CAPN2 correlates with insulin resistance states in PCOS as evidenced by multi-dataset analysis.

OBJECTIVE: IR emerges as a feature in the pathophysiology of PCOS, precipitating ovulatory anomalies and endometrial dysfunctions that contribute to the infertility challenges characteristic of this condition. Despite its clinical significance, a consensus on the precise mechanisms by which IR exacerbates PCOS is still lacking. This study aims to harness bioinformatics tools to unearth key IR-associated genes in PCOS patients, providing a platform for future therapeutic research and potential intervention strategies. METHODS: We retrieved 4 datasets detailing PCOS from the GEO, and sourced IRGs from the MSigDB. We applied WGCNA to identify gene modules linked to insulin resistance, utilizing IR scores as a phenotypic marker. Gene refinement was executed through the LASSO, SVM, and Boruta feature selection algorithms. qPCR was carried out on selected samples to confirm findings. We predicted both miRNA and lncRNA targets using the ENCORI database, which facilitated the construction of a ceRNA network. Lastly, a drug-target network was derived from the CTD. RESULTS: Thirteen genes related to insulin resistance in PCOS were identified via WGCNA analysis. LASSO, SVM, and Boruta algorithms further isolated CAPN2 as a notably upregulated gene, corroborated by biological verification. The ceRNA network involving lncRNA XIST and hsa-miR-433-3p indicated a possible regulatory link with CAPN2, supported by ENCORI database. Drug prediction analysis uncovered seven pharmacological agents, most being significant regulators of the endocrine system, as potential candidates for addressing insulin resistance in PCOS. CONCLUSIONS: This study highlights the pivotal role of CAPN2 in insulin resistance within the context of PCOS, emphasizing its importance as both a critical biomarker and a potential therapeutic target. By identifying CAPN2, our research contributes to the expanding evidence surrounding the CAPN family, particularly CAPN10, in insulin resistance studies beyond PCOS. This work enriches our understanding of the mechanisms underlying insulin resistance, offering insights that bridge gaps in the current scientific landscape.

The effect and mechanism of low-molecular-weight heparin on the decidualization of stromal cells in early pregnancy.

OBJECTIVE: This study aimed to analyze the effect of low-molecular-weight heparin (LMWH) on the decidualization of stromal cells in early pregnancy and explore the effect of LMWH on pregnancy outcomes. METHODS: Recurrent spontaneous abortion (RSA) mouse model (CBA/J × DBA/2) and normal pregnant mouse model (CBA/J × BALB/c) were established. The female mice were checked for a mucus plug twice daily to identify a potential pregnancy. When a mucus plug was found, conception was considered to have occurred 12 h previously. The pregnant mice were divided randomly into a normal pregnancy control group, an RSA model group, and an RSA + LMWH experimental group (n = 10 mice in each group). Halfway through the 12th day of pregnancy, the embryonic loss of the mice was observed; a real-time quantitative polymerase chain reaction was used to detect the messenger ribonucleic acid (mRNA) expressions of prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1) in the decidua of the mice. Additionally, the decidual tissues of patients with RSA and those of normal women in early pregnancy who required artificial abortion were collected and divided into an RSA group and a control group. Decidual stromal cells were isolated and cultured to compare cell proliferation between the two groups, and cellular migration and invasion were detected by membrane stromal cells. Western blotting was used to detect the protein expressions of proliferating cell nuclear antigen (PCNA), cyclin D1, matrix metalloproteinase- (MMP) 2, and MMP-7 in stromal cells treated with LMWH. RESULTS: Compared with the RSA group, LMWH significantly reduced the pregnancy loss rate in the RSA mice (p < 0.05). Compared with the RSA group, the LMWH + RSA group had significantly higher expression levels of PRL and IGFBP1 mRNA (p < 0.01). LMWH promoted the proliferation, migration, and invasion of human decidual stromal cells; compared with the control group, the expression levels of MMP-2, MMP-7, cyclin D1, and PCNA proteins in the decidual stromal cells of the LMWH group increased (p < 0.05). CONCLUSIONS: The use of LMWH can improve pregnancy outcomes by enhancing the proliferation and migration of stromal cells in early pregnancy and the decidualization of stromal cells.

