• BMB Reports
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• v.52 no.1
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• pp.5-12
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• 2019

Organismal aging is accompanied by a host of progressive metabolic alterations and an accumulation of senescent cells, along with functional decline and the appearance of multiple diseases. This implies that the metabolic features of cell senescence may contribute to the organism's metabolic changes and be closely linked to age-associated diseases, especially metabolic syndromes. However, there is no clear understanding of senescent metabolic characteristics. Here, we review key metabolic features and regulators of cellular senescence, focusing on mitochondrial dysfunction and anabolic deregulation, and their link to other senescence phenotypes and aging. We further discuss the mechanistic involvement of the metabolic regulators mTOR, AMPK, and GSK3, proposing them as key metabolic switches for modulating senescence.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.13 no.1
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• pp.43-47
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• 2013

Introduction: ALT/AST enzymes are present inside the cells. AST is found in cardiac and skeletal muscle and red blood cells but the ALT is checked mainly in the liver. In general, the rise of these two indicators shows liver damage. The usual measurements of these enzymes are used in liver function tests, but the levels of AST and ALT do not always reflect liver function. Method and Cases: 17 cases of liver dysfunction transiently were evaluated clinically, biochemically, and imaging study of sonogram in pediatric in-patients for 3 years. Result: Most common causes of transient liver dysfunction were infection, especially viral gastroenteritis, and bacterial infection interfering oral food intake. More often occurred in the children who have infant hyperbilirubinemia, positive history of mitochondrial dysfunction or hypoglycemia. Fasting study in one case of hypoglycemia patient showed reversible liver dysfunction during fasting over 20 hours fasting. Discussion: A significant increase in AST and ALT with normal bilirubin can be observed in clinically healthy people during blunt trauma, viral infection, severe pain, metabolic syndrome, fasting or accidental health screening.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.22
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• pp.10027-10031
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• 2014

Background: We investigated the risk of cancer mortality according to obesity status and metabolic health status using sampled cohort data from the National Health Insurance system. Materials and Methods: Data on body mass index and fasting blood glucose in the sampled cohort database (n=363,881) were used to estimate risk of cancer mortality. Data were analyzed using a Cox proportional hazard model (Model 1 was adjusted for age, sex, systolic blood pressure, diastolic blood pressure, total cholesterol level and urinary protein; Model 2 was adjusted for Model 1 plus smoking status, alcohol intake and physical activity). Results: According to the obesity status, the mean hazard ratios were 0.82 [95% confidence interval (CI), 0.75-0.89] and 0.79 (95% CI, 0.72-0.85) for the overweight and obese groups, respectively, compared with the normal weight group. According to the metabolic health status, the mean hazard ratio was 1.26 (95% CI, 1.14-1.40) for the metabolically unhealthy group compared with the metabolically healthy group. The interaction between obesity status and metabolic health status on the risk of cancer mortality was not statistically significant (p=0.31). Conclusions: We found that the risk of cancer mortality decreased according to the obesity status and increased according to the metabolic health status. Given the rise in the rate of metabolic dysfunction, the mortality from cancer is also likely to rise. Treatment strategies targeting metabolic dysfunction may lead to reductions in the risk of death from cancer.

• Journal of The Korean Society of Inherited Metabolic disease
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• v.22 no.2
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• pp.46-52
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• 2022

Inborn errors of metabolism (IEM) are very rare and genetically transmitted diseases and have man y different symptoms related with multisystemic involvement. More rarely, endocrinopathies can be an early and first symptom of IEM, but presents with signs of later complications in adolescent or adulthood. The mechanisms of endocrine dysfunction in IEM are poorly understood. Hypogonadotropic hypogonadism is common in hemochromatosis, adrenoleukodystrophy, galactosemia, and glycogen storage disease. Many girls with classic galactosemia are at high risk for premature ovarian insufficiency (POI), despite an early diagnosis and good control. Mitochondrial diseases are multisystem disorders and are characterized by hypo- and hypergonadotrophic hypogonadism, thyroid dysfunction and insulin dysregulation. Glycogen storage disorders (GSDs), especially type Ia, Ib, III, V are assocciated with frequent hypoglycemic events. IEM is a growing field and is not yet well recognized despite its consequences for growth, bone metabolism and fertility. For this reason, clinicians should be aware of these diagnoses and potential endocrine dysfunction.

