• Journal of Nutrition and Health
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• v.7 no.2
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• pp.37-51
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• 1974

This Study was carried out to observe the effect of nutritional condition on the change of protein metabolism in the animal body by feeding on imbalanced protein diet. A total 242 growing male albino rats, weighing $115{\sim}120$ gm, were used for the experimental animals. The rats were fed on the standard diet(st), protein flee diet(pf) and imbalanced protein diet(ib) for twelve weeks respectively. Hemoglobin, packed cell volume in blood, and total nitrogen, amino acid nitrogen, urea-nitrogen, creatinine, transaminases(GPT, GOT) in liver and serum, and total nitrogen in small intestine, and total nitrogen, urea-nitrogen In small intestine, and total nitrogen, urea-nitrogen, creatinine, urea-nitrogen/creatinine ratio in urine were measured. The results obtained are as follows; 1. The gained body weight were lower in pf group and ib group than those of st group. The gained body weight fed for 12 weeks, were 80% lower in pf group than those of st group, and the body weight of pf group for $50{\sim}75$ days feeding were $40{\sim}60%$ decreased, compared with the stating weight, and then all of them died. 2. The change of the brain, liver, kidney, spleen and small intestine by feeding on imbalanced diet for 12 weeks were no remarkable difference with the starting weight, but those of protein free diet group were half or more decrease and those were significantly lower in spleen and small intestine especially than the other organ 3. The contents of hemoglobin in pf group for 8 weeks feeding, and the packed cell volume in pf group for 8 weeks feeding and in ib group for 12 weeks feeding were decreased. but those of the other feeding group were almost same value. 4. The total nitrogen in the liver, small intestine and serum of each diet group were no remarkable difference respectively. The contents of amino acid nitrogen in pf group for 2 and 6 weeks feeding were increased. 5. On transaminases: a) The cycle of increase and decrease of GPT activities were come periodically and the interval of cycle were fast in the early stage of feeding and slow there-after. b) The GPT activities were decreased gradually in pf group after feeding and those were increased in ib group for 6 weeks feeding but decreased there-after. The frequency of cycle were more GPT than GOT and specially those of GPT in early stage of feeding were two or three times while GOT was one. c) The interval of increase and decrease in GOT and amino acid nitrogen cycle were similar tendency. 6. The contents of total nitrogen, creatinine and urea-nitrogen of pf group in urine were decreased very sharply from sharting feeding to one week but increased dully from six weeks to eight weeks feeding. The contents of urea-nitrogen of ib group were increased dully by feeding on ten weeks but decreased by feeding on twelve weeks. From the above results, it is concluded that the trend of the metabolic change is maintained equally by homeostatic mechanism using the endogenous protein source during a certain period by imbalanced protein diet feeding. The homeostatic mechanism is come peridically, very fast in early stage of feeing and than slow there-after.

• Journal of Nutrition and Health
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• v.5 no.2
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• pp.91-103
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• 1972

Zinc is one of the essential trace elements in the living organism for growth and health. The first identified metalloenzyme, carbonic anhydrase, is a zinc compound and several others have been described since. Among zinc deficiency syndromes in animals porcine parakeratosis has been successfully treated with zinc supplements, and in man a syndrome of anemia, hypogonadism, hepatosplenomegaly, and dwarfism, prevalent in parts of Iran and Egypt, has been ascribed to lack of zinc in the diet. Dietary zinc excess in the rat is manifested by a hypochromic, microcytic anemia, poor growth, reduction in liver catalase and cytochrome oxidase. The present study is an attempt to delineate the changes of tissue contents of trace elements, especially of iron, copper and zinc in liver and kidneys of the rats. Weanling albino rats, weighing 60 to 80gm. were used in this experiments. The rats were housed in cages with aluminum floors and received feed and distilled water ad libitum. Animals were divided into three groups, control, low zinc diet and high zinc diet groups. The high zinc diet group was subdivided into 0.5% Zn and 0.7%Zn groups. The supplementary copper or iron was added to the high dietary zinc groups. The animals were sacrificed and the tissues were washed several times with deionized water. The wet digested samples were analyzed by Hitachi Model 207 atomic absorption spectro-photometer for the determination of iron, copper and zinc in the liver and kidney. Hemoglobin level in the blood was measured by cyanmethemoglobin method. The results of this study are as follows: 1) All rats fed high zinc diets and low zinc diets gained less weight than control. Weight gain was not improved by the supplementary copper or iron and both. 2) Hemoglobin concentration was decreased significantly in the rats fed high zinc diets and less in the low zinc diet. Supplementary copper and iron to the higher zinc diet appeared to give some improvement of anemia. 3) The iron contents of the liver and kidneys were significantly decreased in the high zinc groups and the reduction was more significantly in the rats receiving higher zinc diet (0.7%). The supplementary copper caused a further depression of liver iron. On the other hand, the iron, added to the high zinc diet lessoned the severity of the decrease in liver iron and caused kidney iron to be maintained almost at the level found in the rats fed by zinc and supplementary copper diet. 4) High zinc diets did not change copper content of the liver and kidney. Supplementary copper elevated the concentration in the liver and kidney and added iron had no effect on the accumulation of copper in the liver and kidneys. 5) The high zinc diets caused marked increases of zinc content in the liver and kidney. Supplementary iron to the high zinc diet caused increases of zinc contents of liver and kidneys.

