• Molecules and Cells
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• v.39 no.12
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• pp.847-854
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• 2016

The early landmark discoveries in cancer metabolism research have uncovered metabolic processes that support rapid proliferation, such as aerobic glycolysis (Warburg effect), glutaminolysis, and increased nucleotide biosynthesis. However, there are limitations to the effectiveness of specifically targeting the metabolic processes which support rapid proliferation. First, as other normal proliferative tissues also share similar metabolic features, they may also be affected by such treatments. Secondly, targeting proliferative metabolism may only target the highly proliferating "bulk tumor" cells and not the slowergrowing, clinically relevant cancer stem cell subpopulations which may be required for an effective cure. An emerging body of research indicates that altered metabolism plays key roles in supporting proliferation-independent functions of cancer such as cell survival within the ischemic and acidic tumor microenvironment, immune system evasion, and maintenance of the cancer stem cell state. As these aspects of cancer cell metabolism are critical for tumor maintenance yet are less likely to be relevant in normal cells, they represent attractive targets for cancer therapy.

• Molecules and Cells
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• v.45 no.11
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• pp.781-788
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• 2022

Proline plays a multifaceted role in protein synthesis, redox balance, cell fate regulation, brain development, and other cellular and physiological processes. Here, we focus our review on proline metabolism in neurons, highlighting the role of dysregulated proline metabolism in neuronal dysfunction and consequently neurological and psychiatric disorders. We will discuss the association between genetic and protein function of enzymes in the proline pathway and the development of neurological and psychiatric disorders. We will conclude with a potential mechanism of proline metabolism in neuronal function and mental health.

• Biomolecules & Therapeutics
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• v.26 no.1
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• pp.4-9
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• 2018

Cancer metabolism as a field of research was founded almost 100 years ago by Otto Warburg, who described the propensity for cancers to convert glucose to lactate despite the presence of oxygen, which in yeast diminishes glycolytic metabolism known as the Pasteur effect. In the past 20 years, the resurgence of interest in cancer metabolism provided significant insights into processes involved in maintenance metabolism of non-proliferating cells and proliferative metabolism, which is regulated by proto-oncogenes and tumor suppressors in normal proliferating cells. In cancer cells, depending on the driving oncogenic event, metabolism is re-wired for nutrient import, redox homeostasis, protein quality control, and biosynthesis to support cell growth and division. In general, resting cells rely on oxidative metabolism, while proliferating cells rewire metabolism toward glycolysis, which favors many biosynthetic pathways for proliferation. Oncogenes such as MYC, BRAF, KRAS, and PI3K have been documented to rewire metabolism in favor of proliferation. These cell intrinsic mechanisms, however, are insufficient to drive tumorigenesis because immune surveillance continuously seeks to destroy neo-antigenic tumor cells. In this regard, evasion of cancer cells from immunity involves checkpoints that blunt cytotoxic T cells, which are also attenuated by the metabolic tumor microenvironment, which is rich in immuno-modulating metabolites such as lactate, 2-hydroxyglutarate, kynurenine, and the proton (low pH). As such, a full understanding of tumor metabolism requires an appreciation of the convergence of cancer cell intrinsic metabolism and that of the tumor microenvironment including stromal and immune cells.

• BMB Reports
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• v.45 no.1
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• pp.51-56
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• 2012

The purpose of this study was to determine the effects of duration and timing of glucocorticoid treatment on the expansion and differentiation of porcine neonatal pancreas cell clusters (NPCCs) into ${\beta}$-cells. After transplantation of NPCCs, the ductal cyst area and ${\beta}$-cell mass in the grafts both showed positive and negative correlations with duration of dexamethasone (Dx) treatment. Pdx-1 and HNF-3${\beta}$ gene expression was significantly downregulated following Dx treatment, whereas PGC-1${\alpha}$ expression increased. Pancreatic duct cell apoptosis significantly increased following Dx treatment, whereas proliferation did not change. Altogether, transdifferentiation of porcine NPCCs into ${\beta}$-cells was influenced by the duration of Dx treatment, which might have been due to the suppression of key pancreatic transcription factors. PGC-1${\alpha}$ plays an important role in the expansion and transdifferentiation of porcine NPCCs, and the initial 2 weeks following transplantation of porcine NPCCs is a critical period in determining the final ${\beta}$-cell mass in grafts.

• Toxicological Research
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• v.32 no.3
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• pp.177-193
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• 2016

After more than half of century since the Warburg effect was described, this atypical metabolism has been standing true for almost every type of cancer, exhibiting higher glycolysis and lactate metabolism and defective mitochondrial ATP production. This phenomenon had attracted many scientists to the problem of elucidating the mechanism of, and reason for, this effect. Several models based on oncogenic studies have been proposed, such as the accumulation of mitochondrial gene mutations, the switch from oxidative phosphorylation respiration to glycolysis, the enhancement of lactate metabolism, and the alteration of glycolytic genes. Whether the Warburg phenomenon is the consequence of genetic dysregulation in cancer or the cause of cancer remains unknown. Moreover, the exact reasons and physiological values of this peculiar metabolism in cancer remain unclear. Although there are some pharmacological compounds, such as 2-deoxy-D-glucose, dichloroacetic acid, and 3-bromopyruvate, therapeutic strategies, including diet, have been developed based on targeting the Warburg effect. In this review, we will revisit the Warburg effect to determine how much scientists currently understand about this phenomenon and how we can treat the cancer based on targeting metabolism.

