Calf immunization protocols with low-virulence isolates of Anaplasma marginale: Analysis of post-inoculation effects and protection against natural challenge.

Bovine anaplasmosis is endemic and is of fundamental importance worldwide. Therefore, measures for controlling and preventing clinical diseases are warranted to ensure the reduction of associated economic losses. The objective of the present study was to assess the post-inoculation effects and protection conferred by three different protocols of inoculation of low-virulence live strains of Anaplasma marginale (UFMG1 and UFMG3) in field-challenged cattle. Sixty-eight Holstein calves with an average age of 17 days were randomly divided into four groups. The groups received two subcutaneous administrations spaced 40 days apart, at a dosage of 2 × 106 infected erythrocytes of the following A. marginale strains: G1 (UFMG1 + UFMG1); G2 (UFMG3 + UFMG3); G3 (UFMG1 + UFMG3); and G4 (control). Every two days, the animals were evaluated for rectal temperature, Packed Cell Volume (PCV), and blood smears. Blood samples were collected prior to inoculation, before the field challenge, and after the challenge period, nPCR and IFAT techniques were performed. There were no significant differences in rickettsemia levels, reduction in PCV, or antibody detection among the different inoculation strategies. Forty days after the second inoculation, 90 %, 84.6 %, and 90.9 % of the animals in G1, G2, and G3, respectively, tested positive using nPCR. After inoculation, the group G2, which received the UFMG3 inoculum, had a higher frequency of treatment (odds ratio of 6.7; 1.198-38.018 CI; p = 0.03), while groups G1 and G3 demonstrated similar treatment frequencies compared to the control. During the natural challenge phase, 13.3 % of animals in group G1 required treatment (odds ratio of 0.108; 0.018-0.635 CI; p = 0.014) compared to 58.8 % of the control group. Considering the results collectively, the protocol using the UFMG1 strain (G1) stands out for its potential to be safe and induce some degree of immunization against A. marginale, reducing the incidence of clinical disease and the need for treatment during natural challenge.

The angiotensin-(1-7)/MasR axis improves pneumonia caused by Pseudomonas aeruginosa: Extending the therapeutic window for antibiotic therapy.

Pseudomonas aeruginosa is a frequent cause of antimicrobial-resistant hospital-acquired pneumonia, especially in critically ill patients. Inflammation triggered by P. aeruginosa infection is necessary for bacterial clearance but must be spatially and temporally regulated to prevent further tissue damage and bacterial dissemination. Emerging data have shed light on the pro-resolving actions of angiotensin-(1-7) [Ang-(1-7)] signaling through the G protein-coupled receptor Mas (MasR) during infections. Herein, we investigated the role of the Ang-(1-7)/Mas axis in pneumonia caused by P. aeruginosa by using genetic and pharmacological approach and found that Mas receptor-deficient animals developed a more severe form of pneumonia showing higher neutrophilic infiltration into the airways, bacterial load, cytokines, and chemokines production and more severe pulmonary damage. Conversely, treatment of pseudomonas-infected mice with Ang-(1-7) was able to decrease neutrophilic infiltration in airways and lungs, local and systemic levels of pro-inflammatory cytokines and chemokines, and increase the efferocytosis rates, mitigating lung damage/dysfunction caused by infection. Notably, the therapeutic association of Ang-(1-7) with antibiotics improved the survival rates of mice subjected to lethal inoculum of P. aeruginosa, extending the therapeutic window for imipenem. Mechanistically, Ang-(1-7) increased phagocytosis of bacteria by neutrophils and macrophages to accelerate pathogen clearance. Altogether, harnessing the Ang-(1-7) pathway during infection is a potential strategy for the development of host-directed therapies to promote mechanisms of resistance and resilience to pneumonia.

Angiotensin-(1-7) decreases inflammation and lung damage caused by betacoronavirus infection in mice.

