BACKGROUND: Beating cardiomyocyte regeneration therapies have revealed as alternative therapeutics for heart transplantation. Nonetheless, the importance of nitric oxide (NO) in cardiomyocyte regeneration has been widely suggested, little has been reported concerning endogenous NO during cardiomyocyte differentiation. METHODS: Here, we used P19CL6 cells and a Myocardiac infarction (MI) model to confirm NO-induced protein modification and its role in cardiac beating. Two tyrosine (Tyr) residues of b2-tubulin (Y106 and Y340) underwent nitrosylation (Tyr-NO) by endogenously generated NO during cardiomyocyte differentiation from pre-cardiomyocyte-like P19CL6 cells. RESULTS: Tyr-NO-b2-tubulin mediated the interaction with Stathmin, which promotes microtubule disassembly, and was prominently observed in spontaneously beating cell clusters and mouse embryonic heart (E11.5d). In myocardial infarction mice, Tyr-NO-b2-tubulin in transplanted cells was closely related with cardiac troponin-T expression with their functional recovery, reduced infarct size and thickened left ventricular wall. CONCLUSION This is the first discovery of a new target molecule of NO, b2-tubulin, that can promote normal cardiac beating and cardiomyocyte regeneration. Taken together, we suggest therapeutic potential of Tyr-NO-b2-tubulin, for ischemic cardiomyocyte, which can reduce unexpected side effect of stem cell transplantation, arrhythmogenesis.

Hair graying is an obvious sign of human aging. Although graying has been investigated extensively, the mechanism remains unclear. Here, we reviewed previous studies on the mechanism of graying and seek to offer some new insights. The traditional view is that hair graying is caused by exhaustion of the pigmentary potential of the melanocytes of hair bulbs. Melanocyte dysfunction may be attributable to the effects of toxic reactive oxygen species on melanocyte nuclei and mitochondria. A recent study suggests that bulge melanocyte stem cells (MSCs) are the key cells in play. Graying may be caused by defective MSC self-maintenance, not by any deficiency in bulbar melanocytes. Our previous study suggested that graying may be principally attributable to active hair growth. Active hair growth may produce oxidative or genotoxic stress in hair bulge. These internal stress may cause eventually depletion of MSC in the hair follicles. Taken together, hair graying may be caused by MSC depletion by genotoxic stress in the hair bulge. Hair graying may also be sometimes caused by dysfunction of the melanocytes by oxidative stress in the hair bulb. In addition, hair graying may be attributable to MSC depletion by active hair growth.
Aging ; DNA Damage ; Hair Follicle ; Hair* ; Humans ; Melanocytes ; Mitochondria ; Oxidative Stress ; Reactive Oxygen Species ; Rivers* ; Stem Cells

Mitochondria are key organelles involved in energy production, functioning as the metabolic hubs of cells. Recent findings emphasize the emerging role of the mitochondrion as a key intracellular signaling platform regulating innate immune and inflammatory responses. Several mitochondrial proteins and mitochondrial reactive oxygen species have emerged as central players orchestrating the innate immune responses to pathogens and damaging ligands. This review explores our current understanding of the roles played by mitochondria in regulation of innate immunity and inflammatory responses. Recent advances in our understanding of the relationship between autophagy, mitochondria, and inflammasome activation are also briefly discussed. A comprehensive understanding of mitochondrial role in toll-like receptor-mediated innate immune responses and NLRP3 inflammasome complex activation, will facilitate development of novel therapeutics to treat various infectious, inflammatory, and autoimmune disorders.
Autophagy ; Immunity, Innate* ; Inflammasomes ; Inflammation* ; Ligands ; Mitochondria ; Mitochondrial Proteins ; Organelles ; Reactive Oxygen Species

