Background: Ribosome stalling on ermBL at the tenth codon (Asp) and mRNA stabilization are believed to be mechanisms by which erythromycin (Ery) induces ermB expression. Expression of ermB is also induced by 16-membered ring macrolides (tylosin, josamycin and spiramycin), but the mechanism underlying this induction is unknown. Methods: We introduced premature termination codons, alanine-scanning mutagenesis and amino acid mutations in ermBL and ermBL2. Results: In this paper, we demonstrated that 16-membered ring macrolides can induce ermB expression but not ermC expression. The truncated mutants of the ermB-coding sequence indicate that the regulatory regions of ermB whose expression is induced by Ery and 16-membered ring macrolides are different. We proved that translation of the N-terminal region of ermBL is key for the induction of ermB expression by Ery, spiramycin (Spi) and tylosin (Tyl). We also demonstrated that ermBL2 is critical for the induction of ermB expression by erythromycin but not by 16-membered ring macrolides. Conclusions: The translation of ermBL and the RNA sequence of the C-terminus of ermBL are critical for the induction of ermB expression by Spi and Tyl.

Introduction: Sepsis-related acute liver injury (SALI) is a severe and life-threatening complication in septic patients, for which current therapeutic options are limited. This study aimed to investigate the potential protective role of taurochenodeoxycholic acid (TCDCA) against SALI and to elucidate the underlying mechanisms. Methods: A cecal ligation and puncture (CLP) mouse model was employed to induce SALI. The effects of TCDCA treatment were assessed by measuring serum liver injury markers (AST, ALT) and pro-inflammatory cytokines (IL-6, TNF-α, IL-1β). Liver histology, hepatocyte apoptosis, and the macrophage response were evaluated. Molecular docking was used to predict the interaction between TCDCA and the receptor TGR5, which was functionally validated using the TGR5 antagonist SBI-115. Transcriptomic analysis and Western blotting were performed to identify the key signaling pathways involved. Results: TCDCA treatment significantly reduced serum levels of AST and ALT, suppressed the production of IL-6, TNF-α, and IL-1β, and alleviated histological liver damage, including lobular disruption, inflammation, and hemorrhage. TCDCA also decreased hepatocyte apoptosis and modulated the liver macrophage response. Molecular docking confirmed a strong interaction between TCDCA and TGR5, and the protective effects of TCDCA were abolished by the TGR5 antagonist SBI-115. Transcriptomic analysis identified 430 differentially expressed genes after TCDCA treatment, with significant enrichment in pyroptosis-related pathways. Accordingly, Western blot analysis demonstrated that TCDCA inhibited the activation of the NLRP3 inflammasome and its downstream pyroptotic proteins, an effect that was also reversed by SBI-115. Discussion: Our findings demonstrate that TCDCA confers a protective effect against SALI by suppressing hepatocyte pyroptosis, and this action is mediated through the TGR5 receptor. These results highlight TCDCA as a promising therapeutic candidate for SALI. However, further research, including clinical trials, is necessary to address potential species-specific differences and to fully elucidate its comprehensive mechanisms of action.

Aims of This Study: A randomized clinical trial was undertaken to investigate the efficacy of acupoint catgut embedding (ACE) as adjunctive therapy to tauroursodeoxycholic acid (TUDCA) therapy on gallbladder emptying and clinical symptoms in patients with gallstone disease. Materials and Methods: Between August 2018 and January 2019, 70 patients with gallstones in our hospital were enrolled in this prospective clinical trial. All the patients were randomly divided into the ACE group (ACE+TUDCA treatment for 8 wk) and the Sham group (Sham ACE+TUDCA treatment for 8 wk). In the ACE group, all the patients were nightly given ACE every 2 weeks, and in 2 groups, every patient took TUDCA 500 mg at bedtime. The parameters about gallbladder emptying were detected by ultrasound before and after the treatment, and the clinical symptom scores were recorded at the same time points. Results: A total of 63 patients with gallstone disease were included in our study, with 33 patients in the ACE group and 30 patients in the Sham group. In the ACE group, the empty volume (EV) and gallbladder ejection fraction (GBEF) were improved after treatment (P<0.05). Almost every symptom score (except symptom 7, P=0.15) and total score were decreased (P<0.05). In the Sham group, the symptom 1, 2, 4, 5 scores, and total score were significantly decreased (P<0.05). Moreover, the residual volume in the ACE group was significantly lower than in the Sham group (P=0.008). The EV and GBEF in the ACE group were higher than that in the Sham group (P<0.05). The score of symptom 6 in the ACE group was lower than that in the Sham group (P=0.008). Conclusion: ACE therapy could more effectively improve the gallbladder emptying with a shorter treatment course. Therefore, ACE+TUDCA therapy might be a time-saving treatment for gallstones.