• Biomolecules & Therapeutics
• /
• v.31 no.1
• /
• pp.73-81
• /
• 2023

Sirtuins (SIRTs) belong to the nicotinamide adenine dinucleotide (NAD+)-dependent class III histone deacetylase family. They are key regulators of cellular and physiological processes, such as cell survival, senescence, differentiation, DNA damage and stress response, cellular metabolism, and aging. SIRTs also influence carcinogenesis, making them potential targets for anticancer therapeutic strategies. In this study, we investigated the anticancer properties and underlying molecular mechanisms of a novel SIRT1 inhibitor, MHY2251, in human colorectal cancer (CRC) cells. MHY2251 reduced the viability of various human CRC cell lines, especially those with wild-type TP53. MHY2251 inhibited SIRT1 activity and SIRT1/2 protein expression, while promoting p53 acetylation, which is a target of SIRT1 in HCT116 cells. MHY2251 treatment triggered apoptosis in HCT116 cells. It increased the percentage of late apoptotic cells and the sub-G1 fraction (as detected by flow cytometric analysis) and induced DNA fragmentation. In addition, MHY2251 upregulated the expression of FasL and Fas, altered the ratio of Bax/Bcl-2, downregulated the levels of pro-caspase-8, -9, and -3 proteins, and induced subsequent poly(ADP-ribose) polymerase cleavage. The induction of apoptosis by MHY2251 was related to the activation of the caspase cascade, which was significantly attenuated by pre-treatment with Z-VAD-FMK, a pan-caspase inhibitor. Furthermore, MHY2251 stimulated the phosphorylation of c-Jun N-terminal kinase (JNK), and MHY2251-triggered apoptosis was blocked by pre-treatment with SP600125, a JNK inhibitor. This finding indicated the specific involvement of JNK in MHY2251-induced apoptosis. MHY2251 shows considerable potential as a therapeutic agent for targeting human CRC via the inhibition of SIRT1 and activation of JNK/p53 pathway.

• Journal of Life Science
• /
• v.33 no.7
• /
• pp.574-585
• /
• 2023

Sarcopenia is a leading cause of increased medical and nursing care costs among the elderly. In Korea, preventive measures for sarcopenia are mostly targeted toward the general elderly population without specific diseases. However, it is also necessary to implement measures for elderly individuals living in nursing homes and hospitals, where the prevalence of sarcopenia is high. Currently, computed tomography and/or magnetic resonance imaging are considered standard diagnostic tools. However, their complexity and time-consuming nature make them unsuitable for clinical use. The exact pathophysiological mechanisms of sarcopenia are unclear, as they involve various molecular biological pathways, including decreased exercise, protein and nutrient intake, changes in testosterone and growth hormone, and inflammation. Sarcopenia symptoms can lead to several diseases, such as osteoporosis, fractures, dementia, diabetes, and cardiovascular disease. Vitamin B deficiency is a significant factor in sarcopenia induction, with B vitamins being directly involved in energy and protein metabolism and nerve function. Vitamin B deficiency can lead to neuromuscular and neurogenic disorders, which often overlap with sarcopenia. Suboptimal intake of B vitamins, malabsorption, and anorexia are common among the elderly. This study aims to provide information on the role of water-soluble B vitamins in preventing and controlling muscle mass loss and deterioration among the elderly with sarcopenia. In addition, we discuss the potential of myokines from the B vitamin family in modulating sarcopenia.

• Animal Bioscience
• /
• v.35 no.9
• /
• pp.1327-1339
• /
• 2022

Objective: Fat deposition in poultry is an important factor in production performance and meat quality research. miRNAs also play important roles in regulating adipocyte differentiation process. This study was to investigate the expression patterns of miRNAs in duck adipocytes after differentiation and explore the role of miR-214 in regulating carnitine palmitoyltransferases 2 (CPT2) gene expression during duck adipocyte differentiation. Methods: Successful systems for the isolation, culture, and induction of duck primary fat cells was developed in the experiment. Using Illumina next-generation sequencing, the miRNAs libraries of duck adipocytes were established. miRanda was used to predict differentially expressed (DE) miRNAs and their target genes. The expression patterns of miR-214 and CPT2 during the differentiation were verified by quantitative real-time polymerase chain reaction and western blot. Luciferase reporter assays were used to explore the specific regions of CPT2 targeted by miR-214. We used a miR-214 over-expression strategy in vitro to further investigate its effect on differentiation process and CPT2 gene transcription. Results: There were 481 miRNAs identified in duck adipocytes, included 57 DE miRNA candidates. And the 1,046 targets genes of DE miRNAs were mainly involved in p53 signaling, FoxO signaling, and fatty acid metabolism pathways. miR-214 and CPT2 showed contrasting expression patterns before and after differentiation, and they were selected for further research. The expression of miR-214 was decreased during the first 3 days of duck adipocytes differentiation, and then increased, while the expression of CPT2 increased both in the transcriptional and protein level. The luciferase assay suggested that miR-214 targets the 3'untranslated region of CPT2. Overexpression of miR-214 not only promoted the formation of lipid droplets but also decreased the protein abundance of CPT2. Conclusion: Current study reports the expression profile of miRNAs in duck adipocytes differentiated for 4 days. And miR-214 has been proved to have the regulator potential for fat deposition in duck.

