ABSTRACT
Objective To investigate whether Danhong injection can enhance the therapeutic effect of neural stem cell (NSC) transplantation in repairing cerebral ischemia injury by regulating the nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Methods Forty male SD rats were randomly divided into the NSC transplantation group (NSC group), Danhong injection group (DH group), NSC+ Danhong injection group (N+D group), NSC+ Danhong injection group +ML385 group(N+D+M group) and PBS control group (PBS group), 8 rats in each group. All rat models of cerebral ischemia were established by embolization of the middle cerebral artery. Reperfusion was performed at 1.5 h after embolization. All rats in each group received corresponding interventions at 3 d after reperfusion. The neurological function score was evaluated before and 1, 2, 4 weeks after NSC transplantation. All rats were sacrificed at 4 weeks after NSC transplantation. The parameters related to oxidative stress were detected. The expression levels of neuron-specific nuclear protein (NeuN) and von Willebrand factor (vWF) were determined by immunofluorescence staining. Results Before NSC transplantation, the neurological function scores did not significantly differ among different groups (all P > 0.05). At postoperative 1, 2 and 4 weeks, the neurological function scores in the NSC, DH and N+D groups were significantly lower than those in the PBS and N+D+M groups (all P < 0.05). Compared with the PBS and N+D+M groups, the malondialdehyde (MDA) levels were significantly decreased, whereas the superoxide dismutase (SOD) and glutathione peroxidase (GPX) levels were considerably increased in the NSC, DH and N+D groups (all P < 0.05). The GPX level in the N+D+M group was significantly lower than that in the PBS group (P < 0.05). Immunofluorescence staining showed that the transplant NSC in the rat brain migrated to the surrounding area of cerebral infarction and survived, and expressed neuronal marker NeuN and neovascularization marker vWF. However, the number of living NSC in the N+D+M group was significantly lower compared with those in the remaining groups. Conclusions Danhong injection may improve the microenvironment of stem cell transplantation, enhance the survival rate of transplant NSC and improve the therapeutic effect of NSC transplantation for cerebral ischemia injury probably by regulating the Nrf2 signaling pathway.
ABSTRACT
Purpose To detect high mobility group protein A2 (HMGA2) expression in breast cancer, and to analyze its relationship with clinicopathological features and the levels of HMGA2 in different molecular subtypes of breast carcinomas. Methods An immu-nohistochemical study was undertaken for measuring the levels of HMGA2 in 58 breast carcinomas. Results ( 1 ) The expression of HMGA2 was 0, 62. 5%, 60. 0%, 100. 0% and 80. 0% in Lum A, Lum B, HER-2-OE, basal-like breast carcinoma (BLBC) and un-classification phenotype respectively ( triple negative breast cancer, 92. 3%) . High expression of HMGA2 was associated with the tri-ple-negative breast cancer (TNBC) subtypes (P<0. 01). (2) An association was identified between high expression of HMGA2, and high tumor grade, lymph node metastasis (P<0. 05), positive Ki-67, CK5/6 and EGFR (P<0. 05), negative ER and PR (P<0. 01), but no association was observed for tumor size and patients’age. Conclusion An association is identified between high ex-pression, and high tumor grade, lymph node metastasis, positive Ki-67, EGFR and CK5/6, negative ER and PR, that means a high expression of HMGA2 is associated with an adverse outcome in breast cancer. High expression of HMGA2 are associated with the TNBC subtypes. Thus recognizing HMGA2 as a rational target in TNBC. The results of the study have implications for therapeutic target iden-tification and the design of future clinical trials for TNBC.
ABSTRACT
Purpose To study the levels and subcellular localization of β-catenin in 5 different molecular subtypes of breast carcino-mas. Methods An immunohistochemical study was undertaken for measuring the levels and subcellular localization ofβ-catenin in 58 breast carcinomas. Results ( 1 ) The cytoplasmic expression of β-catenin was 21. 1%, 50%, 60%, 100% and 60% ( TNBC 84. 6%) in Lumina A, Lumina B, HER-2-OE, basal-like breast carcinoma ( BLBC) and uncl phenotype respectively. High cytoplas-mic expression was associated with the BLBC and TNBC subtypes ( P<0. 05 ) . ( 2 ) An association was identified between high cyto-plasmic expression of β-catenin, and high tumor grade (P<0. 01), abnormal E-cadherin, positive Ki-67 and CK5/6 (P<0. 05), negative ER and PR (P<0. 01), but no association was observed for lymph node metastasis, tumor size and patients’age. Conclu-sion An association is identified between high cytoplasmic expression, and high tumor grade, positive Ki-67 and CK5/6, negative ER and PR, that means a high cytoplasmic expression ofβ-catenin is associated with an adverse outcome in breast cancer. High cytoplas-mic expression are associated with the BLBC and TNBC subtypes whcih recognizing Wnt signaling as a rational target in TNBC and BLBC. The results of the study have implications for therapeutic target identification and the design of future clinical trials for TNBC and BLBC.