• Korean Journal of Clinical Laboratory Science
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• v.53 no.4
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• pp.285-295
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• 2021

Sleep plays an important role in maintaining overall human health. There is increasing interest regarding the impact of sleep related disorders on metabolic diseases. Obstructive sleep apnea (OSA) is a common health problem, and in the last decade, the emergence of increasing obesity rates has further led to a remarkable increase in the prevalence of OSA, along with more prominent metabolic diseases. Obesity is the strongest risk factor for OSA. However, OSA is also known to cause obesity, suggesting an interaction between OSA and obesity. Although the underlying mechanisms leading to OSA-induced metabolic diseases are probably multi-factorial and are yet to be fully elucidated, the activation of inflammation and oxidative stress and the dysregulation of appetite-regulating hormones have emerged as important pathophysiological components of metabolic dysfunction and obesity observed in patients with OSA. Here, we will review the current state of research regarding the association of OSA with metabolic diseases and the possible pathophysiological mechanisms by which OSA could lead to such diseases. This will enhance our understanding of the potential interactions between OSA and obesity and between OSA and metabolic dysfunction.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.1
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• pp.1-13
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• 2016

The evidence for the existence of a common pathway for health issues in men is presented in this review. Several epidemiological studies have shown that conditions like cardiovascular diseases (CVD), metabolic syndrome, diabetes, lower urinary tract symptom (LUTS), erectile dysfunction (ED), prostate cancer, hypogonadism, depression and suicide can be associated as risk factors for each other. Thus, the risk of CVD is significantly increased in men with metabolic syndrome, ED, hypogonadism, prostate cancer and/or LUTS. In addition, the above mentioned conditions are more prevalent in atherosclerotic patients. In addition, growing evidence indicates that low androgen levels can cause metabolic syndrome. In addition, obesity, dyslipidaemia and diabetes can further reduce androgen levels potentiating their adverse effect. Low testosterone levels are also associated with a higher incidence of aggressive prostate cancer on biopsy and on definitive pathology, and lower probability of abiraterone response in the metastatic setting. Several recent studies point towards diffuse endothelial dysfunction and dysregulated pro-inflammatory state as the biological link between all these disorders. Our current hypothesis is that oxidative stress caused by these dysfunctions explains the pathogenesis of each of these conditions.

• Molecules and Cells
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• v.47 no.2
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• pp.100010.1-100010.12
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• 2024

Recently, the incidence of metabolic dysfunction-associated steatotic liver disease (MASLD) is increasing due to the high prevalence of metabolic conditions, such as obesity and type 2 diabetes mellitus. Steatotic liver is a hotspot for cancer metastasis in MASLD. Altered lipid metabolism, a hallmark of MASLD, remodels the tissue microenvironment, making it conducive to the growth of metastatic liver cancer. Tumors exacerbate the dysregulation of hepatic metabolism by releasing extracellular vesicles and particles into the liver. Altered lipid metabolism influences the proliferation, differentiation, and functions of immune cells, contributing to the formation of an immunosuppressive and metastasis-prone liver microenvironment in MASLD. This review discusses the mechanisms by which the steatotic liver promotes liver metastasis progression, focusing on its role in fostering an immunosuppressive microenvironment in MASLD. Furthermore, this review highlights lipid metabolism manipulation strategies for the therapeutic management of metastatic liver cancer.

