• Molecules and Cells
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• v.41 no.6
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• pp.532-544
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• 2018

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumors of the gastrointestinal (GI) tract. In order to investigate a new treatment fot GIST, we hypothesized the effect of miR-374b targeting PTEN gene-mediated PI3K/Akt signal transduction pathway on proliferation and apoptosis of human gastrointestinal stromal tumor (GIST) cells. We obtained GIST tissues and adjacent normal tissues from 143 patients with GIST to measure the levels of miR-374b, PTEN, PI3K, Akt, caspase9, Bax, MMP2, MMP9, ki67, PCNA, P53 and cyclinD1. Finally, cell viability, cell cycle and apoptosis were detected. According to the KFGG analysis of DEGs, PTEN was involved in a variety of signaling pathways and miRs were associated with cancer development. The results showed that MiR-374b was highly expressed, while PTEN was downregulated in the GIST tissues. The levels of miR-374b, PI3K, AKT and PTEN were related to tumor diameter and pathological stage. Additionally, miR-374b increased the mRNA and protein levels of PI3K, Akt, MMP2, MMP9, P53 and cyclinD1, suggesting that miR-374b activates PI3K/Akt signaling pathway in GIST-T1 cells. Moreover, MiR374b promoted cell viability, migration, invasion, and cell cycle entry, and inhibited apoptosis in GIST cells. Taken together, the results indicated that miR-374b promotes viability and inhibits apoptosis of human GIST cells by targeting PTEN gene through the PI3K/Akt signaling pathway. Thus, this study provides a new potential target for GIST treatment.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.339-347
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• 2007

SMEDDS is mixture of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle agitation and digestive motility that would be encountered in the gastro-intestinal(GI) tract. The main purpose of this work is to prepare self-microemulsifying drug delivery system(SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, atorvastatin calcium. Solubility of atorvastatin calcium was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identity the efficient self-emulsification region and particle size distributions of the resultant micro emulsions were determined using a laser diffraction sizer. Optimized formulations for in vitro dissolution and bioavailability assessment were $Capryol^{(R)}$ 90(50%), Tetraglycol(16%), and $Cremophor^{(R)}$ EL(32%). The release rate of atorvastatin from SMEDDS was significantly higher than the conventional tablet ($Lipitor^{(R)}$), 2-fold. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin calcium by the oral route.

• Archives of Pharmacal Research
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• v.26 no.9
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• pp.768-772
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• 2003

Tween 80 (Polysorbate 80) is a hydrophilic nonionic surfactant commonly used as an ingredient in dosing vehicles for pre-clinical in vivo studies (e.g., pharmacokinetic studies, etc.). Tween 80 increased apical to basolateral permeability of digoxin in Caco-2 cells suggesting that Tween 80 is an in vitro inhibitor of P-gp. The overall objective of the present study was to investigate whether an inhibition of P-gp by Tween 80 can potentially influence in vivo absorption of P-gp substrates by evaluating the effect of Tween 80 on the disposition of digoxin (a model P-gp substrate with minimum metabolism) after oral administration in rats. Rats were dosed orally with digoxin (0.2 mg/kg) formulated in ethanol (40％, v/v) and saline mixture with and without Tween 80 (1 or 10％, v/v). Digoxin oral AUC increased 30 and 61％ when dosed in 1 ％ and 10％ Tween 80, respectively, compared to control (P＜0.05). To further examine whether the increase in digoxin AUC after oral administration of Tween 80 is due, in part, to a systemic inhibition of digoxin excretion in addition to an inhibition of P-gp in the GI tract, a separate group of rats received digoxin intravenously (0.2 mg/kg) and Tween 80 (10％ v/v) orally. No significant changes in digoxin IV AUC was noted when Tween 80 was administered orally. In conclusion, Tween 80 significantly increased digoxin AUC and Cmax after oral administration, and the increased AUC is likely to be due to an inhibition of P-gp in the gut (i.e., improved absorption). Therefore, Tween 80 is likely to improve systemic exposure of P-gp substrates after oral administration. Comparing AUC after oral administration with and without Tween 80 may be a viable strategy in evaluating whether oral absorption of P-gp substrates is potentially limited by P-gp in the gut.

• Journal of Radiation Industry
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• v.12 no.4
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• pp.355-363
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• 2018

