BACKGROUND: Inflammatory bowel disease (IBD) is an incurable disease that negatively influences the quality of life of patients. Current and emerging therapies target proinflammatory cytokines and/or receptors to downregulate proinflammatory responses, but insufficient remission requires other therapeutic agents. Herein, we report that the synthetic antiinflammatory peptide 15 (SAP15) is capable of cell penetration and anti-inflammatory activity in human macrophages. METHODS: SAP15 was labeled with fluorescence and administered to human leukemia monocytic cells (THP-1) cells for cell penetration analysis. Using biolayer interferometry analysis, the binding affinity of SAP15 with histone deacetylase 5 (HDAC5) was measured. SAP15-treated THP-1 cells were analyzed by protein phosphorylation assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). In addition, in vivo analysis of the therapeutic effect on IBD was observed in a dextran sulfate sodium (DSS)-induced model. Samples from SAP15-treated mice were analyzed at both the macroscopic and microscopic levels using ELISA, myeloperoxidase (MPO) assays, and histological evaluations. RESULTS: SAP15 was internalized within the cytosol and nucleus of THP-1 cells and bound to the HDAC5 protein. SAP15-treated macrophages were assessed for protein phosphorylation and showed inhibited phosphorylation of HDAC5 and other immune-related proteins, which led to increased M2-like macrophage markers and decreased M1-like macrophage markers and tumor necrosis factor-a and interleukin-6 cytokine levels. The SAP15 treatment on IBD model showed significant recovery of colon length. Further histological analysis of colon demonstrated the therapeutic effect of SAP15 on mucosal layer. Moreover, proinflammatory cytokine levels and MPO activity from the plasma show that SAP15 is effective in reduced proinflammatory responses. CONCLUSION These findings suggest that SAP15 is a novel peptide with a novel cell-penetrating peptide with antiinflammatory property that can be used as a therapeutic agent for IBD and other inflammatory diseases.

Purpose: In this study, we aimed to determine the value of hypoxic liver injury (HLI) in the emergency room (ER) for predicting hypoxic hepatitis (HH) and in-hospital mortality in ST elevation myocardial infarction (STEMI) patients. Materials and Methods: 1537 consecutive STEMI patients were enrolled. HLI in the ER was defined as a ≥2-fold increase in serum aspartate transaminase (AST). HH was defined as a ≥20-fold increase in peak serum transaminase. Patients were divided into four groups according to HLI and HH status (group 1, no HLI or HH; group 2, HLI, but no HH; group 3, no HLI, but HH; group 4, both HLI and HH). Results: The incidences of HLI and HH in the ER were 22% and 2%, respectively. In-hospital mortality rates were 3.1%, 11.8%, 28.6%, and 47.1% for groups 1, 2, 3, and 4, respectively. Patients with HLI and/or HH had worse Killip class, higher cardiac biomarker elevations, and lower left ventricular ejection fraction. Multivariate logistic regression analysis showed that HLI in the ER was an independent predictor of HH [odds ratio 2.572, 95% confidence interval (CI) 1.166–5.675, p=0.019]. The predictive value of HLI in the ER for the development of HH during hospitalization was favorable [area under the curve (AUC) 0.737, 95% CI 0.643–0.830, sensitivity 0.548, specificity 0.805, for cut-off value AST >80]. Furthermore, in terms of in-hospital mortality, predictive values of HLI in the ER and HH during hospitalization were comparable (AUC 0.701 for HLI at ER and AUC 0.674 for HH). Conclusion Among STEMI patients, HLI in the ER is a significant predictor for the development of HH and mortality during hospitalization (INTERSTELLAR ClinicalTrials.gov number, NCT02800421).