• Journal of Yeungnam Medical Science
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• v.41 no.2
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• pp.61-73
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• 2024

Acute kidney ischemia-reperfusion (IR) injury is a life-threatening condition that predisposes individuals to chronic kidney disease. Since the kidney is one of the most energy-demanding organs in the human body and mitochondria are the powerhouse of cells, mitochondrial dysfunction plays a central role in the pathogenesis of IR-induced acute kidney injury. Mitochondrial dysfunction causes a reduction in adenosine triphosphate production, loss of mitochondrial dynamics (represented by persistent fragmentation), and impaired mitophagy. Furthermore, the pathological accumulation of succinate resulting from fumarate reduction under oxygen deprivation (ischemia) in the reverse flux of the Krebs cycle can eventually lead to a burst of reactive oxygen species driven by reverse electron transfer during the reperfusion phase. Accumulating evidence indicates that improving mitochondrial function, biogenesis, and dynamics, and normalizing metabolic reprogramming within the mitochondria have the potential to preserve kidney function during IR injury and prevent progression to chronic kidney disease. In this review, we summarize recent advances in understanding the detrimental role of metabolic reprogramming and mitochondrial dysfunction in IR injury and explore potential therapeutic strategies for treating kidney IR injury.

• Molecules and Cells
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• v.37 no.3
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• pp.234-240
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• 2014

Cisplatin is one of the most potent chemotherapy agents. However, its use is limited due to its toxicity in normal tissues, including the kidney and ear. In particular, nephrotoxicity induced by cisplatin is closely associated with oxidative stress and inflammation. Heme oxygenase-1(HO-1), the rate-limiting enzyme in the heme metabolism, has been implicated in a various cellular processes, such as inflammatory injury and anti-oxidant/oxidant homeostasis. Capsaicin is reported to have therapeutic potential in cisplatin-induced renal failures. However, the mechanisms underlying its protective effects on cisplatin-induced nephrotoxicity remain largely unknown. Herein, we demonstrated that administration of capsaicin ameliorates cisplatin-induced renal dysfunction by assessing the levels of serum creatinine and blood urea nitrogen (BUN) as well as tissue histology. In addition, capsaicin treatment attenuates the expression of inflammatory mediators and oxidative stress markers for renal damage. We also found that capsaicin induces HO-1 expression in kidney tissues and HK-2 cells. Notably, the protective effects of capsaicin were completely abrogated by treatment with either the HO inhibitor ZnPP IX or HO-1 knockdown in HK-2 cells. These results suggest that capsaicin has protective effects against cisplatin-induced renal dysfunction through induction of HO-1 as well as inhibition oxidative stress and inflammation.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.567-577
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• 2017

Obesity is known to induce inhibition of glucose uptake, reduction of lipid metabolism, and progressive loss of skeletal muscle function, which are all associated with mitochondrial dysfunction in skeletal muscle. Mitochondria are dynamic organelles that regulate cellular metabolism and bioenergetics, including ATP production via oxidative phosphorylation. Due to these critical roles of mitochondria, mitochondrial dysfunction results in various diseases such as obesity and type 2 diabetes. Obesity is associated with impairment of mitochondrial function (e.g., decrease in $O_2$ respiration and increase in oxidative stress) in skeletal muscle. The balance between mitochondrial fusion and fission is critical to maintain mitochondrial homeostasis in skeletal muscle. Obesity impairs mitochondrial dynamics, leading to an unbalance between fusion and fission by favorably shifting fission or reducing fusion proteins. Mitophagy is the catabolic process of damaged or unnecessary mitochondria. Obesity reduces mitochondrial biogenesis in skeletal muscle and increases accumulation of dysfunctional cellular organelles, suggesting that mitophagy does not work properly in obesity. Mitochondrial dysfunction and oxidative stress are reported to trigger apoptosis, and mitochondrial apoptosis is induced by obesity in skeletal muscle. It is well known that exercise is the most effective intervention to protect against obesity. Although the cellular and molecular mechanisms by which exercise protects against obesity-induced mitochondrial dysfunction in skeletal muscle are not clearly elucidated, exercise training attenuates mitochondrial dysfunction, allows mitochondria to maintain the balance between mitochondrial dynamics and mitophagy, and reduces apoptotic signaling in obese skeletal muscle.