A novel $N_3S_1$ chelate, Pro-Lys-Cys (PKC) to cyclic RGD to radiolabel with $^{99m}Tc$ was conjugated in an effort to decrease the high intestinal accumulation observed for $^{99m}Tc$-labeled PGC-RGD. The target specificity of the resulting PKC-RGD was similar to that of PGC-RGD as determined by a cell binding assay and a competition binding assay. The $^{99m}Tc$ radiolabeling of PKC-RGD resulted in radiochemical yields of 98% under mild conditions at high specific activities. Biodistribution data in normal mice clearly showed a significant decrease in intestinal uptake at 2 h postinjection for the $^{99m}Tc-PKC-c$ (RGDyK) compared to the $^{99m}Tc-GC-c$ (RGDyK) (from $19.65%ID{\cdot}g^{-1}$ to $7.31%ID{\cdot}g^{-1}$ for the GI tract). The $^{99m}Tc-PKC-c$ (RGDyK) biodistribution was also shown by a higher retention of radioactivity in the whole body, but with kidney accumulation over 8-fold higher than observed with $^{99m}Tc-PGC-c$ (RGDyK) at 2 h ($12.62%ID{\cdot}g^{-1}$ for PKC-RGD and $1.54%ID{\cdot}g^{-1}$ for PGC-RGD, respectively). These results show that the biodistribution may be altered especially concerning lipophilicity resulting in renal rather than hepatobiliary excretion. This comparative study made it possible to explore the effects of lipophilicity on the biodistribution of $^{99m}Tc$-labeled c (RGDyK) through the use of different tripeptide $N_3S_1$ chelators. Therefore, $^{99m}Tc-PKC-c$ (RGDyK) may be an attractive alternative for the in vivo imaging of integrin receptors.

• Korean Journal of Agricultural Science
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• v.46 no.3
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• pp.569-577
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• 2019

The current experiment was conducted to compare nutrient utilization in the aged laying hens with different eggshell strengths or different intensities of brown eggshell color. Two metabolic trials with 96-week-old Hy-Line Brown laying hens were conducted. Twelve hens with a strong eggshell strength (SES) and 12 hens with a weak eggshell strength (WES) were selected and used in the first experiment, whereas 12 hens with dark brown eggshells (DBE) and 12 hens with light brown eggshells (LBE) were selected and used in the second experiment. All hens were fed a common commercial layer diet. Diets included chromic oxide as an indigestible marker to determine the apparent total tract retention (ATTR) of the gross energy (GE), dry matter, acid-hydrolyzed ether extract, nitrogen, neutral detergent fiber, acid detergent fiber, ash, and minerals. The results indicate that the ATTR of Ca in the aged laying hens with SES (59.7%) was greater (p < 0.05) than in the aged laying hens with WES (48.6%). However, the ATTR of the GE and other nutrients was not different between the hens with SES or WES. There were no differences in the ATTR of GE and nutrients between the hens with DBE or LBE. In conclusion, aged laying hens with SES have a greater ability to utilize dietary Ca than those with WES, indicating that the extent of dietary Ca utilization determines the eggshell strength of aged laying hens. However, nutrient utilization in diets may have little impact on eggshell brown coloration in aged laying hens.

• Journal of the Institute of Electronics Engineers of Korea SD
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• v.37 no.4
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• pp.60-70
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• 2000

An 8$\times$8+20-bit MAC is designed with low power design methodologies at each of the system design levels. At algorithm level, a new method for multipl $y_tract operation is proposed, and it saves the transistor counts over conventional methods in hardware realization. A new Booth selector circuit using NMOS pass-transistor logic is also proposed at circuit level. It is superior to other circuits designed by CMOS in power-delay-product. And at architecture level, we adopted an ELM adder that is known to be the most efficient in power consumption, operating frequency, area and design regularity as the final adder. For registers, dynamic CMOS single-edge triggered flip-flops are used because they need less transistors per bit. To increase the operating frequency 2-stage pipeline architecture is adopted, and fast 4：2 compressors are applied in Wallace tree block. As a simulation result, the designed MAC in 0.6${\mu}{\textrm}{m}$ 1-poly 3-metal CMOS process is operated at 200MHz, 3.3V and consumed 35㎽ of power in multiply operation, and operated at 100MHz consuming 29㎽ in MAC operations, respectively.ly.

• Journal of Gastric Cancer
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• v.3 no.4
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• pp.195-200
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• 2003

Purpose: Advancement of computed tomography (CT) hardware and software has allowed thin section scanning and reconstruction of fascinating 2-dimentional (2D) and 3- dimentional (3D) images. Especially, the reconstruction of 3D images of gastrointestinal tract has been used in the detection and diagnosis of pre-malignant and malignant diseases. To compare the efficacy of CT gastrography with conventional upper gastrointenstinal series (UGIs) in gastric cancer patients. Materials and Methods: During Nov. 2002 and Mar. 2003, twenty-seven patients who had gastric cancer received both double contrast upper GI series and CT gastrography prior to radical surgery. Among these patients, nineteen had early gastric cancer (EGC) and 8 had advanced gastric cancer (AGC). Fifteen patients were male and 12 were female. The mean age was 54 yrs (range, $27\∼75$ yrs). The patients were placed on NPO and Stomach was distended with gas in fasting state prior to CT scanning. Double contrast upper GI series were performed as routine manual. CT scan was conducted in all patients using 8 or 16-channel multidetector CT in this study. The collimation and reconstruction for CT scanning were set at 2.5 mm and 1.25 mm, respectively. CT scanning was performed in the supine position. For image processing, CT gastrography, in which raysum and surface rendering images were constructed, virtual and 2D image in coronal and sagittal images were performed. The detectability of gastric cancer was assessed between UGIs and CT gastrography. Results: In AGCs, the detection rate of cancer using CT gastrography and virtual gastroscopy was higher than EGC cases. However, CT gastrography and virtual gastroscopy showed less favorable results than UGIs. Even though only a small number of cases had been studied, we might conclude that CT gastrography and virtual gastroscopy could replace UGIs in the detection of AGC cases. Conclusion: The detection rate used with CT gastrography and Virtual gastroscopy is not better than that of UGIs in early gastric cancer, however, in advanced gastric cancer cases, it is nearly equal to that of UGIs.