Study of platelet-rich plasma application for skin and plastic surgery in recent 20 years: A bibliometric analysis.

BACKGROUND: In recent years, platelet-rich plasma (PRP) has been used in plastic surgery, dermatology, and other treatment procedures worldwide. Since the number of scientific writings has been significantly increasing, it is challenging to generate a manual compilation and systematic review of PRP's therapeutic applications in dermatology and plastic surgeries. This study aimed to make a bibliometric analysis of the literature in the field and evaluate research hotspots and frontiers in this field in the past 20 years. METHODS: Using the Academic Search Premier and ScienceDirect defined search terms, we searched the Web of Science Core Collection (WoSCC) and Scopus databases. All data were analyzed using CiteSpace 5.8.R3 and VOSviewer, including countries, institutions, authors, keywords, cited authors, cited journals, cited references, discovered research hotspots, and frontiers. RESULTS: A total of 1931 studies were retrieved. The number of publications on PRP application in dermatology and plastic surgeries showed a yearly increase. The United States was the most significant contributor to this field, while Italy's contribution was noteworthy. The journal with the highest number of relevant articles in dermatology and plastic surgery included the Journal of Cosmetic Dermatology. However, the Wound Repair and Regeneration and International Journal of Molecular Sciences were the leading journals that should be paid attention to in the future. Author Anitua E from the Tor Vergata University of Rome published the most publications in this field. In the keyword co-occurrence analysis, all keywords were divided into six clusters, and the most common one in recent years was "PRP for facial beauty." Facial rejuvenation, scar, and alopecia were the main hotspots and research trends in this field. CONCLUSIONS: Based on the current global trends, the use of PRP in cosmetics and skin care is receiving increasing attention from researchers and clinicians. Recently, an increasing number of articles on PRP's application in skin tissue repair have been published in the United States and Italy. The number of studies on hair loss, facial rejuvenation, and scar management is increasing, suggesting that these subjects may become research hotspots for PRP in dermatology and cosmetic surgeries in recent years.

Identification of biomarkers associated with macrophage infiltration in non-obstructive azoospermia using single-cell transcriptomic and microarray data.

Background: Non-obstructive azoospermia (NOA) is a common clinical cause of male infertility. Research suggests that macrophages are linked to testicular function; however, their involvement in NOA remains unknown. Methods: To evaluate the importance of macrophages infiltration in NOA and identify the macrophage-related biomarkers, the gene-expression microarray data GSE45885 and the single-cell transcriptomic data GSE149512 were utilized from the Gene Expression Omnibus (GEO). A single-sample gene set enrichment analysis (ssGSEA) was conducted to investigate immune cell proliferation. The Seurat package was used for the single-cell data analysis, and the limma package was used to identify the differentially expressed genes between the NOA and normal samples. Moreover, we conducted a weighted gene co-expression network analysis (WGCNA) to identify the macrophage-related key modules and genes, and conducted Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses for the functional exploration. To identify the macrophage-related biomarkers, we conducted least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature elimination (SVM-RFE) analyses. Real-time quantitative polymerase chain reaction (RT-qPCR) was used to verify the marker genes present in NOA. Results: We confirmed that open reading frame 72 gene on chromosome 9 (C9orf72) [area under the curve (AUC) =0.861] and cartilage-associated protein (CRTAP) (AUC =0.917) were the hub genes of NOA, and the RT-qPCR analysis revealed the critical expression of both genes in NOA. Conclusions: Through the combination of tissue transcriptomic and single-cell RNA-sequencing analyses, we concluded that macrophage infiltration is significant in different subtypes of NOA, and we hypothesized that C9orf72 and CRTAP play critical roles in NOA due to their high expression in macrophages.

