The rupture of the Brumadinho mining tailings dam in Brazil is considered one of the largest mining disasters in the world, resulting in 244 deaths and 26 missing people, in addition to the environmental consequences. The present study aims to evaluate the concentrations of multiple elements and the biological effects on water and sediments of the Paraopeba River after the Brumadinho Dam rupture. The tailings are formed by fine particulate material with large amounts of Fe, Al, Mn, Ti, rare earth metals and toxic metals. In the water, the levels of Fe, Al, Mn, Zn, Cu, Pb, Cd and U were higher than those allowed by Brazilian legislation. In the sediments, Cr, Ni, Cu and Cd levels were higher than the established sediment quality guidelines (TEL-NOAA). The differences in metal concentrations in the water and sediments between the upstream and downstream sides of the dam illustrate the effect of the tailings in the Paraopeba River. Toxicological tests demonstrated that the water and sediments were toxic to different trophic levels, from algae to microcrustaceans and fish. The fish exposed to water and sediments containing mine ore also accumulated metals in muscle tissue. This evaluation emphasizes the necessity of long-term monitoring in the affected area. In less than four years, two major environmental tragedies involving mining dams occurred in Brazil. The first incident is considered the industrial disaster with the greatest environmental impacts in Brazilian history and the largest of the world involving tailings dams. The rupture of the Fundão Dam in the subdistrict of Bento Rodrigues, 35 km from the municipality of Mariana in Minas Gerais State on November 5, 2015, resulted in 19 deaths due to the release of more than 40 million m 3 of tailings that were transported to the mouth of the Doce River 1. The 668 km length of affected water by Fundão tailings is the largest ever recorded 2. The second incident occurred on January 25, 2019, when a tailings dam ("Dam B1") failed at Córrego do Feijão mine in the city of Brumadinho, also in Minas Gerais State, releasing approximately 12 million m 3 , which directly affected the administrative area of the company and parts of the nearby communities 3 , resulting in 244 deaths and 26 missing people, as some bodies were completely buried in the mud and never found 4. Although the previous evaluation by the Brazilian Mining Agency classified Dam B1 in Brumadinho as "low risk of collapse and high potential of associated damage" 5 , the rupture of the Brumadinho Dam led to the release of iron ore tailings into the Feijão stream that is a tributary of the Paraopeba River 6 (Supplementary Video, Fig. 1). Along the way, the volume of tailings led to an immediate increase in water turbidity (Supplementary Fig. S1a), impacts on the water supply in the municipalities provided by the Paraopeba River, and damage to fauna and

Mucositis is an adverse effect of cancer chemotherapies using 5-Fluorouracil (5-FU). It is characterized by mucosal inflammation, pain, diarrhea, and weight loss. Some studies reported promising healing effects of probiotic strains, when associated with prebiotics, as adjuvant treatment of mucositis. We developed a lyophilized symbiotic product, containing skimmed milk, supplemented with whey protein isolate (WPI) and with fructooligosaccharides (FOS), and fermented by Lactobacillus casei BL23, Lactiplantibacillus plantarum B7, and Lacticaseibacillus rhamnosus B1. In a mice 5-FU mucositis model, this symbiotic lyophilized formulation was able to reduce weight loss and intestinal permeability. This last was determined in vivo by quantifying blood radioactivity after oral administration of 99mTc-DTPA. Finally, histological damages caused by 5-FU-induced mucositis were monitored. Consumption of the symbiotic formulation caused a reduced score of inflammation in the duodenum, ileum, and colon. In addition, it decreased levels of pro-inflammatory cytokines IL-1β, IL-6, IL-17, and TNF-α in the mice ileum. The symbiotic product developed in this work thus represents a promising adjuvant treatment of mucositis.

Mucositis is an inflammation of the gastrointestinal mucosa that debilitate the quality of life of patients undergoing chemotherapy treatments. In this context, antineoplastic drugs, such as 5-fluorouracil, provokes ulcerations in the intestinal mucosa that lead to the secretion of pro-inflammatory cytokines by activating the NF-κB pathway. Alternative approaches to treat the disease using probiotic strains show promising results, and thereafter, treatments that target the site of inflammation could be further explored. Recently, studies reported that the protein GDF11 has an anti-inflammatory role in several diseases, including in vitro and in vivo results in different experimental models. Hence, this study evaluated the anti-inflammatory effect of GDF11 delivered by Lactococcus lactis strains NCDO2118 and MG1363 in a murine model of intestinal mucositis induced by 5-FU. Our results showed that mice treated with the recombinant lactococci strains presented improved histopathological scores of intestinal damage and a reduction of goblet cell degeneration in the mucosa. It was also observed a significant reduction of neutrophil infiltration in the tissue in comparison to positive control group. Moreover, we observed immunomodulation of inflammatory markers Nfkb1, Nlrp3, Tnf, and upregulation of Il10 in mRNA expression levels in groups treated with recombinant strains that help to partially explain the ameliorative effect in the mucosa. Therefore, the results found in this study suggest that the use of recombinant L. lactis (pExu:gdf11) could offer a potential gene therapy for intestinal mucositis induced by 5-FU.

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Target delivery of therapeutic agents with anti-inflammatory properties using probiotics as delivery and recombinant protein expression vehicles is a promising approach for the prevention and treatment of many diseases, such as cancer and intestinal immune disorders. Lactococcus lactis , a Lactic Acid Bacteria (LAB) widely used in the dairy industry, is one of the most important microorganisms with GRAS status for human consumption, for which biotechnological tools have already been developed to express and deliver recombinant biomolecules with anti-inflammatory properties. Cytokines, for  example, are immune system communication molecules present at virtually all levels of the immune response. They are essential in cellular and humoral processes, such as hampering inflammation or adjuvating in the adaptive immune response, making them good candidates for therapeutic approaches. This review discusses the advances in the development of new therapies and prophylactic approaches using LAB to deliver/express cytokines for the treatment of inflammatory and autoimmune diseases in the future.