Association between Homocysteine and Vitamin D Levels in Asymptomatic Korean Adults.

An increased homocysteine level is a risk factor for cardiovascular disease, venous thromboembolism, cerebrovascular disease, and chronic kidney disease. In addition, vitamin D deficiency is associated with coronary artery disease and metabolic disorders. The present study included data from 1375 adults (895 men and 480 women) with a mean age of 52.62 ± 9.94 years who visited the Health Promotion Center of the University Hospital in Gyeonggi-do, Republic of Korea from January 2018 to December 2022 for routine checkups that included assessments of their homocysteine and vitamin D levels. Homocysteine levels were positively associated with age, a history of hypertension, a history of diabetes, current smoking habits, and levels of low-density lipoprotein cholesterol, creatinine, uric acid, and high-sensitivity C-reactive protein. By contrast, vitamin D levels were negatively associated with serum levels of homocysteine after adjusting for covariates (ß = -0.033, p < 0.001). Additional long-term prospective studies are needed to elucidate the presence of a causal relationship between vitamin D status and serum levels of homocysteine in asymptomatic Korean adults. An intervention trial is warranted to determine whether the administration of vitamin D is helpful for the primary prevention of cardiovascular disease by lowering the homocysteine level in this population.

Assessment of Fatigue and Associated Factors in Patients with Inflammatory Bowel Disease: A Questionnaire-Based Study.

Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue and associated factors in patients with IBD. A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Among 97 ulcerative colitis patients and 50 Crohn's disease patients, the mean total MFI-K score was 59.0 ± 5.5, which corresponded to a moderate-to-severe level of fatigue. Moderate-to-severe disease activity was found to be significantly associated with a higher general and physical fatigue subscale MFI-K score compared to remission-to-mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, p = 0.009), while the use of biologics was associated with a lower total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, p = 0.031). In multiple linear regression, the total MFI-K score was positively correlated with a history of surgery for IBD, while it was negatively correlated with the use of biologics. Depression was positively correlated with the reduced motivation subscale score. The degree of fatigue in patients with IBD was high. Disease activity, the use of biologics, a history of surgery for IBD, and depression were associated with fatigue.

Reliability and Validity of Korean Version of Crohn's and Ulcerative Colitis Questionnaire-8.

Background: Patients with inflammatory bowel disease (IBD) have a decreased quality of life (QoL), the improvement of which is a treatment goal. The CUCQ-8 is a verified simple and effective QoL measurement tool. We validated the Korean version of CUCQ-8 with the approval of its developer. Methods: We investigated the correlation between the Korean version of CUCQ-8 and the IBDQ-32 in patients with IBD. Results: In all, 147 subjects (male, 97 (66.0%); female, 50 (34.0%); mean age 36.2 ± 13.5 years) were analyzed. Cronbach's alpha coefficient of the CUCQ-8 was 0.833, indicating very high internal consistency. The Korean version of the CUCQ-8 showed a significant correlation with the IBDQ-32 and its subscales (correlation coefficient, >0.75). Conclusions: The Korean version of the CUCQ-8 has high reliability and construct validity and can be used to evaluate the QoL of patients with IBD.

Fat-to-muscle Ratio: A New Indicator for Coronary Artery Disease in Healthy Adults.

Background: Coronary artery disease (CAD) is an important issue in public health. Previous studies have shown that the ratio of fat to muscle mass is a significant predictor of metabolic disease, and it is known to be associated with atherosclerosis. In this study, we evaluated the association between the fat-to-muscle ratio (FMR) and CAD in healthy adults. Methods: A total of 617 participants without diabetes mellitus, hypertension, known CAD, or stroke who visited the Health Promotion Center from 2009 to 2018 were included in this study. Computed tomography imaging and bioelectrical impedance analysis were used to ascertain the coronary artery calcium (CAC) score, degree of CAD, and FMR. Results: Univariate logistic regression analysis showed that old age, male sex, smoking history, creatinine, aspartate aminotransferase, gamma-glutamyl transferase, uric acid, total cholesterol, and low-density lipoprotein cholesterol were significantly associated with CAC. After adjusting for potential confounding covariates, the presence of CAC was independently associated with FMR (OR, 1.014; 95% CI, 1.002-1.026; p = 0.019. The association was maintained even after adjusting for body mass index and waist circumference (odds ratio, 1.019; 95% confidence interval, 1.004 -1.034; P = 0.012). Conclusion: In this study, a high FMR was significantly associated with CAC. A large-scale prospective study on the association with FMR and cardiovascular diseases is necessary to confirm this relationship.

