Ileal inflammation is reduced due to treatment with a metalloprotease from BmooMP-α-I snake venom in an experimental model of Toxoplasma gondii infection.

The selection process for advanced therapies in patients with inflammatory bowel diseases (IBDs) must prioritize safety, especially when considering new biologic agents or oral molecule modulators. In C57BL/6 mice, oral infection with Toxoplasma gondii induces intestinal inflammation through excessive tumor necrosis factor (TNF) production, making TNF neutralization a potential therapeutic intervention. Considering this, the present study aimed to evaluate the therapeutic effects of BmooMP-α-I, a snake venom metalloprotease isolated from Bothrops moojeni, which could promote TNF hydrolysis, in treating T. gondii-induced ileitis. The results showed that C57BL/6 mice orally infected with 50 cysts of T. gondii from the Me49 strain and treated with BmooMP-α-I exhibited prolonged survival and improved morbidity scores. Additionally, the treatment ameliorated both the macroscopic and microscopic aspects of the intestine, reduced macrophage influx, and decreased the production of inflammatory mediators by mesenteric lymph node cells. These findings provide compelling experimental evidence supporting the ability of BmooMP-α-I to alleviate ileal inflammation. Considering that the currently available therapeutic protocols are not completely effective and often result in side effects, the exploration of alternative strategies involving novel therapeutic agents, as demonstrated in this study, has the potential to significantly enhance the quality of life for patients suffering from inflammatory bowel diseases.

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.

Transmission of Toxoplasma gondii Infection Due to Bone Marrow Transplantation: Validation by an Experimental Model.

Toxoplasmosis is an opportunistic infectious disease and may present a fatal outcome for human bone marrow transplant (BMT) recipients, due to the rapid disease course in immunosuppressed individuals. Several reports about occurrence of toxoplasmosis after BMT have been published in the literature, but this disease has been associated mainly due to reactivation of latent infection rather than primary infection. Even though there are reports of acute toxoplasmosis in recipients who were seronegative for T. gondii, suggesting transmission of infection after BMT, the source of infection in those cases has not been clearly demonstrated, whether it is due to the transplantation procedure by itself or from environmental source. Thus, the present study aimed to observe if it could be possible to demonstrate the parasite's ability to infect bone marrow (BM) cells and cause toxoplasmosis, when using an experimental model. Our results showed that 11% of hematopoietic and 7.1% of nonhematopoietic lineages may become infected when using in vitro experiments. Also, in vivo experiments demonstrated that, when C57BL/6 mice were infected with RH-RFP or ME-49-GFP T. gondii strains, the BM cells may be infected at different time points of infection. The parasites were detected by both fluorescent microscopy and qPCR. Also, when those BM samples were collected and used for BMT, the transplanted animals presented high rates of mortality and 87.5% of them became seropositive for T. gondii. Taken together, our results clearly demonstrated that it is possible to acquire primary T. gondii infection from the donor cells after BMT. Therefore, we are emphasizing that, before transplantation, serological screening for T. gondii infection from both donors and recipients, in addition to DNA search for this parasite from donor bone marrow cells, are necessary procedures to avoid the risk of T. gondii infection for immunocompromised patients.

Endogenous resident c-Kit cardiac stem cells increase in mice with an exercise-induced, physiologically hypertrophied heart.

Physical activity evokes well-known adaptations in the cardiovascular system. Although exercise training induces cardiac remodeling, whether multipotent stem cells play a functional role in the hypertrophic process remains unknown. To evaluate this possibility, C57BL/6 mice were subjected to swimming training aimed at achieving cardiac hypertrophy, which was morphologically and electrocardiographically characterized. Subsequently, c-Kit(+)Lin(-) and Sca-1(+)Lin(-) cardiac stem cells (CSCs) were quantified using flow cytometry while cardiac muscle-derived stromal cells (CMSCs, also known as cardiac-derived mesenchymal stem cells) were assessed using in vitro colony-forming unit fibroblast assay (CFU-F). Only the number of c-Kit(+)Lin(-) cells increased in the hypertrophied heart. To investigate a possible extracardiac origin of these cells, a parabiotic eGFP transgenic/wild-type mouse model was used. The parabiotic pairs were subjected to swimming, and the wild-type heart in particular was tested for eGFP(+) stem cells. The results revealed a negligible number of extracardiac stem cells in the heart, allowing us to infer a cardiac origin for the increased amount of detected c-Kit(+) cells. In conclusion, the number of resident Sca-1(+)Lin(-) cells and CMSCs was not changed, whereas the number of c-Kit(+)Lin(-) cells was increased during physiological cardiac hypertrophy. These c-Kit(+)Lin(-) CSCs may contribute to the physiological cardiac remodeling that result from exercise training.

Opposite effects of bone marrow-derived cells transplantation in MPTP-rat model of Parkinson's disease: a comparison study of mononuclear and mesenchymal stem cells.

The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) animal model is a useful tool to study Parkinson's disease (PD) and was used in the present study to investigate the potential beneficial as well as deleterious effects of systemic bone-marrow mononuclear cell (BMMC) or mesenchymal stem cell (BM-MSC) transplantation. MPTP administration resulted in a breakdown of the blood-brain barrier and motor impairment in the open field test 24 h after surgery. Three and 7 days after receiving the lesion, the injured animals showed remaining motor impairment compared to the sham groups along with a significant loss of tyrosine hydroxylase-immunoreactive (TH-ir) cells in the substantia nigra pars compacta (SNpc). The MPTP-lesioned rats treated with BMMCs immediately after lesioning exhibited motor impairment similar to the MPTP-saline group, though they presented a significantly higher loss of TH-ir cells in the SNpc compared to the MPTP-saline group. This increased loss of TH-ir cells in the SNpc was not observed when BMMC transplantation was performed 24 h after MPTP administration. In contrast, in the MPTP animals treated early with systemic BM-MSCs, no loss of TH-ir cells was observed. BMMCs and BM-MSCs previously labeled with CM-DiI cell tracker were found in brain sections of all transplanted animals. In addition, cells expressing CD45, an inflammatory white blood cell marker, were found in all brain sections analyzed and were more abundant in the MPTP-BMMC animals. In these animals, Iba1+ microglial cells showed also marked morphological changes indicating increased microglial activation. These results show that systemic BMMC transplantation did not ameliorate or prevent the lesion induced by MPTP. Instead, BMMC transplantation in MPTP-lesioned rats accelerated dopaminergic neuronal damage and induced motor impairment and immobility behavior. These findings suggest that caution should be taken when considering cell therapy using BMMCs to treat PD. However, systemic BM-MSC transplantation that reaches the injury site and prevents neuronal damage after an MPTP infusion could be considered as a potential treatment for PD during the early stage of disease development.