Yabo Ma

Identifying the specific factors secreted during early pregnancy is an effective method for pregnancy detection in cattle, helping to reduce empty pregnancies in the industry. To systematically investigate metabolic variations between early pregnancy and the estrous cycle and their relationship with pregnancy progression, this study utilized four-dimensional data-independent acquisition (4D-DIA) proteomics and liquid chromatography–tandem mass spectrometry (LC-MS/MS) metabolomics to analyze serum samples collected from Chinese native yellow cattle at day 0 and day 21 post-mating, combining bioinformatics analysis with experimental validation. The platelet activation signaling pathway and angiogenesis-related proteins were significantly upregulated. Among them, fibrinogen alpha/beta/gamma chains (FG) exhibited notable differences, with their branched-chain protein FGB showing highly significant upregulation (p = 0.003, Log₂FC = 2.167) and tending to increase gradually during early pregnancy, suggesting that FGB could be one of the important indicators of early pregnancy in Chinese native yellow cattle. Among the differential metabolites, 11-Deoxy prostaglandin F1α (p < 0.001, Log₂FC = 1.563), Thromboxane B1 (p = 0.002, Log₂FC = 3.335), and Homo-Gamma-Linolenic Acid (C20:3) (p = 0.018, Log₂FC = 1.781) were also increased, indicating their involvement in the regulation of the platelet activation signaling pathway. The platelet activation signaling pathway plays a crucial role in maternal immune tolerance and placental vascularization, which are essential for embryo implantation and placental development. These findings indicate that FGB has the potential to be a valuable biomarker for early cattle pregnancy detection, thereby improving pregnancy diagnosis accuracy, reducing economic losses caused by undetected empty pregnancies and enhancing reproductive efficiency in the cattle industry. Undoubtedly, our research outcomes must be validated with future studies, and a larger sample size as well as the evaluation of the potential endocrine effects induced by the synchronized estrus treatment must be considered.

Pyroptosis is a host immune strategy to defend against Mycobacterium tuberculosis (Mtb) infection. S100A4, a calcium-binding protein that plays an important role in promoting cancer progression as well as the pathophysiological development of various non-tumor diseases, has not been explored in Mtb-infected hosts. In this study, transcriptome analysis of the peripheral blood of patients with pulmonary tuberculosis (PTB) revealed that S100A4 and GSDMD were significantly up-regulated in PTB patients’ peripheral blood. Furthermore, there was a positive correlation between the expression of GSDMD and S100A4. KEGG pathway enrichment analysis showed that differentially expressed genes between PTB patients and healthy controls were significantly related to inflammation, such as the NOD-like receptor signaling pathway and NF-κB signaling pathway. To investigate the regulatory effects of S100A4 on macrophage pyroptosis, THP-1 macrophages infected with Bacillus Calmette-Guérin (BCG) were pre-treated with exogenous S100A4, S100A4 inhibitor or si-S100A4. This research study has shown that S100A4 promotes the pyroptosis of THP-1 macrophages caused by BCG infection and activates NLRP3 inflammasome and NF-κB signaling pathways, which can be inhibited by knockdown or inhibition of S100A4. In addition, inhibition of NF-κB or NLRP3 blocks the promotion effect of S100A4 on BCG-induced pyroptosis of THP-1 macrophages. In conclusion, S100A4 activates the NF-κB/NLRP3 inflammasome signaling pathway to promote macrophage pyroptosis induced by Mtb infection. These data provide new insights into how S100A4 affects Mtb-induced macrophage pyroptosis.

Premature ovarian insufficiency (POI) is a complex disease which causes amenorrhea, hypergonadotropism and infertility in patients no more than 40 years old. Recently, several studies have reported that exosomes have the potential to protect ovarian function using a POI-like mouse model induced by chemotherapy drugs. In this study, the therapeutic potential of exosomes derived from human pluripotent stem cell–mesenchymal stem cells (hiMSC exosomes) was evaluated through a cyclophosphamide (CTX)-induced POI-like mouse model. POI-like pathological changes in mice were determined by serum sex-hormones levels and the available number of ovarian follicles. The expression levels of cellular proliferation proteins and apoptosis-related proteins in mouse ovarian granulosa cells were measured using immunofluorescence, immunohistochemistry and Western blotting. Notably, a positive effect on the preservation of ovarian function was evidenced, since the loss of follicles in the POI-like mouse ovaries was slowed. Additionally, hiMSC exosomes not only restored the levels of serum sex hormones, but also significantly promoted the proliferation of granulosa cells and inhibited cell apoptosis. The current study suggests that the administration of hiMSC exosomes in the ovaries can preserve female-mouse fertility.

Objective: Hyperandrogenemia (HA) is the main pathophysiological change that takes place in polycystic ovary syndrome (PCOS). Cyproterone acetate (CYA) is a drug commonly used to reduce androgen in patients with PCOS. Long-term and continuous exposure to HA can cause ovarian granulosa cells (GCs), pyroptotic death, and follicular dysfunction in PCOS mice. The aim of this study was to investigate whether CYA could ameliorate the hyperandrogenemia-induced pyroptosis of PCOS ovarian GCs by alleviating the activation of the IRE1α signaling pathway. Methods: Firstly, thirty PCOS patients with HA as their main clinical manifestation were selected as the study group, and thirty non-PCOS patients were selected as the control group. The GCs and follicular fluid of the patients were collected, and the expression of pyroptosis-related proteins was detected. Secondly, a PCOS mouse model induced by dehydroepiandrosterone (DHEA) was constructed, and the treatment group model was constructed with the subcutaneous injection of cyproterone acetate in PCOS mice. The expression of pyroptosis-related protein in ovarian GCs was detected to explore the alleviating effect of CYA on the pyroptosis of ovarian GCs in PCOS mice. Thirdly, KGN cells-i.e., from the human GC line-were cultured with dihydrotestosterone, CYA, and ERN1 (IRE1α gene) small interfering RNA in vitro to explore whether CYA can alleviate the activation of the IRE1α signaling pathway and ameliorate the hyperandrogenemia-induced pyroptosis of PCOS ovarian GCs. Results: The expression of pyroptosis-related proteins was significantly increased in ovarian GCs of PCOS patients with HA as the main clinical manifestation, and in the PCOS mouse model induced by DHEA. After treatment with CYA, the expression of pyroptosis-related proteins in the ovarian GCs of mice was significantly lower than that in PCOS mice. In vitro experiments showed that CYA could ameliorate KGN cells’ pyroptosis by alleviating the activation of the IRE1α signaling pathway. Conclusion: This study showed that CYA could ameliorate the activation of the IRE1α signaling pathway in mouse GCs and KGN cells, and also alleviate pyroptosis in ovarian GCs. This study provides a new mechanism and evidential support for CYA in the treatment of PCOS patients.