Andrew Devitt

Diabetic foot ulcers (DFUs) are chronic, non‐healing wounds that represent one of the most debilitating complications of diabetes, frequently progressing to severe infection, lower‐limb amputation, and increased mortality. Current clinical interventions largely focus on symptom management and wound protection but remain insufficient in achieving complete re‐epithelialization or restoring functional skin integrity. Stem cell‐based therapies have demonstrated substantial regenerative promise; however, their broader application is constrained by risks of immune rejection, challenges in sustaining long‐term cell viability, and difficulties in preserving stable cellular phenotypes during expansion. In response to these limitations, cell‐free approaches—particularly extracellular vesicle (EV)‐based therapies—have gained momentum as a next‐generation modality that captures the therapeutic benefits of stem cells while avoiding the drawbacks of cell transplantation. When integrated with advanced biomaterial scaffolds such as nanofibers or hydrogels, EVs can be delivered in a protected, controlled, and bioactive manner, yielding multifunctional dressings or patches that actively modulate the wound microenvironment to promote healing. This review synthesizes current evidence from in vitro, in vivo, and clinical studies on stem cell‐based and EV‐based therapies, with a focus on their synergy with biomaterial scaffolds for advancing the treatment of diabetic wounds.

Mutations in DJ-1 cause autosomal recessive Parkinson’s disease (PD). Several functions have been attributed to DJ-1, including a key role in the protection from oxidative stress. However, how this protein contributes to PD pathogenesis is still unclear. Recently, DJ-1 has been identified at higher concentrations in extracellular vesicles (EV) from biological fluids of PD patients, providing a link between EV and a protein associated with PD. In this study, EV were purified from the medium of control and rotenone-treated wild-type and DJ-1 KO differentiated SH-SY5Y cells. EV quantity was assessed using flow cytometry, and their proteomic cargo was analysed via mass spectrometry. We identified an altered EV response to rotenone in DJ-1 KO cells compared to wild-type. Mass spectrometry analysis identified 116 proteins with significantly altered abundance between the two genotypes, indicating a role for DJ-1 in modulating EV cargo under oxidative stress conditions. Label-free identification of oxidative modifications indicated that DJ-1 clearly influences the oxidative profile of EV proteins. Additionally, we showed that DJ-1 KO alters the ability of the secretome to stimulate macrophage migration, suggesting functional consequences of DJ-1 deficiency in secretome-mediated responses to oxidative stress. The altered EV response to rotenone was confirmed in iPSC-derived neurons lacking DJ-1 compared to isogenic controls. Our results reveal a distinct role for DJ-1 in regulating intercellular communication under oxidative stress, highlighting a novel EV-mediated function of DJ-1 that may contribute to Parkinson’s disease pathogenesis.

Objective: Sun Protection Factor (SPF) of sunscreen products is well recognised by consumers. This study explored how SPF could be applied to ultraviolet radiation (UV) protection from contact lenses (CL-SPF). Methods and analysis: UV transmission through 15 commercially available contact lenses and three spectacle lens materials was measured with a deuterium light source and spectrophotometer. CL-SPF values were calculated using the standard in vitro method used to test and label skin products. Ray tracing was applied to two sunglass designs to assess the effect of solar angle and head orientation on light reaching the ocular surface. Cellular damage profile of human corneal and conjunctival cells across the UV range was assessed in vitro to inform an SPF equivalent for CLs. Results: CLs tested fell into three categories: CL-SPF with no UV blocker=1.0–2.0 (equivalent to using no sunscreen); CL-SPF with Class 2 UV blocker=12.3–24.8 (equivalent to SPF15); and CL-SPF with Class 1 UV blocker=59.6–66.2 (equivalent to SPF 50+). Despite the UV-blocking characteristics of sunglasses, ocular surface protection can be substantially reduced at certain solar angle and head orientation combinations; on average, 76%–89% of light was prevented from reaching the ocular surface depending on the intensity of the tint (80%–20% transmission). The data also suggest that cell damage and death of ocular surface cells has a similar profile to that of the skin, but conjunctival cells are more susceptible to UV damage. Conclusion: CL-SPF is a viable metric to communicate the protection from the absorption/transmission of UV radiation that CLs offer wearers. However, a contact lens will only protect the area of the ocular surface it covers, which is limited to mainly the cornea and internal eye tissues with soft CLs.

