Interstitial lung disease (ILD) involves persistent inflammation and fibrosis, leading to respiratory failure and even death. Adult tissue-derived mesenchymal stem cells (MSCs) show potential in ILD therapeutics but obtaining an adequate quantity of cells for drug application is difficult. Daewoong Pharmaceutical’s MSCs (DW-MSCs) derived from embryonic stem cells sustain a high proliferative capacity following long-term culture and expansion. The aim of this study was to investigate the therapeutic potential of DW-MSCs in experimental mouse models of ILD. DW-MSCs were expanded up to 12 passages for in vivo application in bleomycin-induced pulmonary fibrosis and collagen-induced connective tissue diseaseILD mouse models. We assessed lung inflammation and fibrosis, lung tissue immune cells, fibrosis-related gene/protein expression, apoptosis and mitochondrial function of alveolar epithelial cells, and mitochondrial transfer ability. Intravenous administration of DWMSCs consistently improved lung fibrosis and reduced inflammatory and fibrotic markers expression in both models across various disease stages. The therapeutic effect of DW-MSCs was comparable to that following daily oral administration of nintedanib or pirfenidone.Mechanistically, DW-MSCs exhibited immunomodulatory effects by reducing the number of B cells during the early phase and increasing the ratio of Tregs to Th17 cells during the late phase of bleomycin-induced pulmonary fibrosis. Furthermore, DW-MSCs exhibited antiapoptotic effects, increased cell viability, and improved mitochondrial respiration in alveolar epithelial cells by transferring their mitochondria to alveolar epithelial cells. Our findings indicate the strong potential of DW-MSCs in the treatment of ILD owing to their high efficacy and immunomodulatory and anti-apoptotic effects.

Objectives: Short stature in childhood is defined to the cases in which the stature is below 3 percentiles of the standard value in accordance with that of those in the same age and gender group. The influence of the socioeconomic status on the short stature in childhood are analyzed. Methods: 154 children from the community child center in a region of poor socioeconomic status and 78 children in normal socioeconomic status who visited the Busan Medical Center due to the issue of short stature were selected for examination and analysis. Results: The prevalence rate of short stature at the community child center in 2 municipalities in Busan was confirmed to be 7.3%. In the comparison of the average growth parameters of poor socioeconomic status and normal socioeconomic status in the short stature group, there was no observation of significant difference in terms of the chronological age, midparental height, bone age, bone age/chronological age, height standard deviation score (SDS), body mass index(BMI) percentile and insulin like growth factor binding protein 3 (IGFBP3) SDS. In the short stature suspicious group, there was observation of significant difference in the averages of bone age, weight, BMI percentile , IGFBP3 and IGFBP3 SDS. Conclusions Although the prevalence rate of short stature in children belonging to the poor socioeconomic class was observed to be higher than the existing results, there was no significant difference in the growth parameters associated with the growth of the height from those of the children in normal socioeconomic status.

BACKGROUND: Hepatitis B virus (HBV) infection leads to hepatic and extrahepatic manifestations including chronic kidney disease (CKD). However, the association between HBV and CKD is not clear. This study investigated the association between chronic HBV infection and CKD in a nationwide multicenter study. METHODS: A total of 265,086 subjects who underwent health-check examinations in 33 hospitals from January 2015 to December 2015 were enrolled. HBV surface antigen (HBsAg) positive cases (n = 10,048), and age- and gender-matched HBsAg negative controls (n = 40,192) were identified. CKD was defined as a glomerular filtration rate (GFR) < 60 mL/min/1.73 m² or proteinuria as at least grade 2+ of urine protein. RESULTS: HBsAg positive cases showed a significantly higher prevalence of GFR < 60 mL/min/1.73 m² (3.3%), and proteinuria (18.9%) than that of the controls (2.6%, P < 0.001, and 14.1%, P < 0.001, respectively). In the multivariate analysis, HBsAg positivity was an independent factor associated with GFR < 60 mL/min/1.73 m² along with age, blood levels of albumin, bilirubin, anemia, and hemoglobin A1c (HbA1c). Likewise, HBsAg positivity was an independent factor for proteinuria along with age, male, blood levels of bilirubin, protein, albumin, and HbA1c. A subgroup analysis showed that HBsAg positive men but not women had a significantly increased risk for GFR < 60 mL/min/1.73 m². CONCLUSION: Chronic HBV infection was significantly associated with a GFR < 60 mL/min/1.73 m² and proteinuria (≥ 2+). Therefore, clinical concern about CKD in chronic HBV infected patients, especially in male, is warranted.
Anemia ; Antigens, Surface ; Bilirubin ; Case-Control Studies* ; Female ; Glomerular Filtration Rate ; Hepatitis B Surface Antigens ; Hepatitis B virus ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Humans ; Male ; Multivariate Analysis ; Prevalence ; Proteinuria ; Renal Insufficiency, Chronic*

