression promoted NF-${\kappa}Bp65$ expression through inhibition of its ubiquitination, whereas NF-${\kappa}Bp65$ promoted USP15 expression as a positive regulator. Taken together, the USP15-NF-${\kappa}Bp65$ loop is involved in MM tumorigenesis and may be a potential therapeutic target for MM.

• Archives of Pharmacal Research
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• v.13 no.3
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• pp.233-239
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• 1990

The efect of acute renal failure (ARF) on the pharmacokinetics o sulfobromophthalein (BSP) was investigated in order to elucidate if renal failure modifies the hepatic metabolism of drugs. ARF was induced by intravenous (iv) injection of uranyl nitrate (UN) to rats (5 mg/kg) five days before the experiment. Area under the plasma concentration-time curve (AUC)of BSP after portal vein (pv) injection increased by 2-fold and total body clearance ($CL_1$) decreased one half (p <0.01) in UN-induced ARF (UN-ARF) rate compared to the control rats. But the plasma disappearance of BSP after iv injection did not differ significantly between control and UN-ARF rats. Since BSP is excreted via the liver, $CL_1$ represented the approximate hepatic clearance of BSP. Therefore, the decrease in $CL_1$ represented the approximate hepatic clearance of BSP. Therefore, the decrease in $CL_1$ represents a decrease in hepatic intrinsic clearance ($CL_{int}$) for BSP since plasma free fraction ($f_p$) of BSP was not affected by UN-ARF. The content of hepatic cytoplasmic Y-protein, which catalyzes BSP-glutathione conjugation and limits the trasfer of BSP from blood to bile, increased significantly (p < 0.01), however its binding activity (BA) for BSP was decreased significantly (p <0.01) by UN-ARF. The decrease in $CL_{int}$might have some correlation with the changed characteristics of hepatic Y-protein, specifically its decreased BA for BSP.

• Journal of Microbiology and Biotechnology
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• v.33 no.5
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• pp.582-590
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• 2023

Stress granules (SGs) are cytoplasmic aggregates of RNA-protein complexes that form in response to various cellular stresses and are known to restrict viral access to host translational machinery. However, the underlying molecular mechanisms of SGs during viral infections require further exploration. In this study, we evaluated the effect of SG formation on cellular responses to coxsackievirus B3 (CVB3) infection. Sodium arsenite (AS)-mediated SG formation suppressed cell death induced by tumor necrosis factor-alpha (TNF-a)/cycloheximide (CHX) treatment in HeLa cells, during which G3BP1, an essential SG component, contributed to the modulation of apoptosis pathways. SG formation in response to AS treatment blocked CVB3-mediated cell death, possibly via the reduction of mitochondrial reactive oxygen species. Furthermore, we examined whether AS treatment would affect small extracellular vesicle (sEV) formation and secretion during CVB3 infection and modulate human monocytic cell (THP-1) response. CVB3-enriched sEVs isolated from HeLa cells were able to infect and replicate THP-1 cells without causing cytotoxicity. Interestingly, sEVs from AS-treated HeLa cells inhibited CVB3 replication in THP-1 cells. These findings suggest that SG formation during CVB3 infection modulates cellular response by inhibiting the release of CVB3-enriched sEVs.

• Journal of Veterinary Science
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• v.25 no.3
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• pp.24.1-24.9
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• 2024

Importance: In veterinary forensic science, accurately determining the postmortem interval (PMI) is crucial for identifying the causes of animal deaths. Autolysis, a significant postmortem process, influences PMI estimation, but its relationship with humidity is not well understood. Objective: This study aimed to improve the accuracy of PMI estimates in veterinary forensic cases by looking into how different humidity levels affect autolysis in different organs of rats. Methods: The study involved 38 male rats, examining histopathological changes in their heart, liver, and pancreas. These organs were subjected to controlled humidity levels (20%, 55%, and 80%) at a constant 22℃. Tissue samples were collected at several intervals (0 h, 12 h, 24 h, 3 days, and 8 days) for comprehensive analysis. Results: Distinct autolytic characteristics in animal organs emerged under varying humidity conditions. The low-humidity environment rapidly activated autolysis more than the high-humidity environment. In addition, it was found that lower humidity caused nuclear pyknosis, cytoplasmic disintegration, and myofiber interruption. The liver, in particular, showed portal triad aggregation and hepatocyte individuation. The pancreas experienced cell fragmentation and an enlarged intracellular space. High humidity also caused the loss of striations in cardiac tissues, and the liver showed vacuolation. Under these conditions, the pancreas changed eosinophilic secretory granules. Conclusions and Relevance: The study successfully established a clear connection between the autolytic process in PMIs and relative humidity. These findings are significant for developing a more accurate and predictable method for PMI estimation in the field of veterinary forensic science.

