ABSTRACT
This study aimed to investigate the impact of timing interval to start AED withdraw (TIW) after surgery on the seizure outcome in non-neoplastic drug resistant epilepsy (DRE). TIW were divided into three groups (respectively,<1 year, 1-<2 years, and ≥2 years). The seizure outcome at the different time points after starting AED withdrawal were compared among three groups. Other factors that related to seizure recurrence and TIW were included into the multiple analysis to investigate the predictors of seizure-free. Altogether, 205 patients were involved in the study. 102 individuals (50%) had seizure recurrence and 127 (62%) had seizure-free at the final follow up. 115 of them have attempted AED reduction and had not seizure recurrence before AED reduction. The rate of seizure-free had no significant difference among people with different TIW. Multiple analysis indicated that temporal surgery is a favorable predictor of seizure-free at the first year after starting AED withdrawal, and preoperative secondary generalized seizures is an unfavorable predictor of seizure-free at the final follow up. In patients with non-neoplastic DRE, TIW is not the mainly influence factor on seizure outcome, however, preoperative secondary generalized seizures and extra-temporal surgery are negatively associated with seizure-free.
Subject(s)
Anticonvulsants/therapeutic use , Drug Resistant Epilepsy/drug therapy , Drug Resistant Epilepsy/surgery , Seizures/prevention & control , Substance Withdrawal Syndrome/prevention & control , Adolescent , Adult , Anticonvulsants/administration & dosage , Child , Child, Preschool , China , Drug Resistant Epilepsy/prevention & control , Humans , Middle Aged , Postoperative Period , Recurrence , Retrospective Studies , Seizures/drug therapy , Seizures/surgery , Time Factors , Young AdultABSTRACT
Brain metastases are a frequent and ongoing major complication of non-small cell lung cancer (NSCLC). To deepen our understanding to the underlying mechanisms by which NSCLC cells metastasize to brain and hence to improve the therapy, a high throughput RNAi screening with shRNA library of 153 epigenetic genes was subjected to A549, a NSCLC cell line with high migration ability, to examine the effects of these genes on cell migration by wound-healing assay. The screening results showed that knockdown of 2 genes (KDM5B and SIRT1) dramatically and specifically inhibits A549 migration but not affects the proliferation, which was subsequently confirmed through transwell migration assay. Furthermore, SIRT1 is found to be highly expressed in brain metastasis tissues of NSCLC, compared to the NSCLC tissues, suggesting that SIRT1 may play roles in brain metastasis of NSCLC. The relationship between SIRT1 expression and cell migration ability was further investigated in three NSCLC cell lines and the result indicated that SIRT1 expression is tightly correlated with cell migration ability. Collectively, our work provides potential biomarker and therapeutic target for brain metastasis of NSCLC.
Subject(s)
Biomarkers, Tumor/metabolism , Brain Neoplasms/enzymology , Brain Neoplasms/secondary , Carcinoma, Non-Small-Cell Lung/enzymology , Carcinoma, Non-Small-Cell Lung/secondary , Cell Movement , Lung Neoplasms/enzymology , Lung Neoplasms/pathology , Sirtuin 1/metabolism , Brain Neoplasms/genetics , Carcinoma, Non-Small-Cell Lung/genetics , Cell Line, Tumor , Cell Proliferation , Gene Expression Regulation, Enzymologic , Gene Expression Regulation, Neoplastic , Gene Knockdown Techniques , Humans , Jumonji Domain-Containing Histone Demethylases/genetics , Jumonji Domain-Containing Histone Demethylases/metabolism , Lung Neoplasms/genetics , Neoplasm Invasiveness , Nuclear Proteins/genetics , Nuclear Proteins/metabolism , RNA Interference , Repressor Proteins/genetics , Repressor Proteins/metabolism , Sirtuin 1/genetics , Transfection , Up-Regulation , Wound HealingABSTRACT
BACKGROUND: Chemokines and their receptors have been a research focus in transplantation immunology. Chemokines and their receptors play a role in lymphocyte recruitment and differentiation process. This study aimed to observe whether IL-4 and IL-10 may regulate the expression of chemokine receptors CCR3, CCR5 and CXCR3 on CD4(+) T cells in CBA/JxDBA/2 mouse model and to explore the role of CCR3, CCR5, CXCR3 in immune tolerance in pregnancy. METHODS: The mouse model of spontaneous abortion (CBA/JxDBA/2) and the normal pregnant mouse model (CBA/JxBALB/c) were used. CBA/JxDBA/2 mice were injected with IL-4 (CBA/JxDBA/2-IL-4), IL-4 and IL-10 (CBA/JxDBA/2-IL-4+IL-10), or normal saline (CBA/JxDBA/2-NS) as a control. The expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells from mouse peripheral blood was measured by the double-labelled FCM method, and the embryo resorption rate was also examined. RESULTS: