Identification of Key Genes and Pathways in Persistent Hyperplastic Primary Vitreous of the Eye Using Bioinformatic Analysis.

Background: The failure of the embryonic hyaloid vascular system to regress naturally causes persistent hyperplastic primary vitreous (PHPV), a congenital eye disease. PHPVs molecular pathway, candidate genes, and drug targets are unknown. The current paper describes a comprehensive analysis using bioinformatics to identify the key genes and molecular pathways associated with PHPV, and to evaluate potential therapeutic agents for disease management. Methods: The genes associated with PHPV were identified using the pubmed2ensembl text mining platform. GeneCodis was employed to evaluate the Gene Ontology (GO) biological process terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Search Tool for the Retrieval of Interacting Genes (STRING) constructed a protein-protein interaction (PPI) network from the text mining genes (TMGs) in Cytoscape. The significant modules were clustered using Molecular Complex Detection (MCODE), and the GO and KEGG analysis for the hub genes were analyzed with the Database of Annotation, Visualization and Integrated Discovery (DAVID) tool. ClueGO, CluePedia, and ShinyGo were used to illustrate the functions and pathways of the clustered hub genes in a significant module. The Drug-Gene Interaction database (DGIdb) was used to evaluate drug-gene interactions of the hub genes to identify potential PHPV drug candidates. Results: A total of 50 genes associated with PHPV were identified. Overall, 35 enriched GO terms and 15 KEGG pathways were discovered by the gene functional enrichment analysis. Two gene modules were obtained from the PPI network constructed with 31 nodes with 42 edges using MCODE. We selected 14 hub genes as core candidate genes: TP53, VEGFA, SMAD2, CDKN2A, FOXC, FZD4, LRP5, KDR, FZD5, PAX6, MYCN, NDP, PITX2, and PAX2, primarily associated with camera-type eye morphogenesis, pancreatic cancer, the apoptotic process involved in morphogenesis, and the VEGF receptor signaling pathway. We discovered that 26 Food and Drug Administration (FDA)-approved drugs could target 7 of the 14 hub genes. Conclusions: In conclusion, the results revealed a total of 14 potential genes, 4 major pathways, 7 drug gene targets, and 26 candidate drugs that could provide the basis of novel targeted therapies for targeted treatment and management of PHPV.

Evaluation of body size and temperature on 137Cs uptake in marine animals.

137Cs bioaccumulation and retention in seven different marine animal species, including crustaceans, mollusc larvae, and fish larvae were compared under different temperature conditions (10 °C, 18 °C and 25 °C). Replicate animals were experimentally exposed to 0.5 nM 137Cs dissolved in filtered seawater for 3 days, and their 137Cs contents were periodically measured using gamma spectrometry. Among the seven species, 137Cs bioconcentration factors ranged from 14 to 239 at the end of the exposure periods. Following uptake, the137Cs loss rate constants from the animals ranged from 5 to 50% d-1 and were unaffected by temperature or animal size. The 137Cs bioconcentration factors were directly related to animal size and hence their surface: volume ratios, consistent with the conclusion that Cs sorption from the aqueous phase is the principal uptake mechanism in these animals. With the exception of gastropods, temperature had no major influence on Cs uptake and efflux in the experimental species.

Bioaccumulation and trophic transfer of 137Cs in marine and freshwater plankton.

An experimental study was conducted to investigate the trophic transfer of 137Cs in marine and freshwater food chains, focusing on phytoplankton, zooplankton, and planktivorous fish. Algal concentration factors were 278 in freshwater and 69 in seawater. The weight-normalized uptake rate constants of 137Cs were similar for both freshwater daphnids and marine copepods. Most of the 137Cs in marine copepods was in the exoskeleton followed by polar and non-polar components. In freshwater daphnids, 137Cs was highest in the polar fractions followed by exoskeleton and low amounts in the non-polar components. Fish that fed on contaminated marine copepods assimilated 137Cs with an efficiency of 88%, while 91% was assimilated from freshwater daphnids. A bioaccumulation model demonstrated that diet accounted for ≤3% of the total body burden of 137Cs in marine zooplankton and ≤12% in freshwater zooplankton, but ≥99% of the total body burden in fish. Rate constants of 137Cs loss from fish following aqueous exposure were 0.2 d-1 and 0.4 d-1 in marine and freshwater conditions, respectively, but only 0.06 d-1 and 0.3 d-1, respectively, following dietary exposure. This model also indicates that trophic transfer factors from zooplankton to fish are up to 2.2 for marine conditions and up to 0.6 for freshwater. 137Cs is unusual among metals in that it enters marine food chains primarily from the aqueous phase into zooplankton, from which it is highly assimilated by fish, resulting in detectable 137Cs in fish tissues.