• Pediatric Gastroenterology, Hepatology & Nutrition
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• v.22 no.6
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• pp.501-510
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• 2019

Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in children. The global prevalence of pediatric NAFLD from general populations is 7.6%. In obese children, the prevalence is higher in Asia. NAFLD has a strong heritable component based on ethnic difference in the prevalence and clustering within families. Genetic polymorphisms of patatin-like phospholipase domain-containing protein 3 (PNPLA3), transmembrane 6 superfamily member 2, and glucokinase regulatory protein (GCKR) are associated with the risk of NAFLD in children. Variants of PNPLA3 and GCKR are more common in Asians. Alterations of the gut microbiome might contribute to the pathogenesis of NAFLD. High fructose intake increases the risk of NAFLD. Liver fibrosis is a poor prognostic factor for disease progression to cirrhosis. Magnetic resonance spectroscopy and magnetic resonance proton density fat fraction are more accurate for steatosis quantification than ultrasound. Noninvasive imaging methods to assess liver fibrosis, such as transient elastography, shear-wave elastography, and magnetic resonance elastography are useful in predicting advanced fibrosis, but they need further validation. Longitudinal follow-up studies into adulthood are needed to better understand the natural history of pediatric NAFLD.

• Journal of Microbiology and Biotechnology
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• v.33 no.10
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• pp.1370-1375
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• 2023

In this study, we aimed to enhance the accumulation of chorismate (CHR) and anthranilate (ANT), key intermediates in the shikimate pathway, by modifying a shikimate over-producing recombinant strain of Corynebacterium glutamicum [19]. To achieve this, we utilized a CRISPR-driven genome engineering approach to compensate for the deletion of shikimate kinase (AroK) as well as ANT synthases (TrpEG) and ANT phosphoribosyltransferase (TrpD). In addition, we inhibited the CHR metabolic pathway to induce CHR accumulation. Further, to optimize the shikimate pathway, we overexpressed feedback inhibition-resistant Escherichia coli AroG and AroH genes, as well as C. glutamicum AroF and AroB genes. We also overexpressed QsuC and substituted shikimate dehydrogenase (AroE). In parallel, we optimized the carbon metabolism pathway by deleting the gntR family transcriptional regulator (IolR) and overexpressing polyphosphate/ATP-dependent glucokinase (PpgK) and glucose kinase (Glk). Moreover, acetate kinase (Ack) and phosphotransacetylase (Pta) were eliminated. Through our CRISPR-driven genome re-design approach, we successfully generated C. glutamicum cell factories capable of producing up to 0.48 g/l and 0.9 g/l of CHR and ANT in 1.3 ml miniature culture systems, respectively. These findings highlight the efficacy of our rational cell factory design strategy in C. glutamicum, which provides a robust platform technology for developing high-producing strains that synthesize valuable aromatic compounds, particularly those derived from the shikimate pathway metabolites.

• Journal of Microbiology and Biotechnology
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• v.17 no.12
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• pp.1983-1990
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• 2007

Antidiabetic effects of a novel microbial biopolymer (PGB) 1 excreted from new Enterobacter sp. BL-2 were tested in the db/db mice. The animals were divided into normal control, rosiglitazone (0.005%, wt/wt), low PGB1 (0.1%, wt/wt), and high PGB1 (0.25%, wt/wt) groups. After 5 weeks, the blood glucose levels of high PGB1 and rosiglitazone supplemented groups were significantly lower than those of the control group. In hepatic glucose metabolic enzyme activities, the glucokinase activities of PGB1 supplemented groups were significantly higher than the control group, whereas the PEPCK activities were significantly lower. The plasma insulin and hepatic glycogen levels of the low and high PGB1 supplemented groups were significantly higher compared with the control group. Specifically, the insulin and glycogen increases were dose-responsive to PGB1 supplement. PGB1 supplement did not affect the IPGTT and IPITT compared with the control group; however, rosiglitazone significantly improved IPITT. High PGB1 and rosiglitazone supplementation preserved the appearance of islets and insulin-positive cells in immunohistochemical photographs of the pancreas compared with the control group. These results demonstrated that high PGB1 (0.25% in the diet) supplementation seemingly contributes to preventing the onset and progression of type 2 diabetes by stimulating insulin secretion and enhancing the hepatic glucose metabolic enzyme activities.

• Asian-Australasian Journal of Animal Sciences
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• v.28 no.2
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• pp.207-214
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• 2015

The effects of high carbohydrate diet on growth, serum physiological response, and hepatic heat shock protein 70 expression in Wuchang bream were determined at $25^{\circ}C$ and $30^{\circ}C$. At each temperature, the fish fed the control diet (31% CHO) had significantly higher weight gain, specific growth rate, protein efficiency ratio and hepatic glucose-6-phosphatase activities, lower feed conversion ratio and hepatosomatic index (HSI), whole crude lipid, serum glucose, hepatic glucokinase (GK) activity than those fed the high-carbohydrate diet (47% CHO) (p<0.05). The fish reared at $25^{\circ}C$ had significantly higher whole body crude protein and ash, serum cholesterol and triglyceride, hepatic G-6-Pase activity, lower glycogen content and relative levels of hepatic growth hormone (GH) gene expression than those reared at $30^{\circ}C$ (p<0.05). Significant interaction between temperature and diet was found for HSI, condition factor, hepatic GK activity and the relative levels of hepatic GH gene expression (p<0.05).