BACKGROUND AND PURPOSE: Decreasing the time delay for thrombolysis, including intravenous thrombolysis (IVT) with tissue plasminogen activator and intra-arterial thrombectomy (IAT), is critical for decreasing the morbidity and mortality of patients experiencing acute stroke. We aimed to decrease the in-hospital delay for both IVT and IAT through a multidisciplinary approach that is feasible 24 h/day. METHODS: We implemented the Stroke Alert Team (SAT) on May 2, 2016, which introduced hospital-initiated ambulance prenotification and reorganized in-hospital processes. We compared the patient characteristics, time for each step of the evaluation and thrombolysis, thrombolysis rate, and post-thrombolysis intracranial hemorrhage from January 2014 to August 2016. RESULTS: A total of 245 patients received thrombolysis (198 before SAT; 47 after SAT). The median door-to-CT, door-to-MRI, and door-to-laboratory times decreased to 13 min, 37.5 min, and 8 min, respectively, after SAT implementation (P<0.001). The median door-to-IVT time decreased from 46 min (interquartile range [IQR] 36–57 min) to 20.5 min (IQR 15.8–32.5 min; P<0.001). The median door-to-IAT time decreased from 156 min (IQR 124.5–212.5 min) to 86.5 min (IQR 67.5–102.3 min; P<0.001). The thrombolysis rate increased from 9.8% (198/2,012) to 15.8% (47/297; P=0.002), and the post-thrombolysis radiological intracranial hemorrhage rate decreased from 12.6% (25/198) to 2.1% (1/47; P=0.035). CONCLUSIONS: SAT significantly decreased the in-hospital delay for thrombolysis, increased thrombolysis rate, and decreased post-thrombolysis intracranial hemorrhage. Time benefits of SAT were observed for both IVT and IAT and during office hours and after-hours.
Ambulances ; Cerebral Infarction ; Humans ; Intracranial Hemorrhages ; Mortality ; Stroke* ; Thrombectomy ; Thrombolytic Therapy ; Tissue Plasminogen Activator

PURPOSE: Atopic dermatitis (AD) is a chronic inflammatory skin disorder with a association of genetic, environmental, and immunologic factors in the development of AD. And AD can be classified into IgE mediated and non-IgE mediated. We investigated a difference of clinical characteristics and immune response between the two groups. METHODS: From January 2008 to December 2011, we enrolled 125 children who visited Dong-A University Medical Center and Busan Medical Center, and were diagnosed as AD with the Haniffin and Rajka's criteria. We checked the history of combined asthma and allergic rhinitis and allergic disease of family in patients. We measured serum total IgE, specific IgE by ImmunoCAP or skin prick test. We measured serum interleukin (IL) 4 (IL-4), interferon-gamma (IFN-gamma), IL-10, and IL-17, which are associated with chronic inflammatory disorder by flow cytometry method (Luminex). RESULTS: Eighty (64%) were included in the IgE mediated group, while forty-five (36%) were included in the non-IgE mediated group. The frequency of combined allergic disorder and serum total eosinophil count were relatively higher in IgE mediated group (P=0.023, P=0.032). The incidence of a family history in allergic disease and the mean of SCORing Atopic Dermatitis index had no difference between the two groups. Serum IL-4, IFN-gamma, IL-10, IL-17 were higher in the IgE mediated group, but there were no statistically significant differences between two groups (P>0.05). CONCLUSION: IgE mediated AD showed higher total eosinophil count and higher incidence of bronchial asthma and allergic rhinitis than non IgE mediated AD.
Academic Medical Centers ; Asthma ; Busan ; Child* ; Dermatitis, Atopic* ; Eosinophils ; Flow Cytometry ; Humans ; Immunoglobulin E* ; Immunologic Factors ; Incidence ; Interferon-gamma ; Interleukin-10 ; Interleukin-17 ; Interleukin-4 ; Interleukins ; Methods ; Rhinitis ; Skin

