Combination chemotherapy uses drugs that target different cancer hallmarks, resulting in synergistic or additive toxicity. This strategy enhances therapeutic efficacy as well as minimizes drug ...resistance and side effects. In this study, we investigated whether silver nanoparticles act as a combinatorial partner to cisplatin. In so doing, we compared post-exposure biological endpoints, intracellular drug accumulation, and changes in the proteome profile of tumoral and normal cell lines. Combinatorial exposure corresponded to cytotoxicity and oxidative stress in both cell lines, yet was substantially more effective against tumoral cells. Proteome analysis revealed that proteins related to energy metabolism pathways were upregulated in both cell lines, suggesting that combinatorial exposure corresponded to energetic modulation. However, proteins and upstream regulators involved in the cell cycle were downregulated, indicating reduced cell proliferation. The response to oxidative stress was markedly different in both cell lines; downregulation of antioxidant proteins in tumoral cells, yet upregulation of the antioxidant defense system in normal cells. These outcomes may have avoided higher cell death rates in normal cells. Taken together, our results indicate that combining silver nanoparticles with cisplatin increases the biological activity of the latter, and the combination warrants further exploration for future therapies.
We describe a procedure for ascertaining the extent of diagenesis in archaeological human skeletons through the distribution of Sr, Ba, Cu, Pb, Fe, and Mn in cross-sections of femoral cortical bone. ...Element mapping is performed through Laser Ablation Inductively Coupled Plasma Mass Spectrometry (LA-ICP-MS). Absolute calibrations of element concentrations were obtained using Inductively Coupled Plasma Mass Spectrometry (ICP-MS) on adjacent dissolved bulk bone samples. By comparing a modern individual to five medieval to early modern Danish skeletons, we demonstrate the degree to which concentrations of trace elements are attributable to diagenesis. Invasion from the exterior bone surface into a degraded part of the outer cortical bone is the most frequently occurring diagenetic change. In the archaeological skeletons investigated, diagenetic modification is restricted to, at most, the outer ca. 0.5 mm of bone. In one femur, Haversian channels were filled with diagenetic material, which appears to have entered the bone through a network of cavities largely made up by Haversian and Volkmann’s canals.
Variation in the trace element chemistry of cortical bone microstructure is delineated for interred and non-interred human femora. This was done to investigate the range of element concentrations ...that might occur within single bones, specifically the original laminar bone and later osteons, and its potential for investigating chemical life histories. To do so, femora were chosen from individuals who experienced quite different ways of life over the past two millennia. The distributions of Sr, Ba, Cu, and Pb, mostly in partial (early) and complete (late) osteons, in cross-sections of proximal femora were characterized through Laser Ablation Inductively Coupled Plasma Mass Spectrometry. Absolute calibrations of these data were obtained using solution Inductively Coupled Plasma Mass Spectrometry on adjacent dissolved bulk samples. Chemical life histories were approximated by classifying bone microstructure into four categories: laminar bone and 1st, 2nd, and 3rd generation osteons. This four-part sequence, on average, charts the temporal dimension of an individual’s life. Consistent with recent studies of medieval bones, Sr and Ba are thought to be mainly responsive to diet, presumably related to the consumption of mostly locally produced food, while Cu and Pb do the same for heavy metal exposure often attributable to social status or occupation. No systematic differences in these elements were found between interred and non-interred individuals. The effect of diagenesis on interpretations of life histories based on archaeological bone, therefore, are minimized by plotting element concentrations across cortical bone cross-sections.
Two types of materials were sampled as part of an investigation of the relics of the Holy Catholic Church of the Apostles St Philip and St James in the Basilica dei Santi Apostoli in Rome: bone- and ...mummy-materials and architectural samples. The analyses encompassed radiocarbon dating, thermoluminescence dating, gas and liquid chromatographic separation with mass spectrometric detection, X-Ray fluorescence, X-Ray diffraction, inductively coupled plasma mass spectrometry, Raman spectroscopy, and Fourier transform infrared spectroscopy. The results show that the samples were subjected to a number of conservational and exhibition-related treatments. The alleged femoral bone of St James was dated between AD 214 and 340 (2σ confidence), which shows that this cannot be the bone of St James. An encrustation found in a canal in the reliquary in the high altar construction showed the presence of heavily oxidized rapeseed oil, which was radiocarbon dated between AD 267 and 539 (2σ confidence), and a ceramic shard also found in the high altar construction was TL-dated to AD 314–746 (2σ confidence). The two latter dates are consistent with a
translation
of the relics following the erection of the church at the time of Pope Pelagius I in AD 556–561.
