Unexplained recurrent spontaneous abortion (URSA) is a severe challenge to reproductive females worldwide, and its etiology and pathogenesis have not yet been fully clarified. Abnormal intercellular communication between macrophages (Mφ) and decidual stromal cells (DSCs) or trophoblasts has been supposed to be the key to URSA. However, the exact molecular mechanisms in the crosstalk are not yet well understood. This study aimed to explore the potential molecule mechanism that may be involved in the communication between Mφ and DSC or trophoblast cells and determine their diagnostic characteristics by using the integrated research strategy of bioinformatics analysis, machine learning and experiments. First, microarrays of decidual tissue (GSE26787, GSE165004) and placenta tissue (GSE22490) in patients with URSA, as well as microarrays involving induced decidualization (GSE94644) and macrophage polarization in vitro (GSE30595) were derived from the gene expression omnibus (GEO) database. And 721 decidua-differentially expressed genes (DEGs), 613 placenta-DEGs, 510 Mφ polarization DEGs were obtained in URSA by differential expression analysis. Then, the protein-protein interaction (PPI) network was constructed, and the hub genes were identified by CytoHubba in Cytoscape software and validated by real-time PCR assay. Subsequently, immune enrichment analysis on decidua-DEGs and placenta-DEGs by ClueGO verified their regulation effects on Mφ. Besides, functional enrichment analysis was performed on Mφ polarization DEGs and the essential module genes derived from the weighted gene co-expression network analysis (WGCNA) to uncover the biological function that were related to abnormal polarization of Mφ. Furthermore, we screened out 29, 43 and 22 secreted protein-encoding genes from DSC-DEGs, placenta-DEGs and Mφ polarization DEGs, respectively. Besides, the hub secreted-protein-encoding genes were screened by CytoHubba. Moreover, we conducted functional enrichment analysis on these genes. And spearman correlation analysis between hub secreted-protein-encoding genes from donor cells and hub genes in recipient cells was performed to further understand the molecular mechanism of intercellular communication further. Moreover, signature genes with diagnostic value were screened from secreted protein-encoding genes by machine learning and validated by immunofluorescence co-localization analysis with clinical samples. Finally, three biomarkers of DSCs (FGF9, IL1R2, NID2) and three biomarkers of Mφ (CFB, NID2, CXCL11) were obtained. In conclusion, this project provides new ideas for understanding the mechanism regulatory network of intercellular communication involving macrophages at the maternal-fetal interface of URSA. Also, it provides innovative insights for the diagnosis and treatment of URSA.

Purpose: This bibliometric research aims to delineate global publication trends and emerging research interests in the use of acupuncture for breast cancer (BC)-related symptoms treatment over the past three decades. Furthermore, it identifies influential institutions, potential collaborative partners, and future research trends, thereby providing guidance for relevant, novel research directions. Methods: Scientific publications related to acupuncture for BC-related symptoms were gathered from the Web of Science Core Collection (WoSCC) from 1993 to 2023. Four software applications were principally used to analyze the resulting data: the “bibliometrix” package in the R environment (version 4.2.3), VOSviewer, CiteSpace6.1.R6, and the bibliometrics website. These applications were employed to evaluate different parameters. Results: A total of 621 papers on acupuncture in BC-related symptoms treatment were analyzed. The United States, China, and South Korea contributed the most, with Memorial Sloan Kettering Cancer Center, and Columbia University leading institutions. It is interesting to mention that Mao, Jun J. and Molassiotis, A. feature among the top 10 authors and co-cited authors. JAMA is the leading journal, with an ongoing focus on acupuncture’s effectiveness. Keywords show that the initial research focus was mainly on “vasomotor symptoms”, but in recent years there has been a gradual shift towards “pain”, “chemotherapy-induced peripheral neuropathy (CIPN)”, “electroacupuncture”, and “non-specific effects”. Conclusion: Acupuncture has demonstrated a unique value in the process of adjuvant treatment of BC-related symptoms, and has been shown to be effective in reducing pain, eliminating fatigue, and improving quality of life. The study of the mechanisms of acupuncture and the application of electroacupuncture are possible future research priorities in this field. This study offers a deep perspective on acupuncture for BC research, highlighting key points and future trends.

Unexplained recurrent spontaneous abortion (URSA) is characterized by defective endometrial stromal cell decidualization, with cellular senescence emerging