Purpose: In this study, we aimed to determine the value of hypoxic liver injury (HLI) in the emergency room (ER) for predicting hypoxic hepatitis (HH) and in-hospital mortality in ST elevation myocardial infarction (STEMI) patients. Materials and Methods: 1537 consecutive STEMI patients were enrolled. HLI in the ER was defined as a ≥2-fold increase in serum aspartate transaminase (AST). HH was defined as a ≥20-fold increase in peak serum transaminase. Patients were divided into four groups according to HLI and HH status (group 1, no HLI or HH; group 2, HLI, but no HH; group 3, no HLI, but HH; group 4, both HLI and HH). Results: The incidences of HLI and HH in the ER were 22% and 2%, respectively. In-hospital mortality rates were 3.1%, 11.8%, 28.6%, and 47.1% for groups 1, 2, 3, and 4, respectively. Patients with HLI and/or HH had worse Killip class, higher cardiac biomarker elevations, and lower left ventricular ejection fraction. Multivariate logistic regression analysis showed that HLI in the ER was an independent predictor of HH [odds ratio 2.572, 95% confidence interval (CI) 1.166–5.675, p=0.019]. The predictive value of HLI in the ER for the development of HH during hospitalization was favorable [area under the curve (AUC) 0.737, 95% CI 0.643–0.830, sensitivity 0.548, specificity 0.805, for cut-off value AST >80]. Furthermore, in terms of in-hospital mortality, predictive values of HLI in the ER and HH during hospitalization were comparable (AUC 0.701 for HLI at ER and AUC 0.674 for HH). Conclusion Among STEMI patients, HLI in the ER is a significant predictor for the development of HH and mortality during hospitalization (INTERSTELLAR ClinicalTrials.gov number, NCT02800421).

BACKGROUND AND OBJECTIVES: We aimed to compare outcomes of complete revascularization (CR) versus culprit-only revascularization for ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) in the 2nd generation drug-eluting stent (DES) era. METHODS: From 2009 to 2014, patients with STEMI and MVD, who underwent primary percutaneous coronary intervention (PCI) using a 2nd generation DES for culprit lesions were enrolled. CR was defined as PCI for a non-infarct-related artery during the index admission. Major adverse cardiovascular event (MACE) was defined as cardiovascular (CV) death, non-fatal myocardial infarction, target lesion revascularization, or heart failure during the follow-up year. RESULTS: In total, 705 MVD patients were suitable for the analysis, of whom 286 (41%) underwent culprit-only PCI and 419 (59%) underwent CR during the index admission. The incidence of MACE was 11.5% in the CR group versus 18.5% in the culprit-only group (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.37–0.86; p<0.01; adjusted HR, 0.64; 95% CI, 0.40–0.99; p=0.04). The CR group revealed a significantly lower incidence of CV death (7.2% vs. 12.9%; HR, 0.51; 95% CI, 0.31–0.86; p=0.01 and adjusted HR, 0.57; 95% CI; 0.32–0.97; p=0.03, respectively). CONCLUSIONS: CR was associated with better outcomes including reductions in MACE and CV death at 1 year of follow-up compared with culprit-only PCI in the 2nd generation DES era.
Arteries ; Drug-Eluting Stents ; Follow-Up Studies ; Heart Failure ; Humans ; Incidence ; Myocardial Infarction ; Percutaneous Coronary Intervention

BACKGROUND AND OBJECTIVES: We aimed to compare outcomes of complete revascularization (CR) versus culprit-only revascularization for ST-segment elevation myocardial infarction (STEMI) and multivessel disease (MVD) in the 2nd generation drug-eluting stent (DES) era. METHODS: From 2009 to 2014, patients with STEMI and MVD, who underwent primary percutaneous coronary intervention (PCI) using a 2nd generation DES for culprit lesions were enrolled. CR was defined as PCI for a non-infarct-related artery during the index admission. Major adverse cardiovascular event (MACE) was defined as cardiovascular (CV) death, non-fatal myocardial infarction, target lesion revascularization, or heart failure during the follow-up year. RESULTS: In total, 705 MVD patients were suitable for the analysis, of whom 286 (41%) underwent culprit-only PCI and 419 (59%) underwent CR during the index admission. The incidence of MACE was 11.5% in the CR group versus 18.5% in the culprit-only group (hazard ratio [HR], 0.56; 95% confidence interval [CI], 0.37–0.86; p<0.01; adjusted HR, 0.64; 95% CI, 0.40–0.99; p=0.04). The CR group revealed a significantly lower incidence of CV death (7.2% vs. 12.9%; HR, 0.51; 95% CI, 0.31–0.86; p=0.01 and adjusted HR, 0.57; 95% CI; 0.32–0.97; p=0.03, respectively). CONCLUSIONS CR was associated with better outcomes including reductions in MACE and CV death at 1 year of follow-up compared with culprit-only PCI in the 2nd generation DES era.