• Experimental and Molecular Medicine
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• v.50 no.11
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• pp.8.1-8.14
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• 2018

We previously demonstrated that the direct transplantation of human umbilical cord blood-derived mesenchymal stem cells (hUCB-MSCs) into the dentate gyrus ameliorated the neurological symptoms of Niemann-Pick type C1 (NPC1)-mutant mice. However, the clinical presentation of NPC1-mutant mice was not fully understood with a molecular mechanism. Here, we found 14,15-epoxyeicosatrienoic acid (14,15-EET), a cytochrome P450 (CYP) metabolite, from hUCB-MSCs and the cerebella of NPC1-mutant mice and investigated the functional consequence of this metabolite. Our screening of the CYP2J family indicated a dysregulation in the CYP system in a cerebellar-specific manner. Moreover, in Purkinje cells, CYP2J6 showed an elevated expression level compared to that of astrocytes, granule cells, and microglia. In this regard, we found that one CYP metabolite, 14,15-EET, acts as a key mediator in ameliorating cholesterol accumulation. In confirming this hypothesis, 14,15-EET treatment reduced the accumulation of cholesterol in human NPC1 patient-derived fibroblasts in vitro by suppressing cholesterol synthesis and ameliorating the impaired autophagic flux. We show that the reduced activity within the CYP system in the cerebellum could cause the neurological symptoms of NPC1 patients, as 14,15-EET treatment significantly rescued cholesterol accumulation and impaired autophagy. We also provide evidence that the intranasal administration of hUCB-MSCs is a highly promising alternative to traumatic surgical transplantation for NPC1 patients.

• Laboraroty Animal Research
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• v.34 no.4
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• pp.302-310
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• 2018

CD47 (integrin-associated protein), a multi-spanning transmembrane protein expressed in all cells including red blood cells (RBCs) and leukocytes, interacts with signal regulatory protein ${\alpha}$ ($SIRP{\alpha}$) on macrophages and thereby inhibits phagocytosis of RBCs. Recently, we generated a novel C57BL/6J CD47 knockout ($CD47^{-/-}$ hereafter) mouse line by employing a CRISPR/Cas9 system at Center for Mouse Models of Human Disease, and here report their hematological phenotypes. On monitoring their birth and development, $CD47^{-/-}$ mice were born viable with a natural male-to-female sex ratio and normally developed from birth through puberty to adulthood without noticeable changes in growth, food/water intake compared to their age and sex-matched wild-type littermates up to 26 weeks. Hematological analysis revealed a mild but significant reduction of RBC counts and hemoglobin in 16 week-old male $CD47^{-/-}$ mice which were aggravated at the age of 26 weeks with increased reticulocyte counts and mean corpuscular volume (MCV), suggesting hemolytic anemia. Interestingly, anemia in female $CD47^{-/-}$ mice became evident at 26 weeks, but splenomegaly was identified in both genders of $CD47^{-/-}$ mice from the age of 16 weeks, consistent with development of hemolytic anemia. Additionally, helper and cytotoxic T cell populations were considerably reduced in the spleen, but not in thymus, of $CD47^{-/-}$ mice, suggesting a crucial role of CD47 in proliferation of T cells. Collectively, these findings indicate that our $CD47^{-/-}$ mice have progressive hemolytic anemia and splenic depletion of mature T cell populations and therefore may be useful as an in vivo model to study the function of CD47.

