• Asian Pacific Journal of Cancer Prevention
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• v.14 no.10
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• pp.5687-5692
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• 2013

Type 2 diabetes mellitus (T2DM) has contributed to advanced breast cancer development over the past decades. However, the mechanism underlying this contribution is poorly understood. In this study, we determined that high glucose enhanced proteasome activity was accompanied by enhanced proliferation, migration and invasion, as well as suppressed apoptosis, in human breast cancer MCF-7 cells. Proteasome inhibitor bortezomib (BZM) pretreatment mitigated high glucose-induced MCF-7 cell growth and invasion. Furthermore, high glucose increased protein kinase C delta ($PKC{\delta}$)-phosphorylation. Administration of the specific $PKC{\delta}$ inhibitor rottlerin attenuated high glucose-stimulated cancer cell growth and invasion. In addition, $PKC{\delta}$ inhibition by both rottlerin and $PKC{\delta}$ shRNA significantly suppressed high glucose-induced proteasome activity. Our results suggest that $PKC{\delta}$-dependent ubiquitin proteasome system activation plays an important role in high glucose-induced breast cancer cell growth and metastasis.

• Journal of Physiology & Pathology in Korean Medicine
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• v.23 no.6
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• pp.1305-1313
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• 2009

Saengjihwangeum-ja (SJHEJ) was recorded in DongEuiBoGam as being able to be used for treatment of Sogal whose concept had been applied to Diabetes Mellitus (DM). Modification of proteins by long term circulation of glucose leads to the formation of advanced glycation end product(AGE). Recent immunological studies demonstrated that ligation of AGE play an important role in the development of diabetic complications including atherosclerosis, which includes activation, adhesion, and migration of monocytes. Also, AGE and Maillard reaction product(MRP) could augment monocyte inflammatory responses via ligation of AGE receptor. In this study, the effects of SJHEJ extracts on the expression of inflammatory response-related genes such as tumor necrosis factor-$\alpha$, monocyte chemoattractant protein-1, interferon-g-inducible protein-10, and cyclooxygenase-2 in the human monocyte cell line, THP-1 cells. Reverse transcriptase-polymerase chain reaction revealed that SJHEJ had inhibitory effects on the expression of the TNF-a, MCP-1, IP-10, COX2, IL-1b genes in MRP-induced THP-1 cells. Treatment with SJHEJ had reduced reactive oxygen production in THP-1 cells stimulated by MRP. These inhibitory effects might be exerted via prevention of oxidative stress in activated monocytes. In addition, radical scavenging activity of SJHEJ was increased. These results suggest that SJHEJ has a beneficial effects for improve diabetic vascular complication.

• Journal of Interdisciplinary Genomics
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• v.4 no.2
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• pp.35-38
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• 2022

Background: Prader-Willi syndrome (PWS) is a complex genetic disease associated with growth impairment, severe obesity and metabolic dysfunctions. High proportion of PWS patients are born small for gestational age (SGA) than normal children, which also increase the risk of growth impairment and metabolic dysfunction in PWS. We aimed to compare growth outcome and metabolic profiles between SGA and appropriate for gestational age (AGA) PWS patients. Methods: Data of 55 PWS children and adults aged more than 2 years old (32 male and 23 female, age 2-18.8 years) from single center were studied. Only patients who were treated with GH were included. The clinical characteristics and laboratory findings were reviewed retrospectively. Results: Among 55 subjects, 39 had 15q11-13 deletion and 16 had uniparental disomy (UPD). Twenty (36.3%) were born SGA. All patients received GH treatment, and 11 (20%) discontinued GH treatment. Mean age at GH treatment initiation was 2.5 (range 0.3-12.4) years, and mean duration of treatment was 6.3 (range 1.0-11.3) years. Current height-SDS (-0.36 vs -0.16) and BMI-SDS (1.44 vs 1.33) did not differ between AGA and SGA group. Two patients in SGA group, but none in AGA group had diabetes mellitus. Mean glucose level was also higher in SGA group (100.1 vs 114.4 mg/dL). Conclusion: Our report gives an overview of growth profile and metabolic dysfunctions recorded in GH treated PWS patients. Growth profile did not differ between AGA and SGA group. Glucose level was higher in SGA group, so more careful monitoring and prevention for DM will be required in SGA group.