Fatigue and Mental Status of Caregivers of Severely Chronically Ill Patients.

Background and Aims: Fatigue is an unpleasant experience accompanied by functional deterioration involving both mental and physical factors. Caregivers of patients with severe illnesses who require long-term treatment often experience marked physical and mental fatigue. This study investigated the factors affecting fatigue among caregivers of patients with severe chronic diseases. Methods: The study enrolled 100 caregivers of patients providing home care nursing at a university hospital in Gyeonggi-do of Korea, including 47 caregivers caring for cancer patients and 53 caregivers caring for chronic disease patients (e.g., dementia, amyotrophic lateral sclerosis, and Parkinson's disease). The degree of fatigue was measured using the Korean version of the multidimensional fatigue inventory (MFI-K). Caregiver depression and anxiety were examined using the Hospital Anxiety and Depression Scale. Results: The average MFI-K score of all caregivers was 60.43 ± 13.77 and did not differ significantly between those caring for cancer patients and those caring for patients with severe chronic diseases (62.15 ± 13.27 vs. 58.49 ± 14.20, respectively, p=0.186). The longer the disease duration, the greater the general and physical fatigue of the caregiver (r = 0.284, p=0.004). However, caregiver mental fatigue did not differ according to disease duration (r = 0.169, p=0.094). The main factors affecting caregiver general and physical fatigue were caregiver anxiety and depression and patient's disease duration. Conclusions: The caregivers of patients with cancer or chronic severe illnesses experience high levels of fatigue: the longer the disease duration, the greater the degrees of depression, anxiety, and physical fatigue experienced by the caregivers. Such caregivers need strategies to manage their fatigue and depression.

Factors Affecting Proximal Colon Cleansing Based on Bowel Movement Kinetics: A Prospective Observational Study.

BACKGROUND: Previous studies have suggested that relatively poor bowel preparation in the proximal colon, compared to that in the distal colon, could decrease the usefulness of colonoscopy. The aim of this study was to determine whether the "first defecation time" after polyethylene glycol (PEG) administration affects the cleansing quality in the proximal colon. METHODS: A total of 425 individuals who were scheduled to undergo a screening colonoscopy were enrolled prospectively at the healthcare center of St. Vincent's Hospital, Suwon, Korea, between April 2015 and March 2016. Bowel cleansing was performed using 4 L of PEG. Surveys were conducted to obtain information regarding the "first defecation time." Endoscopists assessed the quality of bowel preparation in each bowel segment. RESULTS: We investigated 425 consecutive eligible cases. The mean "first defecation time" after PEG administration was 54.35 min. The quality of bowel preparation was poorer in the proximal colon than that in the distal colon. The adequate (excellent, good) and inadequate (fair, poor) proximal colon preparation groups comprised 360 (84.7%) and 65 (15.3%) patients, respectively. A multivariate analysis revealed that female gender (P = 0.029), small waist circumference (P = 0.027), and the long "first defecation time" (P = 0.034) were independently associated with inadequate bowel preparation in the proximal colon. CONCLUSION: Our data document that the "first defecation time," female gender, and a small waist circumference affect the quality of preparation in the proximal colon. Inadequate preparation in the proximal colon was more common in females. Patients with these factors undergoing colonoscopy should be monitored carefully.

Reliability and Validity of the Korean Version of the Multidimensional Fatigue Inventory (MFI-20): A Multicenter, Cross-Sectional Study.

