Production of cytotoxic factor for oligodendrocytes by stimulated astrocytes

Stimulation of rat astrocytes in vitro by calcium ionophore A23187 and/or lipopolysaccharide results in the generation of a cytotoxic factor that is functionally similar to the previously described macrophage-derived cytotoxic factor, tumor necrosis factor. Like the macrophage product, the astrocyte cytotoxic factor kills murine L 929 cell targets. In addition, it kills rat oligodendrocytes, the myelin-producing cells of the central nervous system. Human recombinant tumor necrosis factor also has cytotoxic activity directed against rat oligodendrocytes.     

Release of Leukotriene B4 from Sublethally Injured Oligodendrocytes by Terminal Complement Complexes

In the present study, the interaction of the terminal complement complexes with oligodendrocytes was investigated for observation of its effect on membrane lipid hydrolysis. [14C]Arachidonic acid was incorporated into the membrane lipids of cultured oligodendrocytes before sensitization with anti-galactocerebroside antiserum. Cells were then exposed to excess C6-deficient rabbit serum reconstituted with limiting doses of C6 to form various numbers of C5b-9 complexes. Qualitative analysis of the supernatants by HPLC revealed the presence of compounds that coeluted with arachidonic acid and its oxygenated derivatives, prostaglandin E2, leukotrienes E4 and B4, and 15-hydroxyeicosatetraenoic acid. The kinetics of leukotriene B4 release by excess C5b-8 was quantitated by radioimmunoassay. Leukotriene B4 release approached a maximum around 30 min, and C6 dose-response studies performed at 1 h showed that maximal levels of leukotriene B4 were detected over a range of sublytic C5b-9 attack. Maximal release of leukotriene B4 was also achieved by C5b-8 without further enhancement by addition of lytic doses of C9. Results indicate that sublytic attack of oligodendrocytes by complement induces release of lipid-derived inflammatory mediators.     

Vitamin D3 affects mitochondrial biogenesis through mitogen-activated protein kinase in polycystic ovary syndrome mouse model

Polycystic ovarian syndrome (PCOS) is a disorder characterized by oligomenorrhea, anovulation, and hyperandrogenism. Altered mitochondrial biogenesis can result in hyperandrogenism. The goal of this study was to examine the effect of vitamin D3 on mitochondrial biogenesis of the granulosa cells in the PCOS-induced mouse model. Vitamin D3 applies its effect via the mitogen-activated pathway kinase-extracellular signal-regulated kinases (MAPK-ERK1/2) pathway. The PCOS mouse model was induced by the injection of dehydroepiandrosterone (DHEA). Isolated granulosa cells were subsequently treated with vitamin D3, MAPK activator, and MAPK inhibitor. Gene expression levels were measured using real-time polymerase chain reaction. MAPK proteins were investigated by western blot analysis. We also determined reactive oxygen species (ROS) levels with 2′, 7′-dichlorofluorescein diacetate. Mitochondrial membrane potential (mtMP) was also measured by TMJC1. Mitochondrial biogenesis (peroxisome proliferator-activated receptor gamma coactivator 1-α and nuclear respiratory factor), antioxidant (superoxide dismutase, glutathione peroxidase, and catalase), and antiapoptotic (B-cell lymphoma-2) genes were upregulated in the PCOS mice that treated with vitamin D3 compared with the PCOS mice without any treatment. Vitamin D3 and MAPK activator-treated groups also reduced ROS levels compared with the nontreated PCOS group. In summary, vitamin D3 and MAPK activator increased the levels of mitochondrial biogenesis, MAPK pathway, and mtMP markers, while concomitantly decreased ROS levels in granulosa cells of the PCOS-induced mice. This study suggests that vitamin D3 may improve mitochondrial biogenesis through stimulation of the MAPK pathway in cultured granulosa cells of DHEA-induced PCOS mice which yet to be investigated.     

Dosimetric parameters of the new design 103Pd brachytherapy source based on Monte Carlo study

In this study version 5 of the MCNP photon transport simulation was used to calculate the dosimetric parameters for new palladium brachytherapy source design following AAPM Task Group No. 43U1 report. The internal source components include four resin beads of 0.6 mm diameters with ¹⁰³Pd uniformly absorbed inside and one cylindrical copper marker with 1.5 mm length. The resin beads and marker are then encapsulated within 0.8 mm in diameter and 4.5 mm long cylindrical capsule of titanium. The dose rate constant, Λ, line and point-source radial dose function, g_L(r) and g_P(r), and the anisotropy function, F(r,θ) of the IR01-¹⁰³Pd seed have been calculated at distances from 0.25 to 5 cm. All the results are in good agreement with previously published thermoluminescence-dosimeter measured values [3] for the source. The dosimetric parameters calculated in this work showed that in dosimetry point of view, the IR01-¹⁰³Pd seed is suitable for use in brachytherapy of prostate cancer.     

