In mouse pregnancy, pubic symphysis (PS) remodels into an elastic interpubic ligament (IpL) in a temporally regulated process to provide safe delivery. It restores at postpartum to assure reproductive tract homeostasis. Recently, macrophage localization in the IpL and dynamic changes in the expression of inflammatory mediators observed from the end of pregnancy (D18, D19) to early days postpartum (1dpp, 3dpp) highlighted the necessity of the identification of the key molecules involved in innate immune processes in PS remodeling. Therefore, this study uses morphological and high-sensitivity molecular techniques to identify both macrophage association with extracellular matrix (ECM) remodeling and the immunological processes involved in PS changes from D18 to 3dpp. Results showed macrophage association with active gelatinases and ECM components and 25 differentially expressed genes (DEGs) related to macrophage activities in interpubic tissues from D18 to 3dpp. Additionally, microarray and proteomic analysis showed a significant association of interpubic tissue DEGs with complement system activation and differentially expressed proteins (DEPs) with phagocytosis, highlighting the involvement of macrophage-related activities in mouse PS remodeling. Therefore, the findings suggest that PS ECM remodeling is associated with evidence of macrophage modulation that ensures both IpL relaxation and fast PS recovery postpartum for first labor.

Bioactive peptides have been studied in several sources due to their valuable potential in the pharmaceutical and food industries. Abalone viscera, which are normally discarded as byproducts, are a rich source of protein. Thus, the aim of this study was to explore the potential bioactivity of peptides derived from abalone viscera (Haliotis fulgens and Haliotis corrugata) after hydrolysis with a commercial mixture of enzymes. The hydrolysates obtained were fractionated using gel filtration chromatography. The resulting hydrolysate fractions were investigated for their antimicrobial and cytotoxic activities, including the expression of gelatinases mmp-2 and mmp-9 in human prostate cancer cell lines (PC3). Results showed antimicrobial activity for protein fractions of H. corrugata against Proteus mirabilis and Pseudomona aeuroginosa (66.2-116.25 kDa), Bacillus subtilis (6.5-21.5 kDa), and Aspergillus niger (97.4-116.25 kDa), while H. fulgens peptide fractions (200-31 kDa) displayed activity against six bacterial strains, and fractions from 116.25 to 21.5 kDa had effects on the fungus A. niger, Alternaria alternata, and Aspergillus flavus. Additionally, protein fractions displayed cytotoxic activity, inhibiting 30.4-53.8% of PC3 cellular growth. Selected fractions decreased the PMA-induced and not-induced expressions of mmp-2 and mmp-9 in PC3 cells. Abalone viscera, as byproducts, can be used as a potential source of antimicrobial and anticancer peptides.

One of the major challenges in chronic Chagas disease is to understand the mechanisms that predict the clinical evolution from asymptomatic to severe cardiac clinical forms. Our cohort consisted of twenty-eight Chagas disease patients followed for twenty years. Plasma levels of MMP-2 and MMP-9 gelatinases and TIMPs were evaluated by multiplexed immunoassay at two points in time with an average interval of six years. MMP-2 plasma levels, but not MMP-9, increased in cardiac patients over time. TIMP-1 levels diminished in cardiac patients, while TIMP-3 dropped in asymptomatic patients in the course of the evaluated interval. An inversion of time lines was observed relative to the clinical asymptomatic and cardiac forms for MMP-2. Receiver Operating Characteristic (ROC) curve analysis identified MMP-2 as a biomarker to distinguish asymptomatic from cardiac clinical forms, while MMP-9 is a biomarker that segregates infected from non-infected patients. We have pointed out that MMP-2 and MMP-9 together can predict clinical evolution in Chagas disease. MMP-2 was suggested as a biomarker for fibrosis replacement in early remodeling and a sensitive predictor for initial changes in asymptomatic patients that may evolve into the cardiac clinical form. MMP-9 seems to be a biomarker for late fibrosis and severe cardiac remodeling in cardiac patients.

Acute injury in the setting of liver fibrosis is an interesting and still unsettled issue. Most recently, several prominent studies have indicated the favourable effects of liver fibrosis against acute insults. Nevertheless, the underlying mechanisms governing this hepatoprotection remain obscure. In the present study, we hypothesized that macrophages and their M1/M2 activation critically involve in the hepatoprotection conferred by liver fibrosis. Our findings demonstrated that liver fibrosis manifested a beneficial role for host survival and apoptosis resistance. Hepatoprotection in the fibrotic liver was tightly related to innate immune tolerance. Macrophages undertook crucial but divergent roles in homeostasis and fibrosis: depleting macrophages in control mice protected from acute insult; conversely, depleting macrophages in fibrotic liver weakened the hepatoprotection and gave rise to exacerbated liver injury upon insult. The contradictory effects of macrophages can be ascribed, to a great extent, to the heterogeneity in macrophage activation. Macrophages in fibrotic mice exhibited M2-preponderant activation, which was not the case in acutely injured liver. Adoptive transfer of M2-like macrophages conferred control mice conspicuous protection against insult. In vitro, M2-polarized macrophages protected hepatocytes against apoptosis. Together, M2-like macrophages in fibrotic liver exert the protective effects against lethal insults through conferring apoptosis resistance to hepatocytes.