OBJECTIVE: Pro-resolving molecules, including the peptide Angiotensin-(1-7) [Ang-(1-7)], have potential adjunctive therapy for infections. Here we evaluate the actions of Ang-(1-7) in betacoronavirus infection in mice. METHODS: C57BL/6J mice were infected intranasally with the murine betacoronavirus MHV-3 and K18-hACE2 mice were infected with SARS-CoV-2. Mice were treated with Ang-(1-7) (30 µg/mouse, i.p.) at 24-, 36-, and 48-hours post-infection (hpi) or at 24, 36, 48, 72, and 96 h. For lethality evaluation, one additional dose of Ang-(1-7) was given at 120 hpi. At 3- and 5-days post- infection (dpi) blood cells, inflammatory mediators, viral loads, and lung histopathology were evaluated. RESULTS: Ang-(1-7) rescued lymphopenia in MHV-infected mice, and decreased airways leukocyte infiltration and lung damage at 3- and 5-dpi. The levels of pro-inflammatory cytokines and virus titers in lung and plasma were decreased by Ang-(1-7) during MHV infection. Ang-(1-7) improved lung function and increased survival rates in MHV-infected mice. Notably, Ang-(1-7) treatment during SARS-CoV-2 infection restored blood lymphocytes to baseline, decreased weight loss, virus titters and levels of inflammatory cytokines, resulting in improvement of pulmonary damage, clinical scores and lethality rates. CONCLUSION: Ang-(1-7) protected mice from lung damage and death during betacoronavirus infections by modulating inflammation, hematological parameters and enhancing viral clearance.

The effects of inflammation on connexin 43 in chronic Chagas disease cardiomyopathy.

Background: Cardiac arrhythmias are the main cause of sudden death due to Chronic Chagasic Cardiomyopathy (CCC). Here we investigated alterations in connexin 43 (Cx43) expression and phosphorylation in cardiomyocytes as well as associations with cardiac arrhythmias in CCC. Methods: C57Bl/6 mice infected with Trypanosoma cruzi underwent cardiac evaluations at 6 and 12 months after infection via treadmill testing and EKG. Histopathology, cytokine gene expression, and distribution of total Cx43 and its phosphorylated forms Cx43S368 and Cx43S325/328/330 were investigated. Human heart samples obtained from subjects with CCC were submitted to immunofluorescence analysis. In vitro simulation of a pro-inflammatory microenvironment (IL-1ß, TNF, and IFN-γ) was performed in H9c2 cells and iPSC-derived cardiomyocytes to evaluate Cx43 distribution, action potential duration, and Lucifer Yellow dye transfer. Results: Mice chronically infected with T. cruzi exhibited impaired cardiac function associated with increased inflammation, fibrosis and upregulated IL-1ß, TNF, and IFN-γ gene expression. Confocal microscopy revealed altered total Cx43, Cx43S368 and Cx43S325/328/330 localization and phosphorylation patterns in CCC, with dispersed staining outside the intercalated disc areas, i.e., in lateral membranes and the cytoplasm. Reduced co-localization of total Cx43 and N-cadherin was observed in the intercalated discs of CCC mouse hearts compared to controls. Similar results were obtained in human CCC heart samples, which showed Cx43 distribution outside the intercalated discs. Stimulation of human iPSC-derived cardiomyocytes or H9c2 cells with IL-1ß, TNF, and IFN-γ induced alterations in Cx43 localization, reduced action potential duration and dye transfer between adjacent cells. Conclusion: Heart inflammation in CCC affects the distribution and phosphorylation pattern of Cx43, which may contribute to the generation of conduction disturbances in Chagas disease.

Staphylococcus aureus in Dairy Industry: Enterotoxin Production, Biofilm Formation, and Use of Lactic Acid Bacteria for Its Biocontrol.

