Platelet rich plasma alleviates endometritis induced by lipopolysaccharide in mice via inhibiting TLR4/NF-κB signaling pathway.

BACKGROUND: Endometritis is an inflammatory reaction of the lining of uterus, leading to the occurrence of infertility. Platelet rich plasma (PRP) has been proven to exhibit extremely effective for the treatment of endometrium-associated infertility, but the mechanism of its prevention for endometritis remains unclear. OBJECTIVE: The present study aimed to investigate the protective effect of PRP against endometritis induced by lipopolysaccharide (LPS) and elucidate the mechanism underlying these effects. METHODS: Mouse model of endometritis was established by intrauterine perfusion of LPS. PRP intrauterine infusion was administered at 24 h after LPS induction. After another 24 h, the uterine tissues were harvested to observe histopathological changes, production of proinflammatory cytokines, variation of the Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) signaling pathways, and validated the anti-inflammatory effect of PRP. The myeloperoxidase (MPO) activity and concentration of nitric oxide (NO) were determined using assay kit. Proinflammatory chemokines (tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)) were measured by ELISA and Real-Time PCR. The activity of TLR4/NF-κB pathway in uterine tissues was measured by Western blotting. RESULTS: Hematoxylin-eosin staining (H&E) appeared that PRP remarkably relieved the impairment of uterine tissues. Detection of MPO activity and concentration of NO revealed that PRP treatment distinctly mitigated infiltration of inflammatory cells in mice with endometritis induced by LPS. PRP treatment significantly affected the expression of TNF-α, IL-1ß, and IL-6. PRP was also found to suppress LPS-induced activation of TLR4/NF-κB pathway. CONCLUSION: PRP effectively alleviates LPS-induced endometritis via restraining the signal pathway of TLR4/NF-κB. These findings provide a solid foundation for PRP as a potential therapeutic agent for endometritis.

LPS-Induced Activation of the cGAS-STING Pathway is Regulated by Mitochondrial Dysfunction and Mitochondrial DNA Leakage in Endometritis.

Introduction: Chronic endometritis is a common disease in women of childbearing age and can cause pelvic inflammatory disease. The cGAS-STING pathway plays an important role in many inflammatory diseases. Purpose: The aim of this study was to investigate the relationship between the cGAS-STING pathway and endometritis. Methods: We collected endometrium samples from patients with endometritis to detect changes in the cGAS-STING pathway. In vitro, human endometrial stromal cells (HESC) were stimulated with lipopolysaccharide (LPS), and a mouse STING gene-knockout model was established by CRISPR/cas9 for STING to further explore the mechanism underlying its effects in endometritis. We used Western blotting (WB) and immunohistochemical staining to detect the variations in protein levels and real-time PCR to study the variations in gene expression. Results: We observed the activation of the cGAS-STING pathway and an increase in the expression of cytokine-encoding genes, including IL-8, IL-6, IL-1ß, and IFN-ß1, in endometrial tissues of patients with endometritis. Stimulation of HESCs using LPS demonstrated increase in the expression of proteins involved the cGAS-STING pathway and the gene expression of inflammatory cytokines. STING-knockdown experiments demonstrated a decrease in the gene expression levels of inflammatory cytokines. Moreover, we also identified the translocation of IRF3 and STING after LPS stimulation. Regarding mitochondrial function, LPS led to an increase in reactive oxygen species levels and a reduction in mitochondrial membrane potential. However, we observed that the mitochondrial DNA (mtDNA) leaked into the cytoplasm, upregulating the levels of proteins involved in the cGAS-STING pathway upon LPS stimulation. Furthermore, our results showed that LPS induced hyperemia, inflammatory factor production, and expression of Pho-TBK1 in wild-type mice compared with the levels in control mice, and STING gene-knockdown alleviated these effects. Conclusion: LPS induces mitochondrial dysfunction in endometrial stromal cells, resulting in mtDNA leakage and promoting endometritis by stimulating the cGAS-STING pathway.

ß-Klotho Promotes the Development of Intrauterine Adhesions via the PI3K/AKT Signaling Pathway.

Intrauterine adhesion (IUA) refers to injury to the basal layer of the endometrium, which can be caused by various factors. It is often accompanied by clinical symptoms such as abnormal menstruation, infertility, recurrent abortion, and periodic abdominal pain. In recent years, a number of studies have reported the effects of ß-Klotho (KLB) on the occurrence and development of human tumors and fibrotic diseases, but its relationship with endometrial fibroblasts and endometrial fibrosis has not been elucidated. In this study, we compared the expression of KLB in endometrial stromal cells (ESCs) from patients with IUA and normal controls. We constructed animal and cell models of IUA and conducted expression verification and functional experiments on KLB. We found that the expression of KLB was significantly increased in the ESCs of IUA patients and rat models compared with the controls. The overexpression of KLB could promote the proliferation and fibrosis of ESCs. In addition, the overexpression of KLB activated the PI3K/AKT signaling pathway in ESCs. Our study shows that KLB protein is highly expressed in the ESCs of patients with IUA and can enhance stromal cell proliferation and cell fibrosis by activating the PI3K/AKT pathway, thus promoting the development of IUA.

On the Dynamic RSS Feedbacks of Indoor Fingerprinting Databases for Localization Reliability Improvement.

Location data is one of the most widely used context data types in context-aware and ubiquitous computing applications. To support locating applications in indoor environments, numerous systems with different deployment costs and positioning accuracies have been developed over the past decade. One useful method, based on received signal strength (RSS), provides a set of signal transmission access points. However, compiling a remeasurement RSS database involves a high cost, which is impractical in dynamically changing environments, particularly in highly crowded areas. In this study, we propose a dynamic estimation resampling method for certain locations chosen from a set of remeasurement fingerprinting databases. Our proposed method adaptively applies different, newly updated and offline fingerprinting points according to the temporal and spatial strength of the location. To achieve accuracy within a simulated area, the proposed method requires approximately 3% of the feedback to attain a double correctness probability comparable to similar methods; in a real environment, our proposed method can obtain excellent 1 m accuracy errors in the positioning system.

Matrix metalloproteinase 2 expression and survival of patients with osteosarcoma: a meta-analysis.

A number of studies investigated the impact of matrix metalloproteinase 2 (MMP2) expression on the survival of patients with osteosarcoma, but no consistent results were reported. To derive a more precise estimate of the prognostic role of MMP2 expression in patients with osteosarcoma, we systematically reviewed the published studies and carried out a meta-analysis. Cohort studies assessing the prognostic role of MMP2 expression in patients with osteosarcoma were included. Pooled risk ratio (RR) with 95% confidence intervals (95%CI) was used to assess the prognostic role of MMP2 expression. Five cohort studies were eligible in the meta-analysis. Overall, high MMP2 expression was associated with increased risk of mortality in patients with osteosarcoma during the follow-up (fixed effects RR = 2.14, 95%CI 1.66-2.75, P < 0.001). Sensitivity analysis suggested that the pooled RR was stable and omitting a single study did not change the significance of the pooled RR. There was some possibility of publication bias risk in the meta-analysis. In conclusion, the meta-analysis suggests that osteosarcoma patients with high MMP2 expression have poorer prognosis compared with those with low MMP2 expression.