Mitochondrial dysfunction remains a pivotal mechanism in manifold neurodegenerative diseases. Mitochondrial homeostasis within the cell is an essential aspect of cell biology. Mitochondria, the power-generating organelle of the cell, have a dominant role in several processes associated with genomic integrity and cellular equilibrium. They are involved in maintaining optimal cell functioning and ensuring guidance against possible DNA damage, which could lead to mutations and the onset of diseases. Conversely, system perturbations, which could be due to environmental factors or senescence, induce changes in the physiological balance and result in mitochondrial function impairment. As a result, we present a general overview of the pathological pathways involved in Alzheimer's and Parkinson's diseases caused by changes in mitochondrial homeostasis. The focal point of this review is on mitochondrial dysfunction being a significant condition in the onset of neuronal disintegration. We explain the pathways associated with the dysfunction of the mitochondria, which are common among the most recurring neurodegenerative diseases, including Alzheimer's and Parkinson's disease. Are mitochondrial dysfunctions an early event in the progression of neuropathological processes? We discovered that mtDNA mutation is a major contributor to the metabolic pathology of most neurological disorders, causing changes in genes important for physiological homeostasis. As a result, genetic changes in presenilin, Amyloid-, ABAD, DJ-1, PINK-1, PARKIN, alpha-synuclein, and other important controlling genes occur. Therefore, we suggest possible therapeutic solutions.

One of the main objectives of developing new anti-cancer vaccine strategies is to effectively induce CD8+ T cell-mediated anti-tumor immunity. Live recombinant vectors, notably Listeria monocytogenes, have been shown to elicit a robust in vivo CD8+ T-cell response in preclinical settings. Significantly, it has been demonstrated that Listeria induces inflammatory/immunogenic cell death mechanisms such as pyroptosis and necroptosis in immune cells that favorably control immunological responses. Therefore, we postulated that the host’s response to Listeria-based vectors and the subsequent induction of CD8+ T cell-mediated immunity would be compromised by the lack of regulatory or effector molecules involved in pyroptosis or necroptosis. To test our hypothesis, we used recombinant L. monocytogenes carrying the ovalbumin gene (LM.OVA) to vaccinate wild-type (WT), caspase-1/11^−/−, gsdmd^−/−, ripk3^−/−, and mlkl^−/− C57Bl/6 mice. We performed an in vivo cytotoxicity assay to assess the efficacy of OVA-specific CD8+ T lymphocytes in eliminating target cells in wild-type and genetically deficient backgrounds. Furthermore, we evaluated the specific anti-tumor immune response in mice inoculated with the B16F0 and B16F0.OVA melanoma cell lines. Our findings demonstrated that while caspase-1/11 and GSDMD deficiencies interfere with the rapid control of LM.OVA infection, neither of the KOs seems to contribute to the early activation of OVA-specific CTL responses. In contrast, the individual deficiency of each one of these proteins positively impacts the generation of long-lasting effector CD8+ T cells.

Memory T cells are essential for effective and durable immune responses, as they provide long-term immunological surveillance and rapid reactivity upon re-exposure to a given pathogen or cancer cell. In solid tumors, the immunosuppressive tumor microenvironment (TME) often hinders immune activation, making enhancing memory T cell formation and persistence a key goal in cancer immunotherapy. Novel strategies are exploring ways to support these memory T cells, including using Listeria monocytogenes as a cancer vaccine vector. Notably, L. monocytogenes has unique properties that make it an ideal candidate for this purpose: it is highly effective at activating T cells, promoting the differentiation and survival of memory T cells, and modulating the TME to favor immune cell function. Thus, by leveraging the ability of L. monocytogenes to induce a strong, sustained T-cell response, researchers aim to develop vaccines that provide lasting immunity against tumors, reduce recurrence rates, and improve patient survival outcomes. This mini-review highlights the potential of memory T cell-focused cancer immunotherapy and the promising role of L. monocytogenes in advancing these efforts.

One of the main objectives of developing new anti-cancer vaccine strategies is to effectively induce CD8+ T cell-mediated anti-tumor immunity. Live recombinant vectors, notably Listeria mono-cytogenes, have been shown to elicit a robust in vivo CD8+ T cell response in preclinical settings. Significantly, it has been demonstrated that Listeria induces inflammatory/immunogenic cell death mechanisms such as pyroptosis and necroptosis in immune cells that favorably control immunological responses. Therefore, we postulated that the host's response to Listeria-based vec-tors and the subsequent induction of CD8+ T cell-mediated immunity would be compromised by the lack of regulatory or effector molecules involved in pyroptosis or necroptosis. To test our hy-pothesis, we used recombinant L. monocytogenes carrying the ovalbumin gene (LM.OVA) to vac-cinate wild-type (WT), caspase-1/11-/-, gsdmd-/-, ripk3-/-, and mlkl-/- C57Bl/6 mice. We performed an in vivo cytotoxicity assay to assess the efficacy of OVA-specific CD8+ T lymphocytes in eliminat-ing target cells in wild-type and genetically deficient backgrounds. Furthermore, we evaluated the specific anti-tumor immune response in mice inoculated with B16F0 and B16F0.OVA mela-noma cell lines. Our findings demonstrated that while caspase-1/11 and GSDMD deficiencies in-terfere with the rapid control LM.OVA infection, of the KO seems to contribute to the early acti-vation of OVA-specific CTL responses. In contrast, individual deficiency of each one of these pro-teins negatively impact the generation of long-lasting effector CD8+ T cells.

Cytokines are glycoproteins responsible for cellular communication, influenced by exercise. Their levels vary depending on the intensity and type of physical activity in both humans and horses. This review aimed to assess the effects of various types and intensities of exercise on the production of pro- and anti-inflammatory cytokines. A systematic search (2000–2022) was performed using databases such as PubMed, Scopus, and Web of Science. Studies involving horses (n = 3) and/or humans (n = 21) undergoing physical activity were selected, resulting in 24 eligible articles. IL-6, TNF-α, and IL-10 levels increased after high-intensity exercise in both species, while moderate-intensity activity yielded more variable results. Some cytokines, such as IL-1β and IL-17, exhibited species-specific differences. Cytokine production is influenced by exercise intensity and duration. The observed differences between horses and humans suggest physiological divergences, warranting further research in the field of exercise immunology and other related disciplines. As a potential outcome of this work, we propose that horses could serve as an appropriate translational animal model for human athletes in exercise immunology, justifying a more comprehensive comparative approach.