Staphylococcus aureus is a well-known pathogen capable of producing enterotoxins during bacterial growth in contaminated food, and the ingestion of such preformed toxins is one of the major causes of food poisoning around the world. Nowadays 33 staphylococcal enterotoxins (SEs) and SE-like toxins have been described, but nearly 95% of confirmed foodborne outbreaks are attributed to classical enterotoxins SEA, SEB, SEC, SED, and SEE. The natural habitat of S. aureus includes the skin and mucous membranes of both humans and animals, allowing the contamination of milk, its derivatives, and the processing facilities. S. aureus is well known for the ability to form biofilms in food processing environments, which contributes to its persistence and cross-contamination in food. The biocontrol of S. aureus in foods by lactic acid bacteria (LAB) and their bacteriocins has been studied for many years. Recently, LAB and their metabolites have also been explored for controlling S. aureus biofilms. LAB are used in fermented foods since in ancient times and nowadays characterized strains (or their purified bacteriocin) can be intentionally added to prolong food shelf-life and to control the growth of potentially pathogenic bacteria. Regarding the use of these microorganism and their metabolites (such as organic acids and bacteriocins) to prevent biofilm development or for biofilm removal, it is possible to conclude that a complex network behind the antagonistic activity remains poorly understood at the molecular level. The use of approaches that allow the characterization of these interactions is necessary to enhance our understanding of the mechanisms that govern the inhibitory activity of LAB against S. aureus biofilms in food processing environments.

Immobilization of the ß-galactosidase enzyme by encapsulation in polymeric matrices for application in the dairy industry.

Lactose intolerance affects approximately 65% of the global adult population, leading to the demand for lactose-free products. The enzyme ß-galactosidase (ßG) is commonly used in the industry to produce such products, but its recovery after lactose hydrolysis is challenging. In this scenario, the study aims to encapsulate ßG within capsules, varying in dimensions and wall materials, to ensure their suitability for efficient industrial recovery. The enzyme ßG was encapsulated through ionic gelation using alginate and its blends with pectin, maltodextrin, starch, or whey protein as wall materials. The capsules produced underwent evaluation for encapsulation efficiency, release profiles, activity of the ßG enzyme, and the decline in enzyme activity when reused over multiple cycles. Alginate at 5% wt/vol concentrations, alone or combined with polymers such as maltodextrin, starch, or whey protein, achieved encapsulation efficiencies of approximately 98%, 98%, 80%, and 88%, respectively. The corresponding enzyme recovery rates were 34%, 19%, 31%, and 48%. Capsules made with an alginate-pectin blend exhibited no significant hydrolysis and maintained an encapsulation efficiency of 79%. Encapsulation with alginate alone demonstrated on poor retention of enzyme activity, showing a loss of 74% after just 4 cycles of reuse. Conversely, when alginate was mixed with starch or whey protein concentrate, the loss of enzyme activity was less than 40% after 4 reuses. These results highlight the benefits of combining encapsulation materials to improve enzyme recovery and reuse, offering potential economic advantages for the dairy industry.

Mesenchymal Stromal Cell-Based Products: Challenges and Clinical Therapeutic Options.

Mesenchymal stromal cell (MSC)-based advanced therapy medicinal products (ATMPs) are being tried in a vast range of clinical applications. These cells can be isolated from different donor tissues by using several methods, or they can even be derived from induced pluripotent stem cells or embryonic stem cells. However, ATMP heterogeneity may impact product identity and potency, and, consequently, clinical trial outcomes. In this review, we discuss these topics and the need to establish minimal criteria regarding the manufacturing of MSCs so that these innovative therapeutics may be better positioned to contribute to the advancement of regenerative medicine.

Lysine grafted poly(lactic acid): An intrinsically antimicrobial polymer.

Nosocomial infections or healthcare-associated infections, normally develops after the healthcare treatment in the hospital. Most of them are caused by infected medical devices. Plastics are the most common materials for manufacturing these devices because of their good processability, sterilization efficacy, ease of handling and harmlessness, however, it usually do not display antimicrobial properties. Here, in order to infer antimicrobial activity to poly(lactic acid), it was modified by maleation, followed by l-lysine grafting to its structure. The chemical modifications were confirmed by FTIR and 1H NMR analysis, indicating the success of the reactions. The antimicrobial activity was tested using Escherichia coli and Staphylococcus aureus and the results showed that the sample was capable of inhibiting about 99 % of the S. aureus growth by contact. The samples cytotoxicity was also tested using the L929 mouse cells and the results indicated no cytotoxic effect. These results indicated the sample antimicrobial potential, without affect the normal eukaryotic cells. In addition, the processability of the modified PLA (PLA-g-Lys) was improved without compromising its mechanical properties, as shown by thermal analysis and tensile tests. Thus, this novel PLA derivative can be seen as a promising material for future applications in the manufacturing of biomedical devices.

