Does Plasminogen Activator Inhibitor-1 Drive Lymphangiogenesis?

The purpose of this study is to explore the function of plasminogen activator inhibitor-1 (PAI-1) during pathological lymphangiogenesis. PAI-1, the main physiological inhibitor of plasminogen activators is involved in pathological angiogenesis at least by controlling extracellular proteolysis and by regulating endothelial cell survival and migration. Protease system's role in lymphangiogenesis is unknown yet. Thus, based on its important pro-angiogenic effect, we hypothesized that PAI-1 may regulate lymphangiogenesis associated at least with metastatic dissemination of cancer cells. To address this issue, we studied the impact of PAI-1 deficiency in various murine models of tumoral lymphangiogenesis. Wild-type PAI-1 proficient mice were used as controls. We provide for the first time evidence that PAI-1 is dispensable for tumoral lymphangiogenesis associated with breast cancers either induced by mammary carcinoma cell injection or spontaneously appearing in transgenic mice expressing the polyomavirus middle T antigen (PymT) under the control of a mouse mammary tumor virus long-terminal repeat promoter (MMTV-LTR). We also investigated inflammation-related lymphatic vessel recruitment by using two inflammatory models. PAI-1 deficiency did neither affect the development of lymphangioma nor burn-induced corneal lymphangiogenesis. These novel data suggest that vascular remodelling associated with lymphangiogenesis and angiogenesis involve different molecular determinants. PAI-1 does not appear as a potential therapeutic target to counteract pathological lymphangiogenesis

An overview of approaches for assessing the environmental sustainability of diets – a scoping review for Nordic Nutrition Recommendations 2023

Assessing the environmental impacts of food, food systems and diets is highly complex due to the multitude of processes involved, the uncertainty in assessment models, the variability in production systems and the large range of products available. No single assessment method alone can provide a complete evidence base. The increasing number of Life Cycle Assessment and food system analyses, and more recently the integration of planetary boundaries offer insights from which we can draw some robust high-level conclusions, whilst recognising there is a need for more detailed analysis to capture the inherent nuances of more location and context-specific situations. Despite the complexity of assessing the environmental sustainability of food, diets and food systems, there are a number of key considerations that could be used to guide this process, and in doing so, they help to increase utility of the outcomes and limit unintended adverse consequences. We identified five key considerations that can be applied (consider the thresholds, consider the system, consider the variables, consider the context and consider the spillover) to ensure assessments are comprehensive.</p

Nordic Nutrition Recommendations 2023 : Integrating Environmental Aspects

The Nordic Nutrition Recommendations (NNR) constitute the scientific basis for national dietary guidelines and nutrient recommendations in the Nordic and Baltic countries. The NNR2023 is the result of five years of work of several hundred researchers and experts, in the Nordic cooperation’s biggest and most globally spread project. This sixth edition of the NNR gives, for the first time ever, recommendations not only about what food is good for our health, but also what is good for the environment. In addition, dietary reference values for nutrients have been updated, many nutrients have received reference values for the first time, and many more food groups have been analysed than in previous editions – turning NNR2023 into the most comprehensive NNR to date. In short, the NNR2023 recommends:  A predominantly plant-based diet high in vegetables, fruits, berries, pulses, potatoes and whole grains Ample intake of fish and nuts Moderate intake of low-fat dairy products Limited intake of red meat and poultry Minimal intake of processed meat, alcohol, and processed foods containing high amounts of fats, salt and suga

Environmental sustainability of food production and consumption in the nordic and baltic region - a scoping review for nordic nutrition recommendations 2023

This scoping review examines environmental impacts related to food production and consumption in Nordic and Baltic countries. The overarching advice to all Nordic and Baltic countries, in line with the current body of scientific literature, is to shift to a more plant based dietary pattern and avoid food waste. Taking into account current consumption patterns, there is a high potential and necessity to shift food consumption across the countries to minimize its environmental impact. More specifically, a substantial reduction in meat and dairy consumption and increased consumption of legumes/pulses, whole grains, vegetables, fruits, nuts and seeds is suggested as a priority intervention. Reducing the environmental impacts of seafoods is also key and suggestions include a shift to seafoods with lower environmental impacts such as seaweed and bivalves. As part of the suggested transition to a more plant-based diet, the scope for increasing the provision of plant-based foods through increasing the cultivation of legumes/pulses, vegetables and grains and through feed-to-food shifts within the region should be explored

Tumor development after orthotopic injection of VEGF-C overexpressing MCF7 cells or control MCF7 cells implanted in the mammary fat pads (mfp) of PAI-1 WT or PAI-1^−/− mice.

<p>(A): RT-PCR analysis of VEGF-C and 28S mRNA expression by MCF7. (B): Tumor incidence (%) is defined as the percentage of palpable tumor per mfp. (C): Tumor volume was measured as described in Material and <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009653#s2" target="_blank">Methods</a>. (D): Representative figure of a typical metastasis in lymph node (left) and lung (right). (E): Percentage of animal bearing at least a tumor nodule (metastasis% detected in lymph nodes (black boxes) and lungs (white boxes). Number of mfp per condition = 34–38. The mice PAI-1 status (WT or −/−) and the VEGF-C production (VEGF-C) or not (Ctl) by MCF7 cells are indicated below each graph. Data are ± S.E.M. Scale bars: 200 µm. ** P≤0.01, *** P≤0.001, NS = Non Significant.</p

Analysis of intratumoral lymphatic vessels in tumors induced by orthotopic injection of VEGF-C overexpressing MCF7 or control MCF7 cells implanted in the mammary fat pads (mfp) of PAI-1 WT or PAI-1^−/− mice.

<p>(A): Representative images of Lyve-1 positive-vessels at two different magnifications in VEGF-C expressing tumors developed in WT mice (WT) or PAI-1 deficient mice (^−/−), and in control tumors (Ctl). (B–D): Quantification of lymphatic vessels has been performed by computerized image analysis and led to the determination of three parameters: 1- relative vascular area (area occupied by intratumoral lymphatic vessels reported to the total tumor surface) (B); 2- number of lymphatic vessel sections per slide (number of vessels) (C) and; 3- mean lymphatic vessel size (D). The mice PAI-1 status (WT or −/−) and the VEGF-C production (VEGF-C) or not (Ctl) by MCF7 cells are indicated below each graph. Data are ± S.E.M. NS = Non Significant.</p

Development of lymphangioma in PAI-1 WT or PAI-1^−/− mice.

<p>A macroscopic decrease of lymphangioma is observed in PAI-1^−/− as compared to WT (A). Similar recruitment of lymphatic vessels (assessed by Lyve-1 positivity) (B), and of CD45 positive-inflammatory cells (C) was observed in both genotypes. Evaluation of fibrosis was performed by Sirius red staining (D). Representative images are shown on the left and quantifications performed by computerized image analysis are shown on the right Data are ± S.E.M (n = 6). Scale bars: A = 0.5 mm, B–D = 200 µm, ** P≤0.01.</p