Victoria James

Heterotopic bones that are within the cardiac skeleton are termed ossa cordis . This is the first confirmed ossa cordis in nyala ( Tragelaphus angasii ). Three distinct bones (two dextrum and one sinistrum ) were discovered, a novel finding in any species. The present research used high‐resolution X‐ray computed microtomography, hematoxylin, and eosin, Picrosirius red, Masson's trichrome, Alcian blue, Von Kossa, immunohistochemistry, and a phylogenetic tree to investigate ossa cordis . The structural morphology and anatomical investigations showed the novel features of the three bones: one ossa cordis dextrum , one ossa cordis sinistrum , and one additional lower ossa cordis , on the right side of the trigone classified as ossa cordis dextrum inferus . The histological studies confirmed trabeculation, bone marrow, vasculature, collagen types I and III, in addition to acid mucins in the ossa cordis . The cell types within the three ossa cordis , and the associated cartilage, were also described. The discovery of cartilage adjacent to ossa cordis in this, and other species, may help elucidate the process, possibly endochondral ossification, via which ossa cordis may develop. The novel discovery of two ossa cordis dextrum and one ossa cordis sinistrum , and the first histological and computed microtomography study about ossa cordis in the nyala, increases the knowledge about ossa cordis in general and within this species. Although there is much to be elucidated regarding the nyala ossa cordis , especially in relation to prevalence, this study identifies the 23rd species with ossa cordis and describes the structural and histological details of these bones and associated cartilage.

Extracellular vesicles (EVs) are lipid-enclosed particles secreted from a wide variety of cells, with the ability to transfer biologically active content from parent to recipient cells. Lung epithelial-derived EVs (LE-EVs) play an important role in the progression of pulmonary disease, but there is limited evidence regarding the impact of cigarette smoke (CS) and electronic cigarette aerosol (ECA) on epithelial-derived EVs. The aim of this systematic review was to evaluate the current published literature on the impact of cigarette smoke and electronic cigarette aerosol on LE-EVs. Original research studies and clinical data were included, but research involving microparticles or non-epithelial-derived EVs was excluded. A total of 29 articles were identified from three databases (EMBASE, Web of Science and PubMed), of which nine demonstrated that CS exposure leads to molecular changes in epithelial-derived EVs, whereas 21 reported that CS-induced LE-EVs can deliver their cargo to neighbouring cells. The results highlighted that LE-EVs secreted in response to cigarette or e-cigarette exposure presented altered EV cargo, associated with increased cellular damage, inflammation and disease development. The current literature suggests that conventional and electronic cigarettes can influence the secretion of EVs from lung epithelial cells, with these EVs potentially playing a role in the development of lung inflammation. Nonetheless, there is limited research studying the impact of ECA on LE-EVS. Further research examining the impact of electronic cigarettes on lung epithelial-derived EVs, using robust human in vitro models coupled with clinical studies, is required.

Atopic allergy is rising globally and placing a significant strain on healthcare systems, yet the understanding of the underpinning mechanisms of allergic sensitization remains incomplete. Extracellular vesicles (EVs) have recently emerged as important mediators of immune modulation, due to their diverse cargo, and therefore may play a mechanistic role in allergic sensitization development. Thus, this study investigated whether EVs released by activated dendritic cells (DCs) contribute to allergic sensitization of the common egg allergen, ovalbumin (OVA). DCs were generated from human monocytes cultured with GM-CSF and IL-4, then stimulated with LPS and/or OVA. EVs were subsequently isolated using size-exclusion chromatography and added to freshly isolated naive T cells at defined time points. T cell responses were then analyzed using spectral flow cytometry. The results highlight that EVs derived from LPS or LPS + OVA-stimulated DCs enhanced IL-4 production and reduced IFN-γ production in naive T cells from egg-allergic donors, indicating a shift toward a Th2 profile. In healthy donors, LPS-induced DC EVs also suppressed IFN-γ expression. Notably, EVs alone were insufficient to activate T cells without CD3/CD28 co-stimulation, suggesting that EVs may function as a “third signal” shaping T cell polarization. These findings highlight a potential role for DC-derived EVs in initiating allergic sensitization.

