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Background: Hepatic fibrosis and its associated consequences continue to pose a substantial global health challenge. Developing novel approaches to hepatic fibrosis management and prevention is critically necessary. Radix Paeoniae Alba (RPA) is widely used in Traditional Chinese Medicine (TCM) to treat various diseases. Our earlier research found that a bioactive component of RPA had a dose-dependent effect on anti-allergic asthma. RPA reduces allergic asthma by slowing the hepatic wind, according to "Treatise on Febrile Diseases". However, this bioactive fraction's pharmacological effects and mechanisms on the liver are unknown., Aim: This study examined the bioactive fraction MP-40, the methanol extract of RPA (MRPA), on bile duct ligation (BDL) for its anti-hepatic fibrosis activity and potential mechanisms., Methods: First, the effectiveness of MP-40 in treating BDL-induced hepatic fibrosis in mice and rats was evaluated through survival rates, ALT, AST HYP, and pathological changes. Molecular assays were performed using in vitro cultures of HSC-T6 activation. The expression of α-SMA and Collagen I evaluated fibro-tropic factors with HSC activation. Furthermore, the levels of pyroptosis were assessed by examining the expression of the pyroptosis-related proteins, including NLRP3, Cleaved Caspase-1, GSDMD-N, and 1L-1β. Additionally, the effective constituents of MP-40 were identified by extraction, separation, and identification. Finally, PF and TGG, as the delegate compounds of MP-40, were tested to confirm their inhibition effects on HSC-T6 activation., Results: The findings demonstrated that MP-40 and MRPA could lower ALT, AST, and HYP levels, boost survival rates, and reduce liver damage in BDL mice and rats. Furthermore, MP-40 outperforms MRPA. MP-40 was proven to drastically diminish fibrotic α-SMA and Collagen I. The expression of pyroptosis-related proteins NLRP3, Cleaved Caspase-1, TGF-β1, GSDMD-N, and 1L-1β decreased. MP-40 inhibited the synthesis of pyroptosis-related proteins more effectively than MCC950 (an NLRP3-specific inhibitor). Monoterpene glycosides and tannins were shown to be the most potent MP-40 components. Finally, the delegate compounds MP-40, PF, and TGG were shown to have substantial inhibitory effects on HSC-T6 activation., Conclusion: The results proved that MP-40 alleviates BDL-induced cholestatic hepatic fibrosis by inhibiting NLRP3-mediated pyroptosis. PF and TGG play a role in treating BDL-induced cholestatic hepatic fibrosis in MP-40., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wan, Fang, Qin, Zheng, Yang, Peng, Hao, Wang, Zhao, Shi, Han, Sang and Cao.)

Type 2 innate lymphoid cells were found to be members of the innate immune cell family, which is involved in innate and adaptive immunity to resist the invasion of foreign antigens and induce allergic reactions caused by allergens. The advancement of ILC2 research has pointed out that ILC2s have a high degree of diversity, challenging the notion of their homogeneity as a cellular population. An increasing number of studies indicate that ILC2 is a cell population with tissue specificity which can be induced by the tissue microenvironment. In addition, crosstalk between tissues can change ILC2 functions of migration and activation. Here, we emphasize that ILC2 undergoes adaptive changes under the regulation of the tissue microenvironment and distant tissues, thereby coordinating the organization's operation. In addition, ILC2 alterations induced by the tissue microenvironment are not limited to the ILC2 cell population, and ILC2 can also transdifferentiate into another class of ILC cell population (ILC1 or ILC3). In this review, we summarized the tissue-specific effects of ILC2 by tissue microenvironment and focused on the function of ILC2 in inter-tissue crosstalk. Lastly, we discussed the transdifferentiations of ILC2 caused by the abnormal change in tissue environment., (© 2024. The Author(s).)

Ethnopharmacological Relevance: Radix Paeoniae Alba (RPA), a traditional Chinese medicine, has been used frequently in the treatment of asthma. Previous studies demonstrated the dichloromethane fraction of Stir-Frying RPA (FDCM) enhanced the effect of anti-allergic asthma compared with the dichloromethane fraction of RPA (DCM)., Aim of the Study: The significant increasing of Paeoniflorin (PF), ethyl gallate (EG), 1,2,3,4,6-pentagalloylglucose (PGG) had been observed in FDCM. This study aimed to investigate the effects and mechanisms of these compounds from FDCM in ovalbumin (OVA)-induced allergic asthma mouse model., Materials and Methods: The significant difference contents compounds fraction (FB-40) and other fractions in FDCM were enriched by Medium Pressure Liquid Chromatography (MPLC). The pharmacodynamics was verified among all fractions in OVA-induced allergic asthma mice. Moreover, the drug dose dependence of FB-40 (0.42 mg/kg, 0.21 mg/kg, and 0.07 mg/kg), which were the most active fraction from FDCM for anti-allergic asthma, was explored. The expression of IL-6, p-STAT3, and STAT3 was analyzed by Western blot analysis. In addition, the main components of FB-40 were identified by UPLC with standards. Finally, the anti-inflammatory effects of the main components from FB-40 were detected by LPS-stimulated BEAS-2B cells using an Elisa assay., Results: The results showed that FB-40 was the most active fraction from FDCM, which could significantly improve the lung tissue pathological condition, and decrease the number of inflammatory cells in bronchoalveolar lavage fluid (BALF). It had greater pharmacological activity than its main component PF. FB-40 also showed dose dependence and regulated the IL-6/STAT3 signaling pathway in allergic asthma mice. Besides, PF, Albiflorin (AF), PGG, EG, and 1,2,3,6-Tetra-O-galloyl-β-D-glucose (TGG) from FB-40 were identified by UPLC with the standard. At last, in the LPS-induced BEAS-2B cell experiments, EG, PGG, 1,2,3,6-Tetra-O-galloyl-β-D-glucose (TGG) showed stronger inhibiting activities of cytokine than the monoterpenoid glycosides (PF and AF)., Conclusion: The research proved that FB-40 was an active fraction in FDCM, which regulates IL-6/STAT3 Signaling Pathway to ameliorate allergic asthma. Gallic acids including TGG and PGG, and EG also play a role in the treatment of allergic asthma in FB-40., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2022. Published by Elsevier B.V.)

