Both TLR7 and NF-κB hyperactivity are known to contribute to pathogenesis in Systemic Lupus Erythematosus (SLE), driving a pro-interferon response, autoreactive B cell expansion and autoantibody production. UBE2L3 is an SLE susceptibility gene which drives plasmablast/plasma cell expansion in SLE, but its role in TLR7 signalling has not been elucidated. We aimed to investigate the role of UBE2L3 in TLR7-mediated NF-κB activation, and the effect of UBE2L3 inhibition by Dimethyl Fumarate (DMF) on SLE B cell differentiation in vitro.
View Article and Find Full Text PDFObjectives: To evaluate (1) views and perceptions of patients/parents/carers and healthcare professionals on the medicines optimisation (MO) process following virtual outpatient clinic (VOC) during the COVID-19 pandemic and (2) the processes introduced at this time, identifying areas for improvements and suggest potential solutions.
Design: A mixed-methods service evaluation using qualitative and quantitative methods of the MO pathway in children aged 0-18 years following VOC across three specialist children's units.Semi-structured interviews were conducted over the telephone with the participants exploring their experiences and categorised into themes.
Solar ultraviolet radiation (UVR) is a major source of skin damage, resulting in inflammation, premature ageing, and cancer. While several UVR-induced changes, including extracellular matrix reorganisation and epidermal DNA damage, have been documented, the role of different fibroblast lineages and their communication with immune cells has not been explored. We show that acute and chronic UVR exposure led to selective loss of fibroblasts from the upper dermis in human and mouse skin.
View Article and Find Full Text PDFMouse models are critical in pre-clinical studies of cancer therapy, allowing dissection of mechanisms through chemical and genetic manipulations that are not feasible in the clinical setting. In studies of the tumour microenvironment (TME), multiplexed imaging methods can provide a rich source of information. However, the application of such technologies in mouse tissues is still in its infancy.
View Article and Find Full Text PDFThe interplay between extrinsic signaling and downstream gene networks controls the establishment of cell identity during development and its maintenance in adult life. Advances in next-generation sequencing and single-cell technologies have revealed additional layers of complexity in cell identity. Here, we review our current understanding of transcription factor (TF) networks as key determinants of cell identity.
View Article and Find Full Text PDFPurpose: The aim of the study was to assess whether magnetic resonance imaging (MRI) characteristics can distinguish benign from malignant part-solid pulmonary nodules and predict the aggressiveness of the latter. We also sought to compare MRI-derived parameters with morphologic and physiological values derived from conventional examinations such as computed tomography and positron emission tomography/computed tomography.
Materials And Methods: This was an institutional review board-approved pilot study of 28 participants (23 women, mean age 73.