Background: The early detection of cancer remains a critical challenge in clinical oncology, with significant implications for patient survival rates and treatment outcomes. Research focus has shifted to developing minimally invasive diagnostic approaches for cancer detection and prognosis, such as metabolomic analysis of biological fluids and tumour-derived components, including extracellular vesicles (EVs). EVs carry molecular cargo, including metabolites, that reflect the pathophysiological state of their cell of origin. Analysis and characterisation of these metabolites may offer novel insights into cancer biology and facilitate the identification of potential biomarkers. Aim of review: This review systematically examines existing literature on the metabolomic analysis of EVs in the context of cancer to obtain a deeper understanding of potential metabolite biomarkers associated with cancer. Key scientific concepts of review: A comprehensive search of PubMed, Scopus, and Web of Science was conducted using a defined strategy to identify studies analysing EV-derived metabolites in cancer. Twelve eligible studies were included, collectively reporting 1,602 identified metabolites across various cancer types, sample sources, EV isolation methods, and metabolomic techniques. Of these, 333 metabolites were reported to be differentially regulated in EVs derived from patients with cancer, or conditioned medium from cancerous cell lines and their respective healthy controls. The review highlights the potential of EV metabolomics to detect cancer biomarkers but also underscores methodological variability as a major limitation. Differences in isolation and analytical techniques likely contribute to inconsistent findings, emphasising the need for standardised protocols in future research.

Atopic allergy is rising globally and placing a significant strain on healthcare systems, yet the understanding of the underpinning mechanisms of allergic sensitisation remains incomplete. Extracellular vesicles (EVs) have recently emerged as important mediators of immune modulation due to their diverse cargo and therefore may play a mechanistic role in allergic sensitisation development. Thus, this study investigated whether EVs released by activated dendritic cells (DCs) contribute to allergic sensitisation of the common egg allergen, ovalbumin (OVA). DCs were generated from human monocytes cultured with GM-CSF and IL-4, then stimulated with LPS and/or OVA. EVs were subsequently isolated using size-exclusion chromatography and added to freshly isolated naïve T cells at defined time points. T-cell responses were then analysed using spectral flow cytometry. The results highlight EVs derived from LPS or LPS+OVA-stimulated DCs enhanced IL-4 production and reduced IFN-γ production in naïve T cells from egg-allergic donors, indicating a shift toward a Th2 profile. In healthy donors, LPS-induced DC EVs also suppressed IFN-γ expression. Notably, EVs alone were insufficient to activate T cells without CD3/CD28 co-stimulation, suggesting that EVs may function as a “third signal” shaping T-cell polarisation. These findings highlight a potential role for DC-derived EVs in initiating allergic sensitisation.

This study identifies a distinct free radical signature in a D. melanogaster model of Parkinson’s Disease, successfully differentiating Pink1-deficient flies from wild-type controls. This insight was achieved using a robust quantum sensing methodology for the selective detection of free radicals in biological systems. Our approach utilizes optically detected magnetic resonance (ODMR) and magnetic modulation (MM) protocols with nanodiamond nitrogen-vacancy (NV) centres. Selective identification is achieved using the spin probe TEMPOL, a cell-permeable superoxide dismutase 2 (SOD2) mimic that initially quenches the photoluminescence signal. Upon scavenging free radicals like hydroxyl and superoxide, TEMPOL is converted to a diamagnetic adduct, restoring the contrast and thus enabling quantitative detection. The approach was first validated in a chemical system with radical generation confirmed by electron paramagnetic resonance (EPR) spectroscopy. It was then demonstrated across biological scales, from isolated mitochondria and whole glioblastoma cells to the Drosophila model. In these studies, high-resolution respirometry revealed distinct free radical signatures, and findings were compared with NV T1 relaxometry. This work provides new biophysical insight into mitochondrial dysfunction, demonstrating a distinct free radical signature in a neurodegeneration model and connecting it to specific metabolic states.

