OBJECTIVEThe present study was undertaken to design antisense oligodeoxynucleotides (AS-ODNs) of glial glutamate transporter-la (GLT-1a) and to evaluate the effectiveness of the designed AS-ODNs on the expression of GLT-1a.

METHODSFive sequences of GLT-1a AS-ODNs were designed according to the C terminus specific sequences of GLT-1a mRNA using antisense design software of IDT Com- pany. Western blot analysis was used to evaluate the inhibition effects of the five GLT-1a AS-ODNs on the expression of GLT-la.

RESULTSThe sequence of GLT-1a AS-ODNs with sequence of 5'-GGTTCTTCCTCAACACTGCA-3' could specifically inhibit the expression of GLT-1a in the hippocampal CA1 subfield of rats, while it had no effect on the expression of GLT-1b. This sequence showed similar inhibition on the expression of GLT-la in sham and ceftriaxone (Cef)-treated rats. It could also significantly inhibit the cerebral ischemic preconditioning (CIP)-induced up-regulation in the expression of GLT-1a. The magnitude of the inhibition in sham, Cef- or CIP-treated rats was similar by more than 60%.

CONCLUSIONFrom the designed five sequences of GLT-1a AS-ODNs, we obtained an effective sequence which can specifically inhibit the expression of GLT-1a.

Animals ; CA1 Region, Hippocampal ; metabolism ; Excitatory Amino Acid Transporter 2 ; antagonists & inhibitors ; metabolism ; Ischemic Preconditioning ; Oligonucleotides, Antisense ; genetics ; RNA, Messenger ; Rats ; Up-Regulation

ObjectiveTo study the regulatory effect of Tripterygium wilfprdii polyglycoside (TWP) on the expression of EGFR and ErbB-2 induced arthritis rats.The effect of TWP on arthritis was also explored.MethodsAfter the model of CIA rats were established,the expression of EGFR and ErbB-2 in the synovium and articular cartilage were tested by immunohistochemical stain and real time PCR.ANOVA was used for statistical analysis.ResultsThe protein and mRNA expression of EGFR and ErbB-2 in the synovium (EGFR 0.268±0.059,ErbB-2 0.25±0.04,EGFR mRNA:14.2±0.55,ErbB-2 mRNA 23.46±3.64) and articular cartilage (EGFR 0.193±0.018,ErbB-2 0.217±0.033,EGFR mRNA:4.16±0.50,ErbB-2 mRNA 9.23±0.66) of the model group were significantly higher than those of the control group(P＜0.01).After being treated with TWP and MTX,the protein and mRNA expression of the EGFR and ErbB-2 decreased markedly (P＜0.01).Conclusion EGFR and ErbB-2 may play an important role in the pathogenesis of arthritis development.The molecular mechanism that TWP can treat synovitis and bone destruction of RA is related to the inhibition of EGFR and ErbB-2.

Objective The aim of this report was to study the early and mid-term outcome in hospital and follow-up mortality, predictors for late pulmonary stenosis (PAS) and insufficiency of neo-aortic valve (neo-AVI) in patients with transposition of great arteries (TGA) and Taussig-Bing malformation undergoing arterial switch operation ( ASO ). Methods Between January 2004 and December 2007, 169 patients (129 male, 40 female; mean age of [(11.71 ± 26.3 ) months] with TGA or Taussig-Bing malformation underwent ASO. The patients were divided into Group Ⅰ (n = 56 ): TGA with intact ventricular septum and Group Ⅱ ( n = 113 ): TGA with ventricular septal defect (VSD). All patients were followed up in out-patient department by ultrasonic cardiogram. The mean follow-up periods was (27.66 ± 14.6 ) months. Multiple logistic regression analysis was performed to find out the risk factors. Results The overall hospital mortality was 11.24% (19/169)and there was no significant difference between the two Groups. With the improving of perioperative management, the hospital mortality decreased from 16.67% in 2004 to 3.92% in 2007. The overall actuarial survival at 1-, 3- and 5-year follow-up was 94.00%,91.33%, and 91.33%, respectively. The multivariate analysis revealed that age above 6 months was a strong predictor for poor postoperative survival. Predictors for neo-AVI were: combined with VSD, age > 6 months and postoperative neo-AVI Z-score > 1. Predictors for moderate to severe PAS were age ＜ 1 months and pulmonary artery plasty with an unstretchable patch. Conclusion ASO remains the optimal choice for treating various forms of TGA with an acceptable early and mid-term outcome regarding overall survival rate. Patients with TGA should be treated as early as possible. Age >6 months is a predictor for poor postoperative survival and neo-AVI. Mismatch between the neo-aortic root and distal aorta may induce neo-AVI. Unstretchable patch in pulmonary artery plasty may induce PAS.

Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.

