Early Transcriptomic Profile of Mucosal Immune Responses in the Intestine of Japanese Puffer (Takifugu rubripes) Infected With Vibrio harveyi
Japanese puffer (Takifugu rubripes) is an important mariculture species, but the development of the aquaculture industry has been accompanied by serious disease problems. Vibrio harveyi is one of the most important pathogens in T. rubripes. To gain a more comprehensive understanding of the molecular mechanism responsible for intestinal mucosal immunity of T. rubripes during V. harveyi infection, we established a transcriptome of the posterior intestine of T. rubripes after 0, 3, and 24 h of infection with V. harveyi. 12 fish (weighing 300 ± 5.5 g) were randomly selected from 60 T. rubripes and four were assigned to each time point. Transcriptomic analysis revealed 3,042 and 3,342 differentially expressed genes (DEGs) at 3 h and 24 h, respectively, compared with those at 0 h. Enrichment analysis of these DEGs revealed significant mucosal immune‐related pathways, including cytokine–cytokine receptor interaction, phagosome, and cell adhesion molecules (CAMs) signaling pathways. In addition, the intestinal histopathological changes were explored after V. harveyi infection. Further analysis showed that the structure of infected intestines was still integrated, with the majority of the pathological trauma occurring in the submucosa. Our results provided new insights for further study of the mucosal immune defense mechanisms of fish against V. harveyi, promoting our understanding of this severe disease.
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23
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3
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22
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38
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Transcriptome profile analysis of mucosal immune responses in the gill of Takifugu rubripes infected with Vibrio harveyi.
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7
- 10.3389/fgene.2021.654955
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- Frontiers in genetics
Pathological neovascularization in choroid, a leading cause of blindness, is a characteristic of many fundus diseases, such as diabetic retinopathy and age-related macular degeneration. The present study aimed to elucidate the key signaling pathways in choroidal neovascularization (CNV) by analyzing the mRNA profiles of choroid and retina in tree shrews with CNV. We induced choroidal angiogenesis by laser photocoagulation in 15 tree shrews and obtained mRNA profiles of their choroids and retinas by high-throughput transcriptome sequencing. Hierarchical cluster analysis, weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network analysis, hematoxylin and eosin (HE) staining, CD31 immunohistochemistry (IHC), and reverse transcription quantitative PCR (RT-qPCR) were performed. After laser photocoagulation, we obtained a total of 350 differentially expressed genes (DEGs) in the choroid, including 59 genes in Module-FASN (“ME-FASN”) module and 28 genes in Module-RPL (“ME-RPL”) module. A total of 69 DEGs in retina, including 20 genes in Module-SLC (“ME-SLC”) module. Bioinformatics analysis demonstrated that DEGs in choroid were mainly involved in membrane transport; DEGs in “ME-RPL” were prominent in pathways associated with IgA production, antigen presentation, and cell adhesion molecules (CAMs) signaling. DEGs in “ME-FASN” were involved in fatty acid metabolism and PPAR signaling pathway, while DEGs in “ME-SLC” were involved in GABAergic synapse, neuroactive life receptor interaction, cholinergic synapse, and retrograde endocannabinoid signaling pathway. PPI network analysis demonstrated that the ribosomal protein family genes (RPL31, RPL7, RPL26L1, and RPL19) are key factors of “ME-RPL,” acyl-CoA superfamily genes (ACACA, ACAT1, ACAA2, and ACACB) and FASN are key factors of “ME-FASN” and superfamily of solid carrier genes (SLC17A6, SLC32A1, SLC12A5, and SLC6A1) and complement genes (C4A, C3, and C2) are key factors of “ME-SLC.” In conclusion, the present study discovered the important signal transductions (fatty acid metabolic pathway and CAMs signaling) and genes (ribosomal protein family and the complement system) in tree shrew CNV. We consider that our findings hold implications in unraveling molecular mechanisms that underlie occurrence and development of CNV.
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15
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11
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Passive protection of Japanese pufferfish (Takifugu rubripes) against Vibrio harveyi infection using chicken egg yolk immunoglobulins (IgY)
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7
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Large yellow croaker (Larimichthys crocea) is a commercially important fish species worldwide, but high-density cultivation has led to serious diseases especially by Vibrio harveyi. Understanding the molecular response of large yellow croaker to V. harveyi infection is vital for the development of effective measures to combat the disease. In this study, RNA-Seq was performed on the spleen of uninfected and V. harveyi-infected large yellow croaker. A total of 7527 differentially expressed genes (DEGs) were identified, with 4413 up-regulated and 3114 down-regulated genes. Functional enrichment analysis revealed that several immune-related pathways were highlighted, including Toll-like receptors (TLRs) signaling pathway, apoptosis, p53 signaling pathway, and lysosome. In the TLRs signaling pathway, up-regulated genes included IL1b, bactericidal permeability-increasing protein, and IL12b, while down-expressed genes included tlr3 and irf3. The apoptosis pathway showed up-regulated genes such as casp6, bcl-2-like protein, and cytochrome c, and down-expressed genes such as granzyme B, sptan1, and FADD-Fas (tnfrsf6)-associated via death domain. These results suggest that V. harveyi infection induced inflammatory response and apoptotic cell death in the spleen of large yellow croaker. This study provides valuable insights into the molecular mechanisms underlying the immune response of large yellow croaker to V. harveyi infection
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8
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BackgroundPeripheral T‐cell lymphomas (PTCLs) are a heterogeneous group of neoplasms characterized by a poor prognosis. Histone deacetylase (HDAC) inhibitors have emerged as novel therapeutic agents for PTCLs. In this study, we aimed to explore the immunomodulatory effect of the HDAC inhibitor chidamide on circulating PD-1(+) cells from patients with PTCL, as well as its correlation with treatment response.MethodsWe enrolled newly diagnosed patients with PTCLs treated with a combination of chidamide and chemotherapy. Gene expression profile analysis was performed on peripheral blood PD-1(+) cells, both at baseline and at the end of treatment. A list of differentially expressed genes (DEGs) was identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to annotate the biological implications of the DEGs. A gene concept network was constructed to identify the key DEGs for further PCR verification.ResultsA total of 302 DEGs were identified in the complete remission (CR) group, including 162 upregulated and 140 downregulated genes. In contrast, only 12 DEGs were identified in the non-CR group. GO analysis revealed that these upregulated DEGs were mainly involved in chemokine activity, cell chemotaxis, and cellular response to interleukin-1 and interferon-γ. Furthermore, KEGG pathway analysis showed that these DEGs were enriched in cytokine-cytokine receptor interaction and chemokine signaling pathways. The innate immune signaling pathways, including the Toll-like and NOD-like receptor signaling pathways, were also influenced. The gene concept network revealed that the key upregulated genes belonged to the C-C chemokine family.ConclusionOur results showed that chidamide treatment notably enhanced the expression of genes associated with chemokine activity and chemotaxis function of circulating PD-1(+) cells. By recruiting immune cells and improving the innate immune function of PD-1(+) cells, chidamide may reshape the tumor microenvironment to an anti-tumor phenotype and synergize with checkpoint inhibitors.
