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1.
The distribution of copper and zinc among soluble proteins in liver from normal slaughter cattle was examined after gel filtration of the proteins. Gopper- and zinc-binding proteins were mainly separated into three fractions. Varying amounts of zinc were eluted in a fourth fraction of molecular weight less than 2,000. A clear relationship was noted between the amount of copper bound to the low molecular weight fraction (m.w. ~ 10,000) and the total liver zinc concentration. The high molecular weight protein fraction (m.w. > 65,000) dominated in liver with zinc concentrations below 40 µg/g wet weight and total copper concentrations from 16 to 240 µg/g, while in liver with zinc concentrations above 40 µg/g and copper concentrations ranging from 20 to 107 µg/g, the low molecular weight metallothionein-like fraction dominated.  相似文献   
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Endothelial cell activation leading to leukocyte recruitment and adhesion plays an essential role in the initiation and progression of atherosclerosis. Vitamin D has cardioprotective actions, while its deficiency is a risk factor for the progression of cardiovascular damage. Our aim was to assess the role of basal levels of vitamin D receptor (VDR) on the early leukocyte recruitment and related endothelial cell-adhesion-molecule expression, as essential prerequisites for the onset of atherosclerosis. Knockdown of VDR in endothelial cells (shVDR) led to endothelial cell activation, characterized by upregulation of VCAM-1, ICAM-1 and IL-6, decreased peripheral blood mononuclear cell (PBMC) rolling velocity and increased PBMC rolling flux and adhesion to the endothelium. shVDR cells showed decreased IκBα levels and accumulation of p65 in the nucleus compared to shRNA controls. Inhibition of NF-κB activation with super-repressor IκBα blunted all signs of endothelial cell activation caused by downregulation of VDR in endothelial cells. In vivo, deletion of VDR led to significantly larger aortic arch and aortic root lesions in apoE-/- mice, with higher macrophage content. apoE-/-VDR-/-mice showed higher aortic expression of VCAM-1, ICAM-1 and IL-6 when compared to apoE-/-VDR+/+ mice. Our data demonstrate that lack of VDR signaling in endothelial cells leads to a state of endothelial activation with increased leukocyte-endothelial cell interactions that may contribute to the more severe plaque accumulation observed in apoE-/-VDR-/- mice. The results reveal an important role for basal levels of endothelial VDR in limiting endothelial cell inflammation and atherosclerosis.  相似文献   
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BackgroundLiterature data indicate the benefit of magnesium (Mg) supplementation. The aim of this study was to examine the effect of short-term Mg supplementation on iron status in healthy female participants.MethodsOne hundred healthy female students of the University of Belgrade - Faculty of Pharmacy participated the study during eleven intervention days. Students ingested Mg preparations with the same dose of the active substance. The analysis included the measurement of serum iron, unsaturated iron binding capacity (UIBC), total iron binding capacity (TIBC), total Mg (tMg), ionized Mg (iMg), complete blood count, met-, carboxyand oxy-haemoglobin (metHgb, COHgb, O2Hgb). Transferrin concentrations and percentage of transferrin saturation (SAT) were calculated manually. The association among the analyzed biochemical parameters was examined using polynomial regression. A principal component analysis (PCA) was used for the evaluation of interdependence between the analyzed parameters.ResultsA statistically significant trend for change in O2Hgb (%) by tertiles of iMg concentrations was found (P = 0.029). Serum tMg reached significant positive correlation with the SAT at concentration levels greater than 0.9 mmol/L, after 11 days of intervention (R2=0.116). Ionized Mg in a concentration higher than 0.6 mmol/L is positively correlated with SAT and serum Fe (R2=0.214; 0.199, respectively). PCA revealed variability of 64.7% for two axes after 11 days.ConclusionsMg supplementation leads to an improvement in the certain iron status parameters even in individuals with optimal levels of these indices. However, caution should be exercised when supplementing Mg, and laboratory monitoring of the interaction is required.  相似文献   
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BackgroundThe uneven lipid-lowering statin effects and statin intolerance raise interest regarding the involvement of coadministration of statins and dietary supplements. This study aimed to evaluate the effects of octacosanol supplementation on markers of redox status in cardiovascular patients on chronic atorvastatin therapy.MethodsA double-blind, randomized, placebo-controlled, single-centre study was conducted. Redox status homeostasis parameters [i.e., advanced oxidation protein products (AOPP), pro-oxidant-antioxidant balance (PAB), total oxidant status (TOS), total antioxidant status (TAS), superoxide dismutase activity (SOD), total protein sulfhydryl (SHgroups), and paraoxonase 1 (PO N 1) activity] were assessed in 81 patients. According to favorable changes in lipid profile, patients were classified into two groups: responders (n = 35) and non-responders (n = 46), and followed for 13 weeks. A principal component analysis (PCA) was applied to explore the effect of octacosanol supplementation and the relationship between investigated parameters as predictors of responders'' and non-responders'' status.ResultsSignificant decrease in Oxy-score value was found at the endpoint compared to baseline in responders'' group (21.0 (13.4-25.5) versus 15.1 (12.4-18.0); P < 0.01). PCA analysis extracted 4 significant factors in the both groups, whereas extracted factors containing "octacosanol status" variable explained 14.7% and 11.5% of the variance in responders'' and non-responders'' subgroups, respectively.ConclusionsOctacosanol supplementation leads to an improvement of lipid profile and markers of redox status in responders'' group. New studies are needed to validate our results in order to find the best approach for personalized supplementation as a useful adjunct to standard statin therapy.  相似文献   
