Involvement of Inflammatory Cytokines, Renal NaPi-IIa Cotransporter, and TRAIL Induced-Apoptosis in Experimental Malaria-Associated Acute Kidney Injury.

The murine model of experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA was used to investigate the relationship among pro-inflammatory cytokines, alterations in renal function biomarkers, and the induction of the TRAIL apoptosis pathway during malaria-associated acute kidney injury (AKI). Renal function was evaluated through the measurement of plasma creatinine and blood urea nitrogen (BUN). The mRNA expression of several cytokines and NaPi-IIa was quantified. Kidney sections were examined and cytokine levels were assessed using cytometric bead array (CBA) assays. The presence of glomerular IgG deposits and apoptosis-related proteins were investigated using in situ immunofluorescence assays and quantitative real-time PCR, respectively. NaPi-IIa downregulation in the kidneys provided novel insights into the pathogenesis of hypophosphatemia during CM. Histopathological analysis revealed characteristic features of severe malaria-associated nephritis, including glomerular collapse and tubular alterations. Pro-inflammatory cytokines, such as TNF-α, IL-1ß, and IL-6, were upregulated. The TRAIL apoptosis pathway was significantly activated, implicating its role in renal apoptosis. The observed alterations in renal biomarkers and the downregulation of NaPi-IIa shed light on potential mechanisms contributing to renal dysfunction in ECM. The intricate balance between pro- and anti-inflammatory cytokines, along with the activation of the TRAIL apoptosis pathway, highlights the complexity of malaria-associated AKI and provides new therapeutic targets.

Perspectives of FTIR as Promising Tool for Pathogen Diagnosis, Sanitary and Welfare Monitoring in Animal Experimentation Models: A Review Based on Pertinent Literature.

Currently, there is a wide application in the literature of the use of the Fourier Transform Infrared Spectroscopy (FTIR) technique. This basic tool has also proven to be efficient for detecting molecules associated with hosts and pathogens in infections, as well as other molecules present in humans and animals' biological samples. However, there is a crisis in science data reproducibility. This crisis can also be observed in data from experimental animal models (EAMs). When it comes to rodents, a major challenge is to carry out sanitary monitoring, which is currently expensive and requires a large volume of biological samples, generating ethical, legal, and psychological conflicts for professionals and researchers. We carried out a survey of data from the relevant literature on the use of this technique in different diagnostic protocols and combined the data with the aim of presenting the technique as a promising tool for use in EAM. Since FTIR can detect molecules associated with different diseases and has advantages such as the low volume of samples required, low cost, sustainability, and provides diagnostic tests with high specificity and sensitivity, we believe that the technique is highly promising for the sanitary and stress and the detection of molecules of interest of infectious or non-infectious origin.

Mouse Models of Mayaro Virus.

Mayaro virus (MAYV), the etiologic agent of Mayaro fever, leads patients to severe myalgia and arthralgia, which can have a major impact on public health in all the countries where the virus circulates. The emergence and dissemination of new viruses have led the scientific community to develop new in vivo models that can help in the fight against new diseases. So far, mice have been the most used animal model in studies with MAYV and have proved to be an adequate model for recapitulating several aspects of the disease observed in humans. Mice are widely used in in vivo research and, therefore, are well known in the scientific community, which has allowed for different strains to be investigated in the study of MAYV. In this review, we summarize the main studies with MAYV using mice as an experimental model and discuss how they can contribute to the advancement of the understanding of its pathogenesis and the development of new drugs and vaccines.

Identification of bioactive peptides from a Brazilian kefir sample, and their anti-Alzheimer potential in Drosophila melanogaster.

Alzheimer's disease (AD) is the most common form of dementia in the elderly, affecting cognitive, intellectual, and motor functions. Different hypotheses explain AD's mechanism, such as the amyloidogenic hypothesis. Moreover, this disease is multifactorial, and several studies have shown that gut dysbiosis and oxidative stress influence its pathogenesis. Knowing that kefir is a probiotic used in therapies to restore dysbiosis and that the bioactive peptides present in it have antioxidant properties, we explored its biotechnological potential as a source of molecules capable of modulating the amyloidogenic pathway and reducing oxidative stress, contributing to the treatment of AD. For that, we used Drosophila melanogaster model for AD (AD-like flies). Identification of bioactive peptides in the kefir sample was made by proteomic and peptidomic analyses, followed by in vitro evaluation of antioxidant and acetylcholinesterase inhibition potential. Flies were treated and their motor performance, brain morphology, and oxidative stress evaluated. Finally, we performed molecular docking between the peptides found and the main pathology-related proteins in the flies. The results showed that the fraction with the higher peptide concentration was positive for the parameters evaluated. In conclusion, these results revealed these kefir peptide-rich fractions have therapeutic potential for AD.