Allergic reaction to insulin is uncommon since the introduction of human recombinant insulin preparations and is more rare in pregnant than non-pregnant females due to altered immune reaction during pregnancy. Herein, we report two cases of allergic reaction to insulin in gestational diabetes that were successfully managed. One case was a 33-year-old female using isophane-neutral protamine Hagedorn human insulin and insulin lispro. She experienced dyspnea, cough, urticaria and itching sensation at the sites of insulin injection immediately after insulin administration. We discontinued insulin therapy and started oral hypoglycemic agents with metformin and glibenclamide. The other case was a 32-year-old female using insulin lispro and insulin detemer. She experienced pruritus and burning sensation and multiple nodules at the sites of insulin injection. We changed the insulin from insulin lispro to insulin aspart. Assessments including immunoglobulin E (IgE), IgG, eosinophil, insulin antibody level and skin biopsy were performed. In the two cases, the symptoms were resolved after changing the insulin to oral agents or other insulin preparations. We report two cases of allergic reaction to human insulin in gestational diabetes due to its rarity.
Adult ; Biopsy ; Burns ; Cough ; Diabetes, Gestational* ; Dyspnea ; Eosinophils ; Female ; Glyburide ; Humans ; Hypersensitivity* ; Hypersensitivity, Immediate ; Hypoglycemic Agents ; Immunoglobulin E ; Immunoglobulin G ; Immunoglobulins ; Insulin Aspart ; Insulin Lispro ; Insulin* ; Metformin ; Pregnancy ; Pruritus ; Sensation ; Skin ; Urticaria

Treatment by All-trans retinoic acid (ATRA) followed by anthracycline-AraC chemotherapy has improved the outcome of acute promyelocytic leukemia. ATRA is usually well tolerated, but a few major side effects can be observed. Retinoic acid syndrome (RAS) often occurs during the induction chemotherapy of acute promyelocytic leukemia. A pericardial effusion is a common cardiac manifestation but myocarditis has been rarely documented. Here we reports a very rare case of fully recovered myocarditis as a result of RAS related to ATRA administration during induction treatment of acute promyelocytic leukemia which documented by echocardiographic evidence.
Induction Chemotherapy ; Leukemia, Promyelocytic, Acute ; Myocarditis ; Pericardial Effusion ; Tretinoin

OBJECTIVES: To assess the effects of hormone replacement therapy on bone mineral density (BMD), biochemical markers of bone turnover, and lipid profiles in postmenopausal women. METHODS: We retrospectively reviewed the medical records of 199 postmenopausal women who had received care at the Department of Obstetrics and Gynecology of Catholic University Seoul St. Mary's Hospital between January 1994 and December 2008. The patients were divided into the following three groups: group 1 received combined estrogen and progesterone therapy (n = 91); group 2 received estrogen only (n = 65); and group 3 received tibolone (n = 43). We compared the changes in biochemical markers of bone turnover, lipid profiles, and BMD during therapy. RESULTS: The BMD of the lumbar spine increased in groups 1 and 3 by 2.0% and 1.2%, respectively, and the BMD of the total femur increased in groups 1 and 2 by 2.3% and 0.5% from the initial values after 3 years, respectively. However, the BMD of the femoral neck and total femur decreased significantly in group 3 by 4.8% and 1.9%, respectively, 3 years after treatment initiation (P < 0.05). Serum osteocalcin and urinary deoxypyridinoline decreased in all groups 1 year after treatment. In groups 1 and 3, the total cholesterol level decreased and the triglycerides level increased. However, there were no definite changes in the total cholesterol and triglycerides levels in group 2. The high density lipoprotein cholesterol (HDL)-cholesterol level increased in groups 1 and 2, but decreased in group 3. As a result, the BMD of the lumbar spine increased and the total cholesterol level decreased in the combined therapy and tibolone groups. Tibolone had no beneficial effect on the BMD of the femoral neck. CONCLUSION: Our results suggest that each therapy has different effects on BMD, biochemical markers of bone metabolism, and lipid profiles. A prospective study involving a larger group, and considering multiple factors, will be required to obtain more clinically meaningful conclusions.
Amino Acids ; Biomarkers ; Bone Density ; Cholesterol ; Cholesterol, HDL ; Estrogens ; Female ; Femur ; Femur Neck ; Gynecology ; Hormone Replacement Therapy ; Humans ; Lipoproteins ; Medical Records ; Norpregnenes ; Obstetrics ; Osteocalcin ; Progesterone ; Retrospective Studies ; Spine ; Triglycerides

