Activities and polymorphisms of MMP-2 and MMP-9, smoking,diabetes and risk of prostate cancer

Molecular Biology Reports - Matrix metalloproteinases (MMPs) are a group of zinc dependent enzymes that are involved in tumor cell invasion and metastasis. The role of MMP-2 and -9 genetic...     

Effects of temozolomide on U87MG glioblastoma cell expression of CXCR4, MMP2, MMP9, VEGF,anti-proliferatory cytotoxic and apoptotic properties

Molecular Biology Reports - Temozolomide is an alkylating agent which is used in glioblastoma treatment. We aimed to investigate the effects of different concentrations of temozolomide and exposure...     

A Novel Dynamic Neonatal Blood-Brain Barrier on a Chip

Studies of neonatal neural pathologies and development of appropriate therapeutics are hampered by a lack of relevant in vitro models of neonatal blood-brain barrier (BBB). To establish such a model, we have developed a novel blood-brain barrier on a chip (B³C) that comprises a tissue compartment and vascular channels placed side-by-side mimicking the three-dimensional morphology, size and flow characteristics of microvessels in vivo. Rat brain endothelial cells (RBEC) isolated from neonatal rats were seeded in the vascular channels of B³C and maintained under shear flow conditions, while neonatal rat astrocytes were cultured under static conditions in the tissue compartment of the B³C. RBEC formed continuous endothelial lining with a central lumen along the length of the vascular channels of B³C and exhibited tight junction formation, as measured by the expression of zonula occludens-1 (ZO-1). ZO-1 expression significantly increased with shear flow in the vascular channels and with the presence of astrocyte conditioned medium (ACM) or astrocytes cultured in the tissue compartment. Consistent with in vivo BBB, B³C allowed endfeet-like astrocyte-endothelial cell interactions through a porous interface that separates the tissue compartment containing cultured astrocytes from the cultured RBEC in the vascular channels. The permeability of fluorescent 40 kDa dextran from vascular channel to the tissue compartment significantly decreased when RBEC were cultured in the presence of astrocytes or ACM (from 41.0±0.9 x 10⁻⁶ cm/s to 2.9±1.0 x 10⁻⁶ cm/s or 1.1±0.4 x 10⁻⁶ cm/s, respectively). Measurement of electrical resistance in B³C further supports that the addition of ACM significantly improves the barrier function in neonatal RBEC. Moreover, B³C exhibits significantly improved barrier characteristics compared to the transwell model and B³C permeability was not significantly different from the in vivo BBB permeability in neonatal rats. In summary, we developed a first dynamic in vitro neonatal BBB on a chip (B³C) that closely mimics the in vivo microenvironment, offers the flexibility of real time analysis, and is suitable for studies of BBB function as well as screening of novel therapeutics.     

Genetic diversity study of some medicinal plant accessions belong to Apiaceae family based on seed storage proteins patterns

Cumin (Cuminum cyminum L.), Fennel (Foeniculum vulgare L.) and Longleaf (Falcaria vulgaris Bernh) that all belong to Apiaceae family as medicinal plants are very important in many countries. Study of genetic diversity for medicinal plant is important for researches in future. One of the methods to evaluate plant genetic diversity and classification of them is the electrophoresis of seed storage proteins. This research was conducted in order to evaluate seed protein variability in different Iranian Cumin, Fennel and Longleaf accessions and grouping them based on these proteins as a biochemical marker. For this purpose, the samples were first powdered in liquid nitrogen and seed protein was extracted with extraction buffer. Then total soluble proteins were resolved on 12.5?% sodium dodecyl sulphate polyacrylamide gel electrophoresis gels. The electrophoretic protein pattern showed 38 bands that were low polymorphism among the accessions. The result of cluster analysis showed that the accessions were classified in three groups (all 29 Cumin accessions in the first group, three Fennel ecotypes in second group and three Longleaf accessions in the last one).     

Immune complexes present in the sera of autoimmune mice activate rheumatoid factor B cells

The fate of an autoreactive B cell is determined in part by the nature of the interaction of the B cell receptor with its autoantigen. In the lpr model of systemic autoimmunity, as well as in certain human diseases, autoreactive B cells expressing rheumatoid factor (RF) binding activity are prominent. A murine B cell transgenic model in which the B cell receptor is a RF that recognizes IgG2a of the j allotype (IgG2aj), but not the b allotype, was used in this study to investigate how the form of the autoantigen influences its ability to activate B cells. We found that sera from autoimmune mice, but not from nonautoimmune mice, were able to induce the proliferation of these RF+ B cells but did not stimulate B cells from RF- littermate controls. The stimulatory factor in serum was found to be IgG2aj, but the IgG2aj was stimulatory only when in the form of immune complexes. Monomeric IgG2aj failed to stimulate. Immune complexes containing lupus-associated nuclear and cytoplasmic autoantigens were particularly potent B cell activators in this system. Appropriate manipulation of such autoantibody/autoantigen complexes may eventually provide a means for therapeutic intervention in patients with certain systemic autoimmune disorders.     

