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Gallic Acid Pretreatment Mitigates Parathyroid Ischemia-Reperfusion Injury through Signaling Pathway Modulation

ABSTRACT: As a polyphenolic herbal extract, Gallic acid (GA) is known for its antioxidant and anti-inflammatory properties. However, its application in parathyroid ischemia-reperfusion injury (IRI) has not been well examined. This study aimed to elucidate the protective effects of GA pretreatment in a parathyroid IRI model and explore the underlying mechanisms.Hypoxia and hypoxia/reoxygenation models were established with primary parathyroid cells to explore the protective effect of GA.The results from sequencing and bioinformatic analyses indicated that GA might regulate MMP1, MMP9, FOSB, GSY2, DUSP5, TRPV1/3, TIAM1 and multiple signaling pathways in this process such as IL-17, AMPK, MAPK, Transient Receptor Potential (TRP) channels, cAMP and Rap1.

ORGANISM(S): Oryctolagus cuniculus

PROVIDER: GSE240162 | GEO | 2023/08/23

REPOSITORIES: GEO

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Project description:Aspergillus flavus is a common saprophyte and opportunistic pathogen producing aflatoxin (AF) and many other secondary metabolites. 5-Azacytidine (5-AC), a derivative of nucleoside cytidine, is widely used for studies in epigenetics and cancer biology as an inactivator of DNA methyltransferase and is also used for studying secondary metabolism in fungi. Our previous studies showed that 5-AC affects development and inhibits AF production in A. flavus, and that A. flavus lacks DNA methylation. How this common DNA methyltransferase inhibitor affects development and AF production is not clear. In this study, we applied an RNA-Seq approach to elucidate the mechanism of 5-ACM-bM-^@M-^Ys effect on A. flavus. In our current study, we identified 240 significantly differently expressed (Q-value<0.05) genes after 5-AC treatment, including two backbone genes in secondary metabolite clusters #27 and #35, which are involved in development or survival of sclerotia. With 5-AC treatment, about three quarters of the genes in the AF biosynthetic gene cluster in A. flavus were down-regulated to a certain degree. Strikingly, at least two genes aflI and aflLa, were completely inhibited. Interestingly, several genes involved in fungal development were down-regulated, especially veA, which is a gene that encodes protein bridges VelB and LaeA. This result supports the hypothesis that 5-AC affects development and AF production through weakening or even interrupting the connection between VelB and LaeA and then causing dysregulation of the expression pattern of genes involved in development and secondary metabolism. Our results improved the A. flavus genome annotation, provided a comprehensive view of the transcriptome of A. flavus responding to 5-AC and confirmed that fungal development and secondary metabolism are co-regulated. In additon, the RNA-Seq data of another sample treated with gallic acid was used to improve A. flavus genome annotation. mRNA of Aspergillus flavus cultured in three different culture media PDB, PDB+5-AC(5-Azacytidine),and PDB+GA(gallic acid) was subjected to sequence independently.

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Gallic Acid Pretreatment Mitigates Parathyroid Ischemia-Reperfusion Injury through Signaling Pathway Modulation

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