Calomys callosus: An Experimental Animal Model Applied to Parasitic Diseases Investigations of Public Health Concern.

The appearance and spread of parasitic diseases around the world aroused the interest of the scientific community to discover new animal models for improving the quality and specificity of surveys. Calomys callosus is a rodent native to South America, an easy handling model, with satisfactory longevity and reproducibility. C. callosus is susceptible to toxoplasmosis and can be used as experimental model for the study the pathogenesis, treatment, vertical transmission, and ocular toxoplasmosis. C. callosus can also be used to study cutaneous and visceral leishmaniasis, as the animals present cutaneous lesions, as well as parasites in the organs. C. callosus has epidemiological importance in Chagas disease, and since it is a Trypanosoma cruzi natural host in which rodents show high parasitemia and lethality, they are also effective as a model of congenital transmission. In the study of schistosomiasis, Schistosoma mansoni was proven to be a C. callosus natural host; thus, this rodent is a great model for fibrosis, hepatic granulomatous reaction, and celloma associated with lymphomyeloid tissue (CALT) during S. mansoni infection. In this review, we summarize the leading studies of parasitic diseases that used C. callosus as a rodent experimental model, describing the main uses and characteristics that led them to be considered an effective model.

TNF-TNFR1 Signaling Enhances the Protection Against Neospora caninum Infection.

Neospora caninum is a protozoan associated with abortions in ruminants and neuromuscular disease in dogs. Classically, the immune response against apicomplexan parasites is characterized by the production of proinflammatory cytokines, such as IL-12, IFN-γ and TNF. TNF is mainly produced during the acute phases of the infections and binds to TNF receptor 1 (CD120a, p55, TNFR1) activating a variety of cells, hence playing an important role in the induction of the inflammatory process against diverse pathogens. Thus, in this study, we aimed to evaluate the role of TNF in cellular and humoral immune responses during N. caninum infection. For this purpose, we used a mouse model of infection based on wildtype (WT) and genetically deficient C57BL/6 mice in TNFR1 (Tnfr1-/-). We observed that Tnfr1-/- mice presented higher mortality associated with inflammatory lesions and increased parasite burden in the brain after the infection with N. caninum tachyzoites. Moreover, Tnfr1-/- mice showed a reduction in nitric oxide (NO) levels in vivo. We also observed that Tnfr1-/- mice showed enhanced serum concentration of antigen-specific IgG2 subclass, while IgG1 production was significantly reduced compared to WT mice, suggesting that TNFR1 is required for regular IgG subclass production and antigen recognition. Based on our results, we conclude that the TNF-TNFR1 complex is crucial for mediating host resistance during the infection by N. caninum.

Serological evidence of Toxoplasma gondii infection in Melanosuchus niger (Spix, 1825) and Caimam crocodilus (Linnaeus, 1758).

Toxoplasma gondii is a protozoan with worldwide prevalence, known to affect a large variety of warm-blooded hosts. However, its ability to induce long-lasting infections in cold-blooded animals remains unclear. The most likely source of infection is through consumption of meat containing tissue cysts or by ingestion of food or water contaminated with oocysts. The current global climate change trend and the progressive degradation of natural habitats are prone to alter the distribution of ectotherm populations over a short period of time, which may favor contact between these animals and the protozoan. In association, alligator meat is considered a delicacy in many regions and its consumption has been previously related to a diversity of foodborne diseases. In that sense, we proposed in this study to search for specific antibodies against T. gondii in serum samples of two common species of alligators from the Brazilian fauna (Melanosuchus niger and Caimam crocodilus). We obtained the serum samples from 84 alligators from the Araguaia region, which were tested by agglutination assays that do not require species-specific secondary antibodies (Modified Agglutination Test - MAT; Indirect Hemagglutination Assay - IHA). From the 84 samples tested, eight (9.5%) were positive by MAT. From those, seven (87.5% of MAT+, 8.3% of the total) were also positive by IHA, reassuring a probable exposure of these animals to the parasite. Direct parasite detection in muscle fragments of one serologically reactive alligator did not yield positive results. Our results provide serological evidence that Brazilian alligators may be exposed to T. gondii and further studies should be performed to elucidate whether alligators are natural hosts of this ubiquitous protozoan parasite.

