Gavin Stewart Dawe

Bibliometric mapping of 1029 records reveals a shift toward biomaterial-enabled delivery in phytochemical colorectal cancer research. Five carrier classes are reviewed against common performance metrics to frame emerging translational opportunities.

The drug lifecycle imposes a growing environmental burden, evident in pharmaceutical pollution, escalating consumption of finite resources (energy, water, and raw materials) and a substantial carbon footprint. Meeting these challenges requires more than technological fixes; it demands a workforce trained to recognise, evaluate, and reduce the environmental impacts of medicines while safeguarding patient outcomes. However, recent scoping and systematic reviews consistently note a gap in health professions education: few curricula provide structured, evidence-informed approaches for integrating environmental sustainability and planetary health into pharmacology and related training. The discipline of pharmacology is uniquely suited for integrating green and sustainability principles because it sits at the decision-point where molecular mechanisms become real-world medicine use and environmental impact. This paper presents a white paper proposing a Green and Sustainable Pharmacology Curriculum and an actionable strategy for embedding sustainability principles within core pharmacology teaching. Targeted at biomedical scientists, pharmacists, and prescribers, the curriculum is designed to strengthen decision-making across the medicine lifecycle, including greener selection, rational use, and responsible disposal. We outline a curriculum development framework that applies Understanding by Design and outcome-based evaluation through four streamlined steps: (1) needs analysis, (2) curation of priority content topics, (3) constructive alignment of learning activities with intended competencies, and (4) assessment aligned to learning outcomes. By offering an adaptable blueprint for local implementation, this white paper aims to accelerate adoption by pharmacology departments worldwide. Ultimately, the curriculum seeks to shift learners from concerned global citizens to empowered pharmacologists with personal agency implement workplace changes that mitigate environmental harms and to serve as thought leaders advancing sustainable healthcare.

Neurodegenerative diseases (Alzheimer’s disease, Parkinson's disease, Huntington’s disease, etc.) are caused by the progressive loss of neurons, which affects many people worldwide. Therefore, many efforts have focused on neurodegenerative disease mechanisms and therapeutic strategies. Moreover, amyloid precursor proteins and their cleaving products, including APP-C31, may play important roles in neurodegeneration. This review provides a comprehensive introduction to the structure, neurotoxicity, regulatory mechanism, and relevance of APP-C31 to clinical diseases and its therapeutic potential as a drug target. This work will bridge the gap in our understanding of the function of APP-C31, which provides an experimental basis for neurodegenerative disease therapeutics. Meanwhile, a hypothesis is postulated that the APP-C31 functions not merely as a byproduct of caspase cleavage, but as the critical "central executioner" bridging upstream triggers and downstream neurodegeneration. Diverse upstream stressors, initiate the cascade to generate APP-C31. Once generated, C31 acts as a multi-functional signalling hub driving four distinct pathogenic pathways. Consequently, APP-C31 is hypothesized to be the essential mediator that amplifies these molecular damages into macroscopic failures.

Dysregulation of astroglia-mediated neuroinflammation is known to be involved in neurodegenerative diseases. Amongst multiple inflammatory pathways, pyroptosis is characterized by inflammatory cell death following inflammasome activation. Recently, the omega-3 poly-unsaturated fatty acid, DHA, has been identified as a pyroptosis inducer, although the underlying mechanisms remain unclear. In this study, we investigated the role of the alternatively spliced T-isoform of Fyn kinase (FynT) in DHA-induced astroglial pyroptosis. Immortalized normal human astrocytes (iNHA) expressing wild-type FynT (FynT-WT), kinase-dead mutant FynT (FynT-KD), or empty vector (EV) controls were treated with DHA and assessed for pyroptotic activation. We found that DHA-treated FynT-WT cells exhibited significantly reduced cytosolic lactate dehydrogenase release, pyroptotic morphology and markers (cleaved caspase-1 and its substrates, cleaved caspase-3 and gasdermin-D N fragments) compared to either EV or FynT-KD cells. No significant differences in pyroptotic activation were observed between EV and FynT-KD cells. In addition, no differences in immunoreactivities of pro- or anti-apoptotic markers (Bax or Bcl-2) were observed across the DHA-treated cells. In summary, our study postulates a negative regulatory role of FynT kinase in DHA-induced pyroptosis in astrocytes, with implications for further understanding neuroinflammatory mechanisms in neurodegenerative diseases and identification of potential therapeutic targets.