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.
Anoxia ; Brain Neoplasms ; Cell Death* ; Cell Line ; Dichloroacetic Acid ; Glioblastoma* ; Glucose ; Glycolysis ; Metabolism ; Oxidative Phosphorylation ; Oxidoreductases ; Phosphotransferases ; Pyruvic Acid

PURPOSE: To compare the effectiveness of device closure and medical therapy in prevention of recurrent embolic event in the Korean population with cryptogenic stroke and patent foramen ovale (PFO). MATERIALS AND METHODS: Consecutive 164 patients (men: 126 patients, mean age: 48.1 years, closure group: 72 patients, medical group: 92 patients) were enrolled. The primary end point was a composite of death, stroke, transient ischemic attack (TIA), or peripheral embolism. RESULTS: Baseline characteristics were similar in the two groups, except age, which was higher in the medical group (45.3±9.8 vs. 50.2±6.1, p<0.0001), and risk of paradoxical embolism score, which was higher in the closure group (6.2±1.6 vs. 5.7±1.3, p=0.026). On echocardiography, large right-to-left shunt (81.9% vs. 63.0%, p=0.009) and shunt at rest/septal hypermobility (61.1% vs. 23.9%, p<0.0001) were more common in the closure group. The device was successfully implanted in 71 (98.6%) patients. The primary end point occurred in 2 patients (2 TIA, 2.8%) in the closure group and in 2 (1 death, 1 stroke, 2.2%) in the medical group. Event-free survival rate did not differ between the two groups. CONCLUSION: Compared to medical therapy, device closure of PFO in patients with cryptogenic stroke did not show difference in reduction of recurrent embolic events in the real world's setting. However, considering high risk of echocardiographic findings in the closure group, further investigation of the role of PFO closure in the Asian population is needed.
Adult ; Aged ; Aged, 80 and over ; Cardiac Catheterization/adverse effects ; Disease-Free Survival ; Embolism/etiology/*prevention & control ; Female ; Fibrinolytic Agents/adverse effects/*therapeutic use ; Foramen Ovale, Patent/complications/*drug therapy/mortality/*surgery ; Humans ; Ischemic Attack, Transient/*drug therapy/mortality/*surgery ; Male ; Middle Aged ; Republic of Korea/epidemiology ; Risk ; Secondary Prevention/methods ; *Septal Occluder Device/adverse effects ; Stroke/etiology/prevention & control ; Treatment Outcome

BACKGROUND: A lipo-prostaglandin E1 agonist is effective for the treatment of neurological symptoms of spinal stenosis when administered by an oral or intravenous route. we would like to reveal the therapeutic effect of an epidural injection of lipo-prostaglandin E1 on hyperalgesia in foraminal stenosis. METHODS: A total of 40 male Sprague-Dawley rats were included. A small stainless steel rod was inserted into the L5/L6 intervertebral foramen to produce intervertebral foraminal stenosis and chronic compression of the dorsal root ganglia (DRG). The rats were divided into three groups: epidural PGE1 (EP) (n = 15), saline (n = 15), and control (n = 10). In the EP group, 0.15 microg.kg-1 of a lipo-PGE1 agonist was injected daily via an epidural catheter for 10 days from postoperative day 3. In the saline group, saline was injected. Behavioral tests for mechanical hyperalgesia were performed for 3 weeks. Then, the target DRG was analyzed for the degree of chromatolysis, chronic inflammation, and fibrosis in light microscopic images. RESULTS: From the fifth day after lipo-PGE1 agonist injection, the EP group showed significant recovery from mechanical hyperalgesia, which was maintained for 3 weeks (P < 0.05). Microscopic analysis showed much less chromatolysis in the EP group than in the saline or control groups. CONCLUSIONS: An epidurally administered lipo-PGE1 agonist relieved neuropathic pain, such as mechanical hyperalgesia, in a rat foraminal stenosis model, with decreasing chromatolysis in target DRG. We suggest that epidurally administered lipo-PGE1 may be a useful therapeutic candidate for patients with spinal stenosis.
Alprostadil ; Animals ; Catheters ; Constriction, Pathologic ; Diagnosis-Related Groups ; Fibrosis ; Ganglia, Spinal ; Humans ; Hyperalgesia ; Inflammation ; Injections, Epidural ; Male ; Neuralgia ; Rats* ; Rats, Sprague-Dawley ; Spinal Stenosis* ; Stainless Steel

