Involvement of NADPH oxidase in up-regulation of plasminogen activator inhibitor-1 and heat shock factor-1 in mouse embryo fibroblasts induced by oxidized LDL and in apolipoprotein E-deficient mice

The present study demonstrated that oxidized LDL (oLDL) increased the generation of superoxide and hydrogen peroxide (H(2)O(2)), the abundances of NADPH oxidase (NOX)4, NOX2, p22-phox and lectin-like oLDL receptor-1 (LOX-1) in wild-type or heat shock factor-1 (HSF1)-deficient mouse embryo fibroblasts (MEF). LOX-1 antibody inhibited LDL or oLDL-induced expression of NOX components in MEF. Abundance of HSF1 or plasminogen activator inhibitor-1 (PAI-1) was increased by oLDL in wild-type, but not in HSF1-deficient MEF. Diphenyleneiodonium or siRNA for NOX or p22-phox inhibited oLDL-induced increases of HSF1, PAI-1 and H(2)O(2) in MEF. Increased NOX4, NOX2, LOX1, HSF1 and PAI-1 were detected in aortae and hearts of apolipoprotein E-knockout (apoE-KO) mice compared to controls, which were associated with increased serum cholesterol or plasma PAI-1. The results suggest that NOX is required for oLDL-induced HSF1 or PAI-1 expression in MEF, which was supported by the up-regulation of NOX, LOX-1, HSF1 and PAI-1 in apoE-KO mice.     

Species-related variations in antioxidant components of gastric and duodenal mucosa

Enzymatic and non-enzymatic antioxidant profiles of the gastric and duodenal mucosa of rat, rabbit, cat and pig were investigated and found to exhibit significant variations. Rat gastric and duodenal mucosa exhibited the highest levels of basal glutathione of the various tissues examined. The highest activity of glutathione reductase was found in the gastric and duodenal mucosa of rat as compared with that in these tissues from the other species. The gastric mucosa of cat and pig showed similar activities of glutathione peroxidase, which was significantly lower than those in rat or rabbit gastric mucosa. The activity of this antioxidant enzyme was similar in rat, rabbit and pig duodenal mucosa and lower than that in cat duodenal mucosa. Strong correlations were found between activities of the functionally coupled antioxidant enzymes glutathione peroxidase and glutathione reductase in gastric but not in duodenal mucosa. The activity of superoxide dismutase showed negligible regional or species-related variations in activity.     

Aspergillus terreus and its toxic metabolites as a food contaminant in some Egyptian Bakery products and grains

A. terreus isolates isolated from some bakery products, corn and rice were found to be able to produce territrems. 90% of theA. terreus isolated from bakery products were able to produce territrem A, with a mean of 0.09 ppm, while 80% ofA. terreus isolates produce territrem B with a mean of 0.24 ppm. On the other hand 31.8% of the isolates ofA. terreus from corn were able to produce territrem A with a mean of 0.44 ppm. ConcerningA. terreus isolates from rice, 66.7% were found to produce territrem A, with a mean of 5.28 ppm, and 77.8% of the isolates produced territrem B with a mean of 1.79 ppm.     

Lack of regression of atherosclerotic lesions in phytosterol-treated apo E-deficient mice

We evaluated the effects of a phytosterol mixture (FCP-3PI) on the regression of atherosclerotic lesions in male apo E-deficient mice. Atherosclerosis was induced in fifteen mice by a "Western-type" diet containing 9% (w/w) fat and 0.15% (w/w) cholesterol over a period of 18 weeks (Induction phase). Then, two mice were used to evaluate the development of atherosclerosis, and the rest was divided into the control (n=6) and treated (n=7) groups. The control group was fed mouse chow (4.5% w/w fat) and the treated group fed the same chow supplemented with 2% (w/w) FCP-3PI for an additional 25 weeks (Regression phase). The mice developed severe hypercholesterolemia and advanced atherosclerotic lesions over the induction phase. During the first 6 weeks of regression phase, plasma cholesterol concentrations decreased at a similar rate (35%) in both groups of control and phytosterol-treated mice. Although evidence of lesion regression was not observed in either group of mice, the treated group had slightly smaller lesion size than the controls. During the induction phase, each mouse developed atherosclerotic lesions averaging 0.025 mm2 per week. However, during the regression phase, this was decreased to approximately one fifth and one third in the treated and control groups, respectively. Thus, compared to the end of the induction phase, the control group had a 40% increase in the lesion size, while this increase was only 28% in the treated animals. In conclusion, our previous findings along with a small decrease in the atherosclerotic lesion size observed in the treated group in the present study suggest that FCP-3PI treatment may slow the development of atherosclerotic lesions in apo E-deficient mice; however, a longer regression period may yield a greater benefit.     