Influence of different culture media on the antimicrobial activity of Pediococcus pentosaceus ST65ACC against Listeria monocytogenes.

Pediococcus pentosaceus ST65ACC is a bacteriocinogenic lactic acid bacteria (LAB) isolated from Brazilian artisanal cheese that is capable of inhibiting different food pathogens, mainly Listeria monocytogenes. The production of bacteriocins can be influenced by several growth conditions, such as temperature, pH, and medium composition. This study aimed to evaluate the effect of different culture media on the production of bacteriocins and antimicrobial activity of P. pentosaceus ST65ACC on L. monocytogenes Scott A. The strains were inoculated alone and in coculture in four different media: BHI broth, MRS broth, meat broth, and reconstituted skim milk (RSM) 10% (w/v). The culture media were then incubated at 37 °C for 96 h, and count analysis, pH measurement, and bacteriocin production were performed at 0, 24, 48, 72 and 96 h. L. monocytogenes was inhibited to nondetectable levels in coculture with P. pentosaceus ST65ACC in MRS broth within 96 h, consistent with the high production of bacteriocin throughout the analysis period (3,200-12,800 AU/mL). However, lower inhibitory activities of P. pentosaceus ST65ACC on L. monocytogenes Scott A were recorded in BHI, RSM, and meat broth, with low or no production of bacteriocins at the analyzed times. The composition of these culture media may have repressed the production and activity of bacteriocins and, consequently, the antagonist activity of P. pentosaceus ST65ACC on L. monocytogenes Scott A. The results showed that the antimicrobial activity was more effective in MRS broth, presenting greater production of bacteriocins and less variability when compared to the other media analyzed.

Nursing interventions to empower the family caregiver of person with lower limb amputation: scoping review.

OBJECTIVES: to map nursing interventions that empower the Family caregiver of the person with lower limb amputation for is role. METHODS: scoping review guided by Joanna Briggs Institute methodology conducted in different databases (including gray literature). RESULTS: six studies published between 2009 and 2021 were included. Interventions of counselling and support for patients and family; peer support interventions performed by a certified pair; involvement of caregivers or family members in support groups; and key interventions for patient and family caregiver psychological balance. Two studies discussed the importance of caregiver and amputee training and development of coping skills. Another study recommended Interventions of informative support for caregivers regarding care for the amputee and adaptation to home. CONCLUSIONS: results of this review allow the identification of recommendations (guidelines) for practice and recommendations/suggestions for interventions according with identified needs of family caregivers of patients with lower limb amputation.

Hemopathogens in naturally infected bovine fetuses in Brazil.

The transplacental transmission of parasites and hemoparasites is crucial for understanding the epidemiology of diseases. This study aimed to assess the prevalence of hemopathogens in bovine fetuses at various gestational periods. Samples were obtained from a slaughterhouse in the state of Minas Gerais, Brazil, and a total of 236 fetuses were collected. DNA extracted from blood samples (145) and organ samples (a pool of brain and spleen) (236) underwent a nested PCR (nPCR) assay to detect Babesia spp., Theileria spp., Trypanosoma vivax, Anaplasma marginale, Anaplasma bovis, Anaplasma phagocytophilum, Ehrlichia minasensis, and hemotropic Mycoplasma spp. Additionally, serological analysis of 145 plasma samples was conducted using the indirect fluorescent antibody test-IFAT to detect IgG against Babesia bovis, Babesia bigemina, A. marginale, and Trypanosoma vivax. The observed prevalence of transplacental transmission was 19.3 %, 6.2 %, 42.7 % and 2.7 %, for A. marginale, B. bigemina, 'Candidatus M. haemobos', and Mycoplasma wenyonii, respectively. The prevalence of A. marginale by gestational trimester was 16 % (13/81) in the second trimester and 23 % (14/60) in the third trimester, with no positive samples in the first trimester. Regarding the species B. bovis and B. bigemina, all evaluated animals tested negative by nPCR, and no serological evidence for B. bovis was found by the IFAT. Babesia bigemina demonstrated an overall seroprevalence of 6.2 % (9/145), with 4.8 % (7/145) in the last trimester and 1.3 % (2/145) in the second trimester of pregnancy. In total, 42.7 % (62/145) of blood samples were positive for 'Candidatus M. haemobos', with 42 % (34/81) in the middle trimester, and 43 % (26/60) in the final trimester of pregnancy. Mycoplasma wenyonni was detected in 2.7 % (4/145) blood samples, all in coinfection with 'C. M. haemobos'. The prevalence by pregnancy trimester was 25 % (1/4) in the first trimester; 1.2 % (1/81) in the second trimester and 3.3 % (2/60) in the third trimester of pregnancy. Hemopathogen DNA was detected in fetus blood samples but not the brain or spleen samples. All the samples were negative for T. vivax, Theileria spp., Anaplasma spp. and Ehrlichia spp. Overall, in this study, approximately 70 % of fetuses were positive for one or more of the studied parasites. No significant associations were observed between pairs of pathogens, except 'C. M. haemobos' and A. marginale.

