Sodium valproate is effective against Botrytis cinerea infection of tomato by enhancing histone H3 acetylation-directed gene transcription and triggering tomato fruits immune response

2022 ◽  
Author(s):  
Yang Xu ◽  
Yameng Wang ◽  
Lulu Wang ◽  
Wenxing Liang ◽  
Qianqian Yang

Botrytis cinerea causes grey mold resulting in enormous financial loss. Fungicide resistance of B. cinerea has become a serious issue in food safety and agricultural environmental protection. Sodium valproate (SV) has been used in clinical trials, thus it is excellent candidate for fungicide development considering its safety. However, the antifungal activity remains unclear. SV was effective against B. cinerea by enhancing acetylation of histone H3, including H3K9ac, H3K14ac, and H3K56ac. A transcriptomics analysis revealed that the expression of 1,557 genes changed significantly in response to SV. A pathway enrichment analysis identified 16 significant GO terms, in which molecular functions were mainly involved. In addition, the expression levels of 13 genes involved in B. cinerea virulence and 5 genes involved in tomato immune response were altered by the SV treatment. These results indicate that SV inhibits B. cinerea by enhancing acetylation of histone H3 and modifying gene transcription. Thus, SV is an effective, safe potential antifungal agent for control of both pre- and post-harvest losses caused by B. cinerea.

2008 ◽  
Vol 409 (3) ◽  
pp. 779-788 ◽  
Author(s):  
Qiuju Han ◽  
Jun Lu ◽  
Jizhou Duan ◽  
Dongmei Su ◽  
Xiaozhe Hou ◽  
...  

The purpose of this study was to elucidate the mechanisms by which histone acetylation participates in transcriptional regulation of hsp70 (heat-shock protein 70) genes SSA3 and SSA4 in yeast. Our results indicated that histone acetylation was required for the transcriptional activation of SSA3 and SSA4. The HATs (histone acetyltransferases) Gcn5 (general control non-derepressible 5) and Elp3 (elongation protein 3) modulated hsp70 gene transcription by affecting the acetylation status of histone H3. Although the two HATs possessed overlapping function regarding the acetylation of histone H3, they affected hsp70 gene transcription in different ways. The recruitment of Gcn5 was Swi/Snf-dependent and was required for HSF (heat-shock factor) binding and affected RNAPII (RNA polymerase II) recruitment, whereas Elp3 exerted its roles mainly through affecting RNAPII elongation. These results provide insights into the effects of Gcn5 and Elp3 in hsp70 gene transcription and underscore the importance of histone acetylation for transcriptional initiation and elongation in hsp genes.


2020 ◽  
Author(s):  
Na Liu ◽  
Yunhong Zeng ◽  
Ting Huang ◽  
Wanyun Zuo ◽  
Yunbin Xiao ◽  
...  

Abstract BackgroundDespite its functional importance in various fundamental bioprocesses, studies of N6-methyladenosine (m6A) in the pulmonary arterial hypertension (PAH) are lacking. Here we studied the potential relevance of m6A RNA methylation and immune response in PAH development.MethodsWe constructed a monocrotaline (MCT) induced PAH rat model and performed Methylated RNA immunoprecipitation sequencing (MeRIP-Seq). The 18 idiopathic PAH (IPAH) microarray data obtained from the GEO database was used to construct co-expression networks by weighted gene co-expression network analysis (WGCNA). CIBERSORT was used to investigate the effect of m6A methylation on immune cell infiltration during PAH.ResultsA differential pattern of m6A abundance, mainly up-methylation, was observed in the lung tissues of rats with MCT induced PAH. By WGCNA, multi-list pathway enrichment analysis and protein-protein interaction (PPI) analysis, we found that m6A methylation modification may play important roles in mediating immune response during PAH. CYBERSORT algorithm indicated that the m6A methylation can drive monocyte to form M1 macrophage, which may be mediated by CCR5 and CXCL9.ConclusionCollectively, m6A landscape is altered in PAH. We summarize newly discovered m6A in controlling immune response, which caused activation of M1 macrophage during PAH. It’s provided a novel insight into the therapeutic mechanisms of PAH.