• BMB Reports
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• v.44 no.11
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• pp.713-718
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• 2011

In this study, the effects of sitagliptin analogue (SITA) or pioglitazone (PIO) treatment on glucose homeostasis and ${\beta}$-cell dynamics in animal models of type 2 diabetes-Akita and db/db mice were evaluated. After 4-6 weeks of treatment, both SITA and PIO were shown to lower non-fasting glucose levels and reduced glycemic excursion in the intraperitoneal glucose tolerance test. In addition, both drugs preserved normal islet structure and the proportion of ${\beta}$-cells in the islets. Compared to the controls, SITA treatment induced a higher ${\beta}$-cell proliferation rate in Akita mice and a lower rate of apoptosis in db/db mice, whereas PIO treatment induced a lower rate of apoptosis in db/db mice and reduced proliferation rates in Akita mice. In conclusion, both SITA and PIO appear to exert some beneficial effects on the islet structure in addition to glycemic control via different mechanisms that involve ${\beta}$-cell dynamics in Akita and db/db mice.

• Journal of Korean Traditional Oncology
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• v.20 no.1
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• pp.81-88
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• 2015

Generally, normal cells synthesize adenosine triphosphate (ATP) through oxidative phosphorylation in the mitochondria. However, they produce ATP through lactic acid fermentation on hypoxic condition. Interestingly, many cancer cells rely on aerobic glycolysis for ATP generation instead of mitochondrial oxidative phosphorylation, which is termed as "Warburg effect". According to results from recent researches on differences of cancer cell metabolism from normal cell metabolism and because chemotherapy to suppress rapidly growing cells, as a side effect of cancer treatment, can still target healthy cells, there is merit in the development of small-molecule inhibitors targeting metabolic enzymes such as pyruvate dehydrogenase kinase (PDHK), lactate dehydrogenase (LDH) and monocarboxylate transporter (MCT). For new anticancer therapy, in this review, we show recent advances in study on cancer cell metabolism and molecules targeting metabolic enzymes which are importantly associated with cancer metabolism for cancer therapy. Furthermore, we would also like to emphasize the necessity of development of molecules targeting metabolic enzymes using herbal medicines and their constituents for anticancer drugs.

• BMB Reports
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• v.51 no.7
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• pp.319-326
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• 2018

Increasing evidence suggests that cancer stem cell (CSC) theory represents an important mechanism underlying the observed failure of existing therapeutic modalities to fully eradicate cancers. In addition to their more established role in maintaining minimal residual disease after treatment and forming the new bulk of the tumor, CSCs might also critically contribute to tumor recurrence and metastasis. For this reason, specific elimination of CSCs may thus represent one of the most important treatment strategies. Emerging evidence has shown that CSCs have a different metabolic phenotype to that of differentiated bulk tumor cells, and these specific metabolic activities directly participate in the process of CSC transformation or support the biological processes that enable tumor progression. Exploring the role of CSC metabolism and the mechanism of the metabolic plasticity of CSCs has become a major focus in current cancer research. The targeting of CSC metabolism may provide new effective therapies to reduce the risk of recurrence and metastasis. In this review, we summarize the most significant discoveries regarding the metabolism of CSCs and highlight recent approaches in targeting CSC metabolism.

• Microbiology and Biotechnology Letters
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• v.50 no.4
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• pp.477-487
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• 2022

Probiotics provide a symbiotic relationship and beneficial effects by balancing the human intestinal microbiota. The relationships between microbiota changes and various diseases may predict health abnormalities and diseases. Treatment with vitamins and probiotics is one therapeutic approach. To evaluate the effect of probiotics on vitamin absorption, we chose Lactobacillus rhamnosus CBT-LR5 treatment, which has resistance to vitamin C-inducible toxicity, with vitamins in high-fat diet (HFD)-induced obesity models. CBT-LR5 affected the absorption of micronutrients, such as ionic minerals and water-soluble vitamins. An increase in vitamin C absorption by CBT-LR5 enhanced the antioxidant response in HFD-induced obesity models. Increased vitamin B absorption by CBT-LR5 regulated lipid metabolism in HFD-induced obesity models. These favorable effects of CBT-LR5 on the absorption of vitamins should be investigated as candidate therapeutic target treatments for metabolic diseases.

• Journal of Nutrition and Health
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• v.31 no.1
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• pp.5-12
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• 1998

This study was designed to examine how dietary protein levels affect organ growth and protein metabolism in early and normally weaned rats. Early and normally weaned rats separated fro the dam on the 15th and 121st day postpartum, respectively. were fed diets containing three levels of protein : low(10%) , normal (20%),and high(40%) . On the 35th day, the weight and DNA, RNA and protein contents in brain , liver, and kidney were determined to ascertain organ and cellular growth. Furthermore, serum total protein , albumin , $\alpha$-amino N and creatine and urinary urea N, and creatinine were determined in order to ascertain protein metabolism and renal functions. Dietary protein levels were not observed to significantly affect total DNA content, which may represent an index of cell number in the liver, brain and kidney. Fresh weight and protein/DNA ratio, which may represent indices of cell size, significantly increased in proportion to dietary protein in the kidney. As for the early weaned rats , the liver cell size significantly decreased. Dietary protein levels and weaning periods did not affect serum total protein and albumin . However, serum urea-N significantly increased in proportion to dietary protein levels whereas serum $\alpha$-amino N was decreased by early weaning . Nitrogen retention was lower in early weaned rats fed low or high levels of protein than in normally weaned rats. The results demonstrate that low or high levels of dietary protein have less desirable effects on protein metabolism in prematurely weaned rats.