• BMB Reports
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• v.52 no.4
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• pp.289-294
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• 2019

The present study evaluated the role of AHNAK in Bartonella henselae infection. Mice were intraperitoneally inoculated with $2{\times}10^8$ colony-forming units of B. henselae Houston-1 on day 0 and subsequently on day 10. Blood and tissue samples of the mice were collected 8 days after the final B. henselae injection. B. henselae infection in the liver of Ahnak-knockout and wild-type mice was confirmed by performing polymerase chain reaction, with Bartonella adhesion A as a marker. The proportion of B. henselae-infected cells increased in the liver of the Ahnak-knockout mice. Granulomatous lesions, inflammatory cytokine levels, and liver enzyme levels were also higher in the liver of the Ahnak-knockout mice than in the liver of the wild-type mice, indicating that Ahnak deletion accelerated B. henselae infection. The proportion of CD4+interferon-${\gamma}$ ($IFN-{\gamma}^+$) and $CD4^+$ interleukin $(IL)-4^+$ cells was significantly lower in the B. henselae-infected Ahnak-knockout mice than in the B. henselae-infected wild-type mice. In vitro stimulation with B. henselae significantly increased $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected wild-type mice, but did not increase $IFN-{\gamma}$ and IL-4 secretion in the splenocytes obtained from the B. henselae-infected Ahnak-KO mice. In contrast, $IL-1{\alpha}$, $IL-1{\beta}$, IL-6, IL-10, RANTES, and tumor necrosis $factor-{\alpha}$ secretion was significantly elevated in the splenocytes obtained from both B. henselae-infected wild-type and Ahnak-knockout mice. These results indicate that Ahnak deletion promotes B. henselae infection. Impaired $IFN-{\gamma}$ and IL-4 secretion in the Ahnak-knockout mice suggests the impairment of Th1 and Th2 immunity in these mice.

• BMB Reports
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• v.55 no.9
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• pp.453-458
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• 2022

Diabetes mellitus (DM) is a serious disease in which blood sugar levels rise abnormally because of failed insulin production or decreased insulin sensitivity. Although many studies are being conducted for the treatment or early diagnosis of DM, it is not fully understood how mitochondrial genome (mtDNA) abnormalities appear in patients with DM. Here, we induced iPSCs from fibroblasts, PBMCs, or pancreatic cells of three patients with type 2 DM (T2D) and three patients with non-diabetes counterpart. The mtDNA mutations were detected randomly without any tendency among tissues or patients. In T2D patients, 62% (21/34) of iPSC clones harbored multiple mtDNA mutations, of which 37% were homoplasmy at the 100% mutation level compared to only 8% in non-diabetes. We next selected iPSC clones that were a wild type or carried mutations and differentiated into pancreatic cells. Oxygen consumption rates were significantly lower in cells carrying mutant mtDNA. Additionally, the mutant cells exhibited decreased production of insulin and reduced secretion of insulin in response to glucose. Overall, the results suggest that screening mtDNA mutations in iPSCs from patients with T2D is an essential step before pancreatic cell differentiation for disease modeling or autologous cell therapy.

• The Korea Journal of Herbology
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• v.33 no.6
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• pp.61-70
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• 2018

Objectives : Non-alcoholic fatty liver disease (NAFLD) is characterized by the accumulation of hepatic triglycerides (TG) that leads to inflammation and fibrosis. Crataegi Fructus ethanol extract (CE) is a korean traditional herb that used for digestive diseases. It has been investigated that CE has the effect that prevent hepatotoxicity caused by CCl4 or GaIN and regulate the inflammatory in several organs. However, a hypolipidemic effect of CF has not been reported. Methods : The purpose of this study is that examine the lipid accumulation inhibitory effect of CE on NAFLD. We checked the body and liver weight change of MCD-diet induced mice with/without administration of CE. The blood lipid levels of C57BL/6J mice were checked by biochemistry. Also we observed the liver histology of MCD-diet induced mice and investigate the molecular mechanisms in MCD-diet-induced NAFLD in C57BL/6J mice. Results : CE improved MCD-diet-induced lipid accumulation and TG and TC levels. Also, CE decreased hepatic lipogenesis such as SREBP-1, $C/EBP{\alpha}$, $PPAR{\gamma}$, ACC and FAS. Besides, we also found out that CE increased AMPK phosphorylation. These results indicated that CE has the same ability to activate AMPK and then reduce SREBP-1, and FAS expression, finally leading to inhibit hepatic lipogenesis and hepatic antioxidative ability. Conclusions : In this report, we found CE exerted a regulatory effect on lipid accumulation by decreasing lipogenesis in MCD-diet induced NAFLD model. Therefore, CE extract may be active in the prevention of fatty liver.

