Chemopreventive and renal protective effects for docosahexaenoic acid (DHA): implications of CRP and lipid peroxides

Background

The fish oil-derived ω-3 fatty acids, like docosahexanoic (DHA), claim a plethora of health benefits. We currently evaluated the antitumor effects of DHA, alone or in combination with cisplatin (CP) in the EAC solid tumor mice model, and monitored concomitant changes in serum levels of C-reactive protein (CRP), lipid peroxidation (measured as malondialdehyde; MDA) and leukocytic count (LC). Further, we verified the capacity of DHA to ameliorate the lethal, CP-induced nephrotoxicity in rats and the molecular mechanisms involved therein.

Results

EAC-bearing mice exhibited markedly elevated LC (2-fold), CRP (11-fold) and MDA levels (2.7-fold). DHA (125, 250 mg/kg) elicited significant, dose-dependent reductions in tumor size (38%, 79%; respectively), as well as in LC, CRP and MDA levels. These effects for CP were appreciably lower than those of DHA (250 mg/kg). Interestingly, DHA (125 mg/kg) markedly enhanced the chemopreventive effects of CP and boosted its ability to reduce serum CRP and MDA levels. Correlation studies revealed a high degree of positive association between tumor growth and each of CRP (r = 0.85) and leukocytosis (r = 0.89), thus attesting to a diagnostic/prognostic role for CRP. On the other hand, a single CP dose (10 mg/kg) induced nephrotoxicity in rats that was evidenced by proteinuria, deterioration of glomerular filtration rate (GFR, -4-fold), a rise in serum creatinine/urea levels (2–5-fold) after 4 days, and globally-induced animal fatalities after 7 days. Kidney-homogenates from CP-treated rats displayed significantly elevated MDA- and TNF-α-, but reduced GSH-, levels. Rats treated with DHA (250 mg/kg, but not 125 mg/kg) survived the lethal effects of CP, and showed a significant recovery of GFR; while their homogenates had markedly-reduced MDA- and TNF-α-, but -increased GSH-levels. Significant association was detected between creatinine level and those of MDA (r = 0.81), TNF-α ) r = 0.92) and GSH (r = -0.82); implying causal relationships.

Conclusion

DHA elicited prominent chemopreventive effects on its own, and appreciably augmented those of CP as well. The extent of tumor progression in various mouse groups was highly reflected by CRP levels (thus implying a diagnostic/prognostic role for CRP). Further, this study is the first to reveal that DHA can obliterate the lethal CP-induced nephrotoxicity and renal tissue injury. At the molecular level, DHA appears to act by reducing leukocytosis, systemic inflammation, and oxidative stress.     

感染球孢白僵菌后红火蚁体内蛋白质含量的变化

为了解球孢白僵菌Beauveria bassiana成功感染红火蚁Solenopsis invicta的生理生化机制, 本研究在室内条件下测定了经球孢白僵菌感染后红火蚁工蚁、蛹和幼蚁体内蛋白质含量的变化。结果表明: 红火蚁各虫态感染球孢白僵菌后体内蛋白质含量变化存在差异。在接种后12-72 h, 工蚁体内蛋白质含量在24 h时最高, 为47.12 mg/g, 显著低于对照的56.40 mg/g(P＜0.05), 此后呈下降趋势, 72 h时蛋白质含量下降至25.16 mg/g。幼蚁在接种36 h时体内蛋白质含量最高, 为24.13 mg/g, 此后呈下降趋势, 72 h时蛋白质含量为8.95 mg/g, 显著低于对照的24.80 mg/g。蛹感染球孢白僵菌后体内蛋白质含量一直呈下降趋势, 从12 h的36.57 mg/g降到72 h的10.42 mg/g, 与对照的38.61 mg/g相比差异显著(P＜0.05)。结果显示球孢白僵菌感染能显著降低红火蚁各虫态体内蛋白质含量。     

Cicada ear geometry: species and sex effects

Many insect species rely on their sense of audition to find a mate, to localize prey or to escape from a predator. Cicadas are particularly known for their loud call and the conspicuous tympanal hearing system located in their abdomen. The vibration pattern of the tympanal membrane (TM) has been investigated recently revealing mechanical properties specific to species and sex. Although TM size and shape is likely to affect these patterns, the geometry of the cicada ear has never been examined per se. Focusing on three Mediterranean cicada species, namely Cicadatra atra, Cicada orni and Lyristes plebejus, we investigated the structure of TM shape variation at two levels, within and across species. Applying an elliptic Fourier analysis to the outlines of both male and female TMs, we estimated sexual dimorphism and species effects. Cicadatra atra showed a large TM compared with its small size, probably as a result of selective constraints related to the role of the TM in sound production. Sexual dimorphism seemed to be greater than interspecific variation, indicating that constraints operating on sex might be more selective than those acting on species identification. In addition, C. orni appeared to be significantly different from the two other species. This morphological peculiarity could be related to the unique vibrational pattern of its membrane. This would establish for the first time a direct link between the shape and mechanism of a hearing organ. © 2010 The Linnean Society of London, Biological Journal of the Linnean Society, 2010, 101 , 922–934.     

