Analysis of neuron-like differentiation of human bone marrow mesenchymal stem cells

The objective of the study was to evaluate differentiation of human bone marrow mesenchymal stem cells into true or pseudo neurons after treating with chemical induction medium in vitro. The morphological changes were assessed using interference contrast microscopy. Immunocytochemistry and Western blotting were performed using neuronal markers. Further evaluation was conducted with proteomic profiling, DNA microarray analysis and the whole-cell patch clamp test. After three hours of treatment with chemical induction medium, nearly three-fourths of the hMSCs changed to cells with a neuronal phenotype. The results of immunocytochemistry and Western blotting showed a high expression of neuronal markers in these cells at 3 h which decreased at 24 h. The proteomics analysis showed no change of proteins related to neuronal differentiation. DNA microarray showed downregulation of neuron related genes. The patch clamp test was unable to demonstrate any similarity to true neurons. Our findings suggest that neuron-like cells derived from chemical induction of hMSCs are not the genuine neurons as they resemble true neurons phenotypically but are different in genotypic and electrophysiological characteristics.     

Oncogenic Pathway Combinations Predict Clinical Prognosis in Gastric Cancer

Many solid cancers are known to exhibit a high degree of heterogeneity in their deregulation of different oncogenic pathways. We sought to identify major oncogenic pathways in gastric cancer (GC) with significant relationships to patient survival. Using gene expression signatures, we devised an in silico strategy to map patterns of oncogenic pathway activation in 301 primary gastric cancers, the second highest cause of global cancer mortality. We identified three oncogenic pathways (proliferation/stem cell, NF-κB, and Wnt/β-catenin) deregulated in the majority (>70%) of gastric cancers. We functionally validated these pathway predictions in a panel of gastric cancer cell lines. Patient stratification by oncogenic pathway combinations showed reproducible and significant survival differences in multiple cohorts, suggesting that pathway interactions may play an important role in influencing disease behavior. Individual GCs can be successfully taxonomized by oncogenic pathway activity into biologically and clinically relevant subgroups. Predicting pathway activity by expression signatures thus permits the study of multiple cancer-related pathways interacting simultaneously in primary cancers, at a scale not currently achievable by other platforms.     

Amyloid beta peptide (Abeta42) activates PLC-delta1 promoter through the NF-kappaB binding site

The abnormal deposition of amyloid beta peptide (Abeta) is a hallmark of Alzheimer's disease (AD). Phospholipase C-delta1 (PLC-delta1) is also known to abnormally accumulate in the brains of AD patients, but no report has addressed the relationship between these two events. This study investigated the effect of Abeta42 on the PLC-delta1 expression in human neuroblastoma cell lines. The PLC-delta1 mRNA level was increased by treatment with Abeta42 in a RT-PCR analysis. In the reporter assay, Abeta42 was found to activate the PLC-delta1 promoter activity in a dose-dependent manner. A novel NF-kappaB binding site in the PLC-delta1 promoter appeared to be responsible for the Abeta42 activity. First, the dominant negative forms of the NF-kappaB activating molecules, dominant negative TGF-beta activated kinase 1 (dnTAK1) and dnNIK (dominant negative NF-kappaB-inducing kinase), abolished the Abeta42 activity in the reporter assay. Second, the Abeta42 augmented a factor binding on the NF-kappaB site in the electrophoretic mobility shift assay (EMSA), which was abolished by a molar excess of the unlabeled consensus NF-kappaB oligonucleotide. These results suggest that the PLC-delta1 promoter is under the control of NF-kappaB, which mediates the expression of PLC-delta due to the Abeta42 treatment.     

