Therapeutic effect of vegetable oils and ubiquinone-9 on radiation injuries

The comparison was made of the protective (the administration 3 h before irradiation with a dose of 7.3 Gy) and therapeutic (the administration immediately and later after exposure) effects of soya oil (150 mg/kg) and oil solution of ubiquinone-9 (100-200 mg/kg) on survival of exposed rats. It was shown that soya oil and ubiquinone-9 increased the survival rate of rats when administered before and, to a lesser extent, immediately after irradiation. Corn oil administered immediately after exposure increased the survival rate as well. DMF for the therapeutic effect of soya oil solution of ubiquinone-9 was 1.08.     

Molecular Hazard Identification of Non-O157 Shiga Toxin-Producing Escherichia coli (STEC)

The complexity regarding Shiga toxin-producing Escherichia coli (STEC) in food safety enforcement as well as clinical care primarily relates to the current inability of an accurate risk assessment of individual strains due to the large variety in serotype and genetic content associated with (severe) disease. In order to classify the clinical and/or epidemic potential of a STEC isolate at an early stage it is crucial to identify virulence characteristics of putative pathogens from genomic information, which is referred to as ‘predictive hazard identification’. This study aimed at identifying associations between virulence factors, phylogenetic groups, isolation sources and seropathotypes. Most non-O157 STEC in the Netherlands belong to phylogroup B1 and are characterized by the presence of ehxA, iha and stx ₂, but absence of eae. The large variability in the number of virulence factors present among serogroups and seropathotypes demonstrated that this was merely indicative for the virulence potential. While all the virulence gene associations have been worked out, it appeared that there is no specific pattern that would unambiguously enable hazard identification for an STEC strain. However, the strong correlations between virulence factors indicate that these arrays are not a random collection but are rather specific sets. Especially the presence of eae was strongly correlated to the presence of many of the other virulence genes, including all non-LEE encoded effectors. Different stx-subtypes were associated with different virulence profiles. The factors ehxA and ureC were significantly associated with HUS-associated strains (HAS) and not correlated to the presence of eae. This indicates their candidacy as important pathogenicity markers next to eae and stx _2a.     

Novel soluble epoxide hydrolase inhibitor protects mitochondrial function following stress

Epoxyeicosatrienoic acids (EETs) are active metabolites of arachidonic acid that are inactivated by soluble epoxide hydrolase enzyme (sEH) to dihydroxyeicosatrienoic acid. EETs are known to render cardioprotection against ischemia reperfusion (IR) injury by maintaining mitochondrial function. We investigated the effect of a novel sEH inhibitor (sEHi) in limiting IR injury. Mouse hearts were perfused in Langendorff mode for 40 min and subjected to 20 min of global no-flow ischemia followed by 40 min of reperfusion. Hearts were perfused with 0.0, 0.1, 1.0 and 10.0 μmol·L(-1) of the sEHi N-(2-chloro-4-methanesulfonyl-benzyl)-6-(2,2,2-trifluoro-ethoxy)-nicotinamide (BI00611953). Inhibition of sEH by BI00611953 significantly improved postischemic left-ventricular-developed pressure and reduced infarct size following IR compared with control hearts, and similar to hearts perfused with 11,12-EETs (1 μmol·L(-1)) and sEH(-/-) mice. Perfusion with the putative EET receptor antagonist 14,15-epoxyeicosa-5(Z)-enoic acid (14,15-EEZE, 10 μmol·L(-1)), or the plasma membrane K(ATP) channels (pmK(ATP)) inhibitor (glibenclamide, 10 μmol·L(-1)) abolished the improved recovery by BI00611953 (1 μmol·L(-1)). Mechanistic studies in H9c2 cells demonstrated that BI0611953 decreased ROS generation, caspase-3 activity, proteasome activity, increased HIF-1∝ DNA binding, and delayed the loss of mitochondrial membrane potential (ΔΨ(m)) caused by anoxia-reoxygenation. Together, our data demonstrate that the novel sEHi BI00611953, a nicotinamide-based compound, provides significant cardioprotection against ischemia reperfusion injury.     

Palmitate- and lipopolysaccharide-activated macrophages evoke contrasting insulin responses in muscle cells

Factors secreted by macrophages contribute to whole body insulin resistance, acting in part on adipose tissue. Muscle is the major tissue for glucose disposal, but how macrophage-derived factors impact skeletal muscle glucose uptake is unknown, or whether the macrophage environment influences this response. We hypothesized that conditioned medium from macrophages pretreated with palmitate or LPS would directly affect insulin action and glucose uptake in muscle cells. L6-GLUT4myc myoblasts were exposed to conditioned medium from RAW 264.7 macrophages pretreated with palmitate or LPS. Conditioned medium from palmitate-treated RAW 264.7 macrophages inhibited myoblast insulin-stimulated glucose uptake, GLUT4 translocation, and Akt phosphorylation while activating JNK p38 MAPK, decreasing IkappaBalpha, and elevating inflammation markers. Surprisingly, and opposite to its effects on adipose cells, conditioned medium from LPS-treated macrophages stimulated myoblast insulin-stimulated glucose uptake, GLUT4 translocation, and Akt phosphorylation without affecting stress kinases or inflammation indexes. This medium had markedly elevated IL-10 levels, and IL-10, alone, potentiated insulin action in myoblasts and partly reversed the insulin resistance imparted by medium from palmitate-treated macrophages. IL-10 neutralizing antibodies blunted the positive influence of LPS macrophage-conditioned medium. We conclude that myoblasts and adipocytes respond differently to cytokines. Furthermore, depending on their environment, macrophages negatively or positively influence muscle cells. Macrophages exposed to palmitate produce a mixture of proinflammatory cytokines that reduce insulin action in muscle cells; conversely, LPS-activated macrophages increase insulin action, likely via IL-10. Macrophages may be an integral element in glucose homeostasis in vivo, relaying effects of circulating factors to skeletal muscle.     