Over one half the patients with rheumatoid arthritis (RA) are being treated with methotrexate (MTX). Although well proven, the efficacy of MTX varies in individual patients. This study examined the metabolic biomarkers that can be used to predict the therapeutic effect of MTX by using metabolomic analysis. Rats were immunized with collagen to rapidly cause collagen-induced arthritis (CIA) and then treated with 0.1 mg/kg MTX for 4 weeks. The clinical signs and the histopathological features of CIA were observed to evaluate the therapeutic effects. Urine samples of CIA rats were collected, and analyzed by using 600 M (1)H-nuclear magnetic resonance ((1)H-NMR) for spectral binning after the therapy. The urine spectra were divided into spectral bins, and 20 endogenous metabolites were assigned by Chenomx Suite. Multivariate analyses were performed to identify the spectral pattern of endogenous metabolites related to MTX therapy. The results showed that the clustering of the spectra of the urine samples from the responsive rats (n=20) was different from that from the non-responsive rats (n=11). Multivariate analysis showed difference in metabolic profiles between the responsive and non-responsive rats by using partial least squares-discrimination analysis (PLS-DA) (R(2)=0.812, Q(2)=0.604). In targeted profiling, 13 endogenous metabolites (uric acid, taurine, histidine, methionine, glycine, etc.) were selected as putative biomarkers for predicting therapeutic response to MTX. It was suggested that (1)H-NMR-based metabolomic analysis can be used to predict the therapeutic effect of MTX, and several metabolites were found to be related to the therapeutic effects of MTX.
Animals ; Antirheumatic Agents ; administration & dosage ; Arthritis ; chemically induced ; drug therapy ; urine ; Biomarkers ; urine ; Collagen Type II ; Dose-Response Relationship, Drug ; Immunosuppressive Agents ; administration & dosage ; Magnetic Resonance Spectroscopy ; methods ; Male ; Metabolome ; Methotrexate ; administration & dosage ; Proteome ; analysis ; Protons ; Rats ; Rats, Sprague-Dawley ; Reproducibility of Results ; Sensitivity and Specificity ; Treatment Outcome

Apogossypolone (ApoG2), a novel derivative of gossypol, has been shown to be a potent inhibitor of antiapoptotic Bcl-2 family proteins and to have antitumor activity in multiple types of cancer cells. Recent reports suggest that gossypol stimulates the generation of cellular reactive oxygen species (ROS) in leukemia and colorectal carcinoma cells; however, gossypol-mediated cell death in leukemia cells was reported to be ROS-independent. This study was conducted to clarify the effect of ApoG2-induced ROS on mitochondria and cell viability, and to further evaluate its utility as a treatment for nasopharyngeal carcinoma (NPC). We tested the photocytotoxicity of ApoG2 to the poorly differentiated NPC cell line CNE-2 using the ROS-generating TL/10 illumination system. The rapid ApoG2-induced cell death was partially reversed by the antioxidant N-acetyl-L-cysteine (NAC), but the ApoG2-induced reduction of mitochondrial membrane potential (MMP) was not reversed by NAC. In the presence of TL/10 illumination, ApoG2 generated massive amounts of singlet oxygen and was more effective in inhibiting cell growth than in the absence of illumination. We also determined the influence of light on the anti-proliferative activity of ApoG2 using a CNE-2-xenograft mouse model. ApoG2 under TL/10 illumination healed tumor wounds and suppressed tumor growth more effectively than ApoG2 treatment alone. These results indicate that the ApoG2-induced CNE-2 cell death is partly ROS-dependent. ApoG2 may be used with photodynamic therapy (PDT) to treat NPC.
Animals ; Antineoplastic Agents ; pharmacology ; Cell Death ; drug effects ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Gossypol ; analogs & derivatives ; pharmacology ; Humans ; Light ; Membrane Potential, Mitochondrial ; drug effects ; Mice ; Mice, Nude ; Nasopharyngeal Neoplasms ; metabolism ; pathology ; Neoplasm Transplantation ; Photochemotherapy ; Reactive Oxygen Species ; metabolism ; Singlet Oxygen ; metabolism ; Tumor Burden ; drug effects

OBJECTIVETo explore the clinical characteristics and prognostic factors of patients diagnosed with squamous cell carcinoma (SCC) and presented malignancy-associated hypercalcemia (MAH).

METHODSWe retrospectively analyzed the clinical data of 36 patients with biopsy-proven SCC and presented MAH who were treated at the our department from January 2001 to December 2010. The survival were analyzed using the Kaplan-Meier method and Cox analysis.

RESULTSAmong these 36 patients, the median blood calcium level was 2.94 mmol/L (2.77-4.87 mmol/L), and the median survival time was only 45 days (1-839 d). Log-rank test showed that central nervous system symptoms, bone metastasis, and hypercalcemia occurring over 160 days after cancer diagnosis were predictors for poor survival(p=0.003, P=0.049, P=0.005). In the COX proportional hazard model analysis, central nervous system symptoms and hypercalcemia occurring over 160 days after cancer diagnosis were independent prognostic factors for survival time (RR=5.721, P=0.000; RR=4.624, P=0.001).

CONCLUSIONSPatients with squamous cell carcinoma (SCC) and presented MAH have poor prognosis. Central nervous system symptoms and hypercalcemia occurring over 160 days after cancer diagnosis are independent predictors of the prognosis.