• Journal of Life Science
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• v.30 no.3
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• pp.250-259
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• 2020

Diabetes is a well-known risk factor for dementia and cognitive impairment. Diabetic polyneuropathy (DPN) is the most prevalent microvascular complication in type 2 diabetes mellitus (T2DM) patients. The purpose of this study was to evaluate the relation between diabetic peripheral polyneuropathy and cognitive factors in T2DM patients. Retrospective chart review of type 2 diabetic patients with results of a nerve conduction study (NCS) and a neurocognitive study. A total of 19 patients were included. DPN was defined using data from a nerve conduction study: a score of less than 24 in the Korean version of the Mini-Mental State Examination (K-MMSE) was considered as an indicator of cognitive impairment (CI). The mean age of the 19 patients was 71.6±5.0 years. The mean duration of diabetes was 8.4±9.1 years, and the mean HbA1c level was 8.1±1.8%. DPN was present in 7 of the 19 patients. Based on the K-MMSE score, CI was diagnosed in eight patients. The mean K-MMSE scores and the prevalence of CI was not different between the groups with and without DPN. There was no significant difference in DPN prevalence between the groups with and without CI. Education was significantly correlated with cognitive factors. Only the digit span-forward among the cognitive factors showed a significant negative correlation with nerve conduction velocity. In conclusion, the longer education period was associated with higher cognitive function and no significant correlation was observed between diabetic peripheral neuropathy and cognitive dysfunction in type 2 diabetic patients. Further prospective research is needed in the future.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.33 no.6
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• pp.478-482
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• 2011

Purpose: Free flap reconstruction is performed on defects including benign and malignant tumors as well as trauma in the department of oral and maxillofacial surgery, but there are few reports of free flap reconstruction cases for oral cancer in patients in Korea. Methods: This study was designed to retrospectively analyze surgical outcomes and complications of 164 free-flap reconstructions performed at the Oral Oncology Clinic, National Cancer Center, during 2002~2011. A total of 164 free flaps were performed for reconstruction of oral and maxillofacial defects which were caused by oral cancer and osteoradionecrosis in 155 patients. Results: The present study had 162 successful cases and 2 failed cases for a total of 164 cases. The study had a success rate of 98.8% for free-flap reconstructions. Flap donor sites included radial forearm free flap (n=93), fibula osteocutaneous free flap (n=25), anterolateral thigh flap (n=18), latissimus dorsi myocutaneous flap (n=16) and other locations (n=12). Postoperative medical complications were generally pneumonia and delirium. Postoperative local complications occurred including partial flap necrosis, delayed wound healing of the donor site, infection of the recipient site and salivary fistula. The incidence of postoperative complications and patient-related characteristics including age, sex, smoking, history of radiotherapy, hypertension (HTN) and diabetes Mellitus (DM) were retrospectively analyzed. Patient age ($P$=0.003) and DM ($P$=0.000) and HTN ($P$=0.021) were significant risk factors for complications overall. Conclusion: The present study had no mortality and confirms that free-flap reconstructions are extremely reliable in achieving successful results.

• BMB Reports
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• v.49 no.5
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• pp.297-302
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• 2016

Loss of pancreatic β-cells by oxidative stress or cytokines is associated with diabetes mellitus (DM). DJ-1 is known to as a multifunctional protein, which plays an important role in cell survival. We prepared cell permeable wild type (WT) and mutant type (M26I) Tat-DJ-1 proteins to investigate the effects of DJ-1 against combined cytokines (IL-1β, IFN-γ and TNF-α)-induced RINm5F cell death. Both Tat-DJ-1 proteins were transduced into RINm5F cells. WT Tat-DJ-1 proteins significantly protected against cell death from cytokines by reducing intracellular toxicities. Also, WT Tat-DJ-1 proteins markedly regulated cytokines-induced pro- and anti-apoptosis proteins. However, M26I Tat-DJ-1 protein showed relatively low protective effects, as compared to WT Tat-DJ-1 protein. Our experiments demonstrated that WT Tat-DJ-1 protein protects against cytokine-induced RINm5F cell death by suppressing intracellular toxicities and regulating apoptosisrelated protein expression. Thus, WT Tat-DJ-1 protein could potentially serve as a therapeutic agent for DM and cytokine related diseases.