OBJECTIVES: To assess the effects of hormone replacement therapy on bone mineral density (BMD), biochemical markers of bone turnover, and lipid profiles in postmenopausal women. METHODS: We retrospectively reviewed the medical records of 199 postmenopausal women who had received care at the Department of Obstetrics and Gynecology of Catholic University Seoul St. Mary's Hospital between January 1994 and December 2008. The patients were divided into the following three groups: group 1 received combined estrogen and progesterone therapy (n = 91); group 2 received estrogen only (n = 65); and group 3 received tibolone (n = 43). We compared the changes in biochemical markers of bone turnover, lipid profiles, and BMD during therapy. RESULTS: The BMD of the lumbar spine increased in groups 1 and 3 by 2.0% and 1.2%, respectively, and the BMD of the total femur increased in groups 1 and 2 by 2.3% and 0.5% from the initial values after 3 years, respectively. However, the BMD of the femoral neck and total femur decreased significantly in group 3 by 4.8% and 1.9%, respectively, 3 years after treatment initiation (P < 0.05). Serum osteocalcin and urinary deoxypyridinoline decreased in all groups 1 year after treatment. In groups 1 and 3, the total cholesterol level decreased and the triglycerides level increased. However, there were no definite changes in the total cholesterol and triglycerides levels in group 2. The high density lipoprotein cholesterol (HDL)-cholesterol level increased in groups 1 and 2, but decreased in group 3. As a result, the BMD of the lumbar spine increased and the total cholesterol level decreased in the combined therapy and tibolone groups. Tibolone had no beneficial effect on the BMD of the femoral neck. CONCLUSION: Our results suggest that each therapy has different effects on BMD, biochemical markers of bone metabolism, and lipid profiles. A prospective study involving a larger group, and considering multiple factors, will be required to obtain more clinically meaningful conclusions.
Amino Acids ; Biomarkers ; Bone Density ; Cholesterol ; Cholesterol, HDL ; Estrogens ; Female ; Femur ; Femur Neck ; Gynecology ; Hormone Replacement Therapy ; Humans ; Lipoproteins ; Medical Records ; Norpregnenes ; Obstetrics ; Osteocalcin ; Progesterone ; Retrospective Studies ; Spine ; Triglycerides

BACKGROUND: LKB1(STK11) is a serine/threonine kinase that functions as a tumor growth suppressor. The functions of LKB1 in lung cancer are not completely understood. This study evaluated the relationship between LKB1 protein expression and the clinicopathological features in lung cancer tissues. METHODS: The expression of LKB1 was studied in paraffin-embedded tumor blocks, which were obtained from 77 patients who had undergone surgery at Wonkwang University Hospital. The expression of the LKB1 protein was considered positive if the staining intensity in the tumor tissue adjacent to the normal airway epithelium was >30%. RESULTS: The LKB1 expression was positive in 31 (40%) of samples. Loss of LKB1 expression was significantly associated with being male, smoking history, and squamous cell carcinoma. In the peripheral sites, the loss of LKB1 expression was strongly associated with a smoking history. A loss of LKB1 expression was more frequently associated with progression according to TNM staging, particularly more than T2, N progression. CONCLUSION: There was a significant relationship between the loss of the LKB1 protein and gender, smoking history, and histological type in primary lung cancer. Although LKB1 expression was not found to be a significant prognostic factor, further studies with a larger cohort of patient's lung cancer tissue samples will be needed to confirm this.
Carcinoma, Squamous Cell ; Cohort Studies ; Epithelium ; Humans ; Lung ; Lung Neoplasms ; Male ; Neoplasm Staging ; Phosphotransferases ; Smoke ; Smoking