PSP94融合蛋白在大肠杆菌中的表达及其抗前列腺癌活性分析

在从成年人正常前列腺组织中获得人９４个氨基酸的前列腺分泌蛋白（ＰＳＰ９４）ｃＤＮＡ基础上,利用ＰＬ表达系统,实现了人ＰＳＰ９４成熟肽Ｎ 末端带有１９个外源氨基酸的融合蛋白在大肠杆菌中的表达。目的蛋白在细胞中主要以包涵体形式存在,表达量约占菌体总蛋白的３０％,分子量约为１６－５ｋＤ。表达产物在人前列腺癌细胞ＰＣ ３上活性分析表明,该融合蛋白能明显抑制前列腺癌细胞的生长。     

Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions

Dietary flaxseed has been shown to have potent antiatherogenic effects in rabbits. The purpose of the present study was to investigate the antiatherogenic capacity of flaxseed in an animal model that more closely represents the human atherosclerotic condition, the LDL receptor-deficient mouse (LDLrKO), and to identify the cellular mechanisms for these effects. LDLrKO mice were administered a regular diet (RG), a 10% flaxseed-supplemented diet (FX), or an atherogenic diet containing 2% cholesterol alone (CH) or supplemented with 10% flaxseed (CF), 5% flaxseed (CF5), 1% flaxseed (CF1), or 5% coconut oil (CS) for 24 wk. LDLrKO mice fed a cholesterol-supplemented diet exhibited a rise in plasma cholesterol without a change in triglycerides and an increase in atherosclerotic plaque formation. The CS mice exhibited elevated levels of plasma cholesterol, triglycerides, and saturated fatty acids and an increase in plaque development. Supplementation of the cholesterol-enriched diet with 10% (wt/wt) ground flaxseed lowered plasma cholesterol and saturated fatty acids, increased plasma ALA, and inhibited plaque formation in the aorta and aortic sinus compared with mice fed a diet supplemented with only dietary cholesterol. The expression of proliferating cell nuclear antigen (PCNA) and the inflammatory markers IL-6, mac-3, and VCAM-1 was increased in aortic tissue from CH and CS mice. This expression was significantly reduced or normalized when flaxseed was included in the diet. Our results demonstrate that dietary flaxseed can inhibit atherosclerosis in the LDLrKO mouse through a reduction of circulating cholesterol levels and, at a cellular level, via antiproliferative and anti-inflammatory actions.     

Vasospasm is a significant factor in cyclosporine-induced neurotoxicity: Case report

Background

The aetiology of central nervous system lesions observed in cerebral cyclosporine neurotoxicity remains controversial.

Case presentation

We report a 48-year-old woman with a non-severe aplastic anaemia who presented with stroke-like episodes while on cyclosporine treatment.Transcranial Doppler ultrasound revealed severely elevated flow velocities in several cerebral vessels, consistent with vasospasm. Immediately after reducing the cyclosporine dose, the stroke-like episodes disappeared. Only after cyclosporine withdrawal the transcranial Doppler ultrasound abnormalities fully resolved.

Conclusions

This case demonstrates a significant role of vasospasm in the pathway of cyclosporine-induced neurotoxicity. Transcranial Doppler ultrasound is an effective tool for the diagnosis and follow-up of cyclosporine-induced vasospasm.

     

Sources of fish in the ephemeral western iishana region of the Cuvelai–Etosha Basin in Angola and Namibia

The triangle between the Kavango and Kunene rivers is drained by the Cuvelai, an ephemeral and deltaic drainage system covering more than 100 000 km². In good rainfall years, the area becomes populated by fish communities dominated by five species migrating southward towards the endorheic Etosha Pan, the basin’s terminal sump. When water dries up, fish subsequently die-off and their sudden appearance in rainy years has captivated scientists for decades. The current study was prompted by hitherto untapped indigenous knowledge through narratives of opportunistic fish harvesting of migrating fish at temporary connections between the Kunene River and the Cuvelai- Etosha Basin. A reconnaissance fish survey in 2017 was complemented by digital satellite images and elevation data analyses. Results support the presence of at least three major ephemeral fish migration routes. The dominant fish genera migrating upstream in Kunene tributaries comprise Enteromius, Oreochromis and Clarias, all eurytopic and known to undertake upstream, lateral and downstream migrations on floodplains. Although other notable fish refugia in the Cuvelai–Etosha Basin are yet to be identified, there is a necessity for the protection and management of these migration routes in tandem with studies on the nature and extent of this inter-basin fish migration under climate change and variability.     

The molecular organization of the beta-globin complex of the deer mouse, Peromyscus maniculatus

Recombinant DNA clones have been isolated that contain 80 kb of the beta-globin complex from the deer mouse, Peromyscus maniculatus. Comparisons of this complex with that from the laboratory mouse, Mus domesticus (with an order 5'-Hbby, Hbb-bhO, Hbb-bhl, Hbb-bh2, Hbb-bh3, Hbb-bl, Hbb-b2 3') highlight organizational trends in the beta-globin complex since the two species diverged. Unlike other mammals studied thus far, the deer mouse possesses three adult genes. Partial sequence analysis indicates that each of the three adult genes is intact and hence may be functional. Hybridization of one of the two Mus pseudogenes, Hbb-bh3, to genomic blots from Peromyscus reveals that it has a homologous counterpart in Peromyscus. Homologous genes to the two gamma-like Mus genes, Hbb-bhO and Hbb-bhl, are also found in Peromyscus. The strong hybridization between the Hbb-bhl genes and significant nucleotide similarity between the Hbb-bhO genes suggest that both pairs are important for the ontogeny of these mice although no known product has been identified for the Hbb-bhO genes. The presence of Hbb-bhO and Hbb-bhl in Peromyscus suggests that the duplication that created this related gene set occurred before the two lineages diverged. A single gene for Hbb-y has been isolated from Peromyscus. The adult region in Peromyscus has undergone significant divergence from the same region in Mus, having three rather than two adult genes, the acquisition of at least 15 kb of extra DNA relative to Mus, and possibly the loss of the Hbb-bh2 pseudogene. The nonadult region of the complex, in contrast, contains the same set of genes apparently distributed over the same amount of DNA as in the Mus beta- globin complex. This observation suggests that the embryonic region of the complex is more evolutionarily stable than the adult region.