La consolation dans les tombeaux poétiques en Italie, en France et dans les Îles britanniques (1590-1640)

Dans la philosophie antique, la parole apparaît comme un médecin qui soigne les souffrances de l’âme. Ainsi, au début de la consolation à Apollonius, Plutarque dit que « le discours est un bon médecin pour l’âme malade, si on le tient au bon moment pour apaiser un cœur » (« Psukhès nosousès eisin iatroi logoi, hotan tis en kairô ge malthassèi kear »). En particulier, l’orateur et le philosophe sont des interlocuteurs privilégiés pour ceux qui sont en deuil ou qui redoutent leur propre mort. A..

The myofibroblast, multiple origins for major roles in normal and pathological tissue repair

Myofibroblasts differentiate, invade and repair injured tissues by secreting and organizing the extracellular matrix and by developing contractile forces. When tissues are damaged, tissue homeostasis must be re-established, and repair mechanisms have to rapidly provide harmonious mechanical tissue organization, a process essentially supported by (myo)fibroblasts. Under physiological conditions, the secretory and contractile activities of myofibroblasts are terminated when the repair is complete (scar formation) but the functionality of the tissue is only rarely perfectly restored. At the end of the normal repair process, myofibroblasts disappear by apoptosis but in pathological situations, myofibroblasts likely remain leading to excessive scarring. Myofibroblasts originate from different precursor cells, the major contribution being from local recruitment of connective tissue fibroblasts. However, local mesenchymal stem cells, bone marrow-derived mesenchymal stem cells and cells derived from an epithelial-mesenchymal transition process, may represent alternative sources of myofibroblasts when local fibroblasts are not able to satisfy the requirement for these cells during repair. These diverse cell types probably contribute to the appearance of myofibroblast subpopulations which show specific biological properties and which are important to understand in order to develop new therapeutic strategies for treatment of fibrotic and scarring diseases

Dispersal limitation induces long-term biomass collapse in overhunted Amazonian forests

Tropical forests are the global cornerstone of biological diversity, and store 55% of the forest carbon stock globally, yet sustained provisioning of these forest ecosystem services may be threatened by hunting-induced extinctions of plant-animal mutualisms that maintain long-term forest dynamics. Large-bodied Atelinae primates and tapirs in particular offer nonredundant seed-dispersal services for many large-seeded Neotropical tree species, which on average have higher wood density than smaller-seeded and wind-dispersed trees. We used field data and models to project the spatial impact of hunting on large primates by ∼1 million rural households throughout the Brazilian Amazon. We then used a unique baseline dataset on 2,345 1-ha tree plots arrayed across the Brazilian Amazon to model changes in aboveground forest biomass under different scenarios of hunting-induced large-bodied frugivore extirpation. We project that defaunation of the most harvest-sensitive species will lead to losses in aboveground biomass of between 2.5-5.8% on average, with some losses as high as 26.5-37.8%. These findings highlight an urgent need to manage the sustainability of game hunting in both protected and unprotected tropical forests, and place full biodiversity integrity, including populations of large frugivorous vertebrates, firmly in the agenda of reducing emissions from deforestation and forest degradation (REDD+) programs

The significance of macrophage polarization subtypes for animal models of tissue fibrosis and human fibrotic diseases.

The systemic and organ-specific human fibrotic disorders collectively represent one of the most serious health problems world-wide causing a large proportion of the total world population mortality. The molecular pathways involved in their pathogenesis are complex and despite intensive investigations have not been fully elucidated. Whereas chronic inflammatory cell infiltration is universally present in fibrotic lesions, the central role of monocytes and macrophages as regulators of inflammation and fibrosis has only recently become apparent. However, the precise mechanisms involved in the contribution of monocytes/macrophages to the initiation, establishment, or progression of the fibrotic process remain largely unknown. Several monocyte and macrophage subpopulations have been identified, with certain phenotypes promoting inflammation whereas others display profibrotic effects. Given the unmet need for effective treatments for fibroproliferative diseases and the crucial regulatory role of monocyte/macrophage subpopulations in fibrogenesis, the development of therapeutic strategies that target specific monocyte/macrophage subpopulations has become increasingly attractive. We will provide here an overview of the current understanding of the role of monocyte/macrophage phenotype subpopulations in animal models of tissue fibrosis and in various systemic and organ-specific human fibrotic diseases. Furthermore, we will discuss recent approaches to the design of effective anti-fibrotic therapeutic interventions by targeting the phenotypic differences identified between the various monocyte and macrophage subpopulations

Phenotypic differences between dermal fibroblasts from different body sites determine their responses to tension and TGFβ1

