Glioblastoma multiforme (GBM) is the most aggressive form of adult primary malignant brain tumour with poor prognosis. Extracellular vesicles (EVs) are a key-mediator through which GBM cells promote a pro-oncogenic microenvironment. Peptidylarginine deiminases (PADs), which catalyze the post-translational protein deimination of target proteins, are implicated in cancer, including via EV modulation. Pan-PAD inhibitor Cl-amidine affected EV release from GBM cells, and EV related microRNA cargo, with reduced pro-oncogenic microRNA21 and increased anti-oncogenic microRNA126, also in combinatory treatment with the chemotherapeutic agent temozolomide (TMZ). The GBM cell lines under study, LN18 and LN229, differed in PAD2, PAD3 and PAD4 isozyme expression. Various cytoskeletal, nuclear and mitochondrial proteins were identified to be deiminated in GBM, including prohibitin (PHB), a key protein in mitochondrial integrity and also involved in chemo-resistance. Post-translational deimination of PHB, and PHB protein levels, were reduced after 1 h treatment with pan-PAD inhibitor Cl-amidine in GBM cells. Histone H3 deimination was also reduced following Cl-amidine treatment. Multifaceted roles for PADs on EV-mediated pathways, as well as deimination of mitochondrial, nuclear and invadopodia related proteins, highlight PADs as novel targets for modulating GBM tumour communication.

Glioblastoma multiforme (GBM) is the most common and aggressive form of primary malignant brain tumor in adults, with poor prognosis. Extracellular vesicles (EVs) are key-mediators for cellular communication through transfer of proteins and genetic material. Cancers, such as GBM, use EV release for drug-efflux, pro-oncogenic signaling, invasion and immunosuppression; thus the modulation of EV release and cargo is of considerable clinical relevance. As EV-inhibitors have been shown to increase sensitivity of cancer cells to chemotherapy, and we recently showed that cannabidiol (CBD) is such an EV-modulator, we investigated whether CBD affects EV profile in GBM cells in the presence and absence of temozolomide (TMZ). Compared to controls, CBD-treated cells released EVs containing lower levels of pro-oncogenic miR21 and increased levels of anti-oncogenic miR126; these effects were greater than with TMZ alone. In addition, prohibitin (PHB), a multifunctional protein with mitochondrial protective properties and chemoresistant functions, was reduced in GBM cells following 1 h CBD treatment. This data suggests that CBD may, via modulation of EVs and PHB, act as an adjunct to enhance treatment efficacy in GBM, supporting evidence for efficacy of cannabinoids in GBM.

The detection of early molecular mechanisms and potential biomarkers in Parkinson’s disease (PD) remains a challenge. Recent research has pointed to novel roles for post-translational citrullination/deimination caused by peptidylarginine deiminases (PADs), a family of calcium-activated enzymes, in the early stages of the disease. The current study assessed brain-region-specific citrullinated protein targets and their associated protein–protein interaction networks alongside PAD isozymes in the 6-hydroxydopamine (6-OHDA) induced rat model of pre-motor PD. Six brain regions (cortex, hippocampus, striatum, midbrain, cerebellum and olfactory bulb) were compared between controls/shams and the pre-motor PD model. For all brain regions, there was a significant difference in citrullinated protein IDs between the PD model and the controls. Citrullinated protein hits were most abundant in cortex and hippocampus, followed by cerebellum, midbrain, olfactory bulb and striatum. Citrullinome-associated pathway enrichment analysis showed correspondingly considerable differences between the six brain regions; some were overlapping for controls and PD, some were identified for the PD model only, and some were identified in control brains only. The KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways identified in PD brains only were associated with neurological, metabolic, immune and hormonal functions and included the following: “Axon guidance”; “Spinocerebellar ataxia”; “Hippo signalling pathway”; “NOD-like receptor signalling pathway”; “Phosphatidylinositol signalling system”; “Rap1 signalling pathway”; “Platelet activation”; “Yersinia infection”; “Fc gamma R-mediated phagocytosis”; “Human cytomegalovirus infection”; “Inositol phosphate metabolism”; “Thyroid hormone signalling pathway”; “Progesterone-mediated oocyte maturation”; “Oocyte meiosis”; and “Choline metabolism in cancer”. Some brain-region-specific differences were furthermore observed for the five PAD isozymes (PADs 1, 2, 3, 4 and 6), with most changes in PAD 2, 3 and 4 when comparing control and PD brain regions. Our findings indicate that PAD-mediated protein citrullination plays roles in metabolic, immune, cell signalling and neurodegenerative disease-related pathways across brain regions in early pre-motor stages of PD, highlighting PADs as targets for future therapeutic avenues.

Degree awarding gaps highlight the inequitable outcomes of higher education (HE) for racially minoritized students in the UK. This ongoing issue has been described as a “wicked problem”, directly related to structural racism, or policies and practices that continually disadvantage racialized students. Movements to decolonize the curriculum bring hope and the tools to rebuild more socially-just institutions and societies. However, it is sometimes questioned whether the field of science, with its guise of objectivity, needs decolonizing, or what that process involves. We argue that student partnerships are central to building decolonized science curricula that are critical, anti-racist and will evoke social change. In this study, conducted with life sciences students in a UK HE institution, we share critical reflections captured through a mixed methods approach to address how we create an education that is through and for social justice. Education through social justice aims to create equitable learning environments by addressing how structures and curricula invite, engage and support racially minoritized students to be partners in the learning journey. Whereas education for social justice is about co-creating curricula, teaching practices and principles that lead to change makers and fostering more socially-just societies. Our research indicates that an education that is both through and for social justice requires co-creation where traditional power hierarchies are dismantled, and mattering is emphasized. Partnerships and curricula must be centered in anti-racist practices, with a structured and intentional approach to developing critical thinking skills for continual reflection, self-development and actions to promote inclusion and equity in life sciences and society.