Identification of hypoxanthine as a urine marker for non-Hodgkin lymphoma by low-mass-ion profiling

<p>Abstract</p> <p>Background</p> <p>Non-Hodgkin lymphoma (NHL) is a hematologic malignancy for which good diagnostic markers are lacking. Despite continued improvement in our understanding of NHL, efforts to identify diagnostic markers have yielded dismal results. Here, we translated low-mass-ion information in urine samples from patients with NHL into a diagnostic marker.</p> <p>Methods</p> <p>To minimize experimental error, we tested variable parameters before MALDI-TOF analysis of low-mass ions in urine. Urine from 30 controls and 30 NHL patients was analyzed as a training set for NHL prediction. All individual peak areas were normalized to total area up to 1000 m/z. The training set analysis was repeated four times. Low-mass peaks that were not affected by changes in experimental conditions were collected using MarkerView™ software. Human Metabolome Database (HMDB) searches and ESI LC-MS/MS analyses were used to identify low-mass ions that exhibited differential patterns in control and NHL urines. Identified low-mass ions were validated in a blinded fashion in 95 controls and 66 NHL urines to determine their ability to discriminate NHL patients from controls.</p> <p>Results</p> <p>The 30 highest-ranking low-mass-ion peaks were selected from the 60-urine training set, and three low-mass-ion peaks with high intensity were selected for identification. Of these, a 137.08-m/z ion showed lower mass-peak intensity in urines of NHL patients, a result that was validated in a 161-urine blind validation set (95 controls and 66 NHL urines). The 130.08-m/z ion was identified from HMDB searches and ESI LC-MS/MS analyses as hypoxanthine (HX). The HX concentration in urines of NHL patients was significantly decreased (P < 0.001) and was correlated with the mass-peak area of the 137.08-m/z ion. At an HX concentration cutoff of 17.4 μM, sensitivity and specificity were 79.2% and 78.4%, respectively.</p> <p>Conclusions</p> <p>The present study represents a good example of low-mass-ion profiling in the setting of disease screening using urine. This technique can be a powerful non-invasive diagnostic tool with high sensitivity and specificity for NHL screening. Furthermore, HX identified in the study may be a useful single urine marker for NHL screening.</p

Protective Effect of the Ethyl Acetate Fraction of Sargassum muticum Against Ultraviolet B–Irradiated Damage in Human Keratinocytes

The aim of this study was to investigate the cytoprotective properties of the ethyl acetate fraction of Sargassum muticum (SME) against ultraviolet B (UVB)-induced cell damage in human keratinocytes (HaCaT cells). SME exhibited scavenging activity toward the 1,1-diphenyl-2-picrylhydrazyl radicals and hydrogen peroxide (H2O2) and UVB-induced intracellular reactive oxygen species (ROS). SME also scavenged the hydroxyl radicals generated by the Fenton reaction (FeSO4 + H2O2), which was detected using electron spin resonance spectrometry. In addition, SME decreased the level of lipid peroxidation that was increased by UVB radiation, and restored the level of protein expression and the activities of antioxidant enzymes that were decreased by UVB radiation. Furthermore, SME reduced UVB-induced apoptosis as shown by decreased DNA fragmentation and numbers of apoptotic bodies. These results suggest that SME protects human keratinocytes against UVB-induced oxidative stress by enhancing antioxidant activity in cells, thereby inhibiting apoptosis

A Case of Non-Functioning Huge Adrenocortical Carcinoma Extending Into Inferior Vena Cava and Right Atrium

Primary adrenocortical carcinoma (ACC) is a rare tumor and its usual sites of metastasis are the lung (71%), lymph node (68%), liver (42%), and bone (26%). However, intracaval invasion extending into the right atrium is very rare and spontaneous regression of tumor burden in adrenal carcinoma is also rare. We report a case of ACC with direct invasion of the inferior vena cava and right atrium. A 34-yr-old male patient presented with progressive dyspnea, weight loss, and poor oral intake over 3 months. Non-functioning ACC with direct invasion of the inferior vena cava and right atrium was confirmed by imaging, pathologic, and hormonal study. Chemo-radio-therapy was attempted. However, tumor burden was not changed, but rather toxic hepatitis and thrombocytopenia were developed. His subjective symptoms and general conditions were improved after 1 month of conservative management and the patient was discharged. During clinical follow-up, this tumor showed spontaneous regression

Fermentation by Lactobacillus enhances anti-inflammatory effect of Oyaksungisan on LPS-stimulated RAW 264.7 mouse macrophage cells