PURPOSE: In a previous study, we have shown that anticancer agents inhibiting topoisomerases improve survival of tumor cells under hypoxic condition. In the present study, we evaluated whether and how cell survival effect of the anticancer agents under hypoxic conditions could be eliminated by the addition of nitroimidazoles, a class of bioreductive agents. METHODS: Human hepatocellular carcinoma cells (HepG2) were incubated with different combinations of pimonidazole (1~1,000 microg/ml) and doxorubicin (0.1 or 1 microg/ml) concentrations under different O2 concentrations [1, 3, 5, 10 and 21 O2]. Then cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured, and DNA fragmentation assay was performed. Finally, different combinations of nitroimidazoles, such as pimonidazole, misonidazole, etanidazole, tinidazole, metronidazole, ornidazole or dimetridazole, and anticancer agents, such as doxorubicin, campothecin, epirubicin, dactinomycin, etoposide or mitomycin C was added to the cell culture medium under hypoxic conditions (1% O2). RESULTS: Pimonidazole at a concentration of 100 microg/ml eliminated cell survival effect of doxorubicin at the concentrations of 0.1 and 1 microg/ml under hypoxic condition (1% O2) by promoting apoptosis. Almost all the cells died even after 24 hours of incubation for all the oxygen concentrations at a combination of 100 microg/ml pimonidazole and 1 microg/ml doxorubicin. Finally, pimonidazole at a concentration of 100 microg/ml, and misonidazole or etanidazole at a concentration of 1,000 microg/ml eliminated cell survival effect of all the anticancer agents tested under hypoxic condition. CONCLUSION: Combination therapy of doxorubicin (adriamycin) with pimonidazole can maximize dororubicin efficacy by eliminating cell survival effect of doxorubicin under hypoxic conditions in treating solid tumors, such as breast cancer.
Anoxia ; Antineoplastic Agents ; Apoptosis ; Breast Neoplasms ; Carcinoma, Hepatocellular ; Cell Count ; Cell Culture Techniques ; Cell Survival ; Dactinomycin ; Dimetridazole ; DNA Fragmentation ; Doxorubicin ; Epirubicin ; Etanidazole ; Etoposide ; Glucose ; Humans ; Lactic Acid ; Metronidazole ; Misonidazole ; Mitomycin ; Nitroimidazoles ; Ornidazole ; Oxygen ; Tinidazole

Primary Hyperparathyroidism is the metabolism abnormality of calcium, phosphate, and bone due to the high synthesis of parathyroid hormone, a rare endocrine disease in children. It scarcely occurs in children so that till now it was reported only 4 cases in Korea, especially with abdominal symptoms. We report this case of primary hyperparathyroidism with brief review of literatures.
Abdominal Pain ; Calcium ; Child ; Endocrine System Diseases ; Humans ; Hyperparathyroidism, Primary ; Korea ; Parathyroid Hormone ; Parathyroid Neoplasms

OBJECTIVE: Tamoxifen is a nonsteroidal hormone that functions as a selective estrogen-receptor (ER) modulator in breast tissue. It is the first-choice drug for the postoperative treatment of ER-positive breast cancer patients. However, tamoxifen, if administered for a prolonged duration, has estrogen-like effects on the uterus, leading to an increased risk for the development of endometrial diseases such as endometrial hyperplasia, endometrial polyp, and endometrial cancer. This study was designed to investigate the effects of tamoxifen treatment on endometrium in breast cancer patients. METHODS: Fifty-five tamoxifen-treated breast cancer patients visited an outpatient gynecology clinic. We analyzed the endometrial pathology with consideration to the duration of tamoxifen treatment the patient symptoms and the endometrial thickness, as measured by transvaginal ultrasonography. Endometrial polypectomy was performed to obtained polyps from women presenting with abnormal bleeding (17 polyps from postmenopausal women who had not been treated with tamoxifen and 14 from women who had been treated with this drug). To investigate the effects of tamoxifen treatment on the endometrial polyps, we performed immunohistochemical staining for ER, the progesterone receptor (PR), and Ki67 on the polyps obtained from both groups of women. RESULTS: In 29 (52.7%) of 55 tamoxifen-treated breast cancer patients, the endometrium was more than 10 mm thick, and in 19 (65.5%) of these patients, the abnormalities noted comprised 11 endometrial polyps, 5 endometrial carcinomas, 2 submucosal myomas, and 1 endometrial hyperplasia. The incidence of endometrial proliferation was significantly higher in patients who had been treated with tamoxifen for less than 1 year (P=0.037) than in those who had been treated for more than 1 year. Although the endometrial carcinomas, submucosal myomas, and endometrial hyperplasia were found in the patients who had been treated for more than 1 year, this result was not statistically significantwhen compared with the other group. As compared to the endometrial polyps obtained from women who had not received tamoxifen treatment, those obtained from patients who had received the treatment exhibited significantly lower levels of ER expression (P=0.000) in the glands and increased levels of PR (P=0.031) and Ki-67 expression (P=0.000) in the stroma. CONCLUSIONS: During tamoxifen treatment for breast cancer, the endometrial pathology should be investigated if transvaginal ultrasonography reveals the tissue to be more than 10 mm thick. Although tamoxifen has significant effects on the expression of hormone receptors, the mechanism underlying the development of endometrial polyps does not appear to be mediated by the ER.
Breast ; Breast Neoplasms ; Endometrial Hyperplasia ; Endometrial Neoplasms ; Endometrium ; Female ; Gynecology ; Hemorrhage ; Humans ; Incidence ; Myoma ; Outpatients ; Polyps ; Receptors, Progesterone ; Tamoxifen ; Uterine Diseases ; Uterine Hemorrhage ; Uterus

