Could human umbilical cord mesenchymal stem cell-derived exosomes (hucMSC-Ex) accelerate vaginal epithelium cell (VK2) growth? HucMSC-Ex play a significant role in promoting proliferation of VK2 cells by accelerating the cell cycle and inhibiting apoptosis through exosomal microRNAs in vitro. Numerous studies have reported that MSC-Ex play an important role in tissue injury repair. hucMSC and exosomes isolated from their conditioned medium were used to treat a vaginal epithelial cell line (VK2). Normal human fibroblasts (HFF-1) were used as negative control to hucMSC. VK2 cells were co-cultured with hucMSC whose paracrine effect on the viability, cell cycle and cell apoptosis of VK2 vaginal epithelial cells was further assessed by the CCK-8 assay and flow cytometry. HucMSC-Ex isolated from culture medium by ultracentrifuge were characterized by transmission electron microscopy, nanoparticle tracking analysis and Western blot. HucMSC-Ex at different concentrations and HFF-1 exosomes were used to treat VK2 cells. High-throughput RNA sequencing was utilized to reveal the profile of microRNAs in hucMSC, hucMSC-Ex, HFF-1 and HFF-1 exosomes and GO analysis was applied to demonstrate their functions. To evaluate the function of these specific microRNAs in hucMSC-Ex, VK2 cells were treated with RNA-interfered-hucMSC-Ex (RNAi-hucMSC-Ex) and their proliferation was measured by Label-free Real-time Cellular Analysis System. The study showed that hucMSC stimulate VK2 cell growth possibly through a paracrine route by promoting cell cycle and inhibiting apoptosis. Compared with control and low dose groups, hucMSC-Ex of high concentration (more than 1000 ng/ml) significantly increased VK2's growth after treatment in a dose-depended manner (P < 0.05). HucMSC-Ex raised the proportion of cells in S-phase and reduced the percentage of apoptotic cells in VK2 cells in comparison with the HFF-1 exosomes and control groups (P < 0.05). microRNAs, including miR-100 (16.92%), miR-146a (9.21%), miR-21 (6.67%), miR-221 (6.39%) and miR-143 (4.63%), were found to be specifically enriched (P < 0.05) in hucMSC-Ex and their functions concentrated on cell cycle, development and differentiation. Collectively, our findings indicate that hucMSC-Ex may play a significant role in accelerating VK2's proliferation by promoting cell cycle and inhibiting apoptosis through exosomal microRNAs in vitro. N/A. Our study did not confirm the function of hucMSC-Ex or specifically enriched exosomal microRNAs in vivo. miR-100 and miR-146a are well-known immunomodulatory miRNAs that participate in the regulation of inflammatory disorders and may enhance the therapeutic effect of hucMSC-Ex by promoting the surgical injury repair after vaginal reconstruction. But whether it acts through anti-inflammatory responses needs further study. This finding supports the potential use of hucMSC-Ex as a cell-free therapy of Meyer-Rokitansky-Küster-Hauser syndrome (MRKHS) after vaginoplasty. This study was supported by the Chinese National Nature Sciences Foundation (grant number 91440107, 81471416 and 81771524) and the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB19040102). All authors state that there is no conflict of interest to disclose.

Background: Although HPV testing and cytology detection are successful for cervical screening in China, additional procedures are urgently required to avoid misdiagnosis and overtreatment. In this multicenter study, we collected cervical samples during screening in clinics. A total of 588 women with HPV16/18+ and/or cytology result ≥HSIL+ (high-grade squamous intraepithelial lesion or worse) were referred to colposcopy for pathological diagnosis. Methylation of S5 was quantified by pyrosequencing. Results: The S5 classifier separates women with ≥HSIL+ from <HSIL with a high area under the curve (AUC) of 0.86 (95% CI 0.840–0.910). The cutoff of 2.85 was conducted in our study. Remarkably, all cancer cases (n = 67) were detected by S5. The sensitivity of S5 for “≥HSIL+” was 89.1% (95% CI 86.2–92.4%), and the specificity was 76.6% (95% CI 72.2–78.9%). S5 could reduce unnecessary colposcopy referrals by 74% (95% CI 71.3–78.1%) with virtually no loss of sensitivity for HSIL+, and the follow-up data support the utility of the S5 classifier. Conclusion: The S5 classifier with high sensitivity and specificity provided increasing diagnostic information for women with HPV16/18+ and/or cytology results and could reduce the numerous unnecessary colposcopy referrals and avoid overtreatment.