<p>Abstract</p> <p>Background</p> <p>Oyaksungisan (OY) has been used as a traditional drug in east-Asian countries. However, its effect on inflammation still remains unknown. In this study, to provide insight into the biological effects of OY and OY fermented by <it>Lactobacillus</it>, we investigated their effects on lipopolysaccharide (LPS)-mediated inflammation in the RAW 264.7 murine macrophage cells.</p> <p>Methods</p> <p>The investigation was focused on whether OY and fermented OYs could inhibit the production of pro-inflammatory mediators such as nitric oxide (NO) and prostaglandin (PG) E₂as well as the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2, tumor necrosis factor (TNF)-α, interleukin (IL)-6, nuclear factor (NF)-κB and mitogen-activated protein kinases (MAPKs) in LPS-stimulated RAW 264.7 cells.</p> <p>Results</p> <p>We found that OY inhibits a little LPS-induced NO, PGE₂, TNF-α and IL-6 productions as well as the expressions of iNOS and COX-2. Interestingly, the fermentation significantly increased its inhibitory effect on the expression of all pro-inflammatory mediators. Furthermore, the fermented OYs exhibited elevated inhibition on the translocation of NF-κB p65 through reduced IκBα degradation as well as the phosphorylations of extracellular signal-regulated kinase (ERK), p38 and c-Jun NH₂-terminal kinase (JNK) MAPKs than untreated control or original OY.</p> <p>Conclusions</p> <p>Finally, the fermentation by <it>Lactobacillus </it>potentiates the anti-inflammatory effect of OY by inhibiting NF-κB and MAPK activity in the macrophage cells.</p

Prediction Model for the Risk of Scapular Winging in Young Women Based on the Decision Tree

Background: Scapular winging (SW) could be caused by tightness or weakness of the periscapular muscles. Although data mining techniques are useful in classifying or predicting risk of musculoskeletal disorder, predictive models for risk of musculoskeletal disorder using the results of clinical test or quantitative data are scarce. Objects: This study aimed to (1) investigate the difference between young women with and without SW, (2) establish a predictive model for presence of SW, and (3) determine the cutoff value of each variable for predicting the risk of SW using the decision tree method. Methods: Fifty young female subjects participated in this study. To classify the presence of SW as the outcome variable, scapular protractor strength, elbow flexor strength, shoulder internal rotation, and whether the scapula is in the dominant or nondominant side were determined. Results: The classification tree selected scapular protractor strength, shoulder internal rotation range of motion, and whether the scapula is in the dominant or nondominant side as predictor variables. The classification tree model correctly classified 78.79% (p = 0.02) of the training data set. The accuracy obtained by the classification tree on the test data set was 82.35% (p = 0.04). Conclusion: The classification tree showed acceptable accuracy (82.35%) and high specificity (95.65%) but low sensitivity (54.55%). Based on the predictive model in this study, we suggested that 20% of body weight in scapular protractor strength is a meaningful cutoff value for presence of SW

Relationship Between the Closed Kinetic Chain Upper Extremity Stability Test and Strength of Serratus Anterior and Triceps Brachii Muscles

Background: The CKCUES test evaluates the functional performance of the shoulder joint. The CKCUES test scores CKC exercises of the upper limbs to examine shoulder stability. Although the CKCUES test provides quantitative data on functional ability and performance, no study has determined the relationship between CKCUES scores and SA and TB muscle strength. Objects: The objective of this study is to determine the relationship between the CKCUES test scores and the strength of the SA and TB muscles in the CKCUES and unilateral CKCUES tests. Methods: Sixty-six healthy male volunteers participated in the study. A Smart KEMA strength sensor measured SA and TB muscle strength. Two parallel lines on the floor indicated the initial hand placement to start CKCUES tests. For 15 seconds, the subject raises one hand and reaches over to touch the supporting hand, then returns to the starting position. Results: The correlation between the CKCUES test scores and the strength of the SA was strong (r = 0.650, p < 0.001), and the TB was moderate (r = 0.438, p < 0.001). The correlation between the unilateral CKCUES test and the strength of the SA of the supporting side was strong (r = 0.605, p < 0.001), and swing side was strong (r = 0.681, p < 0.001). The correlation between the unilateral CKCUES test and the strength of the TB of the supporting side was moderate (r = 0.409, p < 0.001), and swing side was moderate (r = 0.482, p < 0.001). Conclusion: Our study showed that the CKCUES test had a strong association with isometric strength of SA and moderate association with that of TB. These findings suggest that the CKCUES test can evaluate the function of the SA. Moreover, the unilateral CKCUES test can evaluate unilateral shoulder function