Increased Dickkopf-1 expression in breast cancer bone metastases

The aim of this study was to determine whether Dickkopf-1 (Dkk-1) expression in breast cancer was associated with bone metastases. We first analysed Dkk-1 expression by human breast cancer cell lines that induce osteolytic or osteoblastic lesions in animals. Dickkopf-1 levels were then measured in the bone marrow aspirates of hind limbs from eight NMRI mice inoculated with breast cancer cells that induced bone metastases and 11 age-matched non-inoculated control animals. Finally, Dkk-1 was measured in the serum of 17 women with breast cancer in complete remission, 19 women with breast cancer and bone metastases, 16 women with breast cancer and metastases at non-bone sites and 16 healthy women. Only breast cancer cells that induce osteolytic lesions in animals produced Dkk-1. There was a six-fold increase in Dkk-1 levels in the bone marrow from animals inoculated with MDA-B02 cells when compared with that of control non-inoculated animals (P=0.003). Median Dkk-1 levels in the serum of patients with breast cancer and bone metastases were significantly higher than levels of patients in complete remission (P=0.016), patients with breast cancer having metastases at non-bone sites (P<0.0001) and healthy women (P=0.047), although there was a large overlap in individual levels between the different groups. In conclusion, Dkk-1 is secreted by osteolytic human breast cancer cells lines and increased circulating levels are associated with the presence of bone metastases in patients with breast cancer. Measurements of circulating Dkk-1 levels may be useful for the clinical investigation of patients with breast cancer and bone metastases

Porphyromonas gingivalis Participates in Pathogenesis of Human Abdominal Aortic Aneurysm by Neutrophil Activation. Proof of Concept in Rats

International audienceBACKGROUND: Abdominal Aortic Aneurysms (AAAs) represent a particular form of atherothrombosis where neutrophil proteolytic activity plays a major role. We postulated that neutrophil recruitment and activation participating in AAA growth may originate in part from repeated episodes of periodontal bacteremia. METHODS AND FINDINGS: Our results show that neutrophil activation in human AAA was associated with Neutrophil Extracellular Trap (NET) formation in the IntraLuminal Thrombus, leading to the release of cell-free DNA. Human AAA samples were shown to contain bacterial DNA with high frequency (11/16), and in particular that of Porphyromonas gingivalis (Pg), the most prevalent pathogen involved in chronic periodontitis, a common form of periodontal disease. Both DNA reflecting the presence of NETs and antibodies to Pg were found to be increased in plasma of patients with AAA. Using a rat model of AAA, we demonstrated that repeated injection of Pg fostered aneurysm development, associated with pathological characteristics similar to those observed in humans, such as the persistence of a neutrophil-rich luminal thrombus, not observed in saline-injected rats in which a healing process was observed. CONCLUSIONS: Thus, the control of periodontal disease may represent a therapeutic target to limit human AAA progression

Limits to reproduction and seed size-number trade-offs that shape forest dominance and future recovery

International audienceThe relationships that control seed production in trees are fundamental to understanding the evolution of forest species and their capacity to recover from increasing losses to drought, fire, and harvest. A synthesis of fecundity data from 714 species worldwide allowed us to examine hypotheses that are central to quantifying reproduction, a foundation for assessing fitness in forest trees. Four major findings emerged. First, seed production is not constrained by a strict trade-off between seed size and numbers. Instead, seed numbers vary over ten orders of magnitude, with species that invest in large seeds producing more seeds than expected from the 1:1 trade-off. Second, gymnosperms have lower seed production than angiosperms, potentially due to their extra investments in protective woody cones. Third, nutrient-demanding species, indicated by high foliar phosphorus concentrations, have low seed production. Finally, sensitivity of individual species to soil fertility varies widely, limiting the response of community seed production to fertility gradients. In combination, these findings can inform models of forest response that need to incorporate reproductive potential

Prevalence and 6-month recovery of olfactory dysfunction: a multicentre study of 1363 COVID-19 patients

Objective: To investigate prevalence and recovery of olfactory dysfunction (OD) in COVID-19 patients according to the disease severity. Methods: From 22 March to 3 June 2020, 2581 COVID-19 patients were identified from 18 European hospitals. Epidemiological and clinical data were extracted at baseline and within the 2-month post-infection. Results: The prevalence of OD was significantly higher in mild form (85.9%) compared with moderate-to-critical forms (4.5–6.9%; P&nbsp;=&nbsp;0.001). Of the 1916 patients with OD, 1363 completed the evaluations (71.1%). A total of 328 patients (24.1%) did not subjectively recover olfaction 60&nbsp;days after the onset of the dysfunction. The mean duration of self-reported OD was 21.6&nbsp;±&nbsp;17.9&nbsp;days. Objective olfactory evaluations identified hyposmia/anosmia in 54.7% and 36.6% of mild and moderate-to-critical forms, respectively (P&nbsp;=&nbsp;0.001). At 60&nbsp;days and 6&nbsp;months, 15.3% and 4.7% of anosmic/hyposmic patients did not objectively recover olfaction, respectively. The higher baseline severity of objective olfactory evaluations was strongly predictive of persistent OD (P&nbsp;&lt;&nbsp;0.001). Conclusion: OD is more prevalent in mild COVID-19 forms than in moderate-to-critical forms. OD disappeared in 95% of patients regarding objective olfactory evaluations at 6&nbsp;months