Genes ◽  
2021 ◽  
Vol 12 (12) ◽  
pp. 2008
Author(s):  
Wojciech Strojny ◽  
Kinga Kwiecińska ◽  
Przemysław Hałubiec ◽  
Wojciech Kowalczyk ◽  
Karol Miklusiak ◽  
...  

Hematopoietic stem cell transplantation (HSCT) is an effective treatment method used in many neoplastic and non-neoplastic diseases that affect the bone marrow, blood cells, and immune system. The procedure is associated with a risk of adverse events, mostly related to the immune response after transplantation. The aim of our research was to identify genes, processes and cellular entities involved in the variety of changes occurring after allogeneic HSCT in children by performing a whole genome expression assessment together with pathway enrichment analysis. We conducted a prospective study of 27 patients (aged 1.5–18 years) qualified for allogenic HSCT. Blood samples were obtained before HSCT and 6 months after the procedure. Microarrays were used to analyze gene expressions in peripheral blood mononuclear cells. This was followed by Gene Ontology (GO) functional enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein–protein interaction (PPI) analysis using bioinformatic tools. We found 139 differentially expressed genes (DEGs) of which 91 were upregulated and 48 were downregulated. “Blood microparticle”, “extracellular exosome”, “B-cell receptor signaling pathway”, “complement activation” and “antigen binding” were among GO terms found to be significantly enriched. The PPI analysis identified 16 hub genes. Our results provide insight into a broad spectrum of epigenetic changes that occur after HSCT. In particular, they further highlight the importance of extracellular vesicles (exosomes and microparticles) in the post-HSCT immune response.


Insects ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 728
Author(s):  
Wenhao Xing ◽  
Dingding Zhou ◽  
Qi Long ◽  
Minghui Sun ◽  
Rui Guo ◽  
...  

Here, a comparative transcriptome investigation was conducted based on high-quality deep sequencing data from the midguts of Apis cerana cerana workers at 7 d post-inoculation (dpi) and 10 dpi with Nosema ceranae and corresponding un-inoculated midguts. PCR identification and microscopic observation of paraffin sections confirmed the effective infection of A. c. cerana worker by N. ceranae. In total, 1127 and 957 N. ceranae-responsive genes were identified in the infected midguts at 7 dpi and 10 dpi, respectively. RT-qPCR results validated the reliability of our transcriptome data. GO categorization indicated the differentially expressed genes (DEGs) were respectively engaged in 34 and 33 functional terms associated with biological processes, cellular components, and molecular functions. Additionally, KEGG pathway enrichment analysis showed that DEGs at 7 dpi and 10 dpi could be enriched in 231 and 226 pathways, respectively. Moreover, DEGs in workers’ midguts at both 7 dpi and 10 dpi were involved in six cellular immune pathways such as autophagy and phagosome and three humoral immune pathways such as the Toll/Imd signaling pathway and Jak-STAT signaling pathway. In addition, one up-regulated gene (XM_017055397.1) was enriched in the NF-κB signaling pathway in the workers’ midgut at 10 dpi. Further investigation suggested the majority of these DEGs were engaged in only one immune pathway, while a small number of DEGs were simultaneously involved in two immune pathways. These results together demonstrated that the overall gene expression profile in host midgut was altered by N. ceranae infection and some of the host immune pathways were induced to activation during fungal infection, whereas some others were suppressed via host–pathogen interaction. Our findings offer a basis for clarification of the mechanism underlying the immune response of A. c. cerana workers to N. ceranae infection, but also provide novel insights into eastern honeybee-microsporodian interaction.


2021 ◽  
Author(s):  
Heather Jackson ◽  
Irene Rivero Calle ◽  
Claire Broderick ◽  
Dominic Habgood-Coote ◽  
Giselle D'Souza ◽  
...  

Infection with SARS-CoV-2 has highly variable clinical manifestations, ranging from asymptomatic infection through to life-threatening disease. Host whole blood transcriptomics can offer unique insights into the biological processes underpinning infection and disease, as well as severity. We performed whole blood RNA Sequencing of individuals with varying degrees of COVID-19 severity. We used differential expression analysis and pathway enrichment analysis to explore how the blood transcriptome differs between individuals with mild, moderate, and severe COVID-19, performing pairwise comparisons between groups. Increasing COVID-19 severity was characterised by an abundance of inflammatory immune response genes and pathways, including many related to neutrophils and macrophages, in addition to an upregulation of immunoglobulin genes. Our insights into COVID-19 severity reveal the role of immune dysregulation in the progression to severe disease and highlight the need for further research exploring the interplay between SARS-CoV-2 and the inflammatory immune response.


