Gut microbial bile acid metabolite skews macrophage polarization and contributes to high-fat dietinduced colonic inflammation,

The precipitation of calcium oxalate can be either grown into structural support in plants or precipitated as stones in human kidneys. Previously, citrate, an effective inhibitor for oxalate stone formation, was suggested to alter the crystallization pathway of calcium oxalate and enhance the formation of less stable calcium oxalate trihydrate; however, the underlying mechanism is unknown. Herein we investigated the role of citric acid on crystallization pathways of calcium oxalate hydrates and the effect of supersaturation. It was found that the presence of citric acid can modulate the water content of amorphous nucleated precipitates by TEM and XRD and hence promote the formation of different calcium oxalate hydrates. The remaining water content in amorphous precipitates depends upon the amount of citric acid employed. FTIR and XRD analyses further reveal the extreme structural similarities between amorphous precipitates and the resultant hydrates. Additionally, the role of citric acid on crystallization pathways could be completely changed by supersaturation of calcium oxalate. High supersaturation dominated by homogeneous nucleation can diminish or even invalidate citric acid roles. The findings highlight the interplay of roles between additives and supersaturations, and could improve current understandings on the formation mechanism of oxalate stone.

We recently have proved that excessive fecal DCA caused by high-fat diet may serve as an endogenous danger-associated molecular pattern to activate NLRP3 inflammasome and thus contributes to the development of inflammatory bowel disease (IBD). Moreover, the effect of DCA on inflammasome activation is mainly mediated through bile acid receptor sphingosine-1-phosphate receptor 2 (S1PR2); however, the intermediate process remains unclear. Here, we sought to explore the detailed molecular mechanism involved and examine the effect of S1PR2 blockage in a colitis mouse model. In this study, we found that DCA could dose dependently upregulate S1PR2 expression. Meanwhile, DCA-induced NLRP3 inflammasome activation is at least partially achieved through stimulating extracellular regulated protein kinases (ERK) signaling pathway downstream of S1PR2 followed by promoting of lysosomal cathepsin B release. DCA enema significantly aggravated DSS-induced colitis in mice and S1PR2 inhibitor as well as inflammasome inhibition by cathepsin B antagonist substantially reducing the mature IL-1β production and alleviated colonic inflammation superimposed by DCA. Therefore, our findings suggest that S1PR2/ERK1/2/cathepsin B signaling plays a critical role in triggering inflammasome activation by DCA and S1PR2 may represent a new potential therapeutic target for the management of intestinal inflammation in individuals on a high-fat diet.

Herein, we developed the strategy of additive-induced polymorph, realizing the selective crystallization of elusive Form-II of γ-aminobutyric acid, a potent bioactive compound. A series of sodium carboxylate additives with different carbon chain lengths (C2–C8) were identified to induce the crystallization of Form-II. It was found that additive molecules will inhibit the growth of the centrosymmetric Form-I at two opposite ends, thereby precluding it, but they will inhibit the growth of the polar Form-II at only one end so that it survives. Notably, these sodium carboxylate additives exhibited distinct inducing ability for Form-II; that is, the effective critical addition amount required to induce Form-II increases with the increase of carbon chain length. However, the sodium formate is an exception and it cannot induce the Form-II. The difference of the inducing ability of additives was rationalized based on the competition of attachment and detachment behavior of additives on the growth end of Form-I. When the extent to which the attachment is more favorable than the detachment is larger, the corresponding additive exhibits a better inhibition effect on Form-I and more remarkable inducing ability for Form-II.