CircRNAs have been reported to be related to hepatocellular carcinoma (HCC) development. Limited studies have revealed the expression profile of circRNAs in tumor and para-tumor normal samples in HCC patients. We found that circASPH was significantly increased in HCC tumor samples and that the level of circASPH was closely related to the overall survival of HCC patients. Mechanistically, circASPH could regulate the methylation of the promoter and expression of hydrocyanic oxidase 2 (HAO2) to promote HCC progression by acting as a sponge for miR-370-3p, and miR-370-3p could target DNMT3b and increase the 5mC level. In summary, our study determined that circASPH could regulate the methylation and expression of HAO2 and it could be considered an important epigenetic regulator in HCC progression., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zhuo, Xia, Zhang, Tang, Han, Zheng, Zhu, Zhang, Xu, Sun, Tan and Wu.)

Background: Gallbladder cancer (GBC) is highly malignant, its early diagnosis is difficult, and the 5-year survival rate is less than 5%. For patients with advanced GBC (GBCa), combined chemotherapy, radiotherapy, targeted therapy, and immunotherapy are needed to improve the overall survival (OS) rate of patients., Methods: Data were collected from 53 patients with GBCa who had volunteered to receive programmed death protein-1 (PD-1)-based treatment at the First Affiliated Hospital of Nanjing Medical University from February 2018 to February 2021. Statistical analysis of the collected data, including Kaplan-Meier method, log-rank test, Cox proportional hazard regression model and other methods., Results: The objective response rates (ORRs) and disease control rates (DCRs) of 53 participants 3 months after receiving immunotherapy were 30.2% and 79.2%, respectively. The ORRs and DCRs of the combined treatment group were higher than those of the camrelizumab group (CG) (P<0.05). The DCRs of the camrelizumab plus apatinib group (CAG) at 3 and 6 months were 90.9% and 45.5% (P=0.003), respectively, while the DCRs at 3 and 6 months of the camrelizumab plus chemotherapy group (CCG) were 85.7% and 71.4% (P=0.450), respectively. After treatment, there were statistically significant differences before and after CA199 for each group (P<0.05). The median progression-free survival (mPFS) of the 53 participants was 7 months, and the median overall survival (mOS) was 12 months. The mPFS and mOS of the CAG and the CCG were greater than those in the CG (6 vs. 3 months, P<0.001, 12 vs. 8 months, P=0.019; 9 vs. 3 months, P<0.001, 13 vs. 8 months, P<0.001, respectively). A total of 16 cases had grade 1 or 2 adverse events, and 3 cases had grade 3 and higher adverse events., Conclusions: For GBCa patients, PD-1 combined with targeted therapy or chemotherapy is more effective than immunotherapy alone. The targeted therapy group has more obvious early effects on the disease control rate, and combined chemotherapy can achieve sustained effects, providing new ideas for the future GBCa application of immune, targeted, and chemotherapy sequential therapy., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://dx.doi.org/10.21037/atm-21-4747). All authors reported that the project was supported by the National Natural Science Foundation of China (81871259 and 820706752), and the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences (2019-I2M-5-035). Dr. LL serves as an unpaid Associate Editors-in-Chief of Annals of Translational Medicine from Jun 2019 to May 2024. The authors have no other conflicts of interest to declare., (2021 Annals of Translational Medicine. All rights reserved.)

Background: Prostate cancer (PCa) is the second lethal heterogeneous cancer among males worldwide, and approximately 20% of PCa patients following radical prostatectomy (RP) will undergo biochemical recurrence (BCR). This study is aimed to identify the immune-related gene signature that can predict BCR in localized PCa following RP., Methods: Expression profile of genes together with clinical parameters from The Cancer Genome Atlas (TCGA) and the Gene Expression Omnibus database (GEO) and the immune-related genes from the Molecular Signatures Database v4.0 were applied to construct and validate the gene signature. The Cox regression analyses were conducted to identify the candidate genes and establish the gene signature. To estimate the prognostic power of the risk score, the time-dependent receiver operating characteristic (ROC) analysis and Harrell's index of concordance (C-index) were utilized. We also established a nomogram to forecast the probability of patients' survival., Results: A total of 268 patients from the TCGA and 77 patients from GSE70770 and six immune-related genes ( SCIN, THY1, TBX1, NOTCH4, MAL, BNIP3L ) were eventually selected. The Kaplan-Meier analysis demonstrated that patients in the low-risk group had a significantly longer recurrence-free survival (RFS) compared to those in the high-risk group. In the multivariate Cox model, the signature was identified as an independent prognostic factor, which was significantly associated with RFS (TCGA: HR =5.232, 95% CI: 1.762-15.538, P=0.003; GSE70770: HR =2.158, 95% CI: 1.051-4.432, P=0.036). Moreover, the C-index got improved after incorporating the risk score into original clinicopathological parameters. In addition, the novel nomogram was constructed to better predict the 1-, 3- and 5-year RFS., Conclusions: This signature could serve as an independent prognostic factor for BCR. Incorporation of our signature into traditional risk classification might further stratify patients with different prognosis, which could assist practitioners in developing clinical decision-making., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/tau-20-1231). The authors have no other conflicts of interest to declare., (2021 Translational Andrology and Urology. All rights reserved.)