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Introduction: Endometriosis (EM) is a chronic estrogen-dependent condition characterized by the growth of endometrial-like tissue outside the uterus, posing a significant burden on reproductive-aged women. Previous research has shown a correlation between gut microbiota dysbiosis and interleukin-17A (IL-17A) in EM patients. IL-17A, a promising immunomodulatory molecule, exerts dual roles in human physiology, driving inflammatory diseases. However, the functions and origins of IL-17A in EM remain poorly characterized. Methods: Single-cell data analysis was employed to characterize IL-17A activity in EM lesions. Fecal microbiota transplantation was conducted to explore the impact of gut microbiota on EM. Gut microbiota and bile acid metabolism were assessed via 16S rRNA sequencing and targeted metabolomics. Th17 cell proportions were measured using flow cytometry. Results: High expression of IL-17 receptor A (IL-17RA) was observed in myeloid cell subpopulations within EM lesions and may be involved in the migration and recruitment of inflammatory cells in lesions. Elevated IL-17A levels were further validated in peritoneal and follicular fluids of EM patients. Dysregulated bile acid levels, particularly elevated chenodeoxycholic acid (CDCA) and ursodeoxycholic acid (UDCA), were found in the gut and peritoneal fluid of EM mouse models. Additional CDCA administration reduced EM lesions and modulated Th17 cell proportions, while UDCA showed no significant effects. Discussion: Our findings shed light on the origins and functions of IL-17A in EM, implicating its involvement in lesion migration and recruitment. Dysregulated bile acid metabolism may contribute to EM pathogenesis, with CDCA exhibiting therapeutic potential. [ABSTRACT FROM AUTHOR]

On the basis of the previous research, the Traditional Chinese Medicine theory was used to improve the drug composition for gastrointestinal acute radiation syndrome (GI-ARS). The purpose of this study was to study the therapeutic mechanism of Liangxue-Guyuan-Yishen decoction (LGYD) on GI-ARS and to provide a new scheme for the treatment of radiation injury. Here, we investigated the effects of LGYD on intestinal stem cells (ISCs) in a GI-ARS rat model. Rat health and survival and the protective efficacy of LGYD on the intestines were analyzed. The active principles in LGYD were detected using liquid chromatography-mass spectrometry (LC–MS). ISC proliferation, intestinal epithelial tight junction (TJ) protein expression and regulatory pathways were explored using immunohistochemistry, western blotting (WB) and reverse transcription quantitative polymerase chain reaction (RT-qPCR), respectively. Involvement of the WNT and MEK/ERK pathways in intestinal recovery was screened using network pharmacology analysis and validated by WB and RT-qPCR. LGYD administration significantly improved health and survival in GI-ARS rats. Pathological analysis showed that LGYD ameliorated radiation-induced intestinal injury and significantly promoted LGR5+ stem cell regeneration in the intestinal crypts, upregulated TJ protein, and accelerated crypt reconstruction in the irradiated rats. LC–MS revealed ≥13 constituents that might contribute to LGYD's protective effects. Collectively, LGYD can promote crypt cell proliferation and ISCs after radiation damage, the above effect may be related to WNT and MEK/ERK pathway. [ABSTRACT FROM AUTHOR]

Objective. To explore the mechanisms of follicular fluids (FFs) on granulose cell (GC) apoptosis in endometriosis-associated infertility. Materials and Methods. 60 infertile women were enrolled. The FFs from 30 endometriosis-associated infertility (EI) patients were collected and processed by ELISA hormone assay and proteomic profiling. The ovary GCs collected from 30 tubal-associated infertility (TI) patients were cultured in follicular fluids of endometriosis-associated infertility patients (EI-FFs), and the apoptosis mechanisms were explored by flow cytometry assay, real-time PCR, Western blotting, and protein–protein interaction (PPI) network analysis. Results. Our results showed that the expression of 22 specific proteins was significantly different in the FFs from EI and TI patients, and the level of testosterone and anti-Müllerian hormone was not obviously different between the two groups. EI-FFs could accelerate the apoptosis process of granulose cells of tubal-associated infertility patients (TI-GCs) by regulating the expression of 5 apoptosis-related proteins including BCL2, BAX, CASP3, CASP9, and TP53. The correlation of these 22 specific proteins and 5 apoptosis-related proteins was analyzed by PPI, and 5 protein biomarkers (INS, CXCL10, ICAM1, WIF1, and TNFRSF13C) and 5 signaling pathways (cytokine-cytokine receptor interaction, apoptosis, regulation of actin cytoskeleton, MAPK, and p53 signaling pathway) were predicted. Conclusion. This research clarified the effect and explored the mechanisms of EI-FFs on the apoptosis of TI-GCs and indicated the protein biomarkers and signaling pathways for further study. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to investigate whether curcumin has a therapeutic effect on endometriosis (EM) and to determine the specific mechanism., Methods: Network pharmacology was used to obtain the core targets of curcumin for the treatment of EM and the specific biologic processes involved. A mouse model of EM was constructed and divided into different groups, as follows: control, negative control, curcumin, and denogestrel. The number, volume, and degree of adhesions of the lesions in each group were measured. The levels of IL-1β, IL-6, and VEGFA in the peritoneal cavity were measured by enzyme-linked immunosorbent assay (ELISA). Western blot and Q-PCR were used to detect HIF-1α and VEGFA proteins and gene expression levels in the lesion tissues., Results: Network pharmacology suggested that curcumin treated EM through the HIF signaling pathway, of which IL-6, HIF-1α, and VEGFA are key targets. The number of lesions, volume, and degree of adhesions were significantly reduced in the curcumin group compared to the negative control group and the control group (P < 0.05). IL-6, IL-1β, and VEGFA levels were reduced in the peritoneal fluid (P < 0.05). HIF-1α and VEGFA protein and gene levels were significantly reduced in the lesions (P < 0.05). No modulation of HIF-1α was shown by denogestins., Conclusion: Curcumin played a role in the treatment of EM by modulating the HIF signaling pathway, improving the local hypoxia of the lesion, and reducing the inflammatory state of EM., Competing Interests: None., (AJTR Copyright © 2022.)

Immune reactions are a key factor in determining the destiny of bone substitute materials after implantation. Macrophages, the most vital factor in the immune response affecting implants, are critical in bone formation, as well as bone biomaterial-mediated bone repair. Therefore, it is critical to design materials with osteoimmunomodulatory properties to reduce host-to-material inflammatory responses by inducing macrophage polarization. Our previous study showed that calcium silicate (CS) bioceramics could significantly promote osteogenesis. Herein, we further investigated the effects of CS on the behavior of macrophages and how macrophages regulated osteogenesis. Under CS extract stimulation, the macrophage phenotype was converted to the M2 extreme. Stimulation by a macrophage-conditioned medium that was pretreated by CS extracts resulted in a significant enhancement of osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), indicating the important role of macrophage polarization in biomaterial-induced osteogenesis. Mechanistically, oncostatin M (OSM) in the macrophage-conditioned medium promoted osteogenic differentiation of BMSCs through the ERK1/2 and JAK3 pathways. This in vivo study further demonstrated that CS bioceramics could stimulate osteogenesis better than β-TCP implants by accelerating new bone formation at defective sites in the femur. These findings improve our understanding of immune modulation of CS bioactive ceramics and facilitate strategies to improve the in vitro osteogenesis capability of bone substitute materials., Competing Interests: The authors have no competing financial interests to declare., (© 2020 [The Author/The Authors].)