• The Journal of Internal Korean Medicine
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• v.22 no.3
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• pp.423-430
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• 2001

Objects: The purpose of this case-control study was done to examine the relationship between stroke prevalence and the anthropometric indices(body mass index(BMI), modified Broca's method(Broca's index), waist circumference(WC), waist-hip ratio(WHR)), dyslipidemia, past medical history(heart disease, hypertension, diabetes mellitus(DM)), life-style factors(smoking, drinking) in Korean adults. Methods : The study group consisted of neurologically confirmed 116 stroke patients as the case group and 116 non-stroke patients as control group. Obesity were defined as $BMI{\geq}25kg/m^2,\;Broca's\;index{\geq}30%$, WC >94cm in male and WC >80cm in female, $WHR{\geq}0.9$ in male and $WHR{\geq}0.8$ in female. Oyslipidemia were defined as total $cholesterol{\geq}200mg/dl,\;triglyceride{\geq}200mg/dl,\;HDL-cholesterol {\leq}35mg/dl,\;LDL-cholesterol{\geq}160mg/dl$. Information on life-style factors and past medical history was obtained from personal interview. The analysis of the data was done by means of chi-square test(Pearson's chi-square test, Fisher's exact test) and student t-test. Results: The results were as follow. In the study group: Hypertension had a 4:05 odds ratio, Broca's $index{\geq}30%$ had a 1.98 odds ratio, WC >94cm in male had a 2.17 odds ratio, WC >80cm in female had a 2.80 odds ratio, $WHR{\geq}0.9$ in male had a 4.66 odds ratio, $WHR{\geq}0.8$ in female had a 5.35 odds ratio, but heart disease, DM, life-style factors, serum lipid and 8MI had no direct relationship with odds ratio(nonsignificant). By student t-test, risk factors for stroke were found to be total cholesterol(p=0,025), LDL-cholesterol(p=0.013), WC(p=0.000) and WHR(p=0.000). Conclusions: This study suggests that people should be advised to control hyperlitension, hyperlipidemia and obesity since these carry a risk of stroke.

• Journal of Korean Neurosurgical Society
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• v.62 no.5
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• pp.536-544
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• 2019

Objective : The objective of this study was to evaluatelong-term radiologic prognosis and characteristics of in-stent stenosis (ISS) after stent assisted coiling (SAC) for cerebral aneurysm and analyze its risk factors. Methods : Radiological records of 362 cases of SAC during 10 years were retrospectively reviewed. Patients were included in this study if they had follow-up angiogram using catheter selected angiography at least twice. All subjected were followed up from 12 months to over 30 months. Of 120 patients, 123 aneurysms were enrolled. Patient data including age, sex, aneurysm size, neck size, procedural complication, kinds of stent, ISS associated symptom, ruptured state, location of ISS, degree of ISS, radiologic prognosis of ISS, follow-up period of time, and medical comorbidities such as hypertension, diabetes mellitus (DM), dyslipidemia, and smoking were collected.Statistical comparisons of group clinical characteristics were conducted for the total population. Results : Among 123 casesof aneurysm, 22 cases (17.9%) of ISS were revealed on follow-up angiography. Multiple stenting was performed in three cases and intra-procedural rupture occurred in two cases. Most cases were asymptomatic and symptomatic stenosis was identified in only one case. Sixteen cases were ruptured aneurysm. Mild stenosis was observed in 11 cases. Moderate stenosis was found in eight cases and severe stenosis was identified in three cases. Mean timing of identification of ISS was 8.90 months. The most common type was proximal type. Most cases were improved or not changed on follow-up angiography. Only one case was aggravated from mild stenosis to occlusion of parent artery. Mean follow-up period was 44.3 months. We compared risk factors and characteristic between ISS group and non-ISS group using univariate analysis. Multiple stenting was performed for three cases (13.6%) of the ISS group and four cases (4.0%) of the non-ISS group, showing no statistical difference between the two groups (p=0.108). Additionally, the proportion of patients who had more than two risk factors among four medical risk factors (hypertension, DM, dyslipidemia, and smoking) was higher in the ISS group than that in the non-ISS group, the difference between the two was not statistically significant either (31.8% vs. 12.9%, p=0.05). Conclusion : Clinical course and long-term prognosis of ISS might be benign. Most cases of ISS could be improved or not aggravated. Control of medical co-morbidity might be important. To the best of our knowledge, our study had more cases with longer follow-up period of time than other reports.

