• Asian Pacific Journal of Cancer Prevention
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• v.14 no.2
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• pp.747-752
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• 2013

Oncostatin M (OSM) is a multifunctional cellular regulator acting on a wide variety of cells, which has potential roles in the regulation of gene activation, cell survival, proliferation and differentiation. Previous studies have shown that OSM can induce morphological and/or functional differentiation and maturation of many tumor cells. However, the action of OSM on the induction of differentiation of human hepatocellular carcinoma (HCC) has not been reported. Here, we investigated the effects of different concentrations of OSM on human HCC cell line SMMC-7721 growth, proliferation, cell cycling, apoptosis and differentiation in vitro. Cell growth was determined via MTT assay, proliferation by cell cycle analysis, apoptosis by flow cytometry, morphology by transmission electronic microscopy, and cell function by detection of biochemical markers. Our results demonstrated that OSM strongly inhibited the growth of SMMC-7721 cells in a dose-dependent manner, associated with decreased clonogenicity. Cell cycle analysis revealed a decreased proportion of cells in S phase, with arrest at G0/G1. The apotosis rate was increased after OSM treatment compared to the control. These changes were associated with striking changes in cellular morphology, toward a more mature hepatic phenotype, accompanied by significant reduction of the expression of AFP and specific activity of ${\gamma}$-GT, with remarkable increase in secretion of albumin and ALP activity. Taken together, our findings indicate that OSM could induce the differentiation and reduce cell viability of SMMC-7721 cells, suggesting that differentiation therapy with OSM offers the opportunity for therapeutic intervention in HCC.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.13 no.1
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• pp.48-53
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• 2013

Tyrosinemia I (fumarylacetoacetate hydrolase deficiency) is an autosomal recessive inborn error of tyrosine metabolism that produces liver failure in infancy or a more chronic course of liver disease with cirrhosis, often complicated by hepatocellular carcinoma in childhood or early adolescence. We studied a 37-year-old woman with tyrosinemia I whose severe liver disease in infancy and rickets during childhood were resolved with dietary therapy. From 14 years of age, she resumed unrestricted diet with the continued presence of the biochemical features of tyrosinemia, yet maintained normal liver function. In adult years, she accumulated only a small amount of succinylacetone. Despite this evolution to a mild biochemical and clinical phenotype, she eventually developed hepatocellular carcinoma. Her fumarylacetoacetate hydrolase genotype consists of a splice mutation, IVS6-1G>T, and a novel missense mutation, p.Q279R. Studies of resected liver revealed the absence of hydrolytic activity and immunological expression of fumarylacetoacetate hydrolase in tumour. In the non-tumoral areas, however, 53% of normal hydrolytic activity and immunologically present fumarylacetoacetate hydrolase were found. This case demonstrates the high risk of liver cancer in tyrosinemia I even in a seemingly favorable biological environment. In this study of tyrosinemia I, Case 2 with negative succinylacetone accumulation and the recovery of acute liver failure was compared with Case 1. Diet restriction and NTBC treatment are crucial to prevent hepatocellular carcinoma until liver transplant can take place and cure the condition. Further studies are needed to examine cases where liver cancer did not result despite clinical symptoms/signs of tyrosinemia type I.

• Journal of Microbiology and Biotechnology
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• v.30 no.12
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• pp.1885-1895
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• 2020

Rumex japonicus Houtt (RJH) is a valuable plant used in traditional medicine to treat several diseases, such as scabies and jaundice. In this study, Jurkat cell growth inhibitory extracts of R. japonicus roots were subjected to bioassay-guided fractionation, resulting in the isolation of three naphthalene derivatives (3-5) along with one anthraquinone (6) and two phenolic compounds (1 and 2). Among these compounds, 2-methoxystypandrone (5) exhibited potent anti-proliferative effects on Jurkat cells. Analysis by flow cytometry confirmed that 2-methoxystypandrone (5) could significantly reduce mitochondrial membrane potential and promote increased levels of mitochondrial reactive oxygen species (ROS), suggesting a strong mitochondrial depolarization effect. Real-time quantitative polymerase chain reaction (qPCR) analysis was also performed, and the results revealed that the accumulation of ROS was caused by reduced mRNA expression levels of heme oxygenase (HO-1), catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD). In addition, 2-methoxystypandrone (5) triggered strong apoptosis that was mediated by the arrest of the G0/G1 phase of the cell cycle. Furthermore, 2-methoxystypandrone (5) downregulated p-IκB-α, p-NF-κB p65, Bcl2, and Bcl-xl and upregulated BAX proteins. Taken together, these findings revealed that 2-methoxystypandrone (5) isolated from RJH could potentially serve as an early lead compound for leukemia treatment involving intracellular signaling by increasing mitochondrial ROS and exerting anti-proliferative effects.