• Journal of Chest Surgery
• /
• v.41 no.3
• /
• pp.354-359
• /
• 2008

Background: Warfarin is used as an anticoagulant and it is mainly excreted by the liver metabolism (the R-form is mainly metabolized by cytochrome p450 3A4, and the S form by cytochrome p450 2C9). Rifampin is usually used for tuberculosis or endocarditis, and it is a representative drug that induces the CYP families, including 3A4 and 2C9. The anticoagulation effect of warfarin decreases through the increased metabolism that's due to the induction of enzymes, and this iscaused by rifampin when patients take these two medicines together. No one has suggested appropriate guidelines regarding this drug interaction even though an appropriate adjustment of warfarin's dosage is needed. We examined the drug interaction in patients who received warfarin-rifampin combination therapy according to the time interval, and the factors affecting drug interaction were analyzed. Based on the data, we tried to determine the clinically available warfarin dosage guidelines before and after taking this drug combination. Material and Method: We reviewed the OO University Hospital anticoagulation service team's follow up sheets that were filled out from Jan '1998 to Sep 2006 for the patient who took warfarin - rifampin combination therapy (n=15). Result: The average INR of all the patient before rifampin administration was $2.25{\pm}0.52$ $(mean{\pm}SD)$, and that value for the first 100 days after rifampin administration was $1.98{\pm}0.28$. The p value for these two sets of data showed no correlation (paired t-test, p>0.05). The average INR of all the patient before rifampin cessation was $2.19{\pm}0.34$, and the value after rifampin cessation was $2.49{\pm}0.43$. The p value of these two showed correlation (paired t-test, p<0.05) but the average INR falls between the therapeutic INR range. Conclusion: The warfarin dose adjustment equation of before and after warfarin-rifampin combination therapy was derived based on this study's results because the warfarin dosage adjustment of the anticoagulation service team was considered appropriate.

• KOREAN JOURNAL OF CROP SCIENCE
• /
• v.52 no.1
• /
• pp.69-80
• /
• 2007

Among the photoactive semiconductors such as $TiO_2,\;ZnO,\;Fe_2O_3,\;WO_3,\;and\;CdSe,\;TiO_2$ is the most widely used as photocatalyst in different media, because of its lack of toxicity and stability. In this study, the effects of titanium dioxide were investigated to obtain the information of physiological change in rice plant. Light-adapted Chlorophyll flourescence index decreased and relative electron transport rate of rice leaves was activated by titanium dioxide under $2,400\;{\mu}mol\;m^{-2}\;s^{-1}$ PAR (Photosynthetic active radiation). Relative electron transport rate of rice leaf treated with titanium dioxide 10 ppm was high in order of $2,400\;{\mu}mol\;m^{-2}\;s^{-1}\;PAR,\;2,200\;{\mu}mol\;m^{-2}\;s^{-1}\;PAR,\;450\;{\mu}mol\;m^{-2}\;s^{-1}\;PAR$ and titanium dioxide 10 ppm (45.1%), control (32.4%), diuron 10 ppm (15.3%) under $2,400\;{\mu}mol\;m^{-2}\;s^{-1}\;PAR$. Titanium dioxide increased photosynthesis of the rice leaf under $13.6\;KJ\;m^{-2}\;day^{-1}$ UV-B only. With titanium dioxide 20 ppm, reduced UV-B ($0.15\;KJ\;m^{-2}\;day^{-1}$) intensity changed the induction of proteins and twenty-five proteins were identified. Among them, seventy proteins were up-regulated, four proteins were down-regulated and four proteins were newly synthesized. Function of these proteins was related to photosynthesis (52%), carbohydrate metabolism (4%), stress/defense (8%), secondary metabolism (4%), energy/electron transport (4%), and miscellaneous (28%).