Introduction: A nonspecific symptom, fatigue accompanies a variety of diseases, including cancer, and can have a grave impact on patients' quality of life. As for multidimensional instruments, one of the most widely used is the Multidimensional Fatigue Inventory (MFI). This study aims to verify the reliability and validity of the MFI Korean (MFI-K) version. Materials and Method: This study was performed at four university hospitals in the Republic of Korea. Among outpatients visiting the Department of Family Medicine, those complaining of fatigue or visiting a chronic care clinic were enrolled in this study. A total of 595 participants were included, and the mean age was 42.2 years. Results: The Cronbach's alpha coefficient of the MFI-K was 0.88. The MFI-K had good convergent validity. Most subscales of the MFI-K were significantly correlated with the Visual Analogue Scale (VAS) and Fatigue Severity Scale (FSS). In particular, general and physical fatigue had the greatest correlation with the VAS and FSS. Although the English version of MFI had five subscales, the factor analysis led to four subscales in the Korean version. Conclusion: This study demonstrated the clinical usefulness of MFI-K instrument, particularly in assessing the degree of fatigue and performing a multidimensional assessment of fatigue.

Association between the Time of Length since Smoking Cessation and Insulin Resistance in Asymptomatic Korean Male Ex-Smokers.

AIM: Smoking is a major risk factor for diabetes mellitus, mainly due to decreased insulin secretion and increased insulin resistance. However, there has been little research on the effects of smoking cessation period on changes in insulin resistance. In this study, we investigated the relationships between the length of time since smoking cessation period and insulin resistance in asymptomatic Korean male ex-smokers. METHODS: A total of 851 male adults were included in this study. We considered several factors that can affect insulin resistance, and through multiple linear regression analysis, we assessed the effect the length of time since smoking cessation on insulin resistance in ex-smokers. Insulin resistance was represented as the insulin resistance index estimated by homeostasis model assessment. RESULTS: HOMA-IR values showed a statistically significant negative correlation with the length of time since smoking cessation (p = 0.009) in ex-smokers. After performing multiple linear regression analysis using factors that could potentially influence insulin resistance, we found that waist circumference (p = 0.026) and the length of time since smoking cessation (p = 0.039) were independent predictors of HOMA-IR in asymptomatic male ex-smokers. CONCLUSION: The longer the smoking cessation period, the more the insulin resistance tended to decrease in asymptomatic Korean male ex-smokers.

Efficacy and safety of fermented garlic extract on hepatic function in adults with elevated serum gamma-glutamyl transpeptidase levels: a double-blind, randomized, placebo-controlled trial.

PURPOSE: Alcoholic liver disease or non-alcoholic fatty liver disease/non-alcoholic steatohepatitis are well-known risk factors for liver fibrosis or cirrhosis and hepatocellular carcinoma; it is a major global health concern, but there are few effective and safe management options. Therefore, we aimed to investigate the effects of fermented garlic extracts (FGEs) on hepatic function in adults with mild hepatic dysfunction without underlying hepatic disease. METHODS: In this double-blind, randomized, placebo-controlled study, seventy-five adults with elevated serum gamma-glutamyl transpeptidase (GGT) levels were included in a FGE-administered group (n = 36) or a placebo group (n = 39), and received either two sachets/day containing FGEs or placebo over a 12-week period. Primary endpoint was the change in serum GGT levels. Data were analysed using a generalized linear mixed effects model. RESULTS: Significant group × time interactions for serum levels of GGT (F = 3.98, P = 0.022) and alanine aminotransferase (ALT; F = 3.28, P = 0.043) were observed with an improvement in levels of GGT (P = 0.066) and ALT (P = 0.014) in the FGE group compared to that reported for the placebo group at the 12-week visits. There was no intergroup difference in the prevalence of adverse events. CONCLUSIONS: Intake of FGEs improved serum GGT and ALT levels in adults with mildly elevated serum GGT level without reported adverse side effects. FGEs might be effective and safe management options for mild hepatic dysfunction.