For medieval and post-medieval Denmark and northern Germany, trace elements can potentially contribute to our understanding of diet, migration, social status, exposure to urban settings, and disease ...treatment. Copper, of particular interest as a marker of access to everyday metal items, can be used to clarify socioeconomic distinctions between and within communities. Postmortem alteration of bone (diagenesis), however, must be ruled out before the elements can be used to characterize life in the past. Femoral cortical bone samples of ca. 40 mg were thoroughly decontaminated, and the concentrations of Al, Ca, Mn, Fe, Cu, As, Sr, Ba, and Pb were measured using inductively coupled plasma mass spectrometry. The concentrations of these elements were quantified in bone samples from 553 skeletons from 9 rural and urban cemeteries, and 34 soil samples obtained near three burials. Copper, the primary element of interest in this work, is generally absent from the femoral cortical bone of rural people, although it occurs in high concentrations in the skeletons of the inhabitants of towns. The Cu in medieval to post-medieval bones likely originated from everyday objects, notably kitchen utensils. A rural to urban distinction in Cu concentrations, found repeatedly at two sites, likely resulted from differential access to much-desired, although still utilitarian, household items. An uneven distribution of metal objects used in domestic contexts, demonstrated through bone chemistry, was greater between rural and urban communities than it was within urban centres, at least among the socioeconomic positions sampled in this study.
Individuals buried in two 17th–18th Century private chapels, each attached to a Franciscan Friary—one in Italy the other in Denmark—have been studied and sampled for trace element analysis. This ...selection of individuals allows a comparison of the trace element inventory of members of noble families against friars and townspeople, as well as a comparison between two very similar situations in Denmark and Italy. The relevance of this study is to see if and how differences in social status, and therefore likely differences in dietary habits, are reflected in the trace element chemistry of the bones. Samples of cortical and trabecular tissues have been procured from a long bone, preferentially the femur. The samples have been thoroughly decontaminated. 87 samples from 69 individuals have been analysed for Ca, Mn, Fe, Cu, Sr, Ba, and Pb by ICP-MS and Hg by CV-AAS. Sex and age at death have been established by anthropological analysis for all members of the two noble families. We find systematic differences between the noble family members and the friars (or townspeople) in both Italy and Denmark. The noble families are in both cases low in Sr and Ba compared to the friars and townspeople, which is interpreted as a dietary signal resulting from higher meat consumption than in the comparative groups. Lead concentrations are found to be higher in the noble family members than in the comparative groups, and the Pb concentration seems to increase with age in the Italian noble family, where both young and middle-aged individuals were investigated. Mercury concentrations are higher in some of the Italian noble family members compared to friars and townspeople; whereas in Denmark it seems that Hg was equally available to the noble family members and the friars alike. This is the first comprehensive and comparative study of post-medieval noble families in Denmark and Italy. The results show that there are distinct similarities in the trace element distribution patterns in the noble family members irrespective of country, which is tentatively suggested to be due to their higher social status.
The aim of this paper is to investigate five new cases of possible treponematosis in early medieval Denmark. A total of 1018 skeletons from Danish and present day German cemeteries have been ...examined, and five candidates of pre-Columbian individuals have been selected from three Danish burial sites on Funen, Jutland and Zealand. The five individuals with a possible infection with treponematoses have been analysed anthropological and chemically.
Two of the skeletons exhibited cranial lesions,
i.e.
serpiginous and focal superficial cavitation. The other three only displayed periosteal reactions of varying degrees on the postcranial skeleton. Computed tomography scans showed focal obliteration of the periosteum on the long bones as well as on the affected skulls. Radiocarbon dates and stable isotope analyses indicate that three of the four analysed skeletons predate AD 1493. High levels of mercury in three of the individuals suggest that medical treatment with Hg-containing medicine took place.
Considering the climate and geography at the sites, venereal syphilis might be the treponemal disease causing the pathologies on the skeletal remains. However, the historical background, the bone lesions and their prevalence point to the presence of a less aggressive, maybe non-venereal, form of treponematosis. Consequently, the hypothesis that pre-Columbian venereal syphilis existed among the analysed skeletal material is rejected with the help of various archaeometric analyses.
Silver nanoparticles (AgNPs) have been reported to penetrate the central nervous system (CNS) and induce neurotoxicity. However, there is a paucity of understanding of the toxicity of AgNPs and their ...effect on the blood-brain barrier (BBB) including the underlying molecular mechanism(s) of action. Such information is important for the formulation of new strategies for delivery of biological therapeutics to central nervous system (CNS) targets. Using an in vitro BBB model and mass spectrometry-based proteomics, we investigated alterations in the proteomes of brain endothelial cells and astrocytes at different time points after AgNPs exposure (24 and 48 h). Our data showed that several proteins involved in neurodisorders and neurodegeneration were significantly upregulated in endothelial cells (e.g. 7-dehydrocholesterol reductase, zinc transporters 1 and 6), while proteins responsible for maintaining brain homeostasis were significantly downregulated (e.g anti-oxidative proteins glutathione peroxidase 1 and glutathione peroxidase 4). Many inflammatory pathways were significantly upregulated at 24 h post-AgNPs exposure (C9 pathway), while at 48 h proteins involved in BBB damage and anti-inflammatory responses were upregulated (quinoneoxidoreductase1 and glutamate cysteine ligase catalytic subunit) suggesting that by the later time point, cellular protection pathways had been activated to rescue the cells from AgNPs-induced toxicity. Our study suggests that in the initial stage of exposure, AgNPs exerted direct cellular stress on the endothelial cells by triggering a pro-inflammatory cascade. This study provides detailed insight into the toxic potency of AgNPs on in vitro BBB model and adds to the understanding of the adaptive role of BBB with regards to AgNPs-mediated toxicity.
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