Objective To explore the association of the inherent cellular level of reactive oxygen species (ROS) with the sensitivity of the gastric and esophageal carcinoma cells to arsenic trioxide (As 2O 3). Methods The difference of sensitivity to apoptosis induction by low concentration (2 ?mol/L) of As 2O 3 between the gastric carcinoma cell line SGC7901 and MKN45, and between the esophageal carcinoma cell line EC/CUHK1 and EC1867 was firstly demonstrated. SGC7901 was more sensitive than MKN45, and EC/CUHK1 more sensitive than EC1867 to As 2O 3. Then dihydrogenrhodamine 123 (DHR123), as a ROS capture, was incubated with the cells in the absence of As 2O 3. The fluorescent intensity of rhodamine 123, the product of cellular oxidation of DHR 123, was assayed by flow cytometry. The ROS levels was thus detected. Results Inherent cellular ROS level is higher in SGC7901 and EC/CUHK1. They are more sensitive to As 2O 3, than the corresponding cell line MKN45 and EC1867. Conclusions The difference in inherent cellular ROS level of gastric and esophageal carcinoma cells is associated with the cellular sensitivity to apoptosis induced by As2O 3.

Objective To explore any protective effect of hyperbaric oxygen in traumatic brain injury and its effect on the expression of silent information regulator 1 ( SIRT1) . Methods Sixty mice were randomly divided into a control group (n=20), a brain injury group (TBI, n=20) and a hyperbaric oxygen therapy group (TBI+HBO, n=20) . The mice in the TBI and TBI + HBO groups were given massive blows to establish closed brain injuries, while in the control group the scalp was incised and a bone window was removed without brain damage. The mice in the TBI + HBO group were given hyperbaric oxygen treatment twice per day for five days, while those in the TBI and control groups were put in the hyperbaric chamber but not given HBO treatment. At one hour after the trauma and on 5 days afterward, the neurological functioning of the mice was measured to generate neurological severity scores. Brain tissue was resected for triphenyl tetrazolium staining to measure the infarct area. Cortical neurons were isolated to eval-uate the SIRT1 expression using immunofluorescence and Western blotting. Results No significant difference in the average NSS score was observed between the TBI and TBI+HBO groups one hour after modeling. The average NSS score in the TBI group subsequently increased and then decreased gradually until the fifth day. The average NSS score of the TBI+HBO group was significantly lower than that of the TBI group after the onset of the treatment at the differ-ent time points, decreasing to (2.11±0.43) on the 5thday compared with (4.06±0.54) in the TBI+HBO group. On the 2nd day after the trauma, the cerebral infarction areas of the TBI and TBI+HBO groups were significantly larger than in the control group. During the treatment, the infarction area of the TBI+HBO group decreased gradually until on the 5th day it was significantly smaller than that of the TBI group. Traumatic brain injury significantly down-regula-ted SIRT1 protein compared with the control group, but the hyperbaric oxygen therapy significantly increased the ex-pression of SIRT1 compared with the TBI group. Conclusion Hyperbaric oxygen therapy can significantly relieve traumatic brain injury, reducing NSS scores and the infarcted area and enhancing SIRT1 expression, at least in mice.

Purpose:To explore the association of the inherent cellular level of reactive oxygen species (ROS) with the susceptibility of the tumor cells to apoptosis induced by arsenic trioxide (As 2O 3). Methods:Low concentration(2 ?mol/L) of As 2O 3 was administrated to a pair of the leukemic cell lines, NB4 versus U937, and a pair of the esophageal carcinoma cell line, EC/CUHK1 versus EC1867, to confirm the difference in their susceptibility to apoptosis induced by As 2O 3. Dihydrogenrhodamine123 (DHR123), used as a ROS capture, was incubated with the cells in the absence of As 2O 3 administration. The fluorescent intensity of rhodamine123, which was the product of cellular oxidation of DHR123, was detected by flow cytometry, and ROS was thus measured. Results:For apoptosis induction by 2 ?mol/L of As 2O 3 ,NB4 was more sensitive than U937,and EC/CUHK1 more sensitive than EC1867. The inherent cellular ROS level was higher in NB4 than in U937, and also higher in EC/CUHK1 than in EC1867. Conclusions:The difference in cellular ROS level is associated with the cellular susceptibility to apoptosis induction by As 2O 3.