• Biomolecules & Therapeutics
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• v.16 no.2
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• pp.147-160
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• 2008

The present study was designed to examine effects of polyphenolic compounds isolated from red wine (PCRW) on the release of catecholamines (CA) from the isolated perfused model of the rat adrenal medulla, and to clarify its mechanism of action. PCRW (20${\sim}$180 ${\mu}$g/mL), given into an adrenal vein for 90 min, caused inhibition of the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (a direct membrane-depolarizer, 56 mM), DMPP (a selective neuronal nicotinic $N_N$ receptor agonist, 100 ${\mu}$M) and McN-A-343 (a selective muscarinic $M_1$ receptor agonist, 100 ${\mu}$M) in dose- and time-dependent fashion. PCRW itself did not affect basal CA secretion (data not shown). Following the perfusion of PCRW (60 ${\mu}$g/mL), the secretory responses of CA evoked by Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, 10 ${\mu}$M), cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, 10 ${\mu}$M) and veratridine (an activator of voltage-dependent $Na^+$ channels, 10 ${\mu}$M) were also markedly blocked, respectively. Interestingly, in the simultaneous presence of PCRW (60 ${\mu}$g/mL) and L-NAME (a selective inhibitor of NO synthase, 30 ${\mu}$M), the inhibitory responses of PCRW on the CA secretion evoked by ACh, high $K^+$, DMPP, McN-A-343, Bay-K-8644 and cyclpiazonic acid were recovered to considerable level of the corresponding control release compared with those effects of PCRW-treatment alone. Practically, the amount of NO released from adrenal medulla after loading of PCRW (180 ${\mu}$g/mL) was significantly increased in comparison to the corresponding basal released level. Collectively, these results obtained here demonstrate that PCRW inhibits the CA secretory responses evoked by stimulation of cholinergic (both muscarinic and nicotinic) receptors as well as by direct membrane-depolarization from the isolated perfused adrenal gland of the normotensive rats. It seems that this inhibitory effect of PCRW is mediated by blocking the influx of both ions through $Na^+$ and $Ca^+{2$} channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the release of $Ca^{2+}$ from the cytoplasmic calcium store, which are due at least partly to the increased NO production through the activation of nitric oxide synthase. Based on these data, it is also thought that PCRW may be beneficial to prevent or alleviate the cardiovascular diseases, such as hypertension and angina pectoris.

• Journal of the korean academy of Pediatric Dentistry
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• v.24 no.1
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• pp.204-219
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• 1997