• The Korea Journal of Herbology
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• v.36 no.6
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• pp.27-37
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• 2021

Objectives : In the current study, we performed the 13-week repeated oral dose toxicity test and a 4-week recovery test of standardized Cornus officinalis Sieb. et Zucc. and Psoralea corylifolia L. 30 % ethanol extract (SCP) in Sprague-Dawley (SD) rats owing to aims for verifying no observed adverse effect level (NOAEL). Methods : The animal study was performed according to OECD guidelines for the testing of chemicals section 4 health effects test No.408 repeated dose 90-day oral toxicity study in rodents (03 October 2008). In the repeated dose toxicity study, SCP was orally administered to female and male rats at dose levels of 1,000, 2,000, and 4,000 mg/kg/day for 13-week. The control group and high dose (4,000 mg/kg/day) group were then monitored for 4 extra weeks to determine recovery time after the study period. 1) Results : Compared with the control group, there were no treatment-related adverse effects in clinical signs, body weight, hematology, serum biochemistry (Aspartate aminotransferase, Alanine aminotransferase, Alkaline phosphatase, 𝛾-Glutamyl transpeptidase, Blood urea nitrogen, Creatinine, Glucose, Total cholesterol, Total protein, Creatine phosphokinase, Albumin, Total bilirubin, Triglyceride, Inorganic phosphorus, Albumin/Globulin ratio, Calcium ion, Sodium ion, Potassium ion, Chloride ion), necropsy findings and organ weight (Ovary, Adrenal gland, Pituitary, Thymus, Prostate, Testis, Epididymis, Spleen, Kidney, Heart, Lung, Brain, Liver) at any dose tested. Conclusions : Taken together, these results suggest that the NOAEL of SCP in both genders was considered as over 4,000 mg/kg. Results from this study provide scientific evidence for the safety of SCP.

• Herbal Formula Science
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• v.32 no.1
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• pp.63-82
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• 2024

Objective : Saengkankunbi-tang (SKT) is used as a traditional Korean herbal formula for treatment of liver diseases. We investigated the hepatoprotective effects of SKT plus Epimedium koreanum Nakai (EKE) against arachidonic acid (AA) + iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl₄)-mediated acute liver damage in mice. Methods : The cyto-protective effects of SKT + EKE were determined by MTT assay, western blot and fluorescence activated cell sorting analysis. In mice, blood biochemistry and western blot were assessed in CCl₄-induced acute hepatic damage. The animal groups included vehicle-treated control, CCl₄, SKT (200 mg/kg/day), EKE (100 mg/kg/day), SKT (200 mg/kg/day) + EKE (100 mg/kg/day) and silymarin (200 mg/kg/day). Results : In HepG2 cells, pretreatment with SKT + EKE significantly suppressed cytotoxicity induced by AA + iron and reduced the expression of proteins related to apoptosis. In addition, pretreatment with SKT + EKE significantly prevented the increase in H₂O₂ production, GSH depletion, and lower mitochondrial membrane potential induced by AA + iron. In CCl₄-induced liver damage mice, the administration of SKT + EKE prevented the liver damage by inhibition of hepatocyte damage and expression of apoptosis proteins in liver. More importantly, in vitro and in vivo assay, SKT + EKE showed significant effect compare with SKT alone or EKE alone in all parameters. Conclusions : These results indicated that SKT + EKE could protect against oxidative stress-induced liver damage, and SKT + EKE is more effective than SKT alone or EKE alone.

• Journal of Life Science
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• v.34 no.10
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• pp.744-754
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• 2024

Cancer cells exhibit a unique metabolic process for uncontrolled cell division, providing bioenergy and intermediates, which are significantly different from normal cells. Here an aerobic glycolysis converts most of the pyruvate produced from glucose into lactate and inefficiently produced ATP. Cancer cells counter their lack of energy through glutamine metabolism, together with glucose. Glutamine is the most abundant amino acid in the blood and is used for the synthesis of amino acids, nucleotides, and lipids, as well as bioenergy through glutaminolysis. Cancer cells rely on glutamine rather than normal cells, showing more than half of the tricarboxylic acid cycle metabolites derived from glutamine, called glutamine addiction. Oncogenes c-Myc also regulates the expression of various genes involved in glutamine metabolism and promotes the absorption of glutamine. Whether glutaminase (GLS) causes or inhibits tumors is controversial. However, GLS1 is a promising treatment target due to its higher carcinogenic incidence, whereas GLS2 is known to act as a tumor suppressor. The 4th-generation metabolic anti-cancer therapy, which has been actively investigated since the mid-2010s, is based on a complex and sophisticated network of cancer metabolites. These drugs directly regulate the energy metabolism of cancer cells to maximize anti-cancer effects without side effects. GLS is a crucial enzyme for cancer metabolism and tumor progression that catalyzes the first stage in the process of glutaminolysis. The development of anti-cancer drugs targeting GLS enzymes has emerged as a promising strategy.