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BackgroundHormones and immune imbalance are critical factors in polycystic ovary syndrome (PCOS). The alternation of immune microenvironment of oocytes may play a significant role in infertility of PCOS patients.ObjectiveThis study explores the role of follicular fluid microenvironment change in inflammatory pathways activation of granulosa cells (GCs) in PCOS women infertility.MethodsWe enrolled 27 PCOS patients and 30 controls aged 22 to 38 years who underwent IVF and collected their luteinized granulosa cells (LGCs). Meanwhile, a granulosa-like tumor cell line (KGN) as a cell-model assisted this study. Key inflammatory markers in human ovarian GCs and follicular fluid were detected by RT-qPCR, Western blotting, or ELISA. The KGN cells were treated with follicle supernatant mixed with normal medium to simulate the microenvironment of GCs in PCOS patients, and the inflammation indicators were observed. The assembly of NLRP3 inflammasomes was detected by immunofluorescence techniques. Dihydroethidium assay and EdU proliferation assay were used to detect ROS and cell proliferation by flow cytometry.ResultsCompared with normal controls (n = 19), IL-1β (P = 0.0005) and IL-18 (P = 0.021) in the follicular fluid of PCOS patients (n = 20) were significantly increased. The NF-κB pathway was activated, and NLRP3 inflammasome was formatted in ovarian GCs of PCOS patients. We also found that inflammation of KGN cells was activated with LPS irritation or stimulated by follicular fluid from PCOS patients. Finally, we found that intracellular inflammation process damaged mitochondrial structure and function, which induced oxidative stress, affected cellular metabolism, and impaired cell proliferation.ConclusionInflammatory microenvironment alteration in the follicular fluid of PCOS patients leads to activated inflammatory pathway in GCs, serving as a crucial factor that causes adverse symptoms in patients. This study provides a novel mechanism in the inflammatory process of PCOS.

Pelvic organ prolapse (POP) and urinary incontinence (UI) are common disorders that significantly impact women’s quality of life. Studies have demonstrated that cytokines, including pro- and anti-inflammatory immune mediators, play a role in illness genesis and progression. Research on the inflammatory milieu of the pelvic floor has shown that POP patients have increased inflammation in vaginal tissues. This evidence revealed that significant changes in the inflammatory milieu of the pelvic floor are an aspect of the pathogenesis of POP. POP patients exhibit increased levels of inflammatory cytokines (IL-1, TNF, IFN, and others) in the front vaginal wall, which may alter collagen metabolism and contribute to POP. Studies indicate that cytokines such as IL-6, IL-10, and TGF, which are involved in inflammation, remodelling, and repair, have dual effects on POP and UI. They can promote tissue healing and regeneration but also exacerbate inflammation and fibrosis, contributing to the progression of these conditions. Understanding the dual roles of these cytokines could help us improve the vaginal microenvironment of women and treat POP and UI. Given the considerable changes in these cytokines, this review addresses studies published between 2000 and 2024 on the molecular mechanisms by which pro- and anti-inflammatory cytokines affect women with POP and UI. Furthermore, we explain novel therapeutic strategies for cytokine regulation, emphasizing the possibility of personalized treatments that address the underlying inflammatory milieu of the vagina in POP and UI patients. This thorough analysis aims to establish a foundation for future research and clinical applications, ultimately improving patient outcomes via designed cytokine-based therapies.