Association between metabolic syndrome, smoking status and coronary artery calcification.

Coronary artery calcification (CAC), an indicator of coronary artery stenosis, is an independent risk factor of ischemic heart disease. Smoking increases the risk of metabolic syndrome (MS) and cardiovascular disease. Almost no previous studies have evaluated the combined effect of MS and smoking status on CAC. Therefore, in this study we examined the relationships between CAC, MS, and smoking. This study included 775 adult males without histories of cardiovascular disease who visited the Health Promotion Center at the University Hospital in Gyeonggi-do, Republic of Korea from January 2, 2010 to December 31, 2012. All subjects were screened for CAC by multi-detector computed tomography (MDCT). CAC increased significantly with age and body mass index (BMI). Among MS components, abdominal obesity and elevated fasting blood glucose were correlated with CAC. After adjusting for age and BMI, MS was associated with a 1.46-fold increase in CAC (95% CI:1.02-2.09), abdominal obesity was associated with a 1.45-fold increase (95% CI:1.04-2.04), elevated fasting blood glucose was associated with a 2-fold increase (95% CI:1.36-2.94), and MS and smoking combined were associated with 2.44-fold increase in CAC. Thus, the combination of smoking and MS had a greater impact on CAC than any single factor alone. MS is correlated with an increased risk of CAC, and a combination of MS and smoking is associated with even greater risk. These findings can be used to prevent cardiovascular disease in adults.

Clinical characteristics and natural history of asymptomatic erosive esophagitis.

BACKGROUND/AIMS: This study was designed to investigate risk factors related to asymptomatic erosive esophagitis and the natural history of both endoscopic findings and reflux-related symptoms in subjects with asymptomatic erosive esophagitis. MATERIALS AND METHODS: On a retrospective basis, data were gathered from patients with erosive esophagitis (Los Angeles classification 3A) who had undergone endoscopic follow-up at St. Vincent Hospital. Data from 313 subjects with erosive esophagitis were investigated. RESULTS: Most patients had mild esophagitis (grade A or B, Los Angeles classification); 198 (63.3%) had reflux symptoms, and 115 (36.7%) lacked typical or atypical symptoms. Asymptomatic erosive esophagitis was associated with non-smoking (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.4-3.9) and lower body mass index (body mass index (BMI); OR, 1.5; 95% CI, 1.0-2.4), while 26% of subjects had recurring reflux-related symptoms. Younger subjects were more likely to have reflux-related symptoms (p<0.05). CONCLUSION: Non-smoking and lower BMI are associated with asymptomatic reflux esophagitis. Most asymptomatic subjects with erosive esophagitis remained stable and exhibited unchanged endoscopic findings.

Administration of mesenchymal stem cells and ziprasidone enhanced amelioration of ischemic brain damage in rats.

Ziprasidone is a benzisothiazolyl piperazine derivative that was developed from the chemically related antipsychotic drug tiospirone, and it improves neurological functions of the ischemic brain and is effective in treatment of schizophrenia. Mesenchymal stem cells (MSCs) are considered as a leading candidate for neurological regenerative therapy because of their neural differentiation properties in damaged brain. We investigated whether the transplantation of neural progenitor cells (NPCs) derived from adipose mesenchymal stem cells combined with ziprasidone enhances neuroprotective effects in an animal model of focal cerebral ischemia. In combination therapy groups, significant reduction of infarct volume and improvement of neurological functions were observed at 3 days after middle cerebral artery occlusion (MCAO) compared with monotherapy. Co-administration of ziprasidone and NPCs enhanced the anti-apoptotic effect and reduced the number of terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL)-positive apoptotic cells compared with the NPCs alone group at 7 days after MCAO. Ziprasidone or the combination of ziprasidone and NPCs induced the expression of endogenous neurotrophic factor gene brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and glial cell-derived neurotrophic factor (GDNF). The immunohistochemical investigation revealed that the ziprasidone and NPCs attenuated the increased intensity of microglial marker (Iba-1) in the infarcted cortical area. Moreover, the number of transplanted NPCs on day 7 with combination therapy was significantly higher than with NPCs alone. These effects might be responsible for improved functional behavior and increased survival of NPCs. Our finding indicates that combination therapy of ziprasidone and NPCs enhances neuroprotection against ischemic brain injury.