Dectin-1 Compromises Innate Responses and Host Resistance against Neospora caninum Infection.

Neospora caninum is an intracellular protozoan parasite that has drawn increasing interest due to its association with worldwide repetitive bovine abortions, which cause billionaire losses to the meat and dairy industries annually. Innate immunity plays an important role in infection control, and N. caninum activates the production of inflammatory mediators through toll-like receptors, NOD-like receptors, and mitogen-activated protein kinase signaling pathways. Advances in the knowledge of initial host-parasite interactions are desirable for the design of control measures against the infection, obliterating its pathogenesis. In that sense, we here aimed to describe the role of the innate C-type lectin receptor Dectin-1 during the infection by N. caninum. With that intent, we observed that the absence of Dectin-1, observed in genetically depleted (Dectin-1-/-) mice or competitively inhibited by an inert agonist [laminarin (LAM)], rescued 50% of the mice infected with lethal doses of N. caninum. Dectin-1-/- and LAM-treated mice also presented a reduction in the parasite load during acute and chronic phases, associated with decreased inflammatory scores in the central nervous system. Among all the cell phenotypes that migrated to the initial site of infection, dendritic cells and macrophages gained subpopulations with high Dectin-1 surface expression. The impairment of the receptor in these cells led to a decreased parasite burden, as well as augmented production of IL-12p40. We also found that Dectin-1+ cells produced less reactive oxygen species (ROS) at the initial site of the infection, while mice deficient in NADPH oxidase isoform 2 (NOX2-/-) were not able to control parasite replication and produce IL-12p40, even upon LAM treatment. Interestingly, the absence of functional Dectin-1 did not alter the susceptibility of mice against closely related Toxoplasma gondii. In conclusion, the gathered data suggest that Dectin-1 is involved in the parasite-induced downmodulation of ROS, and other key molecules triggered for the control of N. caninum infection and are a promising target for future development of protocols intended for intervention against neosporosis.

Interaction between TNF and BmooMP-Alpha-I, a Zinc Metalloprotease Derived from Bothrops moojeni Snake Venom, Promotes Direct Proteolysis of This Cytokine: Molecular Modeling and Docking at a Glance.

Tumor necrosis factor (TNF) is a major cytokine in inflammatory processes and its deregulation plays a pivotal role in several diseases. Here, we report that a zinc metalloprotease extracted from Bothrops moojeni venom (BmooMP-alpha-I) inhibits TNF directly by promoting its degradation. This inhibition was demonstrated by both in vitro and in vivo assays, using known TLR ligands. These findings are supported by molecular docking results, which reveal interaction between BmooMP-alpha-I and TNF. The major cluster of interaction between BmooMP-alpha-I and TNF was confirmed by the structural alignment presenting Ligand Root Mean Square Deviation LRMS = 1.05 Å and Interactive Root Mean Square Deviation IRMS = 1.01 Å, this result being compatible with an accurate complex. Additionally, we demonstrated that the effect of this metalloprotease on TNF is independent of cell cytotoxicity and it does not affect other TLR-triggered cytokines, such as IL-12. Together, these results indicate that this zinc metalloprotease is a potential tool to be further investigated for the treatment of inflammatory disorders involving TNF deregulation.

Serological status of mares in parturition and the levels of antibodies (IgG) against protozoan family Sarcocystidae from their pre colostral foals.

Protozoa from the family Sarcocystidae are agents of reproductive and neurological disorders in horses. The transmission of these protozoa may occur via horizontal or vertical means, and the frequency and potential of the later is not fully elucidated in horses. Thus, the aim of study was to correlation levels of antibodies in mares with pre colostral foals seropositive and assess the level and distribution of antibodies against Neospora spp., Sarcocystis neurona and Toxoplasma gondii, in mares and pre colostral foals at the parturition. The blood samples were collected from mares immediately after parturition and from newborns before the ingestion of colostrum, and sera were analyzed for the presence of IgG by ELISA. It was found that 21.5%, 33.7% and 27.6% of mares were seropositive for Neospora spp., S. neurona and T. gondii, respectively; foals had antibodies at a rate of 8.3%, 6.6% and 6.6% for Neospora spp., S. neurona and T. gondii, respectively. Additionally, paired samples from mares and pre-colostral foals revealed an overall negative correlation between the serum reactivity against these three parasites and suggested that seronegative mares, or those with low to intermediate antibody levels, have a higher risk of giving birth to seropositive foals.