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- Jankovic, Nicole, et al.
(author)
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Adherence to the WCRF/AICR Dietary Recommendations for Cancer Prevention and Risk of Cancer in Elderly from Europe and the United States : A Meta-Analysis within the CHANCES Project
- 2017
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In: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 26:1, s. 136-144
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Journal article (peer-reviewed)abstract
- BACKGROUND: It is unknown if dietary recommendations for cancer prevention are applicable to the elderly. We analyzed WCRF/AICR recommendations in cohorts of European and US adults aged 60 years and above.METHODS: Individual participant data meta-analysis including 362,114 participants (43% women), from seven prospective cohort studies, free from cancer at enrollment. The WCRF/AICR diet score was based on: 1) energy-dense foods and sugary drinks, 2) plant foods, 3) red and processed meat 4) alcoholic drinks. Cox proportional hazards regression was used to examine the association between the diet score and cancer risks. Adjusted, cohort-specific hazard ratios (HR) were pooled using random-effects meta-analysis. Risk Advancement Periods (RAP) were calculated to quantify the time period by which the risk of cancer was postponed among those adhering to the recommendations.RESULTS: After a median follow-up of 11 to 15 years across cohorts, 69,708 cancer cases were identified. Each one-point increase in the WCRF/AICR diet score [range 0 (no) to 4 (complete adherence)] was significantly associated with a lower risk of total cancer (HR: 0.94, 95% CI: 0.92-0.97), cancers of the colorectum (HR: 0.84, 95% CI: 0.80-0.89), prostate (HR: 0.94, 95% CI: 0.92-0.97), but not breast or lung. Adherence to an additional component of the WCRF/AICR diet score significantly postponed the incidence of cancer at any site by 1.6 years (RAP: -1.6, 95% CI: -4.09 to -2.16).CONCLUSION: Adherence to WCRF/AICR dietary recommendations is associated with lower risk of cancer among older adults.IMPACT: Dietary recommendations for cancer prevention are applicable to the elderly.
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| 3. |
- Lacy, Michael, et al.
(author)
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Cell-specific and divergent roles of the CD40L-CD40 axis in atherosclerotic vascular disease
- 2021
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In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 12:1
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Journal article (peer-reviewed)abstract
- Atherosclerosis is a major underlying cause of cardiovascular disease. Previous studies showed that inhibition of the co-stimulatory CD40 ligand (CD40L)-CD40 signaling axis profoundly attenuates atherosclerosis. As CD40L exerts multiple functions depending on the cell-cell interactions involved, we sought to investigate the function of the most relevant CD40L-expressing cell types in atherosclerosis: T cells and platelets. Atherosclerosis-prone mice with a CD40L-deficiency in CD4+ T cells display impaired Th1 polarization, as reflected by reduced interferon-γ production, and smaller atherosclerotic plaques containing fewer T-cells, smaller necrotic cores, an increased number of smooth muscle cells and thicker fibrous caps. Mice with a corresponding CD40-deficiency in CD11c+ dendritic cells phenocopy these findings, suggesting that the T cell-dendritic cell CD40L-CD40 axis is crucial in atherogenesis. Accordingly, sCD40L/sCD40 and interferon-γ concentrations in carotid plaques and plasma are positively correlated in patients with cerebrovascular disease. Platelet-specific deficiency of CD40L does not affect atherogenesis but ameliorates atherothrombosis. Our results establish divergent and cell-specific roles of CD40L-CD40 in atherosclerosis, which has implications for therapeutic strategies targeting this pathway.
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| 6. |
- Toonen, W. H. J., et al.
(author)
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Amenhotep III's Mansion of Millions of Years in Thebes (Luxor, Egypt) : Submergence of high grounds by river floods and Nile sediments
- 2019
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In: Journal of Archaeological Science. - : ELSEVIER SCIENCE BV. - 2352-409X .- 2352-4103. ; 25, s. 195-205
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Journal article (peer-reviewed)abstract
- New Kingdom royal cult temples in Thebes (Luxor, Egypt) are all located on the lower desert edge. Kom el-Hettan (Amenhotep III: reign 1391-1353 BCE, 18th Dynasty) is an exception, as it is located in the present Nile floodplain. Its anomalous position has puzzled Egyptologists, as has the termination of its use, which traditionally has been attributed to natural hazards such as flooding or earthquakes. Geoarchaeological analyses of the subsurface shows that Amenhotep III's temple was initially founded on a wadi fan that stood several metres above the contemporary surrounding floodplain landscape. The temple was fronted by a minor branch of the Nile, which connected the temple to the wider region, but the temple itself was relatively safe from the annual flood of the Nile. This geoarchaeological study comprised a coring programme to determine the c. 4000-yr landscape history of the local area. Chronological control was provided by the analysis of ceramic fragments recovered from within the sediments. This study shows that the New Kingdom period was, at least locally, characterised by extremely high sedimentation rates that caused a rapid rise of the floodplain and gradual submergence of the pre-existing high temple grounds. This is, however, not a plausible reason for the destruction of the temple, as frequent inundation did not begin until the temple was already out of use and largely dismantled.
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| 7. |
- Braumann, S, et al.
(author)
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Nitro-Oleic Acid (NO2-OA) Improves Systolic Function in Dilated Cardiomyopathy by Attenuating Myocardial Fibrosis
- 2021
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In: International journal of molecular sciences. - : MDPI AG. - 1422-0067. ; 22:16
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Journal article (peer-reviewed)abstract
- Nitro-oleic acid (NO2-OA), a nitric oxide (NO)- and nitrite (NO2−)-derived electrophilic fatty acid metabolite, displays anti-inflammatory and anti-fibrotic signaling actions and therapeutic benefit in murine models of ischemia-reperfusion, atrial fibrillation, and pulmonary hypertension. Muscle LIM protein-deficient mice (Mlp−/−) develop dilated cardiomyopathy (DCM), characterized by impaired left ventricular function and increased ventricular fibrosis at the age of 8 weeks. This study investigated the effects of NO2-OA on cardiac function in Mlp−/− mice both in vivo and in vitro. Mlp−/− mice were treated with NO2-OA or vehicle for 4 weeks via subcutaneous osmotic minipumps. Wildtype (WT) littermates treated with vehicle served as controls. Mlp−/− mice exhibited enhanced TGFβ signalling, fibrosis and severely reduced left ventricular systolic function. NO2-OA treatment attenuated interstitial myocardial fibrosis and substantially improved left ventricular systolic function in Mlp−/− mice. In vitro studies of TGFβ-stimulated primary cardiac fibroblasts further revealed that the anti-fibrotic effects of NO2-OA rely on its capability to attenuate fibroblast to myofibroblast transdifferentiation by inhibiting phosphorylation of TGFβ downstream targets. In conclusion, we demonstrate a substantial therapeutic benefit of NO2-OA in a murine model of DCM, mediated by interfering with endogenously activated TGFβ signaling.
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