As a common female reproductive system malignancy, cervical cancer (CC) disturbs numerous womens health. This study demonstrates the role of the vaginal microbial environment (Peptostreptococcus anaerobius) in cervical cancer. Functional assays, including cell proliferation assay, tube formation assay, and immunofluorescence staining, revealed the effect of Peptostreptococcus anaerobius-treated macrophages on cell proliferation and the angiogenesis process. The tube formation assay disclosed the function of Peptostreptococcus anaerobius-treated macrophages on angiogenesis. In vivo assays were also established to explore the impact of Peptostreptococcus anaerobius-treated macrophages on tumor migration. The results revealed that Peptostreptococcus anaerobius-induced macrophages boosted cervical cancer migration and angiogenesis both in vitro and in vivo. Then, this study unveiled that Peptostreptococcus anaerobius-induced macrophage secreted VEGF to stimulate the angiogenesis in cervical cancer. As a whole, Peptostreptococcus anaerobius-induced macrophage facilitates cervical cancer development through modulation of VEGF expression.

While increasing numbers of studies have established that adipose tissue plays a vital role in balancing energy intake and energy expenditure as both an energy and an endocrine organ, the detailed functions of adipose tissue remain unclear. Adipose tissues are complex, with multiple resident cell populations that communicate to diverse cells and organs via local and systemic metabolic, thermal, and inflammatory signaling. In normal physiology, adipose tissue-derived extracellular vesicles mediate the regulation of energy storage/consumption in adipose tissue, liver, and muscle. In a pathological sense, fat-derived extracellular vesicles can promote the progression of obesity, endocrine diseases, cancer, and reproductive system disorders. In this review, we demonstrate that adipocyte-derived extracellular vesicles function not only in physiological balance but also in the pathological process. We aim to illustrate the impact of adipocyte-derived extracellular vesicles and their value in understanding both homeostasis and disorders.

Most cervical cancers are related to the persistent infections of high-risk Human Papillomavirus (HPV) infections. Increasing evidence has witnessed the immunosuppressive effectiveness of HPV in the oncogenesis steps and progression steps. Here we review the immune response in HPV-related cervical malignancies and discuss the crosstalk between HPVs and the host immune response. Furthermore, we describe the identification and development of current immunotherapies in cervical cancer. Above all, we hope to provide a novel insight of the display between HPV infections and the host immune system.

Primary ovarian insufficiency (POI) is a pathological condition characterized by the early loss of functional ovarian follicles, leading to infertility and systemic consequences affecting reproductive, skeletal, cardiovascular, and neurocognitive helath. Aberrant immune activation, particularly an augmented T cell response in the ovary, plays a critical role in POI pathogenesis. In this context, therapeutic modulation of immune responses through immune checkpoint ligands has garnered interest. In the present study, we identified Lamp2b as an optimal scaffold for engineering extracellular vesicles (EVs). By genetically modifying HEK-293 T-derived EVs to present PD-L1 and Gal-9, enabling them to suppress ovarian autoreactive T lymphocytes and protect ovarian cells from immune-mediated destruction. Functionally, the bioengineered nanoplatform demonstrated potent immunosuppressive effects by promoting apoptosis of effector T cells, reducing intraovarian CD8⁺ T cell infiltration and reinstating serum anti-Müllerian hormone (AMH) levels in POI models. These combined actions effectively halted disease progression, ultimately preventing POI progression and preserving ovarian function.