• Asian-Australasian Journal of Animal Sciences
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• v.26 no.9
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• pp.1320-1328
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• 2013

Three experiments were conducted to evaluate the ME value, standardized ileal digestibility (SID) of amino acids (AA) of fish meal, and the effects of single cell protein (Prosin and Protide) replacing fish meal in diet on growth performance, nutrient digestibility and intestinal morphology in weaned piglets. In Exp. 1, twenty-four barrows with initial BW of $30.8{\times}2.6kg$ were allotted to one of four dietary treatments. Diet 1 contained corn as the only energy source. The other three diets replaced 20% of the corn in diet 1 with one of the three protein feeds (fish meal, Prosin and Protide), and the DE and ME contents were determined by difference. In Exp. 2, eight barrows (initial BW of $25.6{\pm}3.2kg$) were fitted with ileal T-cannulas and allotted to a replicated $4{\times}4$ Latin square design. Three cornstarch-based diets were formulated using each of the protein feeds as the sole source of AA. A nitrogen-free diet was also formulated to measure endogenous losses of AA. In Exp. 3, one hundred and eighty piglets (initial BW of $7.95{\pm}1.59kg$) weaned at $28{\times}2d$ were blocked by weight and assigned to one of five treatments for a 28-d growth performance study, each treatment was fed to six pens with six pigs (three barrows and three gilts) per pen. The five treatments consisted of the control group (CON), which was a corn-soybean meal diet containing 5% fish meal, and the other four treatments, which replaced a set amount of fish meal with either Prosin (2.5% or 5%) or Protide (2.5% or 5%). The diets were formulated to provide same nutrient levels. The results showed that on a DM basis, both of the DE and ME contents were lower in Prosin and Protide than that of fish meal (p<0.05). The SID of CP and all essential AA were greater in fish meal than in Prosin and Protide (p<0.05). The pigs fed CON diet had greater weight gain and lower feed conversion rate (FCR) than pigs fed 5% Prosin and 5% Protide diets (p<0.05). The digestibility of CP was greater in pigs fed CON, 2.5% Prosin and 2.5% Protide diets than the pigs fed 5% Prosin and 5% Protide diets (p<0.05). Villus height in jejunum and ileum, and villus height to crypt depth ratio in the jejunum were higher (p<0.05) in pigs fed CON, 2.5% Prosin and 2.5% Protide diets compared with the 5% Prosin and 5% Protide diets. Pigs fed CON diet had greater villus height to crypt depth ratio in the ileum than the pigs fed 5% Prosin and 5% Protide diets (p<0.05). In conclusion, although Prosin and Protide contained lower ME content and SID of AA than fish meal, Prosin and Protide replacing 50% of fish meal in diet with identical nutrient levels could obtain similar performance, nutrient digestibility and intestinal morphology in weaned pigs.

• The korean journal of orthodontics
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• v.30 no.2 s.79
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• pp.215-222
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• 2000

The purpose of this study was to determine whether the application of chlorhexidine varnish affects the shear bond strength and failure pattern of orthodontic brackets or not. The experimental group consisted of 22 human premolars which extracted after chlorhexidine varnish application (4 times for 1 week interval) in vivo, and the control group consisted of 22 human premolars which extracted without any pre-treatment. After all teeth were etched with $37\%$ phosphoric acid gel, metal orthodontic brackets (Q-3002, RMO, USA) were bonded to each tooth using auto-polymerizing orthodontic resin (Ortho-One, Bisco, USA) with the same bonding procedure. The shear bond strength was measured with Instron universal testing machine (model 4466, Instron Ltd., England), and the failure pattern of each bracket was examined with Scanning Electron Microscope (SM 840A, JEOL, Japan). The data were analysed statistically with t-test. The results were as follows : 1. Application of chlorhexidine varnish had no significant effect on the shear bond strength of the orthodontic bracket. 2. There was no significant difference in the failure pattern of orthodontic bracket between the experimental group and the control group.

