Catholic University of Daegu

About: Catholic University of Daegu is a education organization based out in Gyeongsan-si, South Korea. It is known for research contribution in the topics: Population & Apoptosis. The organization has 2745 authors who have published 5670 publications receiving 80311 citations.

Differential in vitro and cellular effects of iron chelators for hypoxia inducible factor hydroxylases

Abstract: Hypoxia inducible factor 1α (HIF-1α), an essential transcriptional factor, is negatively regulated by two different types of oxygen and Fe(2+) -dependent HIF hydroxylases, proline hydroxylase (PHD) and factor inhibiting HIF (FIH), under normoxia. Iron chelators have therefore been used for inducing HIF-1α expression by inhibiting the hydroxylases. In this study, the iron chelators displayed differential effects for PHD and FIH in cells depending on their iron specificity and membrane permeability rather than their in vitro potencies. The membrane permeability of the strict Fe(2+) -chelator potentially inhibited both hydroxylases, whereas the membrane impermeable one showed no inhibitory effect in cells. In contrast, the depletion of the extracellular Fe(3+) ion was mainly correlated to PHD inhibition, and the membrane permeable one elicited low efficacy for both enzymes in cells. The 3'-hydroxyl group of quercetin, a natural flavonoid, was critical for inhibition of intracellular hydroxylases. Since the 3'-methylation of quercetin is induced by catechol-O-methyl transferase, the enzyme may regulate the intracellular activity of quercetin. These data suggest that the multiple factors of iron-chelators may be responsible for regulating the intracellular activity HIF hydroxylases.

Serum TWEAK as a biomarker for disease activity of systemic lupus erythematosus.

Abstract: This study aimed to identify serum and urine biomarkers that correlate with disease activity in female patients with systemic lupus erythematosus (SLE). Serum and urine levels of interferon γ-induced protein-10 (IP-10), TNF-like weak inducer of apoptosis (TWEAK), and monocyte chemotactic protein-1 (MCP-1) of 70 patients with SLE and 61 healthy controls were measured with enzyme-linked immunosorbent assays. The serum and urine levels of TWEAK, IP-10, and MCP-1 in both high and low SLE disease activity index (SLEDAI) groups of SLE patients were markedly higher compared with those of healthy controls. Moreover, the serum TWEAK level was positively correlated with the serum IP and serum MCP-1 levels (p < 0.001 for both). The serum TWEAK levels, SLEDAI scores, and urine protein/creatinine levels were significantly different between the SLE group with non-renal involvement and with renal involvement (p = 0.034, p < 0.001, and p < 0.001, respectively). The serum TWEAK level was a crucial determinant for a high SLEDAI score and renal involvement (p = 0.044 and p = 0.046, respectively). Serum TWEAK might be a serologic biomarker candidate that reflects disease activity and renal involvement in patients with SLE.

Alkaloids from Piper nigrum Exhibit Antiinflammatory Activity via Activating the Nrf2/HO-1 Pathway.

Abstract: In the present study, ten alkaloids, namely chabamide (1), pellitorine (2), retrofractamide A (3), pyrroperine (4), isopiperolein B (5), piperamide C9:1 (8E) (6), 6,7­dehydrobrachyamide B (7), 4,5-dihydropiperine (8), dehydropipernonaline (9), and piperine (10), were isolated from the fruits of Piper nigrum. Among these, chabamide (1), pellitorine (2), retrofractamide A (3), isopiperolein B (5), and 6,7­dehydrobrachyamide B (7) exhibited significant inhibitory activity on lipopolysaccharide-induced nitric oxide (NO) production in RAW264.7 cells, with IC50 values of 6.8, 14.5, 30.2, 23.7, and 38.5 μM, respectively. Furthermore, compound 1 inhibited lipopolysaccharide-induced NO production in bone marrow-derived macrophages with IC50 value of 9.5 μM. Consistent with NO inhibition, treatment of RAW264.7 cells with chabamide (1), pellitorine (2), and 6,7­dehydrobrachyamide B (7) suppressed expression of inducible NO synthase and cyclooxygenase-2. Chabamide (1), pellitorine (2), and 6,7­dehydrobrachyamide B (7) induced heme-oxygenase-1 expression at the transcriptional level. In addition, compound 1 induced the nuclear translocation of nuclear factor-E2-related factor 2 (Nrf2) and upregulated the expression of Nrf2 target genes, NAD(P)H:quinone oxidoreductase 1 and γ-glutamyl cysteine synthetase catalytic subunit, in a concentration-dependent manner in RAW264.7 cells. These findings suggest that chabamide (1) from P. nigrum exert antiinflammatory effects via the activation of the Nrf2/heme-oxygenase-1 pathway; hence, it might be a promising candidate for the treatment of inflammatory diseases. Copyright © 2017 John Wiley & Sons, Ltd.

