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Abstract: The expression of major histocompatibility complex (MHC) on human neural stem cells (hNSCs) is tightly related to the fate of these cells in transplantation, therefore strategies to relieve rejection and promote graft survival are necessary to be applied. This study investigated the effect of carbamylated erythropoietin (CEPO) on MHC expression and differentiation of hNSCs with or without IFN-γ incubation. Results showed that low levels of MHC molecules were expressed on hNSCs and increased by IFN-γ. CEPO enhanced MHC-I antigens in both proliferative and differentiated hNSCs, but decreased MHC-II antigens in differentiated hNSCs and those cells exposed to IFN-γ. Furthermore, CEPO promoted neural differentiation of hNSCs and outgrowth of neurites. Western blot analysis revealed activation of Stat3, Stat5 and Akt during these processes. These results suggest that CEPO may have immunoregulatory function in hNSCs besides its neuroprotection. [Copyright &y& Elsevier]

Nuclear hormone receptors are ligand-dependent transcription factors that require coactivators to regulate target gene expression. The steroid receptor coactivator-3 (SRC-3), also known as p/CIP, RAC3, AIB1, ACTR and TRAM-1, is a cancer-amplified coactivator in the SRC gene family that also contains SRC-1 and TIF2/GRIP1. SRC-3 interacts with nuclear receptors and certain other transcription factors, recruits histone acetyltransferases and methyltransferases for chromatin remodeling and facilitates target gene transcription. Accumulated results from both ex vivo and animal model studies indicate that SRC-3 plays important roles in many biological processes involving cell proliferation, cell migration, cell differentiation, somatic growth, sexual maturation, female reproductive function, vasoprotection and breast cancer. This article summarizes our current knowledge about SRC-3 under the following topics: molecular cloning and characterization; molecular structure and functional mechanisms; SRC-3 as a molecular target of growth factors and cytokines; organization and expression of the SRC-3 gene; generation and characterization of SRC-3 knockout mice; role of SRC-3 in the vasoprotective effects of estrogen; role of SRC-3 in cell migration, proliferation and cancers. [Copyright &y& Elsevier]

Introduction: Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α) plays an important role in Parkinson's disease (PD). The aim of the study was to evaluate PGC-1α gene expression in the peripheral blood of PD patients. We also investigated PGC-1α-related gene variants and identified whether they are associated with PGC-1α gene expression.Methods: 259 PD patients and 253 healthy controls were included in this study. PPARGC1A (the gene encoding PGC-1α) expression levels were tested using real-time PCR. Single nucleotide polymorphisms (SNPs) of the PGC-1α-related genes (PPARGC1A, PPARG and SIRT1) were genotyped by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS).Results: PPARGC1A levels were significantly decreased in PD patients (P = 0.000) and negatively correlated with the patients' H&Y stage (r = -0.212, P = 0.039) and UPDRS-III score (r = -0.208, P = 0.044), after correcting, these correlations disappeared. The genotype frequencies of PGC-1α-related gene variants were not associated with the risk of PD. PPARGC1A rs2970870 variant was associated with the NMS score (P = 0.026), SIRT1 rs7895833 variant was associated with HAMA score (P = 0.029). PPARG rs4684847 variant was associated with MMSE score (P = 0.031). PPARG rs1801282, rs4684847, rs3856806 variants were associated with MoCA score. After correcting, only the association between PPARG rs4684847 and MoCA score remained significant (FDR = 0.048). PGC-1α-related gene variants had no effect on PGC-1α gene expression.Conclusion: The decreased expression of PGC-1α may not be due to its related gene variants. PGC-1α could become a candidate blood-based biomarker for diagnosis and monitoring disease progression. [ABSTRACT FROM AUTHOR]