• Clinical and Experimental Reproductive Medicine
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• v.48 no.4
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• pp.374-379
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• 2021

Objective: We aimed to evaluate associations between the ratio of serum estrone (E1) to estradiol (E2) and parameters related to serum glucose metabolism and insulin resistance in women with polycystic ovary syndrome (PCOS). Methods: In total, 133 women between the ages of 18 and 35 diagnosed with PCOS were enrolled in this study. All participants with PCOS underwent blood tests to determine hormonal and biochemical metabolic parameters and a standard 2-hour 75-g oral glucose tolerance test. They were divided into two groups according to the serum E1-to-E2 ratio: group 1 (E1/E2 ratio <2.0) and group 2 (E1/E2 ratio ≥2.0). Results: In the comparative analysis, the waist-to-hip ratio (WHR) was the only clinical variable that was significantly different between the two groups. Patients with a higher E1/E2 ratio showed higher fasting insulin levels, homeostasis model for insulin resistance, and postprandial glucose level at 2 hours (PPG2). In a correlation analysis, only PPG2 was significantly related to the serum E1/E2 ratio. However, after controlling for the confounding effects of body mass index (BMI) and WHR, fasting glucose was also significantly correlated with the serum E1/E2 ratio. Conclusion: Women with PCOS with a higher serum E1/E2 ratio were found to be more likely to show higher fasting insulin and postprandial glucose levels. Significant correlations were found between the serum E1/E2 ratio and both fasting and postprandial serum glucose levels after adjusting for BMI and WHR in women with PCOS.

• Korean Journal of Acupuncture
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• v.35 no.4
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• pp.187-202
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• 2018

Objectives : Non-invasive transcranial electrical stimulation is one of therapeutic interventions to change in neural excitability of the cortex. Transcranial electro-acupuncture (TEA) can modulate brain functions through changes in cortical excitability as a model of non-invasive transcranial electrical stimulation. Some composites of fermented Scutellaria baicalenis (FSB) can activate intercellular signaling pathways for activation of brain-derived neurotrophic factor that is critical for formation of neural plasticity in stroke patients. This study was aimed at evaluation of combinatory treatment of TEA and FSB on behavior recovery and cortical neural excitability in rodent focal stroke model. Methods : Focal ischemic stroke was induced by photothrombotic injury to the motor cortex of adult rats. Application of TEA with 20 Hz and $200{\mu}A$ in combination with daily oral treatment of FBS was given to stroke animals for 3 weeks. Motor recovery was evaluated by rotating bean test and ladder working test. Electrical activity of cortical pyramidal neurons of stroke model was evaluated by using multi-channel extracellular recording technique and thallium autometallography. Results : Compared with control stroke group who did not receive any treatment, Combination of TEA and FSB treatment resulted in more rapid recovery of forelimb movement following focal stroke. This combination treatment also elicited increase in spontaneous firing rate of putative pyramidal neurons. Furthermore expression of metabolic marker for neural excitability was upregulated in peri-infract area under thallium autometallography. Conclusions : These results suggest that combination treatment of TEA and FSB can be a possible remedy for motor recovery in focal stroke.

• Molecules and Cells
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• v.42 no.8
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• pp.604-616
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• 2019

Phosphoserine phosphatase (PSPH) is one of the key enzymes of the L-serine synthesis pathway. PSPH is reported to affect the progression and survival of several cancers in an L-serine synthesis-independent manner, but the mechanism remains elusive. We demonstrate that PSPH promotes lung cancer progression through a noncanonical L-serine-independent pathway. PSPH was significantly associated with the prognosis of lung cancer patients and regulated the invasion and colony formation of lung cancer cells. Interestingly, L-serine had no effect on the altered invasion and colony formation by PSPH. Upon measuring the phosphatase activity of PSPH on a serine-phosphorylated peptide, we found that PSPH dephosphorylated phospho-serine in peptide sequences. To identify the target proteins of PSPH, we analyzed the protein phosphorylation profile and the PSPH-interacting protein profile using proteomic analyses and found one putative target protein, IRS-1. Immunoprecipitation and immunoblot assays validated a specific interaction between PSPH and IRS-1 and the dephosphorylation of phospho-IRS-1 by PSPH in lung cancer cells. We suggest that the specific interaction and dephosphorylation activity of PSPH have novel therapeutic potential for lung cancer treatment, while the metabolic activity of PSPH, as a therapeutic target, is controversial.