Adult ; Aged ; Carcinoma, Squamous Cell ; complications ; Female ; Humans ; Hypercalcemia ; etiology ; Male ; Middle Aged ; Prognosis ; Retrospective Studies

Objective To explore the effect of nursing intervention based on the integrated theory of health behavior change(ITHBC)on the health behavior of patients with diabetes retinopathy(DR).Methods 157 patients with diabetes retinopathy admitted from July to December 2022 in a tertiary A hospital in Wuhan,Hubei Province,were selected as the experimental group by convenience sampling method,while 156 patients with diabetes retinopathy hospitalized from January to June 2022 were selected as the control group,and routine nursing was caried out.The disease cognition scale scores,self-management scale scores,and quality of life scale scores were compared between the 2 groups before and after 6 months of intervention.Results After 6 months of intervention,the disease cognition scale scores,self-management scale scores,and quality of life scale scores of both groups improved,and the results in the experimental group were better than these in the control group,and the difference is statistically significant(P＜0.05).Conclusion Nursing interventions based on the ITHBC theory can help improve the disease cognition of DR patients,establish and maintain healthy behaviors,improve their self-management level,and improve their quality of life.

OBJECTIVE: To explore the inhibitive effects of 1,3,8-trihydroxy-5-methoxyxanthone (TMX) on cytochrome P450s (CYP450s) in human liver microsomes. METHODS: Probe drugs were incubated with and without adding TMX to determine the changes of enzyme activities. The concentration ratio of metabolites to probe drugs was used to present enzyme activities. Concentrations of the probe drugs and their metabolites in the incubated mixture were detected by high performance liquid chromatography. RESULTS: The variations (mean, 95%CI) of the activities of CYP1A2, CYP2C9, CYP2C19, CYP2E1 and CYP3A4 were 2.95 x 10(-3) (2.03 x 10(-3), 3.88 x 10(-3)), 3.14 x 10(-2) (1.87 x 10(-2), 4.42 x 10(-2)), 2.27 x 10(-3) (-1.4 x 10(-2),1.81 x 10(-2)), 7.72 x 10(-2) (-0.83 x 10(-2), 0.2374), and -0.2548 (-2.9802, 2.4707), respectively. The activities of CYP1A2 and CYP2C9 were significantly reduced in the present of TMX. CONCLUSION TMX (10 micromol/L) has significant inhibitive effect on the activities of CYP1A2 and CYP2C9, but no significant inhibitive effect on the activities of CYP2C19, CYP2E1 and CYP3A4.
Cytochrome P-450 Enzyme System ; metabolism ; Humans ; Microsomes, Liver ; drug effects ; enzymology ; Xanthones ; pharmacology

OBJECTIVETo examine the number and function of circulating endothelial progenitor cells (EPCs) in children with cyanotic congenital heart diseases (CHD) and study their correlation with serum levels of vascular endothelial growth factor (VEGF) and stromal cell derived factor-1 (SDF-1).

METHODSFifteen children with tetralogy of Fallot (cyanotic group) and 15 age-and sex-matched children with ventricular septal defect (control group) were enrolled. Serum levels of VEGF and SDF-1 were measured using ELISA. Mononuclear cells were isolated from peripheral blood by Ficoll density gradient centrifugation and cultured in vitro. EPCs were identified by immunofluorescence and were counted under a microscope. Modified Boyden chamber assay and the MTT assay were used to measure the migration and proliferation capacities of EPCs. EPCs adhesion ability assay was performed by replating cells on fibronectin-coated dishes, and then adherent cells were counted. The correlations of serum levels of VEGF and SDF-1 with the number and function of circulating EPCs were assessed by linear regression analysis.

RESULTSSerum levels of VEGF (201.42+/-44.74 ng/L vs 113.56+/-35.62 ng/L; P<0.05) and SDF-1 (3.45+/-1.07 ng/L vs 1.05+/-0.99 ng/L; P<0.05) in the cyanotic group were higher than those in the control group. There was a positive correlation between serum levels of VEGF and SDF-1(r=0.675, P<0.01). The number of EPCs (*200 field) in the cyanotic group significantly increased compared with that of the control group (72.2+/-9.73 vs 51.2+/-3.83; P<0.01). The functional activities of EPCs, including proliferation, migration and adhesion capacities, were augmented in the cyanotic group compared with those in the control group. The increased number and function of EPCs and the increased serum levels of VEGF and SDF-1 were consistent in the cyanotic group, with a correlation coefficient of 0.8395, 0.5491, 0.6376 and 0.7392 respectively.

CONCLUSIONSThe number and functional activity of EPCs as well as serum levels of VEGF and SDF-1 increased in children with cyanotic CHD. Serum levels of VEGF and SDF-1 were correlated to the number and functional activity of EPCs. Serum VEGF and SDF-1 together with circulating EPCs may play important roles in the pathology and physiology in these patients.

Chemokine CXCL12 ; blood ; physiology ; Cyanosis ; blood ; Endothelial Cells ; cytology ; physiology ; Heart Defects, Congenital ; blood ; Humans ; Stem Cells ; physiology ; Vascular Endothelial Growth Factor A ; blood ; physiology