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The original strategies developed by Helicobacter pylori to persistently colonise its host and to deregulate its cellular functions make this bacterium an outstanding model to study host‐pathogen interaction and the mechanisms responsible for bacterial‐induced carcinogenesis. During the last year, significant results were obtained on the role of bacterial factors essential for gastric colonisation such as spiral shape maintenance, orientation through chemotaxis and the formation of bacteria clonal population islands inside the gastric glands. Particularities of the H pylori cell surface, a structure important for immune escape, were demonstrated. New insights in the bacterial stress response revealed the importance of DNA methylation‐mediated regulation. Further findings were reported on H pylori components that mediate natural transformation and mechanisms of bacterial DNA horizontal transfer which maintain a high level of H pylori genetic variability. Within‐host evolution was found to be niche‐specific and probably associated with physiological differences between the antral and oxyntic gastric mucosa. In addition, with the progress of CryoEM, high‐resolution structures of the major virulence factors, VacA and CagT4SS, were obtained. The use of gastric organoid models fostered research revealing, preferential accumulation of bacteria at the site of injury during infection. Several studies further characterised the role of CagA in the oncogenic properties of H pylori, identifying the activation of novel CagA‐dependent pathways, leading to the promotion of genetic instabilities, epithelial‐to‐mesenchymal transition and finally carcinogenesis. Recent studies also highlight that microRNA‐mediated regulation and epigenetic modifications, through DNA methylation, are key events in the H pylori‐induced tumorigenesis process.  相似文献   
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BackgroundThe progression of the nonalcoholic fatty liver disease to nonalcoholic steatohepatitis (NASH) is multifactorial, and there is still a lack of approved medications for its treatment. The study aimed to evaluate the impact of combined treatment with Pentoxifylline and Metformin on biochemical parameters in patients with Nash. Setting: Outpatient hepatology clinic.MethodsA prospective trial was conducted. The first cohort included patients with biopsy-proven Nash, while the second cohort consisted of patients with biopsy-confirmed NAFLD. Blood tests were checked at baseline and every three months. Pentoxifylline at a dosage of 400 mg t.i.d. and Metformin at the dosage of 500 mg t.i.d. were introduced for six months in Nash group. The impact of the treatment was assessed based on biochemical results after combined treatment with low-cost medications.ResultsAll 33 Nash patients completed 24 weeks of treatment. We observed significant improvement (p<0.05) of median values after treatment for the following parameters: serum uric acid levels decreased by 51.0 mmol/L, calcium decreased for 0.27 mmoL/L, magnesium showed an increase of 0.11 mmoL/L. Insulin resistance improved as a reduction of HOMA - IR by 1.3 was detected. A significant decrease of median in liver enzymes, alanine aminotransferase, aspartate aminotransferase and gamma-glutamyltransferase by 24.0 U/L, 9.1 U/L, 10.8 U/L respectively, was noted.ConclusionsPentoxifylline and Metformin may provide possible treatment option in Nash. Some new potential benefit of the therapy in improving liver function whilst decreasing cardiovascular risk was perceived.  相似文献   
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Molecular Biology Reports - Actinidin (Act d 1), a highly abundant cysteine protease from kiwifruit, is one of the major contributors to the development of kiwifruit allergy. Many studies have...  相似文献   
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Dozens of studies have documented that brood parasites are well adapted to a brood parasitic lifestyle but not all parasitism events are successful. Co-evolution between brood parasites and their hosts is a dynamic process so it is reasonable to expect that a female brood parasite may commit errors during egg deposition by laying her eggs outside the laying period of the host, with consequent impacts on her fitness. Using an extensive dataset from a long-term study, we evaluated egg-laying patterns and errors related to the timing of egg-laying in the Common Cuckoo Cuculus canorus (hereafter ‘Cuckoo’). Specifically, we tested whether the Cuckoo avoids laying before or on the day of host clutch initiation to reduce the risk of rejection of parasitic eggs, whether laying errors will be more frequent in periods with a lack of active host nests, and whether the laying errors will be more frequent in periods with intense Cuckoo parasitism and a consequent lack of suitable host nests. We found that about one-third of Cuckoo eggs were laid on the host clutch initiation day or 1 day before, and the percentage of Cuckoo eggs laid decreased thereafter. Surprisingly, the probability of Cuckoo egg acceptance by the hosts was not affected by the egg-laying stage of the host clutch. Errors in the timing of egg-laying with fatal consequences (i.e. those precluding Cuckoo hatching because of laying in incubated or deserted clutches) were recorded in about 5% of cases. Only laying date of a Cuckoo egg had a significant effect on the probability of errors, which increased during the breeding season. This may be related to the higher number of deserted and incubated host nests at the site at the end of the breeding season. Errors in egg-laying may be attributed to young and inexperienced females but also impaired body condition or intraspecific competition may cause this behaviour. Future studies, which will test these possible explanations, will help to understand better the mechanism of co-evolutionary arms races and differences between host specialist and generalist brood parasites in various host–parasite systems.  相似文献   
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