Background: Preeclampsia (PE) is known to arise from insufficient trophoblast invasion as uterine spiral arteries lack remodeling. A significant reduction in placental perfusion induces an ischemic placental microenvironment due to reduced oxygen delivery to the placenta and fetus, leading to oxidative stress. Mitochondria are involved in the regulation of cellular metabolism and the production of reactive oxygen species (ROS). NME/NM23 nuceloside diphosphate kinase 4 (NME4) gene is known to have the ability to supply nucleotide triphosphate and deoxynucleotide triphosphate for replication and transcription of mitochondria. Our study aimed to investigate changes in NME4 expression in PE using trophoblast stem-like cells (TSLCs) from induced pluripotent stem cells (iPSCs) as a model of early pregnancy and peripheral blood mononuclear cells (PBMNCs) as a model of late preterm pregnancy. Methods: Transcriptome analysis using TSLCs was performed to identify the candidate gene associated with the possible pathophysiology of PE. Then, the expression of NME4 associated with mitochondrial function, p53 associated with cell death, and thioredoxin (TRX) linked to ROS were investigated through qRT-PCR, western blotting and deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick end labelling (TUNEL) assay. Results: In patients with PE, NME4 was significantly downregulated in TSLCs but upregulated in PBMNCs. p53 was shown to be upregulated in TSLCs and PBMNCs of PE. In addition, western blot analysis confirmed that TRX expression had the tendency to increase in TSLCs of PE. Similarly, TUNEL analysis confirmed that the dead cells were higher in PE than in normal pregnancy. Conclusion Our study showed that the expression of the NME4 differed between models of early and late preterm pregnancy of PE, and suggests that this expression pattern may be a potential biomarker for early diagnosis of PE.

The gastrointestinal tract is the most common extranodal site for lymphomas, and mucosa-associated lymphoid tissue lymphoma is the second most common histological lymphoma subtype. However, primary esophageal mucosa-associated lymphoid tissue lymphomas are extremely rare. Few such cases are documented, and the reports demonstrate inconsistent diagnostic and therapeutic strategies. Herein, a 54-year-old man was referred to our hospital for treatment of dysphagia. Esophagogastroduodenoscopy revealed a large, horseshoe-shaped subepithelial mass in the upper esophagus. Endoscopic ultrasonography and computed tomography revealed that the mass was well-demarcated and confined to the muscularis mucosa, with no abnormalities in other organs or lymph nodes. The mass was presumptively diagnosed as benign, and the patient underwent endoscopic mucosal dissection for pathological confirmation and symptom relief. Pathological examination of the dissection specimen revealed that it was a primary esophageal mucosa-associated lymphoid tissue lymphoma. As the patient had an elevated immunoglobulin G level and Helicobacter pylori infection, we administered adjuvant eradication therapy. The patient remains under surveillance and is free of lymphoma recurrence 36 months postoperatively. This case report demonstrates that endoscopic resection and H. pylori eradication are effective treatment strategies for early-stage esophageal mucosa-associated lymphoid tissue lymphoma.

Purpose: Mycoplasma pneumoniae pneumonia (MP) is a major cause of community-acquired pneumonia (CAP) in children and is associated with extrapulmonary manifestations (EPM). The incidence and risk factors for EPM in children are unknown. Methods: This was a retrospective study involving 65,243 pediatric patients with CAP between 2010 and 2015 at 23 nationwide hospitals in South Korea. Medical records were reviewed to collect information regarding the clinical characteristics, radiological results, and laboratory findings. Logistic regression with multivariate analysis was performed to evaluate the risk factors associated with EPM in MP. Results: The incidence of EPM was 23.9%, including elevation of liver enzymes (18.1%), mucocutaneous manifestations (4.4%), proteinuria (4.1%), cardiovascular and neurological manifestations (0.4%), hematologic manifestations (0.2%), and arthritis (0.2%). Statistical analysis showed that mucocutaneous manifestations significantly increased with elevated alanine aminotransferase (adjusted odds ratio [aOR], 3.623; 95% confidence interval [CI], 1.933-6.790) and atopic sensitization (aOR, 2.973; 95% CI, 1.615–5.475) and decreased with respiratory virus coinfection (aOR, 0.273; 95% CI, 0.084–0.887). Elevated liver enzymes were significantly associated with elevated lactate dehydrogenase (aOR, 3.055; 95% CI, 2.257–4.137), presence of pleural effusion (aOR, 2.635; 95% CI, 1.767–3.930), and proteinuria with respiratory virus coinfection (aOR, 2.245; 95% CI, 1.113–4.527). Conclusion Approximately 24% of pediatric patients with MP had various EPM. As the risk factors associated with each EPM were different, it is necessary to evaluate the various clinical aspects and findings of MP to predict and prepare for the occurrence of EPM.