BACKGROUND/AIMS: Despite of increasing numbers of reports on intraductal papillary mucinous tumor (IPMT), there is still difficulty in its' diagnosis, treatment and prediction of prognosis. The purpose of this multicenter study was to evaluate the clinico-pathological features of IPMT in Korea and suggest the prediction criteria of malignancy in IPMT. METHODS: We retrospectively reviewed the clinico-pathological data of 208 patients who underwent operations with IPMT between 1993 and 2002 at 28 institutes in Korea. RESULTS: Of the 208 patients with a mean age of 60.5+/-9.7 years, 147 were men and 61 were women. 124 patients underwent pancreatoduodenectomy, 42 distal pancreatectomy, 17 total pancreatectomy, 25 limited pancreas resection. Benign cases were 128 (adenoma (n=62), borderline (n=66)) and malignant cases were 80 (non-invasive (n=29), invasive (n=51)). A significant difference in 5-year survival was observed between benign and malignant group (92.6% vs. 65.3%; p=0.006). Of the 6 factors (age, location, duct dilatation, tumor appearance, main duct type, and tumor size) that showed the statistical difference in univariate analysis between benign and malignant group, we found three significant factors (tumor appearance (p=0.009), tumor size (p=0.023), and dilated duct size (p=0.010)) by multivariate analysis. CONCLUSION: Although overall prognosis of IPMT is superior to ordinary pancreatic cancer, more curative surgery is recommended in malignant IPMT. Tumor appearance (papillary), tumor size (> or =30 mm) and dilated duct size (> or = 12 mm) can be used as preoperative indicators of malig-nancy in IPMT.
Academies and Institutes ; Diagnosis ; Dilatation ; Female ; Humans ; Korea* ; Male ; Mucins* ; Multivariate Analysis ; Pancreas* ; Pancreatectomy ; Pancreatic Neoplasms ; Pancreaticoduodenectomy ; Prognosis ; Retrospective Studies

OBJECTIVE: Malnutrition and nutritional disorder may cause problem of fertility and therefore adequate nutrition is very important during pregnancy. In this study, we investigated effects of supplemental diet contained folic acid, zinc, calcium, Iron, DHA and taurine on fertility outcome in the female rats and learning ability of their offsprings. METHODS: The female rats at 4 week were fed by two group divided control (AIN-76 diet) and supplement diet. The male rats were taken pellet type diet. After 3 weeks, female rats and male rats were mated. Then, at 3 weeks after mating, parturition was begun. After paturition, sex and birth weight of offsprings were examined for their offsprings. When the offsprings were 3 weeks of age, position reversional test in a water maze was done for 4 weeks. After female rats were fed experimental diet for 4 weeks, their follicle, corpus luteum, corpus albicans, progesterone, estradiol and ovary weight were measured. RESULTS: 22 rats of 30 in supplemental diet group succeeded on parturition, and 11 rats of 30 in control group succeeded. Pregnancy outcome was fine in both group. There was no significant difference in weight of major bowels and femur length of their offspring. The position reversional test of offsprings in a water maze showed a significant difference between control group and supplement group. Elapsed time and errorneous response to reach the escape platform were significantly lowered in supplemental group than control group. CONCLUSION: This result suggest that supplementation contained folic acid, multivitamins, DHA and taurine may increase fertility rate in the maternal rats and also learning ability in offsprings.
Animals ; Birth Rate* ; Birth Weight ; Calcium ; Child ; Corpus Luteum ; Diet ; Estradiol ; Female ; Femur ; Fertility* ; Folic Acid* ; Humans ; Iron ; Learning* ; Male ; Malnutrition ; Nutrition Disorders ; Ovary ; Parturition ; Pregnancy ; Pregnancy Outcome ; Progesterone ; Rats* ; Taurine ; United Nations ; Zinc