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12
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We aimed to screen the differential expressed genes (DEGs) and transcriptional factors (TFs) related to gastric cancer. GSE19826 microarray data downloaded from Gene Expression Omnibus was used to identify the differentially expressed genes (DEGs) and PPI network of DEGs were constructed by the Retrieval of Interacting Genes database. Pathway enrichment analysis of DEGs were performed by Gene Set Enrichment Analysis. Then, the transcriptional regulatory network was constructed based on TRANSFAC database. Finally, regulatory impact factor (RIF) of TF was calculated. We identified 446 DEGs including 209 up- and 237 down-regulated genes. These DEGs were mainly significantly enriched in 5 pathways including ECM receptor interaction (p=0.013899), spliceosome (p=0.025591), bladder cancer (p=0.026316), focal adhesion (p=0.047809) and WNT signaling pathway (p=0.048077). PPI network with 247 nodes and 913 edges were constructed and COL5A2 was the hub node. Transcriptional regulatory network with 6 differently expressed TFs, 58 non-differently expressed TFs, 44 DEGs and 735 non-DEGs was constructed. Finally, top 5 TFs including CRX, TFAP4, NKX2-1, MYB and RARG with higher ZRIF were screened. The identified DEGs such as COL5A2 and TOP2A, and TFs including EGR2, FOXM1, NKX2-1 and TFAP4 might be the critical genes and TFs for gastric cancer.
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1
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58
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To identify candidate genes and pathways involved in testicular development in Takifugu rubripes, a comparative transcription analysis was conducted across the various developmental stages of the testis (stages II to V). A total of 9520 differentially expressed genes (DEGs) were identified among the different stages, and they were significantly clustered into six clusters (P < 0.05). One thousand four hundred eleven DEGs such as gndf, wnt1, and cyp17b1 were found to be decreased from stage II to V. In contrast, 994 DEGs such as fn1, ift81, and cdc25a were found to be increased from stage II to V. Six thousand three hundred eighteen DEGs (e.g., dmrt1, sdk2, and chrna1) were identified as being expressed at similar levels at stages II and III. However, they were subsequently found to be decreased from stage III to IV. Four hundred one DEGs exhibited a significant upregulation trend from stage II to III. These genes were expressed at similar levels in stages III, IV, and V, including chrnd, wnt4a, and cyp7a1. The highest expression levels of 200 DEGs (e.g., ccnb2, cdk1, and sycp2) were observed in stage IV, while 196 DEGs (e.g., chmp1b, hsd17b3, and zp3) exhibited the highest expression level in stage III. Those DEGs were mainly enriched in the pathways (e.g., neuroactive ligand-receptor interaction, cell adhesion molecules, and calcium signaling pathways) associated with testicular development. Quantitative polymerase chain reaction of eight randomly selected genes validated the RNA sequencing results. This study may provide new insights into the molecular regulatory mechanisms governing testicular development and spermatogenesis in T. rubripes.
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8
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Vibrio harveyi, a recently discovered pathogenic bacterium isolated from American eels (Anguilla rostrata), poses uncertainties regarding its pathogenesis in American eel and the molecular mechanisms underlying host defense against V. harveyi infection. This study aimed to determine the LD50 of V. harveyi in American eel and assess the bacterial load in the liver, spleen, and kidney post-infection with the LD50 dose. The results showed that the LD50 of V. harveyi via intraperitoneal injection in American eels over a 14d period was determined to be 1.24 × 103cfu/g body weight (6.2 × 104cfu/fish). The peak bacterial load occurred at 36h post-infection (hpi) in all three organs examined. Histopathology analysis revealed hepatic vein congestion and thrombi, tubular vacuolar degeneration, and splenic bleeding. Moreover, quantitative reverse transcription polymerase chain reaction (qRT-PCR) results indicated significant up or downregulation of 18 host immune- or anti-infection-related genes post 12 to 60 hpi following the infection. Additionally, RNA sequencing (RNA-seq) unveiled 7 hub differentially expressed genes (DEGs) and 11 encoded proteins play crucial roles in the anti-V. harveyi response in American eels. This study firstly represents the comprehensive report on the pathogenicity of V. harveyi to American eels and RNA-seq of host's response to V. harveyi infection. These findings provide valuable insights into V. harveyi pathogenesis and the strategies employed by the host's immune system at the transcriptomic level to combat V. harveyi infection.
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