Synthesis and antibacterial activity of new fluoroquinolones containing a substituted N-(phenethyl)piperazine moiety

N-(Phenethyl)piperazinyl quinolone derivatives that bear a methoxyimino-substituent have been synthesized and evaluated for antimicrobial activity against Gram-positive and Gram-negative microorganisms. In addition, to define structure-activity relationships, ciprofloxacin derivatives containing 2-oxo-2-phenylethyl or 2-hydroxyimino-2-phenylethyl moieties at N-4 position of piperazine ring were prepared and tested. Ciprofloxacin derivatives, containing a N-(chloro-substituted phenethyl) residue, showed in vitro Gram-positive and Gram-negative activity generally comparable or superior to that of reference quinolones.     

Radio-protective effects of melatonin against irradiation-induced oxidative damage in rat peripheral blood

During radiotherapy, ionizing irradiation interacts with biological systems to produce free radicals, which attacks various cellular components. The hematopoietic system is well-known to be radiosensitive and its damage may be life-threatening. Melatonin synergistically acts as an immunostimulator and antioxidant. In this study we used a total of 120 rats with 20 rats in each group. Group 1 did not receive melatonin or irradiation (Control group), Group 2 received only 10 mg/kg melatonin (Mel group), Group 3 exposed to dose of 2 Gy irradiation (2 Gy Rad group), Group 4 exposed to 8 Gy irradiation (8 Gy Rad group), Group 5 received 2 Gy irradiation plus 10 mg/kg melatonin (Mel +2 Gy Rad group) and Group 6 received 8 Gy irradiation plus 10 mg/kg melatonin (Mel+8 Gy Rad group). Following exposure to radiation, five rats from each group were sacrificed at 4, 24, 48 and 72 h. Exposure to different doses of irradiation resulted in a dose-dependent decline in the antioxidant enzymes activity and lymphocyte count (LC) and an increase in the nitric oxide (NO) levels of the serum. Pre-treatment with melatonin (10 mg/kg) ameliorates harmful effects of 2 and 8 Gy irradiation by increasing lymphocyte count(LC) as well as antioxidant enzymes activity and decreasing NO levels at all time-points. In conclusion 10 mg/kg melatonin is likely to be a threshold concentration for significant protection against lower dose of 2 Gy gamma irradiation compared to higher dose of 8 Gy. Therefore, it seems that radio-protective effects of melatonin are dose-dependent.     

Curvelet Based Offline Analysis of SEM Images

Manual offline analysis, of a scanning electron microscopy (SEM) image, is a time consuming process and requires continuous human intervention and efforts. This paper presents an image processing based method for automated offline analyses of SEM images. To this end, our strategy relies on a two-stage process, viz. texture analysis and quantification. The method involves a preprocessing step, aimed at the noise removal, in order to avoid false edges. For texture analysis, the proposed method employs a state of the art Curvelet transform followed by segmentation through a combination of entropy filtering, thresholding and mathematical morphology (MM). The quantification is carried out by the application of a box-counting algorithm, for fractal dimension (FD) calculations, with the ultimate goal of measuring the parameters, like surface area and perimeter. The perimeter is estimated indirectly by counting the boundary boxes of the filled shapes. The proposed method, when applied to a representative set of SEM images, not only showed better results in image segmentation but also exhibited a good accuracy in the calculation of surface area and perimeter. The proposed method outperforms the well-known Watershed segmentation algorithm.     

Mucin 20 modulates proteasome capacity through c-Met signalling to increase carfilzomib sensitivity in mantle cell lymphoma

Mantle cell lymphoma (MCL) is a haematologic malignancy. The proteasome inhibitor (PI) bortezomib has been approved to treat MCL, but resistance has emerged through mechanisms that remain unclear. This study aimed to explore the mechanism of PI resistance in MCL and identify new targets for this patient subgroup. Carfilzomib-resistant (CR) MCL cell lines and primary samples were used for both in vitro and in vivo experiments to identify gene expression and explore their related signalling pathways. We first identified mucin 20 (MUC20) suppression in carfilzomib-resistant MCL models. MUC20 overexpression sensitized cells to carfilzomib in vitro and in vivo. MUC20 expression was inversely related to activation of c-Met and the downstream p44/42 MAPK pathway. c-Met activation with hepatocyte growth factor (HGF) induced PI resistance, while c-Met inhibition restored PI sensitivity. Carfilzomib resistance and depressed MUC20 expression were associated with enhanced proteasome activity and higher expression of proteassemblin (POMP), a chaperone for catalytically active proteasome assembly. c-Met and POMP were associated through binding and induction of MAPK-regulated ELK1 to the POMP promoter. Our data reveal that c-Met signalling activation enhanced proteasome capacity as a mechanism of PI resistance, and MUC20 expression may be a useful biomarker for PI therapy.