• Journal of Nutrition and Health
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• v.6 no.1
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• pp.15-29
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• 1973

Albio rats right after weaning, weighing $50{\sim}55g$, were divided into the control, high-carbohydrate-, high-lipid-, and high-protein-fed groups. and were fed for 12 weeks with the respective diets to observe the increase in body weights as well as changes in the chemical constituentes and enzyme activities in the liver tissue, with the following results. (1) There was little difference in the rate of increase in the body weights among the groups, showing normal growth, except the high-protein-fed group which showed decrease in rate of body weight increase from the 7th week after feeding. (2) The liver weight was either increased after 12 weeks of feeding with the high-carbohydrate and high-Lipid diets, or showed no difference with the high-protein diet, as compared to the control weight. (3) The liver cytosol protein content was increased when fed with the high-protein diet, but decreased when fed with the high-carbohydrate and high lipid diets, as compared to the control content. (4) The triglyceride and cholesterol contents in the liver were decreased in the high-protein-fed group, but increased markedly in the high-carbohydrate- and high-lipid-fed groups as compared to the control values. (5) The hepatic glucokinase, G6PD, LDH, and fatty acid synthetase activities were increased in the high-carbohydrate and high-lipid-fed groups, and GOT and CPT activities were increased in the high-protein-fed group. From the above results. it was known that the high-carbohydrate and high-lipid diets stimulated the hepatic lipid metabolism, giving rise to lipogenesis, but the high- protein diet could prevent the lipogeuesis leading to the body weight increase.

• The Journal of Korean Medicine
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• v.28 no.3 s.71
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• pp.216-231
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• 2007

Objectives : Chengsimyeunja-eum and Sunghyangjungi-san are prescriptions used for cerebral infarction clinically; it is known that these formulas reduce ischemic damage. According to previous research data, controlling certain types of glucose is considered to decrease the risk of cerebral infarction. Based on this fact, we investigated the effects of Chengsimyeunja-eum and Sunghyangjungi-san extracts on reperfusion following ischemic damage to diabetic rats, the change of c-FOS and Bax positive neurons in the hippocampus and cerebral cortex and protein through immunohistochemical methods, changes of serum glucose level, serum triglyceride level, and hepatic glucokinase activity. Methods : We induced ischemic damaged in diabetic rats, and the rats were administered Chengsimyeunja-eum and Sunghyangjungi-san extracts. Results : Chengsimyeunja-eum demonstrated significant decrease of c-Fos positive neurons in both hippocampus and cerebral cortex as well as a significant decrease of Bax positive neurons in hippocampus after ischemic damage on diabetic rats and decrease of serum glucose level after ischemic damage on diabetic rats. Sunghyangjungi-san demonstrated significant decreases of c-Fos and Bax positive neurons in both hippocampus and cerebral cortex after ischemic damage on diabetic rats. Conclusions : Chengsimyeunja-eum, effect on glucose level control, has a remarkable effect of protection of neurons not effective on glucose level. Sunghyangjungi-san showed neuroprotective effect through preventing neuronal cell death.

• Journal of Ginseng Research
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• v.17 no.2
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• pp.101-108
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• 1993

This study was made to understand a hypoglycemic action of the fat soluble fraction of Panax ginseng C.A. Meyer in streptozotocin induced diabetic rats by determining the activities of several enzymes related to carbohydrate and lipid metabolism as well as several blood component levels such as glucose and ketone bodies, and non-esterified fatty acids. Albino rats (Sprague Dawley, 170-200g, 3) were injected once with 70mg streptozotocinhg body weight intraperitoneally and fed with ordinary diet for 7 days, and then the fat soluble fraction (5 mg~20 mg/day/rat) was injected intraperitoneally once a day for three days to rats having high blood glucose level over 340 mg/100ml. After a final injection of the fat soluble fraction, rats u.ere starved for 16 hours followed by the analysis of blood serum and liver enzymes. It was found that increased levels of glucose, ketone bodies and free fatty acids in streptozotocin induced rats were decreased appreciably by administration of the fat soluble fraction. However, the amount of administered fat soluble fraction did not show any significantly different hypoglycemic action. Decreased activities of glucokinase, phosphofructokinase, pyruvate kinase, 6-phosphogluconate dehydrogenase and acetyl CoA carboxylase of the liver of streptozotocin induced diabetic rats were greatly modified suggesting that a hypoglycemic action of the fat soluble fraction was also appreciable as ginseng saponin fraction. We also compared a hypoglycemic action of the fat soluble fraction prepared from American ginseng and Chinese ginseng with that of Korean pain ginseng. 핀o significant difference of the hypoglycemic activity was observed between the above ginseng fat soluble fractions, suggesting that a study of the fat soluble fraction might be one of the most interesting subjects relating to diabetic hyperglycemia in the near future.