• Investigative Magnetic Resonance Imaging
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• v.23 no.2
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• pp.100-113
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• 2019

Sarcoidosis is a multisystem disease characterized by noncaseating granulomas. Cardiac involvement is known to have poor prognosis because it can manifest as a serious condition such as the conduction abnormality, heart failure, ventricular arrhythmia, or sudden cardiac death. Although early diagnosis and early treatment is critical to improve patient prognosis, the diagnosis of CS is challenging in most cases. Diagnosis usually relies on endomyocardial biopsy (EMB), but its diagnostic yield is low due to the incidence of patchy myocardial involvement. Guidelines for the diagnosis of CS recommend a combination of clinical, electrocardiographic, and imaging findings from various modalities, if EMB cannot confirm the diagnosis. Especially, the role of advanced imaging such as cardiac magnetic resonance (CMR) imaging and positron emission tomography (PET), has shown to be important not only for the diagnosis, but also for monitoring treatment response and prognostication. CMR can evaluate cardiac function and fibrotic scar with good specificity. Late gadolinium enhancement (LGE) in CMR shows a distinctive enhancement pattern for each disease, which may be useful for differential diagnosis of CS from other similar diseases. Effectively, T1 or T2 mapping techniques can be also used for early recognition of CS. In the meantime, PET can detect and quantify metabolic activity and can be used to monitor treatment response. Recently, the use of a hybrid CMR-PET has introduced to allow identify patients with active CS with excellent co-localization and better diagnostic accuracy than CMR or PET alone. However, CS may show various findings with a wide spectrum, therefore, radiologists should consider the possible differential diagnosis of CS including myocarditis, dilated cardiomyopathy (DCM), hypertrophic cardiomyopathy, amyloidosis, and arrhythmogenic right ventricular cardiomyopathy. Radiologists should recognize the differences in various diseases that show the characteristics of mimicking CS, and try to get an accurate diagnosis of CS.

• Toxicological Research
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• v.35 no.4
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• pp.395-402
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• 2019

Subcutaneous adipose tissue (SAT) accumulation is a constitutional disorder resulting from metabolic syndrome. Although surgical and non-surgical methods for reducing SAT exist, patients remain non-compliant because of potential adverse effects and cost. In this study, we developed a new minimally-invasive approach to achieve SAT reduction, using a microneedle (MN) patch prepared from gelatin, which is capable of regulating fat metabolism. Four gelatin types were used: three derived from fish (SA-FG, GT-FG 220, and GT-FG 250), and one from swine (SM-PG 280). We applied gelatin-based MN patches five times over 4 weeks to rats with high-fat diet (HD)-induced obesity, and determined the resulting amount of SAT. We also investigated the histological features and determined the expression levels of fat metabolism-associated genes in SAT using hematoxylin and eosin staining and western blotting, respectively. SAT decreased following treatment with all four gelatin MN patches. Smaller adipocytes were observed in the regions treated with SA-FG, GT-FG 250, and SM-PG 280 MNs, demonstrating a decline in fat accumulation. The expression levels of fat metabolism-associated genes in the MN-treated SAT revealed that GT-FG 220 regulates fatty acid synthase (FASN) protein levels. These findings suggest that gelatin MN patches aid in decreasing the quantity of unwanted SAT by altering lipid metabolism and fat deposition.

• Archives of Obesity and Metabolism
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• v.1 no.2
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• pp.78-82
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• 2022

Liraglutide (Saxenda^R) is prescribed to induce and sustain weight loss in obese patients. The starting dose of liraglutide is 0.6 mg/day for 1 week, which is increased by 0.6 mg/day every week until the full maintenance dose of 3 mg/day is achieved. Such dose titration is needed to prevent side effects, which primarily include gastrointestinal problems such as nausea, diarrhea, constipation, vomiting, dyspepsia, and abdominal pain. A 35-year-old, reportedly healthy obese man receiving liraglutide treatment for obesity visited the emergency room complaining of generalized weakness and dizziness accompanied by repeated diarrhea and vomiting. He reported over 20 episodes of diarrhea starting the day after liraglutide dose escalation from 1.2 mg/day to 1.8 mg/day. Laboratory findings suggested pre-renal acute kidney injury, including serum creatinine 4.77 mg/dl, blood urea nitrogen (BUN) 37 mg/dl, estimated glomerular filtration rate (eGFR) 15 ml/min/1.73 m², and Fractional excretion of sodium 0.08. After volume repletion therapy, his renal function recovered to a normal range with laboratory values of creatinine 1.08 mg/dl, BUN 14 mg/dl, and eGFR 88 ml/min/1.73 m². This case emphasizes the need for caution when prescribing glucagon-like peptide-1 receptor agonists, including liraglutide, given the risk of serious renal impairments induced by volume depletion and dehydration through severe-grade diarrhea and vomiting.

