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Intranasal administration of antiseizure drugs using new formulation trends: one step closer to reach clinical trials.
Expert Opin Drug Deliv
January 2025
CICS-UBI - Health Sciences Research Centre, University of Beira Interior, Covilhã, Portugal.
Introduction: Although there are numerous options for epilepsy treatment, its effective control continues unsatisfactory. Thus, search for alternative therapeutic options to improve the efficacy/safety binomial of drugs becomes very attractive to investigate. In this context, intranasal administration of antiseizure drugs formulated on state-of-the-art nanosystems can be a promising strategy.
View Article and Find Full Text PDFPancreatic stellate cell: Update on molecular investigations and clinical translation in pancreatic cancer.
Int J Cancer
January 2025
Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Early Drug Development Center, Peking University Cancer Hospital and Institute, Beijing, China.
Pancreatic cancer is a particularly aggressive tumor, distinguished by the presence of a prominent collagenous stroma and desmoplasia that envelops the tumor cells. Pancreatic stellate cell (PSC) contributes to the formation of a dense fibrotic stroma and has been demonstrated to facilitate tumor progression. As the significance of PSCs is increasingly revealed, more explorations are focused on the complex molecular mechanisms and tumor-stromal crosstalk in order to guide potential therapeutic approaches through deactivating or reprogramming PSCs.
View Article and Find Full Text PDFSotatercept in pulmonary hypertension and beyond.
Eur J Clin Invest
January 2025
Department of Surgical, Medical and Molecular Pathology and Critical Area, Laboratory of Biochemistry, University of Pisa, Pisa, Italy.
Sotatercept binds free activins by mimicking the extracellular domain of the activin receptor type IIA (ACTRIIA). Additional ligands are BMP/TGF-beta, GDF8, GDF11 and BMP10. The binding with activins leads to the inhibition of the signalling pathway and the deactivation of the bone morphogenic protein (BMP) receptor type 2.
View Article and Find Full Text PDFENHANCED RESTORATION OF VISUAL CODE AFTER TARGETING ON BIPOLAR CELLS COMPARED TO RETINAL GANGLION CELLS WITH OPTOGENETIC THERAPY.
Mol Ther
January 2025
Faculty of Biology, Medicine & Health, University of Manchester, Manchester, M13 9PT, UK. Electronic address:
Optogenetic therapy is a promising vision restoration method where light sensitive opsins are introduced to the surviving inner retina following photoreceptor degeneration. The cell type targeted for opsin expression will likely influence the quality of restored vision. However, a like-for-like pre-clinical comparison of visual responses evoked following equivalent opsin expression in the two major targets, ON bipolar (ON BCs) or retinal ganglion cells (RGCs), is absent.
View Article and Find Full Text PDFCharacterisation of the ocular inflammatory response to AAV reveals divergence by sex and age.
Mol Ther
January 2025
Academic Unit of Ophthalmology, Translational Health Sciences, University of Bristol, Bristol, BS8 1TD, UK; NIHR Biomedical Research Centre of Ophthalmology, Moorfields Eye Hospital, London, EC1V 2PD, UK. Electronic address:
Progress for ocular AAV gene therapy has been hindered by AAV-induced inflammation, limiting dose escalation and long-term efficacy. Broadly, the extent of inflammatory responses alters with age and sex, yet these factors are poorly represented in pre-clinical development of ocular AAV gene therapies. Here, we combined clinical imaging, flow cytometry and bulk-sequencing of sorted microglia to interrogate the longitudinal inflammatory response following intravitreal delivery of AAV2 in young (3-month), middle aged (9-month) and old (18-month) Cx3cr1-creER:R26tdTomato+/- mice of both sexes.
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