2013 ◽  
Vol 40 (12) ◽  
pp. 1256
Author(s):  
XiaoDong JIA ◽  
XiuJie CHEN ◽  
Xin WU ◽  
JianKai XU ◽  
FuJian TAN ◽  
...  

2019 ◽  
Vol 22 (6) ◽  
pp. 411-420 ◽  
Author(s):  
Xian-Jun Wu ◽  
Xin-Bin Zhou ◽  
Chen Chen ◽  
Wei Mao

Aim and Objective: Cardiovascular disease is a serious threat to human health because of its high mortality and morbidity rates. At present, there is no effective treatment. In Southeast Asia, traditional Chinese medicine is widely used in the treatment of cardiovascular diseases. Quercetin is a flavonoid extract of Ginkgo biloba leaves. Basic experiments and clinical studies have shown that quercetin has a significant effect on the treatment of cardiovascular diseases. However, its precise mechanism is still unclear. Therefore, it is necessary to exploit the network pharmacological potential effects of quercetin on cardiovascular disease. Materials and Methods: In the present study, a novel network pharmacology strategy based on pharmacokinetic filtering, target fishing, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, compound-target-pathway network structured was performed to explore the anti- cardiovascular disease mechanism of quercetin. Results:: The outcomes showed that quercetin possesses favorable pharmacokinetic profiles, which have interactions with 47 cardiovascular disease-related targets and 12 KEGG signaling pathways to provide potential synergistic therapeutic effects. Following the construction of Compound-Target-Pathway (C-T-P) network, and the network topological feature calculation, we obtained top 10 core genes in this network which were AKT1, IL1B, TNF, IL6, JUN, CCL2, FOS, VEGFA, CXCL8, and ICAM1. KEGG pathway enrichment analysis. These indicated that quercetin produced the therapeutic effects against cardiovascular disease by systemically and holistically regulating many signaling pathways, including Fluid shear stress and atherosclerosis, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, MAPK signaling pathway, IL-17 signaling pathway and PI3K-Akt signaling pathway.


2019 ◽  
Vol 19 (12) ◽  
pp. 1463-1472 ◽  
Author(s):  
Nil Kiliç ◽  
Yasemin Ö. Islakoğlu ◽  
İlker Büyük ◽  
Bala Gür-Dedeoğlu ◽  
Demet Cansaran-Duman

Objective: Breast Cancer (BC) is the most common type of cancer diagnosed in women. A common treatment strategy for BC is still not available because of its molecular heterogeneity and resistance is developed in most of the patients through the course of treatment. Therefore, alternative medicine resources as being novel treatment options are needed to be used for the treatment of BC. Usnic Acid (UA) that is one of the secondary metabolites of lichens used for different purposes in the field of medicine and its anti-proliferative effect has been shown in certain cancer types, suggesting its potential use for the treatment. Methods: Anti-proliferative effect of UA in BC cells (MDA-MB-231, MCF-7, BT-474) was identified through MTT analysis. Microarray analysis was performed in cells treated with the effective concentration of UA and UA-responsive miRNAs were detected. Their targets and the pathways that they involve were determined using a miRNA target prediction tool. Results: Microarray experiments showed that 67 miRNAs were specifically responsive to UA in MDA-MB-231 cells while 15 and 8 were specific to BT-474 and MCF-7 cells, respectively. The miRNA targets were mostly found to play role in Hedgehog signaling pathway. TGF-Beta, MAPK and apoptosis pathways were also the prominent ones according to the miRNA enrichment analysis. Conclusion: The current study is important as being the first study in the literature which aimed to explore the UA related miRNAs, their targets and molecular pathways that may have roles in the BC. The results of pathway enrichment analysis and anti-proliferative effects of UA support the idea that UA might be used as a potential alternative therapeutic agent for BC treatment.


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