The use of fluoride is one of the most effective methods for caries prevention. Fluoridation of public water supply has been recognized, for many years, as an effective way to reduce dental caries. The fluoride supplement has been recommended when the natural fluoride was unavailable or below the optimal range. However the mechanism of caries prevention by fluoride has not yet been clarified and it is well known that an overdose of fluoride results inacute and chronic toxicity, especially dental fluorosis. Fluoride mouthrinsing solution is widely used in dentistry due to its effectiveness in carrying anticariogenic action. Understanding the effects of fluoride mouthrinsing solution on human gingival fibroblasts will provide the safety rationale for its use during the caries preventive therapy. The purpose of this study was to evaluate the cytotoxic effect of fluoride mouthrinsing solution on the human gingival fibroblast in vitro. The human gingival fibroblasts were cultured from healthy gingiva on the extracted deciduous teeth of children. Cells were inoculated into a 24-well plate with $1{\times}10^4cells/well$ of medium at $37^{\circ}C$, 100% humidity, 5% $CO_2$ incubator for 24 hours. And the cells were counted by using the hemocytometer at each designed study. Human gingival fibroblasts were cultured in growth medium after one minute application range of 0.02%-0.2% NaF solution and 0.1% $SnF_2$ solution. The cells used in this study were between fifth to eighth passage number. The cell morphology was examined by inverted microscope and cell proliferation was measured by incorporating $[^3H]$-thymidine into DNA. DNA synthesis by human gingival fibroblasts was assessed by $[^3H]$-thymidine uptake assays while the cell activity was measured by MTT assay. Each concentrated fluoride mouthrinsing solution was estimated for its biocompatability with fibroblasts by the tissue culture technique. The results of this study were as follows : 1. It was observed that at 0.05%, 0.2% NaF mouthrinsing solution the cytoplasmic processes became globular. When 0.1% $SnF_2$ mouthrinsing solution was applied, the cytoplasmic process and cell morphology were disappeared. 2. DNA synthetic activity was reduced regardless of the concentration of the fluoride mouthrinsing solution. However, the result is statistically insignificant except 0.1% $SnF_2$ mouthrinsing solution(p<0.05). 3. Our results indicate that 0.02%, 0.05% concentrations of NaF mouthrinsing solution caused minimal cytotoxicity. But 0.2% NaF and 0.1% $SnF_2$ concentration were a significant difference between the cell activity in the experimental group and control group (p<0.05). 4. After appling 0.05% & 0.02% NaF fluoride mouthrinsing solution, cell activity was restored to the control groups level according to incubating time. The results suggest that direct exposure to fluoride solution inhibits gingival fibroblast activity. Therefore, for the most effective use of fluoride use, lowering the concentration of fluoride mouthrinsing is advisable because it maintains biocompatability and free ion in the oral fluid.

• The Korean Journal of Physiology and Pharmacology
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• v.17 no.1
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• pp.99-109
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• 2013

The aim of this study was to determine whether fimasartan, a newly developed $AT_1$ receptor blocker, can affect the CA release in the isolated perfused model of the adrenal medulla of spontaneously hypertensive rats (SHRs). Fimasartan (5~50 ${\mu}M$) perfused into an adrenal vein for 90 min produced dose- and time-dependently inhibited the CA secretory responses evoked by ACh (5.32 mM), high $K^+$ (56 mM, a direct membrane depolarizer), DMPP (100 ${\mu}M$) and McN-A-343 (100 ${\mu}M$). Fimasartan failed to affect basal CA output. Furthermore, in adrenal glands loaded with fimasartan (15 ${\mu}M$), the CA secretory responses evoked by Bay-K-8644 (10 ${\mu}M$, an activator of L-type $Ca^{2+}$ channels), cyclopiazonic acid (10 ${\mu}M$, an inhibitor of cytoplasmic $Ca^{2+}$-ATPase), and veratridine (100 ${\mu}M$, an activator of $Na^+$ channels) as well as by angiotensin II (Ang II, 100 nM), were markedly inhibited. In simultaneous presence of fimasartan (15 ${\mu}M$) and L-NAME (30 ${\mu}M$, an inhibitor of NO synthase), the CA secretory responses evoked by ACh, high $K^+$, DMPP, Ang II, Bay-K-8644, and veratridine was not affected in comparison of data obtained from treatment with fimasartan (15 ${\mu}M$) alone. Also there was no difference in NO release between before and after treatment with fimasartan (15 ${\mu}M$). Collectively, these experimental results suggest that fimasartan inhibits the CA secretion evoked by Ang II, and cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization from the rat adrenal medulla. It seems that this inhibitory effect of fimasartan may be mediated by blocking the influx of both $Na^+$ and $Ca^{2+}$ through their ion channels into the rat adrenomedullary chromaffin cells as well as by inhibiting the $Ca^{2+}$ release from the cytoplasmic calcium store, which is relevant to $AT_1$ receptor blockade without NO release.