• Ocean and Polar Research
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• v.34 no.1
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• pp.93-99
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• 2012

The effect of water temperature and body weight on oxygen consumption by the fasted olive flounder Paralichthys olivaceus was investigated in order to assess the metabolic rate of this species under different conditions. The oxygen consumption rate (OCR) was measured at three different water temperatures (15, 20 and $25^{\circ}C$) and two different body weights [$9.1{\pm}1.2$ g (mean${\pm}$SD) for the juvenile group and $266.4{\pm}29.3$ g for the immature group] at an interval of 5 minutes for 24 hours using a closed flow-through respirometer. For each treatment condition, three replicates were set up and 135 fish in the juvenile group and 18 fish in the immature group were used. The OCRs exhibited a linear increase described by OCR=-82.06+28.30T ($r^2$=0.96, p<0.001) in the juvenile group and OCR=-52.52+14.73T ($r^2$=0.97, p<0.001) in the immature group. The OCRs decreased with increasing body weights at a given water temperature (p<0.001). The metabolic rate was related to the body weight of the fish as a power function with a weight exponent of between 0.77 and 0.82. $Q_{10}$ values ranged 1.67~2.28 when the temperature was between 15 and $20^{\circ}C$, 1.57~1.93 when the temperature was between 20 and $250^{\circ}C$, and 1.79~1.89 when the temperature was between 15 and $250^{\circ}C$. The energy expenditure by respiration increased with increasing water temperature and decreasing body weight (p<0.001). The mean energy loss rates at 15, 20 and $25^{\circ}C$ were 115.9, 149.8 and 208.2 kJ $kg^{-1}d^{-1}$ in the juvenile groups and 53.8, 81.2 and 101.9 kJ $kg^{-1}d^{-1}$ in the immature groups.

• Asian-Australasian Journal of Animal Sciences
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• v.29 no.12
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• pp.1761-1767
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• 2016

Two experiments were conducted to evaluate effects of coated compound proteases (CC protease) on apparent total tract digestibility (ATTD) of nitrogen (N) and energy, and apparent ileal digestibility (AID) of amino acids (AA) and nutrients in diets for pigs. In Exp. 1, 12 crossbred barrows (initial body weight: $20.79{\pm}1.94kg$) were housed in individual metabolism crates and allotted into 2 treatments with 6 piglets per treatment according to weight in a randomized complete block design. The 2 diets were corn-soybean meal basal diets with (0.2 g/kg) or without CC protease supplementation. The CC protease supplementation increased (p<0.05) the digestible and metabolizable N and energy values and the digestibility and retention rate of N in the diet. The ATTD of energy and nutrients had been improved (p<0.05) in the diet supplemented with CC protease. In Exp. 2, 12 crossbred barrows (initial body weight: $20.79{\pm}1.94kg$), fitted with T-cannulas at the distal ileum, were blocked by body weight into 2 groups with 6 pigs each. The diets were the same as those in Exp. 1. The CC protease increased (p<0.05) the AID of crude protein and some essential AA including arginine, isoleucine and leucine. The AID and ATTD of energy and nutrients had been improved (p<0.05) by supplemental CC protease, but the hindgut digestibility of nutrients was unaffected. Overall, the CC protease improved the ATTD of N and energy and AID of some indispensible AA and nutrients in the corn-soybean meal diet for pigs. Therefore, the CC protease supplement could improve the utilization of protein in the corn-soybean meal diet and thus contribute to lower N excretion to the environment.

• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.23 no.6
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• pp.558-566
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• 2020

Purpose: Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic autosomal recessive disease caused by mutations in ATP8B1, ABCB11 or ABCB4. Mutational analysis of these genes is a reliable approach to identify the disorder. Methods: We collected and analyzed relevant data related to clinical diagnosis, biological investigation, and molecular determination in nine children carrying these gene mutations, who were from unrelated families in South China. Results: Of the nine patients (five males, four females) with PFIC, one case of PFIC1, four cases of PFIC2, and four cases of PFIC3 were diagnosed. Except in patient no. 8, jaundice and severe pruritus were the major clinical signs in all forms. γ-glutamyl transpeptidase was low in patients with PFIC1/PFIC2, and remained mildly elevated in patients with PFIC3. We identified 15 different mutations, including nine novel mutations (p.R470HfsX8, p.Q794X and p.I1170T of ABCB11 gene mutations, p.G319R, p.A1047P, p.G1074R, p.T830NfsX11, p.A1047PfsX8 and p.N1048TfsX of ABCB4 gene mutations) and six known mutations (p.G446R and p.F529del of ATP8B1 gene mutations, p.A588V, p.G1004D and p.R1057X of ABCB11 gene mutations, p.P479L of ABCB4 gene mutations). The results showed that compared with other regions, these three types of PFIC genes had different mutational spectrum in China. Conclusion: The study expands the genotypic spectrum of PFIC. We identified nine novel mutations of PFIC and our findings could help in the diagnosis and treatment of this disease.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.2 no.1
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• pp.77-79
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• 2002