OBJECTIVES: Recurrent miscarriage is a multifactorial condition, with immune dysregulation proposed as a potential contributing factor. This study investigates the causal relationship between immune cell phenotypes and miscarriage risk using Mendelian randomization (MR). MATERIAL AND METHODS: We performed a two-sample MR analysis using genome-wide association study (GWAS) summary statistics from publicly available datasets. The exposure data for immune cell phenotypes were obtained from the ebi-a-GCST90001599 dataset in the IEU GWAS database, which included over 3,000 individuals of predominantly European ancestry from multiple cohorts within the UK Biobank. The outcome data for miscarriage risk were sourced from the UKB-B-419 dataset in the MRC-IEU GWAS database, which analysed the number of spontaneous miscarriages in 78,700 individuals of predominantly European ancestry from the United Kingdom. The primary MR analysis was conducted using inverse-variance weighted (IVW) regression, complemented by Wald ratio and MR-Egger regression methods to assess robustness. MR-PRESSO was used to test for pleiotropy, while sensitivity analyses evaluated instrument validity and heterogeneity. RESULTS: MR-Egger regression did not provide statistically significant evidence for a causal association between immune cell phenotypes and miscarriage risk. However, IVW and Wald ratio analyses identified statistically significant associations between specific immune cell profiles and miscarriage risk. A higher proportion of HLA DR+ CD4+ and CD8+ T cells was associated with an increased risk of miscarriage (p < 0.005), while a higher absolute lymphocyte count was linked to a decreased risk (p = 0.011). Additionally, elevated levels of TCRgd T cells and FSC-A on CD4+ T cells were potentially protective against miscarriage (p < 0.01). Conversely, lower proportions of granulocytes and FSC-A on myeloid dendritic cells were associated with an increased miscarriage risk (p < 0.05). MR-PRESSO detected significant pleiotropy (global test p < 0.001), suggesting that some genetic variants may influence other traits, potentially biasing the initial MR estimates. CONCLUSIONS: Our findings suggest a complex interplay between immune cell composition and miscarriage risk, providing new insights into the immunological mechanisms contributing to pregnancy loss. These results highlight the need for further research to confirm these associations and explore potential therapeutic targets for immune-related pregnancy complications.

This study was designed to investigate the role of miR-671-5p in in vitro and in vivo models of ischemic stroke (IS). Middle cerebral artery occlusion and reperfusion (MCAO/R) in C57BL/6 mice as well as oxygen–glucose deprivation and reoxygenation (OGD/R) in a mouse hippocampal HT22 neuron line were used as in vivo and in vitro models of IS injury, respectively. miR-671-5p agomir, miR-671-5p antagomir, pcDNA3.1-NF-κB, and negative controls were transfected into cells using riboFECT CP reagent. miR-671-5p agomir, pcDNA3.1-NF-κB, and negative vectors were administered into MCAO/R mice via intracerebroventricular injection. The results showed that miR-671-5p was significantly downregulated and that miR-671-5p agomir alleviated injury and neuroinflammation induced by ischemic reperfusion. A dual-luciferase reporter assay confirmed that NF-κB is a direct target of miR-671-5p. Reverse experiments showed that miR-671-5p agomir reduced neuroinflammation via suppression of NF-κB expression in both in vitro and in vivo models of IS. Our data suggest that miR-671-5p may be a viable therapeutic target for diminishing neuroinflammation in patients with IS.

The Lobster Eye Imager for Astronomy (LEIA) detected a new X-ray transient on 2022 November 7, identified as a superflare event occurring on a nearby K-type giant star HD 251108. The flux increase was also detected in follow-up observations at X-ray, UV, and optical wavelengths. The flare lasted for about 40 days in soft X-ray observations, reaching a peak luminosity of ∼1.1 × 1034 erg s−1 in 0.5–4.0 keV, which is roughly 60 times the quiescent luminosity. Optical brightening was observed for only one night. The X-ray light curve is well described by a double fast rise and exponential decay model, attributed to the cooling process of a loop arcade structure formed subsequent to the initial large loop with a half-length of ∼1.9 × 1012 cm. Time-resolved X-ray spectra were fitted by a four-temperature apec model (with three components being the quiescent background), showing significant evolution of plasma temperature and emission measure over time. The estimated energy released in the LEIA band is ∼3 × 1039 erg, suggesting that this is likely the most energetic X-ray stellar flare with the longest duration detected to date.