Fully functional neural competence and integrity requires a complex array of communication means among neurons, with extracellular vesicles (EVs) emerging as a relevant mechanism for cell-cell interaction in the CNS. Despite the growing number of studies demonstrating the presence of miRNAs in axon and EVs, the molecular mechanisms of those microRNAs present in EVs and their functional role in nervous system development has not been fully explored. In this study, we investigated whether neuronal EVs can have a role in neuron-to-neuron communication during the development of neuron connectivity in mouse primary cortical neuron cultures. Our results demonstrate how miR-99a can regulate axonal growth via its EV-mediated delivery and through the targeting of HS3ST2, a heparan sulphate glucosamine 3-O-sulphotransferase, which is predominantly expressed in the brain and generates rare 3-O-sulphated domains in heparan sulphate proteoglycans, with growing importance in development and neurodegenerative mechanisms. Importantly, we show how in compartmentalised microfluidic cultures, where axons are isolated from neuronal somas, the growth-promoting effects of neuron-derived EVs are local to the axon. These findings establish that neuronal EVs can deliver miRNAs to discrete subcellular domains to acutely modulate local gene expression, thereby driving axonal growth and shaping neurodevelopment.

Objectives: Parental exposure to tobacco smoke is a significant public health concern, with over 1.1 billion smokers worldwide. The aim of this systematic review was to evaluate the impact of maternal, paternal, and dual-parental cigarette smoke exposure on offspring reproductive health. Methods: Original human clinical and animal research studies were included; titles and abstracts were manually scanned for relevance to the effect of parental smoking on offspring reproductive outcomes (Date of search:18/03/2025). Results: This systematic review incorporates 30 studies identified from three databases (PubMed, Web of Science, and Scopus). The results indicate that male offspring exhibit reduced spermatogenic capacity, characterized by decreased testicular size, lower sperm count, and impaired hormonal biosynthesis, with reductions of 30–40% in sperm production. Dual-parental smoking exacerbates these effects, with sperm counts averaging 85 million per ml in human male offspring from dual-smoking households, compared to 111 million per ml in single-smoking households. Animal studies provide mechanistic insights, revealing reduced testis weight in nicotine-exposed male rats and increased oxidative stress in offspring. Conclusions: This review highlights the dose-dependent and sex-specific effects of smoking on the fertility of offspring and underscores the need for standardized protocols to enhance the consistency and comparability of future research in both human and animal studies.

The aim of this systematic review was to evaluate the impact of maternal, paternal and dual-parental cigarette smoke exposure on offspring reproductive health. Original human clinical and animal research studies were included; titles and abstracts were manually scanned for relevance to the effect of parental smoking on offspring’s reproductive outcomes (Date of search:18/03/2025). This systematic review incorporates 31 studies identified from three databases (PubMed, Web of Science, and Scopus). The results indicate that male offspring exhibit reduced spermatogenic capacity, characterised by decreased testicular size, lower sperm count, and impaired hormonal biosynthesis, with reductions of 30–40% in sperm production. Dual-parental smoking exacerbates these effects, with sperm counts averaging 85 million per ml in human male offspring from dual-smoking households compared to 111 million per ml in single-smoking households. Animal studies provide mechanistic insights, revealing reduced testis weight in nicotine-exposed male rats and increased oxidative stress in offspring. This review highlights the dose-dependent and sex-specific effects of smoking on fertility of the offspring and underscores the need for standardised protocols to enhance the consistency and comparability of future research in both human and animal studies.

The aim of this systematic review was to evaluate the current evidence for the involvement of epithelial-derived extracellular vesicles (EVs) in Immunoglobulin E (IgE)-mediated allergic sensitisation. Original clinical and research studies specifically examining the effect of epithelial-derived EVs in IgE-mediated allergic sensitisation were included. Non-IgE mediated allergies, abstracts and review articles were excluded. A total of 18 publications were identified from three databases (EMBASE, Web of Science and PubMed) that indicate epithelial-derived EVs have the potential to promote tolerance or allergic sensitisation. For example, epithelial-derived EVs have the potential to promote IgE-mediated allergic sensitisation by delivering mRNAs that promote T helper 2 (Th2) polarisation and cytokine secretion, or promote tolerance through the induction of T regulatory (Treg) cells. The results also indicate that the potential role of epithelial-derived EVs in IgE-mediated allergic sensitisation may be dependent on the barrier, with all publications related to intestinal epithelium driving tolerance, but publications on nasal and bronchial/alveolar epithelia gaving mixed effects. No publications were found on cutaneous epithelia. Taken together, the literature suggests that epithelial-derived EVs play a key role in influencing IgE-mediated allergic sensitisation. Further research examining all epithelial barriers, using both robust human in vitro models that give more biologically relevant information, as well as clinical studies, are required to further characterise the role of epithelial-derived EVs in IgE-mediated allergic sensitisation.