Evaluation of the therapeutic potential effect of Fas receptor gene knockdown in experimental model of non-alcoholic steatohepatitis

Aim: Stimulation of Fas death receptor is introduced as a major cause of non-alcoholic steatohepatitis (NASH) progression through suppression of cell viability. Therefore, the blocking of death pathways is hypothesised to be express new approaches to NASH therapy. For this purpose, current experiment applied synthetic small interference RNA (SiRNA) to trigger Fas death receptor and to show its potential therapeutic role in designed NASH model.

Methods: Male mice were placed on a western diet (WD) for 8 weeks and exposed to cigarette smoke during the last 4 weeks of feeding to induce NASH model. In the next step, Fas SiRNA was injected to mice aiming to examine specific Fas gene silencing, after 8 weeks. As a control, mice received scrambled SiRNA. Reversible possibility of disease was examined by 3 weeks of recovery.

Results: Analysis of data is accompanied with the significant histopathological changes (steatosis, ballooning and inflammation), increased lipid profile and hepatic enzyme activities (AST, ALT, ALP) plus TBARS as well as decreased antioxidants levels in NASH model. Upon Fas-SiRNA injection, almost all measured parameters of NASH such as overexpression of Fas receptor, caspase3, NF-kB genes and marked increase of hepatic TNF-α were significantly restored and were remained nearly unchanged following recovery liking as scrambled groups.

Conclusions: The suppression of Fas receptor signalling subsequent RNAi therapy may represent an applicable strategy to decline hepatocyte damages and so NASH progression in mice.     

Digestive proteolytic and amylolytic activities and feeding responses of Helicoverpa armigera (Lepidoptera: Noctuidae) on different host plants

Digestive proteolytic and amylolytic activities and feeding responses of fifth instar larvae of Helicoverpa armigera (Hübner) on different host plants including chickpea (cultivars Arman, Hashem, Azad, and Binivich), common bean (cultivar Khomein), white kidney bean (cultivar Dehghan), red kidney bean (cultivar Goli), cowpea (cultivar Mashhad), tomato (cultivar Meshkin), and potato (cultivars Agria and Satina) were studied under laboratory conditions (25 +/- 1 degrees C, 65 +/- 5% RH and a photoperiod of 16:8 [L:D] h). Our results showed that the highest protease activity in optimal pH was on cultivar Dehghan (8.717 U/mg) and lowest one was on Meshkin (3.338 U/mg). In addition, the highest amylase activity in optimal pH was on cultivar Dehghan (0.340 mU/mg) and lowest was on Meshkin (0.088 mU/mg). The larval weight of fifth instar H. armigera showed significant difference, being heaviest on Binivich (125.290 +/- 5.050 mg) and lightest on Meshkin (22.773 +/- 0.575 mg). Furthermore, the highest and lowest values of food consumed were on Goli (362.800 +/- 27.500 mg) and Satina (51.280 +/- 4.500 mg), respectively. In addition, the lowest values of prepupal and pupal weight were on Meshkin (32.413 +/- 0.980 and 41.820 +/- 1.270 mg, respectively). The results indicated that tomato (Meshkin) was unsuitable host for feeding fifth instar larvae of H. armigera.     

Design and synthesis of novel nitrogen-containing polyhydroxylated aromatics as HIV-1 integrase inhibitors from caffeic acid phenethyl ester

A series of nitrogen-containing polyhydroxylated aromatics from caffeic acid phenethyl ester were designed and synthesized as HIV-1 integrase inhibitors. Most of these compounds exhibited potent inhibitory activities at micromolar concentrations against HIV-1 integrase in the 3′-end processing and the strand transfer. Their key structure–activity relationship was also discussed.     

DNA cleavage activity of VO(acac)2 and derivatives

The DNA cleavage activity of several β-diketonate vanadyl complexes is examined. Vanadyl acetylacetonate, V^IVO(acac)₂, 1, shows a remarkable activity in degrading plasmid DNA in the absence of any activating agents, air and photoirradiation. The cleaving activity of several related complexes V^IVO(hd)₂ (2, Hhd = 3,5-heptanedione), V^IVO(acac-NH₂)₂ (3, Hacac-NH₂ = acetoacetamide) and V^IVO(acac-NMe₂)₂ (4, Hacac-NMe₂ = N,N-dimethylacetoacetamide) is also evaluated. It is shown that 2 exhibits an activity similar to 1, while 3 and 4 are much less efficient cleaving agents. The different activity of the complexes is related to their stability towards hydrolysis in aqueous solution, which follows the order 1∼2 ? 3∼4. The nature of the pH buffer was also found to be determinant in the nuclease activity of 1 and 2. In a phosphate buffered medium DNA cleavage by these agents is much more efficient than in tris, hepes, mes or mops buffers. The reaction seems to take place through a mixed mechanism, involving the formation of reactive oxygen species (ROS), namely OH radicals, and possibly also direct cleavage at phosphodiester linkages induced by the vanadium complexes.     

Identification of FABP7 in fibroblastic reticular cells of mouse lymph nodes

Fatty acids and their metabolites regulate immune cell function. The present study was undertaken to examine the detailed distribution of fatty acid binding proteins (FABPs), the cytosolic chaperones of fatty acids, in mouse peripheral immune organs. Using immunohistochemistry, FABP7 was localized to the alpha-smooth muscle actin (SMA)⁺ fibroblastic reticular cells, which construct the stromal reticula in the T cell areas of the peripheral lymph nodes and spleen. Immunoelectron microscopy showed that FABP7⁺ cells enclosed the collagen fibers, forming a conduit system, which transport lymph and associated low-molecular-mass proteins. In contrast, FABP5⁺ cells were distributed throughout the lymph node and contained well-developed lysosome and phagocytic materials within the cytoplasm. The mesenteric lymph nodes of FABP7 knockout mice showed normal histological features, but the percentage of CD4⁺ cells was significantly increased compared with that in wild-type mice. These data indicate that FABP7 may be involved in T cell homeostasis, possibly by modulating lipid metabolism in fibroblastic reticular cells within the peripheral lymph nodes.     

Development of preincubated chicken eggs following exposure to 50 Hz electromagnetic fields with 1.33-7.32 mT flux densities

The effects of applying extremely low-frequency (50 Hz) electromagnetic fields (ELF-EMF) for 24 hr and different densities (1.33-7.32 mT) were examined on healthy, freshly fertilized white leghorn chicken eggs (55-65 g). Results showed no increase in the rate of abnormalities in exposed groups, but were only significant in 4.19, 5.32 and 5.86, 6.65 mT densities. Alizarin red S and alcian blue 8GX staining showed some embryos with extra ribs, defects in ribs and vertebrae, anuria and abnormal beaks. Study of egg weight, after 9 days of incubation, showed no significant differences between control, sham-exposed and experimental groups. Analysis of crown-rump, beak-occipital length and weight of embryo, showed significant decrease in weight at 4.39 and 5.52 mT intensities, comparing with control and sham-exposed groups. These results revealed that 50 Hz electromagnetic fields can even induce developmental alterations in preincubated chick embryos and confirm that its strength could be a determinant factor for the embryonic response to extremely low frequency EMFs (window effects) prior to incubation.