见血封喉乳汁脂溶性成分及其抗氧化活性研究

首次采用气相色谱.质谱联用技术(GC-MS)对见血封喉(Antiaris toxicaria(Pers.)Lesch.)乳汁的脂溶性成分进行了分析,共鉴定了27个化学成分,占其总量的91.7%.用清除DPPH自由基能力的方法测定了见血封喉乳汁脂溶性部位的抗氧化活性,结果显示出一定的抗氧化活性,SC50值为500μg ml-1.     

Inhibition of Krebs cycle and activation of glyoxylate cycle in the course of chronological aging of Saccharomyces cerevisiae. Compensatory role of succinate oxidation

We investigated oxidative processes in mitochondria of Saccharomyces cerevisiae grown on ethanol in the course of chronological aging. We elaborated a model of chronological aging that avoids the influence of exhaustion of medium, as well as the accumulation of toxic metabolites during aging. A decrease in total respiration of cells and, even more, of the contribution of respiration coupled with ATP-synthesis was observed during aging. Aging is also related with the decrease of the contribution of malonate-insensitive respiration. Activities of citrate-synthase (CS), alpha-ketoglutarate dehydrogenase (KGDH) and malate dehydrogenase (MDH) were threefold decreased. The activity of NADP-dependent isocitrate dehydrogenase (NADP-ICDH) decreased more significantly, while the activity of NAD-dependent isocitrate dehydrogenase (NAD-ICDH) fell even greater, being completely inactivated on the third week of aging. In contrast, succinate dehydrogenase (SDH), enzymes of glyoxylate cycle (GCL) (isocitrate lyase (ICL) and malate synthase (MLS)), and enzymes of ethanol oxidation (alcohol dehydrogenase (ADH) and acetaldehyde dehydrogenase (ACDH)), were activated by 50% or more. The behavior of oxidative enzymes and metabolic pathways are apparently inherent to a more viable, long-lived cells in population, selected in the course of chronological aging. This selection allows cells to reveal the mechanism of their higher viability as caused by shunting of complete Krebs cycle by glyoxylate cycle, with a concomitant increased rate of the most efficient energy source, namely succinate formation and oxidation. Thiobarbituric-reactive species (TAR species) increased during aging. We supposed that to be the immediate cause of damage of a part of yeast population. These data show that a greater succinate contribution to respiration in more active cells is a general property of yeast and animal tissues.     

The role of Ixodes trianguliceps tick larvae in circulation of Babesia microti in the Middle Urals

The nested PCR method with primers flanking a conserved fragment of the Babesia microti ss-rDNA gene was used to examine 834 larvae of Ixodes trianguliceps ticks engorged to a varying degree, taken off 237 hosts of 12 species (rodents and insectivores). The hosts were collected in southern taiga forests in the lowmountain area of the Middle Urals (Chusovoi District, Perm Province) in 2003–2010. Babesia DNA was detected in 89 (10.7%) larvae from 8 species of small mammals. According to the data obtained by PCR and microscopic methods, either B. microti DNA or the parasites themselves were found in the blood of 45.2% of the mammals. The nucleotide sequences of 15 amplicons of Babesia DNA obtained from larvae of I. trianguliceps ticks and their hosts were identical to those of B. microti available in GenBank. In 13 cases, they were similar to B. microti US-type (a human pathogen) and in two cases (those from I. trianguliceps and from the vole Clethrionomys rufocanus from which it was removed), to B. microti of the Munich strain which is not pathogenic to humans. The duration of feeding on small mammals seems to exert the main influence on the infection rate of I. trianguliceps larvae. The fully engorged larvae contained B. microti DNA more often and usually in greater amounts than those collected during the first days of blood-sucking. The latter usually revealed Babesia DNA in the minimum quantity (< 0.064 ng/μl). According to the data obtained, transovarial transmission of Babesia in I. trianguliceps is unlikely. The processes of horizontal and transstadial transmission appear to be of crucial importance for the functioning of the natural foci of babesiosis.     

Ubiquinone-9 and ergosterol from Candida paralipolytica yeasts

Ubiquinone-9 and ergosterol were extracted with hexane from the yeast Candida paralipolytica after hydrolysis with KOH in EtOH with the yield 0.026 and 0.14%, respectively. Ubiquinone-9 was purified by chromatography and recrystallization from absolute alcohol.