Cell therapeutic agents for treating degenerative brain diseases using neural stem cells are actively being developed. However, few systems have been developed to monitor in real time whether the transplanted neural stem cells are actually differentiated into neurons. Therefore, it is necessary to develop a technology capable of specifically monitoring neuronal differentiation in vivo. In this study, we established a system that expresses cell membrane-targeting red fluorescent protein under control of the Synapsin promoter in order to specifically monitor differentiation from neural stem cells into neurons. In order to overcome the weak expression level of the tissue-specific promoter system, the partial 5′ UTR sequence of Creb was added for efficient expression of the cell surface-specific antigen. This system was able to track functional neuronal differentiation of neural stem cells transplanted in vivo, which will help improve stem cell therapies.
Antigens, Surface* ; Brain Diseases ; Neural Stem Cells ; Neurons* ; Stem Cells

Secondary hyperparathyroidism (HPT) usually result from parathyroid gland hyperplasia that produces excess parathyroid hormone (PTH). Decreased renal function leads to elevate serum phosphate levels and reduce vitamin D production, which results in hypocalcemia. Skeletal resistance to PTH results in persistently and frequently extremely elevated PTH levels and renal osteopathy. Treatment of choice for secondary HPT is medical management including calcitriol and vitamin D. However, for some cases in calciphylaxis and the failure including PTH >800 pg/mL or osteoporosis under maximal medical management surgical intervention could be an alternative option. We described a case of 47-year-old woman with surgical intervention for secondary hyperparathyroidism.
Autografts ; Calciphylaxis ; Calcitriol ; Female ; Humans ; Hyperparathyroidism, Secondary ; Hyperplasia ; Hypocalcemia ; Middle Aged ; Osteoporosis ; Parathyroid Glands ; Parathyroid Hormone ; Parathyroidectomy ; Transplantation, Autologous ; Vitamin D

PURPOSE: Rearrangement of the proto-oncogene rearranged during transfection (RET) has been newly identified potential driver mutation in lung adenocarcinoma. Clinically available tyrosine kinase inhibitors (TKIs) target RET kinase activity, which suggests that patients with RET fusion genes may be treatable with a kinase inhibitor. Nevertheless, the mechanisms of resistance to these agents remain largely unknown. Thus, the present study aimed to determine whether epidermal growth factor (EGF) and hepatocyte growth factor (HGF) trigger RET inhibitor resistance in LC-2/ad cells with CCDC6-RET fusion genes. MATERIALS AND METHODS: The effects of EGF and HGF on the susceptibility of a CCDC6-RET lung cancer cell line to RET inhibitors (sunitinib, E7080, vandetanib, and sorafenib) were examined. RESULTS: CCDC6-RET lung cancer cells were highly sensitive to RET inhibitors. EGF activated epidermal growth factor receptor (EGFR) and triggered resistance to sunitinib, E7080, vandetanib, and sorafenib by transducing bypass survival signaling through ERK and AKT. Reversible EGFR-TKI (gefitinib) resensitized cancer cells to RET inhibitors, even in the presence of EGF. Endothelial cells, which are known to produce EGF, decreased the sensitivity of CCDC6-RET lung cancer cells to RET inhibitors, an effect that was inhibited by EGFR small interfering RNA (siRNA), anti-EGFR antibody (cetuximab), and EGFR-TKI (Iressa). HGF had relatively little effect on the sensitivity to RET inhibitors. CONCLUSION: EGF could trigger resistance to RET inhibition in CCDC6-RET lung cancer cells, and endothelial cells may confer resistance to RET inhibitors by EGF. E7080 and other RET inhibitors may provide therapeutic benefits in the treatment of RET-positive lung cancer patients.
Adenocarcinoma/drug therapy/*genetics ; Cell Line, Tumor ; Cetuximab/pharmacology ; Drug Resistance, Neoplasm/drug effects/*genetics ; Epidermal Growth Factor/metabolism/*pharmacology ; *Gene Rearrangement ; Hepatocyte Growth Factor/*pharmacology ; Humans ; Indoles/pharmacology ; Lung Neoplasms/drug therapy/*genetics ; MAP Kinase Signaling System ; *Mutation ; Niacinamide/analogs & derivatives/pharmacology ; Phenylurea Compounds/pharmacology ; Piperidines/pharmacology ; Protein Kinase Inhibitors/therapeutic use ; Proto-Oncogene Proteins c-ret/*antagonists & inhibitors/genetics ; Pyrroles/pharmacology ; Quinazolines/pharmacology ; RNA, Small Interfering/pharmacology ; Receptor, Epidermal Growth Factor/genetics/metabolism ; Signal Transduction/drug effects ; fms-Like Tyrosine Kinase 3/metabolism