Phylogeography of the mottled spinefoot Siganus fuscescens: Pleistocene divergence and limited genetic connectivity across the Philippine archipelago

Historical isolation during Pleistocene low sea level periods is thought to have contributed to divergence among marine basin populations across the Coral Triangle. In the Philippine archipelago, populations in the South China Sea, Sulu Sea–inland seas, and Philippine Sea‐Celebes Sea basins might have been partially isolated. Meanwhile, present‐day broadscale oceanographic circulation patterns suggest connectivity between these basins. To evaluate hypotheses regarding the influence of historical and contemporary factors on genetic structure, phylogeographic patterns based on mitochondrial control region sequences for a reef‐associated fish, Siganus fuscescens, were analysed. Three distinct lineages were recovered. One lineage was identified as the morphologically similar species Siganus canaliculatus, while two lineages are monophyletic with S. fuscescens. Clade divergence and demographic expansion in S. fuscescens occurred during the Pleistocene. A strong signal of latitudinal structure was detected (Φ_CT = 0.188), driven by marked differences in clade distribution: one clade is widely distributed (clade A), while a second clade (clade B) has a restricted northern distribution. Regional structure of clade A is consistent with the basin isolation hypothesis (Φ_CT = 0.040) and suggests isolation of the South China Sea (Φ_CT = 0.091). Fine‐scale structure was observed in the South China Sea and south Philippine Sea, while Sulu Sea and inland seas were unstructured. Genetic structure across multiple spatial scales (archipelagic, regional, and fine‐scale within basins) suggests the influence of vicariant barriers and contemporary limits to gene flow in S. fuscescens that may be influenced by oceanographic circulation, geographical distance between available habitats, and latitudinal temperature differences.     

<Emphasis Type="Italic">In vitro</Emphasis> and <Emphasis Type="Italic">ex vivo</Emphasis> effect of hyaluronic acid on erythrocyte flow properties

Background  

Hyaluronic acid (HA) is present in many tissues; its presence in serum may be related to certain inflammatory conditions, tissue damage, sepsis, liver malfunction and some malignancies. In the present work, our goal was to investigate the significance of hyaluronic acid effect on erythrocyte flow properties. Therefore we performed in vitro experiments incubating red blood cells (RBCs) with several HA concentrations. Afterwards, in order to corroborate the pathophysiological significance of the results obtained, we replicated the in vitro experiment with ex vivo RBCs from diagnosed rheumatoid arthritis (RA) patients, a serum HA-increasing pathology.     

1590名农村中老年人生存质量调查分析(英文)

目的:采用SF-36量表中文版评价农村中老年人生存质量,并为提高农村中老年人的生存质量和健康水平提供科学依据和建议。方法:采用随机抽样的方法,采用面对面访谈的形式,记分方法参照国际生存质量评价计划(IQOLA)的制定标准,评价其生理和心理健康状况。结果:1590名农村中老年人男性生存质量得分高于女性。经济水平对农村中老年人的生理健康的影响大于对其心理健康的影响。配偶健在的农村中老年人的各维度得分均高于无配偶者。农村中老年人的各维度得分随教育水平的升高呈升高趋势。结论:农村中老年人的生存质量与年龄成负相关,同时也受文化程度和经济水平等多个因素的影响。因而,对农村中老年人这一弱势群体应该给予更多关注。     

Identifying chironomids (Diptera: Chironomidae) for biological monitoring with PCR-RFLP

Chironomids are excellent biological indicators for the health of aquatic ecosystems, but their use at finer taxonomic levels is hindered by morphological similarity of species at each life stage. Molecular markers have the potential to overcome these problems by facilitating species identification particularly in large-scale surveys. In this study, the potential of the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) approach was tested to rapidly distinguish among chironomids within a geographic area, by considering chironomid species from Melbourne, Australia. By comparing molecular markers with diagnostic morphological traits, RFLP profiles of the cytochrome oxidase I (COI) region were identified that were specific to genera and some common species. These profiles were used to develop an RFLP-based key, which was validated by testing the markers on samples from several wetlands and streams. As well as allowing for rapid identification of species that are difficult to separate on morphological grounds, this approach also has the potential to resolve current taxonomic ambiguities.     