• Journal of Chest Surgery
• /
• v.31 no.6
• /
• pp.553-559
• /
• 1998

Introduction: The most dramatic application of hypothermia in cardiac surgery is in deep hypothermic circulatory arrest(DHCA). Because man in natural circumstances is never exposed to this extreme hypothermic condition, one of the controversial aspects of clinical hypothermia is appropriate acid-base management($\alpha$-stat versus pH-stat). This study aims to compare $\alpha$-stat with pH-stat for: (1) brain cooling and re-warming speed during hypothermia induction and re-warming by cardiopulmonary bypass (CPB); (2) cerebral perfusion, metabolism, and their coupling; and (3) the extent of development of cerebral edema after circulatory arrest, in young pigs. Materials & Methods: Fourteen young pigs were assigned to one of two strategies of gas manipulation. Cerebral blood flow was measured with a cerebral venous outflow technique. After a median sternotomy, CPB was established. Core cooling was initiated and continued until nasopHaryngeal temperature fell below $20^{\circ}C$. The flow rate was set at 2,500 ml/min. Once their temperatures were below $20^{\circ}C$, the animals were subjected to DHCA for 40 mins. During cooling, acid-base balance was maintained according to either $\alpha$-STAT or pH-STAT strategies. After DHCA, the body was re-warmed to normal body temperature. The animals were then sacrificed, and their brains measured for edema. Cerebral perfusion and metabolism were measured before the onset of CPB, before cooling, before DHCA, 15 mins after re-warming, and upon completion of re-warming. Results & Conclusion: Cooling time was significantly shorter with $\alpha$-stat than with pH-stat strategy, while there were no significant differences in rewarming time between the two groups. Nosignificant differences were found in cerebral blood flow, metabolic rate, or flow/ metabolic rate ratio between two groups. Temperature-related differences were significant in cerebral blood flow, metabolic rate, and flow/metabolic rate ratio within each group. Brain water content showed no significant differences between two groups.

• The Journal of Korean Obstetrics and Gynecology
• /
• v.15 no.4
• /
• pp.61-75
• /
• 2002

Recombinant human $interleukin-1{\beta}$ $(rhIL-1{\beta})$ regulates several activities of the osteoblast cells derived from mouse calvarial bone explants in vitro. $rhIL-1{\beta}$ stimulated cellular proliferation and the synthesis of prostaglandin $E_2(PGE_2)$ and plasminogen activator activity in the cultured cells in a dose-dependent manner. However, the induction of osteocalcin synthesis and alkaine phosphatase activity in response to vitamine D, two characteristics of the osteoblast phenotype, were antagonized by $rhIL-1{\beta}$ over a similar dose range. This study supports the role of $IL-1{\beta}$ in the pathological modulation of bone cell metabolism, with regard to implication in the pathogenesis of osteoporosis by $IL-1{\beta}$. When the mouse calvarial bone cells were used, the bone resorption induced by $IL-1{\beta}$ was strongly inhibited by calcitonin treatment, indicating osteoclast-mediated bone resorption. On the other hand, the medicinal extracts of Taeyoungjon-Jahage (T.Y.J-J.H.G extracts) was tested for whether they could inhibit $IL-1{\beta}-induced$ $PGE_2$ production. Cell viability was not significantly affected by treatment with the indicated concentration of the extracts. The T.Y.J.-J.H.G. extracts were shown to have the inhibitory effects against the synthesis of $PGE_2$. We also examined the effect of the pretreatment with a various concentrations of the T.Y.J.-J.H.G. extracts then treated the $PGE_2-induction$ agents. Pretreatment of the T.Y.J.-J.H.G. extracts for 1 h, which by itself had little effect on cell survival, did not enhance the synthesis of $PGE_2$. Furthermore, the T.Y.J-J.H.G. extracts were shown to have the protective effects against plasminogen dependent fibrinolysis induced by the bone resorption agents of $IL-1{\beta}$. Pretreatment of the T.Y.J.-J.H.G. extracts for 1 h did not enhance the plasminogen dependent fibrinolysis. Finally, calcitonin showed the inhibitory activity the $IL-1{\beta}-stimulated$ bone resorption in the mouse calvarial bone cells having both of the osteoblast and osteoclast cells. Seemingly, pretreatment of the T.Y.J.-J.H.G. extracts for 1 h reduced the bone resorption. These results clearly indicated that calcitonin and T.Y.J.-J.H.G. extracts play key roles in inhibition of the osteoclast-mediated bone resorption.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.45 no.4
• /
• pp.484-491
• /
• 2016

