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AbstractBackground Abnormal stromal-epithelial cell communication is a pathogenic mechanism in endometriosis, and metformin can modulate it. Insulin-like growth factor binding protein-1 (IGFBP1) plays a role in endometriosis, but the exact mechanism is unknown. IGFBP1 is reportedly a downstream target of metformin in some diseases. We aimed to investigate the role of IGFBP1 in endometriosis development, whether it is associated with abnormal communication, and whether metformin affects IGFBP1 expression.Methods Patients who underwent surgical treatment for endometriosis or other diseases were enrolled. Ten patients with ovarian-type endometriosis and eight patients each who underwent surgical treatment for other lesions with or without endometriosis were selected, and their tissues taken for cell proliferation, western blotting, polymerase chain reaction, and knockdown experiments.Results Ectopic and eutopic stromal cells (EcSCs and EuSCs) lost their ability to inhibit epithelial cell proliferation, and IGFBP1 expression was downregulated in both groups of stromal cells compared to that in normal stromal cells (NSCs; 1.09 vs. 0.25, p = .0002 1.09 vs. 0.57, p = .0029). In an EcSC IGFBP1 overexpression model, the ability of EcSCs to inhibit epithelial cell proliferation was enhanced (EdU positivity decreased from 38% to 25%, p = .0001). Furthermore, adenosine 5’-monophosphate-activated protein kinase (AMPK) phosphorylation was downregulated in EcSCs and EuSCs compared to that in NSCs (0.99 vs. 0.42, p = .0006/0.99 vs. 0.57, p = 0.0032). Treatment of EcSCs with metformin increased AMPK phosphorylation (0.47 vs. 1.04, p = .0107) while upregulating IGFBP1 expression (0.69 vs. 1.01, p = .0164), whereas pre-treatment with an AMPK phosphorylation inhibitor abrogated metformin-induced IGFBP1 upregulation.Conclusions IGFBP1 mediates aberrant stromal-epithelial communication in endometriosis. Metformin can upregulate IGFBP1 expression in EcSCs by activating AMPK, and upregulated IGFBP1 enhances the inhibition of epithelial cell proliferation. IGFBP1 is expected to be a therapeutic target for endometriosis.

Objective To investigate the expression of transforming growth factor-beta 1 in endometrial fibrosis in rats and related mechanisms. Methods Sprague-Dawley female rats were randomly divided into sham operation group (n=12) and model group (n=12). Uterine tissues were collected on days 7, 14 and 18 after surgery. HE staining and Masson staining were measured the number of endometrial glands and degree of endometrial fibrosis. The protein expression of TGF-β1 and α-SMA were measured by immunohistochemistry. Results Compared with the sham operation group, the uterine structure of the rats in the model group was significantly disrupted; there was a significant increase in TGF-β1 expression in the model group at 7 days,14 days, and 28 days of modeling; the number of endometrial glands decreased, the fibrotic area of endometrium increased and the expression of α-SMA was significantly higher at 14 days and 28 days of modeling. Conclusions TGF-β1 may promote endometrial fibrosis by activating myofibroblasts.

Fully grown oocytes have the natural ability to transform 2 terminally differentiated gametes into a totipotent zygote representing the acquisition of totipotency. This process wholly depends on maternal-effect factors (MFs). MFs stored in the eggs are therefore likely to be able to induce cellular reprogramming to a totipotency state. Here we report the generation of totipotent-like stem cells from mESCs using 4MFs Hsf1 , Zar1 , Padi6 , and Npm2 , designated as MFiTLSCs. MFiTLSCs exhibited a unique and inherent capability to differentiate into embryonic and extraembryonic derivatives. Transcriptomic analysis revealed that MFiTLSCs are enriched with 2-cell-specific genes that appear to synergistically induce a transcriptional repressive state, in that parental genomes are remodeled to a poised transcriptional repression state while totipotency is established following fertilization. This method to derive MFiTLSCs could help advance the understanding of fate determinations of totipotent stem cells in a physiological context and establish a foundation for the development of oocyte biology-based reprogramming technology. [ABSTRACT FROM AUTHOR]

N6‐methylated adenosine (m6A) is a crucial RNA modification in eukaryotes, particularly in cancer. However, its role in cervical cancer (CC) is unclear. We aimed to elucidate the part of m6A in CC by analyzing methyltransferase‐like 3 (METTL3) expression, identifying downstream targets, and exploring the underlying mechanism. We assessed METTL3 expression in CC using western blotting, quantitative polymerase chain reaction (qPCR), and immunohistochemistry. In vitro and in vivo experiments examined METTL3's role in CC. We employed RNA sequencing, methylated RNA immunoprecipitation sequencing, qPCR, and RNA immunoprecipitation qPCR to explore METTL3's mechanism in CC. METTL3 expression was upregulated in CC, promoting cell proliferation and metastasis. METTL3 knockdown inhibited human cervical cancer by inactivating AKT/mTOR signaling pathway. METTL3‐mediated m6A modification was observed in CC cells, targeting phosphodiesterase 3A (PDE3A). METTL3 catalyzed m6A modification on PDE3A mRNA through YTH domain family protein 3 (YTHDF3). Our study indicated the mechanism of m6A modification in CC and suggested the METTL3/YTHDF3/PDE3A axis as a potential clinical target for CC treatment. [ABSTRACT FROM AUTHOR]

Key Clinical Message: We present a rare case of a female pelvic solitary fibrous tumor unsuccessfully resected using single‐port laparoscopy, requiring conversion to laparotomy. Although the resection was successful, the surgical approach could have been improved. For large tumors, minimally invasive results are possible with flexible choices of equipment and incision position. [ABSTRACT FROM AUTHOR]

The contamination of aquatic environments by heavy metals can have detrimental effects on fish, impacting their growth and overall health, including the regulation of antioxidant genes. An investigation was carried out to assess the distribution and habitat of Gymnocypris eckloni in the Yellow River basin. Simultaneously, heavy metal concentrations in its habitat and in selected locations within the upper Yellow River were measured. In an effort to explore the potential roles of specific genes in antioxidant responses, G. eckloni was exposed to low concentrations of copper (Cu2+) and lead (Pb2+) for varying durations (12, 24, and 48 hours). The mRNA levels of GeCu/Zn-SOD, GeMn-SOD, GeHsp90, and GeMT were quantified in the gills, kidneys, and liver through qRT-PCR. The findings suggest that the habitat of G. eckloni is generally safe; however, occasional exceedances of safety standards could pose a potential threat to its growth. Importantly, the expression of GeCu/Zn-SOD, GeMn-SOD, GeHsp90, and GeMT exhibited responses to the low concentrations of copper-induced and lead-induced stress. Notably, GeCu/Zn-SOD, GeMn-SOD, and GeMT demonstrated heightened sensitivity to lead compared to copper. Furthermore, the expression of these genes displayed tissue-specific responses under identical metal stress conditions. These results indicate that GeCu/Zn-SOD, GeMn-SOD, GeHsp90, and GeMT genes have the potential to serve as early, sensitive biomarkers for the detection of metal toxicity induced by Cu2+ and Pb2+. This study also provides valuable insights into the functioning of antioxidant genes under oxidative stress in fish. [ABSTRACT FROM AUTHOR]