Impaired decidualization was recognized as one of the crucial pathomechanisms accounting for unexplained recurrent spontaneous abortion (URSA). Currently, the exact molecular mechanism and targeted clinical decision are still in exploration. Bushen Huoxue decoction (BSHXD) has previously been proved effective in treating URSA, but its mechanism remains to be elucidated. This study aimed to explore the regulation mechanism of BSHXD in decidualization from its intervention in autophagy so as to rationalize its potential as a novel therapeutic regime for URSA. Decidua tissues were collected from patients with URSA and healthy pregnant women who underwent legal terminations for non-medical reasons at the first trimester. Besides, cell line T-hESCs was utilized to establish induced decidualization model, and were randomly divided into ESC group, DSC group, 3-MA group, AMPK siRNA group, scrambled siRNA group and AMPK siRNA + BSHXD group. Transmission electron microscopy, Monodansylcadaverine (MDC) assay, qRT-PCR, immunohistochemistry, immunofluorescence and Western blotting were used to evaluate the level of decidualization, autophagy and activation of AMPK signaling pathway in decidua tissues and cell experiments. Experiments on decidua tissues showed that decidualization was impaired in URSA with inhibited autophagy. Besides, pAMPK T172 and pULK1 S556 were decreased, and pmTOR S2448 and pULK1 S757 were increased. Cell experiments showed that the level of autophagy increased during induced decidualization, but when autophagy was inhibited, decidualization was impaired. In addition, AMPK/mTOR/ULK1 affected decidualization by mediating autophagy, and BSHXD improved decidualization through this mechanism. In conclusion, this study clarified that the inhibition of autophagy mediated by AMPK/mTOR/ULK1 was associated with impaired decidualization, and the intervention of BSHXD on this pathological process may be a vital mechanism for its treatment of URSA. This study laid the foundation for further research and application of BSHXD.
Unexplained recurrent pregnancy loss (URPL) is a complex pathological condition that poses significant challenges for women of childbearing age. As a critical component of epigenetics, post-translational modifications (PTMs) not only regulate protein expression and enhance its diversity but also modulate interactions between proteins and other molecules. PTMs play an essential role in the onset and progression of URPL. For example, methylation modifications can hinder decidualization and regulate trophoblast migration and invasion. Phosphorylation modifications can balance regulatory T cells (Treg)/T helper 17 cells (Th17), polarize macrophages, alter dendritic cell populations, and promote trophoblast apoptosis. Acetylation modifications can induce trophoblasts autophagy and suppress M2 macrophage polarization. Ubiquitination modifications can modulate trophoblast migration and invasion and disrupt the immune microenvironment. Glycosylation modifications can inhibit trophoblast migration and invasion, while lactylation modifications maintain endometrial receptivity. The role of PTMs in URPL highlights their potential as a research entry point and therapeutic target for this condition.
In orthodontics treatment, scholars have tried to introduce nano antibacterial materials into the materials used in orthodontics to reduce the occurrence of enamel demineralization, caries and periodontitis. The experiment investigated the effect of adding titanium dioxide nanoparticles in different proportions on the flexural strength, compressive strength, surface hardness, tribological properties, adhesion properties, fluorine release properties and antibacterial properties of glass ionomer cement. The effect of water cement on orthodontics, the experiment added different proportions of titanium dioxide nanoparticles to traditional glass ion cement, which greatly improved the mechanical strength of glass ion cement, and significantly improved the antibacterial effect of glass ion cement, bending strength, compressive strength and surface hardness. The addition of titanium dioxide nanoparticles produced a significant antibacterial effect on Streptococcus mutants. Nano-TiO 2 glass ionomer cement has a significant effect on orthodontics, and the damage to patients’ teeth is significantly lower, which is worthy of clinical popularization.
Abstract The bromodomain‐containing protein 4 (BRD4) is highly expressed in oral squamous cell carcinoma (OSCC) and plays a crucial role in tumour progression. However, the impact of BRD4 on the efficacy of chemotherapy and radiotherapy by regulating the expression of programmed cell death‐ligand 1 (PD‐L1) in OSCC remains unclear. In this study, we found that the BRD4 inhibitor JQ1 effectively enhanced the inhibitory effects of cisplatin and radiotherapy on cell proliferation and promoted the apoptosis of OSCC cells by cisplatin and radiotherapy. Furthermore, treatment with JQ1 reversed the increase of the expression of PD‐L1 by cisplatin and radiotherapy, whereas the overexpression of PD‐L1 partially countered the beneficial effects of JQ1 on the anticancer efficacy of cisplatin and radiotherapy. These results demonstrate that the inhibition of BRD4 improves the anticancer effect of chemotherapy and radiotherapy by suppressing the expression of PD‐L1 in OSCC, suggesting that targeting BRD4 could be a promising therapeutic approach for chemo/radioresistant OSCC.
By modulating the metal centers to adjust the coordination surroundings of the products, two mixed-linker coordination polymers [Cu2(L)(biz)(OH)]·H2O (1) and [Zn(HL)(biz)] (2) (H3L = 5-(4-carboxybenzyloxy)isophthalic acid, biz = benzimidazole), have been produced under mild hydrothermal conditions. To develop new candidates for the acute oral mucositis during orthodontic process, the acute oral mucositis rat model was constructed and the enzyme linked immunosorbent assay (ELISA) was used to find out the release levels of inflammatory cytokines Tumor Necrosis Factor-α (TNF-α) and Interleukin-1β (IL-1β). Next, the activation of the AKT signaling pathway was estimated through judging the relative expression of the inflammatory genes in the oral mucosa cells via reverse transcription-polymerase chain reaction (RT-PCR). After compounds treatment, the expression level of the AKT signaling pathway was evaluated by a western blot. Finally, the quantity of the reactive oxygen species (ROS) in the oral mucosa cells was gauged with ROS detection kit. All the results in this research indicated the much more excellent treatment activity of compound 1 than 2 on the acute oral mucositis.
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