Background: Among women of childbearing age, polycystic ovary syndrome (PCOS) is the predominant etiology of anovulatory infertility. Recent research has elucidated the role of melatonin as a medicinal agent in PCOS, especially hyperandrogenism. However, the precise mechanisms underlying its therapeutic efficacy remain largely unknown. This study integrated network pharmacology, molecular docking, molecular dynamics simulations, and laboratory confirmation to explore the pharmacological mechanisms of melatonin in PCOS.Methods: First, we conducted animal studies to evaluate the therapeutic efficacy of melatonin by administering it to circadian disruption-induced PCOS-like rats. Prospective medicinal targets of melatonin were acquired from databases such as DrugBank, Traditional Chinese Medicine Systems Pharmacology, PharmMapper, and SwissTarget Prediction. Targets related to PCOS were extracted from three databases: DisGeNET, GeneCards, and the National Center for Biotechnology Information gene. To visualize the relationships between proteins, a protein-protein interaction network was generated using the STRING database. Further investigation of these targets involved analyzing protein-protein interaction networks and conducting GO/KEGG enrichment analysis. Molecular docking techniques were employed to examine the interactions between melatonin and crucial targets. Molecular dynamics simulations were performed to confirm the stability of the association between the hub targets and the melatonin ligand. Finally, animal studies validated the effect of melatonin on the identified targets.Results: Animal experiments showed that melatonin ameliorated hyperandrogenism and ovarian dysfunction in constant darkness-induced PCOS-like rats. Network pharmacology analysis demonstrated that melatonin exhibited multiple modulatory effects on circadian rhythm, reproductive processes, metabolic processes, and oocyte maturation. Cytoscape network analysis revealed seven key targets, of which AR and CYP19A1 showed the highest affinity for melatonin by molecular docking. The stability of the AR/CYP19A1-melatonin complex was verified through computational simulations using molecular dynamics techniques. Furthermore, animal experiments have validated that melatonin can regulate key genes associated with hyperandrogenism, including AR and CYP19A1.Conclusion: Through network pharmacology, molecular docking, and experimental validation, this study reveals how melatonin may ameliorate PCOS and hyperandrogenism. Results suggest melatonin’s effects involve androgen excess mitigation, though further validation is needed. This work provides insight into melatonin’s actions in circadian-associated PCOS.

Background: Decidualization deficiency is a key pathological feature of pre-eclampsia (PE) and is closely associated with aberrant regulation of cell fate. PANoptosis is a recently characterized form of inflammatory programmed cell death that has been implicated in several pregnancy-related disorders. However, its potential involvement in decidualization deficiency in PE remains poorly understood. This study aimed to explore the association between PANoptosis-related genes and decidualization deficiency in PE, and to identify candidate biomarkers and potential therapeutic targets related to PANoptosis. Methods: Datasets containing decidual tissue samples derived from women with PE and normal controls were acquired in the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified and subjected to enrichment analysis. After that, PANoptosis-related genes were intersected with DEGs derived from the decidual tissue of PE, followed by protein–protein interaction (PPI) network construction and correlation analysis. Next, the immune infiltration landscape and its association with PANoptosis-related DEGs were assessed. Furthermore, three machine learning algorithms, including support vector machine-recursive feature elimination (SVM-RFE), the least absolute shrinkage and selection operator (LASSO), and the random forest (RF) algorithms, were adopted to identify potential diagnostic biomarkers for PE. Artificial neural network (ANN) and nomogram models were then constructed and evaluated in testing datasets, which included decidual stromal cell samples derived from women with PE and normal controls. Additionally, the expression of PANoptosis-related signature genes and decidualization-related markers was experimentally validated in primary human decidual stromal cells (HDSCs) derived from PE patients and healthy controls. In addition, consensus clustering analysis was conducted on the basis of signature genes, and immune infiltration landscape analysis of different subtypes of PE was performed. Ultimately, the candidate compounds targeting the signature genes were screened and then further verified in vivo and in vitro models. Results: 430 DEGs were determined, and enrichment analysis indicated that these DEGs were mainly involved in inflammation, apoptosis, and dysfunction of decidual tissue in PE. Then, 10 PANoptosis-related DEGs in PE were further screened. Following that, immune landscape analysis revealed an aberrant abundance of various immunocytes and the levels of immune checkpoints in the decidual tissue of PE, which were closely associated with the PANoptosis-related DEGs. Next, through machine learning, nine PANoptosis-related signature genes ( MAPK3 , RIPK1 , RIPK3 , PYCARD , BAX , TUG1 , CDK1 , MAPK1 , and TAB2 ) were identified with favorable predictive performance. Besides, the ANN and nomogram models were constructed, and demonstrated high discriminative ability in the training dataset (AUC = 0.999, 95% CI: 0.995–1.000). Consistently, validation in primary HDSCs derived from PE patients and healthy controls confirmed dysregulated expression of these signature genes, accompanied by reduced decidualization markers ( PRL , IGFBP1 ). Furthermore, on the basis of the analysis of nine signature genes, two different subtypes of PE were acquired, in which subtype B showed an immune hyperactivity state compared to subtype A. Furthermore, melatonin was identified as a candidate compound targeting PANoptosis-related genes and showed protective effects in vivo and in vitro , including improved blood pressure, reduced proteinuria, partial restoration of decidualization markers (PRL, IGFBP1, and F-actin), and declined expressions of PANoptosis-related signature genes (BAX, MAPK1, and MAPK3). Importantly, functional experiments demonstrated that MAPK3 knockdown markedly attenuated PANoptosis-associated inflammatory cytokine production, reduced BAX expression, and partially restored F-actin organization and decidualization markers under PANoptosis-inducing conditions. Conclusion: This study suggests a potential association between PANoptosis-related molecular dysregulation and decidualization deficiency in PE. The identified PANoptosis-related signature genes may serve as candidate biomarkers with predictive relevance, and melatonin may represent a potential therapeutic candidate targeting PANoptosis-related pathways. These findings provide a foundation for future mechanistic and translational studies on PE.