Bile acid-activated receptors in innate and adaptive immunity: targeted drugs and biological agents.

Bile acid-activated receptors (BARs) such as a G-protein bile acid receptor 1 and the farnesol X receptor are activated by bile acids (BAs) and have been implicated in the regulation of microbiota-host immunity in the intestine. The mechanistic roles of these receptors in immune signaling suggest that they may also influence the development of metabolic disorders. In this perspective, we provide a summary of recent literature describing the main regulatory pathways and mechanisms of BARs and how they affect both innate and adaptive immune system, cell proliferation, and signaling in the context of inflammatory diseases. We also discuss new approaches for therapy and summarize clinical projects on BAs for the treatment of diseases. In parallel, some drugs that are classically used for other therapeutic purposes and BAR activity have recently been proposed as regulators of immune cells phenotype. Another strategy consists of using specific strains of gut bacteria to regulate BA production in the intestine.

CD31 orchestrates metabolic regulation in autophagy pathways of rheumatoid arthritis.

Synovitis is characterized by a distinctmetabolic profile featuring the accumulation of lactate, a byproduct of cellular metabolism within inflamed joints. This study reveals that the activation of the CD31 signal by lactate instigates a metabolic shift, specifically initiating endothelial cell autophagy. This adaptive process plays a pivotal role in fulfilling the augmented energy and biomolecule demands associated with the formation of new blood vessels in the synovium of Rheumatoid Arthritis (RA). Additionally, the amino acid substitutions in the CD31 cytoplasmic tail at the Y663F and Y686F sites of the immunoreceptor tyrosine-based inhibitory motifs (ITIM) alleviate RA. Mechanistically, this results in the downregulation of glycolysis and autophagy pathways. These findings significantly advance our understanding of potential therapeutic strategies for modulating these processes in synovitis and, potentially, other autoimmune diseases.

Extraction of Flavonoids from the Saccharification of Rice Straw Is an Integrated Process for Straw Utilization.

To date, bioethanol is not economically competitive. One strategy to overcome this limitation is co-producing ethanol and high value-added products as an integrated process. The results of this study demonstrated that flavonoids could be extracted from rice straw, and the flavonoids apigenin and kaempferol were detected by HPLC. Compared with untreated straw, ball-milling slightly increased the total amount of flavonoids and antioxidant activity measured by ABTS, DPPH, and FRAP assays. The saccharification step in the bioconversion of straw strongly affected the extraction of flavonoids from straw. The residue obtained after saccharification of ball-milled straw for glucose production was more suitable for flavonoid extraction than untreated and ball-milled straw. The yield of flavonoids from the residue was 1.51-fold higher than that from untreated straw. The antioxidant activity of flavonoids derived from the residue was similar to that of flavonoid-rich biomasses such as rice bran and wheat bran. More importantly, saccharification may significantly affect the conditions of flavonoid extraction. In this respect, treatment with cellulase may reduce the extraction time from 2.0 to 0.5 h and the extraction temperature from 80 to 30 °C. Therefore, saccharification in the bioconversion of straw may be considered as an enzyme pretreatment step for the efficient extraction of flavonoids from straw, serving as a sustainable process for straw utilization.

Tapping the Bioactivity Potential of Residual Stream from Its Pretreatments May Be a Green Strategy for Low-Cost Bioconversion of Rice Straw.

In this study, it was found that the residual stream from pretreatments of rice straw exhibited high antioxidant activity. Assays based on the Folin-Ciocalteu colorimetric method confirmed that the residual stream contained large amounts of phenolic compounds. Three antioxidant assays were employed to evaluate the bioactivity of the residual stream. Strong linear correlations existed among the release of phenolic compounds, saccharification efficiency, and antioxidant activity. The alkaline pretreatment provided a much greater release of phenolic compounds, especially phenolic acids, compared to the acid pretreatment, and consequently, it had stronger linear correlations than the acid pretreatment. Antibacterial experiments demonstrated the ability of the phenolic compounds in the residual stream to inhibit the growth of microorganisms, indicating the potential of these compounds as antimicrobial agents. To discuss the possibility of the co-production of antimicrobial agents and biofuels/biochemicals, both acid and alkaline pretreatments were optimized using response surface methodology. Under the optimal conditions, 285.7 g glucose could be produced from 1 kg rice straw with the co-production of 3.84 g FA and 6.98 g p-CA after alkaline pretreatment. These results show that the recovery of phenolic compounds from the residual stream could be a green strategy for the low-cost bioconversion of rice straw.

