Androgenetic alopecia (AGA) is the most common type of hair loss, and there is a lack of ideal treatment options. The damage and shedding of hair follicles are closely associated with niche dysregulation, including reactive oxygen species (ROS) accumulation, microvascular damage, and persistent inflammation. In this study, a biocomposite microneedle system comprising hypoxic extracellular vesicle (EV)-encapsulated selenium nanozyme (Se-HEVs-AMN) was designed to create a favorable perifollicular microenvironment. The novel Se-HEVs-AMN biocomposite patch features microneedles with sufficient mechanical strength, tailored dissolution properties, and a convenient detachable backing layer. The microneedles are modified with Astragalus polysaccharide (APS) and loaded with hypoxia-induced EVs containing selenium nanozyme. When applied to the dorsal skin of AGA mice, the microneedles rapidly dissolve, releasing active ingredients that increase hair density and enlarge hair follicle diameter through regulating inflammation, promoting angiogenesis, scavenging ROS, and resisting androgen.
Protein ubiquitination with general existence in virtually all eukaryotic cells serves as a significant post-translational modification of cellular proteins, which leads to the degradation of proteins via the ubiquitin–proteasome system. Deubiquitinating enzymes (DUBs) can reverse the ubiquitination effect by removing the ubiquitin chain from the target protein. Together, these two processes participate in regulating protein stability, function, and localization, thus modulating cell cycle, DNA repair, autophagy, and transcription regulation. Accumulating evidence indicates that the ubiquitination/deubiquitination system regulates reproductive processes, including the cell cycle, oocyte maturation, oocyte-sperm binding, and early embryonic development, primarily by regulating protein stability. This review summarizes the extensive research concerning the role of ubiquitin and DUBs in gametogenesis and early embryonic development, which helps us to understand human pregnancy further.
Objective: To identify the prevalence and risk factors for chronic endometritis (CE) with tubal factors and the correlation between chronic endometritis and tubal factors among infertile populations. Method: A total of 52 patients with chronic endometritis (CE group) who underwent laparoscopy and hysteroscopic surgery were recruited between July 2020 and December 2021. A total of 38 patients without chronic endometritis (non-CE group) were included as a control. Patients with endometriosis and intra-uterine abnormalities were excluded. Endometrial samples were collected during surgery for CD138 immunohistochemistry staining for the diagnosis of CE. Preoperative information (including age, reproductive health characteristics, previous medical and surgical history), intra-operative information (including the patency of the fallopian tube, the presence of hydrosalpinx, score and the grade of tubal lesion condition) and post-operative information (counts of CD138-positive HPF in the endometrial specimen) were collected. Result: A multivariate analysis revealed that tubal factors with unilateral or bilateral occlusion were significantly higher in the CE group (OR 3.066, 95% CI 1.020–9.213, p = 0.046). The bilateral occlusion of fallopian tubes (OR 8.785, 95% CI 1.408–54.818, p = 0.020) rather than unilateral occlusion (OR 2.860, 95% CI 0.893–9.162, p = 0.077) was significantly associated with chronic endometritis. The presence of a hydrosalpinx on one side (OR 7.842, 95% CI 1.279–48.086, p = 0.026) or both sides (OR 9.450, 95% CI 1.037–86.148, p = 0.046) was significantly associated with chronic endometritis. The comparison of CD138-positive HPF counts among the tubal occlusion patients without hydrosalpinx, patients with unilateral hydrosalpinx and patients with bilateral hydrosalpinx were as follows: 1 HPF (50.00% vs. 12.50% vs. 11.11%, p = 0.051), 2 HPF (38.89% vs. 25.00% vs. 22.22%, p = 0.615), ≥3 HPF (11.11% vs. 62.50% vs. 66.67%, p = 0.005). The stage of tubal condition was positively correlated with CD138-positive HPF counts in women with chronic endometritis (r = 0.460, p = 0.001). Conclusion: CE was closely related to the blockage of fallopian tubes and hydrosalpinx. The severity degree of the fallopian lesion condition was associated with inflammation of the endometrium.
Background: This study aimed to examine the differential variations in the metabolic composition of follicular fluid (FF) among normal-weight patients with polycystic ovary syndrome (PCOS) and controls and to identify potential biomarkers that may offer insights into the early identification and management of these patients. Methods: We collected FF samples from 45 normal-weight women with PCOS and 36 normal-weight controls without PCOS who were undergoing in vitro fertilization–embryo transfer. An untargeted metabolomic study of collected FF from infertile women was performed using high-performance liquid chromatography–tandem spectrometry (LC-MS). The tendency of the two groups to separate was demonstrated through multivariate analysis. Univariate analysis and variable importance in projection were used to screen out differential metabolites. Metabolic pathway analysis was conducted using the Kyoto Encyclopedia of Genes and Genomes (KEGG), and a diagnostic model was established using the random forest algorithm. Results: The metabolomics analysis revealed an increase in the expression of 23 metabolites and a decrease in that of 10 metabolites in the FF of normal-weight women with PCOS. According to the KEGG pathway analysis, these differential metabolites primarily participated in the metabolism of glycerophospholipids and the biosynthesis of steroid hormones. Based on the biomarker combination of the top 10 metabolites, the area under the curve value was 0.805. The concentrations of prostaglandin E2 in the FF of individuals with PCOS exhibited an inverse association with the proportion of high-quality embryos (p < 0.05). Conclusions: Our research identified a distinct metabolic profile of the FF from normal-weight women with PCOS. The results offer a broader comprehension of the pathogenesis and advancement of PCOS, and the detected differential metabolites could be potential biomarkers and targets for the treatment of PCOS.