Key Genes of Immunity Associated with Pterygium and Primary Sjögren's Syndrome.

Pterygium and primary Sjögren's Syndrome (pSS) share many similarities in clinical symptoms and ocular pathophysiological changes, but their etiology is unclear. To identify the potential genes and pathways related to immunity, two published datasets, GSE2513 containing pterygium information and GSE176510 containing pSS information, were selected from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) of pterygium or pSS patients compared with healthy control conjunctiva, and the common DEGs between them were analyzed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted for common DEGs. The protein-protein interaction (PPI) network was constructed using the STRING database to find the hub genes, which were verified in clinical samples. There were 14 co-upregulated DEGs. The GO and KEGG analyses showed that these common DEGs were enriched in pathways correlated with virus infection, antigen processing and presentation, nuclear factor-kappa B (NF-κB) and Th17 cell differentiation. The hub genes (IL1R1, ICAM1, IRAK1, S100A9, and S100A8) were selected by PPI construction. In the era of the COVID-19 epidemic, the relationship between virus infection, vaccination, and the incidence of pSS and pterygium growth deserves more attention.

Small-Molecule Induction Promotes Corneal Endothelial Cell Differentiation From Human iPS Cells.

Purpose: Corneal endothelial cells (CECs) serve as a barrier and foothold for the corneal stroma to maintain the function and transparency of the cornea. Loss of CECs during aging or disease states leads to blindness, and cell replacement therapy using either donated or artificially differentiated CECs remains the only curative approach. Methods: Human induced pluripotent stem cells (hiPSCs) that were cultured in chemically defined medium were induced with dual-SMAD inhibition to differentiate into neural crest cells (NCCs). A small-molecule library was screened to differentiate the NCCs into corneal endothelial-like cells. The characteristics of these cells were identified with real-time PCR and immunofluorescence. Western blotting was applied to detect the signaling pathways and key factors regulated by the small molecules. Results: We developed an effective protocol to differentiate hiPSCs into CECs with defined small molecules. The hiPSC-CECs were characterized by ZO-1, AQP1, Vimentin and Na+/K+-ATPase. Based on our small-molecule screen, we identified a small-molecule combination, A769662 and AT13148, that enabled the most efficient production of CECs. The combination of A769662 and AT13148 upregulated the PKA/AKT signaling pathway, FOXO1 and PITX2 to promote the conversion of NCCs to CECs. Conclusion: We established an efficient small molecule-based method to differentiate hiPSCs into corneal endothelial-like cells, which might facilitate drug discovery and the development of cell-based therapies for corneal diseases.

Risk factors associated with postoperative recurrence in atypical intracranial meningioma: analysis of 263 cases at a single neurosurgical centre.

OBJECTIVE: Atypical meningioma (AM) has a high rate of local recurrence after surgery, and the role of adjuvant radiotherapy in AM remains controversial. We analysed progression-free survival (PFS) and identified the factors associated with postoperative recurrence in AM patients. METHODS: Data were obtained from 263 AM patients who underwent surgery at our institution between October 2009 and September 2018. Analyses included factors such as the extent of surgical resection, MIB-1 labelling index, brain invasion and therapy modality. Univariate and multivariate analyses were used to assess recurrence-related prognostic factors. RESULT: The median follow-up duration was 41 months, and the median PFS was 28 months. Gross total resection (GTR) was achieved in 213 (81.0%) patients, and 86 (32.7%) patients received postoperative radiation therapy (RT). During follow-up, there were 61 (23.2%) tumour recurrences. In a Cox multivariate analysis, MIB-1 labelling index (hazard ratio = 2.637; p < 0.001), secondary tumour (hazard ratio = 3.541; p < 0.001), tumour size (hazard ratio = 1.818; p = 0.032) and extent of resection (hazard ratio = 2.861; p < 0.001) were independent significant predictors of tumour recurrence. RT was associated with reduced tumour recurrence in subtotal resection (STR) (p = 0.023) but not GTR (p = 0.923). An analysis of 6 meningioma patients who underwent more than 3 operations suggested that the recurrence time became shorter and the MIB-1 labelling index increased as the number of recurrences increased. CONCLUSIONS: MIB-1 labelling index, secondary tumour, tumour size and extent of resection were powerful predictors of recurrence in AM patients. Postoperative RT did not decrease the risk of recurrence in GTR patients.