Dysregulation of astroglia-mediated neuroinflammation is known to be involved in neurodegen-erative diseases. Amongst multiple inflammatory pathways, pyroptosis is characterized by in-flammatory cell death following inflammasome activation. Recently, the omega-3 poly-unsaturated fatty acid, DHA, has been identified as a pyroptosis inducer, although the un-derlying mechanisms remain unclear. In this study, we investigated the role of the alternative-ly-spliced T-isoform of Fyn kinase (FynT) in DHA-induced astroglial pyroptosis. Immortalized normal human astrocytes (iNHA) expressing wild-type FynT (FynT-WT), kinase-dead mutant FynT (FynT-KD), or empty vector (EV) controls were treated with DHA and assessed for pyrop-totic activation. We found that DHA-treated FynT-WT cells exhibited significantly reduced cyto-solic lactate dehydrogenase release, pyroptotic morphology and markers (cleaved caspase-1 and its substrates, cleaved caspase-3 and gasdermin-D N fragments) compared to either EV or FynT-KD cells. No significant differences in pyroptotic activation were observed between EV and FynT-KD cells. In addition, no differences in immunoreactivities of pro- or anti-apoptotic markers (Bax or Bcl-2) were observed across the DHA-treated cells. In summary, our study postulates a negative regulatory role of FynT kinase on DHA-induced pyroptosis in astrocytes, with implica-tions for further understanding neuroinflammatory mechanisms in neurodegenerative diseases and identification of potential therapeutic targets.

Vascular cognitive impairment (VCI) is the second leading cause of dementia with limited treatment options, characterised by cerebral hypoperfusion-induced white matter rarefaction (WMR). Subcortical VCI is the most common form of VCI, but the underlying reasons for region susceptibility remain elusive. Recent studies employing the bilateral cortical artery stenosis (BCAS) method demonstrate that various inflammasomes regulate white matter injury and blood-brain barrier dysfunction but whether caspase-1 inhibition will be beneficial remains unclear. To address this, we performed BCAS on C57/BL6 mice to study the effects of Ac-YVAD-cmk, a caspase-1 inhibitor, on the subcortical and cortical regions. Cerebral blood flow (CBF), WMR, neuroinflammation and the expression of tight junction-related proteins associated with blood-brain barrier integrity were assessed 15 days post BCAS. We observed that Ac-YVAD-cmk restored CBF, attenuated BCAS-induced WMR and restored subcortical myelin expression. Within the subcortical region, BCAS activated the NLRP3/caspase-1/interleukin-1beta axis only within the subcortical region, which was attenuated by Ac-YVAD-cmk. Although we observed that BCAS induced significant increases in VCAM-1 expression in both brain regions that were attenuated with Ac-YVAD-cmk, only ZO-1 and occludin were observed to be significantly altered in the subcortical region. Here we show that caspase-1 may contribute to subcortical regional susceptibility in a mouse model of VCI. In addition, our results support further investigations into the potential of Ac-YVAD-cmk as a novel treatment strategy against subcortical VCI and other conditions exhibiting cerebral hypoperfusion-induced WMR.

BioStudies – one package for all the data supporting a study

The neuropeptide relaxin-3 is composed of an A chain and a B chain held together by disulfide bonds, and it modulates functions such as anxiety and food intake by binding to and activating its cognate receptor RXFP3, mainly through the B chain. Biased ligands of RXFP3 would help to determine the molecular mechanisms underlying the activation of G proteins and β-arrestins downstream of RXFP3 that lead to such diverse functions. We showed that the i, i+4 stapled relaxin-3 B chains, 14s18 and d(1-7)14s18, were Gα _i/o -biased agonists of RXFP3. These peptides did not induce recruitment of β-arrestin1/2 to RXFP3 by GPCR kinases (GRKs), in contrast to relaxin-3, which enabled the GRK2/3-mediated recruitment of β-arrestin1/2 to RXFP3. Relaxin-3 and the previously reported peptide 4 (an i, i+4 stapled relaxin-3 B chain) did not exhibit biased signaling. The staple linker of peptide 4 and parts of both the A chain and B chain of relaxin-3 interacted with extracellular loop 3 (ECL3) of RXFP3, moving it away from the binding pocket, suggesting that unbiased ligands promote a more open conformation of RXFP3. These findings highlight roles for the A chain and the N-terminal residues of the B chain of relaxin-3 in inducing conformational changes in RXFP3, which will help in designing selective biased ligands with improved therapeutic efficacy.