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The present study shows the factors that modulate the photodamage promoted by phenothiazines. Cytochrome c was irradiated with UV light for 120 min, over a pH range from 4.0 to 8.0, in the absence and in the presence of different concentrations of thioridazine (TR) and fluphenazine (FP). In the absence of phenothiazines, the maximal rate of a Soret band blue shift (nm/min) from 409 to 406 nm was obtained at pH 4.0 (0.028 nm/min). The presence of phenothiazines at the concentration range 10-25 µmol/L amplified and accelerated a cytochrome c blue shift (409 to 405 nm, at a rate = 0.041 nm/min). Above 25 µmol/L, crescent concentrations of phenothiazines contributed to cytochrome c protection with (maximal at 2500 µmol/L). Scanning electronic microscopy revealed the formation of nanostructures. The pH also influenced the effect of low phenothiazine concentrations on cytochrome c. Thus, the predominance of phenothiazine-promoted cytochrome c damage or protection depends on a balance of the following factors: the yield of photo-generated drug cation radicals, which is favored by acidic pH; the stability of the cation radicals, which is favored by the drug aggregation; and the cytochrome c structure, modulated by the pH.  相似文献   
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The epidermal growth factor receptor is involved in morphogenesis, proliferation and cell migration. Its up-regulation during tumorigenesis makes this receptor an interesting therapeutic target. In the absence of the ligand, the inhibition of phosphatidic acid phosphohydrolase activity by propranolol treatment leads to internalization of empty/inactive receptors. The molecular events involved in this endocytosis remain unknown. Here, we quantified the effects of propranolol on the mobility of single quantum-dot labelled receptors before the actual internalization took place. The single receptors showed a clear stop-and-go motion; their diffusive tracks were continuously interrupted by sub-second stalling events, presumably caused by transient clustering. In the presence of propranolol we found that: i) the diffusion rate reduced by 22 %, which indicates an increase in drag of the receptor. Atomic force microscopy measurements did not show an increase of the effective membrane tension, such that clustering of the receptor remains the likely mechanism for its reduced mobility. ii) The receptor got frequently stalled for longer periods of multiple seconds, which may signal the first step of the internalization process.  相似文献   
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Understanding the role that breastfeeding and bottle feeding play in the development of dental caries during childhood is essential in helping dentists and parents and care providers prevent the disease, and also for the development of effective public health policies. However, the issue is not yet fully understood. The aim of this systematic review and meta-analysis was to search for scientific evidence in response to the question: Do bottle fed children have more dental caries in primary dentition than breastfed children? Seven electronic databases and grey literature were used in the search. The protocol number of the study is PROSPERO CRD 42014006534. Two independent reviewers selected the studies, extracted data and evaluated risk of bias by quality assessment. A random effect model was used for meta-analysis, and the summary effect measure were calculated by odds ratio (OR) and 95% CI. Seven studies were included: five cross-sectional, one case-control and one cohort study. A meta-analysis of cross-sectional studies showed that breastfed children were less affected by dental caries than bottle fed children (OR: 0.43; 95%CI: 0.23–0.80). Four studies showed that bottle fed children had more dental caries (p<0.05), while three studies found no such association (p>0.05). The scientific evidence therefore indicated that breastfeeding can protect against dental caries in early childhood. The benefits of breastfeeding until age two is recommended by WHO/UNICEF guidelines. Further prospective observational cohort studies are needed to strengthen the evidence.  相似文献   
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