Helicobacter pylori Infection Enhances Gastric Mucosal Inflammation in Individuals Carrying the 260-T Allele of the CD14 Gene.

BACKGROUND/AIMS: We aim to evaluate the association between promoter polymorphism of the clusters of differentiation 14 (CD14) gene and Helicobacter pylori-induced gastric mucosal inflammation in a healthy Korean population. METHODS: The study population consisted of 267 healthy subjects who visited our hospital for free nationwide gastric cancer screening. Promoter polymorphism at -260 C/T of the CD14 gene was determined by polymerase chain reaction and restriction fragment length polymorphism analysis. The severity of gastric mucosal inflammation was estimated by a gastritis score based on the sum of the values of the grade and activity of the gastritis. Expression of soluble CD14 (sCD14) was assessed by quantitative sandwich ELISA. RESULTS: CD14 polymorphism was not associated with H. pylori infection. There were no significant differences in gastritis scores among the genotype subgroups, but subjects carrying the CD14 -260 CT/TT genotype had significantly higher sCD14 levels than those carrying the CC genotype. Subjects with the 260-T allele of the CD14 gene and H. pylori infection had significantly higher sCD14 levels than those with the same genotype but without infection. CONCLUSIONS: In individuals with the T allele at the -260 site of the promoter region of the CD14 gene, H. pylori infection accentuates gastric mucosal inflammation.

Assessment of lifestyle effects on the levels of free oxygen radicals in the korean population.

BACKGROUND: As many studies revealed that oxidative stress due to the imbalance of reactive oxygen species (ROS) and antioxidant capacity is related with pathologic processes such as cardiovascular diseases, diabetes, as well as aging and obesity, the relationship between lifestyle and oxidative stress has recently gained much medical attention. However, little information exists on the effects of lifestyle on ROS in Korea. In this study, we investigated the effects of lifestyle on free oxygen radical levels in men and women in Korea. METHODS: A total of 138 adults participated in this study from September 2007 to June 2010 at a health promotion center and department of family medicine. Information on the lifestyle of each participant was obtained by questionnaire. Biochemical markers and a free oxygen radical test (FORT) were also measured. RESULTS: The average age was 47.28 ± 10.85 years and 79.7% were male. High sensitivity C-reactive protein (hs-CRP; r = 0.418, P = 0.012), triglycerides (r = -0.243, P = 0.008), hemoglobin (r = -0.445, P < 0.001), total protein (r = 0.210, P = 0.036), creatinine (r = -0.294, P = 0.001), fruit intake per day (P = 0.047), and smoking (P = 0.003) were related to the FORT levels in univariate analysis. Multiple linear regression analysis showed that hs-CRP (P = 0.039) was an independent predictor of serum FORT values. This statistical model can explain 78% of the variance in FORT values. CONCLUSION: This result suggests that hs-CRP showed a statistically significant positive association with FORT values. Further studies on the relationship between lifestyle and antioxidant capacity as well as ROS seem to be warranted to evaluate the overall effect of oxidative stress.

p-Hydroxybenzyl alcohol prevents brain injury and behavioral impairment by activating Nrf2, PDI, and neurotrophic factor genes in a rat model of brain ischemia.