The urea cycle, consisting of a series of six enzymatic reactions, plays key roles to prevent the accumulation of toxic nitrogenous compound and synthesize arginine de novo. Five well characterized diseases have been described, resulting from an enzymatic defect in the biosynthesis of one of the normally expressed enzyme. This presentation will focus on two representative diseases; ornithine transcarbamylase(OTC) deficiency and citrullinemia(argininosuccinate synthetase deficiency). OTC deficiency is one of the most common inborn error of urea cycle, which is inherited in X-linked manner. We identified 17 different mutations in 20 unrelated Korean patients with OTC deficiency; L9X, R26P, R26X, T44I, R92X, G100R, R141Q, G195R, M205T, H214Y, D249G, R277W, F281S, 853 del C, R320X, V323M and 10 bp del at nt. 796-805. These mutations occur at well conserved nucleotide sequences across species or CpG hot spot. The L9X and R26X lead to the disruption of leader sequences, required for directing mitochondrial localization of the OTC precursor. Their phenotypes are severe, and neonatal onset. The G100R, R277W and V323M mutations were uniquely identified in patients with late onset OTC deficiency. The other genotypes are associated with neonatal onset. Out of 20 patients with OTC deficiency, only 6 patients are alive; two were liver transplanted, and normal in growth and development at 2, 4 years after transplantation respectively. Citrullinemia is an autosomal recessive disease, caused by the mutations in the argininosuccinate synthetase(ASS) gene. We identified in 3 major mutations in 11 unrelated Korean patients with citrullinemia; G324S, $IVS6^{-2}$ A to G, and 67 bp ins at nt 1125-1126. Among these, the 67 base pair insertion mutation is novel. The allele frequency of each mutation is; G324S(45%), IVS6-2 A to G(32%), and 67 base pair insertion(14%). All patients are diagnosed at neonatal or infantile age. Interestingly, two patients presented with stroke like episode. Out of 11 patients, 5 patients died. Among 6 patients alive, one patient was successfully liver transplanted.

• Journal of Soil and Groundwater Environment
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• v.21 no.1
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• pp.28-39
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• 2016

Struvite (MgNH₄PO₄ ⋅ 6H₂O) and hydroxyapatite (HAP, Ca₁₀(PO₄)₆(OH)₂) precipitation in urine-separating toilets (NoMix toilets) causes severe maintenance problems and also reduce the phosphate and calcium content. Application of urine separating technique and extraction of by-products from human urine is a cost effective technique in waste water treatment. In this study, we extract urine calcite from human urine by batch scale method, using urease producing microbes to trigger the precipitation and calcite formation process. Extracted urine calcite (calcining at 800℃) is a potential adsorbent for removal of heavy metal(loid)s like (Cd²⁺, Cu²⁺, Ni²⁺, Pb²⁺, Zn²⁺ and As³⁺) along with additional leaching analysis of total nitrogen (T-N), phosphate (T-P) and chemical oxygen demand (COD). The transformations of calcite during synthesis were confirm by characterization using XRD, SEM-EDAX and FT-IR techniques. In additional, the phosphate leaching potential and adsorbate (nitrate) efficiency in aqueous solution was investigated using the calcinedurine calcite. The results indicate that the calcite was effectively remove heavy metal(loid)s lead up to 96.8%. In addition, the adsorption capacity (q_e) of calcite was calculated and it was found to be 203.64 Pb, 110.96 Cd, 96.02 Zn, 104.2 As, 149.54 Cu and 162.68 Ni mg/g, respectively. Hence, we suggest that the calcite obtain from the human urine will be a suitable absorbent for heavy metal(loid)s removal from aqueous solution.