BACKGROUND/AIMS: Angiodysplasia is important in the differential diagnosis of upper gastrointestinal bleeding (UGIB), but the clinical features and outcomes associated with UGIB from angiodysplasia have not been characterized. We aimed to analyze the clinical characteristics and outcomes of angiodysplasia presented as UGIB. METHODS: Between January 2004 and December 2013, a consecutive series of patients admitted with UGIB were retrospectively analyzed. Thirty-five patients with bleeding from angiodysplasia were enrolled. We compared them with an asymptomatic control group (incidental finding of angiodysplasia in health screening, n = 58) and bleeding control group (simultaneous finding of angiodysplasia and peptic ulcer bleeding, n = 28). RESULTS: When patients with UGIB from angiodysplasia were compared with the asymptomatic control group, more frequent rates of nonantral location and large sized lesion (≥ 1 cm) were evident in multivariate analysis. When these patients were compared with the bleeding control group, they were older (mean age: 67.94 ± 9.16 years vs.55.07 ± 13.29 years, p = 0.03) and received less transfusions (p = 0.03). They also had more frequent rate of recurrence (40.0% vs. 20.7%, p = 0.02). CONCLUSIONS: Non-antral location and large lesions (≥ 1 cm) could be risk factors of UGIB of angiodysplasia. UGIB due to angiodysplasia was more common in older patients. Transfusion requirement would be less and a tendency of clinical recurrence might be apparent.
Angiodysplasia* ; Diagnosis, Differential ; Endoscopy ; Hemorrhage* ; Humans ; Mass Screening ; Multivariate Analysis ; Peptic Ulcer ; Recurrence ; Retrospective Studies ; Risk Factors*

PURPOSE: HM781-36B is a novel and irreversible pan-human epidermal growth factor receptor (HER) inhibitor with TEC cytoplasmic kinase inhibition. The aim of this study is to evaluate the antitumor activity and mechanism of action for HM781-36B in colorectal cancer (CRC) cell lines. MATERIALS AND METHODS: The CRC cell lines were exposed to HM781-36B and/or oxaliplatin (L-OHP), 5-fluorouracil (5-FU), SN-38. The cell viability was examined by Cell Titer-Glo luminescent cell viability assay kit. Change in the cell cycle and protein expression was determined by flow cytometry and immunoblot analysis, respectively. Synergism between 2 drugs was evaluated by the combination index. RESULTS: The addition of HM781-36B induced potent growth inhibition in both DiFi cells with EGFR overexpression and SNU-175 cells (IC50 = 0.003 and 0.005 microM, respectively). Furthermore, HM781-36B induced G1 arrest of the cell cycle and apoptosis, and reduced the levels of HER family and downstream signaling molecules, pERK and pAKT, as well as nonreceptor/cytoplasmic tyrosine kinase, BMX. The combination of HM781-36B with 5-FU, L-OHP, or SN-38 showed an additive or synergistic effect in most CRC cells. CONCLUSION: These findings suggest the potential roles of HM781-36B as the treatment for EGFR-overexpressing colon cancer, singly or in combination with chemotherapeutic agents. The role of BMX expression as a marker of response to HM781-36B should be further explored.
Apoptosis ; Cell Cycle ; Cell Line ; Cell Survival ; Colonic Neoplasms ; Colorectal Neoplasms* ; Cytoplasm ; Flow Cytometry ; Fluorouracil ; Humans ; Phosphotransferases ; Protein-Tyrosine Kinases ; Receptor, Epidermal Growth Factor

In the adult mammalian brain, neural-lineage cells are continuously generated in the subventricular zone (SVZ) and dentate gyrus of the hippocampus. These cells in vivo arising from the adult SVZ may be regulated by environmental enrichment (EE). EE is a method of raising animals in a huge cage containing novel objects, running wheels and social interaction with a complex combination of physical, cognitive, and social stimulations. EE can affect neural plasticity via overexpression of growth factors such as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF-1), fibroblast growth factor-2 (FGF-2), and synaptic activity-regulating genes. EE also have advanced effects on brain functions including the enhancement of motor and cognitive functions in normal and pathological states. Additionally, behavioral changes by EE are related with molecular changes including neurogenesis, gliogenesis, angiogenesis, axonal sprouting, and dendritic branching in the adult brain. In this review, we focus on brain plasticity and neurorestoration associated with molecular changes of neurotrophic growth factors such as BDNF, VEGF, IGF-1, FGF-2 and synaptic activity-regulating genes that occurs in interaction to EE.
Adult ; Animals ; Axons ; Brain* ; Brain-Derived Neurotrophic Factor ; Dentate Gyrus ; Fibroblast Growth Factor 2 ; Hippocampus ; Humans ; Insulin-Like Growth Factor I ; Intercellular Signaling Peptides and Proteins ; Interpersonal Relations ; Neurogenesis ; Plastics* ; Running ; Vascular Endothelial Growth Factor A

The incidence of Clostridium difficile infection is increasing worldwide, and its severity and resulting mortality are also on the rise. Metronidazole and oral vancomycin remain the treatments of choice, but there are concerns about treatment failure and the appearance of resistant strains. Furthermore, antibiotic therapy results in recurrence rates of at least 20%. Fecal transplantation may be a feasible treatment option for recurrent C. difficile infection; moreover, it may be an early treatment option for severe C. difficile infection. We report a case of severe C. difficile infection treated with fecal transplantation using a nasoenteric tube during an initial episode. This is the first reported case of fecal transplantation using a nasoenteric tube during an initial episode of C. difficile infection in Korea.
Clostridium difficile* ; Clostridium* ; Incidence ; Korea ; Metronidazole ; Mortality ; Recurrence ; Treatment Failure ; Vancomycin