• Archives of Obesity and Metabolism
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• v.1 no.1
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• pp.14-25
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• 2022

In 1971, Dr. Akira Endo succeeded in isolating a cholesterol synthesis inhibitor, compactin. Later, compactin was renamed mevastatin, meaning that it stops the synthesis of mevalonate, which is considered the first statin. However, mevastatin is not commercially released, whereas lovastatin, developed by Alfred Albert of Merk in 1979, was the first commercially developed statin. After the 4S study, the first largescale clinical trial with statins conducted in Scandinavia showed a dramatic secondary preventive effect against cardiovascular disease, and the effectiveness of statins in patients with dyslipidemia was repeatedly demonstrated. Subsequently, many oral drugs that affect blood lipid concentration; statins and ezetimibe aimed at reducing low-density lipoprotein (LDL)) cholesterol; fibrates and omega 3 formulations aimed at reducing triglycerides were widely developed and used in Korea. In this article, we review the results of clinical studies on representative cardiovascular diseases for four types of oral drugs for dyslipidemia, which are currently the most commonly used in Korea.

• The Journal of Internal Korean Medicine
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• v.43 no.4
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• pp.751-760
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• 2022

Objective: To show a decrease in tumor recurrence and improvement in quality of life in patients with recurrent cervical cancer. Method: A 58-year-old female patient diagnosed with recurrent cervical cancer in February 2021 was treated for 14 months with integrative cancer treatment (ICT) to decrease the tumor size and improve chemotherapy-induced peripheral neuropathy (CIPN) and nausea. The patient underwent chemotherapy or concomitant chemoradiation therapy (CCRT) with ICT. Radiologic outcomes were assessed by abdomen & pelvis computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography-computed tomography (PET-CT) based on the Response Evaluation Criteria in Solid Tumors (RECIST) protocol. Clinical outcomes were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Event (NCI-CTCAE), Eastern Cooperative Oncology Group (ECOG), and a numeric rating scale (NRS). Result: During the 14 months of treatment, the size and metabolic activity of the recurrent tumor decreased and underwent partial remission based on RECIST. The NRS scores for CIPN and nausea were improved, and the ECOG score improved from grade 2 to 1. No serious side effects of grade 3 or higher were noted on the NCI-CTCAE test. Conclusion: This case suggests that ICT may have a synergetic effect with chemotherapy or radiotherapy for recurrent cervical cancer.

• Journal of Genetic Medicine
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• v.19 no.2
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• pp.94-99
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• 2022

Lesch-Nyhan disease (LND) is a rare X-linked recessive inherited purine metabolic disorder that accompanies neurodevelopmental problems. Neurofibromatosis type 1 (NF1) is a relatively common autosomal dominant inherited genetic disorder characterized by tumors in various systems. Some children with NF1 also accompanies neurodevelopmental problems. Here, we describe a 5-year-old boy with a maternally inherited pathogenic variant in NF1 and hypoxanthine-guanine phosphoribosyltransferase (HPRT). He was referred for severe neurodevelopmental impairment and hyperuricemia. His mother was diagnosed with NF1 and the patient was also suspected of having NF1 because of cafe au lait macules. He had dystonia, rigidity, cognitive deficit, and speech/language impairment. Serum and urine uric acid concentrations were elevated. He had more severe neurodevelopmental delay than patients with only NF1, so his clinical symptoms could not be fully understood by the disease alone. To find the cause of his neurologic symptoms and hyperuricemia, the patient and his mother underwent a whole-exome sequencing test. As a result, the pathogenic variant c.151C>T (p.Arg51Ter) in HPRT1 was identified as hemizygote in the patient and heterozygote in his mother. The pathogenic variant c.7682C>G (p.Ser2561Ter) in NF-1 was identified as heterozygotes in both of them. Although the clinical symptoms of both diseases were overlapping and complicated, genetic testing was helpful for accurate diagnosis and treatment. Therefore, we suggest to consider preemptive genetic evaluation if there are symptoms not sufficiently explained by known existing diseases. And it is considered valuable to review this rare case to understand the clinical course and possible synergic effects of these diseases.

• Journal of Applied Biological Chemistry
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• v.65 no.4
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• pp.387-396
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• 2022

Skeletal muscle accounts for about 40-50% of body weight and is an important tissue that performs various functions, such as maintaining posture, supporting soft tissues, maintaining body temperature, and respiration. Cancer, which occurs widely around the world, causes cancer cachexia accompanied by muscular atrophy, which reduces the effectiveness of anticancer drugs and greatly reduces the quality of life and survival rate of cancer patients. Therefore, research to improve cancer cachexia is ongoing. However, there are few studies on the link between cancer and muscle atrophy. Cancer cells exhibit distinct microenvironment and metabolism from tumor cells, including tumor-associated macrophages (TAM), tumor-associated neutrophils (TAN), and insulin resistance due to the Warburg effect. Therefore, we summarize the microenvironment and metabolic characteristics of cancer cells, and the molecular mechanisms of muscle atrophy that can be affected by cytokine and insulin resistance. In addition, this suggests the possibility of improving cancer cachexia of substances affecting TAM, TAN, and Warburg effect. We also summarize the mechanisms identified so far through single agents and the signaling pathways mediated by them that may ameliorate cancer cachexia.