PURPOSE: Current treatment of glioblastoma after surgery consists of a combination of fractionated radiotherapy and temozolomide. However, it is difficult to completely remove glioblastoma because it has uncertain boundaries with surrounding tissues. Moreover, combination therapy is not always successful because glioblastoma has diverse resistances. To overcome these limitations, we examined the combined effects of chemotherapy and knockdown of mitogen-activated protein kinase phosphatase-1 (MKP-1). MATERIALS AND METHODS: We used ten different anti-cancer drugs (cisplatin, cyclophosphoamide, doxorubicin, epirubicin, etoposide, 5-fluorouracil, gemcitabine, irinotecan, mitomycin C, and vincristine) to treat glioblastoma multiforme (GBM) cells. Knockdown of MKP-1 was performed using siRNA and lipofectamine. The basal level of MKP-1 in GBM was analyzed based on cDNA microarray data obtained from the Gene Expression Omnibus (GEO) databases. RESULTS: Anti-cancer drug-induced cell death was significantly enhanced by knockdown of MKP-1, and this effect was most prominent in cells treated with irinotecan and etoposide. Treatment with these two drugs led to significantly increased phosphorylation of c-Jun N-terminal kinase (JNK) in a time-dependent manner, while pharmacological inhibition of JNK partially inhibited drug-induced cell death. Knockdown of MKP-1 also enhanced drug-induced phosphorylation of JNK. CONCLUSION: Increased MKP-1 expression levels could be the cause of the high resistance to conventional chemotherapeutics in human GBM. Therefore, MKP-1 is an attractive target for overcoming drug resistance in this highly refractory malignancy.
Apoptosis ; Camptothecin ; Cell Death ; Dacarbazine ; Deoxycytidine ; Doxorubicin ; Drug Resistance ; Drug Resistance, Multiple ; Dual Specificity Phosphatase 1 ; Epirubicin ; Etoposide ; Fluorouracil ; Gene Expression ; Glioblastoma ; Humans ; JNK Mitogen-Activated Protein Kinases ; Lipids ; Mitomycin ; Oligonucleotide Array Sequence Analysis ; Phosphorylation ; Phosphotransferases ; Protein Kinases ; RNA, Small Interfering

Background and purpose: The availability and promise of effective treatments for neurodegenerative disorders are increasing the importance of early diagnosis. Having molecular and biochemical markers of Alzheimer's disease (AD) would complement clinical approaches, and further the goals of early and accurate diagnosis. Combining multiple biomarkers in evaluations significantly increases the sensitivity and specificity of the biochemical tests. Methods: In this study, we used color-coded bead-based Luminex technology to test the potential of using chemokines and cytokines as biochemical markers of AD. We measured the levels of 22 chemokines and cytokines in the serum and cerebrospinal fluid (CSF) of 32 de novo patients (13 controls, 11 AD, and 8 Parkinson's disease [PD]). Results: MCP-1 was the only cytokine detectable in CSF, and its levels did not differ between control and disease groups. However, the serum concentration of eotaxin was significantly higher in AD patients than in the control group. Conclusions: The analysis of multiple inflammatory mediators revealed marginal differences in their CSF and serum concentrations for the differential diagnosis of AD and PD. These results provide evidence that immunological responses are not major contributors to the pathogenesis of AD and PD.
Alzheimer Disease ; Biomarkers ; Chemokines ; Complement System Proteins ; Cytokines ; Diagnosis, Differential ; Early Diagnosis ; Humans ; Neurodegenerative Diseases ; Parkinson Disease ; Sensitivity and Specificity

Alveolar Bone Loss ; Alveolar Process ; Alveolar Ridge Augmentation ; Bone Regeneration ; Dentistry ; Female ; Humans ; Inlays ; Mandible ; Osteoblasts ; Osteogenesis ; Osteogenesis, Distraction ; Polytetrafluoroethylene ; Titanium ; Transplants

Objective: To validate a simplified ordinal scoring method, referred to as modified length-based grading, for assessing coronary artery calcium (CAC) severity on non-electrocardiogram (ECG)-gated chest computed tomography (CT). Materials and Methods: This retrospective study enrolled 120 patients (mean age ± standard deviation [SD], 63.1 ± 14.5 years; male, 64) who underwent both non-ECG-gated chest CT and ECG-gated cardiac CT between January 2011 and December 2021. Six radiologists independently assessed CAC severity on chest CT using two scoring methods (visual assessment and modified length-based grading) and categorized the results as none, mild, moderate, or severe. The CAC category on cardiac CT assessed using the Agatston score was used as the reference standard. Agreement among the six observers for CAC category classification was assessed using Fleiss kappa statistics. Agreement between CAC categories on chest CT obtained using either method and the Agatston score categories on cardiac CT was assessed using Cohen’s kappa. The time taken to evaluate CAC grading was compared between the observers and two grading methods. Results: For differentiation of the four CAC categories, interobserver agreement was moderate for visual assessment (Fleiss kappa, 0.553 [95% confidence interval {CI}: 0.496–0.610]) and good for modified length-based grading (Fleiss kappa, 0.695 [95% CI: 0.636–0.754]). The modified length-based grading demonstrated better agreement with the reference standard categorization with cardiac CT than visual assessment (Cohen’s kappa, 0.565 [95% CI: 0.511–0.619 for visual assessment vs. 0.695 [95% CI: 0.638–0.752] for modified length-based grading). The overall time for evaluating CAC grading was slightly shorter in visual assessment (mean ± SD, 41.8 ± 38.9 s) than in modified length-based grading (43.5 ± 33.2 s) (P < 0.001). Conclusion The modified length-based grading worked well for evaluating CAC on non-ECG-gated chest CT with better interobserver agreement and agreement with cardiac CT than visual assessment.