The therapeutic goal in treating cerebral ischemia is to reduce the extent of brain injury and thus minimize neurological impairment. We examined the effects of p-hydroxybenzyl alcohol (HBA), an active component of Gastrodia elata Blume, on transient focal cerebral ischemia-induced brain injury with respect to the involvement of protein disulphide isomerase (PDI), nuclear factor-E2-related factor 2 (Nrf2), and neurotrophic factors. All animals were ovariectomized 14 days before ischemic injury. Ischemic injury was induced for 1 h by middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion. Three days before MCAO, the vehicle-treated and the HBA-treated groups received intramuscular sesame oil and HBA (25 mg/kg BW), respectively. 2,3,5-Triphenyltetrazolium chloride (TTC) staining showed decreased infarct volume in the ischemic lesion of HBA-treated animals. HBA pretreatment also promoted functional recovery, as measured by the modified neurological severity score (mNSS; p < 0.05). Moreover, expression of PDI, Nrf2, BDNF, GDNF, and MBP genes increased by HBA treatment. In vitro, H(2)O(2)-induced PC12 cell death was prevented by 24 h HBA treatment, but bacitracin, a PDI inhibitor, attenuated this cytoprotective effect in a dose-dependent manner. HBA treatment for 2 h also induced nuclear translocation of Nrf2, possibly activating the intracellular antioxidative system. These results suggest that HBA protects against brain damage by modulating cytoprotective genes, such as Nrf2 and PDI, and neurotrophic factors.

The Relationship between Menopausal Symptoms and Heart Rate Variability in Middle Aged Women.

BACKGROUND: The study of the correlation of menopausal symptoms with heart rate variability (HRV) has not been adequate. The aim of this study was to investigate the relationship between postmenopausal symptoms measured by the menopause rating scale (MRS) and HRV. METHODS: We assessed postmenopausal symptoms (using MRS) with age, BMI, educational status, occupation, marital status, alcohol and caffeine consumption, smoking history, exercise, duration of sleep and amenorrhea, degree of anxiety and depression, menarcheal age, and heart rate variability. For evaluation of HRV, the record of electrocardiogram for 5 minutes in the resting state was divided into temporal categories and frequency categories, and analyzed. RESULTS: No significant differences in age, BMI, duration of amenorrhea, heart rate, systolic blood pressure, diastolic blood pressure, fasting blood sugar, triglyceride, and high-density lipoprotein were observed between two groups, which were divided according to menopausal symptoms. Low frequency/high frequency (LF/HF) ratio was significantly higher in symptomatic women, compared with asymptomatic women (P < 0.05). No significant differences of HRV index by the severity of postmenopausal symptoms were observed. LF/HF ratio of HRV parameters showed a significant increase in moderate or severe degree of "hot flashes" and "sleep problem" score (P < 0.05). Anxiety scale in symptomatic women was significantly higher than in asymptomatic women (P < 0.05). CONCLUSION: The above data suggest that postmenopausal symptoms are associated with altered autonomic control of heart rate. In particular, hot flashes and sleep problems in moderate or severe degree are related to increase of sympathetic nerve activity.

The Relationship between Metabolic Syndrome and Cognitive Function.

BACKGROUND: Metabolic syndrome has been reported to have adverse effects on cognitive function, although the results are conflicting. The purpose of this study was to examine the relationship between metabolic syndrome and cognitive function in elderly Korean participants older than 60 years. METHODS: We examined elderly participants who visited the health promotion center in Gyeonggi-do province. We categorized the participants into two groups based on the presence of metabolic syndrome (48 participants in the metabolic syndrome group and 45 in the control group). Cognitive function was assessed in all participants using the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD-K). RESULTS: Compared with those without metabolic syndrome, participants with metabolic syndrome had lower mean total CERAD-K scores (64.2 ± 11.1 vs. 69.8 ± 9.2, P = 0.010). In the comparison of CERAD-K items, significantly lower scores were observed in the verbal fluency test, the construction recall test, the word list learning test, and trail making B in the group with metabolic syndrome. After controlling age, sex, education, smoking, alcohol, physical activity and the Korean version of the Short Geriatric Depression Scale of Korean, multiple regression analysis showed that metabolic syndrome was independently associated with cognitive function (P = 0.014). Alcohol intake (P = 0.002) and education years (P = 0.001) were also contributing factors to cognitive function. CONCLUSION: This study found a significant relationship between cognitive function and metabolic syndrome. It will be necessary to perform a prospective study to determine whether metabolic syndrome causes cognitive dysfunction or if the correction of metabolic syndrome can improve cognitive function.

