RESUMEN
BACKGROUND: Age-related macular degeneration (AMD) is a prevalent source of visual impairment among the elderly population, and its incidence has risen in tandem with the increasing longevity of humans. Despite the progress made with anti-VEGF therapy, clinical outcomes have proven to be unsatisfactory. METHOD: We obtained differentially expressed genes (DEGs) of AMD patients and healthy controls from the GEO database. GO and KEGG analyses were used to enrich the DEGs. Weighted gene coexpression network analysis (WGCNA) was used to identify modules related to AMD. SVM, random forest, and least absolute shrinkage and selection operator (LASSO) were employed to screen hub genes. Gene set enrichment analysis (GSEA) was used to explore the pathways in which these hub genes were enriched. CIBERSORT was utilized to analyze the relationship between the hub genes and immune cell infiltration. Finally, Western blotting and RTâPCR were used to explore the expression of hub genes in AMD mice. RESULTS: We screened 1084 DEGs in GSE29801, of which 496 genes were upregulated. These 1084 DEGs were introduced into the WGCNA, and 94 genes related to AMD were obtained. Seventy-nine overlapping genes were obtained by the Venn plot. These 79 genes were introduced into three machine-learning methods to screen the hub genes, and the genes identified by the three methods were TNC, FAP, SREBF1, and TGF-ß2. We verified their diagnostic function in the GSE29801 and GSE103060 datasets. Then, the hub gene co-enrichment pathways were obtained by GO and KEGG analyses. CIBERSORT analysis showed that these hub genes were associated with immune cell infiltration. Finally, we found increased expression of TNC, FAP, SREBF1, and TGF-ß2 mRNA and protein in the retinas of AMD mice. CONCLUSION: We found that four hub genes, namely, FAP, TGF-ß2, SREBF1, and TNC, have diagnostic significance in patients with AMD and are related to immune cell infiltration. Finally, we determined that the mRNA and protein expression of these hub genes was upregulated in the retinas of AMD mice.
Asunto(s)
Degeneración Macular , Factor de Crecimiento Transformador beta2 , Humanos , Anciano , Animales , Ratones , Factor de Crecimiento Transformador beta2/genética , Degeneración Macular/genética , Retina , Western Blotting , ARN MensajeroRESUMEN
Abstract Resource amendments commonly promote plant invasions, raising concerns over the potential consequences of nitrogen (N) deposition; however, it is unclear whether invaders will benefit from N deposition more than natives. Growth is among the most fundamental inherent traits of plants and thus good invaders may have superior growth advantages in response to resource amendments. We compared the growth and allocation between invasive and native plants in different N regimes including controls (ambient N concentrations). We found that invasive plants always grew much larger than native plants in varying N conditions, regardless of growth- or phylogeny-based analyses, and that the former allocated more biomass to shoots than the latter. Although N addition enhanced the growth of invasive plants, this enhancement did not increase with increasing N addition. Across invasive and native species, changes in shoot biomass allocation were positively correlated with changes in whole-plant biomass; and the slope of this relationship was greater in invasive plants than native plants. These findings suggest that enhanced shoot investment makes invasive plants retain a growth advantage in high N conditions relative to natives, and also highlight that future N deposition may increase the risks of plant invasions.
Resumo As alterações de recursos geralmente promovem invasões de plantas, suscitando preocupações quanto às conseqüências potenciais da deposição de nitrogênio (N); No entanto, não está claro se os invasores se beneficiarão da deposição de N mais do que com os nativos. O crescimento é um dos traços inerentes mais fundamentais das plantas e, portanto, os bons invasores podem ter vantagens de crescimento superiores em resposta a alterações de recursos. Comparamos o crescimento e a alocação entre plantas invasivas e nativas em diferentes regimes de N, incluindo controles (concentrações ambientais de N). Descobrimos que as plantas invasivas sempre cresceram muito mais do que as plantas nativas em diferentes condições de N, independentemente das análises baseadas em crescimento ou filogenia, e que o primeiro atribuiu mais biomassa aos rebentos do que o segundo. Embora N aumentou o crescimento de plantas invasivas, esse aumento não aumentou com o aumento da adição de N. Através das espécies invasivas e nativas, as mudanças na alocação da biomassa do extrato foram correlacionadas positivamente com as mudanças na biomassa da planta inteira; e a inclinação desse relacionamento foi maior em plantas invasivas do que plantas nativas. Essas descobertas sugerem que o aumento do investimento em lançamentos faz com que as plantas invasivas mantenham uma vantagem de crescimento em altas condições de N em relação aos nativos, e também destacar que a futura deposição de N pode aumentar os riscos de invasões de plantas.