OBJECTIVES: Abnormal bone turnover and mineralization is the characteristic of the end-stage renal disease (ESRD) patients receiving dialysis treatment. Reduced bone mineral density (BMD) has been reported in ESRD patients in many recent studies. Recent study has demonstrated hypoxia increases the loss of bone mass whereas the use of erythropoietin (EPO) increases bone marrow mesenchymal stem cell in vitro, which is the commonly found in ESRD patients. The objective of the present study is to analyze the relationship between erythropoiesis and calcium, phosphorus, parathyroid hormone (PTH) status in ESRD patients. METHODS: This study was a cross-sectional analysis of 183 ESRD patients (78 males, 105 females) on dialysis with mean age of 52 +/- 13 years and mean dialysis duration of 3.4 +/- 3.0 years. Duration and dose of EPO administration, hemoglobin, serum ferritin, and iron were checked in all subjects. BMD was evaluated by DXA. RESULTS: Age was negatively, and body weight and c-calcium positively associated with spine and femur neck and total hip BMD. Hemoglobin was positively correlated with femur neck and total hip BMD. Total dose of EPO, iPTH, and alkaline phosphatase had no significant association with BMD. However, according to tertile of serum PTH concentration, BMD were worst in third tertile group. In multivariate linear regression analysis, age, weight, and serum PTH affect BMD. CONCLUSIONS: BMD was independently related with age and weight. Hemoglobin correlated positively with femur neck and total hip BMD. However, treatment with EPO had no association with BMD. Increased PTH was related with reduced BMD.
Alkaline Phosphatase ; Anoxia ; Body Weight ; Bone Density ; Bone Marrow ; Calcium ; Cross-Sectional Studies ; Dialysis ; Erythropoiesis ; Erythropoietin ; Femur Neck ; Ferritins ; Hemoglobins ; Hip ; Humans ; Iron ; Kidney Failure, Chronic ; Linear Models ; Male ; Mesenchymal Stromal Cells ; Parathyroid Hormone ; Phosphorus ; Spine

PURPOSE: This study was conducted in order to investigate the diuretic effects of Erythritol (ET) salt on urinary electrolyte excretion in Sprague-Dawley Rats. METHODS: Animals were divided into two groups: Salt group (n = 7) and Salt + ET fed group (n = 7). Animals were provided food and water ad libitum. Supplements were administered orally to animals for one week. RESULTS: Body weights were not statistically different between groups either on Day 1 or Day 7. However, water consumption of the Salt + ET group was significantly higher than that of the Salt group on Day 1 and Day 7. Urine volume of the Salt + ET group was approximately 27% and 38% higher than that of the Salt group on Day 1 and Day 7. In addition, we found that the total amounts of urinary electrolytes, such as sodium and potassium, of the Salt + ET group were significantly higher than those of the Salt group on Day 7. We also found that serum electrolyte concentrations did not differ between two groups. These results demonstrated that salt intake with ET was effective in increasing urinary electrolyte excretion, which might be caused by higher water intake and diuretic effect inhibiting reabsorption of water, sodium, and potassium in renal tubules. CONCLUSION: The results suggest that short-term supplementation of ET salt can be a potential diuretic agent by inhibiting sodium and potassium reabsorption and inducing loss of water.
Animals ; Body Weight ; Diuretics ; Drinking ; Electrolytes ; Erythritol ; Hypertension ; Potassium ; Rats* ; Rats, Sprague-Dawley ; Sodium ; Water

PURPOSE: The objective of this study was to investigate the effects of xyloologosaccharide (XOS)-sugar mixture on glycemic index (GI) and blood glucose in human subjects. METHODS: Randomized double-blind cross-over studies were conducted to examine the effect of sucrose with 14% xyloologosaccharide powder (Xylo 14) and sucrose with 20% xylooligosaccharide powder (Xylo 20) on GI and postprandial glucose response at 15, 30, 45, 60, 90, and 120 min. RESULTS: GIs of Xylo 14 and Xylo 20 were 60.0 +/- 23.5 classified within medium GI range, and 54.3 +/- 17.7 within low GI range, respectively. Xylo 14 and Xylo 20 showed significantly lower area under the glucose curve (AUC) for 0-15 min (p = 0.0113), 0-30 min (p = 0.0004), 0-45 min (p < 0.0001), 0-60 min (p < 0.0001), 0-90 min (p < 0.0001), and 0-120 min (p = 0.0001). In particular, compared with glucose, the blood glucose levels of Xylo 14 and Xylo 20 were significantly lower at every time point between 15 and 120 min. CONCLUSION: The results of this study suggested that Xylo 14 and Xylo 20 had an acute suppressive effect on GI and the postprandial glucose surge.
Adult* ; Blood Glucose* ; Cross-Over Studies ; Glucose ; Glycemic Index* ; Humans ; Sucrose