BACKGROUND AND OBJECTIVES: We investigated the predictors of the recovery of depressed left ventricular ejection fraction (LVEF) in patients with moderate or severe left ventricular (LV) systolic dysfunction after acute myocardial infarction (MI). SUBJECTS AND METHODS: We analyzed 1307 patients, who had moderately or severely depressed LVEF (<45%) on echocardiography soon after acute MI and who underwent a follow-up echocardiography, among 27369 patients from the Korea Working Group on the Myocardial Infarction Registry. Patients were categorized into two groups according to recovery of LVEF: group I with consistently depressed LVEF (<45%) at the follow-up echocardiography and group II with a recovery of LVEF (> or =45%). RESULTS: Recovery of LV systolic dysfunction was observed in 51% of the subjects (group II, n=663; DeltaLVEF, 16.2+/-9.3%), whereas there was no recovery in the remaining subjects (group I, n=644; DeltaLVEF, 0.6+/-7.1%). In the multivariate analysis, independent predictors of recovery of depressed LVEF were as follows {odds ratio (OR) [95% confidence interval (CI)]}: moderate systolic dysfunction {LVEF > or =30% and <45%; 1.73 (1.12-2.67)}, Killip class I-II {1.52 (1.06-2.18)}, no need for diuretics {1.59 (1.19-2.12)}, non-ST-segment elevation MI {1.55 (1.12-2.16)}, lower peak troponin I level {<24 ng/mL, median value; 1.55 (1.16-2.07)}, single-vessel disease {1.53 (1.13-2.06)}, and non-left anterior descending (LAD) culprit lesion {1.50 (1.09-2.06)}. In addition, the use of statin was independently associated with a recovery of LV systolic dysfunction {OR (95% CI), 1.46 (1.07-2.00)}. CONCLUSION: Future contractile recovery of LV systolic dysfunction following acute MI was significantly related with less severe heart failure at the time of presentation, a smaller extent of myonecrosis, or non-LAD culprit lesions rather than LAD lesions.
Diuretics ; Echocardiography ; Follow-Up Studies ; Heart Failure ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Korea ; Multivariate Analysis ; Myocardial Infarction ; Prognosis ; Stroke Volume ; Troponin I

The aims of this study were; 1) to develop the final version of the Korean Roland-Morris Disability Questionnaire (RDQ), and 2) to compare the responsiveness between the RDQ and the Oswestry Disability Index (ODI) scores in patients having low back pain. The psychometric properties of the final Korean RDQ were evaluated in 221 patients. Among them, 30 patients were reliability tested. Validity was evaluated using an 11-point numerical rating scale (NRS) and the Korean ODI. The receiver operating characteristic (ROC) curve analysis of the RDQ and the ODI was compared in 54 patients with lumbar zygapophyseal (facet) joint pain. There was a moderate relationship between the RDQ and NRS (r = 0.59, P < 0.01) and a strongly positive correlation between the RDQ and the ODI (r = 0.76, P < 0.001). The Korean RDQ with the higher area under the ROC curve showed a better overall responsive performance than did the ODI in patients with lumbar facet joint pain after medial branch radiofrequency neurotomy (P < 0.01). The results of the study present the final version of the Korean RDQ is valid for assessing functional status in a Korean population with chronic low back pain.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Disability Evaluation ; Disabled Persons ; Female ; Humans ; Low Back Pain/*diagnosis ; Male ; Middle Aged ; *Pain Measurement ; Psychometrics ; Questionnaires ; Republic of Korea ; Research Design ; Severity of Illness Index