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Disseminated leishmaniasis (DL) is an aggressive form of tegumentary leishmaniasis associated with multiple and polymorphic cutaneous lesions (acneiform and inflammatory papules, nodules, and ulcers) in [greater than or equal to] [...]

Simple Summary: A tumor's extracellular matrix (ECM) serves as a vital connection and support network, orchestrating events that regulate tumor activity. Versican (VCAN), a proteoglycan found within the ECM, plays a crucial role in invasion and metastasis. Like the ECM, VCAN can undergo cleavage by metalloproteinases, such as a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS). This proteolytic process produces a bioactive fragment known as versikine (VKINE). Remarkably, this fragment exhibits immunomodulatory activity in certain cancer types. Consequently, the proteolysis of VCAN and associated factors may be valuable indicators of tumor progression. Background: The present study investigates VKINE, a bioactive proteolytic fragment of the proteoglycan VCAN, as a novel and significant element in the tumor extracellular matrix (ECM). Although VKINE has been recognized for its immunomodulatory potential in certain tumor types, its impact on ECM degradation and prognostic implications remains poorly understood. Objectives: This study aimed to evaluate VCAN proteolysis and its association with ADAMTS enzymes involved in extracellular matrix remodeling in spontaneous canine mammary gland cancer. Methods: The expression levels of VKINE, ADAMTS enzymes, and collagen fibers were comparatively analyzed in situ and in invasive areas of carcinoma in mixed tumor (CMT) and carcinosarcoma (CSS) with different prognoses. Results: VKINE was notably expressed in the stroma adjacent to the invasion areas in CMT, whereas ADAMTS-15 was identified as the enzyme associated with VCAN proteolysis. Inverse correlations were observed between type III collagen and VCAN expression in in situ areas. Conclusions: Our findings suggest that VKINE and ADAMTS-15 play crucial roles in the tumor microenvironment, influencing invasiveness and type III collagen deposition. This study contributes to a better understanding of the dynamics within the ECM, paving the way for potential new tools in diagnosing and treating human and canine mammary tumors. [ABSTRACT FROM AUTHOR]

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This article explores the relationship between institutional funding for research and community-based or co-enquiry research practice. It examines the implementation of co-enquiry research in the COMBIOSERVE project, which was funded by the European Commission's Seventh Framework Programme for research and innovation, between the years 2012 and 2015. Research partnerships between Latin American and European civil society organisations, research institutions, and Latin American rural communities are analysed. Challenges for effective collaboration in co-enquiry and lessons learned for research policy and practice are outlined. Based on our case study we suggest that: (1) the established values and practices of academia seem largely unfavourable towards alternative forms of research, such as co-enquiry; (2) the policies and administrative practices of this European Commission funding are unsuitable for adopting participatory forms of enquiry; and (3) the approach to research funding supports short engagements with communities whereas long-term collaborations are more desirable. Based on our case study, we propose more flexible funding models that support face-to-face meetings between researchers and communities from the time of proposal drafting, adaptation of research processes to local dynamics, adaptation of administrative processes to the capacities of all participants, and potential for long-term collaborations. Large-scale funding bodies such as European Commission research programmes are leaders in the evolution of research policy and practice. They have the power and the opportunity to publicly acknowledge the value of partnerships with civil society organisations and communities, actively support co-enquiry, and foment interest in innovative forms of research.

Brazil is a country with marked social asymmetries, which have an impact on the impoverishment of basic educational proficiencies. We present a snapshot in a cross-sectional documentary study that registered the risk of distorting educational processes even more intensely, due to the easing of political and pedagogical decision-making. Planning and thinking about how to keep our teachers and students learning during the isolation and the post-pandemic period, implies the redesigning of education scenarios, searching for balance in teaching and in the use of technologies and resources. Until now, we have noticed an enlarged reproduction of pre-existing educational asymmetries. People who live in a situation of social vulnerability and digital exclusion are facing many more difficulties in the isolation period, as well as in managing to keep learning, than those in better financial conditions and with broadband internet access. It is a time that requires collective reinvention, bringing together policies and practices in a resolutive and equitable way.

Disseminated leishmaniasis (DL) caused by L. braziliensis is characterized by the presence of 10 to more than 1000 lesions spread on the body. While protection against Leishmania is mediated by macrophages upon activation by IFN-γ produced by CD4+T cells, the pathology of disseminated leishmaniasis (DL) could be mediated by macrophages, NK, and CD8+T cells. Herein, we evaluate the participation of senescent CD8+T cells in the pathogenesis of DL. Methods: Peripheral blood mononuclear cells (PBMCs), biopsies, co-cultures of CD8+T cells with uninfected and infected macrophages (MØ), and PBMC cultures stimulated with soluble L. braziliensis antigen (SLA) for 72 h from patients with cutaneous leishmaniasis (CL) and DL were used to characterize senescent CD8+T cells. Statistical analysis was performed using the Mann–Whitney and Kruskal–Wallis tests, followed by Dunn's. Results: Patients with DL have an increase in the frequency of circulating CD8+T cells that present a memory/senescent phenotype, while lesions from DL patients have an increase in the frequency of infiltrating CD8+T cells with a senescent/degranulation phenotype. In addition, after specific stimuli, DL patients' circulating CD8+T with memory/senescent profile, showing degranulation characteristics, increased upon SLA stimuli, and those specific CD8+T cells from DL patients had an increased degranulation phenotype, causing more apoptosis of infected target cells. Conclusions: DL patients show a higher frequency of cytotoxic senescent CD8+T cells compared to CL patients, and that could promote the lysis of infected cells, although without parasite killing, releasing Leishmania to the extracellular compartment, contributing to the spread of parasites. [ABSTRACT FROM AUTHOR]