• Journal of the Korean Applied Science and Technology
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• v.31 no.2
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• pp.277-284
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• 2014

The ethanol extraction yield of Meliae toosendan fructus(MT) was about 24.5% by extract apparatus. This study was done to investigate the carbohydrate metabolism related enzyme activities and antioxidative effects of MT in streptozotocin (STZ)-induced diabetic rats. The contents of serum glucose, triglyceride (TG) were significantly decreaed in MT treated group compared to the those of STZ-control group, also content of Total cholesterol was decreased. High density lipoprotein (HDL)-cholesterol was increased in MT treated group. The activity of glucose-6-pase(G-6-Pase) was significantly decreased in MT treated group. Also the activities of glucose-6-phosphate dehydrogenase(G-6-PDH) and glucokinase(Gk) were increaed in MT treated group. The content of hepatic glycogen was significantly increaed in MT treated group, in addition, content of malondialdehyde(MDA) was significanly decreased in MT treated group. Also, content of glutathione(GSH)was dereased in MT treated froup. whereas, activity of catalase(CAT) was significantly increaed in MT treated group compared to the those of STZ-control group. activity of glutathione peroxidase(GSH-Px) was inecreaed. In conclusion, these results indicated that ethanol extract of MT would have carbohydrate metabolism antioxidative effects in STZ-induced diabetic rats.

• Korean Journal of Pharmacognosy
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• v.40 no.2
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• pp.128-136
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• 2009

This study was carried out to investigate the antidiabetic and antioxidative effect of Lycii fructus in the Streptozotocin(STZ)-induced diabetic rats. The effective fractions were prepared as a form of organic solvents of $CH_{3}(CH_{2})_{4}CH_{3}$ $CHCI_{3}$, EtOAc, BuOH and $H_{2}O$ fractions prepared from the EtOH extract of Lycii fructus and The diabetes were induced by an tail-intravenous injection of STZ with a dose of 45 mg/kg dissolved in citrate buffer. The various fractions of Lycii fructus were orally administrated once a day for 7 days. The contents of serum glucose, and triglyceride in the $CHCI_{3}$ fraction and hepatic lipid peroxidation in the EtOAc, BuOH and $H_{2}O$ fractions treated rats were significantly decreased when compared to those of the STZ-control group In addition, an activity of hepatic GST in the BuOH fraction treated rats was significantly increased compared to that of the STZ-control group. whereas, activities of hepatic catalase, GSH-Px in the BuOH fraction treated rats were significantly decreased compared to those of the STZ-control group. Meanwhile, The content of hepatic glycogen and avtivity of hepatic glucokinase in $CHCI_{3}$ fraction treated rats were significantly increased, but activity of glucose-6-pase was significantly decreased in the $CHCI_{3}$ fraction treated rats. In conclusion, these results indicated that the BuOH fraction of Lycii fructus was effective for the antioxidation, and also the $CHCI_{3}$ fraction of Lycii fructus was effective for the antidiabetes in the STZ-induced diabetic rats.

• The Microorganisms and Industry
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• v.25 no.1
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• pp.2-9
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• 1999

A study was made on enzymes of carbohydrate metabolism in T. concretivorus grown with and without glucose. The present results show that T. concretivorus possesses high activities of pentose shunt pathway and related enzymes, glucokinase, G-6-P dehydrogenase, 6-PG dehydrogenase, and phosphoglucoisomerase, but low activities of enzymes unique to EMP(fructose-1,6-diphosphate aldolase). Although the synthesis of the latter enzymes remains largely unaffected by the growth enviroment, that of the former is stimulated by glucose. And the failure to detect ED pathway enzymes in cells grown in thiosulate or thiosulfate-glucose medium eliminates the ED pathway as a significant route of glucose catabolism in T.concretivorus. These results suggest that pentose shunt pathway performs an energetic role in glucose metabolism by T.concretivorus with EMP as a subway. The absence of ED pathway and the presence of pentose shunt pathway which is the major route of catabolism in T.concretivorus are similar to those of other obligately chemolitho-trophic thiobacilli. The G-6-P and 6-PG dehydrogenase are both NAD and NADP specific, but MAD predominant. However, the 3-PGAL dehydrogenase is only NAD specific. Since the specific activity of 3-PGAL generated from glucose is converted mainly into pyruvate which is channeled into the TCA cycle. All enzymes of the TCA cycle tested and NADH oxidase are detected in the cells of T.concretivorus grown in thiosulfate. The specific activities of fumarase and isocitrate dehydrogenase are high and others are low. The presence of two isocitrate dehydrogenase (NAD-and NADP-linked) may have important regulatory function for this organism. The activity of NAD-oxidase, which is implicated in the energy generating metabolism, was very high in the crude cell-free extract of T.concretivorus, recording 55.11 m.mu. mole/min/mg protein. This well coincides with the fact that activities of NAD-linked G-6-P dehydrogenase, 6-PG dehydrogenase and 3-PGAL dehydrogenase were high.