Biopesticide spinosad: Unraveling ecotoxicological effects on zebrafish, Danio rerio.

Biopesticides are natural compounds considered more safe and sustainable for the environment. Spinosad (SPI) is a bioinsecticide used in marketed worldwide, to eradicate a variety of pests. This study aimed to assess the impacts of the SPI on the non-target organism zebrafish (Danio rerio). Several concentrations of SPI were tested to evaluate the acute (0.07-1.0 mg/L) and chronic (0.006-0.100 mg/L) ecotoxicological effects. To evaluate sub-individual effects, antioxidant defense, lipid peroxidation, energy sources, and cholinergic biomarkers were quantified. In both exposures, SPI induced significant effects on antioxidant defense indicating oxidative stress, disrupting energy pathways, and exhibiting neurotoxic effects, under environmentally relevant conditions. Integrated Biomarker Response (IBRv2) showed that with increasing SPI concentrations, an increase in impacts on organisms was recorded. This study demonstrates the vulnerability of a non-target organism to SPI, a bioinsecticide considered environmentally safe. Further research is essential to fully understand the implications of spinosad to aquatic biota.

Challenges and opportunities for access to Advanced Therapy Medicinal Products in Brazil.

BACKGROUND AIMS: The marketing authorization of Advanced Therapy Medicinal Products (ATMPs) in Brazil is recent. The features of these therapies impose specialized regulatory action and are consequently challenging for developers. The goal of this study was to identify the industry's experience in clinical development, marketing authorization and access to ATMPs through the Unified Health System (SUS, acronym in Portuguese), from a regulatory perspective. METHODS: A survey containing structured questions was conducted among research participants who work at companies that commercialize ATMPs. A descriptive analysis was performed. RESULTS: We invited 15 foreign pharmaceutical companies, of which 10 agreed to participate. Overall, participants assessed that Brazil has a well-established regulatory system, especially the sanitary registration by the National Health Surveillance Agency (Anvisa), which ensures the quality, safety, and efficacy of the products. The Agency's good interaction with the regulated sector, the harmonization of sanitary and ethical assessment systems with other countries, and the analysis time in the biosafety assessment of Genetically Modified Organisms (GMOs) stand out as positive in industry's evaluation. On the other hand, it is important to advance the pricing regulation for these products since Brazilian regulations do not establish specific criteria for ATMP. One of the biggest challenges is the difficulty for the SUS in reimbursing these very high-cost therapies, especially using current Health Technology Assessment (HTA) methods. CONCLUSIONS: Considering the increasing number of approvals of cell and gene therapies in Brazil in the coming years, a close dialogue between the industry and the public sector is recommended to advance regulatory improvements (pricing and HTA). Additionally, the construction of policies to promote the national Health Economic-Industrial Complex, based on a mission-oriented vision that encourages innovative models of financing, especially those that consider risk-sharing and co-financing technologies, will help provide the population with universal, equitable and sustainable access to ATMP in the SUS.