NR4A1 Affects Endometrial Receptivity by Participating in Mesenchymal-Epithelial Transition of Endometrial Stromal Cells.

Decidualization is a substantive differentiation process experienced by endometrium to prepare for pregnancy. During this process, the endometrial stromal cells are transformed to endometrial epithelial cells. The receptivity of endometrium is necessary for the decidualization and successful implantation of endometrium, while the main hormones coordinating this process are estrogen and progesterone (P). In our study, the immunofluorescence, qPCR, and western blot experiments were conducted on different types of clinical endometrial tissue samples. The experimental results show that in the endometrium of normal subjects during the luteal phase, the protein level and serum P4 level of the orphan nuclear receptor NR4A1 messenger RNA were all significantly higher than those of patients with endometriosis or primary infertility, and the two levels presented positive correlation. Through decidualization induction of the human endometrial stromal cells (hESCs) cultured in vitro and additional P treatment, the results of chromatin immunoprecipitation and other experiments show that the P treatment could upregulate the expression of NR4A1 in hESCs, and this process was mediated under the direct effect of progesterone receptor (PR) and NR4A1. When the NR4A1 in hESCs was silenced, the promotion of hESC proliferation by P was inhibited. P and overexpressed NR4A1 increased the expression of epithelial cell marker in decidual hESCs, and qPCR showed that NR4A1's response to P was earlier than that of the epithelial cell marker. The results of spheroid adhesion assay show that the silent NR4A1 had reduced the adhesion of decidual hESCs induced in vitro to embryo. To sum it up, NR4A1 participated in the decidualization process by responding to the P regulation via and by promoting the hESCs' mesenchymal-epithelial transition, so as to further influence the receptivity of endometrium.

Thicker endometrium on hCG trigger day improves the live birth rate of fresh cleavage embryo transfer in GnRH-agonist regimen of normogonadotrophic women.

BACKGROUND: Luteinizing hormone (LH) and progesterone (PROG) on human chorionic gonadotropin (hCG) trigger day are significantly correlated with assisted reproductive technology (ART) outcome. Moreover, LH and PROG are also involved in the functional preparation of the endometrium during the implantation window; however, whether they are related to endometrial thickness (EMT) is still unknown. The aim of the present study was to assess whether EMT has a positive correlation on the live birth rate following fresh embryo transfer (ET), and whether LH and PROG have an impact on EMT. METHODS: A total of 2,260 normogonadotrophic women were treated with a GnRH agonist for in vitro fertilization (IVF)/intracytoplasmic sperm injection. Patients with advanced age and poor ovarian reserve were excluded. The levels of LH, PROG, and EMT on the hCG trigger day were divided into binary variables, respectively, by the cutoff values, and which were obtained based on receiver operating characteristic curve analysis of live birth among LH, PROG and EMT levels on the hCG trigger day, respectively. Multivariate binary logistic regression was used to confirm the role of LH, PROG, and EMT on the live birth, and stratified analysis was used to determine whether LH and PROG have an impact on EMT. RESULTS: EMT and LH were protective factors for live births, with odds ratios (OR) of 1.11 [95% confidence interval (CI): 1.066-1.157] and 1.696 (95% CI: 1.345-2.139), respectively. However, PROG was a risk factor for live birth, with an OR of 0.635 (95% CI: 0.526-0.766). The hierarchical cross-table analysis indicated that EMT had no significant difference for live birth in the combination of low LH and high PROG group. In the other subgroups, thick EMT was associated with a higher live birth rate (P<0.05). CONCLUSIONS: On hCG trigger day, EMT, LH, and PROG all were independent factors that affected the live birth of fresh ETs. Thick EMT can significantly increase the live birth rate. However, multivariate logistic regression analysis showed that EMT does not affect the live birth rate in combination of low LH and high PROG environment.