• The Korean Journal of Physiology and Pharmacology
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• v.13 no.6
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• pp.517-526
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• 2009

The present study was attempted to investigate whether polyphenolic compounds isolated from wine, which is brewed from Rubus coreanum Miquel (PCRC), may affect the release of catecholamines (CA) from the isolated perfused adrenal medulla of the spontaneously hypertensive rats (SHRs), and to establish its mechanism of action. PCRC $(20\sim180\;{\mu}g/ml)$ perfused into an adrenal vein for 90 min relatively dose-dependently inhibited the CA secretory responses to ACh (5.32 mM), high $K^+$ (56 mM), DMPP $(100\;{\mu}M)$ and McN-A-343 $(100\;{\mu}M)$. PCRC itself did not affect basal CA secretion (data not shown). Also, in the presence of PCRC $(60\;{\mu}g/ml)$, the CA secretory responses to veratridine (a selective $Na^+$ channel activator $(10\;{\mu}M)$, Bay-K-8644 (a L-type dihydropyridine $Ca^{2+}$ channel activator, $10\;{\mu}M$), and cyclopiazonic acid (a cytoplasmic $Ca^{2+}$-ATPase inhibitor, $10\;{\mu}M$) were significantly reduced, respectively. In the simultaneous presence of PCRC $(60\;{\mu}g/ml)$ and L-NAME (an inhibitor of NO synthase, $30\;{\mu}M$), the inhibitory responses of PCRC on the CA secretion evoked by ACh, high $K^+$, DMPP, and Bay-K-8644 were considerably recovered to the extent of the corresponding control secretion compared with that of PCRC-treatment alone. The level of NO released from adrenal medulla after the treatment of PCRC $(60\;{\mu}g/ml)$ was greatly elevated compared with the corresponding basal level. Taken together, these results demonstrate that PCRC inhibits the CA secretion from the isolated perfused adrenal medulla of the SHRs evoked by stimulation of cholinergic receptors as well as by direct membrane-depolarization. It seems that this inhibitory effect of PCRC is mediated by blocking the influx of calcium and sodium into the adrenal medullary chromaffin cells of the SHRs as well as by inhibition of $Ca^{2+}$ release from the cytoplasmic calcium store at least partly through the increased NO production due to the activation of NO synthase.

• KSBB Journal
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• v.24 no.1
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• pp.80-88
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• 2009

Human prostatic acid phosphatase (PAP), with comprehensive homology to glandular kallikrein, are representative serum biomarkers of prostate cancer. Dendritic cell (DC), which is the potent antigen-presenting cells(APC) in the immune system, can induce strong T cell responses against viruses, microbial pathogens, and tumors. Therefore, the immunization using DC loaded with tumor-associated antigens is a powerful method for inducing anti-tumor immunity. The CTP (Cytoplasmic Transduction Peptide) technology developed by Creagene which can transport attached bio-polymers like nucleic acids or proteins into the cell with high permeation efficiency. As the active forms of PAP can mediate apoptotic processing, we used multimer forms of PAP as an inactive form for antigen pulsing of DCs. In this study, multimeric forms of CTP-rhPAP was obtained according to the advanced purification process and subsequently confirmed by gel filtration chromatography, western blot and Dynamic Light Scattering. Therefore, CTP-conjugated PA multimers transduced into the cytoplasm were efficiently presented on the cell surface without any harm effect on cells via MHC class I molecules and result in induction of a large number of effector cell.

• Journal of the Korean Society of Food Science and Nutrition
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• v.30 no.2
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• pp.331-337
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• 2001

The effect of Phellinus linteus methanol extract on the lipid metabolism in the liver of rat was investigated in this study. Rats were randomly divided into 6 groups including the control, $CCl_4$and high fat group plus sub-groups with Phellinus linteus methanol extract administration. Methanol extracts of Phellinus linteus were fed 50mg/kg B.W daily via drinking water. A 1.2mL of $CCl_4/kg$ body weight was administered by oral intubation twice a week for total six times. The administration of $CCl_4$ increased total cholesterol, TG, LDL and LDL-phospholipid. However, the level of liver cholesterol and triglycerides were significantly decreased while HDL-cholesterol was increased by the extract feeding. The activities of GOT, GPT, AP and LDH were greatly enhanced by the extract feeding. Electronmicrograph showed that $CCl_4$ treatment deteriorated the structure of cytoplasmic matrix with its uneven distribution. However, the extract treatment reconstituted the damaged cytoplasm and stimulated mitochondriagenesis. From these results, it was suggested that Phellinus linteus can help to recover the damaged liver function and further may help to prevent senescence diseases such as fatty liver, hypertension and hyperlipidemia.