Estrogen-dependent transcription of the NEL-like 2 (NELL2) gene and its role in protection from cell death.

NELL2 (neural tissue-specific epidermal growth factor-like repeat domain-containing protein) is a secreted glycoprotein that is predominantly expressed in neural tissues. We reported previously that NELL2 mRNA abundance in brain is increased by estrogen (E2) treatment and that NELL2 is involved in the E2-dependent organization of a sexually dimorphic nucleus in the preoptic area. In this study we cloned the mouse NELL2 promoter and found it to contain two half-E2 response elements. Electrophoretic mobility shift assays and promoter assays showed that E2 and its receptors (ERalpha and ERbeta) stimulated NELL2 transcription by binding to the two half-E2 response elements. Hippocampal neuroprogenitor HiB5 cells expressing recombinant NELL2 showed increased cell survival under cell death-inducing conditions. Blockade of endogenous synthesis of NELL2 in HiB5 cells abolished the cell survival effect of E2 and resulted in a decrease in phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2). These data suggest that the NELL2 gene is trans-activated by E2 and contributes to mediating the survival promoting effects of E2 via intracellular signaling pathway of ERK.

Insulin-secreting cells from human eyelid-derived stem cells alleviate type I diabetes in immunocompetent mice.

Various attempts have been made to develop stem cell-based therapy to alleviate type I diabetes using animal models. However, it has been a question whether human insulin produced from explanted cells is solely responsible for the normoglycemia of diabetic animals. In this study, we isolated neural crest-like stem cells from the human eyelid fat and examined their therapeutic potentials for diabetes. The human eyelid adipose-derived stem cells (HEACs) displayed characteristics of neural crest cells. Using a two-step culture condition combined with nicotinamide, activin, and/or GLP-1, we differentiated HEACs into insulin-secreting cells and examined in vivo effects of differentiated cells by transplantation experiments. Following differentiation in vitro, HEACs released insulin and c-peptide in a glucose-dependent manner. Upon their transplantation under kidney capsules of streptozotocin-treated immunocompetent mice, we observed normalization of hyperglycemia in 10 of 20 recipient mice until sacrifice after 2 months. Only the human, but not the mouse, insulin and c-peptide were detected in the blood of recipient mice. Removal of the kidneys transplanted with HEACs resulted in a sharp increase of blood glucose level. Removed kidney tissues showed distinct expression of various human genes including insulin, and colocalization of the human insulin and the human nuclear protein in many cells. However, they showed diminished or null expression of some immune-related genes. In conclusion, human insulin alone produced from eyelid-derived stem cells following differentiation into insulin-secreting cells and transplantation could normalize type I diabetes in mice.

Expression and role of TTF-1 in the rat suprachiasmatic nucleus.

We have previously reported that TTF-1, a homeodomain-containing transcription factor, regulates circadian rhythm of pituitary adenylate cyclase-activating polypeptide gene expression in the rat hypothalamus. In this study we found that TTF-1 mRNA was specifically expressed in the rat suprachiasmatic nucleus (SCN) and colocalized with Period 2 (Per2), a circadian feedback loop controller. Interaction between TTF-1 and Per1 and Per2 was demonstrated by immunoprecipitation and immunoblot assays. Moreover, TTF-1 and Per proteins additively stimulated a transcriptional activity of angiotensinogen (AoGen) gene. TTF-1 also activated in vitro rhythm of AoGen transcription determined by secretary alkaline phosphatase (SEAP) reporter system in the NIH3T3 cells. These results suggest that TTF-1 plays a role in the circadian rhythm regulation of the AoGen gene expression via interacting with Per proteins in the rat SCN.