Research on human placenta-derived mesenchymal stem cells transfected with pIRES2-EGFP-VEGF165 using liposome

The experiment adopting reverse transcription polymerase chain reaction (RT-PCR) technology, amplified hVEGF165 gene fragments from human leukemia cells HL-60. hVEGF165 gene was reconstructed in pIRES2-EGFP and transferred into the human placenta-derived mesenchymal stem cells (HPMSCs) by liposome-mediated method successfully. The mRNA and protein of hVEGF165 in the transferred cells was detected by RT-PCR and Western blot, and the results showed that hVEGF165mRNA and the protein expressed by HPMSCs transfected with pIRES2-EGFP-hVEGF165 was significantly more than HPMSCs transfected with pIRES2-EGFP. EGFP expression was observed under fluorescence microscope, which proved that the report gene was successfully transferred to the target cells. hVEGF biology activity and cell proliferation activity of HPMSCS transfected with pIRES2-EGFPhVEGF165 was detected by MTT array, which showed that hVEGF165 can promote the proliferation of HPMSCS; however, hVEGF165 biology activity of HPMSCS transfected with pIRES2-EGFP-hVEGF165 was significantly more than HPMSCs transfected with pIRES2-EGFP.  Identification of multipotentiality showed that HPMSCS transfected with pIRES2-EGFP-VEGF165 still maintained multipotentiality.Key words: Transfect, human placenta-derived mesenchymal stem cells, hVEGF165

Serum Cholesterol and Nigrostriatal R2* Values in Parkinson's Disease

The occurrence of Parkinson's disease (PD) is known to be associated both with increased nigrostriatal iron content and with low serum cholesterol and PD, but there has been no study to determine a potential relationship between these two factors.High-resolution MRI (T1-, T2, and multiple echo T2*-weighted imaging) and fasting lipid levels were obtained from 40 patients with PD and 29 healthy controls. Iron content was estimated from mean R2* values (R2* = 1/T2*) calculated for each nigrostriatal structure including substantia nigra, caudate, putamen, and globus pallidus. This was correlated with serum cholesterol levels after controlling for age, gender, and statin use.In patients with PD, higher serum cholesterol levels were associated with lower iron content in the substantia nigra (R = -0.43, p = 0.011 for total-cholesterol, R = -0.31, p = 0.080 for low-density lipoprotein) and globus pallidus (R = -0.38, p = 0.028 for total-cholesterol, R = -0.27, p = 0.127 for low-density lipoprotein), but only a trend toward significant association of higher total-cholesterol with lower iron content in the striatum (R = -0.34, p = 0.052 for caudate; R = -0.32, p = 0.061 for putamen). After adjusting for clinical measures, the cholesterol-iron relationships held or became even stronger in the substantia nigra and globus pallidus, but weaker in the caudate and putamen. There was no significant association between serum cholesterol levels and nigrostriatal iron content for controls.The data show that higher serum total-cholesterol concentration is associated with lower iron content in substantia nigra and globus pallidus in Parkinson's disease patients. Further studies should investigate whether this is mechanistic or epiphenomenological relationship

Synergy as a new and sensitive marker of basal ganglia dysfunction: A study of asymptomatic welders

Multi-digit synergies, a recently developed, theory-based method to quantify stability of motor action, are shown to reflect basal ganglia dysfunction associated with parkinsonian syndromes. In this study, we tested the hypothesis that multi-digit synergies may capture early and subclinical basal ganglia dysfunction. We chose asymptomatic welders to test the hypothesis because the basal ganglia are known to be most susceptible to neurotoxicity caused by welding-related metal accumulation (such as manganese and iron)

Interaction of Brn3a and HIPK2 mediates transcriptional repression of sensory neuron survival

The Pit1-Oct1-Unc86 domain (POU domain) transcription factor Brn3a controls sensory neuron survival by regulating the expression of Trk receptors and members of the Bcl-2 family. Loss of Brn3a leads to a dramatic increase in apoptosis and severe loss of neurons in sensory ganglia. Although recent evidence suggests that Brn3a-mediated transcription can be modified by additional cofactors, the exact mechanisms are not known. Here, we report that homeodomain interacting protein kinase 2 (HIPK2) is a pro-apoptotic transcriptional cofactor that suppresses Brn3a-mediated gene expression. HIPK2 interacts with Brn3a, promotes Brn3a binding to DNA, but suppresses Brn3a-dependent transcription of brn3a, trkA, and bcl-xL. Overexpression of HIPK2 induces apoptosis in cultured sensory neurons. Conversely, targeted deletion of HIPK2 leads to increased expression of Brn3a, TrkA, and Bcl-xL, reduced apoptosis and increases in neuron numbers in the trigeminal ganglion. Together, these data indicate that HIPK2, through regulation of Brn3a-dependent gene expression, is a critical component in the transcriptional machinery that controls sensory neuron survival

Combined R2* and Diffusion Tensor Imaging Changes in the Substantia Nigra in Parkinson's Disease

Recent magnetic resonance imaging (MRI) studies suggest increased transverse relaxation rate (R2*) and reduced diffusion tensor imaging (DTI) fractional anisotropy (FA) values in the SN in PD. The R2* and FA changes may reflect different aspects of PD-related pathological processes (i.e., tissue iron deposition and microstructure disorganization). This study investigated the combined changes of R2* and FA in the SN in PD

Imaging nigral pathology and clinical progression in Parkinson's disease

The pattern of dopamine cell loss in Parkinson's disease is known to be prominent in the ventrolateral and caudal substantia nigra, but less severe in the dorsal and rostral region. Both diffusion tensor imaging and R2* relaxometry of the substantia nigra have been reported as potential markers for Parkinson's disease, but their relative ability to mark disease progression and differences in pathophysiological bases remains unclear