Advanced cell and gene therapies in cardiology.

We review the evidence for the presence of stem/progenitor cells in the heart and the preclinical and clinical data using diverse cell types for the therapy of cardiac diseases. We highlight the failure of adult stem/progenitor cells to ameliorate heart function in most cardiac diseases, with the possible exception of refractory angina. The use of pluripotent stem cell-derived cardiomyocytes is analysed as a viable alternative therapeutic option but still needs further research at preclinical and clinical stages. We also discuss the use of direct reprogramming of cardiac fibroblasts into cardiomyocytes and the use of extracellular vesicles as therapeutic agents in ischemic and non-ischemic cardiac diseases. Finally, gene therapies and genome editing for the treatment of hereditary cardiac diseases, ablation of genes responsible for atherosclerotic disease, or modulation of gene expression in the heart are discussed.

Prevalence and impact of sarcopenia in individuals with heart failure with reduced ejection fraction (the SARC-HF study): A prospective observational study protocol.

Sarcopenia, a clinical syndrome primarily associated with reduced muscle mass in the elderly, has a negative impact on quality of life and survival. It can occur secondarily to other diseases such as heart failure (HF), a complex clinical syndrome with high morbidity and mortality. The simultaneous occurrence of these two conditions can worsen the prognosis of their carriers, especially in the most severe cases of HF, as in patients with reduced left ventricular ejection fraction (LVEF). However, due to the heterogeneous diagnostic criteria for sarcopenia, estimates of its prevalence present a wide variation, leading to new criteria having been recently proposed for its diagnosis, emphasizing muscle strength and function rather than skeletal muscle mass. The primary objective of this study is to evaluate the prevalence of sarcopenia and/or dynapenia in individuals with HF with reduced LVEF according to the most recent criteria, and compare the gene and protein expression of those patients with and without sarcopenia. The secondary objectives are to evaluate the association of sarcopenia and/or dynapenia with the risk of clinical events and death, quality of life, cardiorespiratory capacity, ventilatory efficiency, and respiratory muscle strength. The participants will answer questionnaires to evaluate sarcopenia and quality of life, and will undergo the following tests: handgrip strength, gait speed, dual-energy X-ray absorptiometry, respiratory muscle strength, cardiopulmonary exercise, as well as genomic and proteomic analysis, and dosage of N-terminal pro-B-type natriuretic peptide and growth differentiation factor-15. An association between sarcopenia and/or dynapenia with unfavorable clinical evolution is expected to be found, in addition to reduced quality of life, cardiorespiratory capacity, ventilatory efficiency, and respiratory muscle strength.

Serious Games for Developing Social Skills in Children and Adolescents with Autism Spectrum Disorder: A Systematic Review.

Serious games represent a promising avenue for intervention with children diagnosed with autism spectrum disorder, a neurodevelopmental disorder marked by persistent challenges in social communication and the presence of restricted, repetitive behaviors. Despite this potential, comprehensive reviews on this subject are scarce. This systematic review aims to evaluate the effectiveness of serious games and their specific characteristics in enhancing social skills among children and adolescents with autism. Employing PICO strategies and adhering to PRISMA guidelines, we screened 149 studies initially identified through PubMed and EBSCOhost databases. Nine studies met inclusion criteria and found a positive influence of serious games on social skills and related domains, encompassing emotion recognition/encoding/decoding, emotional regulation, eye gaze, joint attention, and behavioral skills. Nevertheless, despite these promising results, the limited available evidence underscores the need for rigorous study designs to consolidate findings and integrate evidence-based intervention strategies.

Exploring the impact of high-energy diets on cattle: Insights into subacute rumen acidosis, insulin resistance, and hoof health.