The c-Jun N-terminal kinases (JNKs) are a family of proteins that, once activated by stress stimuli, can alter neuronal functions and survival. The JNK cascade plays a crucial role in the post-synaptic neuronal compartment by altering its structural organization and leading, at worst, to an overall impairment of neuronal communication. Increasing evidence suggests that synaptic impairment is the first neurodegenerative event in Alzheimer’s disease (AD). To better elucidate this mechanism, we longitudinally studied 5xFAD mice at three selected time points representative of human AD symptom progression. We tested the mice cognitive performance by using the radial arm water maze (RAWM) in parallel with biochemical evaluations of post-synaptic enriched protein fraction and total cortical parenchyma. We found that 5xFAD mice presented a strong JNK activation at 3.5 months of age in the post-synaptic enriched protein fraction. This JNK activation correlates with a structural alteration of the post-synaptic density area and with memory impairment at this early stage of the disease that progressively declines to cause cell death. These findings pave the way for future studies on JNK as a key player in early neurodegeneration and as an important therapeutic target for the development of new compounds able to tackle synaptic impairment in the early phase of AD pathology.

Liposomes are a strong supporting tool in vaccine technology, as they are a versatile system that not only act as antigen delivery systems but also adjuvants that can be highly effective at stimulating both innate and adaptive immune responses. Their ability to induce cell-mediated immunity makes their use in vaccines a useful tool in the development of novel, more effective vaccines against intracellular infections (e.g. HIV, malaria and tuberculosis). Currently, screening of novel liposome formulations uses murine in vivo models which generate data that often correlates poorly with human data. In addition, these models are both high cost and low throughput, making them prohibitive for large scale screening of formulation libraries. This study uses the cationic liposome formulation DDA:TDB (known as cationic adjuvant formulation 01 (CAF01)), as a lead formulation, along with other liposome formulations of known in vivo efficacy to develop an in vitro screening tool for liposome formulation development. THP-1-derived macrophages were the model antigen presenting cell used to assess the ability of the liposome formulations to attract, associate with and activate antigen presenting cells in vitro, crucial steps necessary for an effective immune response to antigen. By using a combination of in vitro functions, the study highlights the potential use of an in vitro screening tool, to predict the in vivo efficacy of novel liposome formulations. CAF01 was predicted as the most effective liposome formulation when assessing all in vitro functions and a measure of in vitro activation was able to predict 80% of the liposome correctly for their ability to induce an in vivo IFN-ү response.

Fascioliasis is a neglected zoonotic disease that infects humans and ruminant species worldwide. In the absence of vaccines, control of fascioliasis is primarily via anthelminthic treatment with triclabendazole (TCBZ). Parasitic flatworms, including Fasciola hepatica, are active secretors of extracellular vesicles (EVs), but research has not been undertaken investigating EV anthelmintic sequestration. Adult F. hepatica were cultured in lethal and sub-lethal doses of TCBZ and its active metabolites, in order to collect EVs and evaluate their morphological characteristics, production and anthelmintic metabolite content. Transmission electron microscopy demonstrated that F. hepatica exposed to TCBZ and its metabolites produced EVs of similar morphology, compared to non-TCBZ exposed controls, even though TCBZ dose and/or TCBZ metabolite led to measurable structural changes in the treated F. hepatica tegument. qNano particle analysis revealed that F. hepatica exposed to TCBZ and its metabolites produced at least five times greater EV concentrations than non-TCBZ controls. A combined mass spectrometry and qNano particle analysis confirmed the presence of TCBZ and the TCBZ–sulphoxide metabolite in anthelmintic exposed EVs, but limited TCBZ sulphone was detectable. This data suggests that EVs released from adult F. hepatica have a biological role in the sequestration of TCBZ and additional toxic xenobiotic metabolites.