Recent Advances in Microbial Degradation of 4-hydroxybenzoate-a Review

4-Hydroxybenzoate （4HBA） is a naturally occurring aromatic compound, as a key intermediate metabolite not only for natural products but also for arti- ficial products. There are four metabolic pathways for 4HBA： protocatechuate cleavage pathway; catechol cleavage pathway; anaerobic degradation pathway in anaerobes ; and gentisate cleavage pathway. The last pathway including a NIH shift reaction remains to be elucidated. In this review we emphasized on the NIH shift reaction involved in the 4HBA degrdation. The key enzymes of each 4HBA metabolic pathway also were introduced. Finnaly, we described the thermophilic Bacillus sp. B1 strain which was capable of degrading varous aromatic compounds including gHBA, and presented a direction for the research of NIH shift reaction.

Mechanism of Gentisic Acidon Rheumatoid Arthritis BasedonmiR-19b-3p/RAF1 Axis

Objective To investigate the therapeutic effect of gentisic acid(GA)on rheumatoid arthritis(RA)based on the miR-19b-3p/RAF1 axis.Methods The cell counting kit-8 method was used to detect the growth inhibitory effect of different concentrations of GA on MH7A cells,and the drug concentration of GA was determined in the experiment.The quantificational real-time polymerase chain reaction(qRT-PCR)was used to detect the expression of miR-19b-3p and RAF1.RAF1,extracellular regulated protein kinases1/2(ERK1/2)and phospho-ERK1/2(p-ERK1/2)were examined by Western blotting.Three methods(dual-luciferase assay,qRT-PCR and Western blot analysis)were used to verify miR-19b-3p targeting RAF1.Flow cytometry was performed to detect MH7A cell apoptosis.Transwell and wound healing assays were used to determine the invasion and migration capacities of MH7A cells.Results The growth of MH7A cells was gradually inhibited with increasing GA concentration.When the GA concentration exceeded 80 mmol/L,GA was significantly cytotoxic to MH7A cells,so the half maximal inhibitory concentration of GA for MH7A cells was calculated as 67.019 mmol/L.GA upregulated miR-19b-3p expression,downregulated RAF1 expression,inhibited ERK1/2 phosphorylation,induced MH7A cell apoptosis and suppressed MH7A cell invasion and migration(P<0.05 or P<0.01).RAF1 was identified as the target of miR-19b-3p and reversed inhibitory effects on miR-19b-3p expression(P<0.05 or P<0.01).The miR-19b-3p inhibitor upregulated RAF1 expression and ERK1/2 phosphorylation,suppressed MH7A cell apoptosis and induced MH7A cell invasion and migration(P<0.01).Conclusion GA regulated miR-19b-3p/RAF1 axis to mediate ERK pathway and inhibit the development of RA.