Objective. To evaluate the role of CCAAT/enhancer-binding protein β (C/EBP β) in retinal neovascularization (RNV) in an oxygen-induced retinopathy (OIR) model. Methods. Rats with OIR were exposed to alternating hypoxic and hyperopic conditions for 14 days. Then, the rats with OIR were assigned randomly to groups that received intravitreal injections of either shRNA lentiviral particles targeting C/EBP β (LV.shC/EBP β) or control particles (LV.shScrambled). The effectiveness of transduction using intravitreal injection of C/EBP β shRNA was examined in rats with OIR. The retinal vascular damage and accumulation of RNV were determined by retinal fluorescein-dextran perfusion, retinal ADPase staining, and periodic acid-Schiff (PAS) staining. Retinal function was recorded by electroretinogram responses to full-field light flashes. Reverse transcriptase-polymerase chain reaction (RT-PCR) and western blot analyses were used to measure mRNA and protein levels of C/EBP β and vascular endothelial growth factor (VEGF). The expression of p-C/EBP β was also examined by western blot analyses. The location of C/EBP β expression in the retina was determined by immunohistochemistry. Results. In OIR rats, the expression levels of C/EBP β and VEGF were significantly increased at both the mRNA and protein levels (P<0.01). The p-C/EBP β expression was consistent with the level of C/EBP β. C/EBP β was predominantly localized to the ganglion cell layer (GCL) and the inner nuclear layer (INL). The retinal C/EBP β level was significantly reduced in tissues from rats with OIR transduced with LV.shC/EBP β compared with tissues from those transduced with LV.shScrambled (P<0.01). Compared with those of the rats with OIR in the LV.shScrambled group, nonperfused retinal areas, neovascular tufts, pericyte death, and the ratio of endothelial cells to pericytes in the LV.shC/EBP β group were significantly reduced. In OIR rats, retinal function was impaired. There was no significant change in retinal dysfunction between the LV.shC/EBP β group and the LV.shScrambled group. The levels of VEGF mRNA and protein in the LV.shC/EBP β group were also decreased significantly compared with those of the rats with OIR in the LV.shScrambled group (P<0.01). Conclusions. C/EBP β shRNA inhibits RNV in OIR. A potential mechanism may be that the activity of C/EBP β increases with its overexpression, which in turn aggravates the amount of the retinal vascular damage and promotes transcription of VEGF. C/EBP β might be a new therapeutic target for preventing RNV.

The Lobster Eye Imager for Astronomy (LEIA) detected a new X-ray transient on 2022 November 7, identified as a superflare event occurring on a nearby K-type giant star HD 251108. The flux increase was also detected in follow-up observations at X-ray, UV and optical wavelengths. The flare lasted for about 40 days in soft X-ray observations, reaching a peak luminosity of ~1.1 * 10^34 erg/s in 0.5-4.0 keV, which is roughly 60 times the quiescent luminosity. Optical brightening was observed for only one night. The X-ray light curve is well described by a double fast rise and exponential decay model, attributed to the cooling process of a loop arcade structure formed subsequent to the initial large loop with a half-length of ~1.9 * 10^12 cm. Time-resolved X-ray spectra were fitted by a four-temperature apec model (with three components being the quiescent background), showing significant evolution of plasma temperature and emission measure over time. The estimated energy released in the LEIA band is ~3 * 10^39 erg, suggesting that this is likely the most energetic X-ray stellar flare with the longest duration detected to date.

LEIA (Lobster Eye Imager for Astronomy) detected a new X-ray transient on November 7, 2022, identified as a superflare event occurring on a nearby RS CVn-type binary HD 251108. The flux increase was also detected in follow-up observations at X-ray, UV and optical wavelengths. The flare lasted for about 40 days in soft X-ray observations, reaching a peak luminosity of ~1.1 * 10^34 erg/s in 0.5-4.0 keV, which is roughly 60 times the quiescent luminosity. Optical brightening was observed for only one night. The X-ray light curve is well described by a double \"FRED\" (fast rise and exponential decay) model, attributed to the cooling process of a loop arcade structure formed subsequent to the initial large loop with a half-length of ~1.9 times the radius of the host star. Time-resolved X-ray spectra were fitted with a two-temperature apec model, showing significant evolution of plasma temperature, emission measure, and metal abundance over time. The estimated energy released in the LEIA band is ~3 * 10^39 erg, suggesting this is likely the most energetic X-ray stellar flare with the longest duration detected to date.