Influence of rice straw-derived dissolved organic matter on lactic acid fermentation by Rhizopus oryzae.

Rice straw can be used as carbon sources for lactic acid fermentation. However, only a small amount of lactic acid is produced even though Rhizopus oryzae can consume glucose in rice straw-derived hydrolysates. This study correlated the inhibitory effect of rice straw with rice straw-derived dissolved organic matter (DOM). Lactic acid fermentations with and without DOM were conducted to investigate the effect of DOM on lactic acid fermentation by R. oryzae. Fermentation using control medium with DOM showed a similar trend to fermentation with rice straw-derived hydrolysates, showing that DOM contained the major inhibitor of rice straw. DOM assay indicated that it mainly consisted of polyphenols and polysaccharides. The addition of polyphenols and polysaccharides derived from rice straw confirmed that lactic acid fermentation was promoted by polysaccharides and significantly inhibited by polyphenols. The removal of polyphenols also improved lactic acid production. However, the loss of polysaccharides during the removal of polyphenols resulted in low glucose consumption. This study is the first to investigate the effects of rice straw-derived DOM on lactic acid fermentation by R. oryzae. The results may provide a theoretical basis for identifying inhibitors and promoters associated with lactic acid fermentation and for establishing suitable pretreatment methods.

Release of Polyphenols Is the Major Factor Influencing the Bioconversion of Rice Straw to Lactic Acid.

In this study, we found that p-coumaric acid (p-CA), ferulic acid (FA), and condensed tannins were released from rice straw during saccharification. The presence of polyphenols prolonged the lag phase and lowered the productivity of lactic acid. p-CA was identified as a key inhibitor. Tannins had a lower inhibitory effect than p-CA; FA had little inhibitory effect. Acid, alkaline, and ball milling pretreatments elicited different levels of polyphenol release from rice straw. Due to the different levels of polyphenol release in the pretreatment step, the enzymatic hydrolysates contained different concentrations of polyphenols. Compared with fermentation with a synthetic medium, fermentation with the hydrolysates of ball-milled rice straw provided much lower productivity and yield of lactic acid due to the presence of polyphenols. Removal of these compounds played an important role in lactic acid fermentation. When rice straw was alkaline pretreated, the hydrolysates contained few phenolic compounds, resulting in high productivity and yield of lactic acid (1.8 g/L/h and 26.7 g/100 g straw), which were comparable to those in a synthetic medium. This indicates that there is a correlation between removal of phenolic compounds and efficiency in lactic acid fermentation.

Effects of different cellulases on the release of phenolic acids from rice straw during saccharification.

Effects of different cellulases on the release of phenolic acids from rice straw during saccharification were investigated in this study. All cellulases tested increased the contents of phenolic acids during saccharification. However, few free phenolic acids were detected, as they were present in conjugated form after saccharification when the cellulases from Trichoderma reesei, Trichoderma viride and Aspergillus niger were used. On the other hand, phenolic acids were present in free form when the Acremonium cellulolyticus cellulase was used. Assays of enzyme activity showed that, besides high cellulase activity, the A. cellulolyticus cellulase exhibited high feruloyl esterase (FAE) activity. A synergistic interaction between FAE and cellulase led to the increase in free phenolic acids, and thus an increase in antioxidative and antiradical activities of the phenolic acids. Moreover, a cost estimation demonstrated the feasibility of phenolic acids as value-added products to reduce the total production cost of ethanol.