The present study investigated the effect of Sinetrol-XPur (polyphenolic Citrus spp. and Paullinia cupana Kunth dry extract) and defined the action mode for cyclic adenosine monophosphate (cAMP)-dependent uncoupling protein (UCP)-2 activation. Leptin-deficient obese mice were treated with two different doses, 100 mg/kg body weight (BW) and 300 mg/kg BW of each AIN93G supplement, for 7 weeks. Treatment of obese mice with both low and high doses of Sinetrol-XPur significantly reduced body weight gain compared to control obese mice. White adipose tissue weight of mice was reduced by 30.96% in high dose-supplemented groups. Serum total cholesterol and triglyceride were reduced by a high dose of Sinetrol-XPur by 20.02% and 30.96%, respectively. Serum level of high density lipoprotein (HDL) was significantly increased by treatment with both doses, as the ratio of HDL to low density lipoprotein increased by 138.78% and 171.49%, respectively. Regarding expression of biochemical factors related to lipid metabolism, fatty acid synthase significantly decreased and UCP-2 increased upon treatment with a high dose of Sinetrol-XPur, but there was no significant difference in lipoprotein lipase and hormone-sensitive lipase. To define cellular mechanism, intracellular cAMP levels in 3T3-L1 adipocytes significantly increased in a dose-dependent manner over the range of $50{\sim}250{\mu}m/mL$. The phosphodiesterase (PDE) inhibitor 3-isobutyl-1-methylxanthine clearly blocked cAMP, suggesting that Sinetrol-XPur promotes lipolysis of adipocytes through inhibition of cAMP-dependent PDE, resulting in induction of cAMP response element binding protein and UCP-2. These results suggest that Sinetrol-XPur supplementation is a viable option for reducing body weight and fat by improving serum lipid profiles and genetic expression of lipid metabolic factors, especially activation of cAMP-dependent UCP-2.

• Journal of the Korean Society of Food Science and Nutrition
• /
• v.43 no.11
• /
• pp.1688-1694
• /
• 2014

Jeju Hallabong Tangor (Citrus kiyomi${\times}$ponkan) is a Citrus species with a variety of physiological properties such as anti-oxidant, anti-inflammation, anti-cancer, and anti-obesity. We investigated the anti-obesity effects of Hallabong Tangor peel extracts before (HLB) and after (HLB-C) bioconversion with cytolase based on modulation of adipocyte differentiation and lipid metabolism in 3T3-L1 adipocytes. Treatment with cytolase decreased flavanone rutinoside forms (narirutin and hesperidin) and increased flavanone aglycone forms (naringenin and hesperetin). During adipocyte differentiation, 3T3-L1 cells were treated with 0.5 mg/mL of Sinetrol (a positive control), HLB or HLB-C. Adipocyte differentiation was inhibited in both citrus groups, but not in control and Sinetriol groups. HLB and HLB-C tended to reduce insulin-induced mRNA levels of CCAAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$) and sterol regulatory element-binding protein 1c (SREBP1c). Compared to the control and Sinetrol groups, HLB and HLB-C markedly suppressed insulin-induced protein expression of $C/EBP{\alpha}$ and peroxisome proliferator-activated receptor gamma ($PPAR{\gamma}$). The HLB and Sinetrol groups, but not HLB-C group, significantly increased adipolytic activity with higher release of free glycerol compared to the control group in differentiated 3T3-L1 adipocytes. These results suggest that bio-conversion of Hallabong Tangor peel extracts with cytolase increases aglycone flavonoids. Irrespective of bioconversion, both Hallabong Tangor peel extracts exert anti-obesity effects that may contribute to prevention of obesity through inhibition of adipocyte differentiation or induction of adipolytic activity.

• KOREAN JOURNAL OF CROP SCIENCE
• /
• v.37 no.5
• /
• pp.468-475
• /
• 1992

In order to understand more clearly the integration between N-assmilation and C-metabolism in relation to N fertilization, a pot experiment with 5 different level of N fertilization(0, 5, 10, 25, 50 mM NO$_3$$_{[-10]}$ ) was conducted in Manchester, U.K. The peas (Pisum sativum L., cv. Early Onward) were sown in vermiculate (5 cm depth) and cultivated for 6 days under temperature controlled dark room conditions ($25^{\circ}C$). The plants received frequent irrigation with a nutrient solution: it was fertilized every 2 days, 3 times a day at 10h, 13h, 16h respectively. Elevated NO$_3$$^{[-10]}$ concentration, the activity levels of NR, NiR, total GS(crude extract), GS$_2$(plastid) in both root and shoot were increased and reached the peak in 5～25 mM, except NiR specific activity which increased its activity continually until 50 mM NO$_3$$^{[-10]}$ treatment. Total activities of GS (crude extract) in both root and shoot became higher than those of GS$_2$(Plastid), and the activity ratios of total GS in the crude extract and GS$_2$ in the plastids were 3.0 to 4.3 in root, but 3.2 to 10.6 in shoot. It was concluded that the reductants and A TP from OPPP itself should be enough to achieve the high rate of NR, NiR, GS$_1$, GS$_2$ in plant root and shoot for reduction or assimilation of nitrogen, but these enzyme activities might be inhibited by an excess of NO$_3$$^{[-10]}$ influx over the reduction capacity.