Requirement for the p75 TNF-alpha receptor 2 in the regulation of airway hyperresponsiveness by gamma delta T cells

In a recent study, we found that TNF-alpha negatively regulates airway responsiveness through the activation of gammadelta T cells. The biological activities of TNF-alpha are mediated by two structurally related but functionally distinct receptors, p55 (TNFR1) and p75 (TNFR2), which are independently expressed on the cell surface. However, the relative importance of either TNFR in airway hyperresponsiveness (AHR) is unknown. To investigate the importance of these TNFRs in the development of allergen-induced AHR, p55-deficient and p75-deficient mice were sensitized to OVA by i.p. injection and subsequently challenged with OVA via the airways; airway responsiveness to inhaled methacholine was monitored. p75-deficient mice developed AHR to a similar degree as control mice. In contrast, p55-deficient mice, which were sensitized and challenged with OVA, failed to develop AHR. In p55-deficient mice, both the numbers of eosinophils and levels of IL-5 in bronchoalveolar lavage fluid were significantly lower than in sensitized/challenged control mice (p < 0.05). However, depletion of gammadelta T cells resulted in significant increases in AHR in the p55-deficient mice, whereas no significant effect of gammadelta T cell depletion was evident in the p75-deficient mice. These data indicate that, in the absence of TNFR1 (p55), where TNF-alpha uses the p75 pathway exclusively, the development of AHR is regulated by gammadelta T cells.     

Salt-induced changes in photosynthetic activity and growth in a potential medicinal plant Bishop’s weed (<Emphasis Type="Italic">Ammi majus</Emphasis> L.)

Sixty seven-days-old plants of Ammi majus L. were subjected for 46 d to sand culture at varying concentrations of NaCl, i.e. 0 (control), 40, 80, 120, and 160 mM. Increasing salt concentrations caused a significant reduction in fresh and dry masses of both shoots and roots as well as seed yield. However, the adverse effect of salt was more pronounced on seed yield than biomass production at the vegetative stage. Calculated 50 % reduction in shoot dry mass occurred at 156 mM (ca.15.6 mS cm^?1), whereas that in seed yield was at 104 mM (ca.10.4 mS cm^?1). As in most glycophytes, Na⁺ and Cl^? in both shoots and roots increased, whereas K⁺ and Ca²⁺ decreased consistently with the successive increase in salt level of the growth medium. Plants of A. majusmaintained markedly higher K⁺/Na⁺ ratios in the shoots than those in the roots, and the ratio remained more than 1 even at the highest external salt level (160 mM). Net photosynthetic (P_N) and transpiration (E) rates remained unaffected at increasing NaCl, and thus these attributes had a negative association with salt tolerance of A. majus. Proline content in the shoots increased markedly at the higher concentrations of salt. Essential oil content in the seed decreased consistently with increase in external salt level. Overall, A. majusis a moderately salt tolerant crop whose response to salinity is associated with maintenance of high shoot K⁺/Na⁺ ratio and accumulation of proline in shoots, but P_N had a negative association with the salt tolerance of this crop.     

Peroxisome proliferator-activated receptor gamma: its role in metabolic syndrome

Here we review PPARgamma function in relation to human adipogenesis, insulin sensitization, lipid metabolism, blood pressure regulation and prothrombotic state to perhaps provide justification for this nuclear receptor remaining a key therapeutic target for the continuing development of agents to treat human metabolic syndrome.     

Genetic basis of plant height and its degree of indetermination in mungbean (Vigna radiata (L.) Wilczek)

The genetic basis of plant height at various growth stages and the degree of indetermination of plant height in six mungbean genotypes (NM 92, 6601, NM 89, VC 1560D and VC 3902A) were assessed through half diallel cross. Cultivars, 6601 and NM 92, were the best general combiner for pre-flowering dry matter accumulation and minimum increase in plant height from first flower to 90% pods maturity, respectively. For these traits, the combination NM 92 x NM 89 was the best specific combiner of all the crosses. Both additive and dominant gene effects controlled the inheritance of plant height at first pod and to 90% pods maturity, degree of indetermination of plant height (DDh) from first flower to first pod maturity (DDh1), DDh from first flower to 90% pods maturity (DDh2) and DDh from first pod maturity to 90% pods maturity (DDh3). Plant height at first flower was additively inherited. The additive gene action was predominant as compared to dominant gene action for all the traits examined. High narrow and broad sense heritability estimates for DDh2 showed that better response to selection is possible for the development of mungbean genotypes with minimum increase in plant height during post-flowering development.