Radiation-induced up-regulation of adhesion molecules in brain microvasculature and their modulation by dexamethasone

Little is known about the time course and magnitude of the up-regulation of endothelial cell adhesion molecules (ECAMs) in irradiated brain vasculature and the mechanisms by which dexamethasone modulates this up-regulation. We used antibody-conjugated microspheres and a rat closed cranial window model to determine the time course of functional up-regulation of radiation (20 Gy)-induced ICAM1, E-selectin and P-selectin in the pial vasculature of the rat brain and to determine the relationship between suppression of inflammation by dexamethasone and the expression of these ECAMs. The results indicate that ICAM1, E-selectin and P-selectin were up-regulated to a functional level in the microvasculature with distinct time-course patterns. The number of adherent anti-E-selectin and anti-P-selectin microspheres was 5- 12 times greater than that of IgG microspheres 3-6 h postirradiation, and their expression returned to normal at 48 h. The number of adherent anti-ICAM1 microspheres was five and nine times greater than that of IgG at 24 and 48 h, respectively, and returned to baseline by 7 days. Dexamethasone significantly reduced the number of adhering leukocytes and the number of adhering anti-ICAM1, anti-E-selectin and anti-P-selectin microspheres to background levels. Our findings partially identify a key sequence in radiation-induced inflammatory response and provide a potential means to limit radiation-induced inflammatory responses and their potential side effects in the brain.     

Early effects of ionizing radiation on the microvascular networks in normal tissue

Microvascular networks, which control the delivery of oxygen and nutrients and the removal of metabolic waste, are the most sensitive part of the vascular system to ionizing radiation. Structural and functional changes in microvascular networks were studied in locally irradiated (single 10-Gy dose) hamster cremaster muscles observed 3, 7 and 30 days post-irradiation. Networks were selected in reference to a well-defined location in the tissue to reduce heterogeneity due to spatial variations. Intravital microscopy was used to measure structural and functional parameters in vivo. A factorial design was used to examine the effects of radiation status, time postirradiation, and network vessel type on the structure and function of microvascular networks. While the diameter of microvessels in control animals increased significantly with age, vessel diameter in irradiated vessels decreased significantly with age. Red blood cell velocity in irradiated networks at 3 and 30 days postirradiation was significantly lower than in control networks. There was a significant decrease in capillary surface area and a significant increase in vessel hematocrit in irradiated animals. Blood flow in irradiated vessels was significantly lower than in control vessels. Changes in functional parameters were evident at 3 days postirradiation while changes in structural parameters occurred later. All vessel types were not damaged equally by radiation at every time examined.     

Beating cold by being tough: impact of elevation on leaf characteristics in <Emphasis Type="Italic">Phleum himalaicum</Emphasis> Mez. endemic to Himalaya

Effect of altitude on leaf responses in Phleum himalaicum populations was evaluated at three different elevation levels, viz. (Low 1200 m.a.s.l.), middle (1600 m a.s.l.) and high (1900 m a.s.l.) in western part of Himalaya. We hypothesized that physico-chemical properties of soil varied along elevation and Phleum populations located at high elevation would adapt more distinct morphological and physiological traits than those originating from middle and low elevation sites. Our study revealed that soil pH, Ec Mg, Ca, and P decreased at high elevation however, significant increase was recorded in soil K, organic matter, and total nitrogen along the elevation gradient. A significant correlation between leaf characteristics and elevation sites was recorded along the gradient. The outcomes of this study showed that highland population had better adjustments under low temperature and exhibited adaptive traits. These were, decreased number of leaves and leaf area, increased leaf blade thickness, intensive sclerification, and greater stomatal and trichome density. Apart from these, high elevation population had more physiological adjustment in terms of low stomatal conductance, low transpiration rate, high water use efficiency, and synthesis of more osmolytes in leaf. We argued that certain level of sugar and protein must be attained by high population to dodge the aggressive climatic forces in order to grow successfully at the highest elevation. Furthermore, altitude between 1600 and 1900 m was more likely an optimum zone for vigorous growth of P. himalaicum at the highest level of elevation.     

Generation of neural stem cells from adult astrocytes by using a single reprogramming factor

Generating neural stem cells (NSCs) from astroglia as an abundant cell type in the mammalian brain has a promising outlook to be used in cell-replacement therapy for treatment of neurodegenerative disorders and neuronal trauma. However, little is known about a single reprogramming factor that may lead to the generation of induced NSCs (iNSCs) from adult brain-derived astrocytes in the absence of extrinsic inductive signals. Here, we show that zinc-finger nuclear protein Zfp521 alone is sufficient for converting the adult mouse brain-derived astrocytes into iNSCs. In vitro, Zfp521-iNSCs demonstrated long-term self-renewal and multipotency and expressed related markers. Moreover, single-seeded iNSCs were able to produce NSC colonies. These results suggest that application of Zfp521 to generate iNSCs could be regarded as a new approach for conversion of resident astrocytes into iNSCs in cell therapy for in vivo treatment of neural injuries.