The embryo resorption rate in the CBA/JxDBA/2 group without any treatment was significantly higher than that in the CBA/JxBALB/c group (17.9% vs 3.7%, P < 0.01). The embryo resorption rate in the CBA/JxDBA/2 group immunized with IL-4 or IL-4 together with IL-10 was significantly decreased, compared with that in the control and NS groups respectively. CCR3 expression on CD4(+) T cells in the CBA/JxDBA/2 group without any treatment was significantly lower than that in the CBA/JxBALB/c group (0.3738 +/- 0.3575 vs 1.2190 +/- 0.2772, P < 0.01); both CCR5 (3.0900 +/- 1.5603 vs 1.2390 +/- 0.6361, P < 0.01) and CXCR3 (2.4715 +/- 0.9074 vs 0.9200 +/- 0.5585, P < 0.01) expressions on CD4(+) T cells of the CBA/JxDBA/2 group without any treatment were significantly higher than those of the CBA/JxBALB/c group. Significant up-regulation of CCR3 and down-regulation of CXCR3 were found in the CBA/JxDBA/2 group treated with IL-4 (CCR3: 2.0360 +/- 0.6944, CXCR3: 1.3510 +/- 0.5263, P < 0.01) or IL-4 and IL-10 (CCR3: 1.8160 +/- 1.0947, CXCR3:1.0940 +/- 0.7168, P < 0.01). Because of the CCR5, IL-4 and IL-10 (1.9400 +/- 0.8504 vs 3.0900 +/- 1.5603, P < 0.05), but IL-4 alone (2.5310 +/- 1.3595 vs 3.0900 +/- 1.5603, P > 0.05) treatment significantly decreased the expression of CCR5 in CBA/JxDBA/2. CONCLUSIONS: The abnormal expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells may play an important role in the pathogenesis of spontaneous abortion. The pregnancy immune tolerance may be induced through selective induction of CCR3, CCR5 and CXCR3 expressions by IL-4 together with IL-10.
Subject(s)
CD4-Positive T-Lymphocytes , Embryo Loss/metabolism , Interleukin-10/pharmacology , Interleukin-4/pharmacology , Receptors, CCR3/metabolism , Receptors, CCR5/metabolism , Receptors, CXCR3/metabolism , Animals , CD4-Positive T-Lymphocytes/drug effects , CD4-Positive T-Lymphocytes/metabolism , Cells, Cultured , Embryo, Mammalian , Female , Mice , Mice, Inbred BALB C , PregnancyABSTRACT
BACKGROUND: Previous studies have shown that local immune cells in the feto-maternal interface are recruited from peripheral blood, and that chemokines and their receptors play an initial and key role in this recruitment process. In this study, we aimed to determine whether spontaneous abortion is associated with the expression of chemokine receptors CCR3, CCR5, and CXCR3 on CD4(+) T cells. METHODS: Peripheral blood, spleen, and thymus were collected from the spontaneous abortion mouse model CBA/JxDBA/2 (SA group, n = 14), the normal pregnant mouse model CBA/JxBALB/c (NP group, n = 13), and normal non-pregnant CBA/J mice (NNP group, n = 11). The number of chemokine receptors CCR3, CCR5, and CXCR3 expressed on CD4(+) T cells was measured by double-label flow cytometry (FCM) method. RESULTS: In peripheral blood, the SA group had significantly lower CCR3 expression (P < 0.01) and higher CCR5 and CXCR3 expression (P < 0.01) on CD4(+) T cells than did the NP group. But comparing these chemokines between the SA and NNP groups, there was no significant difference (P > 0.05). In spleen, the SA group expressed significantly lower CCR3 expression (P < 0.01) and higher CCR5 and CXCR3 expression (P < 0.05) on CD4(+) T cells than did the NP group. When compared with the NNP group, the SA group had significantly higher CCR3 expression (P < 0.01), but was not statistically different with regards to the other two chemokines (P > 0.05). In thymus, the SA group had significantly lower CCR3 expression (P < 0.05) and higher CXCR3 expression (P < 0.05) on CD4(+) T cells than the NP group, with no significant difference in CCR5 expression (P > 0.05). Compared with the NNP group, the SA group had higher CCR3 expression (P < 0.01), but there was no statistical difference in CXCR3 and CCR5 expression (P > 0.05) between the two groups. CONCLUSION: The abnormal expression of CCR3, CCR5 and CXCR3 on CD4(+) T cells may play an important role in the pathogenesis of spontaneous abortion.
Subject(s)
CD4-Positive T-Lymphocytes/metabolism , Gene Expression Regulation , Receptors, CCR3/metabolism , Receptors, CCR5/metabolism , Receptors, CXCR3/metabolism , Animals , Embryo Loss , Female , Flow Cytometry , Male , Mice , Mice, Inbred BALB C , Pregnancy , Spleen/metabolism , Thymus Gland/metabolismABSTRACT
As a part of a basic research project on Xeno-transplantion, we have been engaged in the derivation of embryonic stem cell lines from Chinese mini swine. Here, we reported for the first time the establishment of two porcine EG cell lines (BPEG1 and BPEG2) from primordial germ cells of genital ridges of a 28 and a 27 d embryos respectively. Their pluripotent nature has been identified by colony morphology, marker characterization as well as by in vitro and in vivo differentiation. These porcine EG cells are potentially useful for further basic studies.