Inhibition of mitochondrial respiration: a novel strategy to enhance drug-induced apoptosis in human leukemia cells by a reactive oxygen species-mediated mechanism

Cancer cells are under intrinsic increased oxidative stress and vulnerable to free radical-induced apoptosis. Here, we report a strategy to hinder mitochondrial electron transport and increase superoxide O2. radical generation in human leukemia cells as a novel mechanism to enhance apoptosis induced by anticancer agents. This strategy was first tested in a proof-of-principle study using rotenone, a specific inhibitor of mitochondrial electron transport complex I. Partial inhibition of mitochondrial respiration enhances electron leakage from the transport chain, leading to an increase in O2. generation and sensitization of the leukemia cells to anticancer agents whose action involve free radical generation. Using leukemia cells with genetic alterations in mitochondrial DNA and biochemical approaches, we further demonstrated that As2O3, a clinically active anti-leukemia agent, inhibits mitochondrial respiratory function, increases free radical generation, and enhances the activity of another O2.-generating agent against cultured leukemia cells and primary leukemia cells isolated from patients. Our study shows that interfering mitochondrial respiration is a novel mechanism by which As2O3 increases generation of free radicals. This novel mechanism of action provides a biochemical basis for developing new drug combination strategies using As2O3 to enhance the activity of anticancer agents by promoting generation of free radicals.     

Selective retrograde transsynaptic transfer of a protein, tetanus toxin, subsequent to its retrograde axonal transport

The fate of tetanus toxin (mol wt 150,000) subsequent to its retrograde axonal transport in peripheral sympathetic neurons of the rat was studied by both electron microscope autoradiography and cytochemistry using toxin-horseradish peroxidase (HRP) coupling products, and compared to that of nerve growth factor (NGF), cholera toxin, and the lectins wheat germ agglutinin (WGA), phytohaemagglutinin (PHA), and ricin. All these macromolecules are taken up by adrenergic nerve terminals and transported retrogradely in a selective, highly efficient manner. This selective uptake and transport is a consequence of the binding of these macromolecules to specific receptive sites on the nerve terminal membrane. All these ligands are transported in the axons within smooth vesicles, cisternae, and tubules. In the cell bodies these membrane compartments fuse and most of the transported macromolecules are finally incorporated into lysosomes. The cell nuclei, the parallel golgi cisternae, and the extracellular space always remain unlabeled. In case the tetanus toxin, however, a substantial fraction of the labeled material appears in presynaptic cholinergic nerve terminals which innervate the labeled ganglion cells. In these terminals tetanus toxin-HRP is localized in 500-1,000 A diam vesicles. In contrast, such a retrograde transsynaptic transfer is not at all or only very rarely detectable after retrograde transport of cholera toxin, NGF, WGA, PHA, or ricin. An atoxic fragment of the tetanus toxin, which contains the ganglioside-binding site, behaves like intact toxin. With all these macromolecules, the extracellular space and the glial cells in the ganglion remain unlabeled. We conclude that the selectivity of this transsynaptic transfer of tetanus toxin is due to a selective release of the toxin from the postsynaptic dendrites. This release is immediately followed by an uptake into the presynaptic terminals.     

Low density and high density lipoprotein turnover following portacaval shunt in swine.

Turnover of 125I-low density lipoprotein (LDL) and of 131I-high density lipoprotein (HDL) was determined before and after end-to-side portacaval shunt in eight swine. LDL (d 1.019-1.063) and HDL (d.1.09-1.21) were isolated by ultracentrifugation and iodinated by the iodine monochloride technique. Immediately postoperatively there was no consistent change in the fractional catabolic rate (FCR) of LDL compared to preoperative control values, while in all animals FCR of HDL was significantly increased (by as much as 300%). After recovery from surgery, neither LDL nor HDL catabolic rates were significantly elevated above control values in four swine. However, plasma levels of LDL and HDL protein, and of LDL and HDL cholesterol were significantly reduced 10-12 weeks after the portacaval shunt. The reduced levels of LDL and HDL associated with normal fractional clearance rates imply a reduction in synthesis of LDL and HDL following portal diversion.