Genome-wide identification and expression analysis of Sox gene family in the Manila clam (Ruditapes philippinarum).

Sox transcription factors are vital in numerous fundamental biological processes. In this study, nine Sox gene family members were discovered in the Ruditapes philippinarum genome, classified into the SoxB1, SoxB2, SoxC, SoxD, SoxE, and SoxF groups, marking the first genome-wide identification of this gene family in R. philippinarum. Analyses of phylogeny, exon-intron structures, and domains bolster the support for their categorization and annotation. Furthermore, transcriptomic analyses across various developmental stages revealed that RpSox4, RpSox5, RpSox9, and RpSox11 were significantly expressed in the D-larval stage. Additionally, investigations into transcriptomes of clams with different shell colors indicated that most sox genes exhibited their highest expression levels in orange clams, followed by zebra, white zebra, and white clams, and the results of transcriptomes analysis in different tissues indicated that 8 Sox genes (except RpSox17) were highly expressed in the mantle tissue. Moreover, qPCR was used to detect the expression of Sox gene in R. philippinarum at different developmental periods, different shell colors and different tissues, and the results showed consistency with those of the transcriptomes. This study's findings lay the groundwork for additional exploration into the role of the Sox gene in melanin production in R. philippinarum shells.

The lgi-miR-2d is Potentially Involved in Shell Melanin Synthesis by Targeting mitf in Manila Clam Ruditapes philippinarum.

Shell color as an important economic trait is also the crucial target trait for breeding and production. MicroRNA (miRNA) is an endogenous small non-coding RNA that can post-transcriptionally regulate the expression of target genes, it plays important roles in many life activities and physiological processes, such as shell color, stress response, and disease traits. In this study, we investigated the function of lgi-miR-2d in shell melanin formation and the expression patterns of lgi-miR-2d and target gene Rpmitf in Manila clam Ruditapes philippinarum. We further explored and verified the relationship between Rpmitf and lgi-miR-2d and identified the expression level of shell color-related gene changes by RNAi and injecting the antagomir of lgi-miR-2d, respectively. Our results indicated that lgi-miR-2d antagomir affected the expression of its target gene Rpmitf. In addition, the dual-luciferase reporter assay was conducted to confirm the direct interaction between lgi-miR-2d and Rpmitf. The results showed that the expression levels of melanin-related genes such as Rpmitf and tyr were significantly decreased in the positive treatment group compared with the blank control group after the Rpmitf dsRNA injection, indicating Rpmitf plays a crucial role in the melanin synthesis pathway. Taken together, we speculated that lgi-miR-2d might be negatively modulating Rpmitf, which might regulate other shell color-related genes, thereby affecting melanin synthesis in R. philippinarum.

Identification of the key mechanisms of action of Si-Ni-San in uveitis using bioinformatics and network pharmacology.

BACKGROUND: Uveitis is an eye disease with a high rate of blindness, whose pathogenesis is not completely understood. Si-Ni-San (SNS) has been used as a traditional medicine to treat uveitis in China. However, its mechanism of action remains unclear. This study explored the potential mechanisms of SNS in the treatment of uveitis through network pharmacology and bioinformatics. METHODS: Using R language and Perl software, the active components and predicted targets of SNS, as well as the related gene targets of uveitis, were mined through the Traditional Chinese Medicine Systems Pharmacology, Therapeutic Target, Gene Expression Omnibus, GeneCards, and DrugBank databases. The network diagram of active components and intersection targets was constructed using Cytoscape software and the String database. The CytoNCA plug-in was used to conduct topological analysis on the network diagram and screen out the core compounds and key targets. The genes were analyzed for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment. Chemoffice, Pymol, AutoDock, and Vina were used to analyze the molecular docking of key targets and core compounds of diseases through the PubChem database. RESULTS: JUN, RELA, and MAPK may play important roles in the treatment of uveitis by SNS. Kyoto encyclopedia of genes and genomes pathway enrichment analysis showed that core genes were mainly concentrated in MAPK, toll-like receptor, tumor necrosis factor, and nucleotide oligomerization domain-like receptor signaling pathways. In addition, molecular docking results showed that the bioactive compounds (kaempferol, luteolin, naringin, and quercetin) exhibited good binding ability to JUN, RELA, and MAPK. CONCLUSION: Based on these findings, SNS exhibits multi-component and multi-target synergistic action in the treatment of uveitis, and its mechanism may be related to anti-inflammatory and immune regulation.

Analysis of differentially expressed genes in individuals with noninfectious uveitis based on data in the gene expression omnibus database.

Noninfectious uveitis (NIU), an intraocular inflammation caused by immune-mediated reactions to eye antigens, is associated with systemic rheumatism and several autoimmune diseases. However, the mechanisms underlying the pathogenesis of uveitis are poorly understood. Therefore, we aimed to identify differentially expressed genes (DEGs) in individuals with NIU and to explore its etiologies using bioinformatics tools. GSE66936 and GSE18781 datasets from the gene expression omnibus (GEO) database were merged and analyzed. Functional enrichment analysis was performed, and protein-protein interaction (PPI) networks were constructed. A total of 89 DEGs were identified. Gene ontology (GO) enrichment analysis identified 21 enriched gene sets. Kyoto encyclopedia of genes and genomes (KEGG) pathway enrichment analysis identified four core enriched pathways: antigen processing and expression signaling, natural killer (NK) cell-mediated cytotoxicity signaling, glutathione metabolic signal transduction, and arachidonic acid metabolism pathways. PPI network analysis revealed an active component-target network with 40 nodes and 132 edges, as well as several hub genes, including CD27, LTF, NCR3, SLC4A1, CD69, KLRB1, KIR2DL3, KIR3DL1, and GZMK. The eight potential hub genes may be associated with the risk of developing NIU. NK cell-mediated cytotoxicity signaling might be the key molecular mechanism in the occurrence and development of NIU. Our study provided new insights on NIU, its genetics, molecular pathogenesis and new therapeutic targets.

Betalain exerts a protective effect against glaucoma is majorly through the association of inflammatory cytokines.

The present research aimed at evaluating the protective role of betalain on the in vitro glaucoma model using PC12 neuronal cells. The cultured neuronal cells in a customized pressurized chamber were analyzed for the onset of glutathione, myeloperoxidase (MPO), cathepsin, expression of inflammatory enzymes such as cyclooxygenase (COX-1), lipoxygenase (5- LOX), sPLA2 caveolin-1, glaucoma markers and other inflammatory cytokines in the presence and absence of betalain. The results have shown that a significant increase in the expression of oxidative stress with increased activity of cathepsin B and D. On the other hand, the activity of inflammatory enzymes such as COX-1, 5- LOX, sPLA2 were significantly increased in pressure exposed cells. In addition, glaucoma simulated cells demonstrated a significant increase in the VEGF, TGF-ß, BDGF, and neuroserpin compared to control. Moreover, cells predisposed to hydrostatic pressure demonstrated an increase in (p < 0.01) inflammatory cytokines such as IL-6, CXCR4, IL-17, IL-1ß, and TNF-α levels. However, cells pre-treated with betalain improved the glutathione levels with attenuated MPO activity. Simultaneously, the levels of inflammatory cytokines and other glaucoma marker genes found restored in drug pre-treated cells. Thus, the results of the present study demonstrate that the use of betalain on ocular cells can prevent the progression of the disease that can be a suggestive therapeutic for controlling glaucoma like conditions.