Label-free quantitative proteomic analysis of serum exosomes from patients of renal anemia: The Good and the Bad of Roxadustat

Abstract

Background Roxadustat is a new oral anti-renal anemia medication that works by stabilizing hypoxia-inducible factor (HIF) which can activate the expression of more than 100 genes in addition to genes related to anemia. However, the more potential molecular targets of roxadustat are not completely clear. Therefore, it is essential to further reveal its molecular targets to guide its clinical applications. Methods We performed label-free quantification and LC-MS/MS to study the proteomic alterations in serum exosome of renal anemia patients before and after roxadustat therapy. Results were validated by PRM. Results A total of 30 proteins were significantly changed after treatment with roxadustat. Among these proteins, 18 proteins were up-regulated (and 12 were down-regulated). The results are statistically significant (P < 0.05). Then, we validated the result by PRM, the results confirmed that TFRC, HSPA8, ITGB3, COL1A2, and YWHAZ were markedly upregulated, while ITIH2 and CFH were significantly downregulated upon treatment with roxadustat. Conclusions TFRC and HSPA8 could be an important target of the action of roxadustat, and roxadustat may increase cardiovascular risk through its influence on platelet activation. Our results provide a theoretical basis for its wider clinical application and preventing expected side effects.

A DNA nanostructure‐Hif‐1α inducer complex as novel nanotherapy against cisplatin‐induced acute kidney injury

“…Based on the points mentioned above, TFG possesses the potential to reduce the side effects of FG‐4592 and to some extent avoid unnecessary complications caused by drugs. 15 …”

“…These features make nucleic acid nanoparticles an appealing option for researchers to develop tetrahedral‐framework nucleic acid nanostructures to treat renal diseases. Based on the points mentioned above, TFG possesses the potential to reduce the side effects of FG‐4592 and to some extent avoid unnecessary complications caused by drugs 15 …”

“…This hydroxylation process leads to the ubiquitination and subsequent degradation of Hif‐1α. However, its potential cardiovascular and cerebrovascular risks by activating platelets would also cause uncertainty for patients who plan to use this small‐molecule drug in their treatment prescriptions 15 . Therefore, developing an efficient delivery system with low toxicity and high kidney aggregation is needed to expand the application of FG‐4592.…”

Chirality-biased protein expression profile during early stages of bone regeneration

“…To analyse various protein families and pathways, COG, KEGG, and Reactome databases were used ( Huang et al, 2009 ; You et al, 2022 ). The proteome was annotated using the GO database, categorizing proteins based on their molecular function, biological process, and cellular components.…”

Natural Product Aloesin Significantly Inhibits Spore Germination and Appressorium Formation in Magnaporthe oryzae

“…Differentially expressed proteins (DEPs) satisfied the following conditions: average ratio-fold change > 1.2 and p-value < 0.05 (Student's t-test). Gene ontology (GO) annotation of the proteome was derived from the GO database http://www.ebi.ac.uk/QuickGO/ (accessed on 23 September 2022) [28]. The pathway analysis was performed using the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway (http://www.kegg.jp/kegg/pathway.html) (accessed on 23 September 2022) [28] to test the enrichment of the different proteins against all identified proteins by hypergeometric distribution.…”