• Journal of Korean Society for Geospatial Information Science
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• v.23 no.3
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• pp.77-84
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• 2015

The key objective of this research is to review the effectiveness of spatial regression to identify the influencing factors of spatial distribution patterns of floating population. To this end, global and local spatial autocorrelation test were performed using seoul floating population survey(2014) data. The result of Moran's I and Getis-Ord $Gi^*$ as used in the analysis derived spatial heterogeneity and spatial similarities of floating population patterns in a statistically significant range. Accordingly, Geographically Weighted Regression was applied to identify the relationship between land use attributes and population floating. Urbanization area, green tract of land of micro land cover data were aggregated in to $400m{\times}400m$ grid boundary of Seoul. Additionally public transportation variables such as intersection density transit accessibility, road density and pedestrian passage density were adopted as transit environmental factors. As a result, the GWR model derived more improved results than Ordinary Least Square(OLS) regression model. Furthermore, the spatial variation of applied local effect of independent variables for the floating population distributions.

• Journal of Life Science
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• v.31 no.7
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• pp.662-670
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• 2021

Interstitial cells of Cajal (ICCs) are the pacemaking cells in the gastrointestinal (GI) muscles that generate the rhythmic oscillation in membrane potentials known as slow waves. In the present study, we investigated the effects of mirtazapine, a noradrenergic and serotonergic antidepressant, on pacemaking potential in cultured ICCs from the murine small intestine. The whole-cell patch-clamp configuration was used to record pacemaker potential in cultured ICCs. Mirtazapine induced pacemaker potential depolarizations in a concentration-dependent manner in the current clamp mode. Y25130 (a 5-HT3 receptor antagonist), RS39604 (a 5-HT4 receptor antagonist), and SB269970 (a 5-HT7 receptor antagonist) had no effects on mirtazapine-induced pacemaker potential depolarizations. Also, methoctramine, a muscarinic M₂ receptor antagonist, had no effect on mirtazapine-induced pacemaker potential depolarizations, whereas 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP), a muscarinic M₃ receptor antagonist, inhibited the depolarizations. When guanosine 5'-[β-thio] diphosphate (GDP-β-S; 1 mM) was in the pipette solution, mirtazapine-induced pacemaker potential depolarization was blocked. When an external Ca²⁺ free solution or thapsigargin, a Ca²⁺-ATPase inhibitor of the endoplasmic reticulum, was applied, the generation of pacemaker potentials disappeared, and under these conditions, mirtazapine induced pacemaker potential depolarizations. In addition, protein kinase C (PKC) inhibitor, calphostin C, and chelerythrine inhibited mirtazapine-induced pacemaker potential depolarizations. These results suggest that mirtazapine regulates pacemaker potentials through muscarinic M₃ receptor activation via a G protein-dependent and an external or internal Ca²⁺-independent PKC pathway in the ICCs. Therefore, mirtazapine can control GI motility through ICCs.

• Clinical and Experimental Pediatrics
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• v.49 no.7
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• pp.784-789
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• 2006

Purpose : $Henoch-Sch{\ddot{o}}nlein$ purpura(HSP) is a systemic vasculitis involving small vessels of skin, gastrointestinal(GI) tract and kidney. Digestive involvement of HSP can be serious with massive GI bleeding, perforation, and intussusception. However, some patients do not respond to conventional corticosteroid therapy. In this study, we investigated the efficacy of intravenous immunoglobulin (IVIG) for serious digestive manifestations not responding to steroid. Methods : From April 1999 to January 2005, 22 children diagnosed as HSP with severe GI symptoms were included. Initially, all patients were treated with intravenous methylprednisolone. IVIG 2 g/kg of body weight was infused in children refractory to steroid therapy. Clinical data were reviewed retrospectively. Results : Among 22 children, 12 children underwent IVIG therapy. The mean duration of corticosteroid therapy was $5.61{\pm}4.9$ days before IVIG therapy, and 11 of 12 patients experienced disappearance of GI manifestations after the initiation of IVIG infusion. In one patient, IVIG was ineffective in relieving abdominal pain, but melena subsided. Comparison of the duration of hospitalization between IVIG group and corticosteroid group revealed no significant difference($12.8{\pm}7.6$ days vs. $13.2{\pm}7.8$ days, P=0.777). But, the total duration of abdominal pain decreased in IVIG group although the difference between two groups was not significant($8.8{\pm}8.1$ days vs. $14.8{\pm}16.9$ days, P=0.306). Among 10 children treated with steroid only, 2 children were operated for bowel perforation and intussusception. In contrast, there was no perforation in 12 children who underwent IVIG therapy. Conclusion : IVIG could be the alternative therapy to corticosteroids in children with severe digestive manifestations of HSP.