PURPOSE: Antibiotics that kill or suppress the growth of bacteria also affect tumors directly or indirectly. The authors aimed to show whether some antibiotics can improve cancer cell survival under hypoxic conditions, and how the antibiotics improve the cells under hypoxic conditions. METHODS: Human hepatocellular carcinoma cells (HepG2) were grown at 1% oxygen concentration. Cell numbers, glucose concentrations and lactic acid concentrations in the medium were measured at different incubation times, in the absence or presence of aminoglycosides, tetracyclines, quinolones, penicillins, cephalosporins, sulfonamides, or chloramphenicols. DNA fragmentation assay was performed to study the mechanism how some antibiotics improve the cell survival under hypoxic conditions. RESULTS: Of the antibiotics tested, only aminoglycosides, tetracyclines, quinolones and the chloramphenicol improved cell survival under hypoxic conditions. Geneticin (G418), an aminoglycoside chosen as an example, improved cell survival even if glucose in the medium was completely consumed. At the same time, the appearance of DNA ladder was delayed in the presence of geneticin, which was also the same for the other antibiotics that improved cell survival under hypoxic conditions. CONCLUSION: Some antibiotics improved hepatocellular carcinoma cells under ischemic conditions by inhibiting apoptosis. The results implies that the antibiotics might adversely affect solid tumors, by improving cancer cell growth where hypoxic or ischemic conditions occur in the core region. Therefore, we might be cautious in choosing antibiotics for cancer patients with solid tumors, especially when the patients should be treated with antibiotics for a long time.
Aminoglycosides ; Anoxia ; Anti-Bacterial Agents* ; Apoptosis ; Bacteria ; Carcinoma, Hepatocellular* ; Cell Count ; Cell Survival ; Cephalosporins ; Chloramphenicol ; DNA ; DNA Fragmentation ; Glucose ; Humans* ; Lactic Acid ; Oxygen ; Penicillins ; Quinolones ; Sulfonamides ; Tetracyclines

The 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNP), a protein of unknown function in vivo, is abundantly expressed in myelinating glia in two isoforms, CNP1 and CNP2. In this study, immunoblot analysis showed that CNP1 is the major isoform in adult forebrain, and that both isoforms are included in the postsynaptic density (PSD) fraction and tyrosine-phosphorylated at the basal level. However, subcellular distribution and detergent extraction data showed that CNP is nonspecifically associated with the PSD fraction. Immunocytochemistry revealed that CNP is detected, in a weak but punctate pattern, in dissociated rat hippocampal neurons of 3 days to 2 weeks in vitro. The CNP-positive punctae were distributed throughout soma and dendrites, and distinct from PSD95-positive ones. Immunoblot analysis indicated that CNP is also expressed in neuronal stem cell lines, HiB5 and F11. Interestingly, in addition to the known two isoforms, a new CNP isoform of MW 45 kDa was expressed in these cell lines and was the major type of isoform in F11 cells. Taken together, our data suggest that CNP is expressed in the early stage of in vitro development and nonspecifically included in the adult rat PSD fraction.
2',3'-Cyclic-Nucleotide Phosphodiesterases/*metabolism ; Aging/physiology ; Animals ; Cells, Cultured ; Hippocampus/cytology/metabolism ; Immunohistochemistry ; Nerve Tissue Proteins/*metabolism ; Neurons/metabolism ; Phosphotyrosine/metabolism ; Prosencephalon/cytology/*metabolism ; Rats ; Rats, Sprague-Dawley ; Substrate Specificity