Carotenoids, known for their antioxidant properties, have garnered significant attention for their potential antitumour activities. This comprehensive review aims to elucidate the diverse mechanisms by which carotenoids exert antitumour effects, focusing on both well-established and novel findings. We explore their role in inducing apoptosis, inhibiting cell cycle progression and preventing metastasis by affecting oncogenic and tumour suppressor proteins. The review also explores the pro-oxidant function of carotenoids within cancer cells. In fact, although their overall contribution to cellular antioxidant defences is well known and significant, some carotenoids can exhibit pro-oxidant effects under certain conditions and are able to elevate reactive oxygen species (ROS) levels in tumoural cells, triggering mitochondrial pathways that would lead to cell death. The final balance between their antioxidant and pro-oxidant activities depends on several factors, including the specific carotenoid, its concentration and the redox environment of the cell. Clinical trials are discussed, highlighting the conflicting results of carotenoids in cancer treatment and the importance of personalized approaches. Emerging research on rare carotenoids like bacterioruberin showcases their superior antioxidant capacity and selective cytotoxicity against aggressive cancer subtypes, such as triple-negative breast cancer. Future directions include innovative delivery systems, novel combinations and personalized treatments, aiming to enhance the therapeutic potential of carotenoids. This review highlights the promising yet complex landscape of carotenoid-based cancer therapies, calling for continued research and clinical exploration.

The assembly of specific neuronal circuits relies on the expression of complementary molecular programs in presynaptic and postsynaptic neurons. In the cerebral cortex, the tyrosine kinase receptor ErbB4 is critical for the wiring of specific populations of GABAergic interneurons, in which it paradoxically regulates both the formation of inhibitory synapses as well as the development of excitatory synapses received by these cells. Here, we found that Nrg1 and Nrg3, two members of the neuregulin family of trophic factors, regulate the inhibitory outputs and excitatory inputs of interneurons in the mouse cerebral cortex, respectively. The differential role of Nrg1 and Nrg3 in this process is not due to their receptor-binding EGF-like domain, but rather to their distinctive subcellular localization within pyramidal cells. Our study reveals a novel strategy for the assembly of cortical circuits that involves the differential subcellular sorting of family-related synaptic proteins.

Carotenoids are lipophilic pigments naturally occurring in plants and, to a lesser extent, in certain non-photosynthetic organisms. They play a critical role in human health due to their antioxidant and immunomodulatory properties. Key carotenoids such as β-carotene, lycopene, lutein, and zeaxanthin are capable of neutralizing reactive oxygen species, thereby mitigating oxidative stress—a major contributor to the onset and progression of chronic diseases. These compounds also modulate immune responses by influencing lymphocyte proliferation, enhancing natural killer cell activity, and regulating the production of pro- and anti-inflammatory cytokines. Such immunomodulatory effects are associated with a reduced risk of infectious diseases and have shown potential protective roles against inflammatory conditions, cardiovascular and neurodegenerative disorders, and certain types of cancer. Moreover, diets rich in carotenoids are linked to improved immune status, particularly in vulnerable populations such as the elderly and immunocompromised individuals. Despite strong epidemiological evidence, clinical trials involving carotenoid supplementation have produced mixed results, indicating that their effectiveness may depend on the broader dietary context and interactions with other nutrients. In summary, carotenoids are important dietary compounds that contribute to immune regulation and the prevention of various diseases, although further clinical research is needed to determine optimal intake levels and assess their full therapeutic potential.

Mesenchymal stem cells (MSC) are a widely used population in cell therapy for their ability to differentiate into distinct tissues and more lately, for their immunomodulatory properties. However, the use of heterogeneous populations could be responsible for the nondesired outcomes reflected in the literature. Here, we analyse the different capacities of five one-cell-derived MSC clones to exert their immunomodulation ex vivo. We assessed proliferation assays in cocultures of MSC clones and purified cluster of differentiation (CD)3⁺, CD4⁺, or CD8⁺ lymphocytes; analysed the regulatory T (Treg) cells fold change rate; determined the effects on viability of peripheral blood mononuclear cells (PBMC); and also measured the coculture cytokine profiles (Th1/Th2). Conditioned media (CM) of different clones were also used to perform both proliferation assays and to analyse Treg fold change. The five clones analysed in this work were able to generate heterogeneous environments. Different clones inhibited proliferation of CD3⁺ and CD4⁺ lymphocytes, with different intensities. Surprisingly, all clones promoted proliferation of CD8⁺ lymphocytes. Different MSC clones and their CM were able to increase the number of Treg with different intensities. Finally, different clones also promoted different effects on the viability of PBMC treated with ultraviolet light. Considering all these data together, it seems that different clones, even from the same donor, can promote a wide spectrum of responses from anti-inflammatory to proinflammatory character. This fact may be important to standardise the design of personalized cell therapy protocols, thus diminishing the aforementioned undesired outcomes existing nowadays in this type of therapies.

Rheumatoid arthritis (RA) is an autoimmune disease that causes inflammation, pain, and ultimately, bone erosion of the joints. The causes of this disease are multifactorial, including genetic factors, such as the presence of the human leukocyte antigen (HLA)-DRB1*04 variant, alterations in the microbiota, or immune factors including increased cytotoxic T lymphocytes (CTLs), neutrophils, or elevated M1 macrophages which, taken together, produce high levels of pro-inflammatory cytokines. In this review, we focused on the function exerted by osteoclasts on osteoblasts and other osteoclasts by means of the release of exosomal microRNAs (miRNAs). Based on a thorough revision, we classified these molecules into three categories according to their function: osteoclast inhibitors (miR-23a, miR-29b, and miR-214), osteoblast inhibitors (miR-22-3p, miR-26a, miR-27a, miR-29a, miR-125b, and miR-146a), and osteoblast enhancers (miR-20a, miR-34a, miR-96, miR-106a, miR-142, miR-199a, miR-324, and miR-486b). Finally, we analyzed potential therapeutic targets of these exosomal miRNAs, such as the use of antagomiRs, blockmiRs, agomiRs and competitive endogenous RNAs (ceRNAs), which are already being tested in murine and ex vivo models of RA. These strategies might have an important role in reestablishing the regulation of osteoclast and osteoblast differentiation making progress in the development of personalized medicine.

The aim of the present report was to evaluate the inflammatory response to a 2000-m running test considering neutrophil myeloperoxidase as an inflammatory marker, and to verify if supplements rich in antioxidants could modulate Post-test antioxidant and anti-inflammatory responses. To this end, a 21-day homogenization period was carried out with three groups: a control group, a supplemented group taking an almond beverage enriched with vitamins C and E and a third group consuming the same beverage but enriched with Lippia citriodora extract. At the end of this period, participants performed a 2000-m run, and blood samples were obtained the day before and immediately after the running test. Plasma and neutrophils were isolated. As a result, plasma creatine kinase and myoglobin increased, indicating Post-test muscle damage. Plasma oxidative markers were increased in all groups, except in the group supplemented with the almond beverage. Neutrophil antioxidant enzymes were significantly increased only in the control group, suggesting an antioxidant effect of the supplements provided in the other groups. Myeloperoxidase activity was significantly increased after the test in the control group, while increased enzyme levels were detected in plasma of the supplement groups. Therefore, antioxidant consumption seems to favour myeloperoxidase release. The connection of this observation with post-exercise recovery will require further investigation.