• Journal of Ginseng Research
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• v.46 no.6
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• pp.780-789
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• 2022

Background: Incretin impairment, characterized by insufficient secretion of L-cell-derived glucagon-like peptide-1 (GLP-1), is a defining step of type 2 diabetes mellitus (T2DM). Ginsenoside compound K (CK) can stimulate GLP-1 secretion; however, the potential mechanism underlying this effect has not been established. Methods: CK (40 mg/kg) was administered orally to male db/db mice for 4 weeks. The body weight, oral glucose tolerance, GLP-1 secretion, gut microbiota sequencing, bile acid (BA) profiles, and BA synthesis markers of each subject were then analyzed. Moreover, TGR5 expression was evaluated by immunoblotting and immunofluorescence, and L-cell lineage markers involved in L-cell abundance were analyzed. Results: CK ameliorated obesity and impaired glucose tolerance in db/db mice by altering the gut microbiota, especially Ruminococcaceae family, and this changed microbe was positively correlated with secondary BA synthesis. Additionally, CK treatment resulted in the up-regulation of CYP7B1 and CYP27A1 and the down-regulation of CYP8B1, thereby shifting BA biosynthesis from the classical pathway to the alternative pathway. CK altered the BA pool by mainly increasing LCA and DCA. Furthermore, CK induced L-cell number expansion leading to enhanced GLP-1 release through TGR5 activation. These increases were supported by the upregulation of genes governing GLP-1 secretion and L-cell differentiation. Conclusions: The results indicate that CK improves glucose homeostasis by increasing L-cell numbers, which enhances GLP-1 release through a mechanism partially mediated by the gut microbiota-BA-TGR5 pathway. Therefore, that therapeutic attempts with CK might be useful for patients with T2DM.

• Korean Circulation Journal
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• v.53 no.7
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• pp.425-451
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• 2023

Most patients with heart failure (HF) have multiple comorbidities, which impact their quality of life, aggravate HF, and increase mortality. Cardiovascular comorbidities include systemic and pulmonary hypertension, ischemic and valvular heart diseases, and atrial fibrillation. Non-cardiovascular comorbidities include diabetes mellitus (DM), chronic kidney and pulmonary diseases, iron deficiency and anemia, and sleep apnea. In patients with HF with hypertension and left ventricular hypertrophy, renin-angiotensin system inhibitors combined with calcium channel blockers and/or diuretics is an effective treatment regimen. Measurement of pulmonary vascular resistance via right heart catheterization is recommended for patients with HF considered suitable for implantation of mechanical circulatory support devices or as heart transplantation candidates. Coronary angiography remains the gold standard for the diagnosis and reperfusion in patients with HF and angina pectoris refractory to antianginal medications. In patients with HF and atrial fibrillation, longterm anticoagulants are recommended according to the CHA₂DS₂-VASc scores. Valvular heart diseases should be treated medically and/or surgically. In patients with HF and DM, metformin is relatively safer; thiazolidinediones cause fluid retention and should be avoided in patients with HF and dyspnea. In renal insufficiency, both volume status and cardiac performance are important for therapy guidance. In patients with HF and pulmonary disease, beta-blockers are underused, which may be related to increased mortality. In patients with HF and anemia, iron supplementation can help improve symptoms. In obstructive sleep apnea, continuous positive airway pressure therapy helps avoid severe nocturnal hypoxia. Appropriate management of comorbidities is important for improving clinical outcomes in patients with HF.