Platelets promote tumor metastasis by inducing promalignant phenotypes in cancer cells and directly contributing to cancer-related thrombotic complications. Platelet-derived extracellular vesicles ...(EVs) can promote epithelial-mesenchymal transition (EMT) in cancer cells, which confers high-grade malignancy. 12S-hydroxyeicosatetraenoic acid (12-HETE) generated by platelet-type 12-lipoxygenase (12-LOX) is considered a key modulator of cancer metastasis through unknown mechanisms. In platelets, 12-HETE can be esterified into plasma membrane phospholipids (PLs), which drive thrombosis. Using cocultures of human platelets and human colon adenocarcinoma cells (line HT29) and LC-MS/MS, we investigated the impact of platelets on cancer cell biosynthesis of 12S-HETE and its esterification into PLs and whether platelet ability to transfer its molecular cargo might play a role. To this aim, we performed coculture experiments with CFSE5-(and-6)-carboxyfluorescein diacetate, succinimidyl ester-loaded platelets. HT29 cells did not generate 12S-HETE or express 12-LOX. However, they acquired the capacity to produce 12S-HETE mainly esterified in plasmalogen phospholipid forms following the uptake of platelet-derived medium-sized EVs (mEVs) expressing 12-LOX. 12-LOX was detected in plasma mEV of patients with adenomas/adenocarcinomas, implying their potential to deliver the protein to cancer cells in vivo. In cancer cells exposed to platelets, endogenous but not exogenous 12S-HETE contributed to changes in EMT gene expression, mitigated by three structurally unrelated 12-LOX inhibitors. In conclusion, we showed that platelets induce the generation of primarily esterified 12-HETE in colon cancer cells following mEV-mediated delivery of 12-LOX. The modification of cancer cell phospholipids by 12-HETE may functionally impact cancer cell biology and represent a novel target for anticancer agent development.
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.
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.
Platelets are activated by the interaction with cancer cells and release enhanced levels of lipid mediators such as thromboxane (TX)A2 and prostaglandin (PG)E2, generated from arachidonic acid (AA) ...by the activity of cyclooxygenase (COX)-1, granule content, including ADP and growth factors, chemokines, proteases and Wnt proteins. Moreover, activated platelets shed different vesicles, such as microparticles (MPs) and exosomes (rich in genetic material such as mRNAs and miRNAs). These platelet-derived products induce several phenotypic changes in cancer cells which confer high metastatic capacity. A central event involves an aberrant expression of COX-2 which influences cell-cycle progression and contribute to the acquisition of a cell migratory phenotype through the induction of epithelial mesenchymal transition genes and down-regulation of E-cadherin expression. The identification of novel molecular determinants involved in the cross-talk between platelets and cancer cells has led to identify novel targets for anti-cancer drug development.
Background
The Franciscan Friary in Montella near Avellino in Southern Italy is of special interest because according to historical sources it was founded by St. Francis himself in AD 1221–1222. ...Human remains of several hundred individuals interred in the cloister walk have been unearthed during two excavation campaigns conducted in 2007–2008 and 2010. The environs of the friary have remained rural since the foundation preventing much modern contamination. The state of preservation of the skeletons is fair to good making a suite of analyses worthwhile.
Results
The skeletons have been examined anthropologically and tissue samples have been subjected to radiocarbon dating, stable isotope measurements and trace element analyses by Inductively Coupled Plasma Mass Spectrometry and Cold Vapour Atomic Absorption Spectrometry.
Conclusions
The radiocarbon dates are consistent with the historical sources and show that the cemetery in the cloister walk has been in uninterrupted use from the foundation of the friary in AD 1221–1222 and until the cemetery went out of use in AD 1524. The anthropological investigations show that the individuals interred at the friary would have been shorter than other Italians from the same time, and it seems that tuberculosis was more prevalent than leprosy. Isotopic measurements show a mixed agricultural and pastoral diet and none of the individuals were consuming marine protein. Based on the trace element analysis it seems that the people resided mainly at two distinct geographical areas, one of which was Montella. One individual stands out from the rest, because he was born and raised at some third geographical location distinct from Montella and because he sports the second oldest radiocarbon date of AD 1050–1249 (two sigma calibrated range). This date is consistent with the first generation of the founders of the friary—perhaps one of St. Francis’ fellow travellers from Assisi.
Graphical abstract:
Synthesis of the building archaeological observations of the Franciscan Friary at Folloni, Montella. The buildings of the original friary are depicted in
red
; the re-constructed buildings after the 1732 earthquake are depicted in
grey
.
•HUVEC exposed to a GDM milieu in vivo has reduced migratory capacity.•Dysregulated expression of TGF-β receptors is detected.•Human fetal endothelium of GDM women responds abnormally to ...TGF-β1.•Several genes involved in development, cell movement and migration were downregulated.•Altered transcriptome may affect cardiac morphogenesis and placental development.
Enhanced biosynthesis of several cytokines, such as, transforming growth factor-β1 (TGF-β1), is detected in gestational diabetes mellitus (GDM). In this study, we addressed the question of whether the exposure to the abnormal milieu of GDM in vivo affects gene expression pattern of human umbilical vein endothelial cells (HUVEC) in response to TGF-β1. We found that HUVEC isolated from GDM (dHUVEC) had reduced migratory capacity versus those of healthy women (nHUVEC) and this quiescent phenotype was associated with higher expression levels of the TGF-βtype I receptor ALK5 and a slight increase in the endogenous production of TGF-β1 (mainly in its latent form). Moreover, we performed transcriptome analysis, using microarray technology, of dHUVEC versus nHUVEC, after 3h treatment with exogenous TGF-β1 (10ng/ml). The treatment of dHUVEC with TGF-β1 caused downregulation of the transcription of multiple genes involved in development, cell movement and migration of cells versus TGF-β1-treated nHUVEC. These changes in transcriptome profile might contribute to GDM-dependent alterations in cardiac morphogenesis and placental development.
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