Objective To compare the serum peptidome spectrum between nephrotic syndrome patients and normal controls, and to search for their variations. Methods The serum peptide profiling was determined by ClinProt magnetic bead enrichment and matrix assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF MS) in 17 mesangial proliferative glomerulonephritis (MsPGN) patients, 12 minimal change nephrotic syndrome (MCNS) patients, 10 membranous nephropathy (MN) patients, 10 focal segmental glomerulosclerosis (FSGS) patients, and 10 healthy volunteers. Results 5 differentially expressed polypeptides were screened out between MsPGN and normal controls (15.28±7.61, P＜0.01). 7 differentially expressed polypeptides were screened out between MCNS and normal controls (2.16±1.59, P＜0.01). 6 differential expressed polypeptides were screened out between MN and normal controls (35.48±13.71, P＜0.01). 5 differential expressed polypeptides were screened out between FSGS and normal controls (18.06±8.07, P＜0.05). The statistical significance was set at P＜0.05. A Genetic Algorithm was used to set up the classification model between patients and normal controls. The model separated MsPGN, MCNS, MN and FSGS group from normal controls with a cross validation of 96.18%, 100%, 98.53% and 94.12%, respectively. The recognition capabilities were 100%. Conclusions The study established the serum peptidome spectrum for nephrotic syndrome by proteomic technology, and provided a new viewpoint to better understand the pathogenesis of nephrotic syndrome.

OBJECTIVETo explore the association of inherent cellular reactive oxygen species (ROS) levels with susceptibility of the tumor cells to apoptosis induction by arsenic trioxide (As(2)O(3)).

METHODSLow concentration (2 micromol/L) of As(2)O(3) was administered to two cultured leukemic cell lines, NB4 and U937, and two esophageal carcinoma cell lines, EC1.71 (also named EC/CUHK1) and EC1867, to confirm the difference in apoptosis susceptibility of NB4 versus U937 and of EC1.71 versus EC1867. Dihydrogenrhodamine 123 (DHR123), used as a ROS capture agent, was incubated with cells in the absence of As(2)O(3). Fluorescence intensity of rhodamine 123, the product of cellular oxidation of DHR123, was detected by flow cytometry and ROS was measured.

RESULTSLow concentration of As(2)O(3) induced apoptosis was more likely to occur in NB4 and EC1.71 cells than in U937 and EC1867 cells, or NB4 was more sensitive than U937, and EC1.71 more sensitive than EC1867 to As(2)O(3). The inherent cellular ROS level is higher in NB4 than in U937, and also higher in EC1.71 than in EC1867.

CONCLUSIONSThe difference in cellular ROS level is positively associated with cellular susceptibility to apoptosis induction by As(2)O(3). The inherent ROS level might be important in defining apoptotic susceptibility to As(2)O(3).

Antineoplastic Agents ; pharmacology ; Apoptosis ; drug effects ; genetics ; Arsenicals ; pharmacology ; DNA, Neoplasm ; genetics ; Flow Cytometry ; Fluorescent Dyes ; Humans ; Oxides ; pharmacology ; Reactive Oxygen Species ; metabolism ; Rhodamine 123 ; Tumor Cells, Cultured ; drug effects ; metabolism

OBJECTIVETo investigate whether ascorbic acid could enhance the efficacy of arsenic trioxide (As(2)O(3)) combined with 2, 3-dimethoxy-1, 4-naphthoquinone (DMNQ) in inducing the apoptosis of leukemia cell line U937 and its possible mechanism.

METHODSFlow cytometry and electron microscopy were applied to detect apoptosis of U937 cells after treatment with various combinations of As(2)O(3), DMNQ and ascorbic acid for 24 hours.

RESULTSAs(2)O(3) and DMNQ induced-apoptosis of U937 cells was enhanced (35.24%-->61.20%) upon cotreatment with ascorbic acid. Catalase could reverse this effect of DMNQ. Ascorbic acid had no effect on DMNQ-induced apoptosis of U937 cells.

CONCLUSIONAscorbic acid enhanced the apoptosis of U937 cells via reactive oxygen species-dependent pathway in the presence of As(2)O(3).

Apoptosis ; drug effects ; Arsenicals ; pharmacology ; Ascorbic Acid ; pharmacology ; Drug Synergism ; Flow Cytometry ; Humans ; Naphthoquinones ; pharmacology ; Oxides ; pharmacology ; U937 Cells