Cattle lameness remains a significant concern, causing economic losses and compromising animal welfare. Claw horn lesions have been identified as a major cause of lameness in dairy cows, but their correlation with high-energy diets and ruminal acidosis remains unclear. Hence, the primary objective of this study was to assess the effects of a high-starch diet and a conventional diet on the rumen environment, acute-phase proteins, and metabolic alterations, with a particular focus on insulin resistance and the consequent implications for the histology of the hooves in Holstein steers. A total of 16 animals were divided into the high-starch (HS; 37% starch) and conventional (CON; 16.8% starch) groups. Glucose tolerance tests (GTT), blood analyses, rumen fluid analyses, and histological evaluations of the hoof tissue were conducted over a 102-d experimental period. The HS group showed a lower ruminal pH than the CON group, and with values indicating SARA. The plasma glucose and IGF-1 concentrations were higher in the HS group, suggesting an anabolic state. Both groups exhibited an increase in the insulin area under the curve (AUC) after the GTT on d 102. Histological analysis of the hooves showed a reduction in the length and width of the epidermal lamella in both groups. We found a significant negative correlation between the insulin AUC and the length and width of the epidermal lamella. Because both groups were similarly affected, the hypothesis that histological alterations were caused by the experimental diets still needs confirmation. Additionally, the development of SARA was not essential for the observed histological changes in the hoof. Further studies are warranted to thoroughly investigate the role of insulin and IGF-1 imbalances in claw health.

Ecotoxicological Effects of Potassium Dichromate on the Tadpole Shrimp Triops longicaudatus.

The tadpole shrimp Triops longicaudatus is a freshwater crustacean with fast embryonic and larval development, short life cycle, and high fecundity. They are very active swimmers of a reasonable size, easy to spot and record. Such characteristics make it a promising candidate as an experimental model in ecotoxicology to evaluate the effects of aquatic pollutants, particularly using its locomotor behavior as an endpoint. To evaluate the sensitivity of T. longicaudatus and develop endpoints of interest, we conducted exposure experiments with lethal and sub-lethal concentrations of potassium dichromate, a compound known for its ecotoxicological importance and as a hexavalent chromium source. The endpoints evaluated were mortality, growth, sexual maturation, reproductive output, cholinesterase activity and locomotor/swimming behavior. The 96 h median lethal concentration was found to be 65 µg/L. Furthermore, exposure to potassium dichromate at higher concentrations had a significant negative impact on the growth rate of T. longicaudatus in terms of both body mass and length. The time for maturation was also delayed at higher concentrations. In addition, locomotor behavior allowed for the discrimination of all tested chromium concentrations and the control group and from each other, proving to be the most sensitive endpoint. Overall, the data support the potential of T. longicaudatus as a model for ecotoxicity testing, using apical endpoints with impact at the population level; in particular, results suggest that behavior assessments in this species might be useful for detecting hazardous compounds in environmental monitoring of freshwater ecosystems.

Annexin A1 improves immune responses and control of tissue parasitism during Leishmania amazonensis infection in BALB/c mice.

Leishmaniases, a group of diseases caused by the species of the protozoan parasite Leishmania, remains a significant public health concern worldwide. Host immune responses play a crucial role in the outcome of Leishmania infections, and several mediators that regulate inflammatory responses are potential targets for therapeutic approaches. Annexin A1 (AnxA1), an endogenous protein endowed with anti-inflammatory and pro-resolving properties, has emerged as a potential player. We have shown that during L. braziliensis infection, deficiency of AnxA1 exacerbates inflammatory responses but does not affect parasite burden. Here, we have investigated the role of AnxA1 in L. amazonensis infection, given the non-healing and progressive lesions characteristic of this infectious model. Infection of AnxA1 KO BALB/c mice resulted in increased lesion size and tissue damage associated with higher parasite burdens and enhanced inflammatory response. Notably, therapeutic application of the AnxA1 peptidomimetic Ac2-26 improves control of parasite replication and increases IL-10 production in vivo and in vitro, in both WT and AnxA1 KO mice. Conversely, administration of WRW4, an inhibitor of FPR2/3, resulted in larger lesions and decreased production of IL-10, suggesting that the effects of AnxA1 during L. amazonensis infection are associated with the engagement of these receptors. Our study illuminates the role of AnxA1 in L. amazonensis infection, demonstrating its impact on the susceptibility phenotype of BALB/c mice. Furthermore, our results indicate that targeting the AnxA1 pathway by using the Ac2-26 peptide could represent a promising alternative for new treatments for leishmaniasis.