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Leveraging pharmacovigilance data to predict population-scale toxicity profiles of checkpoint inhibitor immunotherapy.
Nat Comput Sci
December 2024
National Clinical Research Center for Ocular Diseases, Eye Hospital, Wenzhou Medical University, Wenzhou, China.
Immune checkpoint inhibitor (ICI) therapies have made considerable advances in cancer immunotherapy, but the complex and diverse spectrum of ICI-induced toxicities poses substantial challenges to treatment outcomes and computational analysis. Here we introduce DySPred, a dynamic graph convolutional network-based deep learning framework, to map and predict the toxicity profiles of ICIs at the population level by leveraging large-scale real-world pharmacovigilance data. DySPred accurately predicts toxicity risks across diverse demographic cohorts and cancer types, demonstrating resilience in small-sample scenarios and revealing toxicity trends over time.
View Article and Find Full Text PDFA Network Biology-Guided Investigation of the Long Noncoding RNAs' Role in Glaucoma.
Methods Mol Biol
December 2024
Department of Biotechnology, Raipur Institute of Technology, Raipur, Chhattisgarh, India.
Glaucoma is a group of eye diseases characterized by progressive harm to the optic nerve that often results in loss of vision and blindness. Recent studies suggest that deregulation in the expression of a particular type of RNAs named long noncoding RNAs (lncRNAs) can impact the development of glaucoma and, hence, are promising targets for drug discovery. LncRNAs are transcripts with a length longer than 200 nucleotides that are not translated into proteins.
View Article and Find Full Text PDFThe Effect of Prostaglandin F2 Analog Treatment on the Immunoexpression of Fibrosis-Associated Factors in Patients with Glaucoma Undergoing Deep Sclerotomy.
Int J Mol Sci
November 2024
Department of Ophtalmology, General Hospital Zadar, Ul. Bože Peričića 5, 23000 Zadar, Croatia.
Long-term use of topical prostaglandins might initiate chronic conjunctival inflammation, leading to poor outcomes of glaucoma surgery. The aim of this study was to evaluate the immunoexpression pattern of HSP70, CTGF, SNAIL, aSMA, cMYB, and HIFa in the conjunctiva, episclera, and deep sclera in patients with glaucoma undergoing deep sclerectomy in order to establish an association between staining intensities and prostaglandin F2 (PGF2) treatment. Double immunofluorescence (HSP70, CTGF, SNAIL, aSMA, cMYB, and HIFa) was performed on conjunctiva, episclera, and deep sclera samples, which were obtained from 23 patients treated with PGF2 and 8 patients without PGF2 treatment.
View Article and Find Full Text PDFCharacterization of the Ocular Phenotype in a Col4a3 Knockout Mouse Model of Alport Syndrome.
Invest Ophthalmol Vis Sci
December 2024
Department of Ophthalmology, Eugene and Marilyn Glick Eye Institute, Indiana University School of Medicine, Indianapolis, Indiana, United States.
Purpose: Alport syndrome (AS) is a genetic condition caused by a dysfunctional collagen (IV) α3α4α5 heterotrimer, leading to basement membrane instability and, ultimately, abnormalities in the kidney, inner ear, and eyes. This study aimed to characterize ocular pathology of AS by focusing on inflammatory and fibrotic markers.
Methods: Col4a3tm1Dec knockout (KO) mice eyes were evaluated for the localization of collagen (IV) α3 and collagen (IV) α4, then stained for transforming growth factor-β1 (TGF-β1), TGF-β2, connective tissue growth factor (CTGF), and β-catenin.
Glucose-Sensing ChREBP Protein in the Pathogenesis of Dia-betic Retinopathy.
bioRxiv
December 2024
Wake Forest University, School of Medicine, Department of Biochemistry.
Glucose-sensing ChREBP and MondoA are transcriptional factors involved in lipogenic, inflammatory, and insulin signaling pathways implicated in metabolic disorders; however, limited ocular studies have been conducted on these proteins. We aimed to investigate the potential role of ChREBP in pathogenesis of diabetic retinopathy (DR). We used diabetic human and mouse retinal cryosections analyzed by immunohistochemistry.
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