BACKGROUND: Wounds in the nonglabrous skin of keloid-prone individuals tend to cause large disordered accumulations of collagen which extend beyond the original margins of the wound. In addition to abnormalities in keloid fibroblasts, comparison of dermal fibroblasts derived from nonwounded glabrous or nonglabrous skin revealed differences that may account for the observed location of keloids. METHODS: Fibroblast apoptosis and the cellular content of α-smooth-muscle actin, TGFβ1 receptorII and ED-A fibronectin were estimated by FACS analysis. The effects of TGFβ1 and serum were examined. RESULTS: In monolayer cultures non-glabrous fibroblasts were slower growing, had higher granularity and accumulated more α-smooth-muscle actin than fibroblasts from glabrous tissues. Keloid fibroblasts had the highest level of α-smooth-muscle actin in parallel with their expression level of ED-A fibronectin. TGFβ1 positively regulated α-smooth-muscle actin expression in all fibroblast cultures, although its effects on apoptosis in fibroblasts from glabrous and non-glabrous tissues were found to differ. The presence of collagen I in the ECM resulted in reduction of α-smooth-muscle actin. A considerable percentage of the apoptotic fibroblasts in attached gels were α-smooth-muscle actin positive. The extent of apoptosis correlated positively with increased cell and matrix relaxation. TGFβ1 was unable to overcome this apoptotic effect of matrix relaxation. CONCLUSION: The presence of myofibroblasts and the apoptosis level can be regulated by both TGFβ1 and by the extracellular matrix. However, reduction of tension in the matrix is the critical determinant. This predicts that the tension in the wound bed determines the type of scar at different body sites

Collagen organization deposited by fibroblasts encapsulated in pH responsive methacrylated alginate hydrogels

The pH of dermal wounds shifts from neutral during the inflammatory phase to slightly basic in the tissue remodeling phase. Stage specific wound treatment can be developed using environmentally responsive alginate hydrogels. The chemistry of these networks dictates swelling behavior. Here, we fabricated alginate hydrogels using chain growth, step growth, and combined mixed mode gelation methods to crosslink methacrylated alginate (ALGMA) and gain control over swelling responses. Methacrylation of the alginate network was confirmed through NMR spectroscopy. Strontium cations were introduced to fabricate stiffer, dually crosslinked hydrogels. Dual crosslinking significantly decreased the swelling response over the pH range of 3–9 for step growth and chain growth hydrogels, with no impact on mixed mode hydrogels. The extent of crosslinking altered the hydrogel degradation profiles under accelerated degradation conditions. Encapsulated NIH/3T3 fibroblasts in the different ALGMA hydrogels remained viable with greater cell proliferation in the stiffer gels. Collagen organization deposited by the NIH/3T3 fibroblasts was monitored using second harmonic generation (SHG) microscopy and was influenced by the crosslinking mechanism. Ionic chain growth and ionic mixed mode crosslinked ALGMA hydrogels caused relatively isotropic collagen organization, particularly 10 days post‐cell encapsulation. Principal component analysis (PCA) was employed to uncover correlations between the observed properties. The ability of these environmentally responsive gels to induce isotropic collagen and respond to pH changes means they hold promise as phase specific wound dressings

The Soluble Tumor Necrosis Factor-Alpha Receptor Suppresses Airway Inflammation in a Murine Model of Acute Asthma

Asthma is a T helper 2 (Th2)-mediated inflammatory airway disease, characterized by airway hyperresponsiveness (AHR), chronic eosinophilic inflammation, episode of reversible bronchoconstriction, and mucus hypersecretion. In these responsies, several cytokines are considered to take part in a pivotal role. Although Th2 cytokines, including interleukin (IL)-4, IL-5 and IL-13, are important in asthma,1 tumor necrosis factor (TNF)-α has been implicated in the inflammatory response, seen in asthma.2 TNF-α is a multifunctional proinflammatory cytokine, and a chemoattractant for neutrophils and eosinophils.3 It increases the cytotoxic effect of eosinophils on endothelial cells,4 epithelial expression of adhesion molecules, such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1),6 and the contractile function of smooth muscles,7 and is involved in the activation of T cells.5 Howarth et al.8 reported that TNF-α concentration in bronchoalveolar lavage fluid (BALF) and TNF-α protein and messenger RNA (mRNA) expression in bronchial biopsy specimens were increased in patients with severe asthma compared those with mild disease

Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer

Pancreatic stellate cells (PSCs) differentiate into cancer-associated fibroblasts (CAFs) that produce desmoplastic stroma, thereby modulating disease progression and therapeutic response in pancreatic ductal adenocarcinoma (PDA). However, it is unknown whether CAFs uniformly carry out these tasks or if subtypes of CAFs with distinct phenotypes in PDA exist. We identified a CAF subpopulation with elevated expression of alpha-smooth muscle actin (alphaSMA) located immediately adjacent to neoplastic cells in mouse and human PDA tissue. We recapitulated this finding in co-cultures of murine PSCs and PDA organoids, and demonstrated that organoid-activated CAFs produced desmoplastic stroma. The co-cultures showed cooperative interactions and revealed another distinct subpopulation of CAFs, located more distantly from neoplastic cells, which lacked elevated alphaSMA expression and instead secreted IL6 and additional inflammatory mediators. These findings were corroborated in mouse and human PDA tissue, providing direct evidence for CAF heterogeneity in PDA tumor biology with implications for disease etiology and therapeutic development