Prognostic Value of Volumetric Parameters Measured by Pretreatment 18F FDG PET/CT in Patients With Cutaneous Malignant Melanoma.

Abstract: Purpose of the report This study was performed to evaluate the prognostic relevance of metabolic tumor volume (MTV) and total lesion glycolysis (TLG) measured using F FDG PET/CT in patients with primary cutaneous malignant melanoma (CMM). Materials and methods We conducted a retrospective review (July 2005 to November 2010) of 41 patients with a histological diagnosis of CMM who underwent pretreatment F FDG PET/CT. PET parameters (maximum standardized uptake value [SUVmax], MTV, and TLG) of the primary tumor were measured. Clinical variables such as age, sex, clinical stage, location and thickness of the primary lesion, and existence of ulceration were also assessed. Univariate and multivariate analyses for disease-free survival (DFS) and melanoma-specific survival (MSS) were performed using the Kaplan-Meier method and Cox proportional hazards models. Results SUVmax and TLG were found to be significantly higher in patients with recurrence than in patients without recurrence (3.98 ± 2.91 vs 1.89 ± 1.35, P = 0.0145; 9.16 ± 8.44 vs 3.72 ± 3.64, P = 0.0249). SUVmax and TLG were also found to be significantly higher in nonsurvivors than in survivors (4.21 ± 3.06 vs 2.00 ± 1.46, P = 0.0260; 10.53 ± 8.83 vs 3.67 ± 3.44, P = 0.0170). The optimal cutoff values for DFS determined using a time-dependent receiver operating characteristic (ROC) curve were 1.8 for SUVmax, 6.07 cm for MTV, and 4.046 for TLG. Sixteen (39%) of the 41 patients experienced recurrence during the follow-up period. In univariate analysis, age (P = 0.0382), male sex (P = 0.0187), ulceration of the primary lesion (P = 0.0001), stage ≥ III (P = 0.0011), SUVmax greater than 1.8 (P = 0.0006), MTV greater than 6.07 cm (P = 0.0136), and TLG greater than 4.046 (P = 0.0010) affected DFS, whereas the other variables (location of the primary lesion and thickness of primary lesion) did not. After adjustment for the effects of the clinical parameters (age, sex, clinical stage, and existence of ulceration), SUVmax, MTV, and TLG were all significant predictors of DFS, and the best predictive factor was SUVmax. Thirteen (32%) of the 41 patients died because of CMM during the follow-up period. The optimal cutoff values for MSS determined using a time-dependent ROC curve were 2.2 for SUVmax, 4.02 cm for MTV, and 4.352 for TLG. In univariate analysis, ulceration of the primary lesion (P = 0.0005), SUVmax greater than 2.2 (P = 0.0001), MTV greater than 4.02 cm (P = 0.0071), and TLG greater than 4.352 (P = 0.0001) affected MSS, whereas the other variables (age, sex, clinical stage, primary lesion site, and thickness of the primary lesion) did not. After adjustment for the effect of the clinical parameter (existence of ulceration), MTV and TLG were significant predictors of MSS, and the best predictive factor of MSS was TLG. Conclusions Pretreatment MTV and TLG may be useful in stratifying the likelihood of recurrence and melanoma-specific death, and TLG was found to be the best predictive marker for predicting melanoma-specific death.